A historical look at the first reported cases of Lassa fever: IgG antibodies 40 years after acute infection.

PubMed

Bond, Nell; Schieffelin, John S; Moses, Lina M; Bennett, Andrew J; Bausch, Daniel G

2013-02-01

Lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. We were able to locate three persons who worked in Nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of Lassa fever in the late 1960s, including the person from whom Lassa virus was first isolated. Two persons had high titers of Lassa virus-specific IgG antibody over 40 years after infection, indicating the potential for long-term duration of these antibodies. One person was likely infected in 1952, 17 years before the first recognized outbreak. We briefly recount the fascinating stories of these three pioneers and their important contribution to our understanding of Lassa fever.

A Historical Look at the First Reported Cases of Lassa Fever: IgG Antibodies 40 Years After Acute Infection

PubMed Central

Bond, Nell; Schieffelin, John S.; Moses, Lina M.; Bennett, Andrew J.; Bausch, Daniel G.

2013-01-01

Lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. We were able to locate three persons who worked in Nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of Lassa fever in the late 1960s, including the person from whom Lassa virus was first isolated. Two persons had high titers of Lassa virus-specific IgG antibody over 40 years after infection, indicating the potential for long-term duration of these antibodies. One person was likely infected in 1952, 17 years before the first recognized outbreak. We briefly recount the fascinating stories of these three pioneers and their important contribution to our understanding of Lassa fever. PMID:23390223

Pathogenesis of Lassa Fever

PubMed Central

Yun, Nadezhda E.; Walker, David H.

2012-01-01

Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents. PMID:23202452

Diagnostics for Lassa Fever: Detecting Host Antibody Responses.

PubMed

Salvato, Maria S; Lukashevich, Igor S; Medina-Moreno, Sandra; Zapata, Juan Carlos

2018-01-01

There are two types of viral diagnostics: (1) those that detect components of the pathogen (like viral RNA or proteins) and (2) those that detect host molecules that rise or fall as a consequence of pathogen infection (like anti-viral antibodies or virus-induced inflammatory cytokines). Quantitative PCR to detect Lassa RNA, and clinical chemistry to detect high liver enzymes (AST/ALT) are commonly used to diagnose Lassa fever. Here, we discuss the various types of diagnostics for Lassa fever and the urgent need for early diagnosis. We also describe a protocol for using the attenuated Lassa vaccine candidate, ML29 , as an antigen for detecting Lassa-specific antibodies. Since antibodies are developed late in the progression of Lassa fever disease, this is not an early diagnostic, but is more useful in surveillance of the population to determine the sero-prevalence of antibodies to Lassa virus (LASV ), and to define treatment options for people in close contact with a Lassa-infected person.

The first cases of Lassa fever in Ghana.

PubMed

Dzotsi, E K; Ohene, S-A; Asiedu-Bekoe, F; Amankwa, J; Sarkodie, B; Adjabeng, M; Thouphique, A M; Ofei, A; Oduro, J; Atitogo, D; Bonney, J H K; Paintsil, S C N; Ampofo, W

2012-09-01

Lassa fever is a zoonotic disease endemic in West Africa but with no previous case reported in Ghana. We describe the first two laboratory confirmed cases of Lassa fever from the Ashanti Region of Ghana detected in October and December, 2011.

Lassa fever presenting as acute abdomen: a case series.

PubMed

Dongo, Andrew E; Kesieme, Emeka B; Iyamu, Christopher E; Okokhere, Peter O; Akhuemokhan, Odigie C; Akpede, George O

2013-04-19

Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission.

Lassa fever presenting as acute abdomen: a case series

PubMed Central

2013-01-01

Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission. PMID:23597024

Laboratory Diagnosis of Lassa Fever

PubMed Central

Koehler, Jeffrey

2017-01-01

ABSTRACT Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa fever can be nonspecific and mimic those of other endemic infections, especially early in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to confirm the diagnosis. An early identification of Lassa fever is crucial for maximizing the benefit of available antiviral therapy, as treatment efficacy rapidly decreases following the clinical onset of the disease. This minireview provides an overview of the currently available diagnostic tests for Lassa fever and their strengths and weaknesses. PMID:28404674

Laboratory Diagnosis of Lassa Fever.

PubMed

Raabe, Vanessa; Koehler, Jeffrey

2017-06-01

Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa fever can be nonspecific and mimic those of other endemic infections, especially early in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to confirm the diagnosis. An early identification of Lassa fever is crucial for maximizing the benefit of available antiviral therapy, as treatment efficacy rapidly decreases following the clinical onset of the disease. This minireview provides an overview of the currently available diagnostic tests for Lassa fever and their strengths and weaknesses. Copyright © 2017 American Society for Microbiology.

Lassa Virus Infection of Rhesus Monkeys: Pathogenesis and Treatment with Ribavirin

DTIC Science & Technology

1980-05-01

virus is a severe, gen- data have suggested that mild or subclinical infec- eralized disease described as Lassa fever [1-31. tions may occur [2...Liberia and Sierra Management of Lassa fever would be facilitated if Leone; serologic data also suggest the presence of an effective antiviral drug...of Laboratory monkey model for human Lassa fever . The results Animal Resources, National Research Council. The facilities are encouraging, suggesting

Development and evaluation of antibody-capture immunoassays for detection of Lassa virus nucleoprotein-specific immunoglobulin M and G

PubMed Central

Gabriel, Martin; Adomeh, Donatus I.; Ehimuan, Jacqueline; Oyakhilome, Jennifer; Omomoh, Emmanuel O.; Ighodalo, Yemisi; Olokor, Thomas; Bonney, Kofi; Pahlmann, Meike; Emmerich, Petra; Lelke, Michaela; Brunotte, Linda; Ölschläger, Stephan; Thomé-Bolduan, Corinna; Becker-Ziaja, Beate; Busch, Carola; Odia, Ikponmwosa; Ogbaini-Emovon, Ephraim; Okokhere, Peter O.; Okogbenin, Sylvanus A.; Akpede, George O.; Schmitz, Herbert; Asogun, Danny A.

2018-01-01

Background The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Therefore, we aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using recombinant Lassa virus nucleoprotein (NP) as antigen. Methodology/Principal findings The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and the IgG ELISA is based on capturing IgG antibody–antigen complexes using rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic (Ghana and Germany) areas. Using the IFA as reference method, we observed 91.5–94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to hospital in an endemic area revealed a clinical sensitivity for the stand-alone IgM ELISA of 31% (95% CI 25–37) and for combined IgM/IgG detection of 26% (95% CI 21–32) compared to RT-PCR. The specificity of IgM and IgG ELISA was estimated at 96% (95% CI 93–98) and 100% (95% CI 99–100), respectively, in non-Lassa fever patients from non-endemic areas. In patients who seroconverted during follow-up, Lassa virus-specific IgM and IgG developed simultaneously rather than sequentially. Consistent with this finding, isolated IgM reactivity, i.e. IgM in the absence of IgG, had no diagnostic value. Conclusions/Significance The ELISAs are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they are of value in diagnosing patients at later stage. The IgG ELISA may be useful for epidemiological studies and clinical trials due its high specificity, and the higher throughput rate and easier operation compared to IFA. PMID:29596412

Imported Case of Lassa Fever in Sweden With Encephalopathy and Sensorineural Hearing Deficit.

PubMed

Grahn, Anna; Bråve, Andreas; Lagging, Martin; Dotevall, Leif; Ekqvist, David; Hammarström, Helena; Karlberg, Helen; Lagerqvist, Nina; Sansone, Martina; Tegnell, Anders; Ulleryd, Peter; Studahl, Marie

2016-10-01

We describe an imported case of Lassa fever with both encephalopathy and bilateral sensorineural hearing deficit. Absence of fever during hospitalization, initially nonspecific symptoms, and onset of hearing deficit in a late stage of disease probably contributed to delayed diagnosis (14 days after admittance to hospital). The pathogenesis of neurological manifestations of Lassa fever is poorly understood and no specific treatment was given. A total of 118 personnel had close contact with the patient, but no secondary cases occurred. This case highlights the importance of considering Lassa fever as a differential diagnosis in patients with recent travel to endemic areas.

Emergence of Lassa Fever Disease in Northern Togo: Report of Two Cases in Oti District in 2016.

PubMed

Patassi, Akouda Akessiwe; Landoh, Dadja Essoya; Mebiny-Essoh Tchalla, Agballa; Halatoko, Wemboo Afiwa; Assane, Hamadi; Saka, Bayaki; Naba, Mouchedou Abdoukarim; Yaya, Issifou; Edou, Kossi Atsissinta; Tamekloe, Tsidi Agbeko; Banla, Abiba Kere; Davi, Kokou Mawule; Manga, Magloire; Kassankogno, Yao; Salmon-Ceron, Dominique

2017-01-01

Lassa fever belongs to the group of potentially fatal hemorrhagic fevers, never reported in Togo. The aim of this paper is to report the first two cases of Lassa fever infection in Togo. The two first Lassa fever cases occurred in two expatriate's health professionals working in Togo for more than two years. The symptoms appeared among two health professionals of a clinic located in Oti district in the north of the country. The absence of clinical improvement after antimalarial treatment and the worsening of clinical symptoms led to the medical evacuation. The delayed diagnosis of the first case led to a fatal outcome. The second case recovered under ribavirin treatment. The emergence of this hemorrhagic fever confirms the existence of Lassa fever virus in Togo. After a period of intensive Ebola virus transmission from 2013 to 2015, this is an additional call for the establishment and enhancement of infection prevention and control measures in the health care setting in West Africa.

Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone

PubMed Central

Rossi, Cynthia A.; Khan, Sheik H.; Goba, Augustine; Fair, Joseph N.

2014-01-01

Sierra Leone in West Africa is in a Lassa fever–hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ≈500–700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%–40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%–70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus. PMID:24959946

Molecular confirmation of Lassa fever imported into Ghana.

PubMed

Bonney, Joseph H K; Nyarko, Edward O; Ohene, Sally-Ann; Amankwa, Joseph; Ametepi, Ralph K; Nimo-Paintsil, Shirley C; Sarkodie, Badu; Agbenohevi, Prince; Adjabeng, Michael; Kyei, Nicholas N A; Bel-Nono, Samuel; Ampofo, William K

2016-01-01

Recent reports have shown an expansion of Lassa virus from the area where it was first isolated in Nigeria to other areas of West Africa. Two Ghanaian soldiers on a United Nations peacekeeping mission in Liberia were taken ill with viral haemorrhagic fever syndrome following the death of a sick colleague and were referred to a military hospital in Accra, Ghana, in May 2013. Blood samples from the soldiers and five asymptomatic close contacts were subjected to laboratory investigations. We report the results of these investigations to highlight the importance of molecular diagnostic applications and the need for heightened awareness about Lassa fever in West Africa. We used molecular assays on sera from the two patients to identify the causative organism. Upon detection of positive signals for Lassa virus ribonucleic material by two different polymerase chain reaction assays, sequencing and phylogenetic analyses were performed. The presence of Lassa virus in the soldiers' blood samples was shown by L-gene segment homology to be the Macenta and las803792 strains previously isolated in Liberia, with close relationships then confirmed by phylogenetic tree construction. The five asymptomatic close contacts were negative for Lassa virus. The Lassa virus strains identified in the two Ghanaian soldiers had molecular epidemiological links to strains from Liberia. Lassa virus was probably responsible for the outbreak of viral haemorrhagic fever in the military camp. These data confirm Lassa fever endemicity in West Africa.

United States Army Medical Materiel Development Activity - 1989

DTIC Science & Technology

1990-01-31

physicians to treat diseases such as Korean Hemorrhagic Fever and Lassa Fever. * J-5 Human Monoclonal Antibody is secreted by cultured hybridomas that were...volunteer studies involving a collaborative effort between WRAIR and the Swiss Serum and Vaccine Institute (SSVI). s Lassa Fever Immune Plasma is an...immune globulin used to treat Lassa fever infections. The collection of human immune plasma in Africa is an ongoing contract effort. USANRIID performs

Knowledge Attitude and Practices Toward Lassa Fever Control and Prevention Among Residents of Ile-Ife, Southwest Nigeria.

PubMed

Olowookere, S A; Adegbenro, C A; Idowu, A; Omisore, A G; Shabi, O M; Ikem, U R; Ekwere, G A; Oderinde, I F

2017-01-01

Lassa fever had been reported as a cause of death especially in endemic parts of Nigeria. This study assessed the knowledge, attitude, and practices toward Lassa fever control and prevention among residents of Ile-Ife, southwest Nigeria. Descriptive cross-sectional study was conducted among consenting randomly selected adults using an interviewer administered questionnaire. Data were analyzed using descriptive and inferential statistics. A total of 400 questionnaires with completed data were analyzed (response rate 96%). Majority, 207 (51.8%), were males while 193 (48.2%) were females. Most, 234 (58.5%), had tertiary education while 148 (37%) had secondary education. Fifty-nine percent had heard of Lassa fever with radio as their major source of information. About 76% had inadequate knowledge, 54% had negative attitude while 51% had poor practice toward Lassa fever. Determinants of knowledge of Lassa fever include having higher education (Adjusted Odd Ratio (AOR) = 11.49, 95% CI [3.10, 42.69], p = .0001), being in civil service (AOR = 0.22, 95% CI [0.09, 0.51], p = .01), and earning higher income (AOR = 4.23, 95% CI [2.61, 6.84], p = .0001). In conclusion, the knowledge, attitude, as well as preventive practices to Lassa fever were poor. It is necessary to increase public education and improve hygienic practices.

Knowledge of Secondary School Children in Edo State on Lassa Fever and its Implications for Prevention and Control.

PubMed

Tobin, E A; Asogun, D A; Esumeh, R; Omuninu, R; Ehidiamen, G; Giwa, R

2015-01-01

Seasonal outbreaks of Lassa fever in West Africa cause significant morbidity and mortality across all ages. In addition to present efforts to raise awareness, school children can be targeted to become peer and family health educators. The study was carried out to determine the knowledge of Lassa fever among secondary school children, and household practices that increase risk of the infection. In a cross sectional survey, 561 secondary school students randomly selected from schools in Edo State were interviewed by means of a self - administered questionnaire that sought information on knowledge of Lassa fever and practices within the home that favour rodent contact . Data were analyzed using Statistical Package for Social Sciences version 15. Knowledge of Lassa fever was poor among 259 (49.4%) respondents, fair in 216 (41.2%) and good in 49 (9.4%). Female gender (< 0.01), monogamous family structure (p < 0.04) , and being in senior secondary class ( p=0.01) were predictors of high knowledge score. Self- reported Lassa fever risk conditions were found to be of low prevalence in 311(55.4%) and high in 250 (44.6%) homes, and associated with educational status of mother ( p=0.00) and father, (p =0.00). School children in endemic communities lack good knowledge of Lassa fever, but when properly guided, have the potential to become peer and family educators.

Re-emerging Lassa fever outbreaks in Nigeria: Re-enforcing "One Health" community surveillance and emergency response practice.

PubMed

Tambo, Ernest; Adetunde, Oluwasegun T; Olalubi, Oluwasogo A

2018-04-28

We evaluated the impact of man-made conflict events and climate change impact in guiding evidence-based community "One Health" epidemiology and emergency response practice against re-/emerging epidemics. Increasing evidence of emerging and re-emerging zoonotic diseases including recent Lassa fever outbreaks in almost 20 states in Nigeria led to 101 deaths and 175 suspected and confirmed cases since August 2015. Of the 75 laboratory confirmed cases, 90 deaths occurred representing 120% laboratory-confirmed case fatality. The outbreak has been imported into neighbouring country such as Benin, where 23 deaths out of 68 cases has also been reported. This study assesses the current trends in re-emerging Lassa fever outbreak in understanding spatio-geographical reservoir(s), risk factors pattern and Lassa virus incidence mapping, inherent gaps and raising challenges in health systems. It is shown that Lassa fever peak endemicity incidence and prevalence overlap the dry season (within January to March) and reduced during the wet season (of May to November) annually in Sierra Leone, Senegal to Eastern Nigeria. We documented a scarcity of consistent data on rodent (reservoirs)-linked Lassa fever outbreak, weak culturally and socio-behavioural effective prevention and control measures integration, weak or limited community knowledge and awareness to inadequate preparedness capacity and access to affordable case management in affected countries. Hence, robust sub/regional leadership commitment and investment in Lassa fever is urgently needed in building integrated and effective community "One Health" surveillance and rapid response approach practice coupled with pest management and phytosanitation measures against Lassa fever epidemic. This offers new opportunities in understanding human-animal interactions in strengthening Lassa fever outbreak early detection and surveillance, warning alerts and rapid response implementation in vulnerable settings. Leveraging on Africa CDC centre, advances in cloud-sourcing and social media tools and solutions is core in developing and integrating evidence-based and timely risk communication, and reporting systems in improving contextual community-based immunization and control decision making policy to effectively defeat Lassa fever outbreak and other emerging pandemics public health emergencies in Africa and worldwide.

Housing equity for health equity: a rights-based approach to the control of Lassa fever in post-war Sierra Leone.

PubMed

Kelly, J Daniel; Barrie, M Bailor; Ross, Rachel A; Temple, Brian A; Moses, Lina M; Bausch, Daniel G

2013-01-02

Poor quality housing is an infringement on the rights of all humans to a standard of living adequate for health. Among the many vulnerabilities of those without adequate shelter is the risk of disease spread by rodents and other pests. One such disease is Lassa fever, an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. Lassa virus is maintained in the rodent Mastomys natalensis, commonly known as the "multimammate rat," which frequently invades the domestic environment, putting humans at risk of Lassa fever. The highest reported incidence of Lassa fever in the world is consistently in the Kenema District of Sierra Leone, a region that was at the center of Sierra Leone's civil war in which tens of thousands of lives were lost and hundreds of thousands of dwellings destroyed. Despite the end of the war in 2002, most of Kenema's population still lives in inadequate housing that puts them at risk of rodent invasion and Lassa fever. Furthermore, despite years of health education and village hygiene campaigns, the incidence of Lassa fever in Kenema District appears to be increasing. We focus on Lassa fever as a matter of human rights, proposing a strategy to improve housing quality, and discuss how housing equity has the potential to improve health equity and ultimately economic productivity in Sierra Leone. The manuscript is designed to spur discussion and action towards provision of housing and prevention of disease in one of the world's most vulnerable populations.

Pediatric Lassa fever: a review of 33 Liberian cases.

PubMed

Monson, M H; Cole, A K; Frame, J D; Serwint, J R; Alexander, S; Jahrling, P B

1987-03-01

Thirty-three cases of pediatric Lassa fever were identified at Curran Lutheran Hospital and Phebe Hospital in Liberia between January 1980 and March 1984. All 18 fetal cases died and the case-fatality rate for 15 childhood cases was 27%. We identified four clinical presentations according to age, including a case of congenital Lassa fever, a condition not reported previously. Two cases of Lassa fever were found serologically during a one-month survey of all pediatric admissions at Curran Lutheran Hospital, 2.4% of those children who had serum pairs collected. We also identified a "swollen baby syndrome" consisting of widespread edema, abdominal distention, and bleeding. This distinctive clinical presentation of Lassa fever ended in death in three of four cases and was present in three of the four childhood deaths in this series. Its absence seems to be a good prognostic indicator in children.

Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone

DTIC Science & Technology

2014-07-01

Sierra Leone in West Africa is in a Lassa fever – hyperendemic region that also includes Guinea and Li- beria. Each year...suspected Lassa fever cases result in submission of ≈500–700 samples to the Kenema Govern- ment Hospital Lassa Diagnostic Laboratory in eastern Si- erra...patients have acute diseases of unknown origin. To investigate what other ar- thropod-borne and hemorrhagic fever viral diseases might cause serious

Lassa fever or lassa hemorrhagic fever risk to humans from rodent-borne zoonoses.

PubMed

El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

2015-04-01

Viral hemorrhagic fevers (VHFs) typically manifest as rapidly progressing acute febrile syndromes with profound hemorrhagic manifestations and very high fatality rates. Lassa fever, an acute hemorrhagic fever characterized by fever, muscle aches, sore throat, nausea, vomiting, diarrhea and chest and abdominal pain. Rodents are important reservoirs of rodent-borne zoonosis worldwide. Transmission rodents to humans occur by aerosol spread, either from the genus Mastomys rodents' excreta (multimammate rat) or through the close contact with infected patients (nosocomial infection). Other rodents of the genera Rattus, Mus, Lemniscomys, and Praomys are incriminated rodents hosts. Now one may ask do the rodents' ectoparasites play a role in Lassa virus zoonotic transmission. This paper summarized the update knowledge on LHV; hopping it might be useful to the clinicians, nursing staff, laboratories' personals as well as those concerned zoonoses from rodents and rodent control.

IGG Subclass and Isotype Specific Immunoglobulin Responses to Lassa Fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunization

DTIC Science & Technology

1991-12-30

AD-A246 912 AD ARMY PROJECT ORDER 88PP8804 TITLE: IGG SUBCLASS AND ISOTYPE SPECIFIC IMMUNOGLOBULIN RESPONSES TO LASSA FEVER AND VENEZUELAN EQUINE ...and Isotype Specific Immunoglobulin responses Army Project Order to Lassa Fever and Venezuelan Equine Encephalitis: 88PP8804 Natual...unlimited 13. ABSTRACT (Maximum 200 words) Venezuelan Equine Encephalitis (VEE) specific inimunoglobulin responses to the two vaccines, TC-83 (A live

[Use of guinea pigs for assessing the efficacy of vaccines against Lassa fever].

PubMed

Firsova, I V; Shatokhina, I V; Borisevich, I V; Evseev, A A; Maksimov, V A; Pantiukhov, V B; Khmelev, A L

2003-01-01

The use of guinea pigs as a laboratory model was proven to be appropriate in investigating the vaccines developed against Lassa fever at the preclinical study stage. An adapted variant of Lassa virus was cultivated, which caused death of guinea pigs with respect for an agent's dose. Finally, it was shown to be possible to investigate the immunogenic and protective properties of the inactivated antigen of Lassa virus in experiments with guinea pigs.

Imported Lassa fever: a report of 2 cases in Ghana.

PubMed

Kyei, Nicholas N A; Abilba, Mark M; Kwawu, Foster K; Agbenohevi, Prince G; Bonney, Joseph H K; Agbemaple, Thomas K; Nimo-Paintsil, Shirley C; Ampofo, William; Ohene, Sally-Ann; Nyarko, Edward O

2015-05-29

Lassa fever is a potentially fatal acute viral illness caused by Lassa virus which is carried by rodents and is endemic in some West African countries. Importation of emerging infections such as Lassa fever, Ebola Virus Disease and other viral hemorrhagic fevers into non endemic regions is a growing threat particularly as international travel and commitments in resolving conflicts in endemic countries in the West Africa sub-region continue. We report the first two recorded imported cases of Lassa fever among Ghanaian Peace keepers in rural Liberia, who became ill while on Peace keeping mission. They were subsequently evacuated to the UN level IV hospital in Accra, where their illnesses were laboratory confirmed. One of the patients recovered with ribavirin treatment and supportive therapy. No secondary clinical cases occurred in Ghana. Healthcare providers at all levels of care should thus have a high index of suspicion for these infectious diseases and adopt standard infection control measures when treating patients in endemic regions or returning travelers from an endemic region with a febrile illness even of a known etiology.

Epidemic preparedness and management: A guide on Lassa fever outbreak preparedness plan.

PubMed

Fatiregun, Akinola Ayoola; Isere, Elvis Efe

2017-01-01

Epidemic prone diseases threaten public health security. These include diseases such as cholera, meningitis, and hemorrhagic fevers, especially Lassa fever for which Nigeria reports considerable morbidity and mortality annually. Interestingly, where emergency epidemic preparedness plans are in place, timely detection of outbreaks is followed by a prompt and appropriate response. Furthermore, due to the nature of spread of Lassa fever in an outbreak setting, there is the need for health-care workers to be familiar with the emerging epidemic management framework that has worked in other settings for effective preparedness and response. This paper, therefore, discussed the principles of epidemic management using an emergency operating center model, review the epidemiology of Lassa fever in Nigeria, and provide guidance on what is expected to be done in preparing for epidemic of the disease at the health facilities, local and state government levels in line with the Integrated Disease Surveillance and Response strategy.

The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.

PubMed

Safronetz, David; Rosenke, Kyle; Westover, Jonna B; Martellaro, Cynthia; Okumura, Atsushi; Furuta, Yousuke; Geisbert, Joan; Saturday, Greg; Komeno, Takashi; Geisbert, Thomas W; Feldmann, Heinz; Gowen, Brian B

2015-10-12

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.

The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset

PubMed Central

Safronetz, David; Rosenke, Kyle; Westover, Jonna B.; Martellaro, Cynthia; Okumura, Atsushi; Furuta, Yousuke; Geisbert, Joan; Saturday, Greg; Komeno, Takashi; Geisbert, Thomas W.; Feldmann, Heinz; Gowen, Brian B.

2015-01-01

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs. PMID:26456301

Aseptic Meningitis Caused by Lassa Virus: Case Series Report

PubMed Central

Bankole, Idowu A.; Iruolagbe, Christopher O.; Muoebonam, Benard E.; Okonofua, Martha O.; Dawodu, Simeon O.; Akpede, George O.

2016-01-01

The Lassa virus is known to cause disease in different organ systems of the human body, with varying clinical manifestations. The features of severe clinical disease may include bleeding and/or central nervous system manifestations. Whereas Lassa fever encephalopathy and encephalitis are well described in the literature, there is paucity of data on Lassa virus meningitis. We present the clinical description, laboratory diagnosis, and management of 4 consecutive cases of aseptic meningitis associated with Lassa virus infection without bleeding seen in a region of Nigeria known to be endemic for both the reservoir rodent and Lassa fever. The 4 patients recovered fully following intravenous ribavirin treatment and suffered no neurologic complications. PMID:27957363

Mapping the zoonotic niche of Lassa fever in Africa

PubMed Central

Mylne, Adrian Q. N.; Pigott, David M.; Longbottom, Joshua; Shearer, Freya; Duda, Kirsten A.; Messina, Jane P.; Weiss, Daniel J.; Moyes, Catherine L.; Golding, Nick; Hay, Simon I.

2015-01-01

Background Lassa fever is a viral haemorrhagic illness responsible for disease outbreaks across West Africa. It is a zoonosis, with the primary reservoir species identified as the Natal multimammate mouse, Mastomys natalensis. The host is distributed across sub-Saharan Africa while the virus' range appears to be restricted to West Africa. The majority of infections result from interactions between the animal reservoir and human populations, although secondary transmission between humans can occur, particularly in hospital settings. Methods Using a species distribution model, the locations of confirmed human and animal infections with Lassa virus (LASV) were used to generate a probabilistic surface of zoonotic transmission potential across sub-Saharan Africa. Results Our results predict that 37.7 million people in 14 countries, across much of West Africa, live in areas where conditions are suitable for zoonotic transmission of LASV. Four of these countries, where at-risk populations are predicted, have yet to report any cases of Lassa fever. Conclusions These maps act as a spatial guide for future surveillance activities to better characterise the geographical distribution of the disease and understand the anthropological, virological and zoological interactions necessary for viral transmission. Combining this zoonotic niche map with detailed patient travel histories can aid differential diagnoses of febrile illnesses, enabling a more rapid response in providing care and reducing the risk of onward transmission. PMID:26085474

A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

PubMed

Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

2015-04-01

Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

Lassa Fever Immune Plasma.

DTIC Science & Technology

1984-08-01

three instances, and one each for sickle cell crisis , severe anemia, pyelonephritis, cerebral malaria and tonsillitis. Treatment of LF with LFIP under...diagnosis of 46 LF and Presumptive LF patients treated at CLH April 1983 - March 1984. Clinical diagnosis No. Lassa fever 38 Typhoid fever 3 Sickle cell crisis 1

A fatal case of Lassa fever in London, January 2009.

PubMed

Kitching, A; Addiman, S; Cathcart, S; Bischop, L; Krahé, D; Nicholas, M; Coakley, J; Lloyd, G; Brooks, T; Morgan, D; Turbitt, D

2009-02-12

In January 2009, the eleventh [corrected] case of Lassa fever imported to the United Kingdom was diagnosed in London. Risk assessment of 328 healthcare contacts with potential direct exposure to Lassa virus - through contact with the case or exposure to bodily fluids - was undertaken. No contacts were assessed to be at high risk of infection and no secondary clinical cases identified.

Review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for Lassa fever.

PubMed

Bausch, Daniel G; Hadi, Christiane M; Khan, Sheik Humarr; Lertora, Juan J L

2010-12-15

Lassa fever is an acute viral hemorrhagic illness; the virus is endemic in West Africa and also of concern with regard to bioterrorism. Transmission of Lassa virus between humans may occur through direct contact with infected blood or bodily secretions. Oral administration of the antiviral drug ribavirin is often considered for postexposure prophylaxis, but no systematically collected data or uniform guidelines exist for this indication. Furthermore, the relatively low secondary attack rates for Lassa fever, the restriction of the area of endemicity to West Africa, and the infrequency of high-risk exposures make it unlikely that controlled prospective efficacy trials will ever be possible. Recommendations for postexposure use of ribavirin can therefore be made only on the basis of a thorough understanding and logical extrapolation of existing data. Here, we review the pertinent issues and propose guidelines based on extensive review of the literature, as well as our experience in this field. We recommend oral ribavirin postexposure prophylaxis for Lassa fever exclusively for definitive high-risk exposures. These guidelines may also serve for exposure to other hemorrhagic fever viruses susceptible to ribavirin.

Prevalence and Risk Factors of Lassa Seropositivity in Inhabitants of the Forest Region of Guinea: A Cross-Sectional Study

PubMed Central

Kernéis, Solen; Koivogui, Lamine; Magassouba, N'Faly; Koulemou, Kekoura; Lewis, Rosamund; Aplogan, Aristide; Grais, Rebecca F.; Guerin, Philippe J.; Fichet-Calvet, Elisabeth

2009-01-01

Background Lassa fever is a viral hemorrhagic fever endemic in West Africa. The reservoir host of the virus is a multimammate rat, Mastomys natalensis. Prevalence estimates of Lassa virus antibodies in humans vary greatly between studies, and the main modes of transmission of the virus from rodents to humans remain unclear. We aimed to (i) estimate the prevalence of Lassa virus–specific IgG antibodies (LV IgG) in the human population of a rural area of Guinea, and (ii) identify risk factors for positive LV IgG. Methods and Findings A population-based cross-sectional study design was used. In April 2000, all individuals one year of age and older living in three prefectures located in the tropical secondary forest area of Guinea (Gueckedou, Lola and Yomou) were sampled using two-stage cluster sampling. For each individual identified by the sampling procedure and who agreed to participate, a standardized questionnaire was completed to collect data on personal exposure to potential risk factors for Lassa fever (mainly contact with rodents), and a blood sample was tested for LV IgG. A multiple logistic regression model was used to determine risk factors for positive LV IgG. A total of 1424 subjects were interviewed and 977 sera were tested. Prevalence of positive LV Ig was of 12.9% [10.8%–15.0%] and 10.0% [8.1%–11.9%] in rural and urban areas, respectively. Two risk factors of positive LV IgG were identified: to have, in the past twelve months, undergone an injection (odds ratio [OR] = 1.8 [1.1–3.1]), or lived with someone displaying a haemorrhage (OR = 1.7 [1.1–2.9]). No factors related to contacts with rats and/or mice remained statistically significant in the multivariate analysis. Conclusions Our study underlines the potential importance of person-to-person transmission of Lassa fever, via close contact in the same household or nosocomial exposure. PMID:19924222

Lassa Virus Seroprevalence in Sibirilia Commune, Bougouni District, Southern Mali.

PubMed

Sogoba, Nafomon; Rosenke, Kyle; Adjemian, Jennifer; Diawara, Sory Ibrahim; Maiga, Ousmane; Keita, Moussa; Konaté, Drissa; Keita, Abdoul Salam; Sissoko, Ibrahim; Boisen, Matt; Nelson, Diana; Oottamasathien, Darin; Millett, Molly; Garry, Robert F; Branco, Luis M; Traoré, Sékou F; Doumbia, Seydou; Feldmann, Heinz; Safronetz, David

2016-04-01

Lassa virus (LASV) is endemic to several nations in West Africa. In Mali, LASV was unknown until an exported case of Lassa fever was reported in 2009. Since that time, rodent surveys have found evidence of LASV-infected Mastomys natalensis rats in several communities in southern Mali, near the border with Côte d'Ivoire. Despite increased awareness, to date only a single case of Lassa fever has been confirmed in Mali. We conducted a survey to determine the prevalence of LASV exposure among persons in 3 villages in southern Mali where the presence of infected rodents has been documented. LASV IgG seroprevalence ranged from 14.5% to 44% per village. No sex bias was noted; however, seropositivity rates increased with participant age. These findings confirm human LASV exposure in Mali and suggest that LASV infection/Lassa fever is a potential public health concern in southern Mali.

Movement Patterns of Small Rodents in Lassa Fever-Endemic Villages in Guinea.

PubMed

Mariën, Joachim; Kourouma, Fodé; Magassouba, N'Faly; Leirs, Herwig; Fichet-Calvet, Elisabeth

2018-03-23

The Natal multimammate mouse (Mastomys natalensis) is the reservoir host of Lassa arenavirus, the etiological agent of Lassa fever in humans. Because there exists no vaccine for human use, rodent control and adjusting human behavior are currently considered to be the only options for Lassa fever control. In order to develop efficient rodent control programs, more information about the host's ecology is needed. In this study, we investigated the spatial behavior of M. natalensis and other small rodents in two capture-mark-recapture and four dyed bait (Rhodamine B) experiments in Lassa fever-endemic villages in Upper Guinea. During the capture-mark-recapture studies, 23% of the recaptured M. natalensis moved between the houses and proximate fields. While M. natalensis was found over the entire study grid (2 ha), other rodent species (Praomys daltoni, Praomys rostratus, Lemniscomys striatus, Mus spp.) were mostly trapped in the surrounding fields. Distances between recapture occasions never exceeded 100 m for all rodent species. During the dyed bait experiments, 11% of M. natalensis and 41% of P. daltoni moved from the fields to houses. We conclude that commensal M. natalensis easily moves between houses and proximate fields in Guinea. We therefore consider occasional domestic rodent elimination to be an unsustainable approach to reduce Lassa virus transmission risk to humans, as M. natalensis is likely to reinvade houses quickly from fields in which rodents are not controlled. A combination of permanent rodent elimination with other control strategies (e.g., make houses rodent proof or attract predators) could be more effective for Lassa fever control, but must be further investigated.

Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers.

PubMed

Gale, Trevor V; Horton, Timothy M; Grant, Donald S; Garry, Robert F

2017-09-01

Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients.

Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers

PubMed Central

Gale, Trevor V.; Horton, Timothy M.; Grant, Donald S.

2017-01-01

Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients. PMID:28922385

Control measures following a case of imported Lassa fever from Togo, North Rhine Westphalia, Germany, 2016.

PubMed

Lehmann, Clara; Kochanek, Matthias; Abdulla, Diana; Becker, Stephan; Böll, Boris; Bunte, Anne; Cadar, Daniel; Dormann, Arno; Eickmann, Markus; Emmerich, Petra; Feldt, Torsten; Frank, Christina; Fries, Jochen; Gabriel, Martin; Goetsch, Udo; Gottschalk, René; Günther, Stephan; Hallek, Michael; Häussinger, Dieter; Herzog, Christian; Jensen, Björn; Kolibay, Felix; Krakau, Michael; Langebartels, Georg; Rieger, Toni; Schaade, Lars; Schmidt-Chanasit, Jonas; Schömig, Edgar; Schüttfort, Gundolf; Shimabukuro-Vornhagen, Alexander; von Bergwelt-Baildon, Michael; Wieland, Ulrike; Wiesmüller, Gerhard; Wolf, Timo; Fätkenheuer, Gerd

2017-09-01

In a patient transferred from Togo to Cologne, Germany, Lassa fever was diagnosed 12 days post mortem. Sixty-two contacts in Cologne were categorised according to the level of exposure, and gradual infection control measures were applied. No clinical signs of Lassa virus infection or Lassa specific antibodies were observed in the 62 contacts. Thirty-three individuals had direct contact to blood, other body fluids or tissue of the patients. Notably, with standard precautions, no transmission occurred between the index patient and healthcare workers. However, one secondary infection occurred in an undertaker exposed to the corpse in Rhineland-Palatinate, who was treated on the isolation unit at the University Hospital of Frankfurt. After German authorities raised an alert regarding the imported Lassa fever case, an American healthcare worker who had cared for the index patient in Togo, and who presented with diarrhoea, vomiting and fever, was placed in isolation and medevacked to the United States. The event and the transmission of Lassa virus infection outside of Africa underlines the need for early diagnosis and use of adequate personal protection equipment (PPE), when highly contagious infections cannot be excluded. It also demonstrates that larger outbreaks can be prevented by infection control measures, including standard PPE.

Sensitivity analysis in a Lassa fever deterministic mathematical model

NASA Astrophysics Data System (ADS)

Abdullahi, Mohammed Baba; Doko, Umar Chado; Mamuda, Mamman

2015-05-01

Lassa virus that causes the Lassa fever is on the list of potential bio-weapons agents. It was recently imported into Germany, the Netherlands, the United Kingdom and the United States as a consequence of the rapid growth of international traffic. A model with five mutually exclusive compartments related to Lassa fever is presented and the basic reproduction number analyzed. A sensitivity analysis of the deterministic model is performed. This is done in order to determine the relative importance of the model parameters to the disease transmission. The result of the sensitivity analysis shows that the most sensitive parameter is the human immigration, followed by human recovery rate, then person to person contact. This suggests that control strategies should target human immigration, effective drugs for treatment and education to reduced person to person contact.

Human-monoclonal-antibody therapy protects nonhuman primates against advanced Lassa fever.

PubMed

Mire, Chad E; Cross, Robert W; Geisbert, Joan B; Borisevich, Viktoriya; Agans, Krystle N; Deer, Daniel J; Heinrich, Megan L; Rowland, Megan M; Goba, Augustine; Momoh, Mambu; Boisen, Mathew L; Grant, Donald S; Fullah, Mohamed; Khan, Sheik Humarr; Fenton, Karla A; Robinson, James E; Branco, Luis M; Garry, Robert F; Geisbert, Thomas W

2017-10-01

There are no approved treatments for Lassa fever, which is endemic to the same regions of West Africa that were recently devastated by Ebola. Here we show that a combination of human monoclonal antibodies that cross-react with the glycoproteins of all four clades of Lassa virus is able to rescue 100% of cynomolgus macaques when treatment is initiated at advanced stages of disease, including up to 8 d after challenge.

Lassa Fever Immune Plasma.

DTIC Science & Technology

1986-05-01

obtained and 317 forwarded to USAMRIID, with 272 having LNI’s of 0.3 or higher. Testing of febrile patients for evidence of Lassa virus (LV) infection ...at a rehabilitation center near GWH revealed evidence of previous LV infection in 22 of 288 leprosy patients, 4 of 52 family members of these patients...Virus Infections in the Families of Lassa Fever Patients Annex 3. Record of Household Epidemiology Study 49 Annex 4. Means of Obtaining Samples for IFA

Risk maps of Lassa fever in West Africa.

PubMed

Fichet-Calvet, Elisabeth; Rogers, David John

2009-01-01

Lassa fever is caused by a viral haemorrhagic arenavirus that affects two to three million people in West Africa, causing a mortality of between 5,000 and 10,000 each year. The natural reservoir of Lassa virus is the multi-mammate rat Mastomys natalensis, which lives in houses and surrounding fields. With the aim of gaining more information to control this disease, we here carry out a spatial analysis of Lassa fever data from human cases and infected rodent hosts covering the period 1965-2007. Information on contemporary environmental conditions (temperature, rainfall, vegetation) was derived from NASA Terra MODIS satellite sensor data and other sources and for elevation from the GTOPO30 surface for the region from Senegal to the Congo. All multi-temporal data were analysed using temporal Fourier techniques to generate images of means, amplitudes and phases which were used as the predictor variables in the models. In addition, meteorological rainfall data collected between 1951 and 1989 were used to generate a synoptic rainfall surface for the same region. Three different analyses (models) are presented, one superimposing Lassa fever outbreaks on the mean rainfall surface (Model 1) and the other two using non-linear discriminant analytical techniques. Model 2 selected variables in a step-wise inclusive fashion, and Model 3 used an information-theoretic approach in which many different random combinations of 10 variables were fitted to the Lassa fever data. Three combinations of absenceratiopresence clusters were used in each of Models 2 and 3, the 2 absenceratio1 presence cluster combination giving what appeared to be the best result. Model 1 showed that the recorded outbreaks of Lassa fever in human populations occurred in zones receiving between 1,500 and 3,000 mm rainfall annually. Rainfall, and to a much lesser extent temperature variables, were most strongly selected in both Models 2 and 3, and neither vegetation nor altitude seemed particularly important. Both Models 2 and 3 produced mean kappa values in excess of 0.91 (Model 2) or 0.86 (Model 3), making them 'Excellent'. The Lassa fever areas predicted by the models cover approximately 80% of each of Sierra Leone and Liberia, 50% of Guinea, 40% of Nigeria, 30% of each of Côte d'Ivoire, Togo and Benin, and 10% of Ghana.

Development and evaluation of antibody-capture immunoassays for detection of Lassa virus nucleoprotein-specific immunoglobulin M and G.

PubMed

Gabriel, Martin; Adomeh, Donatus I; Ehimuan, Jacqueline; Oyakhilome, Jennifer; Omomoh, Emmanuel O; Ighodalo, Yemisi; Olokor, Thomas; Bonney, Kofi; Pahlmann, Meike; Emmerich, Petra; Lelke, Michaela; Brunotte, Linda; Ölschläger, Stephan; Thomé-Bolduan, Corinna; Becker-Ziaja, Beate; Busch, Carola; Odia, Ikponmwosa; Ogbaini-Emovon, Ephraim; Okokhere, Peter O; Okogbenin, Sylvanus A; Akpede, George O; Schmitz, Herbert; Asogun, Danny A; Günther, Stephan

2018-03-01

The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Therefore, we aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using recombinant Lassa virus nucleoprotein (NP) as antigen. The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and the IgG ELISA is based on capturing IgG antibody-antigen complexes using rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic (Ghana and Germany) areas. Using the IFA as reference method, we observed 91.5-94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to hospital in an endemic area revealed a clinical sensitivity for the stand-alone IgM ELISA of 31% (95% CI 25-37) and for combined IgM/IgG detection of 26% (95% CI 21-32) compared to RT-PCR. The specificity of IgM and IgG ELISA was estimated at 96% (95% CI 93-98) and 100% (95% CI 99-100), respectively, in non-Lassa fever patients from non-endemic areas. In patients who seroconverted during follow-up, Lassa virus-specific IgM and IgG developed simultaneously rather than sequentially. Consistent with this finding, isolated IgM reactivity, i.e. IgM in the absence of IgG, had no diagnostic value. The ELISAs are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they are of value in diagnosing patients at later stage. The IgG ELISA may be useful for epidemiological studies and clinical trials due its high specificity, and the higher throughput rate and easier operation compared to IFA.

International Disease Surveillance: United States Government Goals and Paths Forward

DTIC Science & Technology

2010-06-01

convincing case to funders (ie, the U.S. Congress) showing how investment in surveillance for routine disease (eg, rotavirus ) prepares countries to detect...Hemorrhagic Fevers (Lassa, Marburg, Ebola) Viral Hemorrhagic Fevers (Lassa, Marburg, Ebola) Rotavirus Center for Biosecurity of UPMC | June 2010 Page 18

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection

PubMed Central

Ibekwe, Titus S.; Nwegbu, Maxwell M.; Asogun, Daniel; Adomeh, Donatus I.; Okokhere, Peter O.

2012-01-01

Background: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. Patients and Methods: A prospective case–control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Results: Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. Conclusion: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF “rapid screening kit” since RT-PCR is unavailable in most centers. In the interim, “high clinical index of suspicion,” irrespective of IgM status, requires urgent referral to confirmatory centers. PMID:23661877

Favipiravir and Ribavirin Treatment of Epidemiologically Linked Cases of Lassa Fever.

PubMed

Raabe, Vanessa N; Kann, Gerrit; Ribner, Bruce S; Morales, Andres; Varkey, Jay B; Mehta, Aneesh K; Lyon, G Marshall; Vanairsdale, Sharon; Faber, Kelly; Becker, Stephan; Eickmann, Markus; Strecker, Thomas; Brown, Shelley; Patel, Ketan; De Leuw, Philipp; Schuettfort, Gundolf; Stephan, Christoph; Rabenau, Holger; Klena, John D; Rollin, Pierre E; McElroy, Anita; Ströher, Ute; Nichol, Stuart; Kraft, Colleen S; Wolf, Timo

2017-09-01

Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.

PubMed

Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean

2007-06-01

Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

Advanced Development of Antiviral Prophylactics and Therapeutics (ADAPT) - Research Area 10

DTIC Science & Technology

2014-11-17

various Prosetta compounds against Rift Valley Fever Virus (RVFV), Lassa virus (LASV) and Marburg virus (MARV), respectively. Activity is demonstrated as...USAMRIID for in vitro efficacy testing against various hemorrhagic fever viruses, including Ebola (EBOV), Marburg (MARV), Lassa (LASV), Rift Valley...unless so designated by other documentation. 14. ABSTRACT The pmpose of the proposed work is to continue the promising anti-hemonhagic fever vims (HFV

Aeromedical evacuation using an aircraft transit isolator of a patient with Lassa fever.

PubMed

Lotz, Eric; Raffin, Hervé

2012-05-01

Lassa fever is a viral hemorrhagic fever only present in West Africa. The mortality rate is 1% and may reach 15% among hospitalized patients. Transmission between humans is mostly due to direct contact with infected body fluids. Aeromedical evacuation of patients with viral hemorrhagic fevers (such as Lassa fever) demands strict isolation measures. Only a few cases of such evacuations have been reported in the literature during the last 40 yr. The use of an aircraft transit isolator device could be helpful. We report the aeromedical evacuation of a confirmed Lassa fever patient from Sierra Leone to Sweden with a dedicated air ambulance using an aircraft transit isolator. The patient was a 30-yr-old physician working for a nonprofit organization. The patient contracted the disease working with infected hospitalized patients. The duration of the mission between activation and arrival at the Swedish hospital was 36 h, which is within the World Health Organization recommendations. Evacuation of patients with potentially lethal contagious infections is possible, but only with strict isolation measures. Specific protective equipment and isolator are mandatory. Medical and technical crews performing such evacuations should be trained in proper equipment use and the isolator should first be used with a low-risk patient to create minimal risk transport conditions.

Lassa fever: the challenges of curtailing a deadly disease.

PubMed

Ibekwe, Titus

2012-01-01

Today Lassa fever is mainly a disease of the developing world, however several imported cases have been reported in different parts of the world and there are growing concerns of the potentials of Lassa fever Virus as a biological weapon. Yet no tangible solution to this problem has been developed nearly half a decade after its identification. Hence, the paper is aimed at appraising the problems associated with LAF illness; the challenges in curbing the epidemic and recommendations on important focal points. A Review based on the documents from the EFAS conference 2011 and literature search on PubMed, Scopus and Science direct. The retrieval of relevant papers was via the University of British Columbia and University of Toronto Libraries. The two major search engines returned 61 and 920 articles respectively. Out of these, the final 26 articles that met the criteria were selected. Relevant information on epidemiology, burden of management and control were obtained. Prompt and effective containment of the Lassa fever disease in Lassa village four decades ago could have saved the West African sub-region and indeed the entire globe from the devastating effect and threats posed by this illness. That was a hard lesson calling for much more proactive measures towards the eradication of the illness at primary, secondary and tertiary levels of health care.

Geographic distribution and genetic characterization of Lassa virus in sub-Saharan Mali.

PubMed

Safronetz, David; Sogoba, Nafomon; Lopez, Job E; Maiga, Ousmane; Dahlstrom, Eric; Zivcec, Marko; Feldmann, Friederike; Haddock, Elaine; Fischer, Robert J; Anderson, Jennifer M; Munster, Vincent J; Branco, Luis; Garry, Robert; Porcella, Stephen F; Schwan, Tom G; Feldmann, Heinz

2013-01-01

Lassa fever is an acute viral illness characterized by multi-organ failure and hemorrhagic manifestations. Lassa fever is most frequently diagnosed in Nigeria, Sierra Leone, Liberia, and Guinea, although sporadic cases have been recorded in other West African countries, including Mali. The etiological agent of Lassa fever is Lassa virus (LASV), an Arenavirus which is maintained in nature and frequently transmitted to humans by Mastomys natalensis. The purpose of this study was to better define the geographic distribution of LASV-infected rodents in sub-Saharan Mali. Small mammals were live-trapped at various locations across Mali for the purpose of identifying potential zoonotic pathogens. Serological and molecular assays were employed and determined LASV infected rodents were exclusively found in the southern Mali near the border of Côte d'Ivoire. Overall, 19.4% of Mastomys natalensis sampled in this region had evidence of LASV infection, with prevalence rates for individual villages ranging from 0 to 52%. Full-length genomic sequences were determined using high throughput sequencing methodologies for LASV isolates generated from tissue samples of rodents collected in four villages and confirmed the phylogenetic clustering of Malian LASV with strain AV. The risk of human infections with LASV is greatest in villages in southern Mali. Lassa fever should be considered in the differential diagnosis for febrile individuals and appropriate diagnostic techniques need to be established to determine the incidence of infection and disease in these regions.

Lassa Fever in Post-Conflict Sierra Leone

PubMed Central

Hartnett, Jessica N.; Levy, Danielle C.; Yenni, Rachael E.; Moses, Lina M.; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J.; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J.; Jones, Abigail B.; Illick, Megan M.; Kulakosky, Peter C.; Haislip, Allyson M.; Bishop, Christopher M.; Elliot, Deborah H.; Brown, Bethany L.; Zhu, Hu; Hastie, Kathryn M.; Andersen, Kristian G.; Gire, Stephen K.; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B.; Spence, Jennifer S.; Cross, Robert W.; Geisbert, Joan B.; Folarin, Onikepe A.; Happi, Christian T.; Pitts, Kelly R.; Geske, F. Jon; Geisbert, Thomas W.; Saphire, Erica Ollmann; Robinson, James E.; Wilson, Russell B.; Sabeti, Pardis C.; Henderson, Lee A.; Khan, S. Humarr; Bausch, Daniel G.; Branco, Luis M.; Garry, Robert F.

2014-01-01

Background Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF. PMID:24651047

Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective, observational cohort study.

PubMed

Okokhere, Peter; Colubri, Andres; Azubike, Chukwuemeka; Iruolagbe, Christopher; Osazuwa, Omoregie; Tabrizi, Shervin; Chin, Elizabeth; Asad, Sara; Ediale, Ehi; Rafiu, Mojeed; Adomeh, Donatus; Odia, Ikponmwosa; Atafo, Rebecca; Aire, Chris; Okogbenin, Sylvanus; Pahlman, Meike; Becker-Ziaja, Beate; Asogun, Danny; Fradet, Terrence; Fry, Ben; Schaffner, Stephen F; Happi, Christian; Akpede, George; Günther, Stephan; Sabeti, Pardis C

2018-03-06

Lassa fever is a viral haemorrhagic disease endemic to west Africa. No large-scale studies exist from Nigeria, where the Lassa virus (LASV) is most diverse. LASV diversity, coupled with host genetic and environmental factors, might cause differences in disease pathophysiology. Small-scale studies in Nigeria suggest that acute kidney injury is an important clinical feature and might be a determinant of survival. We aimed to establish the demographic, clinical, and laboratory factors associated with mortality in Nigerian patients with Lassa fever, and hypothesised that LASV was the direct cause of intrinsic renal damage for a subset of the patients with Lassa fever. We did a retrospective, observational cohort study of consecutive patients in Nigeria with Lassa fever, who tested positive for LASV with RT-PCR, and were treated in Irrua Specialist Teaching Hospital. We did univariate and multivariate statistical analyses, including logistic regression, of all demographic, clinical, and laboratory variables available at presentation to identify the factors associated with patient mortality. Of 291 patients treated in Irrua Specialist Teaching Hospital between Jan 3, 2011, and Dec 11, 2015, 284 (98%) had known outcomes (died or survived) and seven (2%) were discharged against medical advice. Overall case-fatality rate was 24% (68 of 284 patients), with a 1·4 times increase in mortality risk for each 10 years of age (p=0·00017), reaching 39% (22 of 57) for patients older than 50 years. Of 284 patients, 81 (28%) had acute kidney injury and 104 (37%) had CNS manifestations and thus both were considered important complications of acute Lassa fever in Nigeria. Acute kidney injury was strongly associated with poor outcome (case-fatality rate of 60% [49 of 81 patients]; odds ratio [OR] 15, p<0·00001). Compared with patients without acute kidney injury, those with acute kidney injury had higher incidence of proteinuria (32 [82%] of 39 patients) and haematuria (29 [76%] of 38) and higher mean serum potassium (4·63 [SD 1·04] mmol/L) and lower blood urea nitrogen to creatinine ratio (8·6 for patients without clinical history of fluid loss), suggesting intrinsic renal damage. Normalisation of creatinine concentration was associated with recovery. Elevated serum creatinine (OR 1·3; p=0·046), aspartate aminotransferase (OR 1·5; p=0·075), and potassium (OR 3·6; p=0·0024) were independent predictors of death. Our study presents detailed clinical and laboratory data for Nigerian patients with Lassa fever and provides strong evidence for intrinsic renal dysfunction in acute Lassa fever. Early recognition and treatment of acute kidney injury might significantly reduce mortality. German Research Foundation, German Center for Infection Research, Howard Hughes Medical Institute, US National Institutes of Health, and World Bank. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hyperglycemic crisis precipitated by Lassa fever in a patient with previously undiagnosed type 2 diabetes mellitus.

PubMed

Edo, A E; Okaka, E; Ezeani, I U

2014-01-01

Hyperglycemic crisis (HC) is an acute complication of diabetes mellitus (DM) that is commonly precipitated by infections and non-compliance with therapy. Viral precipitant of HC is uncommon. To report a rare case of HC unmasked by Lassa fever in a patient previously not known to have diabetes mellitus. A 54 year old lady presented with complaints of generalized body weakness, inability to pass stool, and fever. There was no abdominal pain, vomiting and nausea. There were no features of DM. She is not a known case of diabetes mellitus or hypertension. Patient does not drink alcoholic beverages. There was no history of bleeding from any orifices. She was acutely ill-looking, afebrile, not pale, anicteric, nil pedal oedema. Pulse rate was 110 beats per minute, regular, normal volume. Blood pressure was 110/80 mmHg. Respiratory rate was 26 cycles/minute, breath sound was vesicular. Abdomen was full and moved with respiration. There were no areas of tenderness, no organomegaly, no ascites, and bowel sounds were normoactive. Neurologic examination revealed a conscious patient who was restless. Casual blood glucose was 600mg/dl. Urinalysis: Glycosuria (+++), HbA1c was 12.4%. Lassa PCR done was positive. Patient was managed for hyperglycemic crisis with intravenous normal saline and soluble insulin. She was also commenced on Ribavirin but died of complications of lassa fever. Lassa fever should be included as a precipitant of hyperglycemic crisis in endemic countries.

Prevalence of Lassa virus among rodents trapped in three South-South States of Nigeria.

PubMed

Agbonlahor, D E; Erah, A; Agba, I M; Oviasogie, F E; Ehiaghe, A F; Wankasi, M; Eremwanarue, O A; Ehiaghe, I J; Ogbu, E C; Iyen, R I; Abbey, S; Tatfeng, M Y; Uhunmwangho, J

2017-01-01

Lassa fever has been endemic in Nigeria since 1969. The rodent Mastomys natalensis has been widely claimed to be the reservoir host of the Lassa virus. This study was designed to investigate the dis- tribution of species of rodents in three states (Edo, Delta and Bayelsa) of Nigeria and to determine the prevalence of Lassa virus amongst trapped rodents in the selected states. Rodents were trapped during November 2015 to October 2016 from the three states in South-South re- gion of Nigeria. Total RNA was extracted from the blood collected from the trapped rodents. Reverse transcription polymerase chain reaction (RT-PCR) was used to confirm the presence of Lassa virus in the rodents. The results revealed that six species of rodents were predominantly present in these geographical locations. Mus musculus (39.4%) had the highest prevalence, closely followed by Rattus rattus (36.1%), R. fuscipus (20.3%), M. natalensis (2%), Myosoricinae soricidae (1.2%) and R. norvegicus (1%). The overall positivity (carrier rate) of Lassa virus was 1.6% amongst the 1500 rodents caught in the three states. In Edo and Delta States, the RT-PCR results showed presence of Lassa virus in R. rattus, M. musculus and M. natalensis. On the other hand, only M. na- talensis was detected with the virus, amongst the species of rodents caught in Bayelsa State. M. natalensis recorded the highest Lassa virus among rodents trapped in Edo (87%), Delta (50%) and Bayelsa (11%) States respectively. The rather low Lassa virus positive among rodents in Bayelsa State of Nigeria may explain the absence of reports of outbreak of Lassa fever over the past 48 yr in the state. The results also confirmed that apart from Mastomys natalensis, other rodents such as Rattus rattus and Mus musculus may also serve as res- ervoirs for Lassa virus. From the findings of this cross-sectional study, it was concluded that a more comprehensive study on rodents as reservoir host, need to be undertaken across the entire states of Nigeria, for better understanding of the epidemiology and endemicity of Lassa fever.

Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates✩

PubMed Central

Lukashevich, Igor S.; Carrion, Ricardo; Salvato, Maria S.; Mansfield, Keith; Brasky, Kathleen; Zapata, Juan; Cairo, Cristiana; Goicochea, Marco; Hoosien, Gia E.; Ticer, Anysha; Bryant, Joseph; Davis, Harry; Hammamieh, Rasha; Mayda, Maria; Jett, Marti; Patterson, Jean

2008-01-01

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever. PMID:18692539

Pathogenesis of Lassa fever in cynomolgus macaques.

PubMed

Hensley, Lisa E; Smith, Mark A; Geisbert, Joan B; Fritz, Elizabeth A; Daddario-DiCaprio, Kathleen M; Larsen, Tom; Geisbert, Thomas W

2011-05-06

Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates. Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease. Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers. The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever

PubMed Central

Zapata, Juan C.; Pauza, C. David; Djavani, Mahmoud M.; Rodas, Juan D.; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S.; Salvato, Maria S.

2011-01-01

Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets. PMID:21820469

DNA vaccines elicit durable protective immunity against individual or simultaneous infections with Lassa and Ebola viruses in guinea pigs.

PubMed

Cashman, Kathleen A; Wilkinson, Eric R; Wollen, Suzanne E; Shamblin, Joshua D; Zelko, Justine M; Bearss, Jeremy J; Zeng, Xiankun; Broderick, Kate E; Schmaljohn, Connie S

2017-12-02

We previously developed optimized DNA vaccines against both Lassa fever and Ebola hemorrhagic fever viruses and demonstrated that they were protective individually in guinea pig and nonhuman primate models. In this study, we vaccinated groups of strain 13 guinea pigs two times, four weeks apart with 50 µg of each DNA vaccine or a mock vaccine at discrete sites by intradermal electroporation. Five weeks following the second vaccinations, guinea pigs were exposed to lethal doses of Lassa virus, Ebola virus, or a combination of both viruses simultaneously. None of the vaccinated guinea pigs, regardless of challenge virus and including the coinfected group, displayed weight loss, fever or other disease signs, and all survived to the study endpoint. All of the mock-vaccinated guinea pigs that were infected with Lassa virus, and all but one of the EBOV-infected mock-vaccinated guinea pigs succumbed. In order to determine if the dual-agent vaccination strategy could protect against both viruses if exposures were temporally separated, we held the surviving vaccinates in BSL-4 for approximately 120 days to perform a cross-challenge experiment in which guinea pigs originally infected with Lassa virus received a lethal dose of Ebola virus and those originally infected with Ebola virus were infected with a lethal dose of Lassa virus. All guinea pigs remained healthy and survived to the study endpoint. This study clearly demonstrates that DNA vaccines against Lassa and Ebola viruses can elicit protective immunity against both individual virus exposures as well as in a mixed-infection environment.

DNA vaccines elicit durable protective immunity against individual or simultaneous infections with Lassa and Ebola viruses in guinea pigs

PubMed Central

Cashman, Kathleen A.; Wilkinson, Eric R.; Wollen, Suzanne E.; Shamblin, Joshua D.; Zelko, Justine M.; Bearss, Jeremy J.; Zeng, Xiankun; Broderick, Kate E.; Schmaljohn, Connie S.

2017-01-01

ABSTRACT We previously developed optimized DNA vaccines against both Lassa fever and Ebola hemorrhagic fever viruses and demonstrated that they were protective individually in guinea pig and nonhuman primate models. In this study, we vaccinated groups of strain 13 guinea pigs two times, four weeks apart with 50 µg of each DNA vaccine or a mock vaccine at discrete sites by intradermal electroporation. Five weeks following the second vaccinations, guinea pigs were exposed to lethal doses of Lassa virus, Ebola virus, or a combination of both viruses simultaneously. None of the vaccinated guinea pigs, regardless of challenge virus and including the coinfected group, displayed weight loss, fever or other disease signs, and all survived to the study endpoint. All of the mock-vaccinated guinea pigs that were infected with Lassa virus, and all but one of the EBOV-infected mock-vaccinated guinea pigs succumbed. In order to determine if the dual-agent vaccination strategy could protect against both viruses if exposures were temporally separated, we held the surviving vaccinates in BSL-4 for approximately 120 days to perform a cross-challenge experiment in which guinea pigs originally infected with Lassa virus received a lethal dose of Ebola virus and those originally infected with Ebola virus were infected with a lethal dose of Lassa virus. All guinea pigs remained healthy and survived to the study endpoint. This study clearly demonstrates that DNA vaccines against Lassa and Ebola viruses can elicit protective immunity against both individual virus exposures as well as in a mixed-infection environment. PMID:29135337

An Outbreak of Ebola Virus Disease in the Lassa Fever Zone.

PubMed

Goba, Augustine; Khan, S Humarr; Fonnie, Mbalu; Fullah, Mohamed; Moigboi, Alex; Kovoma, Alice; Sinnah, Vandi; Yoko, Nancy; Rogers, Hawa; Safai, Siddiki; Momoh, Mambu; Koroma, Veronica; Kamara, Fatima K; Konowu, Edwin; Yillah, Mohamed; French, Issa; Mustapha, Ibraham; Kanneh, Franklyn; Foday, Momoh; McCarthy, Helena; Kallon, Tiangay; Kallon, Mustupha; Naiebu, Jenneh; Sellu, Josephine; Jalloh, Abdul A; Gbakie, Michael; Kanneh, Lansana; Massaly, James L B; Kargbo, David; Kargbo, Brima; Vandi, Mohamed; Gbetuwa, Momoh; Gevao, Sahr M; Sandi, John D; Jalloh, Simbirie C; Grant, Donald S; Blyden, Sylvia O; Crozier, Ian; Schieffelin, John S; McLellan, Susan L; Jacob, Shevin T; Boisen, Matt L; Hartnett, Jessica N; Cross, Robert W; Branco, Luis M; Andersen, Kristian G; Yozwiak, Nathan L; Gire, Stephen K; Tariyal, Ridhi; Park, Daniel J; Haislip, Allyson M; Bishop, Christopher M; Melnik, Lilia I; Gallaher, William R; Wimley, William C; He, Jing; Shaffer, Jeffrey G; Sullivan, Brian M; Grillo, Sonia; Oman, Scott; Garry, Courtney E; Edwards, Donna R; McCormick, Stephanie J; Elliott, Deborah H; Rouelle, Julie A; Kannadka, Chandrika B; Reyna, Ashley A; Bradley, Benjamin T; Yu, Haini; Yenni, Rachael E; Hastie, Kathryn M; Geisbert, Joan B; Kulakosky, Peter C; Wilson, Russell B; Oldstone, Michael B A; Pitts, Kelly R; Henderson, Lee A; Robinson, James E; Geisbert, Thomas W; Saphire, Erica Ollmann; Happi, Christian T; Asogun, Danny A; Sabeti, Pardis C; Garry, Robert F

2016-10-15

 Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs.  Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities.  Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case.  Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever.

PubMed

Oestereich, Lisa; Rieger, Toni; Lüdtke, Anja; Ruibal, Paula; Wurr, Stephanie; Pallasch, Elisa; Bockholt, Sabrina; Krasemann, Susanne; Muñoz-Fontela, César; Günther, Stephan

2016-03-15

We studied the therapeutic potential of favipiravir (T-705) for Lassa fever, both alone and in combination with ribavirin. Favipiravir suppressed Lassa virus replication in cell culture by 5 log10 units. In a novel lethal mouse model, it lowered the viremia level and the virus load in organs and normalized levels of cell-damage markers. Treatment with 300 mg/kg per day, commenced 4 days after infection, when the viremia level had reached 4 log10 virus particles/mL, rescued 100% of Lassa virus-infected mice. We found a synergistic interaction between favipiravir and ribavirin in vitro and an increased survival rate and extended survival time when combining suboptimal doses in vivo. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Prevalence of Lassa Virus Disease (LVD) in Nigerian children with fever or fever and convulsions in an endemic area

PubMed Central

Akhuemokhan, Odigie C.; Ewah-Odiase, Rosemary O.; Akpede, Nosa; Ehimuan, Jacqueline; Adomeh, Donatus I.; Odia, Ikpomwonsa; Olomu, Sylvia C.; Pahlmann, Meike; Becker-Ziaja, Beate; Happi, Christian T.; Asogun, Danny A.; Okogbenin, Sylvanus A.; Okokhere, Peter O.; Dawodu, Osagie S.; Omoike, Irekpono U.; Sabeti, Pardis C.; Günther, Stephan; Akpede, George O.

2017-01-01

Background Convulsions with fever in children are a common neurologic emergency in the tropics, and determining the contribution of endemic viral infections can be challenging. In particular, there is a dearth of data on the prevalence and clinical differentiation of Lassa virus disease (LVD) in febrile children in endemic areas of Nigeria, which has multiple lineages of the virus. The aim of this study was to determine the prevalence and presentation of LVD in febrile children with and without convulsions. Methodology/Principal findings This was a prospective study of consecutive febrile children aged ≥1 month– 15 years admitted to the Children’s Emergency Room of Irrua Specialist Teaching Hospital over a period of 1 year. Febrile children with convulsions (Cases) were compared with those without convulsions (Controls). LVD was defined by the presence of a positive Lassa virus RT-PCR test. Rates were compared between groups using χ2 or Fisher’s exact tests and p <0.05 taken as significant. 373 (40.9%) of 913 admissions had fever. Of these, 108/373 (29%) presented with convulsions. The overall prevalence of LVD was 13/373 (3.5%; 95% CI = 1.9%, 5.7%) in febrile admissions, 3/108 (2.8%) in Cases and 10/265 (3.8%) in Controls [(Odds Ratio (95% Confidence Interval) (OR (95% CI)) of LVD in Cases versus Controls = 0.73 (0.2, 2.7)]. Only vomiting (OR (95% CI) = 0.09 (0.01, 0.70)) and bleeding (OR (95% CI) = 39.56 (8.52, 183.7)) were significantly associated with an increased prevalence of LVD. Conclusions/Significance LVD is an important cause of fever, including undifferentiated fever in children in endemic areas, but it is not significantly associated with convulsions associated with fever. Its prevalence, and lack of clinical differentiation on presentation, underscores the importance of a high index of suspicion in diagnosis. Screening of febrile children with undifferentiated fever in endemic areas for LVD could be an important medical and public health control measure. PMID:28671959

New opportunities for field research on the pathogenesis and treatment of Lassa fever.

PubMed

Khan, Sheik Humarr; Goba, Augustine; Chu, May; Roth, Cathy; Healing, Tim; Marx, Arthur; Fair, Joseph; Guttieri, Mary C; Ferro, Philip; Imes, Tiffany; Monagin, Corina; Garry, Robert F; Bausch, Daniel G

2008-04-01

Unlike many viral hemorrhagic fevers (VHFs), Lassa fever (LF) is not a rare disease that emerges only as sporadic cases or in outbreak form. Although surveillance is inadequate to determine the true incidence, up to 300,000 infections and 5000 deaths from LF are estimated to occur yearly. The highest incidence is in the "Mano River Union (MRU) countries" of Sierra Leone, Liberia, and Guinea. Although civil unrest in this region over the past two decades has impeded capacity building and research, new-found peace in recent years presents new opportunities. In 2004, the Mano River Union Lassa Fever Network (MRU LFN) was established to assist MRU countries in the development of national and regional surveillance, diagnosis, treatment, control, and prevention of LF. Here, we review the present literature on treatment and pathogenesis of LF and outline priorities for future research in the field made possible by the improved research capacity of the MRU LFN.

Synthetic Vaccines for the Control of Arenavirus Infections

DTIC Science & Technology

1992-03-31

is envel- tions. For example. Lassa fever and CH have several sopcd apparently buds from the cytoplasmic membrane (no similarities, including an acutc...course, involvement of mul- intact virions were seen intra-ellularly). has a glycoprotein tiple organs (including liver and spleen), petechial hemor...c fringe ,ontains ribosomelike interna! structures, and has a rhale, (although not prominent in either CH or Lassa fever ). A diameter ranging from 67

Hemorrhagic Fevers

MedlinePlus

... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

The rubber plantation environment and Lassa fever epidemics in Liberia, 2008-2012: a spatial regression.

PubMed

Olugasa, Babasola O; Dogba, John B; Ogunro, Bamidele; Odigie, Eugene A; Nykoi, Jomah; Ojo, Johnson F; Taiwo, Olalekan; Kamara, Abraham; Mulbah, Charles K; Fasunla, Ayotunde J

2014-10-01

As Lassa fever continues to be a public health challenge in West Africa, it is critical to produce good maps of its risk pattern for use in active surveillance and control intervention. We identified eight spatial features related to the rubber plantation environment and used them as explanatory variables for Lassa fever (LF) outbreaks on the Uniroyal Liberian Agricultural Company (LAC) rubber plantation environment in Grand Bassa County, Liberia. We computed classical and spatial lag regression models on all spatial features, including proximity of residential camp to rubber tree-edge, main road in the plantation, LAC hospital, rice farmland, household refuse dump, human population density, post-harvest storage density of rice and density of rodent deterrent on rice storage. We found significant (p=0.0024) spatial autocorrelation between LF cases and the spatial features we have considered. We concluded that the rubber plantation environment influenced Mastomys species' breeding and transmission of Lassa virus along spatial scale to humans. The risk factors identified in this study offered a baseline for more effective surveillance and control of LF in the post-civil conflict Liberia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advanced Vaccine Candidates for Lassa Fever

PubMed Central

Lukashevich, Igor S.

2012-01-01

Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF). LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered. PMID:23202493

Advanced vaccine candidates for Lassa fever.

PubMed

Lukashevich, Igor S

2012-10-29

Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF). LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation

PubMed Central

2012-01-01

Background Travel from countries where viral haemorrhagic fevers (VHF) are endemic has increased significantly over the past decades. In several reported VHF events on airplanes, passenger trace back was initiated but the scale of the trace back differed considerably. The absence of guidance documents to help the decision on necessity and scale of the trace back contributed to this variation. This article outlines the recommendations of an expert panel on Lassa fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in order to advise the relevant stakeholders in the decision and scale of a possible passenger trace back. Method The evidence was collected through review of published literature and through the views of an expert panel. The guidance was agreed by consensus. Results Only a few events of VHF cases during air travel are reported in literature, with no documented infection in followed up contacts, so that no evidence of transmission of VHF during air travel exists to date. Based on this and the expert opinion, it was recommended that passenger trace back was undertaken only if: the index case had symptoms during the flight; the flight was within 21 days after detection of the event; and for Lassa fever if exposure of body fluid has been reported. The trace back should only be done after confirmation of the index case. Passengers and crew with direct contact, seat neighbours (+/− 1 seat), crew and cleaning personal of the section of the index case should be included in the trace back. Conclusion No evidence has been found for the transmission of VHF in airplanes. This information should be taken into account, when a trace back decision has to be taken, because such a measure produces an enormous work load. The procedure suggested by the expert group can guide decisions made in future events, where a patient with suspected VHF infection travelled on a plane. However, the actual decision on start and scale of a trace back always lies in the hands of the responsible people taking all relevant information into account. PMID:23170851

Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses.

PubMed

Hastie, Kathryn M; Bale, Shridhar; Kimberlin, Christopher R; Saphire, Erica Ollmann

2012-04-01

The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention. Copyright © 2012. Published by Elsevier B.V.

Emerging intracellular receptors for hemorrhagic fever viruses.

PubMed

Jae, Lucas T; Brummelkamp, Thijn R

2015-07-01

Ebola virus and Lassa virus belong to different virus families that can cause viral hemorrhagic fever, a life-threatening disease in humans with limited treatment options. To infect a target cell, Ebola and Lassa viruses engage receptors at the cell surface and are subsequently shuttled into the endosomal compartment. Upon arrival in late endosomes/lysosomes, the viruses trigger membrane fusion to release their genome into the cytoplasm. Although contact sites at the cell surface were recognized for Ebola virus and Lassa virus, it was postulated that Ebola virus requires a critical receptor inside the cell. Recent screens for host factors identified such internal receptors for both viruses: Niemann-Pick disease type C1 protein (NPC1) for Ebola virus and lysosome-associated membrane protein 1 (LAMP1) for Lassa virus. A cellular trigger is needed to permit binding of the viral envelope protein to these intracellular receptors. This 'receptor switch' represents a previously unnoticed step in virus entry with implications for host-pathogen interactions and viral tropism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits

PubMed Central

Robinson, James E.; Hastie, Kathryn M.; Cross, Robert W.; Yenni, Rachael E.; Elliott, Deborah H.; Rouelle, Julie A.; Kannadka, Chandrika B.; Smira, Ashley A.; Garry, Courtney E.; Bradley, Benjamin T.; Yu, Haini; Shaffer, Jeffrey G.; Boisen, Matt L.; Hartnett, Jessica N.; Zandonatti, Michelle A.; Rowland, Megan M.; Heinrich, Megan L.; Martínez-Sobrido, Luis; Cheng, Benson; de la Torre, Juan C.; Andersen, Kristian G.; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Gbakie, Michael; Kanneh, Lansana; Koroma, Veronica J.; Fonnie, Richard; Jalloh, Simbirie C.; Kargbo, Brima; Vandi, Mohamed A.; Gbetuwa, Momoh; Ikponmwosa, Odia; Asogun, Danny A.; Okokhere, Peter O.; Follarin, Onikepe A.; Schieffelin, John S.; Pitts, Kelly R.; Geisbert, Joan B.; Kulakoski, Peter C.; Wilson, Russell B.; Happi, Christian T.; Sabeti, Pardis C.; Gevao, Sahr M.; Khan, S. Humarr; Grant, Donald S.; Geisbert, Thomas W.; Saphire, Erica Ollmann; Branco, Luis M.; Garry, Robert F.

2016-01-01

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design. PMID:27161536

Identification of Cell Surface Molecules Involved in Dystroglycan-Independent Lassa Virus Cell Entry

PubMed Central

Ströher, Ute; Ebihara, Hideki; Feldmann, Heinz

2012-01-01

Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa virus receptors advances our understanding of Lassa virus cell entry. PMID:22156524

[Characterization of contacts of the population of Guinea with synanthropic rodents as Lassa fever virus carriers].

PubMed

Inapogui, A P; Konstantinov, O K; Lapshov, V N; Comara, S K

2007-01-01

Questionnaire surveys made in 17 villages from 3 ecological zones of Guinea have provided evidence for the population's contact with synanthropic rodents as Lassa fever virus carriers. Over 100 rodents are quarterly captured in the houses of the traditional type in the villages located in the savanna woodland. Less than 10 specimens are captured at the food warehouses. There are more than 100 rodents in the majority of houses of the traditional type in the villages located in the secondary forest. In the villages of rainy tropical forests, the capture rate is low--10 to 100 rodents. The main rodent capturers are boys and young men (aged 7 to 20 years) who are principal rodent meat eaters; although almost the whole population, particularly in rural areas, consumes this meat in varying degrees. The proportion of captured rats of the genus Mastomys (the carrier of Lassa fever virus) in the town of Kindia is 11%. In the rural area, it is much higher (as high as 94%) in the villages located in the rainy tropical forests. It is estimated that one trapper quarterly catches 0.2 (in the savanna woodland) to 6.9 (in the secondary forests) infected rats, which agrees with the data of a serological survey of Guinea's population. By and large, the majority of the Guinean population may be referred to as a group at risk for Lassa fever due to their permanent contacts with rodents.

The search for animal models for Lassa fever vaccine development

PubMed Central

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

The search for animal models for Lassa fever vaccine development.

PubMed

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates.

Immunobiology of Ebola and Lassa virus infections.

PubMed

Prescott, Joseph B; Marzi, Andrea; Safronetz, David; Robertson, Shelly J; Feldmann, Heinz; Best, Sonja M

2017-03-01

Two of the most important contemporary emerging viruses that affect human health in Africa are Ebola virus (EBOV) and Lassa virus (LASV). The 2013-2016 West African outbreak of EBOV was responsible for more than 11,000 deaths, primarily in Guinea, Sierra Leone and Liberia. LASV is constantly emerging in these and surrounding West African countries, with an estimate of more than 500,000 cases of Lassa fever, and approximately 5,000 deaths, annually. Both EBOV and LASV are zoonotic, and human infection often results in a severe haemorrhagic fever in both cases. However, the contribution of specific immune responses to disease differs between EBOV and LASV. This Review examines innate and adaptive immune responses to these viruses with the goal of delineating responses that are associated with protective versus pathogenic outcomes.

Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection

PubMed Central

2011-01-01

Background Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Results Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Conclusion Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF. PMID:22023795

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

PubMed Central

Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

2010-01-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

Lassa Fever Immune Plasma

DTIC Science & Technology

1988-07-31

cases are likely to be seen. Finally, further studies into the nature of the virus or viruses of LF are needed. Clinical experience suggests that there...OF ReIPRIt r ~M. u iav Is. PAGE COUNT Annual Rpnnrt T FROM 1,.1IR7 j ,O 30 lunB 88-7-31 22 1. SUPPUMENTARY NOTATION 17. COSATI CODES 10. SUSJECT...TERMS (Connimm on nwmw ,o neceiawt &W ide I No& num IELD IGROUP suS.GROUP Lassa fever Immunotherapy RA 1 06 1) 6 LLassa virus Liberia nf i Pl,:m haiman 19

Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever.

PubMed

Branco, Luis M; Grove, Jessica N; Geske, Frederick J; Boisen, Matt L; Muncy, Ivana J; Magliato, Susan A; Henderson, Lee A; Schoepp, Randal J; Cashman, Kathleen A; Hensley, Lisa E; Garry, Robert F

2010-10-20

Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV)-like particle (VLP)-based modular vaccine platform. A mammalian expression system that generated large quantities of LASV VLP in human cells at small scale settings was developed. These VLP contained the major immunological determinants of the virus: glycoprotein complex, nucleoprotein, and Z matrix protein, with known post-translational modifications. The viral proteins packaged into LASV VLP were characterized, including glycosylation profiles of glycoprotein subunits GP1 and GP2, and structural compartmentalization of each polypeptide. The host cell protein component of LASV VLP was also partially analyzed, namely glycoprotein incorporation, though the identity of these proteins remain unknown. All combinations of LASV Z, GPC, and NP proteins that generated VLP did not incorporate host cell ribosomes, a known component of native arenaviral particles, despite detection of small RNA species packaged into pseudoparticles. Although VLP did not contain the same host cell components as the native virion, electron microscopy analysis demonstrated that LASV VLP appeared structurally similar to native virions, with pleiomorphic distribution in size and shape. LASV VLP that displayed GPC or GPC+NP were immunogenic in mice, and generated a significant IgG response to individual viral proteins over the course of three immunizations, in the absence of adjuvants. Furthermore, sera from convalescent Lassa fever patients recognized VLP in ELISA format, thus affirming the presence of native epitopes displayed by the recombinant pseudoparticles. These results established that modular LASV VLP can be generated displaying high levels of immunogenic viral proteins, and that small laboratory scale mammalian expression systems are capable of producing multi-milligram quantities of pseudoparticles. These VLP are structurally and morphologically similar to native LASV virions, but lack replicative functions, and thus can be safely generated in low biosafety level settings. LASV VLP were immunogenic in mice in the absence of adjuvants, with mature IgG responses developing within a few weeks after the first immunization. These studies highlight the relevance of a VLP platform for designing an optimal vaccine candidate against Lassa hemorrhagic fever, and warrant further investigation in lethal challenge animal models to establish their protective potential.

MassTag Polymerase Chain Reaction for Differential Diagnosis of Viral Hemorrhagic Fevers

DTIC Science & Technology

2006-04-01

fever virus (RVFV), Crimean - Congo hemorrhagic fever virus (CCHFV), and hantaviruses (Bunyaviridae); and...ribavirin may be helpful if given early in the course of Lassa fever (9), Crimean - Congo hemorrhagic fever (10), or hemorrhagic fever with renal...I, Erol S, Erdem F, Yilmaz N, Parlak M, et al. Crimean - Congo hemorrhagic fever in eastern Turkey: clinical fea- tures, risk factors and efficacy

Mapping the zoonotic niche of Lassa fever in Africa.

PubMed

Mylne, Adrian Q N; Pigott, David M; Longbottom, Joshua; Shearer, Freya; Duda, Kirsten A; Messina, Jane P; Weiss, Daniel J; Moyes, Catherine L; Golding, Nick; Hay, Simon I

2015-08-01

Lassa fever is a viral haemorrhagic illness responsible for disease outbreaks across West Africa. It is a zoonosis, with the primary reservoir species identified as the Natal multimammate mouse, Mastomys natalensis. The host is distributed across sub-Saharan Africa while the virus' range appears to be restricted to West Africa. The majority of infections result from interactions between the animal reservoir and human populations, although secondary transmission between humans can occur, particularly in hospital settings. Using a species distribution model, the locations of confirmed human and animal infections with Lassa virus (LASV) were used to generate a probabilistic surface of zoonotic transmission potential across sub-Saharan Africa. Our results predict that 37.7 million people in 14 countries, across much of West Africa, live in areas where conditions are suitable for zoonotic transmission of LASV. Four of these countries, where at-risk populations are predicted, have yet to report any cases of Lassa fever. These maps act as a spatial guide for future surveillance activities to better characterise the geographical distribution of the disease and understand the anthropological, virological and zoological interactions necessary for viral transmission. Combining this zoonotic niche map with detailed patient travel histories can aid differential diagnoses of febrile illnesses, enabling a more rapid response in providing care and reducing the risk of onward transmission. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Lassa fever in post-conflict sierra leone.

PubMed

Shaffer, Jeffrey G; Grant, Donald S; Schieffelin, John S; Boisen, Matt L; Goba, Augustine; Hartnett, Jessica N; Levy, Danielle C; Yenni, Rachael E; Moses, Lina M; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J; Jones, Abigail B; Illick, Megan M; Kulakosky, Peter C; Haislip, Allyson M; Bishop, Christopher M; Elliot, Deborah H; Brown, Bethany L; Zhu, Hu; Hastie, Kathryn M; Andersen, Kristian G; Gire, Stephen K; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B; Spence, Jennifer S; Cross, Robert W; Geisbert, Joan B; Folarin, Onikepe A; Happi, Christian T; Pitts, Kelly R; Geske, F Jon; Geisbert, Thomas W; Saphire, Erica Ollmann; Robinson, James E; Wilson, Russell B; Sabeti, Pardis C; Henderson, Lee A; Khan, S Humarr; Bausch, Daniel G; Branco, Luis M; Garry, Robert F

2014-03-01

Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.

Absence of Nosocomial Transmission of Imported Lassa Fever during Use of Standard Barrier Nursing Methods.

PubMed

Grahn, Anna; Bråve, Andreas; Tolfvenstam, Thomas; Studahl, Marie

2018-06-01

Nosocomial transmission of Lassa virus (LASV) is reported to be low when care for the index patient includes proper barrier nursing methods. We investigated whether asymptomatic LASV infection occurred in healthcare workers who used standard barrier nursing methods during the first 15 days of caring for a patient with Lassa fever in Sweden. Of 76 persons who were defined as having been potentially exposed to LASV, 53 provided blood samples for detection of LASV IgG. These persons also responded to a detailed questionnaire to evaluate exposure to different body fluids from the index patient. LASV-specific IgG was not detected in any of the 53 persons. Five of 53 persons had not been using proper barrier nursing methods. Our results strengthen the argument for a low risk of secondary transmission of LASV in humans when standard barrier nursing methods are used and the patient has only mild symptoms.

Understanding the cryptic nature of Lassa fever in West Africa.

PubMed

Gibb, Rory; Moses, Lina M; Redding, David W; Jones, Kate E

2017-09-01

Lassa fever (LF) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of West Africa's poorest communities. However, our knowledge of LF ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on Lassa virus (LASV) zoonotic transmission dynamics. Here, we synthesize current knowledge to show that extrapolations from past research have produced an incomplete picture of the incidence and distribution of LF, with negative consequences for policy planning, medical treatment and management interventions. Although the recent increase in LF case reports is likely due to improved surveillance, recent studies suggest that future socio-ecological changes in West Africa may drive increases in LF burden. Future research should focus on the geographical distribution and disease burden of LF, in order to improve its integration into public policy and disease control strategies.

Conserved residues in Lassa fever virus Z protein modulate viral infectivity at the level of the ribonucleoprotein.

PubMed

Capul, Althea A; de la Torre, Juan Carlos; Buchmeier, Michael J

2011-04-01

Arenaviruses are negative-strand RNA viruses that cause human diseases such as lymphocytic choriomeningitis, Bolivian hemorrhagic fever, and Lassa hemorrhagic fever. No licensed vaccines exist, and current treatment is limited to ribavirin. The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a model for dissecting virus-host interactions in persistent and acute disease. The RING finger protein Z has been identified as the driving force of arenaviral budding and acts as the viral matrix protein. While residues in Z required for viral budding have been described, residues that govern the Z matrix function(s) have yet to be fully elucidated. Because this matrix function is integral to viral assembly, we reasoned that this would be reflected in sequence conservation. Using sequence alignment, we identified several conserved residues in Z outside the RING and late domains. Nine residues were each mutated to alanine in Lassa fever virus Z. All of the mutations affected the expression of an LCMV minigenome and the infectivity of virus-like particles, but to greatly varying degrees. Interestingly, no mutations appeared to affect Z-mediated budding or association with viral GP. Our findings provide direct experimental evidence supporting a role for Z in the modulation of the activity of the viral ribonucleoprotein (RNP) complex and its packaging into mature infectious viral particles.

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

PubMed

Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

2011-02-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

Lassa virus entry requires a trigger-induced receptor switch

PubMed Central

Jae, Lucas T.; Raaben, Matthijs; Herbert, Andrew S.; Kuehne, Ana I.; Wirchnianski, Ariel S.; Soh, Timothy; Stubbs, Sarah H.; Janssen, Hans; Damme, Markus; Saftig, Paul; Whelan, Sean P.; Dye, John M.; Brummelkamp, Thijn R.

2014-01-01

Lassa virus spreads from rodents to humans and can lead to lethal hemorrhagic fever. Despite its broad tropism, chicken cells were reported to resist infection thirty years ago. We show that Lassa virus readily engaged its cell surface receptor α-dystroglycan in avian cells, but virus entry in susceptible species involved a pH-dependent switch to an intracellular receptor, the lysosome-resident protein LAMP1. Iterative haploid screens revealed that the sialyltransferase ST3GAL4 was required for the interaction of the virus glycoprotein with LAMP1. A single glycosylated residue in LAMP1, present in susceptible species but absent in birds, was essential for interaction with the Lassa virus envelope protein and subsequent infection. The resistance of Lamp1-deficient mice to Lassa virus highlights the relevance of this receptor switch in vivo. PMID:24970085

A DNA vaccine delivered by dermal electroporation fully protects cynomolgus macaques against Lassa fever.

PubMed

Cashman, Kathleen A; Wilkinson, Eric R; Shaia, Carl I; Facemire, Paul R; Bell, Todd M; Bearss, Jeremy J; Shamblin, Joshua D; Wollen, Suzanne E; Broderick, Kate E; Sardesai, Niranjan Y; Schmaljohn, Connie S

2017-12-02

Lassa virus (LASV) is an ambisense RNA virus in the Arenaviridae family and is the etiological agent of Lassa fever, a severe hemorrhagic disease endemic to West and Central Africa. 1,2 There are no US Food and Drug Administration (FDA)-licensed vaccines available to prevent Lassa fever. 1,2 in our previous studies, we developed a gene-optimized DNA vaccine that encodes the glycoprotein precursor gene of LASV (Josiah strain) and demonstrated that 3 vaccinations accompanied by dermal electroporation protected guinea pigs from LASV-associated illness and death. Here, we describe an initial efficacy experiment in cynomolgus macaque nonhuman primates (NHPs) in which we followed an identical 3-dose vaccine schedule that was successful in guinea pigs, and a follow-on experiment in which we used an accelerated vaccination strategy consisting of 2 administrations, spaced 4 weeks apart. In both studies, all of the LASV DNA-vaccinated NHPs survived challenge and none of them had measureable, sustained viremia or displayed weight loss or other disease signs post-exposure. Three of 10 mock-vaccinates survived exposure to LASV, but all of them became acutely ill post-exposure and remained chronically ill to the study end point (45 d post-exposure). Two of the 3 survivors experienced sensorineural hearing loss (described elsewhere). These results clearly demonstrate that the LASV DNA vaccine combined with dermal electroporation is a highly effective candidate for eventual use in humans.

Treatment of Lassa virus infection in outbred guinea pigs with first-in-class human monoclonal antibodies.

PubMed

Cross, Robert W; Mire, Chad E; Branco, Luis M; Geisbert, Joan B; Rowland, Megan M; Heinrich, Megan L; Goba, Augustine; Momoh, Mambu; Grant, Donald S; Fullah, Mohamed; Khan, Sheik Humarr; Robinson, James E; Geisbert, Thomas W; Garry, Robert F

2016-09-01

Lassa fever is a significant health threat to West African human populations with hundreds of thousands of annual cases. There are no approved medical countermeasures currently available. Compassionate use of the antiviral drug ribavirin or transfusion of convalescent serum has resulted in mixed success depending on when administered or the donor source, respectively. We previously identified several recombinant human monoclonal antibodies targeting the glycoprotein of Lassa virus with strong neutralization profiles in vitro. Here, we demonstrate remarkable therapeutic efficacy using first-in-class human antibodies in a guinea pig model of Lassa infection thereby presenting a promising treatment alternative. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Management of a Lassa fever outbreak, Rhineland-Palatinate, Germany, 2016.

PubMed

Ehlkes, Lutz; George, Maja; Samosny, Gerhard; Burckhardt, Florian; Vogt, Manfred; Bent, Stefan; Jahn, Klaus; Zanger, Philipp

2017-09-01

Due to rapid diagnosis and isolation of imported cases, community outbreaks of viral haemorrhagic fevers (VHF) are considered unlikely in industrialised countries. In March 2016, the first documented locally acquired case of Lassa fever (LF) outside Africa occurred, demonstrating the disease's potential as a cross-border health threat. We describe the management surrounding this case of LF in Rhineland-Palatinate - the German federal state where secondary transmission occurred. Twelve days after having been exposed to the corpse of a LF case imported from Togo, a symptomatic undertaker tested positive for Lassa virus RNA. Potential contacts were traced, categorised based on exposure risk, and monitored. Overall, we identified 21 contact persons with legal residency in Rhineland-Palatinate: seven related to the index case, 13 to the secondary case, and one related to both. The secondary case received treatment and recovered. Five contacts were quarantined and one was temporarily banned from work. No further transmission occurred. Based on the experience gained during the outbreak and a review of national and international guidelines, we conclude that exposure risk attributable to corpses may currently be underestimated, and we present suggestions that may help to improve the anti-epidemic response to imported VHF cases in industrialised countries.

Genomic profiling of host responses to Lassa virus: therapeutic potential from primate to man

PubMed Central

Zapata, Juan C; Salvato, Maria S

2015-01-01

Lassa virus infection elicits distinctive changes in host gene expression and metabolism. We focus on changes in host gene expression that may be biomarkers that discriminate individual pathogens or may help to provide a prognosis for disease. In addition to assessing mRNA changes, functional studies are also needed to discriminate causes of disease from mechanisms of host resistance. Host responses that drive pathogenesis are likely to be targets for prevention or therapy. Host responses to Lassa or its related arenaviruses have been monitored in cell culture, in animal models of hemorrhagic fever, in Lassa-infected nonhuman primates and, to a limited extent, in infected human beings. Here, we describe results from those studies and discuss potential targets for reducing virus replication and mitigating disease. PMID:25844088

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection.

PubMed

Ibekwe, Titus S; Nwegbu, Maxwell M; Asogun, Daniel; Adomeh, Donatus I; Okokhere, Peter O

2012-10-01

Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. A prospective case-control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF "rapid screening kit" since RT-PCR is unavailable in most centers. In the interim, "high clinical index of suspicion," irrespective of IgM status, requires urgent referral to confirmatory centers.

Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate

PubMed Central

Zapata, Juan Carlos; Carrion, Ricardo; Patterson, Jean L.; Crasta, Oswald; Zhang, Yan; Mani, Sachin; Jett, Marti; Poonia, Bhawna; Djavani, Mahmoud; White, David M.; Lukashevich, Igor S.; Salvato, Maria S.

2013-01-01

Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease. PMID:24069471

Prevalence of Lassa Virus Disease (LVD) in Nigerian children with fever or fever and convulsions in an endemic area.

PubMed

Akhuemokhan, Odigie C; Ewah-Odiase, Rosemary O; Akpede, Nosa; Ehimuan, Jacqueline; Adomeh, Donatus I; Odia, Ikpomwonsa; Olomu, Sylvia C; Pahlmann, Meike; Becker-Ziaja, Beate; Happi, Christian T; Asogun, Danny A; Okogbenin, Sylvanus A; Okokhere, Peter O; Dawodu, Osagie S; Omoike, Irekpono U; Sabeti, Pardis C; Günther, Stephan; Akpede, George O

2017-07-01

Convulsions with fever in children are a common neurologic emergency in the tropics, and determining the contribution of endemic viral infections can be challenging. In particular, there is a dearth of data on the prevalence and clinical differentiation of Lassa virus disease (LVD) in febrile children in endemic areas of Nigeria, which has multiple lineages of the virus. The aim of this study was to determine the prevalence and presentation of LVD in febrile children with and without convulsions. This was a prospective study of consecutive febrile children aged ≥1 month- 15 years admitted to the Children's Emergency Room of Irrua Specialist Teaching Hospital over a period of 1 year. Febrile children with convulsions (Cases) were compared with those without convulsions (Controls). LVD was defined by the presence of a positive Lassa virus RT-PCR test. Rates were compared between groups using χ2 or Fisher's exact tests and p <0.05 taken as significant. 373 (40.9%) of 913 admissions had fever. Of these, 108/373 (29%) presented with convulsions. The overall prevalence of LVD was 13/373 (3.5%; 95% CI = 1.9%, 5.7%) in febrile admissions, 3/108 (2.8%) in Cases and 10/265 (3.8%) in Controls [(Odds Ratio (95% Confidence Interval) (OR (95% CI)) of LVD in Cases versus Controls = 0.73 (0.2, 2.7)]. Only vomiting (OR (95% CI) = 0.09 (0.01, 0.70)) and bleeding (OR (95% CI) = 39.56 (8.52, 183.7)) were significantly associated with an increased prevalence of LVD. LVD is an important cause of fever, including undifferentiated fever in children in endemic areas, but it is not significantly associated with convulsions associated with fever. Its prevalence, and lack of clinical differentiation on presentation, underscores the importance of a high index of suspicion in diagnosis. Screening of febrile children with undifferentiated fever in endemic areas for LVD could be an important medical and public health control measure.

[Microbiological surveillance: viral hemorrhagic fever in Central African Republic: current serological data in man].

PubMed

Nakounné, E; Selekon, B; Morvan, J

2000-01-01

An investigation was conducted between 1994 and 1997 in forested areas of the Central African Republic (CAR) to determine the seroprevalence of IgG antibodies against several haemorrhagic fever viruses present in the region. Sera were obtained from 1762 individuals in two groups (Pygmy and Bantu locuted populations) living in 4 forested areas in the south of the country. Sera were tested for IgG antibodies against Ebola, Marburg, Rift Valley fever (RVF), Yellow fever (YF) and Hantaviruses by enzyme immunoassay (EIA), and against Lassa virus by immunofluorescent assay. The prevalence of IgG antibodies was 5.9% for Ebola, 2% for Marburg, 6.9% pour RVF, 6.5% for YF, 2% for Hantaan. No antibodies were detected against Lassa, Seoul, Puumala and Thottapalayam viruses. No IgM antibodies were detected against RVF and YF viruses. The distribution of antibodies appears to be related to tropical rain forest areas. This study indicates that several haemorrhagic fever viruses are endemic in forested areas of the CAR and could emerge due to environmental modification.

Emerging Infections and Bioterrorism

DTIC Science & Technology

2001-09-01

bioterrorism. Some examples of unusual outbreaks that could have been mistaken for bioterrorism are given below: Event/ Disease Location Year Legionnaires ...Geminiviruses) 1 237 Table 2. Viral Hemorrhagic Fevers Family and/or genus Disease ( s ) Arenaviridae Lassa fever, Bolivian HF (Machupo virus), Argentine HF (Junin...bioterrorist agents: these are the organisms or toxins that cause the diseases anthrax, botulism, brucellosis, plague, Q fever, smallpox, staphylococcal

Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects

PubMed Central

2010-01-01

Background Lassa hemorrhagic fever (LHF) is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV) GP1 (sGP1) in vitro resulting from the expression of the glycoprotein complex (GPC) gene [1,2]. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV), a filovirus that also causes hemorrhagic fever with nearly 90% fatality rates [3-5]. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW), in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. Results It is reasonable to expect that a narrow window exists for detection of sGP1 as the sole protein shed during early arenaviral biogenesis. This phenomenon was clearly distinguishable from virion-associated GP1 only prior to the emergence of de novo viral particles. Despite this restricted time frame, in 2/46 suspected cases in two studies performed in late 2009 and early 2010, soluble glycoprotein component shedding was identified. Differential detection of viral antigens GP1, GP2, and NP by western blot yielded five different scenarios: whole LASV virions (GP1, GP2, NP; i.e. active viremia), different combinations of these three proteins, sGP1 only, NP only, and absence of all three proteins. Four additional samples showed inconclusive evidence for sGP1 shedding due to lack of detection of GP2 and NP by western blot; however, a sensitive LASV NP antigen capture ELISA generated marginally positive signals Conclusions During a narrow window following active infection with LASV, soluble GP1 can be detected in patient sera. This phenomenon parallels other VHF infection profiles, with the actual role of a soluble viral glycoprotein component in vivo remaining largely speculative. The expenditure of energy and cellular resources toward secretion of a critical protein during viral biogenesis without apparent specific function requires further investigation. Future studies will be aimed at systematically identifying the role of LASV sGP1 in the infection process and outcome in vitro and in vivo. PMID:21062490

Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.

PubMed

Pannetier, Delphine; Reynard, Stéphanie; Russier, Marion; Carnec, Xavier; Baize, Sylvain

2014-01-01

The pathogenesis of Lassa fever (LF), a hemorrhagic fever endemic to West Africa, remains unclear. We previously compared Lassa virus (LASV) with its genetically close, but nonpathogenic homolog Mopeia virus (MOPV) and demonstrated that the strong activation of antigen-presenting cells (APC), including type I IFN production, observed in response to MOPV probably plays a crucial role in controlling infection. We show here that human macrophages (MP) produce large amounts of CC and CXC chemokines in response to MOPV infection, whereas dendritic cells (DC) release only moderate amounts of CXC chemokines. However, in the presence of autologous T cells, DCs produced CC and CXC chemokines. Chemokines were produced in response to type I IFN synthesis, as the levels of both mediators were strongly correlated and the neutralization of type I IFN resulted in an inhibition of chemokine production. By contrast, LASV induced only low levels of CXCL-10 and CXCL-11 production. These differences in chemokine production may profoundly affect the generation of virus-specific T-cell responses and may therefore contribute to the difference of pathogenicity between these two viruses. In addition, a recombinant LASV (rLASV) harboring the NP-D389A/G392A mutations, which abolish the inhibition of type I IFN response by nucleoprotein (NP), induced the massive synthesis of CC and CXC chemokines in both DC and MP, confirming the crucial role of arenavirus NP in immunosuppression and pathogenicity. Finally, we confirmed, using PBMC samples and lymph nodes obtained from LASV-infected cynomolgus monkeys, that LF was associated with high levels of CXC chemokine mRNA synthesis, suggesting that the very early synthesis of these mediators may be correlated with a favourable outcome.

Expression and X-Ray Structural Determination of the Nucleoprotein of Lassa Fever Virus.

PubMed

Qi, Xiaoxuan; Wang, Wenjian; Dong, Haohao; Liang, Yuying; Dong, Changjiang; Ly, Hinh

2018-01-01

We describe methods to express the nucleoprotein (NP) of Lassa fever virus (LASV) in E. coli, to purify and crystallize it using the sitting-drop vapor diffusion method. The crystals were screened using Rigaku micro-007 X-ray generator and a dataset was collected at a resolution of 2.36 Å. The crystals belong to space group P3, with the unit cell parameters a = b = 176.35 Å, c = 56.40 Å, α = β = 90°, and γ = 120°. Using the X-ray diffraction method, we constructed a three-dimensional structure of the LASV NP that should aid in the development of novel therapeutic strategies against this virus, for which vaccine and effective treatment modalities are currently unavailable.

Clinical features and patient management of Lujo hemorrhagic fever.

PubMed

Sewlall, Nivesh H; Richards, Guy; Duse, Adriano; Swanepoel, Robert; Paweska, Janusz; Blumberg, Lucille; Dinh, Thu Ha; Bausch, Daniel

2014-01-01

In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. Clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. Due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of Lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation.

Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever.

PubMed

Oestereich, Lisa; Lüdtke, Anja; Ruibal, Paula; Pallasch, Elisa; Kerber, Romy; Rieger, Toni; Wurr, Stephanie; Bockholt, Sabrina; Pérez-Girón, José V; Krasemann, Susanne; Günther, Stephan; Muñoz-Fontela, César

2016-05-01

Lassa fever (LASF) is a highly severe viral syndrome endemic to West African countries. Despite the annual high morbidity and mortality caused by LASF, very little is known about the pathophysiology of the disease. Basic research on LASF has been precluded due to the lack of relevant small animal models that reproduce the human disease. Immunocompetent laboratory mice are resistant to infection with Lassa virus (LASV) and, to date, only immunodeficient mice, or mice expressing human HLA, have shown some degree of susceptibility to experimental infection. Here, transplantation of wild-type bone marrow cells into irradiated type I interferon receptor knockout mice (IFNAR-/-) was used to generate chimeric mice that reproduced important features of severe LASF in humans. This included high lethality, liver damage, vascular leakage and systemic virus dissemination. In addition, this model indicated that T cell-mediated immunopathology was an important component of LASF pathogenesis that was directly correlated with vascular leakage. Our strategy allows easy generation of a suitable small animal model to test new vaccines and antivirals and to dissect the basic components of LASF pathophysiology.

Murine Models for Viral Hemorrhagic Fever.

PubMed

Gonzalez-Quintial, Rosana; Baccala, Roberto

2018-01-01

Hemorrhagic fever (HF) viruses, such as Lassa, Ebola, and dengue viruses, represent major human health risks due to their highly contagious nature, the severity of the clinical manifestations induced, the lack of vaccines, and the very limited therapeutic options currently available. Appropriate animal models are obviously critical to study disease pathogenesis and develop efficient therapies. We recently reported that the clone 13 (Cl13) variant of the lymphocytic choriomeningitis virus (LCMV-Cl13), a prototype arenavirus closely related to Lassa virus, causes in some mouse strains endothelial damage, vascular leakage, platelet loss, and death, mimicking pathological aspects typically observed in Lassa and other HF syndromes. This model has the advantage that the mice used are fully immunocompetent, allowing studies on the contribution of the immune response to disease progression. Moreover, LCMV is very well characterized and exhibits limited pathogenicity in humans, allowing handling in convenient BSL-2 facilities. In this chapter we outline protocols for the induction and analysis of arenavirus-mediated pathogenesis in the NZB/LCMV model, including mouse infection, virus titer determination, platelet counting, phenotypic analysis of virus-specific T cells, and assessment of vascular permeability.

Structural basis for antibody-mediated neutralization of Lassa virus.

PubMed

Hastie, Kathryn M; Zandonatti, Michelle A; Kleinfelter, Lara M; Heinrich, Megan L; Rowland, Megan M; Chandran, Kartik; Branco, Luis M; Robinson, James E; Garry, Robert F; Saphire, Erica Ollmann

2017-06-02

The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health. Copyright © 2017, American Association for the Advancement of Science.

Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.

PubMed

Mahanty, Siddhartha; Hutchinson, Karen; Agarwal, Sudhanshu; McRae, Michael; Rollin, Pierre E; Pulendran, Bali

2003-03-15

Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.

Development of a Threat Assessment Framework Applicable to Dual Use Biotechnology: Results of a Study to Determine the Feasibility, Applicability and Potential Design of a Threat Assessment Framework Concept

DTIC Science & Technology

2007-04-01

Guanarito virus, Lassa fever • Bunyaviruses. Hantaviruses, Rift Valley fever • Flaviviruses. Dengue • Filoviruses. Ebola, Marburg Category B...Viruses V1. Chikungunya virus V2. Congo-Crimean haemorrhagic fever virus V3. Dengue fever virus...current context and an extensive set of interviews with subject matter experts (SME). After preliminary conversations with experts and scanning initial

Molecular pathogenesis of viral hemorrhagic fever.

PubMed

Basler, Christopher F

2017-07-01

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

Mortality Among Confirmed Lassa Fever Cases During the 2015-2016 Outbreak in Nigeria.

PubMed

Buba, Maryam Ibrahim; Dalhat, Mahmood Muazu; Nguku, Patrick Mboya; Waziri, Ndadilnasiya; Mohammad, Jibreel Omar; Bomoi, Idriss Mohammed; Onyiah, Amaka Pamela; Onwujei, Jude; Balogun, Muhammad Shakir; Bashorun, Adebobola Toluwalashe; Nsubuga, Peter; Nasidi, Abdulsalami

2018-02-01

To determine factors associated with mortality among confirmed Lassa fever cases. We reviewed line lists and clinical records of laboratory-confirmed cases of Lassa fever during the 2016 outbreak in Nigeria to determine factors associated with mortality. We activated an incident command system to coordinate response. We documented 47 cases, 28 of whom died (case fatality rate [CFR] = 59.6%; mean age 31.4 years; SD = ±18.4 years). The youngest and the oldest were the most likely to die, with 100% mortality in those aged 5 years or younger and those aged 55 years or older. Patients who commenced ribavirin were more likely to survive (odds ratio [OR] = 0.1; 95% confidence interval [CI] = 0.03, 0.50). Fatality rates went from 100% (wave 1) through 69% (wave 2) to 31% (wave 3; χ 2 for linear trend: P < .01). Patients admitted to a health care center before incident command system activation were more likely to die (OR = 4.4; 95% CI = 1.1, 17.6). The only pregnant patient in the study died postpartum. Effective, coordinated response reduces mortality from public health events. Attention to vulnerable groups during disasters is essential. Public Health Implications. Activating an incident command system improves the outcome of disasters in resource-constrained settings.

Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone

PubMed Central

Dahmane, A.; van Griensven, J.; Van Herp, M.; Van den Bergh, R.; Nzomukunda, Y.; Prior, J.; Alders, P.; Jambai, A.; Zachariah, R.

2014-01-01

Background Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. Methods We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). Results There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. Conclusions These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this ‘neglected disease’. PMID:24535150

Characterization of the Lassa virus matrix protein Z: electron microscopic study of virus-like particles and interaction with the nucleoprotein (NP).

PubMed

Eichler, Robert; Strecker, Thomas; Kolesnikova, Larissa; ter Meulen, Jan; Weissenhorn, Winfried; Becker, Stephan; Klenk, Hans Dieter; Garten, Wolfgang; Lenz, Oliver

2004-03-15

Lassa virus is the causative agent of a hemorrhagic fever endemic in west Africa. The RNA genome of Lassa virus encodes the glycoprotein precursor GP-C, a nucleoprotein (NP), the viral polymerase L and a small protein Z (11 kDa). Here, we analyze the role of Z protein for virus maturation. We have recently shown that expression of Z protein in the absence of other viral proteins is sufficient for the release of enveloped Z-containing particles. In this study, we examined particles secreted into the supernatant of a stably Z protein-expressing CHO cell line by electron microscopy. The observed Z-induced virus-like particles did not significantly differ in their morphology and size from Lassa virus particles. Mutation of two proline-rich domains within Z which are known to drastically reduce the release of virus-like particles, had no effect on the cellular localization of the protein nor on its membrane-association. Furthermore, we present evidence that Z interacts with the NP. We assume that Z recruits NP to cellular membranes where virus assembly takes place. We conclude from our data that Lassa virus Z protein plays an essential role in Lassa virus maturation.

Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection.

PubMed

Branco, Luis M; Grove, Jessica N; Boisen, Matt L; Shaffer, Jeffrey G; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Grant, Donald S; Garry, Robert F

2011-10-24

Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF.

Lassa and Mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on IL-8 and TNF-alpha gene expression.

PubMed

Lukashevich, I S; Maryankova, R; Vladyko, A S; Nashkevich, N; Koleda, S; Djavani, M; Horejsh, D; Voitenok, N N; Salvato, M S

1999-12-01

Cells of the mononuclear and endothelial lineages are targets for viruses which cause hemorrhagic fevers (HF) such as the filoviruses Marburg and Ebola, and the arenaviruses Lassa and Junin. A recent model of Marburg HF pathogenesis proposes that virus directly causes endothelial cell damage and macrophage release of TNF-alpha which increases the permeability of endothelial monolayers [Feldmann et al. , 1996]. We show that Lassa virus replicates in human monocytes/macrophages and endothelial cells without damaging them. Human endothelial cells (HUVEC) are highly susceptible to infection by both Lassa and Mopeia (a non-pathogenic Lassa-related arenavirus). Whereas monocytes must differentiate into macrophages before supporting even low level production of these viruses, the virus yields in the culture medium of infected HUVEC cells reach more than 7 log10 PFU/ml without cellular damage. In contrast to filovirus, Lassa virus replication in monocytes/macrophages fails to stimulate TNF-alpha gene expression and even down-regulates LPS-stimulated TNF-alpha mRNA synthesis. The expression of IL-8, a prototypic proinflammatory CXC chemokine, was also suppressed in Lassa virus infected monocytes/macrophages and HUVEC on both the protein and mRNA levels. This contrasts with Mopeia virus infection of HUVEC in which neither IL-8 mRNA nor protein are reduced. The cumulative down-regulation of TNF-alpha and IL-8 expression could explain the absence of inflammatory and effective immune responses in severe cases of Lassa HF. Copyright 1999 Wiley-Liss, Inc.

Rat-atouille: A Mixed Method Study to Characterize Rodent Hunting and Consumption in the Context of Lassa Fever.

PubMed

Bonwitt, Jesse; Kelly, Ann H; Ansumana, Rashid; Agbla, Schadrac; Sahr, Foday; Saez, Almudena Mari; Borchert, Matthias; Kock, Richard; Fichet-Calvet, Elisabeth

2016-06-01

Lassa fever is a zoonotic hemorrhagic illness predominant in areas across Nigeria, Sierra Leone, Guinea, Liberia, and southern Mali. The reservoir of Lassa virus is the multimammate mouse (Mastomys natalensis), a highly commensal species in West Africa. Primary transmission to humans occurs through direct or indirect contact with rodent body fluids such as urine, feces, saliva, or blood. Our research draws together qualitative and quantitative methods to provide a fuller and more nuanced perspective on these varied points of human-animal contact. In this article, we focus on the hunting, preparation, and consumption of rodents as possible routes of exposure in Bo, Sierra Leone. We found that the consumption of rodents, including the reservoir species, is widespread and does not neatly tally against generational or gender lines. Further, we found that the reasons for rodent consumption are multifactorial, including taste preferences, food security, and opportunistic behavior. We argue that on certain topics, such as rodent consumption, establishing trust with communities, and using qualitative research methods, is key to investigate sensitive issues and situate them in their wider context. To conclude, we recommend ways to refine sensitization campaigns to account for these socio-cultural contexts.

Mapping transmission risk of Lassa fever in West Africa: the importance of quality control, sampling bias, and error weighting.

PubMed

Peterson, A Townsend; Moses, Lina M; Bausch, Daniel G

2014-01-01

Lassa fever is a disease that has been reported from sites across West Africa; it is caused by an arenavirus that is hosted by the rodent M. natalensis. Although it is confined to West Africa, and has been documented in detail in some well-studied areas, the details of the distribution of risk of Lassa virus infection remain poorly known at the level of the broader region. In this paper, we explored the effects of certainty of diagnosis, oversampling in well-studied region, and error balance on results of mapping exercises. Each of the three factors assessed in this study had clear and consistent influences on model results, overestimating risk in southern, humid zones in West Africa, and underestimating risk in drier and more northern areas. The final, adjusted risk map indicates broad risk areas across much of West Africa. Although risk maps are increasingly easy to develop from disease occurrence data and raster data sets summarizing aspects of environments and landscapes, this process is highly sensitive to issues of data quality, sampling design, and design of analysis, with macrogeographic implications of each of these issues and the potential for misrepresenting real patterns of risk.

Deployable, Field-Sustainable, Reverse Transcription-Polymerase Chain Reaction Assays for Rapid Screening and Serotype Identification of Dengue Virus in Mosquitoes

DTIC Science & Technology

2007-03-01

C, Gottig S, Schiiiing S, et ai: Rapid detection and quantiilcation of RNA of Eboia and Marburg viruses, L.assa virus, Crimean - Congo hemorrhagic fever ...the past two decades, dengue fever (DF) and the poten- tially fatal forms ofthe disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome, have...Viroi 2003; 77: i 1436-47. 5. Gubler DJ: Dengue and dengue hemorrhagic fever . Ciin Microbiol Rev 1998; 11: 480-96. 6. Fonseca BA, Fonseca SN: Dengue virus

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

PubMed Central

Leblanc, Pierre; Moise, Leonard; Luza, Cybelle; Chantaralawan, Kanawat; Lezeau, Lynchy; Yuan, Jianping; Field, Mary; Richer, Daniel; Boyle, Christine; Martin, William D; Fishman, Jordan B; Berg, Eric A; Baker, David; Zeigler, Brandon; Mais, Dale E; Taylor, William; Coleman, Russell; Warren, H Shaw; Gelfand, Jeffrey A; De Groot, Anne S; Brauns, Timothy; Poznansky, Mark C

2014-01-01

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4+ T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models. PMID:25483693

VaxCelerate II: rapid development of a self-assembling vaccine for Lassa fever.

PubMed

Leblanc, Pierre; Moise, Leonard; Luza, Cybelle; Chantaralawan, Kanawat; Lezeau, Lynchy; Yuan, Jianping; Field, Mary; Richer, Daniel; Boyle, Christine; Martin, William D; Fishman, Jordan B; Berg, Eric A; Baker, David; Zeigler, Brandon; Mais, Dale E; Taylor, William; Coleman, Russell; Warren, H Shaw; Gelfand, Jeffrey A; De Groot, Anne S; Brauns, Timothy; Poznansky, Mark C

2014-01-01

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4(+) T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models.

Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation.

PubMed

Gilsdorf, Andreas; Morgan, Dilys; Leitmeyer, Katrin

2012-11-21

Travel from countries where viral haemorrhagic fevers (VHF) are endemic has increased significantly over the past decades. In several reported VHF events on airplanes, passenger trace back was initiated but the scale of the trace back differed considerably. The absence of guidance documents to help the decision on necessity and scale of the trace back contributed to this variation.This article outlines the recommendations of an expert panel on Lassa fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in order to advise the relevant stakeholders in the decision and scale of a possible passenger trace back. The evidence was collected through review of published literature and through the views of an expert panel. The guidance was agreed by consensus. Only a few events of VHF cases during air travel are reported in literature, with no documented infection in followed up contacts, so that no evidence of transmission of VHF during air travel exists to date. Based on this and the expert opinion, it was recommended that passenger trace back was undertaken only if: the index case had symptoms during the flight; the flight was within 21 days after detection of the event; and for Lassa fever if exposure of body fluid has been reported. The trace back should only be done after confirmation of the index case. Passengers and crew with direct contact, seat neighbours (+/- 1 seat), crew and cleaning personal of the section of the index case should be included in the trace back. No evidence has been found for the transmission of VHF in airplanes. This information should be taken into account, when a trace back decision has to be taken, because such a measure produces an enormous work load. The procedure suggested by the expert group can guide decisions made in future events, where a patient with suspected VHF infection travelled on a plane. However, the actual decision on start and scale of a trace back always lies in the hands of the responsible people taking all relevant information into account.

Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.

PubMed

Bell, T M; Shaia, C I; Bearss, J J; Mattix, M E; Koistinen, K A; Honnold, S P; Zeng, X; Blancett, C D; Donnelly, G C; Shamblin, J D; Wilkinson, E R; Cashman, K A

2017-05-01

Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

Lassa Fever

MedlinePlus

... in 1969 when two missionary nurses died in Nigeria. The virus is named after the town in Nigeria where the first cases occurred. The virus, a ... west Africa including Sierra Leone, Liberia, Guinea and Nigeria; however, other neighboring countries are also at risk, ...

Lassa Virus Reverse Genetics.

PubMed

Martínez-Sobrido, Luis; Paessler, Slobodan; de la Torre, Juan Carlos

2017-01-01

The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity and mortality. To date, no licensed vaccines are available to LASV infections, and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that is only partially effective. The development of reverse genetics has provided investigators with a novel and powerful approach for the investigation of the molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV minigenome (MG) systems has allowed examining the cis- and trans-acting factors involved in genome replication and gene transcription and the identification of novel drugable LASV targets. Likewise, it is now feasible to rescue infectious recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify antiviral drugs against LASV and the implementation of novel strategies to develop live-attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art experimental procedures for implementation of LASV reverse genetics. In addition, we will briefly discuss some significant translational research developments that have been made possible upon the development of LASV reverse genetics.

Lassa fever-induced sensorineural hearing loss: A neglected public health and social burden.

PubMed

Mateer, Elizabeth J; Huang, Cheng; Shehu, Nathan Y; Paessler, Slobodan

2018-02-01

Although an association between Lassa fever (LF) and sudden-onset sensorineural hearing loss (SNHL) was confirmed clinically in 1990, the prevalence of LF-induced SNHL in endemic countries is still underestimated. LF, a viral hemorrhagic fever disease caused by Lassa virus (LASV), is endemic in West Africa, causing an estimated 500,000 cases and 5,000 deaths per year. Sudden-onset SNHL, one complication of LF, occurs in approximately one-third of survivors and constitutes a neglected public health and social burden. In the endemic countries, where access to hearing aids is limited, SNHL results in a decline of the quality of life for those affected. In addition, hearing loss costs Nigeria approximately 43 million dollars per year. The epidemiology of LF-induced SNHL has not been characterized well. The complication of LF induced by SNHL is also an important consideration for vaccine development and treatments. However, research into the mechanism has been hindered by the lack of autopsy samples and relevant small animal models. Recently, the first animal model that mimics the symptoms of SNHL associated with LF was developed. Preliminary data from the new animal model as well as the clinical case studies support the mechanism of immune-mediated injury that causes SNHL in LF patients. This article summarizes clinical findings of hearing loss in LF patients highlighting the association between LASV infection and SNHL as well as the potential mechanism(s) for LF-induced SNHL. Further research is necessary to identify the mechanism and the epidemiology of LF-induced SNHL.

Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis

DTIC Science & Technology

2011-01-31

PROGRAM ELEMENT NUMBER 6. AUTHOR (S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES... authors and are not necessarily endorsed by the U.S. Army. Address correspondence and reprint requests to Sina Bavari, U. S. Army Medical Research...common finding in many other hemorrhagic fever viruses, in- cluding Lassa, Marburg, Crimean Congo hemorrhagic fever, and some Hantavirus infections

Lassa serology in natural populations of rodents and horizontal transmission.

PubMed

Fichet-Calvet, Elisabeth; Becker-Ziaja, Beate; Koivogui, Lamine; Günther, Stephan

2014-09-01

Lassa virus causes hemorrhagic fever in West Africa. Previously, we demonstrated by PCR screening that only the multimammate mouse, Mastomys natalensis, hosts Lassa virus in Guinea. In the present study, we used the same specimen collection from 17 villages in Coastal, Upper, and Forest Guinea to investigate the Lassa virus serology in the rodent population. The aim was to determine the dynamics of antibody development in M. natalensis and to detect potential spillover infections in other rodent species. Immunoglobulin G (IgG) antibody screening was performed using the indirect immunofluorescence assay with the Guinean Lassa virus strain Bantou 289 as antigen. The overall seroprevalence was 8% (129/1551) with the following rodents testing positive: 109 M. natalensis, seven Mastomys erythroleucus, four Lemniscomys striatus, four Praomys daltoni, three Mus minutoides, and two Praomys rostratus. Nearly all of them (122/129) originated from Bantou, Tanganya, and Gbetaya, where Lassa virus is highly endemic in M. natalensis. The antibody seroprevalence in M. natalensis from this high-endemic area (27%; 108/396) depended on the village, habitat, host age, and host abundance. A main positive factor was age; the maximum seroprevalence reached 50% in older animals. Our data fit with a model implicating that most M. natalensis rodents become horizontally infected, clear the virus within a period significantly shorter than their life span, and develop antibodies. In addition, the detection of antibodies in other species trapped in the habitats of M. natalensis suggests spillover infections.

Mutational Analysis of Lassa Virus Glycoprotein Highlights Regions Required for Alpha-Dystroglycan Utilization.

PubMed

Acciani, Marissa; Alston, Jacob T; Zhao, Guohui; Reynolds, Hayley; Ali, Afroze M; Xu, Brian; Brindley, Melinda A

2017-09-15

Lassa virus (LASV) is an enveloped RNA virus endemic to West Africa and responsible for severe cases of hemorrhagic fever. Virus entry is mediated by the glycoprotein complex consisting of a stable-signal peptide, a receptor-binding subunit, GP1, and a viral-host membrane fusion subunit, GP2. Several cellular receptors can interact with the GP1 subunit and mediate viral entry, including alpha-dystroglycan (αDG) and lysosome-associated membrane protein 1 (LAMP1). In order to define the regions within GP1 that interact with the cellular receptors, we implemented insertional mutagenesis, carbohydrate shielding, and alanine scanning mutagenesis. Eighty GP constructs were engineered and evaluated for GP1-GP2 processing, surface expression, and the ability to mediate cell-to-cell fusion after low-pH exposure. To examine virus-to-cell entry, 49 constructs were incorporated onto vesicular stomatitis virus (VSV) pseudoparticles and transduction efficiencies were monitored in HAP1 and HAP1-ΔDAG1 cells that differentially produce the αDG cell surface receptor. Seven constructs retained efficient transduction in HAP1-ΔDAG1 cells yet poorly transduced HAP1 cells, suggesting that they are involved in αDG utilization. Residues H141, N146, F147, and Y150 cluster at the predicted central core of the trimeric interface and are important for GP-αDG interaction. Additionally, H92A-H93A, 150HA, 172HA, and 230HA displayed reduced transduction in both HAP1 and HAP1-ΔDAG1 cells, despite efficient cell-to-cell fusion activity. These mutations may interfere with interactions with the endosomal receptor LAMP1 or interfere at another stage in entry that is common to both cell lines. Insight gained from these data can aid in the development of more-effective entry inhibitors by blocking receptor interactions. IMPORTANCE Countries in which Lassa virus is endemic, such as Nigeria, Sierra Leone, Guinea, and Liberia, usually experience a seasonal outbreak of the virus from December to March. Currently, there is neither a preventative vaccine nor a therapeutic available to effectively treat severe Lassa fever. One way to thwart virus infection is to inhibit interaction with cellular receptors. It is known that the GP1 subunit of the Lassa glycoprotein complex plays a critical role in receptor recognition. Our results highlight a region within the Lassa virus GP1 protein that interacts with the cellular receptor alpha-dystroglycan. This information may be used for future development of new Lassa virus antivirals. Copyright © 2017 American Society for Microbiology.

Lamp1 Increases the Efficiency of Lassa Virus Infection by Promoting Fusion in Less Acidic Endosomal Compartments.

PubMed

Hulseberg, Christine E; Fénéant, Lucie; Szymańska, Katarzyna M; White, Judith M

2018-01-02

Lassa virus (LASV) is an arenavirus whose entry into host cells is mediated by a glycoprotein complex (GPC) comprised of a receptor binding subunit, GP1, a fusogenic transmembrane subunit, GP2, and a stable signal peptide. After receptor-mediated internalization, arenaviruses converge in the endocytic pathway, where they are thought to undergo low-pH-triggered, GPC-mediated fusion with a late endosome membrane. A unique feature of LASV entry is a pH-dependent switch from a primary cell surface receptor (α-dystroglycan) to an endosomal receptor, lysosomal-associated membrane protein (Lamp1). Despite evidence that the interaction between LASV GP1 and Lamp1 is critical, the function of Lamp1 in promoting LASV infection remains poorly characterized. Here we used wild-type (WT) and Lamp1 knockout (KO) cells to show that Lamp1 increases the efficiency of, but is not absolutely required for, LASV entry and infection. We then used cell-cell and pseudovirus-cell surface fusion assays to demonstrate that LASV GPC-mediated fusion occurs at a significantly higher pH when Lamp1 is present compared to when Lamp1 is missing. Correspondingly, we found that LASV entry occurs through less acidic endosomes in WT (Lamp1-positive) versus Lamp1 KO cells. We propose that, by elevating the pH threshold for fusion, Lamp1 allows LASV particles to exit the endocytic pathway before they encounter an increasingly acidic and harsh proteolytic environment, which could inactivate a significant percentage of incoming viruses. In this manner Lamp1 increases the overall efficiency of LASV entry and infection. IMPORTANCE Lassa virus is the most clinically important member of the Arenaviridae , a family that includes six additional biosafety level 4 (BSL4) hemorrhagic fever viruses. The lack of specific antiviral therapies for Lassa fever drives an urgent need to identify druggable targets, and interventions that block infection at the entry stage are particularly attractive. Lassa virus is only the second virus known to employ an intracellular receptor, the first being Ebola virus. Here we show that interaction with its intracellular receptor, Lamp1, enhances and upwardly shifts the pH dependence of fusion and consistently permits Lassa virus entry into cells through less acidic endosomes. We propose that in this manner, Lamp1 increases the overall efficiency of Lassa virus infection. Copyright © 2018 Hulseberg et al.

Lessons learnt from the management of a case of Lassa fever and follow-up of nosocomial primary contacts in Nigeria during Ebola virus disease outbreak in West Africa.

PubMed

Iroezindu, Michael O; Unigwe, Uche S; Okwara, Celestine C; Ozoh, Gladys A; Ndu, Anne C; Ohanu, Martin E; Nwoko, Ugochukwu O; Okoroafor, Uwadiegwu W; Ejimudo, Esinulo; Tobin, Ekaete A; Asogun, Danny A

2015-11-01

To describe our experiences in the management of a case of Lassa fever (LF) and follow-up of nosocomial primary contacts during the 2014 Ebola outbreak in West Africa. Clinical management of the index case and infection control/surveillance activities for primary contacts are described. Laboratory confirmation was by Lassa virus-specific reverse-transcriptase PCR. A 28-year-old man with a 10-day history of febrile illness was referred to a major tertiary hospital in south-east Nigeria from a city that previously experienced a LF outbreak and was recently affected by Ebola. On observation of haemorrhagic features, clinicians were at a crossroads. Diagnosis of LF was confirmed at a National Reference Centre. The patient died despite initiation of ribavirin therapy. Response activities identified 121 primary contacts comprising 78 (64.5%) hospital staff/interns, 19 (15.7%) medical students, 18 (14.9%) inpatients and 6 (5.0%) relatives. Their mean age was 32.8 ± 6.6 years, and 65.3% were women. Twenty (16.5%) had high-risk exposure and were offered ribavirin as post-exposure prophylaxis. No secondary case of LF occurred. Fatigue (43.8%) and dizziness (31.3%) were the commonest side effects of ribavirin. Response activities contained nosocomial spread of LF, but challenges were experienced including lack of a purpose-built isolation facility, absence of local Lassa virus laboratory capacity, failure to use appropriate protective equipment and stigmatisation of contacts. A key lesson is that the weak health systems of Africa should be comprehensively strengthened; otherwise, we might win the Ebola battle but lose the one against less virulent infections for which effective treatment exists. © 2015 John Wiley & Sons Ltd.

Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola virus in Rhesus Monkeys

DTIC Science & Technology

2016-03-02

distribution to sanctuary sites for viral 46 replication including testes, eye , and brain. In a rhesus monkey model of EVD, once daily 47...including respiratory syncytial virus (RSV), Junin virus (JUNV), Lassa fever virus 121 (LASV) and Middle East respiratory syndrome virus (MERS), with...yellow fever virus, dengue virus type 2), parainfluenza type 3, and severe 124 acute respiratory syndrome (SARS) associated coronavirus but little or

Lassa hemorrhagic fever in a late term pregnancy from northern sierra leone with a positive maternal outcome: case report

PubMed Central

2011-01-01

Lassa fever (LF) is a devastating viral disease prevalent in West Africa. Efforts to take on this public health crisis have been hindered by lack of infrastructure and rapid field deployable diagnosis in areas where the disease is prevalent. Recent capacity building at the Kenema Government Hospital Lassa Fever Ward (KGH LFW) in Sierra Leone has lead to a major turning point in the diagnosis, treatment and study of LF. Herein we present the first comprehensive rapid diagnosis and real time characterization of an acute hemorrhagic LF case at KGH LFW. This case report focuses on a third trimester pregnant Sierra Leonean woman from the historically non-endemic Northern district of Tonkolili who survived the illness despite fetal demise. Employed in this study were newly developed recombinant LASV Antigen Rapid Test cassettes and dipstick lateral flow immunoassays (LFI) that enabled the diagnosis of LF within twenty minutes of sample collection. Deregulation of overall homeostasis, significant hepatic and renal system involvement, and immunity profiles were extensively characterized during the course of hospitalization. Rapid diagnosis, prompt treatment with a full course of intravenous (IV) ribavirin, IV fluids management, and real time monitoring of clinical parameters resulted in a positive maternal outcome despite admission to the LFW seven days post onset of symptoms, fetal demise, and a natural still birth delivery. These studies solidify the growing rapid diagnostic, treatment, and surveillance capabilities at the KGH LF Laboratory, and the potential to significantly improve the current high mortality rate caused by LF. As a result of the growing capacity, we were also able to isolate Lassa virus (LASV) RNA from the patient and perform Sanger sequencing where we found significant genetic divergence from commonly circulating Sierra Leonean strains, showing potential for the discovery of a newly emerged LASV strain with expanded geographic distribution. Furthermore, recent emergence of LF cases in Northern Sierra Leone highlights the need for superior diagnostics to aid in the monitoring of LASV strain divergence with potentially increased geographic expansion. PMID:21843352

Lassa hemorrhagic fever in a late term pregnancy from northern Sierra Leone with a positive maternal outcome: case report.

PubMed

Branco, Luis M; Boisen, Matt L; Andersen, Kristian G; Grove, Jessica N; Moses, Lina M; Muncy, Ivana J; Henderson, Lee A; Schieffellin, John S; Robinson, James E; Bangura, James J; Grant, Donald S; Raabe, Vanessa N; Fonnie, Mbalu; Zaitsev, Eleina M; Sabeti, Pardis C; Garry, Robert F

2011-08-15

Lassa fever (LF) is a devastating viral disease prevalent in West Africa. Efforts to take on this public health crisis have been hindered by lack of infrastructure and rapid field deployable diagnosis in areas where the disease is prevalent. Recent capacity building at the Kenema Government Hospital Lassa Fever Ward (KGH LFW) in Sierra Leone has lead to a major turning point in the diagnosis, treatment and study of LF. Herein we present the first comprehensive rapid diagnosis and real time characterization of an acute hemorrhagic LF case at KGH LFW. This case report focuses on a third trimester pregnant Sierra Leonean woman from the historically non-endemic Northern district of Tonkolili who survived the illness despite fetal demise. Employed in this study were newly developed recombinant LASV Antigen Rapid Test cassettes and dipstick lateral flow immunoassays (LFI) that enabled the diagnosis of LF within twenty minutes of sample collection. Deregulation of overall homeostasis, significant hepatic and renal system involvement, and immunity profiles were extensively characterized during the course of hospitalization. Rapid diagnosis, prompt treatment with a full course of intravenous (IV) ribavirin, IV fluids management, and real time monitoring of clinical parameters resulted in a positive maternal outcome despite admission to the LFW seven days post onset of symptoms, fetal demise, and a natural still birth delivery. These studies solidify the growing rapid diagnostic, treatment, and surveillance capabilities at the KGH LF Laboratory, and the potential to significantly improve the current high mortality rate caused by LF. As a result of the growing capacity, we were also able to isolate Lassa virus (LASV) RNA from the patient and perform Sanger sequencing where we found significant genetic divergence from commonly circulating Sierra Leonean strains, showing potential for the discovery of a newly emerged LASV strain with expanded geographic distribution. Furthermore, recent emergence of LF cases in Northern Sierra Leone highlights the need for superior diagnostics to aid in the monitoring of LASV strain divergence with potentially increased geographic expansion.

The threat of emerging infections.

PubMed

1996-11-01

A variety of newly discovered pathogens and new forms of older infectious agents threaten to reemerge. Typical symptoms of acute infection are fever, headache, malaise, vomiting, and diarrhea. Some of the better-known emerging viral infections include dengue, filoviruses (Ebola, Marburg), hantaviruses, hepatitis B, hepatitis C, HIV, influenza, lassa fever, measles, rift valley fever, rotavirus, and yellow fever. Emerging bacterial infections include cholera, Escherichia coli 0157:H7, legionnaires disease (Legionella), lyme disease, streptococcus infections (group A), tuberculosis, and typhoid. Emerging parasitic infections include cryptosporidium and other waterborne pathogens and malaria. The causes of many diseases are still shrouded in mystery; thus, treatments and cures for them are as yet unknown.

Geospatial Analysis of Urban Land Use Pattern Analysis for Hemorrhagic Fever Risk - a Review

NASA Astrophysics Data System (ADS)

Izzah, L. N.; Majid, Z.; Ariff, M. A. M.; Fook, C. K.

2016-09-01

Human modification of the natural environment continues to create habitats in which vectors of a wide variety of human and animal pathogens (such as Plasmodium, Aedes aegypti, Arenavirus etc.) thrive if unabated with an enormous potential to negatively affect public health. Typical examples of these modifications include impoundments, dams, irrigation systems, landfills and so on that provide enabled environment for the transmission of Hemorrhagic fever such as malaria, dengue, avian flu, Lassa fever etc. Furthermore, contemporary urban dwelling pattern appears to be associated with the prevalence of Hemorrhagic diseases in recent years. These observations are not peculiar to the developing world, as urban expansion also contributes significantly to mosquito and other vectors habitats. This habitats offer breeding ground to some vector virus populations. The key to disease control is developing an understanding of the contribution of human landscape modification to vector-borne pathogen transmission and how a balance may be achieved between human development, public health, and responsible urban land use. A comprehensive review of urban land use Pattern Analysis for Hemorrhagic fever risk has been conducted in this paper. The study found that most of the available literatures dwell more on the impact of urban land use on malaria and dengue fevers; however, studies are yet to be found discussing the implications of urban land use on the risk of Ebola, Lassa and other non-mosquito borne VHFs. A relational model for investigating the influence of urban land use change pattern on the risk of Hemorrhagic fever has been proposed in this study.

Development and validation of serological assays for viral hemorrhagic fevers and determination of the prevalence of Rift Valley fever in Borno State, Nigeria.

PubMed

Bukbuk, David Nadeba; Fukushi, Shuetsu; Tani, Hideki; Yoshikawa, Tomoki; Taniguchi, Satoshi; Iha, Koichiro; Fukuma, Aiko; Shimojima, Masayuki; Morikawa, Shigeru; Saijo, Masayuki; Kasolo, Francis; Baba, Saka Saheed

2014-12-01

Rift Valley fever (RVF) is endemic to the tropical regions of eastern and southern Africa. The seroprevalence of RVF was investigated among the human population in Borno State, Nigeria to determine the occurrence of the disease in the study area in comparison with that of Lassa fever and Crimean-Congo Hemorrhagic fever. Recombinant nucleoprotein (rNP)-based IgG-ELISAs for the detection of serum antibodies against RVF virus (RVFV), Lassa fever virus (LASV), and Crimean-Congo hemorrhagic fever virus (CCHFV) were used to test human sera in Borno State, Nigeria. The presence of neutralizing antibody against the RVFV-glycoprotein-bearing vesicular stomatitis virus pseudotype (RVFVpv) was also determined in the human sera. Of the 297 serum samples tested, 42 (14.1%) were positive for the presence of RVFV-IgG and 22 (7.4%) and 7 (2.4%) of the serum samples were positive for antibodies against LASV and CCHFV, respectively. There was a positive correlation between the titers of neutralizing antibodies obtained using RVFVpv and those obtained using the conventional neutralization assay with the attenuated RVFV-MP12 strain. The seroprevalence of RVF was significantly higher than that of LASV and CCHF in Borno State, Nigeria. The RVFVpv-based neutralization assay developed in this study has the potential to replace the traditional assays based on live viruses for the diagnosis and seroepidemiological studies of RVF. © The Author 2014. 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.

Crystal Structure of the Oligomeric Form of Lassa Virus Matrix Protein Z.

PubMed

Hastie, Kathryn M; Zandonatti, Michelle; Liu, Tong; Li, Sheng; Woods, Virgil L; Saphire, Erica Ollmann

2016-05-01

The arenavirus matrix protein Z is highly multifunctional and occurs in both monomeric and oligomeric forms. The crystal structure of a dodecamer of Z from Lassa virus, presented here, illustrates a ring-like structure with a highly basic center. Mutagenesis demonstrates that the dimeric interface within the dodecamer and a Lys-Trp-Lys triad at the center of the ring are important for oligomerization. This structure provides an additional template to explore the many functions of Z. The arenavirus Lassa virus causes hundreds of thousands of infections each year, many of which develop into fatal hemorrhagic fever. The arenavirus matrix protein Z is multifunctional, with at least four distinct roles. Z exists in both monomeric and oligomeric forms, each of which likely serves a specific function in the viral life cycle. Here we present the dodecameric form of Lassa virus Z and demonstrate that Z forms a "wreath" with a highly basic center. This structure and that of monomeric Z now provide a pair of critical templates by which the multiple roles of Z in the viral life cycle may be interpreted. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Bacterial-based systems for expression and purification of recombinant Lassa virus proteins of immunological relevance

PubMed Central

Branco, Luis M; Matschiner, Alex; Fair, Joseph N; Goba, Augustine; Sampey, Darryl B; Ferro, Philip J; Cashman, Kathleen A; Schoepp, Randal J; Tesh, Robert B; Bausch, Daniel G; Garry, Robert F; Guttieri, Mary C

2008-01-01

Background There is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of Lassa fever. In this regard, recombinant Lassa virus (LASV) proteins may serve as valuable tools in diverse antiviral applications. Bacterial-based systems were engineered for expression and purification of recombinant LASV nucleoprotein (NP), glycoprotein 1 (GP1), and glycoprotein 2 (GP2). Results Full-length NP and the ectodomains of GP1 and GP2 were generated as maltose-binding protein (MBP) fusions in the Rosetta strains of Escherichia coli (E. coli) using pMAL-c2x vectors. Average fusion protein yields per liter of culture for MBP-NP, MBP-GP1, and MBP-GP2 were 10 mg, 9 mg, and 9 mg, respectively. Each protein was captured from cell lysates using amylose resin, cleaved with Factor Xa, and purified using size-exclusion chromatography (SEC). Fermentation cultures resulted in average yields per liter of 1.6 mg, 1.5 mg, and 0.7 mg of purified NP, GP1 and GP2, respectively. LASV-specific antibodies in human convalescent sera specifically detected each of the purified recombinant LASV proteins, highlighting their utility in diagnostic applications. In addition, mouse hyperimmune ascitic fluids (MHAF) against a panel of Old and New World arenaviruses demonstrated selective cross reactivity with LASV proteins in Western blot and enzyme-linked immunosorbent assay (ELISA). Conclusion These results demonstrate the potential for developing broadly reactive immunological assays that employ all three arenaviral proteins individually and in combination. PMID:18538016

25-Hydroxycholesterol Inhibition of Lassa Virus Infection through Aberrant GP1 Glycosylation.

PubMed

Shrivastava-Ranjan, Punya; Bergeron, Éric; Chakrabarti, Ayan K; Albariño, César G; Flint, Mike; Nichol, Stuart T; Spiropoulou, Christina F

2016-12-20

Lassa virus (LASV) infection is a major public health concern due to high fatality rates and limited effective treatment. The interferon-stimulated gene cholesterol 25-hydroxylase (CH25H) encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC). 25HC is involved in regulating cholesterol biosynthesis and has recently been identified as a potent antiviral targeting enveloped virus entry. Here, we show a previously unrecognized role of CH25H in inhibiting LASV glycoprotein glycosylation and the production of infectious virus. Overexpression of CH25H or treatment with 25HC decreased LASV G1 glycoprotein N-glycan maturation and reduced the production of infectious LASV. Depletion of endogenous CH25H using small interfering RNA (siRNA) enhanced the levels of fully glycosylated G1 and increased infectious LASV production. Finally, LASV particles produced from 25HC-treated cells were found to be less infectious, to incorporate aberrantly glycosylated GP1 species, and to be defective in binding alpha-dystroglycan, an attachment and entry receptor. Our findings identify a novel role for CH25H in controlling LASV propagation and indicate that manipulation of the expression of CH25H or the administration of 25HC may be a useful anti-LASV therapy. Lassa fever is an acute viral hemorrhagic fever in humans caused by Lassa virus (LASV). No vaccine for LASV is currently available. Treatment is limited to the administration of ribavirin, which is only effective when given early in the course of illness. Cholesterol 25-hydroxylase (CH25H) is a recently identified interferon-stimulated gene (ISG); it encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC), which inhibits several viruses. Here, we identify a novel antiviral mechanism of 25HC that is dependent on inhibiting the glycosylation of Lassa virus (LASV) glycoprotein and reducing the infectivity of LASV as a means of suppressing viral replication. Since N-linked glycosylation is a critical feature of other enveloped-virus glycoproteins, 25HC may be a broad inhibitor of virus infectivity. Copyright © 2016 Shrivastava-Ranjan et al.

Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever

PubMed Central

Lo Iacono, Giovanni; Cunningham, Andrew A.; Fichet-Calvet, Elisabeth; Garry, Robert F.; Grant, Donald S.; Khan, Sheik Humarr; Leach, Melissa; Moses, Lina M.; Schieffelin, John S.; Shaffer, Jeffrey G.; Webb, Colleen T.; Wood, James L. N.

2015-01-01

Background Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. Methodology/Principal Findings Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) , with a maximum value up to . Conclusions/Significance This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection. PMID:25569707

Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

PubMed

Lee, Andrew M; Cruite, Justin; Welch, Megan J; Sullivan, Brian; Oldstone, Michael B A

2013-08-01

Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. Copyright © 2013 Elsevier Inc. All rights reserved.

Laboratory Diagnosis of Lassa Fever

DTIC Science & Technology

2017-01-30

this type of document. You can upgrade to the latest version of Adobe Reader for Windows®, Mac, or Linux® by visiting http://www.adobe.com/ go ...reader_download. For more assistance with Adobe Reader visit http://www.adobe.com/ go /acrreader. Windows is either a registered trademark or a

Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects.

PubMed

Branco, Luis M; Grove, Jessica N; Moses, Lina M; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Schoepp, Randal J; Bausch, Daniel G; Garry, Robert F

2010-11-09

Lassa hemorrhagic fever (LHF) is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV) GP1 (sGP1) in vitro resulting from the expression of the glycoprotein complex (GPC) gene [1, 2]. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV), a filovirus that also causes hemorrhagic fever with nearly 90 percent fatality rates [3 - 5]. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW), in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. It is reasonable to expect that a narrow window exists for detection of sGP1 as the sole protein shed during early arenaviral biogenesis. This phenomenon was clearly distinguishable from virion-associated GP1 only prior to the emergence of de novo viral particles. Despite this restricted time frame, in 2/46 suspected cases in two studies performed in late 2009 and early 2010, soluble glycoprotein component shedding was identified. Differential detection of viral antigens GP1, GP2, and NP by western blot yielded five different scenarios: whole LASV virions (GP1, GP2, NP; i.e. active viremia), different combinations of these three proteins, sGP1 only, NP only, and absence of all three proteins. Four additional samples showed inconclusive evidence for sGP1 shedding due to lack of detection of GP2 and NP in western blot; however, a sensitive LASV NP antigen capture ELISA generated marginally positive signals. During a narrow window following active infection with LASV, soluble GP1 can be detected in patient sera. This phenomenon parallels other VHF infection profiles, with the actual role of a soluble viral glycoprotein component in vivo remaining largely speculative. The expenditure of energy and cellular resources toward secretion of a critical protein during viral biogenesis without apparent specific function requires further investigation. Future studies will be aimed at systematically identifying the role of LASV sGP1 in the infection process and outcome in vitro and in vivo.

No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their rodent reservoir host in natural conditions.

PubMed

Mariën, Joachim; Borremans, Benny; Gryseels, Sophie; Soropogui, Barré; De Bruyn, Luc; Bongo, Gédéon Ngiala; Becker-Ziaja, Beate; de Bellocq, Joëlle Goüy; Günther, Stephan; Magassouba, N'Faly; Leirs, Herwig; Fichet-Calvet, Elisabeth

2017-04-27

In order to optimize net transmission success, parasites are hypothesized to evolve towards causing minimal damage to their reservoir host while obtaining high shedding rates. For many parasite species however this paradigm has not been tested, and conflicting results have been found regarding the effect of arenaviruses on their rodent host species. The rodent Mastomys natalensis is the natural reservoir host of several arenaviruses, including Lassa virus that is known to cause Lassa haemorrhagic fever in humans. Here, we examined the effect of three arenaviruses (Gairo, Morogoro and Lassa virus) on four parameters of wild-caught Mastomys natalensis: body mass, head-body length, sexual maturity and fertility. After correcting for the effect of age, we compared these parameters between arenavirus-positive (arenavirus RNA or antibody) and negative animals using data from different field studies in Guinea (Lassa virus) and Tanzania (Morogoro and Gairo viruses). Although the sample sizes of our studies (1297, 749 and 259 animals respectively) were large enough to statistically detect small differences in body conditions, we did not observe any adverse effects of these viruses on Mastomys natalensis. We did find that sexual maturity was significantly positively related with Lassa virus antibody presence until a certain age, and with Gairo virus antibody presence in general. Gairo virus antibody-positive animals were also significantly heavier and larger than antibody-free animals. Together, these results suggest that the pathogenicity of arenaviruses is not severe in M. natalensis, which is likely to be an adaptation of these viruses to optimize transmission success. They also suggest that sexual behaviour might increase the probability of M. natalensis to become infected with arenaviruses.

Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development.

PubMed

Hallam, Hoai J; Hallam, Steven; Rodriguez, Sergio E; Barrett, Alan D T; Beasley, David W C; Chua, Arlene; Ksiazek, Thomas G; Milligan, Gregg N; Sathiyamoorthy, Vaseeharan; Reece, Lisa M

2018-01-01

Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family Arenaviridae . It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Seropositive individuals in endemic regions have been shown to have LASV-specific T cells recognizing epitopes for nucleocapsid protein (NP) and glycoprotein precursor (GPC), suggesting that these will be important vaccine immunogens. The role of neutralizing antibodies in protective immunity is still equivocal as recent studies suggest a role for neutralizing antibodies. There is extensive genetic heterogeneity among LASV strains that is of concern in the development of assays to detect and identify all four LASV lineages. Furthermore, the gene disparity may complicate the synthesis of effective vaccines that will provide protection across multiple lineages. Non-human primate models of LASV infection are considered the gold standard for recapitulation of human LF. The most promising vaccine candidates to date are the ML29 (a live attenuated reassortant of Mopeia and LASV), vesicular stomatitis virus (VSV) and vaccinia-vectored platforms based on their ability to induce protection following single doses, high rates of survival following challenge, and the use of live virus platforms. To date no LASV vaccine candidates have undergone clinical evaluation.

Molecular determinants of Pichinde virus infection of guinea pigs--a small animal model system for arenaviral hemorrhagic fevers.

PubMed

Liang, Yuying; Lan, Shuiyun; Ly, Hinh

2009-09-01

Arenaviruses are enveloped single-strand RNA viruses that mostly have natural hosts in rodents. Upon infection of humans, several arenaviruses can cause severe hemorrhagic fever diseases, including Lassa fever that is endemic in West Africa. The virulence mechanism of these deadly arenaviruses can be studied in a safe and economical small animal model-guinea pigs infected by a nonpathogenic arenavirus Pichinde virus (PICV), a virulent strain of which can cause similar disease syndromes in guinea pigs as arenaviral hemorrhagic fevers in humans. We have recently developed molecular clones for both the virulent and avirulent strains of PICV. Using the available reverse genetics tools, we are characterizing the molecular determinants of virulent arenavirus infections in vivo.

Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9).

PubMed

Weber, David J; Rutala, William A; Fischer, William A; Kanamori, Hajime; Sickbert-Bennett, Emily E

2016-05-02

Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Multiple Circulating Infections Can Mimic the Early Stages of Viral Hemorrhagic Fevers and Possible Human Exposure to Filoviruses in Sierra Leone Prior to the 2014 Outbreak

PubMed Central

Boisen, Matthew L.; Schieffelin, John S.; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B.; Shaffer, Jeffrey G.; Hastie, Kathryn M.; Hartnett, Jessica N.; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K.; Andersen, Kristian G.; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W.; Geisbert, Joan B.; Pitts, Kelly R.; Geisbert, Thomas W.; Kulakoski, Peter; Wilson, Russell B.; Henderson, Lee; Sabeti, Pardis C.; Grant, Donald S.; Garry, Robert F.; Saphire, Erica O.; Khan, Sheik Humarr

2015-01-01

Abstract Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction–based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak. PMID:25531344

Vaccine platforms to control Lassa fever.

PubMed

Lukashevich, Igor S; Pushko, Peter

2016-09-01

Lassa virus (LASV), the most prominent human pathogen of the Arenaviridae, is transmitted to humans from infected rodents and can cause Lassa Fever (LF). The sizeable disease burden in West Africa, numerous imported LF cases worldwide, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. There are no licensed LASV vaccines and the antiviral treatment is limited to an off-label use of ribavirin that is only partially effective. LASV vaccine development is hampered by high cost of biocontainment requirement, the absence of appropriate small animal models, genetic diversity of LASV species, and by high HIV-1 prevalence in LASV endemic areas. Over the past 15 years several vaccine platforms have been developed. Natural history of LASV and pathogenesis of the disease provide strong justification for replication-competent (RC) vaccine as one of the most feasible approaches to control LF. Development of LASV vaccine candidates based on reassortant, recombinant, and alphavirus replicon technologies is covered in this review. Expert commentary: Two lead RC vaccine candidates, reassortant ML29 and recombinant VSV/LASV, have been successfully tested in non-human primates and have been recommended by international vaccine experts for rapid clinical development. Both platforms have powerful molecular tools to further secure safety, improve immunogenicity, and cross-protection. These platforms are well positioned to design multivalent vaccines to protect against all LASV strains citculatrd in West Africa. The regulatory pathway of Candid #1, the first live-attenuated arenaviral vaccine against Argentine hemorrhagic, will be a reasonable guideline for LASV vaccine efficacy trials.

Evaluation of Lassa Antiviral Compound ST-193 in a Guinea Pig Model

PubMed Central

Cashman, Kathleen A.; Smith, Mark A.; Twenhafel, Nancy A.; Larson, Ryan A.; Jones, Kevin F.; Allen, Robert D.; Dai, Dongcheng; Chinsangaram, Jarasvech; Bolken, Tove’ C.; Hruby, Dennis E.; Amberg, Sean M.; Hensley, Lisa E.; Guttieri, Mary C.

2012-01-01

Lassa virus (LASV), a member of the Arenaviridae family, causes a viral hemorrhagic fever endemic to West Africa, where as many as 300,000 infections occur per year. Presently, there are no FDA-approved LASV-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. A recently identified small-molecule inhibitor of arenavirus entry, ST-193, exhibits submicromolar antiviral activity in vitro. To determine the antiviral utility of ST-193 in vivo, we tested the efficacy of this compound in the LASV guinea pig model. Four groups of strain 13 guinea pigs were administered 25 or 80 mg/kg ST-193, 25 mg/kg of ribavirin, or the vehicle by the intraperitoneal (i.p.) route before infection with a lethal dose of LASV, strain Josiah, and continuing once daily for 14 days. Control animals exhibited severe disease, becoming moribund between days 10 and 15 postinfection. ST-193-treated animals exhibited fewer signs of disease and enhanced survival when compared to the ribavirin or vehicle groups. Body temperatures in all groups were elevated by day 9, but returned to normal by day 19 postinfection in the majority of ST-193-treated animals. ST-193 treatment mediated a 2- to 3-log reduction in viremia relative to vehicle-treated controls. The overall survival rate for the ST-193-treated guinea pigs was 62.5% (10/16) compared with 0% in the ribavirin (0/8) and vehicle (0/7) groups. These data suggest that ST-193 may serve as an improved candidate for the treatment of Lassa fever. PMID:21371508

Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: Clinical characterization and risk factors for severe disease

PubMed Central

Johnson, Reed F.; Dodd, Lori; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A.; Jett, Catherine; Bernbaum, John G.; Ragland, Dan R.; Claire, Marisa St.; Byrum, Russell; Paragas, Jason; Blaney, Joseph E.; Jahrling, Peter B.

2011-01-01

Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens. PMID:22014505

Immunology and Pathology of Arena Virus Infections.

DTIC Science & Technology

1992-04-15

histopathologic findings; hepatic inflammation, steatosis , lymph node sinus histiocytosis, pneumonitis etc., appeared to be distributed evenly among the two...administration (Tracey, 1988). TNF has been shown to induce hepatic lipogenesis (Feingold, 1987), correlating with the impressive histologic fatty change seen...D. (1990) Lassa Fever. Br. J. Hosp. Med. 43: 186-191. Feingold, K.R., and C. Grunfeld. (1987) Tumor Necrosis Factor Alpha stimulates hepatic

Vaccines for Viral Hemorrhagic Fevers – Progress and Shortcomings

PubMed Central

Falzarano, Darryl; Feldmann, Heinz

2013-01-01

With a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. In the past decade this has not been due to a lack of the ability to develop vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. The two exceptions to this are vaccines against Dengue virus and Rift Valley Fever virus, which recently have seen significant progress in putting forward new and improved vaccines, respectively. Experimental vaccines for filoviruses and Lassa virus do exist but are hindered by a lack of financial interest and only partially or ill-defined correlates/mechanisms of protection that could be assessed in clinical trials. PMID:23773330

The impact of human conflict on the genetics of Mastomys natalensis and Lassa virus in West Africa.

PubMed

Lalis, Aude; Leblois, Raphaël; Lecompte, Emilie; Denys, Christiane; Ter Meulen, Jan; Wirth, Thierry

2012-01-01

Environmental changes have been shown to play an important role in the emergence of new human diseases of zoonotic origin. The contribution of social factors to their spread, especially conflicts followed by mass movement of populations, has not been extensively investigated. Here we reveal the effects of civil war on the phylogeography of a zoonotic emerging infectious disease by concomitantly studying the population structure, evolution and demography of Lassa virus and its natural reservoir, the rodent Mastomys natalensis, in Guinea, West Africa. Analysis of nucleoprotein gene sequences enabled us to reconstruct the evolutionary history of Lassa virus, which appeared 750 to 900 years ago in Nigeria and only recently spread across western Africa (170 years ago). Bayesian demographic inferences revealed that both the host and the virus populations have gone recently through severe genetic bottlenecks. The timing of these events matches civil war-related mass movements of refugees and accompanying environmental degradation. Forest and habitat destruction and human predation of the natural reservoir are likely explanations for the sharp decline observed in the rodent populations, the consequent virus population decline, and the coincident increased incidence of Lassa fever in these regions. Interestingly, we were also able to detect a similar pattern in Nigeria coinciding with the Biafra war. Our findings show that anthropogenic factors may profoundly impact the population genetics of a virus and its reservoir within the context of an emerging infectious disease.

Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.

PubMed

Johnson, Reed F; Dodd, Lori E; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A; Jett, Catherine; Bernbaum, John G; Ragland, Dan R; St Claire, Marisa; Byrum, Russell; Paragas, Jason; Blaney, Joseph E; Jahrling, Peter B

2011-12-20

Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens. Published by Elsevier Inc.

Occupational hazards in hospitals: risk of infection.

PubMed Central

Gestal, J J

1987-01-01

In this review of the risk of infection to hospital staff, attention is drawn to the continuing risk presented by hepatitis B and pulmonary tuberculosis, which are more common than diseases such as typhoid fever, brucellosis, histoplasmosis, whooping cough, infectious gastroenteritis, measles, and parotiditis. Other items considered include the susceptibility of female hospital staff to rubella and the importance of their undergoing screening and vaccination; the risks currently presented by epidemic keratoconjunctivitis and by herpes viruses (herpes simplex, varicella zoster, and cytomegalovirus); and the risk of contracting the new infectious diseases (Legionnaires' disease, Marburg disease, Lassa fever, and the acquired immune deficiency syndrome). PMID:3304395

Categorizing Weapons of Mass Destruction Biological Agents into Postmortem Risk Groups

DTIC Science & Technology

2012-12-20

toxin  •Marburg  • Smallpox  •Brucellosis  •Melioidosis  • Staphylococcal Entertoxin B (SEB)  •Chikungunya  •Mycotoxins  • Tularemia   •Cholera...Marburg, 9.0 Saxitoxin, 6.25   Lassa fever, 8.75 VEE, 6.0   vCJD, 8.75 WEE, 6.0   Smallpox, 8.5 Tularemia , 6.0   Botulinum toxin, 7.75 Junin/Marchupo...WEE, 5.0     VEE, 5.0     Tularemia , 5.0     Junin/Marchupo, 5.0      Ricin, 4.75     Q fever, 4.75     Rift Valley Fever, 4.75      Mycotoxins

[Countermeasure against viral hemorrhagic fever at the border in Japan].

PubMed

Iwasaki, Emiko

2005-12-01

Human have struggled against many infectious diseases such as cholera, plague, dysentery and yellow fever for a long time. And we have spent a lot of energy to control these infectious diseases and developed various tool for them. One of these efforts was Quarantine system that was established in 14th century in Europe. But during recent days, we are suffering from newly emerged diseases. These new infectious diseases are zoonosis and most of them are serious and highly infectious. Viral hemorrhagic fever such as Ebola hemorrhagic fever, Marburg hemorrhagic fever and Lassa fever are typical these emerging serious diseases, and these outbreak always have occurred in Africa and neighboring countries. Fortunately we have never experienced any case, but as these diseases are so serious, we are so nervous diseases entering in Japan. Against these serious diseases, in Japan, Quarantine Station are doing screening examination at airport and port by questionnaire and measuring body temperature, because these viral hemorrhagic fever patients show high fever. If people were suspected viral hemorrhagic fever at Quarantine Station at the border, they will be leaded to hospital for further examination and treatment as soon as possible.

Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone.

PubMed

Dahmane, A; van Griensven, J; Van Herp, M; Van den Bergh, R; Nzomukunda, Y; Prior, J; Alders, P; Jambai, A; Zachariah, R

2014-03-01

Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this 'neglected disease'.

Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.

PubMed

Andersen, Kristian G; Shapiro, B Jesse; Matranga, Christian B; Sealfon, Rachel; Lin, Aaron E; Moses, Lina M; Folarin, Onikepe A; Goba, Augustine; Odia, Ikponmwonsa; Ehiane, Philomena E; Momoh, Mambu; England, Eleina M; Winnicki, Sarah; Branco, Luis M; Gire, Stephen K; Phelan, Eric; Tariyal, Ridhi; Tewhey, Ryan; Omoniwa, Omowunmi; Fullah, Mohammed; Fonnie, Richard; Fonnie, Mbalu; Kanneh, Lansana; Jalloh, Simbirie; Gbakie, Michael; Saffa, Sidiki; Karbo, Kandeh; Gladden, Adrianne D; Qu, James; Stremlau, Matthew; Nekoui, Mahan; Finucane, Hilary K; Tabrizi, Shervin; Vitti, Joseph J; Birren, Bruce; Fitzgerald, Michael; McCowan, Caryn; Ireland, Andrea; Berlin, Aaron M; Bochicchio, James; Tazon-Vega, Barbara; Lennon, Niall J; Ryan, Elizabeth M; Bjornson, Zach; Milner, Danny A; Lukens, Amanda K; Broodie, Nisha; Rowland, Megan; Heinrich, Megan; Akdag, Marjan; Schieffelin, John S; Levy, Danielle; Akpan, Henry; Bausch, Daniel G; Rubins, Kathleen; McCormick, Joseph B; Lander, Eric S; Günther, Stephan; Hensley, Lisa; Okogbenin, Sylvanus; Schaffner, Stephen F; Okokhere, Peter O; Khan, S Humarr; Grant, Donald S; Akpede, George O; Asogun, Danny A; Gnirke, Andreas; Levin, Joshua Z; Happi, Christian T; Garry, Robert F; Sabeti, Pardis C

2015-08-13

The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical sequencing uncovers origins and evolution of Lassa virus

PubMed Central

Andersen, Kristian G.; Shapiro, B. Jesse; Matranga, Christian B.; Sealfon, Rachel; Lin, Aaron E.; Moses, Lina M.; Folarin, Onikepe A.; Goba, Augustine; Odia, Ikponmwonsa; Ehiane, Philomena E.; Momoh, Mambu; England, Eleina M.; Winnicki, Sarah; Branco, Luis M.; Gire, Stephen K.; Phelan, Eric; Tariyal, Ridhi; Tewhey, Ryan; Omoniwa, Omowunmi; Fullah, Mohammed; Fonnie, Richard; Fonnie, Mbalu; Kanneh, Lansana; Jalloh, Simbirie; Gbakie, Michael; Saffa, Sidiki; Karbo, Kandeh; Gladden, Adrianne D.; Qu, James; Stremlau, Matthew; Nekoui, Mahan; Finucane, Hilary K.; Tabrizi, Shervin; Vitti, Joseph J.; Birren, Bruce; Fitzgerald, Michael; McCowan, Caryn; Ireland, Andrea; Berlin, Aaron M.; Bochicchio, James; Tazon-Vega, Barbara; Lennon, Niall J.; Ryan, Elizabeth M.; Bjornson, Zach; Milner, Danny A.; Lukens, Amanda K.; Broodie, Nisha; Rowland, Megan; Heinrich, Megan; Akdag, Marjan; Schieffelin, John S.; Levy, Danielle; Akpan, Henry; Bausch, Daniel G.; Rubins, Kathleen; McCormick, Joseph B.; Lander, Eric S.; Günther, Stephan; Hensley, Lisa; Okogbenin, Sylvanus; Schaffner, Stephen F.; Okokhere, Peter O.; Khan, S. Humarr; Grant, Donald S.; Akpede, George O.; Asogun, Danny A.; Gnirke, Andreas; Levin, Joshua Z.; Happi, Christian T.; Garry, Robert F.; Sabeti, Pardis C.

2015-01-01

Summary The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us how little is known about biosafety level-4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. PMID:26276630

Sequence Variability and Geographic Distribution of Lassa Virus, Sierra Leone

PubMed Central

Stockelman, Michael G.; Moses, Lina M.; Park, Matthew; Stenger, David A.; Ansumana, Rashid; Bausch, Daniel G.; Lin, Baochuan

2015-01-01

Lassa virus (LASV) is endemic to parts of West Africa and causes highly fatal hemorrhagic fever. The multimammate rat (Mastomys natalensis) is the only known reservoir of LASV. Most human infections result from zoonotic transmission. The very diverse LASV genome has 4 major lineages associated with different geographic locations. We used reverse transcription PCR and resequencing microarrays to detect LASV in 41 of 214 samples from rodents captured at 8 locations in Sierra Leone. Phylogenetic analysis of partial sequences of nucleoprotein (NP), glycoprotein precursor (GPC), and polymerase (L) genes showed 5 separate clades within lineage IV of LASV in this country. The sequence diversity was higher than previously observed; mean diversity was 7.01% for nucleoprotein gene at the nucleotide level. These results may have major implications for designing diagnostic tests and therapeutic agents for LASV infections in Sierra Leone. PMID:25811712

Antibodies to the Glycoprotein GP2 Subunit Cross-React between Old and New World Arenaviruses.

PubMed

Amanat, Fatima; Duehr, James; Oestereich, Lisa; Hastie, Kathryn M; Ollmann Saphire, Erica; Krammer, Florian

2018-01-01

Arenaviruses pose a major public health threat and cause numerous infections in humans each year. Although most viruses belonging to this family do not cause disease in humans, some arenaviruses, such as Lassa virus and Machupo virus, are the etiological agents of lethal hemorrhagic fevers. The absence of a currently licensed vaccine and the highly pathogenic nature of these viruses both make the necessity of developing viable vaccines and therapeutics all the more urgent. Arenaviruses have a single glycoprotein on the surface of virions, the glycoprotein complex (GPC), and this protein can be used as a target for vaccine development. Here, we describe immunization strategies to generate monoclonal antibodies (MAbs) that cross-react between the glycoprotein complexes of both Old World and New World arenaviruses. Several monoclonal antibodies isolated from immunized mice were highly cross-reactive, binding a range of Old World arenavirus glycoproteins, including that of Lassa virus. One such monoclonal antibody, KL-AV-2A1, bound to GPCs of both New World and Old World viruses, including Lassa and Machupo viruses. These cross-reactive antibodies bound to epitopes present on the glycoprotein 2 subunit of the glycoprotein complex, which is relatively conserved among arenaviruses. Monoclonal antibodies binding to these epitopes, however, did not inhibit viral entry as they failed to neutralize a replication-competent vesicular stomatitis virus pseudotyped with the Lassa virus glycoprotein complex in vitro In addition, no protection from virus challenge was observed in in vivo mouse models. Even so, these monoclonal antibodies might still prove to be useful in the development of clinical and diagnostic assays. IMPORTANCE Several viruses in the Arenaviridae family infect humans and cause severe hemorrhagic fevers which lead to high case fatality rates. Due to their pathogenicity and geographic tropisms, these viruses remain very understudied. As a result, an effective vaccine or therapy is urgently needed. Here, we describe efforts to produce cross-reactive monoclonal antibodies that bind to both New and Old World arenaviruses. All of our MAbs seem to be nonneutralizing and nonprotective and target subunit 2 of the glycoprotein. Due to the lack of reagents such as recombinant glycoproteins and antibodies for rapid detection assays, our MAbs could be beneficial as analytic and diagnostic tools. Copyright © 2018 Amanat et al.

Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis

DTIC Science & Technology

2010-01-01

apoptosis. Journal of Immunology 184:327-335 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR (S) Bradfute, SB Swanson, PE...R.S.H.) and 4.10022_08_RD_B (to S.B.). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily...viruses, in- cluding Lassa, Marburg, Crimean Congo hemorrhagic fever, and some Hantavirus infections. However, no studies to our knowledge have

Vaccine Platforms to Control Arenaviral Hemorrhagic Fevers.

PubMed

Carrion, Ricardo; Bredenbeek, Peter; Jiang, Xiaohong; Tretyakova, Irina; Pushko, Peter; Lukashevich, Igor S

2012-11-20

Arenaviruses are rodent-borne emerging human pathogens. Diseases caused by these viruses, e.g., Lassa fever (LF) in West Africa and South American hemorrhagic fevers (HFs), are serious public health problems in endemic areas. We have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups "at risk". Our leader LF vaccine candidate, the live reassortant vaccine ML29, is safe and efficacious in all tested animal models including non-human primates. In this study we showed that treatment of fatally infected animals with ML29 two days after Lassa virus (LASV) challenge protected 80% of the treated animals. In endemic areas, where most of the target population is poor and many live far from health care facilities, a single-dose vaccination with ML29 would be ideal solution. Once there is an outbreak, a fast-acting vaccine or post-exposure prophylaxis would be best. The 2(nd) vaccine technology is based on Yellow Fever (YF) 17D vaccine. We designed YF17D-based recombinant viruses expressing LASV glycoproteins (GP) and showed protective efficacy of these recombinants. In the current study we developed a novel technology to clone LASV nucleocapsid within YF17D C gene. Low immunogenicity and stability of foreign inserts must be addressed to design successful LASV/YFV bivalent vaccines to control LF and YF in overlapping endemic areas of West Africa. The 3(rd) platform is based on the new generation of alphavirus replicon virus-like-particle vectors (VLPV). Using this technology we designed VLPV expressing LASV GP with enhanced immunogenicity and bivalent VLPV expressing cross-reactive GP of Junin virus (JUNV) and Machupo virus (MACV), causative agents of Argentinian and Bolivian HF, respectively. A prime-boost regimen required for VLPV immunization might be practical for medical providers, military, lab personnel, and visitors in endemic areas.

Rapid Generation and Testing of a Lassa Fever Vaccine Using VaxCelerate Platform

DTIC Science & Technology

2014-08-28

essentially the same way each time but is capable to producing effective vaccine responses to a range of pathogens, and to do this without the use of...this distributed vaccine development consortium to rapidly produce and test a novel vaccine of relevance to public health responses. In parallel...with this effort, the consortium produced and tested a modified version of its self-assembling vaccine protein that used a subunit of the full

IGG Subclass and Isotype Specific Immunoglobulin Responses to Lassa Fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunization

DTIC Science & Technology

1990-09-30

EQUINE N ENCEPHALOMYELITIS: NATURAL INFECTION AND IMMUNIZATION , I PRINCIPAL INVESTIGATOR: Renata J. Engler, LTC, MC CONTRACTING ORGANIZATION: Uniformed...Services University of the Health Sciences Department of Medicine Bethesda, MD 20814-4799 REPORT DATE: September 30, 1990 ELECTEO 0CT 3 11990 TYPE OF...Uniformed Services University (If applicable) of Health Sciences I 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code

Postexposure prophylaxis for Lassa fever: Experience from a recent outbreak in Nigeria.

PubMed

Isa, Samson E; Okwute, Attah; Iraoyah, Kelly O; Nathan, Shehu Y; Simji, Gomerep S; Okolo, Mark O; Anejo-Okopi, Joseph; Spicola, Daria; Isa, Daisy E

2016-01-01

Secondary transmission of Lassa fever (LF) occurs in the community and in health-care facilities, and is associated with high fatality in Nigeria. We investigated the role of oral ribavirin postexposure prophylaxis (orPEP) in preventing LF among the primary contacts of confirmed cases from December 2015 to March 2016. Epidemiological and clinical data of LF contacts were prospectively collected. However, information regarding ribavirin adverse effects (AEs) were collected retrospectively through a telephone interview. High-risk contacts were clinically monitored ΁ orPEP. Thirty-five (94.6%) out of the 37 individuals enrolled in the study were contacts of confirmed LF cases, and friends and family members (54%) constituted the largest group. However, only 29 (83%) individuals were classified as high-risk contacts. Twenty-one (60%) of contacts were prescribed ribavirin with 6 (28.6%) of them reporting AEs. Body weakness (33%) was the most frequent AE, but there was no incidence of treatment discontinuation due to AE. Furthermore, there were no reported cases of LF among all respondents (0%), whether they had orPEP or not. Secondary transmission of LF seems uncommon and the benefit of orPEP is uncertain. Although AEs of ribavirin may not be uncommon, they are rarely serious enough to cause treatment interruption. More emphasis should be on supporting persons looking after LF cases adopt measures that minimize the risks of exposure.

Integrative modelling for One Health: pattern, process and participation

PubMed Central

Redding, D. W.; Wood, J. L. N.

2017-01-01

This paper argues for an integrative modelling approach for understanding zoonoses disease dynamics, combining process, pattern and participatory models. Each type of modelling provides important insights, but all are limited. Combining these in a ‘3P’ approach offers the opportunity for a productive conversation between modelling efforts, contributing to a ‘One Health’ agenda. The aim is not to come up with a composite model, but seek synergies between perspectives, encouraging cross-disciplinary interactions. We illustrate our argument with cases from Africa, and in particular from our work on Ebola virus and Lassa fever virus. Combining process-based compartmental models with macroecological data offers a spatial perspective on potential disease impacts. However, without insights from the ground, the ‘black box’ of transmission dynamics, so crucial to model assumptions, may not be fully understood. We show how participatory modelling and ethnographic research of Ebola and Lassa fever can reveal social roles, unsafe practices, mobility and movement and temporal changes in livelihoods. Together with longer-term dynamics of change in societies and ecologies, all can be important in explaining disease transmission, and provide important complementary insights to other modelling efforts. An integrative modelling approach therefore can offer help to improve disease control efforts and public health responses. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’. PMID:28584172

The challenges of detecting and responding to a Lassa fever outbreak in an Ebola-affected setting.

PubMed

Hamblion, E L; Raftery, P; Wendland, A; Dweh, E; Williams, G S; George, R N C; Soro, L; Katawera, V; Clement, P; Gasasira, A N; Musa, E; Nagbe, T K

2018-01-01

Lassa fever (LF), a priority emerging pathogen likely to cause major epidemics, is endemic in much of West Africa and is difficult to distinguish from other viral hemorrhagic fevers, including Ebola virus disease (EVD). Definitive diagnosis requires laboratory confirmation, which is not widely available in affected settings. The public health action to contain a LF outbreak and the challenges encountered in an EVD-affected setting are reported herein. In February 2016, a rapid response team was deployed in Liberia in response to a cluster of LF cases. Active case finding, case investigation, contact tracing, laboratory testing, environmental investigation, risk communication, and community awareness raising were undertaken. From January to June 2016, 53 suspected LF cases were reported through the Integrated Disease Surveillance and Response system (IDSR). Fourteen cases (26%) were confirmed for LF, 14 (26%) did not have a sample tested, and 25 (47%) were classified as not a case following laboratory analysis. The case fatality rate in the confirmed cases was 29%. One case of international exportation was reported from Sweden. Difficulties were identified in timely specimen collection, packaging, and transportation (in confirmed cases, the time from sample collection to sample result ranged from 2 to 64 days) and a lack of response interventions for early cases. The delay in response to this outbreak could have been related to a number of challenges in this EVD-affected setting: a need to strengthen the IDSR system, develop preparedness plans, train rapid response teams, and build laboratory capacity. Prioritizing these actions will aid in the timely response to future outbreaks. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Material Proximities and Hotspots: Toward an Anthropology of Viral Hemorrhagic Fevers

PubMed Central

Brown, Hannah; Kelly, Ann H

2014-01-01

This article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as VHFs). It begins by reviewing the social science literature on Ebola, Marburg, and Lassa fevers and charting areas for future ethnographic attention. We theoretically elaborate the hotspot as a way of integrating analysis of the two routes of VHF infection: from animal reservoirs to humans and between humans. Drawing together recent anthropological investigations of human–animal entanglements with an ethnographic interest in the social production of space, we seek to enrich conceptualizations of viral movement by elaborating the circumstances through which viruses, humans, objects, and animals come into contact. We suggest that attention to the material proximities—between animals, humans, and objects—that constitute the hotspot opens a frontier site for critical and methodological development in medical anthropology and for future collaborations in VHF management and control. PMID:24752909

Material proximities and hotspots: toward an anthropology of viral hemorrhagic fevers.

PubMed

Brown, Hannah; Kelly, Ann H

2014-06-01

This article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as VHFs). It begins by reviewing the social science literature on Ebola, Marburg, and Lassa fevers and charting areas for future ethnographic attention. We theoretically elaborate the hotspot as a way of integrating analysis of the two routes of VHF infection: from animal reservoirs to humans and between humans. Drawing together recent anthropological investigations of human-animal entanglements with an ethnographic interest in the social production of space, we seek to enrich conceptualizations of viral movement by elaborating the circumstances through which viruses, humans, objects, and animals come into contact. We suggest that attention to the material proximities-between animals, humans, and objects-that constitute the hotspot opens a frontier site for critical and methodological development in medical anthropology and for future collaborations in VHF management and control. © 2014 by the American Anthropological Association.

Hemorrhagic Fever Virus Budding Studies.

PubMed

Harty, Ronald N

2018-01-01

Independent expression of the VP40 or Z matrix proteins of filoviruses (marburgviruses and ebolaviruses) and arenaviruses (Lassa fever and Junín), respectively, gives rise to the production and release of virus-like particles (VLPs) that are morphologically identical to infectious virions. We can detect and quantify VLP production and egress in mammalian cells by transient transfection, SDS-PAGE, Western blotting, and live cell imaging techniques such as total internal reflection fluorescence (TIRF) microscopy. Since the VLP budding assay accurately mimics budding of infectious virus, this BSL-2 assay is safe and useful for the interrogation of both viral and host determinants required for budding and can be used as an initial screen to identify and validate small molecule inhibitors of virus release and spread.

Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.

PubMed

Caballero, Ignacio S; Yen, Judy Y; Hensley, Lisa E; Honko, Anna N; Goff, Arthur J; Connor, John H

2014-11-06

Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods. In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR. These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.

IGG Subclass and Isotype Specific Immunoglobulin Responses to LASSA fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunication

DTIC Science & Technology

1989-03-01

VENEZUELAN EQUINE ENCEPHALOMYELITIS: NATURAL INFECTION AND IMMUNIZATION PRINCIPAL INVESTIGATOR: Renata J. Engler CONTRACTING ORGANIZATION: Uniformed Services...University of Health Sciences 4301 Jones Bridges Road Bethesda, MD 20814-4799 DTIC REPORT DATE: March 1, 1989 E T E MAR0 6 1990 TYPE OF REPORT...University (if applicable) of Health Sciences I 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) 4301 Jones Bridges Road

TRAINING PROGRAM FOR NURSING STAFF REGARDING VIRAL HEMORRHAGIC FEVERS IN A MILITARY HOSPITAL.

PubMed

El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Saleh, Halla Ahmed Abdullah; Abdelfattah, Magda Abdelhamid; Morsy, Tosson Aly

2015-08-01

Viral hemorrhagic fevers (VHFs) refer to a group of illnesses caused by several distinct families of viruses. In general, the term "viral hemorrhagic fever" is used to describe a severe multisystem syndrome (multisystem in that multiple organ systems in the bpdy are affected). Characteristically, the overall vascular system is damaged, and the body's ability to regulate itself is impaired. These symptoms are often accompanied by hemorrhage (bleeding); however, the bleeding is it rarely life-threatening. While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause severe, life-threatening disease. The selected disaster diseases for this study included: 1-Crimean-Congo hemorrhagic Fever, 2-Dengue Fever, 3-Ebola Fever, 4-Hem-orrhagic Fever with renal syndrome (HFRS), 5-Hantavirus Pulmonary Syndrome, 6-Lassa Fever, 7-Marburg Fever, 8-Rift Valley Fever and 9-Yellow Fever. The educational training program was given over ten sessions to a group of Staff Nurses. The results showed that the program succeeded in enhancing nurse' knowledge, awareness, responsibility, and obligations toward patients with the Viral Hemorrhagic Fevers The results showed a significant impact of training sessions illuminated in the follow-up test on the knowledge score of nurses in all types of diseases except for the Congo hemorrhagic fever, while, statistical significance varied in some diseases in the study when it comes to the comparison between pretest and post-test. All results confirmed on the positive impact of the training program in enhancing the knowledge of nurses toward VHFs patients and their relevant. There was a significant positive impact of the training sessions on changing the attitude of nurses toward patients with VHFs. This result was confirmed on the collective level since the total scores on tests revealed significant positive impact of the study on changing the attitude of nurses toward relevant patients. The relationship included personal data (age, sex, level of education, & years of experiences) and main variables (knowledge scores & attitude change to patients) with the disease in question. This part revealed a significant relationship between all personal data and total knowledge score among nurses except for the level of education, while all results were insignificant for the relationship between the personal data and the nurses' attitude. Difference between the total nurses' attitude change and the total knowledge scores was significant on the three tests' levels; pre, post, and the follow-up. The overall evaluation showed that six criteria were adopted, regarding the educator, the length of presentations, the evaluation of the studied groups regarding the training facilities, the subject matters, the overall training program, and the importance of diseases in question to their practical working environment. The frequency distribution showed that the educator met nurses' expectations; the material tools were plausible enough to satisfy trainees and presentations were fairly short. But, the training facilities were just excellent by the vast majority of trainees. The entire material met specific needs of relevant health care organizations, but about 43% reported that it was difficult. The vast majority of trainees favored the program under almost all criteria studied in the final questionnaire. Above 50% of trainees were not confident enough toward their ability in applying their knowledge acquired practically. The final evaluation showed that the most important were Rift Valley fever, Ebola fever, Hanta virus pulmonary syndrome, Crimean Congo fever and lastly Dengue fever. Lassa and Marburg fevers were of less interest to nurses.

Development of a time-trend model for analyzing and predicting case-pattern of Lassa fever epidemics in Liberia, 2013-2017.

PubMed

Olugasa, Babasola O; Odigie, Eugene A; Lawani, Mike; Ojo, Johnson F

2015-01-01

The objective was to develop a case-pattern model for Lassa fever (LF) among humans and derive predictors of time-trend point distribution of LF cases in Liberia in view of the prevailing under-reporting and public health challenge posed by the disease in the country. A retrospective 5 years data of LF distribution countrywide among humans were used to train a time-trend model of the disease in Liberia. A time-trend quadratic model was selected due to its goodness-of-fit (R2 = 0.89, and P < 0.05) and best performance compared to linear and exponential models. Parameter predictors were run on least square method to predict LF cases for a prospective 5 years period, covering 2013-2017. The two-stage predictive model of LF case-pattern between 2013 and 2017 was characterized by a prospective decline within the South-coast County of Grand Bassa over the forecast period and an upward case-trend within the Northern County of Nimba. Case specific exponential increase was predicted for the first 2 years (2013-2014) with a geometric increase over the next 3 years (2015-2017) in Nimba County. This paper describes a translational application of the space-time distribution pattern of LF epidemics, 2008-2012 reported in Liberia, on which a predictive model was developed. We proposed a computationally feasible two-stage space-time permutation approach to estimate the time-trend parameters and conduct predictive inference on LF in Liberia.

Containing a Lassa fever epidemic in a resource-limited setting: outbreak description and lessons learned from Abakaliki, Nigeria (January-March 2012).

PubMed

Ajayi, Nnennaya A; Nwigwe, Chinedu G; Azuogu, Ben N; Onyire, Benson N; Nwonwu, Elizabeth U; Ogbonnaya, Lawrence U; Onwe, Francis I; Ekaete, Tobin; Günther, Stephan; Ukwaja, Kingsley N

2013-11-01

Despite the epidemic nature of Lassa fever (LF), details of outbreaks and response strategies have not been well documented in resource-poor settings. We describe the course of a LF outbreak in Ebonyi State, Nigeria, during January to March 2012. We analyzed clinical, epidemiological, and laboratory data from surveillance records and hospital statistics during the outbreak. Fisher's exact tests were used to compare proportions and t-tests to compare differences in means. The outbreak response consisted of effective coordination, laboratory testing, active surveillance, community mobilization, contact and suspected case evaluation, and case management. Twenty LF cases (10 confirmed and 10 suspected) were recorded during the outbreak. Nosocomial transmission to six health workers occurred through the index case. Only 1/110 contacts had an asymptomatic infection. Overall, there was high case fatality rate among all cases (6/20; 30%). Patients who received ribavirin were less likely to die than those who did not (p=0.003). The mean delay to presentation for patients who died was 11 ± 3.5 days, while for those who survived was 6 ± 2.6 days (p<0.001). The response strategies contained the epidemic. Challenges to control efforts included poor local laboratory capacity, inadequate/poor quality of protective materials, fear among health workers, and inadequate emergency preparedness. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[Chikungunya fever - A new global threat].

PubMed

Montero, Antonio

2015-08-07

The recent onset of epidemics caused by viruses such as Ebola, Marburg, Nipah, Lassa, coronavirus, West-Nile encephalitis, Saint Louis encephalitis, human immunodeficiency virus, dengue, yellow fever and Venezuelan hemorrhagic fever alerts about the risk these agents represent for the global health. Chikungunya virus represents a new threat. Surged from remote African regions, this virus has become endemic in the Indic ocean basin, the Indian subcontinent and the southeast of Asia, causing serious epidemics in Africa, Indic Ocean Islands, Asia and Europe. Due to their epidemiological and biological features and the global presence of their vectors, chikungunya represents a serious menace and could become endemic in the Americas. Although chikungunya infection has a low mortality rate, its high attack ratio may collapse the health system during epidemics affecting a sensitive population. In this paper, we review the clinical and epidemiological features of chikungunya fever as well as the risk of its introduction into the Americas. We remark the importance of the epidemiological control and mosquitoes fighting in order to prevent this disease from being introduced into the Americas. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Alphavirus vector-based replicon particles expressing multivalent cross-protective Lassa virus glycoproteins

PubMed Central

Wang, Min; Jokinen, Jenny; Tretyakova, Irina; Pushko, Peter; Lukashevich, Igor S.

2018-01-01

Lassa virus (LASV) is the most prevalent rodent-borne arenavirus circulated in West Africa. With population at risk from Senegal to Nigeria, LASV causes Lassa fever and is responsible for thousands of deaths annually. High genetic diversity of LASV is one of the challenges for vaccine R&D. We developed multivalent virus-like particle vectors (VLPVs) derived from the human Venezuelan equine encephalitis TC-83 IND vaccine (VEEV) as the next generation of alphavirus-based bicistronic RNA replicon particles. The genes encoding VEEV structural proteins were replaced with LASV glycoproteins (GPC) from distantly related clades I and IV with individual 26S promoters. Bicistronic RNA replicons encoding wild-type LASV GPC (GPCwt) and C-terminally deleted, non-cleavable modified glycoprotein (ΔGPfib), were encapsidated into VLPV particles using VEEV capsid and glycoproteins provided in trans. In transduced cells, VLPVs induced simultaneous expression of LASV GPCwt and ΔGPfib from 26S alphavirus promoters. LASV ΔGPfib was predominantly expressed as trimers, accumulated in the endoplasmic reticulum, induced ER stress and apoptosis promoting antigen cross-priming. VLPV vaccines were immunogenic and protective in mice and upregulated CD11c+/CD8+ dendritic cells playing the major role in cross-presentation. Notably, VLPV vaccination resulted in induction of cross-reactive multifunctional T cell responses after stimulation of immune splenocytes with peptide cocktails derived from LASV from clades I-IV. Multivalent RNA replicon-based LASV vaccines can be applicable for first responders, international travelers visiting endemic areas, military and lab personnel. PMID:29287681

Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

PubMed

Lo Iacono, Giovanni; Cunningham, Andrew A; Fichet-Calvet, Elisabeth; Garry, Robert F; Grant, Donald S; Khan, Sheik Humarr; Leach, Melissa; Moses, Lina M; Schieffelin, John S; Shaffer, Jeffrey G; Webb, Colleen T; Wood, James L N

2015-01-01

Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Formula: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text]. This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.

Cellular Factors Required for Lassa Virus Budding

PubMed Central

Urata, Shuzo; Noda, Takeshi; Kawaoka, Yoshihiro; Yokosawa, Hideyoshi; Yasuda, Jiro

2006-01-01

It is known that Lassa virus Z protein is sufficient for the release of virus-like particles (VLPs) and that it has two L domains, PTAP and PPPY, in its C terminus. However, little is known about the cellular factor for Lassa virus budding. We examined which cellular factors are used in Lassa virus Z budding. We demonstrated that Lassa Z protein efficiently produces VLPs and uses cellular factors, Vps4A, Vps4B, and Tsg101, in budding, suggesting that Lassa virus budding uses the multivesicular body pathway functionally. Our data may provide a clue to develop an effective antiviral strategy for Lassa virus. PMID:16571837

At Home with Mastomys and Rattus: Human-Rodent Interactions and Potential for Primary Transmission of Lassa Virus in Domestic Spaces

PubMed Central

Bonwitt, Jesse; Sáez, Almudena Mari; Lamin, Joseph; Ansumana, Rashid; Dawson, Michael; Buanie, Jacob; Lamin, Joyce; Sondufu, Diana; Borchert, Matthias; Sahr, Foday; Fichet-Calvet, Elisabeth; Brown, Hannah

2017-01-01

The multimammate mouse (Mastomys natalensis) is the reservoir for Lassa virus (LASV). Zoonotic transmission occurs when humans are directly or indirectly exposed to fluids of the multimammate mouse, such as urine, saliva, and blood. Housing characteristics and domestic organization affect rodent density in and around households and villages, and are likely to be a risk factor for Lassa fever in humans where the reservoir exists. We use semi-structured interviews (N = 51), a quantitative survey (N = 429), direct observations, and a rodent ecology study to provide new insights into how the organization of domestic spaces brings together humans and rodents and creates pathways for infection in rural settlements in Bo District, Sierra Leone. Rodents were frequently reported inside houses (92.4% of respondents), in which we predominantly trapped M. natalensis (57% of trapped rodents) and Rattus rattus (38% of trapped rodents). Building design and materials provide hiding and nesting places for rodents and lead to close proximity with humans. Patterns of contact are both unintentional and intentional and research participants reported high levels of contact with rodents (34.2% of respondents) and rodent fluids (52.8% of respondents). Rodents are also perceived as a serious threat to food security. These results present detailed knowledge about how humans live with and come into contact with rodents, including the LASV reservoir. Our results argue for further collaborative research in housing and environmental modification such as ceiling construction, food storage, and sanitation as prevention against zoonotic LASV transmission. PMID:28167603

Protection of Lassa Virus-Infected Guinea Pigs with Lassa-Immune Plasma of Guinea Pig, Primate, and Human Origin

DTIC Science & Technology

1983-01-01

DTICCS OCT 19 1983ora o ek Viroly 12-93-102 (1963) Protection of Lassa Virus-infected Guinea Pigs With Lassa-Immune Plasma of Guinea Pig , Primate...siotrain 13 guinea pigs were infected with a lethal dose of Lassa virus and treated with various Lassa-immune plasmas obtained from guinea pigs , primates...plaque-forming units (PFU) neutralization index (LNI). All guinea pigs treated with immune plasma 6 mI/kg/treatment on days 0, 3, and 6 after virus

[Highly contagious diseases with human-to-human transmission].

PubMed

Rybka, Aleš; Szanyi, Juraj; Kapla, Jaroslav; Plíšek, Stanislav

2012-12-01

Highly contagious diseases are caused by various biological agents that pose a risk to individuals and may have a potential for public health impact. They result in high mortality and morbidity rates, might cause public panic and therefore require special measures. The pathogens that can be easily disseminated or transmitted from person to person are the riskiest for clinicians (Ebola virus, Marburg virus, Lassa virus, Crimean-Congo hemorrhagic fever virus, Variola major, SARS virus and Yersinia pestis). Human-to-human transmission has not been confirmed for the other biological agents and therefore they pose a very low risk for population.

Serological assays based on recombinant viral proteins for the diagnosis of arenavirus hemorrhagic fevers.

PubMed

Fukushi, Shuetsu; Tani, Hideki; Yoshikawa, Tomoki; Saijo, Masayuki; Morikawa, Shigeru

2012-10-12

The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World (OW) and New World (NW) complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever (VHF) in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques for these virus infections in institutes without BSL-4 facilities. To overcome these difficulties, antibody detection systems in the form of an enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence assay were developed using recombinant nucleoproteins (rNPs) derived from these viruses. Furthermore, several antigen-detection assays were developed. For example, novel monoclonal antibodies (mAbs) to the rNPs of Lassa and Junin viruses were generated. Sandwich antigen-capture (Ag-capture) ELISAs using these mAbs as capture antibodies were developed and confirmed to be sensitive and specific for detecting the respective arenavirus NPs. These rNP-based assays were proposed to be useful not only for an etiological diagnosis of VHFs, but also for seroepidemiological studies on VHFs. We recently developed arenavirus neutralization assays using vesicular stomatitis virus (VSV)-based pseudotypes bearing arenavirus recombinant glycoproteins. The goal of this article is to review the recent advances in developing laboratory diagnostic assays based on recombinant viral proteins for the diagnosis of VHFs and epidemiological studies on the VHFs caused by arenaviruses.

Animal models of viral hemorrhagic fever.

PubMed

Smith, Darci R; Holbrook, Michael R; Gowen, Brian B

2014-12-01

The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures. Copyright © 2014 Elsevier B.V. All rights reserved.

[Epidemiological risk of introduction of dangerous and exotic infectious diseases on the territory of the XXII Olympic Winter Games and XI Paralympic Winter Games 2014 in Sochi].

PubMed

Kuz'kin, B P; Ezhlova, E B; Kulichenko, A N; Maletskaia, O V; Demina, Iu V; Taran, T V; Pakskina, N D; Kharchenko, T V; Grizhebovskiĭ, G M; Savel'ev, V N; Orobeĭ, V G; Klindukhov, V P; Grechanaia, T V; Tesheva, S Ch; Brukhanova, G D

2015-01-01

To assess the epidemiological risk of introduction of serious infectious diseases in the pre-Olympic period defined list of dangerous and exotic infections and held assessment of potential danger threatening. Initial external information to assess the potential risk of skidding were reports, forecasts, posted on the official websites. The risk of skidding and epidemiological complications conditionally designated as high, moderate and minimal risk importation of measles virus-Rate was considered as high. In confirmation of the forecast for the period of the Olympic Games in Sochi have been registered about 100 cases of measles. Moderate risk of importation was determined for poliomyelitis due to wild poliovirus, Lassa fever, cholera, plague, and the minimal--for Dengue fever, yellow fever, the Middle East and respiratory syndrome, diseases caused by viruses Marburg and Ebola. Based on of analysis of previous Olympic Games and subsequent co-events related to the activity of the infectious diseases in the world, mate-cluded that even a slight risk of importation of infectious diseases requires maximum alertness and readiness to conduct adequate epidemiological issues incorporated.

The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone.

PubMed

Li, Wen-Gang; Chen, Wei-Wei; Li, Lei; Ji, Dong; Ji, Ying-Jie; Li, Chen; Gao, Xu-Dong; Wang, Li-Fu; Zhao, Min; Duan, Xue-Zhang; Duan, Hui-Juan

2016-05-10

During the 2014 Ebola virus disease (EVD) outbreak, less than half of EVD-suspected cases were laboratory tested as Ebola virus (EBOV)-negative, but disease identity remained unknown. In this study we investigated the etiology of EVD-like illnesses in EBOV-negative cases. From November 13, 2014 to March 16, 2015, EVD-suspected patients were admitted to Jui Government Hospital and assessed for EBOV infection by real-time PCR. Of 278 EBOV negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%), 114 (41.01%), 59 (21.22%), 35 (12.59%), and 12 (4.32%) reported fever, headache, joint pain, fatigue, nausea/vomiting, diarrhea, hemorrhage, respectively. Furthermore, 121 (43.52%), 44 (15.83%), 36 (12.95%), 33 (11.87%), 23 (8.27%), 10 (3.60%) patients were diagnosed as infection with malaria, HIV, Lassa fever, tuberculosis, yellow fever, and pneumonia, respectively. No significant differences in clinical features and symptoms were found between non-EVD and EVD patients. To the best of our knowledge, the present study is the first to explore the etiology of EVD-like illnesses in uninfected patients in Sierra Leone, highlighting the importance of accurate diagnosis to EVD confirmation.

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

PubMed Central

Das, Sanchita; Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Shigyo, Kristi; Garrison, Aura R.; Paragas, Jason; Smith, Scott K.; Olson, Victoria A.; Larone, Davise H.; Spitzer, Eric D.; Barany, Francis; Golightly, Linnie M.

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID:26381398

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

PubMed

Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

Connaissances et attitudes des relais communautaires sur les fièvres hémorragiques à virus Lassa et Ebola dans le département de la Donga (Nord Bénin)

PubMed Central

Attinsounon, Cossi Angelo; Hounnankan, Cossi Athanase; Dovonou, Comlan Albert; Alassani, Cossi Adébayo; Salifou, Sourakatou

2017-01-01

Introduction L’objectif de cette étude était d’évaluer les connaissances et attitudes des relais communautaires vis-à-vis des fièvres hémorragiques à virus Ebola et Lassa et leur implication dans la mise œuvre des activités de prévention de ces maladies. Méthodes Une enquête transversale descriptive a été menée auprès des relais communautaires recrutés par tirage au sort dans 40 villages du département de la Donga. Ces relais faisaient la prise en charge à domicile des maladies respiratoires, diarrhéiques et du paludisme chez les enfants de moins de cinq ans. Un questionnaire anonyme a été administré par interview directe. Les données ont été analysées à l’aide du logiciel Epi-info 3.5.1. Résultats Au total 58 relais communautaires (RC) ont participé à cette enquête sur les 60 attendus. L’âge moyen était de 38,7±10,6 ans avec un sex-ratio de 3,5. Il y avait majoritairement trente cinq cultivateurs (60,3%) et treize revendeuses (22,4%). Quarante huit enquêtés (82,8%) reconnaissaient les deux maladies comme étant graves, mortelles et transmissibles. Les trois principales voies de transmission citées étaient le contact ou la consommation de gibiers (87,9%), le contact direct avec les personnes infectées (74,1%) ou leurs cadavres (46,6%). Les principaux moyens préventifs énumérés étaient en lien avec les voies de transmission. La fièvre (81,0%), les vomissements (81,0%) et la diarrhée (60,3%) venaient en tête des symptômes cités. Seulement vingt-deux RC (37,9%) disposaient de gants mais les utilisaient rarement pour examiner les enfants malades. Quant à la conduite à tenir devant un cas suspect de fièvre hémorragique virale Lassa ou Ebola, quarante-et-un relais communautaires (70,7%) feraient recours aux agents de santé sans toucher au malade, neuf (15,5%) feraient appel à l’ambulance et huit (13,8%) transporteraient le cas sur leur propre moto ou sur un taxi-moto vers le centre de santé le plus proche. Conclusion Le renforcement des capacités des relais communautaires sur les fièvres hémorragiques virales contribuerait à l’amélioration de leurs connaissances sur ces épidémies mortelles et à la qualité de leurs interventions dans la population. Introduction This study aimed to evaluate the knowledges and attitudes of community volunteers on Lassa and Ebola viral haemorrhagic fevers and their role in the implementation of activities for the prevention of these diseases. Methods We conducted a cross-sectional descriptive survey among community volunteers chosen by lot in 40 villages in the Donga Department. Children under five years of age with respiratory and diarrheal diseases and malaria were treated by these community volunteers in their home. An anonymous questionnaire was administered by direct interview. Data were analyzed using Epi-Info 3.5.1. Results Out of 60 community volunteers potentially participating in this survey a total of 58 effectively participated. The average age of community volunteers was 38.7 ± 10.6 years with a sex-ratio of 3.5. The majority of the community volunteers were farmers (thirty-five, 60.3%) and resellers (thirteen, 22.4%). Forty-eight respondents (82.8%) recognized the two diseases as being serious, life-threatening and transmissible. The three main routes of transmission cited were the contact with or the consumption of bushmeat (87.9%), the direct contact with infected people (74.1%) or with their corpses (46.6%). The main preventive measures listed were related to the routes of transmission. Fever (81.0%), vomiting (81.0%) and diarrhea (60.3%) were at the top of the cited symptoms. Only twenty-two community volunteers (37.9%) had gloves but they rarely used them to examine sick children. As regards the procedure to follow in case of suspected Lassa or Ebola viral haemorrhagic fever , forty-one community volunteers (70.7%) would make use of community-based health workers without touching the patient, nine (15.5%) would call for the ambulance and eight (13.8%) would take the patient to the nearest health center using their own motorcycle or a motorcycle-taxi. Conclusion Strengthening community volunteers’ capacity to manage viral hemorrhagic fevers would contribute to the improvement of their knowledge of these life-threatening epidemics and to the quality of population health interventions. PMID:28690743

Animal health care seeking behavior of pets or livestock owners and knowledge and awareness on zoonoses in a university community.

PubMed

Awosanya, Emmanuel J; Akande, H O

2015-07-01

We investigated the attitude of pets or livestock owning households in a university community to animal health care services and assessed the knowledge and awareness level of the residents on zoonoses. Structured questionnaire was used to obtain information on demography, pet or livestock ownership, animal health care seeking behavior, awareness and knowledge of zoonoses from 246 households. We did descriptive statistics and bivariate analysis to determine the level of association in discrete variables between owners and non-owners of pets or livestock at a significant level of p<0.05. Of the 246 respondents, 80 (32.5%) were either pet or livestock owners. The animal health care seeking behavior of the 80 pets or livestock owners in terms of treatment and vaccination was 70%. Of the 56 (70%) who provided health care services for their animals, about 48 (85.7%) engaged the services of a veterinarian. Dog owning households (42) had the highest frequency of treating their pets against endoparasites (97.6%); ectoparasites (81%) and vaccination against diseases (73.8%). Of the 246 respondents, only 47 (19.1%) have heard of the term zoonoses. Of the considered zoonoses; their awareness of rabies (79.3%) was the highest, followed by Lassa fever (66.3%), the least was pasteurellosis with 18.7%. Having pets or livestock was significantly associated (p=0.04) with rabies awareness. However, there is no significant difference in the level of awareness of zoonoses; knowledge of zoonoses, knowledge of prevention of zoonoses and knowledge of risk of zoonoses between owners and non-owners of pets or livestock. The animal health care seeking behavior of households with pets or livestock is good and should be encouraged. Public education should be created for other zoonoses aside from rabies, Lassa fever, and avian influenza.

Animal health care seeking behavior of pets or livestock owners and knowledge and awareness on zoonoses in a university community

PubMed Central

Awosanya, Emmanuel J.; Akande, H. O.

2015-01-01

Aim: We investigated the attitude of pets or livestock owning households in a university community to animal health care services and assessed the knowledge and awareness level of the residents on zoonoses. Materials and Methods: Structured questionnaire was used to obtain information on demography, pet or livestock ownership, animal health care seeking behavior, awareness and knowledge of zoonoses from 246 households. We did descriptive statistics and bivariate analysis to determine the level of association in discrete variables between owners and non-owners of pets or livestock at a significant level of p<0.05. Results: Of the 246 respondents, 80 (32.5%) were either pet or livestock owners. The animal health care seeking behavior of the 80 pets or livestock owners in terms of treatment and vaccination was 70%. Of the 56 (70%) who provided health care services for their animals, about 48 (85.7%) engaged the services of a veterinarian. Dog owning households (42) had the highest frequency of treating their pets against endoparasites (97.6%); ectoparasites (81%) and vaccination against diseases (73.8%). Of the 246 respondents, only 47 (19.1%) have heard of the term zoonoses. Of the considered zoonoses; their awareness of rabies (79.3%) was the highest, followed by Lassa fever (66.3%), the least was pasteurellosis with 18.7%. Having pets or livestock was significantly associated (p=0.04) with rabies awareness. However, there is no significant difference in the level of awareness of zoonoses; knowledge of zoonoses, knowledge of prevention of zoonoses and knowledge of risk of zoonoses between owners and non-owners of pets or livestock. Conclusion: The animal health care seeking behavior of households with pets or livestock is good and should be encouraged. Public education should be created for other zoonoses aside from rabies, Lassa fever, and avian influenza. PMID:27047163

Mapping of the Lassa virus LAMP1 binding site reveals unique determinants not shared by other old world arenaviruses.

PubMed

Israeli, Hadar; Cohen-Dvashi, Hadas; Shulman, Anastasiya; Shimon, Amir; Diskin, Ron

2017-04-01

Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1. However, when we investigated viruses that are genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.

Comprehensive Panel of Real-Time TaqMan™ Polymerase Chain Reaction Assays for Detection and Absolute Quantification of Filoviruses, Arenaviruses, and New World Hantaviruses

PubMed Central

Trombley, Adrienne R.; Wachter, Leslie; Garrison, Jeffrey; Buckley-Beason, Valerie A.; Jahrling, Jordan; Hensley, Lisa E.; Schoepp, Randal J.; Norwood, David A.; Goba, Augustine; Fair, Joseph N.; Kulesh, David A.

2010-01-01

Viral hemorrhagic fever is caused by a diverse group of single-stranded, negative-sense or positive-sense RNA viruses belonging to the families Filoviridae (Ebola and Marburg), Arenaviridae (Lassa, Junin, Machupo, Sabia, and Guanarito), and Bunyaviridae (hantavirus). Disease characteristics in these families mark each with the potential to be used as a biological threat agent. Because other diseases have similar clinical symptoms, specific laboratory diagnostic tests are necessary to provide the differential diagnosis during outbreaks and for instituting acceptable quarantine procedures. We designed 48 TaqMan™-based polymerase chain reaction (PCR) assays for specific and absolute quantitative detection of multiple hemorrhagic fever viruses. Forty-six assays were determined to be virus-specific, and two were designated as pan assays for Marburg virus. The limit of detection for the assays ranged from 10 to 0.001 plaque-forming units (PFU)/PCR. Although these real-time hemorrhagic fever virus assays are qualitative (presence of target), they are also quantitative (measure a single DNA/RNA target sequence in an unknown sample and express the final results as an absolute value (e.g., viral load, PFUs, or copies/mL) on the basis of concentration of standard samples and can be used in viral load, vaccine, and antiviral drug studies. PMID:20439981

Differential Immune Responses to New World and Old World Mammalian Arenaviruses

PubMed Central

Ly, Hinh

2017-01-01

Some New World (NW) and Old World (OW) mammalian arenaviruses are emerging, zoonotic viruses that can cause lethal hemorrhagic fever (HF) infections in humans. While these are closely related RNA viruses, the infected hosts appear to mount different types of immune responses against them. Lassa virus (LASV) infection, for example, results in suppressed immune function in progressive disease stage, whereas patients infected with Junín virus (JUNV) develop overt pro-inflammatory cytokine production. These viruses have also evolved different molecular strategies to evade host immune recognition and activation. This paper summarizes current progress in understanding the differential immune responses to pathogenic arenaviruses and how the information can be exploited toward the development of vaccines against them. PMID:28498311

Structural drivers of vulnerability to zoonotic disease in Africa.

PubMed

Dzingirai, Vupenyu; Bukachi, Salome; Leach, Melissa; Mangwanya, Lindiwe; Scoones, Ian; Wilkinson, Annie

2017-07-19

This paper argues that addressing the underlying structural drivers of disease vulnerability is essential for a 'One Health' approach to tackling zoonotic diseases in Africa. Through three case studies-trypanosomiasis in Zimbabwe, Ebola and Lassa fever in Sierra Leone and Rift Valley fever in Kenya-we show how political interests, commercial investments and conflict and securitization all generate patterns of vulnerability, reshaping the political ecology of disease landscapes, influencing traditional coping mechanisms and affecting health service provision and outbreak responses. A historical, political economy approach reveals patterns of 'structural violence' that reinforce inequalities and marginalization of certain groups, increasing disease risks. Addressing the politics of One Health requires analysing trade-offs and conflicts between interests and visions of the future. For all zoonotic diseases economic and political dimensions are ultimately critical and One Health approaches must engage with these factors, and not just end with an 'anti-political' focus on institutional and disciplinary collaboration.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'. © 2017 The Authors.

Structural drivers of vulnerability to zoonotic disease in Africa

PubMed Central

Bukachi, Salome; Mangwanya, Lindiwe; Scoones, Ian

2017-01-01

This paper argues that addressing the underlying structural drivers of disease vulnerability is essential for a ‘One Health’ approach to tackling zoonotic diseases in Africa. Through three case studies—trypanosomiasis in Zimbabwe, Ebola and Lassa fever in Sierra Leone and Rift Valley fever in Kenya—we show how political interests, commercial investments and conflict and securitization all generate patterns of vulnerability, reshaping the political ecology of disease landscapes, influencing traditional coping mechanisms and affecting health service provision and outbreak responses. A historical, political economy approach reveals patterns of ‘structural violence’ that reinforce inequalities and marginalization of certain groups, increasing disease risks. Addressing the politics of One Health requires analysing trade-offs and conflicts between interests and visions of the future. For all zoonotic diseases economic and political dimensions are ultimately critical and One Health approaches must engage with these factors, and not just end with an ‘anti-political’ focus on institutional and disciplinary collaboration. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’. PMID:28584177

Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses.

PubMed

Meyer, Bjoern; Ly, Hinh

2016-04-01

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Viral haemorrhagic fevers imported into non-endemic countries: risk assessment and management.

PubMed

Bannister, Barbara

2010-01-01

Viral haemorrhagic fevers (VHFs) are severe infections capable of causing haemorrhagic disease and fatal multi-organ failure. Crimean-Congo, Marburg, Ebola and Lassa viruses cause both sporadic cases and large epidemics over wide endemic areas. Original articles and reviews identified by PubMed search and personal reading; European and United States national guidance and legislation. World Health Organization information, documents and reports. VHFs cause significant morbidity and mortality in their endemic areas; they can cause healthcare-related infections, and their broad diversity and range are increasingly recognized. There is uncertainty about the risks presented by VHFs in non-endemic countries, particularly in healthcare environments. Consensus on the best modes of care and infection control are only slowly emerging. With increasing commerce in rural and low-income areas, VHF outbreaks increasingly expand, causing social and economic damage. New ecologies, viral strains and clinical syndromes are being discovered. There is a great need for rapid diagnostic tests and effective antiviral treatments. Vaccine development programmes are challenged by multiple viral strains and the need for trials in rural communities.

Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles [corrected].

PubMed

Strecker, Thomas; Eichler, Robert; Meulen, Jan ter; Weissenhorn, Winfried; Dieter Klenk, Hans; Garten, Wolfgang; Lenz, Oliver

2003-10-01

Lassa virus is an enveloped virus with glycoprotein spikes on its surface. It contains an RNA ambisense genome that encodes the glycoprotein precursor GP-C, the nucleoprotein NP, the polymerase L, and the Z protein. Here we demonstrate that the Lassa virus Z protein (i). is abundant in viral particles, (ii). is strongly membrane associated, (iii). is sufficient in the absence of all other viral proteins to release enveloped particles, and (iv). contains two late domains, PTAP and PPXY, necessary for the release of virus-like particles. Our data provide evidence that Z is the Lassa virus matrix protein that is the driving force for virus particle release.

Taking forward a 'One Health' approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential.

PubMed

Zumla, Alimuddin; Dar, Osman; Kock, Richard; Muturi, Matthew; Ntoumi, Francine; Kaleebu, Pontiano; Eusebio, Macete; Mfinanga, Sayoki; Bates, Matthew; Mwaba, Peter; Ansumana, Rashid; Khan, Mishal; Alagaili, Abdulaziz N; Cotten, Matthew; Azhar, Esam I; Maeurer, Markus; Ippolito, Giuseppe; Petersen, Eskild

2016-06-01

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a 'One Health' approach to control such zoonotic pathogens with epidemic potential. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Problems associated with the control of rodents in tropical Africa

PubMed Central

Gratz, N. G.; Arata, A. A.

1975-01-01

As elsewhere in the world, rodents are responsible for very considerable economic losses in tropical Africa because of their depredations on both growing crops and stored food products. Unfortunately, few accurate data are available on the extent of these losses but there is evidence that they are considerable. The public health importance of rodents, both as reservoirs and vectors of disease in tropical Africa, is also great; plague, leptospirosis, murine typhus, and Lassa fever are among the diseases associated with rodent hosts. Scientifically based rodent control programmes have been carried out in very few areas of Africa and there is urgent need for studies and demonstrations on rodent control in both urban and rural areas. The problems likely to be encountered are reviewed and methods of control proposed. PMID:1085224

A tribute to Sheik Humarr Khan and all the healthcare workers in West Africa who have sacrificed in the fight against Ebola virus disease: Mae we hush.

PubMed

Bausch, Daniel G; Bangura, James; Garry, Robert F; Goba, Augustine; Grant, Donald S; Jacquerioz, Frederique A; McLellan, Susan L; Jalloh, Simbirie; Moses, Lina M; Schieffelin, John S

2014-11-01

The Kenema Government Hospital Lassa Fever Ward in Sierra Leone, directed since 2005 by Dr. Sheikh Humarr Khan, is the only medical unit in the world devoted exclusively to patient care and research of a viral hemorrhagic fever. When Ebola virus disease unexpectedly appeared in West Africa in late 2013 and eventually spread to Kenema, Khan and his fellow healthcare workers remained at their posts, providing care to patients with this devastating illness. Khan and the chief nurse, Mbalu Fonnie, became infected and died at the end of July, a fate that they have sadly shared with more than ten other healthcare workers in Kenema and hundreds across the region. This article pays tribute to Sheik Humarr Khan, Mbalu Fonnie and all the healthcare workers who have acquired Ebola virus disease while fighting the epidemic in West Africa. Besides the emotional losses, the death of so many skilled and experienced healthcare workers will severely impair health care and research in affected regions, which can only be restored through dedicated, long-term programs. Copyright © 2014. Published by Elsevier B.V.

Isozyme and allozyme markers distinguishing two morphologically similar, medically important Mastomys species (Rodentia: Muridae)

PubMed Central

Smit, Andre A; Van der Bank, Herman FH

2001-01-01

Background Two common southern African mice species, Mastomys coucha and M. natalensis, are widely distributed throughout the subregion and overlap in many areas. They also share a high degree of morphological similarity, making them impossible to distinguish in the field at present. These multimammate mice are documented carriers of serious disease vectors causing Lassa fever, plague and encephalomyocarditis, which coupled to their cohabitation with humans in many areas, could pose a significant health risk. A preliminary study reported the presence of isozyme markers at three loci (GPI-2, PT-2, -3) in one population each of M. coucha and M. natalensis. Two additional populations (from the Vaal Dam and Richards Bay) were sampled to determine the reliability of these markers, and to seek additional genetic markers. Results Fifteen proteins or enzymes provided interpretable results at a total of 39 loci. Additional fixed allele differences between the species were detected at AAT-1, ADH, EST-1, PGD-1, Hb-1 and -2. Average heterozygosities for M. coucha and M. natalensis were calculated as 0.018 and 0.032 respectively, with a mean genetic distance between the species of 0.26. Conclusions The confirmation of the isozyme and the detection of the additional allozyme markers are important contributions to the identification of these two medical and agricultural pest species. PMID:11696236

The model of response to viral haemorrhagic fevers of the National Institute for Infectious Diseases "Lazzaro Spallanzani".

PubMed

Armignacco, O; Lauria, F N; Puro, V; Macrì, G; Petrecchia, A; Ippolito, G

2001-01-01

Viral haemorrhagic fevers (VHF) are severe and life-threatening diseases caused by a range of viruses. However, only four agents of VHF are known to be readily capable of person-to-person spread: Lassa virus, Crimean/Congo haemorrhagic fever virus, Ebola and Marburg viruses. Diseases caused by these viruses are endemic only in few areas in the world, most notably Africa and some rural parts of the Middle East and Eastern Europe. Nonetheless, the increasing volume of international travel presents a greater likelihood for the importation of these infections or of suspected cases in non endemic countries. Four conditions can lead to the importation and to the subsequent recognition of VHF within Europe: 1) patients arriving as a result of a planned medical evacuation; 2) persons who became sick on route to their destination; 3) persons discovered ill when entering a country, for example during routine clinical examination at the airport; 4) persons becoming sick after their arrival. Public health implications and the risk of secondary spread of pathogens in the above reported circumstances are very different. Similarly, preparedness and response should vary. This paper summarizes the present knowledge on the four VHF capable of person-to-person spread, describes the high isolation area constructed at the Italian National Institute for Infectious Diseases Lazzaro Spallanzani in Rome to respond to the occurrence of VHF. A brief overview of procedures and equipment adopted is provided.

Role of LAMP1 Binding and pH Sensing by the Spike Complex of Lassa Virus.

PubMed

Cohen-Dvashi, Hadas; Israeli, Hadar; Shani, Orly; Katz, Aliza; Diskin, Ron

2016-11-15

To effectively infect cells, Lassa virus needs to switch in an endosomal compartment from its primary receptor, α-dystroglycan, to a protein termed LAMP1. A unique histidine triad on the surface of the receptor-binding domain from the glycoprotein spike complex of Lassa virus is important for LAMP1 binding. Here we investigate mutated spikes that have an impaired ability to interact with LAMP1 and show that although LAMP1 is important for efficient infectivity, it is not required for spike-mediated membrane fusion per se Our studies reveal important regulatory roles for histidines from the triad in sensing acidic pH and preventing premature spike triggering. We further show that LAMP1 requires a positively charged His230 residue to engage with the spike complex and that LAMP1 binding promotes membrane fusion. These results elucidate the molecular role of LAMP1 binding during Lassa virus cell entry and provide new insights into how pH is sensed by the spike. Lassa virus is a devastating disease-causing agent in West Africa, with a significant yearly death toll and severe long-term complications associated with its infection in survivors. In recent years, we learned that Lassa virus needs to switch receptors in a pH-dependent manner to efficiently infect cells, but neither the molecular mechanisms that allow switching nor the actual effects of switching were known. Here we investigate the activity of the viral spike complex after abrogation of its ability to switch receptors. These studies inform us about the role of switching receptors and provide new insights into how the spike senses acidic pH. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Arenaviruses. Genes, proteins, and expression

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

Oldstone, M.B.A.

1987-01-01

This book provides a discussion of current knowledge on Arenaviruses. These viruses are the cause of major health problems, such as Lassa fever and Junin virus disease, and have been the Rosetta stone on which many of the major concepts in viral pathogenesis and immunobiology have been built. For example, study of lymphocytic choriomeningitis naturally and experimentally induced infection in the normal mouse host presented the scientific community with the first and definitive work on the following topics: virus induced immune response disease, immunologic tolerance, virus induced immune complex disease, presence and generation of cytotoxic T cells in vitro andmore » in vivo, H-2 restriction and dual recognition phenomena, and viral disease induced by altering physiologic or differential functions of a cell without causing alterations of house keeping or vital functions, i.e. pathology in the absence of cell or tissue lysis.« less

Chimpanzee adenoviral vectors as vaccines for outbreak pathogens

PubMed Central

2017-01-01

ABSTRACT The 2014–15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemics. Here we discuss drivers, strategies and practical considerations for developing vaccines against outbreak pathogens. Chimpanzee adenoviral (ChAd) vectors have been developed as vaccine candidates for multiple infectious diseases and prostate cancer. ChAd vectors are safe and induce antigen-specific cellular and humoral immunity in all age groups, as well as circumventing the problem of pre-existing immunity encountered with human Ad vectors. For these reasons, such viral vectors provide an attractive platform for stockpiling vaccines for emergency deployment in response to a threatened outbreak of an emerging pathogen. Work is already underway to develop vaccines against a number of other outbreak pathogens and we will also review progress on these approaches here, particularly for Lassa fever, Nipah and MERS. PMID:29083948

Mammarenaviruses deleted from their Z gene are replicative and produce an infectious progeny in BHK-21 cells.

PubMed

Zaza, Amélie D; Herbreteau, Cécile H; Peyrefitte, Christophe N; Emonet, Sébastien F

2018-05-01

Mammarenaviruses bud out of infected cells via the recruitment of the endosomal sorting complex required for transport through late domain motifs localized into their Z protein. Here, we demonstrated that mammarenaviruses lacking this protein can be rescued and are replicative, despite a 3-log reduction in virion production, in BHK-21 cells, but not in five other cell lines. Mutations of putative late domain motifs identified into the viral nucleoprotein resulted in the almost complete abolition of infectious virion production by Z-deleted mammarenaviruses. This result strongly suggested that the nucleoprotein may compensate for the deletion of Z. These observations were primarily obtained using the Lymphocytic choriomeningitis virus, and further confirmed using the Old World Lassa and New World Machupo viruses, responsible of human hemorrhagic fevers. Z-deleted viruses should prove very useful tools to investigate the biology of Mammarenaviruses. Copyright © 2018 Elsevier Inc. All rights reserved.

Local disease–ecosystem–livelihood dynamics: reflections from comparative case studies in Africa

PubMed Central

Bett, Bernard; Said, M.; Bukachi, Salome; Sang, Rosemary; Anderson, Neil; Machila, Noreen; Kuleszo, Joanna; Schaten, Kathryn; Mangwanya, Lindiwe; Ntiamoa-Baidu, Yaa; Lawson, Elaine; Amponsah-Mensah, Kofi; Moses, Lina M.; Grant, Donald S.; Koninga, James

2017-01-01

This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human–ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples’ interactions with ecosystems and animals affect their exposure to disease. Cross-case analysis highlights how these dynamics vary by ecosystem type, across a range from humid forest to semi-arid savannah; the significance of interacting temporal and spatial scales; and the importance of mosaic and patch dynamics. Ecosystem interactions and services central to different people's livelihoods and well-being include pastoralism and agro-pastoralism, commercial and subsistence crop farming, hunting, collecting food, fuelwood and medicines, and cultural practices. There are synergies, but also tensions and trade-offs, between ecosystem changes that benefit livelihoods and affect disease. Understanding these can inform ‘One Health’ approaches towards managing ecosystems in ways that reduce disease risks and burdens. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’. PMID:28584171

Local disease-ecosystem-livelihood dynamics: reflections from comparative case studies in Africa.

PubMed

Leach, Melissa; Bett, Bernard; Said, M; Bukachi, Salome; Sang, Rosemary; Anderson, Neil; Machila, Noreen; Kuleszo, Joanna; Schaten, Kathryn; Dzingirai, Vupenyu; Mangwanya, Lindiwe; Ntiamoa-Baidu, Yaa; Lawson, Elaine; Amponsah-Mensah, Kofi; Moses, Lina M; Wilkinson, Annie; Grant, Donald S; Koninga, James

2017-07-19

This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human-ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples' interactions with ecosystems and animals affect their exposure to disease. Cross-case analysis highlights how these dynamics vary by ecosystem type, across a range from humid forest to semi-arid savannah; the significance of interacting temporal and spatial scales; and the importance of mosaic and patch dynamics. Ecosystem interactions and services central to different people's livelihoods and well-being include pastoralism and agro-pastoralism, commercial and subsistence crop farming, hunting, collecting food, fuelwood and medicines, and cultural practices. There are synergies, but also tensions and trade-offs, between ecosystem changes that benefit livelihoods and affect disease. Understanding these can inform 'One Health' approaches towards managing ecosystems in ways that reduce disease risks and burdens.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'. © 2017 The Authors.

A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread.

PubMed

Lo Iacono, Giovanni; Cunningham, Andrew A; Fichet-Calvet, Elisabeth; Garry, Robert F; Grant, Donald S; Leach, Melissa; Moses, Lina M; Nichols, Gordon; Schieffelin, John S; Shaffer, Jeffrey G; Webb, Colleen T; Wood, James L N

2016-09-01

A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.

A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread

PubMed Central

Cunningham, Andrew A.; Fichet-Calvet, Elisabeth; Garry, Robert F.; Grant, Donald S.; Leach, Melissa; Moses, Lina M.; Nichols, Gordon; Schieffelin, John S.; Shaffer, Jeffrey G.; Webb, Colleen T.; Wood, James L. N.

2016-01-01

A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: ‘spillover’, i.e. transmission of pathogens from animals to humans, and ‘stuttering transmission’, i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir. PMID:27588425

Insight into the binding modes of Lassa nucleoprotein complexed with ssRNA by molecular dynamic simulations and free energy calculations.

PubMed

Zhang, Ying; Chen, Hang; Han, Ju-Guang

2015-01-01

Lassa virus (LASV), an arenavirus known to be responsible for a severe hemorrhagic fever, causes thousands of deaths annually and there is no effective vaccine for it so far. The nucleoprotein (NP) of LASV plays an essential role in the replication and transcription of the viral genome. Recent research shows that viral RNA binds in a deep crevice located within the N-terminal domain of NP and suggests a gating mechanism in which NP transforms from a "closed" position to an "open" position to bind RNA. To characterize the molecular mechanisms of how RNA binds to N-terminal domain of NP, two molecular dynamic (MD) simulations of RNA-binding structure and RNA-free structure have been performed. The simulation results show that an important helix α6 interacts with RNA in the "open" conformation, while helix α6 rotates toward the binding crevice and reduces the space of RNA-binding pocket in the "closed" conformation; it appears that helix α6 would clash with RNA while NP is in a "closed" state. In addition, to characterize the role of residues involved in the binding of RNA, the MD simulations of the double-mutant (W164A/F176A) and the single-mutant (G243P) RNA-binding NP complexes have been performed. Our MD simulations and molecular mechanics-generalized born surface area (MM-GBSA) energy calculations exhibit that the three mutant residues increase the binding affinity. Furthermore, we infer that the defect of the replication and transcription of viral genome is possibly due to the change of structural integrity rather than the reduction of RNA-binding affinity.

A Case of Human Lassa Virus Infection With Robust Acute T-Cell Activation and Long-Term Virus-Specific T-Cell Responses.

PubMed

McElroy, Anita K; Akondy, Rama S; Harmon, Jessica R; Ellebedy, Ali H; Cannon, Deborah; Klena, John D; Sidney, John; Sette, Alessandro; Mehta, Aneesh K; Kraft, Colleen S; Lyon, Marshall G; Varkey, Jay B; Ribner, Bruce S; Nichol, Stuart T; Spiropoulou, Christina F

2017-06-15

A nurse who acquired Lassa virus infection in Togo in the spring of 2016 was repatriated to the United States for care at Emory University Hospital. Serial sampling from this patient permitted the characterization of several aspects of the innate and cellular immune responses to Lassa virus. Although most of the immune responses correlated with the kinetics of viremia resolution, the CD8 T-cell response was of surprisingly high magnitude and prolonged duration, implying prolonged presentation of viral antigens. Indeed, long after viremia resolution, there was persistent viral RNA detected in the semen of the patient, accompanied by epididymitis, suggesting the male reproductive tract as 1 site of antigen persistence. Consistent with the magnitude of acute T-cell responses, the patient ultimately developed long-term, polyfunctional memory T-cell responses to Lassa virus. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

PubMed

Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; Mazur, Steven; Deiuliis, Nicole M; Radoshitzky, Sheli R; Lackemeyer, Matthew G; McCluskey, Adam; Robinson, Phillip J; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L; Lauck, Michael; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

2015-01-01

Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin-independent endocytosis, likely with the help of a cellular surface protein. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Shipping lanes or offshore rigs

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

Not Available

1980-09-01

This information was from the Los Angeles Steamship Association (LASSA) luncheon meeting. The problems of limiting access and availability of the Santa Barbara/Santa Catalina channels to commercial vessel traffic and other related uses. LASSA speaks for about 85% of the maritime industry in Southern California. The Association is actively seeking a compromise with the oil companies in keeping the Vessel Traffic Separation Scheme (VTSS) in the channels; however, the Western Oil and Gas Association (WOGA) is seeking to abolish VTSS as currently established in the channels and move the sea lanes outside the Channel Islands, and open up the entiremore » Santa Barbara Channel to unlimited drilling sites. LASSA claims that moving the VTSS sea lanes outside of the Channel Islands would add 18 to 22 miles to the average trip from San Francisco to Los Angeles, with fuel cost etc. would make for a big loss to the merchant ship operators. LASSA has offered to support the concept of opening up the Buffer Zone that separates the Sea Lanes themselves to exploratory drilling. This two mile wide stretch of water is off limits to vessels and it would open new areas to the oil companies heretofore unaccessible to them. (DP)« less

US Federal Travel Restrictions for Persons with Higher-Risk Exposures to Communicable Diseases of Public Health Concern.

PubMed

Vonnahme, Laura A; Jungerman, M Robynne; Gulati, Reena K; Illig, Petra; Alvarado-Ramy, Francisco

2017-12-01

Published guidance recommends controlled movement for persons with higher-risk exposures (HREs) to communicable diseases of public health concern; US federal public health travel restrictions (PHTRs) might be implemented to enforce these measures. We describe persons eligible for and placed on PHTRs because of HREs during 2014-2016. There were 160 persons placed on PHTRs: 142 (89%) involved exposure to Ebola virus, 16 (10%) to Lassa fever virus, and 2 (1%) to Middle East respiratory syndrome coronavirus. Most (90%) HREs were related to an epidemic. No persons attempted to travel; all persons had PHTRs lifted after completion of a maximum disease-specific incubation period or a revised exposure risk classification. PHTR enforced controlled movement and removed risk for disease transmission among travelers who had contacts who refused to comply with public health recommendations. PHTRs are mechanisms to mitigate spread of communicable diseases and might be critical in enhancing health security during epidemics.

A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

PubMed Central

Madrid, Peter B.; Chopra, Sidharth; Manger, Ian D.; Gilfillan, Lynne; Keepers, Tiffany R.; Shurtleff, Amy C.; Green, Carol E.; Iyer, Lalitha V.; Dilks, Holli Hutcheson; Davey, Robert A.; Kolokoltsov, Andrey A.; Carrion, Ricardo; Patterson, Jean L.; Bavari, Sina; Panchal, Rekha G.; Warren, Travis K.; Wells, Jay B.; Moos, Walter H.; Burke, RaeLyn L.; Tanga, Mary J.

2013-01-01

Background The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. Methodology/Principal Findings A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. Conclusions/Significance The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses. PMID:23577127

Lassa-Vesicular Stomatitis Chimeric Virus Safely Destroys Brain Tumors

PubMed Central

Wollmann, Guido; Drokhlyansky, Eugene; Davis, John N.; Cepko, Connie

2015-01-01

ABSTRACT High-grade tumors in the brain are among the deadliest of cancers. Here, we took a promising oncolytic virus, vesicular stomatitis virus (VSV), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic VSV glycoprotein with the glycoprotein from one of five different viruses, including Ebola virus, Marburg virus, lymphocytic choriomeningitis virus (LCMV), rabies virus, and Lassa virus. Based on in vitro infections of normal and tumor cells, we selected two viruses to test in vivo. Wild-type VSV was lethal when injected directly into the brain. In contrast, a novel chimeric virus (VSV-LASV-GPC) containing genes from both the Lassa virus glycoprotein precursor (GPC) and VSV showed no adverse actions within or outside the brain and targeted and completely destroyed brain cancer, including high-grade glioblastoma and melanoma, even in metastatic cancer models. When mice had two brain tumors, intratumoral VSV-LASV-GPC injection in one tumor (glioma or melanoma) led to complete tumor destruction; importantly, the virus moved contralaterally within the brain to selectively infect the second noninjected tumor. A chimeric virus combining VSV genes with the gene coding for the Ebola virus glycoprotein was safe in the brain and also selectively targeted brain tumors but was substantially less effective in destroying brain tumors and prolonging survival of tumor-bearing mice. A tropism for multiple cancer types combined with an exquisite tumor specificity opens a new door to widespread application of VSV-LASV-GPC as a safe and efficacious oncolytic chimeric virus within the brain. IMPORTANCE Many viruses have been tested for their ability to target and kill cancer cells. Vesicular stomatitis virus (VSV) has shown substantial promise, but a key problem is that if it enters the brain, it can generate adverse neurologic consequences, including death. We tested a series of chimeric viruses containing genes coding for VSV, together with a gene coding for the glycoprotein from other viruses, including Ebola virus, Lassa virus, LCMV, rabies virus, and Marburg virus, which was substituted for the VSV glycoprotein gene. Ebola and Lassa chimeric viruses were safe in the brain and targeted brain tumors. Lassa-VSV was particularly effective, showed no adverse side effects even when injected directly into the brain, and targeted and destroyed two different types of deadly brain cancer, including glioblastoma and melanoma. PMID:25878115

Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

PubMed

Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

2012-09-01

Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs.

Shedding of Soluble Glycoprotein 1 Detected During Acute Lassa Virus Infection in Human Subjects

DTIC Science & Technology

2010-11-09

12701 - 12705. 29. Urata S, Noda T , Kawaoka Y, Yokosawa H, Yasuda J: Cellular factors required for Lassa virus budding. J Virol 2006, (8):4191 - 4195...and exposed to HyBlot CL Film (Denville Scientific, Inc). Blots used in reprobing experiments were briefly rinsed in PBS- T (1X PBS, pH 7.4, 0.1...Blots were then washed extensively in PBS- T , re-blocked, and reprobed as outlined above. Blots were reprobed a maximum of three times. - 16

Rapid deployment of a mobile biosafety level-3 laboratory in Sierra Leone during the 2014 Ebola virus epidemic

PubMed Central

Zhang, Yi; Gong, Yan; Wang, Chengyu; Liu, Wensen; Wang, Zhongyi; Xia, Zhiping; Bu, Zhaoyang; Lu, Huijun; Sun, Yang; Zhang, Xiaoguang; Cao, Yuxi; Yang, Fan; Su, Haoxiang; Hu, Yi; Deng, Yongqiang; Zhou, Bo; Zhao, Zongzheng; Fu, Yingying; Kargbo, David; Dafae, Foday; Kargbo, Brima; Kanu, Alex; Qian, Jun; Guo, Zhendong

2017-01-01

Background Ebola virus emerged in West Africa in December 2013. The high population mobility and poor public health infrastructure in this region led to the development of the largest Ebola virus disease (EVD) outbreak to date. Methodology/Principal findings On September 26, 2014, China dispatched a Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which allowed the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving. This laboratory was composed of three container vehicles equipped with advanced ventilation system, communication system, electricity and gas supply system. We strictly applied multiple safety precautions to reduce exposure risks. Personnel, materials, water and air flow management were the key elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols was detected. Potentially contaminated objects were also tested by collecting swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635 suspected EVD cases (824 positive [50.4%]) were tested from September 28 to November 11, 2014, and no member of the diagnostic team was infected with Ebola virus or other pathogens, including Lassa fever. The specimens tested included blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%, respectively. The China mobile laboratory was thus instrumental in the EVD outbreak response by providing timely and reliable diagnostics. Conclusions/Significance The MBSL-3 Lab significantly contributed to establishing a suitable laboratory response capacity during the emergence of EVD in Sierra Leone. PMID:28505171

Disinfection of aircraft : Appropriate disinfectants and standard operating procedures for highly infectious diseases.

PubMed

Klaus, Joachim; Gnirs, Peter; Hölterhoff, Sabine; Wirtz, Angela; Jeglitza, Matthias; Gaber, Walter; Gottschalk, Rene

2016-12-01

For infectious diseases caused by highly pathogenic agents (e. g., Ebola/Lassa fever virus, SARS-/MERS-CoV, pandemic influenza virus) which have the potential to spread over several continents within only a few days, international Health Protection Authorities have taken appropriate measures to limit the consequences of a possible spread. A crucial point in this context is the disinfection of an aircraft that had a passenger on board who is suspected of being infected with one of the mentioned diseases. Although, basic advice on hygiene and sanitation on board an aircraft is given by the World Health Organization, these guidelines lack details on available and effective substances as well as standardized operating procedures (SOP). The purpose of this paper is to give guidance on the choice of substances that were tested by a laboratory of Lufthansa Technik and found compatible with aircraft components, as well as to describe procedures which ensure a safe and efficient disinfection of civil aircrafts. This guidance and the additional SOPs are made public and are available as mentioned in this paper.

Activation of the maternal caregiving system by childhood fever – a qualitative study of the experiences made by mothers with a German or a Turkish background in the care of their children

PubMed Central

2013-01-01

Background Childhood fever represents a frequent cause to consult a primary care physician. “Fever phobia” describes a fearful and irrational view of fever shared by many parents with different cultural backgrounds. The study aims to explain the experiences of mothers of children having a fever and to analyze the role of the mothers’ cultural background with regard to their experiences by comparing the accounts of mothers with a German with those from a Turkish background. Disease and context specific knowledge about the influence of culture can be important for effective counselling. Methods We applied a qualitative approach using in-depth interviews with 11 mothers with a Turkish and 9 with a German background living in Germany. The interviews were conducted at the participants´ homes from May to October 2008. Data was audio-recorded and transcribed verbatim. Grounded Theory was used as a framing methodology including open, axial and selective coding. Analysis was performed in a group with members of different professional and cultural backgrounds. Results Mothers experienced their child’s fever not merely as elevated temperature but as a potentially dangerous event. A deeply rooted urge to protect the child from harm was central to all participants’ experience. The caregiving system model offers a good theoretical foundation to explain the findings as it incorporates the unique relational quality of care giving mothers to their children. The cultural background represents an important context variable influencing the explanatory models and strategies of dealing with fever. The identified culturally influenced concepts sometimes match and sometimes conflict with medical knowledge. Conclusion By applying the caregiving system model which is a part of attachment theory (Bowlby) maternal actions can be understood as an understandable attempt to protect the child from harm. The mothers´ decisions what to do when a child has a fever can be culturally influenced. This may lead either to a frequent use of services or to an underestimation of the child’s state of health. The mothers´ caring role and emotional state should be acknowledged; her concerns, explanatory models and strategies should be elicited and taken seriously in order to maintain a trustful relationship, provide effective counselling and thereby insuring optimal care for the children. PMID:23506372

Fearful or functional - a cross-sectional survey of the concepts of childhood fever among German and Turkish mothers in Germany

PubMed Central

2011-01-01

Background Fever is one of the most common presenting complaints in paediatrics and general practice. In the majority of cases nothing harmful is diagnosed. However, the subjective meaning of fever often varies between doctors and parents. Knowledge of the parents' concept of fever may help tailor counselling to their needs. In this study we determine 1) the influence of socio-economic status and cultural background on two concepts of fever which we labelled "functional" and "fearful", each representing typical experiences of mothers, and 2) the actions taken by the mothers related to these concepts. Methods A standardized interview study was conducted among German and Turkish mothers in Germany in 2009. The questionnaire consisted of 36 questions and 205 items. Interviews were conducted in 16 private practices of paediatricians and 2 paediatric emergency departments in an urban region of Germany. The two fever concepts were represented in 6 statements that could be rated with a six-point Likert scale. The association of the socio-economic status and the cultural background with one of the fever concepts was determined by a multiple logistic regression. Results A total of 338 mothers (49% with a Turkish background) completed the interview (response rate 92%). The average age of mothers with a German background was higher (34.1 years vs. 32.0 years, p = 0.0001). Mothers with a Turkish background were more likely to relate to the concept "fearful" [adjusted Odds Ratio (AOR) 1.99; confidence interval (CI) 1.16-3.44]. Mothers with a middle or high socio-economic status were more likely to respond to the concept "functional" [middle: AOR, 0.53; CI, 0.30-0.92; high: AOR, 0.44; CI, 0.21-0.95]. Mothers adhering to the concept "fearful" more often gave acetaminophen before the recommended interval of 6 hours (46.8% vs. 31.3%, p = 0.005) and visited out-of-hours services more frequently in the preceding 9 months than the other group (0.7 vs. 0.4, p = 0.001). Conclusions A Turkish migrant background and a low socio-economic status are associated with the fever concept "fearful". Mothers with these attributes seem to require specific and reassuring counselling as they use antipyretic drugs extensively and out-of-hours services frequently. PMID:21605413

Activation of the maternal caregiving system by childhood fever--a qualitative study of the experiences made by mothers with a German or a Turkish background in the care of their children.

PubMed

Langer, Thorsten; Pfeifer, Miriam; Soenmez, Aynur; Kalitzkus, Vera; Wilm, Stefan; Schnepp, Wilfried

2013-03-18

Childhood fever represents a frequent cause to consult a primary care physician. "Fever phobia" describes a fearful and irrational view of fever shared by many parents with different cultural backgrounds. The study aims to explain the experiences of mothers of children having a fever and to analyze the role of the mothers' cultural background with regard to their experiences by comparing the accounts of mothers with a German with those from a Turkish background. Disease and context specific knowledge about the influence of culture can be important for effective counselling. We applied a qualitative approach using in-depth interviews with 11 mothers with a Turkish and 9 with a German background living in Germany. The interviews were conducted at the participants' homes from May to October 2008. Data was audio-recorded and transcribed verbatim. Grounded Theory was used as a framing methodology including open, axial and selective coding. Analysis was performed in a group with members of different professional and cultural backgrounds. Mothers experienced their child's fever not merely as elevated temperature but as a potentially dangerous event. A deeply rooted urge to protect the child from harm was central to all participants' experience. The caregiving system model offers a good theoretical foundation to explain the findings as it incorporates the unique relational quality of care giving mothers to their children. The cultural background represents an important context variable influencing the explanatory models and strategies of dealing with fever. The identified culturally influenced concepts sometimes match and sometimes conflict with medical knowledge. By applying the caregiving system model which is a part of attachment theory (Bowlby) maternal actions can be understood as an understandable attempt to protect the child from harm. The mothers' decisions what to do when a child has a fever can be culturally influenced. This may lead either to a frequent use of services or to an underestimation of the child's state of health. The mothers' caring role and emotional state should be acknowledged; her concerns, explanatory models and strategies should be elicited and taken seriously in order to maintain a trustful relationship, provide effective counselling and thereby insuring optimal care for the children.

Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

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

Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

1982-10-01

Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose permore » rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.« less

Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

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

Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

1982-10-01

Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose permore » rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.« less

Comparative Structural and Functional Analysis of Bunyavirus and Arenavirus Cap-Snatching Endonucleases

PubMed Central

Reguera, Juan; Gerlach, Piotr; Rosenthal, Maria; Gaudon, Stephanie; Coscia, Francesca; Günther, Stephan; Cusack, Stephen

2016-01-01

Segmented negative strand RNA viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mRNA transcription by the cap-snatching mechanism. This involves cleavage of host mRNAs close to their capped 5′ end by an endonuclease (EN) domain located in the N-terminal region of the viral polymerase. We present the structure of the cap-snatching EN of Hantaan virus, a bunyavirus belonging to hantavirus genus. Hantaan EN has an active site configuration, including a metal co-ordinating histidine, and nuclease activity similar to the previously reported La Crosse virus and Influenza virus ENs (orthobunyavirus and orthomyxovirus respectively), but is more active in cleaving a double stranded RNA substrate. In contrast, Lassa arenavirus EN has only acidic metal co-ordinating residues. We present three high resolution structures of Lassa virus EN with different bound ion configurations and show in comparative biophysical and biochemical experiments with Hantaan, La Crosse and influenza ENs that the isolated Lassa EN is essentially inactive. The results are discussed in the light of EN activation mechanisms revealed by recent structures of full-length influenza virus polymerase. PMID:27304209

Fearful or functional--a cross-sectional survey of the concepts of childhood fever among German and Turkish mothers in Germany.

PubMed

Langer, Thorsten; Pfeifer, Miriam; Soenmez, Aynur; Tarhan, Bilge; Jeschke, Elke; Ostermann, Thomas

2011-05-23

Fever is one of the most common presenting complaints in paediatrics and general practice. In the majority of cases nothing harmful is diagnosed. However, the subjective meaning of fever often varies between doctors and parents. Knowledge of the parents' concept of fever may help tailor counselling to their needs.In this study we determine 1) the influence of socio-economic status and cultural background on two concepts of fever which we labelled "functional" and "fearful", each representing typical experiences of mothers, and 2) the actions taken by the mothers related to these concepts. A standardized interview study was conducted among German and Turkish mothers in Germany in 2009. The questionnaire consisted of 36 questions and 205 items. Interviews were conducted in 16 private practices of paediatricians and 2 paediatric emergency departments in an urban region of Germany. The two fever concepts were represented in 6 statements that could be rated with a six-point Likert scale. The association of the socio-economic status and the cultural background with one of the fever concepts was determined by a multiple logistic regression. A total of 338 mothers (49% with a Turkish background) completed the interview (response rate 92%). The average age of mothers with a German background was higher (34.1 years vs. 32.0 years, p=0.0001). Mothers with a Turkish background were more likely to relate to the concept "fearful" [adjusted Odds Ratio (AOR) 1.99; confidence interval (CI) 1.16-3.44]. Mothers with a middle or high socio-economic status were more likely to respond to the concept "functional" [middle: AOR, 0.53; CI, 0.30-0.92; high: AOR, 0.44; CI, 0.21-0.95].Mothers adhering to the concept "fearful" more often gave acetaminophen before the recommended interval of 6 hours (46.8% vs. 31.3%, p=0.005) and visited out-of-hours services more frequently in the preceding 9 months than the other group (0.7 vs. 0.4, p=0.001). A Turkish migrant background and a low socio-economic status are associated with the fever concept "fearful". Mothers with these attributes seem to require specific and reassuring counselling as they use antipyretic drugs extensively and out-of-hours services frequently.

Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

PubMed Central

Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A.; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D.

2015-01-01

Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein’s globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy. PMID:26587982

Favipiravir Pharmacokinetics in Nonhuman Primates and Insights for Future Efficacy Studies of Hemorrhagic Fever Viruses.

PubMed

Madelain, Vincent; Guedj, Jérémie; Mentré, France; Nguyen, Thi Huyen Tram; Jacquot, Frédéric; Oestereich, Lisa; Kadota, Takumi; Yamada, Koichi; Taburet, Anne-Marie; de Lamballerie, Xavier; Raoul, Hervé

2017-01-01

Favipiravir is an RNA polymerase inhibitor that showed strong antiviral efficacy in vitro and in small-animal models of several viruses responsible for hemorrhagic fever (HF), including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in nonhuman primates (NHPs) in order to guide future efficacy studies of favipiravir in large-animal models. Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n = 17) or Mauritian (n = 13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg of body weight twice a day (BID). A pharmacokinetic model was developed to predict the plasma concentrations obtained with different dosing regimens, and the model predictions were compared to the 50% effective concentration (EC 50 ) of favipiravir against several viruses. Favipiravir pharmacokinetics were described by a model accounting for concentration-dependent aldehyde oxidase inhibition. The enzyme-dependent elimination rate increased over time and was higher in NHPs of Mauritian origin than in those of Chinese origin. Maintenance doses of 100 and 120 mg/kg BID in Chinese and Mauritian NHPs, respectively, are predicted to achieve median trough plasma free concentrations above the EC 50 for Lassa and Marburg viruses until day 7. For Ebola virus, higher doses are required. After day 7, a 20% dose increase is needed to compensate for the increase in drug clearance over time. These results will help rationalize the choice of dosing regimens in future studies evaluating the antiviral effect of favipiravir in NHPs and support its development against a variety of HF viruses. Copyright © 2016 American Society for Microbiology.

Rapid detection of all known ebolavirus species by reverse transcription-loop-mediated isothermal amplification (RT-LAMP).

PubMed

Oloniniyi, Olamide K; Kurosaki, Yohei; Miyamoto, Hiroko; Takada, Ayato; Yasuda, Jiro

2017-08-01

Ebola virus disease (EVD), a highly virulent infectious disease caused by ebolaviruses, has a fatality rate of 25-90%. Without a licensed chemotherapeutic agent or vaccine for the treatment and prevention of EVD, control of outbreaks requires accurate and rapid diagnosis of cases. In this study, five sets of six oligonucleotide primers targeting the nucleoprotein gene were designed for specific identification of each of the five ebolavirus species using reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay. The detection limits of the ebolavirus species-specific primer sets were evaluated using in vitro transcribed RNAs. The detection limit of species-specific RT-LAMP assays for Zaire ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, and Bundibugyo ebolavirus was 256 copies/reaction, while the detection limit for Reston ebolavirus was 64 copies/reaction, and the detection time for each of the RT-LAMP assays was 13.3±3.0, 19.8±4.6, 14.3±0.6, 16.1±4.7, and 19.8±2.4min (mean±SD), respectively. The sensitivity of the species-specific RT-LAMP assays were similar to that of the established RT-PCR and quantitative RT-PCR assays for diagnosis of EVD and are suitable for field or point-of-care diagnosis. The RT-LAMP assays were specific for the detection of the respective species of ebolavirus with no cross reaction with other species of ebolavirus and other viral hemorrhagic fever viruses such as Marburg virus, Lassa fever virus, and Dengue virus. The species-specific RT-LAMP assays developed in this study are rapid, sensitive, and specific and could be useful in case of an EVD outbreak. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevention of Dengue Fever: An Exploratory School-Community Intervention Involving Students Empowered as Change Agents

ERIC Educational Resources Information Center

Jayawardene, Wasantha P.; Lohrmann, David K.; YoussefAgha, Ahmed H.; Nilwala, Dayani C.

2011-01-01

Background: Dengue fever and dengue hemorrhagic fever (DF/DHF) are epidemic and endemic in tropical and subtropical countries including Sri Lanka. Numerous structural and community interventions have been shown to be effective in interrupting the life cycle of mosquitoes that transmit DF/DHF; however, these interventions are not always implemented…

First Calderón Prize

NASA Astrophysics Data System (ADS)

Rundell, William; Somersalo, Erkki

2008-07-01

The Inverse Problems International Association (IPIA) awarded the first Calderón Prize to Matti Lassas for his outstanding contributions to the field of inverse problems, especially in geometric inverse problems. The Calderón Prize is given to a researcher under the age of 40 who has made distinguished contributions to the field of inverse problems broadly defined. The first Calderón Prize Committee consisted of Professors Adrian Nachman, Lassi Päivärinta, William Rundell (chair), and Michael Vogelius. William Rundell For the Calderón Prize Committee Prize ceremony The ceremony awarding the Calderón Prize. Matti Lassas is on the left. He and William Rundell are on the right. Photos by P Stefanov. Brief Biography of Matti Lassas Matti Lassas was born in 1969 in Helsinki, Finland, and studied at the University of Helsinki. He finished his Master's studies in 1992 in three years and earned his PhD in 1996. His PhD thesis, written under the supervision of Professor Erkki Somersalo was entitled `Non-selfadjoint inverse spectral problems and their applications to random bodies'. Already in his thesis, Matti demonstrated a remarkable command of different fields of mathematics, bringing together the spectral theory of operators, geometry of Riemannian surfaces, Maxwell's equations and stochastic analysis. He has continued to develop all of these branches in the framework of inverse problems, the most remarkable results perhaps being in the field of differential geometry and inverse problems. Matti has always been a very generous researcher, sharing his ideas with his numerous collaborators. He has authored over sixty scientific articles, among which a monograph on inverse boundary spectral problems with Alexander Kachalov and Yaroslav Kurylev and over forty articles in peer reviewed journals of the highest standards. To get an idea of the wide range of Matti's interests, it is enough to say that he also has three US patents on medical imaging applications. Matti is currently professor of mathematics at Helsinki University of Technology, where he has created his own line of research with young talented researchers around him. He is a central person in the Centre of Excellence in Inverse Problems Research of the Academy of Finland. Previously, Matti Lassas has won several awards in his home country, including the prestigious Vaisala price of the Finnish Academy of Science and Letters in 2004. He is a highly esteemed colleague, teacher and friend, and the Great Diving Beetle of the Finnish Inverse Problems Society (http://venda.uku.fi/research/FIPS/), an honorary title for a person who has no fear of the deep. Erkki Somersalo

Fatigue following Acute Q-Fever: A Systematic Literature Review

PubMed Central

Delsing, Corine E.; Bleijenberg, Gijs; Langendam, Miranda; Timen, Aura; Bleeker-Rovers, Chantal P.

2016-01-01

Background Long-term fatigue with detrimental effects on daily functioning often occurs following acute Q-fever. Following the 2007–2010 Q-fever outbreak in the Netherlands with over 4000 notified cases, the emphasis on long-term consequences of Q-fever increased. The aim of this study was to provide an overview of all relevant available literature, and to identify knowledge gaps regarding the definition, diagnosis, background, description, aetiology, prevention, therapy, and prognosis, of fatigue following acute Q-fever. Design A systematic review was conducted through searching Pubmed, Embase, and PsycInfo for relevant literature up to 26th May 2015. References of included articles were hand searched for additional documents, and included articles were quality assessed. Results Fifty-seven articles were included and four documents classified as grey literature. The quality of most studies was low. The studies suggest that although most patients recover from fatigue within 6–12 months after acute Q-fever, approximately 20% remain chronically fatigued. Several names are used indicating fatigue following acute Q-fever, of which Q-fever fatigue syndrome (QFS) is most customary. Although QFS is described to occur frequently in many countries, a uniform definition is lacking. The studies report major health and work-related consequences, and is frequently accompanied by nonspecific complaints. There is no consensus with regard to aetiology, prevention, treatment, and prognosis. Conclusions Long-term fatigue following acute Q-fever, generally referred to as QFS, has major health-related consequences. However, information on aetiology, prevention, treatment, and prognosis of QFS is underrepresented in the international literature. In order to facilitate comparison of findings, and as platform for future studies, a uniform definition and diagnostic work-up and uniform measurement tools for QFS are proposed. PMID:27223465

Using Local History To Understand National Themes: The Yellow Fever Epidemic in Philadelphia in 1793.

ERIC Educational Resources Information Center

Westbury, Susan

2003-01-01

Provides background information for a local history project about the 1793 Philadelphia (Pennsylvania) yellow fever outbreak. Offers potential project topics to help students learn about local history and understand life in the eighteenth century United States. (CMK)

First Identification and Description of Rickettsioses and Q Fever as Causes of Acute Febrile Illness in Nicaragua

PubMed Central

Reller, Megan E.; Chikeka, Ijeuru; Miles, Jeremy J.; Dumler, J. Stephen; Woods, Christopher W.; Mayorga, Orlando; Matute, Armando J.

2016-01-01

Background Rickettsial infections and Q fever present similarly to other acute febrile illnesses, but are infrequently diagnosed because of limited diagnostic tools. Despite sporadic reports, rickettsial infections and Q fever have not been prospectively studied in Central America. Methodology/Principal Findings We enrolled consecutive patients presenting with undifferentiated fever in western Nicaragua and collected epidemiologic and clinical data and acute and convalescent sera. We used ELISA for screening and paired sera to confirm acute (≥4-fold rise in titer) spotted fever and typhus group rickettsial infections and Q fever as well as past (stable titer) infections. Characteristics associated with both acute and past infection were assessed. Conclusions/Significance We enrolled 825 patients and identified acute rickettsial infections and acute Q fever in 0.9% and 1.3%, respectively. Clinical features were non-specific and neither rickettsial infections nor Q fever were considered or treated. Further study is warranted to define the burden of these infections in Central America. PMID:28036394

Rift Valley fever virus-infected mosquito ova and associated pathology: possible implications for endemic maintenance

USDA-ARS?s Scientific Manuscript database

Background: Endemic/enzootic maintenance mechanisms like vertical transmission, pathogen passage from infected adults to their offspring, are central in the epidemiology of zoonotic pathogens. In Kenya, Rift Valley fever virus (RVFV) may be maintained by vertical transmission in ground-pool mosquit...

Blood Meal Analysis of Mosquitoes Involved in a Rift Valley fever Outbreak

USDA-ARS?s Scientific Manuscript database

Background: Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were sc...

Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses

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

Mitchell, S.W.; McCormick, J.B.

1984-09-01

Clinical specimens from patients infected with Lassa, Ebola, or Marburg virus may present a serious biohazard to laboratory workers. The authors have examined the effects of heat, alteration of pH, and gamma radiation on these viruses in human blood and on the electrolytes, enzymes, and coagulation factors measured in laboratory tests that are important in the care of an infected patient. Heating serum at 60 degrees C for 1 h reduced high titers of these viruses to noninfectious levels without altering the serum levels of glucose, blood urea nitrogen, and electrolytes. Dilution of blood in 3% acetic acid, diluent formore » a leukocyte count, inactivated all of these viruses. All of the methods tested for viral inactivation markedly altered certain serum proteins, making these methods unsuitable for samples that are to be tested for certain enzyme levels and coagulation factors.« less

Acaricide resistance and strategies to mitigate economic impact of the southern cattle fever tick (Rhipicephalus microplus) on livestock production systems in the Americas

USDA-ARS?s Scientific Manuscript database

BACKGROUND: The southern cattle fever tick (SCFT), Rhipicephalus microplus, is considered the most economically important external parasite of livestock worldwide. SCFT populations resistant to acaricides complicate efforts to enhance the productivity of livestock. Here, acaricide resistance is summ...

Pigs immunized with a novel E2 subunit vaccine are protected from heterologous classical swine fever virus challenge

USDA-ARS?s Scientific Manuscript database

Background: Classical swine fever (CSF) or hog cholera is a highly contagious swineviral disease. CSF endemic countries have to use routine vaccination with modifiedlive virus (MLV) vaccines to prevent and control CSF. However, it is impossible toserologically differentiate MLV vaccinated pigs from...

Epidemiologic and environmental risk factors of rift valley fever in southern Africa from 2008 to 2011

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Rift Valley fever outbreaks have been associated with periods of widespread and above average rainfall over several months which allows for the virus infected mosquito vector populations to emerge and propagate. This has provided basis to develop complex models based on environmental fa...

Mobile phone-based interactive voice response as a tool for improving access to healthcare in remote areas in Ghana - an evaluation of user experiences.

PubMed

Brinkel, J; May, J; Krumkamp, R; Lamshöft, M; Kreuels, B; Owusu-Dabo, E; Mohammed, A; Bonacic Marinovic, A; Dako-Gyeke, P; Krämer, A; Fobil, J N

2017-05-01

To investigate and determine the factors that enhanced or constituted barriers to the acceptance of an mHealth system which was piloted in Asante-Akim North District of Ghana to support healthcare of children. Four semi-structured focus group discussions were conducted with a total of 37 mothers. Participants were selected from a study population of mothers who subscribed to a pilot mHealth system which used an interactive voice response (IVR) for its operations. Data were evaluated using qualitative content analysis methods. In addition, a short quantitative questionnaire assessed system's usability (SUS). Results revealed 10 categories of factors that facilitated user acceptance of the IVR system including quality-of-care experience, health education and empowerment of women. The eight categories of factors identified as barriers to user acceptance included the lack of human interaction, lack of update and training on the electronic advices provided and lack of social integration of the system into the community. The usability (SUS median: 79.3; range: 65-97.5) of the system was rated acceptable. The principles of the tested mHealth system could be of interest during infectious disease outbreaks, such as Ebola or Lassa fever, when there might be a special need for disease-specific health information within populations. © 2017 John Wiley & Sons Ltd.

Self-Association of Lymphocytic Choriomeningitis Virus Nucleoprotein Is Mediated by Its N-Terminal Region and Is Not Required for Its Anti-Interferon Function

PubMed Central

Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin

2012-01-01

Arenaviruses have a bisegmented, negative-strand RNA genome. Both the large (L) and small (S) genome segments use an ambisense coding strategy to direct the synthesis of two viral proteins. The L segment encodes the virus polymerase (L protein) and the matrix Z protein, whereas the S segment encodes the nucleoprotein (NP) and the glycoprotein precursor (GPC). NPs are the most abundant viral protein in infected cells and virions and encapsidate genomic RNA species to form an NP-RNA complex that, together with the virus L polymerase, forms the virus ribonucleoprotein (RNP) core capable of directing both replication and transcription of the viral genome. RNP formation predicts a self-association property of NPs. Here we document self-association (homotypic interaction) of the NP of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), as well as those of the hemorrhagic fever (HF) arenaviruses Lassa virus (LASV) and Machupo virus (MACV). We also show heterotypic interaction between NPs from both closely (LCMV and LASV) and distantly (LCMV and MACV) genetically related arenaviruses. LCMV NP self-association was dependent on the presence of single-stranded RNA and mediated by an N-terminal region of the NP that did not overlap with the previously described C-terminal NP domain involved in either counteracting the host type I interferon response or interacting with LCMV Z. PMID:22258244

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

PubMed Central

Matsiégui, Pierre-Blaise; Missinou, Michel A; Necek, Magdalena; Mavoungou, Elie; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G

2008-01-01

Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713 PMID:18503714

Predicting postoperative fever and bacterial colonization on packing material following endoscopic endonasal surgery.

PubMed

Nomura, Kazuhiro; Yamanaka, Yurika; Sekine, Yasuhiro; Yamamoto, Hiroki; Esu, Yoshihiko; Hara, Mariko; Hasegawa, Masayo; Shinnabe, Akihiro; Kanazawa, Hiromi; Kakuta, Risako; Ozawa, Daiki; Hidaka, Hiroshi; Katori, Yukio; Yoshida, Naohiro

2017-01-01

Postoperative fever following endoscopic endonasal surgery is a rare occurrence of concern to surgeons. To elucidate preoperative and operative predictors of postoperative fever, we analyzed the characteristics of patients and their perioperative background in association with postoperative fever. A retrospective review of 371 patients who had undergone endoscopic endonasal surgery was conducted. Predictors, including intake of antibiotics, steroids, history of asthma, preoperative nasal bacterial culture, duration of operation, duration of packing and intraoperative intravenous antibiotics on the occurrence of postoperative fever, and bacterial colonization on the packing material, were analyzed retrospectively. Fever (≥38 °C) occurred in 63 (17 %) patients. Most incidences of fever occurred on postoperative day one. In majority of these cases, the fever subsided after removal of the packing material without further antibiotic administration. However, one patient who experienced persistent fever after the removal of packing material developed meningitis. History of asthma, prolonged operation time (≥108 min), and intravenous cefazolin administration instead of cefmetazole were associated with postoperative fever. Odds ratios (ORs) for each were 2.3, 4.6, and 2.0, respectively. Positive preoperative bacterial colonization was associated with postoperative bacterial colonization on the packing material (OR 2.3). Postoperative fever subsided in most patients after removal of the packing material. When this postoperative fever persists, its underlying cause should be examined.

Localizing chronic Q fever: a challenging query

PubMed Central

2013-01-01

Background Chronic Q fever usually presents as endocarditis or endovascular infection. We investigated whether 18F-FDG PET/CT and echocardiography were able to detect the localization of infection. Also, the utility of the modified Duke criteria was assessed. Methods Fifty-two patients, who had an IgG titre of ≥ 1024 against C. burnetii phase I ≥ 3 months after primary infection or a positive PCR ≥ 1 month after primary infection, were retrospectively included. Data on serology, the results of all imaging studies, possible risk factors for developing proven chronic Q fever and clinical outcome were recorded. Results According to the Dutch consensus on Q fever diagnostics, 18 patients had proven chronic Q fever, 14 probable chronic Q fever, and 20 possible chronic Q fever. Of the patients with proven chronic Q fever, 22% were diagnosed with endocarditis, 17% with an infected vascular prosthesis, and 39% with a mycotic aneurysm. 56% of patients with proven chronic Q fever did not recall an episode of acute Q fever. Ten out of 13 18F-FDG PET/CT-scans in patients with proven chronic Q fever localized the infection. TTE and TEE were helpful in only 6% and 50% of patients, respectively. Conclusions If chronic Q fever is diagnosed, 18F-FDG PET/CT is a helpful imaging technique for localization of vascular infections due to chronic Q fever. Patients with proven chronic Q fever were diagnosed significantly more often with mycotic aneurysms than in previous case series. Definite endocarditis due to chronic Q fever was less frequently diagnosed in the current study. Chronic Q fever often occurs in patients without a known episode of acute Q fever, so clinical suspicion should remain high, especially in endemic regions. PMID:24004470

Dr Robert Robertson (1742-1829): Fever Specialist and Philosopher-Experimenter in the Treatment of Fevers with Peruvian Bark in the Latter Eighteenth-century Royal Navy.

PubMed

Short, Bruce

2015-12-01

The life and works of Dr Robert Robertson are reviewed set against the background of the extant British management of fevers during the latter 18th-century. Commencing in 1769, using the febrifuge Peruvian bark (cortex Peruvianus; Jesuit's Powder), he experimented and tested Peruvian bark mono-therapy protocols in the tropics in the cure and prevention of intermittent fever (predominantly malaria). His later work also showed the benefit of the bark in the acute care of developed continuous fevers (largely Ship Fever due to Epidemic Louse-borne Typhus Fever) in both the Temperate and Torrid Zones. In the realm of comparative statistics Robertson first demonstrated the safety and effectiveness of bark therapy against the dangerous depleting processes of the antiphlogistic regimen. He was the first to alert the Admiralty to the efficacy of bark in both the cure of acute fevers as well as a prophylactic in the tropics, and signalled the dangers of bloodletting in treating fevers of the tropics. He authored 13 books devoted to fevers outlining his theory of Febrile Infection and its treatment. The essay concludes with his role as the Physician-in-Charge of the Royal Hospital, Greenwich over a 28-year period, as an acknowledged expert in the small British group of 18th-century fever specialists.

Review of current typhoid fever vaccines, cross-protection against paratyphoid fever, and the European guidelines.

PubMed

Zuckerman, Jane N; Hatz, Christoph; Kantele, Anu

2017-10-01

Typhoid and paratyphoid fever remain a global health problem, which - in non-endemic countries - are mainly seen in travelers, particularly in VFRs (visiting friends and relatives), with occasional local outbreaks occurring. A rise in anti-microbial resistance emphasizes the role of preventive measures, especially vaccinations against typhoid and paratyphoid fever for travelers visiting endemic countries. Areas covered: This state-of-the-art review recapitulates the epidemiology and mechanisms of disease of typhoid and paratyphoid fever, depicts the perspective of non-endemic countries and travelers (VFRs), and collectively presents current European recommendations for typhoid fever vaccination. We provide a brief overview of available (and developmental) vaccines in Europe, present current data on cross-protection to S. Paratyphi, and aim to provide a background for typhoid vaccine decision-making in travelers. Expert commentary: European recommendations are not harmonized. Experts must assess vaccination of travelers based on current country-specific recommendations. Travel health practitioners should be aware of the issues surrounding vaccination of travelers and be motivated to increase awareness of typhoid and paratyphoid fever risks.

Environmental Transmission of Typhoid Fever in an Urban Slum

PubMed Central

Matheson, Alastair I.; Cosmas, Leonard; Macharia, Daniel; Fields, Barry; Bigogo, Godfrey; Mugoh, Maina; John-Stewart, Grace; Walson, Judd L.; Wakefield, Jonathan; Montgomery, Joel M.

2015-01-01

Background Enteric fever due to Salmonella Typhi (typhoid fever) occurs in urban areas with poor sanitation. While direct fecal-oral transmission is thought to be the predominant mode of transmission, recent evidence suggests that indirect environmental transmission may also contribute to disease spread. Methods Data from a population-based infectious disease surveillance system (28,000 individuals followed biweekly) were used to map the spatial pattern of typhoid fever in Kibera, an urban informal settlement in Nairobi Kenya, between 2010–2011. Spatial modeling was used to test whether variations in topography and accumulation of surface water explain the geographic patterns of risk. Results Among children less than ten years of age, risk of typhoid fever was geographically heterogeneous across the study area (p = 0.016) and was positively associated with lower elevation, OR = 1.87, 95% CI (1.36–2.57), p <0.001. In contrast, the risk of typhoid fever did not vary geographically or with elevation among individuals less than 6b ten years of age. Conclusions Our results provide evidence of indirect, environmental transmission of typhoid fever among children, a group with high exposure to fecal pathogens in the environment. Spatially targeting sanitation interventions may decrease enteric fever transmission. PMID:26633656

Periodic Fever: A Review on Clinical, Management and Guideline for Iranian Patients - Part II

PubMed Central

Ahmadinejad, Zahra; Mansouri, Sedigeh; Ziaee, Vahid; Aghighi, Yahya; Moradinejad, Mohammad-Hassan; Fereshteh-Mehregan, Fatemeh

2014-01-01

Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. In the first part of this paper, we presented a guideline for approaching patients with periodic fever and reviewed two common disorders with periodic fever in Iranian patients including familial Mediterranean fever (FMF) and periodic fever syndromes except for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). In this part, we review other autoinflammatory disorders including hyper IgD, tumor necrosis factor receptor–associated periodic syndrome (TRAPS), cryopyrin associated periodic syndromes, autoinflammatory bone disorders and some other rare autoinflammatory disorders such as Sweet’s and Blau syndromes. In cryopyrin associated periodic syndromes group, we discussed chronic infantile neurologic cutaneous and articular (CINCA) syndrome, Muckle-Wells syndrome and familial cold autoinflammatory syndrome. Autoinflammatory bone disorders are categorized to monogenic disorders such as pyogenic arthritis, pyoderma ;gangraenosum and acne (PAPA) syndrome, the deficiency of interleukine-1 receptor antagonist (DIRA) and Majeed syndrome and polygenic background or sporadic group such as chronic recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome are classified in sporadic group. Other autoinflammatory syndromes are rare causes of periodic fever in Iranian system registry. PMID:25562014

The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease

PubMed Central

Seckeler, Michael D; Hoke, Tracey R

2011-01-01

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are significant public health concerns around the world. Despite decreasing incidence, there is still a significant disease burden, especially in developing nations. This review provides background on the history of ARF, its pathology and treatment, and the current reported worldwide incidence of ARF and prevalence of RHD. PMID:21386976

Role of computed tomography of abdomen in difficult to diagnose typhoid fever: a case series.

PubMed

Hafeez, Wajid; Rajalakshmi, S; Sripriya, S; Madhu Bashini, M

2018-04-01

Background and Aim Diagnosis of typhoid is challenging when blood cultures fail to isolate Salmonella species. We report our experience with interpreting computed tomography (CT) abdomen findings in a case series of typhoid fever. Methods The case series consisted of patients who had a CT abdomen done as part of their investigations and a final diagnosis of typhoid fever. The CT films were reviewed and findings evaluated for distinctive features. Results During 2011-2017, 11 patients met the inclusion criteria. Indication for CT was pyrexia of unknown origin in the majority of patients. Review of CT films revealed mesenteric lymphadenopathy (100%), terminal ileum thickening (85%), hepatosplenomegaly (45%), retroperitoneal lymphadenopathy (18%) and ascites (9%). Conclusions Enhancing discrete mesenteric lymphadenopathy and terminal ileum thickening are non-specific findings noted in typhoid fever. Absence of matted necrotic nodes and peritoneal thickening rule out tuberculosis and raise suspicion of typhoid fever in endemic regions.

Knowledge, attitudes and misconceptions of primary care physicians regarding fever in children: a cross sectional study

PubMed Central

2012-01-01

Background Fever is an extremely common sign in paediatric patients and the most common cause for a child to be taken to the doctor. The literature indicates that physicians and parents have too many misconceptions and conflicting results about fever management. In this study we aim to identify knowledge, attitudes and misconceptions of primary care physicians regarding fever in children. Methods This cross-sectional study was conducted in April-May 2010 involving primary care physicians (n=80). The physicians were surveyed using a self-administered questionnaire. Descriptive statistics were used. Results In our study only 10% of the physicians knew that a body temperature of above 37.2°C according to an auxiliary measurement is defined as fever. Only 26.2% of the physicians took into consideration signs and symptoms other than fever to prescribe antipyretics. 85% of the physicians prescribed antipyretics to control fever or prevent complications of fever especially febrile seizures. Most of the physicians (76.3%) in this study reported that the height of fever may be used as an indicator for severe bacterial infection. A great majority of physicians (91.3%) stated that they advised parents to alternate the use of ibuprofen and paracetamol. Conclusions There were misconceptions about the management and complications of fever. There is a perceived need to improve the recognition, assessment, and management of fever with regards to underlying illnesses in children. PMID:22950655

Incorporation of antigens from whole cell lysates and purified virions from MP12 into fluorescence microsphere immunoassays for the detection of antibodies against Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

Background: The purpose of this study was the development of multiplex fluorescence microsphere immunoassay (FMIA) for the detection of Rift Valley fever virus (RVFV) IgG and IgM antibodies by incorporation of antigens from whole cell lysates and purified virions from MP12. Methods and Findings: Vir...

Acute Q fever in febrile patients in northwestern of Iran

PubMed Central

Esmaeili, Saber; Golzar, Farhad; Ayubi, Erfan; Naghili, Behrooz; Mostafavi, Ehsan

2017-01-01

Background Q fever is an endemic disease in different parts of Iran. This study aimed to investigate the prevalence of acute Q fever disease among at-risk individuals in northwestern Iran. Methodology An etiological study was carried out in 2013 in Tabriz County. A total of 116 individuals who were in contact with livestock and had a nonspecific febrile illness were enrolled in the study. IgG phase II antibodies against Coxiella burnetii were detected using ELISA. Principal findings The prevalence of acute Q fever was 13.8% (95% confidence interval [CI]: 8.0, 21.0%). Headache (87.5%) and fatigue and weakness (81.3%) were the dominant clinical characteristics among patients whit acute Q fever. Acute lower respiratory tract infection and chills were poorly associated with acute Q fever. Furthermore, 32% (95% CI: 24, 41%) of participants had a history of previous exposure to Q fever agent (past infection). Consumption of unpasteurized dairy products was a weak risk factor for previous exposure to C. burnetii. Conclusion This study identified patients with acute Q fever in northwestern of Iran. The evidence from this study and previous studies conducted in different regions of Iran support this fact that Q fever is one of the important endemic zoonotic diseases in Iran and needs due attention by clinical physicians and health care system. PMID:28394892

Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance.

PubMed

Rasmussen, Angela L; Okumura, Atsushi; Ferris, Martin T; Green, Richard; Feldmann, Friederike; Kelly, Sara M; Scott, Dana P; Safronetz, David; Haddock, Elaine; LaCasse, Rachel; Thomas, Matthew J; Sova, Pavel; Carter, Victoria S; Weiss, Jeffrey M; Miller, Darla R; Shaw, Ginger D; Korth, Marcus J; Heise, Mark T; Baric, Ralph S; de Villena, Fernando Pardo-Manuel; Feldmann, Heinz; Katze, Michael G

2014-11-21

Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever. Copyright © 2014, American Association for the Advancement of Science.

Development and preliminary evaluation of a multiplexed amplification and next generation sequencing method for viral hemorrhagic fever diagnostics

PubMed Central

Radonić, Aleksandar; Kocak Tufan, Zeliha; Domingo, Cristina

2017-01-01

Background We describe the development and evaluation of a novel method for targeted amplification and Next Generation Sequencing (NGS)-based identification of viral hemorrhagic fever (VHF) agents and assess the feasibility of this approach in diagnostics. Methodology An ultrahigh-multiplex panel was designed with primers to amplify all known variants of VHF-associated viruses and relevant controls. The performance of the panel was evaluated via serially quantified nucleic acids from Yellow fever virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever (CCHF) virus, Ebola virus, Junin virus and Chikungunya virus in a semiconductor-based sequencing platform. A comparison of direct NGS and targeted amplification-NGS was performed. The panel was further tested via a real-time nanopore sequencing-based platform, using clinical specimens from CCHF patients. Principal findings The multiplex primer panel comprises two pools of 285 and 256 primer pairs for the identification of 46 virus species causing hemorrhagic fevers, encompassing 6,130 genetic variants of the strains involved. In silico validation revealed that the panel detected over 97% of all known genetic variants of the targeted virus species. High levels of specificity and sensitivity were observed for the tested virus strains. Targeted amplification ensured viral read detection in specimens with the lowest virus concentration (1–10 genome equivalents) and enabled significant increases in specific reads over background for all viruses investigated. In clinical specimens, the panel enabled detection of the causative agent and its characterization within 10 minutes of sequencing, with sample-to-result time of less than 3.5 hours. Conclusions Virus enrichment via targeted amplification followed by NGS is an applicable strategy for the diagnosis of VHFs which can be adapted for high-throughput or nanopore sequencing platforms and employed for surveillance or outbreak monitoring. PMID:29155823

WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.

PubMed

World Health Organization

2017-10-13

This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper - June 2013″, published in the Weekly Epidemiological Record [1,2]. This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. Copyright © 2017. Published by Elsevier Ltd.

Retrospective Examination of Q Fever Endocarditis: An Underdiagnosed Disease in the Mainland of China

PubMed Central

Han, Xiao; Hsu, Jeffrey; Miao, Qi; Zhou, Bao-Tong; Fan, Hong-Wei; Xiong, Xiao-Lu; Wen, Bo-Hai; Wu, Lian; Yan, Xiao-Wei; Fang, Quan; Chen, Wei

2017-01-01

Background: Q fever endocarditis, a chronic illness caused by Coxiella burnetii, can be fatal if misdiagnosed or left untreated. Despite a relatively high positive rate of Q fever serology in healthy individuals in the mainland of China, very few cases of Q fever endocarditis have been reported. This study summarized cases of Q fever endocarditis among blood culture negative endocarditis (BCNE) patients and discussed factors attributing to the low diagnostic rate. Methods: We identified confirmed cases of Q fever endocarditis among 637 consecutive patients with infective endocarditis (IE) in the Peking Union Medical College Hospital between 2006 and 2016. The clinical findings for each confirmed case were recorded. BCNE patients were also examined and each BCNE patient's Q fever risk factors were identified. The risk factors and presence of Q fever serologic testing between BCNE patients suspected and unsuspected of Q fever were compared using the Chi-squared or Chi-squared with Yates’ correction for continuity. Results: Among the IE patients examined, there were 147 BCNE patients, of whom only 11 patients (7.5%) were suspected of Q fever and undergone serological testing for C. burnetii. Six out of 11 suspected cases were diagnosed as Q fever endocarditis. For the remaining136 BCNE patients, none of them was suspected of Q fever nor underwent relevant testing. Risk factors for Q fever endocarditis were comparable between suspected and unsuspected patients, with the most common risk factors being valvulopathy in both groups. However, significantly more patients had consulted the Infectious Diseases Division and undergone comprehensive diagnostic tests in the suspected group than the unsuspected group (100% vs. 63%, P = 0.03). Conclusions: Q fever endocarditis is a serious yet treatable condition. Lacking awareness of the disease may prevent BCNE patients from being identified, despite having Q fever risk factors. Increasing awareness and guideline adherence are crucial in avoiding misdiagnosing and missed diagnosing of the disease. PMID:28051025

Comparative analysis of disease pathogenesis and molecular mechanisms of New World and Old World arenavirus infections

PubMed Central

McLay, Lisa; Liang, Yuying

2014-01-01

Arenaviruses can cause fatal human haemorrhagic fever (HF) diseases for which vaccines and therapies are extremely limited. Both the New World (NW) and Old World (OW) groups of arenaviruses contain HF-causing pathogens. Although these two groups share many similarities, important differences with regard to pathogenicity and molecular mechanisms of virus infection exist. These closely related pathogens share many characteristics, including genome structure, viral assembly, natural host selection and the ability to interfere with innate immune signalling. However, members of the NW and OW viruses appear to use different receptors for cellular entry, as well as different mechanisms of virus internalization. General differences in disease signs and symptoms and pathological lesions in patients infected with either NW or OW arenaviruses are also noted and discussed herein. Whilst both the OW Lassa virus (LASV) and the NW Junin virus (JUNV) can cause disruption of the vascular endothelium, which is an important pathological feature of HF, the immune responses to these related pathogens seem to be quite distinct. Whereas LASV infection results in an overall generalized immune suppression, patients infected with JUNV seem to develop a cytokine storm. Additionally, the type of immune response required for recovery and clearance of the virus is different between NW and OW infections. These differences may be important to allow the viruses to evade host immune detection. Understanding these differences will aid the development of new vaccines and treatment strategies against deadly HF viral infections. PMID:24068704

Comparative analysis of disease pathogenesis and molecular mechanisms of New World and Old World arenavirus infections.

PubMed

McLay, Lisa; Liang, Yuying; Ly, Hinh

2014-01-01

Arenaviruses can cause fatal human haemorrhagic fever (HF) diseases for which vaccines and therapies are extremely limited. Both the New World (NW) and Old World (OW) groups of arenaviruses contain HF-causing pathogens. Although these two groups share many similarities, important differences with regard to pathogenicity and molecular mechanisms of virus infection exist. These closely related pathogens share many characteristics, including genome structure, viral assembly, natural host selection and the ability to interfere with innate immune signalling. However, members of the NW and OW viruses appear to use different receptors for cellular entry, as well as different mechanisms of virus internalization. General differences in disease signs and symptoms and pathological lesions in patients infected with either NW or OW arenaviruses are also noted and discussed herein. Whilst both the OW Lassa virus (LASV) and the NW Junin virus (JUNV) can cause disruption of the vascular endothelium, which is an important pathological feature of HF, the immune responses to these related pathogens seem to be quite distinct. Whereas LASV infection results in an overall generalized immune suppression, patients infected with JUNV seem to develop a cytokine storm. Additionally, the type of immune response required for recovery and clearance of the virus is different between NW and OW infections. These differences may be important to allow the viruses to evade host immune detection. Understanding these differences will aid the development of new vaccines and treatment strategies against deadly HF viral infections.

High content image-based screening of a protease inhibitor library reveals compounds broadly active against Rift Valley fever virus and other highly pathogenic RNA viruses.

PubMed

Mudhasani, Rajini; Kota, Krishna P; Retterer, Cary; Tran, Julie P; Whitehouse, Chris A; Bavari, Sina

2014-08-01

High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV) and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362), which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their mechanism of action and any possible deleterious effects on host cellular biology.

High Content Image-Based Screening of a Protease Inhibitor Library Reveals Compounds Broadly Active against Rift Valley Fever Virus and Other Highly Pathogenic RNA Viruses

PubMed Central

Mudhasani, Rajini; Kota, Krishna P.; Retterer, Cary; Tran, Julie P.; Whitehouse, Chris A.; Bavari, Sina

2014-01-01

High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV) and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362), which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their mechanism of action and any possible deleterious effects on host cellular biology. PMID:25144302

Time To Move from Presumptive Malaria Treatment to Laboratory-Confirmed Diagnosis and Treatment in African Children with Fever

PubMed Central

D'Acremont, Valérie; Lengeler, Christian; Mshinda, Hassan; Mtasiwa, Deo; Tanner, Marcel; Genton, Blaise

2009-01-01

Background to the debate: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five. PMID:19127974

An outbreak of scarlet fever in a primary school.

PubMed

Lamden, K H

2011-04-01

Scarlet fever, due to infection with an erythrogenic toxin-producing Group A streptococcus, is an uncommon and generally mild illness, although serious sequelae do occur. In March 2009, 57 of the 126 (45%) pupils in a primary school in Lancashire, UK developed scarlet fever over a 4-week period. Infection was transmitted via direct contact between pupils, particularly among the youngest pupils. A significant degree of transmission also occurred between siblings. The median number of days absent from school was 3 (range 1-10 days). No children were hospitalised. Control measures, including hygiene advice to the school and exclusion of pupils for 24h while initiating penicillin treatment, were ineffective. The outbreak occurred against a background of an unusually high incidence of invasive Group A streptococcal infection. While there are national guidelines for the control of invasive disease, none exist for the control of scarlet fever outbreaks. This prolonged outbreak of scarlet fever highlights the need for an evidence based approach to outbreak management.

Clinical Characteristics of Q Fever and Etiology of Community-Acquired Pneumonia in a Tropical Region of Southern Taiwan: A Prospective Observational Study

PubMed Central

Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Wei, Yu-Feng; Chiu, Chien-Tung; Wu, Jiun-Ting; Hsu, Chi-Kuei; Chen, Jung-Yueh; Lee, Ho-Sheng; Lin, Hsi-Hsun; Chen, Yen-Hsu

2014-01-01

Background The clinical characteristics of Q fever are poorly identified in the tropics. Fever with pneumonia or hepatitis are the dominant presentations of acute Q fever, which exhibits geographic variability. In southern Taiwan, which is located in a tropical region, the role of Q fever in community-acquired pneumonia (CAP) has never been investigated. Methodology/Principal Findings During the study period, May 2012 to April 2013, 166 cases of adult CAP and 15 cases of acute Q fever were prospectively investigated. Cultures of clinical specimens, urine antigen tests for Streptococcus pneumoniae and Legionella pneumophila, and paired serologic assessments for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Q fever (Coxiella burnetii) were used for identifying pathogens associated with CAP. From April 2004 to April 2013 (the pre-study period), 122 cases of acute Q fever were also included retrospectively for analysis. The geographic distribution of Q fever and CAP cases was similar. Q fever cases were identified in warmer seasons and younger ages than CAP. Based on multivariate analysis, male gender, chills, thrombocytopenia, and elevated liver enzymes were independent characteristics associated with Q fever. In patients with Q fever, 95% and 13.5% of cases presented with hepatitis and pneumonia, respectively. Twelve (7.2%) cases of CAP were seropositive for C. burnetii antibodies, but none of them had acute Q fever. Among CAP cases, 22.9% had a CURB-65 score ≧2, and 45.8% had identifiable pathogens. Haemophilus parainfluenzae (14.5%), S. pneumoniae (6.6%), Pseudomonas aeruginosa (4.8%), and Klebsiella pneumoniae (3.0%) were the most common pathogens identified by cultures or urine antigen tests. Moreover, M. pneumoniae, C. pneumoniae, and co-infection with 2 pathogens accounted for 9.0%, 7.8%, and 1.8%, respectively. Conclusions In southern Taiwan, Q fever is an endemic disease with hepatitis as the major presentation and is not a common etiology of CAP. PMID:25033402

Individual and Interactive Effects of Socio-Ecological Factors on Dengue Fever at Fine Spatial Scale: A Geographical Detector-Based Analysis

PubMed Central

Li, Xing; Wang, Jin; Lin, Hualiang; Chen, Lingling; Wu, Zhifeng; Ma, Wenjun

2017-01-01

Background: Large spatial heterogeneity was observed in the dengue fever outbreak in Guangzhou in 2014, however, the underlying reasons remain unknown. We examined whether socio-ecological factors affected the spatial distribution and their interactive effects. Methods: Moran’s I was applied to first examine the spatial cluster of dengue fever in Guangzhou. Nine socio-ecological factors were chosen to represent the urbanization level, economy, accessibility, environment, and the weather of the 167 townships/streets in Guangzhou, and then the geographical detector was applied to analyze the individual and interactive effects of these factors on the dengue outbreak. Results: Four clusters of dengue fever were identified in Guangzhou in 2014, including one hot spot in the central area of Guangzhou and three cold spots in the suburban districts. For individual effects, the temperature (q = 0.33) was the dominant factor of dengue fever, followed by precipitation (q = 0.24), road density (q = 0.24), and water body area (q = 0.23). For the interactive effects, the combination of high precipitation, high temperature, and high road density might result in increased dengue fever incidence. Moreover, urban villages might be the dengue fever hot spots. Conclusions: Our study suggests that some socio-ecological factors might either separately or jointly influence the spatial distribution of dengue fever in Guangzhou. PMID:28714925

Typhoid fever in a Tertiary Hospital in Nigeria: Another look at the Widal agglutination test as a preferred option for diagnosis

PubMed Central

Enabulele, Osahon; Awunor, Simeon Nyemike

2016-01-01

Background: Single Widal agglutination test rather than blood culture, is commonly employed to diagnose typhoid fever in Nigeria. We took another look at the Widal agglutination test as a preferred option for diagnosis of typhoid fever by determining the specificity and sensitivity of Widal agglutination test in febrile adult patients. Materials and Methods: Two hundred and seventy-one blood samples from consecutive adults (>18 years) with febrile illness attending the General Practice Clinic of the University of Benin Teaching Hospital were tested using the Widal agglutination test, blood culture, and malaria parasite test on each sample to establish the diagnosis of typhoid fever. Results: Of the 271 blood samples 124 (45.76%) were positive following a Widal agglutination test, 60 (22.10%) blood samples grew Salmonella organisms on blood culture while 55 (20.29%) blood samples showed a co-infection of typhoid fever and malaria. A sensitivity of 35%, specificity of 51%, positive predictive value of 17%, and a negative predictive value of 73% were observed for Widal agglutination test as a diagnostic modality for typhoid fever infection. Conclusion: A single Widal agglutination test is not a valid diagnostic option for typhoid fever while co-infection with malaria parasite is the preponderant microbiological finding in typhoid fever infections. The severity of malaria parasitemia is associated with positive titers on Widal test. PMID:27397952

Individual and Interactive Effects of Socio-Ecological Factors on Dengue Fever at Fine Spatial Scale: A Geographical Detector-Based Analysis.

PubMed

Cao, Zheng; Liu, Tao; Li, Xing; Wang, Jin; Lin, Hualiang; Chen, Lingling; Wu, Zhifeng; Ma, Wenjun

2017-07-17

Background : Large spatial heterogeneity was observed in the dengue fever outbreak in Guangzhou in 2014, however, the underlying reasons remain unknown. We examined whether socio-ecological factors affected the spatial distribution and their interactive effects. Methods : Moran's I was applied to first examine the spatial cluster of dengue fever in Guangzhou. Nine socio-ecological factors were chosen to represent the urbanization level, economy, accessibility, environment, and the weather of the 167 townships/streets in Guangzhou, and then the geographical detector was applied to analyze the individual and interactive effects of these factors on the dengue outbreak. Results : Four clusters of dengue fever were identified in Guangzhou in 2014, including one hot spot in the central area of Guangzhou and three cold spots in the suburban districts. For individual effects, the temperature ( q = 0.33) was the dominant factor of dengue fever, followed by precipitation ( q = 0.24), road density ( q = 0.24), and water body area ( q = 0.23). For the interactive effects, the combination of high precipitation, high temperature, and high road density might result in increased dengue fever incidence. Moreover, urban villages might be the dengue fever hot spots. Conclusions : Our study suggests that some socio-ecological factors might either separately or jointly influence the spatial distribution of dengue fever in Guangzhou.

Pontiac fever: an operational definition for epidemiological studies

PubMed Central

Tossa, Paul; Deloge-Abarkan, Magali; Zmirou-Navier, Denis; Hartemann, Philippe; Mathieu, Laurence

2006-01-01

Background Pontiac fever is usually described in epidemic settings. Detection of Pontiac fever is a marker of an environmental contamination by Legionella and should thereby call for prevention measures in order to prevent outbreak of Legionnaire's disease. The objective of this study is to propose an operational definition of Pontiac fever that is amenable to epidemiological surveillance and investigation in a non epidemic setting. Methods A population of 560 elderly subjects residing in 25 nursing homes was followed during 4 months in order to assess the daily incidence of symptoms associated, in the literature, with Pontiac fever. The water and aerosol of one to 8 showers by nursing home were characterized combining conventional bacterial culture of Legionella and the Fluorescence In Situ Hybridization (FISH) technique that used oligonucleotides probes specific for Legionellaceae. A definition of Pontiac fever was devised based on clinical symptoms described in epidemic investigations and on their timing after the exposure event. The association between incidence of Pontiac fever and shower contamination levels was evaluated to test the relevance of this definition. Results The proposed definition of Pontiac fever associated the following criteria: occurrence of at least one symptom among headache, myalgia, fever and shivers, possibly associated with other 'minor' symptoms, within three days after a shower contaminated by Legionella, during a maximum of 8 days (minimum 2 days). 23 such cases occurred during the study (incidence rate: 0.125 cases per person-year [95% CI: 0.122–0.127]). A concentration of Legionella in water equal to or greater than 104.L-1 (FISH method) was associated with a significant increase of incidence of Pontiac fever (p = 0.04). Conclusion Once validated in other settings, the proposed definition of Pontiac fever might be used to develop epidemiological surveillance and help draw attention on sources of Legionella. PMID:16646972

Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010

PubMed Central

Buckle, Geoffrey C.; Walker, Christa L. Fischer; Black, Robert E.

2012-01-01

Background Typhoid and paratyphoid fever remain important causes of morbidity worldwide. Accurate disease burden estimates are needed to guide policy decisions and prevention and control strategies. Methods We conducted a systematic literature review of the PubMed and Scopus databases using pre-defined criteria to identify population-based studies with typhoid fever incidence data published between 1980 and 2009. We also abstracted data from annual reports of notifiable diseases in countries with advanced surveillance systems. Typhoid and paratyphoid fever input data were grouped into regions and regional incidence and mortality rates were estimated. Incidence data were extrapolated across regions for those lacking data. Age-specific incidence rates were derived for regions where age-specific data were available. Crude and adjusted estimates of the global typhoid fever burden were calculated. Results Twenty-five studies were identified, all of which contained incidence data on typhoid fever and 12 on paratyphoid fever. Five advanced surveillance systems contributed data on typhoid fever; 2 on paratyphoid fever. Regional typhoid fever incidence rates ranged from <0.1/100 000 cases/y in Central and Eastern Europe and Central Asia to 724.6/100 000 cases/y in Sub-Saharan Africa. Regional paratyphoid incidence rates ranged from 0.8/100 000 cases/y in North Africa/Middle East to 77.4/100 000 cases/y in Sub-Saharan Africa and South Asia. The estimated total number of typhoid fever episodes in 2010 was 13.5 million (interquartile range 9.1–17.8 million). The adjusted estimate accounting for the low sensitivity of blood cultures for isolation of the bacteria was 26.9 million (interquartile range 18.3–35.7 million) episodes. These findings are comparable to the most recent analysis of global typhoid fever morbidity, which reported crude and adjusted estimates of 10.8 million and 21.7 million typhoid fever episodes globally in 2000. Conclusion Typhoid fever remains a significant health burden, especially in low- and middle-income countries. Despite the availability of more recent data on both enteric fevers, additional research is needed in many regions, particularly Africa, Latin America and other developing countries. PMID:23198130

Identification of fever and vaccine-associated gene interaction networks using ontology-based literature mining

PubMed Central

2012-01-01

Background Fever is one of the most common adverse events of vaccines. The detailed mechanisms of fever and vaccine-associated gene interaction networks are not fully understood. In the present study, we employed a genome-wide, Centrality and Ontology-based Network Discovery using Literature data (CONDL) approach to analyse the genes and gene interaction networks associated with fever or vaccine-related fever responses. Results Over 170,000 fever-related articles from PubMed abstracts and titles were retrieved and analysed at the sentence level using natural language processing techniques to identify genes and vaccines (including 186 Vaccine Ontology terms) as well as their interactions. This resulted in a generic fever network consisting of 403 genes and 577 gene interactions. A vaccine-specific fever sub-network consisting of 29 genes and 28 gene interactions was extracted from articles that are related to both fever and vaccines. In addition, gene-vaccine interactions were identified. Vaccines (including 4 specific vaccine names) were found to directly interact with 26 genes. Gene set enrichment analysis was performed using the genes in the generated interaction networks. Moreover, the genes in these networks were prioritized using network centrality metrics. Making scientific discoveries and generating new hypotheses were possible by using network centrality and gene set enrichment analyses. For example, our study found that the genes in the generic fever network were more enriched in cell death and responses to wounding, and the vaccine sub-network had more gene enrichment in leukocyte activation and phosphorylation regulation. The most central genes in the vaccine-specific fever network are predicted to be highly relevant to vaccine-induced fever, whereas genes that are central only in the generic fever network are likely to be highly relevant to generic fever responses. Interestingly, no Toll-like receptors (TLRs) were found in the gene-vaccine interaction network. Since multiple TLRs were found in the generic fever network, it is reasonable to hypothesize that vaccine-TLR interactions may play an important role in inducing fever response, which deserves a further investigation. Conclusions This study demonstrated that ontology-based literature mining is a powerful method for analyzing gene interaction networks and generating new scientific hypotheses. PMID:23256563

Long-Term Serological Follow-Up of Acute Q-Fever Patients after a Large Epidemic

PubMed Central

Wielders, Cornelia C. H.; van Loenhout, Joris A. F.; Morroy, Gabriëlla; Rietveld, Ariene; Notermans, Daan W.; Wever, Peter C.; Renders, Nicole H. M.; Leenders, Alexander C. A. P.; van der Hoek, Wim; Schneeberger, Peter M.

2015-01-01

Background Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007–2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever. Methods A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of Coxiella burnetii, as these are considered indicative for possible chronic Q-fever. Results Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6%) were included in the analysis. At any time during the four-year follow-up period, 58 (4.5%) patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I ≥1:1,024 to as serologic criterion for chronic Q-fever). Fifty-two (89.7%) of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months. Conclusions A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I ≥1:512, as they showed the highest risk to progress to chronic Q-fever. PMID:26161658

Arenavirus Diversity and Phylogeography of Mastomys natalensis Rodents, Nigeria

PubMed Central

Obadare, Adeoba; Oyeyiola, Akinlabi; Igbokwe, Joseph; Fasogbon, Ayobami; Igbahenah, Felix; Ortsega, Daniel; Asogun, Danny; Umeh, Prince; Vakkai, Innocent; Abejegah, Chukwuyem; Pahlman, Meike; Becker-Ziaja, Beate; Günther, Stephan; Fichet-Calvet, Elisabeth

2016-01-01

Mastomys natalensis rodents are natural hosts for Lassa virus (LASV). Detection of LASV in 2 mitochondrial phylogroups of the rodent near the Niger and Benue Rivers in Nigeria underlines the potential for LASV emergence in fresh phylogroups of this rodent. A Mobala-like sequence was also detected in eastern Nigeria. PMID:26982388

The history of fever, leukocytic pyrogen and interleukin-1.

PubMed

Dinarello, Charles A

2015-01-01

There has been great progress in the 30 y since the reporting in 1984 of the cDNA for interleukin1 (IL1) β in the human and IL1α in the mouse. However, the history of IL1 begins in the early 1940s with investigations into the nature of an endogenous fever-producing protein released rabbit peritoneal neutrophils. Most researchers in immunology today are unaware that the field of cytokines, particularly the field of inflammatory cytokines. Toll-like receptors and innate immunity traces back to studies on fever. Researchers in infectious diseases wanted to know about an endogenous protein that caused fever, independent of infection. The endogenous fever-producing protein was called by various names: granulocyte, endogenous or leukocytic pyrogen. It is a fascinating and sometimes controversial story for biology and medicine and for the treatment of inflammatory diseases. Few imagined that this fever-producing protein would play such a major role in nearly every cell and in most diseases. This paper reviews the true background and milestones of interleukin1 from the purification of leukocytic pyrogen to the first cDNA of IL1β and the validation of cytokine biology from ill-defined factors to its present day importance.

Comparisons of predictors for typhoid and paratyphoid fever in Kolkata, India

PubMed Central

Sur, Dipika; Ali, Mohammad; von Seidlein, Lorenz; Manna, Byomkesh; Deen, Jacqueline L; Acosta, Camilo J; Clemens, John D; Bhattacharya, Sujit K

2007-01-01

Background: Exposure of the individual to contaminated food or water correlates closely with the risk for enteric fever. Since public health interventions such as water improvement or vaccination campaigns are implemented for groups of individuals we were interested whether risk factors not only for the individual but for households, neighbourhoods and larger areas can be recognised? Methods: We conducted a large enteric fever surveillance study and analyzed factors which correlate with enteric fever on an individual level and factors associated with high and low risk areas with enteric fever incidence. Individual level data were linked to a population based geographic information systems. Individual and household level variables were fitted in Generalized Estimating Equations (GEE) with the logit link function to take into account the likelihood that household factors correlated within household members. Results: Over a 12-month period 80 typhoid fever cases and 47 paratyphoid fever cases were detected among 56,946 residents in two bustees (slums) of Kolkata, India. The incidence of paratyphoid fever was lower (0.8/1000/year), and the mean age of paratyphoid patients was older (17.1 years) than for typhoid fever (incidence 1.4/1000/year, mean age 14.7 years). Residents in areas with a high risk for typhoid fever had lower literacy rates and economic status, bigger household size, and resided closer to waterbodies and study treatment centers than residents in low risk areas. Conclusion: There was a close correlation between the characteristics detected based on individual cases and characteristics associated with high incidence areas. Because the comparison of risk factors of populations living in high versus low risk areas is statistically very powerful this methodology holds promise to detect risk factors associated with diseases using geographic information systems. PMID:17935611

Accuracy of Diagnosis Codes to Identify Febrile Young Infants Using Administrative Data

PubMed Central

Aronson, Paul L.; Williams, Derek J.; Thurm, Cary; Tieder, Joel S.; Alpern, Elizabeth R.; Nigrovic, Lise E.; Schondelmeyer, Amanda C.; Balamuth, Fran; Myers, Angela L.; McCulloh, Russell J.; Alessandrini, Evaline A.; Shah, Samir S.; Browning, Whitney L.; Hayes, Katie L.; Feldman, Elana A.; Neuman, Mark I.

2015-01-01

Background Administrative data can be used to determine optimal management of febrile infants and aid clinical practice guideline development. Objective Determine the most accurate International Classification of Diseases, 9th revision (ICD-9) diagnosis coding strategies for identification of febrile infants. Design Retrospective cross-sectional study. Setting Eight emergency departments in the Pediatric Health Information System. Patients Infants age < 90 days evaluated between July 1, 2012 and June 30, 2013 were randomly selected for medical record review from one of four ICD-9 diagnosis code groups: 1) discharge diagnosis of fever, 2) admission diagnosis of fever without discharge diagnosis of fever, 3) discharge diagnosis of serious infection without diagnosis of fever, and 4) no diagnosis of fever or serious infection. Exposure The ICD-9 diagnosis code groups were compared in four case-identification algorithms to a reference standard of fever ≥ 100.4°F documented in the medical record. Measurements Algorithm predictive accuracy was measured using sensitivity, specificity, negative and positive predictive values. Results Among 1790 medical records reviewed, 766 (42.8%) infants had fever. Discharge diagnosis of fever demonstrated high specificity (98.2%, 95% confidence interval [CI]: 97.8-98.6) but low sensitivity (53.2%, 95% CI: 50.0-56.4). A case-identification algorithm of admission or discharge diagnosis of fever exhibited higher sensitivity (71.1%, 95% CI: 68.2-74.0), similar specificity (97.7%, 95% CI: 97.3-98.1), and the highest positive predictive value (86.9%, 95% CI: 84.5-89.3). Conclusions A case-identification strategy that includes admission or discharge diagnosis of fever should be considered for febrile infant studies using administrative data, though under-classification of patients is a potential limitation. PMID:26248691

Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.

PubMed

Uneke, C J

2008-06-01

Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987-2007), to highlight the diagnostic challenges and the public health implications. Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

Typhoid Fever in South Africa in an Endemic HIV Setting

PubMed Central

Keddy, Karen H.; Sooka, Arvinda; Smith, Anthony M.; Musekiwa, Alfred; Tau, Nomsa P.; Klugman, Keith P.; Angulo, Frederick J.

2016-01-01

Background Typhoid fever remains an important disease in Africa, associated with outbreaks and the emerging multidrug resistant Salmonella enterica serotype Typhi (Salmonella Typhi) haplotype, H58. This study describes the incidence of, and factors associated with mortality due to, typhoid fever in South Africa, where HIV prevalence is high. Methods and Findings Nationwide active laboratory-based surveillance for culture-confirmed typhoid fever was undertaken from 2003–2013. At selected institutions, additional clinical data from patients were collected including age, sex, HIV status, disease severity and outcome. HIV prevalence among typhoid fever patients was compared to national HIV seroprevalence estimates. The national reference laboratory tested Salmonella Typhi isolates for antimicrobial susceptibility and haplotype. Unadjusted and adjusted logistic regression analyses were conducted determining factors associated with typhoid fever mortality. We identified 855 typhoid fever cases: annual incidence ranged from 0.11 to 0.39 per 100,000 population. Additional clinical data were available for 369 (46.8%) cases presenting to the selected sites. Among typhoid fever patients with known HIV status, 19.3% (29/150) were HIV-infected. In adult females, HIV prevalence in typhoid fever patients was 43.2% (19/44) versus 15.7% national HIV seroprevalence (P < .001); in adult males, 16.3% (7/43) versus 12.3% national HIV seroprevalence (P = .2). H58 represented 11.9% (22/185) of Salmonella Typhi isolates tested. Increased mortality was associated with HIV infection (AOR 10.7; 95% CI 2.3–50.3) and disease severity (AOR 9.8; 95% CI 1.6–60.0) on multivariate analysis. Conclusions Typhoid fever incidence in South Africa was largely unchanged from 2003–2013. Typhoid fever mortality was associated disease severity. HIV infection may be a contributing factor. Interventions mandate improved health care access, including to HIV management programmes as well as patient education. Further studies are necessary to clarify relationships between HIV infection and typhoid fever in adults. PMID:27780232

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

PubMed Central

Ferreira, Manuel A. R.; Matheson, Melanie C.; Tang, Clara S.; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K.; Duffy, David L.; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D.; Eriksson, Nicholas; Madden, Pamela A.; Abramson, Michael J.; Holt, Patrick G.; Heath, Andrew C.; Hunter, Michael; Musk, Bill; Robertson, Colin F.; Le Souëf, Peter; Montgomery, Grant W.; Henderson, A. John; Tung, Joyce Y.; Dharmage, Shyamali C.; Brown, Matthew A.; James, Alan; Thompson, Philip J.; Pennell, Craig; Martin, Nicholas G.; Evans, David M.; Hinds, David A.; Hopper, John L.

2014-01-01

Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10−9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. PMID:24388013

Paralytic squint due to abducens nerve palsy : a rare consequence of dengue fever

PubMed Central

2012-01-01

Background Dengue fever is an endemic illness in the tropics with early and post infectious complications affecting multiple systems. Though neurological sequelae including mononeuropathy, encephalopathy, transverse myelitis, polyradiculopathy, Guillain-Barre syndrome , optic neuropathy and oculomotor neuropathy have been reported in medical literature, the abducens nerve despite its notoriety in cranial neuropathies in a multitude of condition due to its long intracranial course had not been to date reported to manifest with lateral rectus paralysis following dengue. Case presentation A previously well 29 year old male with serologically confirmed dengue hemorrhagic fever developed symptomatic right lateral rectus palsy during the critical phase of the illness, which persisted into convalescence and post convalescence with proven deficit on Hess screen. Alternate etiologies were excluded by imaging, serology and electrophysiology. Conclusions The authors detail the first reported case of abducens nerve palsy complicating dengue fever in a previously healthy male from Sri Lanka. In a tropical country with endemic dengue infections, dengue related abducens neuropathy may be considered as a differential diagnosis in cases of acquired lateral rectus palsy after dengue fever. PMID:22799448

Could Homeopathy Become An Alternative Therapy In Dengue Fever? An example Of 10 Case Studies.

PubMed

Mahesh, Seema; Mahesh, Mallappa; Vithoulkas, George

2018-01-01

Background: Dengue fever is one of the most rampant epidemics in India of late and any therapy that may help limit the sickness and hospital admissions is worth considering. In India complementary and alternative medicine physicians are medically trained and hence have a role to play in delivery of public health. Case Series: We present a retrospective case series of 10 Indian patients who were diagnosed with dengue fever and treated exclusively with homeopathic remedies at Bangalore, India. This case series demonstrates with evidence of laboratory reports that even when the platelets dropped considerably there was good result without resorting to any other means. Conclusions: A need for further, larger studies is indicated by this evidence, to precisely define the role of homeopathy in treating dengue fever. This study also emphasises the importance of individualised treatment during an epidemic for favourable results with homeopathy. Abbreviations: DF: dengue fever, NS1: non-structural protein 1 antigen, IgG: immunoglobulin G, IgM: immunoglobulin M, +ve: positive, -ve: negative, WBC: white blood cells, RBC: red blood cells, ESR: erythrocyte sedimentation rate.

Bacterial-based Systems for Expression and Purification of Recombinant Lassa Virus Proteins of Immunological Relevance

DTIC Science & Technology

2008-06-06

sites. Abbreviations include: MBP gene (malE), MBP promoter (Ptac), philamentous phage origin of replication ( M13 ori), bacterial origin of replica...notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display

The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry.

PubMed

Gehring, Gerrit; Rohrmann, Katrin; Atenchong, Nkacheh; Mittler, Eva; Becker, Stephan; Dahlmann, Franziska; Pöhlmann, Stefan; Vondran, Florian W R; David, Sascha; Manns, Michael P; Ciesek, Sandra; von Hahn, Thomas

2014-08-01

Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds. We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant. The ion channel blockers amiodarone, dronedarone and verapamil inhibit filoviral cell entry. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Rural-Urban Differences in Maternal Responses to Childhood Fever in South East Nigeria

PubMed Central

Uzochukwu, Benjamin S. C.; Onwujekwe, Emmanuel O.; Onoka, Chima A.; Ughasoro, Maduka D.

2008-01-01

Background Childhood fevers due to malaria remain a major cause of morbidity and mortality among under-five children in Nigeria. The degree of vulnerability perceived by mothers will affect their perception of the severity and threat of their child's fever and the patterns of health care use. This study was undertaken to compare maternal responses to childhood fever in urban and rural areas of Enugu, south east Nigeria. Methodology/Principal Findings Data was collected with pre-tested interviewer-administered questionnaires from 276 and 124 urban and rural households respectively. In each household, only one woman aged 15–49 years who had lived in each of the urban and rural communities for at least one year and had at least one child less than 5 years old was interviewed. Malaria was mentioned as the commonest cause of childhood fevers. Rural mothers were more likely to recognize danger signs and symptoms than urban mothers. Rural mothers use more of informal than formal health services, and there is more home management of the fever with urban than rural mothers. Chloroquine, ACT, SP and Paracetamol are the main drugs given at home for childhood fevers, but the rural mothers were more likely to use leftover drugs from previous treatment to treat the fevers than urban mothers. The urban respondents were also more likely to use a preventive measure. Urban mothers sought actions faster than rural mothers and the total cost of treatment was also higher in urban areas. Conclusions/Significance Both urban and rural mothers are aware that malaria is the major cause of childhood fevers. Although rural mothers recognize childhood fever and danger signs better than urban mothers, the urban mothers' responses to fever seem to be better than that for rural mothers. These responses and differences may be important for geographical targeting by policy makers for malaria interventions. PMID:18335058

Travel-related mosquito-transmitted disease questionnaire survey among health professionals in Taiwan.

PubMed

Huang, Hsien-Liang; Chiu, Tai-Yuan; Huang, Kuo-Chin; Cheng, Shao-Yi; Yao, Chien-An; Lee, Long-Teng

2011-01-01

Health-care professionals can help travelers by providing accurate pre-travel counseling for mosquito-transmitted diseases such as malaria, yellow fever, and dengue fever. Governments and international organizations will benefit from knowledge survey among health professionals in this field to promote the development of travel health profession. This study investigates physicians' and nurses' knowledge regarding malaria, yellow fever, and dengue fever. A cross-sectional questionnaire survey was distributed to physicians and nurses in Taiwan interested in travel medicine between April and September of 2008. The self-administered, single-choice questionnaire evaluated knowledge regarding epidemiology, prophylactic medication for malaria, yellow fever, and dengue fever, and vaccinations for yellow fever as well as background information of participants. Complete information was collected from 82 physicians and 203 nurses. (Out of 289, effective response rate = 99.9%). The mean percentage of accurate responses was similar for all three diseases: malaria 67.3% (range, 16.8%-90.5%); yellow fever 65.4% (39.6%-79.3%); and dengue fever 74.4% (14.4%-96.5%). The items with the lowest accuracy were (1) behavior of the dengue fever vector Aedes aegypti mosquito (14.4%) and (2) incubation period of malaria (16.8%). There were 60.4% participants who did not know the current revaccination interval for the yellow fever vaccine. The average knowledge scores for all three diseases were statistically significantly higher in the physician group. Analysis of the results revealed significant deficits in travel medicine knowledge among health-care providers. Emphasis on continuing medical education for disease vector behavior, prophylactic drug prescription, and preventative vaccination is important to travel safety. Health professionals in Taiwan should actively participate in the International Society of Travel Medicine to follow the international standard of travel medicine practitioners. This type of survey should be adopted in other countries which would be helpful in improving the quality of care for travelers. © 2010 International Society of Travel Medicine.

Geographic patterns and environmental factors associated with human yellow fever presence in the Americas

PubMed Central

Aldighieri, Sylvain; Machado, Gustavo; Leonel, Deise Galan; Vilca, Luz Maria; Uriona, Sonia; Schneider, Maria Cristina

2017-01-01

Background In the Americas, yellow fever virus transmission is a latent threat due to the proximity between urban and wild environments. Although yellow fever has nearly vanished from North and Central America, there are still 13 countries in the Americas considered endemic by the World Health Organization. Human cases usually occur as a result of the exposure to sylvatic yellow fever in tropical forested environments; but urban outbreaks reported during the last decade demonstrate that the risk in this environment still exists. The objective of this study was to identify spatial patterns and the relationship between key geographic and environmental factors with the distribution of yellow fever human cases in the Americas. Methodology/Principal findings An ecological study was carried out to analyze yellow fever human cases reported to the Pan American Health Organization from 2000 to 2014, aggregated by second administrative level subdivisions (counties). Presence of yellow fever by county was used as the outcome variable and eight geo-environmental factors were used as independent variables. Spatial analysis was performed to identify and examine natural settings per county. Subsequently, a multivariable logistic regression model was built. During the study period, 1,164 cases were reported in eight out of the 13 endemic countries. Nearly 83.8% of these cases were concentrated in three countries: Peru (37.4%), Brazil (28.1%) and Colombia (18.4%); and distributed in 57 states/provinces, specifically in 286 counties (3.4% of total counties). Yellow fever presence was significantly associated with altitude, rain, diversity of non-human primate hosts and temperature. A positive spatial autocorrelation revealed a clustered geographic pattern in 138/286 yellow fever positive counties (48.3%). Conclusions/Significance A clustered geographic pattern of yellow fever was identified mostly along the Andes eastern foothills. This risk map could support health policies in endemic countries. Geo-environmental factors associated with presence of yellow fever could help predict and adjust the limits of other risk areas of epidemiological concern. PMID:28886023

Seroprevalence of Coxiella burnetii antibodies and chronic Q fever among post-mortal and living donors of tissues and cells from 2010 to 2015 in the Netherlands

PubMed Central

van Roeden, Sonja E; Holsboer, Eleonoor W; Oosterheert, Jan Jelrik; van Kats, Jorge P; van Beckhoven, Jacqueline; Hogema, Boris M; van Wijk, Marja J

2018-01-01

Background After a large Q fever outbreak in the Netherlands in the period from 2007 to 2010, the risk of Q fever transmission through tissue and cell transplantation from undiagnosed chronic Q fever cases became a potential issue. Aim: We aimed to evaluate the risk of Q fever transmission through tissue and cell transplantation. Methods: We performed a retrospective observational cohort study among 15,133 Dutch donors of tissues and stem cells from 2010 to 2015 to assess seroprevalence of Coxiella burnetii antibodies, to identify factors associated with presence of C. burnetii antibodies, and to assess the proportion of undiagnosed chronic Q fever cases. Results: The study population consisted of 9,478 (63%) femoral head donors, 5,090 (34%) post-mortal tissue donors and 565 (4%) cord blood donors. Seroprevalence of C. burnetii antibodies gradually decreased after the outbreak, from 2.1% in 2010 to 1.4% in 2015, with a significant trend in time (p < 0.001). Of 301 seropositive donors, seven (2.3%) were newly detected with chronic Q fever (0.05% of all screened donors). Conclusion: This study shows that seroprevalence of C. burnetii antibodies among donors of tissues and cells in the Netherlands after 2014 was similar to pre-outbreak levels in the general population. The proportion of newly detected chronic Q fever patients among donors of tissues and cells was smaller than 0.1%. This study may prompt discussion on when to terminate the screening programme for chronic Q fever in donors of tissues and cells in the Netherlands. PMID:29510781

Seroprevalence of Coxiella burnetii antibodies and chronic Q fever among post-mortal and living donors of tissues and cells from 2010 to 2015 in the Netherlands.

PubMed

van Roeden, Sonja E; Holsboer, Eleonoor W; Oosterheert, Jan Jelrik; van Kats, Jorge P; van Beckhoven, Jacqueline; Hogema, Boris M; van Wijk, Marja J

2018-03-01

BackgroundAfter a large Q fever outbreak in the Netherlands in the period from 2007 to 2010, the risk of Q fever transmission through tissue and cell transplantation from undiagnosed chronic Q fever cases became a potential issue. Aim: We aimed to evaluate the risk of Q fever transmission through tissue and cell transplantation. Methods: We performed a retrospective observational cohort study among 15,133 Dutch donors of tissues and stem cells from 2010 to 2015 to assess seroprevalence of Coxiella burnetii antibodies, to identify factors associated with presence of C. burnetii antibodies, and to assess the proportion of undiagnosed chronic Q fever cases. Results: The study population consisted of 9,478 (63%) femoral head donors, 5,090 (34%) post-mortal tissue donors and 565 (4%) cord blood donors. Seroprevalence of C. burnetii antibodies gradually decreased after the outbreak, from 2.1% in 2010 to 1.4% in 2015, with a significant trend in time (p < 0.001). Of 301 seropositive donors, seven (2.3%) were newly detected with chronic Q fever (0.05% of all screened donors). Conclusion: This study shows that seroprevalence of C. burnetii antibodies among donors of tissues and cells in the Netherlands after 2014 was similar to pre-outbreak levels in the general population. The proportion of newly detected chronic Q fever patients among donors of tissues and cells was smaller than 0.1%. This study may prompt discussion on when to terminate the screening programme for chronic Q fever in donors of tissues and cells in the Netherlands.

Fatigue following Acute Q-Fever: A Systematic Literature Review.

PubMed

Morroy, Gabriella; Keijmel, Stephan P; Delsing, Corine E; Bleijenberg, Gijs; Langendam, Miranda; Timen, Aura; Bleeker-Rovers, Chantal P

2016-01-01

Long-term fatigue with detrimental effects on daily functioning often occurs following acute Q-fever. Following the 2007-2010 Q-fever outbreak in the Netherlands with over 4000 notified cases, the emphasis on long-term consequences of Q-fever increased. The aim of this study was to provide an overview of all relevant available literature, and to identify knowledge gaps regarding the definition, diagnosis, background, description, aetiology, prevention, therapy, and prognosis, of fatigue following acute Q-fever. A systematic review was conducted through searching Pubmed, Embase, and PsycInfo for relevant literature up to 26th May 2015. References of included articles were hand searched for additional documents, and included articles were quality assessed. Fifty-seven articles were included and four documents classified as grey literature. The quality of most studies was low. The studies suggest that although most patients recover from fatigue within 6-12 months after acute Q-fever, approximately 20% remain chronically fatigued. Several names are used indicating fatigue following acute Q-fever, of which Q-fever fatigue syndrome (QFS) is most customary. Although QFS is described to occur frequently in many countries, a uniform definition is lacking. The studies report major health and work-related consequences, and is frequently accompanied by nonspecific complaints. There is no consensus with regard to aetiology, prevention, treatment, and prognosis. Long-term fatigue following acute Q-fever, generally referred to as QFS, has major health-related consequences. However, information on aetiology, prevention, treatment, and prognosis of QFS is underrepresented in the international literature. In order to facilitate comparison of findings, and as platform for future studies, a uniform definition and diagnostic work-up and uniform measurement tools for QFS are proposed.

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

PubMed Central

GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

2017-01-01

Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

Novel Arenavirus Sequences in Hylomyscus sp. and Mus (Nannomys) setulosus from Côte d'Ivoire: Implications for Evolution of Arenaviruses in Africa

PubMed Central

Kouassi, Stéphane K.; Fichet-Calvet, Elisabeth; Becker-Ziaja, Beate; Rieger, Toni; Ölschläger, Stephan; Dosso, Hernri; Denys, Christiane; ter Meulen, Jan; Akoua-Koffi, Chantal; Günther, Stephan

2011-01-01

This study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in Africa. During 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of Côte d'Ivoire. Specimens were screened by pan-Old World arenavirus RT-PCRs targeting S and L RNA segments as well as immunofluorescence assay. Sequences of two novel tentative species of the family Arenaviridae, Menekre and Gbagroube virus, were detected in Hylomyscus sp. and Mus (Nannomys) setulosus, respectively. Arenavirus infection of Mus (Nannomys) setulosus was also demonstrated by serological testing. Lassa virus was not found, although 60% of the captured animals were Mastomys natalensis. Complete S RNA and partial L RNA sequences of the novel viruses were recovered from the rodent specimens and subjected to phylogenetic analysis. Gbagroube virus is a closely related sister taxon of Lassa virus, while Menekre virus clusters with the Ippy/Mobala/Mopeia virus complex. Reconstruction of possible virus–host co-phylogeny scenarios suggests that, within the African continent, signatures of co-evolution might have been obliterated by multiple host-switching events. PMID:21695269

Estimating the Number of Paediatric Fevers Associated with Malaria Infection Presenting to Africa's Public Health Sector in 2007

PubMed Central

Gething, Peter W.; Kirui, Viola C.; Alegana, Victor A.; Okiro, Emelda A.; Noor, Abdisalan M.; Snow, Robert W.

2010-01-01

Background As international efforts to increase the coverage of artemisinin-based combination therapy in public health sectors gather pace, concerns have been raised regarding their continued indiscriminate presumptive use for treating all childhood fevers. The availability of rapid-diagnostic tests to support practical and reliable parasitological diagnosis provides an opportunity to improve the rational treatment of febrile children across Africa. However, the cost effectiveness of diagnosis-based treatment polices will depend on the presumed numbers of fevers harbouring infection. Here we compute the number of fevers likely to present to public health facilities in Africa and the estimated number of these fevers likely to be infected with Plasmodium falciparum malaria parasites. Methods and Findings We assembled first administrative-unit level data on paediatric fever prevalence, treatment-seeking rates, and child populations. These data were combined in a geographical information system model that also incorporated an adjustment procedure for urban versus rural areas to produce spatially distributed estimates of fever burden amongst African children and the subset likely to present to public sector clinics. A second data assembly was used to estimate plausible ranges for the proportion of paediatric fevers seen at clinics positive for P. falciparum in different endemicity settings. We estimated that, of the 656 million fevers in African 0–4 y olds in 2007, 182 million (28%) were likely to have sought treatment in a public sector clinic of which 78 million (43%) were likely to have been infected with P. falciparum (range 60–103 million). Conclusions Spatial estimates of childhood fevers and care-seeking rates can be combined with a relational risk model of infection prevalence in the community to estimate the degree of parasitemia in those fevers reaching public health facilities. This quantification provides an important baseline comparison of malarial and nonmalarial fevers in different endemicity settings that can contribute to ongoing scientific and policy debates about optimum clinical and financial strategies for the introduction of new diagnostics. These models are made publicly available with the publication of this paper. Please see later in the article for the Editors' Summary PMID:20625548

Perception and management of fever in infants up to six months of age: A survey of US pediatricans

PubMed Central

2010-01-01

Background A fever is an increase in the body's temperature above normal. This study examined how US pediatricians perceive and manage fever generally versus fever occurring after vaccination in infants up to six months of age. Methods A web-based survey of 400 US pediatricians subscribing to the Physician Desk Reference was conducted in December 2008. Data were collected on the respondents' socio-demographics, number of years in practice, type of practice, their definition of fever severity in infants, and their recommendations for managing fever. Generalized Estimating Equations were used to estimate the odds of a pediatrician recommending an emergency room visit (ER) or a hospital admission, office visits, or other treatment option, as a function of infant's age, temperature, whether the infant has recently received a vaccine, and whether the fever was reported during or after office hours, adjusting for practice type and socio-demographic variables. Results On average, the 400 responding pediatricians' (64% were female, average age of 49 years, years in practice = 20 years) threshold for extremely serious fever was ≥39.5°C and ≥ 40.0°C for infants 0-2 month and >2-6 month of age respectively. Infants were more likely to be referred to an ER or hospital admission if they were ≤ 2 months of age (Odds Ratio [OR], 29.13; 95% Confidence interval [95% CI], 23.69-35.82) or >2-4 months old (OR 3.37; 95% CI 2.99-3.81) versus > 4 to 6 months old or if they had a temperature ≥ 40.0°C (OR 21.06; 95% CI 17.20-25.79) versus a temperature of 38.0-38.5°C. Fever after vaccination (OR 0.29; 95% CI 0.25-0.33) or reported during office hours (OR 0.17; 95% CI 0.15-0.20) were less likely to result in referral to ER or hospital admission. Conclusion Within this sample of US pediatricians, perception of the severity of fever in infants, as well as the response to infant fever are likely to depend on the infant's age. Recommendations for the management of fever in infants are likely to depend on fever severity level, the infant age, timing in relation to recent vaccination, and the time of day fever is reported. Our results indicate that US pediatricians are more concerned about general fever than fever following vaccination. PMID:21176190

The High Degree of Sequence Plasticity of the Arenavirus Noncoding Intergenic Region (IGR) Enables the Use of a Nonviral Universal Synthetic IGR To Attenuate Arenaviruses

PubMed Central

Iwasaki, Masaharu; Cubitt, Beatrice; Sullivan, Brian M.

2016-01-01

ABSTRACT Hemorrhagic fever arenaviruses (HFAs) pose important public health problems in regions where they are endemic. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. We have recently shown that the noncoding intergenic region (IGR) present in each arenavirus genome segment, the S and L segments (S-IGR and L-IGR, respectively), plays important roles in the control of virus protein expression and that this knowledge could be harnessed for the development of live-attenuated vaccine strains to combat HFAs. In this study, we further investigated the sequence plasticity of the arenavirus IGR. We demonstrate that recombinants of the prototypic arenavirus lymphocytic choriomeningitis virus (rLCMVs), whose S-IGRs were replaced by the S-IGR of Lassa virus (LASV) or an entirely nonviral S-IGR-like sequence (Ssyn), are viable, indicating that the function of S-IGR tolerates a high degree of sequence plasticity. In addition, rLCMVs whose L-IGRs were replaced by Ssyn or S-IGRs of the very distantly related reptarenavirus Golden Gate virus (GGV) were viable and severely attenuated in vivo but able to elicit protective immunity against a lethal challenge with wild-type LCMV. Our findings indicate that replacement of L-IGR by a nonviral Ssyn could serve as a universal molecular determinant of arenavirus attenuation. IMPORTANCE Hemorrhagic fever arenaviruses (HFAs) cause high rates of morbidity and mortality and pose important public health problems in regions where they are endemic. Implementation of live-attenuated vaccines (LAVs) will represent a major step to combat HFAs. Here we document that the arenavirus noncoding intergenic region (IGR) has a high degree of plasticity compatible with virus viability. This observation led us to generate recombinant LCMVs containing nonviral synthetic IGRs. These rLCMVs were severely attenuated in vivo but able to elicit protective immunity against a lethal challenge with wild-type LCMV. These nonviral synthetic IGRs can be used as universal molecular determinants of arenavirus attenuation for the rapid development of safe and effective, as well as stable, LAVs to combat HFA. PMID:26739049

Heart Lesion After the First Attack of the Rheumatic Fever 22 Years Experience in Single Centre

PubMed Central

Bejiqi, Ramush A.; Retkoceri, Ragip; Zeka, Naim; Bejiqi, Hana; Retkoceri, Arber

2015-01-01

Background: Acute rheumatic fever and its sequels, rheumatic heart diseases, remain major unsolved preventable health problems in Kosovo population, particularly among the disadvantages indigenous Albanian and Egyptians people. In Kosovo, despite of performing secondary prophylaxis with benzathine penicillin, acute rheumatic fever hospitalization rates have remained essentially unchanged for the last 20 years. The role of echocardiography in the diagnosis of acute rheumatic carditis was established over the last 20 years. Aims: In this study we aimed to determine the prevalence of rheumatic heart disease in children from Kosovo population with first attack of acute rheumatic fever. Also, we presented that echocardiography examination detects a greater prevalence of rheumatic heart disease than other diagnostic procedures. We aimed to compare the sensitivity and specificity of cardiac auscultation, ECG record, lab analysis to echocardiography and to determine the feasibility of specific age in this setting. Methods: To optimize accurate diagnosis of rheumatic fever and rheumatic heart disease, we utilized two group models. In the first group of 388 children, hospitalized and treated before 1999, diagnosis of rheumatic fever was decided basing on the clinical and laboratory findings whereas in second group (221 children treated from1999 to 2010) clinical and lab diagnosis were amplified also on the detection by echocardiography. Conclusion: In second group, using echocardiography as a method of diagnosis and assessment children with rheumatic fever, we found high rates of undetected rheumatic heart disease in this high-risk group population. Echocardiographic examination of children with rheumatic fever for rheumatic heart disease may over diagnose rheumatic heart disease unless congenital mitral valve anomalies and physiological regurgitation are excluded. PMID:25870479

Parental and medical knowledge and management of fever in Italian pre-school children

PubMed Central

2012-01-01

Background Guidelines for the management of fever in children have been recently published, however “fever phobia” is still spreading. To provide information which may sustain educational interventions tailored to our population we investigated the parental and medical knowledge and management of fever in preschool children. Methods A questionnaire was administered to a convenient sample of Italian parents and paediatricians. The questionnaire elicited information about definition and cause of fever, concerns about fever, method of temperature measurement, and treatment modalities. Results Overall, 388 parents and 480 paediatricians were interviewed. All the parents believed that fever could cause at least one harmful effect and 89.9% (n = 349) believed that, if left untreated, it can cause brain damage or seizures. Parents used multiple resources to obtain information about fever but 67.8% (n = 264) considered paediatricians as their primary resource. Several wrong behaviours were found in the same proportions among parents and paediatricians: 78.5% of paediatricians (n = 377) and 77.8% of parents (n = 302) used physical method to reduce fever (P = 0.867); 27.0% of paediatricians (n = 103) and 21.4% (n = 83) of parents declared to alternate ibuprofen and acetaminophen (P = 0.953). Differently, 73.1% (n = 351) of paediatricians preferred oral to rectal administration of antipyretics compared to 48.7% (n = 190) of parents (P < 0.0001). Worrisomely, 1.4% of paediatricians and 1.2% of parents declared to use acetylsalicylic acid or steroids as second-choice antipyretics (P = 0.937) and 6.7% (n = 26) of parents declared to use table- or teaspoons for determining the dose of drug. Conclusions Paediatricians’ attitudes greatly influence the parental behaviours and beliefs. Implementation of educational programs regarding the management of the febrile child are needed in our setting. PMID:22794080

Detection of fever in children emergency care: comparisons of tactile and rectal temperatures in Nigerian children

PubMed Central

2010-01-01

Background Clinical thermometry is the objective method for temperature measurements but tactile assessment of fever at home is usually the basis for seeking medical attention especially where the cost and level of literacy preclude the use of thermometers. This study was carried out to determine the reliability of tactile perception of fever by caregivers, nurses and house physicians in comparison to rectal thermometry and also the use of commonly practiced surface of the hand in the care of ill children. All caregivers of children aged 6 to 59 months who presented to the emergency department were approached consecutively at the triage stage but 182 children participated. Each child had tactile assessment of fever using palmar and dorsal surfaces of the hand by the caregivers, House Physicians and Nursing Officers. Rectal temperature was also measured and read independently by nurses and house physicians. Comparisons were made between tactile assessments and thermometer readings using a cut-off for fever, 38.0°C and above. Findings The caregivers' perception of fever had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 95%, 23%, 66% and 73%, respectively compared with 93%, 26%, 67% and 69%, respectively for nursing officers. Irrespective of the groups studied, 77.1% of 336 assessors opined that the dorsal surface of the hand was more sensitive in tactile assessment of temperature and the frequently used site for assessment of fever were the head (35.6%) and neck (33.3%). Tactile assessment of temperature over-detected fever in ≥ 24% of cases among the three groups of assessors. Conclusions The present study suggests that tactile assessment of temperature may over estimate the prevalence of fever, it does not detect some cases and the need for objective measurement of temperature is emphasised in paediatric emergency care. PMID:20406473

Large Regional Differences in Serological Follow-Up of Q Fever Patients in The Netherlands

PubMed Central

Morroy, Gabriëlla; Wielders, Cornelia C. H.; Kruisbergen, Mandy J. B.; van der Hoek, Wim; Marcelis, Jan H.; Wegdam-Blans, Marjolijn C. A.; Wijkmans, Clementine J.; Schneeberger, Peter M.

2013-01-01

Background During the Dutch Q fever epidemic more than 4,000 Q fever cases were notified. This provided logistical challenges for the organisation of serological follow-up, which is considered mandatory for early detection of chronic infection. The aim of this study was to investigate the proportion of acute Q fever patients that received serological follow-up, and to identify regional differences in follow-up rates and contributing factors, such as knowledge of medical practitioners. Methods Serological datasets of Q fever patients diagnosed between 2007 and 2009 (N = 3,198) were obtained from three Laboratories of Medical Microbiology (LMM) in the province of Noord-Brabant. One LMM offered an active follow-up service by approaching patients; the other two only tested on physician's request. The medical microbiologist in charge of each LMM was interviewed. In December 2011, 240 general practices and 112 medical specialists received questionnaires on their knowledge and practices regarding the serological follow-up of Q fever patients. Results Ninety-five percent (2,226/2,346) of the Q fever patients diagnosed at the LMM with a follow-up service received at least one serological follow-up within 15 months of diagnosis. For those diagnosed at a LMM without this service, this was 25% (218/852) (OR 54, 95% CI 43–67). Although 80% (162/203) of all medical practitioners with Q fever patients reported informing patients of the importance of serological follow-up, 33% (67/203) never requested it. Conclusions Regional differences in follow-up are substantial and range from 25% to 95%. In areas with a low follow-up rate the proportion of missed chronic Q fever is potentially higher than in areas with a high follow-up rate. Medical practitioners lack knowledge regarding the need, timing and implementation of serological follow-up, which contributes to patients receiving incorrect or no follow-up. Therefore, this information should be incorporated in national guidelines and patient information forms. PMID:23577152

Fever phobia: The impact of time and mortality--a systematic review and meta-analysis.

PubMed

Purssell, Edward; Collin, Jacqueline

2016-04-01

Fever phobia is a term that has been used to describe the exaggerated and unrealistic fear of fever expressed by parents and carers. Since the term was first used in the early 1980s, there have been numerous publications and guidelines stating that fever is not, in itself dangerous, however these fears persist. Investigate the extent of fever phobia and to explore potential associations with time, under-5 mortality rate and geography. Embase (1980 to week 1 2015) and Medline (1946 to week 1 2015) were searched using the terms 'fever' and 'phobia'; and 'fever phobia' as a free text term. One additional paper was published during the review period. Studies giving proportion of parents, carers or professionals expressing fear of fever. Meta-analysis and cluster analysis using metafor, meta and Cluster in R. Fear of brain damage, coma, convulsions, death and dehydration was high across many of the studies; however there was significant variation as shown by the high I(2) scores which exceeded 95%. This was not explained by the two predictive variables of year of publication, or background mortality apart from a reduction in the fear of brain damage (-0.0185, CI -0.0313 to -0.0057, p=0.0046) and dehydration (-0.0831, -0.1477 to -0.0184, p=0.0118) associated with increased child mortality. Studies were all cross-sectional surveys with a high risk of bias. The pooled estimate, although statistically significant is not the outcome of interest and so should be interpreted with caution. Fever phobia is common and has not significantly declined over time. This may suggest that it is a cultural, rather than individually learned trait and that individual educational programmes are unlikely to be successful in the face of widespread cultural transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dipyrone metabolite 4-MAA induces hypothermia and inhibits PGE2-dependent and -independent fever while 4-AA only blocks PGE2-dependent fever

PubMed Central

Malvar, David do C; Aguiar, Fernando A; Vaz, Artur de L L; Assis, Débora C R; de Melo, Miriam C C; Jabor, Valquíria A P; Kalapothakis, Evanguedes; Ferreira, Sérgio H; Clososki, Giuliano C; de Souza, Glória E P

2014-01-01

BACKGROUND AND PURPOSE The antipyretic and hypothermic prodrug dipyrone prevents PGE2-dependent and -independent fever induced by LPS from Escherichia coli and Tityus serrulatus venom (Tsv) respectively. We aimed to identify the dipyrone metabolites responsible for the antipyretic and hypothermic effects. EXPERIMENTAL APPROACH Male Wistar rats were treated i.p. with indomethacin (2 mg·kg−1), dipyrone, 4-methylaminoantipyrine (4-MAA), 4-aminoantipyrine (4-AA) (60–360 mg·kg−1), 4-formylaminoantipyrine, 4-acethylaminoantipyrine (120–360 mg·kg−1) or vehicle 30 min before i.p. injection of LPS (50 μg·kg−1), Tsv (150 μg·kg−1) or saline. Rectal temperatures were measured by tele-thermometry and dipyrone metabolite concentrations determined in the plasma, CSF and hypothalamus by LC-MS/MS. PGE2 concentrations were determined in the CSF and hypothalamus by elisa. KEY RESULTS In contrast to LPS, Tsv-induced fever was not followed by increased PGE2 in the CSF or hypothalamus. The antipyretic time-course of 4-MAA and 4-AA on LPS-induced fever overlapped with the period of the highest concentrations of 4-MAA and 4-AA in the hypothalamus, CSF and plasma. These metabolites reduced LPS-induced fever and the PGE2 increase in the plasma, CSF and hypothalamus. Only 4-MAA inhibited Tsv-induced fever. The higher doses of dipyrone and 4-MAA also induced hypothermia. CONCLUSIONS AND IMPLICATIONS The presence of 4-MAA and 4-AA in the CSF and hypothalamus was associated with PGE2 synthesis inhibition and a decrease in LPS-induced fever. 4-MAA was also shown to be an antipyretic metabolite for PGE2-independent fever induced by Tsv suggesting that it is responsible for the additional antipyretic mechanism of dipyrone. Moreover, 4-MAA is the hypothermic metabolite of dipyrone. PMID:24712707

Monitoring Procalcitonin in Febrile Neutropenia: What Is Its Utility for Initial Diagnosis of Infection and Reassessment in Persistent Fever?

PubMed Central

Bally, Frank; Knaup, Marlies; Calandra, Thierry; Marchetti, Oscar

2011-01-01

Background Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever. Methods PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%). Results At fever onset median PCT was 190 pg/mL (range 30–26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80–86350) vs. FUO (205, 33–771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570–771). A PCT peak >500 pg/mL (1196, 524–11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1–23) vs. 10 (3–22; p = 0.026), respectively. Conclusion While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses. PMID:21541027

Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

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

Gardner, Shea N.; Jaing, Crystal J.; Elsheikh, Maher M.

Background . Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results . A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Eachmore » group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions . This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.« less

Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

DOE PAGES

Gardner, Shea N.; Jaing, Crystal J.; Elsheikh, Maher M.; ...

2014-01-01

Background . Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results . A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Eachmore » group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions . This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.« less

The cost of uncomplicated childhood fevers to Kenyan households: implications for reaching international access targets

PubMed Central

Larson, Bruce A; Amin, Abdinasir A; Noor, Abdisalan M; Zurovac, Dejan; Snow, Robert W

2006-01-01

Background Fever is the clinical hallmark of malaria disease. The Roll Back Malaria (RBM) movement promotes prompt, effective treatment of childhood fevers as a key component to achieving its optimistic mortality reduction goals by 2010. A neglected concern is how communities will access these new medicines promptly and the costs to poor households when they are located in rural areas distant to health services. Methods We assemble data developed between 2001 and 2002 in Kenya to describe treatment choices made by rural households to treat a child's fever and the related costs to households. Using a cost-of-illness approach, we estimate the expected cost of a childhood fever to Kenyan households in 2002. We develop two scenarios to explore how expected costs to households would change if more children were treated at a health care facility with an effective antimalarial within 48 hours of fever onset. Results 30% of uncomplicated fevers were managed at home with modern medicines, 38% were taken to a health care facility (HCF), and 32% were managed at home without the use of modern medicines. Direct household cash expenditures were estimated at $0.44 per fever, while the total expected cost to households (cash and time) of an uncomplicated childhood fever is estimated to be $1.91. An estimated mean of 1.42 days of caretaker time devoted to each fever accounts for the majority of household costs of managing fevers. The aggregate cost to Kenyan households of managing uncomplicated childhood fevers was at least $96 million in 2002, equivalent to 1.00% of the Kenyan GDP. Fewer than 8% of all fevers were treated with an antimalarial drug within 24 hours of fever onset, while 17.5% were treated within 48 hours at a HCF. To achieve an increase from 17.5% to 33% of fevers treated with an antimalarial drug within 48 hours at a HCF (Scenario 1), children already being taken to a HCF would need to be taken earlier. Under this scenario, direct cash expenditures would not change, and total household costs would fall slightly to $1.86 because caretakers also save time with prompt treatment if the child has malaria. Conclusion The management of uncomplicated childhood fevers imposes substantial costs on Kenyan households. Achieving substantial improvements in the numbers of fevers treated within 48 hours at a HCF with an effective antimalarial drug (Scenario 1) will not impose additional costs on households. Achieving additional improvements in fevers treated promptly at a HCF (Scenario 2) will impose additional costs on some households roughly equal to average cash expenses for transportation to a HCF. Additional financing mechanisms that further reduce the costs of accessing care at a HCF and/or that make artemisinin-based combination therapies (ACTs) accessible for home management need to be developed and evaluated as a top priority. PMID:17196105

Atypical Rocky Mountain spotted fever with polyarticular arthritis

PubMed Central

Chaudhry, Muhammad A.; Hal Scofield, R.

2017-01-01

Background Rocky Mountain Spotted Fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare Purpose Describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands, and to review the previously reported patients with rickettsial infection and inflammatory arthritis Patient An 18 year old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on exam as well as an erythematosus macular rash, and occasional fever. Acute and convalescent serology demonstrated Rickettsia rickettsi infection. She was successfully treated with doxycycline. Conclusion Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with eight previously reported patients, only one of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations. PMID:24157965

Statistical modeling of valley fever data in Kern County, California

NASA Astrophysics Data System (ADS)

Talamantes, Jorge; Behseta, Sam; Zender, Charles S.

2007-03-01

Coccidioidomycosis (valley fever) is a fungal infection found in the southwestern US, northern Mexico, and some places in Central and South America. The fungus that causes it ( Coccidioides immitis) is normally soil-dwelling but, if disturbed, becomes air-borne and infects the host when its spores are inhaled. It is thus natural to surmise that weather conditions that foster the growth and dispersal of the fungus must have an effect on the number of cases in the endemic areas. We present here an attempt at the modeling of valley fever incidence in Kern County, California, by the implementation of a generalized auto regressive moving average (GARMA) model. We show that the number of valley fever cases can be predicted mainly by considering only the previous history of incidence rates in the county. The inclusion of weather-related time sequences improves the model only to a relatively minor extent. This suggests that fluctuations of incidence rates (about a seasonally varying background value) are related to biological and/or anthropogenic reasons, and not so much to weather anomalies.

Value of syndromic surveillance within the Armed Forces for early warning during a dengue fever outbreak in French Guiana in 2006

PubMed Central

Meynard, Jean-Baptiste; Chaudet, Hervé; Texier, Gaetan; Ardillon, Vanessa; Ravachol, Françoise; Deparis, Xavier; Jefferson, Henry; Dussart, Philippe; Morvan, Jacques; Boutin, Jean-Paul

2008-01-01

Background A dengue fever outbreak occured in French Guiana in 2006. The objectives were to study the value of a syndromic surveillance system set up within the armed forces, compared to the traditional clinical surveillance system during this outbreak, to highlight issues involved in comparing military and civilian surveillance systems and to discuss the interest of syndromic surveillance for public health response. Methods Military syndromic surveillance allows the surveillance of suspected dengue fever cases among the 3,000 armed forces personnel. Within the same population, clinical surveillance uses several definition criteria for dengue fever cases, depending on the epidemiological situation. Civilian laboratory surveillance allows the surveillance of biologically confirmed cases, within the 200,000 inhabitants. Results It was shown that syndromic surveillance detected the dengue fever outbreak several weeks before clinical surveillance, allowing quick and effective enhancement of vector control within the armed forces. Syndromic surveillance was also found to have detected the outbreak before civilian laboratory surveillance. Conclusion Military syndromic surveillance allowed an early warning for this outbreak to be issued, enabling a quicker public health response by the armed forces. Civilian surveillance system has since introduced syndromic surveillance as part of its surveillance strategy. This should enable quicker public health responses in the future. PMID:18597694

Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na+/K+ transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses

PubMed Central

Iwasaki, Masaharu; Caì, Yíngyún; de la Torre, Juan C.

2018-01-01

Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns in their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines, and current anti-mammarenavirus therapy is limited to off-label use of ribavirin that is only partially effective. Detailed understanding of virus/host-cell interactions may facilitate the development of novel anti-mammarenavirus strategies by targeting components of the host-cell machinery that are required for efficient virus multiplication. Here we document the generation of a recombinant LCMV encoding a nucleoprotein (NP) containing an affinity tag (rLCMV/Strep-NP) and its use to capture the NP-interactome in infected cells. Our proteomic approach combined with genetics and pharmacological validation assays identified ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) and prohibitin (PHB) as pro-viral factors. Cell-based assays revealed that ATP1A1 and PHB are involved in different steps of the virus life cycle. Accordingly, we observed a synergistic inhibitory effect on LCMV multiplication with a combination of ATP1A1 and PHB inhibitors. We show that ATP1A1 inhibitors suppress multiplication of Lassa virus and Candid#1, a live-attenuated vaccine strain of Junín virus, suggesting that the requirement of ATP1A1 in virus multiplication is conserved among genetically distantly related mammarenaviruses. Our findings suggest that clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to treat infections by mammarenaviruses pathogenic for humans. PMID:29462184

The C-terminal region of lymphocytic choriomeningitis virus nucleoprotein contains distinct and segregable functional domains involved in NP-Z interaction and counteraction of the type I interferon response.

PubMed

Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin; de la Torre, Juan Carlos; Martínez-Sobrido, Luis

2011-12-01

Several arenaviruses cause hemorrhagic fever (HF) disease in humans that is associated with high morbidity and significant mortality. Arenavirus nucleoprotein (NP), the most abundant viral protein in infected cells and virions, encapsidates the viral genome RNA, and this NP-RNA complex, together with the viral L polymerase, forms the viral ribonucleoprotein (vRNP) that directs viral RNA replication and gene transcription. Formation of infectious arenavirus progeny requires packaging of vRNPs into budding particles, a process in which arenavirus matrix-like protein (Z) plays a central role. In the present study, we have characterized the NP-Z interaction for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). The LCMV NP domain that interacted with Z overlapped with a previously documented C-terminal domain that counteracts the host type I interferon (IFN) response. However, we found that single amino acid mutations that affect the anti-IFN function of LCMV NP did not disrupt the NP-Z interaction, suggesting that within the C-terminal region of NP different amino acid residues critically contribute to these two distinct and segregable NP functions. A similar NP-Z interaction was confirmed for the HF arenavirus Lassa virus (LASV). Notably, LCMV NP interacted similarly with both LCMV Z and LASV Z, while LASV NP interacted only with LASV Z. Our results also suggest the presence of a conserved protein domain within NP but with specific amino acid residues playing key roles in determining the specificity of NP-Z interaction that may influence the viability of reassortant arenaviruses. In addition, this NP-Z interaction represents a potential target for the development of antiviral drugs to combat human-pathogenic arenaviruses.

Rapid deployment of a mobile biosafety level-3 laboratory in Sierra Leone during the 2014 Ebola virus epidemic.

PubMed

Zhang, Yi; Gong, Yan; Wang, Chengyu; Liu, Wensen; Wang, Zhongyi; Xia, Zhiping; Bu, Zhaoyang; Lu, Huijun; Sun, Yang; Zhang, Xiaoguang; Cao, Yuxi; Yang, Fan; Su, Haoxiang; Hu, Yi; Deng, Yongqiang; Zhou, Bo; Zhao, Zongzheng; Fu, Yingying; Kargbo, David; Dafae, Foday; Kargbo, Brima; Kanu, Alex; Liu, Linna; Qian, Jun; Guo, Zhendong

2017-05-01

Ebola virus emerged in West Africa in December 2013. The high population mobility and poor public health infrastructure in this region led to the development of the largest Ebola virus disease (EVD) outbreak to date. On September 26, 2014, China dispatched a Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which allowed the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving. This laboratory was composed of three container vehicles equipped with advanced ventilation system, communication system, electricity and gas supply system. We strictly applied multiple safety precautions to reduce exposure risks. Personnel, materials, water and air flow management were the key elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols was detected. Potentially contaminated objects were also tested by collecting swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635 suspected EVD cases (824 positive [50.4%]) were tested from September 28 to November 11, 2014, and no member of the diagnostic team was infected with Ebola virus or other pathogens, including Lassa fever. The specimens tested included blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%, respectively. The China mobile laboratory was thus instrumental in the EVD outbreak response by providing timely and reliable diagnostics. The MBSL-3 Lab significantly contributed to establishing a suitable laboratory response capacity during the emergence of EVD in Sierra Leone.

African swine fever: background, present time and prospects

USDA-ARS?s Scientific Manuscript database

The purpose of this monograph is to summarize the existing international and national experience of monitoring, diagnostics, forecasting, and implementing measures of management and control of ASF. This publication contains national and international regulatory documents, reference materials and the...

Beliefs and practices regarding childhood fever among parents: a cross-sectional study from Palestine

PubMed Central

2013-01-01

Background Fever is an extremely common occurrence in paediatric patients and the most common cause for a child to be taken to the doctor. The literature indicates that parents have too many misconceptions and conflicting information about fever management. The aim of this study was to identify parents’ beliefs and practices regarding childhood fever management. Methods We conducted a cross-sectional survey among parents whose children were enrolled and presented for health care at primary health care clinics in the Nablus region of Palestine. Data were collected using structured questionnaire interviews with parents. The questionnaire consisted of ‘yes/no’ responses and multiple-response questions. Descriptive statistics were used. Results Overall, 402 parents were interviewed. All parents believed that fever could cause at least one harmful effect if left untreated. The harmful effects most frequently reported by parents were brain damage (38.1%), dehydration (15.7%), and other organs damage such as liver and kidney damage (14.2%). The study showed that 65.4% of parents would recognise fever by only touching the child, 31.6% would measure the temperature and 3.0% would assess temperature by touching and measuring the child. Antipyretic was preferred to be used by 34.8% of parents, while 49.8% stated that they preferred cold sponges, and 3.2% stated that they preferred homeopathic methods to treat fever. The most common factors influencing frequency of medication administration included physician’s instruction (61.7%), the degree of elevated temperature (14.9%) and instructions on the medication leaflet (13.7%). Of the participant parents, 53.2% believed antipyretics used to reduce fever were harmful. Parents reported the most harmful outcomes from these antipyretics to be allergic reactions (20.9%), effects on the stomach (16.9%), kidney damage (16.2%) and overdose (11.4%). Conclusions Parents were anxious when dealing with a feverish child, which resulted in incorrect or inappropriate practices. Parents require reliable evidence-based information about the care of feverish children. These results indicate a need to develop and evaluate educational programs in our setting that will provide parents with education on fever and fever management. PMID:23622106

Descriptive Epidemiology of Typhoid Fever during an Epidemic in Harare, Zimbabwe, 2012

PubMed Central

Polonsky, Jonathan A.; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J.

2014-01-01

Background Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. Methods A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. Principal Findings We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. Conclusions This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range. PMID:25486292

Seroprevalence of Q fever among human and animal in Iran; A systematic review and meta-analysis

PubMed Central

Mohabbati Mobarez, Ashraf; Bagheri Amiri, Fahimeh; Esmaeili, Saber

2017-01-01

Background Q fever is a main zoonotic disease around the world. The aim of this meta-analysis was to estimate the overall seroprevalence of Coxiella burnetii among human and animal population in Iran. Methods Major national and international databases were searched from 2005 up to August 2016. We extracted the prevalence of Q fever antibodies (IgG) as the main primary outcome. We reported the prevalence of the seropositivity as point and 95% confidence intervals. Results The overall seroprevalence of IgG phase I and II antibodies of Q fever in human was 19.80% (95% CI: 16.35–23.25%) and 32.86% (95% CI: 23.80–41.92%), respectively. The herd and individual prevalence of C. burnetii antibody in goat were 93.42% (95% CI: 80.23–100.00) and 31.97% (95% CI: 20.96–42.98%), respectively. The herd and individual prevalence of Q fever antibody in sheep's were 96.07% (95% CI: 89.11–100.00%) and 24.66% (95% CI: 19.81–29.51%), respectively. The herd and individual prevalence of C. burnetii antibody in cattle were 41.37% (95% CI: 17.88–64.86%) and 13.30% (95% CI: 2.98–23.62%), respectively. Individual seropositivity of Q fever in camel and dog were 28.26% (95% CI: 21.47–35.05) and 0.55% (0.03–2.68), respectively. Conclusion Seroprevalence of Q fever among human and domestic animals is considerable. Preventative planning and control of C. burnetii infections in Iran is necessary. Active surveillance and further research studies are recommended, to more clearly define the epidemiology and importance of C. burnetii infections in animals and people in Iran. PMID:28394889

The antipyretic effect of dipyrone is unrelated to inhibition of PGE2 synthesis in the hypothalamus

PubMed Central

do C Malvar, David; Soares, Denis M; Fabrício, Aline SC; Kanashiro, Alexandre; Machado, Renes R; Figueiredo, Maria J; Rae, Giles A; de Souza, Glória EP

2011-01-01

BACKGROUND AND PURPOSE Bacterial lipopolysaccharide (LPS) induces fever through two parallel pathways; one, prostaglandin (PG)-dependent and the other, PG-independent and involving endothelin-1 (ET-1). For a better understanding of the mechanisms by which dipyrone exerts antipyresis, we have investigated its effects on fever and changes in PGE2 content in plasma, CSF and hypothalamus induced by either LPS or ET-1. EXPERIMENTAL APPROACH Rats were given (i.p.) dipyrone (120 mg·kg−1) or indomethacin (2 mg·kg−1) 30 min before injection of LPS (5 µg·kg−1, i.v.) or ET-1 (1 pmol, i.c.v.). Rectal temperature was measured by tele-thermometry. PGE2 levels were determined in the plasma, CSF and hypothalamus by elisa. KEY RESULTS LPS or ET-1 induced fever and increased CSF and hypothalamic PGE2 levels. Two hours after LPS, indomethacin reduced CSF and hypothalamic PGE2 but did not inhibit fever, while at 3 h it reduced all three parameters. Three hours after ET-1, indomethacin inhibited the increase in CSF and hypothalamic PGE2 levels but did not affect fever. Dipyrone abolished both the fever and the increased CSF PGE2 levels induced by LPS or ET-1 but did not affect the increased hypothalamic PGE2 levels. Dipyrone also reduced the increase in the venous plasma PGE2 concentration induced by LPS. CONCLUSIONS AND IMPLICATIONS These findings confirm that PGE2 does not play a relevant role in ET-1-induced fever. They also demonstrate for the first time that the antipyretic effect of dipyrone was not mechanistically linked to the inhibition of hypothalamic PGE2 synthesis. PMID:21133897

Geriatric Fever Score: A New Decision Rule for Geriatric Care

PubMed Central

Vong, Si-Chon; Yang, Tzu-Meng; Chen, Kuo-Tai; Lin, Hung-Jung; Chen, Jiann-Hwa; Su, Shih-Bin; Guo, How-Ran; Hsu, Chien-Chin

2014-01-01

Background Evaluating geriatric patients with fever is time-consuming and challenging. We investigated independent mortality predictors of geriatric patients with fever and developed a prediction rule for emergency care, critical care, and geriatric care physicians to classify patients into mortality risk and disposition groups. Materials and Methods Consecutive geriatric patients (≥65 years old) visiting the emergency department (ED) of a university-affiliated medical center between June 1 and July 21, 2010, were enrolled when they met the criteria of fever: a tympanic temperature ≥37.2°C or a baseline temperature elevated ≥1.3°C. Thirty-day mortality was the primary endpoint. Internal validation with bootstrap re-sampling was done. Results Three hundred thirty geriatric patients were enrolled. We found three independent mortality predictors: Leukocytosis (WBC >12,000 cells/mm3), Severe coma (GCS ≤ 8), and Thrombocytopenia (platelets <150 103/mm3) (LST). After assigning weights to each predictor, we developed a Geriatric Fever Score that stratifies patients into two mortality-risk and disposition groups: low (4.0%) (95% CI: 2.3–6.9%): a general ward or treatment in the ED then discharge and high (30.3%) (95% CI: 17.4–47.3%): consider the intensive care unit. The area under the curve for the rule was 0.73. Conclusions We found that the Geriatric Fever Score is a simple and rapid rule for predicting 30-day mortality and classifying mortality risk and disposition in geriatric patients with fever, although external validation should be performed to confirm its usefulness in other clinical settings. It might help preserve medical resources for patients in greater need. PMID:25340811

Arthropod Borne Disease: The Leading Cause of Fever in Pregnancy on the Thai-Burmese Border

PubMed Central

McGready, Rose; Ashley, Elizabeth A.; Wuthiekanun, Vanaporn; Tan, Saw Oo; Pimanpanarak, Mupawjay; Viladpai-nguen, Samuel Jacher; Jesadapanpong, Wilarat; Blacksell, Stuart D.; Peacock, Sharon J.; Paris, Daniel H.; Day, Nicholas P.; Singhasivanon, Pratap; White, Nicholas J.; Nosten, François

2010-01-01

Background Fever in pregnancy is dangerous for both mother and foetus. In the 1980's malaria was the leading cause of death in pregnant women in refugee camps on the Thai-Burmese border. Artemisinin combination therapy has significantly reduced the incidence of malaria in the population. The remaining causes of fever in pregnancy are not well documented. Methodology Pregnant women attending antenatal care, where weekly screening for malaria is routine, were invited to have a comprehensive clinical and laboratory screen if they had fever. Women were admitted to hospital, treated and followed up weekly until delivery. A convalescent serum was collected on day 21. Delivery outcomes were recorded. Principal Findings Febrile episodes (n = 438) occurred in 5.0% (409/8,117) of pregnant women attending antenatal clinics from 7-Jan-2004 to 17-May-2006. The main cause was malaria in 55.5% (227/409). A cohort of 203 (49.6% of 409) women had detailed fever investigations and follow up. Arthropod-borne (malaria, rickettsial infections, and dengue) and zoonotic disease (leptospirosis) accounted for nearly half of all febrile illnesses, 47.3% (96/203). Coinfection was observed in 3.9% (8/203) of women, mostly malaria and rickettsia. Pyelonephritis, 19.7% (40/203), was also a common cause of fever. Once malaria, pyelonephritis and acute respiratory illness are excluded by microscopy and/or clinical findings, one-third of the remaining febrile infections will be caused by rickettsia or leptospirosis. Scrub and murine typhus were associated with poor pregnancy outcomes including stillbirth and low birth weight. One woman died (no positive laboratory tests). Conclusion/Significance Malaria remains the leading cause of fever in pregnancy on the Thai-Burmese border. Scrub and murine typhus were also important causes of fever associated with poor pregnancy outcomes. Febrile pregnant women on the Thai-Burmese border who do not have malaria, pyelonephritis or respiratory tract infection should be treated with azithromycin, effective for typhus and leptospirosis. PMID:21103369

Drivers for inappropriate fever management in children: a systematic review.

PubMed

Kelly, M; McCarthy, S; O'Sullivan, R; Shiely, F; Larkin, P; Brenner, M; Sahm, L J

2016-08-01

Background Fever is one of the most common childhood symptoms and accounts for numerous consultations with healthcare practitioners. It causes much anxiety amongst parents as many struggle with managing a feverish child and find it difficult to assess fever severity. Over- and under-dosing of antipyretics has been reported. Aim of the review The aim of this review was to synthesise qualitative and quantitative evidence on the knowledge, attitudes and beliefs of parents regarding fever and febrile illness in children. Method A systematic search was conducted in ten bibliographic databases from database inception to June 2014. Citation lists of studies and consultation with experts were used as secondary sources to identify further relevant studies. Titles and abstracts were screened for inclusion according to pre-defined inclusion and exclusion criteria. Quantitative studies using a questionnaire were analysed using narrative synthesis. Qualitative studies with a semi-structured interview or focus group methodology were analysed thematically. Results Of the 1565 studies which were screened for inclusion in the review, the final review comprised of 14 studies (three qualitative and 11 quantitative). Three categories emerged from the narrative synthesis of quantitative studies: (i) parental practices; (ii) knowledge; (iii) expectations and information seeking. A further three analytical themes emerged from the qualitative studies: (i) control; (ii) impact on family; (iii) experiences. Conclusion Our review identifies the multifaceted nature of the factors which impact on how parents manage fever and febrile illness in children. A coherent approach to the management of fever and febrile illness needs to be implemented so a consistent message is communicated to parents. Healthcare professionals including pharmacists regularly advise parents on fever management. Information given to parents needs to be timely, consistent and accurate so that inappropriate fever management is reduced or eliminated. This review is a necessary foundation for further research in this area.

Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan

PubMed Central

2011-01-01

Background Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure. Methods Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0°C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5°C, 38.0°C and 38.5°C were also estimated. Results The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%. Conclusions The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure. PMID:21539735

Rapid Diagnosis of Arbovirus and Arenavirus Infections by Immunofluorescence.

DTIC Science & Technology

1984-12-31

rivers have been tested against Ebola, Lassa and Marburg viruses . Only positives with Ebola virus were found with the monovalent slides. One serum gave...recognition as a disease entity. DIVELOPMK OF THE ELISA TEST FOR CCHF VIRUSES . We have used detected CCHF virus infected cells by ELISA. This system offers...CCHF) virus was developed using infected, formalin-fixed CER cells as antigen. A retrospective serologic survey of equatorial Africa for antibodies

Systemic Polyarteritis Nodosa as the Cause of Sudden Onset Bilateral Sensorineural Hearing Loss Following Lassa Virus Infection

DTIC Science & Technology

2016-07-05

occlusion of the anterior inferior cerebellar artery (AICA) and downstream vessels leading to cochlear hypoxia (18-24). Relevant to this work, PAN has...macaques showed moderate lymphoplasmacytic to chronic-active perivascular inflammation of the inner ear adjacent to the cochlear nerve The...inflammation occasionally surrounded smaller branches of the cochlear nerve, resembling pathological changes seen in humans diagnosed with PAN (Fig. 3B-E) (21

A possible case of caprine-associated malignant catarrhal fever in a domestic water buffalo (Bubalus bubalis) in Switzerland

PubMed Central

2011-01-01

Background Malignant catarrhal fever (MCF) is a fatal herpesvirus infection, affecting various wild and domestic ruminants all over the world. Water buffaloes were reported to be particularly susceptible for the ovine herpesvirus-2 (OvHV-2) causing the sheep-associated form of MCF (SA-MCF). This report describes the first case of possibly caprine-associated malignant catarrhal fever symptoms in a domestic water buffalo in Switzerland. Case presentation The buffalo cow presented with persistent fever, dyspnoea, nasal bleeding and haematuria. Despite symptomatic therapy, the buffalo died and was submitted to post mortem examination. Major findings were an abomasal ulceration, a mild haemorrhagic cystitis and multifocal haemorrhages on the epicardium and on serosal and mucosal surfaces. Eyes and oral cavity were not affected. Histopathology revealed a mild to moderate lymphohistiocytic vasculitis limited to the brain and the urinary bladder. Although these findings are typical for MCF, OvHV-2 DNA was not detected in peripheral blood lymphocytes or in paraffin-embedded brain, using an OvHV-2 specific real time PCR. With the aid of a panherpesvirus PCR, a caprine herpesvirus-2 (CpHV-2) sequence could be amplified from both samples. Conclusions To our knowledge, this is the first report of malignant catarrhal fever in the subfamily Bovinae, where the presence of CpHV-2 could be demonstrated. The etiological context has yet to be evaluated. PMID:22132808

The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies

PubMed Central

von Kalckreuth, Vera; Konings, Frank; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Breiman, Robert F.; Bjerregaard-Andersen, Morten; Clemens, John D.; Crump, John A.; Cruz Espinoza, Ligia Maria; Deerin, Jessica Fung; Gasmelseed, Nagla; Sow, Amy Gassama; Im, Justin; Keddy, Karen H.; Cosmas, Leonard; May, Jürgen; Meyer, Christian G.; Mintz, Eric D.; Montgomery, Joel M.; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Rakotozandrindrainy, Raphaël; Schütt-Gerowitt, Heidi; Soura, Abdramane Bassiahi; Warren, Michelle R.; Wierzba, Thomas F.; Marks, Florian

2016-01-01

Background. New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. Methods. Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. Results. Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. Conclusions. By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs. PMID:26933028

Abandoning Presumptive Antimalarial Treatment for Febrile Children Aged Less Than Five Years—A Case of Running Before We Can Walk?

PubMed Central

English, Mike; Reyburn, Hugh; Goodman, Catherine; Snow, Robert W

2009-01-01

Background to the debate: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five. PMID:19127977

Expression of intra- and extracellular granzymes in patients with typhoid fever

PubMed Central

Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J.; Parry, Christopher M.; Maude, Rapeephan R.; Dondorp, Arjen M.; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-01-01

Background Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. Methods and principal findings We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. Conclusion The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease. PMID:28749963

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

Role of classic signs as diagnostic predictors for enteric fever among returned travellers: Relative bradycardia and eosinopenia

PubMed Central

Matono, Takashi; Kutsuna, Satoshi; Kato, Yasuyuki; Katanami, Yuichi; Yamamoto, Kei; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Kaku, Mitsuo; Ohmagari, Norio

2017-01-01

Background The lack of characteristic clinical findings and accurate diagnostic tools has made the diagnosis of enteric fever difficult. We evaluated the classic signs of relative bradycardia and eosinopenia as diagnostic predictors for enteric fever among travellers who had returned from the tropics or subtropics. Methods This matched case-control study used data from 2006 to 2015 for culture-proven enteric fever patients as cases. Febrile patients (>38.3°C) with non-enteric fever, who had returned from the tropics or subtropics, were matched to the cases in a 1:3 ratio by age (±3 years), sex, and year of diagnosis as controls. Cunha’s criteria were used for relative bradycardia. Absolute eosinopenia was defined as an eosinophilic count of 0/μL. Results Data from 160 patients (40 cases and 120 controls) were analysed. Cases predominantly returned from South Asia (70% versus 18%, p <0.001). Relative bradycardia (88% versus 51%, p <0.001) and absolute eosinopenia (63% versus 38%, p = 0.008) were more frequent in cases than controls. In multivariate logistic regression analysis, return from South Asia (aOR: 21.6; 95% CI: 7.17–64.9) and relative bradycardia (aOR: 11.7; 95% CI: 3.21–42.5) were independent predictors for a diagnosis of enteric fever. The positive likelihood ratio was 4.00 (95% CI: 2.58–6.20) for return from South Asia, 1.72 (95% CI: 1.39–2.13) for relative bradycardia, and 1.63 (95%CI: 1.17–2.27) for absolute eosinopenia. The negative predictive values of the three variables were notably high (83–92%);. however, positive predictive values were 35–57%. Conclusions The classic signs of relative bradycardia and eosinopenia were not specific for enteric fever; however both met the criteria for being diagnostic predictors for enteric fever. Among febrile returned travellers, relative bradycardia and eosinopenia should be re-evaluated for predicting a diagnosis of enteric fever in non-endemic areas prior to obtaining blood cultures. PMID:28644847

The Association between Environmental Factors and Scarlet Fever Incidence in Beijing Region: Using GIS and Spatial Regression Models

PubMed Central

Mahara, Gehendra; Wang, Chao; Yang, Kun; Chen, Sipeng; Guo, Jin; Gao, Qi; Wang, Wei; Wang, Quanyi; Guo, Xiuhua

2016-01-01

(1) Background: Evidence regarding scarlet fever and its relationship with meteorological, including air pollution factors, is not very available. This study aimed to examine the relationship between ambient air pollutants and meteorological factors with scarlet fever occurrence in Beijing, China. (2) Methods: A retrospective ecological study was carried out to distinguish the epidemic characteristics of scarlet fever incidence in Beijing districts from 2013 to 2014. Daily incidence and corresponding air pollutant and meteorological data were used to develop the model. Global Moran’s I statistic and Anselin’s local Moran’s I (LISA) were applied to detect the spatial autocorrelation (spatial dependency) and clusters of scarlet fever incidence. The spatial lag model (SLM) and spatial error model (SEM) including ordinary least squares (OLS) models were then applied to probe the association between scarlet fever incidence and meteorological including air pollution factors. (3) Results: Among the 5491 cases, more than half (62%) were male, and more than one-third (37.8%) were female, with the annual average incidence rate 14.64 per 100,000 population. Spatial autocorrelation analysis exhibited the existence of spatial dependence; therefore, we applied spatial regression models. After comparing the values of R-square, log-likelihood and the Akaike information criterion (AIC) among the three models, the OLS model (R2 = 0.0741, log likelihood = −1819.69, AIC = 3665.38), SLM (R2 = 0.0786, log likelihood = −1819.04, AIC = 3665.08) and SEM (R2 = 0.0743, log likelihood = −1819.67, AIC = 3665.36), identified that the spatial lag model (SLM) was best for model fit for the regression model. There was a positive significant association between nitrogen oxide (p = 0.027), rainfall (p = 0.036) and sunshine hour (p = 0.048), while the relative humidity (p = 0.034) had an adverse association with scarlet fever incidence in SLM. (4) Conclusions: Our findings indicated that meteorological, as well as air pollutant factors may increase the incidence of scarlet fever; these findings may help to guide scarlet fever control programs and targeting the intervention. PMID:27827946

The Association between Environmental Factors and Scarlet Fever Incidence in Beijing Region: Using GIS and Spatial Regression Models.

PubMed

Mahara, Gehendra; Wang, Chao; Yang, Kun; Chen, Sipeng; Guo, Jin; Gao, Qi; Wang, Wei; Wang, Quanyi; Guo, Xiuhua

2016-11-04

(1) Background: Evidence regarding scarlet fever and its relationship with meteorological, including air pollution factors, is not very available. This study aimed to examine the relationship between ambient air pollutants and meteorological factors with scarlet fever occurrence in Beijing, China. (2) Methods: A retrospective ecological study was carried out to distinguish the epidemic characteristics of scarlet fever incidence in Beijing districts from 2013 to 2014. Daily incidence and corresponding air pollutant and meteorological data were used to develop the model. Global Moran's I statistic and Anselin's local Moran's I (LISA) were applied to detect the spatial autocorrelation (spatial dependency) and clusters of scarlet fever incidence. The spatial lag model (SLM) and spatial error model (SEM) including ordinary least squares (OLS) models were then applied to probe the association between scarlet fever incidence and meteorological including air pollution factors. (3) Results: Among the 5491 cases, more than half (62%) were male, and more than one-third (37.8%) were female, with the annual average incidence rate 14.64 per 100,000 population. Spatial autocorrelation analysis exhibited the existence of spatial dependence; therefore, we applied spatial regression models. After comparing the values of R-square, log-likelihood and the Akaike information criterion (AIC) among the three models, the OLS model (R² = 0.0741, log likelihood = -1819.69, AIC = 3665.38), SLM (R² = 0.0786, log likelihood = -1819.04, AIC = 3665.08) and SEM (R² = 0.0743, log likelihood = -1819.67, AIC = 3665.36), identified that the spatial lag model (SLM) was best for model fit for the regression model. There was a positive significant association between nitrogen oxide ( p = 0.027), rainfall ( p = 0.036) and sunshine hour ( p = 0.048), while the relative humidity ( p = 0.034) had an adverse association with scarlet fever incidence in SLM. (4) Conclusions: Our findings indicated that meteorological, as well as air pollutant factors may increase the incidence of scarlet fever; these findings may help to guide scarlet fever control programs and targeting the intervention.

Direct Medical Costs of Dengue Fever in Vietnam: A Retrospective Study in a Tertiary Hospital

PubMed Central

VO, Nhung Thi Tuyet; PHAN, Trang Ngo Diem; VO, Trung Quang

2017-01-01

Background In Vietnam, dengue fever is a major health concern, yet comprehensive information on its economic costs is lacking. The present study investigated treatment costs associated with dengue fever from the perspective of health care provision. Methods This retrospective study was conducted between January 2013 and December 2015 in Cu Chi General Hospital. The following dengue-related treatment costs were calculated: hospitalisation, diagnosis, specialised services, drug usage and medical supplies. Average cost per case and treatment cost across different age was calculated. Results In the study period, 1672 patients with dengue fever were hospitalised. The average age was 24.98 (SD = 14.10) years, and 47.5% were males (795 patients). Across age groups, the average cost per episode was USD 48.10 (SD = 3.22). The highest costs (USD 56.61, SD = 48.84) were incurred in the adult age group (> 15 years), and the lowest costs (USD 30.10, SD = 17.27) were incurred in the paediatric age group (< 15 years). Conclusion The direct medical costs of dengue-related hospitalisation place a severe economic burden on patients and their families. The probable economic value of dengue management in Vietnam is significant. PMID:28814934

Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey.

PubMed

Canpolat, Mehmet; Gumus, Hakan; Gunduz, Zubeyde; Dusunsel, Ruhan; Kumandas, Sefer; Bayram, Ayşe Kaçar; Yel, Sibel; Poyrazoglu, Hatice Gamze; Yilmaz, Kenan; Doganay, Selim; Yikilmaz, Ali; Dundar, Munis; Per, Huseyin

2017-04-01

Background  Familial Mediterranean fever (FMF) is an inherited inflammatory disorder characterized by attacks of fever with polyserositis. Objective  The purpose of this study was to evaluate pediatric patients with FMF who had central nervous system (CNS) findings. Materials and Methods  Our medical records database for 2003 to 2014 was screened retrospectively. In total, 104 patients with FMF were identified, 22 of whom had undergone neurological examination for CNS symptoms. Results  Neurological findings included headache in 16 patients (72.7%), epilepsy in 6 patients (27.3%), pseudotumor cerebri in 2 patients (9.1%), tremor in 2 patients (9.1%), and multiple sclerosis in 1 patient (4.5%). The most common MEFV gene mutation was homozygous M694V (40.9%). Conclusions  Patients with FMF can present with various CNS manifestations. Further studies that include large populations are needed to elucidate the neurological manifestations of FMF. Georg Thieme Verlag KG Stuttgart · New York.

Molecular Assay on Crimean Congo Hemorrhagic Fever Virus in Ticks (Ixodidae) Collected from Kermanshah Province, Western Iran

PubMed Central

Mohammadian, Maria; Chinikar, Sadegh; Telmadarraiy, Zakkyeh; Vatandoost, Hassan; Oshaghi, Mohammad Ali; Hanafi-Bojd, Ahmad Ali; Sedaghat, Mohammad Mehdi; Noroozi, Mehdi; Faghihi, Faezeh; Jalali, Tahmineh; Khakifirouz, Sahar; Shahhosseini, Nariman; Farhadpour, Firoozeh

2016-01-01

Background: Crimean-Congo Hemorrhagic Fever (CCHF) is a feverous and hemorrhagic disease endemic in some parts of Iran and caused by an arbovirus related to Bunyaviridae family and Nairovirusgenus. The main virus reservoir in the nature is ticks, however small vertebrates and a wide range of domestic and wild animals are regarded as reservoir hosts. This study was conducted to determine the infection rate of CCHF virus in hard ticks of Sarpole-Zahab County, Kermanshah province, west of Iran. Methods: From total number of 851 collected ticks from 8 villages, 131 ticks were selected randomlyand investigated for detection of CCHF virus using RT-PCR. Results: The virus was found in 3.8% of the tested ticks. Hyalommaanatolicum, H. asiaticum and Rhipicephalus sanguineus species were found to have viral infection, with the highest infection rate (11.11%) in Rh. sanguineus. Conclusion: These findings provide epidemiological evidence for planning control strategies of the disease in the study area. PMID:27308296

A Highly Conserved Leucine in Mammarenavirus Matrix Z Protein Is Required for Z Interaction with the Virus L Polymerase and Z Stability in Cells Harboring an Active Viral Ribonucleoprotein.

PubMed

Iwasaki, Masaharu; de la Torre, Juan C

2018-06-01

Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting in a wide range of manifestations from asymptomatic or mild febrile illness to severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein has been shown to be a main driving force of virus budding and to act as a negative regulator of viral RNA synthesis. To gain a better understanding of how the Z protein exerts its several different functions, we investigated the interaction between Z and viral polymerase L protein using the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV). We found that in the presence of an active viral ribonucleoprotein (vRNP), the Z protein translocated from nonionic detergent-resistant, membrane-rich structures to a subcellular compartment with a different membrane composition susceptible to disruption by nonionic detergents. Alanine (A) substitution of a highly conserved leucine (L) at position 72 in LCMV Z protein abrogated Z-L interaction. The L72A mutation did not affect the stability or budding activity of Z when expressed alone, but in the presence of an active vRNP, mutation L72A promoted rapid degradation of Z via a proteasome- and lysosome-independent pathway. Accordingly, L72A mutation in the Z protein resulted in nonviable LCMV. Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required. IMPORTANCE Several mammarenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose important public health concerns in their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. The mammarenavirus matrix Z protein plays critical roles in different steps of the viral life cycle by interacting with viral and host cellular components. Here we report that alanine substitution of a highly conserved leucine residue, located at position 72 in LCMV Z protein, abrogated Z-L interaction. The L72A mutation did not affect Z budding activity but promoted its rapid degradation in the presence of an active viral ribonucleoprotein (vRNP). Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required. Copyright © 2018 American Society for Microbiology.

Changing Patterns in Enteric Fever Incidence and Increasing Antibiotic Resistance of Enteric Fever Isolates in the United States, 2008–2012

PubMed Central

Date, Kashmira A.; Newton, Anna E.; Medalla, Felicita; Blackstock, Anna; Richardson, LaTonia; McCullough, Andre; Mintz, Eric D.; Mahon, Barbara E.

2016-01-01

Background Enteric fever in the United States has been primarily associated with travel and with worrisome changes in global patterns of antimicrobial resistance. We present the first comprehensive report of National Typhoid and Paratyphoid Fever Surveillance System (NTPFS) data for a 5-year period (2008–2012). Methods We reviewed data on laboratory-confirmed cases reported to NTPFS, and related antimicrobial susceptibility results of Salmonella Typhi and Paratyphi A isolates sent for testing by participating public health laboratories to the Centers for Disease Control and Prevention’s National Antimicrobial Resistance Monitoring System laboratory. Results During 2008–2012, 2341 enteric fever cases were reported, 80% typhoid and 20% paratyphoid A. The proportion caused by paratyphoid A increased from 16% (2008) to 22% (2012). Foreign travel within 30 days preceding illness onset was reported by 1961 (86%) patients (86% typhoid and 92% paratyphoid A). Travel to southern Asia was common (82% for typhoid, 97% for paratyphoid A). Among 1091 (58%) typhoid and 262 (56%) paratyphoid A isolates tested for antimicrobial susceptibility, the proportion resistant to nalidixic acid (NAL-R) increased from 2008 to 2012 (Typhi, 60% to 68%; Paratyphi A, 91% to 94%). Almost all NAL-R isolates were resistant or showed decreased susceptibility to ciprofloxacin. Resistance to at least ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug resistant [MDR]) was limited to Typhi isolates, primarily acquired in southern Asia (13%). Most MDR isolates were also NAL-R. Conclusions Enteric fever in the United States is primarily associated with travel to southern Asia, and increasing resistance is adding to treatment challenges. A bivalent typhoid and paratyphoid vaccine is needed. PMID:27090993

Development and preliminary evaluation of a multiplexed amplification and next generation sequencing method for viral hemorrhagic fever diagnostics.

PubMed

Brinkmann, Annika; Ergünay, Koray; Radonić, Aleksandar; Kocak Tufan, Zeliha; Domingo, Cristina; Nitsche, Andreas

2017-11-01

We describe the development and evaluation of a novel method for targeted amplification and Next Generation Sequencing (NGS)-based identification of viral hemorrhagic fever (VHF) agents and assess the feasibility of this approach in diagnostics. An ultrahigh-multiplex panel was designed with primers to amplify all known variants of VHF-associated viruses and relevant controls. The performance of the panel was evaluated via serially quantified nucleic acids from Yellow fever virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever (CCHF) virus, Ebola virus, Junin virus and Chikungunya virus in a semiconductor-based sequencing platform. A comparison of direct NGS and targeted amplification-NGS was performed. The panel was further tested via a real-time nanopore sequencing-based platform, using clinical specimens from CCHF patients. The multiplex primer panel comprises two pools of 285 and 256 primer pairs for the identification of 46 virus species causing hemorrhagic fevers, encompassing 6,130 genetic variants of the strains involved. In silico validation revealed that the panel detected over 97% of all known genetic variants of the targeted virus species. High levels of specificity and sensitivity were observed for the tested virus strains. Targeted amplification ensured viral read detection in specimens with the lowest virus concentration (1-10 genome equivalents) and enabled significant increases in specific reads over background for all viruses investigated. In clinical specimens, the panel enabled detection of the causative agent and its characterization within 10 minutes of sequencing, with sample-to-result time of less than 3.5 hours. Virus enrichment via targeted amplification followed by NGS is an applicable strategy for the diagnosis of VHFs which can be adapted for high-throughput or nanopore sequencing platforms and employed for surveillance or outbreak monitoring.

Differential Epidemiology of Salmonella Typhi and Paratyphi A in Kathmandu, Nepal: A Matched Case Control Investigation in a Highly Endemic Enteric Fever Setting

PubMed Central

Tran Vu Thieu, Nga; Dongol, Sabina; Le Thi Phuong, Tu; Voong Vinh, Phat; Arjyal, Amit; Martin, Laura B.; Rondini, Simona; Farrar, Jeremy J.; Dolecek, Christiane; Basnyat, Buddha; Baker, Stephen

2013-01-01

Background Enteric fever, a systemic infection caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A, is endemic in Kathmandu, Nepal. Previous work identified proximity to poor quality water sources as a community-level risk for infection. Here, we sought to examine individual-level risk factors related to hygiene and sanitation to improve our understanding of the epidemiology of enteric fever in this setting. Methodology and principal findings A matched case-control analysis was performed through enrollment of 103 blood culture positive enteric fever patients and 294 afebrile community-based age and gender-matched controls. A detailed questionnaire was administered to both cases and controls and the association between enteric fever infection and potential exposures were examined through conditional logistic regression. Several behavioral practices were identified as protective against infection with enteric fever, including water storage and hygienic habits. Additionally, we found that exposures related to poor water and socioeconomic status are more influential in the risk of infection with S. Typhi, whereas food consumption habits and migration play more of a role in risk of S. Paratyphi A infection. Conclusions and significance Our work suggests that S. Typhi and S. Paratyphi A follow different routes of infection in this highly endemic setting and that sustained exposure to both serovars probably leads to the development of passive immunity. In the absence of a polyvalent vaccine against S. Typhi and S. Paratyphi A, we advocate better systems for water treatment and storage, improvements in the quality of street food, and vaccination with currently available S. Typhi vaccines. PMID:23991240

Elementary School-Based Influenza Vaccination: Evaluating Impact on Respiratory Illness Absenteeism and Laboratory-Confirmed Influenza

PubMed Central

Kjos, Sonia A.; Irving, Stephanie A.; Meece, Jennifer K.; Belongia, Edward A.

2013-01-01

Background Studies of influenza vaccine effectiveness in schools have assessed all-cause absenteeism rather than laboratory-confirmed influenza. We conducted an observational pilot study to identify absences due to respiratory illness and laboratory-confirmed influenza in schools with and without school-based vaccination. Methods A local public health agency initiated school-based influenza vaccination in two Wisconsin elementary schools during October 2010 (exposed schools); two nearby schools served as a comparison group (non-exposed schools). Absences due to fever or cough illness were monitored for 12 weeks. During the 4 weeks of peak influenza activity, parents of absent children with fever/cough illness were contacted and offered influenza testing. Results Parental consent for sharing absenteeism data was obtained for 937 (57%) of 1,640 students. Fifty-two percent and 28%, respectively, of all students in exposed and non-exposed schools were vaccinated. Absences due to fever or cough illness were significantly lower in the exposed schools during seven of 12 surveillance weeks. Twenty-seven percent of students at exposed schools and 39% at unexposed schools had one or more days of absence due to fever/cough illness (p<0.0001). There was no significant difference in the proportion of students absent for other reasons (p = 0.23). During the 4 week period of influenza testing, respiratory samples were obtained for 68 (42%) of 163 episodes of absence due to fever or cough illness. Influenza was detected in 6 students; 3 attended exposed schools. Conclusions Detection of laboratory-confirmed influenza in schools was challenging due to multiple consent requirements, difficulty obtaining samples from absent children, and a mild influenza season. School-based influenza vaccination was associated with reduced absenteeism due to fever or cough illness, but not absenteeism for other reasons. Although nonspecific, absence due to fever or cough illness may be a useful surrogate endpoint in school-based studies if identification of laboratory confirmed influenza is not feasible. PMID:23991071

Childhood fever: a qualitative study on parents' expectations and experiences during general practice out-of-hours care consultations.

PubMed

de Bont, Eefje G P M; Loonen, Nicole; Hendrix, Dagmar A S; Lepot, Julie M M; Dinant, Geert-Jan; Cals, Jochen W L

2015-10-07

Fever in children is common and mostly caused by benign self-limiting infections. Yet consultation rates in primary care are high, especially during GP out-of-hours care. Therefore, we aimed to explore experiences of parents when having visited GP out-of-hours services with their febrile child. We performed a qualitative study using 20 semi-structured interviews among parents from different backgrounds presenting to GP out-of-hours care with a febrile child <12 years. Questions were directed at parental motivations, expectations and experiences when visiting the GP out-of-hours centre with a febrile child. Interviews were audio-recorded, transcribed and analysed using constant comparison technique. We identified four main categories emerging from the data; (1) cautiously seeking care, (2) discrepancy between rationality and emotion, (3) expecting reassurance from a professional and (4) a need for consistent, reliable information. Not one symptom, but a combination of fever with other symptoms, made parents anxious and drove care seeking. Although parents carefully considered when to seek care, they experienced increased anxiety with increases in their child's temperature. Because parents work during the day and fever typically rises during the early evening, the decision to seek care was often made during out-of-hours care. When parents consulted a GP they did not have any set expectations other than seeking reassurance, however a proper physical examination diminished their anxiety. Parents did not demand antibiotics, but trusted on the expertise of the GP to assess necessity. Parents requested consistent, reliable information on fever and self-management strategies. Parents were inexperienced in self-management strategies and had a subsequent desire for reassurance; this played a pivotal role in out-of-hours help seeking for childhood fever. These factors provide clues to optimise information exchange between GPs and parents, by providing written, tailored, consistent information on self-management strategies for current and future fever episodes. GPs' had incorrect assumptions that parents expected antibiotic treatment.

Mixed Methods Survey of Zoonotic Disease Awareness and Practice among Animal and Human Healthcare Providers in Moshi, Tanzania

PubMed Central

Zhang, Helen L.; Mnzava, Kunda W.; Mitchell, Sarah T.; Melubo, Matayo L.; Kibona, Tito J.; Cleaveland, Sarah; Kazwala, Rudovick R.; Crump, John A.; Sharp, Joanne P.; Halliday, Jo E. B.

2016-01-01

Background Zoonoses are common causes of human and livestock illness in Tanzania. Previous studies have shown that brucellosis, leptospirosis, and Q fever account for a large proportion of human febrile illness in northern Tanzania, yet they are infrequently diagnosed. We conducted this study to assess awareness and knowledge regarding selected zoonoses among healthcare providers in Moshi, Tanzania; to determine what diagnostic and treatment protocols are utilized; and obtain insights into contextual factors contributing to the apparent under-diagnosis of zoonoses. Methodology/Results We conducted a questionnaire about zoonoses knowledge, case reporting, and testing with 52 human health practitioners and 10 livestock health providers. Immediately following questionnaire administration, we conducted semi-structured interviews with 60 of these respondents, using the findings of a previous fever etiology study to prompt conversation. Sixty respondents (97%) had heard of brucellosis, 26 (42%) leptospirosis, and 20 (32%) Q fever. Animal sector respondents reported seeing cases of animal brucellosis (4), rabies (4), and anthrax (3) in the previous 12 months. Human sector respondents reported cases of human brucellosis (15, 29%), rabies (9, 18%) and anthrax (6, 12%). None reported leptospirosis or Q fever cases. Nineteen respondents were aware of a local diagnostic test for human brucellosis. Reports of tests for human leptospirosis or Q fever, or for any of the study pathogens in animals, were rare. Many respondents expressed awareness of malaria over-diagnosis and zoonoses under-diagnosis, and many identified low knowledge and testing capacity as reasons for zoonoses under-diagnosis. Conclusions This study revealed differences in knowledge of different zoonoses and low case report frequencies of brucellosis, leptospirosis, and Q fever. There was a lack of known diagnostic services for leptospirosis and Q fever. These findings emphasize a need for improved diagnostic capacity alongside healthcare provider education and improved clinical guidelines for syndrome-based disease management to provoke diagnostic consideration of locally relevant zoonoses in the absence of laboratory confirmation. PMID:26943334

Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

PubMed Central

2012-01-01

Background Shivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%). Methods From February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol. Results The 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women’s assessment of severity/tolerability of shivering and fever was better with the lower dose. Conclusions 600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified. Trial Registration Clinical trials.gov, Registry No. NCT01080846 PMID:22769055

Yellow fever vaccination coverage following massive emergency immunization campaigns in rural Uganda, May 2011: a community cluster survey

PubMed Central

2013-01-01

Background Following an outbreak of yellow fever in northern Uganda in December 2010, Ministry of Health conducted a massive emergency vaccination campaign in January 2011. The reported vaccination coverage in Pader District was 75.9%. Administrative coverage though timely, is affected by incorrect population estimates and over or under reporting of vaccination doses administered. This paper presents the validated yellow fever vaccination coverage following massive emergency immunization campaigns in Pader district. Methods A cross sectional cluster survey was carried out in May 2011 among communities in Pader district and 680 respondents were indentified using the modified World Health Organization (WHO) 40 × 17 cluster survey sampling methodology. Respondents were aged nine months and above. Interviewer administered questionnaires were used to collect data on demographic characteristics, vaccination status and reasons for none vaccination. Vaccination status was assessed using self reports and vaccination card evidence. Our main outcomes were measures of yellow fever vaccination coverage in each age-specific stratum, overall, and disaggregated by age and sex, adjusting for the clustered design and the size of the population in each stratum. Results Of the 680 survey respondents, 654 (96.1%, 95% CI 94.9 – 97.8) reported being vaccinated during the last campaign but only 353 (51.6%, 95% CI 47.2 – 56.1) had valid yellow fever vaccination cards. Of the 280 children below 5 years, 269 (96.1%, 95% CI 93.7 – 98.7) were vaccinated and nearly all males 299 (96.9%, 95% CI 94.3 – 99.5) were vaccinated. The main reasons for none vaccination were; having travelled out of Pader district during the campaign period (40.0%), lack of transport to immunization posts (28.0%) and, sickness at the time of vaccination (16.0%). Conclusions Our results show that actual yellow fever vaccination coverage was high and satisfactory in Pader district since it was above the desired minimum threshold coverage of 80% according to World Health Organization. Massive emergency vaccination done following an outbreak of Yellow fever achieved high population coverage in Pader district. Active surveillance is necessary for early detection of yellow fever cases. PMID:23497254

Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting

PubMed Central

Andrews, Jason R.; Prajapati, Krishna G.; Eypper, Elizabeth; Shrestha, Poojan; Shakya, Mila; Pathak, Kamal R.; Joshi, Niva; Tiwari, Priyanka; Risal, Manisha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Wen, Shawn; Smith, Amy B.; Maru, Duncan; Basnyat, Buddha; Baker, Stephen; Farrar, Jeremy; Ryan, Edward T.; Hohmann, Elizabeth; Arjyal, Amit

2013-01-01

Background In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Methodology/Principal Findings Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%–97.0%) and 96.0% (92.7%–98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. Conclusions/Significance A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories. PMID:23853696

Human and entomological surveillance of West Nile fever, dengue and chikungunya in Veneto Region, Italy, 2010-2012

PubMed Central

2014-01-01

Background Since 2010 Veneto region (North-Eastern Italy) planned a special integrated surveillance of summer fevers to promptly identify cases of West Nile Fever (WNF), dengue (DENV) and chikungunya (CHIKV). The objectives of this study were (i) To increase the detection rate of imported CHIKV and DENV cases in travellers from endemic areas and promptly identify potential autochthonous cases.(ii) To detect autochthonous cases of WNF, besides those of West Nile Neuroinvasive Disease (WNND) that were already included in a national surveillance. Methods Human surveillance: a traveler who had returned within the previous 15 days from endemic countries, with fever >38°C, absence of leucocytosis (leukocyte count <10,000 μL), and absence of other obvious causes of fever, after ruling out malaria, was considered a possible case of CHIKV or DENV. A possible autochthonous case of WNF was defined as a patient with fever >38°C for <7 days, no recent travel history and absence of other obvious causes of fever. Entomologic surveillance: for West Nile (WNV) it was carried out from May through November placing CDC-CO2 traps in five provinces of Veneto Region, while for DENV and CHIKV it was also performed around residences of viremic cases. Results Human surveillance: between 2010 and 2012, 234 patients with fever after travelling were screened, of which 27 (11,5%) were found infected (24 with DENV and 3 with CHIKV). No autochthonous case of DENV or CHIKV was detected. Autochthonous patients screened for WNF were 408, and 24 (5,9%) were confirmed cases. Entomologic surveillance: the WNV was found in 10, 2 and 11 pools of Culex pipiens from 2010 to 2012 respectively, in sites of Rovigo, Verona, Venezia and Treviso provinces). No infected Aedes albopictus with DENV or CHIKV was found. Conclusions Veneto is the only Italian region reporting WNV human cases every year since 2008. WNV is likely to cause sporadic cases and unforeseeable outbreaks for decades. Including WNF in surveillance provides additional information and possibly an early alert system. Timely detection of DENV and CHIKV should prompt vector control measures to prevent local outbreaks. PMID:24499011

Autoimmune Associated Systemic Vasculitis as the Cause of Sudden onset Bilateral Sensorineural Hearing Loss Following Lassa Virus Exposure in a Cynomolgus Macaque Deafness Model

DTIC Science & Technology

2017-01-10

and IL-15 has been considered as a potential therapeutic target for autoimmune diseases such as rheumatoid arthritis and GPA (36, 41, 42...22(1):19-33. 41. Baslund B, et al. (2005) Targeting interleukin-15 in patients with rheumatoid arthritis : a proof-of-concept study. Arthritis Rheum...Berrettini S, et al. (1998) Progressive sensorineural hearing impairment in systemic vasculitides. Semin Arthritis Rheum 27(5):301-318. 27. Webb AA

Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GP1 Ectodomain Shedding

DTIC Science & Technology

2008-12-23

glycoprotein precursor (GPC) signal peptide (SP) or human IgG signal sequences (s.s.). GP2 was secreted from cells only when (1) the transmembrane (TM) domain... peptide (SP) or human IgG signal sequences (s.s.). GP2 was secreted from cells only when (1) the transmembrane (TM) domain was deleted, the...terminal signal peptide (SP), which directs the precursor to the endoplasmic retic- ulum (ER) for further processing [11]. The SP, which has been

Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GPI Ectodomain Shedding

DTIC Science & Technology

2008-12-23

glycoprotein precursor (GPC) signal peptide (SP) or human IgG signal sequences (s.s.). GP2 was secreted from cells only when (1) the transmembrane (TM) domain...consistent with viral TM fusion proteins [9,10]. GPC con- tains a 58 residue hydrophobic N-terminal signal peptide (SP), which directs the precursor to the...including GPC, GP1, and GP2. Various signal peptides , purification tags, and modifications to internal domains were employed for the generation and

Transfer of scarlet fever-associated elements into the group A Streptococcus M1T1 clone.

PubMed

Ben Zakour, Nouri L; Davies, Mark R; You, Yuanhai; Chen, Jonathan H K; Forde, Brian M; Stanton-Cook, Mitchell; Yang, Ruifu; Cui, Yujun; Barnett, Timothy C; Venturini, Carola; Ong, Cheryl-lynn Y; Tse, Herman; Dougan, Gordon; Zhang, Jianzhong; Yuen, Kwok-Yung; Beatson, Scott A; Walker, Mark J

2015-11-02

The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone, with bacteriophage-encoded determinants DNase Sda1 and superantigen SpeA2 contributing to enhanced virulence and colonization respectively. Outbreaks of scarlet fever in Hong Kong and China in 2011, caused primarily by emm12 GAS, led to our investigation of the next most common cause of scarlet fever, emm1 GAS. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 scarlet fever clones in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements.

Transfer of scarlet fever-associated elements into the group A Streptococcus M1T1 clone

PubMed Central

Ben Zakour, Nouri L.; Davies, Mark R.; You, Yuanhai; Chen, Jonathan H. K.; Forde, Brian M.; Stanton-Cook, Mitchell; Yang, Ruifu; Cui, Yujun; Barnett, Timothy C.; Venturini, Carola; Ong, Cheryl-lynn Y.; Tse, Herman; Dougan, Gordon; Zhang, Jianzhong; Yuen, Kwok-Yung; Beatson, Scott A.; Walker, Mark J.

2015-01-01

The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome123. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone45, with bacteriophage-encoded determinants DNase Sda16 and superantigen SpeA27 contributing to enhanced virulence and colonization respectively. Outbreaks of scarlet fever in Hong Kong and China in 2011, caused primarily by emm12 GAS8910, led to our investigation of the next most common cause of scarlet fever, emm1 GAS89. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 scarlet fever clones1011 in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements. PMID:26522788

Inhibition of the in vitro growth of babesia bigemina, babesia caballi and theileria equi parasites by trifluralin analogues

USDA-ARS?s Scientific Manuscript database

Background: Bovine and equine babesiosis caused by Babesia bovis, B. bigemina and B. caballi, and equine theileriosis caused by Theileria equi are global tick borne hemoprotozoan diseases characterized by fever, anemia, weight losses and abortions. A common feature of these diseases are transition f...

In silico biosynthesis of virenose, a methylated deoxy-sugar unique to Coxiella burnetii lipopolysaccharide

USDA-ARS?s Scientific Manuscript database

Background: Coxiella burnetii is Gram-negative bacterium responsible for the zoonosis Q-fever. While it has an obligate intracellulargrowth habit, it is able to persist for extended periods outside of a host cell and can resist environmental conditions that would be lethal to most prokaryotes. It is...

The E2 glycoprotein of classical swine fever virus is a virulence determinant in swine.

PubMed

Risatti, G R; Borca, M V; Kutish, G F; Lu, Z; Holinka, L G; French, R A; Tulman, E R; Rock, D L

2005-03-01

To identify genetic determinants of classical swine fever virus (CSFV) virulence and host range, chimeras of the highly pathogenic Brescia strain and the attenuated vaccine strain CS were constructed and evaluated for viral virulence in swine. Upon initial screening, only chimeras 138.8v and 337.14v, the only chimeras containing the E2 glycoprotein of CS, were attenuated in swine despite exhibiting unaltered growth characteristics in primary porcine macrophage cell cultures. Additional viral chimeras were constructed to confirm the role of E2 in virulence. Chimeric virus 319.1v, which contained only the CS E2 glycoprotein in the Brescia background, was markedly attenuated in pigs, exhibiting significantly decreased virus replication in tonsils, a transient viremia, limited generalization of infection, and decreased virus shedding. Chimeras encoding all Brescia structural proteins in a CS genetic background remained attenuated, indicating that additional mutations outside the structural region are important for CS vaccine virus attenuation. These results demonstrate that CS E2 alone is sufficient for attenuating Brescia, indicating a significant role for the CSFV E2 glycoprotein in swine virulence.

The microtubule motor protein KIF13A is involved in intracellular trafficking of the Lassa virus matrix protein Z.

PubMed

Fehling, Sarah Katharina; Noda, Takeshi; Maisner, Andrea; Lamp, Boris; Conzelmann, Karl-Klaus; Kawaoka, Yoshihiro; Klenk, Hans-Dieter; Garten, Wolfgang; Strecker, Thomas

2013-02-01

The small matrix protein Z of arenaviruses has been identified as the main driving force to promote viral particle production at the plasma membrane. Although multiple functions of Z in the arenaviral life cycle have been uncovered, the mechanism of intracellular transport of Z to the site of virus budding is poorly understood and cellular motor proteins that mediate Z trafficking remain to be identified. In the present study, we report that the Z protein of the Old World arenavirus Lassa virus (LASV) interacts with the kinesin family member 13A (KIF13A), a plus-end-directed microtubule-dependent motor protein. Plasmid-driven overexpression of KIF13A results in relocalization of Z to the cell periphery, while functional blockage of endogenous KIF13A by overexpression of a dominant-negative mutant or KIF13A-specific siRNA causes a perinuclearaccumulation and decreased production of both Z-induced virus-like particles and infectious LASV. The interaction of KIF13A with Z proteins from both Old and New World arenaviruses suggests a conserved intracellular transport mechanism. In contrast, the intracellular distribution of the matrix proteins of prototypic members of the paramyxo- and rhabdovirus family is independent of KIF13A. In summary, our studies identify for the first time a molecular motor protein as a critical mediator for intracellular microtubule-dependent transport of arenavirus matrix proteins. © 2012 Blackwell Publishing Ltd.

Yellow fever disease: density equalizing mapping and gender analysis of international research output

PubMed Central

2013-01-01

Background A number of scientific papers on yellow fever have been published but no broad scientometric analysis on the published research of yellow fever has been reported. The aim of the article based study was to provide an in-depth evaluation of the yellow fever field using large-scale data analysis and employment of bibliometric indicators of production and quantity. Methods Data were retrieved from the Web of Science database (WoS) and analyzed as part of the NewQis platform. Then data were extracted from each file, transferred to databases and visualized as diagrams. Partially by means of density-equalizing mapping makes the findings clear and emphasizes the output of the analysis. Results In the study period from 1900 to 2012 a total of 5,053 yellow fever-associated items were published by 79 countries. The United States (USA) having the highest publication rate at 42% (n = 751) followed by far from Brazil (n = 203), France (n = 149) and the United Kingdom (n = 113). The most productive journals are the “Public Health Reports”, the “American Journal of Tropical Medicine and Hygiene” and the “Journal of Virology”. The gender analysis showed an overall steady increase of female authorship from 1950 to 2011. Brazil is the only country of the five most productive countries with a higher proportion of female scientists. Conclusions The present data shows an increase in research productivity over the entire study period, in particular an increase of female scientists. Brazil shows a majority of female authors, a fact that is confirmed by other studies. PMID:24245856

Yellow fever virus envelope protein expressed in insect cells is capable of syncytium formation in lepidopteran cells and could be used for immunodetection of YFV in human sera

PubMed Central

2011-01-01

Background Yellow fever is an haemorrhagic disease caused by a virus that belongs to the genus Flavivirus (Flaviviridae family) and is transmitted by mosquitoes. Among the viral proteins, the envelope protein (E) is the most studied one, due to its high antigenic potencial. Baculovirus are one of the most popular and efficient eukaryotic expression system. In this study a recombinant baculovirus (vSynYFE) containing the envelope gene (env) of the 17D vaccine strain of yellow fever virus was constructed and the recombinant protein antigenicity was tested. Results Insect cells infected with vSynYFE showed syncytium formation, which is a cytopathic effect characteristic of flavivirus infection and expressed a polypeptide of around 54 kDa, which corresponds to the expected size of the recombinant E protein. Furthermore, the recombinant E protein expression was also confirmed by fluorescence microscopy of vSynYFE-infected insect cells. Total vSynYFE-infected insect extracts used as antigens detected the presence of antibodies for yellow fever virus in human sera derived from yellow fever-infected patients in an immunoassay and did not cross react with sera from dengue virus-infected patients. Conclusions The E protein expressed by the recombinant baculovirus in insect cells is antigenically similar to the wild protein and it may be useful for different medical applications, from improved diagnosis of the disease to source of antigens for the development of a subunit vaccine. PMID:21619598

Induction of humoral immune response to multiple recombinant rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

USDA-ARS?s Scientific Manuscript database

Background: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiologic agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect fee...

Trapping of Rift Valley Fever (RVF) vectors using Light Emitting Diode (LED) CDC traps in two arboviral disease hot spots in Kenya

USDA-ARS?s Scientific Manuscript database

Background: Mosquitoes’ response to artificial lights including color has been exploited in trap designs for improved sampling of mosquito vectors. Earlier studies suggest that mosquitoes are attracted to specific wavelengths of light and thus the need to refine techniques to increase mosquito captu...

Synthesis and structure-activity relationships of carbohydrazides and 1,3,4-oxadiazole derivatives bearing imidazolidine moiety against the yellow fever and dengue vector, Aedes aegypti

USDA-ARS?s Scientific Manuscript database

BACKGROUND: 1,3,4-oxadiazole and imidazolidine rings are important heterocyclic compounds exhibiting a variety of biological activities. In this study, novel compounds with oxadiazole and imidazolidine rings were synthesized from 3-(methylsulfonyl)-2-oxoimidazolidine-1-carbonyl chloride and screened...

Yellow fever control in Cameroon: Where are we now and where are we going?

PubMed Central

Wiysonge, Charles Shey; Nomo, Emmanuel; Mawo, Jeanne; Ofal, James; Mimbouga, Julienne; Ticha, Johnson; Ndumbe, Peter M

2008-01-01

Background Cameroon is one of 12 African countries that bear most of the global burden of yellow fever. In 2002 the country developed a five-year strategic plan for yellow fever control, which included strategies for prevention as well as rapid detection and response to outbreaks when they occur. We have used data collected by the national Expanded Programme on Immunisation to assess the progress made and challenges faced during the first four years of implementing the plan. Methods In January 2003, case-based surveillance of suspected yellow fever cases was instituted in the whole country. A year later, yellow fever immunisation at nine months of age (the same age as routine measles immunisation) was introduced. Supplementary immunisation activities (SIAs), both preventive and in response to outbreaks, also formed an integral part of the yellow fever control plan. Each level of the national health system makes a synthesis of its activities and sends this to the next higher level at defined regular intervals; monthly for routine data and daily for SIAs. Results From 2004 to 2006 the national routine yellow fever vaccination coverage rose from 58.7% to 72.2%. In addition, the country achieved parity between yellow fever and measles vaccination coverage in 2005 and has since maintained this performance level. The number of suspected yellow fever cases in the country increased from 156 in 2003 to 859 in 2006, and the proportion of districts that reported at least one suspected yellow fever case per year increased from 31.4% to 68.2%, respectively. Blood specimens were collected from all suspected cases (within 14 days of onset of symptoms) and tested at a central laboratory for yellow fever IgM antibodies; leading to confirmation of yellow fever outbreaks in the health districts of Bafia, Méri and Ntui in 2003, Ngaoundéré Rural in 2004, Yoko in 2005 and Messamena in 2006. Owing to constraints in rapidly mobilising the necessary resources, reactive SIAs were only conducted in Bafia and Méri several months after confirmation of the outbreak. In both districts, a total of 60,083 people (representing 88.2% of the 68,103 targeted) were vaccinated. Owing to the same constraints, SIAs were not conducted promptly in response to the outbreaks in Ntui, Ngaoundéré Rural, Yoko and Messamena. However, these four and two other health districts at high risk of yellow fever outbreaks (i.e. Maroua Urban and Ngaoundéré Urban) conducted preventive SIAs in November 2006, vaccinating a total of 752,195 people (92.8% of target population). In both the reactive and preventive SIAs, the mean wastage rates for vaccines and injection material were less than 5% and there was no report of a serious adverse event following immunisation. Conclusion Amidst other competing health priorities, over the past four years Cameroon has successfully planned and implemented evidence-based strategies for preventing yellow fever outbreaks and for detecting and responding to the outbreaks when they occur. In order to sustain these initial successes, the country will have to attain and sustain high routine vaccination coverage in each successive birth cohort in every district. This would require fostering and sustaining high-level political commitment, improving the planning and monitoring of immunisation services at all levels, adequate community mobilisation, and efficient coordination of current and future immunisation partners. PMID:18261201

High-Resolution Genotyping of the Endemic Salmonella Typhi Population during a Vi (Typhoid) Vaccination Trial in Kolkata

PubMed Central

Manna, Byomkesh; Bhattacharya, Sujit K.; Bhaduri, Barnali; Pickard, Derek J.; Ochiai, R. Leon; Ali, Mohammad; Clemens, John D.; Dougan, Gordon

2012-01-01

Background Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas. Methodology We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003–December 2006, vaccinations given December 2004). Principal Findings A diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%), which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole). Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin). Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes. Conclusions Typhoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period. PMID:22303491

Detection of Rickettsia rickettsii, Rickettsia parkeri, and Rickettsia akari in Skin Biopsy Specimens Using a Multiplex Real-time Polymerase Chain Reaction Assay

PubMed Central

Denison, Amy M.; Amin, Bijal D.; Nicholson, William L.; Paddock, Christopher D.

2015-01-01

Background Rickettsia rickettsii, Rickettsia parkeri, and Rickettsia akari are the most common causes of spotted fever group rickettsioses indigenous to the United States. Infected patients characteristically present with a maculopapular rash, often accompanied by an inoculation eschar. Skin biopsy specimens are often obtained from these lesions for diagnostic evaluation. However, a species-specific diagnosis is achieved infrequently from pathologic specimens because immunohistochemical stains do not differentiate among the causative agents of spotted fever group rickettsiae, and existing polymerase chain reaction (PCR) assays generally target large gene segments that may be difficult or impossible to obtain from formalin-fixed tissues. Methods This work describes the development and evaluation of a multiplex real-time PCR assay for the detection of these 3 Rickettsia species from formalin-fixed, paraffin-embedded (FFPE) skin biopsy specimens. Results The multiplex PCR assay was specific at discriminating each species from FFPE controls of unrelated bacterial, viral, protozoan, and fungal pathogens that cause skin lesions, as well as other closely related spotted fever group Rickettsia species. Conclusions This multiplex real-time PCR demonstrates greater sensitivity than nested PCR assays in FFPE tissues and provides an effective method to specifically identify cases of Rocky Mountain spotted fever, rickettsialpox, and R. parkeri rickettsiosis by using skin biopsy specimens. PMID:24829214

Detection of relapsing fever Borrelia spp., Bartonella spp. and Anaplasmataceae bacteria in argasid ticks in Algeria

PubMed Central

Bitam, Idir; Leulmi, Hamza; Lalout, Reda; Mediannikov, Oleg; Chergui, Mohamed; Karakellah, Mohamed; Raoult, Didier

2017-01-01

Background Argasid ticks (soft ticks) are blood-feeding arthropods that can parasitize rodents, birds, humans, livestock and companion animals. Ticks of the Ornithodoros genus are known to be vectors of relapsing fever borreliosis in humans. In Algeria, little is known about relapsing fever borreliosis and other bacterial pathogens transmitted by argasid ticks. Methodology/Principal findings Between May 2013 and October 2015, we investigated the presence of soft ticks in 20 rodent burrows, 10 yellow-legged gull (Larus michahellis) nests and animal shelters in six locations in two different bioclimatic zones in Algeria. Six species of argasid ticks were identified morphologically and through 16S rRNA gene sequencing. The presence and prevalence of Borrelia spp., Bartonella spp., Rickettsia spp. and Anaplasmataceae was assessed by qPCR template assays in each specimen. All qPCR-positive samples were confirmed by standard PCR, followed by sequencing the amplified fragments. Two Borrelia species were identified: Borrelia hispanica in Ornithodoros occidentalis in Mostaganem, and Borrelia cf. turicatae in Carios capensis in Algiers. One new Bartonella genotype and one new Anaplasmataceae genotype were also identified in Argas persicus. Conclusions The present study highlights the presence of relapsing fever borreliosis agents, although this disease is rarely diagnosed in Algeria. Other bacteria of unknown pathogenicity detected in argasid ticks which may bite humans deserve further investigation. PMID:29145396

IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity

PubMed Central

Sun, Yong-Jiang; Kwek, Dyan J. C.; Lim, Poh-Lian; Dimatatac, Frederico; Ng, Lee-Ching; Ooi, Eng-Eong; Choo, Khar-Heng; Her, Zhisheng; Kourilsky, Philippe; Leo, Yee-Sin

2009-01-01

Background Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. Methods and Findings Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. Conclusions This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease. PMID:19156204

Atypical presentations of older adults at the emergency department and associated factors.

PubMed

Limpawattana, Panita; Phungoen, Pariwat; Mitsungnern, Thapanawong; Laosuangkoon, Wannisa; Tansangworn, Natthida

2016-01-01

The objectives were to determine the prevalence of atypical presentations among older adults at the Emergency Department (ED) of a tertiary care hospital and to identify factors associated with these presentations. A retrospective medical record audit was randomly reviewed in 633 patients who were aged ≥ 65 years who attended the ED of Srinagarind Medical School Hospital in 2013. Demographic data were collected and were analyzed using descriptive statistics. Regression analysis was used to analyze the variables associated with the outcomes. The prevalence of an atypical presentation was 28.6% (181/633 cases). The failure to develop fever with a disease known to cause fever was the most common atypical presentation of illness (34.42%). Independent factors associated with atypical presentations were complicated urinary tract infection (UTI) (odds ratios (OR) 4.66, 95% confidence interval (CI) 2.0, 10.84, p=0.00) and a background of dementia (OR 3.48, 95% CI 1.38, 8.77, p=0.008). The prevalence of atypical presentations of older adults at the ED was about a third. The absence of fever with a disease known to cause fever was the most common atypical presentation. Complicated UTI and demented patients were the independent risk factors associated with the atypical presentations. Early awareness of non-specific presentations and applying comprehensive geriatric assessments among older patients at the ED is recommended. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Seroprevalence survey of zoonoses in Extremadura, southwestern Spain, 2002-2003.

PubMed

Asencio, Maria Angeles; Herraez, Oscar; Tenias, Jose Maria; Garduño, Eugenio; Huertas, Maria; Carranza, Rafael; Ramos, Julian Mauro

2015-01-01

Our aims were to determine the seroprevalence rates for the most common types of zoonosis among the population of Extremadura (southwestern Spain) and to identify the associated risk factors. We conducted a seroepidemiological survey to collect information on family background and the habits of people residing in Extremadura between 2002 and 2003. Antibodies to Brucella were determined by Rose Bengal staining and a standard tube agglutination test; a titer of 1/80 was considered to be positive. Antibody titers for spotted fever, leishmaniasis, echinococcosis, and toxoplasmosis were determined by enzyme-immunoassays. Independent risk factors identified were age (younger age for brucellosis), male gender (brucellosis, spotted fever, and toxoplasmosis), occupation and contact with animals (brucellosis and spotted fever for those in contact with goats, hydatidosis for those in contact with sheep, leishmaniasis for those in contact with dogs, and toxoplasmosis for those in contact with cats and pigs), and consuming contaminated food (brucellosis by eating fresh cheese, hydatidosis by eating homemade sausages, and toxoplasmosis by eating pork). Except for leishmaniasis, the other zoonoses were more prevalent in rural areas, and, with the exception of brucellosis, they were all more prevalent in Badajoz. The distribution of zoonoses in Extremadura was strongly influenced by keeping livestock and eating habits. Thus, brucellosis was more prevalent in Caceres (associated with cheese consumption), while toxoplasmosis (pork consumption) and spotted fever (from hunting) were more common in Badajoz.

Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa

PubMed Central

Folarin, Onikepe A.; Grove, Jessica N.; Odia, Ikponmwonsa; Ehiane, Philomena E.; Omoniwa, Omowunmi; Omoregie, Omigie; Jiang, Pan-Pan; Yozwiak, Nathan L.; Matranga, Christian B.; Yang, Xiao; Gire, Stephen K.; Winnicki, Sarah; Tariyal, Ridhi; Schaffner, Stephen F.; Okokhere, Peter O.; Okogbenin, Sylvanus; Akpede, George O.; Asogun, Danny A.; Agbonlahor, Dennis E.; Walker, Peter J.; Tesh, Robert B.; Levin, Joshua Z.; Garry, Robert F.; Sabeti, Pardis C.; Happi, Christian T.

2015-01-01

Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance. PMID:25781465

The Z Proteins of Pathogenic but Not Nonpathogenic Arenaviruses Inhibit RIG-i-Like Receptor-Dependent Interferon Production

PubMed Central

Xing, Junji; Ly, Hinh

2014-01-01

ABSTRACT Arenavirus pathogens cause a wide spectrum of diseases in humans ranging from central nervous system disease to lethal hemorrhagic fevers with few treatment options. The reason why some arenaviruses can cause severe human diseases while others cannot is unknown. We find that the Z proteins of all known pathogenic arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Lassa, Junin, Machupo, Sabia, Guanarito, Chapare, Dandenong, and Lujo viruses, can inhibit retinoic acid-inducible gene 1 (RIG-i) and Melanoma Differentiation-Associated protein 5 (MDA5), in sharp contrast to those of 14 other nonpathogenic arenaviruses. Inhibition of the RIG-i-like receptors (RLRs) by pathogenic Z proteins is mediated by the protein-protein interactions of Z and RLRs, which lead to the disruption of the interactions between RLRs and mitochondrial antiviral signaling (MAVS). The Z-RLR interactive interfaces are located within the N-terminal domain (NTD) of the Z protein and the N-terminal CARD domains of RLRs. Swapping of the LCMV Z NTD into the nonpathogenic Pichinde virus (PICV) genome does not affect virus growth in Vero cells but significantly inhibits the type I interferon (IFN) responses and increases viral replication in human primary macrophages. In summary, our results show for the first time an innate immune-system-suppressive mechanism shared by the diverse pathogenic arenaviruses and thus shed important light on the pathogenic mechanism of human arenavirus pathogens. IMPORTANCE We show that all known human-pathogenic arenaviruses share an innate immune suppression mechanism that is based on viral Z protein-mediated RLR inhibition. Our report offers important insights into the potential mechanism of arenavirus pathogenesis, provides a convenient way to evaluate the pathogenic potential of known and/or emerging arenaviruses, and reveals a novel target for the development of broad-spectrum therapies to treat this group of diverse pathogens. More broadly, our report provides a better understanding of the mechanisms of viral immune suppression and host-pathogen interactions. PMID:25552708

Global research trends of World Health Organization's top eight emerging pathogens.

PubMed

Sweileh, Waleed M

2017-02-08

On December 8 th , 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine - related research with Ebola vaccine being most studied. Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.

Low Socioeconomic Status Is Associated with Prolonged Times to Assessment and Treatment, Sepsis and Infectious Death in Pediatric Fever in El Salvador

PubMed Central

Gavidia, Ronald; Fuentes, Soad L.; Vasquez, Roberto; Bonilla, Miguel; Ethier, Marie-Chantal; Diorio, Caroline; Caniza, Miguela; Howard, Scott C.; Sung, Lillian

2012-01-01

Background Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality. Method This prospective cohort study included children aged 0–16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. Findings Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0–20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0–3.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09–8.63; P = 0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03–1.81; P = 0.031) and in families with an annual household income

Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan

PubMed Central

2009-01-01

Background The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. Results A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2–3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. Conclusion The occurrences of scarlet fever in central Taiwan in 2000–2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003. PMID:19486515

Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin

PubMed Central

2014-01-01

Background Malaria and HIV are two major causes of morbidity and mortality among pregnant women in sub-Saharan Africa. Foetal and neonatal outcomes of this co-infection have been extensively studied. However, little is known about maternal morbidity due to clinical malaria in pregnancy, especially malaria-related fever, in the era of generalized access to antiretroviral therapy and anti-malarial preventive strategies. Methods A cohort study was conducted in order to estimate the incidence rate and to determine the factors associated with malaria-related fever, as well as the maternal morbidity attributable to malaria in a high-transmission setting of South Benin among HIV-infected pregnant women. Four-hundred and thirty-two women who participated in a randomized trial testing strategies to prevent malaria in pregnancy were included and followed until delivery, with at least three scheduled visits during pregnancy. Confirmed malaria-related fever was defined as axillary temperature >37.5°C and a concomitant, positive, thick blood smear or rapid diagnostic test for Plasmodium falciparum. Suspected malaria-related fever was defined as an axillary temperature >37.5°C and the concomitant administration of an anti-malarial treatment in the absence of parasitological investigation. Results Incidence rate for confirmed malaria-related fever was of 127.9 per 1,000 person-year (PY) (95% confidence interval (CI): 77.4-211.2). In multivariate analysis, CD4 lymphocytes (Relative Risk (RR) for a 50 cells/mm3 variation = 0.82; CI: 0.71-0.96), antiretroviral treatment started before inclusion (RR = 0.34; CI: 0.12-0.98) and history of symptomatic malaria in early pregnancy (RR = 7.10; CI: 2.35-22.49) were associated with the incidence of confirmed or suspected malaria-related fever. More than a half of participants with parasitaemia were symptomatic, with fever being the most common symptom. The crude fraction of febrile episodes attributable to malaria was estimated at 91%. Conclusions This work highlights that malaria is responsible for a substantial morbidity in HIV-infected pregnant women, with cellular immunodepression as a major determinant, and establishes the possible advantage offered by the early initiation of antiretroviral treatment. Trial registration PACOME Study has been registered under the number NCT00970879. PMID:24996807

Managing patients with dengue fever during an epidemic: the importance of a hydration tent and of a multidisciplinary approach

PubMed Central

2011-01-01

Background Dengue fever is one of the most common tropical diseases worldwide. Early detection of the disease, followed by intravenous fluid therapy in patients with dengue hemorrhagic fever (DHF) or with warning signs of dengue has a major impact on the prognosis. The purpose of this study is to describe the care provided in a hydration tent, including early detection, treatment, and serial follow-up of patients with dengue fever. Findings The analysis included all patients treated in the hydration tent from April 8 to May 9, 2008. The tent was set up inside the premises of the 2nd Military Firemen Group, located in Meier, a neighborhood in Rio de Janeiro, Brazil. The case form data were stored in a computerized database for subsequent assessment. Patients were referred to the tent from primary care units and from secondary city and state hospitals. The routine procedure consisted of an initial screening including vital signs (temperature, blood pressure, heart rate, and respiratory rate), tourniquet test and blood sampling for complete blood count. Over a 31-day period, 3,393 case recordings were seen at the hydration tent. The mean was 109 patients per day. A total of 2,102 initial visits and 1,291 return visits were conducted. Of the patients who returned to the hydration tent for reevaluation, 850 returned once, 230 returned twice, 114 returned three times, and 97 returned four times or more. Overall, 93 (5.3%) patients with DHF seen at the tent were transferred to a tertiary hospital. There were no deaths among these patients. Discussion As the epidemics were already widespread and there were no technical conditions for routine serology, all cases of suspected dengue fever were treated as such. Implementing hydration tents decrease the number of dengue fever hospitalizations. PMID:21902823

Socio-economic and Climate Factors Associated with Dengue Fever Spatial Heterogeneity: A Worked Example in New Caledonia

PubMed Central

Teurlai, Magali; Menkès, Christophe Eugène; Cavarero, Virgil; Degallier, Nicolas; Descloux, Elodie; Grangeon, Jean-Paul; Guillaumot, Laurent; Libourel, Thérèse; Lucio, Paulo Sergio; Mathieu-Daudé, Françoise; Mangeas, Morgan

2015-01-01

Background/Objectives Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon. Methods We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections. Results The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with people's way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3°C, mean incidence rates during epidemics could double. Conclusion In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries. PMID:26624008

[Louse-borne-relapsing-fever in refugees from the Horn of Africa; a case series of 25 patients].

PubMed

Seilmaier, M; Guggemos, W; Wieser, A; Fingerle, V; Balzer, L; Fenzl, T; Hoch, M; von Both, U; Schmidt, H U; Wendtner, C M; Strobel, E

2016-07-01

Background | Relapsing fever is divided into tick borne relapsing fever (TBRF) and louse borne relapsing fever (LBRF). This report describes 25 refugees from East Africa who were diagnosed to suffer from LBRF within a period of 6 month only at a single hospital in Munich / Germany. Material & Methods | The aim was to point out common clinical features as well as laboratory findings and clinical symptoms before and after initiation of treatment in 25 patients with louse borne relapsing fever (LBRF) who were diagnosed and treated at Klinikum München Schwabing from August 2015 to January 2016. To the best of our knowledge this is the largest case series of LBRF in the western world for decades. Main focus of the investigation was put on clinical aspects. Results | All 25 patients suffered from acute onset of high fever with chills, headache and severe prostration. Laboratory analysis showed high CRP and a marked thrombocytopenia. A Giemsa blood stain was procured immediately in order to look for malaria. In the blood smear spirochetes with typical shape and aspect of borrelia species could be detected.The further PCR analysis confirmed infection with Borrelia recurrentis. Treatment with Doxycycline was started forthwith. The condition improved already on the second day after treatment was started and all were restored to health in less than a week. Apart from a mild to moderate Jarisch-Herxheimer-reaction we didn`t see any side effects of the therapy. Conclusion | LBRF has to be taken into account in feverish patients who come as refugees from East-Africa. It seems that our patients belong to a cluster which probably has its origin in Libya and more patients are to be expected in the near future. As LBRF might cause outbreaks in refugee camps it is pivotal to be aware of this emerging infectious disease in refugees from East-Africa. © Georg Thieme Verlag KG Stuttgart · New York.

Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data

PubMed Central

Garske, Tini; Van Kerkhove, Maria D.; Yactayo, Sergio; Ronveaux, Olivier; Lewis, Rosamund F.; Staples, J. Erin; Perea, William; Ferguson, Neil M.

2014-01-01

Background Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods. Methods and Findings Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone. The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%–31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys. Conclusions With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns. Please see later in the article for the Editors' Summary PMID:24800812

Climate Teleconnections and Recent Patterns of Human and Animal Disease Outbreaks

PubMed Central

Anyamba, Assaf; Linthicum, Kenneth J.; Small, Jennifer L.; Collins, Kathrine M.; Tucker, Compton J.; Pak, Edwin W.; Britch, Seth C.; Eastman, James Ronald; Pinzon, Jorge E.; Russell, Kevin L.

2012-01-01

Background Recent clusters of outbreaks of mosquito-borne diseases (Rift Valley fever and chikungunya) in Africa and parts of the Indian Ocean islands illustrate how interannual climate variability influences the changing risk patterns of disease outbreaks. Although Rift Valley fever outbreaks have been known to follow periods of above-normal rainfall, the timing of the outbreak events has largely been unknown. Similarly, there is inadequate knowledge on climate drivers of chikungunya outbreaks. We analyze a variety of climate and satellite-derived vegetation measurements to explain the coupling between patterns of climate variability and disease outbreaks of Rift Valley fever and chikungunya. Methods and Findings We derived a teleconnections map by correlating long-term monthly global precipitation data with the NINO3.4 sea surface temperature (SST) anomaly index. This map identifies regional hot-spots where rainfall variability may have an influence on the ecology of vector borne disease. Among the regions are Eastern and Southern Africa where outbreaks of chikungunya and Rift Valley fever occurred 2004–2009. Chikungunya and Rift Valley fever case locations were mapped to corresponding climate data anomalies to understand associations between specific anomaly patterns in ecological and climate variables and disease outbreak patterns through space and time. From these maps we explored associations among Rift Valley fever disease occurrence locations and cumulative rainfall and vegetation index anomalies. We illustrated the time lag between the driving climate conditions and the timing of the first case of Rift Valley fever. Results showed that reported outbreaks of Rift Valley fever occurred after ∼3–4 months of sustained above-normal rainfall and associated green-up in vegetation, conditions ideal for Rift Valley fever mosquito vectors. For chikungunya we explored associations among surface air temperature, precipitation anomalies, and chikungunya outbreak locations. We found that chikungunya outbreaks occurred under conditions of anomalously high temperatures and drought over Eastern Africa. However, in Southeast Asia, chikungunya outbreaks were negatively correlated (p<0.05) with drought conditions, but positively correlated with warmer-than-normal temperatures and rainfall. Conclusions/Significance Extremes in climate conditions forced by the El Niño/Southern Oscillation (ENSO) lead to severe droughts or floods, ideal ecological conditions for disease vectors to emerge, and may result in epizootics and epidemics of Rift Valley fever and chikungunya. However, the immune status of livestock (Rift Valley fever) and human (chikungunya) populations is a factor that is largely unknown but very likely plays a role in the spatial-temporal patterns of these disease outbreaks. As the frequency and severity of extremes in climate increase, the potential for globalization of vectors and disease is likely to accelerate. Understanding the underlying patterns of global and regional climate variability and their impacts on ecological drivers of vector-borne diseases is critical in long-range planning of appropriate disease and disease-vector response, control, and mitigation strategies. PMID:22292093

Explaining changes in child health inequality in the run up to the 2015 Millennium Development Goals (MDGs): The case of Zambia

PubMed Central

Hangoma, Peter; Aakvik, Arild; Robberstad, Bjarne

2017-01-01

Background Child health interventions were drastically scaled up in the period leading up to 2015 as countries aimed at meeting the 2015 target of the Millennium Development Goals (MDGs). MDGs were defined in terms of achieving improvements in average health. Significant improvements in average child health are documented, but evidence also points to rising inequality. It is important to investigate factors that drive the increasing disparities in order to inform the post-2015 development agenda of reducing inequality, as captured in the Sustainable Development Goals (SDGs). We investigated changes in socioeconomic inequality in stunting and fever in Zambia in 2007 and 2014. Unlike the huge literature that seeks to quantify the contribution of different determinants on the observed inequality at any given time, we quantify determinants of changes in inequality. Methods Data from the 2007 and 2014 waves of the Zambia Demographic and Health Survey (DHS) were utilized. Our sample consisted of children aged 0–5 years (n = 5,616 in 2007 and n = 12,714 in 2014). We employed multilevel models to assess the determinants of stunting and fever, which are two important child health indicators. The concentration index (CI) was used to measure the magnitude of inequality. Changes in inequality of stunting and fever were investigated using Oaxaca-type decomposition of the CI. In this approach, the change in the CI for stunting/fever is decomposed into changes in CI for each determinant and changes in the effect—measured as an elasticity—of each determinant on stunting/fever. Results While average rates of stunting reduced in 2014 socioeconomic inequality in stunting increased significantly. Inequality in fever incidence also increased significantly, but average rates of fever did not reduce. The increase in the inequality (CI) of determinants accounted for the largest part (42.5%) of the increase in inequality of stunting, while the increase in the effect of determinants explained 35% of the increase. The determinants with the greatest total contribution (change in CI plus change in effect) to the increase in inequality of stunting were mother’s height and weight, wealth, birth order, facility delivery, duration of breastfeeding, and maternal education. For fever, almost all (86%) the increase in inequality was accounted for by the increase in the effect of determinants of fever, while the distribution of determinants mattered less. The determinants with the greatest total contribution to the increase in inequality of fever were wealth, maternal education, birth order and breastfeeding duration. In the multilevel model, we found that the likelihood of a child being stunted or experiencing fever depends on the community in which they live. Conclusions To curb the increase in inequality of stunting and fever, policy may focus on improving levels of, and reducing inequality in, access to facility deliveries, maternal nutrition (which may be related to maternal weight and height), complementary feeding (for breastfed children), wealth, maternal education, and child care (related to birth order effects). Improving overall levels of these determinants contribute to the persistence of inequality if these determinants are unequally concentrated on the well off to begin with. PMID:28170442

The proprotein convertase SKI-1/S1P. In vitro analysis of Lassa virus glycoprotein-derived substrates and ex vivo validation of irreversible peptide inhibitors.

PubMed

Pasquato, Antonella; Pullikotil, Philomena; Asselin, Marie-Claude; Vacatello, Manuela; Paolillo, Livio; Ghezzo, Francesca; Basso, Federica; Di Bello, Carlo; Dettin, Monica; Seidah, Nabil G

2006-08-18

Herein we designed, synthesized, tested, and validated fluorogenic methylcoumarinamide (MCA) and chloromethylketone-peptides spanning the Lassa virus GPC cleavage site as substrates and inhibitors for the proprotein convertase SKI-1/S1P. The 7-mer MCA (YISRRLL-MCA) and 8-mer MCA (IYISRRLL-MCA) are very efficiently cleaved with respect to both the 6-mer MCA (ISRRLL-MCA) and point mutated fluorogenic analogues, except for the 7-mer mutant Y253F. The importance of the P7 phenylic residue was confirmed by digestions of two 16-mer non-fluorogenic peptidyl substrates that differ by a single point mutation (Y253A). Because NMR analysis of these 16-mer peptides did not reveal significant structural differences at recognition motif RRLL, the P7 Tyr residue is likely important in establishing key interactions within the catalytic pocket of SKI-1. Based on these data, we established through analysis of pro-ATF6 and pro-SREBP-2 cellular processing that decanoylated chloromethylketone 7-mer, 6-mer, and 4-mer peptides containing the core RRLL sequence are irreversible and potent ex vivo SKI-1 inhibitors. Although caution must be exercised in using these inhibitors in in vitro reactions, as they can also inhibit the basic amino acid-specific convertase furin, within cells and when used at concentrations < or = 100 microM these inhibitors are relatively specific for inhibition of SKI-1 processing events, as opposed to those performed by furin-like convertases.

Health Beliefs and Practices Related to Dengue Fever: A Focus Group Study

PubMed Central

Wong, Li Ping; AbuBakar, Sazaly

2013-01-01

Background This qualitative study aimed to provide an in-depth understanding of the meaning of dengue fever (DF) amongst people living in a dengue endemic region, dengue prevention and treatment-seeking behaviours. The Health Belief Model was used as a framework to explore and understand dengue prevention behaviours. Methods A total of 14 focus group discussions were conducted with 84 Malaysian citizens of different socio-demographic backgrounds between 16th December, 2011 and 12th May, 2012. Results The study revealed that awareness about DF and prevention measures were high. The pathophysiology of dengue especially dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) were rarely known; as a result, it was seen as deadly by some but was also perceived as easily curable by others without a basis of understanding. Young adults and elderly participants had a low perception of susceptibility to DF. In general, the low perceived susceptibility emerged as two themes, namely a perceived natural ability to withstand infection and a low risk of being in contact with the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self-prevention against dengue prevention that emerged in focus groups were: i) lack of self-efficacy, ii) lack of perceived benefit, iii) low perceived susceptibility, and iv) unsure perceived susceptibility. Low perceived benefit of continued dengue prevention practices was a result of lack of concerted action against dengue in their neighborhood. Traditional medical practices and home remedies were widely perceived and experienced as efficacious in treating DF. Conclusion Behavioural change towards attaining sustainability in dengue preventive practices may be enhanced by fostering comprehensive knowledge of dengue and a change in health beliefs. Wide use of unconventional therapy for DF warrants the need to enlighten the public to limit their reliance on unproven alternative treatments. PMID:23875045

Ecology, biology and distribution of spotted-fever tick vectors in Brazil.

PubMed

Szabó, Matias P J; Pinter, Adriano; Labruna, Marcelo B

2013-01-01

Spotted-fever-caused Rickettsia rickettsii infection is in Brazil the major tick-borne zoonotic disease. Recently, a second and milder human rickettsiosis caused by an agent genetically related to R. parkeri was discovered in the country (Atlantic rainforest strain). Both diseases clearly have an ecological background linked to a few tick species and their environment. Capybaras (Hydrochoerus hydrochaeris) and Amblyomma cajennense ticks in urban and rural areas close to water sources are the main and long-known epidemiological feature behind R. rickettsii-caused spotted-fever. Unfortunately, this ecological background seems to be increasing in the country and disease spreading may be foreseen. Metropolitan area of São Paulo, the most populous of the country, is embedded in Atlantic rainforest that harbors another important R. rickettsii vector, the tick Amblyomma aureolatum. Thus, at the city-forest interface, dogs carry infected ticks to human dwellings and human infection occurs. A role for R. rickettsii vectoring to humans of a third tick species, Rhipicephalus sanguineus in Brazil, has not been proven; however, there is circumstantial evidence for that. A R. parkeri-like strain was found in A. ovale ticks from Atlantic rainforest and was shown to be responsible for a milder febrile human disease. Rickettsia-infected A. ovale ticks are known to be spread over large areas along the Atlantic coast of the country, and diagnosis of human infection is increasing with awareness and proper diagnostic tools. In this review, ecological features of the tick species mentioned, and that are important for Rickettsia transmission to humans, are updated and discussed. Specific knowledge gaps in the epidemiology of such diseases are highlighted to guide forthcoming research.

Ecology, biology and distribution of spotted-fever tick vectors in Brazil

PubMed Central

Szabó, Matias P. J.; Pinter, Adriano; Labruna, Marcelo B.

2013-01-01

Spotted-fever-caused Rickettsia rickettsii infection is in Brazil the major tick-borne zoonotic disease. Recently, a second and milder human rickettsiosis caused by an agent genetically related to R. parkeri was discovered in the country (Atlantic rainforest strain). Both diseases clearly have an ecological background linked to a few tick species and their environment. Capybaras (Hydrochoerus hydrochaeris) and Amblyomma cajennense ticks in urban and rural areas close to water sources are the main and long-known epidemiological feature behind R. rickettsii-caused spotted-fever. Unfortunately, this ecological background seems to be increasing in the country and disease spreading may be foreseen. Metropolitan area of São Paulo, the most populous of the country, is embedded in Atlantic rainforest that harbors another important R. rickettsii vector, the tick Amblyomma aureolatum. Thus, at the city–forest interface, dogs carry infected ticks to human dwellings and human infection occurs. A role for R. rickettsii vectoring to humans of a third tick species, Rhipicephalus sanguineus in Brazil, has not been proven; however, there is circumstantial evidence for that. A R. parkeri-like strain was found in A. ovale ticks from Atlantic rainforest and was shown to be responsible for a milder febrile human disease. Rickettsia-infected A. ovale ticks are known to be spread over large areas along the Atlantic coast of the country, and diagnosis of human infection is increasing with awareness and proper diagnostic tools. In this review, ecological features of the tick species mentioned, and that are important for Rickettsia transmission to humans, are updated and discussed. Specific knowledge gaps in the epidemiology of such diseases are highlighted to guide forthcoming research. PMID:23875178

Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013--recommendations.

PubMed

2015-01-01

This article presents the World Health Organizations (WHO) evidence and recommendations for the use of yellow fever (YF) vaccination from "Vaccines and vaccination against yellow fever: WHO Position Paper - June 2013" published in the Weekly Epidemiological Record. This position paper summarizes the WHO position on the use of YF vaccination, in particular that a single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. A booster dose is not necessary. The current document replaces the position paper on the use of yellow fever vaccines and vaccination published in 2003. Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2013 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2014. Published by Elsevier Ltd.

Illness-related practices for the management of childhood malaria among the Bwatiye people of north-eastern Nigeria

PubMed Central

Akogun, Oladele B; John, Kauna K

2005-01-01

Background A wide range of childhood illnesses are accompanied by fever,, including malaria. Child mortality due to malaria has been attributed to poor health service delivery system and ignorance. An assessment of a mother's ability to recognize malaria in children under-five was carried out among the Bwatiye, a poorly-served minority ethnic group in north-eastern Nigeria. Methods A three-stage research design involving interviews, participatory observation and laboratory tests was used to seek information from 186 Bwatiye mothers about their illness-related experiences with childhood fevers. Results Mothers classified malaria into male (fever that persists for longer than three days) and female (fever that goes away within three days) and had a system of determining when febrile illness would not be regarded as malaria. Most often, malaria would be ignored in the first 2 days before seeking active treatment. Self-medication was the preferred option. Treatment practices and sources of help were influenced by local beliefs, the parity of the mother and previous experience with child mortality. Conclusion The need to educate mothers to suspect malaria in every case of febrile illness and take appropriate action in order to expose the underlying "evil" will be more acceptable than an insistence on replacing local knowledge with biological epidemiology of malaria. The challenge facing health workers is to identify and exploit local beliefs about aetiology in effecting management procedures among culturally different peoples, who may not accept the concept of biological epidemiology. PMID:15723706

Antagonistic Activity of Lactobacillus Isolates against Salmonella typhi In Vitro

PubMed Central

Abdel-Daim, Amira; Hassouna, Nadia; Hafez, Mohamed; Ashor, Mohamed Seif Aldeen; Aboulwafa, Mohammad M.

2013-01-01

Background. Enteric fever is a global health problem, and rapidly developing resistance to various drugs makes the situation more alarming. The potential use of Lactobacillus to control typhoid fever represents a promising approach, as it may exert protective actions through various mechanisms. Methods. In this study, the probiotic potential and antagonistic activities of 32 Lactobacillus isolates against Salmonella typhi were evaluated. The antimicrobial activity of cell free supernatants of Lactobacillus isolates, interference of Lactobacillus isolates with the Salmonella adherence and invasion, cytoprotective effect of Lactobacillus isolates, and possibility of concurrent use of tested Lactobacillus isolates and antibiotics were evaluated by testing their susceptibilities to antimicrobial agents, and their oxygen tolerance was also examined. Results. The results revealed that twelve Lactobacillus isolates could protect against Salmonella typhi infection through interference with both its growth and its virulence properties, such as adherence, invasion, and cytotoxicity. These Lactobacillus isolates exhibited MIC values for ciprofloxacin higher than those of Salmonella typhi and oxygen tolerance and were identified as Lactobacillus plantarum. Conclusion. The tested Lactobacillus plantarum isolates can be introduced as potential novel candidates that have to be subjected for in vivo and application studies for treatment and control of typhoid fever. PMID:24191248

A recombinase polymerase amplification assay for rapid detection of Crimean-Congo Haemorrhagic fever Virus infection

PubMed Central

Afrough, Babak; Mullojonova, Manija; Dzhuraeva, Viktoriya; Tishkova, Farida; Hewson, Roger

2017-01-01

Background Crimean-Congo Haemorrhagic fever Virus (CCHFV) is a rapidly emerging vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting large parts of Europe, Africa, the Middle East and Asia. Methodology/principle findings An isothermal recombinase polymerase amplification (RPA) assay was successfully developed for molecular detection of CCHFV. The assay showed rapid (under 10 minutes) detection of viral extracts/synthetic virus RNA of all 7 S-segment clades of CCHFV, with high target specificity. The assay was shown to tolerate the presence of inhibitors in crude preparations of mock field samples, indicating that this assay may be suitable for use in the field with minimal sample preparation. The CCHFV RPA was successfully used to screen and detect CCHFV positives from a panel of clinical samples from Tajikistan. Conclusions/significance The assay is a rapid, isothermal, simple-to-perform molecular diagnostic, which can be performed on a light, portable real-time detection device. It is ideally placed therefore for use as a field-diagnostic or in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of-need, such as in remote rural regions in affected countries. PMID:29028804

Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar – Aetiologies, Antibiotic Treatment and Outcome

PubMed Central

Elfving, Kristina; Shakely, Deler; Andersson, Maria; Baltzell, Kimberly; Ali, Abdullah S.; Bachelard, Marc; Falk, Kerstin I.; Ljung, Annika; Msellem, Mwinyi I.; Omar, Rahila S.; Parola, Philippe; Xu, Weiping; Petzold, Max; Trollfors, Birger; Björkman, Anders; Lindh, Magnus; Mårtensson, Andreas

2016-01-01

Background Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. Methods We prospectively studied the aetiology of febrile illness in 677 children aged 2–59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. Findings NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. Conclusions This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low. PMID:26821179

Human fascioliasis with biliary complications.

PubMed

Kumari, V; Banerjee, Tuhina; Negi, N; Gupta, M I; Tiwari, K; Gupta, M

2013-01-01

We report a case of human fascioliasis adding to the few of the previously reported cases in India. A young boy from rural background in Bihar presented with diarrhea, vomiting, hepatic tenderness, jaundice and fever along with peripheral eosinophilia. Examination of stool revealed yellow-brown eggs of Fasciola hepatica. Human fascioliasis should be kept in mind in patients with cholangitis and eosinophilia especially in areas of sporadic occurrence.

Travel-acquired infections in Canada: CanTravNet 2011—2012

PubMed Central

Boggild, AK; Geduld, J; Libman, M; Ward, BJ; McCarthy, A; Hajek, J; Ghesquiere, W; Vincelette, J; Kuhn, S; Freedman, DO; Kain, KC

2014-01-01

Background Important gaps remain in our knowledge of the infectious diseases people acquire while travelling and the impact of pathogens imported by Canadian travellers. Objective To provide a surveillance update of illness in a cohort of returned Canadian travellers and new immigrants. Methods Data on returning Canadian travellers and new immigrants presenting to a CanTravNet site between September 2011 and September 2012 were extracted and analyzed by destination, presenting symptoms, common and emerging infectious diseases and disease severity. Results During the study period, 2283 travellers and immigrants presented to a CanTravNet site, 88% (N=2004) of whom were assigned a travel-related diagnosis. Top three destinations for non-immigrant travellers were India (N=132), Mexico (N=103) and Cuba (N=89). Fifty-one cases of malaria were imported by ill returned travellers during the study period, 60% (N=30) of which were Plasmodium falciparum infections. Individuals travelling to visit friends and relatives accounted for 83% of enteric fever cases (15/18) and 41% of malaria cases (21/51). The requirement for inpatient management was over-represented among those with malaria compared to those without malaria (25% versus 2.8%; p<0.0001) and those travelling to visit friends and relatives versus those travelling for other reasons (12.1% versus 2.4%; p<0.0001). Nine new cases of HIV were diagnosed among the cohort, as well as one case of acute hepatitis B. Emerging infections among travellers included hepatitis E virus (N=6), chikungunya fever (N=4) and cutaneous leishmaniasis (N=16). Common chief complaints included gastrointestinal (N=804), dermatologic (N=440) and fever (N=287). Common specific causes of chief complaint of fever in the cohort were malaria (N=47/51 total cases), dengue fever (14/18 total cases), enteric fever (14/17 total cases) and influenza and influenza-like illness (15/21 total cases). Animal bites were the tenth most common diagnosis among tourist travellers. Interpretation Our analysis of surveillance data on ill returned Canadian travellers provides a recent update to the spectrum of imported illness among travelling Canadians. Preventable travel-acquired illnesses and injuries in the cohort include malaria, enteric fever, HIV, hepatitis B, hepatitis A, influenza and animal bites. Strategies to improve uptake of preventive interventions such as malaria chemoprophylaxis, immunizations and arthropod/animal avoidance may be warranted. PMID:29769859

Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model

PubMed Central

De Jong, Hanna K.; Achouiti, Ahmed; Koh, Gavin C. K. W.; Parry, Christopher M.; Baker, Stephen; Faiz, Mohammed Abul; van Dissel, Jaap T.; Vollaard, Albert M.; van Leeuwen, Ester M. M.; Roelofs, Joris J. T. H.; de Vos, Alex F.; Roth, Johannes; van der Poll, Tom; Vogl, Thomas; Wiersinga, Willem Joost

2015-01-01

Background Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. Methods and principal findings S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. Conclusion S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice. PMID:25860480

The influence of different fever definitions on diagnostics and treatment after diagnosis of fever in chemotherapy-induced neutropenia in children with cancer

PubMed Central

Stutz-Grunder, Eveline; Agyeman, Philipp; Leibundgut, Kurt; Teuffel, Oliver; Ammann, Roland A.

2018-01-01

Background There is no evidence-based definition of the temperature limit defining fever (TLDF) in children with neutropenia. Lowering the TLDF is known to increase the number of episodes of fever in neutropenia (FN). This study aimed to investigate the influence of a lower versus standard TLDF on diagnostics and therapy. Methods In a single pediatric cancer center using a high standard TLDF (39°C tympanic-temperature) patients were observed prospectively (NCT01683370). The effect of applying lower TLDFs (range 37.5°C to 38.9°C) versus 39.0°C on these measures was simulated in silicon. Results In reality, 45 FN episodes were diagnosed. Of 3391 temperatures measured, 193 were ≥39.0°C, and 937 ≥38.0°C. For persisting fever ≥24 hours, additional blood cultures were taken in 31 (69%) episodes in reality. This number decreased to 22 (49%) when applying 39.0°C, and increased to 33 for 38.0°C (73%; plus 11 episodes; plus 24%). For persisting fever ≥48 hours, i.v.-antibiotics were escalated in 25 (56%) episodes. This number decreased to 15 (33%) when applying 39.0°C, and increased to 26 for 38.0°C (58%; plus 11 episodes; plus 24%). For persisting fever ≥120 hours, i.v.-antifungals were added in 4 (9%) episodes. This number increased to 6 (13%) by virtually applying 39.0°C, and to 11 for 38.0°C (24%; plus 5 episodes; plus 11%). The median length of stay was 5.7 days (range, 0.8 to 43.4). In 43 episodes with hospital discharge beyond 24 hours, applying 38.0°C led to discharge delay by ≥12 hours in 24 episodes (56%; 95% CI, 40 to 71), with a median delay of 13 hours, and a cumulative delay of 68 days. Conclusion Applying a low versus standard TLDF led to relevant increases of diagnostics, antimicrobial therapy, and length of stay. The differences between management in reality versus simply applying 39.0° as TLDF reflect the important impact of clinical assessment. PMID:29462193

Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Preliminary Report.

PubMed

Ahuka-Mundeke, Steve; Casey, Rebecca M; Harris, Jennifer B; Dixon, Meredith G; Nsele, Pierre M; Kizito, Gabriel M; Umutesi, Grace; Laven, Janeen; Paluku, Gilson; Gueye, Abdou S; Hyde, Terri B; Sheria, Guylain K M; Muyembe-Tanfum, Jean-Jacques; Staples, J Erin

2018-02-14

Background In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. Methods We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and 28 to 35 days after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT 50 ). Participants with a PRNT 50 titer of 10 or higher at baseline were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. Results Among 716 participants who completed follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Conclusions A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in most of the participants who were seronegative at baseline. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

Annual Progress Report--Fiscal Year 1979

DTIC Science & Technology

1979-10-01

fever virus Ebola fever virus Korean hemorrhagic fever virus Rift Valley fever virus Bolivian hemorrhagic fever virus...Machupo) Argentinian hemorrhagic fever virus (Junin) Dengue fever virus Congo/Crimean hemorrhagic fever virus Sand fly fever virus Eastern encephalitis...virus Western encephalitis virus Venezuelan fever virus Japanese B fever virus Chikungunya virus Tacaribe virus Pichinde virus Yellow fever

The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.

PubMed

May, Eric R; Armen, Roger S; Mannan, Aristotle M; Brooks, Charles L

2010-08-01

The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. (c) 2010 Wiley-Liss, Inc.

The Flexible C-terminal Arm of the Lassa Arenavirus Z-Protein Mediates Interactions with Multiple Binding Partners

PubMed Central

May, Eric R.; Armen, Roger S.; Mannan, Aristotle M.; Brooks, Charles L.

2010-01-01

The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics were employed to refine the structures, which were then subsequently clustered. Population weighted ensembles of low energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was indentified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during molecular dynamics trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein binding recognition motifs for Tsg101 and eIF4E, and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. PMID:20544962

Assessment of Recombination in the S-segment Genome of Crimean-Congo Hemorrhagic Fever Virus in Iran

PubMed Central

Chinikar, Sadegh; Shah-Hosseini, Nariman; Bouzari, Saeid; Shokrgozar, Mohammad Ali; Mostafavi, Ehsan; Jalali, Tahmineh; Khakifirouz, Sahar; Groschup, Martin H; Niedrig, Matthias

2016-01-01

Background: Crimean-Congo Hemorrhagic Fever Virus (CCHFV) belongs to genus Nairovirus and family Bunyaviridae. The main aim of this study was to investigate the extent of recombination in S-segment genome of CCHFV in Iran. Methods: Samples were isolated from Iranian patients and those available in GenBank, and analyzed by phylogenetic and bootscan methods. Results: Through comparison of the phylogenetic trees based on full length sequences and partial fragments in the S-segment genome of CCHFV, genetic switch was evident, due to recombination event. Moreover, evidence of multiple recombination events was detected in query isolates when bootscan analysis was used by SimPlot software. Conclusion: Switch of different genomic regions between different strains by recombination could contribute to CCHFV diversification and evolution. The occurrence of recombination in CCHFV has a critical impact on epidemiological investigations and vaccine design. PMID:27047968

The burden of typhoid fever in low- and middle-income countries: A meta-regression approach

PubMed Central

Warren, Joshua L.; Crawford, Forrest W.; Weinberger, Daniel M.; Kürüm, Esra; Pak, Gi Deok; Marks, Florian; Pitzer, Virginia E.

2017-01-01

Background Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs), so model-based estimates offer insights for decision-makers in the absence of readily available data. Methods We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model. Results We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9–48.4 million). Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2–4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models. Conclusions Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases. PMID:28241011

Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash

PubMed Central

Carrol, E; Newland, P; Riordan, F; Thomson, A; Curtis, N; Hart, C

2002-01-01

Background: Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier and better diagnostic marker than C reactive protein (CRP) and white cell count (WCC). This comparison has never been reported in the differentiation of meningococcal disease (MCD) in children presenting with a fever and rash. Aim: To determine if PCT might be a useful marker of MCD in children presenting with fever and rash. Methods: PCT, CRP, and WCC were measured on admission in 108 children. Patients were classified into two groups: group I, children with a microbiologically confirmed clinical diagnosis of MCD (n = 64); group II, children with a self limiting illness (n = 44). Median ages were 3.57 (0.07–15.9) versus 1.75 (0.19–14.22) years respectively. Severity of disease in patients with MCD was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Results: PCT and CRP values were significantly higher in group I than in group II (median 38.85 v 0.27 ng/ml and 68.35 v 9.25 mg/l; p < 0.0005), but there was no difference in WCC between groups. Sensitivity, specificity, and positive and negative predictive values were higher for PCT than CRP and WCC. In group I, procalcitonin was significantly higher in those with severe disease (GMSPS ≥8). Conclusions: PCT is a more sensitive and specific predictor of MCD than CRP and WCC in children presenting with fever and a rash. PMID:11919107

Rocky Mountain Spotted Fever Characterization and Comparison to Similar Illnesses in a Highly Endemic Area—Arizona, 2002–2011

PubMed Central

Traeger, Marc S.; Regan, Joanna J.; Humpherys, Dwight; Mahoney, Dianna L.; Martinez, Michelle; Emerson, Ginny L.; Tack, Danielle M.; Geissler, Aimee; Yasmin, Seema; Lawson, Regina; Hamilton, Charlene; Williams, Velda; Levy, Craig; Komatsu, Kenneth; McQuiston, Jennifer H.; Yost, David A.

2015-01-01

Background Rocky Mountain spotted fever (RMSF) has emerged as a significant cause of morbidity and mortality since 2002 on tribal lands in Arizona. The explosive nature of this outbreak and the recognition of an unexpected tick vector, Rhipicephalus sanguineus, prompted an investigation to characterize RMSF in this unique setting and compare RMSF cases to similar illnesses. Methods We compared medical records of 205 patients with RMSF and 175 with non-RMSF illnesses that prompted RMSF testing during 2002–2011 from 2 Indian reservations in Arizona. Results RMSF cases in Arizona occurred year-round and peaked later (July–September) than RMSF cases reported from other US regions. Cases were younger (median age, 11 years) and reported fever and rash less frequently, compared to cases from other US regions. Fever was present in 81% of cases but not significantly different from that in patients with non-RMSF illnesses. Classic laboratory abnormalities such as low sodium and platelet counts had small and subtle differences between cases and patients with non-RMSF illnesses. Imaging studies reflected the variability and complexity of the illness but proved unhelpful in clarifying the early diagnosis. Conclusions RMSF epidemiology in this region appears different than RMSF elsewhere in the United States. No specific pattern of signs, symptoms, or laboratory findings occurred with enough frequency to consistently differentiate RMSF from other illnesses. Due to the nonspecific and variable nature of RMSF presentations, clinicians in this region should aggressively treat febrile illnesses and sepsis with doxycycline for suspected RMSF. PMID:25697743

Epidemiological investigation of an outbreak of typhoid fever in Jorhat town of Assam, India

PubMed Central

Roy, Jashbeer Singh; Saikia, Lahari; Medhi, Mithu; Tassa, Dipak

2016-01-01

Background & objectives: Typhoid fever is a global health problem and is also endemic in India. An outbreak of fever occurred in January 2014 in Jorhat Town in Assam, India. Here we report the results of an investigation done to find out the aetiology and source of the outbreak. Methods: The affected areas were visited on January 23, 2014 by a team of Jorhat district Integrated Disease Surveillance Project personnel. A total of 13 blood samples from patients with fever as first symptom and six water samples were collected from the affected areas. The blood samples were cultured and isolates were identified using standard biochemical tests. Isolates were also tested for antimicrobial sensitivity. Widal test was performed on 10 of the 13 blood samples collected. Sanitary survey was carried out to find any leakage in the water supply and also the sewage system of the Jorhat town. Results: Blood culture yielded Salmonella enterica serovar Typhi in six (46.15%) patients whereas Widal test was positive in 10 (76.9%) of 13 patients. Water culture showed presumptive coliform count of >180/100 ml in two out of the six samples tested. Salmonella Typhi was also isolated from water culture of these two samples. Sanitary survey carried out in the affected places showed that the water supply pipes of urban water supply were in close proximity to the sewage drainage system and there were few leakages. Interpretation & conclusions: The outbreak occurred due to S. Typhi contaminating the water supply. Sanitation and immunization are the two most important components to be stressed to prevent such outbreaks. PMID:28256469

A multi-country study of the economic burden of dengue fever: Vietnam, Thailand, and Colombia

PubMed Central

Lee, Jung-Seok

2017-01-01

Background Dengue fever is a major public health concern in many parts of the tropics and subtropics. The first dengue vaccine has already been licensed in six countries. Given the growing interests in the effective use of the vaccine, it is critical to understand the economic burden of dengue fever to guide decision-makers in setting health policy priorities. Methods/Principal findings A standardized cost-of-illness study was conducted in three dengue endemic countries: Vietnam, Thailand, and Colombia. In order to capture all costs during the entire period of illness, patients were tested with rapid diagnostic tests on the first day of their clinical visits, and multiple interviews were scheduled until the patients recovered from the current illness. Various cost items were collected such as direct medical and non-medical costs, indirect costs, and non-out-of-pocket costs. In addition, socio-economic factors affecting disease severity were also identified by adopting a logit model. We found that total cost per episode ranges from $141 to $385 for inpatient and from $40 to $158 outpatient, with Colombia having the highest and Thailand having the lowest. The percentage of the private economic burden of dengue fever was highest in the low-income group and lowest in the high-income group. The logit analyses showed that early treatment, higher education, and better knowledge of dengue disease would reduce the probability of developing more severe illness. Conclusions/Significance The cost of dengue fever is substantial in the three dengue endemic countries. Our study findings can be used to consider accelerated introduction of vaccines into the public and private sector programs and prioritize alternative health interventions among competing health problems. In addition, a community would be better off by propagating the socio-economic factors identified in this study, which may prevent its members from developing severe illness in the long run. PMID:29084220

Shifts in Geographic Distribution and Antimicrobial Resistance during a Prolonged Typhoid Fever Outbreak — Bundibugyo and Kasese Districts, Uganda, 2009–2011

PubMed Central

Walters, Maroya Spalding; Routh, Janell; Mikoleit, Matthew; Kadivane, Samuel; Ouma, Caroline; Mubiru, Denis; Mbusa, Ben; Murangi, Amos; Ejoku, Emmanuel; Rwantangle, Absalom; Kule, Uziah; Lule, John; Garrett, Nancy; Halpin, Jessica; Maxwell, Nikki; Kagirita, Atek; Mulabya, Fred; Makumbi, Issa; Freeman, Molly; Joyce, Kevin; Hill, Vince; Downing, Robert; Mintz, Eric

2014-01-01

Background Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo. Methodology/Principal Findings A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009–December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1–December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates. Conclusions/Significance Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure, should be considered to minimize the risk of prolonged outbreaks in the future. PMID:24603860

Asthma, hay fever, and food allergy are associated with caregiver-reported speech disorders in US children

PubMed Central

Strom, Mark A.; Silverberg, Jonathan I.

2016-01-01

Background Children with asthma, hay fever, and food allergy may have several factors that increase their risk of speech disorder, including allergic inflammation, ADD/ADHD, and sleep disturbance. However, few studies have examined a relationship between asthma, allergic disease, and speech disorder. We sought to determine whether asthma, hay fever, and food allergy are associated with speech disorder in children and whether disease severity, sleep disturbance, or ADD/ADHD modified such associations. Methods We analyzed cross-sectional data on 337,285 children aged 2–17 years from 19 US population-based studies, including the 1997–2013 National Health Interview Survey and the 2003/4 and 2007/8 National Survey of Children’s Health. Results In multivariate models, controlling for age, demographic factors, healthcare utilization, and history of eczema, lifetime history of asthma (odds ratio [95% confidence interval]: 1.18 [1.04–1.34], p = 0.01), and one-year history of hay fever (1.44 [1.28–1.62], p < 0.0001) and food allergy (1.35 [1.13–1.62], p = 0.001) were associated with increased odds of speech disorder. Children with current (1.37 [1.15–1.59] p = 0.0003) but not past (p = 0.06) asthma had increased risk of speech disorder. In one study that assessed caregiver-reported asthma severity, mild (1.58 [1.20–2.08], p = 0.001) and moderate (2.99 [1.54–3.41], p < 0.0001) asthma were associated with increased odds of speech disorder; however, severe asthma was associated with the highest odds of speech disorder (5.70 [2.36–13.78], p = 0.0001). Conclusion Childhood asthma, hay fever, and food allergy are associated with increased risk of speech disorder. Future prospective studies are needed to characterize the associations. PMID:27091599

Euthermic Endocarditis

PubMed Central

DeSimone, Daniel C.; Baddour, Larry M.; Lahr, Brian D.; Chung, Heath H.; Wilson, Walter R.; Steckelberg, James M.

2013-01-01

Background Most patients with infective endocarditis (IE) manifest fever. Comparison of endocarditis patients with and without fever, and whether the lack of fever in IE is a marker for poorer outcomes, such as demonstrated in other severe infectious diseases, have not been defined. Methods and Results Cases from the Mayo Clinic, Rochester, Minnesota, Division of Infectious Diseases IE registry, a single-center database that contains all cases of IE treated at our center. Diagnosis date between 1970 and 2006, which met the modified Duke criteria for definite endocarditis, without fever was included. There were 240 euthermic endocarditis cases included in this analysis, with 282 febrile controls selected by frequency matching on gender and decade of diagnosis. Euthermic patients had a median age of 63.6 years (±16.1) as compared to 59.0 years (±16.4) in the febrile control group (p=0.001). Median (IQR) symptom duration prior to diagnosis was 4.0 (1.0, 12.0) weeks in the euthermic group compared to 3.0 (1.0, 8.0) weeks in the febrile controls (p= 0.006). From unadjusted analyses, survival rates were 87% in euthermic cases versus 83% in febrile controls across 28-day follow-up (p=0.164), and 72% in euthermic group cases versus 69% in febrile controls across 1-year follow-up (p=0.345). Also unadjusted, the 1-year cumulative incidence rate of valve surgery was higher in euthermic cases versus febrile controls (50% vs. 39%, p= 0.004). Conclusions Patients with euthermic endocarditis are older, and lack of fever was associated with longer symptom duration and delayed diagnosis prior to IE diagnosis. Despite a higher unadjusted rate of valve surgery in euthermic patients, the result was not significant when adjusting for baseline confounders. Differences in survival rates at both 28-days and 365-days were not statistically significant between the two groups. PMID:24244630

The clinical and microbiological characteristics of enteric fever in Cambodia, 2008-2015

PubMed Central

Phe, Thong; Veng, Chhun H.; Lim, Kruy; Ieng, Sovann; Kham, Chun; Fawal, Nizar; Fabre, Laetitia; Le Hello, Simon; Vlieghe, Erika; Weill, François-Xavier; Jacobs, Jan; Peetermans, Willy E.

2017-01-01

Background Enteric fever remains a major public health problem in low resource settings and antibiotic resistance is increasing. In Asia, an increasing proportion of infections is caused by Salmonella enterica serovar Paratyphi A, which for a long time was assumed to cause a milder clinical syndrome compared to Salmonella enterica serovar Typhi. Methodology A retrospective chart review study was conducted of 254 unique cases of blood culture confirmed enteric fever who presented at a referral adult hospital in Phnom Penh, Cambodia between 2008 and 2015. Demographic, clinical and laboratory data were collected from clinical charts and antibiotic susceptibility testing was performed. Whole genome sequence analysis was performed on a subset of 121 isolates. Results One-hundred-and-ninety unique patients were diagnosed with Salmonella Paratyphi A and 64 with Salmonella Typhi. In the period 2008–2012, Salmonella Paratyphi A comprised 25.5% of 47 enteric fever cases compared to 86.0% of 207 cases during 2013–2015. Presenting symptoms were identical for both serovars but higher median leukocyte counts (6.8 x 109/L vs. 6.3 x 109/L; p = 0.035) and C-reactive protein (CRP) values (47.0 mg/L vs. 36 mg/L; p = 0.034) were observed for Salmonella Typhi infections. All but one of the Salmonella Typhi isolates belonged to haplotype H58 associated with multidrug resistance (MDR) (i.e. resistance to ampicillin, chloramphenicol and co-trimoxazole).;42.9% actually displayed MDR compared to none of the Salmonella Paratyphi A isolates. Decreased ciprofloxacin susceptibility (DCS) was observed in 96.9% (62/64) of Salmonella Typhi isolates versus 11.5% (21/183) of Salmonella Paratyphi A isolates (all but one from 2015). All isolates were susceptible to azithromycin and ceftriaxone. Conclusions In Phnom Penh, Cambodia, Salmonella Paratyphi A now causes the majority of enteric fever cases and decreased susceptibility against ciprofloxacin is increasing. Overall, Salmonella Typhi was significantly more associated with MDR and DCS compared to Salmonella Paratyphi A. PMID:28931025

Modelling the Impact and Cost-Effectiveness of Biomarker Tests as Compared with Pathogen-Specific Diagnostics in the Management of Undifferentiated Fever in Remote Tropical Settings

PubMed Central

Lubell, Yoel; Althaus, Thomas; Blacksell, Stuart D.; Paris, Daniel H.; Mayxay, Mayfong; Pan-Ngum, Wirichada; White, Lisa J.; Day, Nicholas P. J.; Newton, Paul N.

2016-01-01

Background Malaria accounts for a small fraction of febrile cases in increasingly large areas of the malaria endemic world. Point-of-care tests to improve the management of non-malarial fevers appropriate for primary care are few, consisting of either diagnostic tests for specific pathogens or testing for biomarkers of host response that indicate whether antibiotics might be required. The impact and cost-effectiveness of these approaches are relatively unexplored and methods to do so are not well-developed. Methods We model the ability of dengue and scrub typhus rapid tests to inform antibiotic treatment, as compared with testing for elevated C-Reactive Protein (CRP), a biomarker of host-inflammation. Using data on causes of fever in rural Laos, we estimate the proportion of outpatients that would be correctly classified as requiring an antibiotic and the likely cost-effectiveness of the approaches. Results Use of either pathogen-specific test slightly increased the proportion of patients correctly classified as requiring antibiotics. CRP testing was consistently superior to the pathogen-specific tests, despite heterogeneity in causes of fever. All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively. Conclusions Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients. Testing for prevalent bacterial pathogens can be cost-effective, having the benefit of informing not only whether treatment is required, but also as to the most appropriate antibiotic; this advantage, however, varies widely in response to heterogeneity in causes of fever. Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections. PMID:27027303

Comparison of early and late intravenous gamma globulin treatment of Kawasaki disease on fever and cardiovascular complications

PubMed Central

Mohammadzadeh, Iraj; Noei, Somayyeh; Babazadeh, Kazem; Zamani, Hassan; Barari-Savadkoohi, Rahim; Alizadeh-Navaei, Reza

2016-01-01

Background: Cardiac involvement was the major leading cause of death in patients with Kawasaki and IVIG administration reduces cardiac complications. The objective of this study was to determine the frequency of cardiovascular complications and duration of fever with regard to the time of intravenous immunoglobulin (IVIG) administration of patients with Kawasaki disease. Methods: This follow-up study was done on all patients with Kawasaki disease who were hospitalized at Amirkola Children’s Hospital between 2006 and 2011. Diagnosis of Kawasaki was clinical and included fever more than 5 days with 4 of 5 signs containing mucosal changes, scaling and skin rash, bilateral nonexudative conjunctivitis, cervical lymph adenopathy and edema in lower extremities. After diagnosis of Kawasaki, all patients received standard treatment (intravenous immunoglobulins and aspirin) and undergoing cardiac echocardiography in 2 weeks, 2 months and 6 months. Information including age, sex, sign of diseases, laboratory findings, and cardiac complications in echocardiography were recorded. Results: This study was performed on 100 patients (61 boys and 39 girls) with Kawasaki disease. The mean age of children was 2.8±2.6 years. Cardiac complication rate was 47% at the onset of the disease and had reached to 7% at the end of the sixth month (P=0.000). Distribution of cardiovascular complications in the second week, the second month and the sixth month after treatment was not significantly different according to the start of time of treatment (p>0.05). Duration of fever in patients who received treatment before 10th day (1.5±1.3) did not have significant difference (P=0.78) with patients who received after 10th day (1.6±0.9). Conclusion: Result shows that most of patients (99%) responded to the treatment with IVIG and ASA and cardiovascular complication ratio decreased. There was not significant relationship between duration of fever and time of IVIG treatment initiation. PMID:27757208

Atmospheric Moisture Variability and Transmission of Hemorrhagic Fever with Renal Syndrome in Changsha City, Mainland China, 1991–2010

PubMed Central

Li, Xiu-Jun; Tong, Shi-Lu; Gao, Li-Dong; Qin, Jian-Xin; Lin, Xiao-Ling; Liu, Hai-Ning; Zhang, Xi-Xing

2013-01-01

Background The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by environmental determinants. This study aimed to explore the association between atmospheric moisture variability and the transmission of hemorrhagic fever with renal syndrome (HFRS) for the period of 1991–2010 in Changsha, China. Methods and Findings Wavelet analyses were performed by using monthly reported time series data of HFRS cases to detect and quantify the periodicity of HFRS. A generalized linear model with a Poisson distribution and a log link model were used to quantify the relationship between climate and HFRS cases, highlighting the importance of moisture conditions. There was a continuous annual oscillation mode and multi-annual cycle around 3–4 years from 1994 to 1999. There was a significant association of HFRS incidence with moisture conditions and the Multivariate El Niño–Southern Oscillation Index (MEI). Particularly, atmospheric moisture has a significant effect on the propagation of HFRS; annual incidence of HFRS was positively correlated with annual precipitation and annual mean absolute humidity. Conclusions The final model had good accuracy in forecasting the occurrence of HFRS and moisture condition can be used in disease surveillance and risk management to provide early warning of potential epidemics of this disease. PMID:23755316

Genetic analysis and epidemiology of Crimean Congo hemorrhagic fever viruses in Baluchistan province of Pakistan

PubMed Central

2013-01-01

Background Pakistan is considered as an endemic country for Crimean-Congo Hemorrhagic fever with numerous outbreaks and sporadic cases reported during the past two decades. Majority of cases are reported from Baluchistan province with subsequent transmissions to non-endemic regions mainly through infected animals directly or via infested ticks. We hereby describe the molecular investigations of CCHF cases reported during 2008 in Quetta city of Baluchistan province. Methods Serum Samples from 44 patients, with clinical signs of hemorrhagic fever attending a tertiary care hospital in Quetta city, were collected and tested for CCHF virus antigen and genomic RNA, using capture IgM EIA kit and standard RT-PCR assay, respectively. The partial S-gene fragments were directly sequenced to get information related to the prevailing CCHFV genotypes and their molecular epidemiology in Pakistan. Results Out of the total forty four, sixteen (36%) samples were found positive for CCHF IgM. Similarly, viral RNA was detected in six (16%) samples. Phylogenetic analysis revealed that all study viruses belong to genotype Asia-1 with closest similarity (99-100%) to the previously reported strains from Pakistan, Afghanistan and Iran. Conclusion We conclude that CCHF virus remains endemic within Baluchistan and its neighboring regions of Afghanistan warranting a need of incessant surveillance activities. PMID:23641865

IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

PubMed Central

Estrada-Jiménez, Tania; Sedeño-Monge, Virginia; Moreno, Margarita; Manjarrez, María del Consuelo; González-Ochoa, Guadalupe; Millán-Pérez Peña, Lourdes

2017-01-01

Background Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs) that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. Objective To explore the association of cytokine and socs levels with disease severity in dengue patients. Methods Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN-) γ, and tumor necrosis factor- (TNF-) α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. Results Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF) with respect to those with dengue fever (DF) (p < 0.05). Negative correlations were found between socs1 and both IL-10 and socs3 (p < 0.01). The cutoff values of socs3 (>199.8-fold), socs1 (<1.94-fold), and IL-10 (>134 pg/ml) have the highest sensitivity and specificity to discriminate between DF and DHF. Conclusion Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity. PMID:28827898

Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever

PubMed Central

Wijedoru, Lalith; Mallett, Sue; Parry, Christopher M

2017-01-01

Background Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. Objectives To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. Selection criteria We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Data collection and analysis Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. Main results Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75% (median prevalence 24%, interquartile range (IQR) 11% to 46%). The included studies evaluated 16 different RDTs, and 16 studies compared two or more different RDTs. Only three studies used the Grade 1 reference standard, and only 11 studies recruited unselected febrile patients. Most included studies were from Asia, with five studies from sub-Saharan Africa. All of the RDTs were designed to detect S.Typhi infection only. Most studies evaluated three RDTs and their variants: TUBEX in 14 studies; Typhidot (Typhidot, Typhidot-M, and TyphiRapid-Tr02) in 22 studies; and the Test-It Typhoid immunochromatographic lateral flow assay, and its earlier prototypes (dipstick, latex agglutination) developed by the Royal Tropical Institute, Amsterdam (KIT) in nine studies. Meta-analyses showed an average sensitivity of 78% (95% confidence interval (CI) 71% to 85%) and specificity of 87% (95% CI 82% to 91%) for TUBEX; and an average sensitivity of 69% (95% CI 59% to 78%) and specificity of 90% (95% CI 78% to 93%) for all Test-It Typhoid and prototype tests (KIT). Across all forms of the Typhidot test, the average sensitivity was 84% (95% CI 73% to 91%) and specificity was 79% (95% CI 70% to 87%). When we based the analysis on the 13 studies of the Typhidot test that either reported indeterminate test results or where the test format means there are no indeterminate results, the average sensitivity was 78% (95% CI 65% to 87%) and specificity was 77% (95% CI 66% to 86%). We did not identify any difference in either sensitivity or specificity between TUBEX, Typhidot, and Test-it Typhoid tests when based on comparison to the 13 Typhidot studies where indeterminate results are either reported or not applicable. If TUBEX and Test-it Typhoid are compared to all Typhidot studies, the sensitivity of Typhidot was higher than Test-it Typhoid (15% (95% CI 2% to 28%), but other comparisons did not show a difference at the 95% level of CIs. In a hypothetical cohort of 1000 patients presenting with fever where 30% (300 patients) have enteric fever, on average Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results will miss the diagnosis in 66 patients with enteric fever, TUBEX will miss 66, and Test-It Typhoid and prototype (KIT) tests will miss 93. In the 700 people without enteric fever, the number of people incorrectly diagnosed with enteric fever would be 161 with Typhidot tests, 91 with TUBEX, and 70 with Test-It Typhoid and prototype (KIT) tests. The CIs around these estimates were wide, with no difference in false positive results shown between tests. The quality of the data for each study was evaluated using a standardized checklist called QUADAS-2. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. Authors' conclusions In 37 studies that evaluated the diagnostic accuracy of RDTs for enteric fever, few studies were at a low risk of bias. The three main RDT tests and variants had moderate diagnostic accuracy. There was no evidence of a difference between the average sensitivity and specificity of the three main RDT tests. More robust evaluations of alternative RDTs for enteric fever are needed. The accuracy of rapid diagnostic tests for detecting typhoid and paratyphoid (enteric) fever Cochrane researchers assessed the accuracy of commercially-available rapid diagnostic tests and their prototypes (including TUBEX, Typhidot, Typhidot-M, Test-it Typhoid, and other tests) for detecting typhoid and paratyphoid (enteric) fever in people living in countries where the estimated number of individuals with the disease at any one time is greater than 10 per 100,000 population. If accurate, they could replace the current World Health Organization (WHO)-recommended diagnostic test: culture (growing the bacteria that causes the infection from a patient’s blood or bone marrow). Background Typhoid fever and paratyphoid fever are infections caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A respectively. The term ‘enteric fever’ is used to describe both infections. Enteric fever can be difficult to diagnose as the signs and symptoms are similar to those of other infectious diseases that cause fever such as malaria. The recommended test to confirm if a person has enteric fever is to grow the Salmonella from their blood. It takes at least 48 hours to give a result, so cannot help healthcare workers make a diagnosis the same day the blood culture is taken. Blood cultures may give a negative result even though a person has enteric fever. The test also requires a laboratory and trained staff, which are often unavailable in communities where enteric fever is common. Rapid diagnostic tests (RDTs) are designed to be easy to use, and to deliver a quick result without the need for a blood culture laboratory. The cost of an enteric fever RDT would be significantly less than a blood culture, and requires less training to perform. Study characteristics Cochrane researchers searched the available literature up to 4 March 2016 and included 37 studies. Most studies recruited participants from South Asia. Most participants were adults, with 22 studies including children. All of the RDTs evaluated detected Salmonella Typhi (typhoid fever) only. Quality of the evidence The Cochrane researchers evaluated the quality of the data for each study using a standardized checklist called QUADAS-2. High quality studies that compared different types of RDT in the same patients were few in number. Two-thirds of the included studies did not evaluate the RDTs in the context of patients who are typically tested for the disease. Many studies utilized a particular study design (a case control study) which risks overestimating RDT accuracy. In the studies evaluating the Typhidot RDT, it was often unclear how many test results were indeterminate, when the test cannot distinguish a current episode of infection from a previous disease episode. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. Key results Sensitivity indicates the percentage of patients with a positive test result who are correctly diagnosed with disease. Specificity indicates the percentage of patients who are correctly identified as not having disease. TUBEX showed an average sensitivity of 78% and specificity of 87%. Typhidot studies, grouped together to include Typhidot, Typhidot-M, and TyphiRapid-Tr02, showed an average sensitivity of 84% and specificity of 79%. When Typhidot studies with clear reporting of indeterminate results are considered, the average sensitivity and specificity of Typhidot was 78% and 77% respectively. Test-It Typhoid and prototypes (KIT) showed an average sensitivity of 69% and specificity of 90%. Based on these results, in 1000 patients with fever where 30% (300 patients) have enteric fever, we would expect Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results to, on average, miss the diagnosis (give a false negative result) in 66 patients with enteric fever, TUBEX to miss 66, and Test-It Typhoid and prototypes (KIT) to miss 93. In the 700 people without enteric fever, the number of people incorrectly given a diagnosis of enteric fever (a false positive result) would be on average 161 with these Typhidot tests, 91 with TUBEX, and 70 with the Test-It Typhoid and prototypes (KIT). These differences in the number of false negative and false positive results in patients from the different tests are not statistically important. The RDTs evaluated are not sufficiently accurate to replace blood culture as a diagnostic test for enteric fever. PMID:28545155

Usefulness and applicability of the revised dengue case classification by disease: multi-centre study in 18 countries

PubMed Central

2011-01-01

Background In view of the long term discussion on the appropriateness of the dengue classification into dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), the World Health Organization (WHO) has outlined in its new global dengue guidelines a revised classification into levels of severity: dengue fever with an intermediary group of "dengue fever with warning sings", and severe dengue. The objective of this paper was to compare the two classification systems regarding applicability in clinical practice and surveillance, as well as user-friendliness and acceptance by health staff. Methods A mix of quantitative (prospective and retrospective review of medical charts by expert reviewers, formal staff interviews), semi-quantitative (open questions in staff interviews) and qualitative methods (focus group discussions) were used in 18 countries. Quality control of data collected was undertaken by external monitors. Results The applicability of the DF/DHF/DSS classification was limited, even when strict DHF criteria were not applied (13.7% of dengue cases could not be classified using the DF/DHF/DSS classification by experienced reviewers, compared to only 1.6% with the revised classification). The fact that some severe dengue cases could not be classified in the DF/DHF/DSS system was of particular concern. Both acceptance and perceived user-friendliness of the revised system were high, particularly in relation to triage and case management. The applicability of the revised classification to retrospective data sets (of importance for dengue surveillance) was also favourable. However, the need for training, dissemination and further research on the warning signs was highlighted. Conclusions The revised dengue classification has a high potential for facilitating dengue case management and surveillance. PMID:21510901

The Epidemiology and Geographic Distribution of Relapsing Fever Borreliosis in West and North Africa, with a Review of the Ornithodoros erraticus Complex (Acari: Ixodida)

PubMed Central

Trape, Jean-François; Diatta, Georges; Arnathau, Céline; Bitam, Idir; Sarih, M’hammed; Belghyti, Driss; Bouattour, Ali; Elguero, Eric; Vial, Laurence; Mané, Youssouph; Baldé, Cellou; Pugnolle, Franck; Chauvancy, Gilles; Mahé, Gil; Granjon, Laurent; Duplantier, Jean-Marc

2013-01-01

Background Relapsing fever is the most frequent bacterial disease in Africa. Four main vector / pathogen complexes are classically recognized, with the louse Pediculus humanus acting as vector for B. recurrentis and the soft ticks Ornithodoros sonrai, O. erraticus and O. moubata acting as vectors for Borrelia crocidurae, B. hispanica and B. duttonii, respectively. Our aim was to investigate the epidemiology of the disease in West, North and Central Africa. Methods And Findings From 2002 to 2012, we conducted field surveys in 17 African countries and in Spain. We investigated the occurrence of Ornithodoros ticks in rodent burrows in 282 study sites. We collected 1,629 small mammals that may act as reservoir for Borrelia infections. Using molecular methods we studied genetic diversity among Ornithodoros ticks and Borrelia infections in ticks and small mammals. Of 9,870 burrows investigated, 1,196 (12.1%) were inhabited by Ornithodoros ticks. In West Africa, the southern and eastern limits of the vectors and Borrelia infections in ticks and small mammals were 13°N and 01°E, respectively. Molecular studies revealed the occurrence of nine different Ornithodoros species, including five species new for science, with six of them harboring Borrelia infections. Only B. crocidurae was found in West Africa and three Borrelia species were identified in North Africa: B. crocidurae, B. hispanica, and B. merionesi. Conclusions Borrelia Spirochetes responsible for relapsing fever in humans are highly prevalent both in Ornithodoros ticks and small mammals in North and West Africa but Ornithodoros ticks seem absent south of 13°N and small mammals are not infected in these regions. The number of Ornithodoros species acting as vector of relapsing fever is much higher than previously known. PMID:24223812

The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study

PubMed Central

Bowles, Cayley C.; Grenfell, Bryan T.; Basnyat, Buddha; Arjyal, Amit; Dongol, Sabina; Karkey, Abhilasha; Baker, Stephen; Pitzer, Virginia E.

2017-01-01

Background A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu. Methods We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors. Results Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections. Conclusions Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease. PMID:28475605

Fever Is Associated with Reduced, Hypothermia with Increased Mortality in Septic Patients: A Meta-Analysis of Clinical Trials

PubMed Central

Rumbus, Zoltan; Matics, Robert; Hegyi, Peter; Zsiboras, Csaba; Szabo, Imre; Illes, Anita; Petervari, Erika; Balasko, Marta; Marta, Katalin; Miko, Alexandra; Parniczky, Andrea; Tenk, Judit; Rostas, Ildiko; Solymar, Margit

2017-01-01

Background Sepsis is usually accompanied by changes of body temperature (Tb), but whether fever and hypothermia predict mortality equally or differently is not fully clarified. We aimed to find an association between Tb and mortality in septic patients with meta-analysis of clinical trials. Methods We searched the PubMed, EMBASE, and Cochrane Controlled Trials Registry databases (from inception to February 2016). Human studies reporting Tb and mortality of patients with sepsis were included in the analyses. Average Tb with SEM and mortality rate of septic patient groups were extracted by two authors independently. Results Forty-two studies reported Tb and mortality ratios in septic patients (n = 10,834). Pearson correlation analysis revealed weak negative linear correlation (R2 = 0.2794) between Tb and mortality. With forest plot analysis, we found a 22.2% (CI, 19.2–25.5) mortality rate in septic patients with fever (Tb > 38.0°C), which was higher, 31.2% (CI, 25.7–37.3), in normothermic patients, and it was the highest, 47.3% (CI, 38.9–55.7), in hypothermic patients (Tb < 36.0°C). Meta-regression analysis showed strong negative linear correlation between Tb and mortality rate (regression coefficient: -0.4318; P < 0.001). Mean Tb of the patients was higher in the lowest mortality quartile than in the highest: 38.1°C (CI, 37.9–38.4) vs 37.1°C (CI, 36.7–37.4). Conclusions Deep Tb shows negative correlation with the clinical outcome in sepsis. Fever predicts lower, while hypothermia higher mortality rates compared with normal Tb. Septic patients with the lowest (< 25%) chance of mortality have higher Tb than those with the highest chance (> 75%). PMID:28081244

Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans

PubMed Central

Darton, Thomas C.; Blohmke, Christoph J.; Giannoulatou, Eleni; Waddington, Claire S.; Jones, Claire; Sturges, Pamela; Webster, Craig; Drakesmith, Hal; Pollard, Andrew J.; Armitage, Andrew E.

2015-01-01

Background Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/Principal Findings Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/Significance We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi. PMID:26394303

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

PubMed Central

Yang, Jin; Acosta, Camilo J; Si, Guo-ai; Zeng, Jun; Li, Cui-yun; Liang, Da-bin; Ochiai, R Leon; Page, Anne-Laure; Danovaro-Holliday, M Carolina; Zhang, Jie; Zhou, Bao-de; Liao, He-zhuang; Wang, Ming-liu; Tan, Dong-mei; Tang, Zhen-zhu; Gong, Jian; Park, Jin-Kyung; Ali, Mohammad; Ivanoff, Bernard; Liang, Gui-chen; Yang, Hong-hui; Pang, Tikki; Xu, Zhi-yi; Donner, Allan; Galindo, Claudia M; Dong, Bai-qing; Clemens, John D

2005-01-01

Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China. PMID:15904514

Clinical Forms of Chikungunya in Gabon, 2010

PubMed Central

Caron, Mélanie; Grard, Gilda; Mombo, Illich; Bikié, Branly; Paupy, Christophe; Becquart, Pierre; Bisvigou, Ulrich; Leroy, Eric Maurice

2012-01-01

Background Chikungunya virus (CHIKV) has caused multiple outbreaks in tropical and temperate areas worldwide, but the clinical and biological features of this disease are poorly described, particularly in Africa. We report a prospective study of clinical and biological features during an outbreak that occurred in Franceville, Gabon in 2010. Methodology/Principal Findings We collected, in suspect cases (individuals presenting with at least one of the following symptoms or signs: fever, arthralgias, myalgias, headaches, rash, fatigue, nausea, vomiting, diarrhea, bleeding, or jaundice), blood samples, demographic and clinical characteristics and outcome. Hematological and biochemical tests, blood smears for malaria parasites and quantitative PCR for CHIKV then dengue virus were performed. CHIKV+ patients with concomitant malaria and/or dengue were excluded from the study. From May to July 2010, data on 270 laboratory-confirmed CHIK patients were recorded. Fever and arthralgias were reported by respectively 85% and 90% of patients, while myalgias, rash and hemorrhage were noted in 73%, 42% and 2% of patients. The patients were grouped into 4 clinical categories depending on the existence of fever and/or joint pain. On this basis, mixed forms accounted for 78.5% of cases, arthralgic forms 12.6%, febrile forms 6.7% and unusual forms (without fever and arthralgias) 2.2%. No cases of organ failure or death were reported. Elevated liver enzyme and creatinine levels, anemia and lymphocytopenia were the predominant biological abnormalities, and lymphocytopenia was more severe in patients with high viral loads (p = 0.01). Conclusions/Significance During CHIK epidemics, some patients may not have classical symptoms. The existence of unusual forms and the absence of severe forms of CHIK call for surveillance to detect any change in pathogenicity. PMID:22348166

Prevalence of asthma-like symptoms with ageing

PubMed Central

Newson, Roger; Janson, Christer; Corsico, Angelo; Heinrich, Joachim; Anto, Josep M; Abramson, Michael J; Kirsten, Anne-Marie; Zock, Jan Paul; Bono, Roberto; Demoly, Pascal; Leynaert, Bénédicte; Raherison, Chantal; Pin, Isabelle; Gislason, Thorarinn; Jogi, Rain; Schlunssen, Vivi; Svanes, Cecilie; Watkins, John; Weyler, Joost; Pereira-Vega, Antonio; Urrutia, Isabel; Gullón, Jose A; Forsberg, Bertil; Probst-Hensch, Nicole; Boezen, H Marike; Martinez-Moratalla Rovira, Jesús; Accordini, Simone; de Marco, Roberto; Burney, Peter

2018-01-01

Background Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy. Methods The European Community Respiratory Health Survey collected information on prevalent asthma-like symptoms from representative samples of adults aged 20–44 years (29 centres in 13 European countries and Australia) at baseline and 10 and 20 years later (n=7844). Net changes in symptom prevalence were determined using generalised estimating equations (accounting for non-response through inverse probability weighting), followed by meta-analysis of centre level estimates. Findings Over 20 years the prevalence of ‘wheeze’ and ‘wheeze in the absence of a cold’ decreased (−2.4%, 95% CI −3.5 to −1.3%; −1.5%, 95% CI −2.4 to −0.6%, respectively) but the prevalence of asthma attacks, use of asthma medication and hay fever/nasal allergies increased (0.6%, 95% CI 0.1 to 1.11; 3.6%, 95% CI 3.0 to 4.2; 2.7%, 95% CI 1.7 to 3.7). Changes were similar in the first 10 years compared with the second 10 years, except for hay fever/nasal allergies (increase seen in the first 10 years only). Decreases in these wheeze-related symptoms were largely seen in the group who gave up smoking, and were seen in those who reported hay fever/nasal allergies at baseline. Interpretation European adults born between 1946 and 1970 have, over the last 20 years, experienced less wheeze, although they were more likely to report asthma attacks, use of asthma medication and hay fever. Decrease in wheeze is largely attributable to smoking cessation, rather than improved treatment of asthma. It may also be influenced by reductions in atopy with ageing. PMID:28974648

Etiology and Clinical Course of Febrile Neutropenia in Children with Cancer

PubMed Central

Hakim, Hana; Flynn, Patricia M.; Knapp, Katherine M.; Srivastava, Deo Kumar; Gaur, Aditya

2009-01-01

Background The etiology, clinical course and outcome of fever and neutropenia (FN) in children with cancer using the current FN guidelines and diagnostic resources in the United States have not been well described. Patients and Methods Medical records of one randomly selected FN episode per patient during 2004–2005 at a pediatric oncology center were reviewed. Patients were managed as per institutional FN guidelines and blood cultures collected in continuously-read BACTEC™ bottles. Results Of 337 FN episodes, infection was proven in 86 (25%) and probable in 75 (22%). 177 episodes (53%) were judged fever of unknown origin (FUO). Bacteremia accounted for most (41) of the proven bacterial episodes, with viridans streptococci (13), Pseudomonas spp (6) and E. coli (6) the most frequently isolated organisms. The median time to positivity of blood cultures was 12 hrs (range 5.4 – 143.7) with 93% positive within 24 hours of incubation. Viral pathogens were identified in 29 (34%) episodes. Compared to other patients, those with FUO had shorter median duration of fever (0.5 vs. 2.0 days; p<0.0001) and hospitalization (3 vs. 6 days; p<0.0001), longer median duration since last chemotherapy (6.0 vs. 4.0 days; p=0.01) and were less likely to have a diagnosis of acute myelogenous leukemia (AML) (11% vs 22%; p=0.009) or develop a clinical complication (5.1% vs 24.4%; p<0.0001). Conclusion Despite currently available diagnostic resources, the majority of patients with FN have FUO marked by a low rate of clinical complications and no infection-related mortality. Emergence of viridans streptococci as the most common blood isolate has affected FN treatment recommendations. Study findings will help further development of strategies for risk stratified management of fever with neutropenia in pediatric patients. PMID:19644403

Investigation of Scarlet Fever Outbreak in a Kindergarten

PubMed Central

2018-01-01

Background Scarlet fever is caused by a group A streptococcal (GAS) infection. On April 3, 2017, an outbreak among children in a kindergarten was reported to the local health department. An epidemiologic investigation was conducted to identify the possible transmission route of this outbreak and to recommend appropriate control measures. Materials and Methods A retrospective cohort study was conducted using questionnaires including age, sex, the classroom attended at a kindergarten, and date and type of symptoms developed. A case-patient is defined as a child having sore throat, fever, skin rash, or strawberry tongue with or without laboratory confirmation of GAS infection between March 28 and April 28, 2017. Results The index case-patients developed symptoms on March 28, 2017, and this outbreak persisted over a period of 16 days. The outbreak affected 21 out of 158 children (13.3%) in the kindergarten, with the mean age of 4.2 (range 3–5) years; 12 (57.1%) of them were boys. The common symptoms reported were fever (71.4%), sore throat (71.4%), reddened tonsil (57.1%), and skin rash (52.4%). The epidemiologic analysis showed that children attending one of the classrooms in the kindergarten were 14.12 times affected than the other classrooms (relative risk, 14.12; 95% confidence interval, 4.99–33.93; P <0.01). All case-patients were recommended to stay away from the kindergarten and its social activities for >24 hours after starting appropriate antibiotic treatment, and all the children in the kindergarten were instructed to keep strict personal hygiene practices. Conclusion Our results suggest that the outbreak likely affected from the index case-patients who attended to one of the classrooms in the kindergarten. This highlights the importance of immediate notification of outbreak to prevent large number of patients. PMID:29637751

Body Temperature and Mortality in Patients with Acute Respiratory Distress Syndrome

PubMed Central

Schell-Chaple, Hildy M.; Puntillo, Kathleen A.; Matthay, Michael A.; Liu, Kathleen D.

2015-01-01

Background Little is known about the relationship between body temperature and outcomes in patients with acute respiratory distress syndrome (ARDS). A better understanding of this relationship may provide evidence for fever suppression or warming interventions, which are commonly applied in practice. Objective To examine the relationship between body temperature and mortality in patients with ARDS. Methods Secondary analysis of body temperature and mortality using data from the ARDS Network Fluid and Catheter Treatment Trial (n =969). Body temperature at baseline and on study day 2, primary cause of ARDS, severity of illness, and 90-day mortality were analyzed by using multiple logistic regression. Results Mean baseline temperature was 37.5°C (SD, 1.1°C; range, 27.2°C-40.7°C). At baseline, fever (≥ 38.3°C) was present in 23% and hypothermia (< 36°C) in 5% of the patients. Body temperature was a significant predictor of 90-day mortality after primary cause of ARDS and score on the Acute Physiology and Chronic Health Evaluation III were adjusted for. Higher temperature was associated with decreased mortality: for every 1°C increase in baseline temperature, the odds of death decreased by 15% (odds ratio, 0.85; 95% CI, 0.73-0.98, P = .03). When patients were divided into 5 temperature groups, mortality was lower with higher temperature (P for trend=.02). Conclusions Early in ARDS, fever is associated with improved survival rates. Fever in the acute phase response to lung injury and its relationship to recovery may be an important factor in determining patients' outcome and warrants further study. PMID:25554550

[Important issues of biological safety].

PubMed

Onishchenko, G G

2007-01-01

The problem of biological security raises alarm due to the real growth of biological threats. Biological security includes a wide scope of problems, the solution of which becomes a part of national security as a necessary condition for the constant development of the country. A number of pathogens, such as human immunodeficiency virus, exotic Ebola and Lassa viruses causing hemorrhagic fever,rotaviruses causing acute intestinal diseases, etc. were first discovered in the last century. Terrorist actions committed in the USA in 2001 using the anthrax pathogen made the problem of biological danger even more important. In Russian Federation, biological threats are counteracted through the united state policy being a part of general state security policy. The biological Security legislation of Russian Federation is chiefly based on the 1992 Federal Law on Security. On the basis of cumulated experience, the President of Russia ratified Basics of Russian Federation's State Policy for Chemical and Biological Security for the Period through 2010 and Beyond on 4 December, 2003. The document determines the main directions and stages of the state development in the area of chemical and biological security. The Federal target program Russian Federation's National Program for Chemical and Biological Security is being developed, and its development is to be completed soon in order to perfect the national system for biological security and fulfill Basics of Russian Federation's State Policy for Chemical and Biological Security for the Period through 2010 and Beyond, ratified by the President. The new global strategy for control over infectious diseases, presented in the materials of Saint Petersburg summit of the Group of Eight, as well as the substantive part of its elements in Sanitary International Standards, are to a large degree an acknowledgement of the Russian Federation's experience and the algorithm for fighting extremely dangerous infections. This Russia's experience has resulted in the following global achievements: smallpox elimination in the USSR (1936); the USSR's suggestions on the program of smallpox elimination in the world and 2 billion doses of the vaccine transferred to the possession of the WHO (since 1958); the global elimination of the disease (1980); effective control over avian influenza at the epizootic stage, recognized internationally at Beijing International Congress, 17-18 January, 2006.

Detection of viruses in used ventilation filters from two large public buildings.

PubMed

Goyal, Sagar M; Anantharaman, Senthilvelan; Ramakrishnan, M A; Sajja, Suchitra; Kim, Seung Won; Stanley, Nicholas J; Farnsworth, James E; Kuehn, Thomas H; Raynor, Peter C

2011-09-01

Viral and bacterial pathogens may be present in the air after being released from infected individuals and animals. Filters are installed in the heating, ventilation, and air-conditioning (HVAC) systems of buildings to protect ventilation equipment and maintain healthy indoor air quality. These filters process enormous volumes of air. This study was undertaken to determine the utility of sampling used ventilation filters to assess the types and concentrations of virus aerosols present in buildings. The HVAC filters from 2 large public buildings in Minneapolis and Seattle were sampled to determine the presence of human respiratory viruses and viruses with bioterrorism potential. Four air-handling units were selected from each building, and a total of 64 prefilters and final filters were tested for the presence of influenza A, influenza B, respiratory syncytial, corona, parainfluenza 1-3, adeno, orthopox, entero, Ebola, Marburg, Lassa fever, Machupo, eastern equine encephalitis, western equine encephalitis, and Venezuelan equine encephalitis viruses. Representative pieces of each filter were cut and eluted with a buffer solution. Attempts were made to detect viruses by inoculation of these eluates in cell cultures (Vero, MDCK, and RK-13) and specific pathogen-free embryonated chicken eggs. Two passages of eluates in cell cultures or these eggs did not reveal the presence of any live virus. The eluates were also examined by polymerase chain reaction or reverse-transcription polymerase chain reaction to detect the presence of viral DNA or RNA, respectively. Nine of the 64 filters tested were positive for influenza A virus, 2 filters were positive for influenza B virus, and 1 filter was positive for parainfluenza virus 1. These findings indicate that existing building HVAC filters may be used as a method of detection for airborne viruses. As integrated long-term bioaerosol sampling devices, they may yield valuable information on the epidemiology and aerobiology of viruses in air that can inform the development of methods to prevent airborne transmission of viruses and possible deterrents against the spread of bioterrorism agents. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Malaria in rural Mozambique. Part I: Children attending the outpatient clinic

PubMed Central

Guinovart, Caterina; Bassat, Quique; Sigaúque, Betuel; Aide, Pedro; Sacarlal, Jahit; Nhampossa, Tacilta; Bardají, Azucena; Nhacolo, Ariel; Macete, Eusébio; Mandomando, Inácio; Aponte, John J; Menéndez, Clara; Alonso, Pedro L

2008-01-01

Background Malaria represents a huge burden for the health care services across Africa. Describing malaria attending health services contributes to quantify the burden and describe the epidemiology and clinical presentation. Methods Retrospective analysis of data collected through the Manhiça morbidity surveillance system (Mozambique) on all paediatric visits (<15 years) to the outpatient clinic from June 2003 to May 2005. Age-specific minimum community-based incidence rates (MCBIRs) of malaria were calculated using demographic surveillance system data. Malaria was defined as fever or history of fever in the preceding 24 hours with asexual Plasmodium falciparum parasitaemia of any density in the blood smear. Results A total of 94,941 outpatient visits were seen during the study period, of which 30.5% had malaria. Children younger than three years accounted for almost half of the total malaria cases and children aged ≥ 5 years represented 36.4% of the cases. Among children who presented with malaria, 56.7% had fever and among children who presented with fever or a history of fever only 37.2% had malaria. The geometric mean parasitaemia in malaria cases was 8582.2 parasites/μL, peaking in children aged two to three years. 13% of malaria cases had a PCV<25% and the mean PCV in malaria cases increased gradually with age, ranging from 27.8% in children aged 2–12 months to 34.4% in ≥ 5 years. The percentage of cases admitted or transferred showed a clear decreasing trend with age. MCBIRs of outpatient malaria per 1,000 child years at risk for the whole study period were of 394 in infants, 630 in children aged 1 to <5 years and 237 in children aged five years or more. A clustering of the cases was observed, whereby most children never had malaria, some had a few episodes and very few had many episodes. Conclusion Preventive measures should be targeted at children younger than three years, as they carry the highest burden of malaria. Children aged 5–15 years represent around a third of the malaria cases and should also be included in control programmes. Concern should be raised about presumptive treatment of fever cases with artemisinin-combination therapies, as many children will, according to IMCI guidelines, receive treatment unnecessarily. PMID:18302770

A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria

PubMed Central

Mbonye, Anthony K.; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S.; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E.

2015-01-01

Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. Methods A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), p<0·001. The majority of patients with fever in the intervention arm accepted to purchase an mRDT (97·8%), of whom 58·5% tested mRDT-positive. Drug shop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), p<0·001) compared to drug shop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT. Trial Registration ClinicalTrials.gov NCT01194557. PMID:26200467

Medical Surveillance Monthly Report (MSMR). Volume 9, Number 3, April 2003

DTIC Science & Technology

2003-04-01

Rocky Mountain spotted fever , dengue, typhus, yellow fever, Rift Valley fever, or other hemorrhagic fevers among active duty servicemembers. During...Valley fever . . . . . E. coli O157:H7 3 3 9 3 1 Rocky Mountain spotted fever 2 . 12 2 . Ehrlichiosis 2 1 2 3 1 Rubella . . . . . Encephalitis...Dengue fever . . . 1 . Rheumatic fever, acute . . 1 . . Diphtheria . . . . . Rift Valley fever . . . . . E. coli O157:H7 . 1 1 1 . Rocky Mountain spotted

Context dependency and generality of fever in insects.

PubMed

Stahlschmidt, Z R; Adamo, S A

2013-07-01

Fever can reduce mortality in infected animals. Yet, despite its fitness-enhancing qualities, fever often varies among animals. We used several approaches to examine this variation in insects. Texas field crickets (Gryllus texensis) exhibited a modest fever (1 °C increase in preferred body temperature, T pref) after injection of prostaglandin, which putatively mediates fever in both vertebrates and invertebrates, but they did not exhibit fever during chronic exposure to heat-killed bacteria. Further, chronic food limitation and mating status did not affect T pref or the expression of behavioural fever, suggesting limited context dependency of fever in G. texensis. Our meta-analysis of behavioural fever studies indicated that behavioural fever occurs in many insects, but it is not ubiquitous. Thus, both empirical and meta-analytical results suggest that the fever response in insects 'is widespread, although certainly not inevitable' (Moore 2002). We highlight the need for future work focusing on standardizing an experimental protocol to measure behavioural fever, understanding the specific mechanism(s) underlying fever in insects, and examining whether ecological or physiological costs often outweigh the benefits of fever and can explain the sporadic nature of fever in insects.

Context dependency and generality of fever in insects

NASA Astrophysics Data System (ADS)

Stahlschmidt, Z. R.; Adamo, S. A.

2013-07-01

Fever can reduce mortality in infected animals. Yet, despite its fitness-enhancing qualities, fever often varies among animals. We used several approaches to examine this variation in insects. Texas field crickets ( Gryllus texensis) exhibited a modest fever (1 °C increase in preferred body temperature, T pref) after injection of prostaglandin, which putatively mediates fever in both vertebrates and invertebrates, but they did not exhibit fever during chronic exposure to heat-killed bacteria. Further, chronic food limitation and mating status did not affect T pref or the expression of behavioural fever, suggesting limited context dependency of fever in G. texensis. Our meta-analysis of behavioural fever studies indicated that behavioural fever occurs in many insects, but it is not ubiquitous. Thus, both empirical and meta-analytical results suggest that the fever response in insects `is widespread, although certainly not inevitable' (Moore 2002). We highlight the need for future work focusing on standardizing an experimental protocol to measure behavioural fever, understanding the specific mechanism(s) underlying fever in insects, and examining whether ecological or physiological costs often outweigh the benefits of fever and can explain the sporadic nature of fever in insects.

Effects of ion exchange on stream solute fluxes in a basin receiving highway deicing salts

USGS Publications Warehouse

Shanley, J.B.

1994-01-01

At Fever Brook, a 1260-ha forested basin in central Massachusetts, highway deicing salt application increased the solute flux in streamflow by 120% above background flux (equivalent basis) during a 2-yr period. Attempts to isolate the nonsalt component of stream solute fluxes have commonly subtracted salt contributions based on the net Cl flux (Cl output in streamflow minus Cl input in precipitation). In these studies, any net Na flux in excess of the amount needed to balance the net Cl flux has been attributed to weathering. At Fever Brook, however, the net output of Na was less than the net output of Cl, suggesting a loss of Na within the basin. The Na sink was inferred to be cation exchange of Na for Ca and Mg in the soil. A method was developed to quantify the exchange based on a Na budget, which included an independent estimate of the Na flux from weathering. The amount of exchange was apportioned to Ca and Mg based on their relative concentrations in the stream. The background fluxes of Ca and Mg (i.e., those that would occur in the absence of deicing salts) were calculated by subtracting the amounts from ion exchange plus the much smaller direct contributions in deicing salts from the observed fluxes. Ion exchange and direct salt contributions increased the net output fluxes of Ca and Mg, each by 44% above background. In basins that receive deicing salts, failure to account for cation exchange thus may result in an underestimate of the flux of Na from weathering and overestimates of the fluxes of Ca and Mg from weathering.

Coxiella burnetii in Humans and Ticks in Rural Senegal

PubMed Central

Mediannikov, Oleg; Fenollar, Florence; Socolovschi, Cristina; Diatta, Georges; Bassene, Hubert; Molez, Jean-François; Sokhna, Cheikh; Trape, Jean-François; Raoult, Didier

2010-01-01

Background Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. Epidemiologically, animals are considered reservoirs and humans incidental hosts. Methodology/Principal Findings We investigated Q fever in rural Senegal. Human samples (e.g., sera, saliva, breast milk, feces) were screened in the generally healthy population of two villages of the Sine-Saloum region. Ticks were collected in four regions. Seroprevalence was studied by immunofluorescence, and all other samples were tested by two qPCR systems for detection of C. burnetii. Positive samples were genotyped (multispacer typing) by amplification and sequencing of three spacers. Strains were isolated by cell culture. We found that the seroprevalence may be as high as 24.5% (59 of 238 studied) in Dielmo village. We identified spontaneous excretion of C. burnetii by humans through faeces and milk. Hard and soft ticks (8 species) were infected in 0–37.6%. We identified three genotypes of C. burnetii. The previously identified genotype 6 was the most common in ticks in all studied regions and the only one found in human samples. Three strains of genotype 6 of C. burnetii were also recovered from soft tick Ornithodoros sonrai. Two other genotypes found in ticks, 35 and 36, were identified for the first time. Conclusions/Significance Q fever should be considered a significant public health threat in Senegal. Humans, similar to other mammals, may continuously excrete C. burnetii. PMID:20386603

Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination.

PubMed

Kongsgaard, Michael; Bassi, Maria R; Rasmussen, Michael; Skjødt, Karsten; Thybo, Søren; Gabriel, Mette; Hansen, Morten Bagge; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Buus, Soren; Stryhn, Anette

2017-04-06

Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.

Visceral leishmaniasis in a patient with systemic lupus erythematosus.

PubMed

Santos Silva, André Filipe; Figueiredo Dias, João Paulo Branco Calheiros; Nuak, João Miguel Neves Gonçalves Santos; Rocha Aguiar, Francisca; Araújo Pinto, José António; Sarmento, António Carlos Eugénio Megre

2015-01-01

Visceral leishmaniasis is an infection with an insidious and disabling course caused by parasites of the genus Leishmania. In Europe, it is mostly associated with HIV infection. Systemic lupus erythematosus and its treatment are associated with increased risk of infection, neoplastic and concomitant autoimmune disorders. The association of these diseases may go unnoticed. A 60 year-old Caucasian woman with lupus presented with a one-year history of fever, malaise, weakness and weight loss. The highlights on physical examination were pallor, palpable hepatosplenomegaly and low-grade fever. Blood tests showed pancytopenia, hyperproteinemia with hypoalbuminemia and hypergammaglobulinemia; electrophoresis showed a polyclonal gamma curve. Full-body CT scan revealed massive hepatosplenomegaly. Microbiology investigation was negative for the most common pathogens, including tuberculosis. There were no signs of hematologic malignancy in the bone marrow smear. PCR for Leishmania infantum was positive both in blood and bone marrow. The patient was treated with liposomal amphotericin B, and immunosuppression was adjusted. She showed rapid clinical improvement and 6 months later had no signs of disease. The differential diagnosis in a patient with lupus presenting with fever and multisystemic manifestations includes infectious or neoplastic disorders. The patient lived in an endemic area of Leishmania, and typical clinical and analytical changes were all present, making this case highly educational. The case highlights the importance of a patient's epidemiological background and how it can lead to the diagnosis and timely treatment of a rare disease.

Medical Surveillance Monthly Report (MSMR). Volume 7, Number 1, January 2001

DTIC Science & Technology

2001-01-01

fever - 1 1 - Rheumatic fever, acute - - - - Diphtheria - - - - Rift valley fever - - - - E. Coli O157:H7 2 4 10 2 Rocky mountain spotted fever - 5 11...1 Rheumatic fever, acute - - - - Diphtheria - - - - Rift valley fever - - - - E. Coli O157:H7 2 10 9 9 Rocky mountain spotted fever - 3 13 3

Histoplasmosis Presenting as Granulomatous Hepatitis: Case Report and Review of the Literature

PubMed Central

Rihana, Nancy A.; Kandula, Manasa; Velez, Ana; Dahal, Kumud; O'Neill, Edward B.

2014-01-01

Background. Histoplasma capsulatum is the most common endemic mycosis in the United States and is a frequent cause of opportunistic infection in immunodeficient hosts. Histoplasmosis is most often self-limiting and goes unrecognized in the immunocompetent population but can progress to disseminated histoplasmosis in patients with an impaired immune system. Liver involvement as a part of disseminated histoplasmosis which usually originates in the lung is well known. However, extrapulmonary hepatic histoplasmosis as a primary manifestation is extremely rare. Case Presentation. We report a rare case of histoplasmosis that presented as persistent fever and abnormal liver function tests in a 66-year-old female with rheumatoid arthritis, receiving infliximab. Conclusion. Emphasizing histoplasmosis as a major cause of acute granulomatous hepatitis and fever of unknown origin in cell mediated immunodeficient population, this case highlights the need for high index of suspicion and the importance of prompt diagnosis since any delay of treatment can be life threatening in this population. PMID:25013413

Histoplasmosis presenting as granulomatous hepatitis: case report and review of the literature.

PubMed

Rihana, Nancy A; Kandula, Manasa; Velez, Ana; Dahal, Kumud; O'Neill, Edward B

2014-01-01

Background. Histoplasma capsulatum is the most common endemic mycosis in the United States and is a frequent cause of opportunistic infection in immunodeficient hosts. Histoplasmosis is most often self-limiting and goes unrecognized in the immunocompetent population but can progress to disseminated histoplasmosis in patients with an impaired immune system. Liver involvement as a part of disseminated histoplasmosis which usually originates in the lung is well known. However, extrapulmonary hepatic histoplasmosis as a primary manifestation is extremely rare. Case Presentation. We report a rare case of histoplasmosis that presented as persistent fever and abnormal liver function tests in a 66-year-old female with rheumatoid arthritis, receiving infliximab. Conclusion. Emphasizing histoplasmosis as a major cause of acute granulomatous hepatitis and fever of unknown origin in cell mediated immunodeficient population, this case highlights the need for high index of suspicion and the importance of prompt diagnosis since any delay of treatment can be life threatening in this population.

Seroepidemiololgy of rickettsioses in Sri Lanka: a patient based study

PubMed Central

2011-01-01

Background Rickettsioses are emerging infections in Sri Lanka as shown by the increase in the number of clinically diagnosed rickettsial patients being reported to the Epidemiology Unit, Sri Lanka. However, mapping the disease for the whole island with laboratory confirmed cases has not been previously carried out. Methods 615 samples received from 23 hospital representing 8 provinces were tested using ELISA or IFA methods and clinical data was collected using a validated questionnaire. Results Rash was found among more spotted fever seropositive patients than scrub typhus seropositive patients while the opposite was true for the presence of eschar. Spotted fever and scrub typhus was found in a geographically restricted manner. Consistent temporal patterns were seen for the presentation of patients with rickettsioses in Kandy and Kurunegala districts for 2009 and 2010. Conclusions This study expanded knowledge on the distribution of rickettsioses in Sri Lanka and their clinical profiles which in turn helps in the clinical diagnosis of these infections. PMID:22118601

Phytochemical analysis and in-vitro anti-African swine fever virus activity of extracts and fractions of Ancistrocladus uncinatus, Hutch and Dalziel (Ancistrocladaceae)

PubMed Central

2013-01-01

Background African swine fever (ASF), a highly contagious fatal acute haemorrhagic viral disease of pigs currently has no treatment or vaccination protocol and it threatens the pig industry worldwide. Recent outbreaks were managed by farmers with ethnoveterinary preparations with various claims of effectiveness. Results We identified 35 compounds using GC-MS protocol and ASF virus (NIG 99) was significantly reduced by some extracts and fractions of the plant. However, the plant was poorly extracted by water and cytotoxicity was found to be a major problem with the use of the plant since its extracts also reduced the primary cells used in the assay. Conclusion It is confirmed that the plant has antiviral potentials against ASF virus and farmers’ claims seem to have certain degree of veracity, but finding the best means of exploring the potential of the plant while reducing its cytotoxic effect in-vitro and in-vivo will be necessary. PMID:23777548

Chronic Q Fever in the Netherlands 5 Years after the Start of the Q Fever Epidemic: Results from the Dutch Chronic Q Fever Database

PubMed Central

Delsing, Corine E.; Groenwold, Rolf H. H.; Wegdam-Blans, Marjolijn C. A.; Bleeker-Rovers, Chantal P.; de Jager-Leclercq, Monique G. L.; Hoepelman, Andy I. M.; van Kasteren, Marjo E.; Buijs, Jacqueline; Renders, Nicole H. M.; Nabuurs-Franssen, Marrigje H.; Oosterheert, Jan Jelrik; Wever, Peter C.

2014-01-01

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P = 0.004 and 0.010), proven chronic Q fever (P = 0.020 and 0.002), vascular chronic Q fever (P = 0.024 and 0.005), acute presentation with chronic Q fever (P = 0.002 and P < 0.001), and surgical treatment of chronic Q fever (P = 0.025 and P < 0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively. PMID:24599987

Dengue and Other Common Causes of Acute Febrile Illness in Asia: An Active Surveillance Study in Children

PubMed Central

Capeding, Maria Rosario; Chua, Mary Noreen; Hadinegoro, Sri Rezeki; Hussain, Ismail I. H. M.; Nallusamy, Revathy; Pitisuttithum, Punnee; Rusmil, Kusnandi; Thisyakorn, Usa; Thomas, Stephen J.; Huu Tran, Ngoc; Wirawan, Dewa Nyoman; Yoon, In-Kyu; Bouckenooghe, Alain; Hutagalung, Yanee; Laot, Thelma; Wartel, Tram Anh

2013-01-01

Background Common causes of acute febrile illness in tropical countries have similar symptoms, which often mimic those of dengue. Accurate clinical diagnosis can be difficult without laboratory confirmation and disease burden is generally under-reported. Accurate, population-based, laboratory-confirmed incidence data on dengue and other causes of acute fever in dengue-endemic Asian countries are needed. Methods and principal findings This prospective, multicenter, active fever surveillance, cohort study was conducted in selected centers in Indonesia, Malaysia, Philippines, Thailand and Vietnam to determine the incidence density of acute febrile episodes (≥38°C for ≥2 days) in 1,500 healthy children aged 2–14 years, followed for a mean 237 days. Causes of fever were assessed by testing acute and convalescent sera from febrile participants for dengue, chikungunya, hepatitis A, influenza A, leptospirosis, rickettsia, and Salmonella Typhi. Overall, 289 participants had acute fever, an incidence density of 33.6 per 100 person-years (95% CI: 30.0; 37.8); 57% were IgM-positive for at least one of these diseases. The most common causes of fever by IgM ELISA were chikungunya (in 35.0% of in febrile participants) and S. Typhi (in 29.4%). The overall incidence density of dengue per 100 person-years was 3.4 by nonstructural protein 1 (NS1) antigen positivity (95% CI: 2.4; 4.8) and 7.3 (95% CI: 5.7; 9.2) by serology. Dengue was diagnosed in 11.4% (95% CI: 8.0; 15.7) and 23.9% (95% CI: 19.1; 29.2) of febrile participants by NS1 positivity and serology, respectively. Of the febrile episodes not clinically diagnosed as dengue, 5.3% were dengue-positive by NS1 antigen testing and 16.0% were dengue-positive by serology. Conclusions During the study period, the most common identified causes of pediatric acute febrile illness among the seven tested for were chikungunya, S. Typhi and dengue. Not all dengue cases were clinically diagnosed; laboratory confirmation is essential to refine disease burden estimates. PMID:23936565

Epidemiology of Brucellosis and Q Fever in Linked Human and Animal Populations in Northern Togo

PubMed Central

Dean, Anna S.; Bonfoh, Bassirou; Kulo, Abalo E.; Boukaya, G. Aboudou; Amidou, Moussa; Hattendorf, Jan; Pilo, Paola; Schelling, Esther

2013-01-01

Background Although brucellosis (Brucella spp.) and Q Fever (Coxiella burnetii) are zoonoses of global importance, very little high quality data are available from West Africa. Methods/Principal Findings A serosurvey was conducted in Togo’s main livestock-raising zone in 2011 in 25 randomly selected villages, including 683 people, 596 cattle, 465 sheep and 221 goats. Additionally, 464 transhumant cattle from Burkina Faso were sampled in 2012. The serological analyses performed were the Rose Bengal Test and ELISA for brucellosis and ELISA and the immunofluorescence assay (IFA) for Q Fever Brucellosis did not appear to pose a major human health problem in the study zone, with only 7 seropositive participants. B. abortus was isolated from 3 bovine hygroma samples, and is likely to be the predominant circulating strain. This may explain the observed seropositivity amongst village cattle (9.2%, 95%CI:4.3–18.6%) and transhumant cattle (7.3%, 95%CI:3.5–14.7%), with an absence of seropositive small ruminants. Exposure of livestock and people to C. burnetii was common, potentially influenced by cultural factors. People of Fulani ethnicity had greater livestock contact and a significantly higher seroprevalence than other ethnic groups (Fulani: 45.5%, 95%CI:37.7–53.6%; non-Fulani: 27.1%, 95%CI:20.6–34.7%). Appropriate diagnostic test cut-off values in endemic settings requires further investigation. Both brucellosis and Q Fever appeared to impact on livestock production. Seropositive cows were more likely to have aborted a foetus during the previous year than seronegative cows, when adjusted for age. This odds was 3.8 times higher (95%CI: 1.2–12.1) for brucellosis and 6.7 times higher (95%CI: 1.3–34.8) for Q Fever. Conclusions This is the first epidemiological study of zoonoses in Togo in linked human and animal populations, providing much needed data for West Africa. Exposure to Brucella and C. burnetii is common but further research is needed into the clinical and economic impact. PMID:23951177

Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years

PubMed Central

Simpson, Angela; Lazic, Nevena; Belgrave, Danielle C.M.; Johnson, Phil; Bishop, Christopher; Mills, Clare; Custovic, Adnan

2015-01-01

Background The relationship between sensitization to allergens and disease is complex. Objective We sought to identify patterns of response to a broad range of allergen components and investigate associations with asthma, eczema, and hay fever. Methods Serum specific IgE levels to 112 allergen components were measured by using a multiplex array (Immuno Solid-phase Allergen Chip) in a population-based birth cohort. Latent variable modeling was used to identify underlying patterns of component-specific IgE responses; these patterns were then related to asthma, eczema, and hay fever. Results Two hundred twenty-one of 461 children had IgE to 1 or more components. Seventy-one of the 112 components were recognized by 3 or more children. By using latent variable modeling, 61 allergen components clustered into 3 component groups (CG1, CG2, and CG3); protein families within each CG were exclusive to that group. CG1 comprised 27 components from 8 plant protein families. CG2 comprised 7 components of mite allergens from 3 protein families. CG3 included 27 components of plant, animal, and fungal origin from 12 protein families. Each CG included components from different biological sources with structural homology and also nonhomologous proteins arising from the same biological source. Sensitization to CG3 was most strongly associated with asthma (odds ratio [OR], 8.20; 95% CI, 3.49-19.24; P < .001) and lower FEV1 (P < .001). Sensitization to CG1 was associated with hay fever (OR, 12.79; 95% CI, 6.84-23.90; P < .001). Sensitization to CG2 was associated with both asthma (OR, 3.60; 95% CI, 2.05-6.29) and hay fever (OR, 2.52; 95% CI, 1.38-4.61). Conclusions Latent variable modeling with a large number of allergen components identified 3 patterns of IgE responses, each including different protein families. In 11-year-old children the pattern of response to components of multiple allergens appeared to be associated with current asthma and hay fever but not eczema. PMID:25935108

Temporal Fluctuation of Multidrug Resistant Salmonella Typhi Haplotypes in the Mekong River Delta Region of Vietnam

PubMed Central

Chau, Tran Thuy; Duy, Pham Thanh; La, Tran Thi Phi; Hoang, Nguyen Van Minh; Nga, Tran Vu Thieu; Campbell, James I.; Manh, Bui Huu; Vinh Chau, Nguyen Van; Hien, Tran Tinh; Farrar, Jeremy; Dougan, Gordon; Baker, Stephen

2011-01-01

Background Typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. Principal Findings The population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. Significance The H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam. PMID:21245916

Risk factors for the development of severe typhoid fever in Vietnam

PubMed Central

2014-01-01

Background Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever. Methods We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993–1995 and 1997–1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission. Results The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00-2.57; p = 0.035). Conclusions In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was independently associated with disease severity. During this period many patients were being treated with fluoroquinolones prior to hospital admission. Ciprofloxacin and ofloxacin should be used with caution in patients infected with S. Typhi that have intermediate susceptibility to ciprofloxacin. PMID:24512443

[The Brugada Syndrome in a Teenager].

PubMed

Miklashevich, I M; Kuleshova, E V; Termosesov, S A; Shkolnikova, M A

2017-02-01

The Brugada syndrome (BS) belongs to the group of hereditary channelopathies associated with elevated risk of sudden death (SD) in the absence of structural heart diseases. The disorder phenotypically manifests by specific electrocardiographic pattern, associated with ventricular tachycardia (VT). VT can be accompanied by loss of conscience, and after transformation to ventricular fibrillation result in SD. BS is extremely rare among children and adolescents. We present here a clinical case of teenager (age 17 years) with BS manifested by syncopal state at the background of fever.

Fever in Infants and Children

MedlinePlus

... or higher that is unresponsive to fever-reducing medicine?YesNoDoes your child have a low-grade fever (up to 101°) ... fever, give your child a nonaspirin fever-reducing medicine. Call your child’s doctor after 24 hours if the fever continues ...

Tri-phasic fever in dengue fever.

PubMed

D, Pradeepa H; Rao, Sathish B; B, Ganaraj; Bhat, Gopalakrishna; M, Chakrapani

2018-04-01

Dengue fever is an acute febrile illness with a duration of 2-12 days. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and compared this with 26 others with fever due to a non-dengue aetiology. A tri-phasic fever pattern was seen among two-thirds of dengue fever patients, but in only one with an inflammatory disease. One-third of dengue fever patients exhibited a single peak temperature. Continuous temperature monitoring and temperature pattern analysis in clinical settings can aid in the early differentiation of dengue fever from non-dengue aetiology.

Discriminating fever behavior in house flies.

PubMed

Anderson, Robert D; Blanford, Simon; Jenkins, Nina E; Thomas, Matthew B

2013-01-01

Fever has generally been shown to benefit infected hosts. However, fever temperatures also carry costs. While endotherms are able to limit fever costs physiologically, the means by which behavioral thermoregulators constrain these costs are less understood. Here we investigated the behavioral fever response of house flies (Musca domestica L.) challenged with different doses of the fungal entomopathogen, Beauveria bassiana. Infected flies invoked a behavioral fever selecting the hottest temperature early in the day and then moving to cooler temperatures as the day progressed. In addition, flies infected with a higher dose of fungus exhibited more intense fever responses. These variable patterns of fever are consistent with the observation that higher fever temperatures had greater impact on fungal growth. The results demonstrate the capacity of insects to modulate the degree and duration of the fever response depending on the severity of the pathogen challenge and in so doing, balance the costs and benefits of fever.

Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

PubMed Central

Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

2015-01-01

Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

Rat-bite fever

MedlinePlus

Streptobacillary fever; Streptobacillosis; Haverhill fever; Epidemic arthritic erythema; Spirillary fever; Sodoku ... Rat-bite fever can be caused by either of 2 different bacteria, Streptobacillus moniliformis or Spirillum minus. Both of these are ...

Dengue fever (image)

MedlinePlus

Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

Medical Surveillance Monthly Report (MSMR). Volume 8, Number 1, January/February 2002

DTIC Science & Technology

2002-02-01

fever, acute - - - - Diphtheria - - - - Rift valley fever - - - - E. Coli 0157:H7 2 4 3 2 Rocky mountain spotted fever 1 - 1...Rheumatic fever, acute - - - - Diphtheria - - - - Rift valley fever - - - - E. Coli 0157:H7 8 9 2 9 Rocky mountain spotted fever 13 3 2

A review of the physiology of fever in birds.

PubMed

Gray, David A; Marais, Manette; Maloney, Shane K

2013-04-01

While fever is known to occur in invertebrates and vertebrates, the mechanisms of fever in animals other than mammals have received scant attention. We look initially at the recognition, by the avian immune system, of pathogen associated molecular patterns and the likely role of toll-like receptors in signaling the presence of bacteria and viruses. Several mediators of fever are subsequently released by immune cells, including interleukin-6 and interleukin-1β, that eventually reach the brain and alter thermoregulatory function. As is the case in mammals, prostaglandins appear to be the ultimate mediators of fever in birds, since the febrile response is attenuated when prostaglandin synthesis is inhibited. Ambient temperature modulates the fever response, with larger fevers at higher, and smaller fevers at lower ambient temperatures. Glucocorticoid levels are increased during fever and seem to play an important role by modulating the extent of fever generation, possibly playing a role in the attenuation of fever after repeated exposure to a pathogen in a process termed tolerance, suggesting that the fever process can be phenotypically adapted to likely future conditions. While fever has an ancient phylogenetic history and many of the underling mechanisms in birds appear similar to mammals, there are several important differences that suggest fever has evolved quite differently in these two homeothermic classes.

Deer ticks (image)

MedlinePlus

Diseases are often carried by ticks, including Rocky Mountain Spotted Fever, Colorado Tick Fever, Lyme disease, and tularemia. Less common or less frequent diseases include typhus, Q-fever, relapsing fever, viral encephalitis, hemorrhagic fever, ...

Ebola (For Parents)

MedlinePlus

... Kids Teens Malaria Typhoid Fever First Aid: Fever Dengue Fever Cholera Do My Kids Need Vaccines Before Traveling? Staying Healthy While You Travel Fevers Ebola Dengue Fever Cholera Ebola View more About Us Contact ...

Identification of factors for physicians to facilitate early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever in Taiwan.

PubMed

Chang, Ko; Lee, Nan-Yao; Ko, Wen-Chien; Tsai, Jih-Jin; Lin, Wei-Ru; Chen, Tun-Chieh; Lu, Po-Liang; Chen, Yen-Hsu

2017-02-01

Dengue fever, rickettsial diseases, and Q fever are acute febrile illnesses with similar manifestations in tropical areas. Early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever may be made by understanding the distinguishing clinical characteristics and the significance of demographic and weather factors. We conducted a retrospective study to identify clinical, demographic, and meteorological characteristics of 454 dengue fever, 178 scrub typhus, 143 Q fever, and 81 murine typhus cases in three Taiwan hospitals. Case numbers of murine typhus and Q fever correlated significantly with temperature and rainfall; the scrub typhus case number was only significantly related with temperature. Neither temperature nor rainfall correlated with the case number of dengue fever. The rarity of dengue fever cases from January to June in Taiwan may be a helpful clue for diagnosis in the area. A male predominance was observed, as the male-to-female rate was 2.1 for murine typhus and 7.4 for Q fever. Multivariate analysis revealed the following six important factors for differentiating the rickettsial diseases and Q fever group from the dengue fever group: fever ≥8 days, alanine aminotransferase > aspartate aminotransferase, platelets >63,000/mL, C-reactive protein >31.9 mg/L, absence of bone pain, and absence of a bleeding syndrome. Understanding the rarity of dengue in the first half of a year in Taiwan and the six differentiating factors may help facilitate the early differential diagnosis of rickettsial diseases and Q fever from dengue fever, permitting early antibiotic treatment. Copyright © 2015. Published by Elsevier B.V.

Factors Associated with Fever in Intracerebral Hemorrhage.

PubMed

Gillow, Sabreena J; Ouyang, Bichun; Lee, Vivien H; John, Sayona

2017-06-01

Fever is common in patients with intracerebral hemorrhage (ICH). We sought to identify predictors of fever in patients hospitalized with ICH, and compare infectious fever with noninfectious fever. A retrospective review on consecutive spontaneous ICH patients from April 2009 to March 2010 was performed. Fever was defined as temperature 100.9°F or higher and attributed to infectious versus noninfectious etiology, based upon the National Healthcare Safety Network criteria. Univariate analysis and multivariable logistic regression model were used to determine factors associated with fever and with infection. Among the 351 ICH patients, 136 (39%) developed fever. Factors associated with fever included mean ICH volume, intraventricular hemorrhage (IVH), external ventricular drain (EVD) placement or surgical evacuation, positive microbial cultures, longer length of stay (LOS), and higher in-hospital mortality. Among patients with fever, 96 (71%) were noninfectious and 40 (29%) were infectious. Infectious fever was associated with higher LOS. Noninfectious fever was associated with higher in-hospital mortality. In multivariable analysis, ICH volume (OR = 1.01, P = .04), IVH (OR = 2.0, P = .03), EVD (OR = 3.7, P < .0001), and surgical evacuation (OR = 6.78, P < .0001) were significant predictors of fever. Infectious fever (OR = 5.26, P = .004), EVD (OR = 4.86, P = .01), and surgical evacuation (OR = 4.77, P = .04) correlated with prolonged LOS when dichotomized using a median of 15 days. Fever is common in ICH patients and is not associated with a clear infectious etiology in the majority of patients. Patients with noninfectious fever have higher in-hospital mortality, but survivors have shorter LOS. Further studies are warranted to better understand fevers in ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Clinical factors and incidence of prolonged fever in neurosurgical patients.

PubMed

Wang, Zhuo; Shen, Meifen; Qiao, Meizhen; Zhang, Haiyin; Tang, Zaixiang

2017-02-01

To describe the incidence of prolonged fever in patients admitted to the neurosurgery department, and the corresponding risk indicators. Prolonged fever was defined as a temperature higher than 38·3°C lasting more than five days. Prolonged fever is a common phenomenon and could lead to worsened outcomes in specific patient groups, especially for those with brain injury. However, the studies on prolonged fever in neurosurgical patients are limited and insufficient. A retrospective observational study. Retrospective data were collected from 1 January 2014 to 31 December 2014, at the neurosurgical department of a large teaching hospital. We performed univariate and multivariate analyses to identify independent indicators for prolonged fever vs. short-term fever. Among 2845 patients, prolonged fever occurred in 466 (16%). The older patients were associated with longer duration of mechanical ventilation and hospital stay. It predominantly occurred in patients with subarachnoid haemorrhage (SAH) and traumatic brain injury. Patients receiving antibiotic treatment tended to manifest prolonged fever more frequently. Multivariate analysis revealed that the use of antibiotics, central venous catheter and prolonged mechanical ventilation were independent risk predictors for prolonged fever. Patients diagnosed with brain tumour seemed to be not associated with prolonged fever. Prolonged fever is the common complication in neurosurgical patients. The risks of prolonged fever in patients are attributed to antibiotic therapy, use of central venous catheter and prolonged mechanical ventilation. Indicators of prolonged fever are helpful for better identification of high-risk patients and fever control. A better reveal on the epidemiology and predictable factors of prolonged fever in neurosurgical patients will provide a better understanding on those patients who are most at risk, and therefore contribute to fever control and better outcome. © 2016 John Wiley & Sons Ltd.

The Acylated/Unacylated Ghrelin Ratio Is Similar in Patients With Acromegaly During Different Treatment Regimens.

PubMed

Muhammad, Ammar; Delhanty, Patric J D; Huisman, Martin; Visser, Jenny A; Jan van der Lelij, Aart; Neggers, Sebastian J C M M

2017-07-01

Data on plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in acromegaly are limited. High AG/UAG ratios are linked with type 2 diabetes, obesity, and hyperphagia (e.g., in Prader-Willi syndrome). To assess fasting plasma AG and UAG levels, and the AG/UAG ratio in acromegaly patients receiving combination treatment of long-acting somatostatin analogs (LA-SSAs) and pegvisomant (PEGV; n = 60). We used as controls acromegaly patients whose disease was controlled with PEGV monotherapy and medically naïve patients with active acromegaly. Fasting venous blood samples were collected and directly stabilized to inhibit deacylation of AG. Plasma AG and UAG levels were determined by double-antibody sandwich enzyme immunoassay, and the AG/UAG ratio was calculated. Plasma AG and UAG levels were significantly lower in patients with acromegaly receiving combination treatment [median, interquartile range (IQR): AG: 8.5 pg/mL, 2.9 to 21.1 pg/mL; UAG: 26.9 pg/mL, 11.2 to 42.1 pg/mL] compared with patients using PEGV alone [AG: 60.5 pg/mL (IQR, 58.8 to 77.4 pg/mL); UAG: 153.7 pg/mL (IQR, 127.3 to 196.0 pg/mL)] and medically naïve patients with acromegaly [AG: 24.0 pg/mL (IQR, 12.6 to 49.7 pg/mL); UAG: 56.3 pg/mL (IQR, 43.4 to 61.5 pg/mL)]. However, AG/UAG ratios were similar in all groups. Although plasma AG and UAG are suppressed during combination treatment with LA-SSAs and PEGV, the AG/UAG ratio remained similar. This shows that SSAs decrease both AG and UAG levels, which suggests that they do not alter metabolism significantly in acromegaly patients. Copyright © 2017 Endocrine Society

Yellow Fever

MedlinePlus

... Testing Vaccine Information Testing for Vaccine Adverse Events Yellow fever Vaccine Continuing Education Course Yellow Fever Home Prevention Vaccine Vaccine Recommendations Reactions to Yellow Fever Vacine Yellow Fever Vaccine, Pregnancy, & ... Transmission Symptoms, Diagnosis, & Treatment Maps Africa ...

Fever--an update.

PubMed

Becker, John H; Wu, Stephanie C

2010-01-01

Fever is an active yet nonspecific response of the body to infections and other insults that cause immune cells to release cytokines, resulting in a brain prostanoid-mediated rise in body temperature. The causes, types, clinical management, and postoperative consequences of fever are reviewed in this article. Physicians use fever as a clinical sign for diagnoses and prognoses, but "fevers of unknown origin" continue to be problematic. Fevers that arise 1 or 2 days after surgery are usually due to stress and trauma, but later postoperative fevers often have more serious causes and consequences, such as wound infection. Fever is commonly encountered by podiatric physicians and surgeons, and certain procedures with the lower extremity are more likely to eventuate in fever.

Development of Special Biological Products

DTIC Science & Technology

1981-01-01

Rocky Mountain Spotted Fever (RMSF) 20. Continued B. Tissue Culture / ?Two production lots of FRhL-2 dnd three of MRC-5 were stabilized...104) was potency tested. J. Q Fever Vaccine Storage Stability Potency Testing Q fever vaccine (NDBR 105) was put on potency test. K. Rocky Mountain Spotted Fever (RMSF...Fever Vaccine Storage Stability Potency Testing Two lots of Q fever vaccine (NDBR 105) were put on potency test. K. Rocky Mountain Spotted Fever

Dengue Fever

MedlinePlus

... Staying Safe Videos for Educators Search English Español Dengue Fever KidsHealth / For Parents / Dengue Fever What's in ... Print en español Fiebre del dengue What Is Dengue Fever? Dengue (DEN-gee) fever is a tropical ...

CAREGIVERS' KNOWLEDGE AND HOME MANAGEMENT OF FEVER IN CHILDREN.

PubMed

Koech, P J; Onyango, F E; Jowi, C

2014-05-01

Fever is one of the most common complaints presented to the Paediatric Emergency Unit (PEU). It is a sign that there is an underlying pathologic process, the most common being infection. Many childhood illnesses are accompanied by fever, many of which are treated at home prior to presentation to hospital. Most febrile episodes are benign. Caregivers are the primary contacts to children with fever. Adequate caregivers' knowledge and proper management of fever at home leads to better management of febrile illnesses and reduces complications. To determine the caregivers' knowledge and practices regarding fever in children. A cross-sectional study. Peadiatric Emergency Unit at Kenyatta National Hospital (KNH) SUBJECTS: Two hundred and fifty caregivers of children under 12 years presenting with fever in August to October 2011 to the PEU. Three quarters of the caregivers' defined fever correctly. Their knowledge on the normal body was at 47.6%. Infection was cited as the leading cause of fever (95.2%). Brain damage (77.6%) and dehydration (65.6%) were viewed as the most common complication. Fever was treated at home by 97.2% of caregivers, most of them used medication. Fever was defined correctly by 75.2% of the study participants and a majority of them used touch to detect fever. Fever was managed at home with medications. Public Health Education should be implemented in order to enlighten caregivers on fever and advocate for the use of a clinical thermometer to monitor fever at home.

The Impact of Retail-Sector Delivery of Artemether–Lumefantrine on Malaria Treatment of Children under Five in Kenya: A Cluster Randomized Controlled Trial

PubMed Central

Kangwana, Beth P.; Kedenge, Sarah V.; Noor, Abdisalan M.; Alegana, Victor A.; Nyandigisi, Andrew J.; Pandit, Jayesh; Fegan, Greg W.; Todd, James E.; Brooker, Simon; Snow, Robert W.; Goodman, Catherine A.

2011-01-01

Background It has been proposed that artemisinin-based combination therapy (ACT) be subsidised in the private sector in order to improve affordability and access. This study in western Kenya aimed to evaluate the impact of providing subsidized artemether–lumefantrine (AL) through retail providers on the coverage of prompt, effective antimalarial treatment for febrile children aged 3–59 months. Methods and Findings We used a cluster-randomized, controlled design with nine control and nine intervention sublocations, equally distributed across three districts in western Kenya. Cross-sectional household surveys were conducted before and after the delivery of the intervention. The intervention comprised provision of subsidized packs of paediatric ACT to retail outlets, training of retail outlet staff, and community awareness activities. The primary outcome was defined as the proportion of children aged 3–59 months reporting fever in the past 2 weeks who started treatment with AL on the same day or following day of fever onset. Data were collected using structured questionnaires and analyzed based on cluster-level summaries, comparing control to intervention arms, while adjusting for other covariates. Data were collected on 2,749 children in the target age group at baseline and 2,662 at follow-up. 29% of children experienced fever within 2 weeks before the interview. At follow-up, the percentage of children receiving AL on the day of fever or the following day had risen by 14.6% points in the control arm (from 5.3% [standard deviation (SD): 3.2%] to 19.9% [SD: 10.0%]) and 40.2% points in the intervention arm (from 4.7% [SD: 3.4%] to 44.9% [SD: 11.7%]). The percentage of children receiving AL was significantly greater in the intervention arm at follow-up, with a difference between the arms of 25.0% points (95% confidence interval [CI]: 14.1%, 35.9%; unadjusted p = 0.0002, adjusted p = 0.0001). No significant differences were observed between arms in the proportion of caregivers who sought treatment for their child's fever by source, or in the child's adherence to AL. Conclusions Subsidizing ACT in the retail sector can significantly increase ACT coverage for reported fevers in rural areas. Further research is needed on the impact and cost-effectiveness of such subsidy programmes at a national scale. Trial Registration Current Controlled Trials ISRCTN59275137 and Kenya Pharmacy and Poisons Board Ethical Committee for Clinical Trials PPB/ECCT/08/07. Please see later in the article for the Editors' Summary PMID:21655317

Characteristics of Patients Referred to a Pediatric Infectious Diseases Clinic With Unexplained Fever.

PubMed

Statler, Victoria A; Marshall, Gary S

2016-09-01

Older case series established diagnostic considerations for children meeting a priori definitions of fever of unknown origin (FUO). No recent study has examined the final diagnoses of children referred for unexplained fever. This study was conducted with a retrospective chart review of patients referred to a pediatric infectious diseases clinic from 2008 to 2012 for unexplained fever. Sixty-nine of 221 patients were referred for "prolonged" unexplained fever. Ten of these were not actually having fever, and 11 had diagnoses that were readily apparent at the initial visit. The remaining 48 were classified as having FUO. The median duration of reported fever for these patients was 30 days; 15 had a diagnosis made, 5 of which were serious. None of the serious FUO diagnoses were infections. Of 152 patients with "recurrent" unexplained fever, 92 had an "intermittent" fever pattern, and most of these had sequential, self-limited viral illnesses or no definitive diagnosis made. Twenty of the 60 patients with a "periodic" fever pattern were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Overall, 166 patients either were not having fever, had self-limited illnesses, or ultimately had no cause of fever discovered. Only 12 had a serious illness, 2 of which were infections (malaria and typhoid fever). Most children referred with unexplained fever had either self-limited illnesses or no specific diagnosis established. Serious diagnoses were unusual, suggesting that these diagnoses rarely present with unexplained fever alone, or that, when they do, the diagnoses are made by primary care providers or other subspecialists. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Refining the Association of Fever with Functional Outcome in Aneurysmal Subarachnoid Hemorrhage.

PubMed

Kramer, Christopher L; Pegoli, Marianna; Mandrekar, Jay; Lanzino, Giuseppe; Rabinstein, Alejandro A

2017-02-01

We analyzed the impact of cause, severity, and duration of fever on functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Fever characteristics were analyzed in 584 consecutive patients with aSAH. Fever was defined as core body temperature ≥38.3 °C on ≥2 consecutive days. Subfebrile measurements were those between 37 and 38.2 °C. Febrile and subfebrile loads were the number of hours with fever or subfebrile measurements, respectively. Univariate and multivariate logistic regression models were developed to define predictors of outcome using various categorizations of fever cause, severity, and duration. Febrile measurements were observed in 281/584 (48.1 %) patients, recurring over a mean duration of 2.1 ± 3.0 days. Early fever within 24 and 72 h was encountered in 69 (11.9 %) and 110 (18.9 %) of patients, respectively. An infectious source was discovered in 126 (44.8 %) febrile patients. On univariate analysis, days of fever, febrile load, and fever onset within 24 and 72 h were associated with poor outcome (all p < 0.001); but subfebrile load was not (p = 0.56). On multivariate model constructed with all variables associated with outcome on univariate analyses, days of fever remained independently associated with poor outcome (OR 1.14 of poor outcome per day of fever, 95 % CI 1.06-1.22; p = 0.0006) displacing all other fever measures from the final model. Early onset of fever, number of hours with fever, and especially days of fever are associated with poor functional outcome. Conversely, subfebrile load does not influence clinical outcome. These data suggest prolonged fever should be avoided, but subfebrile temperatures may not justify intervention.

Association between infection and fever in terminations of pregnancy using misoprostol: a retrospective cohort study.

PubMed

Nijman, Tobias A J; Voogdt, Kevin G J A; Teunissen, Pim W; van der Voorn, Patrick J Jp; de Groot, Christianne J M; Bakker, Petra C A M

2017-01-05

Fever is a well-known side effect of misoprostol, but clinically difficult to distinguish from an intra uterine infection. The aim of this study was to determine the incidence of fever in terminations of pregnancy (TOP) using misoprostol and to evaluate fever as indication of intra uterine infection. A retrospective cohort study was performed. Consecutive second trimester TOP with misoprostol between January 2008 and October 2012 were selected. We included 403 cases and determined the incidence of fever. To examine intra uterine infection as plausible cause of fever, pathological examination reports of placentas were reviewed for signs of infections. The incidence of fever was 42%. Logistic regression showed a dose dependent association between dosage misoprostol and degree of fever (OR 1.86; 95% CI: 1.3-2.7). There was no association between fever and epidural analgesia. Fever has a sensitivity of 55% and a specificity of 58% as a marker of intra uterine infection. The positive predictive value of fever for an intra uterine infection is 4% and the negative predictive value is 98%. Administration of misoprostol for the indication TOP is strongly associated with fever during labor. Fever is a poor predictor of intra uterine infection in the context of TOP.

Dysregulation of Serum Gamma Interferon Levels in Vascular Chronic Q Fever Patients Provides Insights into Disease Pathogenesis

PubMed Central

Kremers, Marjolein N. T.; Hodemaekers, Hennie M.; Hagenaars, Julia C. J. P.; Koning, Olivier H. J.; Renders, Nicole H. M.; Hermans, Mirjam H. A.; de Klerk, Arja; Notermans, Daan W.; Wever, Peter C.; Janssen, Riny

2015-01-01

A large community outbreak of Q fever occurred in the Netherlands in the period 2007 to 2010. Some of the infected patients developed chronic Q fever, which typically includes pathogen dissemination to predisposed cardiovascular sites, with potentially fatal consequences. To identify the immune mechanisms responsible for ineffective clearance of Coxiella burnetii in patients who developed chronic Q fever, we compared serum concentrations of 47 inflammation-associated markers among patients with acute Q fever, vascular chronic Q fever, and past resolved Q fever. Serum levels of gamma interferon were strongly increased in acute but not in vascular chronic Q fever patients, compared to past resolved Q fever patients. Interleukin-18 levels showed a comparable increase in acute as well as vascular chronic Q fever patients. Additionally, vascular chronic Q fever patients had lower serum levels of gamma interferon-inducible protein 10 (IP-10) and transforming growth factor β (TGF-β) than did acute Q fever patients. Serum responses for these and other markers indicate that type I immune responses to C. burnetii are affected in chronic Q fever patients. This may be attributed to an affected immune system in cardiovascular patients, which enables local C. burnetii replication at affected cardiovascular sites. PMID:25924761

9 CFR 94.8 - Pork and pork products from regions where African swine fever exists or is reasonably believed to...

Code of Federal Regulations, 2012 CFR

2012-01-01

... where African swine fever exists or is reasonably believed to exist. 94.8 Section 94.8 Animals and... NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE... where African swine fever exists or is reasonably believed to exist. African swine fever exists or the...

Q fever: a contemporary case series from a Belgian hospital.

PubMed

Vanderbeke, Lore; Peetermans, Willy E; Saegeman, Veroniek; De Munter, Paul

2016-04-27

Q fever is a global zoonosis that can cause both acute and chronic infections in humans through aerogenic transmission. Although Q fever was discovered already 80 years ago, this infectious disease remains largely unknown. We studied a case series in a Belgian tertiary care hospital. A laboratory and file query at our department was performed to detect patients who were newly diagnosed with Q fever from 01 January 2005 to 01 October 2014. In total, 10 acute Q fever and 5 chronic Q fever infections were identified. An aspecific flu-like illness was the prevailing manifestation of acute Q fever, while this was infective endocarditis in chronic Q fever cases. Noteworthy are the high percentage of myocarditis cases in the acute setting and one case of amyloidosis as a manifestation of chronic Q fever. No evolution from acute to chronic Q fever was noted; overall outcome for both acute and chronic Q fever was favourable with a 94% survival rate. Q fever is an infectious disease characterised by a variable clinical presentation. Detection requires correct assessment of the clinical picture in combination with a laboratory confirmation. Treatment and follow-up are intended to avoid a negative outcome.

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue

PubMed Central

Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C.

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection. PMID:27936002

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

PubMed

Ng, Deborah Hl; Wong, Joshua Gx; Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection.