Molecular Characterization of Staphylococcus aureus Isolates Transmitted between Patients with Buruli Ulcer.

PubMed

Amissah, Nana Ama; Chlebowicz, Monika A; Ablordey, Anthony; Sabat, Artur J; Tetteh, Caitlin S; Prah, Isaac; van der Werf, Tjip S; Friedrich, Alex W; van Dijl, Jan Maarten; Rossen, John W; Stienstra, Ymkje

2015-01-01

Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans. The wounds of most BU patients are colonized with different microorganisms, including Staphylococcus aureus. This study investigated possible patient-to-patient transmission events of S. aureus during wound care in a health care center. S. aureus isolates from different BU patients with overlapping visits to the clinic were whole-genome sequenced and analyzed by a gene-by-gene approach using SeqSphere(+) software. In addition, sequence data were screened for the presence of genes that conferred antibiotic resistance. SeqSphere(+) analysis of whole-genome sequence data confirmed transmission of methicillin resistant S. aureus (MRSA) and methicillin susceptible S. aureus among patients that took place during wound care. Interestingly, our sequence data show that the investigated MRSA isolates carry a novel allele of the fexB gene conferring chloramphenicol resistance, which had thus far not been observed in S. aureus.

Multicenter External Quality Assessment Program for PCR Detection of Mycobacterium ulcerans in Clinical and Environmental Specimens

PubMed Central

Eddyani, Miriam; Lavender, Caroline; de Rijk, Willem Bram; Bomans, Pieter; Fyfe, Janet; de Jong, Bouke; Portaels, Françoise

2014-01-01

Background Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a necrotizing disease of the skin, soft tissue and bone. PCR is increasingly used in the diagnosis of BU and in research on the mode of transmission and environmental reservoir of M. ulcerans. Methodology/Principal Findings The aim of this study was to evaluate the performance of laboratories in detecting M. ulcerans using molecular tests in clinical and environmental samples by implementing sequential multicenter external quality assessment (EQA) programs. The second round of the clinical EQA program revealed somewhat improved performance. Conclusions/Significance Ongoing EQA programs remain essential and continued participation in future EQA programs by laboratories involved in the molecular testing of clinical and environmental samples for M. ulcerans for diagnostic and research purposes is strongly encouraged. Broad participation in such EQA programs also benefits the harmonization of quality in the BU research community and enhances the credibility of advances made in solving the transmission enigma of M. ulcerans. PMID:24586755

Land Use, Water Quality, and Incidence of Buruli Ulcer in Gold-Mining Regions of Ghana

NASA Astrophysics Data System (ADS)

Hagarty, J.; Voegborlo, R.; Smithwick, E. A.; Singha, K.

2011-12-01

Buruli ulcer, an emerging bacterial disease caused by Mycobacterium ulcerans, affects populations in many equatorial countries, predominantly in western Africa. Occurring in over thirty countries worldwide, it is the third most common Mycobacterial disease after tuberculosis and leprosy. The disease causes ulcerative lesions and can lead to severe deformity if untreated. While methods of treatment for Buruli ulcer are well known and have a high rate of success, the mode of transmission of Buruli ulcer remains elusive. Multiple hypotheses have been put forward in the search for the vector for this disease. Studies of Buruli ulcer to date seem to conclude that water is, in some way, closely related to the transmission of this disease. In particular, changes in water quality due to changes in land use may contribute to the emergence of Buruli ulcer. We hypothesize that stagnant pools, especially those with low dissolved oxygen and high metals, nitrogen, and phosphorus concentrations, will provide a favorable environment for M. ulcerans growth and transmission. To explore how climate, land use, and soil and water quality interact to create a favorable environment for Buruli ulcer emergence, we explore seasonal and annual variability in rainfall and temperature, land use, and physical and chemical properties of soil and water at five sites within the country: four in the southern part of the country (three Buruli-endemic communities and one control) and one non-endemic community in the north. The southern control accounts for differences between endemic and non-endemic communities with similar land uses and geological setting. The northern community has experienced massive floods in recent years, and we suspect that, due to this, Buruli ulcer may start to appear in the community. Results from groundwater data indicate that aquifer rock type does not strongly correlate with groundwater chemistry and that groundwater chemistry does not relate to incidence of Buruli ulcer, thus highlighting that the problems are likely largely surface water based. Analyses of rainfall data collected from eleven stations throughout Ghana show that patterns of annual rainfall do not vary greatly between Buruli-endemic and non-endemic areas, suggesting that normal rainfall patterns do not affect incidence of disease, and that event-based precipitation may be a driving factor for the onset of Buruli ulcer. Analysis of localized soil and water chemistry is ongoing, with samples collected from mining pits, farms, rivers, ponds, swamps, and wells in our five communities within Ghana.

[Ecology and transmission of Mycobacterium ulcerans].

PubMed

Marsollier, L; Aubry, J; Saint-André, J-P; Robert, R; Legras, P; Manceau, A-L; Bourdon, S; Audrain, C; Carbonnelle, B

2003-10-01

Mycobacterium ulcerans is an environmental pathogen concerning mainly the tropical countries; it is the causative agent of Buruli ulcer, which has become the third most important mycobacterial disease. In spite of water-linked epidemiological studies to identify the sources of M. ulcerans, the reservoir and the mode of transmission of this organism remain elusive. To determine the ecology and the mode of transmission of M. ulcerans we have set up an experimental model. This experimental model demonstrated that water bugs were able to transmit M. ulcerans by bites. In insects, the bacilli were localized exclusively within salivary glands, where it could both multiply contrary to other mycobacteria species. In another experimental study, we report that the crude extracts from aquatic plants stimulate in vitro the growth of M. ulcerans as much as the biofilm formation by M. ulcerans has been observed on aquatic plants. Given that the water bugs are essentially carnivorous, it is difficult to imagine a direct contact in the contamination of aquatic bugs and plants. It seems very likely that an intermediate host exists. In an endemic area of Daloa in Côte d'Ivoire, our observations were confirmed.

A Landscape-based model for predicting Mycobacterium ulcerans infection (Buruli Ulcer disease) presence in Benin, West Africa.

PubMed

Wagner, Tyler; Benbow, M Eric; Burns, Meghan; Johnson, R Christian; Merritt, Richard W; Qi, Jiaguo; Small, Pamela L C

2008-03-01

Mycobacterium ulcerans infection (Buruli ulcer [BU] disease) is an emerging tropical disease that causes severe morbidity in many communities, especially those in close proximity to aquatic environments. Research and control efforts are severely hampered by the paucity of data regarding the ecology of this disease; for example, the vectors and modes of transmission remain unknown. It is hypothesized that BU presence is associated with altered landscapes that perturb aquatic ecosystems; however, this has yet to be quantified over large spatial scales. We quantified relationships between land use/land cover (LULC) characteristics surrounding individual villages and BU presence in Benin, West Africa. We also examined the effects of other village-level characteristics which we hypothesized to affect BU presence, such as village distance to the nearest river. We found that as the percent urban land use in a 50-km buffer surrounding a village increased, the probability of BU presence decreased. Conversely, as the percent agricultural land use in a 20-km buffer surrounding a village increased, the probability of BU presence increased. Landscape-based models had predictive ability when predicting BU presence using validation data sets from Benin and Ghana, West Africa. Our analyses suggest that relatively small amounts of urbanization are associated with a decrease in the probability of BU presence, and we hypothesize that this is due to the increased availability of pumped water in urban environments. Our models provide an initial approach to predicting the probability of BU presence over large spatial scales in Benin and Ghana, using readily available land use data.

Chemical and mineralogical characteristics of French green clays used for healing

USGS Publications Warehouse

Williams, Lynda B.; Haydel, Shelley E.; Giese, Rossman F.; Eberl, Dennis D.

2008-01-01

The worldwide emergence of infectious diseases, together with the increasing incidence of antibiotic-resistant bacteria, elevate the need to properly detect, prevent, and effectively treat these infections. The overuse and misuse of common antibiotics in recent decades stimulates the need to identify new inhibitory agents. Therefore, natural products like clays, that display antibacterial properties, are of particular interest.The absorptive properties of clay minerals are well documented for healing skin and gastrointestinal ailments. However, the antibacterial properties of clays have received less scientific attention. French green clays have recently been shown to heal Buruli ulcer, a necrotic or ‘flesh-eating’ infection caused by Mycobacterium ulcerans. Assessing the antibacterial properties of these clays could provide an inexpensive treatment for Buruli ulcer and other skin infections.Antimicrobial testing of the two clays on a broad-spectrum of bacterial pathogens showed that one clay promotes bacterial growth (possibly provoking a response from the natural immune system), while another kills bacteria or significantly inhibits bacterial growth. This paper compares the mineralogy and chemical composition of the two French green clays used in the treatment of Buruli ulcer.Mineralogically, the two clays are dominated by 1Md illite and Fe-smectite. Comparing the chemistry of the clay minerals and exchangeable ions, we conclude that the chemistry of the clay, and the surface properties that affect pH and oxidation state, control the chemistry of the water used to moisten the clay poultices and contribute the critical antibacterial agent(s) that ultimately debilitate the bacteria.

Risk factors for Mycobacterium ulcerans infection (Buruli Ulcer) in Togo ─ a case-control study in Zio and Yoto districts of the maritime region.

PubMed

Maman, Issaka; Tchacondo, Tchadjobo; Kere, Abiba Banla; Piten, Ebekalisai; Beissner, Marcus; Kobara, Yiragnima; Kossi, Komlan; Badziklou, Kossi; Wiedemann, Franz Xaver; Amekuse, Komi; Bretzel, Gisela; Karou, Damintoti Simplice

2018-01-19

Buruli ulcer (BU) is a neglected mycobacterial skin infection caused by Mycobacterium ulcerans. This disease mostly affects poor rural populations, especially in areas with low hygiene standards and sanitation coverage. The objective of this study was to identify these risk factors in the districts of Zio and Yoto of the Maritime Region in Togo. We conducted a case-control study in Zio and Yoto, two districts proved BU endemic from November 2014 to May 2015. BU cases were diagnosed according to the WHO clinical case definition at the Centre Hospitalier Régional de Tsévié (CHR Tsévié) and confirmed by Ziehl-Neelsen (ZN) microscopy and IS2404 polymerase chain reaction (PCR). For each case, up to two controls matched by sex and place of residence were recruited. Socio-demographic, environmental or behavioral data were collected and conditional logistic regression analysis was used to identify and compare risk factors between BU cases and controls. A total of 83 cases and 128 controls were enrolled. The median age was 15 years (range 3-65 years). Multivariate conditional logistic regression analysis after adjustment for potential confounders identified age (< 10 years (OR =11.48, 95% CI = 3.72-35.43) and 10-14 years (OR = 3.63, 95% CI = 1.22-10.83)), receiving insect bites near a river (OR = 7.8, 95% CI = 1.48-41.21) and bathing with water from open borehole (OR = 5.77, (1.11-29.27)) as independent predictors of acquiring BU infection. This study identified age, bathing with water from open borehole and receiving insect bites near a river as potential risk of acquiring BU infection in Zio and Yoto districts of the Maritime Region in south Togo.

Molecular Characterization of Staphylococcus aureus Isolates Transmitted between Patients with Buruli Ulcer

PubMed Central

Amissah, Nana Ama; Chlebowicz, Monika A.; Ablordey, Anthony; Sabat, Artur J.; Tetteh, Caitlin S.; Prah, Isaac; van der Werf, Tjip S.; Friedrich, Alex W.; van Dijl, Jan Maarten

2015-01-01

Background Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans. The wounds of most BU patients are colonized with different microorganisms, including Staphylococcus aureus. Methodology This study investigated possible patient-to-patient transmission events of S. aureus during wound care in a health care center. S. aureus isolates from different BU patients with overlapping visits to the clinic were whole-genome sequenced and analyzed by a gene-by-gene approach using SeqSphere+ software. In addition, sequence data were screened for the presence of genes that conferred antibiotic resistance. Principal Findings SeqSphere+ analysis of whole-genome sequence data confirmed transmission of methicillin resistant S. aureus (MRSA) and methicillin susceptible S. aureus among patients that took place during wound care. Interestingly, our sequence data show that the investigated MRSA isolates carry a novel allele of the fexB gene conferring chloramphenicol resistance, which had thus far not been observed in S. aureus. PMID:26360794

Global and local environmental changes as drivers of Buruli ulcer emergence.

PubMed

Combe, Marine; Velvin, Camilla Jensen; Morris, Aaron; Garchitorena, Andres; Carolan, Kevin; Sanhueza, Daniel; Roche, Benjamin; Couppié, Pierre; Guégan, Jean-François; Gozlan, Rodolphe Elie

2017-04-26

Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways. Using the case of Buruli ulcer disease, we review how land-use changes, climatic patterns and biodiversity alterations contribute to disease emergence in many parts of the world. Here we clearly show that Mycobacterium ulcerans is an environmental pathogen characterized by multi-host transmission dynamics and that its infectious pathways to humans rely on the local effects of global environmental changes. We show that the interplay between habitat changes (for example, deforestation and agricultural land-use changes) and climatic patterns (for example, rainfall events), applied in a local context, can lead to abiotic environmental changes and functional changes in local biodiversity that favor the pathogen's prevalence in the environment and may explain disease emergence.

Support needs of people living with Mycobacterium ulcerans (Buruli ulcer) disease in a Ghana rural community: a grounded theory study.

PubMed

Effah, Alex; Ersser, Steven J; Hemingway, Ann

2017-12-01

Mycobacterium ulcerans (also known as Buruli ulcer) disease is a rare skin disease which is prevalent in rural communities in the tropics mostly in Africa. Mortality rate is low, yet morbidity and consequent disabilities affect the quality of life of sufferers. The aim of this paper is to use the grounded theory method to explore the support needs of people living with the consequences of Buruli ulcer in an endemic rural community in Ghana. We used the grounded theory research approach to explore the experiences of people living with Mycobacterium ulcerans in a rural district in Ghana and provide a basis to understand the support needs of this group. The key support needs identified were: functional limitations, fear and frequency of disease recurrence, contracture of limbs and legs, loss of sensation and numbness in the affected body area, lack of information from health professionals about self-care, feeling tired all the time, insomnia, lack of good diet, lack of access to prostheses, having to walk long distances to access health services, and loss of educational opportunities. The study discusses how the systematically derived qualitative data has helped to provide a unique insight and advance our understanding of the support needs of people living with BU and how they live and attempt to adapt their lives with disability. We discuss how the availability of appropriate interventions and equipment could help them self-manage their condition and improve access to skin care services. The support needs of this vulnerable group were identified from a detailed analysis of how those living with BU coped with their lives. A key issue is the lack of education to assist self-management and prevent deterioration. Further research into the evaluation of interventions to address these support needs is necessary including self-management strategies. © 2017 The International Society of Dermatology.

The incubation period of Buruli ulcer (Mycobacterium ulcerans infection) in Victoria, Australia - Remains similar despite changing geographic distribution of disease.

PubMed

Loftus, Michael J; Trubiano, Jason A; Tay, Ee Laine; Lavender, Caroline J; Globan, Maria; Fyfe, Janet A M; Johnson, Paul D R

2018-03-01

Buruli ulcer (BU) is a geographically-restricted infection caused by Mycobacterium ulcerans; contact with an endemic region is the primary risk factor for disease acquisition. Globally, efforts to estimate the incubation period of BU are often hindered as most patients reside permanently in endemic areas. However, in the south-eastern Australian state of Victoria, a significant proportion of people who acquire BU are visitors to endemic regions. During a sustained outbreak of BU on the Bellarine peninsula we estimated a mean incubation period of 4.5 months. Since then cases on the Bellarine peninsula have declined but a new endemic area has developed centred on the Mornington peninsula. Retrospective review of 443 cases of BU notified in Victoria between 2013 and 2016. Telephone interviews were performed to identify all cases with a single visit to an endemic region, or multiple visits within a one month period. The incubation period was defined as the time between exposure to an endemic region and symptom onset. Data were subsequently combined with those from our earlier study incorporating cases from 2002 to 2012. Among the 20 new cases identified in short-term visitors, the mean incubation period was 143 days (4.8 months), very similar to the previous estimate of 135 days (4.5 months). This was despite the predominant exposure location shifting from the Bellarine peninsula to the Mornington peninsula. We found no association between incubation period and age, sex, location of exposure, duration of exposure to an endemic region or location of BU lesion. Our study confirms the mean incubation period of BU in Victoria to be between 4 and 5 months. This knowledge can guide clinicians and suggests that the mode of transmission of BU is similar in different geographic regions in Victoria.

The contribution of community health workers to the control of Buruli ulcer in the Ngoantet area, Cameroon.

PubMed

Vouking, Marius Zambou; Takougang, Innocent; Mbam, Léonard Mbam; Mbuagbaw, Lawrence; Tadenfok, Carine Nouboudem; Tamo, Claire Violette

2013-01-01

Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. It is the third most common mycobacterial infection after tuberculosis and leprosy. Community Health Workers (CHWs) hold the potential to support patients and their families at the community level. We conducted a cross-sectional descriptive study to assess the participation of CHWs in the early diagnosis and treatment of BU in Ngoantet, Cameroon. The CHWs performance was measured using: the number of cases referred to the Ngoantet Health Centre, the percentage of accomplished referrals, the percentage of cases referred by CHWs confirmed by the staff of Ngoantet Health Centre. Data was analyzed using Epi-info version 3.4.1. and Microsoft Office Excel 2003. The study focused on 51 CHWs in the Ngoantet health area. The referral rate was 95.0%. Most of the suspicious cases (91.5%) referred were confirmed by health workers. Most CHWs (78.4%) declared that they had identified at least one presumptive case of BU infection. We conclude that the CHWs can play a key role in scaling up BU control activities using a referral system. This study confirms the role of home visits and inspections in the early detection and treatment of BU.

Family relationship, water contact and occurrence of Buruli ulcer in Benin.

PubMed

Sopoh, Ghislain Emmanuel; Barogui, Yves Thierry; Johnson, Roch Christian; Dossou, Ange Dodji; Makoutodé, Michel; Anagonou, Sévérin Y; Kestens, Luc; Portaels, Françoise

2010-07-13

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). Case control study. Department of Atlantique, Benin. BU-confirmed cases that were diagnosed and followed up at the BU detection and treatment center (CDTUB) of Allada (Department of the Atlantique, Benin) during the period from January 1st, 2006, to June 30th, 2008, with three matched controls (persons who had no signs or symptoms of active or inactive BU) for age, gender and village of residence per case. Contact with natural water sources, BU history in the family and the practice of consanguineous marriages. A total of 416 participants were included in this study, including 104 cases and 312 controls. BU history in the family (p<0.001), adjusted by daily contact with a natural water source (p = 0.007), was significantly associated with higher odds of having BU (OR; 95% CI = 5.5; 3.0-10.0). The practice of consanguineous marriage was not associated with the occurrence of BU (p = 0.40). Mendelian disorders could explain this finding, which may influence individual susceptibility by impairing immunity. This study suggests that a combination of genetic factors and behavioral risk factors may increase the susceptibility for developing BU.

Multiple Introductions and Recent Spread of the Emerging Human Pathogen Mycobacterium ulcerans across Africa

PubMed Central

Meehan, Conor J.; Eddyani, Miriam; Affolabi, Dissou; Phanzu, Delphin Mavinga; Eyangoh, Sara; Jordaens, Kurt; Portaels, Françoise; Mangas, Kirstie; Seemann, Torsten; Marsollier, Laurent; Marion, Estelle; Chauty, Annick; Landier, Jordi; Fontanet, Arnaud; Leirs, Herwig; Stinear, Timothy P.; de Jong, Bouke C.

2017-01-01

Buruli ulcer (BU) is an insidious neglected tropical disease. Cases are reported around the world but the rural regions of West and Central Africa are most affected. How BU is transmitted and spreads has remained a mystery, even though the causative agent, Mycobacterium ulcerans, has been known for more than 70 years. Here, using the tools of population genomics, we reconstruct the evolutionary history of M. ulcerans by comparing 165 isolates spanning 48 years and representing 11 endemic countries across Africa. The genetic diversity of African M. ulcerans was found to be restricted due to the bacterium’s slow substitution rate coupled with its relatively recent origin. We identified two specific M. ulcerans lineages within the African continent, and inferred that M. ulcerans lineage Mu_A1 existed in Africa for several hundreds of years, unlike lineage Mu_A2, which was introduced much more recently, approximately during the 19th century. Additionally, we observed that specific M. ulcerans epidemic Mu_A1 clones were introduced during the same time period in the three hydrological basins that were well covered in our panel. The estimated time span of the introduction events coincides with the Neo-imperialism period, during which time the European colonial powers divided the African continent among themselves. Using this temporal association, and in the absence of a known BU reservoir or—vector on the continent, we postulate that the so-called "Scramble for Africa" played a significant role in the spread of the disease across the continent. PMID:28137745

Virulence potential of Staphylococcus aureus isolates from Buruli ulcer patients.

PubMed

Amissah, Nana Ama; Chlebowicz, Monika A; Ablordey, Anthony; Tetteh, Caitlin S; Prah, Isaac; van der Werf, Tjip S; Friedrich, Alex W; van Dijl, Jan Maarten; Stienstra, Ymkje; Rossen, John W

2017-06-01

Buruli ulcer (BU) is a necrotizing infection of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU wounds may also be colonized with other microorganisms including Staphylococcus aureus. This study aimed to characterize the virulence factors of S. aureus isolated from BU patients. Previously sequenced genomes of 21 S. aureus isolates from BU patients were screened for the presence of virulence genes. The results show that all S. aureus isolates harbored on their core genomes genes for known virulence factors like α-hemolysin, and the α- and β-phenol soluble modulins. Besides the core genome virulence genes, mobile genetic elements (MGEs), i.e. prophages, genomic islands, pathogenicity islands and a Staphylococcal cassette chromosome (SCC) were found to carry different combinations of virulence factors, among them genes that are known to encode factors that promote immune evasion, superantigens and Panton-Valentine Leucocidin. The present observations imply that the S. aureus isolates from BU patients harbor a diverse repertoire of virulence genes that may enhance bacterial survival and persistence in the wound environment and potentially contribute to delayed wound healing. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Evolution of Mycobacterium ulcerans and Other Mycolactone-Producing Mycobacteria from a Common Mycobacterium marinum Progenitor▿ †

PubMed Central

Yip, Marcus J.; Porter, Jessica L.; Fyfe, Janet A. M.; Lavender, Caroline J.; Portaels, Françoise; Rhodes, Martha; Kator, Howard; Colorni, Angelo; Jenkin, Grant A.; Stinear, Tim

2007-01-01

It had been assumed that production of the cytotoxic polyketide mycolactone was strictly associated with Mycobacterium ulcerans, the causative agent of Buruli ulcer. However, a recent study has uncovered a broader distribution of mycolactone-producing mycobacteria (MPM) that includes mycobacteria cultured from diseased fish and frogs in the United States and from diseased fish in the Red and Mediterranean Seas. All of these mycobacteria contain versions of the M. ulcerans pMUM plasmid, produce mycolactones, and show a high degree of genetic relatedness to both M. ulcerans and Mycobacterium marinum. Here, we show by multiple genetic methods, including multilocus sequence analysis and DNA-DNA hybridization, that all MPM have evolved from a common M. marinum progenitor to form a genetically cohesive group among a more diverse assemblage of M. marinum strains. Like M. ulcerans, the fish and frog MPM show multiple copies of the insertion sequence IS2404. Comparisons of pMUM and chromosomal gene sequences demonstrate that plasmid acquisition and the subsequent ability to produce mycolactone were probably the key drivers of speciation. Ongoing evolution among MPM has since produced at least two genetically distinct ecotypes that can be broadly divided into those typically causing disease in ectotherms (but also having a high zoonotic potential) and those causing disease in endotherms, such as humans. PMID:17172337

Multiple Introductions and Recent Spread of the Emerging Human Pathogen Mycobacterium ulcerans across Africa.

PubMed

Vandelannoote, Koen; Meehan, Conor J; Eddyani, Miriam; Affolabi, Dissou; Phanzu, Delphin Mavinga; Eyangoh, Sara; Jordaens, Kurt; Portaels, Françoise; Mangas, Kirstie; Seemann, Torsten; Marsollier, Laurent; Marion, Estelle; Chauty, Annick; Landier, Jordi; Fontanet, Arnaud; Leirs, Herwig; Stinear, Timothy P; de Jong, Bouke C

2017-03-01

Buruli ulcer (BU) is an insidious neglected tropical disease. Cases are reported around the world but the rural regions of West and Central Africa are most affected. How BU is transmitted and spreads has remained a mystery, even though the causative agent, Mycobacterium ulcerans, has been known for more than 70 years. Here, using the tools of population genomics, we reconstruct the evolutionary history of M. ulcerans by comparing 165 isolates spanning 48 years and representing 11 endemic countries across Africa. The genetic diversity of African M. ulcerans was found to be restricted due to the bacterium's slow substitution rate coupled with its relatively recent origin. We identified two specific M. ulcerans lineages within the African continent, and inferred that M. ulcerans lineage Mu_A1 existed in Africa for several hundreds of years, unlike lineage Mu_A2, which was introduced much more recently, approximately during the 19th century. Additionally, we observed that specific M. ulcerans epidemic Mu_A1 clones were introduced during the same time period in the three hydrological basins that were well covered in our panel. The estimated time span of the introduction events coincides with the Neo-imperialism period, during which time the European colonial powers divided the African continent among themselves. Using this temporal association, and in the absence of a known BU reservoir or-vector on the continent, we postulate that the so-called "Scramble for Africa" played a significant role in the spread of the disease across the continent. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Clinical patterns of cutaneous nontuberculous mycobacterial infections.

PubMed

Bartralot, R; García-Patos, V; Sitjas, D; Rodríguez-Cano, L; Mollet, J; Martín-Casabona, N; Coll, P; Castells, A; Pujol, R M

2005-04-01

Cutaneous nontuberculous mycobacterial infections result from external inoculation, spread of a deeper infection, or haematogenous spread of a disseminated infection. There are two species-specific infections (fish-tank or swimming-pool granuloma, due to Mycobacterium marinum, and Buruli ulcer, caused by M. ulcerans). Most infections, however, produce a nonspecific clinical picture. To define clinical patterns of cutaneous disease in nontuberculous mycobacterial infections. Fifty-one patients with cutaneous nontuberculous mycobacterial infections were reviewed. Clinical and histopathological features of normal hosts and immunosuppressed patients were compared. Two subgroups of immunosuppressed patients were distinguished: patients with cutaneous infection and patients with a disseminated infection and cutaneous involvement. In immunosuppressed patients the number of lesions was significantly higher. Abscesses and ulceration were also more frequently observed. Different species were found in normal hosts and immunosuppressed patients. Several clinical patterns of cutaneous infection were defined: lymphocutaneous or sporotrichoid lesions; nonlymphocutaneous lesions at the site of trauma; folliculitis and furunculosis involving the lower extremities; disseminated lesions on the extremities in immunosuppressed patients. Two patterns were observed in patients with a disseminated infection: localized cutaneous lesions and disseminated cutaneous and mucosal lesions. Cutaneous manifestations of nontuberculous mycobacterial infections may be classified according to criteria such as cutaneous lesions and immune status.

Proteomic analysis of the action of the Mycobacterium ulcerans toxin mycolactone: targeting host cells cytoskeleton and collagen.

PubMed

Gama, José B; Ohlmeier, Steffen; Martins, Teresa G; Fraga, Alexandra G; Sampaio-Marques, Belém; Carvalho, Maria A; Proença, Fernanda; Silva, Manuel T; Pedrosa, Jorge; Ludovico, Paula

2014-08-01

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. The tissue damage characteristic of BU lesions is known to be driven by the secretion of the potent lipidic exotoxin mycolactone. However, the molecular action of mycolactone on host cell biology mediating cytopathogenesis is not fully understood. Here we applied two-dimensional electrophoresis (2-DE) to identify the mechanisms of mycolactone's cellular action in the L929 mouse fibroblast proteome. This revealed 20 changed spots corresponding to 18 proteins which were clustered mainly into cytoskeleton-related proteins (Dync1i2, Cfl1, Crmp2, Actg1, Stmn1) and collagen biosynthesis enzymes (Plod1, Plod3, P4ha1). In line with cytoskeleton conformational disarrangements that are observed by immunofluorescence, we found several regulators and constituents of both actin- and tubulin-cytoskeleton affected upon exposure to the toxin, providing a novel molecular basis for the effect of mycolactone. Consistent with these cytoskeleton-related alterations, accumulation of autophagosomes as well as an increased protein ubiquitination were observed in mycolactone-treated cells. In vivo analyses in a BU mouse model revealed mycolactone-dependent structural changes in collagen upon infection with M. ulcerans, associated with the reduction of dermal collagen content, which is in line with our proteomic finding of mycolactone-induced down-regulation of several collagen biosynthesis enzymes. Our results unveil the mechanisms of mycolactone-induced molecular cytopathogenesis on exposed host cells, with the toxin compromising cell structure and homeostasis by inducing cytoskeleton alterations, as well as disrupting tissue structure, by impairing the extracellular matrix biosynthesis.

Aquatic macroinvertebrate assemblages of Ghana, West Africa: understanding the ecology of a neglected tropical disease.

PubMed

Eric Benbow, M; Kimbirauskas, Ryan; McIntosh, Mollie D; Williamson, Heather; Quaye, Charles; Boakye, Daniel; Small, Pamela L C; Merritt, Richard W

2014-06-01

Buruli ulcer (BU) is an emerging, but neglected tropical disease, where there has been a reported association with disturbed aquatic habitats and proposed aquatic macroinvertebrate vectors such as biting Hemiptera. An initial step in understanding the potential role of macroinvertebrates in the ecology of BU is to better understand the entire community, not just one or two taxa, in relation to the pathogen, Mycobacterium ulcerans, at a large spatial scale. For the first time at a country-wide scale this research documents that M. ulcerans was frequently detected from environmental samples taken from BU endemic regions, but was not present in 30 waterbodies of a non-endemic region. There were significant differences in macroinvertebrate community structure and identified potential indicator taxa in relation to pathogen presence. These results suggest that specific macroinvertebrate taxa or functional metrics may potentially be used as aquatic biological indicators of M. ulcerans. Developing ecological indicators of this pathogen is a first step for understanding the disease ecology of BU and should assist future studies of transmission.

Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

PubMed

Hart, Bryan E; Lee, Sunhee

2016-12-01

Buruli ulcer (BU) vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU) cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A) displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

The incubation period of Buruli ulcer (Mycobacterium ulcerans infection).

PubMed

Trubiano, Jason A; Lavender, Caroline J; Fyfe, Janet A M; Bittmann, Simone; Johnson, Paul D R

2013-01-01

Buruli Ulcer (BU) is caused by the environmental microbe Mycobacterium ulcerans. Despite unclear transmission, contact with a BU endemic region is the key known risk factor. In Victoria, Australia, where endemic areas have been carefully mapped, we aimed to estimate the Incubation Period (IP) of BU by interviewing patients who reported defined periods of contact with an endemic area prior to BU diagnosis. A retrospective review was undertaken of 408 notifications of BU in Victoria from 2002 to 2012. Telephone interviews using a structured questionnaire and review of notification records were performed. Patients with a single visit exposure to a defined endemic area were included and the period from exposure to disease onset determined (IP). We identified 111 of 408 notified patients (27%) who had a residential address outside a known endemic area, of whom 23 (6%) reported a single visit exposure within the previous 24 months. The median age of included patients was 30 years (range: 6 to 73) and 65% were male. 61% had visited the Bellarine Peninsula, currently the most active endemic area. The median time from symptom onset to diagnosis was 71 days (range: 34-204 days). The midpoint of the reported IP range was utilized to calculate a point estimate of the IP for each case. Subsequently, the mean IP for the cohort was calculated at 135 days (IQR: 109-160; CI 95%: 113.9-156), corresponding to 4.5 months or 19.2 weeks. The shortest IP recorded was 32 days and longest 264 days (Figure 1 & 2). IP did not vary for variables investigated. The estimated mean IP of BU in Victoria is 135 days (IQR: 109-160 days), 4.5 months. The shortest recorded was IP 34 days and longest 264 days. A greater understanding of BU IP will aid clinical risk assessment and future research.

The puzzle of Buruli ulcer transmission, ethno-ecological history and the end of "love" in the Akonolinga district, Cameroon.

PubMed

Giles-Vernick, Tamara; Owona-Ntsama, Joseph; Landier, Jordi; Eyangoh, Sara

2015-03-01

The "One World One Health Initiative" has attended little to the priorities, concepts and practices of resource-poor communities confronting disease and the implications of these concerns for its biomedical, ecological and institutional approach to disease surveillance and control. Using the example of Buruli ulcer (BU) and its bacterial etiology, Mycobacterium ulcerans, in south-central Cameroon, we build on debates about the contributions of "local knowledge" and "alternative models" to biomedical knowledge of disease transmission. BU's mode of transmission remains poorly understood. Our approach employs ethno-ecological histories - local understandings of the putative emergence and expansion of a locally important, neglected disease. We develop these histories from 52 individual and small group interviews, group discussions, and participant-observation of daily and seasonal activities, conducted in 2013-2013. These histories offer important clues about past environmental and social change that should guide further ecological, epidemiological research. They highlight a key historical moment (the late 1980s and 1990s); specific ecological transformations; new cultivation practices in unexploited zones that potentially increased exposure to M. ulcerans; and ecological degradation that may have lowered nutritional standards and heightened susceptibility to BU. They also recast transmission, broadening insight into BU and its local analog, atom, by emphasizing the role of social change and economic crisis in its emergence and expansion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exploring the Buruli Ulcer Incidence across a socio-ecological landscape in Ghana

NASA Astrophysics Data System (ADS)

Naithani, K. J.; Konzelman, C.; Tschakert, P.; Smithwick, E. A. H.

2016-12-01

The Buruli Ulcer (BU) disease is one of the most prevalent, but poorly understood mycobacterial infections in the world. Fundamental ecological aspects of the disease causing bacteria (Mycobacterium ulcerans) are not understood completely, but its emergence is attributed to unidentified thresholds in human and natural systems. We explored the network of these interactions across socio-ecological landscapes of Ghana to understand the movement of bacteria and the emergence of BU in response to climate, disturbance, social and economic factors. We chose five communities, three endemic and two control, and explored the correlations of disease incidence with climate, landscape disturbance, water quality and social factors using path analysis. Our results show that water quality is strongly linked to disease emergence with high alkalinity, PO43-, NH4+, F, Mn, S, Cd, Fe, Pb, and Se were associated with higher disease incidents and high Cu concentration was associated with low or healthy communities. Contrary to previous studies, arsenic concentration in water was not linked to higher disease incidence. Water quality was linked to climate, type of mining, and agricultural practices. Higher annual precipitation and lower air temperature were found linked to higher disease incidence across communities. Our exploratory work provides insight into how human land use, social practices, demographics, and climatic factors influence the BU disease spread.

Mycobacterium ulcerans Disease, Peru

PubMed Central

Guerra, Humberto; Palomino, Juan Carlos; Falconí, Eduardo; Bravo, Francisco; Donaires, Ninoska; Van Marck, Eric

2008-01-01

Eight adult patients (ages 18–58, 5 women) with Buruli ulcer (BU) confirmed by at least 2 diagnostic methods were seen in a 10-year period. Attempts to culture Mycobacterium ulcerans failed. Five patients came from jungle areas, and 3 from the swampy northern coast of Peru. The patients had 1–5 lesions, most of which were on the lower extremities. One patient had 5 clustered gluteal lesions; another patient had 2 lesions on a finger. Three patients were lost to follow-up. All 5 remaining patients had moderate disease. Diverse treatments (antituberculous drugs, World Health Organization [WHO] recommended antimicrobial drug treatment for BU, and for 3 patients, excision surgery) were successful. Only 1 patient (patient 7) received the specific drug treatment recommended by WHO. BU is endemic in Peru, although apparently infrequent. Education of populations and training of health workers are first needed to evaluate and understand the full extent of BU in Peru. PMID:18325248

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

PubMed

Anand, U; Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

2016-01-01

Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Mycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection. © The Author(s) 2016.

Implementation of a decentralized community-based treatment program to improve the management of Buruli ulcer in the Ouinhi district of Benin, West Africa

PubMed Central

Amoussouhoui, Arnaud Setondji; Wadagni, Anita Carolle; Johnson, Roch Christian; Aoulou, Paulin; Agbo, Inès Elvire; Houezo, Jean-Gabin; Boyer, Micah; Nichter, Mark

2018-01-01

Background Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin’s most endemic districts previously served by centralized hospital-based care. Methodology/Principal findings We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. Conclusions/Significance This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control. PMID:29529087

Implementation of a decentralized community-based treatment program to improve the management of Buruli ulcer in the Ouinhi district of Benin, West Africa.

PubMed

Amoussouhoui, Arnaud Setondji; Sopoh, Ghislain Emmanuel; Wadagni, Anita Carolle; Johnson, Roch Christian; Aoulou, Paulin; Agbo, Inès Elvire; Houezo, Jean-Gabin; Boyer, Micah; Nichter, Mark

2018-03-01

Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin's most endemic districts previously served by centralized hospital-based care. We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control.

Experimental demonstration of the possible role of Acanthamoeba polyphaga in the infection and disease progression in Buruli Ulcer (BU) using ICR mice

PubMed Central

Azumah, Bright K.; Addo, Phyllis G.; Dodoo, Alfred; Awandare, Gordon; Mosi, Lydia; Boakye, Daniel A.

2017-01-01

The transmission of Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), remains puzzling although a number of hypothesis including through bites of infected aquatic insects have been proposed. We report the results of experiments using ICR mice that give credence to our hypothesis that Acanthamoeba species may play a role in BU transmission. We cocultured MU N2 and MU 1615 which expresses red fluorescent protein (RFP) and Acanthamoeba polyphaga (AP), and confirmed infected AP by Ziehl-Neelsen (ZN) staining. We tested for viability of MU inside AP and observed strong RFP signals inside both trophozoites and cysts after 3 and 42 days of coculturing respectively. ICR mice were topically treated, either on shaved intact or shaved pinpricked rumps, with one of the following; MU N2 only (2.25 x 106 colony forming units [CFU] / ml), MU N2:AP coculture (2.96 x 104 CFU: 1.6 x 106 cells/ml), AP only (1.6 x 106 cells/ml), PYG medium and sterile distilled water. Both MU N2 only and MU N2:AP elicited reddening on day (D) 31; edema on D 45 and D 44 respectively, and ulcers on D 49 at pinpricked sites only. To ascertain infectivity and pathogenicity of MU N2 only and MU N2:AP, and compare their virulence, the standard mouse footpad inoculation method was used. MU N2:AP elicited reddening in footpads by D 3 compared to D 14 with MU N2 only of the same dose of MU N2 (2.96 x 104 CFU). ZN-stained MU were observed in both thin sectioned and homogenized lesions, and aspirates from infected sites. Viable MU N2 were recovered from cultures of the homogenates and aspirates. This study demonstrates in ICR mice MU transmission via passive infection, and shows that punctures in the skin are prerequisite for infection, and that coculturing of MU with AP enhances pathogenesis. PMID:28329001

Geographic Distribution, Age Pattern and Sites of Lesions in a Cohort of Buruli Ulcer Patients from the Mapé Basin of Cameroon

PubMed Central

Bratschi, Martin W.; Bolz, Miriam; Minyem, Jacques C.; Grize, Leticia; Wantong, Fidèle G.; Kerber, Sarah; Njih Tabah, Earnest; Ruf, Marie-Thérèse; Mou, Ferdinand; Noumen, Djeunga; Um Boock, Alphonse; Pluschke, Gerd

2013-01-01

Buruli ulcer (BU), a neglected tropical disease of the skin, caused by Mycobacterium ulcerans, occurs most frequently in children in West Africa. Risk factors for BU include proximity to slow flowing water, poor wound care and not wearing protective clothing. Man-made alterations of the environment have been suggested to lead to increased BU incidence. M. ulcerans DNA has been detected in the environment, water bugs and recently also in mosquitoes. Despite these findings, the mode of transmission of BU remains poorly understood and both transmission by insects or direct inoculation from contaminated environment have been suggested. Here, we investigated the BU epidemiology in the Mapé basin of Cameroon where the damming of the Mapé River since 1988 is believed to have increased the incidence of BU. Through a house-by-house survey in spring 2010, which also examined the local population for leprosy and yaws, and continued surveillance thereafter, we identified, till June 2012, altogether 88 RT-PCR positive cases of BU. We found that the age adjusted cumulative incidence of BU was highest in young teenagers and in individuals above the age of 50 and that very young children (<5) were underrepresented among cases. BU lesions clustered around the ankles and at the back of the elbows. This pattern neither matches any of the published mosquito biting site patterns, nor the published distribution of small skin injuries in children, where lesions on the knees are much more frequent. The option of multiple modes of transmission should thus be considered. Analyzing the geographic distribution of cases in the Mapé Dam area revealed a closer association with the Mbam River than with the artificial lake. PMID:23785529

Genetic diversity of Staphylococcus aureus in Buruli ulcer.

PubMed

Amissah, Nana Ama; Glasner, Corinna; Ablordey, Anthony; Tetteh, Caitlin S; Kotey, Nana Konama; Prah, Isaac; van der Werf, Tjip S; Rossen, John W; van Dijl, Jan Maarten; Stienstra, Ymkje

2015-02-01

Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Previous studies have shown that wounds of BU patients are colonized with M. ulcerans and several other microorganisms, including Staphylococcus aureus, which may interfere with wound healing. The present study was therefore aimed at investigating the diversity and topography of S. aureus colonizing BU patients during treatment. We investigated the presence, diversity, and spatio-temporal distribution of S. aureus in 30 confirmed BU patients from Ghana during treatment. S. aureus was isolated from nose and wound swabs, and by replica plating of wound dressings collected bi-weekly from patients. S. aureus isolates were characterized by multiple-locus variable number tandem repeat fingerprinting (MLVF) and spa-typing, and antibiotic susceptibility was tested. Nineteen (63%) of the 30 BU patients tested positive for S. aureus at least once during the sampling period, yielding 407 S. aureus isolates. Detailed analysis of 91 isolates grouped these isolates into 13 MLVF clusters and 13 spa-types. Five (26%) S. aureus-positive BU patients carried the same S. aureus genotype in their anterior nares and wounds. S. aureus isolates from the wounds of seven (37%) patients were distributed over two different MLVF clusters. Wounds of three (16%) patients were colonized with isolates belonging to two different genotypes at the same time, and five (26%) patients were colonized with different S. aureus types over time. Five (17%) of the 30 included BU patients tested positive for methicillin-resistant S. aureus (MRSA). The present study showed that the wounds of many BU patients were contaminated with S. aureus, and that many BU patients from the different communities carried the same S. aureus genotype during treatment. This calls for improved wound care and hygiene.

Seasonal Pattern of Mycobacterium ulcerans, the Causative Agent of Buruli Ulcer, in the Environment in Ghana.

PubMed

Aboagye, Samuel Yaw; Ampah, Kobina Assan; Ross, Amanda; Asare, Prince; Otchere, Isaac Darko; Fyfe, Janet; Yeboah-Manu, Dorothy

2017-08-01

This study aimed to contribute to the understanding of Mycobacterium ulcerans (MU) ecology by analysing both clinical and environmental samples collected from ten communities along two major river basins (Offin and Densu) associated with Buruli ulcer (BU) at different seasons. We collected clinical samples from presumptive BU cases and environmental samples from ten communities. Following DNA extraction, clinical samples were confirmed by IS2404 PCR and environmental samples were confirmed by targeting MU-specific genes, IS2404, IS2606 and the ketoreductase (KR) using real-time PCR. Environmental samples were first analysed for IS2404; after which, IS2404-positive samples were multiplexed for the IS2606 and KR gene. Our findings indicate an overall decline in BU incidence along both river basins, although incidence at Densu outweighs that of Offin. Overall, 1600 environmental samples were screened along Densu (434, 27 %) and Offin (1166, 73 %) and MU was detected in 139 (9 %) of the combined samples. The positivity of MU along the Densu River basin was 89/434 (20.5 %), whilst that of the Offin River basin was 50/1166 (4.3 %). The DNA was detected mainly in snails (5/6, 83 %), moss (8/40, 20 %), soil (55/586, 9 %) and vegetation (55/675, 8 %). The proportion of MU positive samples recorded was higher during the months with higher rainfall levels (126/1175, 11 %) than during the dry season months (13/425, 3 %). This study indicates for the first time that there is a seasonal pattern in the presence of MU in the environment, which may be related to recent rainfall or water in the soil.

Buruli ulcer disease prevalence in Benin, West Africa: Associations with land use/cover and the identification of disease clusters

USGS Publications Warehouse

Wagner, T.; Benbow, M.E.; Brenden, T.O.; Qi, J.; Johnson, R.C.

2008-01-01

Background: Buruli ulcer (BU) disease, caused by infection with the environmental mycobacterium M. ulcerans, is an emerging infectious disease in many tropical and sub-tropical countries. Although vectors and modes of transmission remain unknown, it is hypothesized that the transmission of BU disease is associated with human activities in or around aquatic environments, and that characteristics of the landscape (e.g., land use/cover) play a role in mediating BU disease. Several studies performed at relatively small spatial scales (e.g., within a single village or region of a country) support these hypotheses; however, if BU disease is associated with land use/cover characteristics, either through spatial constraints on vector-host dynamics or by mediating human activities, then large-scale (i.e., country-wide) associations should also emerge. The objectives of this study were to (1) investigate associations between BU disease prevalence in villages in Benin, West Africa and surrounding land use/cover patterns and other map-based characteristics, and (2) identify areas with greater and lower than expected prevalence rates (i.e., disease clusters) to assist with the development of prevention and control programs. Results: Our landscape-based models identified low elevation, rural villages surrounded by forest land cover, and located in drainage basins with variable wetness patterns as being associated with higher BU disease prevalence rates. We also identified five spatial disease clusters. Three of the five clusters contained villages with greater than expected prevalence rates and two clusters contained villages with lower than expected prevalence rates. Those villages with greater than expected BU disease prevalence rates spanned a fairly narrow region of south-central Benin. Conclusion: Our analyses suggest that interactions between natural land cover and human alterations to the landscape likely play a role in the dynamics of BU disease. For example, urbanization, potentially by providing access to protected water sources, may reduce the likelihood of becoming infected with BU disease. Villages located at low elevations may have higher BU disease prevalence rates due to their close spatial proximity to high risk environments. In addition, forest land cover and drainage basins with variable wetness patterns may be important for providing suitable growth conditions for M. ulcerans, influencing the distribution and abundance of vectors, or mediating vector-human interactions. The identification of disease clusters in this study provides direction for future research aimed at better understanding these and other environmental and social determinants involved in BU disease outbreaks. ?? 2008 Wagner et al; licensee BioMed Central Ltd.

Buruli ulcer disease prevalence in Benin, West Africa: associations with land use/cover and the identification of disease clusters

PubMed Central

Wagner, Tyler; Benbow, M Eric; Brenden, Travis O; Qi, Jiaguo; Johnson, R Christian

2008-01-01

Background Buruli ulcer (BU) disease, caused by infection with the environmental mycobacterium M. ulcerans, is an emerging infectious disease in many tropical and sub-tropical countries. Although vectors and modes of transmission remain unknown, it is hypothesized that the transmission of BU disease is associated with human activities in or around aquatic environments, and that characteristics of the landscape (e.g., land use/cover) play a role in mediating BU disease. Several studies performed at relatively small spatial scales (e.g., within a single village or region of a country) support these hypotheses; however, if BU disease is associated with land use/cover characteristics, either through spatial constraints on vector-host dynamics or by mediating human activities, then large-scale (i.e., country-wide) associations should also emerge. The objectives of this study were to (1) investigate associations between BU disease prevalence in villages in Benin, West Africa and surrounding land use/cover patterns and other map-based characteristics, and (2) identify areas with greater and lower than expected prevalence rates (i.e., disease clusters) to assist with the development of prevention and control programs. Results Our landscape-based models identified low elevation, rural villages surrounded by forest land cover, and located in drainage basins with variable wetness patterns as being associated with higher BU disease prevalence rates. We also identified five spatial disease clusters. Three of the five clusters contained villages with greater than expected prevalence rates and two clusters contained villages with lower than expected prevalence rates. Those villages with greater than expected BU disease prevalence rates spanned a fairly narrow region of south-central Benin. Conclusion Our analyses suggest that interactions between natural land cover and human alterations to the landscape likely play a role in the dynamics of BU disease. For example, urbanization, potentially by providing access to protected water sources, may reduce the likelihood of becoming infected with BU disease. Villages located at low elevations may have higher BU disease prevalence rates due to their close spatial proximity to high risk environments. In addition, forest land cover and drainage basins with variable wetness patterns may be important for providing suitable growth conditions for M. ulcerans, influencing the distribution and abundance of vectors, or mediating vector-human interactions. The identification of disease clusters in this study provides direction for future research aimed at better understanding these and other environmental and social determinants involved in BU disease outbreaks. PMID:18505567

[Skin and Soft Tissue Infections Due to Corynebacterium ulcerans - Case Reports].

PubMed

Jenssen, Christian; Schwede, Ilona; Neumann, Volker; Pietsch, Cristine; Handrick, Werner

2017-10-01

History and clinical findings  We report on three patients suffering from skin and soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans strains. In all three patients, there was a predisposition due to chronic diseases. Three patients had domestic animals (cat, dog) in their households. Investigations and diagnosis  A mixed bacterial flora including Corynebacterium ulcerans was found in wound swab samples. Diphtheric toxin was produced by the Corynebacterium ulcerans strains in all three cases. Treatment and course  In all three patients, successful handling of the skin and soft tissue infections was possible by combining local treatment with antibiotics. Diphtheria antitoxin was not administered in any case. Conclusion  Based on a review of the recent literature pathogenesis, clinical symptoms and signs, diagnostics and therapy of skin and soft tissue infections due to Corynebacterium ulcerans are discussed. Corynebacterium ulcerans should be considered as a potential cause of severe skin and soft tissue infections. Occupational or domestic animal contacts should be evaluated. © Georg Thieme Verlag KG Stuttgart · New York.

Efficacy of Rifampin Plus Clofazimine in a Murine Model of Mycobacterium ulcerans Disease

PubMed Central

Converse, Paul J.; Tyagi, Sandeep; Xing, Yalan; Li, Si-Yang; Kishi, Yoshito; Adamson, John; Nuermberger, Eric L.; Grosset, Jacques H.

2015-01-01

Treatment of Buruli ulcer, or Mycobacterium ulcerans disease, has shifted from surgical excision and skin grafting to antibiotic therapy usually with 8 weeks of daily rifampin (RIF) and streptomycin (STR). Although the results have been highly favorable, administration of STR requires intramuscular injection and carries the risk of side effects, such as hearing loss. Therefore, an all-oral, potentially less toxic, treatment regimen has been sought and encouraged by the World Health Organization. A combination of RIF plus clarithromycin (CLR) has been successful in patients first administered RIF+STR for 2 or 4 weeks. Based on evidence of efficacy of clofazimine (CFZ) in humans and mice with tuberculosis, we hypothesized that the combination of RIF+CFZ would be effective against M. ulcerans in the mouse footpad model of M. ulcerans disease because CFZ has similar MIC against M. tuberculosis and M. ulcerans. For comparison, mice were also treated with the gold standard of RIF+STR, the proposed RIF+CLR alternative regimen, or CFZ alone. Treatment was initiated after development of footpad swelling, when the bacterial burden was 4.64±0.14log10 CFU. At week 2 of treatment, the CFU counts had increased in untreated mice, remained essentially unchanged in mice treated with CFZ alone, decreased modestly with either RIF+CLR or RIF+CFZ, and decreased substantially with RIF+STR. At week 4, on the basis of footpad CFU counts, the combination regimens were ranked as follows: RIF+STR>RIF+CLR>RIF+CFZ. At weeks 6 and 8, none of the mice treated with these regimens had detectable CFU. Footpad swelling declined comparably with all of the combination regimens, as did the levels of detectable mycolactone A/B. In mice treated for only 6 weeks and followed up for 24 weeks, there were no relapses in RIF+STR treated mice, one (5%) relapse in RIF+CFZ-treated mice, but >50% in RIF+CLR treated mice. On the basis of these results, RIF+CFZ has potential as a continuation phase regimen for treatment of M. ulcerans disease. PMID:26042792

A Community Based Study on the Mode of Transmission, Prevention and Treatment of Buruli Ulcers in Southwest Cameroon: Knowledge, Attitude and Practices.

PubMed

Akoachere, Jane-Francis K T; Nsai, Frankline S; Ndip, Roland N

2016-01-01

Buruli ulcer (BU) is a neglected tropical disease affecting the skin, tissues and in some cases the bones, caused by the environmental pathogen Mycobacterium ulcerans (M. ulcerans). Its mode of transmission is still elusive. Delayed treatment may cause irreversible disabilities with consequent social and economic impacts on the victim. Socio-cultural beliefs, practices and attitudes in endemic communities have been shown to influence timely treatment causing disease management, prevention and control a great challenge. An assessment of these factors in endemic localities is important in designing successful intervention strategies. Considering this, we assessed the knowledge, attitude and practices regarding BU in three endemic localities in the South West region, Cameroon to highlight existing misconceptions that need to be addressed to enhance prompt treatment and facilitate effective prevention and control. A cross-sectional study was executed in three BU endemic health districts. Using qualitative and quantitative approaches we surveyed 320 randomly selected household heads, interviewed BU patients and conducted three focus group discussions (FGDs) to obtain information on awareness, beliefs, treatment, and attitudes towards victims. The influence of socio-demographic factors on these variables was investigated. Respondents (84.4%) had a good knowledge of BU though only 65% considered it a health problem while 49.4% believed it is contagious. Socio-demographic factors significantly (P<0.05) influenced awareness of BU, knowledge and practice on treatment and attitudes towards victims. Although the majority of respondents stated the hospital as the place for appropriate treatment, FGDs and some BU victims preferred witchdoctors/herbalists and prayers, and considered the hospital as the last option. We documented beliefs about the disease which could delay treatment. Though we are reporting a high level of knowledge of BU, there exist fallacies about BU and negative attitudes towards victims in communities studied. Efforts towards disease eradication must first of all target these misconceptions.

A Community Based Study on the Mode of Transmission, Prevention and Treatment of Buruli Ulcers in Southwest Cameroon: Knowledge, Attitude and Practices

PubMed Central

Akoachere, Jane-Francis K. T.; Nsai, Frankline S.; Ndip, Roland N.

2016-01-01

Background Buruli ulcer (BU) is a neglected tropical disease affecting the skin, tissues and in some cases the bones, caused by the environmental pathogen Mycobacterium ulcerans (M. ulcerans). Its mode of transmission is still elusive. Delayed treatment may cause irreversible disabilities with consequent social and economic impacts on the victim. Socio-cultural beliefs, practices and attitudes in endemic communities have been shown to influence timely treatment causing disease management, prevention and control a great challenge. An assessment of these factors in endemic localities is important in designing successful intervention strategies. Considering this, we assessed the knowledge, attitude and practices regarding BU in three endemic localities in the South West region, Cameroon to highlight existing misconceptions that need to be addressed to enhance prompt treatment and facilitate effective prevention and control. Methods and Findings A cross-sectional study was executed in three BU endemic health districts. Using qualitative and quantitative approaches we surveyed 320 randomly selected household heads, interviewed BU patients and conducted three focus group discussions (FGDs) to obtain information on awareness, beliefs, treatment, and attitudes towards victims. The influence of socio-demographic factors on these variables was investigated. Results Respondents (84.4%) had a good knowledge of BU though only 65% considered it a health problem while 49.4% believed it is contagious. Socio-demographic factors significantly (P<0.05) influenced awareness of BU, knowledge and practice on treatment and attitudes towards victims. Although the majority of respondents stated the hospital as the place for appropriate treatment, FGDs and some BU victims preferred witchdoctors/herbalists and prayers, and considered the hospital as the last option. We documented beliefs about the disease which could delay treatment. Conclusion Though we are reporting a high level of knowledge of BU, there exist fallacies about BU and negative attitudes towards victims in communities studied. Efforts towards disease eradication must first of all target these misconceptions. PMID:27227429

Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical microbiome analysis of a skin disease.

PubMed

Van Leuvenhaege, Chloé; Vandelannoote, Koen; Affolabi, Dissou; Portaels, Françoise; Sopoh, Ghislain; de Jong, Bouke C; Eddyani, Miriam; Meehan, Conor J

2017-01-01

Buruli ulcer (BU) is an infectious disease caused by Mycobacterium ulcerans and considered the third most prevalent mycobacterial disease in humans. Secondary bacterial infections in open BU lesions are the main cause of pain, delayed healing and systemic illness, resulting in prolonged hospital stay. Thus, understanding the diversity of bacteria, termed the microbiome, in these open lesions is important for proper treatment. However, adequately studying the human microbiome in a clinical setting can prove difficult when investigating a neglected tropical skin disease due to its rarity and the setting. Using 16S rRNA sequencing, we determined the microbial composition of 5 BU lesions, 3 non-BU lesions and 3 healthy skin samples. Although no significant differences in diversity were found between BU and non-BU lesions, the former were characterized by an increase of Bacteroidetes compared to the non-BU wounds and the BU lesions also contained significantly more obligate anaerobes. With this molecular-based study, we were also able to detect bacteria that were missed by culture-based methods in previous BU studies. Our study suggests that BU may lead to changes in the skin bacterial community within the lesions. However, in order to determine if such changes hold true across all BU cases and are either a cause or consequence of a specific wound environment, further microbiome studies are necessary. Such skin microbiome analysis requires large sample sizes and lesions from the same body site in many patients, both of which can be difficult for a rare disease. Our study proposes a pipeline for such studies and highlights several drawbacks that must be considered if microbiome analysis is to be utilized for neglected tropical diseases.

Environmental Distribution and Seasonal Prevalence of Mycobacterium ulcerans in Southern Louisiana

PubMed Central

Hennigan, Caroline E.; Myers, Leann

2013-01-01

Mycobacterium ulcerans is an emerging environmental pathogen that causes debilitating, ulcerative disease in humans and other vertebrates. The majority of human cases occur in tropical and temperate regions of Africa and Australia, and outbreaks of piscine mycobacteriosis caused by M. ulcerans have been reported in disparate geographic locations spanning the globe. While exposure to a natural body of water is the most common risk factor for human infection, the environmental distribution of M. ulcerans in aquatic habitats has not been extensively studied. Although no human cases have been reported in the United States, a strain of M. ulcerans has been identified as the cause of a piscine mycobacteriosis in Striped bass (Morone saxatilis) within the Chesapeake Bay. Infected fish exhibit bright red ventral and lateral dermal lesions. We observed a possible outbreak causing similar lesions on red drum (Sciaenops ocellatus) in wetlands of southern Louisiana and detected M. ulcerans-specific genetic markers in lesion samples from these fish. Based on these findings, we studied the geographic and seasonal prevalence of these markers across southern Louisiana. M. ulcerans was detected in each of the nine areas sampled across the state. M. ulcerans prevalence was significantly lower in the fall samples, and the low prevalence coincided with decreased nutrient levels and an increase in water temperature. To our knowledge, this is the first study of M. ulcerans biomarkers in the southern United States. PMID:23396345

Toxigenic Corynebacterium ulcerans in a fatal human case and her feline contacts, France, March 2014.

PubMed

Vandentorren, S; Guiso, N; Badell, E; Boisrenoult, P; Micaelo, M; Troché, G; Lecouls, P; Moquet, M J; Patey, O; Belchior, E

2014-09-25

In March 2014, a person in their eighties who was diagnosed with extensive cellulitis due to toxigenic Corynebacterium ulcerans died from multiple organ failure. Environmental investigation also isolated C. ulcerans in biological samples from two stray cats in contact with the case. This finding provides further evidence that pets can carry toxigenic C. ulcerans and may be a source of the infection in humans.

[Corynebacterium ulcerans pulmonary infection].

PubMed

Thouvenin, Maxime; Beilouny, Bassam; Badell, Edgar; Guiso, Nicole

2016-01-01

Corynebacterium ulcerans is a bacterium able to infect humans by inducing a disease close to diphtheria. We describe the case of a 83-year-old patient hospitalized as a matter of urgency in intensive care for which C. ulcerans was isolated in pure culture in its bronchial samples. Even if the isolate was not secreting toxin in vitro, it possesses the tox gene which motivated the use of specific antitoxin serum. After two months of intensive care the patient went out of the service. It is about a remarkable case of clinicobiologic collaboration.

Functional Diversity as a New Framework for Understanding the Ecology of an Emerging Generalist Pathogen.

PubMed

Morris, Aaron; Guégan, Jean-François; Benbow, M Eric; Williamson, Heather; Small, Pamela L C; Quaye, Charles; Boakye, Daniel; Merritt, Richard W; Gozlan, Rodolphe E

2016-09-01

Emerging infectious disease outbreaks are increasingly suspected to be a consequence of human pressures exerted on natural ecosystems. Previously, host taxonomic communities have been used as indicators of infectious disease emergence, and the loss of their diversity has been implicated as a driver of increased presence. The mechanistic details in how such pathogen-host systems function, however, may not always be explained by taxonomic variation or loss. Here we used machine learning and methods based on Gower's dissimilarity to quantify metrics of invertebrate functional diversity, in addition to functional groups and their taxonomic diversity at sites endemic and non-endemic for the model generalist pathogen Mycobacterium ulcerans, the causative agent of Buruli ulcer. Changes in these metrics allowed the rapid categorisation of the ecological niche of the mycobacterium's hosts and the ability to relate specific host traits to its presence in aquatic ecosystems. We found that taxonomic diversity of hosts and overall functional diversity loss and evenness had no bearing on the mycobacterium's presence, or whether the site was in an endemic area. These findings, however, provide strong evidence that generalist environmentally persistent bacteria such as M. ulcerans can be associated with specific functional traits rather than taxonomic groups of organisms, increasing our understanding of emerging disease ecology and origin.

Contribution of the community health volunteers in the control of Buruli ulcer in Bénin.

PubMed

Barogui, Yves Thierry; Sopoh, Ghislain Emmanuel; Johnson, Roch Christian; de Zeeuw, Janine; Dossou, Ange Dodji; Houezo, Jean Gabin; Chauty, Annick; Aguiar, Julia; Agossadou, Didier; Edorh, Patrick A; Asiedu, Kingsley; van der Werf, Tjip S; Stienstra, Ymkje

2014-10-01

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Usually BU begins as a painless nodule, plaque or edema, ultimately developing into an ulcer. The high number of patients presenting with ulcers in an advanced stage is striking. Such late presentation will complicate treatment and have long-term disabilities as a consequence. The disease is mainly endemic in West Africa. The primary strategy for control of this disease is early detection using community village volunteers. In this retrospective, observational study, information regarding Buruli ulcer patients that reported to one of the four BU centers in Bénin between January 2008 and December 2010 was collected using the WHO/BU01 forms. Information used from these forms included general characteristics of the patient, the results of diagnostic tests, the presence of functional limitations at start of treatment, lesion size, patient delay and the referral system. The role of the different referral systems on the stage of disease at presentation in the hospital was analyzed by a logistic regression analysis. About a quarter of the patients (26.5%) were referred to the hospital by the community health volunteers. In our data set, patients referred to the hospital by community health volunteers appeared to be in an earlier stage of disease than patients referred by other methods, but after adjustment by the regression analysis for the health center, this effect could no longer be seen. The Polymerase Chain Reaction (PCR) for IS2404 positivity rate among patients referred by the community health volunteers was not systematically lower than in patients referred by other systems. This study clarifies the role played by community health volunteers in Bénin, and shows that they play an important role in the control of BU.

Draft Genome Sequence of Corynebacterium ulcerans FRC58, Isolated from the Bronchitic Aspiration of a Patient in France

PubMed Central

Silva, Andréia do Socorro de Sousa; Baraúna, Rafael Azevedo; de Sá, Pablo Caracciolo Gomes; das Graças, Diego Assis; Carneiro, Adriana Ribeiro; Thouvenin, Maxime; Azevedo, Vasco; Badell, Edgar; Guiso, Nicole; da Silva, Artur Luiz da Costa

2014-01-01

Corynebacterium ulcerans is a bacterial species with high importance because it causes infections in animals and, rarely, in humans. Its virulence mechanisms remain unclear. The current study describes the draft genome of C. ulcerans FRC58, which was isolated from the bronchitic aspiration of a patient in France. PMID:24407640

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons

PubMed Central

Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

2016-01-01

Background Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Results Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Conclusion Mycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection. PMID:27325560

Multilocus Variable-Number Tandem Repeat Typing of Mycobacterium ulcerans

PubMed Central

Ablordey, Anthony; Swings, Jean; Hubans, Christine; Chemlal, Karim; Locht, Camille; Portaels, Françoise; Supply, Philip

2005-01-01

The apparent genetic homogeneity of Mycobacterium ulcerans contributes to the poorly understood epidemiology of M. ulcerans infection. Here, we report the identification of variable number tandem repeat (VNTR) sequences as novel polymorphic elements in the genome of this species. A total of 19 potential VNTR loci identified in the closely related M. marinum genome sequence were screened in a collection of 23 M. ulcerans isolates, one Mycobacterium species referred to here as an intermediate species, and five M. marinum strains. Nine of the 19 loci were polymorphic in the three species (including the intermediate species) and revealed eight M. ulcerans and five M. marinum genotypes. The results from the VNTR analysis corroborated the genetic relationships of M. ulcerans isolates from various geographical origins, as defined by independent molecular markers. Although these results further highlight the extremely high clonal homogeneity within certain geographic regions, we report for the first time the discrimination of the two South American strains from Surinam and French Guyana. These findings support the potential of a VNTR-based genotyping method for strain discrimination within M. ulcerans and M. marinum. PMID:15814964

Identification of Ser/Thr kinase and Forkhead Associated Domains in Mycobacterium ulcerans: Characterization of Novel Association between Protein Kinase Q and MupFHA

PubMed Central

Singhal, Anshika; Joshi, Jayadev; Virmani, Richa; Gupta, Meetu; Verma, Nupur; Maji, Abhijit; Misra, Richa; Baronian, Grégory; Pandey, Amit K.; Molle, Virginie; Singh, Yogendra

2014-01-01

Background Mycobacterium ulcerans, the causative agent of Buruli ulcer in humans, is unique among the members of Mycobacterium genus due to the presence of the virulence determinant megaplasmid pMUM001. This plasmid encodes multiple virulence-associated genes, including mup011, which is an uncharacterized Ser/Thr protein kinase (STPK) PknQ. Methodology/Principal Findings In this study, we have characterized PknQ and explored its interaction with MupFHA (Mup018c), a FHA domain containing protein also encoded by pMUM001. MupFHA was found to interact with PknQ and suppress its autophosphorylation. Subsequent protein-protein docking and molecular dynamic simulation analyses showed that this interaction involves the FHA domain of MupFHA and PknQ activation loop residues Ser170 and Thr174. FHA domains are known to recognize phosphothreonine residues, and therefore, MupFHA may be acting as one of the few unusual FHA-domain having overlapping specificity. Additionally, we elucidated the PknQ-dependent regulation of MupDivIVA (Mup012c), which is a DivIVA domain containing protein encoded by pMUM001. MupDivIVA interacts with MupFHA and this interaction may also involve phospho-threonine/serine residues of MupDivIVA. Conclusions/Significance Together, these results describe novel signaling mechanisms in M. ulcerans and show a three-way regulation of PknQ, MupFHA, and MupDivIVA. FHA domains have been considered to be only pThr specific and our results indicate a novel mechanism of pSer as well as pThr interaction exhibited by MupFHA. These results signify the need of further re-evaluating the FHA domain –pThr/pSer interaction model. MupFHA may serve as the ideal candidate for structural studies on this unique class of modular enzymes. PMID:25412098

Burden and Historical Trend of Buruli Ulcer Prevalence in Selected Communities along the Offin River of Ghana.

PubMed

Ampah, Kobina Assan; Asare, Prince; Binnah, Daniel De-Graft; Maccaulley, Samuel; Opare, William; Röltgen, Katharina; Pluschke, Gerd; Yeboah-Manu, Dorothy

2016-04-01

Buruli ulcer (BU) is a neglected tropical skin disease caused by Mycobacterium ulcerans with more than two thirds of the global cases reported in West Africa. A nationwide active BU case search conducted in 1999 identified two health districts along the Offin River as two of the three most endemic districts in Ghana. Based on recent anecdotal accounts that transmission is unstable along the Offin River, we conducted from March to June 2013 an exhaustive household survey and active case search in 13 selected communities within a five-kilometer radius along the Offin River. The overall prevalence of BU was 2.3% among the surveyed population of 20,390 inhabitants and 477 of the total 480 cases detected (99.4%) were historical (healed) cases. By estimating the year of occurrence for each case per community and taking into account available passive surveillance records of health facilities and the District Health Directorate, we observed a general trend of continuous emergence of cases in communities located midstream the Offin River whereas downstream communities showed more sporadic patterns. We monitored the incidence of cases after the survey and recorded a cumulative incidence rate of 0.04% for the 13 communities over a 17-month active surveillance period from August 2013 to December 2014. Our data reveal an overall decline in BU incidence along the Offin River similar to the general decline in BU incidence in recent years reported by the World Health Organization for West Africa.

A Simple PCR Method for Rapid Genotype Analysis of Mycobacterium ulcerans

PubMed Central

Stinear, Timothy; Davies, John K.; Jenkin, Grant A.; Portaels, Françoise; Ross, Bruce C.; OppEdIsano, Frances; Purcell, Maria; Hayman, John A.; Johnson, Paul D. R.

2000-01-01

Two high-copy-number insertion sequences, IS2404 and IS2606, were recently identified in Mycobacterium ulcerans and were shown by Southern hybridization to possess restriction fragment length polymorphism between strains from different geographic origins. We have designed a simple genotyping method that captures these differences by PCR amplification of the region between adjacent copies of IS2404 and IS2606. We have called this system 2426 PCR. The method is rapid, reproducible, sensitive, and specific for M. ulcerans, and it has confirmed previous studies suggesting a clonal population structure of M. ulcerans within a geographic region. M. ulcerans isolates from Australia, Papua New Guinea, Malaysia, Surinam, Mexico, Japan, China, and several countries in Africa were easily differentiated based on an array of 4 to 14 PCR products ranging in size from 200 to 900 bp. Numerical analysis of the banding patterns suggested a close evolutionary link between M. ulcerans isolates from Africa and southeast Asia. The application of 2426 PCR to total DNA, extracted directly from M. ulcerans-infected tissue specimens without culture, demonstrated the sensitivity and specificity of this method and confirmed for the first time that both animal and human isolates from areas of endemicity in southeast Australia have the same genotype. PMID:10747130

Evaluation of the medicinal use of clay minerals as antibacterial agents

PubMed Central

Williams, Lynda B.; Haydel, Shelley E.

2010-01-01

Natural clays have been used to heal skin infections since the earliest recorded history. Recently our attention was drawn to a clinical use of French green clay (rich in Fe-smectite) for healing Buruli ulcer, a necrotizing fasciitis (‘flesh-eating’ infection) caused by Mycobacterium ulcerans. These clays and others like them are interesting as they may reveal an antibacterial mechanism that could provide an inexpensive treatment for this and other skin infections, especially in global areas with limited hospitals and medical resources. Microbiological testing of two French green clays, and other clays used traditionally for healing, identified three samples that were effective at killing a broad-spectrum of human pathogens. A clear distinction must be made between ‘healing clays’ and those we have identified as antibacterial clays. The highly adsorptive properties of many clays may contribute to healing a variety of ailments, although they are not antibacterial. The antibacterial process displayed by the three identified clays is unknown. Therefore, we have investigated the mineralogical and chemical compositions of the antibacterial clays for comparison with non-antibacterial clays in an attempt to elucidate differences that may lead to identification of the antibacterial mechanism(s). The two French green clays used to treat Buruli ulcer, while similar in mineralogy, crystal size, and major element chemistry, have opposite effects on the bacterial populations tested. One clay deposit promoted bacterial growth whereas another killed the bacteria. The reasons for the difference in antibacterial properties thus far show that the bactericidal mechanism is not physical (e.g., an attraction between clay and bacteria), but by a chemical transfer or reaction. The chemical variables are still under investigation. Cation exchange experiments showed that the antibacterial component of the clay can be removed, implicating exchangeable cations in the antibacterial process. Furthermore, aqueous leachates of the antibacterial clays effectively kill the bacteria. Progressively heating the clay leads first to dehydration (200°C), then dehydroxylation (550°C or more), and finally to destruction of the clay mineral structure by (~900°C). By identifying the elements lost after each heating step, and testing the bactericidal effect of the heated product, we eliminated many toxins from consideration (e.g., microbes, organic compounds, volatile elements) and identified several redox-sensitive refractory metals that are common among antibacterial clays. We conclude that the pH and oxidation state buffered by the clay mineral surfaces is key to controlling the solution chemistry and redox related reactions occurring at the bacterial cell wall. PMID:20640226

Evaluation of the medicinal use of clay minerals as antibacterial agents.

PubMed

Williams, Lynda B; Haydel, Shelley E

2010-07-01

Natural clays have been used to heal skin infections since the earliest recorded history. Recently our attention was drawn to a clinical use of French green clay (rich in Fe-smectite) for healing Buruli ulcer, a necrotizing fasciitis ('flesh-eating' infection) caused by Mycobacterium ulcerans. These clays and others like them are interesting as they may reveal an antibacterial mechanism that could provide an inexpensive treatment for this and other skin infections, especially in global areas with limited hospitals and medical resources.Microbiological testing of two French green clays, and other clays used traditionally for healing, identified three samples that were effective at killing a broad-spectrum of human pathogens. A clear distinction must be made between 'healing clays' and those we have identified as antibacterial clays. The highly adsorptive properties of many clays may contribute to healing a variety of ailments, although they are not antibacterial. The antibacterial process displayed by the three identified clays is unknown. Therefore, we have investigated the mineralogical and chemical compositions of the antibacterial clays for comparison with non-antibacterial clays in an attempt to elucidate differences that may lead to identification of the antibacterial mechanism(s).The two French green clays used to treat Buruli ulcer, while similar in mineralogy, crystal size, and major element chemistry, have opposite effects on the bacterial populations tested. One clay deposit promoted bacterial growth whereas another killed the bacteria. The reasons for the difference in antibacterial properties thus far show that the bactericidal mechanism is not physical (e.g., an attraction between clay and bacteria), but by a chemical transfer or reaction. The chemical variables are still under investigation.Cation exchange experiments showed that the antibacterial component of the clay can be removed, implicating exchangeable cations in the antibacterial process. Furthermore, aqueous leachates of the antibacterial clays effectively kill the bacteria. Progressively heating the clay leads first to dehydration (200 degrees C), then dehydroxylation (550 degrees C or more), and finally to destruction of the clay mineral structure by (~900 degrees C). By identifying the elements lost after each heating step, and testing the bactericidal effect of the heated product, we eliminated many toxins from consideration (e.g., microbes, organic compounds, volatile elements) and identified several redox-sensitive refractory metals that are common among antibacterial clays. We conclude that the pH and oxidation state buffered by the clay mineral surfaces is key to controlling the solution chemistry and redox related reactions occurring at the bacterial cell wall.

Toxigenic Corynebacterium ulcerans isolated from a hunting dog and its diphtheria toxin antibody titer.

PubMed

Katsukawa, Chihiro; Komiya, Takako; Umeda, Kaoru; Goto, Minami; Yanai, Tokuma; Takahashi, Motohide; Yamamoto, Akihiko; Iwaki, Masaaki

2016-03-01

Toxigenic Corynebacterium ulcerans is a zoonotic pathogen that produces diphtheria toxin and causes a diphtheria-like illness in humans. The organism is known to infect and circulate among dogs, which can then transmit it to humans. Furthermore, previous studies have found that C. ulcerans is carried by wild animals, including game animals. In the present study, we tested hunting and companion dogs for the presence of toxigenic C. ulcerans and succeeded in isolating the bacterium from a hunting dog. Moreover, several hunting dogs had serum diphtheria antitoxin titers that were higher than the titers required for protection in humans, suggesting a history of exposure to toxigenic Corynebacterium strains. Notably, ribotyping, pulsed-field gel electrophoresis and tox gene sequencing demonstrated that the isolate from the hunting dog clustered with previously characterized C. ulcerans strains isolated from wild animals, as opposed to groups of isolates from humans and companion dogs. Interestingly, the wild animal cluster also contains an isolate from an outdoor breeding dog, which could have formed a bridge between isolates from wild animals and those from companion dogs. The results presented herein provide insight into the mechanism by which the zoonotic pathogen C. ulcerans circulates among wild animals, hunting and companion dogs, and humans. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Ethnopharmacological reports on anti-Buruli ulcer medicinal plants in three West African countries.

PubMed

Tsouh Fokou, Patrick Valere; Nyarko, Alexander Kwadwo; Appiah-Opong, Regina; Tchokouaha Yamthe, Lauve Rachel; Addo, Phyllis; Asante, Isaac K; Boyom, Fabrice Fekam

2015-08-22

Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control. A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA, Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans. This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro. This review covered the available literature up to December 2014. The majority of reports originated from the three most affected West African countries (Cote d'Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the pharmacological studies were performed only on 54 species. To a lesser extent, ethnopharmacological knowledge was validated in vitro for only 13 species. Of those, seven species including Ricinus comminus, Cyperus cyperoides (cited as Mariscus alternifolius), Nicotiana tabacum, Mangifera indica, Solanum rugosum, Carica papaya, and Moringa oleifera demonstrated efficacy in hospitalised BU patients. Four isolated and characterized compounds were reported to have moderate bioactivity in vitro against M. ulcerans. This review compiles for the first time ethnopharmacologically useful plants against BU. The phamacological potential of 13 of them has been demonstrated in vitro and support BU evidence-based traditional medicines. In addition, 7 species showed activity in BU patients and have emerged as a promising source of the traditional medicine for treatment of BU. Yet, further safety and efficacy study should be initiated prior any approval as alternative therapy. Overall, a huge gap in knowledge appeared, suggesting further well-planned and detailed investigations of the in vitro, in vivo, and safety properties of the claimed anti-BU plants. Therefore, plants with medicinal potential should be scrutinized for biologically active compounds, using bioassay-guided fractionation approach to provide new insights to find novel therapeutics for BU control. Copyright © 2015. Published by Elsevier Ireland Ltd.

[Emerging infectious diseases: complex, unpredictable processes].

PubMed

Guégan, Jean-François

2016-01-01

In the light of a double approach, at first empirical, later theoretical and comparative, illustrated by the example of the Buruli ulcer and its mycobacterial agent Mycobacterium ulcerans on which I focused my research activity these last ten years by studying determinants and factors of emerging infectious or parasitic diseases, the complexity of events explaining emerging diseases will be presented. The cascade of events occurring at various levels of spatiotemporal scales and organization of life, which lead to the numerous observed emergences, nowadays requires better taking into account the interactions between host(s), pathogen(s) and the environment by including the behavior of both individuals and the population. In numerous research studies on emerging infectious diseases, microbial hazard is described rather than infectious disease risk, the latter resulting from the confrontation between an association of threatening phenomena, or hazards, and a susceptible population. Beyond, the theme of emerging infectious diseases and its links with global environmental and societal changes leads to reconsider some well-established knowledge in infectiology and parasitology. © Société de Biologie, 2017.

Ulcerative cutaneous mycobacteriosis due to Mycobacterium ulcerans: report of two Mexican cases.

PubMed

Coloma, Josefa Novales-Santa; Navarrete-Franco, Gisela; Iribe, Pedro; López-Cepeda, Larissa Dorina

2005-03-01

We report two patients from Central Mexico, with ulcerated cutaneous lesions containing acid-fast bacilli (AFB) and ultimately diagnosed as Mycobacterium ulcerans disease. The first patient had a long history (11 years) of disease involving multiple lesions of both upper and lower extremities. Histopathological changes included necrosis of the subcutaneous tissue with large numbers of extracellular AFB. Cultures at 32 degrees C were "positive for mycobacteria," but were not further identified. The polymerase chain reaction for M. ulcerans performed on skin bopsies was positive. The lesions improved after treatment with rifampin and isoniazid (INH) for one month, followed by ethambutol and streptomycin. The second case followed trauma to the right hand, which spread over 2 years to the right upper extremity, the back, and both legs, with a loss of digits and metacarpal bones of the right hand. The histopathological findings were similar to the first case, including presence of AFB. PCR for M. ulcerans on extracts of skin biopsies was positive. Rifampin, INH, pyrazinamide, and levofloxacin resulted in marked improvement of the ulcer; ethambutol and streptomycin were later used, also. We report these cases because they are rare (approximately 6 previous cases were reported from Mexico), and both are unusually disseminated. They are significant in alerting the medical community to M. ulcerans infection, which is still active in Mexico, and the treatment used has not been reported previously.

Risk factors for buruli ulcer in Ghana-a case control study in the Suhum-Kraboa-Coaltar and Akuapem South Districts of the eastern region.

PubMed

Kenu, Ernest; Nyarko, Kofi Mensah; Seefeld, Linda; Ganu, Vincent; Käser, Michael; Lartey, Margaret; Calys-Tagoe, Benedict Nii Laryea; Koram, Kwodwo; Adanu, Richard; Razum, Oliver; Afari, Edwin; Binka, Fred N

2014-01-01

Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. Its exact mode of transmission is not known. Previous studies have identified demographic, socio-economic, health and hygiene as well as environment related risk factors. We investigated whether the same factors pertain in Suhum-Kraboa-Coaltar (SKC) and Akuapem South (AS) Districts in Ghana which previously were not endemic for BU. We conducted a case control study. A case of BU was defined as any person aged 2 years or more who resided in study area (SKC or AS District) diagnosed according to the WHO clinical case definition for BU and matched with age- (+/-5 years), gender-, and community controls. A structured questionnaire on host, demographic, environmental, and behavioural factors was administered to participants. A total of 113 cases and 113 community controls were interviewed. Multivariate conditional logistic regression analysis identified presence of wetland in the neighborhood (OR=3.9, 95% CI=1.9-8.2), insect bites in water/mud (OR=5.7, 95% CI=2.5-13.1), use of adhesive when injured (OR=2.7, 95% CI=1.1-6.8), and washing in the Densu river (OR=2.3, 95% CI=1.1-4.96) as risk factors associated with BU. Rubbing an injured area with alcohol (OR=0.21, 95% CI=0.008-0.57) and wearing long sleeves for farming (OR=0.29, 95% CI=0.14-0.62) showed protection against BU. This study identified the presence of wetland, insect bites in water, use of adhesive when injured, and washing in the river as risk factors for BU; and covering limbs during farming as well as use of alcohol after insect bites as protective factors against BU in Ghana. Until paths of transmission are unraveled, control strategies in BU endemic areas should focus on these known risk factors.

Mycobacterium ulcerans Ecological Dynamics and Its Association with Freshwater Ecosystems and Aquatic Communities: Results from a 12-Month Environmental Survey in Cameroon

PubMed Central

Garchitorena, Andrés; Roche, Benjamin; Kamgang, Roger; Ossomba, Joachim; Babonneau, Jérémie; Landier, Jordi; Fontanet, Arnaud; Flahault, Antoine

2014-01-01

Background Mycobacterium ulcerans (MU) is the agent responsible for Buruli Ulcer (BU), an emerging skin disease with dramatic socioeconomic and health outcomes, especially in rural settings. BU emergence and distribution is linked to aquatic ecosystems in tropical and subtropical countries, especially to swampy and flooded areas. Aquatic animal organisms are likely to play a role either as host reservoirs or vectors of the bacilli. However, information on MU ecological dynamics, both in space and time, is dramatically lacking. As a result, the ecology of the disease agent, and consequently its mode of transmission, remains largely unknown, which jeopardizes public health attempts for its control. The objective of this study was to gain insight on MU environmental distribution and colonization of aquatic organisms through time. Methodology/Principal Findings Longitudinal sampling of 32 communities of aquatic macro-invertebrates and vertebrates was conducted from different environments in two BU endemic regions in Cameroon during 12 months. As a result, 238,496 individuals were classified and MU presence was assessed by qPCR in 3,084 sample-pools containing these aquatic organisms. Our study showed a broad distribution of MU in all ecosystems and taxonomic groups, with important regional differences in its occurrence. Colonization dynamics fluctuated along the year, with the highest peaks in August and October. The large variations observed in the colonization dynamics of different taxonomic groups and aquatic ecosystems suggest that the trends shown here are the result of complex ecological processes that need further investigation. Conclusion/Perspectives This is the largest field study on MU ecology to date, providing the first detailed description of its spatio-temporal dynamics in different aquatic ecosystems within BU endemic regions. We argue that coupling this data with fine-scale epidemiological data through statistical and mathematical models will provide a major step forward in the understanding of MU ecology and mode of transmission. PMID:24831924

Membrane perturbing properties of toxin mycolactone from Mycobacterium ulcerans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez, Cesar A.; Unkefer, Clifford J.; Swanson, Basil I.

Mycolactone is the exotoxin produced by Mycobacterium ulcerans and is the virulence factor behind the neglected tropical disease Buruli ulcer. The toxin has a broad spectrum of biological effects within the host organism, stemming from its interaction with at least two molecular targets and the inhibition of protein uptake into the endoplasmic reticulum. Although it has been shown that the toxin can passively permeate into host cells, it is clearly lipophilic. Association with lipid carriers would have substantial implications for the toxin’s distribution within a host organism, delivery to cellular targets, diagnostic susceptibility, and mechanisms of pathogenicity. Yet the toxin’smore » interactions with, and distribution in, lipids are unknown. Herein we have used coarse-grained molecular dynamics simulations, guided by all-atom simulations, to study the interaction of mycolactone with pure and mixed lipid membranes. Using established techniques, we calculated the toxin’s preferential localization, membrane translocation, and impact on membrane physical and dynamical properties. The computed water-octanol partition coefficient indicates that mycolactone prefers to be in an organic phase rather than in an aqueous environment. Our results show that in a solvated membrane environment the exotoxin mainly localizes in the water-membrane interface, with a preference for the glycerol moiety of lipids, consistent with the reported studies that found it in lipid extracts of the cell. The calculated association constant to the model membrane is similar to the reported association constant for Wiskott-Aldrich syndrome protein. Mycolactone is shown to modify the physical properties of membranes, lowering the transition temperature, compressibility modulus, and critical line tension at which pores can be stabilized. It also shows a tendency to behave as a linactant, a molecule that localizes at the boundary between different fluid lipid domains in membranes and promotes inter-mixing of domains. This property has implications for the toxin’s cellular access, T-cell immunosuppression, and therapeutic potential.« less

Membrane perturbing properties of toxin mycolactone from Mycobacterium ulcerans

DOE PAGES

Lopez, Cesar A.; Unkefer, Clifford J.; Swanson, Basil I.; ...

2018-02-05

Mycolactone is the exotoxin produced by Mycobacterium ulcerans and is the virulence factor behind the neglected tropical disease Buruli ulcer. The toxin has a broad spectrum of biological effects within the host organism, stemming from its interaction with at least two molecular targets and the inhibition of protein uptake into the endoplasmic reticulum. Although it has been shown that the toxin can passively permeate into host cells, it is clearly lipophilic. Association with lipid carriers would have substantial implications for the toxin’s distribution within a host organism, delivery to cellular targets, diagnostic susceptibility, and mechanisms of pathogenicity. Yet the toxin’smore » interactions with, and distribution in, lipids are unknown. Herein we have used coarse-grained molecular dynamics simulations, guided by all-atom simulations, to study the interaction of mycolactone with pure and mixed lipid membranes. Using established techniques, we calculated the toxin’s preferential localization, membrane translocation, and impact on membrane physical and dynamical properties. The computed water-octanol partition coefficient indicates that mycolactone prefers to be in an organic phase rather than in an aqueous environment. Our results show that in a solvated membrane environment the exotoxin mainly localizes in the water-membrane interface, with a preference for the glycerol moiety of lipids, consistent with the reported studies that found it in lipid extracts of the cell. The calculated association constant to the model membrane is similar to the reported association constant for Wiskott-Aldrich syndrome protein. Mycolactone is shown to modify the physical properties of membranes, lowering the transition temperature, compressibility modulus, and critical line tension at which pores can be stabilized. It also shows a tendency to behave as a linactant, a molecule that localizes at the boundary between different fluid lipid domains in membranes and promotes inter-mixing of domains. This property has implications for the toxin’s cellular access, T-cell immunosuppression, and therapeutic potential.« less

Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013

PubMed Central

Both, Leonard; Collins, Sarah; de Zoysa, Aruni; White, Joanne; Mandal, Sema

2014-01-01

Human infections caused by toxigenic corynebacteria occur sporadically across Europe. In this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in England between January 2007 and December 2013. Epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. Molecular characterization was performed using multilocus sequence typing (MLST) alongside traditional phenotypic methods. In total, there were 20 cases of toxigenic corynebacteria; 12 (60.0%) were caused by Corynebacterium ulcerans, where animal contact was the predominant risk factor. The remaining eight (40.0%) were caused by Corynebacterium diphtheriae strains; six were biovar mitis, which were associated with recent travel abroad. Adults 45 years and older were particularly affected (55.0%; 11/20), and typical symptoms included sore throat and fever. Respiratory diphtheria with the absence of a pharyngeal membrane was the most common presentation (50.0%; 10/20). None of the eight C. diphtheriae cases were fully immunized. Diphtheria antitoxin was issued in two (9.5%) cases; both survived. Two (9.5%) cases died, one due to a C. diphtheriae infection and one due to C. ulcerans. MLST demonstrated that the majority (87.5%; 7/8) of C. diphtheriae strains represented new sequence types (STs). By adapting several primer sequences, the MLST genes in C. ulcerans were also amplified, thereby providing the basis for extension of the MLST scheme, which is currently restricted to C. diphtheriae. Despite high population immunity, occasional toxigenic corynebacterium strains are identified in England and continued surveillance is required. PMID:25502525

Caenorhabditis elegans star formation and negative chemotaxis induced by infection with corynebacteria.

PubMed

Antunes, Camila Azevedo; Clark, Laura; Wanuske, Marie-Therès; Hacker, Elena; Ott, Lisa; Simpson-Louredo, Liliane; de Luna, Maria das Gracas; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Hodgkin, Jonathan; Burkovski, Andreas

2016-01-01

Caenorhabditis elegans is one of the major model systems in biology based on advantageous properties such as short life span, transparency, genetic tractability and ease of culture using an Escherichia coli diet. In its natural habitat, compost and rotting plant material, this nematode lives on bacteria. However, C. elegans is a predator of bacteria, but can also be infected by nematopathogenic coryneform bacteria such Microbacterium and Leucobacter species, which display intriguing and diverse modes of pathogenicity. Depending on the nematode pathogen, aggregates of worms, termed worm-stars, can be formed, or severe rectal swelling, so-called Dar formation, can be induced. Using the human and animal pathogens Corynebacterium diphtheriae and Corynebacterium ulcerans as well as the non-pathogenic species Corynebacterium glutamicum, we show that these coryneform bacteria can also induce star formation slowly in worms, as well as a severe tail-swelling phenotype. While C. glutamicum had a significant, but minor influence on survival of C. elegans, nematodes were killed after infection with C. diphtheriae and C. ulcerans. The two pathogenic species were avoided by the nematodes and induced aversive learning in C. elegans.

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

PubMed

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-07-18

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.

Update on Medicinal Plants with Potency on Mycobacterium ulcerans

PubMed Central

Tsouh Fokou, Patrick Valere; Nyarko, Alexander Kwadwo; Appiah-Opong, Regina; Tchokouaha Yamthe, Lauve Rachel; Ofosuhene, Mark; Boyom, Fabrice Fekam

2015-01-01

Mycobacterium ulcerans disease has been a serious threat for people living in rural remote areas. Due to poverty or availability of traditional medicine these populations rely on herbal remedies. Currently, data on the anti-Mycobacterium ulcerans activity of plants, so far considered community-based knowledge, have been scientifically confirmed, concomitantly with some medicinal plants used to treat infectious diseases in general. Products derived from plants usually responsible for the biological properties may potentially control Mycobacterium ulcerans disease; numerous studies have aimed to describe the chemical composition of these plant antimicrobials. Thus, the present work provides the first compilation of medicinal plants that demonstrated inhibitory potential on Mycobacterium ulcerans. This work shows that the natural products represent potential alternatives to standard therapies for use as curative medicine for Mycobacterium ulcerans disease. PMID:26779539

Notes from the field: respiratory diphtheria-like illness caused by toxigenic Corynebacterium ulcerans --- Idaho, 2010.

PubMed

2011-01-28

On September 12, 2010, the Idaho Department of Health and Welfare was notified of a case of respiratory diphtheria-like illness in an Idaho man aged 80 years whose pharyngeal specimens yielded Corynebacterium ulcerans. Although C. ulcerans is zoonotic, the patient reported no animal contact or consumption of an unpasteurized dairy product. His vaccination history was unknown. Respiratory diphtheria-like illness from C. ulcerans is uncommon but has been reported in industrialized countries where respiratory diphtheria is rare. The last case of diphtheria-like illness caused by C. ulcerans in the United States was reported in 2005.

Risk Factors for Buruli Ulcer in Ghana—A Case Control Study in the Suhum-Kraboa-Coaltar and Akuapem South Districts of the Eastern Region

PubMed Central

Kenu, Ernest; Nyarko, Kofi Mensah; Seefeld, Linda; Ganu, Vincent; Käser, Michael; Lartey, Margaret; Calys-Tagoe, Benedict Nii Laryea; Koram, Kwodwo; Adanu, Richard; Razum, Oliver; Afari, Edwin; Binka, Fred N.

2014-01-01

Background Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. Its exact mode of transmission is not known. Previous studies have identified demographic, socio-economic, health and hygiene as well as environment related risk factors. We investigated whether the same factors pertain in Suhum-Kraboa-Coaltar (SKC) and Akuapem South (AS) Districts in Ghana which previously were not endemic for BU. Methods We conducted a case control study. A case of BU was defined as any person aged 2 years or more who resided in study area (SKC or AS District) diagnosed according to the WHO clinical case definition for BU and matched with age- (+/−5 years), gender-, and community controls. A structured questionnaire on host, demographic, environmental, and behavioural factors was administered to participants. Results A total of 113 cases and 113 community controls were interviewed. Multivariate conditional logistic regression analysis identified presence of wetland in the neighborhood (OR = 3.9, 95% CI = 1.9–8.2), insect bites in water/mud (OR = 5.7, 95% CI = 2.5–13.1), use of adhesive when injured (OR = 2.7, 95% CI = 1.1–6.8), and washing in the Densu river (OR = 2.3, 95% CI = 1.1–4.96) as risk factors associated with BU. Rubbing an injured area with alcohol (OR = 0.21, 95% CI = 0.008–0.57) and wearing long sleeves for farming (OR = 0.29, 95% CI = 0.14–0.62) showed protection against BU. Conclusion This study identified the presence of wetland, insect bites in water, use of adhesive when injured, and washing in the river as risk factors for BU; and covering limbs during farming as well as use of alcohol after insect bites as protective factors against BU in Ghana. Until paths of transmission are unraveled, control strategies in BU endemic areas should focus on these known risk factors. PMID:25411974

Household cost of out-patient treatment of Buruli ulcer in Ghana: a case study of Obom in Ga South Municipality

PubMed Central

2013-01-01

Background The economic burden of diseases has become increasingly relevant to policy makers as healthcare expenditure keep rising in the face of limited and competing resources. Buruli ulcer (BU), a neglected but treatable tropical disease caused by Mycobacterium ulcerans, the only known environmental mycobacterium is capable of causing long term disability when left untreated. However, most BU studies have tended to focused on its bacteriology, epidemiology, entomology and other social determinants to the neglect of its economic evaluation. This paper reports estimated the household economic costs of BU and describe the intangible cost suffered by BU patients in an endemic area. Methods Retrospective one year cost data was used. A total of 63 confirmed BU cases were randomly sampled for the study. Economic cost and cost burden of BU were estimated. Sensitivity analysis was conducted to test the robustness of the cost estimates. Intangible cost measured stigmatization, pain, functional limitation and social isolation of children. Results The annual total household economic cost was US$35,915.98, of which about 65% was cost incurred by children with a mean cost of US$521.04. The mean annual household cost was US$570.09. The direct cost was 96% of the total cost. Non-medical cost accounts for about 97% of the direct cost with a mean cost of US$529.27. The mean medical cost was US$18.94. The main cost drivers of the household costs were transportation (78%) and food (12%). Caregivers and adult patients lost a total of 535 productive days seeking care, which gives an indirect cost valued at US$1,378.67 with a mean of US$21.88. A total of 365 school days (about 1 year) were lost by 19 BU patients (mean, 19.2 days). Functional loss and pain were low, and stigma rated moderate. Most children suffering from BU (84%) were socially isolated. Conclusion Household cost burden of out-patient BU ulcer treatment was high. Household cost of BU is therefore essential in the design of its intervention. BU afflicted children experience social isolation. PMID:24313975

Dermatologic Infectious Diseases in International Travelers.

PubMed

Wilson, Mary E.; Chen, Lin H.

2004-02-01

Skin lesions provide an important clue to the diagnoses of many infections in returned travelers. New information related to epidemiology, recognition, diagnosis, or management is described for the systemic infections--dengue fever, several of the rickettsial infections, African trypanosomiasis, and coccidioidomycosis. Many pathogens cause focal skin findings. Recent findings are presented for cutaneous leishmaniasis, Buruli ulcer, gnatho-stomiasis, cutaneous larva migrans, myiasis, tungiasis, and scabies. This paper describes the most common skin problems in returning travelers and outlines the types of infections that cause skin lesions, as defined by morphologic characteristics.

Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections

PubMed Central

2013-01-01

Background Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. Results A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). Conclusions This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin. PMID:23924370

Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections.

PubMed

Sina, Haziz; Ahoyo, Théodora A; Moussaoui, Wardi; Keller, Daniel; Bankolé, Honoré S; Barogui, Yves; Stienstra, Ymkje; Kotchoni, Simeon O; Prévost, Gilles; Baba-Moussa, Lamine

2013-08-08

Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin.

New Foci of Buruli Ulcer, Angola and Democratic Republic of Congo

PubMed Central

Kibadi, Kapay; Panda, Mbutu; Tamfum, Jean-Jacques Muyembe; Fraga, Alexandra G.; Filho, Adhemar Longatto; Anyo, Gladys; Pedrosa, Jorge; Nakazawa, Yoshinori; Suykerbuyk, Patrick; Meyers, Wayne M.

2008-01-01

We report 3 patients with laboratory-confirmed Buruli ulcer in Kafufu/Luremo, Angola, and Kasongo-Lunda, Democratic Republic of Congo. These villages are near the Kwango/Cuango River, which flows through both countries. Further investigation of artisanal alluvial mining as a risk factor for Buruli ulcer is recommended. PMID:18976574

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone

PubMed Central

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J.; Lesport, Pierre; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-01-01

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics. PMID:28718822

Persisting Social Participation Restrictions among Former Buruli Ulcer Patients in Ghana and Benin

PubMed Central

de Zeeuw, Janine; Omansen, Till F.; Douwstra, Marlies; Barogui, Yves T.; Agossadou, Chantal; Sopoh, Ghislain E.; Phillips, Richard O.; Johnson, Christian; Abass, K. Mohammed; Saunderson, Paul; Dijkstra, Pieter U.; van der Werf, Tjip S.; Stientstra, Ymkje

2014-01-01

Background Buruli ulcer may induce severe disabilities impacting on a person's well-being and quality of life. Information about long-term disabilities and participation restrictions is scanty. The objective of this study was to gain insight into participation restrictions among former Buruli ulcer patients in Ghana and Benin. Methods In this cross-sectional study, former Buruli ulcer patients were interviewed using the Participation Scale, the Buruli Ulcer Functional Limitation Score to measure functional limitations, and the Explanatory Model Interview Catalogue to measure perceived stigma. Healthy community controls were also interviewed using the Participation Scale. Trained native interviewers conducted the interviews. Former Buruli ulcer patients were eligible for inclusion if they had been treated between 2005 and 2011, had ended treatment at least 3 months before the interview, and were at least 15 years of age. Results In total, 143 former Buruli ulcer patients and 106 community controls from Ghana and Benin were included in the study. Participation restrictions were experienced by 67 former patients (median score, 30, IQR; 23;43) while 76 participated in social life without problems (median score 5, IQR; 2;9). Most restrictions encountered related to employment. Linear regression showed being female, perceived stigma, functional limitations, and larger lesions (category II) as predictors of more participation restrictions. Conclusion Persisting participation restrictions were experienced by former BU patients in Ghana and Benin. Most important predictors of participation restrictions were being female, perceived stigma, functional limitations and larger lesions. PMID:25392915

Toxigenic Corynebacterium ulcerans isolated from a free-roaming red fox (Vulpes vulpes).

PubMed

Sting, Reinhard; Ketterer-Pintur, Sandra; Contzen, Matthias; Mauder, Norman; Süss-Dombrowski, Christine

2015-01-01

Corynebacterium (C.) ulcerans could be isolated from the spleen of a red fox (Vulpes vulpes) that had been found dead in the state of Baden-Württemberg, Germany. Pathohistological examination suggested that the fox had died of distemper, as was confirmed by PCR. The isolate was identified biochemically, by MALDI-TOF MS, FT-IR and by partial 16S rRNA, rpoB and tox gene sequencing. Using the Elek test the C. ulcerans isolate demonstrated diphtheria toxin production. FT-IR and sequencing data obtained from the C. ulcerans isolate from the red fox showed higher similarity to isolates from humans than to those from wild game.

The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa.

PubMed

O'Brien, Daniel P; Comte, Eric; Serafini, Micaela; Ehounou, Geneviève; Antierens, Annick; Vuagnat, Hubert; Christinet, Vanessa; Hamani, Mitima D; du Cros, Philipp

2014-05-01

Despite great advances in the diagnosis and treatment of Buruli ulcer, it is one of the least studied major neglected tropical diseases. In Africa, major constraints in the management of Buruli ulcer relate to diagnosis and treatment, and accessibility, feasibility, and delivery of services. In this Personal View, we outline key areas for clinical, diagnostic, and operational research on this disease in Africa and propose a research agenda that aims to advance the management of Buruli ulcer in Africa. A model of care is needed to increase early case detection, to diagnose the disease accurately, to simplify and improve treatment, to reduce side-effects of treatment, to deal with populations with HIV and tuberculosis appropriately, to decentralise care, and to scale up coverage in populations at risk. This approach will require commitment and support to strategically implement research by national Buruli ulcer programmes and international technical and donor organisations, combined with adaptations in programme design and advocacy. A critical next step is to build consensus for a research agenda with WHO and relevant groups experienced in Buruli ulcer care or related diseases, and we call on on them to help to turn this agenda into reality. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Epidemiology of Buruli Ulcer from Benin (2005-2013): Effect of Time-Delay to Diagnosis on Clinical Forms and Severe Phenotypes.

PubMed

Capela, Carlos; Sopoh, Ghislain E; Houezo, Jean G; Fiodessihoué, René; Dossou, Ange D; Costa, Patrício; Fraga, Alexandra G; Menino, João F; Silva-Gomes, Rita; Ouendo, Edgard M; Rodrigues, Fernando; Pedrosa, Jorge

2015-01-01

Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter ≤15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation.

Buruli ulcer in Nigeria: results of a pilot case study in three rural districts.

PubMed

Ukwaja, Kingsley N; Meka, Anthony O; Chukwuka, Alphonsus; Asiedu, Kingsley B; Huber, Kristina L; Eddyani, Miriam; Chukwu, Joseph N; Anyim, Moses C; Nwafor, Charles C; Oshi, Daniel C; Madichie, Nelson O; Ekeke, Ngozi; Njoku, Martin; Ntana, Kentigern

2016-04-22

Buruli ulcer (BU), also known as Mycobacterium ulcerans disease, is the third most common mycobacterial disease worldwide. Although BU disease has been diagnosed among Nigerians in neighbouring West African countries, data on the burden of the disease in Nigeria itself are scanty. This study aimed to assess the magnitude and epidemiology of BU in the South South region of Nigeria. We conducted a cross-sectional survey in the Ogoja territory (comprising 31 communities). We undertook sensitisation programmes centred on BU in 10 of the communities. Participants were asked to identify community members with long-standing ulcers, who were then invited for evaluation. We also contacted traditional healers to refer their clients who had non-healing ulcers. All suspected cases had a full clinical evaluation and laboratory testing. Confirmed cases were given treatment in a referral hospital in the territory. We diagnosed 41 clinical BU cases; 36 (87.8 %) of which were confirmed by quantitative polymerase chain reaction (qPCR). These 36 PCR-confirmed cases were diagnosed in a total population of 192,169 inhabitants. Therefore, the estimated crude prevalence of BU was 18.7 per 100,000 population, varying from 6.0 to 41.4 per 100,000 in the districts surveyed. The majority (66.7 %) of the cases were females. About 92 % of the BU lesions were located on the patients' extremities. No differences were observed between the sexes in terms of the location of the lesions. The age of the patients ranged from four to 60 years, with a median age of 17 years. All 35 (100 %) patients who consented to treatment completed chemotherapy as prescribed. Of the treated cases, 29 (82.9 %) needed and received surgery. All cases healed, but 29 (82.9 %) had some limitations in movement. Healing with limitations in movement occurred in 18/19 (94.7 %) and 8/10 (80.0 %) of patients with lesions >15 cm (Category III) and 6-15 cm in diameter (Category II), respectively. The median duration of treatment was 130 (87-164) days for children and 98 (56-134) days for adults (p = 0.15). In Nigeria, BU is endemic but its severity is underestimated-at least in the study setting. There is a need to identify and map BU endemic regions in Nigeria. A comprehensive BU control programme is also urgently needed.

Screening of antifungal azole drugs and agrochemicals with an adapted alamarBlue-based assay demonstrates antibacterial activity of croconazole against Mycobacterium ulcerans.

PubMed

Scherr, Nicole; Röltgen, Katharina; Witschel, Matthias; Pluschke, Gerd

2012-12-01

An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen Mycobacterium ulcerans. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for M. ulcerans.

Screening of Antifungal Azole Drugs and Agrochemicals with an Adapted alamarBlue-Based Assay Demonstrates Antibacterial Activity of Croconazole against Mycobacterium ulcerans

PubMed Central

Röltgen, Katharina; Witschel, Matthias; Pluschke, Gerd

2012-01-01

An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen Mycobacterium ulcerans. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for M. ulcerans. PMID:23006761

Broad-spectrum in vitro antibacterial activities of clay minerals against antibiotic-susceptible and antibiotic-resistant bacterial pathogens

PubMed Central

HAYDEL, SHELLEY E.; REMENIH, CHRISTINE M.; WILLIAMS, LYNDA B.

2008-01-01

SYNOPSIS Objectives The capacity to properly address the worldwide incidence of infectious diseases lies in the ability to detect, prevent, and effectively treat these infections. Therefore, identifying and analyzing inhibitory agents are worthwhile endeavors in an era when few new classes of effective antimicrobials have been developed. The use of geological nanomaterials to heal skin infections has been evident since the earliest recorded history, and specific clay minerals may prove valuable in the treatment of bacterial diseases, including infections for which there are no effective antibiotics, such as Buruli ulcer and multi-drug resistant infections. Methods We have subjected two iron-rich clay minerals, which have previously been used to treat Buruli ulcer patients, to broth culture testing of antibiotic-susceptible and -resistant pathogenic bacteria to assess the feasibility of using clay minerals as therapeutic agents. Results One specific mineral, CsAg02, demonstrated bactericidal activity against pathogenic Escherichia coli, extended-spectrum β-lactamase (ESBL) E. coli, S. enterica serovar Typhimurium, Pseudomonas aeruginosa, and Mycobacterium marinum and a combined bacteriostatic/bactericidal effect against Staphylococcus aureus, penicillin-resistant S. aureus (PRSA), methicillin-resistant S. aureus (MRSA), and Mycobacterium smegmatis, while another mineral with similar structure and bulk crystal chemistry, CsAr02, had no effect on or enhanced bacterial growth. The <0.2 μm fraction of CsAg02 and CsAg02 heated to 200°C or 550°C retained bactericidal activity, while cation-exchanged CsAg02 and CsAg02 heated to 900°C no longer killed E. coli. Conclusions Our results indicate that specific mineral products have intrinsic, heat-stable antibacterial properties, which could provide an inexpensive treatment against numerous human bacterial infections. PMID:18070832

Diphtheria in the Postepidemic Period, Europe, 2000–2009

PubMed Central

White, Joanne M.; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S.; Neal, Shona; Efstratiou, Androulla

2012-01-01

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000–2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae infections. PMID:22304732

Rapid Detection and Molecular Differentiation of Toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans Strains by LightCycler PCR ▿

PubMed Central

Sing, Andreas; Berger, Anja; Schneider-Brachert, Wulf; Holzmann, Thomas; Reischl, Udo

2011-01-01

The systemic symptoms of diphtheria are caused by the tox-encoded diphtheria toxin (DT) which is produced by toxigenic Corynebacterium spp. Besides the classical agent C. diphtheriae, the zoonotic pathogen C. ulcerans has increasingly been reported as an emerging pathogen for diphtheria. The reliable detection of toxigenic Corynebacterium spp. is of substantial importance for both diphtheria surveillance in the public health sector and the clinical workup of a patient with diphtherialike symptoms. Since the respective tox genes of C. diphtheriae and C. ulcerans differ from each other in both DNA and amino acid sequence, both tox genes should be covered by novel real-time PCR methods. We describe the development and validation of a LightCycler PCR assay which reliably recognizes tox genes from both C. diphtheriae and C. ulcerans and differentiates the respective target genes by fluorescence resonance energy transfer (FRET) hybridization probe melting curve analysis. PMID:21593261

Diagnosis delay and duration of hospitalisation of patients with Buruli ulcer in Nigeria.

PubMed

Meka, Anthony O; Chukwu, Joseph N; Nwafor, Charles C; Oshi, Daniel C; Madichie, Nelson O; Ekeke, Ngozi; Anyim, Moses C; Alphonsus, Chukwuka; Mbah, Obinna; Uzoukwa, Glory C; Njoku, Martin; Ntana, Kentigern; Ukwaja, Kingsley N

2016-09-01

Delayed diagnosis of Buruli ulcer can worsen clinical presentation of the disease, prolong duration of management, and impose avoidable additional costs on patients and health providers. We investigated the profile, delays in diagnosis, duration of hospitalisation, and associated factors among patients with Buruli ulcer in Nigeria. This was a prospective cohort study of patients with Buruli ulcer who were identified from a community-based survey. Data on the patients' clinical profile, delays in diagnosis and duration of hospitalisation were prospectively collected. Of 145 patients notified, 125 (86.2%) were confirmed by one or more laboratory tests (81.4% by PCR). The median age of the patients was 20 years, 88 (60.7%) were >15years old and 85 (58.6%) were females. In addition, 137 (94.5%) were new cases, 119 (82.1%) presented with ulcers and 110 (75.9%) had lower limb lesions. The mean time delay to diagnosis was 50.6 (±101.9) weeks. The mean duration of hospitalisation was 108 (±60) days. Determinants of time delay to diagnosis were higher disease category (p=0.001) and laboratory confirmation of disease (p=0.02). Determinants of longer hospitalisation were; multiple lesions (p=0.035), and having functional limitation at diagnosis and undertaking surgery (p=0.003). Patients with Buruli ulcer have very long time delays to diagnosis and long hospitalisation during treatment. This calls for early case-finding and improved access to Buruli ulcer services in Nigeria. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The potent effect of mycolactone on lipid membranes

PubMed Central

Maniti, Ofelia; Marion, Estelle; Marsollier, Laurent; Dufourc, Erick J.; Canaan, Stéphane

2018-01-01

Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease. Mycolactone has pleiotropic effects on fundamental cellular processes (cell adhesion, cell death and inflammation). Various cellular targets of mycolactone have been identified and a literature survey revealed that most of these targets are membrane receptors residing in ordered plasma membrane nanodomains, within which their functionalities can be modulated. We investigated the capacity of mycolactone to interact with membranes, to evaluate its effects on membrane lipid organization following its diffusion across the cell membrane. We used Langmuir monolayers as a cell membrane model. Experiments were carried out with a lipid composition chosen to be as similar as possible to that of the plasma membrane. Mycolactone, which has surfactant properties, with an apparent saturation concentration of 1 μM, interacted with the membrane at very low concentrations (60 nM). The interaction of mycolactone with the membrane was mediated by the presence of cholesterol and, like detergents, mycolactone reshaped the membrane. In its monomeric form, this toxin modifies lipid segregation in the monolayer, strongly affecting the formation of ordered microdomains. These findings suggest that mycolactone disturbs lipid organization in the biological membranes it crosses, with potential effects on cell functions and signaling pathways. Microdomain remodeling may therefore underlie molecular events, accounting for the ability of mycolactone to attack multiple targets and providing new insight into a single unifying mechanism underlying the pleiotropic effects of this molecule. This membrane remodeling may act in synergy with the other known effects of mycolactone on its intracellular targets, potentiating these effects. PMID:29320578

Molecular Species Delimitation and Morphology of Aquatic and Sub-Aquatic Bugs (Heteroptera) in Cameroon

PubMed Central

Le Gall, Philippe; Chen, Ping-Ping; Nieser, Nico; Guilbert, Eric; Njiokou, Flobert; Marsollier, Laurent; Guégan, Jean-François; Pluot-Sigwalt, Dominique; Eyangoh, Sara; Harry, Myriam

2016-01-01

Aquatic and semi-aquatic bugs (Heteroptera) represent a remarkable diversity and a resurging interest has been given to documenting at the species level these insects inhabiting Cameroon in Central Africa due to their potential implication in the transmission of the bacterium Mycobacterium ulcerans, the causal agent of Buruli ulcer, an emerging human disease. A survey was carried out over two years in Cameroon. Morphological analyses were done in two steps. A first step consisted in separating the specimens based on broadly shared characters into morphotypes. The specimens were then separated into two independent batches containing each the same representation of each morphotype. One batch (309 specimens) was used by taxonomy experts on aquatic bugs for species level identification and/or to reconcile nymph with their corresponding adult species. The second batch (188 specimens) was used to define species based on the COI DNA sequences (standard sequence used for “DNA barcoding”) and using the Automatic Barcode Gap Discovery (ABGD) method. The first morphological analysis step separated the specimens into 63 different morphotypes (49 adults and 14 nymphs), which were then found to belong to 54 morphological species in the infra-orders Gerromorpha and Nepomorpha based on the species-level morphological identification, and 41–45 putative molecular species according to the gap value retained in the ABGD. Integrating morphology and “DNA barcoding” reconciled all the specimens into 62 aquatic bug species in Cameroon. Generally, we obtained a good congruence between species a priori identified based on morphology from adult morphotypes and molecular putative species. Moreover, molecular identification has allowed the association of 86% of nymphs with adults. This work illustrates the importance of integrative taxonomy. PMID:27149077

Identification of nonlipophilic corynebacteria isolated from dairy cows with mastitis.

PubMed

Hommez, J; Devriese, L A; Vaneechoutte, M; Riegel, P; Butaye, P; Haesebrouck, F

1999-04-01

Nonlipophilic corynebacteria associated with clinical and subclinical mastitis in dairy cows were found to belong to four species: Corynebacterium amycolatum, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis, and Corynebacterium minutissimum. These species may easily be confused. However, clear-cut differences between C. ulcerans and C. pseudotuberculosis were found in their acid production from maltotriose and ethylene glycol, susceptibility to vibriostatic agent O129, and alkaline phosphatase. Absence of growth at 20 degrees C and lack of alpha-glucosidase and 4MU-alpha-D-glycoside hydrolysis activity differentiated C. amycolatum from C. pseudotuberculosis and C. ulcerans. The mastitis C. pseudotuberculosis strains differed from the biovar equi and ovis reference strains and from caprine field strains in their colony morphologies and in their reduced inhibitory activity on staphylococcal beta-hemolysin. C. amycolatum was the most frequently isolated nonlipophilic corynebacterium.

Identification of Nonlipophilic Corynebacteria Isolated from Dairy Cows with Mastitis

PubMed Central

Hommez, Jozef; Devriese, Luc A.; Vaneechoutte, Mario; Riegel, Philippe; Butaye, Patrick; Haesebrouck, Freddy

1999-01-01

Nonlipophilic corynebacteria associated with clinical and subclinical mastitis in dairy cows were found to belong to four species: Corynebacterium amycolatum, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis, and Corynebacterium minutissimum. These species may easily be confused. However, clear-cut differences between C. ulcerans and C. pseudotuberculosis were found in their acid production from maltotriose and ethylene glycol, susceptibility to vibriostatic agent O129, and alkaline phosphatase. Absence of growth at 20°C and lack of α-glucosidase and 4MU-α-d-glycoside hydrolysis activity differentiated C. amycolatum from C. pseudotuberculosis and C. ulcerans. The mastitis C. pseudotuberculosis strains differed from the biovar equi and ovis reference strains and from caprine field strains in their colony morphologies and in their reduced inhibitory activity on staphylococcal β-hemolysin. C. amycolatum was the most frequently isolated nonlipophilic corynebacterium. PMID:10074508

Antibiotic complications during the treatment of Mycobacterium ulcerans disease in Australian patients.

PubMed

O'Brien, Daniel P; Friedman, Deborah; Hughes, Andrew; Walton, Aaron; Athan, Eugene

2017-09-01

Antibiotics are the recommended first-line treatment for Mycobacterium ulcerans disease. Antibiotic toxicity is common in Australian patients, yet antibiotic complication rates and their risk factors have not been determined. To determine the incidence rate and risk factors for antibiotic toxicity in Australian patients treated for M. ulcerans disease. An analysis of severe antibiotic complications was performed using data from a prospective cohort of M. ulcerans cases managed at Barwon Health from 1 January 1998 to 30 June 2016. A severe antibiotic complication was defined as an antibiotic adverse event that required its cessation. Antibiotic complication rates and their associations were assessed using a Poisson regression model. A total of 337 patients was included; 184 (54.6%) males and median age 57 years (interquartile range (IQR) 36-73 years). Median antibiotic treatment duration was 56 days (IQR 49-76 days). Seventy-five (22.2%) patients experienced severe antibiotic complications after a median 28 days (IQR 17-45 days) at a rate of 141.53 per 100 person-years (95% confidence interval (CI) 112.86-177.47). Eleven (14.7%) patients required hospitalisation. Compared with rifampicin/clarithromycin combinations, severe complication rates were not increased for rifampicin/ciprofloxacin (rate ratio (RR) 1.49, 95% CI 0.89-2.50, P = 0.13) or rifampicin/moxifloxacin (RR 2.54, 95% CI 0.76-8.50, P = 0.13) combinations, but were significantly increased for 'other' combinations (RR 2.53, 95% CI 1.13-5.68, P = 0.03). In a multivariable analysis, severe complication rates were significantly increased with reduced estimated glomerular filtration rates (EGFR) (adjusted rate ratio (aRR) 2.65, 95% CI 1.24-5.65 for EGFR 60-89 mL/min and aRR 1.31, 95% CI 0.49-3.53 for EGFR 0-59 mL/min compared with EGFR ≥90 mL/min, P < 0.01) and female gender (aRR 2.15, 95% CI 1.38-3.30, P < 0.01). Severe antibiotic complications during M. ulcerans treatment are high with increased rates independently associated with reduced renal function and female gender. © 2017 Royal Australasian College of Physicians.

Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

PubMed

Haywood, Matthew James; Vijendren, Ananth; Acharya, Vikas; Mulla, Rohinton; Panesar, Miss Jaan

2017-03-06

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans , with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery. 2017 BMJ Publishing Group Ltd.

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis.

PubMed

Tomczyk, Sara; Deribe, Kebede; Brooker, Simon J; Clark, Hannah; Rafique, Khizar; Knopp, Stefanie; Utzinger, Jürg; Davey, Gail

2014-01-01

The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROSPERO International prospective register of systematic reviews CRD42012003338.

Association between Footwear Use and Neglected Tropical Diseases: A Systematic Review and Meta-Analysis

PubMed Central

Brooker, Simon J.; Clark, Hannah; Rafique, Khizar; Knopp, Stefanie; Utzinger, Jürg; Davey, Gail

2014-01-01

Background The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. Methodology We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. Principal Findings Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR = 0.15; 95% CI: 0.08–0.29), CLM (OR = 0.24; 95% CI: 0.06–0.96), tungiasis (OR = 0.42; 95% CI: 0.26–0.70), hookworm infection (OR = 0.48; 95% CI: 0.37–0.61), any STH infection (OR = 0.57; 95% CI: 0.39–0.84), strongyloidiasis (OR = 0.56; 95% CI: 0.38–0.83), and leptospirosis (OR = 0.59; 95% CI: 0.37–0.94). No significant association between footwear use and podoconiosis (OR = 0.63; 95% CI: 0.38–1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. Conclusions/Significance Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. Protocol Registration PROSPERO International prospective register of systematic reviews CRD42012003338 PMID:25393620

40 CFR 725.421 - Introduced genetic material.

Code of Federal Regulations, 2010 CFR

2010-07-01

... elongation factor 2, leading to inhibition of protein synthesis in target respiratory, heart, kidney, and... protein synthesis inhibitor. Sequence Source Toxin Name Corynebacterium diphtheriae & C. ulcerans...

Health Facility Cost of Buruli Ulcer Wound Treatment in Ghana: A Case Study.

PubMed

Asare, Kofi Hene; Aikins, Moses

2014-09-01

To estimate the wound treatment cost borne by the Buruli Ulcer Treatment Centre of the Amasaman Government Hospital, Ghana. Three different types of data collection approaches were used, namely, 1) observation checklist, 2) in-depth interviews, and 3) expenditure data review. Wound dressing processes were observed. Retrospective health facility cost data of Buruli ulcer (BU) wound treatment for the year 2011 were used. Cost data gathered covered medical and nonmedical items. Cost analyses were carried out to determine the health facility's financial and economic costs. The total annual financial cost was US $121,189.16, of which 99% was recurrent cost. This constitutes about 13% of the expenditure by the Amasaman Government Hospital for the year 2011. The total annual economic cost was US $143,609.22, of which 93% was recurrent cost. The main cost driver for both financial and economic costs was personnel. The annual BU wound treatment costs per capita were US $1615.86 for financial cost and US $1914.79 for economic cost, respectively. The study did not cover household patient costs. The cost of BU wound treatment takes a considerable amount of the hospital's expenditure. This shows the importance of health facility cost as one of the decision-making tools for both resource allocation and mobilization. Hospital management must therefore constantly examine its staffing norms and the associated cost to improve the hospital's resource allocation. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Pathogenesis of tuberculosis and other mycobacteriosis.

PubMed

Cardona, Pere-Joan

2018-01-01

The evolution between Mycobacterium tuberculosis infection and active tuberculosis is multifactorial and involves different biological scales. The synthesis of ESAT-6 or the induction of alveolar macrophage necrosis are key, but to understand it, it is necessary to consider the dynamics of endogenous and exogenous reinfection, drainage of lung parenchyma and respiratory mechanics, local fibrosis processes and blood supply. Paradoxically, the immune response generated by the infection is highly protective (90%) against active tuberculosis, although as it is essentially based on the proliferation of Th1 lymphocytes, it cannot prevent reinfection. Severe immunosuppression can only explain 10% of active tuberculosis cases, while the remainder are attributable to comorbidities, a proinflammatory environment and an unknown genetic propensity. The pathogenic capacity of environmental mycobacteria is discrete, linked to deficits in the innate and acquired immune response. The ability to generate biofilms and the ability of M. ulcerans to generate the exotoxin mycolactone is remarkable. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

[Nursing perspective on the care of people with leprosy in Ivory Coast].

PubMed

Lecocq, Dan

Lucien Gbadié is a nurse at the Raoul-Follereau Institute in Adzopé, Ivory Coast. In this article, he describes how people with leprosy or Buruli ulcer are treated and supported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Landscape Fragmentation as a Risk Factor for Buruli Ulcer Disease in Ghana

PubMed Central

Wu, Jianyong; Smithwick, Erica A. H.

2016-01-01

Land cover and its change have been linked to Buruli ulcer (BU), a rapidly emerging tropical disease. However, it is unknown whether landscape structure affects the disease prevalence. To examine the association between landscape pattern and BU presence, we obtained land cover information for 20 villages in southwestern Ghana from high resolution satellite images, and analyzed the landscape pattern surrounding each village. Eight landscape metrics indicated that landscape patterns between BU case and reference villages were different (P < 0.05) at the broad spatial extent examined (4 km). The logistic regression models showed that landscape fragmentation and diversity indices were positively associated with BU presence in a village. Specifically, for each increase in patch density and edge density by 100 units, the likelihood of BU presence in a village increased 2.51 (95% confidence interval [CI] = 1.36–4.61) and 4.18 (95% CI = 1.63–10.76) times, respectively. The results suggest that increased landscape fragmentation may pose a risk to the emergence of BU. PMID:27185767

Combining PCR with Microscopy to Reduce Costs of Laboratory Diagnosis of Buruli Ulcer

PubMed Central

Yeboah-Manu, Dorothy; Asante-Poku, Adwoa; Asan-Ampah, Kobina; Ampadu, Emelia Danso Edwin; Pluschke, Gerd

2011-01-01

The introduction of antibiotic therapy as first-line treatment of Buruli ulcer underlines the importance of laboratory confirmation of clinical diagnosis. Because smear microscopy has very limited sensitivity, the technically demanding and more expensive IS2404 diagnostic polymerase chain reaction (PCR) has become the main method for confirmation. By optimization of the release of mycobacteria from swab specimen and concentration of bacterial suspensions before smearing, we were able to improve the detection rate of acid-fast bacilli by microscopy after Ziehl–Neelsen staining. Compared with IS2404 PCR, which is the gold standard diagnostic method, the sensitivity and specificity of microscopy with 100 concentrated specimens were 58.4% and 95.7%, respectively. We subsequently evaluated a stepwise laboratory confirmation algorithm with detection of AFB as first-line method and IS2404 PCR performed only with those samples that were negative in microscopic analysis. This stepwise approach reduced unit cost by more than 50% to $5.41, and the total costs were reduced from $917 to $433. PMID:22049046

Situated knowledge of pathogenic landscapes in Ghana: Understanding the emergence of Buruli ulcer through qualitative analysis.

PubMed

Tschakert, Petra; Ricciardi, Vincent; Smithwick, Erica; Machado, Mario; Ferring, David; Hausermann, Heidi; Bug, Leah

2016-02-01

Successfully addressing neglected tropical diseases requires nuanced understandings of pathogenic landscapes that incorporate situated, contexualized community knowledge. In the case of Buruli ulcer (BU), the role of social science is vital to investigate complex human-environment interactions and navigate different ways of knowing. We analyze a set of qualitative data from our interdisciplinary project on BU in Ghana, drawing from participatory mapping, focus group discussions, semi-structured interviews, and open-ended survey questions to explore how people in endemic and non-endemic areas see themselves embedded in changing environmental and social landscapes. We pay particular attention to landscape disturbance through logging and small-scale alluvial gold mining. The results from our participatory research underscore the holistic nature of BU emergence in landscapes, encapsulated in partial and incomplete local descriptions, the relevance of collective learning to distill complexity, and the potential of rich qualitative data to inform quantitative landscape-disease models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Health-related biotechnologies for infectious disease control in Africa: Ethical, Legal and Social Implications (ELSI) of transfer and development.

PubMed

Sommerfeld, J; Oduola, A M J

2007-01-01

The African continent is disproportionately affected by infectious diseases. Malaria, HIV/AIDS, tuberculosis, and more "neglected" diseases including African trypanosomiasis, Buruli ulcer, leishmaniasis, onchocerciasis and trachoma continue to dramatically impact social and economic development on the continent. Health biotechnologies provide potential to develop effective strategies for the fight against the vicious circle of poverty and infections by helping in the development and improvement of novel affordable drugs, diagnostics and vaccines against these diseases. As the prospects of this emerging biotechnology research and deployment of its products become a reality in Africa, there is a need to consider the ethical, legal and social implications of both the scientific and technological advances and their use in the communities. The article provides a short overview of the potential values of biotechnology, issues involved in its transfer and presents the rationale, design and recommendations of the international workshop/symposium held in April 2005 at the International Institute for Tropical Agriculture (IITA) in Ibadan, Nigeria.

Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa

PubMed Central

Garchitorena, Andrés; Ngonghala, Calistus N.; Guegan, Jean-Francois; Texier, Gaëtan; Bellanger, Martine; Bonds, Matthew; Roche, Benjamin

2015-01-01

Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well-documented economic impacts. However, much less is known about the population-level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual-based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions. PMID:26538592

Assessment of water, sanitation, and hygiene practices and associated factors in a Buruli ulcer endemic district in Benin (West Africa).

PubMed

Johnson, Roch Christian; Boni, Gratien; Barogui, Yves; Sopoh, Ghislain Emmanuel; Houndonougbo, Macaire; Anagonou, Esai; Agossadou, Didier; Diez, Gabriel; Boko, Michel

2015-08-19

Control of neglected tropical diseases (NTDs) requires multiple strategic approaches including water, sanitation and hygiene services (WASH). Buruli ulcer (BU), one of the 17 NTDs, remains a public health issue in Benin particularly in the district of Lalo. The availability of water as well as good hygiene are important for the management of Buruli ulcer particularly in the area of wound care one of the main component of the treatment of BU lesions. Given the growing importance of WASH in controlling NTDs and in order to assess the baseline for future cross-cutting interventions, we report here on the first study evaluating the level of WASH and associated factors in Lalo, one of the most BU-endemic districts in Benin. A cross-sectional study was carried to assess WASH practices and associated factors in the district of Lalo. Data were collected from 600 heads of household using structured pretested questionnaire and observations triangulated with qualitative information obtained from in-depth interviews of patients, care-givers and community members. Univariate and multivariate analysis were carried to determine the relationships between the potential associated factors and the sanitation as well as hygiene status. BU is an important conditions in the district of Lalo with 917 new cases detected from 2006 to 2012. More than 49 % of the household surveyed used unimproved water sources for their daily needs. Only 8.7 % of the investigated household had improved sanitation facilities at home and 9.7 % had improved hygiene behavior. The type of housing as an indicator of the socioeconomic status, the permanent availability of soap and improved hygiene practices were identified as the main factors positively associated with improved sanitation status. In the district of Lalo in Benin, one of the most endemic for BU, the WASH indicators are very low. This study provides baseline informations for future cross-cutting interventions in this district.

A unique Mycobacterium species isolated from an epizootic of striped bass (Morone saxatilis).

PubMed Central

Rhodes, M. W.; Kator, H.; Kotob, S.; van Berkum, P.; Kaattari, I.; Vogelbein, W.; Floyd, M. M.; Butler, W. R.; Quinn, F. D.; Ottinger, C.; Shotts, E.

2001-01-01

We isolated a Mycobacterium sp. resembling Mycobacterium marinum and M. ulcerans from diseased striped bass (Morone saxatilis) during an epizootic of mycobacteriosis in the Chesapeake Bay. This isolate may represent an undescribed Mycobacterium species, based on phenotypic characteristics and comparative 16S rRNA gene sequence. PMID:11747708

Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors

PubMed Central

Garchitorena, Andrés; Guégan, Jean-François; Léger, Lucas; Eyangoh, Sara; Marsollier, Laurent; Roche, Benjamin

2015-01-01

Host–parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in climate or abiotic conditions in water and soil, which confounds our understanding of the main drivers of many multi-host pathogens. Here, we take advantage of a combination of large environmental data sets on Mycobacterium ulcerans (MU), an environmentally persistent microorganism associated to freshwater ecosystems and present in a large variety of aquatic hosts, to characterize abiotic and biotic factors driving the dynamics of this pathogen in two regions of Cameroon. We find that MU dynamics are largely driven by seasonal climatic factors and certain physico-chemical conditions in stagnant and slow-flowing ecosystems, with an important role of pH as limiting factor. Furthermore, water conditions can modify the effect of abundance and diversity of aquatic organisms on MU dynamics, which suggests a different contribution of two MU transmission routes for aquatic hosts (trophic vs environmental transmission) depending on local abiotic factors. DOI: http://dx.doi.org/10.7554/eLife.07616.001 PMID:26216042

Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa.

PubMed

Garchitorena, Andrés; Ngonghala, Calistus N; Guegan, Jean-Francois; Texier, Gaëtan; Bellanger, Martine; Bonds, Matthew; Roche, Benjamin

2015-11-07

Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well-documented economic impacts. However, much less is known about the population-level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual-based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions. © 2015 The Author(s).

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

PubMed

Conti, Francesca; Lugo-Reyes, Saul Oswaldo; Blancas Galicia, Lizbeth; He, Jianxin; Aksu, Güzide; Borges de Oliveira, Edgar; Deswarte, Caroline; Hubeau, Marjorie; Karaca, Neslihan; de Suremain, Maylis; Guérin, Antoine; Baba, Laila Ait; Prando, Carolina; Guerrero, Gloria G; Emiroglu, Melike; Öz, Fatma Nur; Yamazaki Nakashimada, Marco Antonio; Gonzalez Serrano, Edith; Espinosa, Sara; Barlan, Isil; Pérez, Nestor; Regairaz, Lorena; Guidos Morales, Héctor Eduardo; Bezrodnik, Liliana; Di Giovanni, Daniela; Dbaibo, Ghassan; Ailal, Fatima; Galicchio, Miguel; Oleastro, Matias; Chemli, Jalel; Danielian, Silvia; Perez, Laura; Ortega, Maria Claudia; Soto Lavin, Susana; Hertecant, Joseph; Anal, Ozden; Kechout, Nadia; Al-Idrissi, Eman; ElGhazali, Gehad; Bondarenko, Anastasia; Chernyshova, Liudmyla; Ciznar, Peter; Herbigneaux, Rose-Marie; Diabate, Aminata; Ndaga, Stéphanie; Konte, Barik; Czarna, Ambre; Migaud, Mélanie; Pedraza-Sánchez, Sigifredo; Zaidi, Mussaret Bano; Vogt, Guillaume; Blanche, Stéphane; Benmustapha, Imen; Mansouri, Davood; Abel, Laurent; Boisson-Dupuis, Stéphanie; Mahlaoui, Nizar; Bousfiha, Ahmed Aziz; Picard, Capucine; Barbouche, Ridha; Al-Muhsen, Saleh; Espinosa-Rosales, Francisco J; Kütükçüler, Necil; Condino-Neto, Antonio; Casanova, Jean-Laurent; Bustamante, Jacinta

2016-07-01

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Our objective was to assess the effect of mycobacterial disease in patients with CGD. We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A modified Elek test for detection of toxigenic corynebacteria in the diagnostic laboratory.

PubMed

Engler, K H; Glushkevich, T; Mazurova, I K; George, R C; Efstratiou, A

1997-02-01

The detection of toxigenicity among Corynebacterium diphtheriae and Corynebacterium ulcerans strains is the most important test for the microbiological diagnosis of diphtheria. Difficulties with current methods, in particular the Elek test, are well documented. We therefore describe a modified Elek test which provides an accurate result after only 16 h of incubation, in contrast to 48 h for the conventional test.

Synthesis and biological activity of alkynoic acids derivatives against mycobacteria

PubMed Central

Vilchèze, Catherine; Leung, Lawrence W.; Bittman, Robert; Jacobs, William R.

2015-01-01

2-alkynoic acids have bactericidal activity against Mycobacterium smegmatis but their activity fall sharply as the length of the carbon chain increased. In this study, derivatives of 2- alkynoic acids were synthesized and tested against fast- and slow-growing mycobacteria. Their activity was first evaluated in M. smegmatis against their parental 2-alkynoic acids, as well as isoniazid, a first-line antituberculosis drug. The introduction of additional unsaturation or heteroatoms into the carbon chain enhanced the antimycobacterial activity of longer chain alkynoic acids (more than 19 carbons long). In contrast, although the modification of the carboxylic group did not improve the antimycobacterial activity, it significantly reduced the toxicity of the compounds against eukaryotic cells. Importantly, 4-(alkylthio)but-2-ynoic acids, had better bactericidal activity than the parental 2-alkynoic acids and on a par with isoniazid against the slow-grower Mycobacterium bovis BCG. These compounds had also low toxicity against eukaryotic cells, suggesting that they could be potential therapeutic agents against other types of topical mycobacterial infections causing skin diseases including Mycobacterium abscessus, Mycobacterium ulcerans, and Mycobacterium leprae. Moreover, they provide a possible scaffold for future drug development. PMID:26256431

Mycobacterium shottsii sp. nov., a slowly growing species isolated from Chesapeake Bay striped bass (Morone saxatilis)

USGS Publications Warehouse

Rhodes, M.W.; Kator, H.; Kotob, S.; van Berkum, P.; Kaattari, I.; Vogelbein, W.; Quinn, F.; Floyd, M.M.; Butler, W.R.; Ottinger, C.A.

2003-01-01

Slowly growing, non-pigmented mycobacteria were isolated from striped bass (Morone saxatilis) during an epizootic of mycobacteriosis in the Chesapeake Bay. Growth characteristics, acid-fastness and results of 16S rRNA gene sequencing were consistent with those of the genus Mycobacterium. A unique profile of biochemical reactions was observed among the 21 isolates. A single cluster of eight peaks identified by analysis of mycolic acids (HPLC) resembled those of reference patterns but differed in peak elution times from profiles of reference species of the Mycobacterium tuberculosis complex. One isolate (M175T) was placed within the slowly growing mycobacteria by analysis of aligned 16S rRNA gene sequences and was proximate in phylogeny to Mycobacterium ulcerans and Mycobacterium marinum. However, distinct nucleotide differences were detected in the 16S rRNA gene sequence among M175T, M. ulcerans and M. marinum (99.2% similarity). Isolate M175T could be differentiated from other slowly growing, non-pigmented mycobacteria by its inability to grow at 37??C, production of niacin and urease, absence of nitrate reductase and resistance to isoniazid (1 ??g ml-1), thiacetazone and thiophene-2-carboxylic hydrazide. Based upon these genetic and phenotypic differences, isolate M175T (= ATCC 700981T = NCTC 13215T) is proposed as the type strain of a novel species, Mycobacterium shottsii sp. nov.

Rapid microbiochemical identification of Corynebacterium diphtheriae and other medically important corynebacteria.

PubMed Central

Thompson, J S; Gates-Davis, D R; Yong, D C

1983-01-01

A rapid biochemical method based on the fermentation of carbohydrates, the hydrolysis of urea, and the reduction of nitrate was used to identify Corynebacterium diphtheriae, C. ulcerans, C. pseudodiphtheriticum, C. haemolyticum, C. pseudotuberculosis, C. pyogenes, C. ovis, the Centers for Disease Control JK group, and Rhodococcus (Corynebacterium) equi. With this procedure identification was confirmed for 133 stock cultures and clinical isolates of corynebacteria. Most were identified within 1 h and all were identified within 4 h after inoculation into the test substrates. PMID:6355166

Prevention and control of neglected tropical diseases: overview of randomized trials, systematic reviews and meta-analyses

PubMed Central

Kappagoda, Shanthi

2014-01-01

Abstract Objective To analyse evidence from randomized controlled trials (RCTs) on the prevention and control of neglected tropical diseases (NTDs) and to identify areas where evidence is lacking. Methods The Cochrane Central Register of Controlled Trials and PubMed were searched for RCTs and the Cochrane Database of Systematic Reviews and PubMed were searched for meta-analyses and systematic reviews, both from inception to 31 December 2012. Findings Overall, 258 RCTs were found on American trypanosomiasis, Buruli ulcer, dengue, geohelminth infection, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis or trachoma. No RCTs were found on cysticercosis, dracunculiasis, echinococcosis, foodborne trematodes, or human African trypanosomiasis. The most studied diseases were geohelminth infection (51 RCTs) and leishmaniasis (46 RCTs). Vaccines, chemoprophylaxis and interventions targeting insect vectors were evaluated in 113, 99 and 39 RCTs, respectively. Few addressed how best to deliver preventive chemotherapy, such as the choice of dosing interval (10) or target population (4), the population coverage needed to reduce transmission (2) or the method of drug distribution (1). Thirty-one publications containing 32 systematic reviews (16 with and 16 without meta-analyses) were found on American trypanosomiasis, dengue, geohelminths, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis or trachoma. Together, they included only 79 of the 258 published RCTs (30.6%). Of 36 interventions assessed, 8 were judged effective in more than one review. Conclusion Few RCTs on the prevention or control of the principal NTDs were found. Trials on how best to deliver preventive chemotherapy were particularly rare. PMID:24839325

Development, validation and implementation of a quadruplex real-time PCR assay for identification of potentially toxigenic corynebacteria.

PubMed

De Zoysa, Aruni; Efstratiou, Androulla; Mann, Ginder; Harrison, Timothy G; Fry, Norman K

2016-12-01

Toxigenic corynebacteria are uncommon in the UK; however, laboratory confirmation by the national reference laboratory can inform public health action according to national guidelines. Standard phenotypic tests for identification and toxin expression of isolates can take from ≥24 to ≥48 h from receipt. To decrease the time to result, a real-time PCR (qPCR) assay was developed for confirmation of both identification of Corynebacterium diphtheriae and Corynebacterium ulcerans/Corynebacterium pseudotuberculosis and detection of the diphtheria toxin gene. Target genes were the RNA polymerase β-subunit-encoding gene (rpoB) and A-subunit of the diphtheria toxin gene (tox). Green fluorescent protein DNA (gfp) was used as an internal process control. qPCR results were obtained within 3 to 4 h after receipt of isolate. The assay was validated according to published guidelines and demonstrated high diagnostic sensitivity (100 %), high specificity (98-100 %) and positive and negative predictive values of 91 to 100 % and 100 %, respectively, compared to both block-based PCR and the Elek test, together with a greatly reduced time from isolate receipt to reporting. Limitations of the qPCR assay were the inability to distinguish between C. ulcerans and C. pseudotuberculosis and that the presence of the toxin gene as demonstrated by qPCR may not always predict toxin expression. Thus, confirmation of expression of diphtheria toxin is always sought using the phenotypic Elek test. The new qPCR assay was formally introduced as the front-line test for putative toxigenic corynebacteria to inform public health action in England and Wales on 1 April 2014.

Corynebacterium species nasopharyngeal carriage in asymptomatic individuals aged ≥ 65 years in Germany.

PubMed

Teutsch, Barbara; Berger, Anja; Marosevic, Durdica; Schönberger, Katharina; Lâm, Thiên-Trí; Hubert, Kerstin; Beer, Steffi; Wienert, Peter; Ackermann, Nikolaus; Claus, Heike; Drayß, Maria; Thiel, Kathrin; van der Linden, Mark; Vogel, Ulrich; Sing, Andreas

2017-10-01

The prevalence of protective anti-diphtheria toxin antibodies decreases with age. Therefore, the elderly might serve as reservoir for potentially toxigenic Corynebacterium (C.) species (C. diphtheriae, C. ulcerans, and C. pseudotuberculosis). This study aimed to examine the colonization rate of the nasopharynx with corynebacteria of individuals aged 65 years and older. In the period from October 2012 to June 2013, nasal and throat swabs were taken from 714 asymptomatic subjects aged 65-106 years (average age 77.2) at three regions in Germany and investigated for Corynebacterium species. A total of 402 strains of Corynebacterium species were isolated from 388 out of 714 asymptomatic subjects (carriage rate 54.3%). The carriage rate was significantly higher in study participants living in retirement homes (68.4%) compared to those living autonomously at home (51.1%). Strains were isolated mostly from the nose (99%). Corynebacterium accolens was the most often isolated species (39.8%), followed by C. propinquum (24.1%), C. pseudodiphtheriticum (19.4%), and C. tuberculostearicum (10.2%). No C. diphtheriae, C. ulcerans, and C. pseudotuberculosis strains were isolated. A subsample of 74 subjects was tested serologically for anti-diphtheria antibodies. Protective anti-diphtheria toxin antibodies were found in 29.7% of the subjects; 70.3% showed no protective immunity. These results suggest that carriage of potentially toxigenic corynebacteria is very rare among people aged 65 and older in Germany. However, the low prevalence of protective anti-diphtheria toxin antibodies might pose a risk for acquiring diphtheria especially for the elderly.

Evaluation of invertebrate infection models for pathogenic corynebacteria.

PubMed

Ott, Lisa; McKenzie, Ashleigh; Baltazar, Maria Teresa; Britting, Sabine; Bischof, Andrea; Burkovski, Andreas; Hoskisson, Paul A

2012-08-01

For several pathogenic bacteria, model systems for host-pathogen interactions were developed, which provide the possibility of quick and cost-effective high throughput screening of mutant bacteria for genes involved in pathogenesis. A number of different model systems, including amoeba, nematodes, insects, and fish, have been introduced, and it was observed that different bacteria respond in different ways to putative surrogate hosts, and distinct model systems might be more or less suitable for a certain pathogen. The aim of this study was to develop a suitable invertebrate model for the human and animal pathogens Corynebacterium diphtheriae, Corynebacterium pseudotuberculosis, and Corynebacterium ulcerans. The results obtained in this study indicate that Acanthamoeba polyphaga is not optimal as surrogate host, while both Caenorhabtitis elegans and Galleria larvae seem to offer tractable models for rapid assessment of virulence between strains. Caenorhabtitis elegans gives more differentiated results and might be the best model system for pathogenic corynebacteria, given the tractability of bacteria and the range of mutant nematodes available to investigate the host response in combination with bacterial virulence. Nevertheless, Galleria will also be useful in respect to innate immune responses to pathogens because insects offer a more complex cell-based innate immune system compared with the simple innate immune system of C. elegans. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Preliminary investigation into the prevalence of mucormycosis in the platypus (Ornithorhynchus anatinus) in three catchments in north-west Tasmania.

PubMed

Macgregor, J W; Holyoake, C S; Munks, S A; Robertson, I D; Warren, K S

2010-05-01

To investigate the distribution and prevalence of mucormycosis in platypus (Ornithorhynchus anatinus) from the Inglis, Emu and Black-Detention catchment areas in north-west Tasmania. A field study was performed and resulted in the examination of 44 wild platypuses; in addition, one dead platypus and two live platypuses were examined after they were independently submitted to a local veterinary clinic. No cases of mucormycosis were conclusively diagnosed. One platypus with signs consistent with those previously described in cases of mucormycosis was captured in the Emu River catchment. However, laboratory tests did not provide a definitive diagnosis for the lesion. Two platypuses from the Inglis catchment area had signs very similar to those previously described in cases of mucormycosis, but laboratory tests found Corynebacterium ulcerans to be the likely cause of the cutaneous ulcers on one of these platypuses and an unidentified fungal agent to be the cause of a cutaneous nodule in the other. These findings do not prove that mucormycosis is absent from the populations studied. However, they may indicate that the prevalence of disease is low. The possibility that Mucor amphibiorum is present in a subclinical form in platypuses, or infecting another reservoir, is not excluded. The findings also suggest that caution should be exercised when diagnosing mucormycosis based on clinical findings alone and raise the possibility that some cases may have been incorrectly diagnosed.

Antimycobacterial potency and cytotoxicity study of three medicinal plants.

PubMed

Tsouh Fokou, Patrick Valere; Appiah-Opong, Regina; Yeboah-Manu, Dorothy; Kissi-Twum, Abena Adomah; Yamthe, Lauve Rachel Tchokouaha; Mokale Kognou, Aristide Laurel; Addo, Phyllis; Boyom, Fabrice Fekam; Nyarko, Alexander Kwadwo

2016-12-01

Mycobacterial infections including tuberculosis, leprosy, and buruli ulcer are among the most prevalent, debilitating, and deadly tropical diseases, especially in Sub-Saharan Africa. The development of drug resistance to the currently available drugs and the poor compliance emphasize the need for new chemotherapeutic agents. This study was designed to evaluate the in vitro activity of Cleistopholis patens, Annona reticulata, and Greenwayodendron suaveolens against Mycobacterium smegmatis. The safety on normal liver cells was also assessed. The crude extracts, fractions, and subfractions were tested against M. smegmatis and for cell cytotoxicity on WRL-68, normal human hepatocyte using microdilution resazurin-based assays. The phytochemical screening was performed using standard methods. Most of the extracts, fractions, and subfractions inhibited the growth of M. smegmatis with minimum inhibitory concentration (MIC) values ranging from 6.25μg/mL to 125μg/mL. The subfractions P12 and P29 from G. suaveolens twig were more potent with MIC values of 6.25μg/mL and 25μg/mL, respectively. Fruit crude extract and root CH 2 Cl 2 fraction from A. reticulata also showed activity with MIC values of 50μg/mL and 25μg/mL, respectively. Crude extracts from the twig and stem bark of C. patens displayed inhibition at MIC values of 125μg/mL and 100μg/mL, respectively. Majority of active extracts showed no cell cytotoxicity, except the extract from C. patens with IC 50 ranging from 41.40μg/mL to 93.78μg/mL. The chemical investigation of the promising extracts revealed the presence of phenols, alkaloids, glycosides, triterpenes, and acetogenins. The results achieved from this preliminary antimycobacterial drug discovery study supported the traditional claims of C. patens, A. reticulata, and G. suaveolens in the treatment of mycobacterial infections. Meanwhile, further fractionation is required to characterize the active ingredients. Copyright © 2016.

Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo, Ghana and Togo

PubMed Central

Phillips, Richard Odame; Phanzu, Delphin Mavinga; Beissner, Marcus; Badziklou, Kossi; Luzolo, Elysée Kalundieko; Sarfo, Fred Stephen; Halatoko, Wemboo Afiwa; Amoako, Yaw; Frimpong, Michael; Kabiru, Abass Mohammed; Piten, Ebekalisai; Maman, Issaka; Bidjada, Bawimodom; Koba, Adjaho; Awoussi, Koffi Somenou; Kobara, Basile; Nitschke, Jörg; Wiedemann, Franz Xaver; Kere, Abiba Banla; Adjei, Ohene; Löscher, Thomas; Fleischer, Bernhard; Bretzel, Gisela; Herbinger, Karl-Heinz

2015-01-01

Background The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guérin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD. Methodology The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. Principal Findings After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31), sex (p = 0.24), age (p = 0.96), and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions. Conclusions In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD. PMID:25569674

Contribution to the taxonomy of haemolytic corynebacteria.

PubMed

Julák, J; Mára, M; Patocka, F; Potuzníková, B; Zadrazil, S

1978-01-01

In an attempt to assess the taxonomic relationships among human (Corynebacterium haemolyticum), animal (Corynebacterium pyogenes bovis) haemolytic corynebacteria, typical corynebacteria (Corynebacterium diphteriae mitis, C. ovis, C. ulcerans) and group A and G streptococci, a number of biochemical parameters were established: the DNA content of G + C, the presence of the cytochrome system, composition of fatty acids in free lipids and production of carboxylic acids as end products of fermentation. It was found that according to the above criteria, streptococci differed significantly from the corynebacteria studied. In addition, it was possible to differentiate a subgroup of typically aerobic haemolytic corynebacteria (different from both human and animal corynebacteria), possessing a complete cytochrome system, producing propionic acid and having a different composition of fatty acids.

Contribution to the taxonomy of haemolytic corynebacteria.

PubMed

Julák, J; Mára, M; Patočka, F; Potužníková, B; Zadražil, S

1978-05-01

In an attempt to assess the taxonomic relationships among human (Corynebacterium haemolyticum), animal (Corynebacterium pyogenes bovis) haemolytio corynebacteria, typical corynebacteria (Corynebacterium diphteriae mitis, C. ovis, C. ulcerans) and group A and G streptococci, a number of biochemical parameters were established: the DNA content of G + C, the presence of the cytochrome system, composition of fatty acids in free lipids and production of carboxylic acids as end products of fermentation. It was found that according to the above criteria, streptococci differed significantly from the corynebacteria studied. In addition, it was possible to differentiate a subgroup of typically aerobic haemolytic corynebacteria (different from both human and animal corynebacteria), possessing a complete cytochrome system, producing propionic acid and having a different composition of fatty acids.

Implementation of a National Reference Laboratory for Buruli Ulcer Disease in Togo

PubMed Central

Badziklou, Kossi; Halatoko, Wemboo Afiwa; Maman, Issaka; Vogel, Felix; Bidjada, Bawimodom; Awoussi, Koffi Somenou; Piten, Ebekalisai; Helfrich, Kerstin; Mengele, Carolin; Nitschke, Jörg; Amekuse, Komi; Wiedemann, Franz Xaver; Diefenhardt, Adolf; Kobara, Basile; Herbinger, Karl–Heinz; Kere, Abiba Banla; Prince-David, Mireille; Löscher, Thomas; Bretzel, Gisela

2013-01-01

Background In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo. Methodology Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions “Maritime” and “Central,” standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory. Principal Findings The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%. Conclusions High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory. PMID:23359828

Implementation of a national reference laboratory for Buruli ulcer disease in Togo.

PubMed

Beissner, Marcus; Huber, Kristina Lydia; Badziklou, Kossi; Halatoko, Wemboo Afiwa; Maman, Issaka; Vogel, Felix; Bidjada, Bawimodom; Awoussi, Koffi Somenou; Piten, Ebekalisai; Helfrich, Kerstin; Mengele, Carolin; Nitschke, Jörg; Amekuse, Komi; Wiedemann, Franz Xaver; Diefenhardt, Adolf; Kobara, Basile; Herbinger, Karl-Heinz; Kere, Abiba Banla; Prince-David, Mireille; Löscher, Thomas; Bretzel, Gisela

2013-01-01

In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo. Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions "Maritime" and "Central," standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory. The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%. High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory.

Loop-Mediated Isothermal Amplification for Laboratory Confirmation of Buruli Ulcer Disease—Towards a Point-of-Care Test

PubMed Central

Beissner, Marcus; Phillips, Richard Odame; Battke, Florian; Bauer, Malkin; Badziklou, Kossi; Sarfo, Fred Stephen; Maman, Issaka; Rhomberg, Agata; Piten, Ebekalisai; Frimpong, Michael; Huber, Kristina Lydia; Symank, Dominik; Jansson, Moritz; Wiedemann, Franz Xaver; Banla Kere, Abiba; Herbinger, Karl-Heinz; Löscher, Thomas; Bretzel, Gisela

2015-01-01

Background As the major burden of Buruli ulcer disease (BUD) occurs in remote rural areas, development of point-of-care (POC) tests is considered a research priority to bring diagnostic services closer to the patients. Loop-mediated isothermal amplification (LAMP), a simple, robust and cost-effective technology, has been selected as a promising POC test candidate. Three BUD-specific LAMP assays are available to date, but various technical challenges still hamper decentralized application. To overcome the requirement of cold-chains for transport and storage of reagents, the aim of this study was to establish a dry-reagent-based LAMP assay (DRB-LAMP) employing lyophilized reagents. Methodology/Principal Findings Following the design of an IS2404 based conventional LAMP (cLAMP) assay suitable to apply lyophilized reagents, a lyophylization protocol for the DRB-LAMP format was developed. Clinical performance of cLAMP was validated through testing of 140 clinical samples from 91 suspected BUD cases by routine assays, i.e. IS2404 dry-reagent-based (DRB) PCR, conventional IS2404 PCR (cPCR), IS2404 qPCR, compared to cLAMP. Whereas qPCR rendered an additional 10% of confirmed cases and samples respectively, case confirmation and positivity rates of DRB-PCR or cPCR (64.84% and 56.43%; 100% concordant results in both assays) and cLAMP (62.64% and 52.86%) were comparable and there was no significant difference between the sensitivity of the assays (DRB PCR and cPCR, 86.76%; cLAMP, 83.82%). Likewise, sensitivity of cLAMP (95.83%) and DRB-LAMP (91.67%) were comparable as determined on a set of 24 samples tested positive in all routine assays. Conclusions/Significance Both LAMP formats constitute equivalent alternatives to conventional PCR techniques. Provided the envisaged availability of field friendly DNA extraction formats, both assays are suitable for decentralized laboratory confirmation of BUD, whereby DRB-LAMP scores with the additional advantage of not requiring cold-chains. As validation of the assays was conducted in a third-level laboratory environment, field based evaluation trials are necessary to determine the clinical performance at peripheral health care level. PMID:26566026

Vectorborne diseases in West Africa: geographic distribution and geospatial characteristics.

PubMed

Ratmanov, Pavel; Mediannikov, Oleg; Raoult, Didier

2013-05-01

This paper provides an overview of the methods in which geographic information systems (GIS) and remote sensing (RS) technology have been used to visualise and analyse data related to vectorborne diseases (VBD) in West Africa and to discuss the potential for these approaches to be routinely included in future studies of VBDs. GIS/RS studies of diseases that are associated with a specific geographic landscape were reviewed, including malaria, human African trypanosomiasis, leishmaniasis, lymphatic filariasis, Loa loa filariasis, onchocerciasis, Rift Valley fever, dengue, yellow fever, borreliosis, rickettsioses, Buruli ulcer and Q fever. RS data and powerful spatial modelling methods improve our understanding of how environmental factors affect the vectors and transmission of VBDs. There is great potential for the use of GIS/RS technologies in the surveillance, prevention and control of vectorborne and other infectious diseases in West Africa.

Comparison of Phenotypic and Genotypic Methods for Detection of Diphtheria Toxin among Isolates of Pathogenic Corynebacteria

PubMed Central

Efstratiou, Androulla; Engler, Kathryn H.; Dawes, Charlotte S.; Sesardic, Dorothea

1998-01-01

We have compared molecular, immunochemical, and cytotoxic assays for the detection of diphtheria toxin from 55 isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans originally isolated in five different countries. The suitabilities and accuracies of these assays for the laboratory diagnosis of diphtheria were compared and evaluated against the “gold standard” in vivo methods. The in vivo and Vero cell cytotoxicity assays were accurate in their abilities to detect diphtheria toxin but were time-consuming; however, the cytotoxicity assay is a suitable in vitro alternative to the in vivo virulence test. There was complete concordance between all the phenotypic methods. Genotypic tests based upon PCR were rapid; however, PCR must be used with caution because some isolates of C. diphtheriae possessed toxin genes but failed to express a biologically active toxin. Therefore, phenotypic confirmation of toxigenicity for the microbiological diagnosis of diphtheria is recommended. PMID:9774560

Comparison of phenotypic and genotypic methods for detection of diphtheria toxin among isolates of pathogenic corynebacteria.

PubMed

Efstratiou, A; Engler, K H; Dawes, C S; Sesardic, D

1998-11-01

We have compared molecular, immunochemical, and cytotoxic assays for the detection of diphtheria toxin from 55 isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans originally isolated in five different countries. The suitabilities and accuracies of these assays for the laboratory diagnosis of diphtheria were compared and evaluated against the "gold standard" in vivo methods. The in vivo and Vero cell cytotoxicity assays were accurate in their abilities to detect diphtheria toxin but were time-consuming; however, the cytotoxicity assay is a suitable in vitro alternative to the in vivo virulence test. There was complete concordance between all the phenotypic methods. Genotypic tests based upon PCR were rapid; however, PCR must be used with caution because some isolates of C. diphtheriae possessed toxin genes but failed to express a biologically active toxin. Therefore, phenotypic confirmation of toxigenicity for the microbiological diagnosis of diphtheria is recommended.

Illness meanings and experiences for pre-ulcer and ulcer conditions of Buruli ulcer in the Ga-West and Ga-South Municipalities of Ghana.

PubMed

Ackumey, Mercy M; Gyapong, Margaret; Pappoe, Matilda; Kwakye-Maclean, Cynthia; Weiss, Mitchell G

2012-05-11

Ghana is a Buruli ulcer (BU) endemic country yet there is paucity of socio-cultural research on BU. Examining distinctive experiences and meanings for pre-ulcers and ulcers of BU may clarify the disease burden, illness experience and local perceptions of causes and spread, and environmental features of BU, which are useful to guide public health programmes and future research. This study aimed to explain local meanings and experiences of BU for persons with pre-ulcers and ulcers in the Ga-West and Ga-South municipalities in Accra. Semi-structured interviews based on the Explanatory Model Interview Catalogue framework were administered to 181 respondents comprising 15 respondents with pre-ulcers and 166 respondents with ulcers. The Wilcoxon rank-sum test was used to compare categories of illness experiences (PD) and perceived causes (PC) among respondents with pre-ulcer and ulcer conditions. The Fisher's exact test was used to compare the most troubling PD and the most important PC variables. Qualitative phenomenological analysis of respondents' narratives clarified illness experiences and meanings with reference to PC and PD variables. Families of respondents with pre-ulcers and the respondents themselves were often anxious about disease progression, while families of respondents with ulcers, who had to give care, worried about income loss and disruption of school attendance. Respondents with pre-ulcers frequently reported swimming in ponds and rivers as a perceived cause and considered it as the most important PC (53.3%). Respondents with ulcers frequently attributed their BU illness to witchcraft (64.5%) and respondents who claimed they had no water contact, questioned the credibility of health messages Affected persons with pre-ulcers are likely to delay treatment because of social and financial constraints and the absence of pain. Scepticism on the role of water in disease contagion and prolonged healing is perceived to make ideas of witchcraft as a PC more credible, among respondents with ulcers. Health messages should address issues of locally perceived risk and vulnerability. Guided by study findings, further research on the role of environmental, socio-cultural and genetic factors in BU contagion, is also needed to clarify and formulate health messages and strengthen public health initiatives.

Illness meanings and experiences for pre-ulcer and ulcer conditions of Buruli ulcer in the Ga-West and Ga-South Municipalities of Ghana

PubMed Central

2012-01-01

Background Ghana is a Buruli ulcer (BU) endemic country yet there is paucity of socio-cultural research on BU. Examining distinctive experiences and meanings for pre-ulcers and ulcers of BU may clarify the disease burden, illness experience and local perceptions of causes and spread, and environmental features of BU, which are useful to guide public health programmes and future research. This study aimed to explain local meanings and experiences of BU for persons with pre-ulcers and ulcers in the Ga-West and Ga-South municipalities in Accra. Methods Semi-structured interviews based on the Explanatory Model Interview Catalogue framework were administered to 181 respondents comprising 15 respondents with pre-ulcers and 166 respondents with ulcers. The Wilcoxon rank-sum test was used to compare categories of illness experiences (PD) and perceived causes (PC) among respondents with pre-ulcer and ulcer conditions. The Fisher’s exact test was used to compare the most troubling PD and the most important PC variables. Qualitative phenomenological analysis of respondents’ narratives clarified illness experiences and meanings with reference to PC and PD variables. Results Families of respondents with pre-ulcers and the respondents themselves were often anxious about disease progression, while families of respondents with ulcers, who had to give care, worried about income loss and disruption of school attendance. Respondents with pre-ulcers frequently reported swimming in ponds and rivers as a perceived cause and considered it as the most important PC (53.3%). Respondents with ulcers frequently attributed their BU illness to witchcraft (64.5%) and respondents who claimed they had no water contact, questioned the credibility of health messages Conclusions Affected persons with pre-ulcers are likely to delay treatment because of social and financial constraints and the absence of pain. Scepticism on the role of water in disease contagion and prolonged healing is perceived to make ideas of witchcraft as a PC more credible, among respondents with ulcers. Health messages should address issues of locally perceived risk and vulnerability. Guided by study findings, further research on the role of environmental, socio-cultural and genetic factors in BU contagion, is also needed to clarify and formulate health messages and strengthen public health initiatives. PMID:22471884

Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Christopher P.; Ferré-D'Amaré, Adrian R.

The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. In this paper, we report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg 2+ ion. We show that themore » affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. Finally, the ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression.« less

Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains

DOE PAGES

Jones, Christopher P.; Ferré-D'Amaré, Adrian R.

2015-08-17

The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. In this paper, we report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg 2+ ion. We show that themore » affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. Finally, the ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression.« less

Polymerase chain reaction for screening clinical isolates of corynebacteria for the production of diphtheria toxin.

PubMed

Pallen, M J; Hay, A J; Puckey, L H; Efstratiou, A

1994-04-01

To assess the performance of the polymerase chain reaction (PCR) when used to screen rapidly large numbers of corynebacteria for toxin production; and to determine the incidence of false positive PCR results with non-toxigenic Corynebacterium diphtheriae isolates. Eighty seven recent British isolates of corynebacteria were assayed by PCR. All isolates were assayed from both blood and tellurite agar within a five day period. Thirty three non-toxigenic isolates of C diphtheriae from six countries were also tested by PCR and by the Elek immunodiffusion assay. There was complete concordance between the results of PCR and traditional methods on the recent British isolates, with one exception: an Elek positive "C ulcerans" isolate, which was PCR positive from tellurite but not from blood agar. One of the thirty three (3%) non-toxigenic isolates of C diphtheriae was PCR positive. These results suggest that PCR compares favourably with traditional methods for the detection of toxigenic corynebacteria and that it represents a powerful new tool in the diagnosis of an old disease.

Polymerase chain reaction for screening clinical isolates of corynebacteria for the production of diphtheria toxin.

PubMed Central

Pallen, M J; Hay, A J; Puckey, L H; Efstratiou, A

1994-01-01

AIMS--To assess the performance of the polymerase chain reaction (PCR) when used to screen rapidly large numbers of corynebacteria for toxin production; and to determine the incidence of false positive PCR results with non-toxigenic Corynebacterium diphtheriae isolates. METHODS--Eighty seven recent British isolates of corynebacteria were assayed by PCR. All isolates were assayed from both blood and tellurite agar within a five day period. Thirty three non-toxigenic isolates of C diphtheriae from six countries were also tested by PCR and by the Elek immunodiffusion assay. RESULTS--There was complete concordance between the results of PCR and traditional methods on the recent British isolates, with one exception: an Elek positive "C ulcerans" isolate, which was PCR positive from tellurite but not from blood agar. One of the thirty three (3%) non-toxigenic isolates of C diphtheriae was PCR positive. CONCLUSIONS--These results suggest that PCR compares favourably with traditional methods for the detection of toxigenic corynebacteria and that it represents a powerful new tool in the diagnosis of an old disease. Images PMID:8027375

Definitive or conservative surgery for perforated gastric ulcer?--An unresolved problem.

PubMed

Sarath Chandra, Sistla; Kumar, S Siva

2009-04-01

Gastric ulcer perforation has not been the focus of many studies. In addition there is a need to analyze the results of gastric perforation separately and not along with duodenal perforations, to identify the factors influencing the outcome and to develop strategies for its management. Retrospective analysis of 54 patients presenting with gastric perforation. Mean age of the patients was 44.5 years with male preponderance. Morbidity following Closure of the perforation, acid reduction surgery and resection was not significantly different. Overall mortality was 16.6% with highest mortality 24.1% following simple closure. Mortality following simple closure and definitive surgery was not significantly different. Univariate analysis revealed preoperative shock, associated medical illness and surgical delay to be significant factors for mortality whereas on multivariate analysis, preoperative shock was the only independent predictor of mortality. Mortality increased with increasing Boey score but the association between the type of surgery and probability of survival was not statistically significant. Boey risk score is useful in predicting the outcome of surgical treatment for gastric perforation. Definitive surgery is not associated with greater morbidity or mortality compared to simple closure.

Skin disease prevalence study in schoolchildren in rural Côte d'Ivoire: Implications for integration of neglected skin diseases (skin NTDs).

PubMed

Yotsu, Rie Roselyne; Kouadio, Kouamé; Vagamon, Bamba; N'guessan, Konan; Akpa, Amari Jules; Yao, Aubin; Aké, Julien; Abbet Abbet, Rigobert; Tchamba Agbor Agbor, Barbine; Bedimo, Roger; Ishii, Norihisa; Fuller, L Claire; Hay, Roderick; Mitjà, Oriol; Drechsler, Henning; Asiedu, Kingsley

2018-05-01

Early detection of several skin-related neglected tropical diseases (skin NTDs)-including leprosy, Buruli ulcer, yaws, and scabies- may be achieved through school surveys, but such an approach has seldom been tested systematically on a large scale in endemic countries. Additionally, a better understanding of the spectrum of skin diseases and the at-risk populations to be encountered during such surveys is necessary to facilitate the process. We performed a school skin survey for selected NTDs and the spectrum of skin diseases, among primary schoolchildren aged 5 to 15 in Côte d'Ivoire, West Africa. This 2-phase survey took place in 49 schools from 16 villages in the Adzopé health district from November 2015 to January 2016. The first phase involved a rapid visual examination of the skin by local community healthcare workers (village nurses) to identify any skin abnormality. In a second phase, a specialized medical team including dermatologists performed a total skin examination of all screened students with any skin lesion and provided treatment where necessary. Of a total of 13,019 children, 3,504 screened positive for skin lesions and were listed for the next stage examination. The medical team examined 1,138 of these children. The overall prevalence of skin diseases was 25.6% (95% CI: 24.3-26.9%). The predominant diagnoses were fungal infections (n = 858, prevalence: 22.3%), followed by inflammatory skin diseases (n = 265, prevalence: 6.9%). Skin diseases were more common in boys and in children living along the main road with heavy traffic. One case of multi-bacillary type leprosy was detected early, along with 36 cases of scabies. Our survey was met with very good community acceptance. We carried out the first large-scale integrated, two-phase pediatric multi-skin NTD survey in rural Côte d'Ivoire, effectively reaching a large population. We found a high prevalence of skin diseases in children, but only limited number of skin NTDs. With the lessons learned, we plan to expand the project to a wider area to further explore its potential to better integrate skin NTD screening in the public health agenda.

Steps Toward Creating A Therapeutic Community for Inpatients Suffering from Chronic Ulcers: Lessons from Allada Buruli Ulcer Treatment Hospital in Benin

PubMed Central

Amoussouhoui, Arnaud Setondji; Johnson, Roch Christian; Sopoh, Ghislain Emmanuel; Agbo, Ines Elvire; Aoulou, Paulin; Houezo, Jean-Gabin; Tingbe-Azalou, Albert; Boyer, Micah; Nichter, Mark

2016-01-01

Background Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. Methods A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients’ understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question–answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. Results Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This knowledge gap surprised clinic staff members, who assumed someone had provided this information. Individual counseling and weekly education sessions corrected this information gap and reduced patient concerns about their treatment and the status of their healing process. This led to positive changes in staff–patient interactions. There was widespread consensus among both patients and staff that the quality of communication had increased significantly. Open forums providing an opportunity for patients and staff to air grievances were likewise popular and patient representative meetings resulted in productive problem solving supported by the hospital administration. Some systemic problems, however, remained persistent challenges. Patients with ulcers unrelated to BU questioned why BU patients were receiving preferential treatment, given special medicines, and charged less for their care. The idea of subsidized treatment for one disease and not another was hard to justify, especially given that BU is not contagious. Conclusion This pilot project illustrates the basic principles necessary for transforming long term residential hospitals into therapeutic communities. Although the focus of this case study was patients suffering from chronic ulcers, the model presented is relevant for other types of patients with cultural adaptation. PMID:27367809

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases

PubMed Central

Sokolow, S. H.; Ngonghala, C. N.; Jocque, M.; Lund, A.; Barry, M.; Mordecai, E. A.; Daily, G. C.; Andrews, J. R.; Bendavid, E.; Luby, S. P.; LaBeaud, A. D.; Seetah, K.; Guégan, J. F.; De Leo, G. A.

2017-01-01

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’. PMID:28438917

Prevalence of antibiotic resistance genes and bacterial pathogens in long-term manured greenhouse soils as revealed by metagenomic survey.

PubMed

Fang, Hua; Wang, Huifang; Cai, Lin; Yu, Yunlong

2015-01-20

Antibiotic resistance genes (ARGs), human pathogenic bacteria (HPB), and HPB carrying ARGs pose a high risk to soil ecology and public health. Here, we used a metagenomic approach to investigate their diversity and abundance in chicken manures and greenhouse soils collected from Guli, Pulangke, and Hushu vegetable bases with different greenhouse planting years in Nanjing, Eastern China. There was a positive correlation between the levels of antibiotics, ARGs, HPB, and HPB carrying ARGs in manures and greenhouse soils. In total, 156.2–5001.4 μg/kg of antibiotic residues, 22 classes of ARGs, 32 HPB species, and 46 species of HPB carrying ARGs were found. The highest relative abundance was tetracycline resistance genes (manures) and multidrug resistance genes (greenhouse soils). The dominant HPB and HPB carrying ARGs in the manures were Bacillus anthracis, Bordetella pertussis, and B. anthracis (sulfonamide resistance gene, sul1), respectively. The corresponding findings in greenhouse soils were Mycobacterium tuberculosis and M. ulcerans, M. tuberculosis (macrolide-lincosamide-streptogramin resistance protein, MLSRP), and B. anthracis (sul1), respectively. Our findings confirmed high levels of antibiotics, ARGs, HPB, and HPB carrying ARGs in the manured greenhouse soils compared with those in the field soils, and their relative abundance increased with the extension of greenhouse planting years.

A case of surgically treated peristomal pyoderma gangrenosum in a patient with rheumatoid arthritis

PubMed Central

Khajehnoori, Masoomeh; O'Brien, Tim

2016-01-01

Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is difficult to diagnose and treat. It is characterized by the rapid progression of painful necrotic ulcer surrounding an area of abdominal stoma. It is almost exclusively associated with inflammatory bowel disease even after bowel surgery and is associated with significant morbidity. Diagnosis of pyoderma gangrenosum is based on exclusion of other disorders replicating some of its clinical features and histopathological evidence. This is a case report of a 56-year-old lady with rheumatoid arthritis who presented with rapidly progressing abdominal ulcer 8 months after a Hartmanns procedure for perforated diverticulitis. The ulcer had formed a large cavity causing faecal filling in the dependent defect. The other causes of ulcer were excluded with negative histopathology, negative polymerase chain reaction for Mycobacterium ulcerans and negative acid fast bacillus (AFB) test. She was diagnosed with PPG which is routinely treated medically due to risk of setting off a second focus of pyoderma if surgically intervened. However due to increased risk of faecal peritonitis, it was decided to proceed with surgical debridement. This article will discuss the case in more detail and briefly discuss diagnosis and treatment options for PPG. PMID:27302499

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases.

PubMed

Garchitorena, A; Sokolow, S H; Roche, B; Ngonghala, C N; Jocque, M; Lund, A; Barry, M; Mordecai, E A; Daily, G C; Jones, J H; Andrews, J R; Bendavid, E; Luby, S P; LaBeaud, A D; Seetah, K; Guégan, J F; Bonds, M H; De Leo, G A

2017-06-05

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Author(s).

Social stigma towards neglected tropical diseases: a systematic review.

PubMed

Hofstraat, Karlijn; van Brakel, Wim H

2016-03-01

People affected by neglected tropical diseases (NTDs) are frequently the target of social stigmatization. To date not much attention has been given to stigma in relation to NTDs. The objective of this review is to identify the extent of social stigma and the similarities and differences in the causes, manifestations, impact of stigma and interventions used between the NTDs. A systematic review was conducted in Pubmed, ScienceDirect, PsycINFO and Web of Knowledge. The search encompassed 17 NTDs, including podoconiosis, but not leprosy as this NTD has recently been reviewed. However, leprosy was included in the discussion. The 52 selected articles provided evidence on stigma related to lymphatic filariasis (LF), podoconiosis, Buruli ulcer, onchocerciasis, schistosomiasis, leishmaniasis, Chagas disease, trachoma, soil-transmitted helminthiasis (STH) and human African trypanosomiasis. The similarities predominated in stigma related to the various NTDs; only minimal differences in stigma reasons and measures were found. These similarities suggest that joint approaches to reduce stigmatization may be feasible. Lessons from leprosy and other stigmatized health conditions can be used to plan such joint approaches. Further research will be necessary to study the efficacy of joint interventions and to investigate stigma related to NTDs for which no evidence is available yet. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Nomadic plastic surgery: 1 NGO, 10 years, 30 missions].

PubMed

Knipper, P; Antoine, P; Carré, C; Baudet, J

2015-06-01

This publication presents the results of 10 years of nomadic plastic surgery missions by a small French non-governmental organization: Interplast-France/surgery without borders (www.Interplast-France.net). This NGO is specialized in reconstructive surgery in challenging conditions and works in developing countries. We present a view of 10 years of missions carried out between 2003 and 2013. This experience covers a uniform period both by the objectives proposed and the regularity of missions observed. This work shows the way surgical missions take place and the methodology used. We carried out 30 missions. We made more than 4000 consultations and we operated 1500 patients. Interventions are divided into one quarter cleft, one quarter tumors, one quarter burn injuries and one quarter of various diseases such as noma and Buruli ulcer. We show some adaptations such as autonomy during missions, the adjustment guidance in relation to this new environment and the integration of local traditions in our therapeutic action. We offer practical notions on the surgical procedures and some reflections on the societal level. This work aims primarily to pay tribute to all the invisible actors in this long chain of humanity, and thanks to the simple intervention of men, a patient can have the same medical treatment whether he is in an industrial country or in some isolated place on this earth. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Evaluation of the Andromas Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry System for Identification of Aerobically Growing Gram-Positive Bacilli

PubMed Central

Farfour, E.; Leto, J.; Barritault, M.; Barberis, C.; Meyer, J.; Dauphin, B.; Le Guern, A.-S.; Leflèche, A.; Badell, E.; Guiso, N.; Leclercq, A.; Le Monnier, A.; Lecuit, M.; Rodriguez-Nava, V.; Bergeron, E.; Raymond, J.; Vimont, S.; Bille, E.; Carbonnelle, E.; Guet-Revillet, H.; Lécuyer, H.; Beretti, J.-L.; Vay, C.; Berche, P.; Ferroni, A.; Nassif, X.

2012-01-01

Matrix-associated laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a rapid and simple microbial identification method. Previous reports using the Biotyper system suggested that this technique requires a preliminary extraction step to identify Gram-positive rods (GPRs), a technical issue that may limit the routine use of this technique to identify pathogenic GPRs in the clinical setting. We tested the accuracy of the MALDI-TOF MS Andromas strategy to identify a set of 659 GPR isolates representing 16 bacterial genera and 72 species by the direct colony method. This bacterial collection included 40 C. diphtheriae, 13 C. pseudotuberculosis, 19 C. ulcerans, and 270 other Corynebacterium isolates, 32 L. monocytogenes and 24 other Listeria isolates, 46 Nocardia, 75 Actinomyces, 18 Actinobaculum, 11 Propionibacterium acnes, 18 Propionibacterium avidum, 30 Lactobacillus, 21 Bacillus, 2 Rhodococcus equi, 2 Erysipelothrix rhusiopathiae, and 38 other GPR isolates, all identified by reference techniques. Totals of 98.5% and 1.2% of non-Listeria GPR isolates were identified to the species or genus level, respectively. Except for L. grayi isolates that were identified to the species level, all other Listeria isolates were identified to the genus level because of highly similar spectra. These data demonstrate that rapid identification of pathogenic GPRs can be obtained without an extraction step by MALDI-TOF mass spectrometry. PMID:22692743

Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids.

PubMed

Schick, Judith; Etschel, Philipp; Bailo, Rebeca; Ott, Lisa; Bhatt, Apoorva; Lepenies, Bernd; Kirschning, Carsten; Burkovski, Andreas; Lang, Roland

2017-07-01

Nontoxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans cause invasive disease in humans and animals. Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the order Corynebacterineae (e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle. Here, we show that glycolipid extracts from the cell walls of several pathogenic and nonpathogenic Corynebacterium strains directly bound to recombinant Mincle in vitro Macrophages deficient in Mincle or its adapter protein Fc receptor gamma chain (FcRγ) produced severely reduced amounts of granulocyte colony-stimulating factor (G-CSF) and of nitric oxide (NO) upon challenge with corynebacterial glycolipids. Consistently, cell wall extracts of a particular C. diphtheriae strain (DSM43989) lacking mycolic acid esters neither bound Mincle nor activated macrophages. Furthermore, TLR2 but not TLR4 was critical for sensing of cell wall extracts and whole corynebacteria. The upregulation of Mincle expression upon encountering corynebacteria required TLR2. Thus, macrophage activation by the corynebacterial cell wall relies on TLR2-driven robust Mincle expression and the cooperative action of both receptors. Copyright © 2017 American Society for Microbiology.

Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids

PubMed Central

Schick, Judith; Etschel, Philipp; Bailo, Rebeca; Ott, Lisa; Bhatt, Apoorva; Lepenies, Bernd; Kirschning, Carsten

2017-01-01

ABSTRACT Nontoxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans cause invasive disease in humans and animals. Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the order Corynebacterineae (e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle. Here, we show that glycolipid extracts from the cell walls of several pathogenic and nonpathogenic Corynebacterium strains directly bound to recombinant Mincle in vitro. Macrophages deficient in Mincle or its adapter protein Fc receptor gamma chain (FcRγ) produced severely reduced amounts of granulocyte colony-stimulating factor (G-CSF) and of nitric oxide (NO) upon challenge with corynebacterial glycolipids. Consistently, cell wall extracts of a particular C. diphtheriae strain (DSM43989) lacking mycolic acid esters neither bound Mincle nor activated macrophages. Furthermore, TLR2 but not TLR4 was critical for sensing of cell wall extracts and whole corynebacteria. The upregulation of Mincle expression upon encountering corynebacteria required TLR2. Thus, macrophage activation by the corynebacterial cell wall relies on TLR2-driven robust Mincle expression and the cooperative action of both receptors. PMID:28483856

More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia

PubMed Central

Kantsone, Ieva; Lucenko, Irina; Perevoscikovs, Jurijs

2016-01-01

In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1–14.8), with the highest incidence in age groups 5–19 and 40–49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey. PMID:27934582

Mycobacterium pseudoshottsii sp. nov., a slowly growing chromogenic species isolated from Chesapeake Bay striped bass (Morone saxatilis)

USGS Publications Warehouse

Rhodes, M.W.; Kator, H.; McNabb, A.; Deshayes, C.; Reyrat, J.-M.; Brown-Elliott, B. A.; Wallace, R.; Trott, K.A.; Parker, J.M.; Lifland, B.; Osterhout, G.; Kaattari, I.; Reece, K.; Vogelbein, W.; Ottinger, C.A.

2005-01-01

A group of slowly growing photochromogenic mycobacteria was isolated from Chesapeake Bay striped bass (Morone saxatilis) during an epizootic of mycobacteriosis. Growth characteristics, acid-fastness and 16S rRNA gene sequencing results were consistent with those of the genus Mycobacterium. Biochemical reactions, growth characteristics and mycolic acid profiles (HPLC) resembled those of Mycobacterium shottsii, a non-pigmented mycobacterium also isolated during the same epizootic. Sequencing of the 16S rRNA genes, the gene encoding the exported repeated protein (erp) and the gene encoding the 65 kDa heat-shock protein (hsp65) and restriction enzyme analysis of the hsp65 gene demonstrated that this group of isolates is unique. Insertion sequences associated with Mycobacterium ulcerans, IS2404 and IS2606, were detected by PCR. These isolates could be differentiated from other slowly growing pigmented mycobacteria by their inability to grow at 37 ??C, production of niacin and urease, absence of nitrate reductase, negative Tween 80 hydrolysis and resistance to isoniazid (1 ??g ml-1), p-nitrobenzoic acid, thiacetazone and thiophene-2-carboxylic hydrazide. On the basis of this polyphasic study, it is proposed that these isolates represent a novel species, Mycobacterium pseudoshottsii sp. nov. The type strain, L15T, has been deposited in the American Type Culture Collection as ATCC BAA-883T and the National Collection of Type Cultures (UK) as NCTC 13318T. ?? 2005 IUMS.

The hmuQ and hmuD Genes from Bradyrhizobium japonicum Encode Heme-Degrading Enzymes

PubMed Central

Puri, Sumant; O'Brian, Mark R.

2006-01-01

Utilization of heme by bacteria as a nutritional iron source involves the transport of exogenous heme, followed by cleavage of the heme macrocycle to release iron. Bradyrhizobium japonicum can use heme as an iron source, but no heme-degrading oxygenase has been described. Here, bioinformatics analyses of the B. japonicum genome identified two paralogous genes renamed hmuQ (bll7075) and hmuD (bll7423) that encode proteins with weak similarity to the heme-degrading monooxygenase IsdG from Staphylococcus aureus. The hmuQ gene is clustered with known heme transport genes in the genome. Recombinant HmuQ bound heme with a Kd value of 0.8 μM and showed spectral properties consistent with a heme oxygenase. In the presence of a reductant, HmuQ catalyzed the degradation of heme and the formation of biliverdin. The hmuQ and hmuD genes complemented a Corynebacterium ulcerans heme oxygenase mutant in trans for utilization of heme as the sole iron source for growth. Furthermore, homologs of hmuQ and hmuD were identified in many bacterial genera, and the recombinant homolog from Brucella melitensis bound heme and catalyzed its degradation. The findings show that hmuQ and hmuD encode heme oxygenases and indicate that the IsdG family of heme-degrading monooxygenases is not restricted to gram-positive pathogenic bacteria. PMID:16952937

Bacteriophage-based vectors for site-specific insertion of DNA in the chromosome of Corynebacteria.

PubMed

Oram, Mark; Woolston, Joelle E; Jacobson, Andrew D; Holmes, Randall K; Oram, Diana M

2007-04-15

In Corynebacterium diphtheriae, diphtheria toxin is encoded by the tox gene of some temperate corynephages such as beta. beta-like corynephages are capable of inserting into the C. diphtheriae chromosome at two specific sites, attB1 and attB2. Transcription of the phage-encoded tox gene, and many chromosomally encoded genes, is regulated by the DtxR protein in response to Fe(2+) levels. Characterizing DtxR-dependent gene regulation is pivotal in understanding diphtheria pathogenesis and mechanisms of iron-dependent gene expression; although this has been hampered by a lack of molecular genetic tools in C. diphtheriae and related Coryneform species. To expand the systems for genetic manipulation of C. diphtheriae, we constructed plasmid vectors capable of integrating into the chromosome. These plasmids contain the beta-encoded attP site and the DIP0182 integrase gene of C. diphtheriae NCTC13129. When these vectors were delivered to the cytoplasm of non-lysogenic C. diphtheriae, they integrated into either the attB1 or attB2 sites with comparable frequency. Lysogens were also transformed with these vectors, by virtue of the second attB site. An integrated vector carrying an intact dtxR gene complemented the mutant phenotypes of a C. diphtheriae DeltadtxR strain. Additionally, strains of beta-susceptible C. ulcerans, and C. glutamicum, a species non-permissive for beta, were each transformed with these vectors. This work significantly extends the tools available for targeted transformation of both pathogenic and non-pathogenic Corynebacterium species.

More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia.

PubMed

Kantsone, Ieva; Lucenko, Irina; Perevoscikovs, Jurijs

2016-12-01

In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1-14.8), with the highest incidence in age groups 5-19 and 40-49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey. This article is copyright of The Authors, 2016.

Bacteriophage-based Vectors for Site-specific Insertion of DNA in the Chromosome of Corynebacteria

PubMed Central

Oram, Mark; Woolston, Joelle E.; Jacobson, Andrew D.; Holmes, Randall K.; Oram, Diana M.

2007-01-01

In Corynebacterium diphtheriae, diphtheria toxin is encoded by the tox gene of some temperate corynephages such as β. β-like corynephages are capable of inserting into the C. diphtheriae chromosome at two specific sites, attB1 and attB2. Transcription of the phage-encoded tox gene, and many chromosomally-encoded genes, is regulated by the DtxR protein in response to Fe2+ levels. Characterizing DtxR-dependent gene regulation is pivotal in understanding diphtheria pathogenesis and mechanisms of iron-dependent gene expression; although this has been hampered by a lack of molecular genetic tools in C. diphtheriae and related Coryneform species. To expand the systems for genetic manipulation of C. diphtheriae, we constructed plasmid vectors capable of integrating into the chromosome. These plasmids contain the β-encoded attP site and the DIP0182 integrase gene of C. diphtheriae NCTC13129. When these vectors were delivered to the cytoplasm of non-lysogenic C. diphtheriae, they integrated into either the attB1 or attB2 sites with comparable frequency. Lysogens were also transformed with these vectors, by virtue of the second attB site. An integrated vector carrying an intact dtxR gene complemented the mutant phenotypes of a C. diphtheriae ΔdtxR strain. Additionally, strains of β-susceptible C. ulcerans, and C. glutamicum, a species non-permissive for β, were each transformed with these vectors. This work significantly extends the tools available for targeted transformation of both pathogenic and non-pathogenic Corynebacterium species. PMID:17275217

Mycobacterial species as case-study of comparative genome analysis.

PubMed

Zakham, F; Belayachi, L; Ussery, D; Akrim, M; Benjouad, A; El Aouad, R; Ennaji, M M

2011-02-08

The genus Mycobacterium represents more than 120 species including important pathogens of human and cause major public health problems and illnesses. Further, with more than 100 genome sequences from this genus, comparative genome analysis can provide new insights for better understanding the evolutionary events of these species and improving drugs, vaccines, and diagnostics tools for controlling Mycobacterial diseases. In this present study we aim to outline a comparative genome analysis of fourteen Mycobacterial genomes: M. avium subsp. paratuberculosis K—10, M. bovis AF2122/97, M. bovis BCG str. Pasteur 1173P2, M. leprae Br4923, M. marinum M, M. sp. KMS, M. sp. MCS, M. tuberculosis CDC1551, M. tuberculosis F11, M. tuberculosis H37Ra, M. tuberculosis H37Rv, M. tuberculosis KZN 1435 , M. ulcerans Agy99,and M. vanbaalenii PYR—1, For this purpose a comparison has been done based on their length of genomes, GC content, number of genes in different data bases (Genbank, Refseq, and Prodigal). The BLAST matrix of these genomes has been figured to give a lot of information about the similarity between species in a simple scheme. As a result of multiple genome analysis, the pan and core genome have been defined for twelve Mycobacterial species. We have also introduced the genome atlas of the reference strain M. tuberculosis H37Rv which can give a good overview of this genome. And for examining the phylogenetic relationships among these bacteria, a phylogenic tree has been constructed from 16S rRNA gene for tuberculosis and non tuberculosis Mycobacteria to understand the evolutionary events of these species.

Hydrostatic Hyperbaric Chamber Ventilation System

NASA Technical Reports Server (NTRS)

Sarguisingh, Miriam J.

2012-01-01

The hydrostatic hyperbaric chamber (HHC) represents the merger of several technologies in development for NASA aerospace applications, harnessed to directly benefit global health. NASA has significant experience developing composite hyperbaric chambers for a variety of applications. NASA also has researched the application of water-filled vessels to increase tolerance of acceleration forces. The combination of these two applications has resulted in the hydrostatic chamber, which has been conceived as a safe, affordable means of making hyperbaric oxygen therapy (HBOT) available in the developing world for the treatment of a variety of medical conditions. Specifically, HBOT is highly-desired as a possibly curative treatment for Buruli Ulcer, an infectious condition that afflicts children in sub-Saharan Africa. HBOT is simply too expensive and too dangerous to implement in the developing world using standard equipment. The HHC technology changes the paradigm. The HHC differs from standard hyperbaric chambers in that the majority of its volume is filled with water which is pressurized by oxygen being supplied in the portion of the chamber containing the patient s head. This greatly reduces the amount of oxygen required to sustain a hyperbaric atmosphere, thereby making the system more safe and economical to operate. An effort was taken to develop an HHC system to apply HBOT to children that is simple and robust enough to support transport, assembly, maintenance and operation in developing countries. This paper details the concept for an HHC ventilation and pressurization system to provide controlled pressurization and adequate washout of carbon dioxide while the subject is enclosed in the confined space during the administration of the medical treatment. The concept took into consideration operational complexity, safety to the patient and operating personnel, and physiological considerations. The simple schematic, comprised of easily acquired commercial hardware, supports sustainability.

A biosensor assay for the detection of Mycobacterium avium subsp. paratuberculosis in fecal samples

PubMed Central

Kumanan, Vijayarani; Nugen, Sam R.; Baeumner, Antje J.

2009-01-01

A simple, membrane-strip-based lateral-flow (LF) biosensor assay and a high-throughput microtiter plate assay have been combined with a reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of a small number (ten) of viable Mycobacterium (M.) avium subsp. paratuberculosis (MAP) cells in fecal samples. The assays are based on the identification of the RNA of the IS900 element of MAP. For the assay, RNA was extracted from fecal samples spiked with a known quantity of (101 to 106) MAP cells and amplified using RT-PCR and identified by the LF biosensor and the microtiter plate assay. While the LF biosensor assay requires only 30 min of assay time, the overall process took 10 h for the detection of 10 viable cells. The assays are based on an oligonucleotide sandwich hybridization assay format and use either a membrane flow through system with an immobilized DNA probe that hybridizes with the target sequence or a microtiter plate well. Signal amplification is provided when the target sequence hybridizes to a second DNA probe that has been coupled to liposomes encapsulating the dye, sulforhodamine B. The dye in the liposomes provides a signal that can be read visually, quantified with a hand-held reflectometer, or with a fluorescence reader. Specificity analysis of the assays revealed no cross reactivity with other mycobacteria, such as M. avium complex, M. ulcerans, M. marium, M. kansasii, M. abscessus, M. asiaticum, M. phlei, M. fortuitum, M. scrofulaceum, M. intracellulare, M. smegmatis, and M. bovis. The overall assay for the detection of live MAP organisms is comparatively less expensive and quick, especially in comparison to standard MAP detection using a culture method requiring 6-8 weeks of incubation time, and is significantly less expensive than real-time PCR. PMID:19255522

Mycolactone displays anti-inflammatory effects on the nervous system

PubMed Central

Isaac, Caroline; Mauborgne, Annie; Grimaldi, Alfonso; Ade, Kemy; Pohl, Michel; Limatola, Cristina; Boucher, Yves; Demangel, Caroline

2017-01-01

Background Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investigated whether mycolactone similarly affects the inflammatory responses of the nervous cell subsets involved in pain perception, transmission and maintenance. We also investigated the effects of mycolactone on the neuroinflammation that is associated with chronic pain in vivo. Methodology/ Principle findings Sensory neurons, Schwann cells and microglia were isolated from mice for ex vivo assessment of mycolactone cytotoxicity and immunomodulatory activity by measuring the production of proalgesic cytokines and chemokines. In all cell types studied, prolonged (>48h) exposure to mycolactone induced significant cell death at concentrations >10 ng/ml. Within the first 24h treatment, nanomolar concentrations of mycolactone efficiently suppressed the cell production of pro-inflammatory mediators, without affecting their viability. Notably, mycolactone also prevented the pro-inflammatory polarization of cortical microglia. Since these cells critically contribute to neuroinflammation, we next tested if mycolactone impacts this pathogenic process in vivo. We used a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. Here, mycolactone was injected daily for 3 days in the spinal canal, to ensure its proper delivery to spinal cord. While this treatment failed to prevent injury-induced neuroinflammation, it decreased significantly the local production of inflammatory cytokines without inducing detectable cytotoxicity. Conclusion/ Significance The present study provides in vitro and in vivo evidence that mycolactone suppresses the inflammatory responses of sensory neurons, Schwann cells and microglia, without affecting the cell viability. Together with previous studies using peripheral blood leukocytes, our work implies that mycolactone-mediated analgesia may, at least partially, be explained by its anti-inflammatory properties. PMID:29149212

Hydrostatic Hyperbaric Chamber Ventilation System

NASA Technical Reports Server (NTRS)

Sargusingh, Miriam M.

2011-01-01

The hydrostatic hyperbaric chamber (HHC) represents the merger of several technologies in development for NASA aerospace applications, harnessed to directly benefit global health. NASA has significant experience developing composite hyperbaric chambers for a variety of applications, including the treatment of medical conditions. NASA also has researched the application of water-filled vessels to increase tolerance of acceleration forces. The combination of these two applications has resulted in the hydrostatic chamber, which has been conceived as a safe, affordable means of making hyperbaric oxygen therapy available in the developing world for the treatment of a variety of medical conditions. Specifically, hyperbaric oxygen therapy is highly-desired as a possibly curative treatment for Buruli Ulcer, an infectious condition that afflicts children in sub-Saharan Africa. Hyperbaric oxygen therapy is simply too expensive and too dangerous to implement in the developing world using standard equipment. The hydrostatic hyperbaric chamber technology changes the paradigm. The HHC differs from standard hyperbaric chambers in that the majority of its volume is filled with water which is pressurized by oxygen being supplied in the portion of the chamber containing the patient s head. This greatly reduces the amount of oxygen required to sustain a hyperbaric atmosphere, thereby making the system more safe and economical to operate. An effort was taken to develop an HHC system to apply HBOT to children that is simple and robust enough to support transport, assembly, maintenance and operation in developing countries. This paper details the concept for an HHC ventilation and pressurization system that will provide controlled pressurization of the system, and provide adequate washout of carbon dioxide while the subject is enclosed in the confined space during the administration of the medical treatment. The concept took into consideration operational complexity, safety to the patient and operating personnel, and physiological considerations. The simple schematic, comprised of easily acquired commercial hardware, supports sustainability.

Patent landscape of neglected tropical diseases: an analysis of worldwide patent families.

PubMed

Akinsolu, Folahanmi Tomiwa; de Paiva, Vitor Nobre; Souza, Samuel Santos; Varga, Orsolya

2017-11-14

"Neglected Tropical Diseases" (NTDs) affect millions of people in Africa, Asia and South America. The two primary ways of strategic interventions are "preventive chemotherapy and transmission control" (PCT), and "innovative and intensified disease management" (IDM). In the last 5 years, phenomenal progress has been achieved. However, it is crucial to intensify research effort into NTDs, because of the emerging drug resistance. According to the World Health Organization (WHO), the term NTDs covers 17 diseases, namely buruli ulcer, Chagas disease, dengue, dracunculiasis, echinococcosis, trematodiasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthes, taeniasis, trachoma, and yaws. The aim of this study is to map out research and development (R&D) landscape through patent analysis of these identified NTDs. To achieve this, analysis and evaluation have been conducted on patenting trends, current legal status of patent families, priority countries by earliest priority years and their assignee types, technological fields of patent families over time, and original and current patent assignees. Patent families were extracted from Patseer, an international database of patents from over 100 patent issuing authorities worldwide. Evaluation of the patents was carried out using the combination of different search terms related to each identified NTD. In this paper, a total number of 12,350 patent families were analyzed. The main countries with sources of inventions were identified to be the United States (US) and China. The main technological fields covered by NTDs patent landscape are pharmaceuticals, biotechnology, organic fine chemistry, analysis of biological materials, basic materials chemistry, and medical technology. Governmental institutions and universities are the primary original assignees. Among the NTDs, leishmaniasis, dengue, and rabies received the highest number of patent families, while human African trypanosomiasis (sleeping sickness), taeniasis, and dracunciliasis received the least. The overall trend of patent families shows an increase between 1985 and 2008, and followed by at least 6 years of stagnation. The filing pattern of patent families analyzed undoubtedly reveals slow progress on research and development of NTDs. Involving new players, such as non-governmental organizations may help to mitigate and reduce the burden of NTDs.

Central line infections - hospitals

MedlinePlus

... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

Infective Endocarditis

MedlinePlus

... Center > Infective Endocarditis Menu Topics Topics FAQs Infective Endocarditis En español Infective endocarditis is an infection of ... time, congestive heart failure (CHF). What causes infective endocarditis? The infection that leads to endocarditis can be ...

Pseudomonas aeruginosa infections of intact skin.

PubMed

Agger, W A; Mardan, A

1995-02-01

Pseudomonas aeruginosa infections of healthy skin are uncommon. We report four cases of P. aeruginosa infections of intact skin. These cases illustrate the clinical spectrum of these cutaneous infections: localized, mild epidermal infections (the green nail syndrome and webbed space infections), moderately serious infections (cutaneous folliculitis and otitis externa), and, in immunocompromised patients, extremely serious infections (malignant otitis externa, perirectal infection, and ecthyma gangrenosum).

[The risk of infection to the mother prior, during and after delivery. A registration of nosocomial infections].

PubMed

Hirsch, H A; Niehues, U

1982-09-01

During 5 1/2 years all infections arising in the hospital (nosocomial infections) were registered prospectively by an infection control nurse. The incidence of all nosocomial infections in 3192 maternity patients was 2.1%. In 10,569 women following vaginal deliveries 2.6% and in 1,353 women following Caesarean section 21.1%. The commonest infections were urinary tract infections, endometritis, infections of the abdominal wound or the episiotomy, and a phlebitis of the intravenous infusion site. Measures to prevent infection resulted in a steadily decreasing incidence of infections during the 6 years of registration of nosocomial infections.

Fosfomycin i.v. for Treatment of Severely Infected Patients

ClinicalTrials.gov

2018-05-08

Bacterial Infections; Bone Diseases, Infectious; Osteomyelitis; Central Nervous System Bacterial Infections; Meningitis, Bacterial; Encephalitis; Brain Abscess; Urinary Tract Infections; Respiratory Tract Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Intraabdominal Infections; Sepsis; Bacteremia; Endocarditis, Bacterial

Immune responses induced by co-infection with Capillaria hepatica in Clonorchis sinensis-infected rats.

PubMed

Moon, E-K; Lee, S-H; Goo, T W; Quan, F-S

2018-07-01

Clonorchis sinensis and Capillaria hepatica are zoonotic parasites that mainly infect the liver and cause serious liver disorders. However, immunological parameters induced by co-infection with these parasites remain unknown. In this study, for the first time, we investigated immunological profiles induced by co-infection with C. hepatica (CH) in C. sinensis (CS)-infected rats (Sprague-Dawley). Rats were infected primarily with 50 metacercariae of C. sinensis; 4 weeks later, they were subsequently infected with 1000 infective C. hepatica eggs. Significantly higher levels of C. sinensis- or C. hepatica-specific IgG antibodies were found in the sera of rats. Interestingly, no cross-reacting antibody was observed between C. sinensis and C. hepatica infections. Significantly raised eosinophil levels were found in the blood of C. sinensis/C. hepatica co-infected rats (CS + CH) compared to the blood of rats infected singly with C. sinensis. Co-infected rats showed significantly higher levels of lymphocyte proliferation and cytokine production compared to a single C. sinensis infection. The worm burden of C. sinensis was significantly reduced in co-infected rats compared to the single C. sinensis infection. These results indicate that the eosinophils, lymphocyte proliferation and cytokine production induced by subsequent infection with C. hepatica in C. sinensis-infected rats might contribute to the observed C. sinensis worm reduction.

Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model

PubMed Central

Slade, Jessica; Hall, Jennifer V.; Kintner, Jennifer; Schoborg, Robert V.

2016-01-01

Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans. PMID:26726882

Symptomatic Versus Inapparent Outcome in Repeat Dengue Virus Infections Is Influenced by the Time Interval between Infections and Study Year

PubMed Central

Mercado, Juan Carlos; Williams, Katherine L.; Vargas, Maria José; Gutierrez, Gamaliel; Kuan, Guillermina; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

2013-01-01

Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Dengue Fever to severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants of inapparent versus symptomatic DENV infection outcome. Here, we analyzed over 2,000 DENV infections from 2004 to 2011 in a prospective pediatric cohort study in Managua, Nicaragua. Symptomatic cases were captured at the study health center, and paired healthy annual samples were examined on a yearly basis using serological methods to identify inapparent DENV infections. Overall, inapparent and symptomatic DENV infections were equally distributed by sex. The mean age of infection was 1.2 years higher for symptomatic DENV infections as compared to inapparent infections. Although inapparent versus symptomatic outcome did not differ by infection number (first, second or third/post-second DENV infections), substantial variation in the proportion of symptomatic DENV infections among all DENV infections was observed across study years. In participants with repeat DENV infections, the time interval between a first inapparent DENV infection and a second inapparent infection was significantly shorter than the interval between a first inapparent and a second symptomatic infection. This difference was not observed in subsequent infections. This result was confirmed using two different serological techniques that measure total anti-DENV antibodies and serotype-specific neutralizing antibodies, respectively. Taken together, these findings show that, in this study, age, study year and time interval between consecutive DENV infections influence inapparent versus symptomatic infection outcome, while sex and infection number had no significant effect. Moreover, these results suggest that the window of cross-protection induced by a first infection with DENV against a second symptomatic infection is approximately 2 years. These findings are important for modeling dengue epidemics and development of vaccines. PMID:23951377

Symptomatic versus inapparent outcome in repeat dengue virus infections is influenced by the time interval between infections and study year.

PubMed

Montoya, Magelda; Gresh, Lionel; Mercado, Juan Carlos; Williams, Katherine L; Vargas, Maria José; Gutierrez, Gamaliel; Kuan, Guillermina; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

2013-01-01

Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Dengue Fever to severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants of inapparent versus symptomatic DENV infection outcome. Here, we analyzed over 2,000 DENV infections from 2004 to 2011 in a prospective pediatric cohort study in Managua, Nicaragua. Symptomatic cases were captured at the study health center, and paired healthy annual samples were examined on a yearly basis using serological methods to identify inapparent DENV infections. Overall, inapparent and symptomatic DENV infections were equally distributed by sex. The mean age of infection was 1.2 years higher for symptomatic DENV infections as compared to inapparent infections. Although inapparent versus symptomatic outcome did not differ by infection number (first, second or third/post-second DENV infections), substantial variation in the proportion of symptomatic DENV infections among all DENV infections was observed across study years. In participants with repeat DENV infections, the time interval between a first inapparent DENV infection and a second inapparent infection was significantly shorter than the interval between a first inapparent and a second symptomatic infection. This difference was not observed in subsequent infections. This result was confirmed using two different serological techniques that measure total anti-DENV antibodies and serotype-specific neutralizing antibodies, respectively. Taken together, these findings show that, in this study, age, study year and time interval between consecutive DENV infections influence inapparent versus symptomatic infection outcome, while sex and infection number had no significant effect. Moreover, these results suggest that the window of cross-protection induced by a first infection with DENV against a second symptomatic infection is approximately 2 years. These findings are important for modeling dengue epidemics and development of vaccines.

Infective endocarditis in drug addicts: role of HIV infection and the diagnostic accuracy of Duke criteria.

PubMed

Cecchi, Enrico; Imazio, Massimo; Tidu, Massimo; Forno, Davide; De Rosa, Francesco Giuseppe; Dal Conte, Ivano; Preziosi, Costantina; Lipani, Filippo; Trinchero, Rita

2007-03-01

Intravenous drug users (IVDUs) are at increased risk of infective endocarditis. Moreover, HIV infection is common in IVDUs, with a reported prevalence of 40-90%. The clinical features of IVDUs with infective endocarditis and HIV infection may be peculiar. Few data have been reported on the diagnostic accuracy of Duke criteria in IVDUs with or without HIV infection, and a comparison of these two populations is lacking. The present study aimed to compare prospectively the clinical features of patients with infective endocarditis with or without HIV infection and to evaluate the diagnostic accuracy of Duke criteria in these patients. The study population consisted of 201 consecutive adult IVDUs with a suspected infective endocarditis (102 patients with HIV infection and 99 patients without HIV infection). Infective endocarditis was the final diagnosis in 40 of 102 patients (38.2%) with HIV infection and in 55 of 99 HIV-negative patients (55.6%). Despite similar baseline features, longer vegetations were recorded in infective endocarditis without HIV infection (23.7 +/- 7.1 mm versus 13.6 +/- 6.8 mm; P = 0.001). Patients with infective endocarditis and HIV infection had a higher total mortality at 2 months (respectively 12.5% versus 1.8%; P = 0.09); almost all the deaths were recorded in patients with AIDS or a CD4 cell count below 200 per microl, and no deaths were recorded in patients with HIV infection and a CD4 cell count > 500 per microl. Despite no identical clinical features, Duke criteria had a similar sensitivity, specificity and diagnostic accuracy in IVDUs with and without HIV infection.

Protective cellular responses to Burkholderia mallei infection.

PubMed

Rowland, Caroline A; Lever, M Stephen; Griffin, Kate F; Bancroft, Gregory J; Lukaszewski, Roman A

2010-10-01

Burkholderia mallei is a Gram-negative bacillus causing the disease glanders in humans. During intraperitoneal infection, BALB/c mice develop a chronic disease characterised by abscess formation where mice normally die up to 70 days post-infection. Although cytokine responses have been investigated, cellular immune responses to B. mallei infection have not previously been characterised. Therefore, the influx and activation status of splenic neutrophils, macrophages and T cells was examined during infection. Gr-1+ neutrophils and F4/80+ macrophages infiltrated the spleen 5 h post-infection and an increase in activated macrophages, neutrophils and T cells occurred by 24 h post-infection. Mice depleted of Gr-1+ cells were acutely susceptible to B. mallei infection, succumbing to the infection 5 days post-infection. Mice depleted of both CD4 and CD8 T cells did not succumb to the infection until 14 days post-infection. Infected μMT (B cell) and CD28 knockout mice did not differ from wildtype mice whereas iNOS-2 knockout mice began to succumb to the infection 30 days post-infection. The data presented suggests that Gr-1+ cells, activated early in B. mallei infection, are essential for controlling the early, innate response to B. mallei infection and T cells or nitric oxide are important during the later stages of infection. Crown Copyright © 2010. Published by Elsevier SAS. All rights reserved.

The influence of dual infection with herpes and influenza viruses on the differential blood cell count of mice.

PubMed

Ančicová, L; Dugovičová, V; Briestenská, K; Kostolanský, F; Varečková, E; Mistríková, J

Based on our previous results, which confirmed the role of latent gammaherpesvirus infection in alteration of immune homeostasis, we studied the influence of simultaneous infection with gammaherpes and influenza viruses on selected parameters of innate immunity, particularly on the subpopulations of peripheral blood cell leukocytes. The aim was to analyze changes of differential blood cell count of BALB/c mice persistently infected with murine gammaherpesvirus 68 (MHV-68) and subsequently co-infected with influenza A virus (IAV), in comparison to mice infected with MHV-68 or with IAV only. Our results showed that ongoing gammaherpesvirus latency in mice caused a decreased number of leukocytes after acute infection with IAV in comparison to a single acute IAV infection. However, increased proportion of neutrophils was measured in peripheral blood of IAV- infected and co-infected mice. Dual infection had no effect on the proportion of monocytes or basophilic and eosinophilic granulocytes. The number of atypical lymphocytes, usually accompanying the persistent infection with MHV-68, decreased in co-infected mice as a consequence of the acute infection with IAV. Persistent infection with gammaherpesvirus may thus modulate the host immune response to influenza A virus and the acute IAV infection can influence the immune homeostasis established by latent MHV-68 infection.

Hematologic abnormalities associated with Simian Immunodeficieny Virus (SIV) Infection mimic those in HIV infection

PubMed Central

Gill, Amy F.; Ahsan, Muhammad H.; Lackner, Andrew A.; Veazey, Ronald S.

2012-01-01

Studies of hematologic abnormalities in HIV infected patients are confounded by a multitude of factors. A retrospective data analysis of SIV infected Rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. Hematologic data from rhesus macaques inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared to non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggest that, like in HIV infection, hematologic abnormalities are major complications of SIV infection. PMID:22620272

Hematologic abnormalities associated with simian immunodeficieny virus (SIV) infection mimic those in HIV infection.

PubMed

Gill, Amy F; Ahsan, Muhammad H; Lackner, Andrew A; Veazey, Ronald S

2012-06-01

Studies of hematologic abnormalities in HIV-infected patients are confounded by a multitude of factors. A retrospective data analysis of simian immunodeficieny virus (SIV)-infected rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. Hematologic data from RM inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared with non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggests that, like in HIV infection, hematologic abnormalities are major complications of SIV infection. © 2012 John Wiley & Sons A/S.

Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

ClinicalTrials.gov

2018-04-02

Adenovirus; Anesthesia; Anxiety; Anxiolysis; Autism; Autistic Disorder; Bacterial Meningitis; Bacterial Septicemia; Benzodiazepine; Bipolar Disorder; Bone and Joint Infections; Central Nervous System Infections; Convulsions; Cytomegalovirus Retinitis; Early-onset Schizophrenia Spectrum Disorders; Epilepsy; General Anesthesia; Gynecologic Infections; Herpes Simplex Virus; Infantile Hemangioma; Infection; Inflammation; Inflammatory Conditions; Intra-abdominal Infections; Lower Respiratory Tract Infections; Migraines; Pain; Pneumonia; Schizophrenia; Sedation; Seizures; Skeletal Muscle Spasms; Skin and Skin-structure Infections; Thromboprophylaxis; Thrombosis; Treatment-resistant Schizophrenia; Urinary Tract Infections; Withdrawal; Sepsis; Gram-negative Infection; Bradycardia; Cardiac Arrest; Cardiac Arrhythmia; Staphylococcal Infections; Nosocomial Pneumonia; Neuromuscular Blockade; Methicillin Resistant Staphylococcus Aureus; Endocarditis; Neutropenia; Headache

Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

PubMed

Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

2016-04-18

HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison to HIV mono-infection while remaining similar to HCV mono-infection. Thus, HIV-HCV co-infection is able to modulate the phenotype of CD56(bright) NK cell subset in a unique way such that NKp46 and CXCR3 expressions are distinct for co-infection while both mono-infections have an additive effect on CD56(bright), CD69 with CD95 expressions. HCV mono-infection has a dominant effect on NKp30 expression while NKG2D and CD127 expressions remained same in all the groups.

Anal Human Papillomavirus Infection among HIV-Infected Men in Korea

PubMed Central

Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun ju; Lee, Su jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

2016-01-01

Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. Results A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001). High-risk HPV (HR-HPV) prevalence was higher among MSM (47.4%) than MSW (25.0%; P = 0.002). The HR-HPV types identified most frequently were HPV 16 (11%), HPV 18 (9.9%), and HPV 58 (5%) in MSM, and HPV 58(11%) and HPV 16 (8.9%) in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001). Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001). In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Conclusion Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age. PMID:27548632

Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

PubMed

Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun Ju; Lee, Su Jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

2016-01-01

Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001). High-risk HPV (HR-HPV) prevalence was higher among MSM (47.4%) than MSW (25.0%; P = 0.002). The HR-HPV types identified most frequently were HPV 16 (11%), HPV 18 (9.9%), and HPV 58 (5%) in MSM, and HPV 58(11%) and HPV 16 (8.9%) in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001). Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001). In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

Sequential dengue virus infections detected in active and passive surveillance programs in Thailand, 1994-2010.

PubMed

Bhoomiboonchoo, Piraya; Nisalak, Ananda; Chansatiporn, Natkamol; Yoon, In-Kyu; Kalayanarooj, Siripen; Thipayamongkolgul, Mathuros; Endy, Timothy; Rothman, Alan L; Green, Sharone; Srikiatkhachorn, Anon; Buddhari, Darunee; Mammen, Mammen P; Gibbons, Robert V

2015-03-14

The effect of prior dengue virus (DENV) exposure on subsequent heterologous infection can be beneficial or detrimental depending on many factors including timing of infection. We sought to evaluate this effect by examining a large database of DENV infections captured by both active and passive surveillance encompassing a wide clinical spectrum of disease. We evaluated datasets from 17 years of hospital-based passive surveillance and nine years of cohort studies, including clinical and subclinical DENV infections, to assess the outcomes of sequential heterologous infections. Chi square or Fisher's exact test was used to compare proportions of infection outcomes such as disease severity; ANOVA was used for continuous variables. Multivariate logistic regression was used to assess risk factors for infection outcomes. Of 38,740 DENV infections, two or more infections were detected in 502 individuals; 14 had three infections. The mean ages at the time of the first and second detected infections were 7.6 ± 3.0 and 11.2 ± 3.0 years. The shortest time between sequential infections was 66 days. A longer time interval between sequential infections was associated with dengue hemorrhagic fever (DHF) in the second detected infection (OR 1.3, 95% CI 1.2-1.4). All possible sequential serotype pairs were observed among 201 subjects with DHF at the second detected infection, except DENV-4 followed by DENV-3. Among DENV infections detected in cohort subjects by active study surveillance and subsequent non-study hospital-based passive surveillance, hospitalization at the first detected infection increased the likelihood of hospitalization at the second detected infection. Increasing time between sequential DENV infections was associated with greater severity of the second detected infection, supporting the role of heterotypic immunity in both protection and enhancement. Hospitalization was positively associated between the first and second detected infections, suggesting a possible predisposition in some individuals to more severe dengue disease.

Assessment of selected biochemical parameters and humoral immune response of Nile crocodiles (Crocodylus niloticus) experimentally infected with Trichinella zimbabwensis.

PubMed

La Grange, Louis J; Mukaratirwa, Samson

2014-08-21

Fifteen crocodiles were randomly divided into three groups of five animals. They represented high-infection, medium-infection and low-infection groups of 642 larvae/kg, 414 larvae/kg and 134 larvae/kg bodyweight, respectively. The parameters assessed were blood glucose, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT). The humoral immune response to Trichinella zimbabwensis infection was evaluated in all three groups by an indirect ELISA method. The results showed deviations from normal parameters of blood glucose, CPK, LDH, AST and ALT when compared with reported levels in uninfected reptiles. Contrary to studies involving mammals, hypoglycaemia was not observed in the infected groups in this study. Peak values of blood glucose were reached on post-infection (PI) Day 49, Day 42 and Day 35 in the high-infection, medium-infection and low-infection groups, respectively. Peak values of LDH and AST were observed on PI Day 56, Day 49 and Day 42 in the high-infection, medium-infection and low-infection groups, respectively. Peak values of CPK were observed on Day 35 PI in all three groups. Peak ALT values were reached on Day 56 in the high-infection group and on Day 28 PI in both the medium-infection and low-infection groups. No correlations between the biochemical parameters and infection intensity were observed. Peak antibody titres were reached on Day 49 PI in the medium-infection group, and on Day 42 PI in both the high-infection and low-infection groups. Infection intensity could not be correlated with the magnitude of the humoral immune response or time to sero-conversion. Results from this study were in agreement with results reported in mammals infected with other Trichinella species and showed that antibody titres could not be detected indefinitely.

Characteristics of infection and its impact on short-term outcome in patients with acute-on-chronic liver failure.

PubMed

Cai, Junjun; Zhang, Mengchen; Han, Tao; Jiang, Hui-Qing

2017-09-01

Bacterial infections are an important cause of mortality in liver failure. However, the type of infection, predictors of infection, and their impact on outcomes in patients with acute-on-chronic liver failure (ACLF) are limited.A total of 389 patients with ACLF were admitted in this retrospective, corhort study. Once admitted, clinical data including first infection site, type (community-acquired, healthcare-associated, or nosocomial), and second infection occurrence during hospitalization were collected. The outcome was mortality within 90 days. Multivariable logistic regression models were preformed to predict second infection development and 90-day mortality. Survival probability curves were calculated by the Kaplan-Meier method.Among 389 patients, 316 (81.2%) patients had infection. The 90-day mortality of patients with and without infection was 52.2% and 16.4%, respectively (P <.001). The most common first infection was healthcare associated (51.3%), followed by nosocomial (30.1%) and community-acquired infections (18.7%). Respiratory tract infection, spontaneous bacterial peritonitis, and urinary tract infection were most prevalent. Gram-positive organism was more frequently seen than gram-negative organisms. Of note, fungi accounted for 15.9% of the total infection cases. During hospitalization, 26.6% patients developed second infections. The 90-day mortality of patients developed or did not develop a second infection were 67.9% and 46.6%, respectively (P <.001). Independent predictors of 90-day mortality in infected patients with ACLF were age, white blood cell (WBC) count, model for end-stage liver disease (MELD) score, hepatic encephalopathy (HE), and second infection.Infections (regardless of first or second infection) can increase the 90-day mortality significantly in patients with ACLF. And age, WBC count, MELD score, HE, and the presence of second infection are independent risk factors affecting 90-day mortality in patients with ACLF showing infection.

Why are there so few Rickettsia conorii conorii-infected Rhipicephalus sanguineus ticks in the wild?

PubMed

Socolovschi, Cristina; Gaudart, Jean; Bitam, Idir; Huynh, Thi Phong; Raoult, Didier; Parola, Philippe

2012-01-01

Rickettsia conorii conorii is the etiological agent of Mediterranean spotted fever, which is transmitted by the brown dog tick, Rhipicephalus sanguineus. The relationship between the Rickettsia and its tick vector are still poorly understood one century after the first description of this disease. An entomological survey was organized in Algeria to collect ticks from the houses of patients with spotted fever signs. Colonies of R. conorii conorii-infected and non-infected ticks were established under laboratory conditions. Gimenez staining and electron microscopy on the ovaries of infected ticks indicated heavy rickettsial infection. The transovarial transmission of R. conorii conorii in naturally infected Rh. sanguineus ticks was 100% at eleven generations, and the filial infection rate was up to 99% according to molecular analyses. No differences in life cycle duration were observed between infected and non-infected ticks held at 25°C, but the average weight of engorged females and eggs was significantly lower in infected ticks than in non-infected ticks. The eggs, larvae and unfed nymphs of infected and non-infected ticks could not tolerate low (4°C) or high (37°C) temperatures or long starvation periods. R. conorii conorii-infected engorged nymphs that were exposed to a low or high temperature for one month experienced higher mortality when they were transferred to 25°C than non-infected ticks after similar exposure. High mortality was observed in infected adults that were maintained for one month at a low or high temperature after tick-feeding on rabbits. These preliminary results suggest that infected quiescent ticks may not survive the winter and may help explain the low prevalence of infected Rh. sanguineus in nature. Further investigations on the influence of extrinsic factors on diapaused R. conorii-infected and non-infected ticks are required.

Classification of infections in intensive care units: a comparison of current definition of hospital-acquired infections and carrier state criterion.

PubMed

Zurek, Jiří; Fedora, Michal

2012-06-01

The rate of nosocomial infection appears to depend on whether it is calculated using the Center for Disease Control (CDC) or carrier state criteria. The objective of this study was to differentiate between primary endogenous (PE), secondary endogenous (SE) and exogenous (EX) infections, and to compare this classification with CDC criteria for nosocomial infections. Children hospitalized for more than 72 h at pediatric intensive care unit during 2004-2005 were enrolled. Children, who had the infection before the admission, and or did not develop an infection within the hospitalization were excluded. Surveillance samples were sampled on admission, and then twice a week. Diagnostic samples were obtained when infection was suspected based on the clinical condition and laboratory findings. Infections were evaluated as PE, SE and EX, and their incidences were compared with CDC criteria for nosocomial infections. One hundred seventy eight patients were enrolled in the study. Forty-four patients (24.7%) develop infection. Twenty-seven patients (61.3%) had PE, 10 patients (22.7%) had SE, and 7 patients (15.9%) had EX infection. Secondary endogenous and EX infections are considered as nosocomial, thus 17 patients (38.6%) had a nosocomial infection. Thirty-one patients (70.5%) met CDC criteria for nosocomial infections. Seventeen patients (55%) were classified as PE, and 14 patients (45%) as SE or EX infections. Seventy percent of infections (31 out of 44 patients) met the CDC criteria for nosocomial infections, but only 39% of infections (17 out of 44 patients) were classified as nosocomial based on carrier state classification.

Does a feline leukemia virus infection pave the way for Bartonella henselae infection in cats?

PubMed

Buchmann, Alexandra U; Kershaw, Olivia; Kempf, Volkhard A J; Gruber, Achim D

2010-09-01

Domestic cats serve as the reservoir hosts of Bartonella henselae and may develop mild clinical symptoms or none after experimental infection. In humans, B. henselae infection can result in self-limiting cat scratch disease. However, immunocompromised patients may suffer from more-severe courses of infection or may even develop the potentially lethal disease bacillary angiomatosis. It was reasoned that cats with immunocompromising viral infections may react similarly to B. henselae infection. The aim of our study was to investigate the influence of the most important viruses known to cause immunosuppression in cats-Feline leukemia virus (FeLV), Feline immunodeficiency virus (FIV), and Feline panleukopenia virus (FPV)-on natural B. henselae infection in cats. Accordingly, 142 cats from animal shelters were necropsied and tested for B. henselae and concurrent infections with FeLV, FIV, or FPV by PCR and immunohistochemistry. A significant association was found between B. henselae and FeLV infections (P = 0.00028), but not between B. henselae and FIV (P = 1.0) or FPV (P = 0.756) infection, age (P = 0.392), or gender (P = 0.126). The results suggest that susceptibility to B. henselae infection is higher in cats with concurrent FeLV infections, regardless of whether the infection is latent or progressive. Histopathology and immunohistochemistry for B. henselae failed to identify lesions that could be attributed specifically to B. henselae infection. We conclude that the course of natural B. henselae infection in cats does not seem to be influenced by immunosuppressive viral infections in general but that latent FeLV infection may predispose cats to B. henselae infection or persistence.

MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

PubMed

Westerdahl, Helena; Stjernman, Martin; Råberg, Lars; Lannefors, Mimi; Nilsson, Jan-Åke

2013-01-01

Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load) and infection status (infected or not). It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

MHC-I Affects Infection Intensity but Not Infection Status with a Frequent Avian Malaria Parasite in Blue Tits

PubMed Central

Westerdahl, Helena; Stjernman, Martin; Råberg, Lars; Lannefors, Mimi; Nilsson, Jan-Åke

2013-01-01

Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load) and infection status (infected or not). It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts. PMID:24023631

Primary versus non-primary maternal cytomegalovirus infection as a cause of symptomatic congenital infection - register-based study from Finland.

PubMed

Puhakka, Laura; Renko, Marjo; Helminen, Merja; Peltola, Ville; Heiskanen-Kosma, Tarja; Lappalainen, Maija; Surcel, Heljä-Marja; Lönnqvist, Tuula; Saxen, Harri

2017-06-01

Both primary and non-primary maternal cytomegalovirus (CMV) infection during pregnancy can lead to vertical transmission. We evaluated the proportion of maternal primary/non-primary infections among 26 babies with symptomatic congenital CMV infection born in Finland from 2000 to 2012. We executed a database search on hospital records from all five university hospitals in Finland to identify infants with congenital CMV infection. The preserved maternal serum samples drawn at the end of the first trimester were analysed for CMV antibodies. Maternal infection was classified to be non-primary, if there was high avidity CMV immunoglobulin G (IgG) in the early pregnancy samples. Infection was considered primary in the case of either low avidity IgG (primary infection in the first trimester or near conception) or absent CMV IgG at the end of the first trimester (primary infection in the second or third trimester). The majority of the symptomatic congenital CMV infections (54%) were due to maternal non-primary infection, 27% due to maternal primary infection in the first trimester or near conception, and 19% during the second or third trimester. Long-term sequelae occurred in 59% of patients: in 6/7 after primary infection in the first trimester, in 0/5 after primary infection in the second or third trimester, and in 9/14 after non-primary infection. In this register-based cohort, non-primary infections caused the majority of symptomatic congenital CMV infections, and resulted in significant morbidity.

Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi.

PubMed

Buchwald, Andrea G; Sixpence, Alick; Chimenya, Mabvuto; Damson, Milius; Sorkin, John D; Wilson, Mark L; Seydel, Karl; Hochman, Sarah; Mathanga, Don P; Taylor, Terrie E; Laufer, Miriam K

2018-05-16

Asymptomatic Plasmodium falciparum infections are common in Malawi, however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for two years. During follow-up visits, participants with malaria symptoms were tested and treated if positive. Samples from all visits were tested for parasites using both microscopy and PCR, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (HR 0.50, p < 0.001). When asymptomatic infections preceded malaria illness, newly acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly acquired infections (OR 1.4, 95%CI 1.3-1.5) than to persistent infections. Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness but do not protect against disease when new infection occurs.

Evolution of HBV S-gene in the backdrop of HDV co-infection.

PubMed

Baig, Samina; Abidi, Syed H; Azam, Zahid; Majid, Shahid; Khan, Saeed; Khanani, Muhammad R; Ali, Syed

2018-04-16

HBV-HDV co-infected people have a higher chance of developing cirrhosis, fulminant hepatitis, and hepatocellular carcinoma (HCC) compared to those infected only with HBV. The present study was conducted to investigate HBV genotypes and phylogeny among HBV mono-infected and HBV-HDV co-infected patients, as well as analyze mutations in the surface gene of HBV in mono-infected and co-infected patients. A total of 100 blood samples (50 co-infected with HBV and HDV, and 50 mono-infected with HBV only) were collected for this study. HBV DNA was extracted from patient sera and partial surface antigen gene was amplified from HBV genome using polymerase chain reaction. HBV S gene was sequenced from 49 mono-infected and 36 co-infected patients and analyzed to identify HBV genotypes and phylogenetic patterns. Subsequently, HBV S amino acid sequences were analyzed for mutational differences between sequences from mono- and co-infected patients. HBV genotype D was predominantly found in both mono-infected as well as co-infected patients. Phylogenetic analysis showed the divergence of HBV sequences, between mono- and co-infected patients, into two distinct clusters. HBV S gene mutation analysis revealed certain mutations in HBV-HDV co-infected subjects to be distinct from those found in mono-infected patients. This might indicate the evolution of HBV S gene under selection pressures generated from HDV coinfection. © 2018 Wiley Periodicals, Inc.

Analysis of the transmission of Trypanosoma cruzi infection through hosts and vectors.

PubMed

Fabrizio, María C; Schweigmann, Nicolás J; Bartoloni, Norberto J

2016-08-01

Calculating epidemiological measures of infection by Trypanosoma cruzi, the causative agent of Chagas disease, is complex, because it involves several species, different stages of infection in humans and multiple transmission routes. Using the next-generation matrix method, we analysed a model which considers the three stages of human infection, triatomines and dogs (the main domestic reservoirs of T. cruzi when triatomines are present) and the main transmission routes. We derived R 0 and type-reproduction numbers T. We deduced formulas for the number of new infections generated through each transmission route by each infected individual. We applied our findings in Argentine Gran Chaco. The expressions achieved allowed quantifying the high infectivity of dogs and emphasizing the epidemiological importance of the long and asymptomatic chronic indeterminate stage in humans in the spread of the infection. According to the model, it is expected that one infected human infects 21 triatomines, that 100 infected triatomines are necessary to infect one human and 34 to infect a dog, and that each dog infects on average one triatomine per day. Our results may allow quantifying the effect of control measures on infected humans, triatomines and dogs (or other highly infected vertebrate) or on a specific route of transmission, in other scenarios.

Transcriptome analysis of Aedes aegypti in response to mono-infections and co-infections of dengue virus-2 and chikungunya virus.

PubMed

Shrinet, Jatin; Srivastava, Pratibha; Sunil, Sujatha

2017-10-28

Chikungunya virus (CHIKV) and Dengue virus (DENV) spread via the bite of infected Aedes mosquitoes. Both these viruses exist as co-infections in the host as well as the vector and are known to exploit their cellular machinery for their replication. While there are studies reporting the changes in Aedes transcriptome when infected with DENV and CHIKV individually, the effect both these viruses have on the mosquitoes when present as co-infections is not clearly understood. In the present study, we infected Aedes aegypti mosquitoes with DENV and CHIKV individually and as co-infection through nanoinjections. We performed high throughput RNA sequencing of the infected Aedes aegypti to understand the changes in the Aedes transcriptome during the early stages of infection, i.e., 24 h post infection and compared the transcriptome profiles during DENV and CHIKV mono-infections with that of co-infections. We identified 190 significantly regulated genes identified in CHIKV infected library, 37 genes from DENV library and 100 genes from co-infected library and they were classified into different pathways. Our study reveal that distinct pathways and transcripts are being regulated during the three types of infection states in Aedes aegypti mosquitoes. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection.

PubMed

Kimura, Hiroshi; Hoshino, Yo; Hara, Shinya; Sugaya, Naomi; Kawada, Jun-Ichi; Shibata, Yukiko; Kojima, Seiji; Nagasaka, Tetsuro; Kuzushima, Kiyotaka; Morishima, Tsuneo

2005-02-15

Infections of T cells and natural killer (NK) cells play a central role in the pathogenesis of chronic active Epstein-Barr virus (CAEBV) infection. To characterize the virologic and cytokine profiles of T cell-type and NK cell-type infection, 39 patients with CAEBV infection were analyzed. Patients with T cell-type infection had higher titers of immunoglobulin G against early and late EBV antigens, suggesting lytic cycle infection. However, the pattern of EBV gene expression was latency type II; BZLF1, which is a hallmark of lytic cycle infection, could not be detected in any patients, regardless of infection type. Patients with CAEBV infection had high concentrations of proinflammatory, T helper cell type 1, and anti-inflammatory cytokines. The cytokine profile in patients with NK cell-type infection was similar to that in patients with T cell-type infection, but the concentration of IL-13 was high in patients with NK cell-type infection. These findings should help to clarify the pathogenesis of CAEBV infection and facilitate the development of more-effective treatments.

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

PubMed Central

Ruffner, Melanie A.; Sullivan, Kathleen E.; Henrickson, Sarah E.

2017-01-01

Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs. PMID:28674531

Dynamics of gamete production and mating in the parasitic protist Trypanosoma brucei.

PubMed

Peacock, Lori; Bailey, Mick; Gibson, Wendy

2016-07-20

Sexual reproduction in Plasmodium falciparum and Trypanosoma brucei occurs in the insect vector and is important in generating hybrid strains with different combinations of parental characteristics. Production of hybrid parasite genotypes depends on the likelihood of co-infection of the vector with multiple strains. In mosquitoes, existing infection with Plasmodium facilitates the establishment of a second infection, although the asynchronicity of gamete production subsequently prevents mating. In the trypanosome/tsetse system, flies become increasingly refractory to infection as they age, so the likelihood of a fly acquiring a second infection also decreases. This effectively restricts opportunities for trypanosome mating to co-infections picked up by the fly on its first feed, unless an existing infection increases the chance of successful second infection as in the Plasmodium/mosquito system. Using green and red fluorescent trypanosomes, we compared the rates of trypanosome infection and hybrid production in flies co-infected on the first feed, co-infected on a subsequent feed 18 days after emergence, or fed sequentially with each trypanosome clone 18 days apart. Infection rates were highest in the midguts and salivary glands (SG) of flies that received both trypanosome clones in their first feed, and were halved when the infected feed was delayed to day 18. In flies fed the two trypanosome clones sequentially, the second clone often failed to establish a midgut infection and consequently was not present in the SG. Nevertheless, hybrids were recovered from all three groups of infected flies. Meiotic stages and gametes were produced continuously from day 11 to 42 after the infective feed, and in sequentially infected flies, the co-occurrence of gametes led to hybrid formation. We found that a second trypanosome strain can establish infection in the tsetse SG 18 days after the first infected feed, with co-mingling of gametes and production of trypanosome hybrids. Establishment of the second strain was severely compromised by the strong immune response of the fly to the existing infection. Although sequential infection provides an opportunity for trypanosome mating, the easiest way for a tsetse fly to acquire a mixed infection is by feeding on a co-infected host.

Multistate Point-Prevalence Survey of Health Care–Associated Infections

PubMed Central

Magill, Shelley S.; Edwards, Jonathan R.; Bamberg, Wendy; Beldavs, Zintars G.; Dumyati, Ghinwa; Kainer, Marion A.; Lynfield, Ruth; Maloney, Meghan; McAllister-Hollod, Laura; Nadle, Joelle; Ray, Susan M.; Thompson, Deborah L.; Wilson, Lucy E.; Fridkin, Scott K.

2015-01-01

BACKGROUND Currently, no single U.S. surveillance system can provide estimates of the burden of all types of health care–associated infections across acute care patient populations. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care–associated infections in acute care hospitals and generate updated estimates of the national burden of such infections. METHODS We defined health care–associated infections with the use of National Healthcare Safety Network criteria. One-day surveys of randomly selected inpatients were performed in participating hospitals. Hospital personnel collected demographic and limited clinical data. Trained data collectors reviewed medical records retrospectively to identify health care–associated infections active at the time of the survey. Survey data and 2010 Nationwide Inpatient Sample data, stratified according to patient age and length of hospital stay, were used to estimate the total numbers of health care–associated infections and of inpatients with such infections in U.S. acute care hospitals in 2011. RESULTS Surveys were conducted in 183 hospitals. Of 11,282 patients, 452 had 1 or more health care–associated infections (4.0%; 95% confidence interval, 3.7 to 4.4). Of 504 such infections, the most common types were pneumonia (21.8%), surgical-site infections (21.8%), and gastrointestinal infections (17.1%). Clostridium difficile was the most commonly reported pathogen (causing 12.1% of health care–associated infections). Device-associated infections (i.e., central-catheter–associated bloodstream infection, catheter-associated urinary tract infection, and ventilator-associated pneumonia), which have traditionally been the focus of programs to prevent health care–associated infections, accounted for 25.6% of such infections. We estimated that there were 648,000 patients with 721,800 health care–associated infections in U.S. acute care hospitals in 2011. CONCLUSIONS Results of this multistate prevalence survey of health care–associated infections indicate that public health surveillance and prevention activities should continue to address C. difficile infections. As device- and procedure-associated infections decrease, consideration should be given to expanding surveillance and prevention activities to include other health care–associated infections. PMID:24670166

The Relative Contribution of Symptomatic and Asymptomatic Plasmodium vivax and Plasmodium falciparum Infections to the Infectious Reservoir in a Low-Endemic Setting in Ethiopia.

PubMed

Tadesse, Fitsum G; Slater, Hannah C; Chali, Wakweya; Teelen, Karina; Lanke, Kjerstin; Belachew, Mulualem; Menberu, Temesgen; Shumie, Girma; Shitaye, Getasew; Okell, Lucy C; Graumans, Wouter; van Gemert, Geert-Jan; Kedir, Soriya; Tesfaye, Addisu; Belachew, Feleke; Abebe, Wake; Mamo, Hassen; Sauerwein, Robert; Balcha, Taye; Aseffa, Abraham; Yewhalaw, Delenasaw; Gadisa, Endalamaw; Drakeley, Chris; Bousema, Teun

2018-06-01

The majority of Plasmodium vivax and Plasmodium falciparum infections in low-endemic settings are asymptomatic. The relative contribution to the infectious reservoir of these infections compared to clinical malaria cases is currently unknown. We assessed infectivity of passively recruited symptomatic malaria patients (n = 41) and community-recruited asymptomatic individuals with microscopy-detected (n = 41) and polymerase chain reaction (PCR)-detected infections (n = 82) using membrane feeding assays with Anopheles arabiensis mosquitoes in Adama, Ethiopia. Malaria incidence and prevalence data were used to estimate the contributions of these populations to the infectious reservoir. Overall, 34.9% (29/83) of P. vivax- and 15.1% (8/53) P. falciparum-infected individuals infected ≥1 mosquitoes. Mosquito infection rates were strongly correlated with asexual parasite density for P. vivax (ρ = 0.63; P < .001) but not for P. falciparum (ρ = 0.06; P = .770). Plasmodium vivax symptomatic infections were more infectious to mosquitoes (infecting 46.5% of mosquitoes, 307/660) compared to asymptomatic microscopy-detected (infecting 12.0% of mosquitoes, 80/667; P = .005) and PCR-detected infections (infecting 0.8% of mosquitoes, 6/744; P < .001). Adjusting for population prevalence, symptomatic, asymptomatic microscopy-detected, and PCR-detected infections were responsible for 8.0%, 76.2%, and 15.8% of the infectious reservoir for P. vivax, respectively. For P. falciparum, mosquito infections were sparser and also predominantly from asymptomatic infections. In this low-endemic setting aiming for malaria elimination, asymptomatic infections were highly prevalent and responsible for the majority of onward mosquito infections. The early identification and treatment of asymptomatic infections might accelerate elimination efforts.

Multiple Periprosthetic Joint Infections: Evidence for Decreasing Prevalence.

PubMed

Haverstock, John P; Somerville, Lyndsa E; Naudie, Douglas D; Howard, James L

2016-12-01

Multiple periprosthetic joint infections (MPJIs) are uncommon. We determine the prevalence of developing a second-site periprosthetic joint infection. Our institutional arthroplasty database was reviewed. Those who developed a second-site infection had a retrospective chart review to determine the pathogen, timing of infection, comorbidities, and results of treatment. Thirteen of 206 (6.3%) patients at-risk for MPJI experienced a second periprosthetic joint infection. Mode of the second infection was hematogenous in 6, all of whom were being treated for the index periprosthetic joint infection. Seven secondary infections did not relate to the index infection. Two patients were lost to follow-up, 5 continued on suppressive antibiotics, and 6 successfully cleared infection. The prevalence of MPJI has decreased compared with previous reports. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple Human Papillomavirus Infection Is Associated with High-Risk Infection in Male Genital Warts in Ulsan, Korea

PubMed Central

Moon, Kyung Hyun; Yang, Sung-Hak; Roh, Min Cheol; Lee, Sang Hoon; Kim, Je Won; Kim, In Kyu; Roh, Kyoung Ho

2016-01-01

Further understanding of male human papillomavirus (HPV) infection is necessary to prevent infection in men, as well as transmission to women. In our current study, we investigated patterns of HPV infection and genotype distributions in male genital warts using the Anyplex II HPV28 Detection kit. We reviewed the medical records of 80 male patients who presented to 5 neighborhood clinics in Ulsan, Korea, for the treatment of genital warts between April 2014 and January 2015. All patients underwent HPV genotyping. The prevalence and characteristics of HPV infection were analyzed, and the patterns of HPV infection according to age were assessed. Among the study patients, 13 (16.3%) were negative for HPV infection, 46 (57.3%) were infected with low-risk HPV, and 21 (26.3%) were infected with high-risk HPV. Patients with multiple HPV infection were more likely to have high-risk HPV infection (P = 0.001). The prevalence of HPV infection was much higher in samples obtained by tissue excision due to a definite lesion (P = 0.001). There were no differences in high-risk HPV infection (P = 0.459), multiple HPV infection (P = 0.185), and recurrence at diagnosis (P = 0.178) according to age. HPV-6 and HPV-11 were the most common type overall (39.7% and 13.8%, respectively). HPV-16 and HPV-18 were the most common high-risk infections (both 3.4%). HPV infection is not only commonly encountered in male genital warts, but is also accompanied by high-risk HPV and multiple infections. PMID:26955236

Multiple Human Papillomavirus Infection Is Associated with High-Risk Infection in Male Genital Warts in Ulsan, Korea.

PubMed

Kwon, Taekmin; Moon, Kyung Hyun; Yang, Sung-Hak; Roh, Min Cheol; Lee, Sang Hoon; Kim, Je Won; Kim, In Kyu; Roh, Kyoung Ho; Park, Sungchan

2016-03-01

Further understanding of male human papillomavirus (HPV) infection is necessary to prevent infection in men, as well as transmission to women. In our current study, we investigated patterns of HPV infection and genotype distributions in male genital warts using the Anyplex II HPV28 Detection kit. We reviewed the medical records of 80 male patients who presented to 5 neighborhood clinics in Ulsan, Korea, for the treatment of genital warts between April 2014 and January 2015. All patients underwent HPV genotyping. The prevalence and characteristics of HPV infection were analyzed, and the patterns of HPV infection according to age were assessed. Among the study patients, 13 (16.3%) were negative for HPV infection, 46 (57.3%) were infected with low-risk HPV, and 21 (26.3%) were infected with high-risk HPV. Patients with multiple HPV infection were more likely to have high-risk HPV infection (P = 0.001). The prevalence of HPV infection was much higher in samples obtained by tissue excision due to a definite lesion (P = 0.001). There were no differences in high-risk HPV infection (P = 0.459), multiple HPV infection (P = 0.185), and recurrence at diagnosis (P = 0.178) according to age. HPV-6 and HPV-11 were the most common type overall (39.7% and 13.8%, respectively). HPV-16 and HPV-18 were the most common high-risk infections (both 3.4%). HPV infection is not only commonly encountered in male genital warts, but is also accompanied by high-risk HPV and multiple infections.

21 CFR 522.2610 - Trimethoprim and sulfadiazine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... for use. For the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, and acute septicemia due... tract infections, acute urogenital infections, and wound infections and abscesses. (iii) Limitations...

21 CFR 522.2610 - Trimethoprim and sulfadiazine.

Code of Federal Regulations, 2012 CFR

2012-04-01

... for use. For the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, and acute septicemia due... tract infections, acute urogenital infections, and wound infections and abscesses. (iii) Limitations...

21 CFR 522.2610 - Trimethoprim and sulfadiazine.

Code of Federal Regulations, 2013 CFR

2013-04-01

... for use. For the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, and acute septicemia due... tract infections, acute urogenital infections, and wound infections and abscesses. (iii) Limitations...

21 CFR 522.2610 - Trimethoprim and sulfadiazine.

Code of Federal Regulations, 2011 CFR

2011-04-01

... for use. For the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, and acute septicemia due... tract infections, acute urogenital infections, and wound infections and abscesses. (iii) Limitations...

Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

PubMed

Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

2017-06-15

Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We studied CMV acquisition in infants and found that infections are usually brief and self-limited and are successfully established relatively rarely. Thus, although most people eventually acquire CMV infection, it usually requires numerous exposures. Our analyses indicate that this is because the virus is surprisingly inefficient, barely replicating well enough to spread to neighboring cells in the mouth. Greater knowledge of why CMV infection usually fails may provide insight into how to prevent it from succeeding. Copyright © 2017 American Society for Microbiology.

Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells

PubMed Central

Mayer, Bryan T.; Krantz, Elizabeth M.; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T.

2017-01-01

ABSTRACT Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We studied CMV acquisition in infants and found that infections are usually brief and self-limited and are successfully established relatively rarely. Thus, although most people eventually acquire CMV infection, it usually requires numerous exposures. Our analyses indicate that this is because the virus is surprisingly inefficient, barely replicating well enough to spread to neighboring cells in the mouth. Greater knowledge of why CMV infection usually fails may provide insight into how to prevent it from succeeding. PMID:28381570

Increasing incidence of late-onset neonatal invasive group B streptococcal infections in Iceland.

PubMed

Óladóttir, Guđrún Lilja; Erlendsdóttir, Helga; Pálsson, Gestur; Björnsdóttir, Erla Soffía; Kristinsson, Karl G; Haraldsson, Ásgeir

2011-08-01

Group B streptococci (GBS) may cause life-threatening invasive infections in infants. The incidence of these infections has been increasing during the last decades. The aim of the study was to determine the epidemiology of neonatal GBS infections to be able to implement therapeutic and preventive measures more effectively. A retrospective case study was conducted in Iceland that included all neonates with positive GBS cultures from blood or cerebrospinal fluid during the period 1975 to 2006. Serotyping of all available GBS isolates was performed. A total of 87 children with 89 infections were included in the study. In all, 53 infants had early-onset (EO) GBS infections (occurring <7 days after birth) and 34 had late-onset (LO) infections (occurring on days 7-90). EO infections increased during the first 3 quartiles of the study period but decreased during the last quartile. LO infections increased throughout the entire study period. GBS was cultured from cerebrospinal fluid in 21 patients; 9 with EO and 12 with LO infections. Premature infants comprised 15 with EO and 14 with LO infections. Eight children died of GBS infection, 7 with EO and 1 with LO infections; no correlation with serotypes was found. Serotype III was most common for both EO (34%) and LO infections (62%). The number of GBS infections increased during the study period. The decrease in EO infections in recent years could be attributed to intrapartum antibiotic treatment. The increasing number of LO infections is a concern.

Permissive cytomegalovirus infection of primary villous term and first trimester trophoblasts.

PubMed

Hemmings, D G; Kilani, R; Nykiforuk, C; Preiksaitis, J; Guilbert, L J

1998-06-01

Forty percent of women with primary cytomegalovirus (CMV) infections during pregnancy infect their fetuses with complications for the baby varying from mild to severe. How CMV crosses the syncytiotrophoblast, the barrier between maternal blood and fetal tissue in the villous placenta, is unknown. Virus may cross by infection of maternal cells that pass through physical breaches in the syncytiotrophoblast or by direct infection of the syncytiotrophoblast, with subsequent transmission to underlying fetal placental cells. In this study, we show that pure (>99.99%), long-term and healthy (>3 weeks) cultures of syncytiotrophoblasts are permissively infected with CMV. Greater than 99% of infectious progeny virus remained cell associated throughout culture periods up to 3 weeks. Infection of term trophoblasts required a higher virus inoculum, was less efficient, and progressed more slowly than parallel infections of placental and human embryonic lung fibroblasts. Three laboratory strains (AD169, Towne, and Davis) and a clinical isolate from a congenitally infected infant all permissively infected trophoblasts, although infection efficiencies varied. The infection of first trimester syncytiotrophoblasts with strain AD169 occurred at higher frequency and progressed more rapidly than infection of term cells but less efficiently and rapidly than infection of fibroblasts. These results show that villous syncytiotrophoblasts can be permissively infected by CMV but that the infection requires high virus titers and proceeds slowly and that progeny virus remains predominantly cell associated.

Infections do not predict shedding in co-infections with two helminths from a natural system.

PubMed

Cattadori, Isabella M; Wagner, Benjamin R; Wodzinski, Laura A; Pathak, Ashutosh K; Poole, Adam

2014-06-01

Given the health and economic burden associated with the widespread occurrence of co-infections in humans and agricultural animals, understanding how coinfections contribute to host heterogeneity to infection and transmission is critical if we are to assess risk of infection based on host characteristics. Here, we examine whether host heterogeneity to infection leads to similar heterogeneity in transmission in a population of rabbits single and co-infected with two helminths and monitored monthly for eight years. Compared to single infections, co-infected rabbits carried higher Trichostrongylus retortaeformis intensities, shorter worms with fewer eggs in utero, and shed similar numbers of parasite eggs. In contrast, the same co-infected rabbits harbored fewer Graphidium strigosum with longer bodies and more eggs in utero, and shed more eggs of this helminth. A positive density-dependent relationship between fecundity and intensity was found for T. retortaeformis but not G. strigosum in co-infected rabbits. Juvenile rabbits contributed to most of the infection and shedding of T. retortaeformis, while adult hosts were more important for G. strigosum dynamics of infection and transmission, and this pattern was consistent in single and co-infected individuals. This host-parasite system suggests that we cannot predict the pattern of parasite shedding during co-infections based on intensity of infection alone. We suggest that a mismatching between susceptibility and infectiousness should be expected in helminth coinfections and should not be overlooked.

Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus.

PubMed

Rivera-Benitez, José Francisco; De la Luz-Armendáriz, Jazmín; Saavedra-Montañez, Manuel; Jasso-Escutia, Miguel Ángel; Sánchez-Betancourt, Ivan; Pérez-Torres, Armando; Reyes-Leyva, Julio; Hernández, Jesús; Martínez-Lara, Atalo; Ramírez-Mendoza, Humberto

2016-02-29

Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV. Copyright © 2016 Elsevier B.V. All rights reserved.

Systematic Search for Primary Immunodeficiency in Adults With Infections

ClinicalTrials.gov

2018-05-15

Complement Deficiency; Antibody Deficiency; Chronic Sinus Infection; Meningitis, Bacterial; Pneumonia, Bacterial; Otitis Media; Streptococcal Infection; Neisseria Infections; Haemophilus Influenza; Pneumococcal Infections

Factors Associated with Acquisition of Human Infective and Animal Infective Trypanosome Infections in Domestic Livestock in Western Kenya

PubMed Central

von Wissmann, Beatrix; Machila, Noreen; Picozzi, Kim; Fèvre, Eric M.; deC. Bronsvoort, Barend M.; Handel, Ian G.; Welburn, Susan C.

2011-01-01

Background Trypanosomiasis is regarded as a constraint on livestock production in Western Kenya where the responsibility for tsetse and trypanosomiasis control has increasingly shifted from the state to the individual livestock owner. To assess the sustainability of these localised control efforts, this study investigates biological and management risk factors associated with trypanosome infections detected by polymerase chain reaction (PCR), in a range of domestic livestock at the local scale in Busia, Kenya. Busia District also remains endemic for human sleeping sickness with sporadic cases of sleeping sickness reported. Results In total, trypanosome infections were detected in 11.9% (329) out of the 2773 livestock sampled in Busia District. Multivariable logistic regression revealed that host species and cattle age affected overall trypanosome infection, with significantly increased odds of infection for cattle older than 18 months, and significantly lower odds of infection in pigs and small ruminants. Different grazing and watering management practices did not affect the odds of trypanosome infection, adjusted by host species. Neither anaemia nor condition score significantly affected the odds of trypanosome infection in cattle. Human infective Trypanosoma brucei rhodesiense were detected in 21.5% of animals infected with T. brucei s.l. (29/135) amounting to 1% (29/2773) of all sampled livestock, with significantly higher odds of T. brucei rhodesiense infections in T. brucei s.l. infected pigs (OR = 4.3, 95%CI 1.5-12.0) than in T. brucei s.l. infected cattle or small ruminants. Conclusions Although cattle are the dominant reservoir of trypanosome infection it is unlikely that targeted treatment of only visibly diseased cattle will achieve sustainable interruption of transmission for either animal infective or zoonotic human infective trypanosomiasis, since most infections were detected in cattle that did not exhibit classical clinical signs of trypanosomiasis. Pigs were also found to be reservoirs of infection for T. b. rhodesiense and present a risk to local communities. PMID:21311575

Hepatitis C virus infection in HIV-infected patients.

PubMed

Sulkowski, Mark S

2007-10-01

The hepatitis C virus (HCV) is a spherical enveloped RNA virus of the Flaviviridae family, classified within the Hepacivirus genus. Since its discovery in 1989, HCV has been recognized as a major cause of chronic hepatitis and hepatic fibrosis that progresses in some patients to cirrhosis and hepatocellular carcinoma. In the United States, approximately 4 million people have been infected with HCV, and 10,000 HCVrelated deaths occur each year. Due to shared routes of transmission, HCV and HIV co-infection are common, affecting approximately one third of all HIV-infected persons in the United States. In addition, HIV co-infection is associated with higher HCV RNA viral load and a more rapid progression of HCV-related liver disease, leading to an increased risk of cirrhosis. HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons because the incidence of infection is increased and the natural history of HCV infection is accelerated in co-infected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed among HIV/HCV co-infected individuals.

Inter- and intraspecific conflicts between parasites over host manipulation

PubMed Central

Hafer, Nina; Milinski, Manfred

2016-01-01

Host manipulation is a common strategy by which parasites alter the behaviour of their host to enhance their own fitness. In nature, hosts are usually infected by multiple parasites. This can result in a conflict over host manipulation. Studies of such a conflict in experimentally infected hosts are rare. The cestode Schistocephalus solidus (S) and the nematode Camallanus lacustris (C) use copepods as their first intermediate host. They need to grow for some time inside this host before they are infective and ready to be trophically transmitted to their subsequent fish host. Accordingly, not yet infective parasites manipulate to suppress predation. Infective ones manipulate to enhance predation. We experimentally infected laboratory-bred copepods in a manner that resulted in copepods harbouring (i) an infective C plus a not yet infective C or S, or (ii) an infective S plus a not yet infective C. An infective C completely sabotaged host manipulation by any not yet infective parasite. An infective S partially reduced host manipulation by a not yet infective C. We hence show experimentally that a parasite can reduce or even sabotage host manipulation exerted by a parasite from a different species. PMID:26842574

Prevalence and Predictors of Intestinal Helminth Infections Among Human Immunodeficiency Virus Type 1–Infected Adults in an Urban African Setting

PubMed Central

Modjarrad, Kayvon; Zulu, Isaac; Redden, David T.; Njobvu, Lungowe; Freedman, David O.; Vermund, Sten H.

2009-01-01

Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1–infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data from 297 HIV-1–infected adults (mean age = 31.1 years, 69% female) living in Lusaka, Zambia to assess the prevalence and associated predictors of helminth infection. We found at least one type of intestinal helminth in 24.9% of HIV-infected adults. Thirty-nine (52.7%) were infected with Ascaris lumbricoides, and 29 (39.2%) were infected with hookworm. More than 80% were light-intensity infections. A recent visit to a rural area, food shortage, and prior history of helminth infection were significant predictors of current helminth status. The high helminth prevalence and potential for adverse interactions between helminths and HIV suggests that helminth diagnosis and treatment should be part of routine HIV care. PMID:16222025

Lack of preference for infective faeces in Hymenolepis diminuta-infected beetles (Tenebrio molitor).

PubMed

Shea, John F

2007-09-01

The beetle-tapeworm life cycle provides a convenient system to study how host behaviour influences the probability of re-infection because initial and secondary infections can be tracked. The beetle, Tenebrio molitor, is infected with the tapeworm Hymenolepis diminuta when it ingests rat faeces containing tapeworm eggs, which upon hatching undergo five morphologically distinct stages while developing inside the beetle. In a series of preference trials, both individual and groups of previously infected beetles were exposed to baits of infective (faeces with eggs) and uninfective faeces. Beetles did not differ in the amount of time spent or in the number of occurrences at each bait type, suggesting that infected beetles show no preference for infective faeces. This may be a host adaptation to avoid further infection, parasite manipulation to avoid competition for host resources, or both. Further, once infected, beetles are no more or no less likely to become re-infected than uninfected beetles. An analysis of the mean and variance of infection suggests that some individuals are highly susceptible to and some are highly resistant to infection, with males being more variable than females. This could explain the higher load of cysticercoids observed in males.

Infections Complicating the Care of Combat Casualties During Operations Iraqi Freedom and Enduring Freedom

DTIC Science & Technology

2011-07-01

nos 75 510 Empyema with fistula 3 510.9 Empyema w/o fistula 10 513 Abscess of lung 2 V46.1 Dependence on respirator 1 Other 041.89 Infection bacteria...recorded deaths (16 with infections). Infections were commonly gram-negative bacteria (47.6%) involving skin/wound infections (26.7%), and lung infections...trauma is primarily associated with gram-negative bacteria typically involving infections of wounds or other skin structures and lung infections such

The effect of dietary betaine on intestinal and plasma levels of betaine in uninfected and coccidia-infected broiler chicks.

PubMed

Fetterer, R H; Augustine, P C; Allen, P C; Barfield, R C

2003-07-01

Chicks fed betaine supplemented diets and infected with Eimeria acervulina and Eimeria maxima had markedly higher levels of betaine in the duodenum and mid-gut than unsupplemented, infected chicks. Uninfected chicks fed betaine exhibited almost twice the levels of betaine in the gut as infected chicks. Plasma betaine levels were lower in E. maxima-infected chicks than in E. acervulina-or Eimeria tenella-infected chicks. Betaine supplementation reversed the decrease in weight gain in E. maxima- infected chicks but had no effect on the decrease in weight gains in E acervulina- and E. tenella-infected chicks. Coccidia-infected birds on normal diets regularly exhibit increases in plasma NO(2)(+)NO(3). This increase was abolished in E.tenella-infected birds on betaine supplement. Betaine feeding did not alter this effect in E. acervulina- and E. maxima-infected birds. Results indicate that betaine supplementation has a positive effect on gut betaine levels in birds infected with E. acervulina and E. maxima. In all treatment groups, infection lowered the levels of betaine.

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections

PubMed Central

Greenwood, Edward J. D.; Schmidt, Fabian; Kondova, Ivanela; Niphuis, Henk; Hodara, Vida L.; Clissold, Leah; McLay, Kirsten; Guerra, Bernadette; Redrobe, Sharon; Giavedoni, Luis D.; Lanford, Robert E.; Murthy, Krishna K.; Rouet, François; Heeney, Jonathan L.

2015-01-01

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in ‘natural host’ species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections. PMID:26360709

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

PubMed

Greenwood, Edward J D; Schmidt, Fabian; Kondova, Ivanela; Niphuis, Henk; Hodara, Vida L; Clissold, Leah; McLay, Kirsten; Guerra, Bernadette; Redrobe, Sharon; Giavedoni, Luis D; Lanford, Robert E; Murthy, Krishna K; Rouet, François; Heeney, Jonathan L

2015-09-01

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.

Diagnoses of HIV-1 and HIV-2 in England, Wales, and Northern Ireland associated with west Africa.

PubMed

Dougan, S; Patel, B; Tosswill, J H; Sinka, K

2005-08-01

To describe HIV diagnoses, including those of HIV-2 infection, made in England, Wales, and Northern Ireland (E,W&NI) among those probably infected in west Africa, and to consider whether there is evidence for ongoing heterosexual transmission within the United Kingdom. Reports of new HIV diagnoses received at the Communicable Disease Surveillance Centre were analysed. Individuals probably infected in west Africa and those infected through heterosexual intercourse within the United Kingdom by a heterosexual partner infected in west Africa were included. Between 1985 and 2003 inclusive, 1324 individuals diagnosed and reported with HIV had probably been infected in west Africa, with 222 diagnoses made in 2003. 917 (69%) were HIV-1 infected and 52 (6%) HIV-2 or HIV-1/HIV-2 co-infected. For 355 (27%) the HIV type was not reported. The proportion of HIV-2 and HIV-1/HIV-2 infections varied by country of infection (p<0.001): ranging from the Gambia (11.7%-15.2%) to Nigeria (0.7%-1.0%). A further 130 individuals were probably infected through heterosexual intercourse within the United Kingdom by a heterosexual partner infected in west Africa. 89 (68%) were HIV-1 infected and three (2%) HIV-2 infected or HIV-1/HIV-2 co-infected. For 38 (29%) HIV type was not reported. The number of people infected with HIV in west Africa and diagnosed in E,W&NI has increased in recent years, and there is evidence of heterosexual transmission within the United Kingdom from people infected in west Africa. While numbers of HIV-2 diagnoses remain relatively low, an appreciable proportion of people infected in some west African countries and diagnosed in the United Kingdom may be HIV-2 positive, with implications for prognosis and treatment.

Both Influenza-Induced Neutrophil Dysfunction and Neutrophil-Independent Mechanisms Contribute to Increased Susceptibility to a Secondary Streptococcus pneumoniae Infection▿

PubMed Central

McNamee, Lynnelle A.; Harmsen, Allen G.

2006-01-01

Since secondary Streptococcus pneumoniae infections greatly increase the mortality of influenza infections, we determined the relative roles of neutrophil-dependent and -independent mechanisms in increased susceptibility to S. pneumoniae during influenza infection. Mice infected with influenza for 6 days, but not 3 days, showed a significant increase in susceptibility to S. pneumoniae infection compared to mice not infected with influenza. There was significant neutrophil accumulation in the lungs of S. pneumoniae-infected mice regardless of whether or not they were infected with influenza for 3 or 6 days. Depletion of neutrophils in these mice resulted in increased susceptibility to S. pneumoniae in both the non-influenza-infected mice and mice infected with influenza for 3 days but not in the mice infected with influenza for 6 days, indicating that a prior influenza infection of 6 days may compromise neutrophil function, resulting in increased susceptibility to a S. pneumoniae infection. Neutrophils from the lungs of mice infected with influenza for 3 or 6 days exhibited functional impairment in the form of decreased phagocytosis and intracellular reactive oxygen species generation in response to S. pneumoniae. In addition, neutrophil-depleted mice infected with influenza for 6 days were more susceptible to S. pneumoniae than neutrophil-depleted mice not infected with influenza, indicating that neutrophil-independent mechanisms also contribute to influenza-induced increased susceptibility to S. pneumoniae. Pulmonary interleukin-10 levels were increased in coinfected mice infected with influenza for 6 days but not 3 days. Thus, an influenza infection of 6 days increases susceptibility to S. pneumoniae by both suppression of neutrophil function and by neutrophil-independent mechanisms such as enhanced cytokine production. PMID:16982840

Community-Onset Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Invasive Infections in Children in a University Hospital in France.

PubMed

Toubiana, Julie; Timsit, Sandra; Ferroni, Agnès; Grasseau, Marie; Nassif, Xavier; Lortholary, Olivier; Zahar, Jean-Ralph; Chalumeau, Martin

2016-03-01

Limited data is available on pediatric community-onset infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), but such infections may affect both the efficacy of empiric antibiotic therapy and the rational use of antibiotics.We retrospectively analyzed data from 2007 to 2012 for all children ≤16 years old with a positive ESBL-PE strain from usually sterile sites within 48 hours of admission in a tertiary hospital in France. We analyzed healthcare- and community-associated infections among community-onset infections. In total, 3612 Enterobacteriaceae isolates were collected; the prevalence of ESBL-PE infection increased over the study period, from 2.4% to 5.1% (P < 0.001). Among the 90 children with a first community-onset ESBL-PE infection, 58% (n = 52) had a healthcare-associated infection, and 87% of isolates were susceptible to amikacin. As compared with patients with community-associated infections, those with healthcare-associated infections had fewer urinary tract infections (UTIs) (86% vs 97%) and Escherichia coli infections (35% vs 84%) and more Klebsiella pneumoniae infections (46% vs 8%). Inappropriate empiric treatment was prescribed for 54 patients (64%), but a favorable outcome was observed in 46 of 49 (94%) and 1 of 5 (20%) patients with UTIs and non-UTIs, respectively (P < 0.001). Among patients with community-associated infections, 85% had at least 1 risk factor for ESBL-PE infections. In conclusion, the prevalence of community-onset ESBL-PE infections doubled during the study period. These infections mainly occurred among children with healthcare-associated criteria or identified risk factors. Amikacin is an alternative to carbapenems for empiric treatment because most of these infections involved urinary tract and susceptible isolates.

Community-Onset Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Invasive Infections in Children in a University Hospital in France

PubMed Central

Toubiana, Julie; Timsit, Sandra; Ferroni, Agnès; Grasseau, Marie; Nassif, Xavier; Lortholary, Olivier; Zahar, Jean-Ralph; Chalumeau, Martin

2016-01-01

Abstract Limited data is available on pediatric community-onset infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), but such infections may affect both the efficacy of empiric antibiotic therapy and the rational use of antibiotics. We retrospectively analyzed data from 2007 to 2012 for all children ≤16 years old with a positive ESBL-PE strain from usually sterile sites within 48 hours of admission in a tertiary hospital in France. We analyzed healthcare- and community-associated infections among community-onset infections. In total, 3612 Enterobacteriaceae isolates were collected; the prevalence of ESBL-PE infection increased over the study period, from 2.4% to 5.1% (P < 0.001). Among the 90 children with a first community-onset ESBL-PE infection, 58% (n = 52) had a healthcare-associated infection, and 87% of isolates were susceptible to amikacin. As compared with patients with community-associated infections, those with healthcare-associated infections had fewer urinary tract infections (UTIs) (86% vs 97%) and Escherichia coli infections (35% vs 84%) and more Klebsiella pneumoniae infections (46% vs 8%). Inappropriate empiric treatment was prescribed for 54 patients (64%), but a favorable outcome was observed in 46 of 49 (94%) and 1 of 5 (20%) patients with UTIs and non-UTIs, respectively (P < 0.001). Among patients with community-associated infections, 85% had at least 1 risk factor for ESBL-PE infections. In conclusion, the prevalence of community-onset ESBL-PE infections doubled during the study period. These infections mainly occurred among children with healthcare-associated criteria or identified risk factors. Amikacin is an alternative to carbapenems for empiric treatment because most of these infections involved urinary tract and susceptible isolates. PMID:27015202

Does Stone Removal Help Patients with Recurrent Urinary Tract Infections?

PubMed

Omar, Mohamed; Abdulwahab-Ahmed, Abdullahi; Chaparala, Hemant; Monga, Manoj

2015-10-01

We evaluated the impact of surgical extraction of nonobstructing asymptomatic stones on recurrent urinary tract infections and identified predictors of patients who may be rendered infection-free. We retrospectively reviewed charts to identify patients with recurrent urinary tract infections who underwent surgical stone extraction and were rendered stone-free. Demographic variables as well as procedure, infectious etiology, stone composition and the systemic inflammatory response syndrome rate were also recorded. Patients were divided into 2 groups. Group 1 had no evidence of recurrent infection following surgery while recurrent infection developed in group 2. Univariate analysis was performed using the Wilcoxon signed rank and Fisher exact tests. Logistic regression was used for multivariate analysis. We identified 120 patients with recurrent urinary tract infections and a nonobstructive renal stone. Surgical management included shock wave lithotripsy in 32% of cases, ureteroscopy in 7% and percutaneous nephrolithotomy in 61%. Of the 120 patients 58 (48%) remained infection-free after surgery while 62 (52%) experienced recurrent infection. Factors associated with a higher risk of recurrent infections included type 2 diabetes mellitus (OR 1.73, p = 0.01), hypertension (OR 2.8, p = 0.007) and black ethnicity (OR 13.7, p = 0.009). Escherichia coli infections were more likely to resolve (OR 0.34, p = 0.01). In contrast, Enterococcus infections were more likely to persist (OR 2.5, p = 0.04). On multiple logistic regression analysis only race, hypertension and E. coli infections were significant predictors of infection clearance. Of patients with recurrent urinary tract infections and asymptomatic renal calculi 50% may be rendered infection-free following stone extraction. Patients with risk factors for recurrent infections after surgery should be counseled that stone extraction might not eradicate the infection. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Infection Rate in 1033 Elective Neurosurgical Procedures at a University Hospital in South China.

PubMed

Zhu, Hongwei; Liu, Xiyao; Wang, Zhanxiang

2017-09-01

Objective  Infection following surgery is a serious complication, especially in neurosurgery. The aim of the study is to report the change of incidence rates of infection in patients undergoing elective neurosurgical procedures at a university hospital in South China as well as the risk factors. Material and Methods  The medical records and postoperative courses for patients undergoing 1,033 neurosurgical procedures from 2008 to 2014 were reviewed retrospectively to determine the incidence of neurosurgical infection, the identity of the offending organisms, and the factors associated with infection. Results  A total of 33 patients (40 cases) experienced postoperative infection representing 3.19% of the study population. Twenty cases were incision infections (1.94%), and 20 were cranial/spinal infections (1.94%) including 15 intracranial infections and 5 intraspinal infections. The 2.4-fold greater incidence of postoperative infection in 2008 to 2010 was compared with that in 2011 to 2014 with perioperative antibiotic prophylaxis ( p <0.01). The neurosurgical procedure associated with the highest rate of infection was cranioplasty (6.85%); the lowest rate of infection was associated with functional neurosurgery (1.08%). The most common offending organism was Staphylococcus aureus (27.5%). Foreign body implantation, operative time > 4 hours, and cerebrospinal fluid (CSF) leak (13 infections in 158 patients; p <0.001) were risk factors for infections ( p <0.05). Conclusion  The neurosurgical infection rate is usually low with perioperative antibiotic prophylaxis even in developing countries. Less foreign body implantation, shorter operative times, and controlling CSF leak could reduce infection rates. Georg Thieme Verlag KG Stuttgart · New York.

Detection and Characterization of Infections and Infection Susceptibility

ClinicalTrials.gov

2018-06-26

Immune Disorders; Chronic Granulomatous Disease; Genetic Immunological Deficiencies; Hyperimmunoglobulin-E Recurrent Infection Syndrome; Recurrent Infections; Unknown Immune Deficiency; GATA2 Deficiency (MonoMAC); Nontuberculous Mycobacterial Infections; Hyper IgE (Job s) Syndrome; Leukocyte Adhesion Deficiency; Susceptibility to Disseminated Infections; Primary Immune Deficiency Disease (PIDD)

Airborne Transmission of Highly Pathogenic Influenza Virus during Processing of Infected Poultry

PubMed Central

Bertran, Kateri; Balzli, Charles; Kwon, Yong-Kuk; Tumpey, Terrence M.; Clark, Andrew

2017-01-01

Exposure to infected poultry is a suspected cause of avian influenza (H5N1) virus infections in humans. We detected infectious droplets and aerosols during laboratory-simulated processing of asymptomatic chickens infected with human- (clades 1 and 2.2.1) and avian- (clades 1.1, 2.2, and 2.1) origin H5N1 viruses. We detected fewer airborne infectious particles in simulated processing of infected ducks. Influenza virus–naive chickens and ferrets exposed to the air space in which virus-infected chickens were processed became infected and died, suggesting that the slaughter of infected chickens is an efficient source of airborne virus that can infect birds and mammals. We did not detect consistent infections in ducks and ferrets exposed to the air space in which virus-infected ducks were processed. Our results support the hypothesis that airborne transmission of HPAI viruses can occur among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry. PMID:29047426

Airborne Transmission of Highly Pathogenic Influenza Virus during Processing of Infected Poultry.

PubMed

Bertran, Kateri; Balzli, Charles; Kwon, Yong-Kuk; Tumpey, Terrence M; Clark, Andrew; Swayne, David E

2017-11-01

Exposure to infected poultry is a suspected cause of avian influenza (H5N1) virus infections in humans. We detected infectious droplets and aerosols during laboratory-simulated processing of asymptomatic chickens infected with human- (clades 1 and 2.2.1) and avian- (clades 1.1, 2.2, and 2.1) origin H5N1 viruses. We detected fewer airborne infectious particles in simulated processing of infected ducks. Influenza virus-naive chickens and ferrets exposed to the air space in which virus-infected chickens were processed became infected and died, suggesting that the slaughter of infected chickens is an efficient source of airborne virus that can infect birds and mammals. We did not detect consistent infections in ducks and ferrets exposed to the air space in which virus-infected ducks were processed. Our results support the hypothesis that airborne transmission of HPAI viruses can occur among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry.

Association Between Parental Hospital-Treated Infection and the Risk of Schizophrenia in Adolescence and Early Adulthood

PubMed Central

Nielsen, Philip R.; Laursen, Thomas M.; Mortensen, Preben B.

2013-01-01

It has been suggested that infection during perinatal life may lie at the etiological root of schizophrenia. It has thus been hypothesized that the origin of schizophrenia may lie either in direct fetal infection and/or in a generally increased familial susceptibility to infections, some of which may occur during pregnancy. We explored these 2 hypotheses by assessing maternal infection during pregnancy and maternal as well as paternal infection in general as predictors of schizophrenia in their offspring. We found a slightly increased risk to be associated with prenatal infection exposure. However, the effect of prenatal infection exposure was not statistically significantly different from the effect of infection exposure in general. Parental infection appeared to be associated with development of schizophrenia in adolescence and early adulthood. Our study does not exclude a specific effect of infection during fetal life; yet, it does suggest that schizophrenia is associated with an increased familial liability to develop severe infection. PMID:22021661

Preventing infections in nursing homes: A survey of infection control practices in southeast Michigan

PubMed Central

Mody, Lona; Langa, Kenneth M.; Saint, Sanjay; Bradley, Suzanne F.

2012-01-01

Background Studies on adherence to infection control policies in nursing homes (NHs) are limited. This pilot study explores the use of various infection control practices and the role of infection control practitioners in southeast Michigan NHs. Methods A 43-item self-administered questionnaire and explanatory cover letter were mailed to 105 licensed NHs in southeast Michigan. A second mailing was sent to the nonresponders 4 weeks later. Results Significant variability existed in adoption of various infection control measures with respect to time spent in infection control activities (50% of facilities having a full-time infection control practitioner), definitions used in monitoring infections, and immunization rates (influenza: range, 0%–100%; mean, 73.2%; pneumococcal: range, 0%–100%; mean, 38.5%). Conclusion Although strides have been made in infection control research in NHs, significant variations exist in implementation of infection control methods and guidelines. Future research should focus on identifying barriers to infection control in NHs. PMID:16216667

Activity of superoxide dismutase in Galleria mellonella larvae infected with entomopathogenic nematodes Steinernema affinis and S. feltiae.

PubMed

Zółtowska, Krystyna; Grochla, Paulina; Łopieńska-Biernat, Elzbieta

2006-01-01

The influence of infection with two species of entomopathogenic nematodes of Steinernematidae family on the activity of superoxide dismutase (SOD) of the host was studied. Last instar larvae of Galleria mellonella were experimentally infected with Steinernema affinis and S. feltiae at 20 invasive juveniles per insect. At 6, 12, 18, 24 and 36 h after infection activity of SOD was determined in extracts from infected and control insects. The activity of SOD decreased gradually in the controls during the experiment. The activity of enzyme was 2-4-times higher in insects from both infected groups than in the control. During the first 12 h of infection the activity of SOD in insects infected with S. feltiae was higher than in those infected with S. affinis, then the activity of enzyme in the insects of both infected groups stayed at a similar level. A significant decrease of SOD activity in infected was recorded in second day of the infection.

Hampered performance of migratory swans: intra- and inter-seasonal effects of avian influenza virus

PubMed Central

Hoye, Bethany J.; Munster, Vincent J.; Huig, Naomi; de Vries, Peter; Oosterbeek, Kees; Tijsen, Wim; Klaassen, Marcel; Fouchier, Ron A. M.; van Gils, Jan A.

2016-01-01

The extent to which animal migrations shape parasite transmission networks is critically dependent on a migrant’s ability to tolerate infection and migrate successfully. Yet, sub-lethal effects of parasites can be intensified through periods of increased physiological stress. Long-distance migrants may, therefore, be especially susceptible to negative effects of parasitic infection. Although a handful of studies have investigated the short-term, transmission-relevant behaviors of wild birds infected with low-pathogenic avian influenza viruses (LPAIV), the ecological consequences of LPAIV for the hosts themselves remain largely unknown. Here, we assessed the potential effects of naturally-acquired LPAIV infections in Bewick’s swans, a long-distance migratory species that experiences relatively low incidence of LPAIV infection during early winter. We monitored both foraging and movement behavior in the winter of infection, as well as subsequent breeding behavior and inter-annual resighting probability over 3 years. Incorporating data on infection history we hypothesized that any effects would be most apparent in naïve individuals experiencing their first LPAIV infection. Indeed, significant effects of infection were only seen in birds that were infected but lacked antibodies indicative of prior infection. Swans that were infected but had survived a previous infection were indistinguishable from uninfected birds in each of the ecological performance metrics. Despite showing reduced foraging rates, individuals in the naïve-infected category had similar accumulated body stores to re-infected and uninfected individuals prior to departure on spring migration, possibly as a result of having higher scaled mass at the time of infection. And yet individuals in the naïve-infected category were unlikely to be resighted 1 year after infection, with 6 out of 7 individuals that never resighted again compared to 20 out of 63 uninfected individuals and 5 out of 12 individuals in the re-infected category. Collectively, our findings indicate that acute and superficially harmless infection with LPAIV may have indirect effects on individual performance and recruitment in migratory Bewick’s swans. Our results also highlight the potential for infection history to play an important role in shaping ecological constraints throughout the annual cycle. PMID:27252210

A Case of Systemic Infection Caused by Streptococcus pyogenes Oral Infection in an Edentulous Patient.

PubMed

Inagaki, Yumi; Abe, Masanobu; Inaki, Ryoko; Zong, Liang; Suenaga, Hideyuki; Abe, Takahiro; Hoshi, Kazuto

2017-08-18

Infections in the oral and maxillofacial region can sometimes extend beyond the oral cavity, with serious consequences. Most oral infections are odontogenic, occurring through the root apex of the tooth or the periodontal pocket. It thus makes sense that edentulous patients have a much lower risk of oral bacterial infection. For this reason, while there are many reports on systemic infections caused by oral infections, few of these describe such infections in edentulous patients. We present a case of oral and maxillofacial cellulitis followed by sepsis due to Streptococcus pyogenes infection in an 89-year-old Japanese edentulous woman. S. pyogenes was detected in the wound of left maxilla and the blood sample. S. pyogenes has been reported to be one of the most common and influential aerobic bacteria associated with deep neck infection and subsequent systemic infection. Left maxillary sinusitis was observed, and this could be the origin of the S. pyogenes infection. S. pyogenes derived from the sinusitis and leaked to the oral cavity might have caused systemic infection through wounding of the oral mucosa. Fortunately, intensive antibiotic therapy was effective, and the patient recovered without any surgical procedures. We experienced a rare case of oral and maxillofacial cellulitis followed by sepsis due to a Streptococcus pyogenes infection in an old edentulous woman. This result indicated that, while edentulous patients are considered to have no risk of odontogenic infection, they still carry a risk of bacterial infection.

High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

PubMed

Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

2012-01-01

Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.

[Infections which humans in the household transmit to dogs and cats].

PubMed

Mayr, A

1989-04-01

An overview of the most important infections which can be transmitted from humans to pet dogs and cats is presented. Two quite different sources of infection stand diametrically opposite each other: 1. The transmission of active human infections to dogs and cats and 2. the transmission of infectious agents by feeding raw meat, offal, unsterilized milk products, kitchen scraps and contaminated feedstuffs. Humans can be the source of the following infections: 1. Zoonoses with reciprocal modes of transmission, e.g. Campylobacter and E. coli infections, trichophyton and microsporum infections, reo-, parainfluenza-, adeno, rota- and corona infections. 2. Zoonoses in which the main direction of infection is human----animal, e.g. tuberculosis and influenza A. 3. Infections originally pathogenic to humans which meet an impasse in dogs and cats (blind alley hosts), e.g. herpes simplex, varicella-zoster, measles and Corynebacterium diphtheriae. Listeria, salmonella, campylobacteria, toxoplasma, fungi, yeasts and viruses are transmitted via feed. The most dangerous virus infection to be transmitted to cats and dogs via raw pork leftovers is Aujeszky's disease. The dog or cat, which is the last link in the infection chain, suffers an agonizing death. The other infections originating from feed must be assessed quite differently. They are links in infection chains, which spread pathogens and endanger the health of man and animal in turn. A typical example is toxoplasmosis. Man becomes infected via sporulated oocysts from feces. Pet cats mainly become infected via raw pork containing cysts.

Controlled Human Infection for Vaccination Against Streptococcus Pyogenes

ClinicalTrials.gov

2018-06-26

Streptococcus Pyogenes Pharyngitis; Streptococcus Pharyngitis; Strep Throat; Streptococcus Pyogenes Infection; Group A Streptococcus: B Hemolytic Pharyngitis; Group A Streptococcal Infection; Gram-Positive Bacterial Infections; Bacterial Infections

Horizontal pollen transmission of Gentian ovary ring-spot virus is initiated during penetration of the stigma and style by infected pollen tubes.

PubMed

Isogai, Masamichi; Kamata, Yukie; Ando, Syunpei; Kamata, Misaki; Shirakawa, Asuka; Sekine, Ken-Taro; Yoshikawa, Nobuyuki

2017-03-01

Gentian ovary ring-spot virus (GORV) infected gentian plants by pollination with GORV-infected gentian pollen grains, but the virus was not horizontally transmitted to gentian plants by transfer of pollen from GORV-infected Nicotiana benthamiana plants. However, N. benthamiana plants were infected with the virus by pollination with infected gentian pollen as well as by pollination with infected N. benthamiana pollen. When infected gentian pollen grains were placed on N. benthamiana stigmas, germinating pollen tubes penetrated into the stigmas and the styles (stigma-style). Virus infection occurred during penetration of the stigma-style, and the virus subsequently spread systemically to the mother plant. On the other hand, most infected N. benthamiana pollen grains failed to germinate on gentian stigmas, and virus infections were not detected in the stigma-style. Copyright © 2017 Elsevier Inc. All rights reserved.

Executive summary: Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

PubMed

Iribarren, José Antonio; Rubio, Rafael; Aguirrebengoa, Koldo; Arribas, Jose Ramón; Baraia-Etxaburu, Josu; Gutiérrez, Félix; Lopez Bernaldo de Quirós, Juan Carlos; Losa, Juan Emilio; Miró, José Ma; Moreno, Santiago; Pérez Molina, José; Podzamczer, Daniel; Pulido, Federico; Riera, Melchor; Rivero, Antonio; Sanz Moreno, José; Amador, Concha; Antela, Antonio; Arazo, Piedad; Arrizabalaga, Julio; Bachiller, Pablo; Barros, Carlos; Berenguer, Juan; Caylá, Joan; Domingo, Pere; Estrada, Vicente; Knobel, Hernando; Locutura, Jaime; López Aldeguer, José; Llibre, Josep Ma; Lozano, Fernando; Mallolas, Josep; Malmierca, Eduardo; Miralles, Celia; Miralles, Pilar; Muñoz, Agustín; Ocampo, Agustín; Olalla, Julián; Pérez, Inés; Pérez Elías, Ma Jesús; Pérez Arellano, José Luis; Portilla, Joaquín; Ribera, Esteban; Rodríguez, Francisco; Santín, Miguel; Sanz Sanz, Jesús; Téllez, Ma Jesús; Torralba, Miguel; Valencia, Eulalia; Von Wichmann, Miguel Angel

2016-10-01

Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Procalcitonin as a diagnostic and prognostic marker in diabetic foot infection. A current literature review.

PubMed

Velissaris, Dimitrios; Pantzaris, Nikolaos-Dimitrios; Platanaki, Christina; Antonopoulou, Nikolina; Gogos, Charalampos

2018-03-01

Diabetic foot ulcers (DFUs) are a very common cause of mortality and morbidity. The distinction between infected and non-infected DFU remains a very challenging task for clinicians in everyday practice. Even when infection is documented, the spectrum of diabetic foot infection is wide, ranging from cellulitis and soft tissue infection to osteomyelitis. Procalcitonin (PCT), a well-established sepsis biomarker, has been used in the diagnosis of several infections including osteomyelitis in patients with diabetes mellitus. This review gathers and presents all the relevant data, up until now, regarding the use of PCT as an assessment tool in diabetic patients with foot infection. Current evidence suggests that PCT levels could aid clinicians in distinguishing infected from non-infected DFUs as well as in the distinction between soft tissue infection and bone involvement, but further and larger studies are warranted to confirm these findings.

[The prevalence of nosocomial infection in Intensive Care Units in the State of Rio Grande do Sul].

PubMed

Lisboa, Thiago; Faria, Mario; Hoher, Jorge A; Borges, Luis A A; Gómez, Jussara; Schifelbain, Luciele; Dias, Fernando S; Lisboa, João; Friedman, Gilberto

2007-12-01

To determine the prevalence of intensive care unit (ICU)-acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. A 1-day point prevalence study. Sixteen ICU of the State of Rio Grande do Sul-Brazil, excluding coronary care and pediatric units. All patients < 12 yrs occupying an ICU bed over a 24-hour period. The 16 ICU provided 174 case reports. rates of ICU-acquired infection, resistance patterns of microbiological isolates, and potential risks factors for ICU-acquired infection and death. A total of 122 patients (71%) was infected and 51 (29%) had ICU-acquired infection. Pneumonia (58.2%), lower tract respiratory infection (22.9%), urinary tract infection (18%) were the most frequents types of ICU infection. Most frequently microorganisms reported were staphylococcus aureus (42% [64% resistant to oxacilin]) and pseudomonas aeruginosa (31%). Six risk factors for ICU acquired infection were identified: urinary catheterization, central vascular line, tracheal intubation for prolonged time (> 4 days), chronic disease and increased length of ICU stay (> 30 days). The risks factors associated with death were age, APACHE II, organ dysfunction, and tracheal intubation with or without mechanical ventilation. ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. This study may serve as an epidemiological reference to help the discussion of regional infection control policies.

Effect of HIV infection on tolerability and bacteriologic outcomes of tuberculosis treatment.

PubMed

Bliven-Sizemore, E E; Johnson, J L; Goldberg, S; Burman, W J; Villarino, M E; Chaisson, R E

2012-04-01

Two international, multicenter Phase 2 clinical trials examining fluoroquinolone-containing regimens in adults with smear-positive pulmonary tuberculosis (TB), conducted from July 2003 to March 2007. Both trials enrolled human immunodeficiency virus (HIV) infected participants who were not receiving antiretroviral therapy (ART) at TB treatment initiation. To assess the impact of HIV infection on TB treatment outcomes in Phase 2 clinical trials. Cross-protocol analysis comparing the safety, tolerability and outcomes of anti-tuberculosis treatment by HIV status. Of 750 participants who received at least one dose of study treatment, 123 (16%) were HIV-infected. Treatment completion rates were similar by HIV status (81% infected vs. 85% non-infected), as were rates of week 8 culture conversion (66% infected vs. 63% non-infected), and treatment failure (5% infected vs. 3% non-infected). Among HIV-infected participants, treatment failure detected using liquid media was more frequent in those treated thrice weekly (14% thrice weekly vs. 2% daily, P = 0.03). HIV-infected participants more frequently experienced an adverse event during the intensive phase treatment than non-HIV-infected participants (30% vs. 15%, P < 0.01). HIV-infected persons not receiving ART had more adverse events during the intensive phase of anti-tuberculosis treatment, but tolerated treatment well. Failure rates were higher among HIV-infected persons treated with thrice-weekly intensive phase therapy.

Spinoculation Enhances HBV Infection in NTCP-Reconstituted Hepatocytes.

PubMed

Yan, Ran; Zhang, Yongmei; Cai, Dawei; Liu, Yuanjie; Cuconati, Andrea; Guo, Haitao

2015-01-01

Hepatitis B virus (HBV) infection and its sequelae remain a major public health burden, but both HBV basic research and the development of antiviral therapeutics have been hindered by the lack of an efficient in vitro infection system. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the HBV receptor. We herein report that we established a NTCP-complemented HepG2 cell line (HepG2-NTCP12) that supports HBV infection, albeit at a low infectivity level following the reported infection procedures. In our attempts to optimize the infection conditions, we found that the centrifugation of HepG2-NTCP12 cells during HBV inoculation (termed "spinoculation") significantly enhanced the virus infectivity. Moreover, the infection level gradually increased with accelerated speed of spinoculation up to 1,000g tested. However, the enhancement of HBV infection was not significantly dependent upon the duration of centrifugation. Furthermore, covalently closed circular (ccc) DNA was detected in infected cells under optimized infection condition by conventional Southern blot, suggesting a successful establishment of HBV infection after spinoculation. Finally, the parental HepG2 cells remained uninfected under HBV spinoculation, and HBV entry inhibitors targeting NTCP blocked HBV infection when cells were spinoculated, suggesting the authentic virus entry mechanism is unaltered under centrifugal inoculation. Our data suggest that spinoculation could serve as a standard protocol for enhancing the efficiency of HBV infection in vitro.

Spinoculation Enhances HBV Infection in NTCP-Reconstituted Hepatocytes

PubMed Central

Yan, Ran; Zhang, Yongmei; Cai, Dawei; Liu, Yuanjie; Cuconati, Andrea; Guo, Haitao

2015-01-01

Hepatitis B virus (HBV) infection and its sequelae remain a major public health burden, but both HBV basic research and the development of antiviral therapeutics have been hindered by the lack of an efficient in vitro infection system. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the HBV receptor. We herein report that we established a NTCP-complemented HepG2 cell line (HepG2-NTCP12) that supports HBV infection, albeit at a low infectivity level following the reported infection procedures. In our attempts to optimize the infection conditions, we found that the centrifugation of HepG2-NTCP12 cells during HBV inoculation (termed “spinoculation”) significantly enhanced the virus infectivity. Moreover, the infection level gradually increased with accelerated speed of spinoculation up to 1,000g tested. However, the enhancement of HBV infection was not significantly dependent upon the duration of centrifugation. Furthermore, covalently closed circular (ccc) DNA was detected in infected cells under optimized infection condition by conventional Southern blot, suggesting a successful establishment of HBV infection after spinoculation. Finally, the parental HepG2 cells remained uninfected under HBV spinoculation, and HBV entry inhibitors targeting NTCP blocked HBV infection when cells were spinoculated, suggesting the authentic virus entry mechanism is unaltered under centrifugal inoculation. Our data suggest that spinoculation could serve as a standard protocol for enhancing the efficiency of HBV infection in vitro. PMID:26070202

Schistosoma japonicum infection in the pig: the effect of a patent primary infection on a challenge infection.

PubMed

Willingham, A L; Bøgh, H O; Johansen, M V; Christensen, N O; Nansen, P

1997-06-24

The response of pigs to a challenge infection of Schistosoma japonicum following a primary infection was assessed using parasitological parameters and eosinophil counts. Twenty-five Danish Landrace/Yorkshire/Duroc crossbred pigs were divided into four groups. Group A (n = 10) received a primary infection, group B (n = 5) received both a primary and challenge infection, group C (n = 5) received a challenge control infection and group D (n = 5) received no infection serving as helminth-free controls. A dose of 850 cercariae was administered by intramuscular injection at the primary infection (week 0) and challenge infection (week 12). The pigs were perfused at week 21, except for half of the group A pigs which were slaughtered at week 12. Challenge infection did not result in higher worm burdens or tissue egg counts in group B than group A at week 21 and mature/immature worm ratios were similar for the two groups. In addition, no increases in faecal egg counts or eosinophil counts were observed in group B after challenge infection. The results indicate that pigs are able to mount a very rapid and effective response to reinfection with S. japonicum following a patent primary infection resulting in prevention of establishment of challenge infection schistosomes. An anti-worm effect appears to be the main feature of this regulatory host response.

Nasopharyngeal polymicrobial colonization during health, viral upper respiratory infection and upper respiratory bacterial infection.

PubMed

Xu, Qingfu; Wischmeyer, Jareth; Gonzalez, Eduardo; Pichichero, Michael E

2017-07-01

We sought to understand how polymicrobial colonization varies during health, viral upper respiratory infection (URI) and acute upper respiratory bacterial infection to understand differences in infection-prone vs. non-prone patients. Nasopharyngeal (NP) samples were collected from 74 acute otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (Mcat) were identified by culture. NP colonization rates of multiple otopathogens during health were significantly lower than during viral URI, and during URI they were lower than at onset of upper respiratory bacterial infection in both AOM infection-prone and non-prone children. AOM infection-prone children had higher polymicrobial colonization rates than non-prone children during health, viral URI and AOM. Polymicrobial colonization rates of AOM infection-prone children during health were equivalent to that of non-prone children during viral URI, and during viral URI were equivalent to that of non-prone during AOM infection. Spn colonization was positively associated with NTHi and Mcat colonization during health, but negatively during AOM infection. The infection-prone patients more frequently have multiple potential bacterial pathogens in the NP than the non-prone patients. Polymicrobial interaction in the NP differs during health and at onset of infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Epidemiology of equine Cryptosporidium and Giardia infections.

PubMed

Xiao, L; Herd, R P

1994-01-01

Prevalence and infection patterns of Cryptosporidium and Giardia infections in horses were studied by a direct immunofluorescence staining method. Faecal examinations of 222 horses of different age groups revealed Cryptosporidium infection rates of 15-31% in 66 foals surveyed in central Ohio, southern Ohio and central Kentucky, USA. Only 1 of 39 weanlings, 0 of 46 yearlings, and 0 of 71 mares were positive. Giardia infection was found in all age groups, although the infection rates for foals were higher (17-35%). Chronological study of infection in 35 foals showed that foals started to excrete Cryptosporidium oocysts between 4 and 19 weeks and Giardia cysts between 2 and 22 weeks of age. The cumulative infection rates of Cryptosporidium and Giardia in foals were each 71%. Some foals were concurrently infected with both parasites and excretion of oocysts or cysts was intermittent and long-lasting. The longest duration of excretion was 14 weeks for Cryptosporidium and 16 weeks for Giardia. Excretion of Cryptosporidium oocysts stopped before weaning, while excretion of Giardia cysts continued thereafter. Infected foals were considered the major source of Cryptosporidium infection in foals, whereas infected mares were deemed the major source of Giardia infection in foals. The high infection rate of Giardia in nursing mares suggested a periparturient relaxation of immunity. The results indicated that Cryptosporidium and Giardia infections are common in horses.

Reduced Risk of Disease During Postsecondary Dengue Virus Infections

PubMed Central

Olkowski, Sandra; Forshey, Brett M.; Morrison, Amy C.; Rocha, Claudio; Vilcarromero, Stalin; Halsey, Eric S.; Kochel, Tadeusz J.; Scott, Thomas W.; Stoddard, Steven T.

2013-01-01

Background. Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1–4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission. Methods. DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness. Results. Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]). Conclusions. Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics. PMID:23776195

[Frequency of opportunistic infections in children with immune neutropenia and their mothers].

PubMed

Kalugina, M Iu; Karazhas, N V; Rybalkina, T N; Bosh'ian, R E; Mamedova, E A; Polovtseva, T V; Finogenova, N A

2012-01-01

Determine the frequency of opportunistic infections among children with immune neutropenia and their mothers. 66 mothers and 66 children with immune neutropenia diagnosis were examined for the presence of herpes (HV) and pneumocystic infection. Opportunistic infections markers (IgM, IgG, early and late antigens, virus reproduction) were determined by enzyme immunoassay, immunofluorescence reaction and rapid culture method (vero, u937, human fibroblasts). Pneumocystosis was the most active infection in the group. Among mothers 26 (39.3%) cases of pneumocystic infection in acute form were detected, among children - 18 (27.3%) cases. Infection occurred only in acute form during primary infection; there were no cases of its reactivation, which is an indication of recent pneumocystosis infection. Analysis of data on detection of acute and recent herpes infections showed that HV infection markers were determined in a relatively large number of mothers and their children: herpes simplex virus - 21.2%, Epstein-Barr virus - 12.0%, cytomegalovirus - 15.0%, Human herpesvirus 6 - 10.6%, Pneumocystis carinii - 21.2%. The data provided give evidence on a possible family pattern of the infection. A necessity of examination of mothers and their children suffering from immune neutropenia was shown because the specified opportunistic infections can form intra-family foci. The presence of acute form of infection in mother may be one of the conditions of development of this infection in the child.

Comparison of Stable and Transient Wolbachia Infection Models in Aedes aegypti to Block Dengue and West Nile Viruses.

PubMed

Joubert, Dirk Albert; O'Neill, Scott L

2017-01-01

Pathogen replication and transmission in Wolbachia infected insects are currently studied using three Wolbachia infection systems: naturally infected Wolbachia hosts, hosts transinfected with Wolbachia (stably maintained and inherited infections) and hosts transiently infected with Wolbachia. All three systems have been used to test the effect of Wolbachia on mosquito transmitted pathogens such as dengue virus (DENV), West Nile virus (WNV) and Plasmodium. From these studies it is becoming increasingly clear that the interaction between a particular pathogen and Wolbachia is heavily influenced by the host-Wolbachia interaction and the model of infection. In particular, there is some evidence that under very specific conditions, Wolbachia can enhance pathogen infection in some hosts. In this study, we compared the effect of Wolbachia in two infection models (stable transinfected and transiently infected) on the replication, infection- and transmission rates of two flaviviruses, DENV and WNV (Kunjin strain). Our results indicate that Wolbachia had similar blocking effects in both stable and transient models of infection, however, the magnitude of the blocking effect was significantly lower in mosquitoes transiently infected with Wolbachia. More importantly, no evidence was found for any enhancement of either DENV or WNV (Kunjin strain) infection in Ae. aegypti infected with Wolbachia, supporting a role for Wolbachia as an effective and safe means for restricting transmission of these viruses.

Fish tapeworm infection

MedlinePlus

Fish tapeworm infection is an intestinal infection with a parasite found in fish. ... The fish tapeworm ( Diphyllobothrium latum ) is the largest parasite that infects humans. Humans become infected when they eat raw ...

[Prospective study on the impact of infantile cytomegalovirus infection on growth and development of infants].

PubMed

2010-05-01

To understand the situation of postnatal cytomegalovirus (CMV) infection in Beijing and its impact on infant. From November 2004 to March 2008, a multicenter cohort study on maternal, neonatal and infantile CMV infection was carried out in four hospitals in Beijing. Two hundred and ten infants without congenital infections were enrolled into this study. Their serum IgG antibody to CMV was determined at the age of 1 year. According to the results of CMV DNA at 12 weeks of age and the CMV IgG results at 1 year of age, they were divided into three groups, perinatal infection group, postnatal infection group and postnatal non-infection group. The information of their mothers, the data of their growth and development at 1 year of age, development quotient, their eyes and their auditory function were analyzed. The risk factors of the postnatal cytomegalovirus infection were analyzed by multi-factorial logistic regression. Of the 210 infants, 42 had perinatal infection, 98 had postnatal infection and 70 had no infection. The postnatal cytomegalovirus infection rate was 46.40%, taken into account the congenital infection rate and perinatal infection rate, the total cytomegalovirus infection rate was 66.85% at 1 year of age. The clinical manifestation, developmental status and the quotient of development from three groups at birth and at 1 year of age were analyzed. No significant difference was found. In postnatal cytomegalovirus infection group the rates of breast feeding, mixed feeding and formula feeding were 87.76%, 9.18% and 3.06%, respectively; while in no infection group the rates were 61.43%, 21.43% and 17.14%, respectively(chi(2) = 17.040, P < 0.01). CMV infection is present widely in China. Non-breast feeding is an important protective factor. Postnatal cytomegalovirus infection in infants had no significant impact on the health and development of infants.

[Clinical application of continuous douche and vacuum sealing drainage in refractory tissue, bone and joint infections after debridement].

PubMed

Yang, Ping-lin; He, Xi-jing; Li, Hao-peng; Wang, Guo-yu; Zang, Quan-jin

2010-01-01

To explore effect and the application value of continuous douche and vacuum sealing drainage (VSD) in refractory tissue, and joint infections after complete debridement. As retrospective analysis of treatment time and restoration or recurrence, from Jan. 2006 to Dec. 2007, 61 cases of refractory tissue, bone and joint infections underwent continuous douche and VSD combined with the treatment of anti-inflammatory and rehabilitation training after debridement in our hospital. The 61 patients included 39 males and 22 females with age ranging from 10 to 58 years with an average of (35 +/- 12) years, among whom 61 identified to have ankle ulcers combined with infections,open fracture combined with infections, sacrococcygeal pressure ulcers combined with infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation were 11, 15, 9, 3, 5 and 18 cases respectively. The course was from 2 weeks to 11 months with an average of 4 months. In all 61 patients,the mean healing time was 17, 36, 42, 24, 32, 29 and 28 days in ankle ulcers and infections, tibia and fibula open fracture and infections, femoral shaft fracture and infections, sacrococcygeal pressure ulcers and infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation respectively. The replacement of VSD was 1, 2-4, 3-5, 1-3, 2-4, 2-3 and 1-3 times in each group respectively. There was no wound recurrence except for 2 cases with recurrent in 61 cases with external fixation nail hole semi-pathological fracture in 1 case of femoral shaft fracture and infection and 1 case of tibia and fibula fracture and infection after follow-up at least one year. Application of continuous douche and VSD can effectively decrease incidence of complications and promote the refractory tissue, bone and joint infections wound growth, healing and considerably shorten the healing time.

Chronic Pseudomonas aeruginosa infection and respiratory muscle impairment in cystic fibrosis.

PubMed

Dassios, Theodore G; Katelari, Anna; Doudounakis, Stavros; Dimitriou, Gabriel

2014-03-01

Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is associated with increased morbidity. Chronic infection can cause limb and respiratory muscle compromise. Respiratory muscle function can be assessed via maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and the pressure-time index of the respiratory muscles (PTImus). We studied the effect of chronic P. aeruginosa infection on respiratory muscle function in patients with CF. This cross-sectional study assessed PImax, PEmax, PTImus, FEV1, FVC, maximum expiratory flow during the middle half of the FVC maneuver, body mass index, and upper arm muscle area in 122 subjects with CF, in 4 subgroups matched for age and sex at different stages of P. aeruginosa infection, according to the Leeds criteria. We compared respiratory muscle function in the subgroups according to P. aeruginosa infection state. Median PImax was significantly lower in CF subjects with chronic P. aeruginosa infection (PImax = 62 cm H2O), compared to subjects who were never infected (PImax = 86 cm H2O, P = .02), free of infection (PImax = 74 cm H2O, P = .01), or intermittently infected (PImax = 72 cm H2O, P = .02). Median PTImus was significantly increased in CF subjects with chronic P. aeruginosa infection (PTImus = .142), compared to subjects who were free of infection (PTImus = .102, P = .006). Median upper-arm muscle area was significantly lower in CF subjects with chronic P. aeruginosa infection (upper-arm muscle area = 2,219 mm(2)), compared to subjects who were never infected (2,754 mm(2), P = .03), free of infection (2,678 mm(2), P = .01), or intermittently infected (2,603 mm(2), P = .04). Multivariate logistic regression revealed P. aeruginosa state of infection as a significant determinant of PTImus (P = .03) independently of sex, upper-arm muscle area, and FEV1. CF subjects with chronic P. aeruginosa infection exhibited impaired respiratory muscle function and decreased inspiratory muscle strength, and chronic P. aeruginosa infection independently impacts respiratory muscle function in subjects with CF.

Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2)

ClinicalTrials.gov

2016-04-13

Acquired Immunodeficiency Syndrome; Lung Diseases; Cardiovascular Diseases; Heart Diseases; Heart Failure; HIV Infections; Cytomegalovirus Infections; Pneumocystis Carinii Infections; Ebstein-Barr Virus Infections

Bladder Morphology Using 2 Different Catheter Designs

ClinicalTrials.gov

2017-04-10

Urologic Injuries; Urologic Diseases; Bladder Infection; Urinary Tract Infections; Mucosal Inflammation; Mucosal Infection; Bladder Injury; Catheter-Related Infections; Catheter Complications; Catheter; Infection (Indwelling Catheter); Pelvic Floor Disorders; Urinary Incontinence

The hbhA Gene of Mycobacterium tuberculosis Is Specifically Upregulated in the Lungs but Not in the Spleens of Aerogenically Infected Mice

PubMed Central

Delogu, Giovanni; Sanguinetti, Maurizio; Posteraro, Brunella; Rocca, Stefano; Zanetti, Stefania; Fadda, Giovanni

2006-01-01

We report that hbhA is differentially regulated during Mycobacterium tuberculosis infection. Upregulation was observed in epithelial cell infection but not in macrophage infection and in the lungs but not in the spleens of infected mice, and it was greater during the early steps of infection, when bacilli disseminate from the site of primary infection. PMID:16622240

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

DOE PAGES

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

2017-11-18

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

Proteome of Aedes aegypti in response to infection and coinfection with microsporidian parasites

PubMed Central

Duncan, Alison B; Agnew, Philip; Noel, Valérie; Demettre, Edith; Seveno, Martial; Brizard, Jean-Paul; Michalakis, Yannis

2012-01-01

Hosts are frequently infected with more than one parasite or pathogen at any one time, but little is known as to how they respond to multiple immune challenges compared to those involving single infections. We investigated the proteome of Aedes aegypti larvae following infection with either Edhazardia aedis or Vavraia culicis, and coinfections involving both. They are both obligate intracellular parasites belonging to the phylum microsporidia and infect natural populations of Ae. aegypti. The results found some proteins only showing modified abundance in response to infections involving E. aedis, while others were only differentially abundant when infections involved V. culicis. Some proteins only responded with modified abundance to the coinfection condition, while others were differentially abundant in response to all three types of infection. As time since infection increased, the response to each of the single parasite infections diverged, while the response to the E. aedis and coinfection treatments converged. Some of the proteins differentially abundant in response to infection were identified. They included two vacuolar ATPases, proteins known to have a role in determining the infection success of intracellular parasites. This result suggests microsporidia could influence the infection success of other intracellular pathogens infecting vector species of mosquito, including viruses, Plasmodium and Wolbachia. PMID:22837817

Fungal Skin Infections

MedlinePlus

... Skin Infections Overview of Fungal Skin Infections Candidiasis (Yeast Infection) Dermatophytid Reaction Intertrigo Tinea Versicolor Overview of ... breasts. Common fungal skin infections are caused by yeasts (such as Candida or Malassezia furfur ) or dermatophytes , ...

Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

PubMed Central

Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

2013-01-01

The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

[Surgical site infections after cesarean section: results of a five-year prospective surveillance].

PubMed

Barbut, F; Carbonne, B; Truchot, F; Spielvogel, C; Jannet, D; Goderel, I; Lejeune, V; Milliez, J

2004-10-01

To determine the incidence of surgical site infections and to identify risk factors for infections. A prospective study of surgical site infections (SSI) after cesarean section was carried out from September 1997 to September 1998 (pilot study) and from January 2000 to August 2003, using the methodology of the American National Nosocomial Infection Surveillance System. Follow up of women was performed by midwives until discharge and during the post-natal visit. Suspected surgical site infections were confirmed by surgeons and infection control practitioners. The microbiological file of each patient was edited 30 days after cesarean section. Risk factors were analyzed using a logistic regression model. During the pilot study, infection rate was estimated at 3.2%. At multivariate analysis, factors independently associated with an increased risk of SSI were ASA score > 1, performance of cesarean section in a room not dedicated to this activity, and use of an open urine drainage system. During the following years (2000-2003), infection rates progressively decreased to reach 1.9% in 2003. Infections included superficial wound infections (involving skin and subcutaneous tissue) (47%), deep wound infections (involving deep and soft tissue (fascia and muscle) (20%) and organ/space infections (i.e. endometritis, pelvic abscess) (33%). Infections occurred after patient discharge in 47.5% of cases and diagnosis was based only on clinical findings in 30% of cases. Infected patients were hospitalized longer (median: 6 days) than non infected patients. Prospective surveillance of SSI led to better awareness of infectious problems among health care workers, to identification of risk factors and evaluation of health procedures. Surveillance contributed to a decrease in nosocomial infections.

Toxoplasma gondii antibody profile in HIV-1-infected and uninfected pregnant women and the impact on congenital toxoplasmosis diagnosis in Rio de Janeiro, Brazil.

PubMed

Fernandes, Márcia Antunes; Batista, Giovanni Inácio; Carlos, Juliano da Costa Silveira; Gomes, Ivete Martins; Azevedo, Kátia Martins Lopes de; Setúbal, Sérgio; Oliveira, Solange Artimos de; Velarde, Luis Guilhermo Coca; Cardoso, Claudete Aparecida Araújo

2012-01-01

Compare the anti-T. gondii IgG titer between HIV-1 infected and non HIV-1 infected pregnant women and report three cases of congenital toxoplasmosis resulting from reactivation of infection during pregnancy of HIV-1 infected women. This study was conducted among 2,270 pregnant women with chronic Toxoplasma gondii infection (absence of IgM and presence of IgG), including 82 HIV-1 infected and 2,188 non-infected women. The average anti-T. gondii IgG titer was 127 for the 2,188 non-HIV-1 infected women, and 227 for the 82 HIV-1-infected women (p = 0,007). These results suggested that higher anti-T. gondii IgG titers in HIV-1-infected pregnant women may not be indicative of an elevated risk for fetal infection. In this study three cases of congenital toxoplasmosis that resulted from infection reactivation during pregnancy of HIV-1-infected women were manifested by fetal death, symptomatic infection, and infant without symptoms, respectively. In two of these women, a ten-fold increase in IgG levels above used cutoff was observed (2,320 UI/mL and 3,613 UI/mL, respectively). In the third pregnant women anti-T. gondii IgG titers during pregnancy did not rise despite the occurrence of congenital toxoplasmosis (204; 198; 172 UI/mL). Congenital toxoplasmosis resulting reactivation of infection during pregnancy in the studied group leads us to believe that it is a public health problem, especially in our population, in which seroprevalence of T. gondii infections is high. These findings also suggest that special attention is necessary during pregnancy, because the serologic diagnosis may not be indicative of toxoplasmosis reactivation.

Clinical and Microbiological Characterization of Late Breast Implant Infections after Reconstructive Breast Cancer Surgery.

PubMed

Franchelli, Simonetta; Pesce, Marianna; Savaia, Serena; Marchese, Anna; Barbieri, Ramona; Baldelli, Ilaria; De Maria, Andrea

2015-10-01

Implant infections represent a relevant problem after immediate breast cancer reconstruction. In addition to difficulties in distinguishing early infections from other post-surgical complications (such as hematoma, seroma, and liponecrosis) late breast implant infections still represent a grey area of our knowledge with regards to heir definition and management. To address this issue, we prospectively monitored breast cancer patients at their center. Between February 1, 2009, and May 31, 2013, we enrolled all patients undergoing breast implant reconstruction or expander-to-prosthesis substitution. Patients without at least 6 mo of post-operative observation were excluded. We collected data from patient records including age, days from surgery (DFS), chemotherapy/radiotherapy, infecting microorganism, type of implant, antibiotic management and eventual implant removal. Sixty days from surgery were defined as the clinical threshold between early and late infection. Infections were further classified according to a graded scale into possible, probable and microbiologically proved. Seventy-eight infections were recorded out of 766 surgical procedures (10.2%). Fifty-three (67%) cases occurred early ≤60 DFS, and 25 (33%) occurred late (i.e., beyond 60 d). By defining infection types as possible, probable or proved, the majority of late infections were classified as proved (84%) compared with 56% of early infections (p=0.0014). Microbiological isolate distribution was similar in proved early infections compared with proved late infections. Among late infections, a delayed occurrence was observed after prosthesis placement compared with expander insertion. Late infections were fraught with lower treatment success rates (12% vs. 41%, p=0.009). Late infection represents a consistent proportion of infections after immediate breast implant reconstruction or prosthesis placement and bear lower chance of salvage after treatment. An increased attention is warranted to improve prevention and treatment strategies.

Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

PubMed

Souquière, Sandrine; Makuwa, Maria; Sallé, Bettina; Lepelletier, Yves; Mortreux, Franck; Hermine, Olivier; Kazanji, Mirdad

2014-04-01

Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. Copyright © 2014 Elsevier Inc. All rights reserved.

Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis.

PubMed

Motzkus, Christine A; Luckmann, Roger

2017-09-01

Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic.

Infection of Hysterectomized Mice with Chlamydia muridarum and Chlamydia trachomatis

PubMed Central

Yang, Chunfu; Whitmire, William M.; Sturdevant, Gail L.; Bock, Kevin; Moore, Ian

2017-01-01

ABSTRACT We studied infection and immunity of hysterectomized mice infected with Chlamydia muridarum and Chlamydia trachomatis to determine if there were differences between these species in their ability to infect vaginal squamous epithelial cells in vivo independently of proximal upper genital tract tissues. We found that C. muridarum readily colonized and infected vaginal squamous epithelial cells, whereas C. trachomatis did not. Primary infection of the vaginal epithelium with C. muridarum produced infections of a duration longer than that reported for normal mice. Infection resulted in an inflammatory response in the vagina characterized by neutrophils and infiltrating submucosal plasma cells consisting primarily of T cells. Despite the delayed clearance, rechallenged C. muridarum-infected mice were highly immune. Mice vaginally infected with C. muridarum produced serum and vaginal wash antibodies and an antigen-specific gamma interferon-dominated Th1-biased T cell response. By comparison, mice vaginally infected with C. trachomatis exhibited transient low-burden infections, produced no detectable tissue inflammatory response, and failed to seroconvert. We discuss how these marked differences in the biology of vaginal infection between these otherwise genetically similar species are possibly linked to pathogen-specific virulence genes and how they may influence pathology and immunity in the upper genital tract. PMID:28461392

Risk of Cerebral Palsy and Childhood Epilepsy Related to Infections before or during Pregnancy

PubMed Central

Wu, Chun S.; Pedersen, Lars H.; Miller, Jessica E.; Sun, Yuelian; Streja, Elani; Uldall, Peter; Olsen, Jørn

2013-01-01

Background and Aim Maternal infections during pregnancy have been associated with several neurological disorders in the offspring. However, given the lack of specificity for both the exposures and the outcomes, other factors related to infection such as impaired maternal immune function may be involved in the causal pathway. If impaired maternal immune function plays a role, we would expect infection before pregnancy to be associated with these neurological outcomes. Methods/Principal Findings The study population included all first-born singletons in Denmark between January 1 1982 and December 31 2004. We identified women who had hospital-recorded infections within the 5 year period before pregnancy, and women who had hospital-recorded infections during pregnancy. We grouped infections into either infections of the genitourinary system, or any other infections. Cox models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence interval (CI). Maternal infection of the genitourinary system during pregnancy was associated with an increased risk of cerebral palsy (aHR = 1.63, 95% CI: 1.34–1.98) and epilepsy (aHR = 1.27, 95% CI: 1.13–1.42) in the children, compared to children of women without infections during pregnancy. Among women without hospital-recorded infections during pregnancy, maternal infection before pregnancy was associated with an increased risk of epilepsy (aHR = 1.35, 95% CI: 1.21–1.50 for infections of the genitourinary system, and HR = 1.12, 95% CI: 1.03–1.22 for any other infections) and a slightly higher risk of cerebral palsy (aHR = 1.20, 95% CI: 0.96–1.49 for infections of the genitourinary system, and HR = 1.23, 95% CI: 1.06–1.43 for any other infections) in the children, compared to children of women without infections before (and during) pregnancy. Conclusions These findings indicate that the maternal immune system, maternal infections, or factors related to maternal immune function play a role in the observed associations between maternal infections before pregnancy and cerebral diseases in the offspring. PMID:23460873

Nodal infection in Markovian susceptible-infected-susceptible and susceptible-infected-removed epidemics on networks are non-negatively correlated

NASA Astrophysics Data System (ADS)

Cator, E.; Van Mieghem, P.

2014-05-01

By invoking the famous Fortuin, Kasteleyn, and Ginibre (FKG) inequality, we prove the conjecture that the correlation of infection at the same time between any pair of nodes in a network cannot be negative for (exact) Markovian susceptible-infected-susceptible (SIS) and susceptible-infected-removed (SIR) epidemics on networks. The truth of the conjecture establishes that the N-intertwined mean-field approximation (NIMFA) upper bounds the infection probability in any graph so that network design based on NIMFA always leads to safe protections against malware spread. However, when the infection or/and curing are not Poisson processes, the infection correlation between two nodes can be negative.

Nodal infection in Markovian susceptible-infected-susceptible and susceptible-infected-removed epidemics on networks are non-negatively correlated.

PubMed

Cator, E; Van Mieghem, P

2014-05-01

By invoking the famous Fortuin, Kasteleyn, and Ginibre (FKG) inequality, we prove the conjecture that the correlation of infection at the same time between any pair of nodes in a network cannot be negative for (exact) Markovian susceptible-infected-susceptible (SIS) and susceptible-infected-removed (SIR) epidemics on networks. The truth of the conjecture establishes that the N-intertwined mean-field approximation (NIMFA) upper bounds the infection probability in any graph so that network design based on NIMFA always leads to safe protections against malware spread. However, when the infection or/and curing are not Poisson processes, the infection correlation between two nodes can be negative.

Confirmed Transmission of Bacterial or Fungal Infection to Kidney Transplant Recipients from Donated After Cardiac Death (DCD) Donors in China: A Single-Center Analysis.

PubMed

Wan, Qiquan; Liu, Huanmiao; Ye, Shaojun; Ye, Qifa

2017-08-03

BACKGROUND We aimed to investigate blood and urine cultures of donated after cardiac death (DCD) donors and report the cases of confirmed (proven/probable) transmission of bacterial or fungal infection from donors to kidney recipients. MATERIAL AND METHODS Seventy-eight DCD donors between 2010 and 2016 were included. Sixty-one DCD donors underwent blood cultures and 22 episodes of bacteremias developed in 18 donors. Forty-three donors underwent urine cultures and 14 donors experienced 17 episodes of urinary infections. RESULTS Seven of 154 (4.5%) kidney recipients developed confirmed donor-derived bacterial or fungal infections. Inappropriate use of antibiotics in donor was a risk factor for donor-derived infection (p=0.048). The use of FK506 was more frequent in recipients without donor-derived infection than those with donor-derived infection (p=0.033). Recipients with donor-derived infection were associated with higher mortality and graft loss (42.9% and 28.6%, respectively), when compared with those without donor-derived infection (4.8% each). Three kidney recipients with donor-derived infection died; one death was due to multi-organ failure caused by Candida albicans, and two were related to rupture of the renal artery; two of them did not receive appropriate antimicrobial therapy after infection. CONCLUSIONS Our kidney recipients showed high occurrence rates of donor-derived infection. Recipients with donor-derived infection were associated with higher mortality and graft loss than those without donor-derived infection. The majority of recipients with donor-derived infection who died did not receive appropriate antimicrobial therapy after infection.

Infections and exposure to anti-infective agents and the risk of severe mental disorders: a nationwide study.

PubMed

Köhler, O; Petersen, L; Mors, O; Mortensen, P B; Yolken, R H; Gasse, C; Benros, M E

2017-02-01

Severe infections are associated with increased risks of mental disorders; however, this is the first large-scale study investigating whether infections treated with anti-infective agents in the primary care setting increase the risks of schizophrenia and affective disorders. We identified all individuals born in Denmark 1985-2002 (N = 1 015 447) and studied the association between infections treated with anti-infective agents and the subsequent risk of schizophrenia and affective disorders during 1995-2013. Cox regression analyses were adjusted for important confounders. Infections treated with anti-infective agents were associated with increased risks of schizophrenia by a hazard rate ratio (HRR) of 1.37 (95%-CI = 1.20-1.57) and affective disorders by a HRR of 1.64 (95%-CI = 1.48-1.82), fitting a dose-response and temporal relationship (P < 0.001). The excess risk was primarily driven by infections treated with antibiotics, whereas infections treated with antivirals, antimycotics, and antiparasitic agents were not significant after mutual adjustment. Individuals with infections requiring hospitalization had the highest risks for schizophrenia (HRR = 2.05; 95%-CI = 1.77-2.38) and affective disorders (HRR = 2.59; 95%-CI = 2.31-2.89). Infections treated with anti-infective agents and particularly infections requiring hospitalizations were associated with increased risks of schizophrenia and affective disorders, which may be mediated by effects of infections/inflammation on the brain, alterations of the microbiome, genetics, or other environmental factors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Timing and Predictors of Fever and Infection after Craniotomy for Epilepsy in Children

PubMed Central

Phung, Jennifer; Mathern, Gary W.; Krogstad, Paul

2013-01-01

Background Fevers and leukocytosis after pediatric craniotomy trigger diagnostic evaluation and antimicrobial therapy for possible brain infection. This study determined the incidence and predictors of infection in infants and children undergoing epilepsy neurosurgery. Methods We reviewed the postoperative course of 100 consecutive surgeries for pediatric epilepsy, comparing those with and without infections for clinical variables and daily maximum temperatures, blood WBC and differential, and cerebrospinal fluid (CSF) studies. Results Infections were the most common adverse events following these surgeries. Four patients (4%) had CSF infections and 12 had non-CSF infections (including one with distinct CSF and bloodstream infections). Most (88%) infections occurred before postoperative day 12 and were associated with larger resections involving ventriculostomies. Fevers (T ≥38.5°C) were observed in the first 12-days postsurgery in 43 % of cases, and were associated with patients undergoing hemispherectomy and multilobar resections. Fevers in the first three days postsurgery identified infections with 73% sensitivity, 69% specificity, and 70% accuracy; two (13%) patients with infections never developed fevers. Peripheral blood WBC >15,000 was found in 49% of patients and 5 cases of infections never had elevated WBC counts. WBC differential, CSF protein, RBC, WBC, and RBC/WBC ratios were poor predictors of infections. Longer hospital stays were associated with infections and hemispherectomy and multilobar resections. Patients with and without infections were equally likely to be seizure free after surgery. Conclusions Fevers and elevated blood WBC counts were common after pediatric epilepsy surgery, but CSF infections were uncommon. Positive cultures and other confirmatory microbiologic tests should drive changes in antimicrobial therapy after surgery. PMID:23348815

Diabetes mellitus and infection: an evaluation of hospital utilization and management costs in the United States.

PubMed

Korbel, Lindsey; Spencer, John David

2015-03-01

The objective of this study is to evaluate the number of diabetics that seek medical treatment in emergency departments or require hospitalization for infection management in the United States. This study also assesses the socioeconomic impact of inpatient infection management among diabetics. We accessed the Healthcare Cost and Utilization Project's Nationwide Emergency Department Sample database and the Nationwide Inpatient Sample database to perform a retrospective analysis on diabetics presenting to the emergency department or hospitalized for infection management from 2006 to 2011. Emergency Department: Since 2006, nearly 10 million diabetics were annually evaluated in the emergency department. Infection was the primary reason for presentation in 10% of these visits. Among those visits, urinary tract infection was the most common infection, accounting for over 30% of emergency department encounters for infections. Other common infections included sepsis, skin and soft tissue infections, and pneumonia. Diabetics were more than twice as likely to be hospitalized for infection management than patients without diabetes. Hospitalization: Since 2006, nearly 6 million diabetics were annually hospitalized. 8-12% of these patients were hospitalized for infection management. In 2011, the inpatient care provided to patients with DM, and infection was responsible for over $48 billion dollars in aggregate hospital charges. Diabetics commonly present to the emergency department and require hospitalization for infection management. The care provided to diabetics for infection management has a large economic impact on the United States healthcare system. More efforts are needed to develop cost-effective strategies for the prevention of infection in patients with diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

Early-life exposures and Johne's disease risk in zoo ruminants.

PubMed

Burgess, Tristan L; Witte, Carmel L; Rideout, Bruce A

2018-01-01

Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic, progressive bacterial enteritis of ruminants that can cause serious losses in both livestock and exotic species. Infection risk in exotic ruminants is associated with maternal infection status, but the effect of other herdmates on risk of infection has not been reported, to our knowledge. We conducted a retrospective cohort study to evaluate the association between MAP infection status and early-life contact with infected herdmates. The study population included 3,234 individuals representing 128 species at San Diego Zoo Global facilities between 1991 and 2010. Animal movement, health, and pathology records were used to trace enclosure-sharing contacts between members of the study population and any MAP-infected animal. Contact-days were counted by age of the reference animal and the number of unique infected individuals contacted. Herdmate infection status was stratified by stage of infection (180 d prior to diagnosis), age, and whether relevant lesions were found at autopsy. Having an infected herdmate was a strong risk factor for infection (OR = 4.4; 95% CI: 1.9-10.3), and each method of defining herdmate infection status showed significant differences in infection risk. The best predictor was number of contact-days within the first week of life, with a 2-fold increase in risk associated with each doubling in the number of contact-days (OR = 2.1; 95% CI: 1.1-4.0). We conclude that early contact with infected animals is an important predictor of MAP infection risk, although the effect size is smaller than that previously described for maternal infection status.

Marek's disease virus infection of phagocytes: a de novo in vitro infection model.

PubMed

Chakraborty, Pankaj; Vervelde, Lonneke; Dalziel, Robert G; Wasson, Peter S; Nair, Venugopal; Dutia, Bernadette M; Kaiser, Pete

2017-05-01

Marek's disease virus (MDV) is an alphaherpesvirus that induces T-cell lymphomas in chickens. Natural infections in vivo are caused by the inhalation of infected poultry house dust and it is presumed that MDV infection is initiated in the macrophages from where the infection is passed to B cells and activated T cells. Virus can be detected in B and T cells and macrophages in vivo, and both B and T cells can be infected in vitro. However, attempts to infect macrophages in vitro have not been successful. The aim of this study was to develop a model for infecting phagocytes [macrophages and dendritic cells (DCs)] with MDV in vitro and to characterize the infected cells. Chicken bone marrow cells were cultured with chicken CSF-1 or chicken IL-4 and chicken CSF-2 for 4 days to produce macrophages and DCs, respectively, and then co-cultured with FACS-sorted chicken embryo fibroblasts (CEFs) infected with recombinant MDV expressing EGFP. Infected phagocytes were identified and sorted by FACS using EGFP expression and phagocyte-specific mAbs. Detection of MDV-specific transcripts of ICP4 (immediate early), pp38 (early), gB (late) and Meq by RT-PCR provided evidence for MDV replication in the infected phagocytes. Time-lapse confocal microscopy was also used to demonstrate MDV spread in these cells. Subsequent co-culture of infected macrophages with CEFs suggests that productive virus infection may occur in these cell types. This is the first report of in vitro infection of phagocytic cells by MDV.

Hormones in Infection. Chapter 8. Alterations in Hormone Production and Utilization during Infection,

DTIC Science & Technology

1980-08-28

AD-AU90 848 ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FR--ETC F/6 6/5 HORMONES IN INFECTION . CHAPTER A. ALTERATIONS IN HORMONE PROOUC-ETC(U...PERIOD COVERED Alterations in Hormone Production and Publication Utilization during Infection S. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(e) 0. CONTRACT...the severity and duration of infections , differences related to the kind of infection , and endocrine- usociated complications of infection . I ,R

Magnetic resonance imaging of appendicular musculoskeletal infection.

PubMed

Lalam, Radhesh K; Cassar-Pullicino, Victor N; Tins, Bernhard J

2007-06-01

Appendicular skeletal infection includes osseous and extraosseous infections. Skeletal infection needs early diagnosis and appropriate management to prevent long-term morbidity. Magnetic resonance imaging is the best imaging modality to diagnose skeletal infection early in most circumstances. This article describes the role of magnetic resonance imaging in relation to the other available imaging modalities in the diagnosis of skeletal infection. Special circumstances such as diabetic foot, postoperative infection, and chronic recurrent multifocal osteomyelitis are discussed separately.

Prevalence of feline immunodeficiency virus and feline leukaemia virus among client-owned cats and risk factors for infection in Germany.

PubMed

Gleich, Sabine E; Krieger, Stefan; Hartmann, Katrin

2009-12-01

This study was conducted to determine prevalence and risk factors for retrovirus infection of infected cats in a large cat population in Germany by evaluation of 17,462 client-owned cats that were tested for the presence of feline immunodeficiency virus (FIV) antibodies or feline leukaemia virus (FeLV) antigen. The owners of a subset of 100 cats were contacted to determine their cat's survival times. Prevalence of FIV and FeLV was 3.2% and 3.6%, respectively, remaining stable for FIV, but decreasing for FeLV (6-1%) over 10 years. Median age was 6 years in FIV- and 3 years in FeLV-infected cats. Risk factors for FIV infection were male gender, older age, mixed breed, access to outdoor, aggressive behaviour, and FeLV co-infection; and for FeLV infection contact to other cats, aggressive behaviour, and FIV co-infection. Median survival time of FIV-infected cats was not significantly different to non-infected cats, whereas FeLV-infected cats had significantly shorter median survival times than non-infected cats.

Infecting Pacific Herring with Ichthyophonus sp. in the laboratory

USGS Publications Warehouse

Hershberger, Paul; Hart, Lucas; Mackenzie, Ashley; Yanney, M.L.; Conway, Carla M.; Elliott, Diane G.

2015-01-01

The protistan parasite Ichthyophonus sp. occurs in coastal populations of Pacific Herring Clupea pallasii throughout the northeast Pacific region, but the route(s) by which these planktivorous fish become infected is unknown. Several methods for establishing Ichthyophonus infections in laboratory challenges were examined. Infections were most effectively established after intraperitoneal (IP) injections with suspended parasite isolates from culture or after repeated feedings with infected fish tissues. Among groups that were offered the infected tissues, infection prevalence was greater after multiple feedings (65%) than after a single feeding (5%). Additionally, among groups that were exposed to parasite suspensions prepared from culture isolates, infection prevalence was greater after exposure by IP injection (74%) than after exposure via gastric intubation (12%); the flushing of parasite suspensions over the gills did not lead to infections in any of the experimental fish. Although the consumption of infected fish tissues is unlikely to be the primary route of Ichthyophonus sp. transmission in wild populations of Pacific Herring, this route may contribute to abnormally high infection prevalence in areas where juveniles have access to infected offal.

Epidemiology, surveillance, and prevention of hepatitis C virus infections in hemodialysis patients.

PubMed

Patel, Priti R; Thompson, Nicola D; Kallen, Alexander J; Arduino, Matthew J

2010-08-01

Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the United States; the prevalence in maintenance hemodialysis patients substantially exceeds that in the general population. In hemodialysis patients, HCV infection has been associated with increased occurrence of cirrhosis and hepatocellular carcinoma and increased mortality. Injection drug use and receipt of blood transfusions before 1992 has accounted for most prevalent HCV infections in the United States. However, HCV transmission among patients undergoing hemodialysis has been documented frequently. Outbreak investigations have implicated lapses in infection control practices as the cause of HCV infections. Preventing these infections is an emerging priority for renal care providers, public health agencies, and regulators. Adherence to recommended infection control practices is effective in preventing HCV transmission in hemodialysis facilities. In addition, adoption of routine screening to facilitate the detection of incident HCV infections and hemodialysis-related transmission is an essential component of patient safety and infection prevention efforts. This article describes the current epidemiology of HCV infection in US maintenance hemodialysis patients and prevention practices to decrease its incidence and transmission. Published by Elsevier Inc.

Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.

PubMed

Diaz, Fernando M; Knipe, David M

2016-01-15

Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved. Copyright © 2015 Elsevier Inc. All rights reserved.

Infections in hemodialysis: a concise review - Part 1: bacteremia and respiratory infections

PubMed Central

Eleftheriadis, T; Liakopoulos, V; Leivaditis, K; Antoniadi, G; Stefanidis, I

2011-01-01

Hemodialysis (HD) patients are particularly predisposed to infections. It seems that the HD procedure per se as well as disturbances in both innate and adaptive immunity significantly contribute to this susceptibility. Infections are the major cause of morbidity and the second cause of death following cardiovascular events in HD patients. Episodes of bacteremia and pneumonia account for the majority of severe infections in this population. In addition to these bacterial infections another common problem in HD units is the blood transmitted viral infections, particularly infections caused by hepatitis B virus, hepatitis C virus and Human immunodeficiency virus. A number of safety concerns exist for limiting the spread of these viral infections among HD patients and the staff of the unit. The aim of the present review is to present in a concise albeit practical form the difficult aspect of infections in HD. For practical reasons the review is separated in two parts. The present first part covers bacteremia and respiratory infections, while the second part will cover blood transmitted viral infections. PMID:21607029

Otitis

MedlinePlus

Ear infection; Infection - ear ... of the ear. The condition can be: Acute ear infection. Starts suddenly and lasts for a short period of time. It is often painful. Chronic ear infection. Occurs when the ear infection does not go ...

Variation in the reproductive potential of Schistocephalus infected male sticklebacks is associated with 11-ketotestosterone titre.

PubMed

Macnab, V; Scott, A P; Katsiadaki, I; Barber, I

2011-09-01

Parasites can impact host reproduction by interfering with host endocrine systems, but the adaptive nature of such effects is disputed. Schistocephalus solidus plerocercoids are parasites of three-spined sticklebacks Gasterosteus aculeatus that are often associated with impaired host reproduction. Here, we relate reproductive behavior and physiology to levels of the androgen 11-ketotestosterone (11KT) in naturally infected and non-infected male sticklebacks from two UK populations. In one population infected males harbored heavy infections and showed uniformly reduced 11KT titres and kidney spiggin (nesting glue protein) content compared to non-infected fish. However in a second population infection levels were more variable and males with smaller infections recorded 11KT and spiggin titres that overlapped those of non-infected fish; among infected males from this population 11KT and kidney spiggin also both correlated negatively with infection severity. Male reproductive behavior correlated closely with 11KT titre in both populations, and infected males with high 11KT levels exhibited normal reproductive behavior. Our results suggest that Schistocephalus infection per se does not block reproductive development in male sticklebacks, and that some male fish may have the ability to breed whilst infected. Our results are not consistent with the hypothesis that Schistocephalus adaptively castrates male hosts via endocrine disruption; rather they support the hypothesis that reproductive disruption is a side effect of the energetic costs of infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Diagnostic and prognostic value of procalcitonin for early intracranial infection after craniotomy

PubMed Central

Yu, Y.; Li, H.J.

2017-01-01

Intracranial infection is a common clinical complication after craniotomy. We aimed to explore the diagnostic and prognostic value of dynamic changing procalcitonin (PCT) in early intracranial infection after craniotomy. A prospective study was performed on 93 patients suspected of intracranial infection after craniotomy. Routine peripheral venous blood was collected on the day of admission, and C reactive protein (CRP) and PCT levels were measured. Cerebrospinal fluid (CSF) was collected for routine biochemical, PCT and culture assessment. Serum and CSF analysis continued on days 1, 2, 3, 5, 7, 9, and 11. The patients were divided into intracranial infection group and non-intracranial infection group; intracranial infection group was further divided into infection controlled group and infection uncontrolled group. Thirty-five patients were confirmed with intracranial infection after craniotomy according to the diagnostic criteria. The serum and cerebrospinal fluid PCT levels in the infected group were significantly higher than the non-infected group on day 1 (P<0.05, P<0.01). The area under curve of receiver operating characteristics was 0.803 for CSF PCT in diagnosing intracranial infection. The diagnostic sensitivity and specificity of CSF PCT was superior to other indicators. The serum and CSF PCT levels have potential value in the early diagnosis of intracranial infection after craniotomy. Since CSF PCT levels have higher sensitivity and specificity, dynamic changes in this parameter could be used for early detection of intracranial infection after craniotomy, combined with other biochemical indicators. PMID:28443989

Cervical Dysplasia and High-Risk Human Papillomavirus Infections among HIV-Infected and HIV-Uninfected Adolescent Females in South Africa

PubMed Central

Mrubata, Megan; Williamson, Anna-Lise; Bekker, Linda-Gail

2014-01-01

Background. HIV-infected adolescents may be at higher risk for high-grade cervical lesions than HIV-uninfected adolescents. The purpose of this study was to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear abnormalities between these two groups. Methods. In this cross-sectional study, we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV-uninfected adolescents in order to determine the prevalence of HR-HPV genotypes and cervical cytological abnormalities. Comparisons were made using Pearson χ 2 and independent-samples t-tests analyses, and associations between demographic and behavioral characteristics and HPV infections were examined. Results. HIV-infected participants were more likely to be infected with any HPV (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%; P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections. Abnormal Pap test results were more common among HIV-infected participants (28.8% versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV infection. Conclusions. HIV-infected adolescents have an increased risk of infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV infections among our participants would not be prevented by the currently available vaccinations against HPV. PMID:25389377

A Model of Superinfection of Virus-Infected Zebrafish Larvae: Increased Susceptibility to Bacteria Associated With Neutrophil Death

PubMed Central

Boucontet, Laurent; Passoni, Gabriella; Thiry, Valéry; Maggi, Ludovico; Herbomel, Philippe; Levraud, Jean-Pierre; Colucci-Guyon, Emma

2018-01-01

Enhanced susceptibility to bacterial infection in the days following an acute virus infection such as flu is a major clinical problem. Mouse models have provided major advances in understanding viral-bacterial superinfections, yet interactions of the anti-viral and anti-bacterial responses remain elusive. Here, we have exploited the transparency of zebrafish to study how viral infections can pave the way for bacterial co-infections. We have set up a zebrafish model of sequential viral and bacterial infection, using sublethal doses of Sindbis virus and Shigella flexneri bacteria. This virus induces a strong type I interferons (IFN) response, while the bacterium induces a strong IL1β and TNFα-mediated inflammatory response. We found that virus-infected zebrafish larvae showed an increased susceptibility to bacterial infection. This resulted in the death with concomitant higher bacterial burden of the co-infected fish compared to the ones infected with bacteria only. By contrast, infecting with bacteria first and virus second did not lead to increased mortality or microbial burden. By high-resolution live imaging, we showed that neutrophil survival was impaired in Sindbis-then-Shigella co-infected fish. The two types of cytokine responses were strongly induced in co-infected fish. In addition to type I IFN, expression of the anti-inflammatory cytokine IL10 was induced by viral infection before bacterial superinfection. Collectively, these observations suggest the zebrafish larva as a useful animal model to address mechanisms underlying increased bacterial susceptibility upon viral infection. PMID:29881380

Experimental evidence of hepatitis A virus infection in pigs.

PubMed

Song, Young-Jo; Park, Woo-Jung; Park, Byung-Joo; Kwak, Sang-Woo; Kim, Yong-Hyeon; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Seo, Kun-Ho; Kang, Young-Sun; Park, Choi-Kyu; Song, Jae-Young; Choi, In-Soo

2016-04-01

Hepatitis A virus (HAV) is the leading cause of acute viral hepatitis worldwide, with HAV infection being restricted to humans and nonhuman primates. In this study, HAV infection status was serologically determined in domestic pigs and experimental infections of HAV were attempted to verify HAV infectivity in pigs. Antibodies specific to HAV or HAV-like agents were detected in 3.5% of serum samples collected from pigs in swine farms. When the pigs were infected intravenously with 2 × 10(5) 50% tissue culture infectious dose (TCID50 ) of HAV, shedding of the virus in feces, viremia, and seroconversion were detected. In pigs orally infected with the same quantity of HAV, viral shedding was detected only in feces. HAV genomic RNA was detected in the liver and bile of intravenously infected pigs, but only in the bile of orally infected pigs. In further experiments, pigs were intravenously infected with 6 × 10(5) TCID50 of HAV. Shedding of HAV in feces, along with viremia and seroconversion, were confirmed in infected pigs but not in sentinel pigs. HAV genomic RNA was detected in the liver, bile, spleen, lymph node, and kidney of the infected pigs. HAV antigenomic RNA was detected in the spleen of one HAV-infected pig, suggesting HAV replication in splenic cells. Infiltration of inflammatory cells was observed in the livers of infected pigs but not in controls. This is the first experimental evidence to demonstrate that human HAV strains can infect pigs. © 2015 Wiley Periodicals, Inc.

Prosthetic vascular graft infection and prosthetic joint infection caused by Pseudomonas stutzeri.

PubMed

Bonares, Michael J; Vaisman, Alon; Sharkawy, Abdu

2016-01-01

Pseudomonas stutzeri is infrequently isolated from clinical specimens, and if isolated, more likely represents colonization or contamination rather than infection. Despite this, there are dozens of case reports which describe clinically significant P. stutzeri infections at variable sites. A 69-year-old man had a P. stutzeri infection of a prosthetic vascular graft infection, which he received in Panama City. He was successfully treated with a single antipseudomonal agent for 6 weeks and the removal of the infected vascular graft. A 70-year-old man had a P. stutzeri infection of a prosthetic joint, which was successfully treated with a single anti-pseudomonal agent for 6 weeks. There is only one other documented case of a prosthetic vascular graft infection secondary to P. stutzeri . There are 5 documented cases of P. stutzeri prosthetic joint infections. The previous cases were treated with antibiotics and variably, source control with the removal of prosthetic material. Most cases of P. stutzeri infection are due to exposure in health care settings. Immunocompromised states such as HIV or hematological and solid tumor malignancies are risk factors for P. stutzeri infection. Infections caused by P. stutzeri are far less frequent and less fatal than those caused by P. aeruginosa. The etiology of a P. stutzeri infection could be exposure to soil and water, but also contaminated material in the health care setting or an immunocompromised state. Iatrogenic infections that are secondary to health care tourism are a potential cause of fever in the returned traveler.

Induced Release of a Plant-Defense Volatile ‘Deceptively’ Attracts Insect Vectors to Plants Infected with a Bacterial Pathogen

PubMed Central

Mann, Rajinder S.; Ali, Jared G.; Hermann, Sara L.; Tiwari, Siddharth; Pelz-Stelinski, Kirsten S.; Alborn, Hans T.; Stelinski, Lukasz L.

2012-01-01

Transmission of plant pathogens by insect vectors is a complex biological process involving interactions between the plant, insect, and pathogen. Pathogen-induced plant responses can include changes in volatile and nonvolatile secondary metabolites as well as major plant nutrients. Experiments were conducted to understand how a plant pathogenic bacterium, Candidatus Liberibacter asiaticus (Las), affects host preference behavior of its psyllid (Diaphorina citri Kuwayama) vector. D. citri were attracted to volatiles from pathogen-infected plants more than to those from non-infected counterparts. Las-infected plants were more attractive to D. citri adults than non-infected plants initially; however after feeding, psyllids subsequently dispersed to non-infected rather than infected plants as their preferred settling point. Experiments with Las-infected and non-infected plants under complete darkness yielded similar results to those recorded under light. The behavior of psyllids in response to infected versus non-infected plants was not influenced by whether or not they were carriers of the pathogen. Quantification of volatile release from non-infected and infected plants supported the hypothesis that odorants mediate psyllid preference. Significantly more methyl salicylate, yet less methyl anthranilate and D-limonene, was released by infected than non-infected plants. Methyl salicylate was attractive to psyllids, while methyl anthranilate did not affect their behavior. Feeding on citrus by D. citri adults also induced release of methyl salicylate, suggesting that it may be a cue revealing location of conspecifics on host plants. Infected plants were characterized by lower levels of nitrogen, phosphorus, sulfur, zinc, and iron, as well as, higher levels of potassium and boron than non-infected plants. Collectively, our results suggest that host selection behavior of D. citri may be modified by bacterial infection of plants, which alters release of specific headspace volatiles and plant nutritional contents. Furthermore, we show in a laboratory setting that this apparent pathogen-mediated manipulation of vector behavior may facilitate pathogen spread. PMID:22457628

Infection with high proportion of multidrug-resistant bacteria in conflict-related injuries is associated with poor outcomes and excess resource consumption: a cohort study of Syrian patients treated in Jordan.

PubMed

Älgå, Andreas; Wong, Sidney; Shoaib, Muhammad; Lundgren, Kalle; Giske, Christian G; von Schreeb, Johan; Malmstedt, Jonas

2018-05-22

Armed conflicts are a major contributor to injury and death globally. Conflict-related injuries are associated with a high risk of wound infection, but it is unknown to what extent infection directly relates to sustainment of life and restoration of function. The aim of this study was to investigate the outcome and resource consumption among civilians receiving acute surgical treatment due to conflict-related injuries. Patients with and without wound infections were compared. We performed a cohort study using routinely collected data from 457 consecutive Syrian civilians that received surgical treatment for acute conflict-related injuries during 2014-2016 at a Jordanian hospital supported by Médecins Sans Frontières. We defined wound infection as clinical signs of infection verified by a positive culture. We used logistic regression models to evaluate infection-related differences in outcome and resource consumption. Wound infection was verified in 49/457 (11%) patients. Multidrug-resistance (MDR) was detected in 36/49 (73%) of patients with infection. Among patients with infection, 11/49 (22%) were amputated, compared to 37/408 (9%) without infection, crude relative risk = 2.62 (95% confidence interval 1.42-4.81). Infected patients needed 12 surgeries on average, compared to five in non-infected patients (p < .00001). Mean length of stay was 77 days for patients with infection, and 35 days for patients without infection (p = .000001). Among Syrian civilians, infected conflict-related wounds had a high prevalence of MDR bacteria. Wound infection was associated with poor outcomes and high resource consumption. These results could guide the development of antibiotic protocols and adaptations of surgical management to improve care for wound infections in conflict-related injuries. ClinicalTrials.gov ( NCT02744144 ). Registered April 13, 2016. Retrospectively registered.

[Risk factors of invasive fungal infections in patients admitted to non- hematological oncology department and pediatric intensive care unit].

PubMed

Zhao, Cheng-song; Zhao, Shun-ying; Liu, Gang; Xi-Wei, Xu

2013-08-01

To determine risk factors of invasive fungal infections (IFI) in patients admitted to non-hematological oncology department and pediatric intensive care unit (PICU), in order to improve diagnostic level of invasive fungal infections. We retrospectively assessed 85 hospitalized pediatric patients with invasive fungal infections in Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2007 to Nov.2012. All the cases were either from non-hematological oncology department or the PICU.We reviewed risk factors of invasive fungal infections. Among 85 patients, 42 had invasive candida infection, 20 invasive aspergillus infection, 21 cryptococcus infection, 1 Histoplasma capsulatum infection and 1 Mucor mucedo infection.In the 42 patients with invasive candida infection, 5 were young infants, 3 had combined immunodeficiency, 1 cellular immunodeficiency, 25 secondary infection due to long term use of corticosteroids and/or combined use of more than 2 kinds of antibiotics with primary disease, 5 prior intestinal tract surgery or chronic diarrheal disease, 1 reflux gastritis.In the 20 patients with invasive aspergillosis infection, 10 patients had chronic granulomatous disease, 5 long term use of corticosteroids ≥ 1 month, 3 long term use of corticosteroids and combined use of more than 2 kinds of antibiotics, 2 had no apparent host factors.In the 21 patients with cryptococcus infection, 2 patients had used corticosteroids ≥ 1 month, 2 had immunodeficiency mainly for lack of antibodies, while others had no apparent host factors. The child with Mucor mucedo infection had diabetes mellitus. And the one with Histoplasma capsulatum infection had immunodeficiency. High risk factors for IFI in patients admitted to non-hematological oncology department and PICU are primary immunodeficiency disease and long term use of corticosteroids and/or long term combined use of more than 2 kinds of antibiotics. Besides, young infant is also a high risk factor for invasive candida infection. Most of the cryptococcus infections and certain aspergillosis had no obvious host factors.

Induced release of a plant-defense volatile 'deceptively' attracts insect vectors to plants infected with a bacterial pathogen.

PubMed

Mann, Rajinder S; Ali, Jared G; Hermann, Sara L; Tiwari, Siddharth; Pelz-Stelinski, Kirsten S; Alborn, Hans T; Stelinski, Lukasz L

2012-01-01

Transmission of plant pathogens by insect vectors is a complex biological process involving interactions between the plant, insect, and pathogen. Pathogen-induced plant responses can include changes in volatile and nonvolatile secondary metabolites as well as major plant nutrients. Experiments were conducted to understand how a plant pathogenic bacterium, Candidatus Liberibacter asiaticus (Las), affects host preference behavior of its psyllid (Diaphorina citri Kuwayama) vector. D. citri were attracted to volatiles from pathogen-infected plants more than to those from non-infected counterparts. Las-infected plants were more attractive to D. citri adults than non-infected plants initially; however after feeding, psyllids subsequently dispersed to non-infected rather than infected plants as their preferred settling point. Experiments with Las-infected and non-infected plants under complete darkness yielded similar results to those recorded under light. The behavior of psyllids in response to infected versus non-infected plants was not influenced by whether or not they were carriers of the pathogen. Quantification of volatile release from non-infected and infected plants supported the hypothesis that odorants mediate psyllid preference. Significantly more methyl salicylate, yet less methyl anthranilate and D-limonene, was released by infected than non-infected plants. Methyl salicylate was attractive to psyllids, while methyl anthranilate did not affect their behavior. Feeding on citrus by D. citri adults also induced release of methyl salicylate, suggesting that it may be a cue revealing location of conspecifics on host plants. Infected plants were characterized by lower levels of nitrogen, phosphorus, sulfur, zinc, and iron, as well as, higher levels of potassium and boron than non-infected plants. Collectively, our results suggest that host selection behavior of D. citri may be modified by bacterial infection of plants, which alters release of specific headspace volatiles and plant nutritional contents. Furthermore, we show in a laboratory setting that this apparent pathogen-mediated manipulation of vector behavior may facilitate pathogen spread.

Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India.

PubMed

Sarkar, Jayeeta; Saha, Debraj; Bandyopadhyay, Bhaswati; Saha, Bibhuti; Kedia, Deepika; Guha Mazumder, D N; Chakravarty, Runu; Guha, Subhasish Kamal

2016-05-01

Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. the present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients. Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination. HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (p<0.001) and APRI (p<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype. HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to initiate appropriate ART regimen.

Single-Cell Analysis Uncovers Extensive Biological Noise in Poliovirus Replication

PubMed Central

Schulte, Michael B.

2014-01-01

ABSTRACT Viral infections often begin with a very small number of initiating particles. Accordingly, the outcome of an infection is likely to be affected by variability in the initial molecular interactions between virus and host. In this study, we investigated the range of outcomes upon infection of single cells. We isolated individual cells infected with poliovirus at low or high multiplicities of infection (MOI) and measured viral genomic replication and infectious viral progeny in each cell. We first determined that at 7 h postinfection, the ratio of positive to negative strands in individual cells varies from 5:1 to more than 190:1, with and average of 20:1, suggesting a significant variability in RNA synthesis. We further found that while virus genome production is higher in cells infected at a high multiplicity, the production of infectious particles is largely independent of the number of viruses infecting each cell. Strikingly, by correlating RNA and particle production within individual infections, we uncovered a significant contribution of stochastic noise to the outcome of infection. At low MOI, stochastic influences appear as kinetic effects which are most critical at the initial steps in infection. At high MOI, stochastic influences appear to dictate the virus's ability to harness cellular resources. We conclude that biological noise is a critical determinant of the overall productivity of viral infections. The distinct nature of stochasticity in the outcome of infection by low and high numbers of viral particles may have important implications for our understanding of the determinants of successful viral infections. IMPORTANCE By correlating genome and particle production in single-cell infections, we elucidated sources of noise in viral infections. When a cell was infected by only a single infectious particle, variation in the kinetics of the initial steps of replication contributed significantly to the overall productivity of the infection. Additionally, variation in the distribution of subcellular resources impacted infections initiated by one or many infectious particles. We also observed that when a cell was infected with multiple particles, more genomes were produced, while particle production was hindered by an apparent cellular resource limit. Understanding variations in viral infections may illuminate the dynamics of infection and pathogenesis and has implications for virus adaptation and evolution. PMID:24648454

Hampered performance of migratory swans: intra- and inter-seasonal effects of avian influenza virus.

PubMed

Hoye, Bethany J; Munster, Vincent J; Huig, Naomi; de Vries, Peter; Oosterbeek, Kees; Tijsen, Wim; Klaassen, Marcel; Fouchier, Ron A M; van Gils, Jan A

2016-08-01

The extent to which animal migrations shape parasite transmission networks is critically dependent on a migrant's ability to tolerate infection and migrate successfully. Yet, sub-lethal effects of parasites can be intensified through periods of increased physiological stress. Long-distance migrants may, therefore, be especially susceptible to negative effects of parasitic infection. Although a handful of studies have investigated the short-term, transmission-relevant behaviors of wild birds infected with low-pathogenic avian influenza viruses (LPAIV), the ecological consequences of LPAIV for the hosts themselves remain largely unknown. Here, we assessed the potential effects of naturally-acquired LPAIV infections in Bewick's swans, a long-distance migratory species that experiences relatively low incidence of LPAIV infection during early winter. We monitored both foraging and movement behavior in the winter of infection, as well as subsequent breeding behavior and inter-annual resighting probability over 3 years. Incorporating data on infection history we hypothesized that any effects would be most apparent in naïve individuals experiencing their first LPAIV infection. Indeed, significant effects of infection were only seen in birds that were infected but lacked antibodies indicative of prior infection. Swans that were infected but had survived a previous infection were indistinguishable from uninfected birds in each of the ecological performance metrics. Despite showing reduced foraging rates, individuals in the naïve-infected category had similar accumulated body stores to re-infected and uninfected individuals prior to departure on spring migration, possibly as a result of having higher scaled mass at the time of infection. And yet individuals in the naïve-infected category were unlikely to be resighted 1 year after infection, with 6 out of 7 individuals that never resighted again compared to 20 out of 63 uninfected individuals and 5 out of 12 individuals in the re-infected category. Collectively, our findings indicate that acute and superficially harmless infection with LPAIV may have indirect effects on individual performance and recruitment in migratory Bewick's swans. Our results also highlight the potential for infection history to play an important role in shaping ecological constraints throughout the annual cycle. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Parasites and personality in periwinkles (Littorina littorea): Infection status is associated with mean-level boldness but not repeatability.

PubMed

Seaman, Ben; Briffa, Mark

2015-06-01

We demonstrate the presence of animal personality in an inter-tidal gastropod, Littorina littorea, both in a sample of individuals infected by the trematode Cryptocotyle lingua and in an uninfected sample. On average infected individuals behaved more cautiously than individuals free of infection, but the parasite did not affect repeatability. Although the parasite is not associated with greater diversity of behaviour amongst infected individuals, infection might be associated with state-dependent personality differences between infected and non-infected individuals. Copyright © 2015. Published by Elsevier B.V.

Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

PubMed Central

Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

2013-01-01

ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

Characteristics of HPV infection in women at risk in Western Algeria.

PubMed

Masdoua, N; Boublenza, L; Hassaine, H; Ngou, J; Nahet, A; Segondy, M; Razik, F; Regagba, D; Sadouki, N; Mouhammedi, D

2017-02-01

We aimed to characterize HPV infections and cervical lesions in Western Algeria. A total of 96 cervical samples obtained from women at risk of HPV infection (HIV-1-infected or presenting with a gynecological disease) were analyzed to characterize this infection and search for cytological abnormalities. A total of 60% of women at risk had an HPV infection. The rate of high-risk HPV (HR-HPV) infection among these women was 84.5% and that of intraepithelial lesions was 29.3%. The frequency of HPV infection was significantly higher among HIV-1-infected patients. An association between the presence of HR-HPV and the polygamy of the partner was observed. An association between cytological abnormalities and the use of oral contraceptives was observed among HIV-1-infected women. Given the high frequency of HPV infection in this at risk population, close monitoring and regular gynecological screening are essential. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Immunology of Pediatric HIV Infection

PubMed Central

Tobin, Nicole H.; Aldrovandi, Grace M.

2013-01-01

Summary Most infants born to human immunodeficiency virus (HIV)-infected women escape HIV infection. Infants evade infection despite an immature immune system and, in the case of breastfeeding, prolonged repetitive, exposure. If infants become infected, the course of their infection and response to treatment differs dramatically depending upon the timing (in utero, intrapartum, or during breastfeeding) and potentially the route of their infection. Perinatally acquired HIV infection occurs during a critical window of immune development. HIV’s perturbation of this dynamic process may account for the striking age-dependent differences in HIV disease progression. HIV infection also profoundly disrupts the maternal immune system upon which infants rely for protection and immune instruction. Therefore, it is not surprising that infants who escape HIV infection still suffer adverse effects. In this review, we highlight the unique aspects of pediatric HIV transmission and pathogenesis with a focus on mechanisms by which HIV infection during immune ontogeny may allow discovery of key elements for protection and control from HIV. PMID:23772619

The relevance and applicability of oocyst prevalence as a read-out for mosquito feeding assays

NASA Astrophysics Data System (ADS)

Stone, Will J. R.; Eldering, Maarten; van Gemert, Geert-Jan; Lanke, Kjerstin H. W.; Grignard, Lynn; van de Vegte-Bolmer, Marga G.; Siebelink-Stoter, Rianne; Graumans, Wouter; Roeffen, Will F. G.; Drakeley, Chris J.; Sauerwein, Robert W.; Bousema, Teun

2013-12-01

Mosquito feeding assays are important in evaluations of malaria transmission-reducing interventions. The proportion of mosquitoes with midgut oocysts is commonly used as an outcome measure, but in natural low intensity infections the effect of oocyst non-rupture on mosquito infectivity is unclear. By identifying ruptured as well as intact oocysts, we show that in low intensity P. falciparum infections i) 66.7-96.7% of infected mosquitoes experienced oocyst rupture between 11-21 days post-infection, ii) oocyst rupture led invariably to sporozoite release, iii) oocyst rupture led to salivary gland infections in 97.8% of mosquitoes, and iv) 1250 (IQR 313-2400) salivary gland sporozoites were found per ruptured oocyst. These data show that infectivity can be predicted with reasonable certainty from oocyst prevalence in low intensity infections. High throughput methods for detecting infection in whole mosquitoes showed that 18s PCR but not circumsporozoite ELISA gave a reliable approximation of mosquito infection rates on day 7 post-infection.

Murine neonatal infection provides an efficient model for congenital ocular toxoplasmosis.

PubMed

Lahmar, Ibtissem; Guinard, Marie; Sauer, Arnaud; Marcellin, Luc; Abdelrahman, Tamer; Roux, Michel; Mousli, Marc; Moussa, Adnan; Babba, Hamouda; Pfaff, Alexander W; Candolfi, Ermanno

2010-02-01

Congenital infection is one of the most serious settings of infection with the apicomplexan parasite Toxoplasma gondii. Ocular diseases, such as retinochoroiditis, are the most common sequels of such infection in utero. However, while numerous studies have investigated the physiopathology of acquired toxoplasmosis, congenital infection has been largely neglected so far. Here, we establish a mouse model of congenital ocular toxoplasmosis. Parasite load and ocular pathology have been followed for the first 4 weeks of life. Ocular infection developed slowly compared to cerebral infection. Even after 4 weeks, not all eyes were infected and ocular parasite load was low. Therefore, we evaluated a scheme of neonatal infection to overcome problems associated with congenital infection. Development of infection and physiopathology was similar, but at a higher, more reliable rate. In summary, we have established a valuable model of neonatal ocular toxoplasmosis, which facilitates the research of the underlying physiopathological mechanisms and new diagnostic approaches of this pathology. Copyright 2009 Elsevier Inc. All rights reserved.

Dynamics of Salmonella infection of macrophages at the single cell level.

PubMed

Gog, Julia R; Murcia, Alicia; Osterman, Natan; Restif, Olivier; McKinley, Trevelyan J; Sheppard, Mark; Achouri, Sarra; Wei, Bin; Mastroeni, Pietro; Wood, James L N; Maskell, Duncan J; Cicuta, Pietro; Bryant, Clare E

2012-10-07

Salmonella enterica causes a range of diseases. Salmonellae are intracellular parasites of macrophages, and the control of bacteria within these cells is critical to surviving an infection. The dynamics of the bacteria invading, surviving, proliferating in and killing macrophages are central to disease pathogenesis. Fundamentally important parameters, however, such as the cellular infection rate, have not previously been calculated. We used two independent approaches to calculate the macrophage infection rate: mathematical modelling of Salmonella infection experiments, and analysis of real-time video microscopy of infection events. Cells repeatedly encounter salmonellae, with the bacteria often remain associated with the macrophage for more than ten seconds. Once Salmonella encounters a macrophage, the probability of that bacterium infecting the cell is remarkably low: less than 5%. The macrophage population is heterogeneous in terms of its susceptibility to the first infection event. Once infected, a macrophage can undergo further infection events, but these reinfection events occur at a lower rate than that of the primary infection.

Human Immunodeficiency Virus Infection and Male Hypogonadism: A Review.

PubMed

Kietsiriroje, Noppadol

2015-10-01

Hypogonadism is a common complication among HIV infected patients. The prevalence of hypogonadism is 30 to 50% in HIV infected men with wasting syndrome and 20 to 25% in those without wasting syndrome. HIV infection affects the entire hypothalamus-pituitary-gonadal axis via both direct and indirect effects, which are defined in four categories, 1) direct effect of HIV particles, 2) opportunistic infections, 3) HIV-related malignancy and its treatment, and 4) medications that are used for HIV infection or its opportunistic infection. The association between HIV infection, hypogonadism, and cardiovascular diseases has yet to be determined; however, there are data that HIV infection and its treatment, particularly protease inhibitors, worsened the metabolic profiles, which were surrogate markers of cardiovascular diseases. Considerably more attention should be paid to the diagnosis of hypogonadism in this group particularly because HIV infection increases both sex hormone-binding globulin and total testosterone level. Testosterone replacement shows benefits on mood, body composition, and seems to benefit the metabolic profile in HIV infected men with low body mass index.

Emerging fungal infections among children: A review on its clinical manifestations, diagnosis, and prevention

PubMed Central

Jain, Akansha; Jain, Shubham; Rawat, Swati

2010-01-01

The incidence of fungal infections is increasing at an alarming rate, presenting an enormous challenge to healthcare professionals. This increase is directly related to the growing population of immunocompromised individuals especially children resulting from changes in medical practice such as the use of intensive chemotherapy and immunosuppressive drugs. Although healthy children have strong natural immunity against fungal infections, then also fungal infection among children are increasing very fast. Virtually not all fungi are pathogenic and their infection is opportunistic. Fungi can occur in the form of yeast, mould, and dimorph. In children fungi can cause superficial infection, i.e., on skin, nails, and hair like oral thrush, candida diaper rash, tinea infections, etc., are various types of superficial fungal infections, subcutaneous fungal infection in tissues under the skin and lastly it causes systemic infection in deeper tissues. Most superficial and subcutaneous fungal infections are easily diagnosed and readily amenable to treatment. Opportunistic fungal infections are those that cause diseases exclusively in immunocompromised individuals, e.g., aspergillosis, zygomycosis, etc. Systemic infections can be life-threatening and are associated with high morbidity and mortality. Because diagnosis is difficult and the causative agent is often confirmed only at autopsy, the exact incidence of systemic infections is difficult to determine. The most frequently encountered pathogens are Candida albicans and Aspergillus spp. But other fungi such as non-albicans Candida spp. are increasingly important. PMID:21180463

Oral Candida spp carriage and periodontal diseases in HIV-infected patients in Ribeirão Preto, Brazil

PubMed Central

Lourenço, Alan Grupioni; Ribeiro, Ana Elisa Rodrigues Alves; Nakao, Cristiano; Motta, Ana Carolina Fragoso; Antonio, Luana Grupioni Lourenço; Machado, Alcyone Artioli; Komesu, Marilena Chinali

2017-01-01

ABSTRACT The majority of HIV-infected patients develop Candida spp-associated clinical oral lesions. Studies have shown that asymptomatic oral colonization of Candida spp may lead to oral lesions or become a source of disseminated infections. The aim of this study was to verify the effects of periodontal conditions on Candida spp prevalence and Candida spp carriage in the oral cavity of HIV-infected patients compared to non-infected patients. Twenty-five patients not infected with HIV and 48 HIV-infected patients were classified according to periodontal conditions as being periodontal healthy or with periodontal disease. Candida spp carriage and classification were performed in oral rinse samples. Viral load and CD4+ T lymphocyte (CD4+L) counts were performed in blood samples from HIV-infected patients. No differences in Candida spp prevalence related to HIV status or periodontal condition were detected. However, Candida spp carriage was increased in periodontally affected HIV-infected patients when compared to periodontally healthy HIV-infected patients (p= 0.04). Periodontally healthy HIV-infected patients presented Candida spp carriage in similar levels as healthy or periodontally affected non-HIV-infected patients. Candida spp carriage was correlated with CD4+L counting in HIV-infected patients. We concluded that periodontal disease is associated with increased Candida spp carriage in HIV-infected patients and may be a predisposing factor to clinical manifestations of candidiasis. PMID:28591257

Enhanced protection against Clonorchis sinensis induced by co-infection with Trichinella spiralis in rats.

PubMed

Chu, K-B; Kim, S-S; Lee, S-H; Lee, H-S; Joo, K-H; Lee, J-H; Lee, Y-S; Zheng, S; Quan, F-S

2014-10-01

Although co-infection with multiple parasites is a frequent occurrence, changes in the humoral immune response against a pre-existing parasite induced as a result of a subsequent parasitic infection remain undetermined. Here, we utilized enzyme-linked immunosorbent assay (ELISA) to investigate antibody responses, cytokine production and enhanced resistance in Clonorchis sinensis-infected rats (Sprague-Dawley) upon Trichinella spiralis infection. Higher levels of C. sinensis-specific IgG and IgA were elicited upon T. spiralis infection, and these levels remained higher than in rats infected with C. sinensis alone. Upon subsequent infection with T. spiralis, IgG antibodies against C. sinensis appeared to be rapidly boosted at day 3, and IgA antibodies were boosted at day 7. Challenge infection of C. sinensis-infected rats with T. spiralis induced substantial mucosal IgG and IgA responses in the liver and intestine and increases in antibody-secreting plasma cells in the spleen and bone marrow. Subsequent infection also appeared to confer effective control of liver C. sinensis loads, resulting in enhanced resistance. Memory B cells generated in response to C. sinensis infection were rapidly amplified into antibody-secreting cells upon T. spiralis infection. These results indicate that enhanced C. sinensis clearance induced by co-infection is associated with systemic and mucosal IgG and IgA responses. © 2014 John Wiley & Sons Ltd.

Clonorchis sinensis infection and co-infection with the hepatitis B virus are important factors associated with cholangiocarcinoma and hepatocellular carcinoma.

PubMed

Shi, Yunliang; Jiang, Zhihua; Yang, Yichao; Zheng, Peiqiu; Wei, Haiyan; Lin, Yuan; Lv, Guoli; Yang, Qingli

2017-10-01

To evaluate the contributions of Clonorchis sinensis and hepatitis B virus to the development of cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), C. sinensis and hepatitis B virus infections in 20 clinical liver cancer cases from a C. sinensis- and hepatitis B virus-epidemic region were detected. Eight cases of ICC, 11 cases of HCC and one mixed ICC and HCC case were verified by CT, pathological section and (or) observations during surgery. The C. sinensis infection was detected by stool microscopy and ELISA, and the worms and eggs found during surgery and in pathological sections also allowed for diagnoses. Hepatitis B virus infections were detected by ELISA. In the 20 cases, 18 patients were diagnosed with C. sinensis infections. Eight of the 20 patients were infected with the hepatitis B virus, and seven were co-infected with C. sinensis. In the eight ICC patients, seven were diagnosed with C. sinensis infection, and two had mixed infections with the hepatitis B virus. In the 11 HCC patients, 10 were diagnosed with C. sinensis, four had mixed infections with the hepatitis B virus, and only one HCC patient presented a single infection by the hepatitis B virus. These clinical observations revealed that C. sinensis infection and C. sinensis co-infection with the hepatitis B virus are important factors in ICC and HCC.

Oral Candida spp carriage and periodontal diseases in HIV-infected patients in Ribeirão Preto, Brazil.

PubMed

Lourenço, Alan Grupioni; Ribeiro, Ana Elisa Rodrigues Alves; Nakao, Cristiano; Motta, Ana Carolina Fragoso; Antonio, Luana Grupioni Lourenço; Machado, Alcyone Artioli; Komesu, Marilena Chinali

2017-06-01

The majority of HIV-infected patients develop Candida spp-associated clinical oral lesions. Studies have shown that asymptomatic oral colonization of Candida spp may lead to oral lesions or become a source of disseminated infections. The aim of this study was to verify the effects of periodontal conditions on Candida spp prevalence and Candida spp carriage in the oral cavity of HIV-infected patients compared to non-infected patients. Twenty-five patients not infected with HIV and 48 HIV-infected patients were classified according to periodontal conditions as being periodontal healthy or with periodontal disease. Candida spp carriage and classification were performed in oral rinse samples. Viral load and CD4+ T lymphocyte (CD4+L) counts were performed in blood samples from HIV-infected patients. No differences in Candida spp prevalence related to HIV status or periodontal condition were detected. However, Candida spp carriage was increased in periodontally affected HIV-infected patients when compared to periodontally healthy HIV-infected patients (p= 0.04). Periodontally healthy HIV-infected patients presented Candida spp carriage in similar levels as healthy or periodontally affected non-HIV-infected patients. Candida spp carriage was correlated with CD4+L counting in HIV-infected patients. We concluded that periodontal disease is associated with increased Candida spp carriage in HIV-infected patients and may be a predisposing factor to clinical manifestations of candidiasis.

ABO Blood Groups Influence Macrophage-mediated Phagocytosis of Plasmodium falciparum-infected Erythrocytes

PubMed Central

Branch, Donald R.; Hult, Annika K.; Olsson, Martin L.; Liles, W. Conrad; Cserti-Gazdewich, Christine M.; Kain, Kevin C.

2012-01-01

Erythrocyte polymorphisms associated with a survival advantage to Plasmodium falciparum infection have undergone positive selection. There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection. Based on the hypothesis that enhanced innate clearance of infected polymorphic erythrocytes is associated with protection from severe malaria, we investigated whether P. falciparum-infected O erythrocytes are more efficiently cleared by macrophages than infected A and B erythrocytes. We show that human macrophages in vitro and mouse monocytes in vivo phagocytose P. falciparum-infected O erythrocytes more avidly than infected A and B erythrocytes and that uptake is associated with increased hemichrome deposition and high molecular weight band 3 aggregates in infected O erythrocytes. Using infected A1, A2, and O erythrocytes, we demonstrate an inverse association of phagocytic capacity with the amount of A antigen on the surface of infected erythrocytes. Finally, we report that enzymatic conversion of B erythrocytes to type as O before infection significantly enhances their uptake by macrophages to observed level comparable to that with infected O wild-type erythrocytes. These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria. PMID:23071435

Co-Infection of Mosquitoes with Chikungunya and Dengue Viruses Reveals Modulation of the Replication of Both Viruses in Midguts and Salivary Glands of Aedes aegypti Mosquitoes

PubMed Central

Le Coupanec, Alain; Tchankouo-Nguetcheu, Stéphane; Roux, Pascal; Khun, Huot; Huerre, Michel; Morales-Vargas, Ronald; Enguehard, Margot; Lavillette, Dimitri; Missé, Dorothée

2017-01-01

Arthropod-borne virus (arbovirus) infections cause several emerging and resurgent infectious diseases in humans and animals. Chikungunya-affected areas often overlap with dengue-endemic areas. Concurrent dengue virus (DENV) and chikungunya virus (CHIKV) infections have been detected in travelers returning from regions of endemicity. CHIKV and DENV co-infected Aedes albopictus have also been collected in the vicinity of co-infected human cases, emphasizing the need to study co-infections in mosquitoes. We thus aimed to study the pathogen-pathogen interaction involved in these co-infections in DENV/CHIKV co-infected Aedes aegypti mosquitoes. In mono-infections, we detected CHIKV antigens as early as 4 days post-virus exposure in both the midgut (MG) and salivary gland (SG), whereas we detected DENV serotype 2 (DENV-2) antigens from day 5 post-virus exposure in MG and day 10 post-virus exposure in SG. Identical infection rates were observed for singly and co-infected mosquitoes, and facilitation of the replication of both viruses at various times post-viral exposure. We observed a higher replication for DENV-2 in SG of co-infected mosquitoes. We showed that mixed CHIKV and DENV infection facilitated viral replication in Ae. aegypti. The outcome of these mixed infections must be further studied to increase our understanding of pathogen-pathogen interactions in host cells. PMID:28777313

Co-Infection of Mosquitoes with Chikungunya and Dengue Viruses Reveals Modulation of the Replication of Both Viruses in Midguts and Salivary Glands of Aedes aegypti Mosquitoes.

PubMed

Le Coupanec, Alain; Tchankouo-Nguetcheu, Stéphane; Roux, Pascal; Khun, Huot; Huerre, Michel; Morales-Vargas, Ronald; Enguehard, Margot; Lavillette, Dimitri; Missé, Dorothée; Choumet, Valérie

2017-08-04

Arthropod-borne virus (arbovirus) infections cause several emerging and resurgent infectious diseases in humans and animals. Chikungunya-affected areas often overlap with dengue-endemic areas. Concurrent dengue virus (DENV) and chikungunya virus (CHIKV) infections have been detected in travelers returning from regions of endemicity. CHIKV and DENV co-infected Aedes albopictus have also been collected in the vicinity of co-infected human cases, emphasizing the need to study co-infections in mosquitoes. We thus aimed to study the pathogen-pathogen interaction involved in these co-infections in DENV/CHIKV co-infected Aedes aegypti mosquitoes. In mono-infections, we detected CHIKV antigens as early as 4 days post-virus exposure in both the midgut (MG) and salivary gland (SG), whereas we detected DENV serotype 2 (DENV-2) antigens from day 5 post-virus exposure in MG and day 10 post-virus exposure in SG. Identical infection rates were observed for singly and co-infected mosquitoes, and facilitation of the replication of both viruses at various times post-viral exposure. We observed a higher replication for DENV-2 in SG of co-infected mosquitoes. We showed that mixed CHIKV and DENV infection facilitated viral replication in Ae. aegypti . The outcome of these mixed infections must be further studied to increase our understanding of pathogen-pathogen interactions in host cells.

Hepatitis B and C Virus Infections Among Human Immunodeficiency Virus-Infected People Who Inject Drugs in Lahore, Pakistan.

PubMed

Mansha, Sana; Imran, Muhammad; Shah, Amir Miraj Ul Hussain; Jamal, Muhsin; Ahmed, Fayyaz; Atif, Muhammad; Saleem, Muhammmad; Safi, Sher Zaman; Fatima, Zareen; Bilal Waqar, Ahmed

2017-06-01

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major cause of the global burden of hepatitis. One of the main routes of transmission for both viruses is through exposure to infected blood, which includes sharing blood-contaminated syringes and needles. Human immunodeficiency virus (HIV) attacks the immune system and results in acquired immune deficiency syndrome and opportunistic infections. The objective of this study was to assess the epidemiology of HBV and HCV infections among HIV-infected people who inject drugs (PWID). The study enrolled 100 PWID from different addiction centers of the city of Lahore in Pakistan. All subjects were HIV-infected males and were above 16 years of age. Screening of HBV and HCV infections was performed through immunochromatography tests and enzyme-linked immunosorbent assays. The prevalence of HCV and HBV infections among the 100 HIV-infected PWID was 55% and 6%, respectively. HIV monoinfection was found in 37% of the subjects, while triple infection was detected in 2% of the subjects. Majority of the HIV-infected PWID were using heroin and Avil injections (65%). Half of the subjects had used injection drugs for 1-5 years, while 32% had used injection drugs for 6-10 years. HCV infection was more common than HBV infection among the enrolled subjects. Most of the PWID were practicing heroin and Avil injections.

Assessment of State Perinatal Hepatitis B Prevention Laws.

PubMed

Culp, Lindsay A; Caucci, Lisa; Fenlon, Nancy E; Lindley, Megan C; Nelson, Noele P; Murphy, Trudy V

2016-12-01

Identifying pregnant women with hepatitis B virus (HBV) infection for post-exposure prophylaxis of their infants is critical to preventing mother-to-child transmission of HBV infection. HBV infection in infancy results in premature death from chronic liver disease or cancer in 25% of affected infants. Universal screening of pregnant women for HBV infection is the standard of care, and in many states is supported by laws for screening and reporting these infections to public health. No recent assessment of state screening and reporting laws for HBV infection has been published. In 2014, the authors analyzed laws current through December 31, 2013 from U.S. jurisdictions (50 states and the District of Columbia) related to HBV infection and hepatitis B surface antigen screening and reporting requirements generally and for pregnant women specifically. All states require reporting of cases of HBV infection. Twenty-six states require pregnant women to be screened. Thirty-three states require public health reporting of HBV infections in pregnant women, but only 12 states require reporting pregnancy status of women with HBV infection. This assessment revealed significant variability in laws related to screening and reporting of HBV infection among pregnant women in the U.S. Implementing comprehensive HBV infection screening and reporting laws for pregnant women may facilitate identifying HBV-infected pregnant women and preventing HBV infection in their infants. Published by Elsevier Inc.

Yeast Infection (Vaginal)

MedlinePlus

Yeast infection (vaginal) Overview A vaginal yeast infection is a fungal infection that causes irritation, discharge and intense itchiness ... symptoms Causes The fungus candida causes a vaginal yeast infection. Your vagina naturally contains a balanced mix of yeast, including ...

Soil-Transmitted Helminth Infections

MedlinePlus

... 1.5 billion people, or 24% of the world’s population, are infected with soil-transmitted helminth infections worldwide. ... 1.5 billion people, or 24% of the world’s population, are infected with soil-transmitted helminth infections worldwide. ...

A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis

ClinicalTrials.gov

2017-10-12

Lung Diseases; Pulmonary Disease; Cystic Fibrosis; Cystic Fibrosis Lung; Cystic Fibrosis Pulmonary Exacerbation; Cystic Fibrosis With Exacerbation; Respiratory Tract Disease; Pulmonary Inflammation; Multi-antibiotic Resistance; Antibiotic Resistant Infection; Lung Infection; Lung Infection Pseudomonal; Lung; Infection, Atypical Mycobacterium; Burkholderia Infections; Burkholderia Cepacia Infection; Lung Inflammation

Establishing an infection control structure.

PubMed

Hambraeus, A

1995-06-01

In studies from the USA it has been shown that infection control can lower infection rates by 30%. To achieve this an infection control programme has to be given a firm structure. Judging from the opinions presented by an educational workshop within the International Federation of Infection Control (IFIC) and from the literature there is an international consensus on the basic components of hospital infection control. An infection control team, with the task of identifying areas of concern, providing or initiating work on written policies, educating and advising not only medical staff but also hospital administrators, constructors etc., constitutes the backbone of infection control. However, in most countries the infection control team, should it exist, is usually understaffed. This is false economy, a qualified medical input is a proven investment.

[Overweight, obesity and underweight in HIV infected patients].

PubMed

Kwiatkowska, Wiesława; Knysz, Brygida; Drelichowska-Durawa, Justyna; Czarnecki, Marcin; Gasiorowski, Jacek; Biłyk, Ewa; Karczewski, Maciej; Witkiewicz, Wojciech

2013-01-01

The history of HIV infection has always been associated with patient nutritional problems, initially in the form of wasting syndrome, and since the introduction of highly active antiretroviral therapy such metabolic disorders as lipodystrophy, obesity, insulin resistance, dyslipidemia that are risk factors for cardiovascular diseases have been observed. evaluation of nutritional disorders in HIV infected patients using anthropometric parameters: waist circumference, BMI (body mass index) and WHR (waist-hip ratio). the study included 72 HIV infected patients (48 men, 24 women, average age 39.4). The control group comprised 27 not infected subjects, matched for age and sex. Physical examination with measurements of body mass, height, waist and hip circumference was performed and the values of two anthropometric parameters--body mass index and waist/hip ratio were calculated. BMI in the group of HIV infected patients was significantly lower than in the control group (23.6 vs. 25.6 kg/m2, p = 0.01). These BMI values are normal, but significantly lower in HIV-infected men compared with not infected, and no differences were found between women. Infected men are less likely to be overweight and obese than not infected ones. Underweight was noted in 6.8% of patients from the study group (6% of men and 4% of women). WHR was significantly higher in the study group comparing with the healthy subjects (0.92 vs. 0.86 p = 0.002), which resulted from significantly lower hip circumference among the infected patients (93.0 vs. 98.3, p = 0.002). Waist circumference was similar in both groups (85.1 vs. 84.0). The WHR value in the infected women was a result of insignificantly higher waist circumference and lower hip circumference. HIV infected women have significantly more often too large waist circumference comparing with not infected ones (46% vs 0%, p = 0.01). In the group of infected men, the WHR value was significantly affected only by low hip circumference, and larger waist circumference was observed with the same frequency as in the control group. According to IDF criteria the central obesity was more frequent in HIV infected than in not infected patients. According to the WHO criteria it was more often diagnosed in infected women compared with not infected ones, which was not recorded in the male group. The prevalence of overweight or obesity in the studied cohort of HIV infected patients is significantly lower than among the not infected people. At the same time the HIV infection is significantly more often accompanied by features of central obesity, expressed as abnormal waist circumference value. HIV infected patients have significantly lower BMI and higher WHR values. Higher WHR in the infected group is due to low hip circumference. HIV infected women usually have normal body weight and are significantly more likely than not infected women to show the features of central obesity as a result of increased waist circumference and low hip circumference. Men infected with HIV, compared with not infected ones, are characterized by lower, normal body weight, and their significantly higher WHR is determined by low value of hip circumference. Waist circumference seems to be an appropriate diagnostic criterion for central obesity in the studied population.

Human immunodeficiency virus infection does not worsen prognosis of liver transplantation for hepatocellular carcinoma.

PubMed

Agüero, Fernando; Forner, Alejandro; Manzardo, Christian; Valdivieso, Andres; Blanes, Marino; Barcena, Rafael; Rafecas, Antoni; Castells, Lluis; Abradelo, Manuel; Torre-Cisneros, Julian; Gonzalez-Dieguez, Luisa; Salcedo, Magdalena; Serrano, Trinidad; Jimenez-Perez, Miguel; Herrero, Jose Ignacio; Gastaca, Mikel; Aguilera, Victoria; Fabregat, Juan; Del Campo, Santos; Bilbao, Itxarone; Romero, Carlos Jimenez; Moreno, Asuncion; Rimola, Antoni; Miro, Jose M

2016-02-01

The impact of human immunodeficiency virus (HIV) infection on patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) is uncertain. This study aimed to assess the outcome of a prospective Spanish nationwide cohort of HIV-infected patients undergoing LT for HCC (2002-2014). These patients were matched (age, gender, year of LT, center, and hepatitis C virus (HCV) or hepatitis B virus infection) with non-HIV-infected controls (1:3 ratio). Patients with incidental HCC were excluded. Seventy-four HIV-infected patients and 222 non-HIV-infected patients were included. All patients had cirrhosis, mostly due to HCV infection (92%). HIV-infected patients were younger (47 versus 51 years) and had undetectable HCV RNA at LT (19% versus 9%) more frequently than non-HIV-infected patients. No significant differences were detected between HIV-infected and non-HIV-infected recipients in the radiological characteristics of HCC at enlisting or in the histopathological findings for HCC in the explanted liver. Survival at 1, 3, and 5 years for HIV-infected versus non-HIV-infected patients was 88% versus 90%, 78% versus 78%, and 67% versus 73% (P = 0.779), respectively. HCV infection (hazard ratio = 7.90, 95% confidence interval 1.07-56.82) and maximum nodule diameter >3 cm in the explanted liver (hazard ratio = 1.72, 95% confidence interval 1.02-2.89) were independently associated with mortality in the whole series. HCC recurred in 12 HIV-infected patients (16%) and 32 non-HIV-infected patients (14%), with a probability of 4% versus 5% at 1 year, 18% versus 12% at 3 years, and 20% versus 19% at 5 years (P = 0.904). Microscopic vascular invasion (hazard ratio = 3.40, 95% confidence interval 1.34-8.64) was the only factor independently associated with HCC recurrence. HIV infection had no impact on recurrence of HCC or survival after LT. Our results support the indication of LT in HIV-infected patients with HCC. © 2015 by the American Association for the Study of Liver Diseases.

Confirmed Transmission of Bacterial or Fungal Infection to Kidney Transplant Recipients from Donated After Cardiac Death (DCD) Donors in China: A Single-Center Analysis

PubMed Central

Wan, Qiquan; Liu, Huanmiao; Ye, Shaojun; Ye, Qifa

2017-01-01

Background We aimed to investigate blood and urine cultures of donated after cardiac death (DCD) donors and report the cases of confirmed (proven/probable) transmission of bacterial or fungal infection from donors to kidney recipients. Material/Methods Seventy-eight DCD donors between 2010 and 2016 were included. Sixty-one DCD donors underwent blood cultures and 22 episodes of bacteremias developed in 18 donors. Forty-three donors underwent urine cultures and 14 donors experienced 17 episodes of urinary infections. Results Seven of 154 (4.5%) kidney recipients developed confirmed donor-derived bacterial or fungal infections. Inappropriate use of antibiotics in donor was a risk factor for donor-derived infection (p=0.048). The use of FK506 was more frequent in recipients without donor-derived infection than those with donor-derived infection (p=0.033). Recipients with donor-derived infection were associated with higher mortality and graft loss (42.9% and 28.6%, respectively), when compared with those without donor-derived infection (4.8% each). Three kidney recipients with donor-derived infection died; one death was due to multi-organ failure caused by Candida albicans, and two were related to rupture of the renal artery; two of them did not receive appropriate antimicrobial therapy after infection. Conclusions Our kidney recipients showed high occurrence rates of donor-derived infection. Recipients with donor-derived infection were associated with higher mortality and graft loss than those without donor-derived infection. The majority of recipients with donor-derived infection who died did not receive appropriate antimicrobial therapy after infection. PMID:28771455

Pre-operative urinary tract infection: is it a risk factor for early surgical site infection with hip fracture surgery? A retrospective analysis.

PubMed

Yassa, Rafik Rd; Khalfaoui, Mahdi Y; Veravalli, Karunakar; Evans, D Alun

2017-03-01

The aims of the current study were to determine whether pre-operative urinary tract infections in patients presenting acutely with neck of femur fractures resulted in a delay to surgery and whether such patients were at increased risk of developing post-operative surgical site infections. A retrospective review of all patients presenting with a neck of femur fracture, at a single centre over a one-year period. The hospital hip fracture database was used as the main source of data. UK University Teaching Hospital. All patients ( n  = 460) presenting across a single year study period with a confirmed hip fracture. The presence of pre-operative urinary tract infection, the timing of surgical intervention, the occurrence of post-operative surgical site infection and the pathogens identified. A total of 367 patients were operated upon within 24 hours of admission. Urinary infections were the least common cause of delay. A total of 99 patients (21.5%) had pre-operative urinary tract infection. Post-operatively, a total of 57 (12.4%) patients developed a surgical site infection. Among the latter, 31 (54.4%) did not have a pre-operative urinary infection, 23 (40.4%) patients had a pre-operative urinary tract infection, 2 had chronic leg ulcers and one patient had a pre-operative chest infection. Statistically, there was a strong relationship between pre-operative urinary tract infection and the development of post-operative surgical site infection ( p -value: 0.0005). The results of our study indicate that pre-operative urinary tract infection has a high prevalence amongst those presenting with neck of femur fractures, and this is a risk factor for the later development of post-operative surgical site infection.

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity

PubMed Central

Cao, Dianjun; Cao, Qian M.; Subramaniam, Sakthivel; Yugo, Danielle M.; Heffron, C. Lynn; Rogers, Adam J.; Kenney, Scott P.; Tian, Debin; Matzinger, Shannon R.; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-01-01

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ–specific CD4+ T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α–specific CD8+ T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E. PMID:28630341

Metabolic and cardiovascular risk profiles and hepatitis C virus infection in rural Egypt.

PubMed

Marzouk, D; Sass, J; Bakr, I; El Hosseiny, M; Abdel-Hamid, M; Rekacewicz, C; Chaturvedi, N; Mohamed, M K; Fontanet, A

2007-08-01

To investigate the relationship between lipid profiles and diabetes with past and chronic hepatitis C virus (HCV) infection among village residents of Egypt. Fasting lipids and glucose profiles were compared among adults never infected with HCV (negative HCV antibodies), infected in the past (positive HCV antibodies and negative HCV RNA) and chronically infected (positive HCV antibodies and HCV RNA). Of the 765 participants, 456 (59.6%) were female, and median age was 40 (range 25-88) years. Chronic HCV infection was present in 113 (14.8%) and past infection in 67 (8.8%). After adjustment for age and sex, participants with chronic HCV infection had lower plasma low density lipoproteins (LDL) cholesterol and triglyceride levels compared with those never infected (age and sex adjusted differences (95% CI) were -19.0 (-26.3 to -11.7) mg/dl and -26.2 (-39.0 to -13.3) mg/dl, respectively). In contrast, participants with cleared HCV infection had higher triglyceride levels compared with those never infected (age and sex adjusted difference (95% CI) was +16.0 (0.03 to 31.9) mg/dl). In multivariate analysis, participants with chronic HCV infection were more likely to have diabetes (OR 3.05, 95% CI 1.19 to 7.81) compared with those never infected, independent of LDL cholesterol levels. In conclusion, this community based study has shown that in a single population, chronic HCV infection is associated with glucose intolerance and, despite that, a favourable lipid pattern. An intriguing finding was the high triglyceride levels observed among participants with past infection, suggesting that elevated triglycerides at the time of acute infection may facilitate viral clearance.

Increased Risk of Tics in Children Infected with Enterovirus: A Nationwide Population-Based Study.

PubMed

Lin, Jiun-Nong; Lin, Cheng-Li; Yen, Hung-Rong; Yang, Chi-Hui; Lai, Chung-Hsu; Lin, Hsi-Hsun; Kao, Chia-Hung

2017-05-01

Both tics and enterovirus (EV) infections are common in children. The association between EV infections and tics has been seldom evaluated. The aim of this study was to evaluate the risk of diagnosed tics after EV infections in children. A nationwide retrospective cohort study was conducted to determine the risk of tics after EV infections by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged < 18 years with EV infection during 2000 to 2007 were enrolled. For comparison, non-EV-infected children were randomly selected and matched with EV-infected children at a 1:1 ratio according to sex, age, urbanization level, parental occupation, and the year of EV infection. All patients were followed up until the diagnosis of tics, death, loss to follow-up, withdrawal from the insurance system, or December 31, 2008. A total of 282,321 EV-infected and 282,317 non-EV-infected children were included in this study. The mean age was 2.39 years in both cohorts. The overall incidences of tics were 9.12 and 6.21 per 10,000 person-years in the EV-infected and non-EV-infected cohorts, respectively. Children with EV infection were significantly associated with an increased risk of tics compared with those without EV infection (adjusted hazard ratio, 1.38; 95% confidence interval, 1.27-1.5). Multivariable analyses showed that boys, children living in urbanized areas, children whose parents had white-collar jobs, and children with allergic rhinitis or bronchial asthma exhibited a significantly increased risk of tics. This study revealed an increased risk of tics after EV infection in children.

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

PubMed

Cao, Dianjun; Cao, Qian M; Subramaniam, Sakthivel; Yugo, Danielle M; Heffron, C Lynn; Rogers, Adam J; Kenney, Scott P; Tian, Debin; Matzinger, Shannon R; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-07-03

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4 + T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8 + T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.

Simple Epidemiological Dynamics Explain Phylogenetic Clustering of HIV from Patients with Recent Infection

PubMed Central

Volz, Erik M.; Koopman, James S.; Ward, Melissa J.; Brown, Andrew Leigh; Frost, Simon D. W.

2012-01-01

Phylogenies of highly genetically variable viruses such as HIV-1 are potentially informative of epidemiological dynamics. Several studies have demonstrated the presence of clusters of highly related HIV-1 sequences, particularly among recently HIV-infected individuals, which have been used to argue for a high transmission rate during acute infection. Using a large set of HIV-1 subtype B pol sequences collected from men who have sex with men, we demonstrate that virus from recent infections tend to be phylogenetically clustered at a greater rate than virus from patients with chronic infection (‘excess clustering’) and also tend to cluster with other recent HIV infections rather than chronic, established infections (‘excess co-clustering’), consistent with previous reports. To determine the role that a higher infectivity during acute infection may play in excess clustering and co-clustering, we developed a simple model of HIV infection that incorporates an early period of intensified transmission, and explicitly considers the dynamics of phylogenetic clusters alongside the dynamics of acute and chronic infected cases. We explored the potential for clustering statistics to be used for inference of acute stage transmission rates and found that no single statistic explains very much variance in parameters controlling acute stage transmission rates. We demonstrate that high transmission rates during the acute stage is not the main cause of excess clustering of virus from patients with early/acute infection compared to chronic infection, which may simply reflect the shorter time since transmission in acute infection. Higher transmission during acute infection can result in excess co-clustering of sequences, while the extent of clustering observed is most sensitive to the fraction of infections sampled. PMID:22761556

In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures

PubMed Central

Ni, Chao; Chen, Yuhui; Zeng, Musheng; Pei, Rongjuan; Du, Yong; Tang, Linquan; Wang, Mengyi; Hu, Yazhuo; Zhu, Hanyu; He, Meifang; Wei, Xiawei; Wang, Shan; Ning, Xiangkai; Wang, Manna; Wang, Jufang; Ma, Li; Chen, Xinwen; Sun, Qiang; Tang, Hong; Wang, Ying; Wang, Xiaoning

2015-01-01

Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs. PMID:25916549

Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

PubMed

Sarr, Abdoulaye Dieng; Eisen, Geoffrey; Guèye-Ndiaye, Aissatou; Mullins, Christopher; Traoré, Ibrahima; Dia, Mamadou Ciré; Sankalé, Jean-Louis; Faye, Diegane; Mboup, Souleymane; Kanki, Phyllis

2005-05-01

Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

Occurrence and host specificity of a neogregarine protozoan in four milkweed butterfly hosts (Danaus spp.).

PubMed

Barriga, Paola A; Sternberg, Eleanore D; Lefèvre, Thierry; de Roode, Jacobus C; Altizer, Sonia

2016-10-01

Throughout their global range, wild monarch butterflies (Danaus plexippus) are infected with the protozoan Ophryocystis elektroscirrha (OE). In monarchs, OE infection reduces pupal eclosion, adult lifespan, adult body size and flight ability. Infection of other butterfly hosts with OE is rare or unknown, and the only previously published records of OE infection were on monarch and queen butterflies (D. gilippus). Here we explored the occurrence and specificity of OE and OE-like parasites in four Danaus butterfly species. We surveyed wild D. eresimus (soldier), D. gilippus (queen), D. petilia (lesser wanderer), and D. plexippus (monarch) from five countries to determine the presence of infection. We conducted five cross-infection experiments, on monarchs and queen butterflies and their OE and OE-like parasites, to determine infection probability and the impact of infection on their hosts. Our field survey showed that OE-like parasites were present in D. gilippus, D. petilia, and D. plexippus, but were absent in D. eresimus. Infection probability varied geographically such that D. gilippus and D. plexippus populations in Puerto Rico and Trinidad were not infected or had low prevalence of infection, whereas D. plexippus from S. Florida and Australia had high prevalence. Cross-infection experiments showed evidence for host specificity, in that OE strains from monarchs were more effective at infecting monarchs than queens, and monarchs were less likely to be infected by OE-like strains from queens and lesser wanderers relative to their own natal strains. Our study showed that queens are less susceptible to OE and OE-like infection than monarchs, and that the reduction in adult lifespan following infection is more severe in monarchs than in queens. Copyright © 2016 Elsevier Inc. All rights reserved.

Avian malaria co-infections confound infectivity and vector competence assays of Plasmodium homopolare.

PubMed

Carlson, Jenny S; Nelms, Brittany; Barker, Christopher M; Reisen, William K; Sehgal, Ravinder N M; Cornel, Anthony J

2018-05-29

Currently, there are very few studies of avian malaria that investigate relationships among the host-vector-parasite triad concomitantly. In the current study, we experimentally measured the vector competence of several Culex mosquitoes for a newly described avian malaria parasite, Plasmodium homopolare. Song sparrow (Melospiza melodia) blood infected with a low P. homopolare parasitemia was inoculated into a naïve domestic canary (Serinus canaria forma domestica). Within 5 to 10 days post infection (dpi), the canary unexpectedly developed a simultaneous high parasitemic infection of Plasmodium cathemerium (Pcat6) and a low parasitemic infection of P. homopolare, both of which were detected in blood smears. During this infection period, PCR detected Pcat6, but not P. homopolare in the canary. Between 10 and 60 dpi, Pcat6 blood stages were no longer visible and PCR no longer amplified Pcat6 parasite DNA from canary blood. However, P. homopolare blood stages remained visible, albeit still at very low parasitemias, and PCR was able to amplify P. homopolare DNA. This pattern of mixed Pcat6 and P. homopolare infection was repeated in three secondary infected canaries that were injected with blood from the first infected canary. Mosquitoes that blood-fed on the secondary infected canaries developed infections with Pcat6 as well as another P. cathemerium lineage (Pcat8); none developed PCR detectable P. homopolare infections. These observations suggest that the original P. homopolare-infected songbird also had two un-detectable P. cathemerium lineages/strains. The vector and host infectivity trials in this study demonstrated that current molecular assays may significantly underreport the extent of mixed avian malaria infections in vectors and hosts.

Correlation between the neutrophil-lymphocyte count ratio and bacterial infection in patient with human immunodeficiency virus

NASA Astrophysics Data System (ADS)

Kusnadi, D.; Liwang, M. N. I.; Katu, S.; Mubin, A. H.; Halim, R.

2018-03-01

Parameters for starting antibiotic therapy such as CRP andleukocytosis are considered non-specific. Previous studies have shown the Neutrophil-Lymphocyte Count Ratio (NLCR) can serve as the basis of bacterial infection, the level of infection, and the basis of antibiotic therapy. Compared with the Procalcitonin parameter, this NLCR is rapid, an inexpensive and requires no additional sampling. To determine the correlation between The Neutrophil-LymphocyteCount Ratio to bacterial infection in HIV patients. This study was a cross-sectional observational approach to HIV subject at Wahidin Sudirohusodo and Hasanuddin University Hospital. The subjects performed routine blood, microbiology test,and blood Procalcitonin levels tests. Then performed NLCR calculations based on routine blood results. The subjects then grouped the presence or absence of bacterial infection.In 146 study subjects, there were 78 (53.4%) with bacterial infections and 68 (46.6%) without bacterial infection as controls. Subjects with bacterial infections had higher total neutrophils (84.83) compared with non-bacterial infections. Subjects with bacterial infections had total lymphocytes with an average of 8.51 lower than non-bacterial infections. Subjects with bacterial infections had higher NLCR values with an average of 12.80. The Neutrophil-Lymphocyte Count Ratio can become a marker of bacterial infection in HIV patients.

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

NASA Astrophysics Data System (ADS)

Shrinet, Jatin; Shastri, Jayanthi S.; Gaind, Rajni; Bhavesh, Neel Sarovar; Sunil, Sujatha

2016-11-01

Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management.

A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection

PubMed Central

Baccarella, Alyssa; Craft, Joshua F.; Boyle, Michelle J.; McIntyre, Tara I.; Wood, Matthew D.; Thorn, Kurt S.; Anidi, Chioma; Bayat, Aqieda; Chung, Me Ree; Hamburger, Rebecca; Kim, Chris Y.; Pearman, Emily; Pham, Jennifer; Tang, Jia J.; Boon, Louis; Kamya, Moses R.; Dorsey, Grant; Feeney, Margaret E.; Kim, Charles C.

2016-01-01

In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection. PMID:27583554

[Microbiology of pressure and vascular ulcer infections].

PubMed

Ortiz Balbuena, Jorge; García Madero, Rodrigo; Segovia Gómez, Teresa; Cantero Caballero, Miriea; Sánchez Romero, Isabel; Ramos Martínez, Antonio

2015-01-01

Pressure ulcer (PU) infection is a significant clinical problem in many elderly patients. To determine the microbiology of PU and vascular ulcer (VU) infections by conducting a cross-sectional study of outpatients treated in a chronic wounds unit over an 18 month period. Sixty six patients with PU infection and 159 patients with an infected VU were identified. The PUs were located below the knee in 36 patients (52%). Patients with pressure ulcers had a higher proportion of institutionalization, cognitive impairment, inability to walk, and sphincter incontinence. There was a greater number of infections caused by Enterobacteriaceae (52%, P=.002) and fewer S. aureus infections (24%, P<.001) in patients with a PU compared to those with those with a VU. Forty-one percent of S. aureus strains isolated in all the patients were resistant to methicillin (MRSA). The proportion of Enterobacteriaceae infections was similar in patients with infection of pelvic girdle PU and in those located below the knee. PU patients suffer a higher rate of infection by enterobacteria. The most common pathogen in UV infections is S. aureus. The proportion of MRSA infection in patients with chronic wounds is high. The microbiology of the infection in the pelvic girdle PU is similar to those located below the knee. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

Alteration of cell cycle progression by Sindbis virus infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa

We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Veromore » cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.« less

What Is Infective Endocarditis?

MedlinePlus

ANSWERS by heart Cardiovascular Conditions What Is Infective Endocarditis? Infective (bacterial) endocarditis (IE) is an infection of either the heart’s inner lining (endocardium) or the heart valves. Infective endocarditis is a serious — and sometimes fatal — illness. Two ...

Host, family and community proxies for infections potentially associated with leukaemia.

PubMed

Law, Graham Richard

2008-01-01

Three hypotheses have proposed the involvement of infections in the aetiology of childhood leukaemia, suggesting either a specific leukaemogenic infection or a series of common infections that lead to a dysregulation of the immune system. Much of the evidence for the link with infections has been based on epidemiological observations, often using proxy measures of infection. Proxy measures include population mixing, parental occupation, age distribution of incidence, spatial and space-time clustering of cases, birth order and day care during infancy. This paper discusses the proxies used and examines to what extent a commonly used proxy measure, birth order, is a fair representation of either specific infections or general infectious load. It is clear that although leukaemia, and other diseases, may be linked with infections, one needs to (1) measure specific and general infections with more accuracy and (2) understand how proxy measures relate to real infections in the population.

Actinomyces Species Isolated from Breast Infections.

PubMed

Bing, A U; Loh, S F; Morris, T; Hughes, H; Dixon, J M; Helgason, K O

2015-10-01

Actinomycosis is a chronic infection caused by Actinomyces species characterized by abscess formation, tissue fibrosis, and draining sinuses. The spectrum of infections caused by Actinomyces species ranges from classical invasive actinomycosis to a less invasive form of superficial skin and soft tissue infection. We present a review detailing all Actinomyces species isolated from breast infections in NHS Lothian between 2005 and 2013, Actinomyces species isolated from breast infections referred to the United Kingdom Anaerobe Reference Unit between 1988 and 2014, and cases describing Actinomyces breast infections published in the medical literature since 1994. Actinomyces species are fastidious organisms which can be difficult to identify and are likely to be underascertained as a cause of breast infections. Due to improved diagnostic methods, they are increasingly associated with chronic, recurrent breast infections and may play a more significant role in these infections than has previously been appreciated. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

HIV and co-infections

PubMed Central

Chang, Christina C; Crane, Megan; Zhou, JingLing; Mina, Michael; Post, Jeffrey J; Cameron, Barbara A; Lloyd, Andrew R; Jaworowski, Anthony; French, Martyn A; Lewin, Sharon R

2013-01-01

Summary Despite significant reductions in morbidity and mortality secondary to availability of effective combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection still accounts for 1.5 million deaths annually. The majority of deaths occur in sub-Saharan Africa where rates of opportunistic co-infections are disproportionately high. In this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in HIV-infected patients globally. These include co-infection with Mycobacterium tuberculosis, Cryptococcus neoformans, hepatitis B virus (HBV), hepatitis C virus (HCV), and Plasmodium falciparum. Specifically, we review the natural history of each co-infection in the setting of HIV, the specific immune defects induced by HIV, the effects of cART on the immune response to the co-infection, the pathogenesis of immune restoration disease (IRD) associated with each infection, and advances in the areas of prevention of each co-infection via vaccination. Finally, we discuss the opportunities and gaps for future research. PMID:23772618

Actinomyces Species Isolated from Breast Infections

PubMed Central

Loh, S. F.; Morris, T.; Hughes, H.; Dixon, J. M.

2015-01-01

Actinomycosis is a chronic infection caused by Actinomyces species characterized by abscess formation, tissue fibrosis, and draining sinuses. The spectrum of infections caused by Actinomyces species ranges from classical invasive actinomycosis to a less invasive form of superficial skin and soft tissue infection. We present a review detailing all Actinomyces species isolated from breast infections in NHS Lothian between 2005 and 2013, Actinomyces species isolated from breast infections referred to the United Kingdom Anaerobe Reference Unit between 1988 and 2014, and cases describing Actinomyces breast infections published in the medical literature since 1994. Actinomyces species are fastidious organisms which can be difficult to identify and are likely to be underascertained as a cause of breast infections. Due to improved diagnostic methods, they are increasingly associated with chronic, recurrent breast infections and may play a more significant role in these infections than has previously been appreciated. PMID:26224846

Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

NASA Technical Reports Server (NTRS)

Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

2003-01-01

HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

Klebsiella pneumoniae Infection Leads to a Poor Visual Outcome in Endogenous Endophthalmitis: A 12-year Experience in Southern Taiwan.

PubMed

Chen, Shih-Chou; Lee, Ying-Yen; Chen, Ya-Hsin; Lin, Huey-Shyan; Wu, Tsung-Tien; Sheu, Shwu-Jiuan

2017-12-01

To compare the characteristics, visual outcome, and prognostic factors of patients with endogenous endophthalmitis and to determine the association of endophthalmitis with Klebsiella pneumoniae infection. We retrospectively analyzed records of patients diagnosed with endogenous endophthalmitis from January 2002 to August 2013. A total of 86 patients were diagnosed with endogenous endophthalmitis; 48 patients were infected with K. pneumoniae, 28 patients were infected with other pathogens, and 10 were culture-negative. Diabetes mellitus was more prevalent among patients infected with K. pneumoniae. Liver abscess and urinary tract infection were the leading sources of infection in patients with and without a K. pneumoniae infection, respectively. In patients with endogenous endophthalmitis, poor initial vision (p<0.001) and K. pneumoniae infection (p = 0.048) were significantly associated with a poor visual outcome. Poor initial vision and K. pneumoniae infection were significantly associated with poorer visual outcome for patients with endogenous endophthalmitis.

Anticipating persistent infection

NASA Astrophysics Data System (ADS)

Moitra, Promit; Jain, Kanishk; Sinha, Sudeshna

2018-03-01

We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual within a given range. We focus on the role of synchronization in the persistence of contagion. Our key result is that higher degree of synchronization, both globally in the population and locally in the neighbourhoods, hinders persistence of infection. Importantly, we find that early short-time asynchrony appears to be a consistent precursor to future persistence of infection, and can potentially provide valuable early warnings for sustained contagion in a population patch. Thus, transient synchronization can help anticipate the long-term persistence of infection. Further we demonstrate that when the range of influence of an infected individual is wider, one obtains lower persistent infection. This counterintuitive observation can also be understood through the relation between synchronization and infection burn-out.

HIV and intestinal parasite co-infections among a Chinese population: an immunological profile

PubMed Central

2013-01-01

Background Parasite infections often result in a switch of the human body’s predominant immune reaction from T-helper 1 (Th1)-type to Th2-type. Hence, parasite infections are widely expected to accelerate the progression of human immunodeficiency virus (HIV) infections to acquired immunodeficiency syndrome (AIDS). In the People’s Republic of China, both parasitic diseases and AIDS are epidemic in certain rural areas, and co-infections are relatively common. However, no population-based studies have yet investigated the frequency of HIV and parasite co-infections, and its effects on immune responses. We studied (1) the immune status of an HIV-infected population, and (2) the effect of co-infection of HIV and intestinal parasites on selected parameters of the human immune system. Methods A total of 309 HIV-infected individuals were recruited and compared to an age-matched and sex-matched control group of 315 local HIV-negative individuals. Questionnaires were administered to all participants to obtain information on sociodemographic characteristics, sanitation habits, family income, and recent clinical manifestations. Two consecutive stool samples and 10 ml samples of venous blood were also collected from each individual for the diagnosis of parasite infections and quantitative measurements of selected cytokines and CD4+ T-lymphocytes, respectively. Results During the study period, 79 HIV-infected individuals were not under highly active antiretroviral therapy (HAART) and were thus included in our analysis; the prevalence of intestinal helminth infections was 6.3% and that of protozoa was 22.8%. The most common protozoan infections were Blastocystis hominis (B. hominis) (13.9%) and Cryptosporidium spp. (10.1%). The prevalence of Cryptosporidium spp. in HIV-infected individuals was significantly higher than that in HIV negative individuals (P < 0.05). Compared to the non-co-infected population, no significant difference was found for any of the measured immunological indicators (P > 0.05). However, the following trends were observed: IFN-γ levels were lower, but the IL-4 level was higher, in the population co-infected with HIV and helminths. In the population co-infected with HIV and B. hominis, the IL-2 level was higher. The population co-infected with HIV and Cryptosporidium spp. had markedly lower CD4+ T-lymphocyte counts. Conclusion According to the immunologic profile, co-infection with helminths is disadvantageous to HIV-infected individuals. It was associated with a shift in the Th1/Th2 balance in the same direction as that caused by the virus itself, which might indicate an acceleration of the progress from an HIV infection to AIDS. Co-infection with Cryptosporidium spp. was not associated with a significant change in immune factors but co-infection with Cryptosporidium spp. was associated with a reduced level of CD4 + T-lymphocytes, confirming the opportunistic nature of such infections. Co-infection with B. hominis, on the other hand, was associated with an antagonistic shift in the immunological profile compared to an HIV infection. PMID:23971713

[Correlation between urinary stones and urinary tract infections].

PubMed

Chen, Peilin; Zhang, Liguo; Meng, Bin

2014-05-01

To explore the correlation of urinary stones and urinary tract infections. 300 cases with urinary tract stones received in our hospital from Feb. 2010 to Oct. 2013 were chosen as study samples. Urine routine index, situation of urine positivity and urinary tract infection after surgery were analyzed while, intraoperative cotton swabs were tested after being dipped in liquid near stones. Main components of stones in non-infected and infected stone group were analyzed and compared. Data on urolithiasis was collected. 96 infected stones were found in 300 patients, accounting for 32%, which including 35 cases of E. coli (36.5%), 28 cases of Staphylococcus epidermidis (29.2%), and 15 cases of Proteus mirabilis (15.6%). Numbers of urine abnormalities, urine positivities, positive intraoperative cotton swabs and urinary tract infections in patients in the group with infected stones, were significantly higher than in the group without infected stones and the differences were statistically significant (χ² = 8.203, 73.99, 178.9, 24.26, P < 0.05). The incidence rates of hexahydrate magnesium ammonium phosphate, carbonate apatite and hydroxyapatite stones in the group with infected stones were significantly higher than those in the non-infected-rock group while the incidence rates of calcium oxalate and uric acid stones were found significantly lower than those in the non-infected-stone group, with differences statistically significant (χ² = 167.6, 21.00, 8.586, 73.17, 48.79, P < 0.05). Bacteria could cause urinary tract stones, and infected stones were always associated with urinary tract infections. Bacteria detection in patients with urinary calculi was particularly important to avoid the urinary tract infections.

Study of nosocomial isolates of Staphylococcus aureus with special reference to methicillin resistant S. aureus in a tertiary care hospital in Nepal.

PubMed

Shrestha, B; Pokhrel, B; Mohapatra, T

2009-06-01

To find out the prevalence of Staphylococcus aureus nosocomial infection and methicillin resistant S. aureus (MRSA), clinical samples from nosocomially infected patients were processed by following standard methodology in microbiology laboratory, Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Of 149 S. aureus isolates, skin infection isolates contributed a major part 72.5% making nosocomial infection by S. aureus most prevalent in skin infection followed by lower respiratory tract infection 11.41% and urinary tract infection 8.7%. Overall MRSA prevalence was 45.0%. MRSA prevalence was 42.6% in skin infection, 82.3% in lower respiratory tract infection and 30.8% in urinary tract infection. MRSA infection was found associated with lower respiratory tract infection only. Highest occurrence of nosocomial infection was observed in female surgical ward, surgical out patient department, orthopedic ward, male surgical ward and maternity ward. MRSA isolation was high from lower respiratory tract of patients admitted in intensive care unit, coronary care unit, Sub-acute intensive care unit, intermediate coronary care unit, neurology ward and post-operative ward. Whereas methicillin sensitive S. aureus (MSSA) occurrence was higher in patients admitted in orthopedic, Surgical out patient department, and female surgical ward. The occurrence of MRSA did not differ with age but MRSA was found associated with male patients and MSSA was associated with female patients. Since MRSA prevalence was high, regular surveillance of MRSA and nosocomial infections should be done and universal precautions to control nosocomial infections should be followed.

Construction of the influenza A virus transmission tree in a college-based population: co-transmission and interactions between influenza A viruses.

PubMed

Zhang, Xu-Sheng; De Angelis, Daniela

2016-01-29

Co-infection of different influenza A viruses is known to occur but how viruses interact within co-infection remains unknown. An outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza A: persons infected with pandemic A/H1N1; persons infected with seasonal A/H3N2 viruses; and persons infected with both at the same time (co-infection). This provides data to analyse the possible interaction between influenza A viruses within co-infection. We extend a statistical inference method designed for outbreaks caused by one virus to that caused by two viruses. The method uses knowledge of which subtype each case is infected with (and whether they were co-infected), contact information and symptom onset date of each case in the influenza outbreak. We then apply it to construct the most likely transmission tree during the outbreak in the college campus. Analysis of the constructed transmission tree shows that the simultaneous presence of the two influenza viruses increases the infectivity and the transmissibility of A/H1N1 virus but whether it changes the infectivity of A/H3N2 is unclear. The estimation also shows that co-transmission of both subtypes from co-infection is low and therefore co-infection cannot be sustained on its own. This study suggests that influenza A viruses within co-infected patients can interact in some ways rather than transmit independently, and this can enhance the spread of influenza A virus infection.

Community-acquired methicillin-resistant Staphylococcus aureus infections: 10-years' experience in a children's hospital in the city of Rosario, Argentina.

PubMed

Ensinck, Gabriela; Ernst, Adriana; Lazarte, Gustavo; Romagnoli, Antonela; Sguassero, Yanina; Míguez, Nanci; López Papucci, Santiago; Aletti, Alicia; Chiossone, Ana; Pigozzi, Fernanda; Pinotti, Matías; Cantador, Ana

2018-04-01

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are a common reason for consultation in pediatrics. Most of them present as skin and soft tissue infections; however, invasive infections have increased during the last decade. The main objective was to describe the clinical-epidemiological characteristics of CA-MRSA infections. The secondary objective was to compare prevalence, clinical presentation and antibiotic susceptibility with a pre-study period (1/2004-12/2007). This is a descriptive, prospective, cross-sectional study. Inclusion criteria: children who have been diagnosed with CA-MRSA infection and admitted to Hospital de Niños de Rosario between January 2008 and December 2014. Exclusion criteria: recent hospitalization, previous antibiotic treatment or surgery, comorbidities or immune compromise. Out of 728 cases of children with Staphylococcus aureus infections, 529 (73%) were due to CA-MRSA. The incidence rate of CA-MRSA infections varied from 12.2/10 000 hospital discharges in 2004 to 145/10 000 in 2014: 75% (391) were skin and soft tissue infections; 8% (43) were osteoarticular infections; 6% (30), pleuropulmonary infections; 5% (24), sepsis. There was an increase in the number of invasive infections in the second period, with no statistical significance (OR= 0.895; CI: 0.52-1.53). Gentamicin, clindamycin and erythromycin resistance remained stable throughout both periods. CA-MRSA infections were increasingly more frequent, mainly skin and soft tissue infections. An increase was observed in the number of invasive infections, with no statistical significance. Antibiotic resistance remained stable. Sociedad Argentina de Pediatría.

A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a).

PubMed

Baron, Ellen Jo; Miller, J Michael; Weinstein, Melvin P; Richter, Sandra S; Gilligan, Peter H; Thomson, Richard B; Bourbeau, Paul; Carroll, Karen C; Kehl, Sue C; Dunne, W Michael; Robinson-Dunn, Barbara; Schwartzman, Joseph D; Chapin, Kimberle C; Snyder, James W; Forbes, Betty A; Patel, Robin; Rosenblatt, Jon E; Pritt, Bobbi S

2013-08-01

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Executive summary: a guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a).

PubMed

Baron, Ellen Jo; Miller, J Michael; Weinstein, Melvin P; Richter, Sandra S; Gilligan, Peter H; Thomson, Richard B; Bourbeau, Paul; Carroll, Karen C; Kehl, Sue C; Dunne, W Michael; Robinson-Dunn, Barbara; Schwartzman, Joseph D; Chapin, Kimberle C; Snyder, James W; Forbes, Betty A; Patel, Robin; Rosenblatt, Jon E; Pritt, Bobbi S

2013-08-01

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Addressing the need for an infection prevention and control framework that incorporates the role of surveillance: a discussion paper.

PubMed

Mitchell, Brett G; Gardner, Anne

2014-03-01

To present a discussion on theoretical frameworks in infection prevention and control. Infection prevention and control programmes have been in place for several years in response to the incidence of healthcare-associated infections and their associated morbidity and mortality. Theoretical frameworks play an important role in formalizing the understanding of infection prevention activities. Discussion paper. A literature search using electronic databases was conducted for published articles in English addressing theoretical frameworks in infection prevention and control between 1980-2012. Nineteen papers that included a reference to frameworks were identified in the review. A narrative analysis of these papers was completed. Two models were identified and neither included the role of surveillance. To reduce the risk of acquiring a healthcare-associated infection, a multifaceted approach to infection prevention is required. One key component in this approach is surveillance. The review identified two infection prevention and control frameworks, yet these are rarely applied in infection prevention and control programmes. Only one framework considered the multifaceted approach required for infection prevention. It did not, however, incorporate the role of surveillance. We present a framework that incorporates the role of surveillance into a biopsychosocial approach to infection prevention and control. Infection prevention and control programmes and associated research are led primarily by nurses. There is a need for an explicit infection prevention and control framework incorporating the important role that surveillance has in infection prevention activities. This study presents one framework for further critique and discussion. © 2013 John Wiley & Sons Ltd.

Smoking and human papillomavirus (HPV) infection in the HPV in Men (HIM) study.

PubMed

Schabath, Matthew B; Villa, Luisa L; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Quiterio, Manuel; Giuliano, Anna R

2012-01-01

The influence of smoking on the natural history of HPV infection in men is not well understood. Smoking could influence the incidence and persistence of HPV infections by suppressing local immune function, increased cellular proliferation, upregulated proinflammatory factors, or induced host DNA damage resulting in increased susceptibility to infection. The purpose of this analysis is to assess prevalent HPV infections by smoking status in men, and to determine baseline risk of HPV infection associated with smoking. The HPV in Men (HIM) study is a multinational prospective study of the natural history of HPV infections in men. Samples from the coronal sulcus, glans penis, shaft, and scrotum were combined for HPV DNA testing. Multivariable logistic regression was used to assess the association between smoking and any-, oncogenic-, and nononcogenic HPV infections. Our analyses revealed that current smoking was associated with an increased risk of any HPV infection (OR = 1.19; 95% CI: 1.01-1.41) and oncogenic HPV infection (OR = 1.24; 95% CI: 1.05-1.47). However, the association between smoking and any HPV infection (OR = 1.35; 95% CI: 1.05-1.73) and oncogenic HPV infection (OR = 1.46; 95% CI: 1.11-1.92) was only evident among men reporting fewer lifetime sexual partners. These results suggest that current smokers with the fewest number of sexual partners are associated with an increased risk for oncogenic HPV infection. The relationship between smoking and HPV infection remains understudied in men; these data shed new light on the interplay between smoking, sexual activity, and risk of HPV infection.

Plastic surgeons’ self-reported operative infection rates at a Canadian academic hospital

PubMed Central

Ng, Wendy KY; Kaur, Manraj Nirmal; Thoma, Achilleas

2014-01-01

BACKGROUND: Surgical site infection rates are of great interest to patients, surgeons, hospitals and third-party payers. While previous studies have reported hospital-acquired infection rates that are nonspecific to all surgical services, there remain no overall reported infection rates focusing specifically on plastic surgery in the literature. OBJECTIVE: To estimate the reported surgical site infection rate in plastic surgery procedures over a 10-year period at an academic hospital in Canada. METHODS: A review was conducted on reported plastic surgery surgical site infection rates from 2003 to 2013, based on procedures performed in the main operating room. For comparison, prospective infection surveillance data over an eight-year period (2005 to 2013) for nonplastic surgery procedures were reviewed to estimate the overall operative surgical site infection rates. RESULTS: A total of 12,183 plastic surgery operations were performed from 2003 to 2013, with 96 surgical site infections reported, corresponding to a net operative infection rate of 0.79%. There was a 0.49% surgeon-reported infection rate for implant-based procedures. For non-plastic surgery procedures, surgical site infection rates ranged from 0.04% for cataract surgery to 13.36% for high-risk abdominal hysterectomies. DISCUSSION: The plastic surgery infection rate at the study institution was found to be <1%. This rate was equal to, or somewhat less than, surgical site infection rates. However, these results do not report patterns of infection rates germane to procedures, season, age groups or sex. To provide more in-depth knowledge of this topic, multicentre studies should be conducted. PMID:25535460

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)a

PubMed Central

Baron, Ellen Jo; Miller, J. Michael; Weinstein, Melvin P.; Richter, Sandra S.; Gilligan, Peter H.; Thomson, Richard B.; Bourbeau, Paul; Carroll, Karen C.; Kehl, Sue C.; Dunne, W. Michael; Robinson-Dunn, Barbara; Schwartzman, Joseph D.; Chapin, Kimberle C.; Snyder, James W.; Forbes, Betty A.; Patel, Robin; Rosenblatt, Jon E.; Pritt, Bobbi S.

2013-01-01

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients. PMID:23845951

Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus: implications for AIDS pathogenesis.

PubMed

Gordon, Shari N; Dunham, Richard M; Engram, Jessica C; Estes, Jacob; Wang, Zichun; Klatt, Nichole R; Paiardini, Mirko; Pandrea, Ivona V; Apetrei, Cristian; Sodora, Donald L; Lee, Ha Youn; Haase, Ashley T; Miller, Michael D; Kaur, Amitinder; Staprans, Silvija I; Perelson, Alan S; Feinberg, Mark B; Silvestri, Guido

2008-04-01

Sooty mangabeys (SMs) naturally infected with simian immunodeficiency virus (SIV) do not develop AIDS despite high levels of virus replication. At present, the mechanisms underlying this disease resistance are poorly understood. Here we tested the hypothesis that SIV-infected SMs avoid immunodeficiency as a result of virus replication occurring in infected cells that live significantly longer than human immunodeficiency virus (HIV)-infected human cells. To this end, we treated six SIV-infected SMs with potent antiretroviral therapy (ART) and longitudinally measured the decline in plasma viremia. We applied the same mathematical models used in HIV-infected individuals and observed that SMs naturally infected with SIV also present a two-phase decay of viremia following ART, with the bulk (92 to 99%) of virus replication sustained by short-lived cells (average life span, 1.06 days), and only 1 to 8% occurring in longer-lived cells. In addition, we observed that ART had a limited impact on CD4(+) T cells and the prevailing level of T-cell activation and proliferation in SIV-infected SMs. Collectively, these results suggest that in SIV-infected SMs, similar to HIV type 1-infected humans, short-lived activated CD4(+) T cells, rather than macrophages, are the main source of virus production. These findings indicate that a short in vivo life span of infected cells is a common feature of both pathogenic and nonpathogenic primate lentivirus infections and support a model for AIDS pathogenesis whereby the direct killing of infected cells by HIV is not the main determinant of disease progression.

Short-Lived Infected Cells Support Virus Replication in Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus: Implications for AIDS Pathogenesis▿

PubMed Central

Gordon, Shari N.; Dunham, Richard M.; Engram, Jessica C.; Estes, Jacob; Wang, Zichun; Klatt, Nichole R.; Paiardini, Mirko; Pandrea, Ivona V.; Apetrei, Cristian; Sodora, Donald L.; Lee, Ha Youn; Haase, Ashley T.; Miller, Michael D.; Kaur, Amitinder; Staprans, Silvija I.; Perelson, Alan S.; Feinberg, Mark B.; Silvestri, Guido

2008-01-01

Sooty mangabeys (SMs) naturally infected with simian immunodeficiency virus (SIV) do not develop AIDS despite high levels of virus replication. At present, the mechanisms underlying this disease resistance are poorly understood. Here we tested the hypothesis that SIV-infected SMs avoid immunodeficiency as a result of virus replication occurring in infected cells that live significantly longer than human immunodeficiency virus (HIV)-infected human cells. To this end, we treated six SIV-infected SMs with potent antiretroviral therapy (ART) and longitudinally measured the decline in plasma viremia. We applied the same mathematical models used in HIV-infected individuals and observed that SMs naturally infected with SIV also present a two-phase decay of viremia following ART, with the bulk (92 to 99%) of virus replication sustained by short-lived cells (average life span, 1.06 days), and only 1 to 8% occurring in longer-lived cells. In addition, we observed that ART had a limited impact on CD4+ T cells and the prevailing level of T-cell activation and proliferation in SIV-infected SMs. Collectively, these results suggest that in SIV-infected SMs, similar to HIV type 1-infected humans, short-lived activated CD4+ T cells, rather than macrophages, are the main source of virus production. These findings indicate that a short in vivo life span of infected cells is a common feature of both pathogenic and nonpathogenic primate lentivirus infections and support a model for AIDS pathogenesis whereby the direct killing of infected cells by HIV is not the main determinant of disease progression. PMID:18216113

Urinary Tract Infections (For Teens)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Urinary Tract Infections KidsHealth / For Teens / Urinary Tract Infections What's in ... especially girls — visit a doctor. What Is a Urinary Tract Infection? A bacterial urinary tract infection (UTI) is the ...

Pseudomonal breast infection

PubMed Central

Rastall, S; Catchpole, C; Bright-Thomas, R; Thrush, S

2010-01-01

Breast infection and breast sepsis secondary to Pseudomonas aeruginosa is uncommon. We report two cases of pseudomonal breast infection leading to septic shock and abscess formation in women with non-responding breast infection. The management of breast infection is broad-spectrum antibiotics and ultrasound with aspiration of any collection. To treat breast infection effectively, the causative organism must be isolated to enable appropriate antibiotic therapy. PMID:20412664

Influence of staff infection control training on infection-related quality measures in US nursing homes.

PubMed

Kaur, Jasjit; Stone, Patricia W; Travers, Jasmine L; Cohen, Catherine C; Herzig, Carolyn T A

2017-09-01

Health care-associated infections are a leading cause of morbidity and mortality in US nursing home residents. Ongoing training of nursing home staff is vital to the implementation of infection prevention and control processes. Our aim was to describe associations between methods, frequency, and timing of staff infection prevention and control training and infection-related quality measures. In this national survey of nursing homes, timing of staff infection prevention and control training was associated with reduced indwelling urinary catheter use. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

An unusual renal manifestation of chronic HBV infection.

PubMed

Aravindan, Ananthakrishnapuram; Yong, Jim; Killingsworth, Murray; Strasser, Simone; Suranyi, Michael

2010-08-01

Hepatitis B viral infection is usually a self-limiting disease in immunocompetent individuals. Chronic infection can be seen in up to 5% of infected patients. Renal manifestations of chronic HBV infection are usually glomerular. We describe here an uncommon presentation of a patient with chronic HBV infection with very high viral load and rapidly progressive renal failure. Renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of HBV infection. Entecavir treatment slowed down the progression of his renal disease. Tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with HBV infection. Early antiviral treatment may halt the progression of renal disease.

A Re-entrant Phase Transition in the Survival of Secondary Infections on Networks

NASA Astrophysics Data System (ADS)

Moore, Sam; Mörters, Peter; Rogers, Tim

2018-06-01

We study the dynamics of secondary infections on networks, in which only the individuals currently carrying a certain primary infection are susceptible to the secondary infection. In the limit of large sparse networks, the model is mapped to a branching process spreading in a random time-sensitive environment, determined by the dynamics of the underlying primary infection. When both epidemics follow the Susceptible-Infective-Recovered model, we show that in order to survive, it is necessary for the secondary infection to evolve on a timescale that is closely matched to that of the primary infection on which it depends.

Resistance of human plasmacytoid dendritic CAL-1 cells to infection with lymphocytic choriomeningitis virus (LCMV) is caused by restricted virus cell entry, which is overcome by contact of CAL-1 cells with LCMV-infected cells.

PubMed

Iwasaki, Masaharu; Sharma, Siddhartha M; Marro, Brett S; de la Torre, Juan C

2017-11-01

Plasmacytoid dendritic cells (pDCs), a main source of type I interferon in response to viral infection, are an early cell target during lymphocytic choriomeningitis virus (LCMV) infection, which has been associated with the LCMV's ability to establish chronic infections. Human blood-derived pDCs have been reported to be refractory to ex vivo LCMV infection. In the present study we show that human pDC CAL-1 cells are refractory to infection with cell-free LCMV, but highly susceptible to infection with recombinant LCMVs carrying the surface glycoprotein of VSV, indicating that LCMV infection of CAL-1 cells is restricted at the cell entry step. Co-culture of uninfected CAL-1 cells with LCMV-infected HEK293 cells enabled LCMV to infect CAL-1 cells. This cell-to-cell spread required direct cell-cell contact and did not involve exosome pathway. Our findings indicate the presence of a novel entry pathway utilized by LCMV to infect pDC. Copyright © 2017. Published by Elsevier Inc.

Kinetic Study of Yellow Fever 17DD Viral Infection in Gallus gallus domesticus Embryos

PubMed Central

Manso, Pedro Paulo de Abreu; E. P. Dias de Oliveira, Bárbara Cristina; Carvalho de Sequeira, Patrícia; Rodrigues Maia de Souza, Yuli; dos Santos Ferro, Jessica Maria; da Silva, Igor José; Gonçalves Caputo, Luzia Fátima; Tavares Guedes, Priscila; Araujo Cunha dos Santos, Alexandre; da Silva Freire, Marcos; Bonaldo, Myrna Cristina; Pelajo Machado, Marcelo

2016-01-01

Yellow fever continues to be an important epidemiological problem in Africa and South America even though the disease can be controlled by vaccination. The vaccine has been produced since 1937 and is based on YFV 17DD chicken embryo infection. However, little is known about the histopathological background of virus infection and replication in this model. Here we show by morphological and molecular methods (brightfield and confocal microscopies, immunofluorescence, nested-PCR and sequencing) the kinetics of YFV 17DD infection in chicken embryos with 9 days of development, encompassing 24 to 96 hours post infection. Our principal findings indicate that the main cells involved in virus production are myoblasts with a mesenchymal shape, which also are the first cells to express virus proteins in Gallus gallus embryos at 48 hours after infection. At 72 hours post infection, we observed an increase of infected cells in embryos. Many sites are thus affected in the infection sequence, especially the skeletal muscle. We were also able to confirm an increase of nervous system infection at 96 hours post infection. Our data contribute to the comprehension of the pathogenesis of YF 17DD virus infection in Gallus gallus embryos. PMID:27158977

Use of a patient hand hygiene protocol to reduce hospital-acquired infections and improve nurses' hand washing.

PubMed

Fox, Cherie; Wavra, Teresa; Drake, Diane Ash; Mulligan, Debbie; Bennett, Yvonne Pacheco; Nelson, Carla; Kirkwood, Peggy; Jones, Louise; Bader, Mary Kay

2015-05-01

Critically ill patients are at marked risk of hospital-acquired infections, which increase patients' morbidity and mortality. Registered nurses are the main health care providers of physical care, including hygiene to reduce and prevent hospital-acquired infections, for hospitalized critically ill patients. To investigate a new patient hand hygiene protocol designed to reduce hospital-acquired infection rates and improve nurses' hand-washing compliance in an intensive care unit. A preexperimental study design was used to compare 12-month rates of 2 common hospital-acquired infections, central catheter-associated bloodstream infection and catheter-associated urinary tract infection, and nurses' hand-washing compliance measured before and during use of the protocol. Reductions in 12-month infection rates were reported for both types of infections, but neither reduction was statistically significant. Mean 12-month nurse hand-washing compliance also improved, but not significantly. A hand hygiene protocol for patients in the intensive care unit was associated with reductions in hospital-acquired infections and improvements in nurses' hand-washing compliance. Prevention of such infections requires continuous quality improvement efforts to monitor lasting effectiveness as well as investigation of strategies to eliminate these infections. ©2015 American Association of Critical-Care Nurses.

Decreasing Catheter-Associated Urinary Tract Infections in the Neurological Intensive Care Unit: One Unit's Success.

PubMed

Richards, Brenda; Sebastian, Bindhu; Sullivan, Hillary; Reyes, Rosemarie; D'Agostino, John F; Hagerty, Thomas

2017-06-01

Catheter-associated urinary tract infections are preventable adverse outcomes that increase hospital morbidity, mortality, and costs. These infections are particularly prevalent in intensive care units. To describe the success of an 18-bed neurological intensive care unit in using several nurse-implemented strategies that reduced the number of catheter-associated urinary tract infections. A prospective, interventional design with application of evidence-based practices to reduce catheter-associated urinary tract infections was used. Before implementation of the strategies, 40 catheter-associated urinary tract infections were reported for 2012 and 38 for 2013. The standardized infection ratio was 2.04 for 2012 (95% CI, 1.456-2.775) and 2.34 (95% CI, 1.522-3.312) for 2013. After implementation of the strategies, significantly fewer catheter-associated urinary tract infections were reported. In 2014, a total of 15 infections were reported, and the standardized infection ratio was less than 1.0 (95% CI, 0.685-1.900). Application of current evidence-based practices resulted in a substantial decrease in the number of catheter-associated urinary tract infections and a lower standardized infection ratio. These findings support current recommendations for "bundling" to maximize outcomes. ©2017 American Association of Critical-Care Nurses.

Determination of Viremia and Concentration of Circulating Nonstructural Protein 1 in Patients Infected with Dengue Virus in Mexico

PubMed Central

de la Cruz-Hernández, Sergio I.; Flores-Aguilar, Hilario; González-Mateos, Silvia; López-Martinez, Irma; Alpuche-Aranda, Celia; Ludert, Juan E.; del Angel, Rosa M.

2013-01-01

Higher levels of viremia and circulating nonstructural protein 1 (NS1) have been associated with dengue disease severity. In this study, viremia and circulating NS1 levels were determined in 225 serum samples collected from patients in Mexico infected with dengue virus serotypes 1 and 2 (DENV-1 and DENV-2). Patients with dengue hemorrhagic fever (DHF) who were infected with DENV-1 showed higher levels of circulating NS1 than patients with dengue fever (DF) (P = 0.0175). Moreover, NS1 levels were higher in patients with primary infections with DENV-1 than in patient infected with DENV-2 (P < 0.0001) and in patients with primary infections with DENV-2 than in patients with secondary infections with DENV-2 (P = 0.0051). Unexpectedly, viremia levels were higher in patients with DF than in those with DHF infected with either DENV-1 or DENV-2 (P = 0.0019 and P = 0.001, respectively) and in patients with primary infections than those with secondary DENV-2 infections (P < 0.0001). Results indicate that levels of circulating NS1 vary according to the infecting serotype, immunologic status (primary or secondary infection), and dengue disease severity. PMID:23339203

Determination of viremia and concentration of circulating nonstructural protein 1 in patients infected with dengue virus in Mexico.

PubMed

de la Cruz-Hernández, Sergio I; Flores-Aguilar, Hilario; González-Mateos, Silvia; López-Martinez, Irma; Alpuche-Aranda, Celia; Ludert, Juan E; del Angel, Rosa M

2013-03-01

Higher levels of viremia and circulating nonstructural protein 1 (NS1) have been associated with dengue disease severity. In this study, viremia and circulating NS1 levels were determined in 225 serum samples collected from patients in Mexico infected with dengue virus serotypes 1 and 2 (DENV-1 and DENV-2). Patients with dengue hemorrhagic fever (DHF) who were infected with DENV-1 showed higher levels of circulating NS1 than patients with dengue fever (DF) (P = 0.0175). Moreover, NS1 levels were higher in patients with primary infections with DENV-1 than in patient infected with DENV-2 (P < 0.0001) and in patients with primary infections with DENV-2 than in patients with secondary infections with DENV-2 (P = 0.0051). Unexpectedly, viremia levels were higher in patients with DF than in those with DHF infected with either DENV-1 or DENV-2 (P = 0.0019 and P = 0.001, respectively) and in patients with primary infections than those with secondary DENV-2 infections (P < 0.0001). Results indicate that levels of circulating NS1 vary according to the infecting serotype, immunologic status (primary or secondary infection), and dengue disease severity.

Can the route of Toxoplasma gondii infection affect the ophthalmic outcomes?

PubMed

Ashour, Dalia S; Saad, Abeer E; Bakary, Reda H El; Barody, Mohamed A El

2018-06-14

Ocular toxoplasmosis is the most common cause of retinochoroiditis worldwide in humans. Some studies highlighted the idea that ocular lesions differ according to the route of infection but none of them mimicked the natural route. The current study aimed to investigate the ophthalmic outcomes in congenital and oral routes of infection with Toxoplasma in experimental animals. Mice were divided into three groups; group I: congenital infection, group II: acquired oral infection and group III: non-infected. We used Me49 chronic low-virulence T. gondii strain. We found that retina is the most affected part in both modes of infections. However, the retinal changes are different and more pronounced in case of congenital infection. The congenitally infected mice showed retinal lesions e.g. total detachment of retinal pigment epithelium from the photoreceptor layer and irregular arrangement of retinal layers. More severe damage was observed in mice infected early in pregnancy. While the postnatal orally infected mice showed fewer changes. In conclusion, the routes of Toxoplasma infection affect the ophthalmic outcomes and this may be the case in human disease. Although both are vision threatening, it seems that the prognosis of postnatal acquired ocular toxoplasmosis is better than that of congenital disease.

Vector-borne pathogens in dogs from Costa Rica: first molecular description of Babesia vogeli and Hepatozoon canis infections with a high prevalence of monocytic ehrlichiosis and the manifestations of co-infection.

PubMed

Rojas, Alicia; Rojas, Diana; Montenegro, Víctor; Gutiérrez, Ricardo; Yasur-Landau, Daniel; Baneth, Gad

2014-01-31

Infection with canine vector-borne pathogens was evaluated in dogs from four different regions of Costa Rica by PCR. Demographic data, clinical signs, packed cell volume values, and the presence of tick infestation were recorded for each dog. Forty seven percent (69/146) of the dogs were infected with at least one pathogen and 12% were co-infected with two pathogens. Ehrlichia canis was detected in 34%, Anaplasma platys in 10%, Babesia vogeli in 8%, and Hepatozoon canis in 7.5% of the blood samples. No infection was detected with Leishmania spp. in blood, skin scrapings or conjunctival swabs. Thirty percent of the dogs presented at least one clinical sign compatible with vector-borne disease, and of those, 66% were infected with a pathogen. Subclinical infections were determined in 58% of the infected dogs including 82% (9/11), 58% (29/50), 42% (5/12) and 36% (5/14) of the dogs with H. canis, E. canis, B. vogeli and A. platys infections, respectively. A distinct relationship was found between infection and anemia. The mean PCV values were 34.4% in dogs with no infection, 31.5% in those who had a single infection and 23% in those with co-infection. Co-infected dogs had significantly lower PCV values compared to non-infected and single-infected dogs (p<0.0001). Thirty five percent (51/146) of the dogs were infested with ticks, 82% of them were infested with Rhipicephalus sanguineus sensu lato and 18% with Amblyomma ovale. Dogs infected with A. platys, B. vogeli, or E. canis were significantly associated with R. sanguineus s.l. infestation (p<0.029). This is the first description of infections with B. vogeli and H. canis in Costa Rica as well as in Central America. The results of this study indicate that multiple vector-borne pathogens responsible for severe diseases infect dogs in Costa Rica and therefore, increased owner and veterinarian awareness are needed. Moreover, prevention of tick infestation is recommended to decrease the threat of these diseases to the canine population. Copyright © 2013 Elsevier B.V. All rights reserved.

Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis

PubMed Central

Chan, Grace J.; Lee, Anne CC; Baqui, Abdullah H.; Tan, Jingwen; Black, Robert E.

2013-01-01

Background Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period. Methods and Findings We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors. Conclusions Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis. Please see later in the article for the Editors' Summary PMID:23976885

Distinct Macrophage Fates after in vitro Infection with Different Species of Leishmania: Induction of Apoptosis by Leishmania (Leishmania) amazonensis, but Not by Leishmania (Viannia) guyanensis

PubMed Central

DaMata, Jarina Pena; Mendes, Bárbara Pinheiro; Maciel-Lima, Kátia; Menezes, Cristiane Alves Silva; Dutra, Walderez Ornelas; Sousa, Lirlândia Pires; Horta, Maria Fátima

2015-01-01

Leishmania is an intracellular parasite in vertebrate hosts, including man. During infection, amastigotes replicate inside macrophages and are transmitted to healthy cells, leading to amplification of the infection. Although transfer of amastigotes from infected to healthy cells is a crucial step that may shape the outcome of the infection, it is not fully understood. Here we compare L. amazonensis and L. guyanensis infection in C57BL/6 and BALB/c mice and investigate the fate of macrophages when infected with these species of Leishmania in vitro. As previously shown, infection of mice results in distinct outcomes: L. amazonensis causes a chronic infection in both strains of mice (although milder in C57BL/6), whereas L. guyanensis does not cause them disease. In vitro, infection is persistent in L. amazonensis-infected macrophages whereas L. guyanensis growth is controlled by host cells from both strains of mice. We demonstrate that, in vitro, L. amazonensis induces apoptosis of both C57BL/6 and BALB/c macrophages, characterized by PS exposure, DNA cleavage into nucleosomal size fragments, and consequent hypodiploidy. None of these signs were seen in macrophages infected with L. guyanensis, which seem to die through necrosis, as indicated by increased PI-, but not Annexin V-, positive cells. L. amazonensis-induced macrophage apoptosis was associated to activation of caspases-3, -8 and -9 in both strains of mice. Considering these two species of Leishmania and strains of mice, macrophage apoptosis, induced at the initial moments of infection, correlates with chronic infection, regardless of its severity. We present evidence suggestive that macrophages phagocytize L. amazonensis-infected cells, which has not been verified so far. The ingestion of apoptotic infected macrophages by healthy macrophages could be a way of amastigote spreading, leading to the establishment of infection. PMID:26513474

Co-Infection by Chytrid Fungus and Ranaviruses in Wild and Harvested Frogs in the Tropical Andes

PubMed Central

Warne, Robin W.; LaBumbard, Brandon; LaGrange, Seth; Vredenburg, Vance T.; Catenazzi, Alessandro

2016-01-01

While global amphibian declines are associated with the spread of Batrachochytrium dendrobatidis (Bd), undetected concurrent co-infection by other pathogens may be little recognized threats to amphibians. Emerging viruses in the genus Ranavirus (Rv) also cause die-offs of amphibians and other ectotherms, but the extent of their distribution globally, or how co-infections with Bd impact amphibians are poorly understood. We provide the first report of Bd and Rv co-infection in South America, and the first report of Rv infections in the amphibian biodiversity hotspot of the Peruvian Andes, where Bd is associated with extinctions. Using these data, we tested the hypothesis that Bd or Rv parasites facilitate co-infection, as assessed by parasite abundance or infection intensity within individual adult frogs. Co-infection occurred in 30% of stream-dwelling frogs; 65% were infected by Bd and 40% by Rv. Among terrestrial, direct-developing Pristimantis frogs 40% were infected by Bd, 35% by Rv, and 20% co-infected. In Telmatobius frogs harvested for the live-trade 49% were co-infected, 92% were infected by Bd, and 53% by Rv. Median Bd and Rv loads were similar in both wild (Bd = 101.2 Ze, Rv = 102.3 viral copies) and harvested frogs (Bd = 103.1 Ze, Rv = 102.7 viral copies). While neither parasite abundance nor infection intensity were associated with co-infection patterns in adults, these data did not include the most susceptible larval and metamorphic life stages. These findings suggest Rv distribution is global and that co-infection among these parasites may be common. These results raise conservation concerns, but greater testing is necessary to determine if parasite interactions increase amphibian vulnerability to secondary infections across differing life stages, and constitute a previously undetected threat to declining populations. Greater surveillance of parasite interactions may increase our capacity to contain and mitigate the impacts of these and other wildlife diseases. PMID:26726999

Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo

PubMed Central

Sugata, Kenji; Ueno, Takaharu; Koh, Ki-Ryang; Higuchi, Yusuke; Matsuda, Fumihiko; Melamed, Anat; Bangham, Charles R.

2017-01-01

Human T-cell leukemia virus type 1 (HTLV-1) infects mainly CD4+CCR4+ effector/memory T cells in vivo. However, it remains unknown whether HTLV-1 preferentially infects these T cells or this virus converts infected precursor cells to specialized T cells. Expression of viral genes in vivo is critical to study viral replication and proliferation of infected cells. Therefore, we first analyzed viral gene expression in non-human primates naturally infected with simian T-cell leukemia virus type 1 (STLV-1), whose virological attributes closely resemble those of HTLV-1. Although the tax transcript was detected only in certain tissues, Tax expression was much higher in the bone marrow, indicating the possibility of de novo infection. Furthermore, Tax expression of non-T cells was suspected in bone marrow. These data suggest that HTLV-1 infects hematopoietic cells in the bone marrow. To explore the possibility that HTLV-1 infects hematopoietic stem cells (HSCs), we analyzed integration sites of HTLV-1 provirus in various lineages of hematopoietic cells in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a HTLV-1 carrier using the high-throughput sequencing method. Identical integration sites were detected in neutrophils, monocytes, B cells, CD8+ T cells and CD4+ T cells, indicating that HTLV-1 infects HSCs in vivo. We also detected Tax protein in myeloperoxidase positive neutrophils. Furthermore, dendritic cells differentiated from HTLV-1 infected monocytes caused de novo infection to T cells, indicating that infected monocytes are implicated in viral spreading in vivo. Certain integration sites were re-detected in neutrophils from HAM/TSP patients at different time points, indicating that infected HSCs persist and differentiate in vivo. This study demonstrates that HTLV-1 infects HSCs, and infected stem cells differentiate into diverse cell lineages. These data indicate that infection of HSCs can contribute to the persistence and spread of HTLV-1 in vivo. PMID:29186194

Risk factors for soil-transmitted helminth infections during the first 3 years of life in the tropics; findings from a birth cohort.

PubMed

Menzies, Stefanie K; Rodriguez, Alejandro; Chico, Martha; Sandoval, Carlos; Broncano, Nely; Guadalupe, Irene; Cooper, Philip J

2014-02-01

Soil-transmitted helminths (STH) infect more than 2 billion humans worldwide, causing significant morbidity in children. There are few data on the epidemiology and risk factors for infection in pre-school children. To investigate risk factors for infection in early childhood, we analysed data prospectively collected in the ECUAVIDA birth cohort in Ecuador. Children were recruited at birth and followed up to 3 years of age with periodic collection of stool samples that were examined microscopically for STH parasites. Data on social, demographic, and environmental risk factors were collected from the mother at time of enrollment. Associations between exposures and detection of STH infections were analysed by multivariable logistic regression. Data were analysed from 1,697 children for whom a stool sample was obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of life and the most common infections were caused by A. lumbricoides (33.2% of children) and T. trichiura (21.2%). Hookworm infection was detected in 0.9% of children. Risk of STH infection was associated with factors indicative of poverty in our study population such as Afro-Ecuadorian ethnicity and low maternal educational level. Maternal STH infections during pregnancy were strong risk factors for any childhood STH infection, infections with either A. lumbricoides or T. trichiura, and early age of first STH infection. Children of mothers with moderate to high infections intensities with A. lumbricoides were most at risk. Our data show high rates of infection with STH parasites during the first 3 years of life in an Ecuadorian birth cohort, an observation that was strongly associated with maternal STH infections during pregnancy. The targeted treatment of women of childbearing age, in particular before pregnancy, with anthelmintic drugs could offer a novel approach to the prevention of STH infections in pre-school children.

Distinct Macrophage Fates after in vitro Infection with Different Species of Leishmania: Induction of Apoptosis by Leishmania (Leishmania) amazonensis, but Not by Leishmania (Viannia) guyanensis.

PubMed

DaMata, Jarina Pena; Mendes, Bárbara Pinheiro; Maciel-Lima, Kátia; Menezes, Cristiane Alves Silva; Dutra, Walderez Ornelas; Sousa, Lirlândia Pires; Horta, Maria Fátima

2015-01-01

Leishmania is an intracellular parasite in vertebrate hosts, including man. During infection, amastigotes replicate inside macrophages and are transmitted to healthy cells, leading to amplification of the infection. Although transfer of amastigotes from infected to healthy cells is a crucial step that may shape the outcome of the infection, it is not fully understood. Here we compare L. amazonensis and L. guyanensis infection in C57BL/6 and BALB/c mice and investigate the fate of macrophages when infected with these species of Leishmania in vitro. As previously shown, infection of mice results in distinct outcomes: L. amazonensis causes a chronic infection in both strains of mice (although milder in C57BL/6), whereas L. guyanensis does not cause them disease. In vitro, infection is persistent in L. amazonensis-infected macrophages whereas L. guyanensis growth is controlled by host cells from both strains of mice. We demonstrate that, in vitro, L. amazonensis induces apoptosis of both C57BL/6 and BALB/c macrophages, characterized by PS exposure, DNA cleavage into nucleosomal size fragments, and consequent hypodiploidy. None of these signs were seen in macrophages infected with L. guyanensis, which seem to die through necrosis, as indicated by increased PI-, but not Annexin V-, positive cells. L. amazonensis-induced macrophage apoptosis was associated to activation of caspases-3, -8 and -9 in both strains of mice. Considering these two species of Leishmania and strains of mice, macrophage apoptosis, induced at the initial moments of infection, correlates with chronic infection, regardless of its severity. We present evidence suggestive that macrophages phagocytize L. amazonensis-infected cells, which has not been verified so far. The ingestion of apoptotic infected macrophages by healthy macrophages could be a way of amastigote spreading, leading to the establishment of infection.

Risk Factors for Soil-Transmitted Helminth Infections during the First 3 Years of Life in the Tropics; Findings from a Birth Cohort

PubMed Central

Menzies, Stefanie K.; Rodriguez, Alejandro; Chico, Martha; Sandoval, Carlos; Broncano, Nely; Guadalupe, Irene; Cooper, Philip J.

2014-01-01

Background Soil-transmitted helminths (STH) infect more than 2 billion humans worldwide, causing significant morbidity in children. There are few data on the epidemiology and risk factors for infection in pre-school children. To investigate risk factors for infection in early childhood, we analysed data prospectively collected in the ECUAVIDA birth cohort in Ecuador. Methods and Findings Children were recruited at birth and followed up to 3 years of age with periodic collection of stool samples that were examined microscopically for STH parasites. Data on social, demographic, and environmental risk factors were collected from the mother at time of enrolment. Associations between exposures and detection of STH infections were analysed by multivariable logistic regression. Data were analysed from 1,697 children for whom a stool sample was obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of life and the most common infections were caused by A. lumbricoides (33.2% of children) and T. trichiura (21.2%). Hookworm infection was detected in 0.9% of children. Risk of STH infection was associated with factors indicative of poverty in our study population such as Afro-Ecuadorian ethnicity and low maternal educational level. Maternal STH infections during pregnancy were strong risk factors for any childhood STH infection, infections with either A. lumbricoides or T. trichiura, and early age of first STH infection. Children of mothers with moderate to high infections intensities with A. lumbricoides were most at risk. Conclusions Our data show high rates of infection with STH parasites during the first 3 years of life in an Ecuadorian birth cohort, an observation that was strongly associated with maternal STH infections during pregnancy. The targeted treatment of women of childbearing age, in particular before pregnancy, with anthelmintic drugs could offer a novel approach to the prevention of STH infections in pre-school children. PMID:24587469

Worm Burden-Dependent Disruption of the Porcine Colon Microbiota by Trichuris suis Infection

PubMed Central

Wu, Sitao; Li, Robert W.; Li, Weizhong; Beshah, Ethiopia; Dawson, Harry D.; Urban, Joseph F.

2012-01-01

Helminth infection in pigs serves as an excellent model for the study of the interaction between human malnutrition and parasitic infection and could have important implications in human health. We had observed that pigs infected with Trichuris suis for 21 days showed significant changes in the proximal colon microbiota. In this study, interactions between worm burden and severity of disruptions to the microbial composition and metabolic potentials in the porcine proximal colon microbiota were investigated using metagenomic tools. Pigs were infected by a single dose of T. suis eggs for 53 days. Among infected pigs, two cohorts were differentiated that either had adult worms or were worm-free. Infection resulted in a significant change in the abundance of approximately 13% of genera detected in the proximal colon microbiota regardless of worm status, suggesting a relatively persistent change over time in the microbiota due to the initial infection. A significant reduction in the abundance of Fibrobacter and Ruminococcus indicated a change in the fibrolytic capacity of the colon microbiota in T. suis infected pigs. In addition, ∼10% of identified KEGG pathways were affected by infection, including ABC transporters, peptidoglycan biosynthesis, and lipopolysaccharide biosynthesis as well as α-linolenic acid metabolism. Trichuris suis infection modulated host immunity to Campylobacter because there was a 3-fold increase in the relative abundance in the colon microbiota of infected pigs with worms compared to naïve controls, but a 3-fold reduction in worm-free infected pigs compared to controls. The level of pathology observed in infected pigs with worms compared to worm-free infected pigs may relate to the local host response because expression of several Th2-related genes were enhanced in infected pigs with worms versus those worm-free. Our findings provided insight into the dynamics of the proximal colon microbiota in pigs in response to T. suis infection. PMID:22532855

Targeted photodynamic therapy of established soft-tissue infections in mice

NASA Astrophysics Data System (ADS)

Gad, Faten; Zahra, Touqir; Hasan, Tayyaba; Hamblin, Michael R.

2004-06-01

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to < 5% of that seen in control infections) not seen in untreated or light alone treated infections, but in some cases the infection recurred. Conjugate alone led to a lesser reduction in bioluminescence. Infections treated with free chlorin(e6) responded less and the infection subsequently increased over the succeeding days, probably due to PDT-mediated tissue damage. PDT-treated infected legs healed better than legs with untreated infections. This data shows that PDT may have applications in drug-resistant soft-tissue infections.

Nosocomial infections with metallo-beta-lactamase-producing Pseudomonas aeruginosa: molecular epidemiology, risk factors, clinical features and outcomes.

PubMed

Lucena, A; Dalla Costa, L M; Nogueira, K S; Matos, A P; Gales, A C; Paganini, M C; Castro, M E S; Raboni, S M

2014-08-01

Metallo-β-lactamases (MBLs) have emerged as one of the most important bacterial resistance mechanisms because of their ability to hydrolyse virtually all β-lactam agents. MBL-producing Pseudomonas aeruginosa (MBL-PA) are an important cause of nosocomial infections, particularly in intensive care units (ICUs), where they are associated with serious infections and present a significant clinical risk. To assess the molecular epidemiology, risk factors and outcomes of nosocomial infections caused by MBL-PA in a teaching hospital in Southern Brazil. From January 2001 to December 2008, 142 carbapenem-resistant P. aeruginosa strains were isolated from distinct clinical samples from hospitalized patients. These isolates were screened for MBLs, and underwent polymerase chain reaction, sequencing and pulsed-field gel electrophoresis (PFGE). Patients infected with carbapenem-resistant MBL-PA were considered as cases, and patients infected with non-MBL-PA were considered as controls. Eighty-four of 142 patients with positive carbapenem-resistant P. aeruginosa cultures met the criteria of the Centers for Disease Control and Prevention for infection. Fifty-eight patients were infected with MBL-PA (69%) and 26 patients were infected with non-MBL-PA (31%). Multi-variate analysis revealed that ICU stay [P = 0.003, odds ratio (OR) 4.01, 95% confidence interval (CI) 1.15-14.01] and urinary tract infection (P = 0.001, OR 9.67, 95% CI 1.72-54.48) were important risk factors for MBL-PA infection. Patients infected with MBL-PA showed faster onset of infection (P = 0.002) and faster progression to death (P = 0.04). These results showed the severity of MBL-PA infections, and demonstrated the urgent need for strategies to improve infection control measures to prevent an increase in these nosocomial infections. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Estimation of Extra Length of Stay Attributable to Hospital-Acquired Infections in Adult ICUs Using a Time-Dependent Multistate Model.

PubMed

Ohannessian, Robin; Gustin, Marie-Paule; Bénet, Thomas; Gerbier-Colomban, Solweig; Girard, Raphaele; Argaud, Laurent; Rimmelé, Thomas; Guerin, Claude; Bohé, Julien; Piriou, Vincent; Vanhems, Philippe

2018-04-10

The objective of the study was to estimate the length of stay of patients with hospital-acquired infections hospitalized in ICUs using a multistate model. Active prospective surveillance of hospital-acquired infection from January 1, 1995, to December 31, 2012. Twelve ICUs at the University of Lyon hospital (France). Adult patients age greater than or equal to 18 years old and hospitalized greater than or equal to 2 days were included in the surveillance. All hospital-acquired infections (pneumonia, bacteremia, and urinary tract infection) occurring during ICU stay were collected. None. The competitive risks of in-hospital death, transfer, or discharge were considered in estimating the change in length of stay due to infection(s), using a multistate model, time of infection onset. Thirty-three thousand four-hundred forty-nine patients were involved, with an overall hospital-acquired infection attack rate of 15.5% (n = 5,176). Mean length of stay was 27.4 (± 18.3) days in patients with hospital-acquired infection and 7.3 (± 7.6) days in patients without hospital-acquired infection. A multistate model-estimated mean found an increase in length of stay by 5.0 days (95% CI, 4.6-5.4 d). The extra length of stay increased with the number of infected site and was higher for patients discharged alive from ICU. No increased length of stay was found for patients presenting late-onset hospital-acquired infection, more than the 25th day after admission. An increase length of stay of 5 days attributable to hospital-acquired infection in the ICU was estimated using a multistate model in a prospective surveillance study in France. The dose-response relationship between the number of hospitalacquired infection and length of stay and the impact of early-stage hospital-acquired infection may strengthen attention for clinicians to focus interventions on early preventions of hospital-acquired infection in ICU.

Volatile fingerprinting of pseudomonas aeruginosa and respiratory syncytial virus infection in an in vitro cystic fibrosis co-infection model.

PubMed

Purcaro, Giorgia; Rees, Christiaan; Melvin, Jeffrey A; Bomberg, Jennifer M; Hill, Jane E

2018-05-08

Volatile molecules in exhaled breath represent potential biomarkers in the setting of infectious diseases, particularly those affecting the respiratory tract. In particular, Pseudomonas aeruginosa is a critically-important respiratory pathogen in specific subsets of the population, such as those with cystic fibrosis. Infections caused by P. aeruginosa can be particularly problematic when co-infection with respiratory syncytial virus (RSV) occurs, as this is correlated with the establishment of chronic P. aeruginosa infection. In the present study, we evaluate the volatile metabolites produced by P. Aeruginosa (PAO1)-infected, RSV-infected, co-infected, or uninfected cystic fibrosis bronchial epithelial (CFBE) cells, in vitro. We identified a volatile metabolic signature that could discriminate between P. aeruginosa-infected and non-P. aeruginosa-infected CFBE with an area under the receiver operating characteristic curve (AUROC) of 0.850, using the machine learning algorithm Random Forest (RF). Although we could not discriminate between RSV-infected and non-RSV-infected CFBE (AUROC = 0.431), we note that sample classification probabilities for RSV-infected cell, generated using RF, were between those of uninfected CFBE and P. aeruginosa-infected CFBE, suggesting that RSV infection may result in a volatile metabolic profile that shares attributes with both of these groups. To more precisely elucidate the biological origins of the volatile metabolites that were discriminatory between P. aeruginosa-infected and non-P. aeruginosa-infected CFBE, we measured the volatile metabolites produced by P. aeruginosa grown in the absence of CFBE. Our findings suggest that the discriminatory metabolites produced likely result from the interaction of P. aeruginosa with the CFBE cells, rather than the metabolism of media components by the bacterium. Taken together, our findings support the notion that P. aeruginosa interacting with CFBE yields a particular volatile metabolic signature. Such a signature may have clinical utility in the monitoring of individuals with cystic fibrosis. © 2018 IOP Publishing Ltd.

Clinical Presentation, Risk Factors, and Outcomes of Hematogenous Prosthetic Joint Infection in Patients with Staphylococcus aureus Bacteremia.

PubMed

Tande, Aaron J; Palraj, Bharath Raj; Osmon, Douglas R; Berbari, Elie F; Baddour, Larry M; Lohse, Christine M; Steckelberg, James M; Wilson, Walter R; Sohail, M Rizwan

2016-02-01

Staphylococcus aureus bacteremia is a life-threatening condition that may lead to metastatic infection, including prosthetic joint infection. To assess clinical factors associated with hematogenous prosthetic joint infection, we retrospectively reviewed all patients with a joint arthroplasty in place at the time of a first episode of S. aureus bacteremia over a 5-year period at our institution. Patients with postsurgical prosthetic joint infection without hematogenous prosthetic joint infection were excluded. There were 85 patients (143 arthroplasties) with either no prosthetic joint infection (n = 50; 58.8%) or hematogenous prosthetic joint infection in at least one arthroplasty (n = 35; 41.2%). The odds of hematogenous prosthetic joint infection was significantly increased among patients with community-acquired S. aureus bacteremia (odds ratio [OR] 18.07; 95% confidence interval [CI] 2.64-infinity; P = .001), as compared with nosocomial S. aureus bacteremia, in which there were no patients with hematogenous prosthetic joint infection. After adjusting for S. aureus bacteremia classification, the presence of ≥3 joint arthroplasties in place was associated with a nearly ninefold increased odds of hematogenous prosthetic joint infection as compared with those with 1-2 joint arthroplasties in place (OR 8.55; 95% CI 1.44-95.71; P = .012). All but one joint with prosthetic joint infection demonstrated at least one clinical feature suggestive of infection. There were 4 additional S. aureus prosthetic joint infections diagnosed during a median of 3.4 years of follow-up post hospitalization for S. aureus bacteremia. Prosthetic joint infection is frequent in patients with existing arthroplasties and concomitant S. aureus bacteremia, particularly with community-acquired S. aureus bacteremia and multiple prostheses. In contrast, occult S. aureus prosthetic joint infection without clinical features suggestive of prosthetic joint infection at the time of S. aureus bacteremia is rare. Copyright © 2016 Elsevier Inc. All rights reserved.

Surgical and Antimicrobial Treatment of Prosthetic Vascular Graft Infections at Different Surgical Sites: A Retrospective Study of Treatment Outcomes

PubMed Central

Elzi, Luigia; Gurke, Lorenz; Battegay, Manuel; Widmer, Andreas F.; Weisser, Maja

2014-01-01

Objective Little is known about optimal management of prosthetic vascular graft infections, which are a rare but serious complication associated with graft implants. The goal of this study was to compare and characterize these infections with respect to the location of the graft and to identify factors associated with outcome. Methods This was a retrospective study over more than a decade at a tertiary care university hospital that has an established multidisciplinary approach to treating graft infections. Cases of possible prosthetic vascular graft infection were identified from the hospital's infectious diseases database and evaluated against strict diagnostic criteria. Patients were divided into groups according to the locations of their grafts: thoracic-aortic, abdominal-aortic, or peripheral-arterial. Statistical analyses included evaluation of patient and infection characteristics, time to treatment failure, and factors associated specifically with cure rates in aortic graft infections. The primary endpoint was cure at one year after diagnosis of the infection. Results Characterization of graft infections according to the graft location did show that these infections differ in terms of their characteristics and that the prognosis for treatment seems to be influenced by the location of the infection. Cure rate and all-cause mortality at one year were 87.5% and 12.5% in 24 patients with thoracic-aortic graft infections, 37.0% and 55.6% in 27 patients with abdominal-aortic graft infections, and 70.0% and 30.0% in 10 patients with peripheral-arterial graft infections. In uni- and multivariate analysis, the type of surgical intervention used in managing infections (graft retention versus graft replacement) did not affect primary outcome, whereas a rifampicin-based antimicrobial regimen was associated with a higher cure rate. Conclusions We recommend that future prospective studies differentiate prosthetic vascular graft infections according to the location of the grafts and that rifampicin-based antimicrobial regimens be evaluated in clinical trials involving vascular graft infections caused by staphylococci. PMID:25393400

Reduced mortality associated with breast-feeding-acquired HIV infection and breast-feeding among HIV-infected children in Zambia.

PubMed

Fox, Matthew P; Brooks, Daniel; Kuhn, Louise; Aldrovandi, Grace; Sinkala, Moses; Kankasa, Chipepo; Mwiya, Mwiya; Horsburgh, Robert; Thea, Donald M

2008-05-01

In developing countries, where mother-to-child transmission of HIV through breast-feeding is common, little is known about the impact of postpartum transmission on child survival. This study assessed whether children infected postpartum have longer survival from time of infection versus those infected during gestation or delivery. We used a prospective cohort study to analyze data from 213 HIV-infected children enrolled in a breast-feeding intervention trial in Lusaka, Zambia (2001 to 2004). We compared mortality 1 year after HIV infection in children stratified by age of infection: 0 to 3 days (intrauterine [IU] group), 4 to 40 days (intrapartum/early postpartum [IP/EPP] group), and >40 days (postpartum [PP] group). A total of 61, 71, and 81 children were infected in the IU, IP/EPP, and PP groups, respectively. Children with intrauterine or intrapartum/early postpartum transmission had higher mortality over the first 12 months after infection than children with postpartum transmission (P = 0.001 and P = 0.006, respectively); no differences were detected between children with intrauterine and intrapartum/early postpartum transmission. Nearly 20% of the IU and IP/EPP groups died by 100 days after infection, whereas nearly 10% of the PP group had died by this time. After adjusting for birth weight, maternal CD4 cell count, breast-feeding, and maternal death, children infected postpartum had one quarter the mortality rate (hazard ratio [HR] = 0.27, 95% confidence interval [CI]: 0.15 to 0.50) of those infected in utero. Stopping breast-feeding increased mortality in infected children (HR = 3.1, 95% CI: 1.8 to 5.3). This study demonstrates a survival benefit among children infected postpartum versus children infected during pregnancy or delivery and a benefit to increased breast-feeding duration among infected children. Testing children for HIV early may provide a means to allow for earlier intervention.

Asymptomatic urinary tract infection: Cause of postoperative wound infection.

PubMed

Ashraf, Irfan; Umer, Masood

2014-12-01

To determine the rate of urinary tract infection in patients given incomplete treatment before undergoing hip fracture surgery. The descriptive case series was conducted at Aga Khan University Hospital, Karachi, From October 25, 2012 to April 24, 2013. 84 postmenopausal women having hip fracture along with asymptomatic urinary tract infection. The infection was treated incompletely and postoperatively wound infection rate was determined. The SPSS version 17 was used to analyze the data. The overall mean age of the 84 patients in the study was 63.57+10.34 years. Overall, 14(16.7%) patients had wound infection after orthopaedic implant surgery for hip fracture. There was a high occurrence of wound infection after hip implant surgery in patients having preoperative asymptomatic urinary tract infection who were treated incompletely.

Vibrio infections in Louisiana: twenty-five years of surveillance 1980-2005.

PubMed

Thomas, Annu; Straif-Bourgeois, Susanne; Sokol, Theresa M; Ratard, Raoult C

2007-01-01

A total of 1,007 Vibrio infections were reported to the Infectious Disease Epidemiology Department at the Louisiana Office of Public Heath, between 1980 and 2005. The most common were Vibrio vulnificus (257 infections), Vibrio parahemolyticus (249 infections), and Vibrio cholerae non O1 (200 cases). Other species were much less common. Vibrio vulnificus infections, which are associated with consumption of raw seafood (particularly oysters) or contact with sea water, and severe immuno-suppression or liver disease were increasing. Septicemia and blood stream infections are the main manifestations of this infection. The number of infections due to Vibrio parahemolyticus on the other hand, causing mostly gastroenteritis, has remained stable. Vibrio cholerae infections are less common and almost always associated with consumption of partially cooked or contaminated crabs.

[Medical technologist as a member of infection control team].

PubMed

Okuzumi, Katsuko; Ieiri, Tamio

2005-11-01

For the prevention of infection at institutions, an Anti-nosocomial Infection Committee or an Infection Control Team (ICT) is organized at each institution according to its scale. We report the present status of the ICT managed mainly by medical technologists engaged in microbiological examination (certified medical microbiological technologists) at Dokkyo University School of Medicine. Since this hospital is an educational hospital, the department of clinical laboratory medicine cooperates with the microbiological laboratory of the clinical laboratory in infection control education of medical workers (such as medical students, nursing students, physicians and nurses) in infection diagnosis, infection control/infection management. Since infection control is achieved by improvement in hygiene knowledge and its practice in all citizens, we also attached importance to publicity activities associated with microbiology for patients, their families, and all medical workers.

[Progress in research of occult hepatitis B virus infection].

PubMed

Huang, X Y; Shi, Q F; Huang, T

2017-05-10

Occult hepatitis B virus infection is a worldwide public health problem, which seriously affects the clinical diagnosis of hepatitis B and threatens the safety of blood transfusion. The concept of occult hepatitis B virus infection, the pathogenesis of occult hepatitis B virus infection, the prevalence of occult hepatitis B virus infection in different groups, including healthy population and different patients, and the possibility of transmission were summarized. The prevalence of occult hepatitis B virus infection was found in healthy population and different patients, and there is possibility of occult hepatitis B virus infection to be transmitted through blood transfusion. The paper provides a comprehensive introduction of the pathogenesis and prevalence of occult hepatitis B virus infection. More attention should be paid to occult hepatitis B virus infection.

Medical consequences of drug abuse and co-occurring infections: research at the National Institute on Drug Abuse.

PubMed

Khalsa, Jag H; Treisman, Glenn; McCance-Katz, Elinore; Tedaldi, Ellen

2008-01-01

Substance abuse still remains one of the major problems in the world today, with millions of people abusing legal and illegal drugs. In addition, a billion people may also be infected with one or more infections. Both drugs of abuse and infections are associated with enormous burden of social, economic, and health consequences. This article briefly discusses a few medical consequences of drugs of abuse and infections such as human immunodeficiency virus, hepatitis C virus, psychiatric complications in hepatitis C infection, pharmacokinetic drug-drug interactions among medications used in the treatment of addiction and infections, and new drugs in development for the treatment of infections. Research is encouraged to study interactions between infections, drugs of abuse, and underlying pathophysiologic and molecular/genetic mechanisms of these interactions.

Syphilis and HIV/Syphilis Co-infection Among Men Who Have Sex With Men (MSM) in Ecuador.

PubMed

Hernandez, Isabel; Johnson, Ayesha; Reina-Ortiz, Miguel; Rosas, Carlos; Sharma, Vinita; Teran, Santiago; Naik, Eknath; Salihu, Hamisu M; Teran, Enrique; Izurieta, Ricardo

2017-07-01

There is a reemergence of syphilis in the Latin American and Caribbean region. There is also very little information about HIV/Syphilis co-infection and its determinants. The aim of this study is to investigate knowledge, attitudes, and practices regarding sexually transmitted infections (STIs), in particular syphilis infection and HIV/Syphilis co-infection, as well as to estimate the prevalence of syphilis among men who have sex with men (MSM) in a city with one of the highest HIV prevalence rates in Ecuador. In this study, questionnaires were administered to 291 adult MSM. Questions included knowledge about STIs and their sexual practices. Blood samples were taken from participants to estimate the prevalence of syphilis and HIV/syphilis co-infection. In this population, the prevalence of HIV/syphilis co-infection was 4.8%, while the prevalence of syphilis as mono-infection was 6.5%. Participants who had syphilis mono-infection and HIV/syphilis co-infection were older. Men who had multiple partners and those who were forced to have sex had increased odds of syphilis and HIV/syphilis co-infection. A high prevalence of syphilis and self-reported STI was observed, which warrants targeted behavioral interventions. Co-infections are a cause for concern when treating a secondary infection in a person who is immunocompromised. These data suggest that specific knowledge, attitudes, and behaviors among MSM are associated with increased odds of STIs (including HIV/syphilis co-infections) in this region of Ecuador.

HIV dynamics with multiple infections of target cells.

PubMed

Dixit, Narendra M; Perelson, Alan S

2005-06-07

The high incidence of multiple infections of cells by HIV sets the stage for rapid HIV evolution by means of recombination. Yet how HIV dynamics proceeds with multiple infections remains poorly understood. Here, we present a mathematical model that describes the dynamics of viral, target cell, and multiply infected cell subpopulations during HIV infection. Model calculations reproduce several experimental observations and provide key insights into the influence of multiple infections on HIV dynamics. We find that the experimentally observed scaling law, that the number of cells coinfected with two distinctly labeled viruses is proportional to the square of the total number of infected cells, can be generalized so that the number of triply infected cells is proportional to the cube of the number of infected cells, etc. Despite the expectation from Poisson statistics, we find that this scaling relationship only holds under certain conditions, which we predict. We also find that multiple infections do not influence viral dynamics when the rate of viral production from infected cells is independent of the number of times the cells are infected, a regime expected when viral production is limited by cellular rather than viral factors. This result may explain why extant models, which ignore multiple infections, successfully describe viral dynamics in HIV patients. Inhibiting CD4 down-modulation increases the average number of infections per cell. Consequently, altering CD4 down-modulation may allow for an experimental determination of whether viral or cellular factors limit viral production.

HIV dynamics with multiple infections of target cells

PubMed Central

Dixit, Narendra M.; Perelson, Alan S.

2005-01-01

The high incidence of multiple infections of cells by HIV sets the stage for rapid HIV evolution by means of recombination. Yet how HIV dynamics proceeds with multiple infections remains poorly understood. Here, we present a mathematical model that describes the dynamics of viral, target cell, and multiply infected cell subpopulations during HIV infection. Model calculations reproduce several experimental observations and provide key insights into the influence of multiple infections on HIV dynamics. We find that the experimentally observed scaling law, that the number of cells coinfected with two distinctly labeled viruses is proportional to the square of the total number of infected cells, can be generalized so that the number of triply infected cells is proportional to the cube of the number of infected cells, etc. Despite the expectation from Poisson statistics, we find that this scaling relationship only holds under certain conditions, which we predict. We also find that multiple infections do not influence viral dynamics when the rate of viral production from infected cells is independent of the number of times the cells are infected, a regime expected when viral production is limited by cellular rather than viral factors. This result may explain why extant models, which ignore multiple infections, successfully describe viral dynamics in HIV patients. Inhibiting CD4 down-modulation increases the average number of infections per cell. Consequently, altering CD4 down-modulation may allow for an experimental determination of whether viral or cellular factors limit viral production. PMID:15928092

Prevalence survey of nosocomial infections in the Inner Mongolia Autonomous Region of China [2012-2014

PubMed Central

Liu, Wei-Ping; Hai, Yun-Ting; Zheng, Zhi-Nan; Cao, Qing-Ling

2015-01-01

Background To investigate the prevalence of nosocomial infections, the distribution of nosocomial infection sites, the use of antibiotic and the situation of detected nosocomial infection pathogens in the Inner Mongolia Autonomous Region of China from 2012 to 2014, to grasp the current conditions of regional nosocomial infections in timely, for the development of infection prevention and control measures to provide a basis for effective hospital. Methods A survey of the prevalence of nosocomial infections was conducted in target hospitals using the combination of a bedside survey and medical record review. Results In total, 101,907 inpatients were surveyed from 2012 to 2014. There were 1,997 cases of nosocomial infections, accounting for an average prevalence of 1.96%. The infection site was mainly the lower respiratory tract. Higher prevalence of nosocomial infections occurred in the comprehensive intensive care unit (ICU), Neurosurgery Department, and Hematology Department. The average rate of antibiotic use was 33.72%, and the average submission rate for bacterial cultures for patients who received therapeutic treatment with antibiotics was 28.26%. The most common pathogens associated with nosocomial infections were Gram-negative (G−) bacteria, and frequently detected bacterial pathogens included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus. Conclusions The survey of the prevalence of nosocomial infections helped to identify problems in the control process of nosocomial infections and to develop targeted measures for the prevention and control of these infections accordingly. PMID:26543614

Syphilis and HIV/Syphilis Co-infection Among Men Who Have Sex With Men (MSM) in Ecuador

PubMed Central

Hernandez, Isabel; Johnson, Ayesha; Reina-Ortiz, Miguel; Rosas, Carlos; Sharma, Vinita; Teran, Santiago; Naik, Eknath; Salihu, Hamisu M.; Teran, Enrique; Izurieta, Ricardo

2016-01-01

There is a reemergence of syphilis in the Latin American and Caribbean region. There is also very little information about HIV/Syphilis co-infection and its determinants. The aim of this study is to investigate knowledge, attitudes, and practices regarding sexually transmitted infections (STIs), in particular syphilis infection and HIV/Syphilis co-infection, as well as to estimate the prevalence of syphilis among men who have sex with men (MSM) in a city with one of the highest HIV prevalence rates in Ecuador. In this study, questionnaires were administered to 291 adult MSM. Questions included knowledge about STIs and their sexual practices. Blood samples were taken from participants to estimate the prevalence of syphilis and HIV/syphilis co-infection. In this population, the prevalence of HIV/syphilis co-infection was 4.8%, while the prevalence of syphilis as mono-infection was 6.5%. Participants who had syphilis mono-infection and HIV/syphilis co-infection were older. Men who had multiple partners and those who were forced to have sex had increased odds of syphilis and HIV/syphilis co-infection. A high prevalence of syphilis and self-reported STI was observed, which warrants targeted behavioral interventions. Co-infections are a cause for concern when treating a secondary infection in a person who is immunocompromised. These data suggest that specific knowledge, attitudes, and behaviors among MSM are associated with increased odds of STIs (including HIV/syphilis co-infections) in this region of Ecuador. PMID:27923971

Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs.

PubMed

Griffith, B P; Lucia, H L; Hsiung, G D

1982-06-01

The virologic and histologic characteristics of congenital cytomegalovirus infection (CMV) were defined in 65 neonatal guinea pigs born from 27 mothers infected pregnancy. Infectious virus or tissue lesions were present in 54% of the neonates tested. Guinea pig CMV was detected most often in the salivary glands (72%) and spleen (33%) of infected guinea pigs. Less frequently, virus was also detected in the brain, lung, pancreas and liver. Tissue lesions were most frequently observed in the brain and kidney, but also occurred in the salivary glands, liver, pancreas, thymus and spleen. The histopathology was identical to that observed in infants with congenital CMV infection. Infectious virus and histopathology were present in newborn guinea pigs born from mothers infected at any time during gestation. Newborns from mothers infected during early stages of gestation and virus present most frequently in the salivary glands, whereas offspring of mothers infected in late pregnancy had virus present in several tissues. Acute maternal guinea pig CMV infection produced generalized CMV infection of the offspring which was followed by persistent infection in neonatal salivary glands. Lesions remained present in several neonatal tissues including the brain. The long term consequences of such lesions in affected guinea pigs remain to be determined. The results of the study emphasize the similarities between human congenital CMV infection and congenital guinea pig CMV infection, thereby underlining the utility of this animal model as a means of understanding human congenital CMV infection.

Sequential acquisition of human papillomavirus (HPV) infection of the anus and cervix: the Hawaii HPV Cohort Study.

PubMed

Goodman, Marc T; Shvetsov, Yurii B; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Thompson, Pamela J; Ning, Lily; Killeen, Jeffrey; Kamemoto, Lori; Hernandez, Brenda Y

2010-05-01

Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection. he association of an incident cervical (or anal) HPV infection with the subsequent risk of a genotype-concordant incident anal (or cervical) HPV infection was examined in a longitudinal cohort study of 751 sexually active women. Age-adjusted hazard ratios, obtained using Cox regression, served as measurements of relative risk (RR). Among women, the RR of acquiring an anal HPV infection after a cervical infection with HPV of the same genotype was 20.5 (95% confidence interval, 16.3-25.7), and the RR of acquiring a cervical HPV infection after an anal infection with HPV of the same genotype was 8.8 (95% confidence interval, 6.4-12.2), compared with women without a previous anal/cervical infection with HPV of a concordant genotype. RRs varied by phylogenetic species, with HPV alpha3/alpha15 and alpha1/alpha8/alpha10 types having a greater likelihood than other types of HPV infecting the anus among women with a previous infection at the cervix with HPV of the same genotype. It appears common for anal and cervical HPV infections to occur consecutively. The high degree of genotype-specific concordance suggests that the cervix (vagina) and anus may serve as reservoirs for HPV infection at the other anatomical site.

Timing of Debridement and Infection Rates in Open Fractures of the Hand

PubMed Central

Ketonis, Constantinos; Dwyer, Joseph; Ilyas, Asif M.

2016-01-01

Background: Literature on open fracture infections has focused primarily on long bones, with limited guidelines available for open hand fractures. In this study, we systematically review the available hand surgery literature to determine infection rates and the effect of debridement timing and antibiotic administration. Methods: Searches of the MEDLINE, EMBASE, and Cochrane computerized literature databases and manual bibliography searches were performed. Descriptive/quantitative data were extracted, and a meta-analysis of different patient cohorts and treatment modalities was performed to compare infection rates. Results: The initial search yielded 61 references. Twelve articles (4 prospective, 8 retrospective) on open hand fractures were included (1669 open fractures). There were 77 total infections (4.6%): 61 (4.4%) of 1391 patients received preoperative antibiotics and 16 (9.4%) of 171 patients did not receive antibiotics. In 7 studies (1106 open fractures), superficial infections (requiring oral antibiotics only) accounted for 86%, whereas deep infections (requiring operative debridement) accounted for 14%. Debridement within 6 hours of injury (2 studies, 188 fractures) resulted in a 4.2% infection rate, whereas debridement within 12 hours of injury (1 study, 193 fractures) resulted in a 3.6% infection rate. Two studies found no correlation of infection and timing to debridement. Conclusions: Overall, the infection rate after open hand fracture remains relatively low. Correlation does exist between the administration of antibiotics and infection, but the majority of infections can be treated with antibiotics alone. Timing of debridement, has not been shown to alter infection rates. PMID:28344521

Central nervous system infections masquerading as cerebrovascular accidents: Case series and review of literature.

PubMed

Hayes, Lisa; Malhotra, Prashant

2014-01-01

Central nervous system (CNS) infections can have various presentations including Cerebrovascular accidents (CVA) which may go unrecognized as a presentation of infection. We describe three cases of different CNS infections complicated by CVA. Case 1 describes a 27-year-old man, presenting with symptoms consistent with a transient ischemic attack found to have racemose neurocysticercosis. Case 2 describes a 55-year-old man with low grade fevers for 4 weeks accompanied by visual and gait disturbances and delayed speech diagnosed with multiple small left thalamocapsular and superior cerebellar infarcts secondary to cryptococcal meningitis. The third case describes a man with pneumococcal meningitis complicated by cerebellar infarcts. CNS vascular compromise secondary to infections may be due to vasculitis, an immune-mediated parainfectious process causing vasospasm or thrombosis, or a hypercoagulable state with endothelial dysfunction. Patients with CVAs are at risk for aspiration pneumonia, urinary tract infections (especially catheter related) and other nosocomial infections and their clinical presentation may be very similar to CNS infections. The cases described demonstrate that CNS infections need to be considered in the differential diagnosis of CVAs presenting with fevers. The signs and symptoms of non-CNS infections associated with CVAs may be clinically indistinguishable from those of CNS infections. The outcomes of untreated CNS infections are extremely poor. It is thus imperative to have a high index of suspicion for CNS infection when evaluating CVAs with fevers or other signs of infection.

Central nervous system infections masquerading as cerebrovascular accidents: Case series and review of literature

PubMed Central

Hayes, Lisa; Malhotra, Prashant

2014-01-01

Introduction Central nervous system (CNS) infections can have various presentations including Cerebrovascular accidents (CVA) which may go unrecognized as a presentation of infection. We describe three cases of different CNS infections complicated by CVA. Presentation Case 1 describes a 27-year-old man, presenting with symptoms consistent with a transient ischemic attack found to have racemose neurocysticercosis. Case 2 describes a 55-year-old man with low grade fevers for 4 weeks accompanied by visual and gait disturbances and delayed speech diagnosed with multiple small left thalamocapsular and superior cerebellar infarcts secondary to cryptococcal meningitis. The third case describes a man with pneumococcal meningitis complicated by cerebellar infarcts. Discussion CNS vascular compromise secondary to infections may be due to vasculitis, an immune-mediated parainfectious process causing vasospasm or thrombosis, or a hypercoagulable state with endothelial dysfunction. Patients with CVAs are at risk for aspiration pneumonia, urinary tract infections (especially catheter related) and other nosocomial infections and their clinical presentation may be very similar to CNS infections. Conclusion The cases described demonstrate that CNS infections need to be considered in the differential diagnosis of CVAs presenting with fevers. The signs and symptoms of non-CNS infections associated with CVAs may be clinically indistinguishable from those of CNS infections. The outcomes of untreated CNS infections are extremely poor. It is thus imperative to have a high index of suspicion for CNS infection when evaluating CVAs with fevers or other signs of infection. PMID:26839779

Neglected Infections of Poverty in the United States of America

PubMed Central

Hotez, Peter J.

2008-01-01

In the United States, there is a largely hidden burden of diseases caused by a group of chronic and debilitating parasitic, bacterial, and congenital infections known as the neglected infections of poverty. Like their neglected tropical disease counterparts in developing countries, the neglected infections of poverty in the US disproportionately affect impoverished and under-represented minority populations. The major neglected infections include the helminth infections, toxocariasis, strongyloidiasis, ascariasis, and cysticercosis; the intestinal protozoan infection trichomoniasis; some zoonotic bacterial infections, including leptospirosis; the vector-borne infections Chagas disease, leishmaniasis, trench fever, and dengue fever; and the congenital infections cytomegalovirus (CMV), toxoplasmosis, and syphilis. These diseases occur predominantly in people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the US–Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia. Preliminary disease burden estimates of the neglected infections of poverty indicate that tens of thousands, or in some cases, hundreds of thousands of poor Americans harbor these chronic infections, which represent some of the greatest health disparities in the United States. Specific policy recommendations include active surveillance (including newborn screening) to ascertain accurate population-based estimates of disease burden; epidemiological studies to determine the extent of autochthonous transmission of Chagas disease and other infections; mass or targeted treatments; vector control; and research and development for new control tools including improved diagnostics and accelerated development of a vaccine to prevent congenital CMV infection and congenital toxoplasmosis. PMID:18575621

Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted for dengue fever - a pilot study.

PubMed

Suppiah, Jeyanthi; Chan, Shie-Yien; Ng, Min-Wern; Khaw, Yam-Sim; Ching, Siew-Mooi; Mat-Nor, Lailatul Akmar; Ahmad-Najimudin, Naematul Ain; Chee, Hui-Yee

2017-06-28

Dengue and leptospirosis infections are currently two major endemics in Malaysia. Owing to the overlapping clinical symptoms between both the diseases, frequent misdiagnosis and confusion of treatment occurs. As a solution, the present work initiated a pilot study to investigate the incidence related to co-infection of leptospirosis among dengue patients. This enables the identification of more parameters to predict the occurrence of co-infection. Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined. The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study. The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.

21 CFR 520.2612 - Trimethoprim and sulfadiazine suspension.

Code of Federal Regulations, 2014 CFR

2014-04-01

... adjunct to surgery or debridement with associated infection. The drug is indicated where control of bacterial infection is required during the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, wound...

Middle Ear Infections (For Parents)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Middle Ear Infections KidsHealth / For Parents / Middle Ear Infections What's ... en español Infecciones del oído medio What Are Middle Ear Infections? Ear infections happen when viruses or bacteria ...

[Study of the prevalence of nosocomial infections and associated factors in the two university hospitals of Lubumbashi, Democratic Republic of Congo].

PubMed

Kakupa, Danny Kasongo; Muenze, Prosper Kalenga; Byl, Baudouin; Wilmet, Michèle Dramaix

2016-01-01

To estimate the prevalence "on any given day" of nosocomial infections and to determine their associated factors. Then, to estimate the prevalence of microorganisms responsible for nosocomial infections in Lubumbashi, Democratic Republic of Congo. A descriptive cross-sectional study was conducted in two hospitals in Lubumbashi in five inpatient units (Surgery, Gynecology and Obstetrics, Internal Medicine, Pediatrics and Recovery). The sample consisted of 171 hospitalized patients who were questioned using a standardized questionnaire. Patient's medical record allowed us to know the type of antibiotic administered to the patient 48 hours after admission. Our study was conducted in February 2010 as part of the first local prevalence survey on nosocomial infections. Our study collected data on 59 patients with nosocomial infection. The overall prevalence was 34.5% (17.0% with acquired nosocomial infection and 17.5% with imported infection). According to the World Health Organization, nosocomial infection is a hospital-acquired infection which was not present or incubating at the time of patient admission. The following risk factors have been associated with acquired nosocomial infections: duration of hospitalization (long stay hospital patients, hospital length of stay of more than seven days has a higher risk than shorter length of stay, hospital length of stay of less than or equal to seven days (prevalence ratio: RP =3.6 [IC A 95%.1.4-8.9])). Among nosocomial infections, surgical site infections were the most common (27.1%), followed by lung infections (22.0%) and urinary tract infections (17.0%). Microbiological examination highlighted five germs responsible for nosocomial infection in infected patients: Escherichia coli (11.9%), Staphylococcus aureus (6.8%), Pseudomonas aeruginosa (5.1%), Shigella spp (5.1%) and Salmonella typhimurium (1.7%). Microbiological examination was performed in 31.0% (n = 59). Cefotaxime, third-generation cephalosporin was the most prescribed antibiotic (37.9%), followed by amoxicillin (19.6%) and ampicillin (16.3%) for monotherapy. Dual and triple therapy was also prescribed. Parenteral route was the most used for anti-infective administration. There was a significant difference in the prevalence of nosocomial infections between the two university hospitals; the prevalence of acquired nosocomial infection was 22.2% in University Clinics of Lubumbashi and 13.1% in Sendwe hospital. In our study, the overall prevalence of nosocomial infections was 34.5%. Surgical site infections were the most common (27,1%). Escherichia coli was the most common germ (11.9%).

Consensus statement on the management of patients with HCV infection in Romania

PubMed Central

Ancuța, Ioan

2017-01-01

Background HCV direct-acting antivirals (DAAs) have made treatment easier for both patients and healthcare practitioners, but have also brought new challenges in terms of patient management and monitoring prior to, during, and after treatment. Methods To sum up and unify the clinical experience of Romanian DAA prescribing physicians, we have organized a Consensus Meeting in November 2016 in Bucharest, Romania. Consensus Statement The Consensus Meeting has provided expert answers to ten significant questions regarding HCV infection, namely: How do we diagnose patients with HCV infection? How do we stage liver disease in patients with HCV infection? How do we monitor patients with HCV infection prior to treatment? Which patients with HCV infection do we treat? When do we start treatment for HCV infection? What regimens do we use for treating HCV infection? How do we monitor patients with HCV infection during treatment? What adverse events should we expect during treatment of HCV infection and how do we prevent/manage them? How do we monitor patients with HCV infection after treatment? How do we expect the landscape of HCV to change in the following years? PMID:28331840

Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

PubMed

Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

2016-02-01

Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. Copyright © 2015 Elsevier B.V. All rights reserved.

Systematic CpT (ApG) depletion and CpG excess are unique genomic signatures of large DNA viruses infecting invertebrates.

PubMed

Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts.

The severe pathogenicity of alveolar macrophage-depleted ferrets infected with 2009 pandemic H1N1 influenza virus.

PubMed

Kim, Heui Man; Kang, Young Myong; Ku, Keun Bon; Park, Eun Hye; Yum, Jung; Kim, Jeong Cheol; Jin, Seo Yeon; Lee, Joo Sub; Kim, Hyun Soo; Seo, Sang Heui

2013-09-01

The in vivo role of alveolar macrophages in the infections with 2009 pandemic H1N1 influenza virus is not as yet known. Ferret study shows that alveolar macrophages are critical for lowering the risk of severe outcomes in 2009 pandemic H1N1 influenza virus infections. Up to 40% of the infected ferrets depleted of alveolar macrophages died, with elevated body temperature and major loss of body weight in contrast to infected ferrets not depleted of alveolar macrophages. The higher viral titers in the lungs were detected in infected ferrets depleted of alveolar macrophages than infected ferrets not depleted of alveolar macrophages 5 days after infection. The inflammatory chemokines were induced at greater levels in the lungs of infected ferrets depleted of alveolar macrophages than in those of infected ferrets not depleted of alveolar macrophages. Our study implies that alveolar macrophages are important for controlling the infections of 2009 pandemic H1N1 influenza virus. © 2013 Elsevier Inc. All rights reserved.

Opportunistic infection of HIV/AIDS patients in West Papua

NASA Astrophysics Data System (ADS)

Witaningrum, A. M.; Khairunisa, S. Q.; Yunifiar, M. Q.; Bramanthi, R.; Rachman, B. E.; Nasronudin

2018-03-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) had a major impact on health problemin Indonesia. HIV type 1 (HIV-1) epidemic is currently infected with HIV viruses developing rapidly in Indonesia.Papua provinces have the highest prevalence rate of human immunodeficiency virus type 1 (HIV-1) infection in Indonesia; however, data on opportunistic infection of HIV-1 are limited. The study using medical records as a research sample was conducted among HIV patients from January 2013 - December 2014 in Sele be Solu hospital among 49 patients. Opportunistic infections commonly occur in HIV-infected patients. The aim of the study was to know theprevalence of opportunistic infection among HIV positive patients in West Papua. Forty-nine HIV-1 patients were collected in Sele be Solu Hospital, West Papua.Opportunistic infection was identified such as tuberculosis, tuberculosis Pulmo, tuberculosis and candidiasis, candidiasis and diarrhea. The clinical sign appeared in HIV infected patients such as itchy, cough and loss weight. The prevalence of opportunistic infection indicated the necessity of monitoring the opportunistic infection of HIV/AIDS patients in Indonesia.

Contributing risk factors for orthopedic device related infections in sina hospital, tehran, iran.

PubMed

Hadadi, A; Zehtab, M J; Babagolzadeh, H; Ashraf, H

2011-02-01

In spite of decreasing incidence of orthopedic device-related infections to 1%, nowadays, device-related infection still remains a diagnostic, therapeutic and cost-related problem. The objective of this study is to evaluate the contributing risk factors for orthopedic device-related infections in Sina Hospital, Tehran, Iran. Three hundred and thirty patients who underwent orthopedic device implantation from 2002-2006 were enrolled; among them, 110 patients were complicated with infection. Descriptive and logistic regression analyses were performed to determine the risk factors for device related infections. Patients with infection were older compared to those without infection. The Staphylococcus aureus was the commonest organism. A correlation was observed between wound infection and external fixation, an underlying health condition, and addiction which were independent risk factors for a device related infection. Orthopedic device-related infection puts a great financial burden on patients and hospital resources and could lead to morbidity and mortality in patients. So, appropriate pre and postoperative wound care for dirty wounds, especially when external fixators are used, and in patients with poor conditions or addiction should be done with more caution.

Equine infectious anemia virus-infected dendritic cells retain antigen presentation capability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivera, Julie A.; McGuire, Travis C.

2005-05-10

To determine if equine monocyte-derived dendritic cells (DC) were susceptible to equine infectious anemia virus (EIAV) infection, ex vivo-generated DC were infected with virus in vitro. EIAV antigen was detected by immunofluorescence 3 days post-infection with maximum antigen being detected on day 4, whereas there was no antigen detected in DC incubated with the same amount of heat-inactivated EIAV. No cytolytic activity was observed after EIAV{sub WSU5} infection of DC. These monocyte-derived DC were more effective than macrophages and B cells in stimulating allogenic T lymphocytes. Both infected macrophages and DC stimulated similar levels of memory CTL responses in mixturesmore » of CD8+ and CD4+ cells as detected with {sup 51}Cr-release assays indicating that EIAV infection of DC did not alter antigen presentation. However, EIAV-infected DC were more effective than infected macrophages when used to stimulate memory CTL in isolated CD8+ cells. The maintenance of antigen processing and presenting function by EIAV-infected DC in vitro suggests that this function is maintained during in vivo infection.« less

After infection with Leishmania infantum, Golden Hamsters (Mesocricetus auratus) become more attractive to female sand flies (Lutzomyia longipalpis).

PubMed

Nevatte, T M; Ward, R D; Sedda, L; Hamilton, J G C

2017-07-21

In Brazil, human and canine visceral leishmaniasis is caused by infection with Leishmania infantum, a Protist parasite transmitted by blood-feeding female Lutzomyia longipalpis sand flies. The objective of this study was to determine if the odour of hamsters, infected with Le. infantum, was more attractive than the odour of the same hamsters, before they were infected. The attractiveness of odour collected from individual hamsters (n = 13), before they were infected, was compared in a longitudinal study, with the attractiveness of the odour of the same hamster in a Y-tube olfactometer bioassay, at a late stage of infection. The odour of six of the golden hamsters was significantly more attractive to 50% of the female sand flies at the end of infection compared to before infection and the odour of four of the golden hamsters was significantly more attractive to 75% of the female sand flies at the end of infection. These results strongly indicate that hamsters infected with Le. infantum become significantly more attractive to a greater proportion of female sand flies as the infection progresses.

Infectious complications of the primary immunodeficiencies.

PubMed

Stiehm, E R; Chin, T W; Haas, A; Peerless, A G

1986-07-01

The primary manifestation of the immunodeficiencies is undue susceptibility to infection. This means too many, too severe, too prolonged, too complicated and too unusual infections. Infections in immunodeficiency have a characteristic cause depending on the nature of the immune deficiency. Antibody deficiencies are associated with infections with gram-positive infections. Cellular immune deficiencies are associated with mycobacterial, protozoan, fungus, virus, and opportunistic bacterial infection. Phagocytic disorders are associated with staphylococcal, fungal, and gram-negative organisms. Complement disorders are associated by neisserial infections. Infections have also been implicated in the pathogenesis of some immunodeficiencies in some circumstances. These include human T lymphotropic virus type III (HTLV-III), rubella virus, cytomegalovirus, and Epstein-Barr virus. Several infectious syndromes in specific immunodeficiencies have been identified. Examples include enteric cytopathic human orphan (ECHO) virus encephalitis in agammaglobulinemia, and meningococcal meningitis in C6 deficiency. Infections can also be induced by live vaccines given in immunodeficiency (e.g., paralytic polio in agammaglobulinemia.) Unusual infectious syndromes will be illustrated including parainfluenza infection in severe combined and immunodeficiency, Legionella pneumonia in chronic granulomatous disease, and Cryptosporidium infection in hyper-IgM immunodeficiency.

Co-infections of haemosporidian and trypanosome parasites in a North American songbird.

PubMed

Soares, Letícia; Ellis, Vincenzo A; Ricklefs, Robert E

2016-12-01

Hosts frequently harbour multiple parasite infections, yet patterns of parasite co-occurrence are poorly documented in nature. In this study, we asked whether two common avian blood parasites, one haemosporidian and one trypanosome, affect each other's occurrence in individuals of a single host species. We used molecular genotyping to survey protozoan parasites in the peripheral blood of yellow-breasted chats (Aves: Passeriformes [Parulidae]: Icteria virens) from the Ozarks of Southern Missouri. We also determined whether single and co-infections differently influence white blood cell and polychromatic erythrocyte counts, the latter being a measure of regenerative anaemia. We found a positive association between the haemosporidian and trypanosome parasites, such that infection by one increases the probability that an individual host is infected by the other. Adult individuals were more likely than juveniles to exhibit haemosporidian infection, but co-infections and single trypanosome infections were not age-related. We found evidence of pathogenicity of trypanosomes in that infected individuals exhibited similar levels of regenerative anaemia as birds infected with haemosporidian parasites of the genus Plasmodium. Counts of white blood cells did not differ with respect to infection status.

CENTRAL NERVOUS SYSTEM INFECTION DURING IMMUNOSUPPRESSION

PubMed Central

Zunt, Joseph R.

2009-01-01

The central nervous system (CNS) is susceptible to bacterial, viral, and fungal infections. Suppression of the immune system by human immunodeficiency virus (HIV) infection or immunosuppressive therapy after transplantation increases susceptibility to CNS infection and modifies the presentation, diagnosis, and recommended treatment of various CNS infections. This chapter discusses how suppression of the host immune status modifies the presentation, diagnosis, and treatment of selected CNS infections. PMID:11754299

[Analysis of the etiological structure of sexually transmitted infections and immunological responsiveness in women with papillomavirus infection of the cervix uteri].

PubMed

Shevchenko, E A; Uspenskaia, O A

2009-01-01

Two sexually transmitted infections or more were more frequently encountered in persistent papillomavirus infection (PVI) than those in transient PVI. The found immunological parameters in PVI arrested further infection progression, suppressed the persistence of human papillomavirus infection types 16 and 18, and prevented related cancer. This might eliminate the virus from the body.

Prosthetic Joint Infections

PubMed Central

Aslam, Saima; Darouiche, Rabih O.

2012-01-01

Prosthetic joint infections represent a major therapeutic challenge for both healthcare providers and patients. This paper reviews the predisposing factors, pathogenesis, microbiology, diagnosis, treatment and prophylaxis of prosthetic joint infection. The most optimal management strategy should be identified based on a number of considerations including type and duration of infection, antimicrobial susceptibility of the infecting pathogen, condition of infected tissues and bone stock, patient wishes and functional status. PMID:22847032

Incidence and clinical implication of nosocomial infections associated with implantable biomaterials – catheters, ventilator-associated pneumonia, urinary tract infections

PubMed Central

Guggenbichler, Josef Peter; Assadian, Ojan; Boeswald, Michael; Kramer, Axel

2012-01-01

Health care associated infections, the fourth leading cause of disease in industrialised countries, are a major health issue. One part of this condition is based on the increasing insertion and implantation of prosthetic medical devices, since presence of a foreign body significantly reduces the number of bacteria required to produce infection. The most significant hospital-acquired infections, based on frequency and potential severity, are those related to procedures e.g. surgical site infections and medical devices, including urinary tract infection in catheterized patients, pneumonia in patients intubated on a ventilator and bacteraemia related to intravascular catheter use. At least half of all cases of nosocomial infections are associated with medical devices. Modern medical and surgical practices have increasingly utilized implantable medical devices of various kinds. Such devices may be utilized only short-time or intermittently, for months, years or permanently. They improve the therapeutic outcome, save human lives and greatly enhance the quality of life of these patients. However, plastic devices are easily colonized with bacteria and fungi, able to be colonized by microorganisms at a rate of up to 0.5 cm per hour. A thick biofilm is formed within 24 hours on the entire surface of these plastic devices once inoculated even with a small initial number of bacteria. The aim of the present work is to review the current literature on causes, frequency and preventive measures against infections associated with intravascular devices, catheter-related urinary tract infection, ventilator-associated infection, and infections of other implantable medical devices. Raising awareness for infection associated with implanted medical devices, teaching and training skills of staff, and establishment of surveillance systems monitoring device-related infection seem to be the principal strategies used to achieve reduction and prevention of such infections. The intelligent use of suitable antiseptics in combination with medical devices may further support reduction and prevention of such infections. In addition to reducing the adverse clinical outcomes related with these infections, such reduction may substantially decrease the economic burden caused by device-related infection for health care systems. PMID:22242099

Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury.

PubMed

Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R; Merriman, Joseph A; Stach, Christopher S; Horswill, Alexander R; Peterson, Marnie L; Schlievert, Patrick M

2013-08-20

Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs' role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763-1771, 2007). Among these infections are sepsis, infective endocarditis, and acute kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and kidney abscess formation. We demonstrate that superantigens are critical in the causation of all three infections. We show that their association results from both superantigenicity and direct toxic effects on endothelial cells, the latter likely contributing to delayed endothelium healing. Our studies contribute significantly to understanding the development of these illnesses and are expected to lead to development of important therapies to treat such illnesses.

Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India

PubMed Central

Sarkar, Jayeeta; Saha, Debraj; Bandyopadhyay, Bhaswati; Saha, Bibhuti; Kedia, Deepika; Guha Mazumder, D.N.; Chakravarty, Runu; Guha, Subhasish Kamal

2016-01-01

Background & objectives: Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. The present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients. Methods: Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination. Results: HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (P<0.001) and APRI (P<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype. Interpretation & conclusions: HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to initiate appropriate ART regimen. PMID:27488008

Infection and Co-infection with Helminths and Plasmodium among School Children in Côte d’Ivoire: Results from a National Cross-Sectional Survey

PubMed Central

Yapi, Richard B.; Hürlimann, Eveline; Houngbedji, Clarisse A.; Ndri, Prisca B.; Silué, Kigbafori D.; Soro, Gotianwa; Kouamé, Ferdinand N.; Vounatsou, Penelope; Fürst, Thomas; N’Goran, Eliézer K.; Utzinger, Jürg; Raso, Giovanna

2014-01-01

Background Helminth infection and malaria remain major causes of ill-health in the tropics and subtropics. There are several shared risk factors (e.g., poverty), and hence, helminth infection and malaria overlap geographically and temporally. However, the extent and consequences of helminth-Plasmodium co-infection at different spatial scales are poorly understood. Methodology This study was conducted in 92 schools across Côte d’Ivoire during the dry season, from November 2011 to February 2012. School children provided blood samples for detection of Plasmodium infection, stool samples for diagnosis of soil-transmitted helminth (STH) and Schistosoma mansoni infections, and urine samples for appraisal of Schistosoma haematobium infection. A questionnaire was administered to obtain demographic, socioeconomic, and behavioral data. Multinomial regression models were utilized to determine risk factors for STH-Plasmodium and Schistosoma-Plasmodium co-infection. Principal Findings Complete parasitological and questionnaire data were available for 5,104 children aged 5-16 years. 26.2% of the children were infected with any helminth species, whilst the prevalence of Plasmodium infection was 63.3%. STH-Plasmodium co-infection was detected in 13.5% and Schistosoma-Plasmodium in 5.6% of the children. Multinomial regression analysis revealed that boys, children aged 10 years and above, and activities involving close contact to water were significantly and positively associated with STH-Plasmodium co-infection. Boys, wells as source of drinking water, and water contact were significantly and positively associated with Schistosoma-Plasmodium co-infection. Access to latrines, deworming, higher socioeconomic status, and living in urban settings were negatively associated with STH-Plasmodium co-infection; whilst use of deworming drugs and access to modern latrines were negatively associated with Schistosoma-Plasmodium co-infection. Conclusions/Significance More than 60% of the school children surveyed were infected with Plasmodium across Côte d’Ivoire, and about one out of six had a helminth-Plasmodium co-infection. Our findings provide a rationale to combine control interventions that simultaneously aim at helminthiases and malaria. PMID:24901333

Differences in Risk Behavior and Demographic Factors between Men who have Sex with Men with Acute and Non-Acute Human Immunodeficiency Virus Infection in a Community-Based Testing Program in Los Angeles

PubMed Central

Davey, Dvora Joseph; Beymer, Matthew; Roberts, Chelsea P; Bolan, Robert K; Klausner, Jeffrey D

2016-01-01

Introduction High viremia combined with HIV-infection status unawareness and increased sexual risk behavior contributes to a disproportionate amount of new HIV infections. Methods From August 2011-July 2015, the Los Angeles LGBT Center conducted 66,546 HIV tests. We compared factors including the presence of concomitant sexually transmitted infections, number of recent sex partners and reported condomless anal intercourse between men who have sex with men (MSM) diagnosed with an acute HIV infection and a non-acute HIV infection using multivariable logistic regression. Results Of 1,082 unique MSM who tested HIV-infected for the first time, 165 (15%) had an acute infection and 917 had a non-acute infection. HIV rapid antibody testing was 84.8% sensitive for detecting HIV infection (95% CI=82.9%-87.1%). Median HIV viral load among acutely infected MSM was 842,000 copies/ml (interquartile range=98,200-4,897,318). MSM with acute infection had twice the number of sex partners in the prior 30-days (median=2), and prior 3-months (median=4) before diagnosis compared to those diagnosed with non-acute infection (p=<0.0001). The odds of acute HIV infection were increased with the numbers of recent sex partners after controlling for age and race/ethnicity (aOR >5 partners in past 30-days=2.74; 95%CI=1.46-5.14; aOR >10 partners in past 3-months=2.41; 95%CI=1.36-4.25). Non-African American MSM had almost double the odds of being diagnosed with an acute HIV infection compared with African-American MSM (aOR=1.97; 95% CI=1.10-3.52). Conclusion MSM with acute HIV infection had nearly twice as many sex partners in the past 30-days and 3-months compared with MSM with newly diagnosed non-acute HIV infection. Those diagnosed with acute HIV infection had decreased odds of being African American MSM. PMID:27861243

Epidemiology and Microbiology of First Ventricular Assist Device Infection and Their Effect on Outcomes

PubMed Central

Guzman, Merilda Blanco; Vader, Justin; Olsen, Margaret; Dubberke, Erik R

2017-01-01

Abstract Background Left ventricular assist devices (VADs) are life-saving for patients with end stage heart failure but their benefits are limited due to infectious complications. Large studies looking at the site of infection and microbiology on outcomes are not available. Methods We conducted a single center retrospective cohort study of patients who underwent VAD implantation from 2009 to 2015. VAD infections were defined according to the criteria by the International Society for Heart and Lung Transplantation (ISHLT). Only the first VAD infection was included. Patients were followed until transplant, death or end of study. Descriptive statistics were performed. Time to event data was analyzed using Kaplan Meier and Cox Proportional Hazards. Results A total of 451 patients had a VAD placed during the study period. Median duration of follow up was 293 days (IQR-503) in patients without infection and 585 days (IQR 577) in those with VAD infection. 175 patients (38.8%) had at least 1 VAD infection, 29.1% involved the endovascular space and 70.9% involved local VAD infection. Median survival time was 1,430 days with local infection, 592 days with endovascular infection and 661 days in patients without infection (P < 0.001, Figure). The most common endovascular infection involved the pump/cannula (52.9%) and the most common local infection involved the superficial driveline (61.3%). Of the infections with a single identifiable organism, 74.5% were Gram-positives, 19.6 % were Gram-negatives and 5.2% were candida species. The predominant microorganisms were Staphylococcus aureus (35.9%), S. epidermidis (8.5%), Pseudomonas aeruginosa (7.8%) and Enterococcus faecalis (6.5%). There was no difference in mortality when Gram-positive, Gram-negative and Candida infections were compared. Conclusion Patients who survive the early post-VAD period frequently develop infectious complications. Patients with endovascular infections had significantly decreased survival compared with those with local infection. Further studies to develop strategies for prevention of VAD infections are needed. Disclosures M. Olsen, Pfizer: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; sanofi pasteur: Grant Investigator, Research grant

Cutaneous Infections in Wrestlers

PubMed Central

Wilson, Eugene K.; deWeber, Kevin; Berry, James W.; Wilckens, John H.

2013-01-01

Context: Cutaneous infections are common in wrestlers. Although many are simply a nuisance in the everyday population, they can be problematic to wrestlers because such infections may result in disqualification from practice or competition. Prompt diagnosis and treatment are therefore important. Evidence Acquisition: Medline and PubMed databases, the Cochrane Database of Systematic Reviews, and UpToDate were searched through 2012 with the following keywords in various combinations: skin infections, cutaneous infections, wrestlers, athletes, methicillin-resistant Staphylococcus aureus, skin and soft tissue infections, tinea corporis, tinea capitis, herpes simplex, varicella zoster, molluscum contagiosum, verruca vulgaris, warts, scabies, and pediculosis. Relevant articles found in the primary search, and selected references from those articles were reviewed for pertinent clinical information. Results: The most commonly reported cutaneous infections in wrestlers are herpes simplex virus infections (herpes gladiatorum), bacterial skin and soft tissue infections, and dermatophyte infections (tinea gladiatorum). The clinical appearance of these infections can be different in wrestlers than in the community at large. Conclusion: For most cutaneous infections, diagnosis and management options in wrestlers are similar to those in the community at large. With atypical presentations, testing methods are recommended to confirm the diagnosis of herpes gladiatorum and tinea gladiatorum. There is evidence to support the use of prophylactic medications to prevent recurrence of herpes simplex virus and reduce the incidence of dermatophyte infections in wrestlers. PMID:24427413

P. vivax malaria and dengue fever co-infection: a cross-sectional study in the Brazilian Amazon.

PubMed

Magalhães, Belisa M L; Siqueira, André M; Alexandre, Márcia A A; Souza, Marcela S; Gimaque, João B; Bastos, Michele S; Figueiredo, Regina M P; Melo, Gisely C; Lacerda, Marcus V G; Mourão, Maria P G

2014-10-01

Malaria and dengue are the most prevalent vector-borne diseases worldwide and represent major public health problems. Both are endemic in tropical regions, propitiating co-infection. Only few co-infection cases have been reported around the world, with insufficient data so far to enhance the understanding of the effects of co-infection in the clinical presentation and severity. A cross-sectional study was conducted (2009 to 2011) in hospitalized patients with acute febrile syndrome in the Brazilian Amazon. All patients were submitted to thick blood smear and PCR for Plasmodium sp. detection, ELISA, PCR and NS1 tests for dengue, viral hepatitis, HIV and leptospirosis. In total, 1,578 patients were recruited. Among them, 176 (11.1%) presented P. vivax malaria mono-infection, 584 (37%) dengue fever mono-infection, and 44 (2.8%) were co-infected. Co-infected patients had a higher chance of presenting severe disease (vs. dengue mono-infected), deep bleeding (vs. P. vivax mono-infected), hepatomegaly, and jaundice (vs. dengue mono-infected). In endemic areas for dengue and malaria, jaundice (in dengue patients) and spontaneous bleeding (in malaria patients) should raise the suspicion of co-infection. Besides, whenever co-infection is confirmed, we recommend careful monitoring for bleeding and hepatic complications, which may result in a higher chance of severity, despite of the fact that no increased fatality rate was seen in this group.

Seasonal migrations, body temperature fluctuations, and infection dynamics in adult amphibians.

PubMed

Daversa, David R; Monsalve-Carcaño, Camino; Carrascal, Luis M; Bosch, Jaime

2018-01-01

Risks of parasitism vary over time, with infection prevalence often fluctuating with seasonal changes in the annual cycle. Identifying the biological mechanisms underlying seasonality in infection can enable better prediction and prevention of future infection peaks. Obtaining longitudinal data on individual infections and traits across seasons throughout the annual cycle is perhaps the most effective means of achieving this aim, yet few studies have obtained such information for wildlife. Here, we tracked spiny common toads ( Bufo spinosus ) within and across annual cycles to assess seasonal variation in movement, body temperatures and infection from the fungal parasite, Batrachochytrium dendrobatidis (Bd) . Across annual cycles, toads did not consistently sustain infections but instead gained and lost infections from year to year. Radio-tracking showed that infected toads lose infections during post-breeding migrations, and no toads contracted infection following migration, which may be one explanation for the inter-annual variability in Bd infections. We also found pronounced seasonal variation in toad body temperatures. Body temperatures approached 0 °C during winter hibernation but remained largely within the thermal tolerance range of Bd . These findings provide direct documentation of migratory recovery (i.e., loss of infection during migration) and escape in a wild population. The body temperature reductions that we observed during hibernation warrant further consideration into the role that this period plays in seasonal Bd dynamics.

Seasonal migrations, body temperature fluctuations, and infection dynamics in adult amphibians

PubMed Central

Daversa, David R.; Monsalve-Carcaño, Camino; Carrascal, Luis M.

2018-01-01

Risks of parasitism vary over time, with infection prevalence often fluctuating with seasonal changes in the annual cycle. Identifying the biological mechanisms underlying seasonality in infection can enable better prediction and prevention of future infection peaks. Obtaining longitudinal data on individual infections and traits across seasons throughout the annual cycle is perhaps the most effective means of achieving this aim, yet few studies have obtained such information for wildlife. Here, we tracked spiny common toads (Bufo spinosus) within and across annual cycles to assess seasonal variation in movement, body temperatures and infection from the fungal parasite, Batrachochytrium dendrobatidis (Bd). Across annual cycles, toads did not consistently sustain infections but instead gained and lost infections from year to year. Radio-tracking showed that infected toads lose infections during post-breeding migrations, and no toads contracted infection following migration, which may be one explanation for the inter-annual variability in Bd infections. We also found pronounced seasonal variation in toad body temperatures. Body temperatures approached 0 °C during winter hibernation but remained largely within the thermal tolerance range of Bd. These findings provide direct documentation of migratory recovery (i.e., loss of infection during migration) and escape in a wild population. The body temperature reductions that we observed during hibernation warrant further consideration into the role that this period plays in seasonal Bd dynamics. PMID:29761041

[Features of Bordetella pertussis, Bordetella spp. infection and whopping cough in Córdoba province, Argentina].

PubMed

Giayetto, Víctor O; Blanco, Sebastián; Mangeaud, Arnaldo; Barbás, María G; Cudolá, Analía; Gallego, Sandra V

2017-04-01

Whooping cough is a re-emerging infection in the world and Latin America. It was considered relevant to investigate the clinical and epidemiological profile of Bordetella spp. and Bordetella pertussis infection in Córdoba province, Argentina; evaluating, at the same time, the co-infection with virus producing respiratory infections that may be confused with whooping cough. All whooping cough suspected cases were studied by Polimerase Chain Reaction, amplifying the repeated insertion sequence (IS) 481 and the promoter gene encoding pertussis toxin, between 2011 and 2013. The data were obtained from the clinical and epidemiological records. From 2,588 whooping cough suspected cases, 11.59% was infected by Bordetella spp. and 9.16% was confirmed as Bordetella pertussis infection. The rate of infection was 7.22 and 1.84 per 100,000 for 2011 and 2012, respectively. The infection presented a seasonal tendency and it was mainly found on the group of children between 13 and 24 months old. The co-infection with virus producing respiratory infections, were uncommon. Paroxysmal cough, cyanosis and/or vomiting were predictors of the infection for Bordetella pertussis. To deal with the re-emergence of whooping cough is important the knowledge of the regional epidemiological situation. This paper shows the situation of these infections in the regional clinical and epidemiological context, and makes the information available for health decision-making.

Prevalence of Helicobacter pylori infection in newly arrived refugees attending the Migrant Health Service, South Australia.

PubMed

Abdul Rahim, Nur R; Benson, Jill; Grocke, Kathryn; Vather, Deeva; Zimmerman, Jessica; Moody, Tessa; Mwanri, Lillian

2017-04-01

To determine the prevalence of Helicobacter pylori infection in the refugee population attending the Migrant Health Service, South Australia, identify demographic factors associated with infection and compare prevalence of infection in refugees with that of the nonrefugee population in Australia. Cross-sectional study conducted between October 2010 and August 2013. Monoclonal stool antigen testing for H. pylori infection is performed as part of a comprehensive health assessment for newly arrived refugees. The sample population included 922 adults and children. Outcome measures were (i) prevalence of H. pylori infection (ii) association between demographic factors such as sex, ethnicity and age, and H. pylori infection. H. pylori infection was detected in 198 (21.5%) participants (95% CI 18.9%-24.3%). The odds of infection were lower in females OR 0.71 (95% CI 0.51-0.98) compared to males. Compared to Middle Eastern participants, the odds of infection were 1.75 (95% CI 1.17-2.62) times higher in African and 1.90 (95% CI 1.10-3.26) times higher in Burmese participants. Infection was not associated with age. H. pylori infection is common among newly arrived refugees. The long latency of infection to development of complications and the availability of testing and relatively effective eradication regimens all add weight to a decision to screen in this population. © 2016 John Wiley & Sons Ltd.

Adults with suspected central nervous system infection: A prospective study of diagnostic accuracy.

PubMed

Khatib, Ula; van de Beek, Diederik; Lees, John A; Brouwer, Matthijs C

2017-01-01

To study the diagnostic accuracy of clinical and laboratory features in the diagnosis of central nervous system (CNS) infection and bacterial meningitis. We included consecutive adult episodes with suspected CNS infection who underwent cerebrospinal fluid (CSF) examination. The reference standard was the diagnosis classified into five categories: 1) CNS infection; 2) CNS inflammation without infection; 3) other neurological disorder; 4) non-neurological infection; and 5) other systemic disorder. Between 2012 and 2015, 363 episodes of suspected CNS infection were included. CSF examination showed leucocyte count >5/mm 3 in 47% of episodes. Overall, 89 of 363 episodes were categorized as CNS infection (25%; most commonly viral meningitis [7%], bacterial meningitis [7%], and viral encephalitis [4%]), 36 (10%) episodes as CNS inflammatory disorder, 111 (31%) as systemic infection, in 119 (33%) as other neurological disorder, and 8 (2%) as other systemic disorders. Diagnostic accuracy of individual clinical characteristics and blood tests for the diagnosis of CNS infection or bacterial meningitis was low. CSF leucocytosis differentiated best between bacterial meningitis and other diagnoses (area under the curve [AUC] 0.95) or any neurological infection versus other diagnoses (AUC 0.93). Clinical characteristics fail to differentiate between neurological infections and other diagnoses, and CSF analysis is the main contributor to the final diagnosis. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Infection Control and Prevention: A Review of Hospital-Acquired Infections and the Economic Implications

PubMed Central

Reed, Deoine; Kemmerly, Sandra A.

2009-01-01

The Centers for Disease Control and Prevention estimates that 2 million patients suffer from hospital-acquired infections every year and nearly 100,000 of them die. Most of these medical errors are preventable. Hospital-acquired infections result in up to $4.5 billion in additional healthcare expenses annually. The U.S. government has responded to this financial loss by focusing on healthcare quality report cards and by taking strong action to curb healthcare spending. The Medicare Program has proposed changes to the Hospital Inpatient Prospective Payment System and Fiscal Year Rates: Proposed Rule CMS 1488-P-Healthcare-associated infection. Payment will be linked to performance. Under the new rule, payment will be withheld from hospitals for care associated with treating certain catheter-associated urinary tract infections, vascular catheter-associated infections, and mediastinitis after coronary artery bypass graft surgery. Infection-prevention strategies are essential. In the healthcare setting, the infection control department is categorized as non-revenue-producing. Funds dedicated to resources such as staff, educational programs, and prevention measures are vastly limited. Hospital leaders will need to balance the upfront cost needed to prevent hospital-related infections with the non-reimbursed expense accrued secondary to potentially preventable infections. The purpose of this paper is to present case studies and cost analysis of hospital-acquired infections and present strategies that reduce infections and cost. PMID:21603406

[Vaginal infections in a Family Health Clinic in the Metropolitan Region, Chile].

PubMed

Villaseca, Rodrigo; Ovalle, Alfredo; Amaya, Fernando; Labra, Bayron; Escalona, Natalia; Lizana, Paola; Montoya, M José; Lillo, Eduardo; Martínez, M Angélica

2015-02-01

Vaginal infections are a frequent cause for consultation, but their prevalence and etiology vary in different populations. To determine the prevalence and etiologies of vaginal infection in women attending a family health center in the Metropolitan Region of Chile. The microbiological diagnosis was made by wet mount and Gram stain. Diagnosis of trichomoniasis was performed by wet mount, culture and polymerase chain reaction. 101 women aged 15-54, not selected by signs or symptoms of vaginal infection, 46 of them pregnant were included. In 47 women (46.5%), vaginal infections were diagnosed. An association was observed between age and frequency of vaginal infection. The proportion of infections among pregnant and non-pregnant women was similar. The most frequent infections were bacterial vaginosis (16.8%), vulvovaginal candidiasis (11.9%) and co-infections (6.9%). We found 5.9% of intermediate microbiota cases, 3% of trichomoniasis and 2% of aerobic vaginitis. Symptoms of vaginal infection had poor agreement with microbiological findings. Otherwise physical signs had good agreement with the presence of infection, but low to moderate concordance with a specific etiology. We found a high prevalence of vaginal infections in the study population. It is necessary to improve the definitions and criteria of microbiological diagnosis of co-infections and intermediate microbiota, for them to be diagnosed in the clinical practice. More descriptive questionnaires are recommended to enhance the usefulness of clinical examination.

Peripheral Leukocyte Migration in Ferrets in Response to Infection with Seasonal Influenza Virus

PubMed Central

Kim, Jin Hyang; York, Ian A.

2016-01-01

In order to better understand inflammation associated with influenza virus infection, we measured cell trafficking, via flow cytometry, to various tissues in the ferret model following infection with an A(H3N2) human seasonal influenza virus (A/Perth/16/2009). Changes in immune cells were observed in the blood, bronchoalveolar lavage fluid, and spleen, as well as lymph nodes associated with the site of infection or distant from the respiratory system. Nevertheless clinical symptoms were mild, with circulating leukocytes exhibiting rapid, dynamic, and profound changes in response to infection. Each of the biological compartments examined responded differently to influenza infection. Two days after infection, when infected ferrets showed peak fever, a marked, transient lymphopenia and granulocytosis were apparent in all infected animals. Both draining and distal lymph nodes demonstrated significant accumulation of T cells, B cells, and granulocytes at days 2 and 5 post-infection. CD8+ T cells significantly increased in spleen at days 2 and 5 post-infection; CD4+ T cells, B cells and granulocytes significantly increased at day 5. We interpret our findings as showing that lymphocytes exit the peripheral blood and differentially home to lymph nodes and tissues based on cell type and proximity to the site of infection. Monitoring leukocyte homing and trafficking will aid in providing a more detailed view of the inflammatory impact of influenza virus infection. PMID:27315117

Peripheral Leukocyte Migration in Ferrets in Response to Infection with Seasonal Influenza Virus.

PubMed

Music, Nedzad; Reber, Adrian J; Kim, Jin Hyang; York, Ian A

2016-01-01

In order to better understand inflammation associated with influenza virus infection, we measured cell trafficking, via flow cytometry, to various tissues in the ferret model following infection with an A(H3N2) human seasonal influenza virus (A/Perth/16/2009). Changes in immune cells were observed in the blood, bronchoalveolar lavage fluid, and spleen, as well as lymph nodes associated with the site of infection or distant from the respiratory system. Nevertheless clinical symptoms were mild, with circulating leukocytes exhibiting rapid, dynamic, and profound changes in response to infection. Each of the biological compartments examined responded differently to influenza infection. Two days after infection, when infected ferrets showed peak fever, a marked, transient lymphopenia and granulocytosis were apparent in all infected animals. Both draining and distal lymph nodes demonstrated significant accumulation of T cells, B cells, and granulocytes at days 2 and 5 post-infection. CD8+ T cells significantly increased in spleen at days 2 and 5 post-infection; CD4+ T cells, B cells and granulocytes significantly increased at day 5. We interpret our findings as showing that lymphocytes exit the peripheral blood and differentially home to lymph nodes and tissues based on cell type and proximity to the site of infection. Monitoring leukocyte homing and trafficking will aid in providing a more detailed view of the inflammatory impact of influenza virus infection.

Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohio, Hinissan P.; Adamson, Amy L., E-mail: aladamso@uncg.edu

As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transportmore » activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.« less

Infection and childhood leukemia: review of evidence

PubMed Central

Maia, Raquel da Rocha Paiva; Wünsch, Victor

2013-01-01

OBJECTIVE To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors "childhood leukemia" and "infection" and later searching for the words "childhood leukemia" and "maternal infection or disease" or "breastfeeding" or "daycare attendance" or "vaccination" resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers' or infants' to infections (or proxy of infection), and risk of leukemia. RESULTS Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori. CONCLUSIONS Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology. PMID:24626555

Multiple Human Papilloma Virus Infections and Their Impact on the Development of High-Risk Cervical Lesions.

PubMed

Salazar, Katrina L; Zhou, Haijun Steve; Xu, Jiaqiong; Peterson, Leif E; Schwartz, Mary R; Mody, Dina R; Ge, Yimin

2015-01-01

Individuals are often infected with multiple genotypes of human papillomavirus (HPV) simultaneously, but the role these infections play in the development of cervical disease is not well established. This study aimed to determine the association of multiple HPV infections with high-risk cervical lesions (hrCLs). HPV genotyping was performed on 798 SurePath specimens collected between December 1, 2009, and April 30, 2011. The cases were classified as hrCL (n = 90) or non-hrCL (n = 708) based on cytology diagnoses. The association between hrCL and HPV infection patterns was analyzed. Multiple HPV infections were frequently encountered (38.2%) in the cohort. Increased frequency of hrCLs was associated with a single high-risk HPV (hrHPV) infection. An additive or synergistic effect was not observed for hrCL in multiple HPV infections. The hrCL rates appeared to decrease in various patterns of multiple HPV infections, but the reduction was not statistically significant. Multiple HPV infections are common with no additive or synergistic effect on the development of hrCL. Conversely, reduced hrCL rates were observed in various patterns of multiple HPV infections compared to their single-genotype infection counterparts, suggestive of possible intergenotypic competition or more effective immune response triggered by multiple infections. Further studies in larger cohorts are needed. © 2015 S. Karger AG, Basel.

Serodiagnosis of dengue infection using rapid immunochromatography test in patients with probable dengue infection.

PubMed

Kidwai, Aneela Altaf; Jamal, Qaiser; Saher; Mehrunnisa; Farooqi, Faiz-ur-rehman; Saleem-Ullah

2010-11-01

To determine the frequency of seropositive dengue infection using rapid immunochromatographic assay in patients with probable dengue infection as per WHO criteria. A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immunochromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results.

Risk factors for anal HPV infection and anal precancer in HIV-infected men who have sex with men.

PubMed

Schwartz, Lauren M; Castle, Philip E; Follansbee, Stephen; Borgonovo, Sylvia; Fetterman, Barbara; Tokugawa, Diane; Lorey, Thomas S; Sahasrabuddhe, Vikrant V; Luhn, Patricia; Gage, Julia C; Darragh, Teresa M; Wentzensen, Nicolas

2013-12-01

Carcinogenic human papillomaviruses (HPVs) cause a large proportion of anal cancers. Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) are at increased risk of HPV infection and anal cancer compared with HIV-negative men. We evaluated risk factors for HPV infection and anal precancer in a population of HIV-infected MSM. Our study included 305 MSM at an HIV/AIDS clinic in the Kaiser Permanente Northern California Health Maintenance Organization. Logistic regression was used to estimate associations of risk factors comparing men without anal HPV infection; men with anal HPV infection, but no precancer; and men with anal precancer. Low CD4 count (<350 cells/mm(3)) and previous chlamydia infection were associated with an increased risk of carcinogenic HPV infection (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.28-10.40 and OR, 4.24; 95% CI, 1.16-15.51, respectively). History of smoking (OR, 2.71 95% CI, 1.43-5.14), duration, recency, and dose of smoking increased the risk of anal precancer among carcinogenic HPV-positive men but had no association with HPV infection. We found distinct risk factors for anal HPV infection and anal precancer. Risk factors for HPV infection and anal precancer are similar to established risk factors for cervical cancer progression.

Energetic cost of ichthyophonus infection in Juvenile Pacific Herring (Clupea pallasii)

USGS Publications Warehouse

Vollenweider, Johanna J.; Gregg, J.L.; Heintz, R.A.; Hershberger, P.K.

2011-01-01

The energetic costs of fasting and Ichthyophonus infection were measured in juvenile Pacific herring (Clupea pallasii) in a lab setting at three temperatures. Infected herring incurred significant energetic costs, the magnitude of which depended on fish condition at the time of infection (fat versus lean). Herring that were fed continually and were in relatively good condition at the time of infection (fat) never stored lipid despite ad libitum feeding. In feeding herring, the energetic cost of infection was a 30 reduction in total energy content relative to controls 52 days post infection. Following food deprivation (lean condition), infection caused an initial delay in the compensatory response of herring. Thirty-one days after re-feeding, the energetic cost of infection in previously-fasted fish was a 32 reduction in total energy content relative to controls. Body composition of infected herring subsequently recovered to some degree, though infected herring never attained the same energy content as their continuously fed counterparts. Fifty-two days after re-feeding, the energetic cost of infection in previously-fasted fish was a 6 reduction in total energy content relative to controls. The greatest impacts of infection occurred in colder temperatures, suggesting Ichthyophonus-induced reductions in body condition may have greater consequences in the northern extent of herring's range, where juveniles use most of their energy reserves to survive their first winter. Copyright ?? 2011 Johanna J. Vollenweider et al.

Mycobacterium tuberculosis infection among persons who inject drugs in San Diego, California.

PubMed

Armenta, R F; Collins, K M; Strathdee, S A; Bulterys, M A; Munoz, F; Cuevas-Mota, J; Chiles, P; Garfein, R S

2017-04-01

Persons who inject drugs (PWID) might be at increased risk for Mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (LTBI) due to their injection drug use. To determine prevalence and correlates of M. tuberculosis infection among PWID in San Diego, California, USA. PWID aged 18 years underwent standardized interviews and serologic testing using an interferon-gamma release assay (IGRA) for LTBI and rapid point-of-care assays for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Independent correlates of M. tuberculosis infection were identified using multivariable log-binomial regression. A total of 500 participants met the eligibility criteria. The mean age was 43.2 years (standard deviation 11.6); most subjects were White (52%) or Hispanic (30.8%), and male (75%). Overall, 86.7% reported having ever traveled to Mexico. Prevalence of M. tuberculosis infection was 23.6%; 0.8% were co-infected with HIV and 81.7% were co-infected with HCV. Almost all participants (95%) had been previously tested for M. tuberculosis; 7.6% had been previously told they were infected. M. tuberculosis infection was independently associated with being Hispanic, having longer injection histories, testing HCV-positive, and correctly reporting that people with 'sleeping' TB cannot infect others. Strategies are needed to increase awareness about and treatment for M. tuberculosis infection among PWID in the US/Mexico border region.

Tuberculosis infection testing in HIV-positive men who have sex with men from Xi'an China.

PubMed

Xin, H N; Li, X W; Zhang, L; Li, Z; Zhang, H R; Yang, Y; Li, M F; Feng, B X; Li, H J; Gao, L

2017-02-01

In individuals with latent tuberculosis (TB) infection, those living with human immunodeficiency virus (HIV) had a 20-37 times higher risk of developing active TB compared to those without HIV infection. Systematic testing and treatment of latent TB infection are priorities in HIV-infected persons. In China, the prevalence of HIV infection in men who have sex with men (MSM) has gradually increased in the past decade. However, the prevalence of TB infection has been studied sparsely in HIV-infected MSM. Hence, we conducted a pilot study in MSM living with HIV infection in Xi'an city to evaluate TB infection status by means of interferon-γ release assay (IGRA). A total of 182 HIV-infected MSM were included in this study, the prevalence of IGRA positivity was observed to be 8·79% (16/182). IGRA quantitative results were not statistically influenced by the CD4 cell counts of the study participants. However, IGRA positivity was found to be lower than our previously reported data from the general population. This suggests that immunological deficiency might decrease the sensitivity of IGRA and thus increase the number of false negatives. Our primary results, suggesting systematic testing and treatment of latent TB infection together with active case-finding, were equally important for TB control in persons living with HIV infection.

Anaerobic Infections in Children with Neurological Impairments.

ERIC Educational Resources Information Center

Brook, Itzhak

1995-01-01

Children with neurological impairments are prone to develop serious infection with anaerobic bacteria. The most common anaerobic infections are decubitus ulcers; gastrostomy site wound infections; pulmonary infections (aspiration pneumonia, lung abscesses, and tracheitis); and chronic suppurative otitis media. The unique microbiology of each of…

21 CFR 520.2612 - Trimethoprim and sulfadiazine oral suspension.

Code of Federal Regulations, 2010 CFR

2010-04-01

... indicated where control of bacterial infection is required during the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, wound infections, and abscesses. (3) Limitations. For oral use only. Administer the...

Clinical and subclinical infections with Giardia and Cryptosporidium in animals

USDA-ARS?s Scientific Manuscript database

Giardia and Cryptosporidium are frequent parasites of livestock, companion animals, and wildlife, raising questions about the clinical significance of such infections. Infections with both parasites have a wide spectrum of symptoms that can vary between asymptomatic infections to serious infection ...

[Epidemiology of nosocomial infections].

PubMed

Astagneau, P

1998-09-15

The frequency of nosocomial infections lies between 5 and 10%, and varies according to the type of hospital and service. Age, underlying disease invasive devices (such as catheters) or procedures are the main risk factors. Common nosocomial infections are urinary tract infections, pneumonia, surgical site infections, bacteremia/septicemia and intravascular catheter-related infections. Gram positive cocci and gram negative bacilli account for one third and two thirds of microorganisms respectively, Staphylococcus aureus being frequently resistant to antibiotics. Prevention is based on a better control of infection risk related to the use of invasive devices.

Wound infections after transplant nephrectomy.

PubMed

Kohlberg, W I; Tellis, V A; Bhat, D J; Driscoll, B; Veith, F J

1980-05-01

Wound infections after transplant nephrectomy were analyzed retrospectively. When prophylactic antibiotics were not used, 20% of the closed nephrectomy wounds became infected. Eighty-one percent of the infections were due to staphylococcal organisms. Wounds containing a preexisting focus of infection or those reoperated on more than once within a month prior to nephrectomy are at such high risk for infection that these wounds should be left open for secondary healing. With the use of prophylactic cefazolin sodium, in the immediate preoperative and postoperative period, no wound infections have occurred in 18 closed transplant nephrectomy wounds.

Type I Interferons and NK Cells Restrict Gammaherpesvirus Lymph Node Infection.

PubMed

Lawler, Clara; Tan, Cindy S E; Simas, J Pedro; Stevenson, Philip G

2016-10-15

Gammaherpesviruses establish persistent, systemic infections and cause cancers. Murid herpesvirus 4 (MuHV-4) provides a unique window into the early events of host colonization. It spreads via lymph nodes. While dendritic cells (DC) pass MuHV-4 to lymph node B cells, subcapsular sinus macrophages (SSM), which capture virions from the afferent lymph, restrict its spread. Understanding how this restriction works offers potential clues to a more comprehensive defense. Type I interferon (IFN-I) blocked SSM lytic infection and reduced lytic cycle-independent viral reporter gene expression. Plasmacytoid DC were not required, but neither were SSM the only source of IFN-I, as IFN-I blockade increased infection in both intact and SSM-depleted mice. NK cells restricted lytic SSM infection independently of IFN-I, and SSM-derived virions spread to the spleen only when both IFN-I responses and NK cells were lacking. Thus, multiple innate defenses allowed SSM to adsorb virions from the afferent lymph with relative impunity. Enhancing IFN-I and NK cell recruitment could potentially also restrict DC infection and thus improve infection control. Human gammaherpesviruses cause cancers by infecting B cells. However, vaccines designed to block virus binding to B cells have not stopped infection. Using a related gammaherpesvirus of mice, we have shown that B cells are infected not via cell-free virus but via infected myeloid cells. This suggests a different strategy to stop B cell infection: stop virus production by myeloid cells. Not all myeloid infection is productive. We show that subcapsular sinus macrophages, which do not pass infection to B cells, restrict gammaherpesvirus production by recruiting type I interferons and natural killer cells. Therefore, a vaccine that speeds the recruitment of these defenses might stop B cell infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Acute Sleep Deprivation Enhances Post-Infection Sleep and Promotes Survival during Bacterial Infection in Drosophila

PubMed Central

Kuo, Tzu-Hsing; Williams, Julie A.

2014-01-01

Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Conclusions: Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection. Citation: Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. SLEEP 2014;37(5):859-869. PMID:24790264

Spraguea (Microsporida: Spraguidae) infections in the nervous system of the Japanese anglerfish, Lophius litulon (Jordan), with comments on transmission routes and host pathology.

PubMed

Freeman, M A; Yokoyama, H; Osada, A; Yoshida, T; Yamanobe, A; Ogawa, K

2011-06-01

Anglerfish from the genus Lophius are a globally important commercial fishery. The microsporidian Spraguea infects the nervous system of these fish resulting in the formation of large, visible parasitic xenomas. Lophius litulon from Japan were investigated to evaluate the intensity and distribution of Spraguea xenomas throughout the nervous system and to assess pathogenicity to the host and possible transmission routes of the parasite. Spraguea infections in L. litulon had a high prevalence; all fish over 403 mm in standard length being infected, with larger fish usually more heavily infected than smaller fish. Seventy percent of all fish examined had some gross visible sign of infection. The initial site of development is the supramedullary cells on the dorsal surface of the medulla oblongata, where all infected fish have parasitic xenomas. As the disease progresses, a number of secondary sites typically become infected such as the spinal, trigeminal and vagus nerves. Fish with infection in the vagus nerve bundles often have simultaneous sites of infection, in particular the spinal nerves and along the ventral nerve towards the urinary bladder. Advanced vagus nerve infections sometimes form xenomas adjacent to kidney tissue. Spraguea DNA was amplified from the contents of the urinary bladders of two fish, suggesting that microsporidian spores may be excreted in the urine. We conclude that supramedullary cells on the hindbrain are the primary site of infection, which is probably initiated at the cutaneous mucous glands where supramedullary cells are known to extend their peripheral axons. The prevalence of Spraguea infections in L. litulon was very high, and infections often extremely heavy; however, no associated pathogenicity was observed, and heavily infected fish were otherwise normal. © 2011 Blackwell Publishing Ltd.

Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function

PubMed Central

McGregor, JulieAnne G.; Negrete-Lopez, Roberto; Poulton, Caroline J.; Kidd, Jason M.; Katsanos, Suzanne L.; Goetz, Lindsey; Hu, Yichun; Nachman, Patrick H.; Falk, Ronald J.; Hogan, Susan L.

2015-01-01

Background Disease control in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with immunosuppression is effective but burdened by adverse events, especially infections. The study goal was to evaluate risks and types of infections in patients with AAV. Methods Biopsy-proven AAV patients (diagnosed 1/1991–6/2011) followed in an inception cohort were evaluated for adverse events. Severe infections (requiring intravenous antibiotics, intensive care unit, or causing death) were recorded. Infection number was grouped as none, 1–2 or ≥3. Cox regression was used to estimate hazard ratios with 95% confidence intervals. Results A total of 489 patients (median age 59; 47% female, 55% myeloperoxidase-ANCA) were followed for 2.8 years (median). At 1, 2 and 5 years cumulative incidence of infection was 51, 58 and 65% and severe infection was 22, 23 and 26%. Pulmonary and upper respiratory infections were most common (42 and 30% ever experienced each, respectively), highest in the first 3 months. Staphylococcus aureus was most frequently seen among positive cultures (41%, 78 S. aureus/192 total positive cultures), and only one Pneumocystis jiroveci pneumonia (6 weeks into treatment). All-cause death in 12 months was associated with infections (% deaths: 0 infections 3%; 1–2 infections 10%, ≥3 infections 13%, P = 0.002). Controlling for age, sex and kidney function, patients with severe infections were 4.2 times more likely to die within 12 months (95% CI 2.0–8.7; P = 0.001). Conclusions More infections increase the risk of a severe infection which increases risk of all-cause mortality. Respiratory and S. aureus infections are dominant. Targeted prophylactic therapy could decrease morbidity. PMID:25805747

Neospora caninum infection during early pregnancy in cattle: how the isolate influences infection dynamics, clinical outcome and peripheral and local immune responses

PubMed Central

2014-01-01

This work studies the influence of Neospora caninum intra-species diversity on abortion outcome, infection dynamics in terms of parasite dissemination and peripheral-local immune responses in pregnant cattle. Animals were intravenously inoculated at day 70 of pregnancy with 107 tachyzoites of two isolates showing marked differences in virulence in vitro and in pregnant mouse models: Nc-Spain7, a high virulence isolate, and Nc-Spain8, a low-to-moderate virulence isolate. After inoculation, pregnancy was monitored, and dams were culled when foetal death was detected. Foetal mortality occurred in all infected heifers between days 24 and 49 post-infection (pi), however, it was detected sooner in Nc-Spain7-infected animals (median day = 34) than those inoculated with Nc-Spain8 (median day = 41) with a trend towards significance (P < 0.11). Similar histological lesions were observed in placentomes and in most of the foetuses from the two infected groups. However, parasites were more frequently detected in the placenta and foetuses by PCR and in the foetal brain by immunohistochemistry in Nc-Spain7-infected animals. Specific antibodies were detected starting at day 13 post-infection in all infected cattle, with higher IgG levels in Nc-Spain7-infected group. IFN-γ and IL-4 profiles also varied between infected groups in PBMC stimulation assays. Infected animals showed significant increases in their cytokine mRNA levels (IFN-γ, IL-4, IL-10, IL-12p40 and TNF-α) in the caruncle at time of foetal death. Differences between the infected groups were also observed for cytokine profiles. These results demonstrate the influence of the N. caninum isolate on foetal death outcome, infection dynamics and immune responses in cattle. PMID:24479988

Risk of infectious diseases among first-degree relatives of transplant recipients who develop CMV infection: is the infectious phenotype inheritable?

PubMed

Ekenberg, C; Lodding, I P; Wareham, N E; Sørensen, S S; Sengeløv, H; Gustafsson, F; Rasmussen, A; Perch, M; Lundgren, J D; Helleberg, M

2017-12-01

Transplant recipients are at high risk of cytomegalovirus (CMV) infection. Mechanisms explaining the variation in risk of infections are far from fully elucidated. We hypothesised that host genetics explains part of the variation in risk of infection and examined if relatives of recipients with CMV infection have higher rates of severe infections compared to relatives of recipients without this infectious phenotype. In a register-based study, we included first-degree relatives of transplant recipients and examined the risk of hospitalisation due to overall infection or viral infection and risk of death among relatives of recipients who developed CMV infection within the first year of transplantation compared to relatives of recipients without CMV. Analyses were adjusted for sex, age and calendar year. We included 4470 relatives who were followed for 103,786 person-years, median follow-up 24 years [interquartile range (IQR) 12-36]. There were a total of 1360 infection-related hospitalisations in the follow-up period, incidence rate (IR) 13.1/1000 person-years [95% confidence interval (CI), 12.4; 13.8]. 206 relatives were hospitalised with viral infection, IR 1.8/1000 person-years (95% CI, 1.6; 2.0). There was no increased risk of hospitalisation due to infections, IR ratio (IRR) 0.99 (95% CI, 0.88; 1.12), nor specifically viral infections, IRR 0.87 (95% CI, 0.63; 1.19), in relatives of recipients with CMV compared to relatives of recipients without CMV. Also, no difference was seen in analyses stratified by transplant type, family relation and CMV serostatus. The risk of hospitalisation due to infection is not increased among first-degree relatives of transplant recipients with CMV infection compared to relatives of recipients without CMV.

Incidence of Staphylococcus aureus nasal colonization and soft tissue infection among high school football players.

PubMed

Lear, Aaron; McCord, Gary; Peiffer, Jeffrey; Watkins, Richard R; Parikh, Arpan; Warrington, Steven

2011-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections have been documented with increasing frequency in both team and individual sports in recent years. It also seems that the level of MRSA skin and soft tissue infections in the general population has increased. One hundred ninety athletes from 6 local high school football teams were recruited for this prospective observational study to document nasal colonization and the potential role this plays in skin and soft tissue infections in football players and, in particular, MRSA infections. Athletes had nasal swabs done before their season started, and they filled out questionnaires regarding potential risk factors for skin and soft tissue infections. Those enrolled in the study were then observed over the course of the season for skin and soft tissue infections. Those infected had data about their infections collected. One hundred ninety of 386 available student athletes enrolled in the study. Forty-four of the subjects had nasal colonization with methicillin-susceptible S. aureus, and none were colonized with MRSA. There were 10 skin and soft tissue infections (8 bacterial and 2 fungal) documented over the course of the season. All were treated as outpatients with oral or topical antibiotics, and none were considered serious. Survey data from the preseason questionnaire showed 21% with skin infection, 11% with methicillin-susceptible S. aureus, and none with MRSA infection during the past year. Three reported a remote history of MRSA infection. We documented an overall skin infection rate of 5.3% among high school football players over a single season. Our results suggest that skin and soft tissue infection may not be widespread among high school athletes in northeast Ohio.

Microbial Characteristics of Nosocomial Infections and Their Association with the Utilization of Hand Hygiene Products: A Hospital-Wide Analysis of 78,344 Cases.

PubMed

Liu, Song; Wang, Meng; Wang, Gefei; Wu, Xiuwen; Guan, Wenxian; Ren, Jianan

Nosocomial infections are the main adverse events during health care delivery. Hand hygiene is the fundamental strategy for the prevention of nosocomial infections. Microbial characteristics of nosocomial infections in the Asia-Pacific region have not been investigated fully. Correlation between the use of hand hygiene products and the incidence of nosocomial infections is still unknown. This study investigates the microbial characteristics of nosocomial infections in the Asia-Pacific region and analyzes the association between the utilization of hand hygiene products and the incidence of nosocomial infections. A total of 78,344 patients were recruited from a major tertiary hospital in China. Microbial characteristics of major types of nosocomial infections were described. The association between the utilization of hand hygiene products and the incidence of nosocomial infections was analyzed using correlation and regression models. The overall incidence of nosocomial infections was 3.04%, in which the incidence of surgical site infection was 1%. Multi-drug resistance was found in 22.8% of all pathogens, in which multi-drug-resistant Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus were 56.6% and 54.9%, respectively. The utilization of hand hygiene products (including hand sanitizer, soap and paper towel) was associated negatively with the incidence of surgical site infection in surgical departments and the incidence of nosocomial infections in non-intensive care unit (ICU) departments (especially in surgical departments). Regression analysis further identified that higher utilization of hand hygiene products correlated with decreased incidence of major types of nosocomial infections. Multi-drug-resistant organisms are emerging in Asia-Pacific health care facilities. Utilization of hand hygiene products is associated with the incidence of nosocomial infections.

Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1.

PubMed

Greenwood, Edward J D; Schmidt, Fabian; Liégeois, Florian; Kondova, Ivanela; Herbert, Anaïs; Ngoubangoye, Barthelemy; Rouet, François; Heeney, Jonathan L

2014-01-01

Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

Systolic blood pressure, routine kidney variables and renal ultrasonographic findings in cats naturally infected with feline immunodeficiency virus.

PubMed

Taffin, Elien Rl; Paepe, Dominique; Ghys, Liesbeth Fe; De Roover, Katrien; Van de Maele, Isabel; Saunders, Jimmy H; Duchateau, Luc; Daminet, Sylvie

2017-06-01

Objectives Hypertension is a common cause of proteinuria in HIV-infected people. In cats, feline immunodeficiency virus (FIV) infection appears to be associated with proteinuria. Therefore, the results from systolic blood pressure (SBP) measurements in naturally infected FIV-positive cats were reviewed to assess whether hypertension contributes to the observed proteinuria in these cats. Ultrasonographic findings in FIV-positive cats were reviewed to complete renal assessment and to extend the scant knowledge on renal ultrasonography in cats. Methods Data from client-owned, naturally infected FIV-positive cats were retrospectively reviewed. To obtain a control group, records were reviewed from age-matched, privately owned, FIV-negative cats. Results Data from 91 FIV-infected and 113 control cats were compared. FIV-infected cats showed a significantly lower SBP ( P <0.0001) and significantly fewer FIV-infected cats were hypertensive (⩾160 mmHg) compared with control cats ( P = 0.025). The prevalence of renal azotaemia did not significantly differ between groups, although FIV-infected cats had significantly lower urine specific gravity (USG) ( P = 0.0273) and a higher incidence of USG below 1.035 ( P = 0.043). Urinary protein:creatinine ratio (UPC) was significantly higher in FIV-infected cats ( P = 0.0005) and proteinuria (UPC >0.4) occurred more frequently in FIV-infected cats ( P <0.001). Renal ultrasonography showed abnormalities in 60/91 FIV-infected cats, with hyperechogenic cortices in 39/91 and enlarged kidneys in 31/91. Conclusions and relevance Hypertension can be excluded as a common cause of renal damage leading to proteinuria in FIV-infected cats. Proteinuria and poorly concentrated urine are common in naturally infected FIV-positive cats, in contrast to azotaemia. Clinicians should cautiously interpret ultrasonographic abnormalities as these occur in over half of FIV-infected cats.

Specific Infectious Organisms Associated With Poor Outcomes in Treatment for Hip Periprosthetic Infection.

PubMed

Cunningham, Daniel J; Kavolus, Joseph J; Bolognesi, Michael P; Wellman, Samuel S; Seyler, Thorsten M

2017-06-01

Periprosthetic hip infection treatment remains a significant challenge for orthopedics. Some studies have suggested that methicillin resistance and gram-negative organism type are associated with increased treatment failure. The aim of this research is to determine if specific organisms were associated with poor outcomes in treatment for hip periprosthetic infection. Records were reviewed of all patients between 2005 and 2015 who underwent treatment for infected partial or total hip arthroplasty. Characteristics of each patient's treatment course were determined including baseline characteristics, infecting organism(s), infection status at final follow-up, surgeries for infection, and time in hospital. Baseline characteristics and organisms that were associated with clinical outcomes in univariate analysis were incorporated into multivariable outcomes models. When compared with patients infected with other organism(s), patients infected with the following organisms had significantly decreased infection-free rates: Pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA), and Proteus. Infection with certain organisms was associated with 1.13-2.58 additional surgeries: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, MRSA, Pseudomonas, Peptostreptococcus, Klebsiella, Candida, diphtheroids, Propionibacterium acnes, and Proteus species. Specific organisms were associated with 8.56-24.54 additional days in hospital for infection: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, Proteus, MRSA, Enterococcus, Pseudomonas, Klebsiella, beta-hemolytic Streptococcus, and diphtheroids. Higher comorbidity score was also associated with greater length of hospitalization. MRSA, Pseudomonas, and Proteus were associated with all 3 outcomes of lower infection-free rate, more surgery, and more time in hospital in treatment for hip periprosthetic infection. Organism-specific outcome information may help individualize patient-physician discussions about the expected course of treatment for hip periprosthetic infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Type I Interferons and NK Cells Restrict Gammaherpesvirus Lymph Node Infection

PubMed Central

Lawler, Clara; Tan, Cindy S. E.; Simas, J. Pedro

2016-01-01

ABSTRACT Gammaherpesviruses establish persistent, systemic infections and cause cancers. Murid herpesvirus 4 (MuHV-4) provides a unique window into the early events of host colonization. It spreads via lymph nodes. While dendritic cells (DC) pass MuHV-4 to lymph node B cells, subcapsular sinus macrophages (SSM), which capture virions from the afferent lymph, restrict its spread. Understanding how this restriction works offers potential clues to a more comprehensive defense. Type I interferon (IFN-I) blocked SSM lytic infection and reduced lytic cycle-independent viral reporter gene expression. Plasmacytoid DC were not required, but neither were SSM the only source of IFN-I, as IFN-I blockade increased infection in both intact and SSM-depleted mice. NK cells restricted lytic SSM infection independently of IFN-I, and SSM-derived virions spread to the spleen only when both IFN-I responses and NK cells were lacking. Thus, multiple innate defenses allowed SSM to adsorb virions from the afferent lymph with relative impunity. Enhancing IFN-I and NK cell recruitment could potentially also restrict DC infection and thus improve infection control. IMPORTANCE Human gammaherpesviruses cause cancers by infecting B cells. However, vaccines designed to block virus binding to B cells have not stopped infection. Using a related gammaherpesvirus of mice, we have shown that B cells are infected not via cell-free virus but via infected myeloid cells. This suggests a different strategy to stop B cell infection: stop virus production by myeloid cells. Not all myeloid infection is productive. We show that subcapsular sinus macrophages, which do not pass infection to B cells, restrict gammaherpesvirus production by recruiting type I interferons and natural killer cells. Therefore, a vaccine that speeds the recruitment of these defenses might stop B cell infection. PMID:27466430

Analysis of the Bovine Monocyte-Derived Macrophage Response to Mycobacterium avium Subspecies Paratuberculosis Infection Using RNA-seq.

PubMed

Casey, Maura E; Meade, Kieran G; Nalpas, Nicolas C; Taraktsoglou, Maria; Browne, John A; Killick, Kate E; Park, Stephen D E; Gormley, Eamonn; Hokamp, Karsten; Magee, David A; MacHugh, David E

2015-01-01

Johne's disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, (MAP), is a chronic intestinal disease of ruminants with serious economic consequences for cattle production in the United States and elsewhere. During infection, MAP bacilli are phagocytosed and subvert host macrophage processes, resulting in subclinical infections that can lead to immunopathology and dissemination of disease. Analysis of the host macrophage transcriptome during infection can therefore shed light on the molecular mechanisms and host-pathogen interplay associated with Johne's disease. Here, we describe results of an in vitro study of the bovine monocyte-derived macrophage (MDM) transcriptome response during MAP infection using RNA-seq. MDM were obtained from seven age- and sex-matched Holstein-Friesian cattle and were infected with MAP across a 6-h infection time course with non-infected controls. We observed 245 and 574 differentially expressed (DE) genes in MAP-infected versus non-infected control samples (adjusted P value ≤0.05) at 2 and 6 h post-infection, respectively. Functional analyses of these DE genes, including biological pathway enrichment, highlighted potential functional roles for genes that have not been previously described in the host response to infection with MAP bacilli. In addition, differential expression of pro- and anti-inflammatory cytokine genes, such as those associated with the IL-10 signaling pathway, and other immune-related genes that encode proteins involved in the bovine macrophage response to MAP infection emphasize the balance between protective host immunity and bacilli survival and proliferation. Systematic comparisons of RNA-seq gene expression results with Affymetrix(®) microarray data generated from the same experimental samples also demonstrated that RNA-seq represents a superior technology for studying host transcriptional responses to intracellular infection.

Analysis of the Bovine Monocyte-Derived Macrophage Response to Mycobacterium avium Subspecies Paratuberculosis Infection Using RNA-seq

PubMed Central

Casey, Maura E.; Meade, Kieran G.; Nalpas, Nicolas C.; Taraktsoglou, Maria; Browne, John A.; Killick, Kate E.; Park, Stephen D. E.; Gormley, Eamonn; Hokamp, Karsten; Magee, David A.; MacHugh, David E.

2015-01-01

Johne’s disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, (MAP), is a chronic intestinal disease of ruminants with serious economic consequences for cattle production in the United States and elsewhere. During infection, MAP bacilli are phagocytosed and subvert host macrophage processes, resulting in subclinical infections that can lead to immunopathology and dissemination of disease. Analysis of the host macrophage transcriptome during infection can therefore shed light on the molecular mechanisms and host-pathogen interplay associated with Johne’s disease. Here, we describe results of an in vitro study of the bovine monocyte-derived macrophage (MDM) transcriptome response during MAP infection using RNA-seq. MDM were obtained from seven age- and sex-matched Holstein-Friesian cattle and were infected with MAP across a 6-h infection time course with non-infected controls. We observed 245 and 574 differentially expressed (DE) genes in MAP-infected versus non-infected control samples (adjusted P value ≤0.05) at 2 and 6 h post-infection, respectively. Functional analyses of these DE genes, including biological pathway enrichment, highlighted potential functional roles for genes that have not been previously described in the host response to infection with MAP bacilli. In addition, differential expression of pro- and anti-inflammatory cytokine genes, such as those associated with the IL-10 signaling pathway, and other immune-related genes that encode proteins involved in the bovine macrophage response to MAP infection emphasize the balance between protective host immunity and bacilli survival and proliferation. Systematic comparisons of RNA-seq gene expression results with Affymetrix® microarray data generated from the same experimental samples also demonstrated that RNA-seq represents a superior technology for studying host transcriptional responses to intracellular infection. PMID:25699042

Actinomyces in Pregnancy: A Review of the Literature.

PubMed

Estrada, Sarah M; Magann, Everett F; Napolitano, Peter G

2017-04-01

Actinomyces is commonly found in many areas of the body where it derives a benefit without harming the host. When it does infect the host during pregnancy, is that infection a threat to the obstetric patient and does that infection cause adverse pregnancy outcomes? The aim of this study was to review what is known about Actinomyces infections and the impact of an Actinomyces infection on pregnancy outcomes. A PubMed search was undertaken with the search years unlimited to April 1, 2016, and restricted to articles in English. The search terms included "actinomyces," "pregnancy," "prenatal," "maternal," "actinomyces infection," "pregnancy," "chorioamnionitis," "preterm labor," "premature birth," or "postpartum actinomyces." Eighteen of the 154 identified articles are the basis of this review. Actinomyces is a rod-like positive bacterium. The diagnosis of an Actinomyces infection can be by culture or Gram stain. Actinomyces is commensal and typically only infects after a mucosal break or lesion. Seventeen cases were identified in pregnancy. Ten cases were complicated by chorioamnionitis and a preterm delivery. A nidus leading to infection was identified in 12 of the cases including women with a cervical cerclage, dental abscesses, appendicitis, renal actinomycosis, and ovarian abscesses. Adverse pregnancy outcomes have been linked with periodontal disease, but treatment did not prevent preterm delivery in a randomized, blinded, controlled trial. Actinomyces infections in pregnancy are rare but, if they occur, have been linked primarily with preterm deliveries. Obstetricians and gynecologists, family physicians. After completing this activity, the learner should be better able to identify the areas of the body where Actinomyces infections occur and how the infections typically occur, identify the pathophysiologic changes that occur during pregnancy that might lead to an Actinomyces infection and how that infection may affect pregnancy outcomes, and describe the treatment for mild and severe Actinomyces infections.

Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity

PubMed Central

Matar, Caline G.; Anthony, Neil R.; O’Flaherty, Brigid M.; Jacobs, Nathan T.; Priyamvada, Lalita; Engwerda, Christian R.; Speck, Samuel H.; Lamb, Tracey J.

2015-01-01

Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV) by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68) infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh) cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i) suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii) plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission. PMID:25996913

Transcriptional Analysis of PRRSV-Infected Porcine Dendritic Cell Response to Streptococcus suis Infection Reveals Up-Regulation of Inflammatory-Related Genes Expression

PubMed Central

Auray, Gaël; Lachance, Claude; Wang, Yingchao; Gagnon, Carl A.; Segura, Mariela; Gottschalk, Marcelo

2016-01-01

The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine pathogens and often serves as an entry door for other viral or bacterial pathogens, of which Streptococcus suis is one of the most common. Pre-infection with PRRSV leads to exacerbated disease caused by S. suis infection. Very few studies have assessed the immunological mechanisms underlying this higher susceptibility. Since antigen presenting cells play a major role in the initiation of the immune response, the in vitro transcriptional response of bone marrow-derived dendritic cells (BMDCs) and monocytes in the context of PRRSV and S. suis co-infection was investigated. BMDCs were found to be more permissive than monocytes to PRRSV infection; S. suis phagocytosis by PRRSV-infected BMDCs was found to be impaired, whereas no effect was found on bacterial intracellular survival. Transcription profile analysis, with a major focus on inflammatory genes, following S. suis infection, with and without pre-infection with PRRSV, was then performed. While PRRSV pre-infection had little effect on monocytes response to S. suis infection, a significant expression of several pro-inflammatory molecules was observed in BMDCs pre-infected with PRRSV after a subsequent infection with S. suis. While an additive effect could be observed for CCL4, CCL14, CCL20, and IL-15, a distinct synergistic up-regulatory effect was observed for IL-6, CCL5 and TNF-α after co-infection. This increased pro-inflammatory response by DCs could participate in the exacerbation of the disease observed during PRRSV and S. suis co-infection. PMID:27213692

Submicroscopic placental infection by non-falciparum Plasmodium spp.

PubMed

Doritchamou, Justin Y A; Akuffo, Richard A; Moussiliou, Azizath; Luty, Adrian J F; Massougbodji, Achille; Deloron, Philippe; Tuikue Ndam, Nicaise G

2018-02-01

Among the Plasmodium species that infect humans, adverse effects of P. falciparum and P. vivax have been extensively studied and reported with respect to poor outcomes particularly in first time mothers and in pregnant women living in areas with unstable malaria transmission. Although, other non-falciparum malaria infections during pregnancy have sometimes been reported, little is known about the dynamics of these infections during pregnancy. Using a quantitative PCR approach, blood samples collected from Beninese pregnant women during the first antenatal visit (ANV) and at delivery including placental blood were screened for Plasmodium spp. Risk factors associated with Plasmodium spp. infection during pregnancy were assessed as well as the relationships with pregnancy outcomes. P. falciparum was the most prevalent Plasmodium species detected during pregnancy, irrespective either of parity, of age or of season during which the infection occurred. Although no P. vivax infections were detected in this cohort, P. malariae (9.2%) and P. ovale (5.8%) infections were observed in samples collected during the first ANV. These non-falciparum infections were also detected in maternal peripheral blood (1.3% for P. malariae and 1.2% for P. ovale) at delivery. Importantly, higher prevalence of P. malariae (5.5%) was observed in placental than peripheral blood while that of P. ovale was similar (1.8% in placental blood). Among the non-falciparum infected pregnant women with paired peripheral and placental samples, P. malariae infections in the placental blood was significantly higher than in the peripheral blood, suggesting a possible affinity of P. malariae for the placenta. However, no assoctiation of non-falciparum infections and the pregnancy outcomes was observed. Overall this study provided insights into the molecular epidemiology of Plasmodium spp. infection during pregnancy, indicating placental infection by non-falciparum Plasmodium and the lack of association of these infections with adverse pregnancy outcomes.

Plasmodium Infections in Natural Populations of Anolis sagrei Reflect Tolerance Rather Than Susceptibility

PubMed Central

Bonneaud, Camille; Sepil, Irem; Wilfert, Lena; Calsbeek, Ryan

2017-01-01

Synopsis Parasites can represent formidable selection pressures for hosts, but the cost of infection is sometimes difficult to demonstrate in natural populations. While parasite exploitation strategies may, in some instances, actually inflict low costs on their hosts, the response of hosts to infection is also likely to determine whether or not these costs can be detected. Indeed, costs of infection may be obscured if infected individuals in the wild are those that are the most tolerant, rather than the most susceptible, to infection. Here we test this hypothesis in two natural populations of Anolis sagrei, one of the most common anole lizard of the Bahamas. Plasmodium parasites were detected in > 7% of individuals and belonged to two distinct clades: P. mexicanum and P. floriensis. Infected individuals displayed greater body condition than non-infected ones and we found no association between infection status, stamina, and survival to the end of the breeding season. Furthermore, we found no significant difference in the immuno-competence (measured as a response to phytohemagglutinin challenge) of infected versus non-infected individuals. Taken together, our results suggest that the infected individuals that are caught in the wild are those most able to withstand the cost of the infection and that susceptible, infected individuals have been removed from the population (i.e., through disease-induced mortality). This study highlights the need for caution when interpreting estimates of infection costs in natural populations, as costs may appear low either when parasites exploitation strategies truly inflict low costs on their hosts or when those costs are so high that susceptible hosts are removed from the population. PMID:28859403

Health gains from screening for infection of the lower genital tract in women attending for termination of pregnancy.

PubMed

Blackwell, A L; Thomas, P D; Wareham, K; Emery, S J

1993-07-24

Infection of the upper genital tract after abortion is well recognised, but routine screening for infection before termination is rare, and few centres are aware of the prevalence of post-abortion complications in their population. We undertook a study to assess the prevalence and sequelae of genital-tract infection in patients undergoing termination of pregnancy and to estimate the costs and potential benefits of introducing screening and prophylaxis for the most commonly found organisms. The study in Swansea, UK, was of 401 consecutive patients attending for termination of pregnancy; only 1 patient refused to take part. Immediately before the termination procedure vaginal and cervical swabs were taken for microscopic examination and culture of Trichomonas vaginalis, Neisseria gonorrhoeae, and candida species. We sought Chlamydia trachomatis by enzyme-linked immunosorbent assay. 112 (28%) women had the typical bacterial flora of anaerobic (bacterial) vaginosis, 95 (24%) had candidal infection, 32 (8%) chlamydial infection, 3 (0.75%) trichomonas infection, and 1 (0.25%) gonorrhoea. Postoperative follow-up of 30 of the women with chlamydial infection showed that pelvic infection developed in 19 (63%), of whom 7 were readmitted to hospital. 9 male partners of women with chlamydial (plus gonococcal in 1 case) infection were examined; 8 were symptom-free, 3 had C trachomatis infection, and 1 N gonorrhoeae. Estimated costs of hospital admissions for complications of chlamydial infection were more than double the costs of providing a routine chlamydia screening programme and prophylactic treatment. Screening for chlamydial infection before termination of pregnancy is essential. Prophylactic treatment for both chlamydial infection and anaerobic vaginosis should also be considered. Male partners of women infected with chlamydia are often symptom-free, but they must be traced to avoid reinfections.

Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients

PubMed Central

Johansen, Jens Brock; Jørgensen, Ole Dan; Møller, Mogens; Arnsbo, Per; Mortensen, Peter Thomas; Nielsen, Jens Cosedis

2011-01-01

Aims Infection is a serious complication of pacemaker (PM) systems. Although the rate of infection has been debated, the figures are largely unknown. We therefore studied the incidence of PM infection and its associated risk factors in the Danish population. Methods and results Since 1982, all PM implantation and removal procedures performed in Denmark have been prospectively recorded in the Danish Pacemaker Register. All patients (n = 46299) who underwent implantation between 1982 and 2007 were included. The total length of surveillance was 236 888 PM-years. The incidence of infection was calculated according to the total number of PM-years. The incidence of surgical site infection (≤365 days after PM implantation) was compared with later infection in first implant and replacement procedures. Multiple-record and multiple-event-per-subject proportional hazards analyses were used to identify the independent risk factors of PM infection. Surgical site infection occurred in 192 cases after first implantation (incidence rate 4.82/1000 PM-years), and in 133 cases after replacement (12.12/1000 PM-years). Infections occurring more than 365 days after the first implantation occurred in 153 cases (1.02/1000 PM-years), and in 118 cases after replacement (3.26/1000 PM-years). Independent factors associated with an increased risk of PM infection were a greater number of PM operations (including replacements), male sex, younger age, implantation during the earliest part of the study period, and absence of antibiotics (P< 0.001). Conclusion The overall risk of infection after PM implantation was low. A greater number of operations augmented the risk of infection. This should be taken into account when considering revisions of PM systems. PMID:21252172

Treatment based on the type of infected TKA improves infection control.

PubMed

Kim, Young-Hoo; Choi, Yoowang; Kim, Jun-Shik

2011-04-01

A classification system with four types of infected TKAs has been commonly used to determine treatment, especially with regard to whether the prosthesis should be removed or retained. We asked whether (1) the classification-dictated treatment of the four types of infection after TKA would control infection and maintain functional TKA; (2) repeated débridement and two-stage TKA would further improve the infection control rate after initial treatment; and (3) fixation of TKA prosthesis to the host bone was achieved. We retrospectively reviewed 114 patients with 116 infected TKAs. We determined the infection control rate after initial treatment, repeated débridement and two-stage TKA. We evaluated the functional and radiographic results using the Knee Society and Hospital for Special Surgery knee scoring systems. The minimum followup was 2 years (mean, 5.6 years; range, 2-8 years). The overall infection control rate was 100% in all patients. All patients with early superficial postoperative infection, 94% of patients with early deep postoperative infection, 96% of patients with late chronic infection, and 86% of patients with acute hematogenous infection maintained functioning knee prosthesis at the final followup. One hundred nine of the 114 patients could walk with no or only slight pain and maintained functioning knee prostheses. These 109 patients had stable fixation of the TKA prosthesis to host bone. The techniques proposed by the classification effectively controlled infection and maintained functional TKA with firm fixation of the TKA prosthesis in most patients. Repeated débridement and two-stage TKA further improved the control of infection and functional TKA after initial treatment. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Infection following percutaneous vertebral augmentation with polymethylmethacrylate.

PubMed

Park, Jae-Woo; Park, Sang-Min; Lee, Hui Jong; Lee, Choon-Ki; Chang, Bong-Soon; Kim, Hyoungmin

2018-04-27

Although the incidence of infection following vertebroplasty or kyphoplasty is rare, postoperative infection and cement augmentation in preexistent spondylitis can cause life-threatening complications in frail patients with notable comorbidities. In such cases, urgent culture and biopsy and the long-term use of proper antibiotics are necessary. Infection following vertebral augmentation with polymethylmethacrylate (PMMA) is rare. We aimed to analyze 11 cases of pyogenic spondylitis and spondylodiscitis that occurred after vertebroplasty or kyphoplasty and to review similar cases in the literature. All cases of postoperative spinal infections in our institution between January 2005 and November 2016 that primarily underwent percutaneous vertebroplasty or kyphoplasty were retrospectively reviewed. Eleven patients (mean age 76.3 years) were included. The incidence of infection following vertebroplasty/kyphoplasty was 0.36%. Postoperative infection occurred in 3 of 826 cases. All patients underwent combined surgical and antibiotic treatment because of neurologic deficit on the initial diagnosis of the infection or failure of prior medical treatment of the infection. The surgical procedure was thorough debridement of infected tissue and material including PMMA following anterior column reconstruction via anterior/posterior/combined approach in 10 patients and percutaneous pedicle screw fixation alone in 1 patient aged 96 years. The mean follow-up period was 21.1 months after the revision operation, excluding one patient who died 17 days after revision surgery. Ten patients recovered from infection. Although the incidence of infection following vertebroplasty or kyphoplasty is rare, postoperative infection and cement augmentation in preexisting spondylitis can develop into a life-threatening complication in frail patients with notable comorbidities. In treating infected vertebroplasty and kyphoplasty, immediate culture and biopsy and the long-term use of proper antibiotics are critical. Prompt surgical treatment should be considered in case of significant neurologic deficit, severe instability due to infected fracture, and resistance to antibiotics.

Genetic characterization of multiple hepatitis C virus infections following acute infection in HIV-infected men who have sex with men.

PubMed

Thomas, Xiomara V; Grady, Bart P X; Van Der Meer, Jan T M; Ho, Cynthia K; Vanhommerig, Joost W; Rebers, Sjoerd P; De Jong, Menno D; Van Der Valk, Marc; Prins, Maria; Molenkamp, Richard; Schinkel, Janke

2015-11-01

High rates of hepatitis C virus (HCV) reinfections among HIV-infected men who have sex with men (MSM) following clearance of a primary infection suggest absence of protective immunity. Here, we investigated the incidence of HCV super and reinfections in 85 HIV-infected MSM with incident HCV infection. Serial sequencing of a fragment of NS5B and the HCV envelope was used to longitudinally characterize the virus. If the primary genotype was still present at the most recent viremic time point, as indicated by the NS5B sequence analysis, serial envelope 2/hypervariable region 1 (E2/HRV1) sequence analysis was performed to distinguish a new infection with the same genotype (clade switch) from intrahost evolution. Incidence rate and cumulative incidence of secondary infections were estimated, and the effect of the primary genotype (1a versus non1) on the risk of acquiring a second infection with the same genotype was determined using Cox proportional-hazards analysis. Among 85 patients with a median follow-up of 4.8 years, incidence rate of secondary infections was 5.39 cases/100 person-years (95% confidence interval 3.34-8.26). Cumulative incidence of genotype switches was markedly higher than the cumulative incidence of clade switches (26.7 versus 4.8% at 5 years, respectively). In patients with HCV-1a as primary infection, the risk for acquiring another HCV-1a infection was reduced compared to those with a primary non-HCV-1a subsequently acquiring HCV-1a (hazard ratio 0.25, 95% confidence interval 0.07-0.93). Risk of acquiring a secondary infection with the primary genotype was strikingly reduced compared with the risk of acquiring a secondary infection with a different genotype.

[Effect of perinatal recurrent infection on the brain development in immature mice].

PubMed

Song, Li-Li; Huang, Zhi-Heng; Pei, Yi-Ling; Chen, Chao

2014-12-01

To study the effects of perinatal recurrent infection on the brain development in immature mice. Six pregnant C57BL6 mice were randomly assigned to three groups: intrauterine infection, perinatal recurrent infection and control. The intrauterine infection group was intraperitoneally injected with LPS (0.5 mg/kg) on the 18th day of pregnancy. The perinatal recurrent infection group was injected with LPS (0.5 mg/kg) on the 18th day of pregnancy and their offsprings were intraperitoneally injected with the same dose of LPS daily from postnatal day 3 to 12. The control group was administered with normal saline at the same time points as the recurrent infection group. The short-time neurobehaviors were assessed on postnatal day 13. The mice were then sacrificed to measure brain weights and neuropathological changes using cresyl violet staining. Western blot was used to evaluate the expression of TNF-α, Caspase-3 and myelin basic protein (MBP). The brain weights of the recurrent infection group were significantly lower than the control and intrauterine infection groups (P<0.05) and the recurrent infection group displayed significant neuropathological changes. Perinatal recurrent infection resulted in increased expression levels of TNF-α and Caspase-3, and decreased expression level of MBP compared with the intrauterine infection and control groups (P<0.01). The neurobehavior test showed that the recurrent infection group used longer time in gait reflex, right reflex and geotaxis reflex compared with the control and intrauterine infection groups on postnatal day 13 (P<0.05). Perinatal recurrent infection may exacerbate inflammatory response and cell death in the immature brain, which may be one of the important factors for perinatal brain injury.

Prospective assessment of clinical symptoms associated with enterovirus and parechovirus genotypes in a multicenter study in Dutch children.

PubMed

de Crom, S C M; Rossen, J W A; de Moor, R A; Veldkamp, E J M; van Furth, A M; Obihara, C C

2016-04-01

Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens of viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children. To compare the clinical symptoms and laboratory data of children with different EV and HPeV genotypes. This study is part of a multicenter prospective cohort study. Children were included in 3 different hospitals in The Netherlands from 2008 to 2011. Of 285 included patients, 140 (49%) had EV and 44 (15%) HPeV infection. Of children with EV infection 9 (6%) had EV-A, 109 (78%) EV-B, 12 (9%) had a non-type able EV and in 10 (7%) no genotyping was performed. Of children with HPeV infection, 24 (55%) had HPeV-3, 6 (14%) HPeV-1, 2 (5%) HPeV-4 and 1 (2%) HPeV-6. Meningitis was more frequent in EV than in HPeV infected children (54% vs. 36%, p=0.046), and in EV-B than EV-A infected children (60 vs. 33%). In contrast gastroenteritis was more frequent in HPeV than EV infected children (30% vs. 15%, p=0.030), and significantly more in HPeV-1 than HPeV-3 infected children (p<0.001). EV infection is more often associated with meningitis and HPeV infection more often with a gastro-enteritis. EV genotype B infection is more often associated with meningitis than EV genotype A infection. HPeV-1 infection was more often associated with gastroenteritis than HPeV-3 infection. Copyright © 2016 Elsevier B.V. All rights reserved.

A rapid, automated approach for quantitation of rotavirus and reovirus infectivity.

PubMed

Iskarpatyoti, Jason A; Willis, Janet Z; Guan, John; Morse, E Ashley; Ikizler, Miné; Wetzel, J Denise; Dermody, Terence S; Contractor, Nikhat

2012-09-01

Current microscopy-based approaches for immunofluorescence detection of viral infectivity are time consuming and labor intensive and can yield variable results subject to observer bias. To circumvent these problems, we developed a rapid and automated infrared immunofluorescence imager-based infectivity assay for both rotavirus and reovirus that can be used to quantify viral infectivity and infectivity inhibition. For rotavirus, monolayers of MA104 cells were infected with simian strain SA-11 or SA-11 preincubated with rotavirus-specific human IgA. For reovirus, monolayers of either HeLa S3 cells or L929 cells were infected with strains type 1 Lang (T1L), type 3 Dearing (T3D), or either virus preincubated with a serotype-specific neutralizing monoclonal antibody (mAb). Infected cells were fixed and incubated with virus-specific polyclonal antiserum, followed by an infrared fluorescence-conjugated secondary antibody. Well-to-well variation in cell number was normalized using fluorescent reagents that stain fixed cells. Virus-infected cells were detected by scanning plates using an infrared imager, and results were obtained as a percent response of fluorescence intensity relative to a virus-specific standard. An expected dose-dependent inhibition of both SA-11 infectivity with rotavirus-specific human IgA and reovirus infectivity with T1L-specific mAb 5C6 and T3D-specific mAb 9BG5 was observed, confirming the utility of this assay for quantification of viral infectivity and infectivity blockade. The imager-based viral infectivity assay fully automates data collection and provides an important advance in technology for applications such as screening for novel modulators of viral infectivity. This basic platform can be adapted for use with multiple viruses and cell types. Copyright © 2012 Elsevier B.V. All rights reserved.

Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

PubMed

Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

2014-01-01

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

Association Between Allogeneic Blood Transfusion and Postoperative Infection in Major Spine Surgery.

PubMed

Fisahn, Christian; Jeyamohan, Shiveindra; Norvell, Daniel C; Tubbs, Richard S; Moisi, Marc; Chapman, Jens R; Page, Jeni; Oskouian, Rod J

2017-08-01

Retrospective cohort study. The objective of this study is to compare the incidence of infection in patients who do and do not receive blood transfusions in major deformity surgery (>8 levels). Postoperative infections increase morbidity and mortality rates in spine surgery and generate additional costs for the health care system. It has been proposed that blood transfusions increase the risk of wound infection, urinary tract infection, pneumonia, and sepsis. A total of 56 patients met the study criteria, receiving spine surgery involving the fusion of 8 levels or more. Patient-specific characteristics, starting and ending hematocrits, number of units transfused and infections including urinary tract infection, wound infection, pneumonia, and sepsis were documented. Differences in infection risk between those who did and did not undergo a transfusion and their 95% confidence intervals were calculated. Groups were similar with respect to baseline and surgical characteristics except for smoking status, operative time, estimated blood loss, and ending hematocrit. The overall infection rate was greater in patients who underwent transfusion than those who did not (36% vs. 10%; P=0.03). Wound infections (n=5) were only observed in those who underwent a transfusion. Smokers were more likely to receive a transfusion and more likely to experience infection. A stratified analysis demonstrated an increased risk of infection associated with transfusion; however, the risk was greater in smokers, suggesting the effect of transfusion on infection could be modified by smoking. Patients undergoing transfusion experienced a significantly longer hospital stay (P=0.01). Allogeneic red blood cell transfusion in major spine surgery could be a risk factor for postoperative infection. This increased risk seems to be magnified in those who smoke. Further studies are warranted, and risks of blood loss and transfusion-related complications in smokers also potentially merit exploration. Level 3.

Ureteral Stents and Foley Catheters-Associated Urinary Tract Infections: The Role of Coatings and Materials in Infection Prevention.

PubMed

Lo, Joey; Lange, Dirk; Chew, Ben H

2014-03-10

Urinary tract infections affect many patients, especially those who are admitted to hospital and receive a bladder catheter for drainage. Catheter associated urinary tract infections are some of the most common hospital infections and cost the health care system billions of dollars. Early removal is one of the mainstays of prevention as 100% of catheters become colonized. Patients with ureteral stents are also affected by infection and antibiotic therapy alone may not be the answer. We will review the current evidence on how to prevent infections of urinary biomaterials by using different coatings, new materials, and drug eluting technologies to decrease infection rates of ureteral stents and catheters.

Simultaneous influenza and respiratory syncytial virus infection in human respiratory tract

NASA Astrophysics Data System (ADS)

Pinky, Lubna Jahan Rashid; Dobrovolny, Hana

2015-03-01

Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is not uncommon in hospitalized patients, although it is not clear whether these infections are more or less severe than single infections. We use mathematical models to study the dynamics of simultaneous influenza (flu) and respiratory syncytial virus (RSV) infection, two of the more common respiratory viruses, in an effort to understand simultaneous infections. We examine the roles of initial viral inoculum, relative starting time, and cell regeneration on the severity of the infection. We also study the effect of antiviral treatment on the course of the infection. This study shows that, unless treated with antivirals, flu always takes over the infection no matter how small the initial dose and how delayed it starts with respect to RSV.

[Decrease in nosocomial infection based on continuous monitoring and control. 7 years' experience in a women's clinic].

PubMed

Hirsch, H A; Niehues, U; Decker, K

1985-12-13

During a seven-year programme of surveillance and control of infection data were collected by a specialist hygiene nurse on 47 551 gynaecological, obstetric and post-partum patients. The infection rate was highest (40.5%) after major surgical procedures. Infection rate after cesarian section was 16%, eight times the rate after vaginal delivery (2%). The most frequent type of infection was of the urinary tract (70%), usually asymptomatic bacteriuria. Next most frequent were pelvic infections, abdominal wound infections, and phlebitis via an intravenous entry in long-term parenteral nutrition. During the period of observation bacteriuria rate decreased by 75%, the other nosocomial infections by 64%, febrile standard morbidity by 81%. The decrease is largely due to the infection surveillance programme with the employment of a specialist hygiene nurse.

Unintended consequences of Helicobacter pylori infection in children in developing countries

PubMed Central

Queiroz, Dulciene MM; Rocha, Andreia MC; Crabtree, Jean E

2013-01-01

Helicobacter pylori infection is predominantly acquired early in life. The prevalence of the infection in childhood is low in developed countries, whereas in developing countries most children are infected by 10 y of age. In poor resource settings, where malnutrition, parasitic/enteropathogen and H. pylori infection co-exist in young children, H. pylori might have potentially more diverse clinical outcomes. This paper reviews the impact of childhood H. pylori infection in developing countries that should now be the urgent focus of future research. The extra-gastric manifestations in early H. pylori infection in infants in poor resource settings might be a consequence of the infection associated initial hypochlorhydria. The potential role of H. pylori infection on iron deficiency, growth impairment, diarrheal disease, malabsorption and cognitive function is discussed in this review. PMID:23988829

Social living mitigates the costs of a chronic illness in a cooperative carnivore

USGS Publications Warehouse

Almberg, Emily S.; Cross, Paul C.; Dobson, Andrew P.; Smith, Douglas W.; Metz, Matthew C; Stahler, Daniel R.; Hudson, Peter J.

2015-01-01

Infection risk is assumed to increase with social group size, and thus be a cost of group living. We assess infection risk and costs with respect to group size using data from an epidemic of sarcoptic mange (Sarcoptes scabiei) among grey wolves (Canis lupus). We demonstrate that group size does not predict infection risk and that individual costs of infection, in terms of reduced survival, can be entirely offset by having sufficient numbers of pack-mates. Infected individuals experience increased mortality hazards with increasing proportions of infected pack-mates, but healthy individuals remain unaffected. The social support of group hunting and territory defence are two possible mechanisms mediating infection costs. This is likely a common phenomenon among other social species and chronic infections, but difficult to detect in systems where infection status cannot be measured continuously over time.

Optimal control analysis of malaria-schistosomiasis co-infection dynamics.

PubMed

Okosun, Kazeem Oare; Smith, Robert

2017-04-01

This paper presents a mathematical model for malaria--schistosomiasis co-infection in order to investigate their synergistic relationship in the presence of treatment. We first analyse the single infection steady states, then investigate the existence and stability of equilibria and then calculate the basic reproduction numbers. Both the single-infection models and the co-infection model exhibit backward bifurcations. We carrying out a sensitivity analysis of the co-infection model and show that schistosomiasis infection may not be associated with an increased risk of malaria. Conversely, malaria infection may be associated with an increased risk of schistosomiasis. Furthermore, we found that effective treatment and prevention of schistosomiasis infection would also assist in the effective control and eradication of malaria. Finally, we apply Pontryagin's Maximum Principle to the model in order to determine optimal strategies for control of both diseases.

The transcriptome of the mosquito Aedes fluviatilis (Diptera: Culicidae), and transcriptional changes associated with its native Wolbachia infection.

PubMed

Caragata, E P; Pais, F S; Baton, L A; Silva, J B L; Sorgine, M H F; Moreira, L A

2017-01-03

Wolbachia is a bacterial endosymbiont that naturally infects a wide range of insect species, and causes drastic changes to host biology. Stable infections of Wolbachia in mosquitoes can inhibit infection with medically important pathogens such as dengue virus and malaria-causing Plasmodium parasites. However, some native Wolbachia strains can enhance infection with certain pathogens, as is the case for the mosquito Aedes fluviatilis, where infection with Plasmodium gallinaceum is enhanced by the native wFlu Wolbachia strain. To better understand the biological interactions between mosquitoes and native Wolbachia infections, and to investigate the process of pathogen enhancement, we used RNA-Seq to generate the transcriptome of Ae. fluviatilis with and without Wolbachia infection. In total, we generated 22,280,160 Illumina paired-end reads from Wolbachia-infected and uninfected mosquitoes, and used these to make a de novo transcriptome assembly, resulting in 58,013 contigs with a median sequence length of 443 bp and an N50 of 2454 bp. Contigs were annotated through local alignments using BlastX, and associated with both gene ontology and KEGG orthology terms. Through baySeq, we identified 159 contigs that were significantly upregulated due to Wolbachia infection, and 98 that were downregulated. Critically, we saw no changes to Toll or IMD immune gene transcription, but did see evidence that wFlu infection altered the expression of several bacterial recognition genes, and immune-related genes that could influence Plasmodium infection. wFlu infection also had a widespread effect on a number of host physiological processes including protein, carbohydrate and lipid metabolism, and oxidative stress. We then compared our data set with transcriptomic data for other Wolbachia infections in Aedes aegypti, and identified a core set of 15 gene groups associated with Wolbachia infection in mosquitoes. While the scale of transcriptional changes associated with wFlu infection might be small, the scope is rather large, which confirms that native Wolbachia infections maintain intricate molecular relationships with their mosquito hosts even after lengthy periods of co-evolution. We have also identified several potential means through which wFlu infection might influence Plasmodium infection in Ae. fluviatilis, and these genes should form the basis of future investigation into the enhancement of Plasmodium by Wolbachia.

Diagnosis and treatment of urinary tract infections across age groups.

PubMed

Chu, Christine M; Lowder, Jerry L

2018-01-02

Urinary tract infections are the most common outpatient infections, but predicting the probability of urinary tract infections through symptoms and test results can be complex. The most diagnostic symptoms of urinary tract infections include change in frequency, dysuria, urgency, and presence or absence of vaginal discharge, but urinary tract infections may present differently in older women. Dipstick urinalysis is popular for its availability and usefulness, but results must be interpreted in context of the patient's pretest probability based on symptoms and characteristics. In patients with a high probability of urinary tract infection based on symptoms, negative dipstick urinalysis does not rule out urinary tract infection. Nitrites are likely more sensitive and specific than other dipstick components for urinary tract infection, particularly in the elderly. Positive dipstick testing is likely specific for asymptomatic bacteriuria in pregnancy, but urine culture is still the test of choice. Microscopic urinalysis is likely comparable to dipstick urinalysis as a screening test. Bacteriuria is more specific and sensitive than pyuria for detecting urinary tract infection, even in older women and during pregnancy. Pyuria is commonly found in the absence of infection, particularly in older adults with lower urinary tract symptoms such as incontinence. Positive testing may increase the probability of urinary tract infection, but initiation of treatment should take into account risk of urinary tract infection based on symptoms as well. In cases in which the probability of urinary tract infection is moderate or unclear, urine culture should be performed. Urine culture is the gold standard for detection of urinary tract infection. However, asymptomatic bacteriuria is common, particularly in older women, and should not be treated with antibiotics. Conversely, in symptomatic women, even growth as low as 10 2 colony-forming unit/mL could reflect infection. Resistance is increasing to fluoroquinolones, beta-lactams, and trimethoprim-sulfamethoxazole. Most uropathogens still display good sensitivity to nitrofurantoin. First-line treatments for urinary tract infection include nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole (when resistance levels are <20%). These antibiotics have minimal collateral damage and resistance. In pregnancy, beta-lactams, nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole can be appropriate treatments. Interpreting the probability of urinary tract infection based on symptoms and testing allows for greater accuracy in diagnosis of urinary tract infection, decreasing overtreatment and encouraging antimicrobial stewardship. Copyright © 2018 Elsevier Inc. All rights reserved.