Elimination of Kala-Azar from the Southeast Asia Region.

PubMed

Bhattacharya, Sujit K; Dash, Aditya Prasad

2017-04-01

AbstractVisceral leishmaniasis (VL), popularly known as kala-azar, is essentially a disease of poverty. Kala-azar is caused by a parasite, Leishmania donovani . Recent review indicates that worldwide 98 countries are endemic for kala-azar. Approximately 0.2-0.4 million new VL cases occur each year worldwide. More than 90% of global VL cases occur in Bangladesh, Brazil, Ethiopia, India, South Sudan, and Sudan. This trend is slowly changing due to the progress in kala-azar elimination in southeast Asia, where Bangladesh has reported an average of some 600 new cases in 2014-2015. With the advancement in our knowledge about the disease and development of tools to diagnose and treat VL, it was considered that elimination of kala-azar was possible from India, Nepal, and Bangladesh. The three countries signed a memorandum of understanding in 2005 for collaboration. Miltefosine is the first ever oral drug developed to treat VL, which was later replaced by lipid amphotericin B. The main components of the strategy are early diagnosis using rK39 strip test and complete treatment utilizing miltefosine for 28 days. Dichlorodiphenyltrichloroethane or pyrethroids were deployed for vector control. There was much to be desired for better performance of the vector control activity. Pharmacovigilance and monitoring of drug resistance were the weakest part of the program. In the post-elimination phase, surveillance reinforced by active case finding will of a crucial factor for sustainability of the elimination. A strong political will is required to ensure elimination of kala-azar from the Indian subcontinent and its sustainability in the post-elimination phase.

Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study

PubMed Central

Das, Sushmita; Mandal, Rakesh; Rabidas, Vidya Nand; Verma, Neena; Pandey, Krishna; Ghosh, Ashok Kumar; Kesari, Sreekant; Kumar, Ashish; Purkait, Bidyut; Lal, Chandra Sekhar; Das, Pradeep

2016-01-01

Background Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients. Methods In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient’s house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development. Results Out of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1–200 μg/L and 200.1–432.0 μg/L were 1.85 (1.13–3.03) and 2.31 (1.39–3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02–2.7; p = 0.04). Conclusion Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar. PMID:27776123

A study on delay in treatment of kala-azar patients in Bangladesh.

PubMed

Arif, Syed M; Basher, Ariful; Rahman, Mohammad R; Faiz, Mohammad A

2012-01-01

Visceral leishmaniasis (kala-azar) continues to be a major rural public health problem in Bangladesh. A cross-sectional study was carried out in two subdistricts of Mymensingh district from January 2006 to June 2007 to evaluate the delay kala-azar treatment. Suspected patients who attended to out patient department (OPD) were subjected to a dipstick test (RK39) for kala-azar. Sixty five from Bhaluka and 60 positive patients from Gafargaon subdistrict were enrolled. Most of the patients (80%) first visited nonqualified private practitioners, while only 15.2% consulted registered doctors. Fifty per cent were referred to the Upazilla health complex (UZHC) by the family members or relatives. About 49% and 43% patients required third and second health-care providers for kala-azar treatment, respectively. Patient delay ranged from 2 to 30 days; median 4 (IQR 3 to 7 days), the system delay ranged from 0 days to 225 days; median 54 (IQR 40-66 days). Residential status (p value <0.05) had impact on patient delay. Educational status and number of treatment providers had impact on system delay (p<0.05). System delay rather than patient delay is the important weakness of the kala-azar control programme in Bangladesh. Residence in rural areas, low educational background and treatment providers are associated with these delays. A proper educational programme may reduce the delay.

Feasibility of a combined camp approach for vector control together with active case detection of visceral leishmaniasis, post kala-azar dermal leishmaniasis, tuberculosis, leprosy and malaria in Bangladesh, India and Nepal: an exploratory study.

PubMed

Banjara, Megha R; Kroeger, Axel; Huda, Mamun M; Kumar, Vijay; Gurung, Chitra K; Das, Murari L; Rijal, Suman; Das, Pradeep; Mondal, Dinesh

2015-06-01

We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Role of remote sensing, geographical information system (GIS) and bioinformatics in kala-azar epidemiology

PubMed Central

Bhunia, Gouri Sankar; Dikhit, Manas Ranjan; Kesari, Shreekant; Sahoo, Ganesh Chandra; Das, Pradeep

2011-01-01

Visceral leishmaniasis or kala-azar is a potent parasitic infection causing death of thousands of people each year. Medicinal compounds currently available for the treatment of kala-azar have serious side effects and decreased efficacy owing to the emergence of resistant strains. The type of immune reaction is also to be considered in patients infected with Leishmania donovani (L. donovani). For complete eradication of this disease, a high level modern research is currently being applied both at the molecular level as well as at the field level. The computational approaches like remote sensing, geographical information system (GIS) and bioinformatics are the key resources for the detection and distribution of vectors, patterns, ecological and environmental factors and genomic and proteomic analysis. Novel approaches like GIS and bioinformatics have been more appropriately utilized in determining the cause of visearal leishmaniasis and in designing strategies for preventing the disease from spreading from one region to another. PMID:23554714

Kala-azar in a Brazilian child

PubMed Central

Meunier, Yann A.; Hole, Michael K.

2011-01-01

We report the case of a six-year-old Brazilian girl referred for splenomegaly who first presented with fever, asthenia, and weight loss. Geographical location, clinical exam, and blood laboratories suggested kala-azar. Serology confirmed kala-azar diagnosis, but direct evidence of the parasites was not made. A treatment by meglumine antimoniate is given under hospital surveillance for two weeks. Thereupon, the patient is asymptomatic and all tests are normal. PMID:24765289

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

PubMed Central

Vijayamahantesh; Amit, Ajay; Dikhit, Manas R.; Pandey, Raj K.; Singh, Kuljit; Mishra, Ritesh; Das, V. N. R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID:27186641

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients.

PubMed

Vijayamahantesh; Amit, Ajay; Dikhit, Manas R; Pandey, Raj K; Singh, Kuljit; Mishra, Ritesh; Das, V N R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.

Snowball Vs. House-to-House Technique for Measuring Annual Incidence of Kala-azar in the Higher Endemic Blocks of Bihar, India: A Comparison.

PubMed

Siddiqui, Niyamat A; Rabidas, Vidya N; Sinha, Sanjay K; Verma, Rakesh B; Pandey, Krishna; Singh, Vijay P; Ranjan, Alok; Topno, Roshan K; Lal, Chandra S; Kumar, Vijay; Sahoo, Ganesh C; Sridhar, Srikantaih; Pandey, Arvind; Das, Pradeep

2016-09-01

Visceral Leishmaniasis, commonly known as kala-azar, is widely prevalent in Bihar. The National Kala-azar Control Program has applied house-to-house survey approach several times for estimating Kala-azar incidence in the past. However, this approach includes huge logistics and operational cost, as occurrence of kala-azar is clustered in nature. The present study aims to compare efficiency, cost and feasibility of snowball sampling approach to house-to-house survey approach in capturing kala-azar cases in two endemic districts of Bihar, India. A community based cross-sectional study was conducted in two highly endemic Primary Health Centre (PHC) areas, each from two endemic districts of Bihar, India. Snowball technique (used to locate potential subjects with help of key informants where subjects are hard to locate) and house-to-house survey technique were applied to detect all the new cases of Kala-azar during a defined reference period of one year i.e. June, 2010 to May, 2011. The study covered a total of 105,035 households with 537,153 populations. Out of total 561 cases and 17 deaths probably due to kala-azar, identified by the study, snowball sampling approach captured only 221 cases and 13 deaths, whereas 489 cases and 17 deaths were detected by house-to-house survey approach. Higher value of McNemar's χ² statistics (64; p<0.0001) for house-to-house survey approach than snowball sampling and relative difference (>1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to-house approach with 13% of omission. Snowball sampling was not found sensitive enough as it captured only about 50% of VL cases. However, it captured about 77% of the deaths probably due to kala-azar and was found more cost-effective than house-to-house approach. Standardization of snowball approach with improved procedure, training and logistics may enhance the sensitivity of snowball sampling and its application in national Kala-azar elimination

Snowball Vs. House-to-House Technique for Measuring Annual Incidence of Kala-azar in the Higher Endemic Blocks of Bihar, India: A Comparison

PubMed Central

Siddiqui, Niyamat A.; Rabidas, Vidya N.; Sinha, Sanjay K.; Verma, Rakesh B.; Pandey, Krishna; Singh, Vijay P.; Ranjan, Alok; Topno, Roshan K.; Lal, Chandra S.; Kumar, Vijay; Sahoo, Ganesh C.; Sridhar, Srikantaih; Pandey, Arvind; Das, Pradeep

2016-01-01

Background Visceral Leishmaniasis, commonly known as kala-azar, is widely prevalent in Bihar. The National Kala-azar Control Program has applied house-to-house survey approach several times for estimating Kala-azar incidence in the past. However, this approach includes huge logistics and operational cost, as occurrence of kala-azar is clustered in nature. The present study aims to compare efficiency, cost and feasibility of snowball sampling approach to house-to-house survey approach in capturing kala-azar cases in two endemic districts of Bihar, India. Methodology/Principal findings A community based cross-sectional study was conducted in two highly endemic Primary Health Centre (PHC) areas, each from two endemic districts of Bihar, India. Snowball technique (used to locate potential subjects with help of key informants where subjects are hard to locate) and house-to-house survey technique were applied to detect all the new cases of Kala-azar during a defined reference period of one year i.e. June, 2010 to May, 2011. The study covered a total of 105,035 households with 537,153 populations. Out of total 561 cases and 17 deaths probably due to kala-azar, identified by the study, snowball sampling approach captured only 221 cases and 13 deaths, whereas 489 cases and 17 deaths were detected by house-to-house survey approach. Higher value of McNemar’s χ² statistics (64; p<0.0001) for house-to-house survey approach than snowball sampling and relative difference (>1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to-house approach with 13% of omission. Conclusion/Significance Snowball sampling was not found sensitive enough as it captured only about 50% of VL cases. However, it captured about 77% of the deaths probably due to kala-azar and was found more cost-effective than house-to-house approach. Standardization of snowball approach with improved procedure, training and logistics may enhance the sensitivity of snowball

Leishmaniasis

MedlinePlus

Kala-azar; Cutaneous leishmaniasis; Visceral leishmaniasis; Old world leishmaniasis; New world leishmaniasis ... Leishmaniasis is caused by a tiny parasite called leishmania protozoa. Protozoa are one-celled organisms. There are ...

Evaluation of latex agglutination test (KAtex) for early diagnosis of kala-azar.

PubMed

Ahsan, M M; Islam, M N; Mollah, A H; Hoque, M A; Hossain, M A; Begum, Z; Islam, M T

2010-07-01

Kala-azar is one of the major public health problem in Bangladesh. But the diagnosis of the problem often is difficult, unusual and time consuming, a simple, noninvasive, easy to perform, reliable and rapid diagnostic test has been a long-felt need of the clinicians. Therefore, the present study was conducted to see the sensitivity and specificity of Latex Agglutination test (KAtex) to detect leishmanial antigen from urine of kala-azar cases. The study was carried out in the department of Paediatrics, Mymensingh Medical College and Hospital, Bangladesh during July to December, 2008. A total of 100 urine samples were collected of which 50 were confirmed kala-azar cases and 50 were age and sex matched controls. Out of 50 kala-azar cases 47 showed positive result of KAtex. The test was also positive in 01 out of 30 healthy controls. None of the febrile controls was positive by KAtex. The sensitivity, specificity, positive predictive value and negative predictive value of the test using presence of LD bodies in splenic and/or bone marrow aspirate as gold standard were 94%, 98%, 97.91% and 94.23% respectively. KAtex is simple, noninvasive, easy to perform, rapid and reliable test for diagnosing kala-azar in endemic area and useful for small, less equipped laboratories as well as for the laboratories with better facilities.

Kala-azar in Darfur: Evidence for indigenous transmission in Al-Malha Locality, North Darfur, western Sudan.

PubMed

Mohammed, Mohammed A; Khalid, Noteila M; Aboud, Mariam A

2018-03-06

Recent reports showed high numbers of visceral leishmaniasis cases in North Darfur, western Sudan. Due to a lack of previous studies, no information is available on local transmission of the disease in these areas. Therefore, a pilot entomological and epidemiological study was conducted in Al-Malha Locality during the year 2013, to investigate possibility of local transmission and places and times of the year where and when people contract the infection. Kala-azar incidence data were obtained from records of Ministry of Health, North Darfur; Al-Malha rural hospital; and the Federal Ministry of Health, Division of Communicable and Non-communicable Diseases. Sand flies were collected using sticky paper and rodent burrow traps from five different microhabitats during three different phases of the year. Species identification was undertaken using appropriate taxonomic keys. Data were statistically analyzed to determine the distribution of kala-azar among different age groups and between sexes, and to compare the species richness and distribution of different sandfly species between the different microhabitats. The most affected age groups with kala-azar during the period 2013-2016 were children between one and five years old and those under one year. Females were found to be more affected than males. A total of 918 sand fly specimens were collected using sticky paper and rodent burrow traps from five microhabitats. Identified specimens belong to 13 species; 5 Phlebotomus and 8 Sergentomyia. Phlebotomus orientalis, the principal vector of visceral leishmaniasis (VL) in Sudan and other East African countries, was found for the first time in the area. No other known vector of VL was found in the collection. The highest number of sand flies was recorded during the summer season (63%), with S. antennata (48%) and S. schwetzi (24.1%) being the most abundant species. Among Phlebotomus species, P. orientalis showed relatively high density (8.6%). A dry seasonal water course

A proteomic map of the unsequenced kala-azar vector Phlebotomus papatasi using cell line.

PubMed

Pawar, Harsh; Chavan, Sandip; Mahale, Kiran; Khobragade, Sweta; Kulkarni, Aditi; Patil, Arun; Chaphekar, Deepa; Varriar, Pratyasha; Sudeep, Anakkathil; Pai, Kalpana; Prasad, T S K; Gowda, Harsha; Patole, Milind S

2015-12-01

The debilitating disease kala-azar or visceral leishmaniasis is caused by the kinetoplastid protozoan parasite Leishmania donovani. The parasite is transmitted by the hematophagous sand fly vector of the genus Phlebotomus in the old world and Lutzomyia in the new world. The predominant Phlebotomine species associated with the transmission of kala-azar are Phlebotomus papatasi and Phlebotomus argentipes. Understanding the molecular interaction of the sand fly and Leishmania, during the development of parasite within the sand fly gut is crucial to the understanding of the parasite life cycle. The complete genome sequences of sand flies (Phlebotomus and Lutzomyia) are currently not available and this hinders identification of proteins in the sand fly vector. The current study utilizes a three frame translated transcriptomic data of P. papatasi in the absence of genomic sequences to analyze the mass spectrometry data of P. papatasi cell line using a proteogenomic approach. Additionally, we have carried out the proteogenomic analysis of P. papatasi by comparative homology-based searches using related sequenced dipteran protein data. This study resulted in the identification of 1313 proteins from P. papatasi based on homology. Our study demonstrates the power of proteogenomic approaches in mapping the proteomes of unsequenced organisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Hyponatremia in visceral leishmaniasis.

PubMed

Verde, Frederico A Lima; Verde, Francisco A A Lima; Veronese, Francisco José V; Neto, Augusto S; Fuc, Galdino; Verde, Emir M Lima

2010-01-01

There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar). This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H₂O, p < 0.05), and high 24-hour urine osmolality (426.0 ± 167.0 vs. 514.6 ± 132.0 mOsm/kg H₂O, p < 0.05) demonstrated persistent antidiuretic hormone secretion. Urinary sodium was high (82.3 ± 44.2 vs.110.3 ± 34.7 mEq/L, p < 0.05). Low seric uric acid occurred in 61.8% of patients and increased fractional urinary uric acid excretion was detected in 74.5% of them. Increased glomerular filtration rate was present in 25.4% of patients. There was no evidence of extracellular volume depletion. Normal plasma ADH levels were observed in kala-azar patients. No endocrine or renal dysfunction was detected. It is possible that most hyponatremic kala-azar patients present the syndrome of inappropriate antidiuretic hormone secretion.

Possibilities and challenges for developing a successful vaccine for leishmaniasis.

PubMed

Srivastava, Saumya; Shankar, Prem; Mishra, Jyotsna; Singh, Sarman

2016-05-12

Leishmaniasis is a vector-borne disease caused by different species of protozoan parasites of the genus Leishmania. It is a major health problem yet neglected tropical diseases, with approximately 350 million people worldwide at risk and more than 1.5 million infections occurring each year. Leishmaniasis has different clinical manifestations, including visceral (VL or kala-azar), cutaneous (CL), mucocutaneous (MCL), diffuse cutaneous (DCL) and post kala-azar dermal leishmaniasis (PKDL). Currently, the only mean to treat and control leishmaniasis is by rational medications and vector control. However, the number of available drugs is limited and even these are either exorbitantly priced, have toxic side effects or prove ineffective due to the emergence of resistant strains. On the other hand, the vector control methods are not so efficient. Therefore, there is an urgent need for developing a safe, effective, and affordable vaccine for the prevention of leishmaniasis. Although in recent years a large body of researchers has concentrated their efforts on this issue, yet only three vaccine candidates have gone for clinical trial, until date. These are: (i) killed vaccine in Brazil for human immunotherapy; (ii) live attenuated vaccine for humans in Uzbekistan; and (iii) second-generation vaccine for dog prophylaxis in Brazil. Nevertheless, there are at least half a dozen vaccine candidates in the pipeline. One can expect that, in the near future, the understanding of the whole genome of Leishmania spp. will expand the vaccine discovery and strategies that may provide novel vaccines. The present review focuses on the development and the status of various vaccines and potential vaccine candidates against leishmaniasis.

Assessment of quality of life in patients with post kalaazar dermal leishmaniasis.

PubMed

Pal, Biplab; Murti, Krishna; Siddiqui, Niyamat Ali; Das, Pradeep; Lal, Chandra Shekhar; Babu, Rajendra; Rastogi, Manoj Kumar; Pandey, Krishna

2017-07-24

Post kala-azar dermal leishmaniasis (PKDL) is a dermatological disorder caused by protozoal parasite Leishmania donovani. PKDL cases are thought to be a reservoir of parasites and may increase cases of visceral leishmaniasis. The disease is not life threatening but cosmetic disfigurement associated with it may impair the patients' quality of life. This study aimed to assess the health related quality of life in patients with post kalaazar dermal leishmanasis for the first time. A total of 92 PKDL cases and 96 healthy participants filled out the questionnaires. The Dermatology Life Quality Index (DLQI) and SF 36 questionnaire were used to assess the quality of life. Data on socio-demographic and clinical features were also collected. The collected data were analyzed by using SPSS software (version 16), Student's t-test, analysis of variance (ANOVA) was applied for comparison of means. PKDL patients experienced very large impact on their quality of life. The mean score of DLQI was 11.41. Highest impact was found in symptoms and feelings and lowest impact was observed for personal relationship domain. Patients below 20 years age group found to have lower quality of life. There was a significant difference in mean DLQI scores with regard to age and severity of lesions (P < 0.05). No significant difference was observed with respect to gender, duration and location of lesions (p > 0.05). PKDL significantly impaired the patient's quality of life. Further studies to assess the impact of treatment on quality of life in these patients are recommended.

Visceral leishmaniasis with Roth spots

PubMed Central

Meena, Jagdish; Juneja, Monica; Mishra, Devendra; Vats, Pallavi; Pawaria, Arti

2014-01-01

Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. The protozoa is obliged intracellularly and causes a wide spectrum of clinical syndromes: VL (‘kala azar’), cutaneous leishmaniasis and mucocutaneous leishmaniasis (espundia). Kala azar is the most aggressive form and if untreated causes high mortality. Here, we describe a case of VL that presented to us with high-grade fever and found to have Roth spots that were resolved after 15 days of therapy. PMID:25988048

Vector density and the control of kala-azar in Bihar, India.

PubMed

Kumar, V; Kesari, S; Kumar, A J; Dinesh, D S; Ranjan, A; Prasad, M; Sinha, N K; Kumar, R; Das, P

2009-11-01

Bihar, India has been in the grip of kala-azar for many years. Its rampant and severe spread has made life miserable in most parts of the state. Such conditions require a comprehensive understanding of this affliction. The numbers coming out of the districts prone to the disease in the north and south Ganges have provided us with several startling revelations, as there are striking uniformities on both sides, including similar vegetation, water storage facilities, house construction and little change in risk factors. The northern areas have been regularly sprayed with DDT since 1977, but eradication of the disease appears to be a distant dream. In 2007 alone, there were as many as 37,738 cases in that region. In contrast, the southern districts of Patna and Nalanda have never had the disease in its epidemic form and endemic disease has been present in only some pockets of the two districts. In those cases, two rounds of spraying with DDT had very positive results, with successful control and no new established foci. In addition, an eleven-year longitudinal study of the man hour density and house index for the vector Phlebotomus argentipes demonstrated that they were quite high in Patna and Nalanda and quite low in north Bihar. Given these facts, an attempt has been made to unravel the role of P. argentipes saliva (salivary gland) in the epidemiology of kala-azar. It was determined that patchy DDT spraying should be avoided for effective control of kala-azar.

The lost hope of elimination of Kala-azar (visceral leishmaniasis) by 2010 and cyclic occurrence of its outbreak in India, blame falls on vector control practices or co-infection with human immunodeficiency virus or therapeutic modalities?

PubMed

Muniaraj, Mayilsamy

2014-01-01

The Kala-azar/visceral leishmaniasis (VL) turns epidemic form once in every 15 years in the endemic regions of Indian subcontinent. The goal of elimination of Kala-azar from India by 2010 was lost despite paramount efforts taken by the Government of India and World Health Organization and Regional Office for South East Asia. The main objective of this review was to elucidate the possible reason for the failure of Kala-azar elimination program and to suggest possible remedial measures to achieve the goal in future. The annual numbers of VL cases and deaths recorded in India since 1977 were plotted on a graph, to see if the temporal trends could be associated with changes in the vector control practices or co-infection with human immunodeficiency virus (HIV) or therapeutic modalities used against VL. The VL cases flares up whenever the effect of dichlorodiphenyltrichloroethane (DDT) diminished after the withdrawal of spray. The fading effectiveness was clearly correlated with an increasing number of VL cases. Therapeutic modalities were found to be highly correlating with VL mortality not with VL morbidity. The diminishing efficacy of first and second line drugs and the introduction of new drugs and drugs combination were responsible for ups and downs in the VL mortality. The VL mortality is constantly declining since 1993, but cases started increasing from 2003 to 2007 and then recently again from 2010 to 2011. This shows a serious lacuna in the vector control practices applied. The extent of HIV co-infection did not show any correlation with number/trend of VL cases or death over the study period. It is concluded that, by strict vector control practices, the VL cases can be reduced and by applying proper therapeutic strategies, the VL mortality can be reduced. HIV-VL co-infection does not seem to be in a worried stage.

Mapping of risk prone areas of kala-azar (Visceral leishmaniasis) in parts of Bihar State, India: an RS and GIS approach.

PubMed

Sudhakar, S; Srinivas, T; Palit, A; Kar, S K; Battacharya, S K

2006-09-01

The kala-azar fever (Visceral leishmaniasis) is continuing unabated in India for over a century, now being largely confined to the eastern part of India mainly in Bihar state and to some extent in its bordering states like West Bengal and Uttar Pradesh. Two study sites namely Patepur block in Vaishali district with high endemicity in northern part and Lohardagga block in Lohardagga district with absolute non-endemicity in southern part of Bihar were selected for the study with the following objectives : (i) to study the macro-ecosystem in relation to distribution of vector -Phlebotomus argentipes; (ii) to identify/map the risk prone areas or villages in a block for quick remedial measures; and (iii) to make use of satellite remote sensing and GIS to demonstrate the utility for rapid assessment of landuse/landcover and their relation with the incidence of kalaazar leading to the mapping of risk prone areas. Indian Remote Sensing (IRS)-1D LISS III satellite data for the periods of March and November 2000 were analysed in Silicon graphic image processing system using ERDAS software. False color composites (FCC) were generated and landuse/landcover was assessed using Maximum likelihood supervised classification techniques based on ground truth training sets. During the study the GIS functions are used to quantify the remotely sensed landscape proportions of 5 km2 buffer surrounding each known group of villages of high occurrence of sandflies in endemic and nonendemic study sites. Instead of traditional ground based survey methods to vector surveillance, the present study used a combination of remote sensing (RS) and geographical information system (GIS) approach to develop landscape predictors of sandfly abundance-an indicator of human vector contact and as a measure of risk prone areas. Statistical analysis using the remotely sensed landscape variables showed that rural villages surrounded by higher proportion of transitional swamps with soft stemmed edible plants and

Implication of vector characteristics of Phlebotomus argentipes in the kala-azar elimination programme in the Indian sub-continent.

PubMed

Chowdhury, Rajib; Kumar, Vijay; Mondal, Dinesh; Das, Murari Lal; Das, Pradeep; Dash, Aditya Prasad; Kroeger, Axel

2016-05-01

Visceral leishmaniasis (VL), also known as kala-azar in the Indian sub-continent (ISC), is a major public health concern in Bangladesh, India, and Nepal, where it is caused by Leishmania donovani transmitted by the sand fly Phlebotomus argentipes. Various ecological parameters including air temperature, rainfall, wind speed, relative humidity, soil moisture, pH, and organic carbon are known to influence the oviposition of female sand flies, as well as the survival and development of larvae. However, more detailed knowledge on vector behavior, such as biting times, breeding places, and preferred hosts are needed to design optimal evidence-based vector control interventions. In order to facilitate rational decisions regarding VL vector control, a systematic review was conducted to identify the prevailing practice and knowledge gaps in relation to vector bionomics and behavior. Search terms included 'sand fly bionomics', 'habitat', and 'visceral leishmaniasis/kala-azar vector control' using the Boolean operator AND to identify the country of interest, namely: Bangladesh, India, and Nepal. Both PubMed and Google search engines were used. Additional unpublished documents in the three countries were also analyzed. Information on the life cycle of VL vectors, their breeding behavior, infection rate with L. donovani, feeding behavior, and seasonal variation are useful for designing vector control operations. Unfortunately, none of the studies on the life cycle of P. argentipes was conducted in field settings of the ISC, so the publications from other locations had to be used for determining the duration of life cycle and development from egg to adult. However, information about breeding places, seasonal variation of vector densities, and 47 out of the selected 51 papers are available from the ISC and can be used for intelligent design of control operations. Vector control services should undertake routine insecticide resistance monitoring and adapt indoor residual spraying

Implication of vector characteristics of Phlebotomus argentipes in the kala-azar elimination programme in the Indian sub-continent

PubMed Central

Chowdhury, Rajib; Kumar, Vijay; Mondal, Dinesh; Das, Murari Lal; Das, Pradeep; Dash, Aditya Prasad

2016-01-01

Background Visceral leishmaniasis (VL), also known as kala-azar in the Indian sub-continent (ISC), is a major public health concern in Bangladesh, India, and Nepal, where it is caused by Leishmania donovani transmitted by the sand fly Phlebotomus argentipes. Various ecological parameters including air temperature, rainfall, wind speed, relative humidity, soil moisture, pH, and organic carbon are known to influence the oviposition of female sand flies, as well as the survival and development of larvae. However, more detailed knowledge on vector behavior, such as biting times, breeding places, and preferred hosts are needed to design optimal evidence-based vector control interventions. Methods In order to facilitate rational decisions regarding VL vector control, a systematic review was conducted to identify the prevailing practice and knowledge gaps in relation to vector bionomics and behavior. Search terms included ‘sand fly bionomics’, ‘habitat’, and ‘visceral leishmaniasis/kala-azar vector control’ using the Boolean operator AND to identify the country of interest, namely: Bangladesh, India, and Nepal. Both PubMed and Google search engines were used. Additional unpublished documents in the three countries were also analyzed. Results Information on the life cycle of VL vectors, their breeding behavior, infection rate with L. donovani, feeding behavior, and seasonal variation are useful for designing vector control operations. Unfortunately, none of the studies on the life cycle of P. argentipes was conducted in field settings of the ISC, so the publications from other locations had to be used for determining the duration of life cycle and development from egg to adult. However, information about breeding places, seasonal variation of vector densities, and 47 out of the selected 51 papers are available from the ISC and can be used for intelligent design of control operations. Conclusion Vector control services should undertake routine insecticide

A comparative evaluation of end-emic and non-endemic region of visceral leishmaniasis (Kala-azar) in India with ground survey and space technology.

PubMed

Kesari, Shreekant; Bhunia, Gouri Sankar; Kumar, Vijay; Jeyaram, Algarswamy; Ranjan, Alok; Das, Pradeep

2011-08-01

In visceral leishmaniasis, phlebotomine vectors are targets for control measures. Understanding the ecosystem of the vectors is a prerequisite for creating these control measures. This study endeavours to delineate the suitable locations of Phlebotomus argentipes with relation to environmental characteristics between endemic and non-endemic districts in India. A cross-sectional survey was conducted on 25 villages in each district. Environmental data were obtained through remote sensing images and vector density was measured using a CDC light trap. Simple linear regression analysis was used to measure the association between climatic parameters and vector density. Using factor analysis, the relationship between land cover classes and P. argentipes density among the villages in both districts was investigated. The results of the regression analysis indicated that indoor temperature and relative humidity are the best predictors for P. argentipes distribution. Factor analysis confirmed breeding preferences for P. argentipes by landscape element. Minimum Normalised Difference Vegetation Index, marshy land and orchard/settlement produced high loading in an endemic region, whereas water bodies and dense forest were preferred in non-endemic sites. Soil properties between the two districts were studied and indicated that soil pH and moisture content is higher in endemic sites compared to non-endemic sites. The present study should be utilised to make critical decisions for vector surveillance and controlling Kala-azar disease vectors.

Predicting death from kala-azar: construction, development, and validation of a score set and accompanying software.

PubMed

Costa, Dorcas Lamounier; Rocha, Regina Lunardi; Chaves, Eldo de Brito Ferreira; Batista, Vivianny Gonçalves de Vasconcelos; Costa, Henrique Lamounier; Costa, Carlos Henrique Nery

2016-01-01

Early identification of patients at higher risk of progressing to severe disease and death is crucial for implementing therapeutic and preventive measures; this could reduce the morbidity and mortality from kala-azar. We describe a score set composed of four scales in addition to software for quick assessment of the probability of death from kala-azar at the point of care. Data from 883 patients diagnosed between September 2005 and August 2008 were used to derive the score set, and data from 1,031 patients diagnosed between September 2008 and November 2013 were used to validate the models. Stepwise logistic regression analyses were used to derive the optimal multivariate prediction models. Model performance was assessed by its discriminatory accuracy. A computational specialist system (Kala-Cal(r)) was developed to speed up the calculation of the probability of death based on clinical scores. The clinical prediction score showed high discrimination (area under the curve [AUC] 0.90) for distinguishing death from survival for children ≤2 years old. Performance improved after adding laboratory variables (AUC 0.93). The clinical score showed equivalent discrimination (AUC 0.89) for older children and adults, which also improved after including laboratory data (AUC 0.92). The score set also showed a high, although lower, discrimination when applied to the validation cohort. This score set and Kala-Cal(r) software may help identify individuals with the greatest probability of death. The associated software may speed up the calculation of the probability of death based on clinical scores and assist physicians in decision-making.

AmBisome Induced Avascular Necrosis of the Alae of the Nose of a very young girl suffering from Kala-azar - a Case Report.

PubMed

Maruf, Shomik; Nath, Proggananda; Aktar, Fatima; Basher, Ariful

2016-12-01

Although liposomal amphotericin B (AmBisome) is considered as the first-line treatment for New Kala-azar, there is not enough evidence on the dosage formulation in children and its effect on them. Being considered as the safest drug for treatment of Kala-azar, this case of AmBisome-induced avascular necrosis now gives rise to the question; whether it is actually safe enough and if a dosage modification is needed in case of children. This so far, to the best of our knowledge, is the first instance of such severe adverse event due to AmBisome administration.

Childhood visceral leishmaniasis.

PubMed

Bhattacharya, S K; Sur, Dipika; Karbwang, Juntra

2006-03-01

Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. Nearly half of the VL cases occur in children (childhood or paediatric VL). The clinical manifestations of childhood VL are more or less same as in the adults. Prolonged fever with anorexia and loss of appetite are the major presenting features. Marked enlargement of the spleen and liver (spleen larger than liver) with moderate to severe anaemia and changes in hair take place. Bacterial infection is a common coinfection and intestinal parasitic infestations are very common in children with VL. Liver function tests, blood, urine and stool may show abnormalities. Confirmation of diagnosis is made by demonstration of parasite by microscopic examination and culture of materials obtained by bone marrow aspiration or splenic puncture. Sodium antimony gluconate (stibogluconate) has been the drug of choice for over past 50 yr. Pentamidine isothionate, though effective is relatively toxic. Amphotericin B is the most effective drug for the treatment of VL. Miltefosine is the first-ever oral drug, is highly effective. Post kala-azar dermal leishmaniasis (PKDL) in children poses a therapeutic challenge. In the absence of an ideal vaccine for VL, control measures would essentially include prevention of transmission through vector control and community awareness.

Lay perceptions of kala-azar, mosquitoes and bed nets in Bihar, India.

PubMed

Mishra, Rabindra N; Singh, S P; Vanlerberghe, Veerle; Sundar, Shyam; Boelaert, Marleen; Lefèvre, Pierre

2010-07-01

To describe the lay perception of kala-azar (KA) in an endemic area of Muzaffarpur District, Bihar, India: local names, symptoms, affected persons, perceived severity and modes of transmission, as well as perceived mosquito nuisance, modes of protection and use of bed nets. We held 16 focus group discussions (FGD) in eight remote villages with altogether 157 participants in March 2008. Separate FGDs were held according to gender, socio-economic status (SES) and with key informants. Kala-azar is most commonly named pilahi. Poor people were said to be the most affected. Knowledge about symptoms was satisfactory. Fever and prolonged fever were the most stated symptoms. KA was perceived as a life-threatening disease with a heavy economic burden. Mosquito bites were perceived as the main mode of transmission but in lower socio-economic groups, non-vector-related explanations were also provided. The main modes of protection from mosquitoes mentioned were the use of fumes and bed nets. Season was the strongest factor influencing the use of bed nets and non-affordability for not owning them. Although the sand fly is not recognised as the vector, the relatively good awareness of disease transmission by mosquitoes and the nuisance caused by their high density might be an entry point for adopting preventive measures to protect from mosquito bite and thereby indirectly preventing from KA. Educational campaigns targeted to the poorer segments of society are needed to enhance knowledge about KA, its mode of transmission, risks of getting infected and to increase bed net use.

Hormonal disturbances in visceral leishmaniasis (kala-azar).

PubMed

Verde, Frederico Araujo Lima; Verde, Francisco Agenor Araujo Lima; Neto, Augusto Saboia; Almeida, Paulo César; Verde, Emir Mendonça Lima

2011-05-01

This study presents a cross-sectional analysis of the hormonal alterations of patients with visceral leishmaniasis. The diagnosis was established by the bone marrow aspiration and polymerase chain reaction test. Primary adrenal insufficiency was observed in 45.8% of patients; low aldosterone/renin plasma ratio in 69.4%; low daily urinary aldosterone excretion in 61.1%; and low transtubular potassium gradient in 68.0%. All patients had normal plasma antidiuretic hormone (ADH) concentrations, hyponatremia, and high urinary osmolality. Plasma parathyroid hormone was low in 63%; hypomagnesemia was present in 46.4%, and increased Mg(++)(EF) in 100%. Primary thyroid insufficiency was observed in 24.6%, and secondary thyroid insufficiency in 14.1%. Normal follicle-stimulating hormone plasma levels were present in 81.4%; high luteinizing hormone and low testosterone plasma levels in 58.2% of men. There are evidences of hypothalamus-pituitary-adrenal axis abnormalities, inappropriate aldosterone and ADH secretions, and presence of hypoparathyroidism, magnesium depletion, thyroid and testicular insufficiencies.

Clinical and Laboratory Analysis of Patients with Leishmaniasis: A Retrospective Study from a Tertiary Care Center in New Delhi

PubMed Central

GUPTA, Nitin; KANT, Kamla; MIRDHA, Bijay Ranjan

2017-01-01

Background: Leishmaniasis manifests as visceral (VL), cutaneous (CL) or a dermal sequel of VL, known as Post kala-azar dermal leishmaniasis (PKDL). The aim of the study was to analyze the clinical and laboratory features of cases diagnosed with leishmaniasis. Methods: This hospital-based retrospective study included all cases of VL, PKDL, and CL diagnosed between Jan 2011 to Jan 2016 at All India Institute of Medical Sciences, New Delhi. Clinical and laboratory profile of the diagnosed cases were analyzed in detail. All diagnosed cases were mapped according to the state and the district from which the cases originated. Results: A total of 91 VL cases and 4 PKDL cases were reviewed. Only one case of CL (1 female) and mucocutaneous leishmaniasis (1 female) were observed during the study period. Majority of the cases of VL (75/91) originated from Bihar. The most common presenting symptoms in all our patients were fever (97.8%), weight loss (40.6%) and abdominal discomfort (17.6%) while the most common presenting signs were hepatosplenomegaly (45.8%), isolated splenomegaly (23.1%) and skin pigmentation (11%). The most common laboratory abnormality was anaemia followed by thrombocytopenia and leucopenia. Conclusion: VL is globally recognized as a neglected tropical disease. Even after continued effort to bring down its transmission in India, it continues to affect the endemic states with reports from new pockets. PMID:29317889

[Visceral leishmaniasis as a threat for non-endemic countries].

PubMed

Górski, Stanisław; Wiercińska-Drapało, Alicja

2009-01-01

Global warming, globalisation, and constantly increasing number of people involved in long-distance tourism and travel to exotic destinations are likely to increase the number of cases of exotic diseases "imported" to nonendemic countries. One of the often forgotten and neglected diseases has been visceral leishmaniasis (VL or kala-azar). The disease is endemic to 62 countries, with India and Sudan accounting for the majority of the cases. It is typically fatal if left untreated. Each year about 500 000 new cases are reported worldwide, and 50 000 die as a result of the disease. Kala-azar is present in the Mediterranean Europe and 70% of cases are imported to non-endemic countries of European Union from that area. Immunocompromised status of patients, like HIV carriers are the principal prospective target for kala-azar. HIV/VL-coinfected patients have significantly higher relapse rates and decreased life expectancy. There is no formal system of reporting imported cases in Europe, except from Germany. In non-endemic countries, including Poland, there is usually the substantial delay between the onset of symptoms and the final diagnosis, with an average exceeding 3 months. This fact suggests that physicians are not familiar with leishmania infections. Despite progress in vaccine development, the only way to prevent the infection is avoiding sandfly bites. Mosquito nets, wearing appropriate clothes and repellents containing DEET (diethyl toluamide) can reduce number of bites and protect also from the other vector-borne diseases like malaria or dengue. Education concerning kala-azar risk and ways of the disease prevention is a needed for tourists and the other travelers.

Differential Decline in Leishmania Membrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy

PubMed Central

Anam, Khairul; Afrin, Farhat; Banerjee, Dwijadas; Pramanik, Netai; Guha, Subhasis K.; Goswami, Rama P.; Saha, Shiben K.; Ali, Nahid

1999-01-01

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar. PMID:10569788

The Potential Use of Forensic DNA Methods Applied to Sand Fly Blood Meal Analysis to Identify the Infection Reservoirs of Anthroponotic Visceral Leishmaniasis.

PubMed

Inbar, Ehud; Lawyer, Philip; Sacks, David; Podini, Daniele

2016-05-01

In the Indian sub-continent, visceral leishmaniasis (VL), also known as kala azar, is a fatal form of leishmaniasis caused by the kinetoplastid parasite Leishmania donovani and transmitted by the sand fly Phlebotomus argentipes. VL is prevalent in northeast India where it is believed to have an exclusive anthroponotic transmission cycle. There are four distinct cohorts of L. donovani exposed individuals who can potentially serve as infection reservoirs: patients with active disease, cured VL cases, patients with post kala azar dermal leishmaniasis (PKDL), and asymptomatic individuals. The relative contribution of each group to sustaining the transmission cycle of VL is not known. To answer this critical epidemiological question, we have addressed the feasibility of an approach that would use forensic DNA methods to recover human DNA profiles from the blood meals of infected sand flies that would then be matched to reference DNA sampled from individuals living or working in the vicinity of the sand fly collections. We found that the ability to obtain readable human DNA fingerprints from sand flies depended entirely on the size of the blood meal and the kinetics of its digestion. Useable profiles were obtained from most flies within the first 24 hours post blood meal (PBM), with a sharp decline at 48 hours and no readable profiles at 72 hours. This early time frame necessitated development of a sensitive, nested-PCR method compatible with detecting L. donovani within a fresh, 24 hours blood meal in flies fed on infected hamsters. Our findings establish the feasibility of the forensic DNA method to directly trace the human source of an infected blood meal, with constraints imposed by the requirement that the flies be recovered for analysis within 24 hours of their infective feed.

A report on the indoor residual spraying (IRS) in the control of Phlebotomus argentipes, the vector of visceral leishmaniasis in Bihar (India): an initiative towards total elimination targeting 2015 (Series-1).

PubMed

Kumar, V; Kesari, S; Dinesh, D S; Tiwari, A K; Kumar, A J; Kumar, R; Singh, V P; Das, P

2009-09-01

Visceral leishmaniasis, commonly known as kala-azar is endemic in Bihar state, India. Current vector control programme in Bihar focuses mainly on spraying the sandfly infested dwellings with DDT. The Government of India in collaboration with WHO has fixed the target 2015 for total elimination of kala-azar. The present study was carried out to see the impact of DDT and improved IEC in the containment of vector density vis-à-vis disease transmission. Before the start of the spraying operations training was imparted to all the medical and paramedical personnel regarding the methods of spraying operations. Pre- and post-sandfly density was monitored in four selected districts. Incidences of kala-azar cases were compared for pre- and post-spray periods. Social acceptability and perceptions of households was collected through questionnaires from 500 randomly selected households in the study districts. House index in three study districts reduced considerably during post-spray when compared to pre-spray. Kala-azar incidence in many districts was reduced after the DDT spray. Either partial or complete refusal was reported in 14.4%, while 35% were not satisfied with the suspension concentration and coverage; and 46.6% were found satisfied with the spraying procedure. Strengthening the IEC activities to sensitise the community, proper training of health personnel, monitoring of spray, good surveillance, proper treatment of cases and two rounds of DDT spray with good coverage in the endemic districts up to three years are essential to achieve the desired total elimination of kala-azar in Bihar state.

Immunotherapy and Immunochemotherapy in Visceral Leishmaniasis: Promising Treatments for this Neglected Disease

PubMed Central

Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Coura-Vital, Wendel; Ker, Henrique Gama; Moreira, Nádia das Dores; Vitoriano-Souza, Juliana; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa

2014-01-01

Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; visceral leishmaniasis (VL), which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. Human immunodeficiency virus infection augments the severity of VL increasing the risk of developing active disease by 100–2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10) or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand) has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease. PMID:24982655

Risk Zone Modelling and Early Warning System for Visceral Leishmaniasis Kala-Azar Disease in Bihar, India Using Remote Sensing and GIS

NASA Astrophysics Data System (ADS)

Jeyaram, A.; Kesari, S.; Bajpai, A.; Bhunia, G. S.; Krishna Murthy, Y. V. N.

2012-07-01

Visceral Leishmaniasis (VL) commonly known as Kala-azar is one of the most neglected tropical disease affecting approximately 200 million poorest populations 'at risk in 109 districts of three endemic countries namely Bangladesh, India and Nepal at different levels. This tropical disease is caused by the protozoan parasite Leishmania donovani and transmitted by female Phlebotomus argentipes sand flies. The analysis of disease dynamics indicate the periodicity at seasonal and inter-annual temporal scale which forms the basis for development of advanced early warning system. Study area of highly endemic Vaishali district, Bihar, India has been taken for model development. A Systematic study of geo-environmental parameters derived from satellite data in conjunction with ground intelligence enabled modelling of infectious disease and risk villages. High resolution Indian satellites data of IRS LISS IV (multi-spectral) and Cartosat-1 (Pan) have been used for studying environmentally risk parameters viz. peri-domestic vegetation, dwelling condition, wetland ecosystem, cropping pattern, Normalised Difference Vegetation Index (NDVI), detailed land use etc towards risk assessment. Univariate analysis of the relationship between vector density and various land cover categories and climatic variables suggested that all the variables are significantly correlated. Using the significantly correlated variables with vector density, a seasonal multivariate regression model has been carried out incorporating geo-environmental parameters, climate variables and seasonal time series disease parameters. Linear and non-linear models have been applied for periodicity and interannual temporal scale to predict Man-hour-density (MHD) and 'out-of-fit' data set used for validating the model with reasonable accuracy. To improve the MHD predictive approach, fuzzy model has also been incorporated in GIS environment combining spatial geo-environmental and climatic variables using fuzzy membership

[Uncommon cutaneous presentation of visceral Leishmaniasis associated with HIV].

PubMed

Cossart, C; Le Moal, G; Garcia, M; Frouin, E; Hainaut-Wierzbicka, E; Roblot, F

2016-12-01

Visceral leishmaniasis is not normally expressed in skin. Herein, we describe the case of an HIV-positive patient who developed two unusual skin manifestations during an episode of visceral leishmaniasis. A 48-year-old female patient consulted initially for infiltrated purpura of all four limbs. Skin biopsy revealed leukocytoclastic vasculitis with Leishman-Donovan bodies. Laboratory tests showed medullary, splenic, gastric and colic involvement, suggesting systemic disease, and enabling visceral leishmaniasis to be diagnosed. Two years later, despite prolonged treatment, the patient presented maculopapular exanthema, and histology revealed persistent Leishman-Donovan bodies. We report herein an association of two rare skin manifestations in an HIV-positive patient with visceral leishmaniasis: infiltrated purpura and maculopapular exanthema. However, the underlying mechanisms remain hypothetical. The initial leukocytoclastic exanthema could be secondary to either polyclonal hypergammaglobulinaemia or to IgA deposits, or possibly to mechanical impairment of blood vessels by the actual parasite. The maculopapular exanthema occurring later raised the possibility of post-Kala-Azar leishmaniasis due to blood-borne dissemination in an anergic subject or perhaps even immune reconstitution inflammatory syndrome. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Development of monoclonal antibodies against axenic amastigotes of Leishmania infantum strain in Iran: implication for diagnosis of Kala-azar

PubMed Central

Nourizadeh, Ezzat; Zargar, Seyed Jalal; Alimohammadian, Mohammad Hossein; Ajdary, Soheila; Mahdavi, Mahdi

2018-01-01

Objective(s): Leishmaniasis is endemic in 88 countries. Amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection. Monoclonal antibodies are key reagents used in the diagnosis of infectious and non-infectious diseases. The aim of this study was to produce monoclonal antibodies against axenic amastigotes of the Leishmania infantum strain in Iran. Materials and Methods: First, standard strains were cultured and axenic amastigote antigens of L. infantum were obtained. Since then, BALB/c smice were immunized and antibody titers were determined. For hybridoma cell formation, lymphocytes isolated from spleen of immunized mice and myeloma cells were fused at a ratio of 10 to 1 in the presence of polyethylene glycol, followed by limiting dilution for the isolation of monoclones. Subsequently, antibody isotypes were determined by using the isotyping kit. The best clone was injected intraperitoneally to pristane-primed mice for large scale production of monoclonal antibodies. The specificity of antibody was determined with Western blotting. Results: Approximately 25 positive monoclones were obtained, of which four hybrids producing anti-amastigotes L. infantum monoclonal antibodies with high optical density (OD), selected and designated as 8D2 FVI6, 8D2 FVI3, 6G2 FV4 and 6G2 FV3. Results from isotype determination showed the IgG2b sub-class in 6G2FV2 and 8D2FVI6 monoclones. Conclusion: This study produced monoclonal antibody against amastigotes of Iranian strain of L. infantum for the first time. These antibodies have reactivity against Iranian strain of L. infantum and can be used in the diagnosis of Kala-azar.

Visceral Leishmaniasis: Advancements in Vaccine Development via Classical and Molecular Approaches

PubMed Central

Joshi, Sumit; Rawat, Keerti; Yadav, Narendra Kumar; Kumar, Vikash; Siddiqi, Mohammad Imran; Dube, Anuradha

2014-01-01

Visceral leishmaniasis (VL) or kala-azar, a vector-borne protozoan disease, shows endemicity in larger areas of the tropical, subtropical and the Mediterranean countries. WHO report suggested that an annual incidence of VL is nearly 200,000 to 400,000 cases, resulting in 20,000 to 30,000 deaths per year. Treatment with available anti-leishmanial drugs are not cost effective, with varied efficacies and higher relapse rate, which poses a major challenge to current kala-azar control program in Indian subcontinent. Therefore, a vaccine against VL is imperative and knowing the fact that recovered individuals developed lifelong immunity against re-infection, it is feasible. Vaccine development program, though time taking, has recently gained momentum with the emergence of omic era, i.e., from genomics to immunomics. Classical as well as molecular methodologies have been overtaken with alternative strategies wherein proteomics based knowledge combined with computational techniques (immunoinformatics) speed up the identification and detailed characterization of new antigens for potential vaccine candidates. This may eventually help in the designing of polyvalent synthetic and recombinant chimeric vaccines as an effective intervention measures to control the disease in endemic areas. This review focuses on such newer approaches being utilized for vaccine development against VL. PMID:25202307

Cedrus deodara: In vitro antileishmanial efficacy & immumomodulatory activity

PubMed Central

Narayan, Shyam; Thakur, Chandreshwar Prasad; Bahadur, Shiv; Thakur, Meenakshi; Pandey, Shashi Nath; Thakur, Ajit Kumar; Mitra, Dipendra K.; Mukherjee, Pulok K.

2017-01-01

Background & objectives: The existing antileishmanial drugs for complete cure of visceral leishmaniasis (kala-azar) are limited. The available drugs are either toxic or less effective leading to disease relapse or conversion to post-kala-azar dermal leishmaniasis. Several herbal extracts have been shown to have antileishmanial activity, but a herbal drug may not always be safe. In the present study, the extract of Cedrus deodara leaves has been standardized and tested for immunomodulatory antileishmanial activities. Methods: The extracts of C. deodara leaves with different solvents such as benzene, chloroform, ethyl acetate and methanol were made by soxhlation process. Solvents were removed under reduced pressure and temperature using rotary evaporator. The antileishmanial bioassay test was performed with in vitro maintained parasites. Immunomodulatory activity of different extracts was tested by flow cytometry. Standardization of the effective fraction was performed with Linalool as a marker compound through reverse-phase high-performance liquid chromatography. Results: The extract with the use of benzene solvent showed strong antileishmanial activities within a dose 25-200 μg/ml culture with non-significant haemolytic activities and significant immunomodulant activities against the host cells. Linalool was found to be 1.29 per cent in the effective extract of C. deodara. Interpretation & conclusions: The antileishmanial activity of C. deodara, as assessed by bioassay testing on Leishmania donovani parasites and immunomodulatory effect of benzene extract of leaves on host cells indicated that it might be a potential new safe therapeutic target to cure the visceral leishmaniasis. PMID:29664038

Cedrus deodara: In vitro antileishmanial efficacy & immumomodulatory activity.

PubMed

Narayan, Shyam; Thakur, Chandreshwar Prasad; Bahadur, Shiv; Thakur, Meenakshi; Pandey, Shashi Nath; Thakur, Ajit Kumar; Mitra, Dipendra K; Mukherjee, Pulok K

2017-12-01

The existing antileishmanial drugs for complete cure of visceral leishmaniasis (kala-azar) are limited. The available drugs are either toxic or less effective leading to disease relapse or conversion to post-kala-azar dermal leishmaniasis. Several herbal extracts have been shown to have antileishmanial activity, but a herbal drug may not always be safe. In the present study, the extract of Cedrus deodara leaves has been standardized and tested for immunomodulatory antileishmanial activities. The extracts of C. deodara leaves with different solvents such as benzene, chloroform, ethyl acetate and methanol were made by soxhlation process. Solvents were removed under reduced pressure and temperature using rotary evaporator. The antileishmanial bioassay test was performed with in vitro maintained parasites. Immunomodulatory activity of different extracts was tested by flow cytometry. Standardization of the effective fraction was performed with Linalool as a marker compound through reverse-phase high-performance liquid chromatography. The extract with the use of benzene solvent showed strong antileishmanial activities within a dose 25-200 μg/ml culture with non-significant haemolytic activities and significant immunomodulant activities against the host cells. Linalool was found to be 1.29 per cent in the effective extract of C. deodara. The antileishmanial activity of C. deodara, as assessed by bioassay testing on. parasites and immunomodulatory effect of benzene extract of leaves on host cells indicated that it might be a potential new safe therapeutic target to cure the visceral leishmaniasis.

Genetically modified organisms and visceral leishmaniasis.

PubMed

Chhajer, Rudra; Ali, Nahid

2014-01-01

Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniasis namely cutaneous (CL), mucocutaneous (ML), and visceral (VL), caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein, or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.

Status of vaccine research and development of vaccines for leishmaniasis.

PubMed

Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

2016-06-03

A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Species Typing in Dermal Leishmaniasis

PubMed Central

Dujardin, Jean-Claude

2015-01-01

SUMMARY Leishmania is an infectious protozoan parasite related to African and American trypanosomes. All Leishmania species that are pathogenic to humans can cause dermal disease. When one is confronted with cutaneous leishmaniasis, identification of the causative species is relevant in both clinical and epidemiological studies, case management, and control. This review gives an overview of the currently existing and most used assays for species discrimination, with a critical appraisal of the limitations of each technique. The consensus taxonomy for the genus is outlined, including debatable species designations. Finally, a numerical literature analysis is presented that describes which methods are most used in various countries and regions in the world, and for which purposes. PMID:25672782

Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion

PubMed Central

Nath, Proggananda; Harada, Michiyo; Sarkar, Santana; Selim, Shahjada; Maude, Richard J; Noiri, Eisei; Faiz, Abul

2014-01-01

Liposomal amphotericin-B (AmBisome) is now becoming first choice for the treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and less toxicity. The reported incidence of hypersensitivity reactions to liposomal amphotericin-B (AmBisome), especially during therapy, is very rare. We report two patients with kala-azar: one developed breathing difficulties and hypotension followed by shock and the other had facial angioedema with chest tightness during treatment. Both patients were managed with immediate action of injection: adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can cause severe hypersensitivity reactions that warrant proper support and close supervision. PMID:25139411

Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

PubMed Central

Boelaert, Marleen; Matlashewski, Greg; Mondal, Dinesh; Arana, Byron; Kroeger, Axel; Olliaro, Piero

2016-01-01

Background As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ Principal Finding We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. Conclusion/ Significance There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection. PMID:27490264

Viability and Burden of Leishmania in Extralesional Sites during Human Dermal Leishmaniasis

PubMed Central

Romero, Ibeth; Téllez, Jair; Suárez, Yazmín; Cardona, Maria; Figueroa, Roger; Zelazny, Adrian; Gore Saravia, Nancy

2010-01-01

Background The clinical and epidemiological significance of Leishmania DNA in extralesional sites is obscured by uncertainty of whether the DNA derives from viable parasites. To examine dissemination of Leishmania during active disease and the potential participation of human infection in transmission, Leishmania 7SLRNA was exploited to establish viability and estimate parasite burden in extralesional sites of dermal leishmaniasis patients. Methods The feasibility of discriminating parasite viability by PCR of Leishmania 7SLRNA was evaluated in relation with luciferase activity of luc transfected intracellular amastigotes in dose-response assays of Glucantime cytotoxicity. Monocytes, tonsil swabs, aspirates of normal skin and lesions of 28 cutaneous and 2 mucocutaneous leishmaniasis patients were screened by kDNA amplification/Southern blot. Positive samples were analyzed by quantitative PCR of Leishmania 7SLRNA genes and transcripts. Results 7SLRNA amplification coincided with luciferase activity, confirming discrimination of parasite viability. Of 22 patients presenting kDNA in extralesional samples, Leishmania 7SLRNA genes or transcripts were detected in one or more kDNA positive samples in 100% and 73% of patients, respectively. Gene and transcript copy number amplified from extralesional tissues were comparable to lesions. 7SLRNA transcripts were detected in 13/19 (68%) monocyte samples, 5/12 (42%) tonsil swabs, 4/11 (36%) normal skin aspirates, and 22/25 (88%) lesions; genes were quantifiable in 15/19 (79%) monocyte samples, 12/13 (92%) tonsil swabs, 8/11 (73%) normal skin aspirates. Conclusion Viable parasites are present in extralesional sites, including blood monocytes, tonsils and normal skin of dermal leishmaniasis patients. Leishmania 7SLRNA is an informative target for clinical and epidemiologic investigations of human leishmaniasis. PMID:20856851

Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion.

PubMed

Nath, Proggananda; Basher, Ariful; Harada, Michiyo; Sarkar, Santana; Selim, Shahjada; Maude, Richard J; Noiri, Eisei; Faiz, Abul

2014-10-01

Liposomal amphotericin-B (AmBisome) is now becoming first choice for the treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and less toxicity. The reported incidence of hypersensitivity reactions to liposomal amphotericin-B (AmBisome), especially during therapy, is very rare. We report two patients with kala-azar: one developed breathing difficulties and hypotension followed by shock and the other had facial angioedema with chest tightness during treatment. Both patients were managed with immediate action of injection: adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can cause severe hypersensitivity reactions that warrant proper support and close supervision. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Visceral Leishmaniasis in Ethiopia: An Evolving Disease

PubMed Central

Leta, Samson; Dao, Thi Ha Thanh; Mesele, Frehiwot; Alemayehu, Gezahegn

2014-01-01

Visceral leishmaniasis (also known as kala-azar) is classified as one of the most neglected tropical diseases. It is becoming a growing health problem in Ethiopia, with endemic areas that are continually spreading. The annual burden of visceral leishmaniasis (VL) in Ethiopia is estimated to be between 4,500 and 5,000 cases, and the population at risk is more than 3.2 million. There has been a change in the epidemiology of VL in Ethiopia. Over the last decades, almost all cases and outbreaks of VL were reported from arid and semi-arid parts of the country; however, recent reports indicated the introduction of this disease into the highlands. Migration of labourers to and from endemic areas, climatic and environmental changes, and impaired immunity due to HIV/AIDS and malnutrition resulted in the change of VL epidemiology. HIV spurs the spread of VL by increasing the risk of progression from asymptomatic infection towards full VL. Conversely, VL accelerates the onset of AIDS. In Ethiopia, VL epidemiology remains complex because of the diversity of risk factors involved, and its control is becoming an increasing challenge. This paper reviews the changes in epidemiology of VL in Ethiopia and discusses some of the possible explanations for these changes. The prospects for novel approaches to VL control are discussed, as are the current and future challenges facing Ethiopia's public health development program. PMID:25188253

Disseminated Autochthonous Dermal Leishmaniasis Caused by Leishmania siamensis (PCM2 Trang) in a Patient from Central Thailand Infected with Human Immunodeficiency Virus.

PubMed

Supsrisunjai, Chavalit; Kootiratrakarn, Tanawatt; Puangpet, Pailin; Bunnag, Thareena; Chaowalit, Prapaipit; Wessagowit, Vesarat

2017-05-01

AbstractSeveral case reports of autochthonous leishmaniasis in Thailand have been published since 1996. Most of the previous cases presented with visceral leishmaniasis (VL) and were mostly reported in southern part of Thailand. Recently, it has been evident that Leishmania martiniquensis is the main cause of Leishmania infection in Thailand. However, Leishmania siamensis (PCM2 Trang isolate) was found to be of a separate lineage with restricted distribution in southern Thailand and also a cause of disseminated dermal and visceral leishmaniasis in one published case. Here we report the first patient from central Thailand with human immunodeficiency virus infection presenting with disseminated dermal leishmaniasis. Polymerase chain reaction and DNA sequencing analysis (large subunit of RNA polymerase II and 18S ribosomal RNA internal transcribed spacer 1) from the tissue biopsy sample revealed the pathogen sequences to be highly homologous to PCM2 Trang strain previously reported from southern Thailand.

Disseminated Autochthonous Dermal Leishmaniasis Caused by Leishmania siamensis (PCM2 Trang) in a Patient from Central Thailand Infected with Human Immunodeficiency Virus

PubMed Central

Supsrisunjai, Chavalit; Kootiratrakarn, Tanawatt; Puangpet, Pailin; Bunnag, Thareena; Chaowalit, Prapaipit; Wessagowit, Vesarat

2017-01-01

Several case reports of autochthonous leishmaniasis in Thailand have been published since 1996. Most of the previous cases presented with visceral leishmaniasis (VL) and were mostly reported in southern part of Thailand. Recently, it has been evident that Leishmania martiniquensis is the main cause of Leishmania infection in Thailand. However, Leishmania siamensis (PCM2 Trang isolate) was found to be of a separate lineage with restricted distribution in southern Thailand and also a cause of disseminated dermal and visceral leishmaniasis in one published case. Here we report the first patient from central Thailand with human immunodeficiency virus infection presenting with disseminated dermal leishmaniasis. Polymerase chain reaction and DNA sequencing analysis (large subunit of RNA polymerase II and 18S ribosomal RNA internal transcribed spacer 1) from the tissue biopsy sample revealed the pathogen sequences to be highly homologous to PCM2 Trang strain previously reported from southern Thailand. PMID:28138050

Paying for hospital-based care of Kala-azar in Nepal: assessing catastrophic, impoverishment and economic consequences.

PubMed

Adhikari, Shiva R; Maskay, Nephil M; Sharma, Bishnu P

2009-03-01

Households obtaining health care services in developing countries incur substantial costs, despite services generally being provided free of charge by public health institutions. This constitutes an economic burden on low-income households, and contributes to deepening their level of poverty. In addition to the economic burden of obtaining health care, the method of financing these payments has implications for the distribution of household assets. This effect on resource-poor households is amplified since they have decreased access to health insurance. Recent literature, however, ignores the importance of the method of financing health care payments. This paper looks at the case of Nepal and highlights the impact on households of paying for hospital-based care of Kala-azar (KA) by analysing the catastrophic, impoverishment and economic consequences of their coping strategies. The paper utilizes micro-data on a random selection of 50% of the KA-affected households of Siraha and Saptari districts of Nepal. The empirical results suggest that direct costs of hospital-based treatment of KA are catastrophic since they consume 17% of annual household income. This expenditure causes more than 20% of KA-affected households to fall below the poverty line, with the remaining households being pushed into the category of marginal poor; the poverty gap ratio is more than 90%. Further, KA incidence can have prolonged and severe economic consequences for the household economy due to the mechanisms of informal sector financing to which households resort. A heavy burden of loan repayments can lead households on a downward spiral that eventually becomes a poverty trap. In other words, the method of financing health care payments is an important ingredient in understanding the economic burden of disease.

A review of visceral leishmaniasis during the conflict in South Sudan and the consequences for East African countries.

PubMed

Al-Salem, Waleed; Herricks, Jennifer R; Hotez, Peter J

2016-08-22

Visceral leishmaniasis (VL), caused predominantly by Leishmania donovani and transmitted by both Phlebotomus orientalis and Phlebotomus martini, is highly endemic in East Africa where approximately 30 thousands VL cases are reported annually. The largest numbers of cases are found in Sudan - where Phlebotomus orientalis proliferate in Acacia forests especially on Sudan's eastern border with Ethiopia, followed by South Sudan, Ethiopia, Somalia, Kenya and Uganda. Long-standing civil war and unrest is a dominant determinant of VL in East African countries. Here we attempt to identify the correlation between VL epidemics and civil unrest. In this review, literature published between 1955 and 2016 have been gathered from MSF, UNICEF, OCHA, UNHCR, PubMed and Google Scholar to analyse the correlation between conflict and human suffering from VL, which is especially apparent in South Sudan. Waves of forced migration as a consequence of civil wars between 1983 and 2005 have resulted in massive and lethal epidemics in southern Sudan. Following a comprehensive peace agreement, but especially with increased allocation of resources for disease treatment and prevention in 2011, cases of VL declined reaching the lowest levels after South Sudan declared independence. However, in the latest epidemic that began in 2014 after the onset of a civil war in South Sudan, more than 1.5 million displaced refugees have migrated internally to states highly endemic for VL, while 800,000 have fled to neighboring countries. We find a strong relationship between civil unrest and VL epidemics which tend to occur among immunologically naïve migrants entering VL-endemic areas and when Leishmania-infected individuals migrate to new areas and establish additional foci of disease. Further complicating factors in East Africa's VL epidemics include severe lack of access to diagnosis and treatment, HIV/AIDS co-infection, food insecurity and malnutrition. Moreover, cases of post-kala-azar dermal

Noninvasive Diagnosis of Visceral Leishmaniasis: Development and Evaluation of Two Urine-Based Immunoassays for Detection of Leishmania donovani Infection in India

PubMed Central

Ejazi, Sarfaraz Ahmad; Bhattacharya, Pradyot; Bakhteyar, Md. Asjad Karim; Mumtaz, Aquil Ahmad; Pandey, Krishna; Das, Vidya Nand Ravi; Das, Pradeep; Rahaman, Mehebubar; Goswami, Rama Prosad; Ali, Nahid

2016-01-01

Background Visceral Leishmaniasis (VL), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. Post kala-azar dermal leishmaniasis (PKDL), a skin related outcome, is a potential reservoir for the spread of VL. Diagnostic tests available for VL such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. Serological tests although less invasive than tissue aspiration are incompetent to assess cure. Parasitological examination of slit-skin smear along with the clinical symptoms is routinely used for diagnosis of PKDL. Therefore, a noninvasive test with acceptable sensitivity and competency, additionally, to decide cure would be an asset in disease management and control. Methodology/principal findings We describe here, the development of antibody-capture ELISA and field adaptable dipstick test as noninvasive diagnostic tools for VL and PKDL and as a test of cure in VL treatment. Sensitivity and specificity of urine-ELISA were 97.94% (95/97) and 100% (75/75) respectively, for VL. Importantly, dipstick test demonstrated 100% sensitivity (97/97) and specificity (75/75) in VL diagnosis. Degree of agreement of the two methods with tissue aspiration was 98.83% (κ = 0.97) and 100% (κ = 1), for ELISA and dipstick test, respectively. Both the tests had 100% positivity for PKDL (14/14) cases. ELISA and dipstick test illustrated treatment efficacy in about 90% (16/18) VL cases when eventually turned negative after six months of treatment. Conclusions/significance ELISA and dipstick test found immensely effective for diagnosis of VL and PKDL through urine samples thus, may substitute the existing invasive diagnostics. Utility of these tests as indirect methods of monitoring parasite clearance can define infected versus cured. Urine-based dipstick test is simple, sensitive and above all noninvasive method that may help not only in active VL case detection but also to ascertain treatment response

Leukodepletion Filters for Prevention of Transfusion Transmission Of Leishmania

DTIC Science & Technology

2006-11-01

living in an area of endemicity in southern France. J Clin Microbiol 1999; 37(6):1953-1957 18 Hillyer CD, Emmens RK, Zago -Novaretti M , Berkman EM...Kostmann R, Barr M , Bengtsson E, Garnham PCC, Hult G: Kala-azar transferred by exchange blood transfusions in two Swedish infants. Proceedings of the...Dabadie A, Guiguen C, Roussey M : Visceral leishmaniasis in an infant in Brittany: Discussion on the modes of transmission outside of the endemic

Further characterization of Chinese Leishmania isolates by isoenzyme electrophoresis.

PubMed

Xu, Z B; Liu, Z T; Long, J Y; Chai, J J; Chen, W K

1989-09-01

Ten Chinese Leishmania isolates from different endemic areas and hosts are characterized by isoenzyme electrophoresis for 9 enzymes. Seven were isolated from visceral leishmaniasis patients, one from an infected dog, one from a sandfly and one from a naturally infected racoon dog. Eight of the 10 isolates were indistinguishable in isoenzyme profile from the L infantum reference strain. The isoenzyme profiles of the remaining two isolates (from kala azar patients in Xinjiang) could not be characterized in this study and need further research.

Decision-making process of Kala Azar care: results from a qualitative study carried out in disease endemic areas of Nepal

PubMed Central

2013-01-01

Background Analysis of consumer decision making in the health sector is a complex process of comparing feasible alternatives and evaluating the levels of satisfaction associated with the relevant options. This paper makes an attempt to understand how and why consumers make specific decisions, what motivates them to adopt a specific health intervention, and what features they find attractive in each of the options. Method The study used a descriptive-explanatory design to analyze the factors determining the choices of healthcare providers. Information was collected through focus group discussions and in-depth interviews. Results The results suggest that the decision making related to seeking healthcare for Kala Azar (KA) treatment is a complex, interactive process. Patients and family members follow a well-defined road map for decision making. The process of decision making starts from the recognition of healthcare needs and is then modified by a number of other factors, such as indigenous knowledge, healthcare alternatives, and available resources. Household and individual characteristics also play important roles in facilitating the process of decision making. The results from the group discussions and in-depth interviews are consistent with the idea that KA patients and family members follow the rational approach of weighing the costs against the benefits of using specific types of medical care. Conclusion The process of decision making related to seeking healthcare follows a complex set of steps and many of the potential factors affect the decision making in a non-linear fashion. Our analysis suggests that it is possible to derive a generalized road map of the decision-making process starting from the recognition of healthcare needs, and then modifying it to show the influences of indigenous knowledge, healthcare alternatives, and available resources. PMID:23849617

Decision-making process of Kala Azar care: results from a qualitative study carried out in disease endemic areas of Nepal.

PubMed

Adhikari, Shiva Raj; Supakankunti, Siripen; Khan, M Mahmud

2013-07-12

Analysis of consumer decision making in the health sector is a complex process of comparing feasible alternatives and evaluating the levels of satisfaction associated with the relevant options. This paper makes an attempt to understand how and why consumers make specific decisions, what motivates them to adopt a specific health intervention, and what features they find attractive in each of the options. The study used a descriptive-explanatory design to analyze the factors determining the choices of healthcare providers. Information was collected through focus group discussions and in-depth interviews. The results suggest that the decision making related to seeking healthcare for Kala Azar (KA) treatment is a complex, interactive process. Patients and family members follow a well-defined road map for decision making. The process of decision making starts from the recognition of healthcare needs and is then modified by a number of other factors, such as indigenous knowledge, healthcare alternatives, and available resources. Household and individual characteristics also play important roles in facilitating the process of decision making. The results from the group discussions and in-depth interviews are consistent with the idea that KA patients and family members follow the rational approach of weighing the costs against the benefits of using specific types of medical care. The process of decision making related to seeking healthcare follows a complex set of steps and many of the potential factors affect the decision making in a non-linear fashion. Our analysis suggests that it is possible to derive a generalized road map of the decision-making process starting from the recognition of healthcare needs, and then modifying it to show the influences of indigenous knowledge, healthcare alternatives, and available resources.

Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species

PubMed Central

Obonaga, Ricardo; Fernández, Olga Lucía; Valderrama, Liliana; Rubiano, Luisa Consuelo; Castro, Maria del Mar; Barrera, Maria Claudia; Gomez, Maria Adelaida

2014-01-01

Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by Leishmania (Viannia) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six Leishmania (Viannia) braziliensis and six Leishmania (Viannia) panamensis strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults ≥55 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the Leishmania drug transporter genes abca2, abca3, abcc2, abcc3, abcg4, abcg6, and LbMT was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC50], 10.7 μmol/liter) were more susceptible to miltefosine than promastigotes (median EC50, 55.3 μmol/liter) (P < 0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC50 of >32 μmol/liter (the upper limit of intracellular amastigote assay), occurred in L. panamensis infection in a child and in L. braziliensis infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT/β-tubulin, 0.42- to 0.26-fold [P = 0.039] and 0.70- to 0.57-fold [P = 0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype. Leishmania ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (r = −0.605; P = 0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal

Elevated 2,3-diphosphoglycerate concentrations and alteration of structural integrity in the erythrocytes of Indian cases of visceral leishmaniasis.

PubMed

Biswas, T; Ghosh, D K; Mukherjee, N; Ghosal, J

1995-08-01

The visceral leishmaniasis (VL) known as kala-azar in India is characterized by severe anaemia. The anaemia seems to be the result, at least in part, of the relatively short life-time of the erythrocytes, which have weakened cell membranes, possibly because of elevated concentrations of 2,3-diphosphoglycerate (2,3-DPG). There is a negative correlation (r = 0.91; P < 0.01) between erythrocytic 2,3-DPG concentrations and the blood concentration of haemoglobin, and the erythrocytes from infected patients display higher osmotic fragility than those from uninfected controls. Spectrofluorometry, using 1,6-diphenyl 1,3,5-hexatriene as a probe, indicated that fluorescence depolarization and microviscosity are also higher in the erythrocytic membranes from VL cases than in those from the controls. The cholesterol/phospholipid ratio is also relatively high in the membranes from the VL cases and there is degradation of the skeletal components and the major integral protein (band 3). The enhanced concentration of 2,3-DPG may be related to the altered structural integrity of the erythrocytes and this may lead to anisocytosis and the reduction in the erythrocytic half life.

Spatial correlations of population and ecological factors with distribution of visceral leishmaniasis cases in southwestern Iran.

PubMed

Ghatee, Mohammad Amin; Sharifi, Iraj; Haghdoost, Ali Akbar; Kanannejad, Zahra; Taabody, Zahra; Hatam, Gholamreza; Abdollahipanah, Abbas

2013-09-01

Leishmaniasis as a dynamic disease may be markedly influenced by demographic and ecological factors. A geospatial information system study was developed to determine the distribution of visceral leishmaniasis (VL) cases in relation to population, climatic and environmental factors in Fars province, southwest of Iran. The dwelling addresses of 217 VL patients were obtained from hospital files. A hazard map produced by unifying buffers (5 km) around nomads travel routes (NTR) was developed to survey the effect of close proximity to NTR on the distribution of VL. Mean annual rainfall (MAR), mean annual temperature (MAT), four months temperature mean (T4), elevation, slope and landcover were climatic and environmental factors that have been analysed. Finally, data of dwelling foci were extracted from maps and analysed using logistic regression models. Close proximity to NTR was the most important factor influenced on the disease distribution. Climatic factors were in second rank. Among them, temperature especially T4 is the most effective variable and rainfall was also shown to be another effective climatic agent. Most cases of VL were reported from temperate and semiarid areas in western and central regions while arid condition was a confined factor. The environmental factor of landcovers including urban, dry farm and thin forest regions was revealed as the third rank effective factor. Altitude importance was only shown when its effect was studied independently from other factors. These findings present the distribution of VL in Fars province is influenced by combination of ecological and nomads demographical variables although closeness to NTR and nomads role in distribution and continuance of kala-azar are the most important factors.

Positive Influence of Behavior Change Communication on Knowledge, Attitudes, and Practices for Visceral Leishmaniasis/Kala-azar in India.

PubMed

Srinivasan, Raghavan; Ahmad, Tanwir; Raghavan, Vidya; Kaushik, Manisha; Pathak, Ramakant

2018-03-21

Visceral leishmaniasis (VL) is endemic to 54 districts in 4 states of India. Poor awareness of the disease and inappropriate health-seeking behavior are major challenges to eliminating the disease. Between February 2016 and March 2017, we implemented a behavior change communication (BCC) intervention in 33 districts of Bihar, 4 districts of Jharkhand, and 3 districts of West Bengal using a mix of channels, including group and interpersonal communication, to improve knowledge, attitudes, and practices of communities, frontline health workers, and opinion leaders. We conducted an impact assessment in October 2016, after the second indoor residual spraying (IRS) round, in Bihar and Jharkhand to evaluate the effect of the BCC intervention. Villages in 10 districts of Bihar and 4 districts in Jharkhand were selected for inclusion in the assessment. Selected villages were categorized as either intervention or control based on where project activities were conducted. Households were randomly selected proportional to caste composition, and interviewers surveyed the head of the household on whether the house was sprayed during the last IRS round and on knowledge, attitudes, and practices related to VL. We interviewed 700 households in intervention villages and 350 households in control villages and conducted correlation analysis to explore the association between IRS refusal and socioeconomic variables, and tested for association between IRS refusal and exposure to BCC activities. Odds ratios (ORs) were calculated. We reached an estimated 3.3 million contacts in Bihar and Jharkhand through the intervention's BCC activities. IRS refusal rates were significantly lower in intervention households than control households (mean=7.95% vs. 24.45%, respectively; OR, 0.27; 95% confidence interval [CI], 0.11 to 0.62; P <.001). Households in intervention villages were more aware than those in control villages that VL is spread by sand flies (68.4% vs. 7.4%, respectively; P <.001) and

Real-time PCR in detection and quantitation of Leishmania donovani for the diagnosis of Visceral Leishmaniasis patients and the monitoring of their response to treatment

PubMed Central

Ghosh, Prakash; Khan, Md. Anik Ashfaq; Duthie, Malcolm S.; Vallur, Aarthy C.; Picone, Alessandro; Howard, Randall F.; Reed, Steven G.

2017-01-01

Sustained elimination of Visceral Leishmaniasis (VL) requires the reduction and control of parasite reservoirs to minimize the transmission of Leishmania donovani infection. A simple, reproducible and definitive diagnostic procedure is therefore indispensable for the early and accurate detection of parasites in VL, Relapsed VL (RVL) and Post Kala-azar Dermal Leishmaniasis (PKDL) patients, all of whom are potential reservoirs of Leishmania parasites. To overcome the limitations of current diagnostic approaches, a novel quantitative real-time polymerase chain reaction (qPCR) method based on Taqman chemistry was devised for the detection and quantification of L. donovani in blood and skin. The diagnostic efficacy was evaluated using archived peripheral blood buffy coat DNA from 40 VL, 40 PKDL, 10 RVL, 20 cured VL, and 40 cured PKDL along with 10 tuberculosis (TB) cases and 80 healthy endemic controls. Results were compared to those obtained using a Leishmania-specific nested PCR (Ln-PCR). The real time PCR assay was 100% (95% CI, 91.19–100%) sensitive in detecting parasite genomes in VL and RVL samples and 85.0% (95% CI, 70.16–94.29%) sensitive for PKDL samples. In contrast, the sensitivity of Ln-PCR was 77.5% (95% CI, 61.55–89.16%) for VL samples, 100% (95%CI, 69.15–100%) for RVL samples, and 52.5% (95% CI, 36.13–68.49%) for PKDL samples. There was significant discordance between the two methods with the overall sensitivity of the qPCR assay being considerably higher than Ln-PCR. None of the assay detected L. donovani DNA in buffy coats from cured VL cases, and reduced infectious burdens were demonstrated in cured PKDL cases who remained positive in 7.5% (3/40) and 2.5% (1/40) cases by real-time PCR and Ln-PCR, respectively. Both assays were 100% (95% CI, 95.98–100) specific with no positive signals in either endemic healthy control or TB samples. The real time PCR assay we developed offers a molecular tool for accurate detection of circulating L

Molecular and Serological Evidence of Leishmania Infection in Stray Dogs from Visceral Leishmaniasis-Endemic Areas of Bangladesh.

PubMed

Akter, Shirin; Alam, Mohammad Zahangir; Nakao, Ryo; Yasin, Golam; Kato, Hirotomo; Katakura, Ken

2016-10-05

Visceral leishmaniasis (VL), or kala-azar, is mainly caused by two closely related Leishmania species, Leishmania infantum and Leishmania donovani Leishmania infantum is responsible for zoonotic VL, with dogs as the main reservoir host in the Mediterranean, the Middle East, Asia, and South America. In the Indian subcontinent, VL is caused by L. donovani and is considered anthroponotic, although the only known vector, the sand fly, is zoophilic in nature. The role of domestic and stray dogs in VL transmission is still unclear in this area. We screened 50 stray dogs from VL-endemic areas of Bangladesh for serological and molecular evidence of Leishmania infection. We detected anti-Leishmania antibodies in six (12%) dog serum samples using rK39 immunochromatographic tests. We observed Leishmania kinetoplast DNA in 10 (20%) buffy coat DNA samples by real-time polymerase chain reaction (PCR), five of which were positive based on internal transcribed spacer 1-PCR. A sequencing analysis of the amplified products confirmed that the parasitic DNA was derived from L. donovani Our findings support the hypothesis that stray dogs are an animal reservoir for L. donovani in this endemic region. Further studies are required to determine the precise role of dogs in the epidemiology of VL in Bangladesh. © The American Society of Tropical Medicine and Hygiene.

Serological Survey and Associated Risk Factors of Visceral Leish-maniasis in Qom Province, Central Iran.

PubMed

Rakhshanpour, Arash; Mohebali, Mehdi; Akhondi, Behnaz; Rahimi, Mohammad Taghi; Rokni, Mohammad Bagher

2014-01-01

Visceral leishmaniasis (VL) or kala-azar is considered as a parasitic disease caused by the species of Leishmania donovani complex which is intracellular parasites. This systemic disease is endemic in some parts of provinc-es of Iran. The aim of this study was to determine the seroprevalence of VL in Qom Province, central Iran using di-rect agglutination test (DAT). Overall, 1564 serum samples (800 males and 764 females) were collected from selected subjects by random-ized cluster sampling in 2011-2012. Sera were tested and analyzed by DAT. Before sampling; a questionnaire was filled out for each case. Data were analyzed using Chi-square test and multivariate logistic regression for risk factors analysis. Of 1564 individuals, 53 cases (3.38%) showed Leishmania specific antibodies as follows: with 1:400 titer 16 cases (1.02%), with 1:800 titer 20 cases (1.27%), with 1:1600 titer 16 cases (1.02%) whereas only one subject (0.06%) showed titers of ≥ 1:3200. There was no significant association between VL seropositivity and gender, age group and occupation. Binary logistic regression showed that rural areas was 0.44 times at higher risk of infection than urban areas (OR= 0.44; %95 CI= 0.25- 0.78). Although the seroprevalence of VL is relatively low in Qom Province, yet due to the importance of the disease, the surveillance system should be monitored by health authorities.

Serological Survey and Associated Risk Factors of Visceral Leish-maniasis in Qom Province, Central Iran

PubMed Central

RAKHSHANPOUR, Arash; MOHEBALI, Mehdi; AKHONDI, Behnaz; RAHIMI, Mohammad Taghi; ROKNI, Mohammad Bagher

2014-01-01

Abstract Background Visceral leishmaniasis (VL) or kala-azar is considered as a parasitic disease caused by the species of Leishmania donovani complex which is intracellular parasites. This systemic disease is endemic in some parts of provinc-es of Iran. The aim of this study was to determine the seroprevalence of VL in Qom Province, central Iran using di-rect agglutination test (DAT). Methods Overall, 1564 serum samples (800 males and 764 females) were collected from selected subjects by random-ized cluster sampling in 2011-2012. Sera were tested and analyzed by DAT. Before sampling; a questionnaire was filled out for each case. Data were analyzed using Chi-square test and multivariate logistic regression for risk factors analysis. Results Of 1564 individuals, 53 cases (3.38%) showed Leishmania specific antibodies as follows: with 1:400 titer 16 cases (1.02%), with 1:800 titer 20 cases (1.27%), with 1:1600 titer 16 cases (1.02%) whereas only one subject (0.06%) showed titers of ≥ 1:3200. There was no significant association between VL seropositivity and gender, age group and occupation. Binary logistic regression showed that rural areas was 0.44 times at higher risk of infection than urban areas (OR= 0.44; %95 CI= 0.25- 0.78). Conclusion Although the seroprevalence of VL is relatively low in Qom Province, yet due to the importance of the disease, the surveillance system should be monitored by health authorities. PMID:26060679

Leishmania and human immunodeficiency virus coinfection: the first 10 years.

PubMed Central

Alvar, J; Cañavate, C; Gutiérrez-Solar, B; Jiménez, M; Laguna, F; López-Vélez, R; Molina, R; Moreno, J

1997-01-01

Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack

Inaccuracy of Enzyme-Linked Immunosorbent Assay Using Soluble and Recombinant Antigens to Detect Asymptomatic Infection by Leishmania infantum

PubMed Central

Moreno, Elizabeth Castro; Gonçalves, Andréa Vieira; Chaves, Anderson Vieira; Melo, Maria Norma; Lambertucci, José Roberto; Andrade, Antero Silva Ribeiro; Negrão-Corrêa, Deborah; Antunes, Carlos Mauricio de Figueiredo; Carneiro, Mariângela

2009-01-01

Background One of the most important drawbacks in visceral leishmaniasis (VL) population studies is the difficulty of diagnosing asymptomatic carriers. The aim of this study, conducted in an urban area in the Southeast of Brazil, was to evaluate the performance of serology to identify asymptomatic VL infection in participants selected from a cohort with a two-year follow-up period. Methodology Blood samples were collected in 2001 from 136 cohort participants (97 positive and 39 negatives, PCR/hybridization carried out in 1999). They were clinically evaluated and none had progressed to disease from their asymptomatic state. As controls, blood samples from 22 control individuals and 8 patients with kala-azar were collected. Two molecular biology techniques (reference tests) were performed: PCR with Leishmania-generic primer followed by hybridization using L. infantum probe, and PCR with specific primer to L. donovani complex. Plasma samples were tested by ELISA using three different antigens: L. infantum and L. amazonensis crude antigens, and rK39 recombinant protein. Accuracy of the serological tests was evaluated using sensitivity, specificity, likelihood ratio and ROC curve. Findings The presence of Leishmania was confirmed, by molecular techniques, in all kala-azar patients and in 117 (86%) of the 136 cohort participants. Kala-azar patients showed high reactivity in ELISAs, whereas asymptomatic individuals presented low reactivity against the antigens tested. When compared to molecular techniques, the L. amazonensis and L. infantum antigens showed higher sensitivity (49.6% and 41.0%, respectively) than rK39 (26.5%); however, the specificity of rK39 was higher (73.7%) than L. amazonensis (52.6%) and L. infantum antigens (36.8%). Moreover, there was low agreement among the different antigens used (kappa<0.10). Conclusions Serological tests were inaccurate for diagnosing asymptomatic infections compared to molecular methods; this could lead to misclassification bias

Development of a rapid loop-mediated isothermal amplification assay for diagnosis and assessment of cure of Leishmania infection.

PubMed

Verma, Sandeep; Singh, Ruchi; Sharma, Vanila; Bumb, Ram Avtar; Negi, Narendra Singh; Ramesh, V; Salotra, Poonam

2017-03-23

Leishmaniasis is a spectrum of diseases with great relevance to public health. Conventional diagnostic methods are time consuming, needing trained personnel. A robust, rapid and cost effective diagnostic test is warranted for on-time diagnosis and field application. We have developed a loop mediated isothermal amplification (LAMP) assay with primers (n = 6) based on Leishmania donovani kDNA for detection of Leishmania infection, using a closed tube to prevent cross-contamination. The assay was used to detect Leishmania infection in biological samples obtained from patients of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL). The assay was positive for L. donovani, L. tropica and L. major parasites, with the highest sensitivity towards L. donovani (1 fg DNA). The high sensitivity of the assay for detection of L. donovani was reflected in its ability to detect parasite DNA within 30 min of amplification time with a threshold detection limit of ≥25 copies per reaction. The assay detected parasite in 64 of 66 VL blood samples (sensitivity, 96.9%; 95% CI: 89.6-99.2%), 15 of 15 VL bone marrow aspirate samples (sensitivity, 100%; 95% CI:79.6-100%), 65 of 67 PKDL tissue biopsy samples (sensitivity, 97%; 95% CI:89.7-99.2%). The assay was evaluated in a few cases of CL wherein it was found positive in 8 of 10 tissue biopsies (sensitivity, 80%; 95% CI: 49-94.3%). The assay was negative in all control blood (n = 76) and tissue biopsy (n = 24) samples (specificity, 100%; 95% CI: 96.3-100%). Further, the assay was evaluated for its utility in assessment of cure in treated VL and PKDL patients. The assay detected parasite DNA in 2 of 20VL blood samples and 2 of 21 PKDL tissue samples. Out of 4 cases that were positive for parasite DNA at post treatment stage, 2 patients (1VL and 1 PKDL) returned with relapse. The study demonstrated a Leishmania genus specific closed tube LAMP assay for reliable and rapid

Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India

PubMed Central

Jaiswal, Priyank; Datta, Souvik; Sardar, Bikash; Chaudhuri, Surya Jyoti; Maji, Dipankar; Ghosh, Manab; Saha, Bibhuti

2018-01-01

Background Post Kala Azar Dermal Leishmaniasis (PKDL) occurs as dermal consequence of previous Visceral Leishmaniasis (VL) infection and serves as an important reservoir for transmission of VL. Diagnosis of PKDL is often challenging for its symptomatic resemblance to other co-endemic diseases like Leprosy or Vitiligo. Parasitological examination by slit-skin smear and culture are the standard methods but lack high sensitivity. Thus, for efficient control of VL, reliable diagnostic and prognostic assay of PKDL are required. Objective Previously, glycoproteins (9-OAcSA) have been reported as promising biomarkers of Indian VL patients. However, till date, the status of glycans in Indian PKDL patients remains unexplored. Accordingly, in this study, the glyco-profile of PKDL Circulating Immune Complexes (CICs) as compared to other cross diseases like Vitiligo and Leprosyhas been investigated. Further, a novel Glyco CIC assay has been developed for efficient Indian PKDL patient diagnosis. Methods/principal finding In the present study, 90 PKDL patients were enrolled from 3 VL endemic districts of West Bengal during 2015–16. Glycosylation profile of isolated CICs from sera of PKDL patients were initially analyzed through gradient SDS gel electrophoresis followed by PAS silver double staining, which revealed the presence of several glycan rich PKDL specific proteins of varying molecular weights. To further characterize the glyco-profile of acid dissociated affinity purified immuno-reactive antigens present in the CICs, glycosylation was demonstrated in these purified CIC antigens by DIG glycan differentiation kit with or without glycosidase as well as neuraminidase treatment. Diagnostic evaluation of the newly developed colorimetric Glyco CIC assay through Receiver Operating Characteristic (ROC) curve analysis revealed excellent (0.99) AUC value as compared to other conventional serodiagnostic assays like PEG CIC, Parasite ELISA (IgG and IgM). Additionally, longitudinal

Therapeutic immunization with radio-attenuated Leishmania parasites through i.m. route revealed protection against the experimental murine visceral leishmaniasis.

PubMed

Datta, Sanchita; Manna, Madhumita; Khanra, Supriya; Ghosh, Moumita; Bhar, Radhaballav; Chakraborty, Anindita; Roy, Syamal

2012-07-01

After our promising results from prophylactic and therapeutic study (i.p. route) with the radio-attenuated Leishmania donovani parasites against experimental murine visceral leishmaniasis, we prompted to check their therapeutic efficacy through i.m route. BALB/c mice were infected with highly virulent L. donovani parasites. After 75 days, mice were treated with gamma (γ)-irradiated parasites. A second therapeutic immunization was given after 15 days of first immunization. The protection against kala-azar was estimated with the reduction of Leishman-Donovan unit from spleen and liver that scored up to 80% and 93%, respectively, while a twofold increase in nitric oxide (NO) and reactive oxygen species (ROS) productions has been observed in the immunized groups of animals. These groups of mice also showed disease regression by skewing Th2 cytokines (IL-10) towards Th1 cytokine (IFN-γ) bias along with the increased generation of NO and ROS, while the infected control group of mice without such treatment surrendered to the disease. Establishment of Th1 ambience in the treated groups has also been supported from the measured antileishmanial antibody IgG subsets (IgG2a and IgG1) with higher anti-soluble Leishmania antigen-specific IgG2a titer. As seen in our previous studies, doses of attenuation by γ-radiation should be taken into serious consideration. Attenuation of parasites at 50 Gy of absorbed dose of gamma rays has not worked well. Thus, therapeutic use of L. donovani parasites radio-attenuated at particular doses can be exploited as a promising vaccine agent. Absence of any adjuvant may increase its acceptability as vaccine candidate further.

How effective is dog culling in controlling zoonotic visceral leishmaniasis? A critical evaluation of the science, politics and ethics behind this public health policy.

PubMed

Costa, Carlos Henrique Nery

2011-01-01

Zoonotic kala-azar, a lethal disease caused by protozoa of the genus Leishmania is considered out of control in parts of the world, particularly in Brazil, where transmission has spread to cities throughout most of the territory and mortality presents an increasing trend. Although a highly debatable measure, the Brazilian government regularly culls seropositive dogs to control the disease. Since control is failing, critical analysis concerning the actions focused on the canine reservoir was conducted. In a review of the literature, a historical perspective focusing mainly on comparisons between the successful Chinese and Soviet strategies and the Brazilian approach is presented. In addition, analyses of the principal studies regarding the role of dogs as risk factors to humans and of the main intervention studies regarding the efficacy of the dog killing strategy were undertaken. Brazilian political reaction to a recently published systematic review that concluded that the dog culling program lacked efficiency and its effect on public policy were also reviewed. No firm evidence of the risk conferred by the presence of dogs to humans was verified; on the contrary, a lack of scientific support for the policy of killing dogs was confirmed. A bias for distorting scientific data towards maintaining the policy of culling animals was observed. Since there is no evidence that dog culling diminishes visceral leishmaniasis transmission, it should be abandoned as a control measure. Ethical considerations have been raised regarding distorting scientific results and the killing of animals despite minimal or absent scientific evidence.

Mobile suitcase laboratory for rapid detection of Leishmania donovani using recombinase polymerase amplification assay.

PubMed

Mondal, Dinesh; Ghosh, Prakash; Khan, Md Anik Ashfaq; Hossain, Faria; Böhlken-Fascher, Susanne; Matlashewski, Greg; Kroeger, Axel; Olliaro, Piero; Abd El Wahed, Ahmed

2016-05-13

Leishmania donovani (LD) is a protozoan parasite transmitted to humans from sand flies, which causes Visceral Leishmaniasis (VL). Currently, the diagnosis is based on presence of the anti-LD antibodies and clinical symptoms. Molecular diagnosis would require real-time PCR, which is not easy to implement at field settings. In this study, we report on the development and testing of a recombinase polymerase amplification (RPA) assay for the detection of LD. A genomic DNA sample was applied to determine the assay analytical sensitivity. The cross-reactivity of the assay was tested by DNA of Leishmania spp. and of pathogens considered for differential diagnosis. The clinical performance of the assay was evaluated on LD positive and negative samples. All results were compared with real-time PCR. To allow the use of the assay at field settings, a mobile suitcase laboratory (56 × 45.5 × 26.5 cm) was developed and operated at the local hospital in Mymensingh, Bangladesh. The LD RPA assay detected equivalent to one LD genomic DNA. The assay was performed at constant temperature (42 °C) in 15 min. The RPA assay also detected other Leishmania species (L. major, L. aethiopica and L. infantum), but did not identify nucleic acid of other pathogens. Forty-eight samples from VL, asymptomatic and post-kala-azar dermal leishmaniasis subjects were detected positive and 48 LD-negative samples were negative by both LD RPA and real-time PCR assays, which indicates 100 % agreement. The suitcase laboratory was successfully operated at the local hospital by using a solar-powered battery. DNA extraction was performed by a novel magnetic bead based method (SpeedXtract), in which a simple fast lysis protocol was applied. Moreover, All reagents were cold-chain independent. The mobile suitcase laboratory using RPA is ideal for rapid sensitive and specific detection of LD especially at low resource settings and could contribute to VL control and elimination programmes.

Effect of untreated bed nets on blood-fed Phlebotomus argentipes in kala-azar endemic foci in Nepal and India.

PubMed

Picado, Albert; Kumar, Vijay; Das, Murari; Burniston, Ian; Roy, Lalita; Suman, Rijal; Dinesh, Diwakar; Coosemans, Marc; Sundar, Shyam; Shreekant, Kesari; Boelaert, Marleen; Davies, Clive; Cameron, Mary

2009-12-01

Observational studies in the Indian subcontinent have shown that untreated nets may be protective against visceral leishmaniasis (VL). In this study, we evaluated the effect of untreated nets on the blood feeding rates of Phlebotomus argentipes as well as the human blood index (HBI) in VL endemic villages in India and Nepal. The study had a 'before and after intervention' design in 58 households in six clusters. The use of untreated nets reduced the blood feeding rate by 85% (95% CI 76.5-91.1%) and the HBI by 42.2% (95% CI 11.1-62.5%). These results provide circumstantial evidence that untreated nets may provide some degree of personal protection against sand fly bites.

Efficacy and evaluation of environmental management system to control sandfly vector of Kala-azar.

PubMed

Dinesh, D S; Kumari, S; Hassan, F; Kumar, V; Singh, V P; Das, P

2017-10-01

The established vector for visceral leishmaniasis, Phlebotomus argentipes (Diptera: Psychodidae) breeds inside the human dwellings and cattle shed under crevices at the base of the wall. P. argentipes was controlled by plastering the base of wall (9″height × 9″base). The study was conducted in two phases: (i) Screening of plastering materials (ii) validation of the most suitable material. During the first phase (2014); four intervention materials were evaluated in four different arms: (i) cement (ii) brick chimney fly ash (BCFA i.e. waste material from an oven for backing raw earthen brick in charcoal) mixed with lime (95:5) (iii) wire mesh (25 holes/cm 2 ) and (iv) glazed tiles. Ten houses were selected as test and same as control in four different villages for each arm having similar ecotype and similar density of sandflies. The pre and post intervention density of sandflies were evaluated. Significant reduction in sandfly density was found with cement (46.2%) and BCFA (29.6%) plastering (P < 0.05). In the second phase of the study (2015); the two most effective interventions were validated at village level with one control. A significant reduction in the density of P. argentipes was found with cement; 60.2% (Mean ± S.D. = 2.48 ± 2.78, 95% CI = 1.93-3.02) and BCFA; 48.2% (Mean ± S.D. = 1.98 ± 2.20, 95% CI = 1.55-2.41) (P < 0.05). BCFA was found easily accessible, acceptable and cost effective that can be used in any type of wall materials at own cost. This can be implemented as one of the integrated vector control approach in the programme. Copyright © 2017. Published by Elsevier Ltd.

Impact of vectorborne parasitic neglected tropical diseases on child health.

PubMed

Barry, Meagan A; Murray, Kristy O; Hotez, Peter J; Jones, Kathryn M

2016-07-01

Chagas disease, leishmaniasis, onchocerciasis and lymphatic filariasis are all vectorborne neglected tropical diseases (NTDs) that are responsible for significant disease burden in impoverished children and adults worldwide. As vectorborne parasitic diseases, they can all be targeted for elimination through vector control strategies. Examples of successful vector control programmes for these diseases over the past two decades have included the Southern Cone Initiative against Chagas disease, the Kala-azar Control Scheme against leishmaniasis, the Onchocerciasis Control Programme and the lymphatic filariasis control programme in The Gambia. A common vector control component in all of these programmes is the use of adulticides including dichlorodiphenyltrichloroethane and newer synthetic pyrethroid insecticides against the insect vectors of disease. Household spraying has been used against Chagas disease and leishmaniasis, and insecticide-treated bed nets have helped prevent leishmaniasis and lymphatic filariasis. Recent trends in vector control focus on collaborations between programmes and sectors to achieve integrated vector management that addresses the holistic vector control needs of a community rather than approaching it on a disease-by-disease basis, with the goals of increased efficacy, sustainability and cost-effectiveness. As evidence of vector resistance to currently used insecticide regimens emerges, research to develop new and improved insecticides and novel control strategies will be critical in reducing disease burden. In the quest to eliminate these vectorborne NTDs, efforts need to be made to continue existing control programmes, further implement integrated vector control strategies and stimulate research into new insecticides and control methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Expression of matrix metalloproteinase-2 and metalloproteinase-9 in the skin of dogs with visceral leishmaniasis.

PubMed

Jacintho, Ana Paula Prudente; Melo, Guilherme D; Machado, Gisele F; Bertolo, Paulo Henrique Leal; Moreira, Pamela Rodrigues Reina; Momo, Claudia; Souza, Thiago A; Vasconcelos, Rosemeri de Oliveira

2018-06-01

The skin is the first organ to be infected by the parasite in canine visceral leishmaniasis. The enzyme matrix metalloproteinase (MMP) acts towards degradation of the extracellular matrix (ECM) and modulation of the inflammatory response against many kinds of injuries. The aims of this study were to evaluate the expression of MMP-2 and MMP-9 through immunohistochemistry and zymography on the skin (muzzle, ears, and abdomen) of dogs that were naturally infected by Leishmania spp. and to compare these results with immunodetection of the parasite and with alterations to the dermal ECM. Picrosirius red staining was used to differentiate collagen types I and III in three regions of the skin. The parasite load, intensity of inflammation, and production of MMP-2 (latent) and MMP-9 (active and latent) were higher in the ear and muzzle regions. MMP-9 (active) predominated in the infected group of dogs and its production was significantly different to that of the control group. Macrophages, lymphocytes, and plasma cells predominated in the dermal inflammation and formed granulomas in association with degradation of mature collagen (type I) and with discrete deposition of young collagen (type III). This dermal change was more pronounced in dogs with high parasite load in the skin. Therefore, it was concluded that the greater parasite load and intensity of inflammation in the skin led consequently to increased degradation of mature collagen, caused by increased production of MMPs, particularly active MMP-9, in dogs with visceral leishmaniasis. This host response profile possibly favors systemic dissemination of the parasite.

Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease

PubMed Central

Boelaert, Marleen; Verdonck, Kristien; Menten, Joris; Sunyoto, Temmy; van Griensven, Johan; Chappuis, Francois; Rijal, Suman

2014-01-01

KE16 ICT) recruiting 4271 participants (2605 with VL) were included. We carried out a meta-analysis for the rK39 ICT (including 18 studies; 3622 participants) and the latex agglutination test (six studies; 1374 participants). The results showed considerable heterogeneity. For the rK39 ICT, the overall sensitivity was 91.9% (95% confidence interval (95% CI) 84.8 to 96.5) and the specificity 92.4% (95% CI 85.6 to 96.8). The sensitivity was lower in East Africa (85.3%; 95% CI 74.5 to 93.2) than in the Indian subcontinent (97.0%; 95% CI 90.0 to 99.5). For the latex agglutination test, overall sensitivity was 63.6% (95% CI 40.9 to 85.6) and specificity 92.9% (95% CI 76.7 to 99.2). Authors' conclusions The rK39 ICT shows high sensitivity and specificity for the diagnosis of visceral leishmaniasis in patients with febrile splenomegaly and no previous history of the disease, but the sensitivity is notably lower in east Africa than in the Indian subcontinent. Other rapid tests lack accuracy, validation, or both. PLAIN LANGUAGE SUMMARY Rapid diagnostic tests for visceral leishmaniasis Visceral leishmaniasis (or kala-azar) is caused by a parasite, results in fever, a large spleen and other health problems, occuring in India, Bangladesh and Nepal, east Africa, the Mediterranean region and Brazil. Without treatment people die, and proper treatment can result in cure, so diagnosis is important. Many of the tests that are used to determine if a person has visceral leishmaniasis are complicated, costly, painful and sometimes dangerous for the patients. Now rapid diagnostic tests that are safe and easy to perform are available. This Cochrane review describes how accurate these rapid diagnostic tests are for diagnosing visceral leishmaniasis. We summarize those studies that evaluated the rapid tests in people who, according to their physicians, could have the disease. We only included studies in which the researchers had used established methods to distinguish the people with visceral

Utilizing Remote Sensing to Explore Hydrological and Climatic Factors of Visceral Leishmaniasis in South Sudan

NASA Astrophysics Data System (ADS)

Kruczkiewicz, A.; Sweeney, A.; Reid, C.; Seaman, J.; Abubakar, A.; Ritmeijer, K.; Jensen, K.; Schroeder, R.; McDonald, K. C.; Lessel, J.; Thomson, M. C.; Elnaiem, D.; Ceccato, P.

2014-12-01

Recent epidemics of visceral leishmaniasis (VL) in Sudan and South Sudan (locally known as Kala Azar) have caused an estimated 100,000 deaths and have renewed the impetus for defining the ecological boundaries of this vector borne disease. In the past 30 years outbreaks have occurred cyclically within this country, but recent shifts in endemicity have necessitated a more robust understanding of the drivers of the disease. Previous work (e.g. Gebre-Michael et al., 2004; Ashford & Thomson, 1991; Hoogstraal & Heyneman, 1969) has suggested that the primary biological vector in this region, the female sand fly Phlebotomus orientalis, exhibits sensitivities to environmental and climatic variables. Results of this study showed a relationship between precipitation and inundation during months of the transmission season (April-July) and the number of confirmed cases in the following September-January period. Particular months of the transmission season with below-average precipitation were better indicators of lagged reports of VL than others. During VL epidemics (2009, 2010, 2011) the month of June exhibited below average precipitation. The two largest epidemics (2010, 2011) were associated with years of below average precipitation in the month of April. Inundation during April-July (AMJJ) also exhibited a strong inverse relationship with reported VL cases in the following September- January (SONDJ). This relationship was best explored when comparing the VL case data of a specific medical center to the inundation anomalies. Results are typified by the Lankien Medical Center analysis where below average inundation during April displays an inverse relationship with VL cases in the following SONDJ. Drought may lead to below average inundation, which could allow for soils to maintain their fissures, thus maintaining the sand fly breeding habitat, resulting in a sustained breeding season for the sandflies (Quate, 1964). Above-average precipitation and inundation might have the

Leishmania donovani pteridine reductase 1: comparative protein modeling and protein-ligand interaction studies of the leishmanicidal constituents isolated from the fruits of Piper longum.

PubMed

Sahi, Shakti; Tewatia, Parul; Ghosal, Sabari

2012-12-01

Visceral leishmaniasis or kala-azar is caused by the dimorphic parasite Leishmania donovani in the Indian subcontinent. Treatment options for kala-azar are currently inadequate due to various limitations. Currently, drug discovery for leishmaniases is oriented towards rational drug design; the aim is to identify specific inhibitors that target particular metabolic activities as a possible means of controlling the parasites without affecting the host. Leishmania salvages pteridin from its host and reduces it using pteridine reductase 1 (PTR1, EC 1.5.1.33), which makes this reductase an excellent drug target. Recently, we identified six alkamides and one benzenoid compound from the n-hexane fraction of the fruit of Piper longum that possess potent leishmanicidal activity against promastigotes as well as axenic amastigotes. Based on a homology model derived for recombinant pteridine reductase isolated from a clinical isolate of L. donovani, we carried out molecular modeling and docking studies with these compounds to evaluate their binding affinity. A fairly good agreement between experimental data and the results of molecular modeling investigation of the bioactive and inactive compounds was observed. The amide group in the conjugated alkamides and the 3,4-methylenedioxystyrene moiety in the benzenoid compound acts as heads and the long aliphatic chain acts as a tail, thus playing important roles in the binding of the inhibitor to the appropriate position at the active site. The remarkably high activity of a component containing piperine and piperine isomers (3.36:1) as observed by our group prompted us to study the activities of all four isomers of piperine-piperine (2E,4E), isopiperine (2Z,4E), isochavicine (2E,4Z), and chavicine (2Z,4Z)-against LdPTR1. The maximum inhibitory effect was demonstrated by isochavicine. The identification of these predicted inhibitors of LdPTR1 allowed us to build up a stereoview of the structure of the binding site in relation to

Apoptosis-like death in Leishmania donovani promastigotes induced by eugenol-rich oil of Syzygium aromaticum.

PubMed

Islamuddin, Mohammad; Sahal, Dinkar; Afrin, Farhat

2014-01-01

Leishmaniasis consists of a complex spectrum of infectious diseases with worldwide distribution of which visceral leishmaniasis or kala-azar caused by Leishmania donovani is the most devastating. In the absence of vaccines, chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice are expensive and associated with multiple adverse side effects. Because of these limitations, the development of new antileishmanial compounds is imperative and plants offer prospects in this regard. The present work was conducted to study the antileishmanial potential of oil from Syzygium aromaticum flower buds (clove). The S. aromaticum oil was characterized by gas chromatography and GC-MS and eugenol as well as eugenyl acetate were found to be the most abundant compounds, composing 59.75 % and 29.24 %, respectively of the oil. Our findings have shown that eugenol-rich essential oil from S. aromaticum (EROSA) possesses significant activity against L. donovani, with 50 % inhibitory concentration of 21 ± 0.16 µg ml(-1) and 15.24 ± 0.14 µg ml(-1), respectively, against promastigotes and intracellular amastigotes. Alterations in cellular morphology and growth reversibility assay substantiated the leishmanicidal activity of EROSA. The leishmanicidal effect was mediated via apoptosis as confirmed by externalization of phosphatidylserine, DNA nicking by TdT-mediated dUTP nick-end labelling (TUNEL) assay, dyskinetoplastidy, cell cycle arrest at sub-G0-G1 phase, loss of mitochondrial membrane potential and reactive oxygen species generation. EROSA presented no adverse cytotoxic effects against murine macrophages even at 200 µg ml(-1). Our studies authenticate the promising antileishmanial activity of EROSA, which is mediated by programmed cell death, and, accordingly, EROSA may be a source of novel agents for the treatment of leishmaniasis.

Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules.

PubMed

Datta, Sanchita; Roy, Syamal; Manna, Madhumita

2015-01-01

Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly forms of disease among all neglected tropical diseases. There are no satisfactory drugs or vaccine candidates available for this dreaded disease. Our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model. The T-cell proliferation level, the mRNA expression level of inducible nitric oxide synthase (iNOS) and tumor growth factor-beta (TGF-β) genes and finally the phosphorylation levels of phosphoinositide dependent kinase 1 (PDK1), phosphoinositide 3 kinase (PI3K) and p38 mitogen activated protein kinase (p38MAPK) molecules were checked in BALB/c mice model immunized with radio-attenuated Leishmania donovani parasites through I.M. route. Higher T-cell proliferation, increased iNOS level, and suppressed TGF-β level were found in treated infected animal groups (100 and 150Gy) in relation to untreated infected animals. Likewise, phosphorylation levels of PDK1, PI3K and p38MAPK of these two groups were increased when compared to untreated infected controls. The clearance of the parasites from treated infected groups of animals may be mediated by the restoration of T-cell due to therapy with radio-attenuated L. donovani parasites. The killing of parasites was mediated by increase in nitric oxide release through PDK1, PI3K and p38MAPK signaling pathways. A lower TGF-β expression has augmented the restored Th1 ambience in the 100 and 150Gy treated animal groups proving further the efficacy of the candidate vaccine. Copyright © 2015. Published by Elsevier Editora Ltda.

Risk factors of visceral leishmaniasis: a case control study in north-western Ethiopia.

PubMed

Yared, Solomon; Deribe, Kebede; Gebreselassie, Araya; Lemma, Wessenseged; Akililu, Essayas; Kirstein, Oscar D; Balkew, Meshesha; Warburg, Alon; Gebre-Michael, Teshome; Hailu, Asrat

2014-10-14

Visceral leishmaniasis (VL, also called ''kala-azar"), is a life threatening neglected tropical infectious disease which mainly affects the poorest of the poor. VL is prevalent in Ethiopia particularly in the northwest of the country. Understanding the risk factors of VL infection helps in its prevention and control. The aim of the present study was to identify the factors associated with VL. A case-control study was carried out during the period of January-July 2013 in northwest Ethiopia. Cases and controls were diagnosed using clinical presentation, the rk39 rapid diagnostic test and Direct Agglutination Test (DAT). A total of 283 (84.8% males versus 15.2% females) participants were interviewed. 90 cases and 193 controls were involved, matched by age, sex and geographical location with a ratio of 1:2 (case: controls). Univariate and backward multivariate conditional logistic regression were used to identify risk factors of VL. Elevated odds of VL was associated with goat ownership (OR = 6.4; 95%: confidence interval [Cl]: 1.5-28.4), living in houses with cracked wall (OR = 6.4; 95% Cl: 1.6-25.6), increased family size (OR = 1.3; 95% Cl: 1.0-1.8) and the number of days spent in the farm field (OR = 1.1; 95% Cl: 1.0-1.2). However, daily individual activities around the home and farm fields, mainly sleeping on a bed (OR = 0.2; 95%: Cl 0.03-0.9), sleeping outside the house under a bed net (OR = 0.1; 95% Cl: 0.02-0.36)] and smoking plant parts in the house during the night time (OR = 0.1; 95% Cl: 0.01-0.6) were associated with decreased odds of being VL case. Our findings showed that use of bed net and smoke could be helpful for the prevention of VL in the area particularly among individuals who spend most of their time in the farm. VL control effort could be focused on improving housing conditions, such as sealing cracks and crevices inside and outside houses. Further research is warranted to elucidate the role of goats in the transmission

Leishmaniasis Disease

MedlinePlus

... Leishmaniasis General Information Leishmaniasis FAQs Epidemiology & Risk Factors Biology Disease Diagnosis Treatment Prevention & Control Resources for Health Professionals Publications Additional Resources Get ...

Fractional ablative carbon dioxide laser followed by topical sodium stibogluconate application: A treatment option for pediatric cutaneous leishmaniasis.

PubMed

Hilerowicz, Yuval; Koren, Amir; Mashiah, Jacob; Katz, Oren; Sprecher, Eli; Artzi, Ofir

2018-05-01

Leishmaniasis is a protozoan zoonotic parasitic infection with cutaneous, mucocutaneous, and visceral manifestations. Israel is endemic for cutaneous leishmaniasis, which is a self-limited disease but is associated with scarring, which is often a source of psychological and social burden for patients. Scars can be especially devastating for children and teenagers. A wide range of physical and medical approaches is used to treat cutaneous leishmaniasis, among which intralesional injections of sodium stibogluconate rank among the most frequently used. Unfortunately, despite being effective, this therapeutic modality can be very painful. Fractional ablative laser creates a controlled mesh-like pattern of tissue ablation in the skin that promotes dermal remodeling and collagen production while at the same time facilitating enhanced delivery of topically applied medications. Patients were treated with fractional ablative carbon dioxide laser followed by immediate topical application of sodium stibogluconate. All children were diagnosed with cutaneous leishmaniasis prior to treatment initiation.. Ten children were treated. One leishmania tropica-positive girl failed to respond. The other nine patients achieved clinical cure and demonstrated good to excellent final cosmesis. Self-rated patient satisfaction and tolerance were high No adverse effects were observed or reported during treatment. Fractional ablative carbon dioxide laser followed by topical sodium stibogluconate application appears to be a safe and promising treatment for cutaneous leishmaniasis infection in children. Future controlled studies are required to validate these findings and compare this technique with traditional approaches. © 2018 Wiley Periodicals, Inc.

John Alexander Sinton, MD FRS VC (1884-1956).

PubMed

Cook, G C

2016-05-01

Brigadier John Sinton is the only individual in history to have been both awarded the Victoria Cross and also elected to the Royal Society. He qualified at Belfast and afterwards joined the Indian Medical Service (IMS). Serving before and during the Great War (1914-18), he was first posted to the North-West Frontier province, and afterwards as a captain in the Indian Expeditionary force in Mesopotamia (now Iraq). It was there in 1916 that, shot in both arms during an engagement and under heavy gunfire, he remained steadfastly at his post; for this bravery he received the Victoria Cross. Following the war he carried out major researches into malaria in India, and became Director of the Malaria Survey of India Both there and shortly afterwards, Sinton published about 200 papers on various aspects of malaria and leishmaniasis. In England, he later worked at the London School of Hygiene and Tropical Medicine and the Ministry of Health's laboratory at Horton, Epsom. In 1946, he was elected to the Royal Society for his researches into malaria and kala-azar, and following retirement he underwent another distinguished career in Northern Ireland. © The Author(s) 2014.

Therapeutic vaccines for leishmaniasis.

PubMed

Khamesipour, Ali

2014-11-01

Numerous therapeutic strategies are used to treat leishmaniasis. The treatment of cutaneous leishmaniasis (CL) is solely depends on antimonate derivatives with safety issues and questionable efficacy and there is no fully effective modality to treat CL caused by Leishmania tropica and Leishmania braziliensis. There is no prophylactic vaccine available against any form of leishmaniasis. Immunotherapy for CL has a long history; immunotherapy trials of first and second generation vaccines showed promising results. The current article briefly covers the prophylactic vaccines and explains different immunotherapy strategies that have been used to treat leishmaniasis. This paper does not include experimental vaccines and only lays emphasis on human trials and those vaccines which reached human trials. Immunotherapy is currently used to successfully treat several disorders; Low cost, limited side effects and no possibility to develop resistance make immunotherapy a valuable choice especially for infectious disease with chemotherapy problems. Efforts are needed to explore the immunological surrogate marker(s) of cure and protection in leishmaniasis and overcome the difficulties in standardization of crude Leishmania vaccines. One of the reasons for anti-leishmaniasis vaccine failure is lack of an appropriate adjuvant. So far, not enough attention has been paid to develop vaccines for immunotherapy of leishmaniasis.

A serological study of Leishmania infantum in dogs of Khorasan Razavi province, Iran.

PubMed

Sabzevari, S; Razmi, G R; Naghibi, A; Khoshnegah, J

2013-10-01

Leishmania infantum is the principal agent of visceral leishmaniosis (kala-azar) in all areas of Iran. The disease is endemic in Fars, Ardabil, East Azerbaijan and Bushehr provinces while it is sporadic in other parts of the country. Dog as a member of canidae family is the main animal reservoir host of kala-azar. The present study was carried out to determine the sero-prevalence of canine leishmaniosis in Mashhad, the capital city of Khorasan Razavi Province, in the north east of Iran. Two-hundred and nine dogs in two different classes including stray and sheepdogs were selected for this cross-sectional study. The blood samples were collected and tested by indirect immunofluorescent antibody test for detection of anti-Leishmania infantum antibodies. The results showed that 16/209 (7.6 %) of blood samples were positive. The sero-prevalence rates in stray and sheepdogs were 11/94 (11.7 %) and 5/115 (4.3 %), respectively (p < 0.05). Based on the results obtained, it is concluded that visceral leishmaniosis is distributed among dogs of this area, also sero-prevalence of canine leishmaniosis in stray dogs higher than sheepdogs.

The history of leishmaniasis.

PubMed

Steverding, Dietmar

2017-02-15

In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical distribution, initial evidence of the disease in ancient times, first accounts of the infection in the Middle Ages, and the discovery of Leishmania parasites as causative agents of leishmaniasis in modern times. With respect to the origin and dispersal of Leishmania parasites, the three currently debated hypotheses (Palaearctic, Neotropical and supercontinental origin, respectively) are presented. Ancient documents and paleoparasitological data indicate that leishmaniasis was already widespread in antiquity. Identification of Leishmania parasites as etiological agents and sand flies as the transmission vectors of leishmaniasis started at the beginning of the 20 th century and the discovery of new Leishmania and sand fly species continued well into the 21 st century. Lately, the Syrian civil war and refugee crises have shown that leishmaniasis epidemics can happen any time in conflict areas and neighbouring regions where the disease was previously endemic.

Leishmaniasis with oral mucosa involvement.

PubMed

Pellicioli, Ana C A; Martins, Marco A T; Sant'ana Filho, Manoel; Rados, Pantelis V; Martins, Manoela D

2012-06-01

The term leishmaniasis comprises a group of diseases caused by different protozoan species of the genus Leishmania. There are three main clinical forms of leishmaniasis: visceral, cutaneous and mucocutaneous. Exclusive involvement of the mucosa is very rare. To present a case of mucocutaneous leishmaniasis in an elderly patient, discuss the clinical presentation, diagnostic process and treatment emphasizing the distinctions from other granulomatous lesions. A 71-year-old male presenting with a symptomatic lesion on the hard and soft palate, which had developed over a period of 6 months was evaluated. The oral exam revealed a lesion with multiple ulcerated nodules on the hard and soft palate extending to the oropharynx. The diagnostic hypothesis was chronic infectious disease (paracoccidioidomycose, tuberculosis and leishmaniasis) or squamous cell carcinoma. Histopathological, histochemical and immunohistochemical analysis were performed. A chest x-ray revealed a normal pulmonary pattern. The Montenegro skin test was positive. The definitive diagnosis was leishmaniasis with exclusive oral manifestation and the patient was treated with liposomal amphotericin. Localized oral mucosa leishmaniasis is an uncommon event in an immunocompetent patient. Dentists play an important role in the diagnosis of oral leishmaniasis, which has systemic repercussions. © 2012 The Gerodontology Society and John Wiley & Sons A/S.

Oviposition behaviour of Phlebotomus argentipes--a laboratory-based study.

PubMed

Kumar, Vijay; Rama, Aarti; Kesari, Shreekant; Bhunia, Gouri Sankar; Dinesh, Diwakar Singh; Das, Pradeep

2013-12-01

The breeding habitat of sandflies is a little studied and poorly understood phenomenon. More importantly, oviposition behaviour is a largely neglected aspect of sandfly biology and this knowledge gap further undermines our understanding of the biology of sandflies. Pheromones released by the eggs play an important role in identifying good sites for oviposition by female insects. Several recent studies have examined the oviposition pheromone. The present study provides a preliminary report on the oviposition behaviour of Phlebotomus argentipes, the only vector of kala-azar (or visceral leishmaniasis) on the Indian sub-continent. Sandflies prefer to oviposit their eggs on surfaces that contain organic substances, especially substances with an odour of decaying animal products and the remains of conspecific eggs. The results presented here suggest that the odour released by the organic substances of old sandfly colony remains that contain dead flies, old unhatched eggs, larval food containing vertebrate faeces, frass and other organic matter serves as an attractant for the ovipositing females of P. argentipes and hence greatly increases the number of oviposited eggs compared to eggs deposited in controlled oviposition pots. This result will be helpful in maintaining an efficient colony of P. argentipes and may be a promising tool for monitoring and controlling the target insect as part of a synergistic approach.

[Leishmaniasis in Algiers: epidemiologic data].

PubMed

Harrat, Z; Belkaid, M

2003-08-01

The authors review the situation on human and canine leishmaniasis observed in Algiers during the period 1990-1997. 1800 sera have been tested by IFAT. The frequency of canine leishmaniasis rises to 37%. 25% of the positive dogs are asymptomatic. The canine leishmaniasis annual fluctuations seem to vary from one year to another, with an increase of number of cases comparing with the last period. Human leishmaniasis is also increasing in Algiers, where 22 cases of HVL and 40 cases CL have been notified. Nine strains of Leishmania (5 from dogs and 4 from human) were isolated and identified by isoenzymes eletrophoresis technique. All stocks were belonging to Leishmania infantum complex. To complete the study, the seasonal dynamic of phlebotomine sandflies was carried out in the same area where 2959 specimens have been captured. The results showed the predominance of P. perniciosus and P. longicuspis, the main vectors of visceral leishmaniasis in Algeria.

Elimination of neglected tropical diseases in the South-East Asia Region of the World Health Organization.

PubMed

Narain, Jai P; Dash, A P; Parnell, B; Bhattacharya, S K; Barua, S; Bhatia, R; Savioli, L

2010-03-01

The neglected tropical diseases (NTDs), which affect the very poor, pose a major public health problem in the South-East Asia Region of the World Health Organization (WHO). Although more than a dozen NTDs affect the region, over the past five years four of them in particular - leprosy, lymphatic filariasis, visceral leishmaniasis (kala-azar) and yaws - have been targeted for elimination. These four were selected for a number of reasons. First, they affect the WHO South-East Asia Region disproportionately. For example, every year around 67% of all new leprosy cases and 60% of all new cases of visceral leishmaniasis worldwide occur in countries of the region, where as many as 850 million inhabitants are at risk of contracting lymphatic filariasis. In addition, several epidemiological, technological and historical factors that are unique to the region make each of these four diseases amenable to elimination. Safe and effective tools and interventions to achieve these targets are available and concerted efforts to scale them up, singly or in an integrated manner, are likely to lead to success. The World Health Assembly and the WHO Regional Committee, through a series of resolutions, have already expressed regional and global commitments for the elimination of these diseases as public health problems. Such action is expected to have a quick and dramatic impact on poverty reduction and to contribute to the achievement of the Millennium Development Goals. This paper reviews the policy rationale for disease control in the WHO South-East Asia Region, the progress made so far, the lessons learnt along the way, and the remaining challenges and opportunities.

Vaccine candidates for leishmaniasis: a review.

PubMed

Nagill, Rajeev; Kaur, Sukhbir

2011-10-01

Leishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genus Leishmania. The clinical manifestation of the disease varies from self-limiting cutaneous lesions to progressive visceral disease. It is estimated that 350 million people are at risk in 88 countries, with a global incidence of 1-1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. The key control measures mainly rely on early case detection and chemotherapy which has been hampered by the toxicity of drugs, side-effects and by the emergence of drug resistance in parasites. Control of reservoir host and vector is difficult due to operational difficulties and frequent relapses in the host. Therefore, the development of effective and affordable vaccine against leishmaniasis is highly desirable. Although considerable progress has been made over the last decade in understanding immune mechanisms underlying potential candidate antigens, including killed, live attenuated parasites, crude parasites, pure or recombinant Leishmania proteins or DNA encoding leishmanial proteins, as well as immunomodulators from sand fly saliva, very few candidate vaccines have progressed beyond the experimental stage. As such there is no vaccine against any form of human leishmaniasis. In recent years, however, much interest has been stimulated towards vaccination against leishmaniasis focused mainly on cutaneous leishmaniasis with fewer attempts against visceral leishmaniasis. Copyright © 2011 Elsevier B.V. All rights reserved.

Vector control in leishmaniasis.

PubMed

Kishore, K; Kumar, V; Kesari, S; Dinesh, D S; Kumar, A J; Das, P; Bhattacharya, S K

2006-03-01

Indoor residual spraying is a simple and cost effective method of controlling endophilic vectors and DDT remains the insecticide of choice for the control of leishmaniasis. However resistance to insecticide is likely to become more widespread in the population especially in those areas in which insecticide has been used for years. In this context use of slow release emulsified suspension (SRES) may be the best substitute. In this review spraying frequencies of DDT and new schedule of spray have been discussed. Role of biological control and environment management in the control of leishmaniasis has been emphasized. Allethrin (coil) 0.1 and 1.6 per cent prallethrin (liquid) have been found to be effective repellents against Phlebotomus argentipes, the vector of Indian kalaazar. Insecticide impregnated bednets is another area which requires further research on priority basis for the control of leishmaniasis. Role of satellite remote sensing for early prediction of disease by identifying the sandflygenic conditions cannot be undermined. In future synthetic pheromons can be exploited in the control of leishmaniasis.

New Clinicoepidemiologic Profile of Cutaneous Leishmaniasis, Morocco

PubMed Central

Rhajaoui, Mohamed; Fellah, Hajiba; Azmi, Kifaya; Amarir, Fatima; Al-Jawabreh, Amer; Ereqat, Suheir; Planer, Joseph; Abdeen, Ziad

2007-01-01

During the past 20 years, cutaneous leishmaniasis has emerged as a major public health threat in Morocco. We describe distribution of Leishmania major and L. tropica in Morocco and a new focus of cutaneous leishmaniasis due to L. infantum. We recommend using molecular techniques to diagnose suspected leishmaniasis cases. PMID:18252108

Leishmaniasis in humans: drug or vaccine therapy?

PubMed Central

Ghorbani, Masoud; Farhoudi, Ramin

2018-01-01

Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results. PMID:29317800

Bibliography of Leishmania and Leishmanial Diseases. Volume 1

DTIC Science & Technology

1980-06-01

Sea 7 Rev. Med.- Yucatan Paulo, REVISTA MEDICA DE YUCATAN . Merida. Rev, Paliclin, Caracas Rev. Menn. Med. , Brazil REVISTA DE LA POLICLINICA, CARACAc...Parasit., 41(2):126-136. 799 pp. CHAKG, P. Y.; TENG, L. T.; SUNG, Y. (1957A) Interactions T. & LIU, Y. C. (1958A) Kala-azar between nutrition and...of nutrition in experimental Infectivan. Bact. Rev. , 13:99-134. CLINTON, B. A.; STAUBER, L. A.& CLRT .(1959A) Comparative PALCZUK, N. C. (1969A

Autochthonous canine leishmaniasis in Romania: neglected or (re)emerging?

PubMed Central

2014-01-01

Canine leishmaniasis is a vector-borne zoonotic disease caused by the protozoan parasite Leishmania infantum. In Romania between 1955 and 2013, no cases of human autochthonous visceral leishmaniasis were reported. Data regarding canine leishmaniasis is similarly scarce. Since the first report of clinical autochthonous canine leishmaniasis in 1935, there were only three sporadic reports of positive dogs all without any clinical signs. Our study reports the first clinical case of autochthonous canine leishmaniasis in the last 80 years, stressing the importance of a targeted surveillance of Leishmania infection, as infected dogs act as the primary reservoir for zoonotic visceral leishmaniasis. PMID:24684827

Recurrent cutaneous leishmaniasis*

PubMed Central

Gomes, Ciro Martins; Damasco, Fabiana dos Santos; de Morais, Orlando Oliveira; de Paula, Carmen Déa Ribeiro; Sampaio, Raimunda Nonata Ribeiro

2013-01-01

We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because of the challenges imposed by treatment. PMID:23793208

"Chalepa Ta Kala," "Fine Things Are Difficult": Socrates' Insights into the Psychology of Teaching and Learning

ERIC Educational Resources Information Center

Mintz, Avi I.

2010-01-01

The proverb "chalepa ta kala" ("fine things are difficult") is invoked in three dialogues in the Platonic corpus: "Hippias Major," "Cratylus" and "Republic." In this paper, I argue that the context in which the proverb arises reveals Socrates' considerable pedagogical dexterity as he uses the proverb to rebuke his interlocutor in one dialogue but…

Case study for a vaccine against leishmaniasis.

PubMed

Alvar, Jorge; Croft, Simon L; Kaye, Paul; Khamesipour, Ali; Sundar, Shyam; Reed, Steven G

2013-04-18

Leishmaniasis in many ways offers a unique vaccine case study. Two reasons for this are that leishmaniasis is a disease complex caused by several different species of parasite that are highly related, thus raising the possibility of developing a single vaccine to protect against multiple diseases. Another reason is the demonstration that a leishmaniasis vaccine may be used therapeutically as well as prophylactically. Although there is no registered human leishmaniasis vaccine today, immunization approaches using live or killed organisms, as well as defined vaccine candidates, have demonstrated at least some degree of efficacy in humans to prevent and to treat some forms of leishmaniasis, and there is a vigorous pipeline of candidates in development. Current approaches include using individual or combined antigens of the parasite or of salivary gland extract of the parasites' insect vector, administered with or without formulation in adjuvant. Animal data obtained with several vaccine candidates are promising and some have been or will be entered into clinical testing in the near future. There is sufficient scientific and epidemiological justification to continue to invest in the development of vaccines against leishmaniasis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Epidemiological Changes in Leishmaniasis in Spain According to Hospitalization-Based Records, 1997–2011: Raising Awareness towards Leishmaniasis in Non-HIV Patients

PubMed Central

Jimenez, B. Carolina; Granados, Marisol; San Martín, Juan Victor; Aparicio, Pilar

2015-01-01

In Spain, Leishmania infantum is endemic, human visceral and cutaneous leishmaniasis cases occurring both in the Peninsula, as well as in the Balearic Islands. We aimed to describe the clinical characteristics of leishmaniasis patients and the changes in the disease evolution after the introduction of antiretroviral therapy in 1997. In this descriptive study, we used Spanish Centralized Hospital Discharge Database for the hospitalized leishmaniasis cases between 1997 and 2011. We included in the analysis only the records having leishmaniasis as the first registered diagnosis and calculated the hospitalization rates. Disease trend was described taking into account the HIV status. Adjusted odds-ratio was used to estimate the association between clinical and socio-demographic factors and HIV co-infection. Of the total 8010 Leishmaniasis hospitalizations records, 3442 had leishmaniasis as first diagnosis; 2545/3442 (75.6%) were males and 2240/3442 (65.1%) aged between 14-65 years. Regarding disease forms, 2844/3442 (82.6%) of hospitalizations were due to visceral leishmaniasis (VL), while 118/3442 (3.4%) hospitalizations were cutaneous leishmaniasis (CL). Overall, 1737/2844 of VL (61.1%) were HIV negatives. An overall increasing trend was observed for the records with leishmaniasis as first diagnosis (p=0.113). Non-HIV leishmaniasis increased during this time period (p=0.021) while leishmaniasis-HIV co-infection hospitalization revealed a slight descending trend (p=0.717). Leishmaniasis-HIV co-infection was significantly associated with male sex (aOR=1.6; 95% CI: 1.25-2.04), 16-64 years age group (aOR=17.4; 95%CI: 2.1-143.3), visceral leishmaniasis aOR=6.1 (95%CI: 3.27-11.28) and solid neoplasms 4.5 (95% CI: 1.65-12.04). The absence of HIV co-infection was associated with lymph/hematopoietic neoplasms (aOR=0.3; 95%CI:0.14-0.57), other immunodeficiency (aOR=0.04; 95% CI:0.01-0.32) and transplant (aOR=0.01; 95%CI:0.00-0.07). Our findings suggest a significant increase of

Epidemiologic and Clinical Features of Cutaneous Leishmaniasis in Southeastern Tunisia

PubMed Central

Bousslimi, Nadia; Aoun, Karim; Ben-Abda, Imène; Ben-Alaya-Bouafif, Nissaf; Raouane, Mohamed; Bouratbine, Aïda

2010-01-01

Species-specific diagnosis was performed in 66 patients with cutaneous leishmaniasis (CL) living in Tataouine focus in southeastern Tunisia. Leishmania DNA was extracted directly from dermal scrapings (n = 66) and from parasites obtained in culture (n = 12). Species were identified by using polymerase chain reaction–restriction fragment length polymorphism analysis for internal transcribed spacer region 1 and isoenzyme analysis. Leishmania tropica and L. major were identified in 31 (47%) and 35 (53%) cases respectively. Leishmania tropica CL cases were geographically scattered, and L. major CL cases were clustered. Lesions caused by L. tropica were mostly single (83.8%) and face-localized (55.8%), and lesions caused by L. major were multiple (57.1%; P < 0.001) and situated on limbs (83.7%; P < 0.001). For both species, most lesion onsets were reported during June–January. However, lesions that emerged during February–May were mainly caused by L. tropica (83.3%; P < 0.01). Moreover, the delay before seeking medical advice was higher for L. tropica infections than for L. major infections (P < 0.05). PMID:21036833

Liposomal adjuvant development for leishmaniasis vaccines.

PubMed

Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

2017-08-01

Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis.

Liposomal adjuvant development for leishmaniasis vaccines

PubMed Central

Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

2017-01-01

Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis. PMID:29201374

Emergence periodicity of Phlebotomus argentipes annandale and brunetti (Diptera: psychodidae): A laboratory study.

PubMed

Dinesh, D S; Singh, A; Kumar, V; Kesari, S; Kumar, A J; Kishore, K; Roy, S P; Bhattacharya, S K; Das, P

2009-12-01

Phlebotomus argentipes Annandale and Brunetti (Diptera: Psychodidae) is the vector for visceral leishmaniasis in India. The aspects of its biology such as feeding and man vector contact are associated with emergence periodicity of the adult. Hence, the present study was made to find out the actual emergence period of P. argentipes. Wild caught P. argentipes were confined in the rearing pots inside laboratory. The newly emerged adults were collected at hourly intervals and released in to separate polythene bags and were held at 4°C till death. Sand flies were segregated sex-wise after the death under a microscope. The emergence of adult was observed throughout the day. However, the male preferred dawn emergence and the female the dusk. Two peaks of emergence were found in a day; first one in the morning (0900h) and the second one in the evening (1800h). The ratio of both sexes was found to be about equal. The emergence of adult was found to be 77% out of total eggs laid, which was completed within 7-10 days from the 1st day of emergence under laboratory conditions (25°C to 31°C and 70% to 75% relative humidity). This study has important bearings to find out the actual time for personal protection against biting of sand flies to prevent the transmission of Kala-azar.

Identification of L. infantum chagasi proteins in VL patients' urine: a promising antigen discovery approach of vaccine candidates

PubMed Central

Kashino, Suely S.; Abeijon, Claudia; Qin, Lizeng; Kanunfre, Kelly A.; Kubrusly, Flávia S.; Silva, Fernando O.; Costa, Dorcas L.; Campos, Dioclécio; Costa, Carlos H.N.; Raw, Isaias; Campos-Neto, Antonio

2012-01-01

Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in Southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver, and bone marrow lesions and excreted in the patients’ urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1), and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in E. coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2 + BpMPLASE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to kala-azar and opens novel possibilities for vaccine development to other serious infectious diseases. PMID:22443237

New clinico-epidemiologic profile of cutaneous leishmaniasis, Morocco.

PubMed

Rhajaoui, Mohamed; Nasereddin, Abedelmajeed; Fellah, Hajiba; Azmi, Kifaya; Amarir, Fatima; Al-Jawabreh, Amer; Ereqat, Suheir; Planer, Joseph; Abdeen, Ziad

2007-09-01

During the past 20 years, cutaneous leishmaniasis has emerged as a major public health threat in Morocco. We describe distribution of Leishmania major and L. tropica in Morocco and a new focus of cutaneous leishmaniasis due to L. infantum. We recommend using molecular techniques to diagnose suspected leishmaniasis cases.

Monthly activity of Phlebotominae sand flies in Sistan-Baluchistan Province, Southeast Iran.

PubMed

Kassiri, H; Javadian, E; Sharififard, M

2013-01-01

The monthly activity of sand flies, which are vectors of leishmaniasis, was studied from May to October 1997 in three regions (plains, mountainous, coastal) of the Sistan-Bluchistan Province using sticky paper traps. In each village, three houses were selected. 30 sticky traps were installed indoors (bedroom, guestroom, toilet, bathroom) and 30 were installed outdoors (rodent burrows, wall cracks). In total, 8,558 and 1,596 sand fly specimens were collected and identified from outdoors and indoors, respectively. Ten species of Phlebotomus and eight species of Sergentomyia were collected outdoors, and nine species of Phlebotomus and 10 species of Sergentomyia were collected indoors. Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) was the predominant species found indoors in the plains region (58.4% of insects caught in the region) and was active during the whole study period. The P. papatasi peaks of activity were in early May and early October. Sergentomyia clydei (Sinton) was found to be the most abundant species outdoors in the plains region and comprised 64.7% of the total insects caught in the region. Sergentomyia clydei and S. tiberiadis (Alder, Theodor, and Lourie) were the predominant indoor and outdoor, respectively, species from the mountainous region, making up 19.8% and 35%, respectively, of all the insects caught in the region. Phlebotomus sergenti Parrot is a proven vector of urban cutaneous leishmaniasis, and P. alexandri (Sinton) is a probable vector of Kala-Azar, and both were collected during this study. Phlebotomus papatasi was the most predominant species collected indoors in the coastal region (50.8%), its peak activity was in May. Sergentomyia sintoni Pringle was the most predominant species collected outdoors in the coastal region (36.4%), and its peak activity was in October. Awareness of the peak activity times of sand flies can be useful in developing strategies to control the flies.

Monthly Activity of Phlebotominae Sand Flies in Sistan-Baluchistan Province, Southeast Iran

PubMed Central

Kassiri, H.; Javadian, E.; Sharififard, M.

2013-01-01

The monthly activity of sand flies, which are vectors of leishmaniasis, was studied from May to October 1997 in three regions (plains, mountainous, coastal) of the Sistan-Bluchistan Province using sticky paper traps. In each village, three houses were selected. 30 sticky traps were installed indoors (bedroom, guestroom, toilet, bathroom) and 30 were installed outdoors (rodent burrows, wall cracks). In total, 8,558 and 1,596 sand fly specimens were collected and identified from outdoors and indoors, respectively. Ten species of Phlebotomus and eight species of Sergentomyia were collected outdoors, and nine species of Phlebotomus and 10 species of Sergentomyia were collected indoors. Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) was the predominant species found indoors in the plains region (58.4% of insects caught in the region) and was active during the whole study period. The P. papatasi peaks of activity were in early May and early October. Sergentomyia clydei (Sinton) was found to be the most abundant species outdoors in the plains region and comprised 64.7% of the total insects caught in the region. Sergentomyia clydei and S. tiberiadis (Alder, Theodor, and Lourie) were the predominant indoor and outdoor, respectively, species from the mountainous region, making up 19.8% and 35%, respectively, of all the insects caught in the region. Phlebotomus sergenti Parrot is a proven vector of urban cutaneous leishmaniasis, and P. alexandri (Sinton) is a probable vector of Kala-Azar, and both were collected during this study. Phlebotomus papatasi was the most predominant species collected indoors in the coastal region (50.8%), its peak activity was in May. Sergentomyia sintoni Pringle was the most predominant species collected outdoors in the coastal region (36.4%), and its peak activity was in October. Awareness of the peak activity times of sand flies can be useful in developing strategies to control the flies. PMID:24784790

Cutaneous leishmaniasis: an emerging infectious disease in travelers.

PubMed

Ergen, Elizabeth Noble; King, Allison Hutsell; Tuli, Malika

2015-10-01

Leishmaniasis describes any of 3 diseases caused by protozoan parasites of the genus Leishmania, the most common of which is cutaneous leishmaniasis. The majority of cutaneous cases occur in Central and South America, the Mediterranean basin, the Middle East, and Central Asia. Most cases diagnosed among nonmilitary personnel in the United States are acquired in Mexico and Central America. Here, we present the case of an American tourist who developed localized cutaneous leishmaniasis 2 weeks after returning from Costa Rica. After undergoing several unsuccessful rounds of empiric antibiotic treatment for a presumed Staphylococcus aureus skin infection, the patient was referred to our dermatology clinic where cutaneous leishmaniasis was diagnosed by tissue biopsy. This case highlights the importance of cutaneous leishmaniasis as an emerging infectious disease that may be misdiagnosed due to its rarity and varied clinical presentation as well as the limited use of tissue biopsy in general practice. We also provide relevant background information on cutaneous leishmaniasis, a rhyming poem, and an illustration in order to promote greater awareness of this disease and assist clinicians with its diagnosis.

Leishmaniasis FAQs

MedlinePlus

... be spread via contaminated needles (needle sharing) or blood transfusions. Congenital transmission (spread from a pregnant woman to ... care provider and can help with the laboratory testing for leishmaniasis. Tissue specimens—for example, from skin ...

Vector and reservoir control for preventing leishmaniasis

PubMed Central

González, Urbà; Pinart, Mariona; Sinclair, David; Firooz, Alireza; Enk, Claes; Vélez, Ivan D; Esterhuizen, Tonya M; Tristan, Mario; Alvar, Jorge

2015-01-01

Background Leishmaniasis is caused by the Leishmania parasite, and transmitted by infected phlebotomine sandflies. Of the two distinct clinical syndromes, cutaneous leishmaniasis (CL) affects the skin and mucous membranes, and visceral leishmaniasis (VL) affects internal organs. Approaches to prevent transmission include vector control by reducing human contact with infected sandflies, and reservoir control, by reducing the number of infected animals. Objectives To assess the effects of vector and reservoir control interventions for cutaneous and for visceral leishmaniasis. Search methods We searched the following databases to 13 January 2015: Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and WHOLIS, Web of Science, and RePORTER. We also searched trials registers for ongoing trials. Selection criteria Randomized controlled trials (RCTs) evaluating the effects of vector and reservoir control interventions in leishmaniasis-endemic regions. Data collection and analysis Two review authors independently searched for trials and extracted data from included RCTs. We resolved any disagreements by discussion with a third review author. We assessed the quality of the evidence using the GRADE approach. Main results We included 14 RCTs that evaluated a range of interventions across different settings. The study methods were generally poorly described, and consequently all included trials were judged to be at high or unclear risk of selection and reporting bias. Only seven trials reported clinical outcome data which limits our ability to make broad generalizations to different epidemiological settings and cultures. Cutaneous leishmaniasis One four-arm RCT from Afghanistan compared indoor residual spraying (IRS), insecticide-treated bednets (ITNs), and insecticide-treated bedsheets, with no intervention. Over 15 months follow-up, all three insecticide-based interventions had a lower incidence of CL than the control area (IRS: risk

Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.

PubMed

Suh, Mina; Troese, Matthew J; Hall, Debra A; Yasso, Blair; Yzenas, John J; Proctor, Debora M

2014-12-01

Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant. Copyright © 2014 John Wiley & Sons, Ltd.

Leishmaniasis: a review.

PubMed

Torres-Guerrero, Edoardo; Quintanilla-Cedillo, Marco Romano; Ruiz-Esmenjaud, Julieta; Arenas, Roberto

2017-01-01

Leishmaniasis is caused by an intracellular parasite transmitted to humans by the bite of a sand fly. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide, 1.5 to 2 million new cases occur each year, 350 million are at risk of acquiring the disease, and leishmaniasis causes 70,000 deaths per year. Clinical features depend on the species of Leishmania involved and the immune response of the host. Manifestations range from the localized cutaneous to the visceral form with potentially fatal outcomes. Many drugs are used in its treatment, but the only effective treatment is achieved with current pentavalent antimonials.

Leishmaniasis: a review

PubMed Central

Torres-Guerrero, Edoardo; Quintanilla-Cedillo, Marco Romano; Ruiz-Esmenjaud, Julieta; Arenas, Roberto

2017-01-01

Leishmaniasis is caused by an intracellular parasite transmitted to humans by the bite of a sand fly. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide, 1.5 to 2 million new cases occur each year, 350 million are at risk of acquiring the disease, and leishmaniasis causes 70,000 deaths per year. Clinical features depend on the species of Leishmania involved and the immune response of the host. Manifestations range from the localized cutaneous to the visceral form with potentially fatal outcomes. Many drugs are used in its treatment, but the only effective treatment is achieved with current pentavalent antimonials. PMID:28649370

[Leishmaniasis in Ecuador. 5. Leishmaniasis and anthropization on the Pacific coast].

PubMed

Mouchet, J; Le Pont, F; Leon, R; Echeverria, R; Guderian, R H

1994-03-01

We have evaluated the impact of anthropization of the forest on the incidence of leishmaniasis, due to Leishmania panamensis, in three coastal study areas, Corriente Grande (primary forest), Paraiso Escondido and La Tablada (secondary forest). The situation of isolated dwellings, in deforested areas, has also been analysed in the last two stations. In each station, the study of the density of anthropophilic sand flies, specially Lutzomyia trapidoi, has been conducted in the domestic environment, coffee plantations and undergrowth. The incidence of leishmaniasis was nearly non existent in primary forest, though it ranged from 106 to 147% in the more or less cleared forest. At Corriente Grande, none Lu. trapidoi was caught in houses. In the undergrowth, catches were low (8% of the total). At Paraiso Escondido, Lu. trapidoi was the dominant species, with more than 83% of the catches in the undergrowth and in the coffee plantations (41 Man/hour), as well as in dwellings (10.6 M/h). At La Tablada, in the domestic environment, Lu. gomezi, was the dominant species: 2.8 M/h against 0.1 M/h for Lu. trapidoi. In the coffee plantations and in the undergrowth Lu. trapidoi was the main species, 21 M/h and 14 M/h. Thus in the primary rainforest, leishmaniasis transmission can be very low. In disturbed forest, coffee plantations near houses are good biotopes for Lu. trapidoi. The cycle of L. panamensis has been adapted to this new ecological situation, by being closer to the houses. The reservoirs live and circulate throughout coffee plantations. In deforested areas, neither aggressive sand flies have been observed, nor leishmaniasis transmission.

Leishmaniasis

DTIC Science & Technology

1993-01-01

disease are animals such as desert rats, sloths, horses, rodents, foxes and dogs . 14. SUMrCT TERMS IS. NUMBER OF PAGES Leishmaniasis, sandflies... Ketoconazole and Allopurinol)................................... 311 E. Topical Agents (Paromomycin) ...................... 313 F. Liposomes...panamensis), horses (L. braziliensis), rodents (L. mexicana); and foxes and dogs (L. donovani). In India, inadequately treated visceral infection may

[Penile augmentation using acellular dermal matrix].

PubMed

Zhang, Jin-ming; Cui, Yong-yan; Pan, Shu-juan; Liang, Wei-qiang; Chen, Xiao-xuan

2004-11-01

Penile enhancement was performed using acellular dermal matrix. Multiple layers of acellular dermal matrix were placed underneath the penile skin to enlarge its girth. Since March 2002, penile augmentation has been performed on 12 cases using acellular dermal matrix. Postoperatively all the patients had a 1.3-3.1 cm (2.6 cm in average) increase in penile girth in a flaccid state. The penis had normal appearance and feeling without contour deformities. All patients gained sexual ability 3 months after the operation. One had a delayed wound healing due to tight dressing, which was repaired with a scrotal skin flap. Penile enlargement by implantation of multiple layers of acellular dermal matrix was a safe and effective operation. This method can be performed in an outpatient ambulatory setting. The advantages of the acellular dermal matrix over the autogenous dermal fat grafts are elimination of donor site injury and scar and significant shortening of operation time.

Overview of dendritic cell-based vaccine development for leishmaniasis.

PubMed

Bagirova, M; Allahverdiyev, A M; Abamor, E S; Ullah, I; Cosar, G; Aydogdu, M; Senturk, H; Ergenoglu, B

2016-11-01

Leishmaniasis is one of the most serious vector-borne diseases in the world and is distributed over 98 countries. It is estimated that 350 million people are at risk for leishmaniasis. There are three different generation of vaccines that have been developed to provide immunity and protection against leishmaniasis. However, their use has been limited due to undesired side effects. These vaccines have also failed to provide effective and reliable protection and, as such, currently, there is no safe and effective vaccine for leishmaniasis. Dendritic cells (DCs) are a unique population of cells that come from bone marrow and become specialized to take up, process and present antigens to helper T cells in a mechanism similar to macrophages. By considering these significant features, DCs stimulated with different kinds of Leishmania antigens have been used in recent vaccine studies for leishmaniasis with promising results so far. In this review, we aim to review and combine the latest studies about this issue after defining potential problems in vaccine development for leishmaniasis and considering the importance of DCs in the immunopathogenesis of the disease. © 2016 John Wiley & Sons Ltd.

Leishmaniasis, conflict, and political terror: A spatio-temporal analysis.

PubMed

Berry, Isha; Berrang-Ford, Lea

2016-10-01

Leishmaniasis has been estimated to cause the ninth largest burden amongst global infectious diseases. Occurrence of the disease has been anecdotally associated with periods of conflict, leading to its referral as a disease of 'guerrilla warfare.' Despite this, there have been few studies that quantitatively investigate the extent to which leishmaniasis coincides with conflict or political terror. This study employed a longitudinal approach to empirically test for an association between cutaneous and visceral leishmaniasis incidence with occurrence of conflict and political terror at the national level, annually for 15 years (1995-2010). Leishmaniasis incidence data were collected for 54 countries, and combined with UCDP/PRIO Armed Conflict and Amnesty International political terror datasets. Mixed effects negative binomial regression models clustered at the country-level were constructed to evaluate the incidence rate ratios against the predictors, while controlling for wealth. Additionally, to understand how and why conflict-terror may be associated with leishmaniasis incidence, we conducted a historical analysis. We identify and discuss posited causal mechanisms in the literature, and critically assessed pathways by which leishmaniasis might occur in places and times of conflict-terror. There was a significant dose-response relationship for disease incidence based on increasing levels of conflict and terror. Country-years experiencing very high levels of conflict-terror were associated with a 2.38 times higher [95% CI: 1.40-4.05] and 6.02 times higher [95% CI: 2.39-15.15] incidence of cutaneous and visceral leishmaniasis, respectively. Historical analysis indicated that conflict and terror contribute to-or coincide with-leishmaniasis incidence through processes of population displacement and health system deterioration. This research highlights the potentially increased risks for cutaneous and visceral leishmaniasis incidence in areas of high conflict

Dermal reflectivity determined by optical coherence tomography is an indicator of epidermal hyperplasia and dermal edema within inflamed skin

NASA Astrophysics Data System (ADS)

Phillips, Kevin G.; Wang, Yun; Levitz, David; Choudhury, Niloy; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven L.

2011-04-01

Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of inflammation in psoriasis remain unclear. We undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to noninvasively document cutaneous alterations in mouse skin treated topically with Imiquimod (IMQ), an established model of a psoriasis-like disease. Quantitative appraisal of dermal architectural changes was achieved through a two parameter fit of OCT axial scans in the dermis of the form A(x, y, z) = ρ(x, y)exp [ - μ(x, y)z]. Ensemble averaging over 2000 axial scans per mouse in each treatment arm revealed no significant changes in the average dermal attenuation rate, <μ>, however the average local dermal reflectivity <ρ>, decreased significantly following 1, 3, and 6 days of IMQ treatment (p < 0.001) in comparison to vehicle-treated control mice. In contrast, epidermal and dermal thickness changes were only significant when comparing controls and 6-day IMQ treated mice. This suggests that dermal alterations, attributed to collagen fiber bundle enlargement, occur prior to epidermal thickness changes due to hyperplasia and dermal thickness changes due to edema. Dermal reflectivity positively correlated with epidermal hyperplasia (repi2 = 0.78) and dermal edema (rderm2 = 0.86). Our results suggest that dermal reflectivity as measured by OCT can be utilized to quantify a psoriasis-like disease in mice, and thus has the potential to aid in the quantitative assessment of psoriasis in humans.

Social and Economic Burden of Human Leishmaniasis

PubMed Central

Okwor, Ifeoma; Uzonna, Jude

2016-01-01

Leishmaniasis continues to pose a major public health problem worldwide. With new epidemics occurring in endemic areas and the spread of the disease to previously free areas because of migration, tourism, and military activities, there is a great need for the development of an effective vaccine. Leishmaniasis is a disease of the poor, occurring mostly in remote rural villages with poor housing and little or no access to modern health-care facilities. In endemic areas, diagnosis of any form of leishmaniasis puts a huge financial strain on an already meagre financial resource at both the individual and community levels. Most often families need to sell their assets (land and livestock) or take loans from informal financial outfits with heavy interest rates to pay for the diagnosis and treatment of leishmaniasis. Here, we discuss the disease with special emphasis on its socioeconomic impact on the affected individual and community. In addition, we highlight the reasons why continued research aimed at developing an effective Leishmania vaccine is necessary. PMID:26787156

Social and Economic Burden of Human Leishmaniasis.

PubMed

Okwor, Ifeoma; Uzonna, Jude

2016-03-01

Leishmaniasis continues to pose a major public health problem worldwide. With new epidemics occurring in endemic areas and the spread of the disease to previously free areas because of migration, tourism, and military activities, there is a great need for the development of an effective vaccine. Leishmaniasis is a disease of the poor, occurring mostly in remote rural villages with poor housing and little or no access to modern health-care facilities. In endemic areas, diagnosis of any form of leishmaniasis puts a huge financial strain on an already meagre financial resource at both the individual and community levels. Most often families need to sell their assets (land and livestock) or take loans from informal financial outfits with heavy interest rates to pay for the diagnosis and treatment of leishmaniasis. Here, we discuss the disease with special emphasis on its socioeconomic impact on the affected individual and community. In addition, we highlight the reasons why continued research aimed at developing an effective Leishmania vaccine is necessary. © The American Society of Tropical Medicine and Hygiene.

Leishmaniasis vaccines: past, present and future.

PubMed

Modabber, Farrokh

2010-11-01

No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

PubMed

Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

2013-10-01

Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.

A Novel Field Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis

DTIC Science & Technology

2015-10-01

include localized cutaneous leishmaniasis (LCL), and destructive nasal and oropharyngeal lesions of mucosal leishmaniasis (ML). LCL in the New World...the high costs, personnel training and need of sophisticated equipment. Therefore, novel methods to detect leishmaniasis at the POC are urgently needed...To date, there is no field-standardized molecular method based on DNA amplification coupled with Lateral Flow reading to detect leishmaniasis

[Approaches and problems in vaccine development against leishmaniasis].

PubMed

Allahverdiyev, Adil; Bağirova, Melahat; Cakir Koç, Rabia; Oztel, Olga Nehir; Elçıçek, Serhat; Ateş, Sezen Canım; Karaca, Tuğçe Deniz

2010-01-01

Leishmaniasis is a major public health problem of the world and Turkey. Recently there has been increasing interest in vaccine studies among strategies for control of leishmaniasis. Recently the increase of interest in vaccine studies among leishmaniasis control strategies makes the subject more up to date. So the aim of this review is to present information about recent vaccine studies, problems and new strategies for vaccine development studies. There are 3 generations of vaccine against leishmaniasis. First-generation vaccines are killed or live attenuated parasites; second-generation vaccines are recombinant or native antigens and live genetically modified parasites (knock out and suicidal cassettes), third generation vaccines are DNA vaccines. Also vector salivary proteins, dendritic cells and non-pathogenic L. tarentolae have been used as vaccine candidates. However there is still no effective vaccine against leishmaniasis. Since polymer conjugates considerably increase immunogenicity, polymer based vaccine studies have gained importance in recent years. However, there has not been such a study for an antileishmanial vaccine yet. LPG, surface antigen of Leishmania promastigotes, and polymer conjugates may be promising in antileishmanial vaccine studies so we are carrying out a TUBITAK Project on this subject which has been given the number, 1085170SBAG-4007.

Vaccines and vaccination strategies against human cutaneous leishmaniasis.

PubMed

Okwor, Ifeoma; Uzonna, Jude

2009-05-01

One might think that the development of a vaccine against cutaneous leishmaniasis would be relatively straightforward because the type of immune response required for protection is known and natural immunity occurs following recovery from primary infection. However, there is as yet no effective vaccine against the disease in humans. Although vaccination in murine studies has yielded promising results, these vaccines have failed miserably when tested in primates or humans. The reasons behind these failures are unknown and remain a major hurdle for vaccine design and development against cutaneous leishmaniasis. In contrast, recovery from natural, deliberate or experimental infections results in development of long-lasting immunity to re-infection. This so called infection-induced resistance is the strongest anti-Leishmania immunity known. Here, we briefly review the different approaches to vaccination against cutaneous leishmaniasis and argue that vaccines composed of genetically modified (attenuated) parasites, which induce immunity akin to infection-induced resistance, may provide best protection against cutaneous leishmaniasis in humans.

Alternative to Chemotherapy—The Unmet Demand against Leishmaniasis

PubMed Central

Didwania, Nicky; Shadab, Md.; Sabur, Abdus; Ali, Nahid

2017-01-01

Leishmaniasis is a neglected protozoan disease that mainly affects the tropical as well as subtropical countries of the world. The primary option to control the disease still relies on chemotherapy. However, a hindrance to treatments owing to the emergence of drug-resistant parasites, enormous side effects of the drugs, their high cost, and requirement of long course hospitalization has added to the existing problems of leishmaniasis containment program. This review highlights the prospects of immunotherapy and/or immunochemotherapy to address the limitations for current treatment measures for leishmaniasis. In addition to the progress in alternate therapeutic strategies, the possibility and advances in developing preventive measures against the disease have been pointed. The review highlights our recent understandings of the protective immunology that can be exploited to develop an effective vaccine against leishmaniasis. Moreover, an update on the approaches that have evolved over the recent years are predominantly focused to overcome the current challenges in developing immunotherapeutic as well as prophylactic antileishmanial vaccines is discussed. PMID:29312309

Novel hyaluronic acid dermal filler: dermal gel extra physical properties and clinical outcomes.

PubMed

Monheit, Gary D; Baumann, Leslie S; Gold, Michael H; Goldberg, David J; Goldman, Mitchel P; Narins, Rhoda S; Bachtell, Nathan; Garcia, Emily; Kablik, Jeffrey; Gershkovich, Julia; Burkholder, David

2010-11-01

Dermal gel extra (DGE) is a new, tightly cross-linked hyaluronic acid (HA)-based dermal filler containing lidocaine engineered to resist gel deformation and degradation. To develop a firmer gel product (DGE) and compare the efficacy and safety of DGE with nonanimal stabilized HA (NASHA) for correction of nasolabial folds (NLFs). DGE physical properties were characterized, and 140 subjects with moderate to deep NLFs were treated with DGE and NASHA in a randomized, multicenter, split-face design study. Efficacy, pain, and satisfaction were measured using appropriate standard instruments. Adverse events were monitored throughout the study. DGE has a higher modulus and a higher gel:fluid ratio than other HA fillers. Similar optimal correction was observed with DGE and NASHA through 36 weeks (9 months). Study subjects required less volume (p<.001) and fewer touch-ups (p=.005) and reported less injection pain (p<.001) with DGE treatment. Most adverse events were mild to moderate skin reactions. DGE is a firm HA gel that required significantly less volume and fewer touch-ups to provide equivalent efficacy to NASHA for NLF correction; both dermal gels were well tolerated. DGE will provide a comfortable and cost-effective dermal filler option for clinicians and patients. © 2010 by the American Society for Dermatologic Surgery, Inc.

New epidemiological aspects of visceral and cutaneous leishmaniasis in Taza, Morocco.

PubMed

Hakkour, Maryam; Hmamouch, Asmae; El Alem, Mohamed Mahmoud; Rhalem, Abdelkbir; Amarir, Fatima; Touzani, Mohamed; Sadak, Abderrahim; Fellah, Hajiba; Sebti, Faiza

2016-11-29

Leishmaniasis is considered among the main endemic diseases in Morocco. However, further knowledge about epidemiological aspects of this disease is needed in several provinces to plan control and preventive strategies to tackle the disease. The present study aims to determine the epidemiological aspect of cutaneous and visceral leishmaniasis in Taza Province from 2007-2014 and to identify the circulating species in this province. The temporal study from 2007 to 2014 showed that the number of cutaneous leishmaniasis cases increased since 2010. During the period of study, most leishmaniasis cases were detected in both urban and rural areas with 34% of cases detected in two urban localities, Bab Zitouna and Bab tété with 297 and 106 cases, respectively. The molecular study of cutaneous leishmaniasis showed the presence of non-sporadic Leishmania infantum and Leishmania tropica in this province. Regarding visceral leishmaniasis, Leishmania infantum is the species that has been identified. The epidemio-molecular study of leishmaniasis in Taza Province showed the coexistence of two species of Leishmania in the same foci. They also indicated that CL due to Leishmania infantum is more prevalent than reported in the literature. These results will be helpful for the implementation of control strategies by targeting dogs that constitute a reservoir of Leishmania infantum.

Dermal toxicity, eye and dermal irritation and skin sensitization evaluation of a new formulation of Bacillus thuringiensis var israelensis SH-14.

PubMed

Arteaga, M E; Mancebo, A; Molier, T; Gómez, D; González, C; Bada, A M; González, B; Rojas, N M; Rodríguez, G

2014-02-01

Bacillus thuringiensis (Bt) is the best known and most widely used of all pesticidal microbes. The aim of this study was to assess the toxicity of a new formulation of Bacillus thuringiensis var israelensis SH-14 in rats through acute dermal toxicity, dermal and eye irritation experiments. The acute dermal toxicity and dermal and eye irritation studies were performed using rabbits according to the United States Environmental Protection Agency guidelines 885.3100, 870.2500 and 870.2500, respectively. The skin sensitization study was carried out in accordance to the EPA OPPTS 870.2600 using guinea pigs. There was no mortality and no evidence of treatment-related toxicity in acute dermal toxicity test. No dermal responses, including erythema/eschar or edema, were found in rabbits treated with the new formulation of Bti SH-14. Minimum response was observed after eye application of test substance. No skin sensitization reactions were observed after the challenge with the new formulation of Bti SH-14 in the Bti SH-14-treated guinea pigs. In summary, the present study demonstrated that the new formulation of Bti SH-14 is not acutely toxic via dermal route, has low eye irritation and would not cause dermal irritation or hypersensitivity to tested animals. Copyright © 2013 Elsevier Inc. All rights reserved.

Spread of Vector-borne Diseases and Neglect of Leishmaniasis, Europe

PubMed Central

Campino, Lenea; Cañavate, Carmen; Dedet, Jean-Pierre; Gradoni, Luigi; Soteriadou, Ketty; Mazeris, Apostolos; Ozbel, Yusuf; Boelaert, Marleen

2008-01-01

The risk for reintroduction of some exotic vector-borne diseases in Europe has become a hot topic, while the reality of others is neglected at the public health policy level. Leishmaniasis is endemic in all southern countries of Europe, with ≈700 autochthonous human cases reported each year (3,950 if Turkey is included). Asymptomatic cases have been estimated at 30–100/1 symptomatic case, and leishmaniasis has up to 25% seroprevalence in domestic dogs. Even though leishmaniasis is essentially associated with Leishmania infantum and visceral leishmaniasis, new species, such as L. donovani and L. tropica, might colonize European sand fly vectors. Drug-resistant L. infantum strains might be exported outside Europe through dogs. Despite this possibility, no coordinated surveillance of the disease exists at the European level. In this review of leishmaniasis importance in Europe, we would like to bridge the gap between research and surveillance and control. PMID:18598618

Genetics Home Reference: focal dermal hypoplasia

MedlinePlus

... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

Climate and Leishmaniasis in French Guiana

PubMed Central

Roger, Amaury; Nacher, Mathieu; Hanf, Matthieu; Drogoul, Anne Sophie; Adenis, Antoine; Basurko, Celia; Dufour, Julie; Sainte Marie, Dominique; Blanchet, Denis; Simon, Stephane; Carme, Bernard; Couppié, Pierre

2013-01-01

To study the link between climatic variables and the incidence of leishmaniasis a study was conducted in Cayenne, French Guiana. Patients infected between January 1994 and December 2010. Meteorological data were studied in relation to the incidence of leishmaniasis using an ARIMA model. In the final model, the infections were negatively correlated with rainfall (with a 2-month lag) and with the number of days with rainfall > 50 mm (lags of 4 and 7 months). The variables that were positively correlated were temperature and the Multivariate El Niño Southern Oscillation Index with lags of 8 and 4 months, respectively. Significantly greater correlations were observed in March for rainfall and in November for the Multivariate El Niño/Southern Oscillation Index. Climate thus seems to be a non-negligible explanatory variable for the fluctuations of leishmaniasis. A decrease in rainfall is linked to increased cases 2 months later. This easily perceptible point could lead to an interesting prevention message. PMID:23939706

A travel misadventure--visceral leishmaniasis in an immunocompetent patient.

PubMed

Delacour, H; Roche, C; Roche, B; Morand, C; Koeck, J L

2010-09-01

Visceral leishmaniasis is one of the world's most neglected diseases. Over 90% of the 500,000 annual new cases occur in only five countries: India, Nepal, Bangladesh, Sudan and North-Eastern Brazil, but the disease remains endemic in Southern Europe. We report a case of visceral leishmaniasis in an immunocompetent serviceman after a seven-day stay in the Marseilles region of South-Eastern France. This case is intended to alert clinicians to the possibility of visceral leishmaniasis in patients who develop a febrile illness after returning from travel in Southern European countries.

[Topical treatment of persistent cutaneous leishmaniasis with paromomycin].

PubMed

Flaig, M J; Rupec, J; Ruzicka, T; Rupec, R A

2007-08-01

Cutaneous leishmaniasis is an infectious disease with increasing prevalence in Germany. Diagnosis and therapy may be difficult due to the variability of the clinical and histomorphological picture and resistance to therapy. In this case study we report on a female patient with a persistent cutaneous leishmaniasis successfully treated with topical administration of paromomycin.

[Visceral leishmaniasis. Pediatric case report].

PubMed

Gomila H, Andrés; Vanzo, Carolina; Garnero, Analía; Peruzzo, Luisina; Badalotti, Mónica

2017-08-01

La leishmaniasis es una enfermedad causada por parásitos obligados intracelulares pertenecientes al género Leishmania y que reconoce tres formas clínicas principales: cutánea, visceral y mucocutánea. Es una patología del grupo de las "enfermedades desatendidas". Es la única enfermedad tropical transmitida a través de vectores que se ha mantenido endémica por décadas en el sur de Europa. La leishmaniasis visceral representa la forma más grave. Se caracteriza por fiebre, pérdida de peso, anemia y hepatoesplenomegalia. Su período de incubación oscila entre 2 semanas y 18 meses. La leishmaniasis se considera una enfermedad reemergente a nivel mundial. Algunos de los factores que favorecen esta situación son los cambios en las condiciones climáticas, migraciones y urbanizaciones deficitarias en saneamiento ambiental. Se presenta el caso de un niño europeo que estaba vacacionando en Córdoba y fue derivado a nuestro Hospital por fiebre y pancitopenia, lo que generó un abordaje multidisciplinario con resolución clínica favorable. Sociedad Argentina de Pediatría.

Immunopathology of leishmaniasis: an update.

PubMed

Mansueto, P; Vitale, G; Di Lorenzo, G; Rini, G B; Mansueto, S; Cillari, E

2007-01-01

Leishmaniasis represents a severe, increasing, public health problem. The perspective of its control is highly dependent on research progress, on therapeutic manipulations of the immune system, and on vaccine development. There is a correlation between the clinical outcome of Leishmania infection and the cytokine response profile. While a protective immune response against Leishmania has been clearly identified to be related to the influence of a type-1 response and IFN-gamma production, the precise role of T helper (TH) 2 cytokines in non-healing infections requires further exploration. IL-4 and IL-13 (TH2 cytokines) can promote disease progression in cutaneous leishmaniasis, whereas IL-4 would appear to enhance protective type-1 responses in visceral leishmaniasis. Thus, the TH1/TH2 paradigm of resistance/susceptibility to intracellular parasites is probably an oversimplification of a more complicated network of regulatory/counter regulatory interactions. Moreover, the presence of antigen specific regulatory T cell subsets may provide an environment that contributes to the balance between TH1 and TH2 cells. Finally, the involvement of CD8 positive T cells has been described, but the modality of their function in this kind of infection has not been so far elucidated.

Miltefosine: oral treatment of leishmaniasis.

PubMed

Soto, Jaime; Soto, Paula

2006-04-01

The well-known problems of classic treatment of the leishmaniases with pentavalent antimony (reduced efficacy), difficulties of administration and increasing frequency and severity of adverse events have stimulated the search for new drugs to treat these diseases. Other injectable, oral and topical drugs have not been consistently effective, especially in the modern World. Beginning in 1998, Indian researchers conducted several trials with hexadecylphosphocholine (miltefosine) in patients with visceral leishmaniasis, and in 1999, clinical studies were initiated in Colombia for cutaneous disease. More than 2500 patients have been treated, including patients with diffuse cutaneous leishmaniasis, mucosal disease and patients coinfected with HIV. Cure rates between 91 and 100% were reached with a dose of 2.5 mg/kg/day for 28 days, with no difference between treatment-naive and relapsing patients. Mild gastrointestinal events were present in 35-60% of patients and 10-20% had mild transaminase and creatinine elevations. Miltefosine has potent leishmanicidal activity as a consequence of its interference in parasite metabolic pathways and the induction of apoptosis. Miltefosine is the first effective and safe oral agent with the potential to treat all major clinical presentations of leishmaniasis.

A decade bibliometric analysis of global research on leishmaniasis in Web of Science database.

PubMed

Soosaraei, Masoud; Khasseh, Ali Akbar; Fakhar, Mahdi; Hezarjaribi, Hajar Ziaei

2018-02-01

Leishmaniasis is an extremely relevant tropical disease, with global distribution. It still remains a main public health concern in low-income countries, and it is necessary to support more research on this common disease. Thus, a bibliometric analysis of the global scientific production on leishmaniasis was carried out. All the articles registered in Web of Science with the subject of leishmaniasis between 2006 and 2015 were analysed, using Pajek and VOS viewer as tools. 13,658 records in the field of leishmaniasis were indexed in the Web of Science database for this ten-year study period (2006-2015). This shows that studies on leishmaniasis have been growing, from 1071 in 2006 to 1537 in 2015. "Sundar S" is the most active researcher in the field of leishmaniasis, compiling and participating in 232 Articles. Brazil ranks first in scientific production, by performing 3315 studies on leishmaniasis. The United States, United Kingdom and Australia had the most collaboration in performing the studies of leishmaniasis with each other. In addition, PLOS NEGLECTED TROPICAL DISEASES published the most articles, with 483. Our data shows an increase in the number of publications in the field of leishmaniasis. In addition, Brazil, USA, and India lead scientific production on leishmaniasis research.

A case of severe visceral leishmaniasis resulting from travel to Greece

PubMed Central

Hamilton, Alexander; Kelleher, Anthony; Marriott, Debbie

2009-01-01

Visceral leishmaniasis is rare in the developed world, particularly in immunocompetent hosts. It must be considered, however, in patients who are unwell, febrile and unresponsive to conventional antibiotics with a history of travel to areas where leishmaniasis is endemic. A case of more severe clinical manifestations than have been previously reported in Australia is presented here. The recent introduction of PCR technology for the detection of Leishmania in Australia has improved the diagnosis and management of leishmaniasis. Treatment with liposomal amphotericin B proved to be very effective in this severe case of visceral leishmaniasis. PMID:21886664

Reactivation of Mucosal and Cutaneous Leishmaniasis in a Renal Transplanted Patient

PubMed Central

Tuon, Felipe F.; Bombonatto, Giovana Marina; Battaglin, Eveline Roesler; Sakumoto, Marcus Henrique; Amato, Valdir Sabbaga; de Camargo, Raphael Abegão; Nicodemo, Antônio Carlos

2014-01-01

Mucosal leishmaniasis (ML) is a chronic form of tegumentary leishmaniasis, which causes destructive lesions of nasal, pharyngeal, and laryngeal mucosa. We describe a case of leishmaniasis reactivation with simultaneous cutaneous and mucosal forms in a renal transplanted patient with no history of prior leishmaniasis. Reactivation after renal transplantation was not reported in Brazil. A 67-year-old woman receiving prednisone 20 mg/day, tacrolimus 1 mg/day, and mycophenolic acid 360 mg/day presented with nose edema with erythema and cutaneous lesions. Amastigotes were identified on biopsies and the polymerase chain reaction confirmed Leishmania (Viannia) braziliensis. The patient was treated with liposomal amphotericin B but died 3 weeks after as a result of bacterial septic shock. In conclusion, tegumentary leishmaniasis can reactivate with simultaneous cutaneous and mucosal forms in a renal transplanted patient during the immunosuppressant therapy. PMID:24732458

Reevaluating leishmanin skin test as a marker for immunity against cutaneous leishmaniasis.

PubMed

Momeni Boroujeni, Amir; Aminjavaheri, Malih; Moshtaghian, Bahador; Momeni, Arash; Momeni, Ali Z

2013-07-01

The leishmanin skin test (LST) has been used for clinical diagnosis of leishmaniasis and epidemiological studies of the disease. Thus far, evidence has suggested that LST conversion indicates a degree of protection against leishmaniasis. In this study, we have put this assumption to test. A total of 273 participants with positive LST living in a hyperendemic area for leishmaniasis were followed for three years for any occurrence of cutaneous leishmaniasis. Twenty-two of the 273 participants contracted leishmaniasis during the 3-year follow-up. These new cases included participants who had a previous history of active disease, those who had a history of leishmanization, or those who were suspected of having a history of subclinical infection. In this study, the incidence of leishmaniasis in individuals with positive LST was close to the general incidence of the disease in the same hyperendemic area. These results suggest that although LST conversion may be a marker for partial immunity towards leishmaniasis, it may not, however, indicate complete protection against the disease, and consequently there is a need for revision of current vaccine development approaches which are based on rendering vaccinated individuals LST positive. © 2013 The International Society of Dermatology.

Cutaneous leishmaniasis in three Dutch military cohorts following jungle training in Belize.

PubMed

van Thiel, P P A M; Zeegelaar, J E; van Gool, T; Faber, W R; Kager, P A

2011-05-01

Skin lesions occur frequently in travelers to tropical countries. Military personnel acquire skin lesions regularly during jungle training as did Dutch troops who trained in the jungle of Belize in 1998, 2004 and 2009, in an area endemic for cutaneous leishmaniasis. Demographic and clinical data were collected retrospectively. Diagnostic investigations for cutaneous leishmaniasis included Giemsa stain, culture, PCR and NASBA and histopathology of biopsies. Treatment of leishmaniasis was with sodium stibogluconate, given intravenously or intralesionally, the latter with cryotherapy. In 1998 and 2004 cutaneous leishmaniasis due to Leishmania braziliensis and Leishmania mexicana infection was diagnosed in 25 persons out of 99 (attack rate 25.2%) and 14 persons out of 80 (attack rate 17.5%) respectively. In 2009 cutaneous leishmaniasis was not acquired. Skin problems were common during and after jungle training. Cutaneous leishmaniasis was important in the first two cohorts but not observed in the third cohort. Factors that could have played a role in the absence of cutaneous leishmaniasis in the third cohort include variability in transmission and availability of better preventive measures and adherence to these. Sodium stibogluconate treatment, intralesional or intravenous, was effective. Copyright © 2011 Elsevier Ltd. All rights reserved.

The dermal arteries of the human thumb pad

PubMed Central

Geyer, S H; Nöhammer, M M; Tinhofer, I E; Weninger, W J

2013-01-01

The arteries of the skin have been postulated to form a profound plexus at the dermal/hypodermal junction and a superficial plexus in the papillary dermis. Our article aims to rebut this concept and to provide an alternative description of the arrangement of the dermal arteries. Employing a novel technique, we produced digital volume data (volume size: 2739 × 2054 × 3000 μm3; voxel size: 1.07 × 1.07 × 2 μm3) from biopsies of the skin of the thumb pads of 15 body donors. Utilizing these data, we analysed the arrangement of the dermal arteries with the aid of virtual re-sectioning tools, and, in three specimens, with high-quality three-dimensional (3D) surface models. In all specimens we observed a tree-like ramification of discrete dermal arteries. The terminal branches of the arterial trees gave rise to the ascending segments of the capillary loops of the dermal papillae. None of the specimens showed a superficial arterial plexus. This suggests that the skin of the human thumb pad can be split in discrete ‘arterial units’. Each unit represents the zone of the papillary dermis and epidermal/dermal junction, to which blood is supplied exclusively by the branches of a single dermal artery. The concept of dermal arterial units is in contrast to all existing descriptions of the architecture of the dermal arteries. However, whether it can be transferred to the skin of other body parts, remains to be tested. Likewise, the consequences of arterial units for understanding the mechanisms of wound healing and the appearance and genesis of skin diseases remain to be examined. PMID:24205910

ISSUES IN DERMAL EXPOSURE OF INFANTS

EPA Science Inventory

Infants' dermal exposures to environmental contaminants are expected to be different and, in many cases, much higher than adults. Because of the potential importance of the dermal exposure route, there is currently a significant amount of work being conducted to reduce the uncer...

Recent developments in leishmaniasis vaccine delivery systems.

PubMed

Bhowmick, Sudipta; Ali, Nahid

2008-07-01

The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

Dermal uptake of petroleum substances.

PubMed

Jakasa, Ivone; Kezic, Sanja; Boogaard, Peter J

2015-06-01

Petroleum products are complex substances comprising varying amounts of linear and branched alkanes, alkenes, cycloalkanes, and aromatics which may penetrate the skin at different rates. For proper interpretation of toxic hazard data, understanding their percutaneous absorption is of paramount importance. The extent and significance of dermal absorption of eight petroleum substances, representing different classes of hydrocarbons, was evaluated. Literature data on the steady-state flux and permeability coefficient of these substances were evaluated and compared to those predicted by mathematical models. Reported results spanned over 5-6 orders of magnitude and were largely dependent on experimental conditions in particular on the type of the vehicle used. In general, aromatic hydrocarbons showed higher dermal absorption than more lipophilic aliphatics with similar molecular weight. The results showed high variation and were largely influenced by experimental conditions emphasizing the need of performing the experiments under "in use" scenario. The predictive models overestimated experimental absorption. The overall conclusion is that, based on the observed percutaneous penetration data, dermal exposure to petroleum hydrocarbons, even of aromatics with highest dermal absorption is limited and highly unlikely to be associated with health risks under real use scenarios. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Leishmaniasis in Thailand: A Review of Causative Agents and Situations

PubMed Central

Leelayoova, Saovanee; Siripattanapipong, Suradej; Manomat, Jipada; Piyaraj, Phunlerd; Tan-ariya, Peerapan; Bualert, Lertwut; Mungthin, Mathirut

2017-01-01

Before 1999, leishmaniasis was considered an imported disease in Thailand. Since then, autochthonous leishmaniasis was reported in both immmunocompetent and immmunocompromised patients especially in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). A new species was identified and named as Leishmania siamensis consisting of two lineages, that is, lineages TR and PG. Analysis of isoenzymes has clarified the more commonly detected L. siamensis lineage PG as Leishmania martiniquensis (MON-229), a species originally reported from the Martinique Island, whereas the L. siamensis lineage TR has been identified as the true novel species, L. siamensis (MON-324). Both cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) have been found among Thai patients. Disseminated CL and VL could be presented in some reported patients who had HIV/AIDS coinfection. So far, only sporadic cases have been reported; thus, the true prevalence of leishmaniasis should be determined in Thailand among the high-risk populations such as people with HIV/AIDS. A recent survey among animals identified L. martiniquensis DNA in black rats (Rattus rattus) suggesting a potential animal reservoir. In addition, L. martiniquensis DNA was identified in Sergentomyia gemmea and Sergentomyia barraudi, the predominant sandfly species in the affected areas. However, further studies are needed to prove that these sandflies could serve as the vector of leishmaniasis in Thailand. PMID:28093539

Primary cell culture and morphological characterization of canine dermal papilla cells and dermal fibroblasts.

PubMed

Bratka-Robia, Christine B; Mitteregger, Gerda; Aichinger, Amanda; Egerbacher, Monika; Helmreich, Magdalena; Bamberg, Elmar

2002-02-01

Skin biopsies were taken from female dogs, the primary hair follicles isolated and the dermal papilla dissected. After incubation in supplemented Amniomax complete C100 medium in 24-well culture plates, the dermal papilla cells (DPC) grew to confluence within 3 weeks. Thereafter, they were subcultivated every 7 days. Dermal fibroblast (DFB) cultures were established by explant culture of interfollicular dermis in serum-free medium, where they reached confluence in 10 days. They were subcultivated every 5 days. For immunohistochemistry, cells were grown on cover slips for 24 h, fixed and stained with antibodies against collagen IV and laminin. DPC showed an aggregative growth pattern and formation of pseudopapillae. Intensive staining for collagen IV and laminin could be observed until the sixth passage. DFB grew as branching, parallel lines and showed only weak staining for collagen IV and laminin.

Dermal extracellular lipid in birds.

PubMed

Stromberg, M W; Hinsman, E J; Hullinger, R L

1990-01-01

A light and electron microscopic study of the skin of domestic chickens, seagulls, and antarctic penguins revealed abundant extracellular dermal lipid and intracellular epidermal lipid. Dermal lipid appeared ultrastructurally as extracellular droplets varying from less than 1 micron to more than 25 microns in diameter. The droplets were often irregularly contoured, sometimes round, and of relatively low electron density. Processes of fibrocytes were often seen in contact with extracellular lipid droplets. Sometimes a portion of such a droplet was missing, and this missing part appeared to have been "digested away" by the cell process. In places where cells or cell processes are in contact with fact droplets, there are sometimes extracellular membranous whorls or fragments which have been associated with the presence of fatty acids. Occasionally (in the comb) free fat particles were seen in intimate contact with extravasated erythrocytes. Fat droplets were seen in the lumen of small dermal blood and lymph vessels. We suggest that the dermal extracellular lipid originates in the adipocyte layer and following hydrolysis the free fatty acids diffuse into the epidermis. Here they become the raw material for forming the abundant neutral lipid contained in many of the epidermal cells of both birds and dolphins. The heretofore unreported presence and apparently normal utilization of abundant extracellular lipid in birds, as well as the presence of relatively large droplets of neutral lipid in dermal vessels, pose questions which require a thorough reappraisal of present concepts of the ways in which fat is distributed and utilized in the body.

First generation leishmaniasis vaccines: a review of field efficacy trials.

PubMed

Noazin, Sassan; Modabber, Farrokh; Khamesipour, Ali; Smith, Peter G; Moulton, Lawrence H; Nasseri, Kiumarss; Sharifi, Iraj; Khalil, Eltahir A G; Bernal, Ivan Dario Velez; Antunes, Carlos M F; Kieny, Marie Paule; Tanner, Marcel

2008-12-09

First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified. Despite this overall failure, these trials contributed significantly to increasing knowledge on human leishmaniasis immunology. To provide a collective view, this review discusses the methods and findings of field efficacy trials of first generation leishmaniasis vaccine clinical trials conducted in the Old and New Worlds.

Application of nanotechnology in treatment of leishmaniasis: A Review.

PubMed

Akbari, Maryam; Oryan, Ahmad; Hatam, Gholamreza

2017-08-01

Leishmaniasis is a neglected tropical disease caused by a protozoan species of the genus Leishmania affecting mostly the developing countries. The disease with current mortality rate of 50,000 deaths per year threatens approximately 350 million people in more than 90 countries all over the world. Cutaneous, mucocutaneous and visceral leishmaniasis are the most frequent forms of the disease. Chemotherapy still relies on the use of pentavalent antimonials, amphotericin B, liposomal amphotericin B and miltefosin. Treatment of leishmaniasis has remained insufficient since the current antileishmanial agents have several limitations including low efficacy, toxicity, adverse side effects, drug-resistance, length of treatment and cost lines. Consequently, there is an immediate requirement to search for new antileishmanial compounds. New drug delivery devices transport antileishmanial drug to the target cell specifically with minimizing the toxic effects to normal cells. This study attempts to present a comprehensive overview of different approaches of nanotechnology in treatment of leishmaniasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Visceral Leishmaniasis

DTIC Science & Technology

2011-06-01

er than 1:256. These positive IFA tests are readily distin- guishable from the low-titer positive tests occasionally seen in malaria, typhoid fever ...leishmaniasis (VL), a chronic disease caused by parasites of the Leishmania donovani complex, is character- ized by irregular fever , enlargement of the...meaning “black sickness”, although hyperpigmenta- tion is not a common feature of the disease. Descriptive names for VL, such as Burdwan fever , Dumdum

Mesenchymal stem cells induce dermal fibroblast responses to injury

PubMed Central

Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

2009-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury. PMID:19666021

Mesenchymal stem cells induce dermal fibroblast responses to injury

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

Smith, Andria N., E-mail: snosmith@u.washington.edu; Willis, Elise, E-mail: elise.willis@gmail.com; Chan, Vincent T.

2010-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. Whenmore » co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.« less

Bibliometric analysis of leishmaniasis research in Medline (1945-2010)

PubMed Central

2013-01-01

Background Publications are often used as a measure of success of research work. Leishmaniasis is considered endemic in 98 countries, most of which are developing. This article describes a bibliometric review of the literature on leishmaniasis research indexed in PubMed during a 66-year period. Methods Medline was used via the PubMed online service of the US National Library of Medicine. The search strategy was Leishmania [MeSH] or leishmaniasis [MeSH] from 1 January 1945 until 31 December 2010. Neither language nor document type restrictions were employed. Results A total of 20,780 references were retrieved. The number of publications increased steadily over time, with 3,380 publications from 1945-1980 to 8,267 from 2001-2010. Leishmaniasis documents were published in 1,846 scientific journals, and Transactions of the Royal Society of Tropical Medicine and Hygiene (4.9%) was the top one. The USA was the predominant country by considering the first author’s institutional address (16.8%), followed by Brazil (14.9%), and then India (9.0%), however Brazil leads the scientific output in 2001-2010 period (18.5%), followed by the USA (13.5%) and India (10%). The production ranking changed when the number of publications was normalised by population (Israel and Switzerland), by gross domestic product (Nepal and Tunisia), and by gross national income per capita (India and Ethiopia). For geographical area, Europe led (31.7%), followed by Latin America (24.5%). Conclusions We have found an increase in the number of publications in the field of leishmaniasis. The USA and Brazil led scientific production on leishmaniasis research. PMID:23497410

Leishmaniasis in Sri Lanka: spatial distribution and seasonal variations from 2009 to 2016.

PubMed

Galgamuwa, Lahiru Sandaruwan; Dharmaratne, Samath D; Iddawela, Devika

2018-01-25

Leishmaniasis is listed as one of the eight neglected tropical diseases by the World Health Organization and the number of cases in endemic areas has seen a sharp rise in the past decade. More alarmingly, reports have shown that leishmaniasis is spreading to non-endemic areas of the world due to co-infection with HIV. In Sri Lanka, leishmaniasis is considered as a notifiable disease from 2008 and has seen a rising trend of incidence since then. This is the first study describing the burden, seasonal variation and spatial distribution of leishmaniasis in Sri Lanka since the disease has been included as a notifiable disease. Data on health statistics from 2009 to 2016 were obtained from published databases maintained by the Epidemiology Unit of the Ministry of Health in Sri Lanka. Climatic data for Sri Lanka were obtained from the Department of Meteorology and the populations in administrative districts were obtained from the Department of Census and Statistics, Sri Lanka. Descriptive spatiotemporal analysis, correlation between leishmaniasis incidence and climatic variables were analyzed using SPSS statistical software. The total number of people reported with leishmaniasis during the study period was 8487. Cutaneous leishmaniasis is the prominent form in Sri Lanka while few visceral and muco-cutaneous cases were reported. Although leishmaniasis patients were identified from all 25 districts in the island, almost 90% of the total caseload was reported from Anuradhapura, Hambantota, Polonnaruwa, Kurunegala and Matara districts. The highest number of patients was reported from the Anuradhapura district and the highest incidence per 100,000 persons was reported from the Hambantota district. The disease has a seasonal trend, a peak of leishmaniasis occur in July to September in the north-central region and in October to December in the southern region. Maximum temperature, humidity and wind speed are significantly associated climatic variables with leishmaniasis in

[Chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma].

PubMed

Marguglio, A; Hoyoux, C; Dresse, M F; Chantraine, J M; Thiry, A; Gillet, P

1998-03-01

Leishmaniasis refers to a spectrum of diseases caused by Leishmania. Clinically, three types of leishmaniasis can be distinguished: the cutaneous, mucous and visceral leishmaniasis, the latter being caused by Leishmania donovani. An 11-year-old Thai, living in Belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. During a post-chemotherapy bone marrow aplasia, febrile episode with a general condition impairment was noted and first treated by broad-spectrum antibiotherapy, then by amphotericin B, in the absence of any accurate etiology. The outcome first was favorable. Nevertheless, 7 months later, the visceral leishmaniasis diagnosis was made because of the recurrence of the same symptoms. Classical treatments by antimony derivatives (Glucantim), then liposomal amphotericin (Ambisome) proved to be inefficient. A liposomal amphotericin-gamma interferon association suppressed the symptoms without eradicating the parasite. The patient was given a maintenance therapy based on liposomal amphotericin. The stubborn and recurring nature of this chronic visceral leismaniosis can be due to the immune deficit inherent in the polychemotherapy performed in order to treat the metastatic osteosarcoma which currently is in first full remission.

Leishmaniasis: Who Uses Personal Protection among Military Personnel in Colombia?

PubMed

González, Aida M; Solís-Soto, María Teresa; Radon, Katja

Leishmaniasis is common in Colombia, negatively affecting the health of military personnel active in endemic areas. The disease is transmitted by sand fly bites. Therefore, during duty, use of long-sleeved uniforms and other clothes treated with permethrin and application of mosquito repellent are important personal preventive measures. The objective of this study was to assess personal and occupational factors associated with the use of personal protection in male soldiers deployed to Leishmaniasis-endemic areas. Three hundred soldiers participated in a cross-sectional questionnaire study (response 84.3%). The self-administered questionnaire contained questions about sociodemographics, duration of service, compliance with personal mosquito protection, and knowledge about leishmaniasis. Descriptive analyses were followed by multiple logistic regression models adjusted for potential confounders (EpiInfo Version 7.0) FINDINGS: Overall, 23% of the soldiers reported complete use of the recommended personal protection measures. About 83% of the participants had heard about leishmaniasis. In the adjusted regression model, knowledge about leishmaniasis (adjusted odds ratio = 2.9; 95% confidence interval: 1.1-7.2) and being enrolled in the army for more than 5 years (2.2; 1.1-4.1) increased the odds of using personal protection. Improving knowledge about leishmaniasis is one measure to increase use of personal protection, thereby diminishing the risk of infection. Copyright © 2017 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Drug Discovery Algorithm for Cutaneous Leishmaniasis

PubMed Central

Grogl, Max; Hickman, Mark; Ellis, William; Hudson, Thomas; Lazo, John S.; Sharlow, Elizabeth R.; Johnson, Jacob; Berman, Jonathan; Sciotti, Richard J.

2013-01-01

Cutaneous leishmaniasis is clinically widespread but lacks treatments that are effective and well tolerated. Because all present drugs have been grandfathered into clinical use, there are no examples of a pre-clinical product evaluation scheme that lead to new candidates for formal development. To provide oral agents for development targeting cutaneous leishmaniasis, we have implemented a discovery scheme that incorporates in vitro and in vivo testing of efficacy, toxicity, and pharmacokinetics/metabolism. Particular emphasis is placed on in vivo testing, progression from higher-throughput models to those with most clinical relevance, and efficient use of resources. PMID:23390221

American cutaneous leishmaniasis triggered by electrocoagulation.

PubMed

Martins, Sofia Sales; Santos, Adriana de Oliveira; Lima, Beatriz Dolabela; Gomes, Ciro Martins; Sampaio, Raimunda Nonata Ribeiro

2018-01-01

Cutaneous leishmaniasis is usually transmitted by infected phlebotomine sand fly bites that initiate local cutaneous lesions. Few reports in the literature describe other modes of transmission. We report a case of a previously healthy 59-year-old woman who underwent electrocoagulation to remove seborrheic keratosis confirmed by dermatoscopy. Three months later, a skin fragment tested positive for Leishmania culture; the parasite was identified as L. (V.) braziliensis. Trauma may generate inflammatory cascades that favor Leishmania growth and lesion formation in previously infected patients. American cutaneous leishmaniasis is a dynamic disease with unclear pathophysiology because of continually changing environments, demographics, and human behaviors.

Molecular epidemiology for vector research on leishmaniasis.

PubMed

Kato, Hirotomo; Gomez, Eduardo A; Cáceres, Abraham G; Uezato, Hiroshi; Mimori, Tatsuyuki; Hashiguchi, Yoshihisa

2010-03-01

Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses have been performed on sand fly species and genotyping using PCR-RFLP has been applied to the sand fly taxonomy. In addition, a molecular mass screening method has been established that enables both sand fly species and natural leishmanial infections to be identified simultaneously in hundreds of sand flies with limited effort. This paper reviews recent advances in the study of sand flies, vectors of leishmaniasis, using molecular biological approaches.

Molecular Epidemiology for Vector Research on Leishmaniasis

PubMed Central

Kato, Hirotomo; Gomez, Eduardo A; Cáceres, Abraham G; Uezato, Hiroshi; Mimori, Tatsuyuki; Hashiguchi, Yoshihisa

2010-01-01

Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses have been performed on sand fly species and genotyping using PCR-RFLP has been applied to the sand fly taxonomy. In addition, a molecular mass screening method has been established that enables both sand fly species and natural leishmanial infections to be identified simultaneously in hundreds of sand flies with limited effort. This paper reviews recent advances in the study of sand flies, vectors of leishmaniasis, using molecular biological approaches. PMID:20617005

[Visceral leishmaniasis in patient with HIV infection].

PubMed

Olea, Pilar; Pinilla, Jorge

2013-04-01

Leishmaniasis is a parasitic disease caused by the protozoa of the genus Leishmania transmitted by sandfly bites. It causes subclinical infection and diverse clinical manifestations with cutaneous, mucosal or visceral involvement. The last one, called visceral leishmaniasis, is usually fatal without treatment and in VIH patients with deep immunosuppression, has been recognized as an opportunistic infection with a high degree of difficulty in diagnosis and treatment. We present the case of a patient with HIV infection and visceral leishmaniasis. The clinical presentation was a prolonged febril syndrome with hepatosplenomegaly, lymphadenopathy and pancytopenia. The differential diagnosis was made with lymphoma and other opportunistic infections, as mycobacteriosis. The bone marrow aspirate reveled parasite amastigotes. The patient received treatment with amphotericin B deoxycholate for 14 days and 2 months after he relapsed. Then he was treated with the same drug for 21 days and after that he has been in prophylaxis for 29 months with good outcome, without any other relapse.

Simultaneous occurrence of ocular, disseminated mucocutaneous, and multivisceral involvement of leishmaniasis.

PubMed

Philips, Cyriac Abby; Kalal, Chetan Ramesh; Kumar, K N Chandan; Bihari, Chhagan; Sarin, Shiv Kumar

2014-01-01

Leishmaniasis is a tropical infection caused by the protozoan, belonging to the group of Leishmania which causes Old World and New World disease. These are typically divided into cutaneous, mucocutaneous, visceral, viscerotropic, and disseminated disease. Cutaneous leishmaniasis in the presence of visceral disease is a rarity. Isolated case reports have documented this occurrence, in the immunocompromised setting, and few otherwise. The concurrent presence of visceral leishmaniasis (bone marrow involvement) with solitary cutaneous and ocular disease and also solitary cutaneous and visceral disease (bone marrow involvement) has been reported before. Here, we present an immunocompetent patient who was diagnosed to have visceral leishmaniasis (liver and bone marrow involvement) along with simultaneous disseminated mucocutaneous and ocular involvement, a combination that has never been reported before.

Simultaneous Occurrence of Ocular, Disseminated Mucocutaneous, and Multivisceral Involvement of Leishmaniasis

PubMed Central

Kalal, Chetan Ramesh; Kumar, K. N. Chandan; Bihari, Chhagan; Sarin, Shiv Kumar

2014-01-01

Leishmaniasis is a tropical infection caused by the protozoan, belonging to the group of Leishmania which causes Old World and New World disease. These are typically divided into cutaneous, mucocutaneous, visceral, viscerotropic, and disseminated disease. Cutaneous leishmaniasis in the presence of visceral disease is a rarity. Isolated case reports have documented this occurrence, in the immunocompromised setting, and few otherwise. The concurrent presence of visceral leishmaniasis (bone marrow involvement) with solitary cutaneous and ocular disease and also solitary cutaneous and visceral disease (bone marrow involvement) has been reported before. Here, we present an immunocompetent patient who was diagnosed to have visceral leishmaniasis (liver and bone marrow involvement) along with simultaneous disseminated mucocutaneous and ocular involvement, a combination that has never been reported before. PMID:24707415

Pro-apoptotic effect of the landrace Bangla Mahoba of Piper betle on Leishmania donovani may be due to the high content of eugenol.

PubMed

Misra, Pragya; Kumar, Awanish; Khare, Prashant; Gupta, Swati; Kumar, Nikhil; Dube, Anuradha

2009-08-01

In the absence of effective and safe treatment for visceral leishmaniasis or Kala-azar - a devastating parasitic disease caused by Leishmania donovani - the search for anti-leishmanial agents from natural resources in common use is imperative. Recently, the comparative in vitro anti-leishmanial activity of methanolic extracts from two landraces of Piper betle - P. betle landrace Bangla Mahoba (PB-BM) and P. betle landrace Kapoori Vellaikodi (PB-KV) - has been reported. Here, the putative pathway responsible for death induced by the effective extract of PB-BM methanolic extract in promastigotes, as well as the intracellular amastigote form of L. donovani, was assessed using various biochemical approaches. It was found that PB-BM was capable of selectively inhibiting both stages of Leishmania parasites by accelerating apoptotic events by generation of reactive oxygen species targeting the mitochondria without any cytotoxicity towards macrophages. The study was extended to determine the presence or absence of activity of the methanolic extract of PB-BM and PB-KV on the basis of differences in essential oil composition present in the extract assessed by GC and MS. The essential oil from PB-BM was found to be rich in eugenol compared with that from PB-KV. The anti-leishmanial efficacy of PB-BM methanolic extract mediated through apoptosis is probably due to the higher content of eugenol in the active landrace. This observation emphasizes the need to extend studies related to traditional medicines from bioactive plants below the species level to the gender/landrace level for better efficacy and reproducibility.

Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

PubMed

Milan, Aroha Sanchez; Campmany, Ana Cristina Calpena; Naveros, Beatriz Clares

2017-01-01

Melatonin is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective in a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on melatonin for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. This review focuses on nanocarrier production strategies, dermal melatonin application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted melatonin delivery have also been discussed. In the current review, we have revised relevant articles of the available literature using the major scientific databases. One hundred and thirteen papers were included in the review, the majority of which represent latest researches in nanosized platforms for the dermal delivery of melatonin including liposomes, ethosomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles and cyclodextrins. Furthermore, relevant papers reporting in vitro and in vivo application studies of these nano-based melatonin platforms were also discussed. The use of nanoplatforms for the dermal melatonin delivery as antioxidant agent could improve the efficacy of conventional melatonin administration due to the preservation of the drug from premature oxidation and the enhancement of drug permeation through the skin providing greater exposure times. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Eosinophilic inflammation in lymph nodes of dogs with visceral leishmaniasis.

PubMed

Costa, Sidnei Ferro; Trivellato, Gabriel Franco; Rebech, Gabriela Torres; Oliveira Dos Santos Maciel, Marilene; Melo, Larissa Martins; Luvizotto, Maria Cecília Rui; de Lima, Valéria Marçal Felix

2018-06-19

Eosinophils are traditionally associated with the immune response against helminth parasites. However, several studies have demonstrated that these cells have a role regarding protective immunity in leishmaniasis. Here, we examined the relationship between presence of eosinophils and parasite load in biopsy samples from dogs, obtained through fine needle puncture and aspiration of lymph nodes. Histological slides containing biopsy material from lymph nodes of dogs with canine visceral leishmaniasis and healthy dogs were used to obtain baseline eosinophil counts. Subsequently, scrapings were taken from slides for DNA extraction and determination of parasite load, using real-time PCR (qRT-PCR). Additionally, production of nitric oxide (NO) and reactive oxygen species (ROS) levels by eosinophils in the peripheral blood of dogs with canine visceral leishmaniasis and healthy dogs was measured. The eosinophil percentage were higher in lymph nodes of infected group, and the parasite load showed a significant negative correlation with the eosinophil count. The production of NO and ROS by eosinophils in the peripheral blood was higher in the dogs with canine visceral leishmaniasis. All the results together suggest that eosinophils may participate in anti-leishmanial immunity in canine visceral leishmaniasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Emergence of cutaneous leishmaniasis in Polonnaruwa, Sri Lanka 2008-2011.

PubMed

Sandanayaka, Rohana; Kahawita, Indra; Gamage, Ajith; Siribaddana, Sisira; Agampodi, Suneth

2014-02-01

To report cutaneous leishmaniasis (CL) in Polonnaruwa, Sri Lanka. The study population included all patients with CL reported from Polonnaruwa district from January 2008 through April 2012. Data were collected in the dermatology unit of Polonnaruwa General Hospital and the regional epidemiology unit of Polonnaruwa. Four hundred and forty six patients with leishmaniasis were detected; clinical details were available for 362. Mean annual incidence of leishmaniasis between 2008 and 2012 in Polonnaruwa district was 26.2 per 100,000. The case incidence steadily increased during the study period. Case distribution by month peaked between August and November. Cases were geographically clustered in three administrative divisions with a mean annual incidence ranging from 94.7 to 54.1 per 100,000 population. Significantly more (n = 294, 65.9%) males than females were affected (χ(2) for goodness of fit = 48.4, P < 0.001). The commonest type of lesion was nodules (n = 157, 43.4%) followed by crust (n = 116, 32.0%). The majority of patients had lesions on upper limbs (n = 144, 39.8%) or the face (n = 117, 32.3%). Cutaneous leishmaniasis is increasing in Polonnaruwa, with clear spatial and temporal clustering. Sri Lanka needs more vigilant leishmaniasis surveillance. © 2013 John Wiley & Sons Ltd.

Epidemiology of Leishmaniasis in Spain Based on Hospitalization Records (1997–2008)

PubMed Central

Gil-Prieto, Ruth; Walter, Stefan; Alvar, Jorge; de Miguel, Angel Gil

2011-01-01

All the records from the Spanish information system for hospital data of patients diagnosed with leishmaniasis during a 12-year period (1997–2008) were studied. The 2,028 individuals were hospitalized because of leishmaniasis, as indicated by the principal diagnostic code. The average hospitalization rate was 0.41/100,000 inhabitants. One-third of them were co-infected with human immunodeficiency virus (HIV). The incidence of hospitalization in the adult population with leishmaniasis co-infected with HIV increased with age, peaked at 35–39 years of age and subsequently declined. In the pediatric population, all leishmaniasis cases occurred in HIV-negative children. Incidence of hospitalizations was highest in Madrid and in the Mediterranean coast. The cost per inpatient hospital care was $9,601 corresponding to an annual direct cost of more than $1.5 million for inpatient care alone. The economical burden of leishmaniasis is not neglectable and in the 12-year study period it represented more than $19 million. PMID:22049034

Isolated laryngeal leishmaniasis in an immunocompetent patient: a case report.

PubMed

Bajraktari, A; Seccia, V; Casani, A P; Franceschini, S S

Isolated laryngeal leishmaniasis in an immunocompetent patient: a case report. Isolated laryngeal Leishmaniasis presents neither explicit laryngeal lesions nor specific symptoms. In fact, it may mimic many inflammatory and neoplastic diseases. Considering the low incidence of this atypical localization, laryngeal Leishmaniasis, is rarely contemplated by physicians in differential diagnoses of laryngeal tumour lesions. We present the case of a 62-year-old immunocompetent subject who developed a single Leishmania mucosal lesion on the left vocal cord, simulating a laryngeal cancer. A case report and discussion of the clinical case by referring to the literature. Specific therapy with miltefosine led to clinical and endoscopic improvement. We had no relapse after three years of follow-up. This clinical case highlights the need to consider isolated laryngeal Leishmaniasis in the differential diagnoses of laryngeal tumour lesions, even in immunocompetent subjects who live in endemic zones, in order to ensure an early and correct therapeutic approach.

Repeated folding stress-induced morphological changes in the dermal equivalent.

PubMed

Arai, Koji Y; Sugimoto, Mami; Ito, Kanako; Ogura, Yuki; Akutsu, Nobuko; Amano, Satoshi; Adachi, Eijiro; Nishiyama, Toshio

2014-11-01

Repeated mechanical stresses applied to the same region of the skin are thought to induce morphological changes known as wrinkle. However, the underlying mechanisms are not fully understood. To study the mechanisms, we examined effects of repeated mechanical stress on the dermal equivalent. We developed a novel device to apply repeated folding stress to the dermal equivalent. After applying the mechanical stress, morphological changes of the dermal equivalent and expression of several genes related to extracellular matrix turn over and cell contraction were examined. The repeated folding stress induced a noticeable decrease in the width of the dermal equivalent. The mechanical stress altered orientations of collagen fibrils. Hydroxyproline contents, dry weights and cell viability of the dermal equivalents were not affected by the mechanical stress. On the other hand, Rho-associated coiled-coil-containing kinase (ROCK) specific inhibitor Y27632 completely suppressed the decrease in the width of the dermal equivalent. The present results revealed that either degradation of collagen or changes in the number of cells were not responsible for the decrease in the width of the dermal equivalent and indicate that the repeated mechanical stress induces unidirectional contraction in the dermal equivalent through the RhoA-ROCK signaling pathway. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Incidence and Disability-Adjusted Life Years (Dalys) Attributable to Leishmaniasis In Iran, 2013.

PubMed

Heydarpour, Fatemeh; Sari, Ali Akbari; Mohebali, Mehdi; Shirzadi, Mohammadreza; Bokaie, Saied

2016-07-01

Leishmaniasis covers a range of clinical manifestations. Estimation of the burden of leishmaniasis may help guide healthcare management personnel and policy-makers in applying effective interventions. The present study aimed to calculate the incidence and burden of cutaneous and visceral leishmaniasis in Iran in 2013. To evaluate the epidemiological aspects of the disease in Iran, published studies over the past 20 years were searched and the viewpoints of relevant specialists in Iran were obtained. Data were collected from the Ministry of Health and from the Tehran University of Medical Sciences. To calculate years of life lost due to premature death, standard expected years of life lost was used. Standard life table of Global Burden of Disease (GBD) 2010 with the life expectancy of 86.02 years for both sexes was used to calculate the remaining potential years of life at any age from death. The overall incidence of cutaneous and visceral leishmaniasis was calculated as 22 and 0.092 per 100000 population of Iran, respectively. The burden of leishmaniasis was 99.5 years: 95.34 and 4.16 years for cutaneous and visceral, respectively. Sensitivity was analyzed and deaths predicted by the Institute of Health Metrics and Evaluation added, the burden of visceral leishmaniasis was 726 years. The share of leishmaniasis burden in Iran is lower than the global burden of the disease. GBD 2010 standard method is recommended to calculate the burden of leishmaniasis in different countries and set local priorities on the basis of these measures.

Leishmaniasis Gone Viral: Social Media and an Outbreak of Cutaneous Leishmaniasis.

PubMed

Mongkolrattanothai, Kanokporn; Nadipuram, Santhosh M; Krakowski, Andrew C; Stone, Margaret M; Krogstad, Paul; Lehman, Deborah

2016-09-01

This report details how social media communication was used in a group of teens to diagnose cutaneous leishmaniasis that they acquired during a trip to Israel. Their posts quickly brought the cluster to the attention of the teens and their parents, leading to prompt recognition of the true etiology of their lesions and appropriate treatment. © 2016 Wiley Periodicals, Inc.

Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

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

Tashiro, Kanae; Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka; Shishido, Mayumi

2014-01-03

Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Westernmore » blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.« less

Molecular basis of antimony treatment in leishmaniasis.

PubMed

Baiocco, Paola; Colotti, Gianni; Franceschini, Stefano; Ilari, Andrea

2009-04-23

Leishmaniasis is a disease that affects 2 million people and kills 70000 persons every year. It is caused by Leishmania species, which are human protozoan parasites of the trypanosomatidae family. Trypanosomatidae differ from the other eukaryotes in their specific redox metabolism because the glutathione/glutathione reductase system is replaced by the unique trypanothione/trypanothione reductase system. The current treatment of leishmaniasis relies mainly on antimonial drugs. The crystal structures of oxidized trypanothione reductase (TR) from Leishmania infantum and of the complex of reduced TR with NADPH and Sb(III), reported in this paper, disclose for the first time the molecular mechanism of action of antimonial drugs against the parasite. Sb(III), which is coordinated by the two redox-active catalytic cysteine residues (Cys52 and Cys57), one threonine residue (Thr335), and His461' of the 2-fold symmetry related subunit in the dimer, strongly inhibits TR activity. Because TR is essential for the parasite survival and virulence and it is absent in mammalian cells, these findings provide insights toward the design of new more affordable and less toxic drugs against Leishmaniasis.

Emergence of visceral leishmaniasis in Sri Lanka: a newly established health threat.

PubMed

Siriwardana, H V Y D; Karunanayake, P; Goonerathne, L; Karunaweera, N D

2017-09-01

Sri Lanka is a new focus of human cutaneous leishmaniasis caused by a genetic variant of usually visceralizing parasite Leishmania donovani. Over 3000 cases have been reported to our institution alone, during the past two decades. Recent emergence of visceral leishmaniasis is of concern. Patients suspected of having visceral leishmaniasis (n = 120) fulfilling at least two of six criteria (fever > 2 weeks, weight loss, tiredness affecting daily functions, splenomegaly, hepatomegaly and anemia) were studied using clinic-epidemiological, immunological and haematological parameters. Seven cases (four progressive, treated (group A) and 3 non- progressive, potentially asymptomatic and observed (group B) were identified. Clinical cases were treated with systemic sodium stibogluconate or amphotericin B and all were followed up at the leishmaniasis clinic of University of Colombo for 3 years with one case followed up for 9 years. All treated cases responded well to anti leishmanial treatment. Relapses were not noticed. Clinical features subsided in all non-progressive cases and did not develop suggestive clinical features or change of laboratory parameters. Visceral leishmaniasis cases have been originated from different districts within the country. Majority had a travel history to identified local foci of cutaneous leishmaniasis. Visceral leishmaniasis is recognized as an emerging health threat in Sri Lanka. At least a proportion of locally identified strains of L. donovani possess the ability to visceralize. Apparent anti leishmanial sensitivity is encouraging. Timely efforts in disease containment will be important in which accurate understanding of transmission characteristics, increased professional and community awareness, improved diagnostics and availability of appropriate treatment regimens.

Methamphetamine residue dermal transfer efficiencies from household surfaces.

PubMed

Van Dyke, Mike; Martyny, John W; Serrano, Kate A

2014-01-01

Methamphetamine contamination from illegal production operations poses a potential health concern for emergency responders, child protective services, law enforcement, and children living in contaminated structures. The objective of this study was to evaluate dermal transfer efficiencies of methamphetamine from contaminated household surfaces. These transfer efficiencies are lacking for methamphetamine, and would be beneficial for use in exposure models. Surfaces were contaminated using a simulated smoking method in a stainless steel chamber. Household surfaces were carpet, painted drywall, and linoleum. Dermal transfer efficiencies were obtained using cotton gloves for two hand conditions, dry or saliva moistened (wet). In addition, three contact scenarios were evaluated for both hand conditions: one, two, or three contacts with contaminated surfaces. Dermal transfer efficiencies were calculated for both hand conditions and used as inputs in a Stochastic Human Exposure and Dose Simulation model (SHEDS-Multimedia, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, N.C.). Results of this study showed that average dermal transfer efficiencies of methamphetamine ranged from 11% for dry hands to 26% for wet hands. There was a significantly higher wet transfer as compared to dry transfer for all surfaces. For wet hands, dermal transfer depended on surface type with higher transfer from carpet and linoleum as compared to drywall. Based on our estimates of dermal transfer efficiency, a surface contamination clearance level of 1.5 μg/100 cm(2) may not ensure absorbed doses remain below the level associated with adverse health effects in all cases. Additional dermal transfer studies should be performed using skin surrogates that may better predict actual skin transfer.

Genotoxicity, acute oral and dermal toxicity, eye and dermal irritation and corrosion and skin sensitisation evaluation of silver nanoparticles.

PubMed

Kim, Jin Sik; Song, Kyung Seuk; Sung, Jae Hyuck; Ryu, Hyun Ryol; Choi, Byung Gil; Cho, Hyun Sun; Lee, Jin Kyu; Yu, Il Je

2013-08-01

To clarify the health risks related to silver nanoparticles (Ag-NPs), we evaluated the genotoxicity, acute oral and dermal toxicity, eye irritation, dermal irritation and corrosion and skin sensitisation of commercially manufactured Ag-NPs according to the OECD test guidelines and GLP. The Ag-NPs were not found to induce genotoxicity in a bacterial reverse mutation test and chromosomal aberration test, although some cytotoxicity was observed. In acute oral and dermal toxicity tests using rats, none of the rats showed any abnormal signs or mortality at a dose level of ∼ 2000 mg/kg. Similarly, acute eye and dermal irritation and corrosion tests using rabbits revealed no significant clinical signs or mortality and no acute irritation or corrosion reaction for the eyes and skin. In a skin sensitisation test using guinea pigs, one animal (1/20) showed discrete or patchy erythema, thus Ag-NPs can be classified as a weak skin sensitiser.

Dermal exposure assessment to benzene and toluene using charcoal cloth pads.

PubMed

van Wendel de Joode, Berna; Tielemans, Erik; Vermeulen, Roel; Wegh, Hillion; Kromhout, Hans

2005-01-01

Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and toluene in workers of a petrochemical plant. Inhalation and dermal exposure levels to benzene and toluene were assessed for workers of a petrochemical plant performing different jobs. Benzene uptake was assessed by determining S-phenylmercapturic acid in workers' urine samples. Dermal exposure levels on the charcoal pads were adjusted for ambient air levels of benzene and toluene by subtracting the amount of benzene or toluene measured in personal air from the amount of benzene or toluene measured on the charcoal pad. In general, measured external and internal exposure levels were low. The estimated contribution of the dermal route to internal benzene exposure levels was less than 0.06% for all jobs. Toluene personal air concentrations and benzene and toluene dermal exposure levels differed statistically significantly between job titles. For benzene, differences between jobs were larger for adjusted dermal exposures (maximum 17-fold, P = 0.02) than for inhalation exposures (maximum two-fold, P = 0.08). Also for toluene, although less clear, differences between jobs were larger for adjusted dermal exposures (maximum 23-fold, P = 0.01) as compared to inhalation exposures (maximum 10-fold, P = 0.01). Charcoal pads appeared to measure dermal exposures to benzene and toluene in addition to ambient air levels. Future studies applying charcoal cloth pads for the dermal exposure assessment at workplaces with higher dermal exposure to organic solvents may provide more insight into the biological relevance of dermal exposure levels measured by charcoal cloth pads. In addition, the design of the dermal sampler might be improved by configuring a dermal sampler, where part of the

Leishmanization revisited: immunization with a naturally attenuated cutaneous Leishmania donovani isolate from Sri Lanka protects against visceral leishmaniasis.

PubMed

McCall, Laura-Isobel; Zhang, Wen-Wei; Ranasinghe, Shanlindra; Matlashewski, Greg

2013-02-27

Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa and associated with three main clinical presentations: cutaneous, mucocutaneous and visceral leishmaniasis. Visceral leishmaniasis is the second most lethal parasitic disease after malaria and there is so far no human vaccine. Leishmania donovani is a causative agent of visceral leishmaniasis in South East Asia and Eastern Africa. However, in Sri Lanka, L. donovani causes mainly cutaneous leishmaniasis, while visceral leishmaniasis is rare. We investigate here the possibility that the cutaneous form of L. donovani can provide immunological protection against the visceral form of the disease, as a potential explanation for why visceral leishmaniasis is rare in Sri Lanka. Subcutaneous immunization with a cutaneous clinical isolate from Sri Lanka was significantly protective against visceral leishmaniasis in BALB/c mice. Protection was associated with a mixed Th1/Th2 response. These results provide a possible rationale for the scarcity of visceral leishmaniasis in Sri Lanka and could guide leishmaniasis vaccine development efforts. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Transmission of cutaneous leishmaniasis associated with cacao (Theobroma cacao) plantations in Tabasco].

PubMed

Carrada Figueroa, Georgina Del Carmen; Leal Ascencio, Víctor Javier; Jiménez Sastré, Alejandro; López Álvarez, Jorge

2014-01-01

Tabasco is the Mexican state that reported the highest number (37.4%) of patients with leishmaniasis during 1990-2011. Close to 90% of these patients lived in Chontalpa, where the municipality of Cunduacán accounted for the majority of the cases. One of the characteristics of this region is that houses are located within cacao plantations. To determine if cacao plantations are a risk factor for leishmaniasis transmission in locations of Cunduacán, Tabasco. We performed an analytical and retrospective study of 115 locations in Cunduacán, analyzing the number of localities with or without patients with leishmaniasis registered between 2000-2011 and, additionally, if they had cacao plantations, using a map where different crops were georeferenced. We measured the magnitude of the association (odds ratio, 95% CI). During the period 2000-2011, cases of leishmaniasis were reported in 77 (67.0%) Cunduacán locations, of these, 55 (71.4%) had cocoa plantations, five (6.5%) of banana, five (6.5%) of cane, and 12 (15.6%) had no crops georeferenced. We found that cocoa crops are a risk factor for the transmission of leishmaniasis (OR: 3.438; 95% CI: 1,526-7,742). The probability of transmission of leishmaniasis in areas with cocoa crops is greater than in communities without this crop.

Dermal exposure to environmental contaminants in the Great Lakes.

PubMed Central

Moody, R P; Chu, I

1995-01-01

This paper reviews the literature to determine the importance of the dermal route of exposure for swimmers and bathers using Great Lakes waters and summarizes the chemical water contaminants of concern in the Great Lakes along with relevant dermal absorption data. We detail in vivo and in vitro methods of quantifying the degree of dermal absorption and discuss a preference for infinite dose data as opposed to finite dose data. The basic mechanisms of the dermal absorption process, routes of chemical entry, and the environmental and physiological factors affecting this process are also reviewed, and we discuss the concepts of surface slick exposure to lipophilic compounds and the adsorption of contaminants to water sediment. After presenting mathematical constructs for calculating the degree of exposure, we present in vitro data concerning skin absorption of polyaromatic hydrocarbons adsorbed to Great Lakes water sediment to show that in a worst-case scenario exposure via the dermal route can be equally important to the oral route. We have concluded that prolonged exposure of the skin, especially under conditions that may enhance dermal absorption (e.g., sunburn) may result in toxicologically significant amounts of certain water contaminants being absorbed. It is recommended that swimming should be confined to public beaches, people should refrain from swimming if they are sunburned, and skin should be washed with soap as soon as possible following exposure. Future studies should be conducted to investigate the importance of the dermal exposure route to swimmers and bathers. PMID:8635434

Cutaneous Leishmaniasis in an American Adolescent Returning From Israel.

PubMed

Ganjaei, Kimia G; Lawton, Kira; Gaur, Sunanda

2018-06-06

We present here the case of a healthy 16-year-old American girl who returned from an organized trip to Israel with cutaneous leishmaniasis caused by Leishmania major; the infection was treated successfully with paromomycin-gentamicin ointment. She was initially misdiagnosed with staphylococcal and pseudomonal cellulitis. Although cutaneous leishmaniasis is seen only rarely in the United States, it should be considered when diagnosing new skin lesions after travel to affected countries.

Gene Expression Profiling of the Intact Dermal Sheath Cup of Human Hair Follicles.

PubMed

Niiyama, Shiro; Ishimatsu-Tsuji, Yumiko; Nakazawa, Yosuke; Yoshida, Yuzo; Soma, Tsutomu; Ideta, Ritsuro; Mukai, Hideki; Kishimoto, Jiro

2018-04-24

Cells that constitute the dermal papillae of hair follicles might be derived from the dermal sheath, the peribulbar component of which is the dermal sheath cup. The dermal sheath cup is thought to include the progenitor cells of the dermal papillae and possesses hair inductive potential; however, it has not yet been well characterized. This study investigated the gene expression profile of the intact dermal sheath cup, and identified dermal sheath cup signature genes, including extracellular matrix components and BMP-binding molecules, as well as TGF-b1 as an upstream regulator. Among these, GREM2, a member of the BMP antagonists, was found by in situ hybridization to be highly specific to the dermal sheath cup, implying that GREM2 is a key molecule contributing to maintenance of the properties of the dermal sheath cup.

Dermal Discolorations and Burns at Neuromonitoring Electrodes in Pediatric Spine Surgery.

PubMed

Sanders, Austin; Andras, Lindsay; Lehman, Alison; Bridges, Nancy; Skaggs, David L

2017-01-01

Prospective review of consecutive patients. To evaluate the incidence and raise awareness of electrode discoloration that can occur in the operating room when using neuromonitoring. To our knowledge there are no articles that discuss dermal discolorations following spine surgery. Following recognition of dermal discolorations in some patients, a prospective evaluation of all patients undergoing spine surgery with somatosensory-evoked potential and motor-evoked potential neuromonitoring using subdermal needle electrodes was carried out over a 16-month period for quality assurance and improvement. A total of 201 consecutive patients with mean age of 14 years (4-25) were prospectively evaluated. Sixteen percent (33/201) had dermal discolorations associated with neuromonitoring. There were no significant differences in mean age (P = 0.624), height (P = 0.308), weight (P = 0.899), or body mass index (P = 0.571) between the patients with and without dermal discolorations. There was also no difference in prevalence of dermal discoloration by diagnosis (P = 0.490) or location of grounding pad and occurrence of dermal discoloration between groups (P = 0.268). The only difference noted was that patients without dermal discoloration had an average monopolar cautery setting of 46.8 W compared to 40.5 W for patients with dermal discolorations (P = 0.042). Of the 33 patients with a dermal discoloration, 27% (9/33) of these were on both the upper and lower extremities, 21% (7/33) on only the upper extremities, and 52% (17/33) on only the lower extremities. None of the dermal discolorations were painful or tender, and all resolved by 6-month follow-up. One patient did not have any dermal discoloration but did experience two full-thickness burns around the electrodes in one leg. The incidence of burns in this series was 0.5% (1/201). Dermal discolorations occurred in 16% of patients undergoing neuromonitoring for spine surgery. These common

Vaccines for Canine Leishmaniasis

PubMed Central

Palatnik-de-Sousa, Clarisa B.

2012-01-01

Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian urban area

PubMed Central

de Toledo, Celina Roma Sánchez; de Almeida, Andréa Sobral; Chaves, Sergio Augusto de Miranda; Sabroza, Paulo Chagastelles; Toledo, Luciano Medeiros; Caldas, Jefferson Pereira

2017-01-01

ABSTRACT OBJECTIVE To analyze the determinants for the occurrence of human visceral leishmaniasis linked to the conditions of vulnerability. METHODS This is an ecological study, whose spatial analysis unit was the Territorial Analysis Unit in Araguaína, State of Tocantins, Brazil, from 2007 to 2012. We have carried out an analysis of the sociodemographic and urban infrastructure situation of the municipality. Normalized primary indicators were calculated and used to construct the indicators of vulnerability of the social structure, household structure, and urban infrastructure. From them, we have composed a vulnerability index. Kernel density estimation was used to evaluate the density of cases of human visceral leishmaniasis, based on the coordinates of the cases. Bivariate global Moran’s I was used to verify the existence of spatial autocorrelation between the incidence of human visceral leishmaniasis and the indicators and index of vulnerability. Bivariate local Moran’s I was used to identify spatial clusters. RESULTS We have observed a pattern of centrifugal spread of human visceral leishmaniasis in the municipality, where outbreaks of the disease have progressively reached central and peri-urban areas. There has been no correlation between higher incidences of human visceral leishmaniasis and worse living conditions. Statistically significant clusters have been observed between the incidences of human visceral leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012) and the indicators and index of vulnerability. CONCLUSIONS The environment in circumscribed areas helps as protection factor or increases the local vulnerability to the occurrence of human visceral leishmaniasis. The use of methodology that analyzes the conditions of life of the population and the spatial distribution of human visceral leishmaniasis is essential to identify the most vulnerable areas to the spread/maintenance of the disease. PMID:28513764

Ancient Leishmaniasis in a Highland Desert of Northern Chile

PubMed Central

Costa, Maria Antonietta; Matheson, Carney; Iachetta, Lucia; Llagostera, Agustín; Appenzeller, Otto

2009-01-01

Background Leishmaniasis is an infectious disease endemic today in many areas of South America. Methodology We discovered morphologic and molecular evidence of ancient infections in 4 female skulls in the archaeological cemetery of Coyo Oriente, in the desert of San Pedro de Atacama, Northern Chile. The boney facial lesions visible in the skulls could have been caused by a number of chronic infections including chronic Leishmaniasis. This diagnosis was confirmed using PCR-sequenced analyses of bone fragments from the skulls of the affected individuals.Leishmaniasis is not normally found in the high-altitude desert of Northern Chile; where the harsh climate does not allow the parasite to complete its life cycle. The presence of Leishmaniasis in ancient skulls from the region implies infection by the protozoan in an endemic area–likely, in our subjects, to have been the lowlands of North-Eastern Argentina or in Southern Bolivia. Conclusions We propose that the presence of the disease in ancient times in the high altitude desert of San Pedro de Atacama is the result of an exogamic system of patrilocal marriages, where women from different cultures followed their husbands to their ancestral homes, allowing immigrant women, infected early in life, to be incorporated in the Atacama desert society before they became disfigured by the disease. The present globalization of goods and services and the extraordinary facile movement of people across borders and continents have lead to a resurgence of infectious diseases and re-emergence of infections such as Leishmaniasis. We show here that such factors were already present millennia ago, shaping demographic trends and the epidemiology of infections just as they do today. PMID:19746163

Spectrum of PORCN mutations in Focal Dermal Hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

Liposomal amphotericin B as a treatment for human leishmaniasis

PubMed Central

Balasegaram, Manica; Ritmeijer, Koert; Lima, Maria Angeles; Burza, Sakib; Ortiz Genovese, Gemma; Milani, Barbara; Gaspani, Sara; Potet, Julien; Chappuis, François

2012-01-01

Introduction: Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB), alone or in combination with other drugs, has been extensively studied as VL treatment, but data on routine field use are limited, and several challenges to patients' access to this life-saving drug remain. Areas covered: This article provides a review of clinical studies on LAMB for VL and other forms of leishmaniasis. The current development of generic versions of LAMB and related challenges are also discussed. Expert opinion: LAMB proved to be highly efficacious and safe in over 8000 VL patients treated by MÉdecins Sans Frontières in South Asia, and its use was feasible even at primary healthcare level. Despite requiring higher doses, LAMB is the drug of choice to treat vulnerable groups (e.g., pregnant or HIV positive) and relapsing VL patients in East Africa. LAMB should be included in national VL guidelines and registered in all VL endemic countries. Its cost should be further reduced and regulatory pathways to prove bioequivalence for generic LAMB products should be implemented. PMID:23167833

Epidemiological profile of cutaneous leishmaniasis in Morocco, 2004-2013.

PubMed

Laboudi, M

2017-02-01

The main objective of our study is to provide a comprehensive overview of the situation of cutaneous leishmaniasis in Morocco. We therefore conducted a retrospective descriptive study covering the decade 2004-2013. Data were collected from the Moroccan Ministry of Health's annual reports about the national program against leishmaniasis. These data show a regression in the cases due to Leishmania major and the persistence of L. tropica transmission. Mapping cutaneous leishmaniasis cases reported between 2004 and 2013 showed geographical changes ; the number of cases due to L. tropica were concentrated in the regions of Marrakech-Tensift-Elhaouz, Souss Massa-Draa Tadla-Azila, and Taza-Al Hoceima-Taounate. Cutaneous disease due to L. major was most common in the Souss-Massa-Draa region. Continuous monitoring of the epidemiological situation is important to assess the actions taken to reduce its incidence.

Epidemiology of Cutaneous Leishmaniasis in a Colombian Municipality.

PubMed

Medina-Morales, Diego Alejandro; Machado-Duque, Manuel E; Machado-Alba, Jorge Enrique

2017-11-01

This study describes the epidemiological and clinical characteristics of leishmaniasis and the pharmacological treatment of this disease in the municipality of Pueblo Rico, Risaralda, between January 2010 and December 2014. An observational study was conducted using information from the clinical records and epidemiological reports of patients diagnosed and confirmed with leishmaniasis of any age and sex, including sociodemographic, clinical, and pharmacological variables of the therapy received. Univariate and bivariate analyses were performed. A total of 539 cases of leishmaniasis were confirmed, with 29.5% occurring in children under 5 years of age. The median age was 10 years, with predominance in males (55.5%). The indigenous Emberá (aboriginal Americans) were the most affected (50.8%), and 93.3% of cases occurred in people living in scattered rural areas. All lesions corresponded to cutaneous leishmaniasis, of which 251 patients had compromise of the upper limbs (46.6%), 221 of the face (41.0%), and 139 of the lower limbs (25.8%). Pentavalent antimony salts (n-methyl glucamine and sodium stibogluconate) were prescribed in 77.6% ( N = 418) of the cases; miltefosine was the second most frequently prescribed medication (21.5%, N = 116). The inhabitants of rural areas and the indigenous communities are at a higher risk of acquiring the infection, particularly among infants, which highlights the importance of the biological, social, and demographic factors involved in the disease. There is a need to seek effective public health actions and further research this disease.

En bloc excision of a dermal sinus tract.

PubMed

Coumans, Jean-Valery; Walcott, Brian P; Redjal, Navid; Kahle, Kristopher T; Nahed, Brian V

2011-04-01

Dermal sinus tracts are a form of spinal dysraphism that arises from a failure of dysjunction early in embryogenesis. They are diagnosed in pediatric patients and who present with a dimple, infection, or neurologic deficit. The tract is surgically excised en bloc to avoid contamination from the tract, which harbors bacteria. However, dermal sinus tracts typically terminate intradurally, rendering their en bloc excision difficult. To avoid entering the tract, allowing for an en bloc excision, we modified the usual technique employed for accessing the spinal intradural space. An en bloc excision of the dermal sinus tract was successfully performed. The patient recovered from the procedure neurologically intact and her postoperative course was uncomplicated. We conclude that en bloc excision of a dermal sinus tract down to the intradural space is feasible with modifications to standard operative technique. Copyright © 2010 Elsevier Ltd. All rights reserved.

Leishmaniasis acquired by travellers to endemic regions in Europe: a EuroTravNet multi-centre study.

PubMed

Ehehalt, Urs; Schunk, Mirjam; Jensenius, Mogens; van Genderen, Perry J J; Gkrania-Klotsas, Effrossyni; Chappuis, François; Schlagenhauf, Patricia; Castelli, Francesco; Lopez-Velez, Rogelio; Parola, Philippe; Burchard, Gerd D; Cramer, Jakob P

2014-01-01

Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. Clinical manifestations of leishmaniasis include cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). About 90% of cases occur in the tropics or subtropics but the disease is also endemic in the Mediterranean area. No systematic analysis on leishmaniasis in travellers visiting endemic areas in Europe is available. Within the European travel medicine network EuroTravNet, we performed a retrospective analysis in travellers who acquired leishmaniasis within Europe diagnosed between 2000 and 2012. Forty cases of leishmaniasis (30 CL and 10 VL) were identified; the majority were acquired in Spain (n = 20, 50%), Malta and Italy (each n = 7, 18%). Median age was 48 years (range 1-79). Three of eight (37.5%) of the VL patients were on immunosuppressive therapy. The most frequent reason for travel was tourism (83%). Median duration of travel for patients with CL and VL was 2 weeks with ranges of 1-21 weeks in CL and 1-67 weeks in VL, respectively (P = 0.03). Health professionals should include leishmaniasis in the differential diagnosis in patients returning from southern Europe - including short-term travellers - with typical skin lesions or systemic alterations like fever, hepatosplenomegaly and pancytopenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Insecticidal effect of plant extracts on Phlebotomus argentipes (Diptera: Psychodidae) in Bihar, India.

PubMed

Dinesh, Diwakar Singh; Kumari, Seema; Pandit, Vibhishan; Kumar, Jainendra; Kumari, Nisha; Kumar, Prahlad; Hassan, Faizan; Kumar, Vijay; Das, Pradeep

2015-12-01

Phlebotomus argentipes (Diptera: Psychodidae), the established vector for kala-azar is presently being controlled by indoor residual spray of DDT in kala-azar endemic areas in India. Search for non-hazardous and non-toxic biodegradable active molecules from botanicals may provide cost-effective and eco-friendly alternatives to synthetic insecticides. The present study was aimed at evaluating various plant extracts from endemic and non-endemic areas of Bihar for their insecticidal activity against sandfly to identify the most effective plant extract. Bio-assay test was conducted with larvae and adult of P. argentipes with different plant extracts collected in distilled water, hexane, ethyl acetate, acetone and methanol. Thin layer chromatography (TLC), column chromatography and high performance liquid chromatography (HPLC) were conducted for detection of active molecules. Adults and larvae of sandflies exposed to the aqueous extract of Nicotiana tabacum resulted in 100 per cent mortality. The hexane extract of Clerodendrum infortunatum was found to kill 77 per cent adults but was ineffective against larvae. Bio-assay test of the ninth fraction (hexane extract-methanol phase) separated by column chromatography was found to be 63 per cent effective. The purple spot on the TLC of this fraction indicated the presence of a diterpenoid. HPLC of this fraction detected nine compounds with two peaks covering 20.44 and 56.52 per cent areas with retention time of 2.439 and 5.182 min, respectively supporting the TLC results. The column separated 9 [th] fraction of C. infortunatum extract was found to be effective in killing 63 per cent of adult P. argentipes. Compounds of this fraction need to be evaluated further for identification and characterization of the active molecule by conducting individual bio-assay tests followed by further fractionation and HPLC. Once the structure of the active molecule is identified and validated, it may be synthesized and formulated as a product.

[Leishmaniasis transmission focus in El Hobo, Carmen de Bolívar, Bolívar, Colombia].

PubMed

Cortés, Luis Alberto

2006-10-01

The epidemiological characteristics and the importance of the Lutzomyia species present in a leishmaniasis focus in the village El Hobo, Carmen de Bolívar, Department of Bolivar, Colombia, are described. To obtain a preliminary assessment of leishmaniasis transmission in the village of El Hobo, Carmen de Bolívar. Epidemiological data were analyzed and sandflies were collected with CDC traps and on protected human volunteers in the village of El Hobo. Sero prevalence of canine visceral leishmaniasis in dogs was evaluated using indirect inmunofluorescence (IFAT). Nine Lutzomyia species were collected: L. trinidadensis, L. evansi, L. cayennensis, L. venezuelensis, L. gomezi, L. dubitans, L. ylephiletor, L. yuilli, and L. walkeri. The species of greater importance based on their implication in the transmission of cutaneous and visceral leishmaniasis were L. gomezi, and L. evansi respectively. Specimens of L. venezuelensis, L. dubitans, L. ylephiletor, L. yuilli, and L. walkeri are reported for the first time for the Department of Bolivar. The sero prevalence of visceral leishmaniasis in dogs was 36%. According to the epidemiological records, in 2002 the municipality of Carmen de Bolivar presented a 40% increase in cases of cutaneous leishmaniasis and an 80% increase in canine visceral leishmaniasis as compared to 2001, due to the outbreak in the village of El Hobo. The results indicate that the village of El Hobo is an area of potential risk for transmission of both cutaneous and visceral leishmaniasis.

Antigenicity of Leishmania braziliensis Histone H1 during Cutaneous Leishmaniasis: Localization of Antigenic Determinants

PubMed Central

Carmelo, Emma; Martínez, Enrique; González, Ana Cristina; Piñero, José Enrique; Patarroyo, Manuel E.; del Castillo, Antonio; Valladares, Basilio

2002-01-01

The humoral immune response against Leishmania braziliensis histone H1 by patients with cutaneous leishmaniasis is described. For this purpose, the protein was purified as a recombinant protein in a prokaryotic expression system and was assayed by enzyme-linked immunosorbent assay (ELISA) with a collection of sera from patients with cutaneous leishmaniasis and Chagas' disease. The assays showed that L. braziliensis histone H1 was recognized by 66% of the serum samples from patients with leishmaniasis and by 40% of the serum samples from patients with Chagas' disease, indicating that it acts as an immunogen during cutaneous leishmaniasis. In order to locate the linear antigenic determinants of this protein, a collection of synthetic peptides covering the L. braziliensis histone H1sequence was tested by ELISA. The experiments showed that the main antigenic determinant is located in the central region of this protein. Our results show that the recombinant L. braziliensis histone H1 is recognized by a significant percentage of serum samples from patients with cutaneous leishmaniasis, but use of this protein as a tool for the diagnosis of cutaneous leishmaniasis is hampered by the cross-reaction with sera from patients with Chagas' disease. PMID:12093677

Antigenicity of Leishmania braziliensis histone H1 during cutaneous leishmaniasis: localization of antigenic determinants.

PubMed

Carmelo, Emma; Martínez, Enrique; González, Ana Cristina; Piñero, José Enrique; Patarroyo, Manuel E; Del Castillo, Antonio; Valladares, Basilio

2002-07-01

The humoral immune response against Leishmania braziliensis histone H1 by patients with cutaneous leishmaniasis is described. For this purpose, the protein was purified as a recombinant protein in a prokaryotic expression system and was assayed by enzyme-linked immunosorbent assay (ELISA) with a collection of sera from patients with cutaneous leishmaniasis and Chagas' disease. The assays showed that L. braziliensis histone H1 was recognized by 66% of the serum samples from patients with leishmaniasis and by 40% of the serum samples from patients with Chagas' disease, indicating that it acts as an immunogen during cutaneous leishmaniasis. In order to locate the linear antigenic determinants of this protein, a collection of synthetic peptides covering the L. braziliensis histone H1sequence was tested by ELISA. The experiments showed that the main antigenic determinant is located in the central region of this protein. Our results show that the recombinant L. braziliensis histone H1 is recognized by a significant percentage of serum samples from patients with cutaneous leishmaniasis, but use of this protein as a tool for the diagnosis of cutaneous leishmaniasis is hampered by the cross-reaction with sera from patients with Chagas' disease.

Melanogenesis in dermal melanocytes of Japanese Silky chicken embryos.

PubMed

Ortolani-Machado, C F; Freitas, P F; Faraco, C D

2009-08-01

The Japanese Silky chicken (SK) shows dermal and visceral hyperpigmentation. This study characterizes ultrastructurally the melanin granules developing in dermal melanocytes of the dorsal skin of SK, in an attempt to better understand the processes of melanogenesis in these permanently ectopic cells. The steps of melanogenesis are similar to those described for epidermal melanocytes, with melanosomes going from stage I to IV but, in SK, the maturation occurs in the cell body, as well as in the cytoplasmic processes. At stage III, the deposition of melanin is cumulative and can aggregate in rounded structures, which combine to turn into the mature granule. The final destiny of mature melanosomes is still unclear, although it was observed that dermal macrophages can accumulate melanin granules in their phagosomes. Even with the close proximity between melanocytes and other dermal cells, the transference of melanosomes was not observed. Our findings indicate that melanogenesis in dermal melanocytes in SK has the same morphological characteristics found in epidermal melanocytes, but the functional aspect still remains to be elucidated.

IN VITRO DERMAL ABSORPTION OF FLAME RETARDANT CHEMICALS

EPA Science Inventory

ABSTRACT
The use of flame retardant chemicals in furniture fabric could pose a potential health risk to consumers from dermal absorption of these compounds. The objective of this study was to examine the in vitro dermal absorption of two flame retardant chemicals, [14C]-d...

Drug resistance and treatment failure in leishmaniasis: A 21st century challenge

PubMed Central

Ponte-Sucre, Alicia; Gamarro, Francisco; Dujardin, Jean-Claude; Barrett, Michael P.; López-Vélez, Rogelio; García-Hernández, Raquel; Pountain, Andrew W.; Mwenechanya, Roy

2017-01-01

Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of “resistance” related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined. PMID:29240765

Canine Leishmaniasis Progression is Associated with Vitamin D Deficiency.

PubMed

Rodriguez-Cortes, A; Martori, C; Martinez-Florez, A; Clop, A; Amills, M; Kubejko, J; Llull, J; Nadal, J M; Alberola, J

2017-06-13

The relationship between vitamin D deficiency and the risk of suffering from a plethora of health disorders, ranging from autoimmune processes to infectious diseases has been widely described. Nonetheless, the potential role of vitamin D in visceral leishmaniasis remains uncharacterized. In the Mediterranean basin, where the dog is leishmania's main peri-domestic reservoir, control measures against the canine disease have shown beneficial effects on the incidence of human leishmaniasis. In this study, we measured the vitamin D levels in serum samples from a cohort of 68 healthy and disease dogs from a highly endemic area and we have also studied the relationship of these levels with parasitological and immunological parameters. The sick dogs presented significantly lower (P < 0.001) vitamin D levels (19.6 ng/mL) than their non-infected (31.8 ng/mL) and the asymptomatic counterparts (29.6 ng/mL). In addition, vitamin D deficiency correlated with several parameters linked to leishmaniasis progression. However, there was no correlation between vitamin D levels and the Leishmania-specific cellular immune response. Moreover, both the leishmanin skin test and the IFN-γ levels displayed negative correlations with serological, parasitological and clinical signs. Further studies to determine the functional role of vitamin D on the progression and control of canine leishmaniasis are needed.

Vector and reservoir control for preventing leishmaniasis.

PubMed

González, Urbà; Pinart, Mariona; Sinclair, David; Firooz, Alireza; Enk, Claes; Vélez, Ivan D; Esterhuizen, Tonya M; Tristan, Mario; Alvar, Jorge

2015-08-05

Leishmaniasis is caused by the Leishmania parasite, and transmitted by infected phlebotomine sandflies. Of the two distinct clinical syndromes, cutaneous leishmaniasis (CL) affects the skin and mucous membranes, and visceral leishmaniasis (VL) affects internal organs. Approaches to prevent transmission include vector control by reducing human contact with infected sandflies, and reservoir control, by reducing the number of infected animals. To assess the effects of vector and reservoir control interventions for cutaneous and for visceral leishmaniasis. We searched the following databases to 13 January 2015: Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and WHOLIS, Web of Science, and RePORTER. We also searched trials registers for ongoing trials. Randomized controlled trials (RCTs) evaluating the effects of vector and reservoir control interventions in leishmaniasis-endemic regions. Two review authors independently searched for trials and extracted data from included RCTs. We resolved any disagreements by discussion with a third review author. We assessed the quality of the evidence using the GRADE approach. We included 14 RCTs that evaluated a range of interventions across different settings. The study methods were generally poorly described, and consequently all included trials were judged to be at high or unclear risk of selection and reporting bias. Only seven trials reported clinical outcome data which limits our ability to make broad generalizations to different epidemiological settings and cultures. Cutaneous leishmaniasisOne four-arm RCT from Afghanistan compared indoor residual spraying (IRS), insecticide-treated bednets (ITNs), and insecticide-treated bedsheets, with no intervention. Over 15 months follow-up, all three insecticide-based interventions had a lower incidence of CL than the control area (IRS: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.38 to 0.97, 2892 participants, moderate quality

Restricted Outbreak of American Tegumentary Leishmaniasis with High Microfocal Transmission

PubMed Central

Krolewiecki, Alejandro J.; Gil, José F.; Quipildor, Marcelo; Cajal, Silvana P.; Pravia, Carlos; Juarez, Marisa; Villalpando, Carlos; Locatelli, Fabricio M.; Chanampa, Mariana; Castillo, Gabriela; Oreste, María F.; Hoyos, Carlos L.; Negri, Vanesa; Nasser, Julio R.

2013-01-01

Cutaneous leishmaniasis is endemic in Salta, the northwestern province of Argentina. We describe an outbreak involving five recreational hunters whose exposure was limited to several hours in a residual patch of primary forest. All patients presented with typical cutaneous lesions after a mean incubation period of 59 days (range 15–78), and one developed simultaneous mucosal involvement. Polymerase chain reaction analysis of lesions confirmed Leishmania (V.) braziliensis as the etiologic agent in three cases. All patients were cured with anti-Leishmania treatment. Entomologic surveys in the transmission area revealed a predominance of Lutzomyia neivai. This outbreak report confirms a microfocal transmission pattern of tegumentary leishmaniasis in the Americas and based on a well-determined exposure, allows the determination of incubation times for leishmaniasis caused by Leishmania braziliensis. PMID:23339200

Update on botulinum toxin and dermal fillers.

PubMed

Berbos, Zachary J; Lipham, William J

2010-09-01

The art and science of facial rejuvenation is an ever-evolving field of medicine, as evidenced by the continual development of new surgical and nonsurgical treatment modalities. Over the past 10 years, the use of botulinum toxin and dermal fillers for aesthetic purposes has risen sharply. Herein, we discuss properties of several commonly used injectable products and provide basic instruction for their use toward the goal of achieving facial rejuvenation. The demand for nonsurgical injection-based facial rejuvenation products has risen enormously in recent years. Used independently or concurrently, botulinum toxin and dermal filler agents offer an affordable, minimally invasive approach to facial rejuvenation. Botulinum toxin and dermal fillers can be used to diminish facial rhytides, restore facial volume, and sculpt facial contours, thereby achieving an aesthetically pleasing, youthful facial appearance.

Alteration of Skin Properties with Autologous Dermal Fibroblasts

PubMed Central

Thangapazham, Rajesh L.; Darling, Thomas N.; Meyerle, Jon

2014-01-01

Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices. PMID:24828202

Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.

PubMed

Liu, Wei; Krump, Nathan A; MacDonald, Margo; You, Jianxin

2018-02-15

Merkel cell polyomavirus (MCPyV) is the first polyomavirus to be associated with human cancer. Mechanistic studies attempting to fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of animal models for MCPyV infection. In this study, we examined the ability of MCPyV-GFP pseudovirus (containing a green fluorescent protein [GFP] reporter construct), MCPyV recombinant virions, and several MCPyV chimeric viruses to infect dermal fibroblasts isolated from various model animals, including mouse ( Mus musculus ), rabbit ( Oryctolagus cuniculus ), rat ( Rattus norvegicus ), chimpanzee ( Pan troglodytes ), rhesus macaque ( Macaca mulatta ), patas monkey ( Erythrocebus patas ), common woolly monkey ( Lagothrix lagotricha ), red-chested mustached tamarin ( Saguinus labiatus ), and tree shrew ( Tupaia belangeri ). We found that MCPyV-GFP pseudovirus was able to enter the dermal fibroblasts of all species tested. Chimpanzee dermal fibroblasts were the only type that supported vigorous MCPyV gene expression and viral replication, and they did so to a level beyond that of human dermal fibroblasts. We further demonstrated that both human and chimpanzee dermal fibroblasts produce infectious MCPyV virions that can successfully infect new cells. In addition, rat dermal fibroblasts supported robust MCPyV large T antigen expression after infection with an MCPyV chimeric virus in which the entire enhancer region of the MCPyV early promoter has been replaced with the simian virus 40 (SV40) analog. Our results suggest that viral transcription and/or replication events represent the major hurdle for MCPyV cross-species transmission. The capacity of rat dermal fibroblasts to support MCPyV early gene expression suggests that the rat is a candidate model organism for studying viral oncogene function during Merkel cell carcinoma (MCC) oncogenic progression. IMPORTANCE MCPyV plays an important role in the development of a highly aggressive form of skin cancer, Merkel

Dermal exposure and urinary 1-hydroxypyrene among asphalt roofing workers

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

McClean, M.D.; Rinehart, R.D.; Sapkota, A.

2007-07-01

The primary objective of this study was to identify significant determinants of dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the effect of dermal exposure on total absorbed dose. The study population included 26 asphalt roofing workers who performed three primary tasks: tearing off old roofs, putting down new roofs, and operating the kettle at ground level. During multiple consecutive work shifts, dermal patch samples were collected from the underside of each worker's wrists and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same work week, urinemore » samples were collected at pre-shift, post-shift, and bedtime each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects models were used to evaluate the dermal measurements for the purpose of identifying important determinants of exposure, and to evaluate urinary 1-OHP measurements for the purpose of identifying important determinants of total absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary significantly by roofing task and by the presence of an old coal tar pitch roof. For each of the three analytes, the adjusted mean dermal exposures associated with tear-off were approximately four times higher than exposures associated with operating the kettle. Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure, an 8-fold increase in pyrene exposure and a 35-fold increase in BAP exposure. The presence of coal tar pitch was the primary determinant of dermal exposure, particularly for exposure to BAP. However, the task-based differences that were observed while controlling for pitch suggest that exposure to asphalt also contributes to dermal exposures.« less

Laser-induced transepidermal elimination of dermal content by fractional photothermolysis

NASA Astrophysics Data System (ADS)

Hantash, Basil M.; Bedi, Vikramaditya P.; Sudireddy, Vasanthi; Struck, Steven K.; Herron, G. Scott; Chan, Kin Foong

2006-07-01

The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 µm or 140 µm 1/e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically

Leishmaniasis: recognition and management with a focus on the immunocompromised patient.

PubMed

Choi, Christine M; Lerner, Ethan A

2002-01-01

Leishmaniasis is a protozoan disease whose clinical manifestations depend both on the infecting species of Leishmania and the immune response of the host. Transmission of the disease occurs by the bite of a sandfly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis (CL), to the mucous membranes in mucosal leishmaniasis or spread internally in visceral leishmaniasis (VL). In the last 2 decades, leishmaniasis, especially VL, has been recognized as an opportunistic disease in immunocompromised patients, particularly those infected with HIV. Leishmaniasis is characterized by a spectrum of disease phenotypes that correspond to the strength of the host's cell-mediated immune response. Both susceptible and resistant phenotypes exist within human populations. Clinical cutaneous disease ranges from a few spontaneously-healing lesions, to diffuse external or internal disease, to severe mucous membrane involvement. Spontaneously-healing lesions are associated with positive antigen-specific T cell responsiveness, diffuse cutaneous and visceral disease with T cell non-responsiveness, and mucocutaneous disease with T cell hyperresponsiveness. Current research is focused on determining the extent to which this spectrum of host response is genetically determined. In endemic areas, diagnosis is often made on clinical grounds alone including: small number of lesions; on exposed areas; present for a number of months; resistant to all types of attempted treatments; and usually no pain or itching. Multiple diagnostic techniques are available. When evaluating treatment, the natural history of leishmaniasis must be considered. Lesions of CL heal spontaneously over 1 month to 3 years, while lesions of mucocutaneous and VL rarely, if ever, heal without treatment. Consequently, all the latter patients require treatment. Therapy is not always essential in localized CL, although the majority of such patients are treated. Patients with

Estimating terrestrial amphibian pesticide body burden through dermal exposure

EPA Science Inventory

Dermal exposure presents a potentially significant but understudied route for pesticide uptake in terrestrial amphibians. Our study measured dermal uptake of pesticides of varying hydrophobicity (logKow) in frogs. Amphibians were indirectly exposed to one of five pesticide active...

In vitro permissiveness of bovine neutrophils and monocyte derived macrophages to Leishmania donovani of Ethiopian isolate.

PubMed

Tasew, Geremew; Gadisa, Endalamaw; Abera, Adugna; Zewude, Aboma; Chanyalew, Menberework; Aseffa, Abraham; Abebe, Markos; Ritter, Uwe; van Zandbergen, Ger; Laskay, Tamás; Tafess, Ketema

2016-04-18

Epidemiological studies in Ethiopia have documented that the risk of visceral leishmaniasis (VL, Kala-azar) is higher among people living with domestic animals. The recent report on isolation of Leishmania donovani complex DNA and the detected high prevalence of anti-leishmanial antibodies in the blood of domestic animals further strengthen the potential role of domestic animals in the epidemiology of VL in Ethiopia. In mammalian hosts polymorphonuclear cells (PMN) and macrophages are the key immune cells influencing susceptibility or control of Leishmania infection. Thus to substantiate the possible role of cattle in VL transmission we investigate the permissiveness of bovine PMN and monocyte derived macrophages (MDM) for Leishmania (L.) donovani infection. Whole blood was collected from pure Zebu (Boss indicus) and their cross with Holstein Friesian cattle. L. donovani (MHOM/ET/67/HU3) wild and episomal green fluorescent protein (eGFP) labelled stationary stage promastigotes were co-incubated with whole blood and MDM to determine infection of these cells. Engulfment of promastigotes by the cells and their transformation to amastigote forms in MDM was studied with direct microscopy. Microscopy and flow cytometry were used to measure the infection rate while PCR-RLFP was used to confirm the infecting parasite. L. donovani infected bovine whole blood PMN in the presence of plasma factors and all cellular elements. Morphological examinations of stained cytospin smears revealed that PMN engulfed promastigotes. Similarly, we were able to show that bovine MDM can be infected by L. donovani, which transformed to amastigote forms in the cells. The in vitro infection of bovine PMN and MDM by L. donovani further strengthens the possibility that cattle might serve as source of L. donovani infection for humans.

SLC11A1 polymorphisms and host susceptibility to cutaneous leishmaniasis in Pakistan.

PubMed

Sophie, Mariam; Hameed, Abdul; Muneer, Akhtar; Samdani, Azam J; Saleem, Saima; Azhar, Abid

2017-01-07

The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan. Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in 274 patients and 119 healthy controls. Six polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Two single nucleotide polymorphisms were analyzed with newly designed semi-nested PCR assays. Case-control analysis showed no association between selected polymorphisms in SLC11A1 and cutaneous leishmaniasis. No significant difference was observed in the distribution of alleles between leishmaniasis patients and healthy individuals. Strong pairwise linkage disequilibrium was observed between rs2276631 and rs2290708 (r 2  = 64); and rs17235409 and rs17235416 (r 2  = 78). This study shows that genetic variations in the candidate gene SLC11A1 do not affect susceptibility to cutaneous leishmaniasis in the sample population from Pakistan.

Emerging role of amiodarone and dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis.

PubMed

Oryan, A; Bemani, E; Bahrami, S

2018-04-22

Leishmaniasis is a group of human and animal diseases causing 20,000-40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca 2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Osteopontin in Systemic Sclerosis and its Role in Dermal Fibrosis

PubMed Central

Wu, Minghua; Schneider, Daniel J.; Mayes, Maureen D; Assassi, Shervin; Arnett, Frank C.; Tan, Filemon K.; Blackburn, Michael R.; Agarwal, Sandeep K.

2012-01-01

Osteopontin (OPN) is a matricellular protein with proinflammatory and profibrotic properties. Previous reports demonstrate a role for OPN in wound healing and pulmonary fibrosis. Herein, we determined if OPN levels are increased in a large cohort of systemic sclerosis (SSc) patients and if OPN contributes dermal fibrosis. Plasma OPN levels were increased in SSc patients, including patients with limited and diffuse disease, compared to healthy controls. Immunohistology demonstrated OPN on fibroblast-like and inflammatory cells in SSc skin and lesional skin from mice in the bleomycin-induced dermal fibrosis model. OPN deficient (OPN−/−) mice developed less dermal fibrosis compared to wild-type mice in the bleomycin-induced dermal fibrosis model. Additional in vivo studies demonstrated that lesional skin from OPN−/− mice had fewer Mac-3+ cells, fewer myofibroblasts, decreased TGF-beta (TGFβ) and genes in the TGFβ pathway and decreased numbers of cells expressing phosphorylated SMAD2 (pSMAD) and ERK. In vitro, OPN−/− dermal fibroblasts had decreased migratory capacity but similar phosphorylation of SMAD2 by TGFβ. Finally, TGFβ production by OPN deficient macrophages was reduced compared to wild type. These data demonstrate an important role for OPN in the development of dermal fibrosis and suggest that OPN may be a novel therapeutic target in SSc. PMID:22402440

Cutaneous Leishmaniasis: The Truth about the 'Flesh-Eating Disease' in Syria.

PubMed

Mondragon-Shem, Karina; Acosta-Serrano, Alvaro

2016-06-01

Recent news headlines claimed that corpses thrown into Syrian streets are causing cutaneous leishmaniasis (CL) outbreaks. However, leishmaniasis is only transmitted by blood-feeding sandflies, not through human remains. High CL prevalence in Syria may instead be attributed to the absence of disease control programs due to the disruption of health services. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Exploratory study on the micro-remodeling of dermal tissue].

PubMed

Jiang, Yu-zhi; Ding, Gui-fu; Lu, Shu-liang

2009-10-01

To explore the effect of three-dimensional structure of dermal matrix on biological behavior of fibroblasts (Fb) in the microcosmic perspective. The three-dimensional structure of dermal tissue was analyzed by plane geometric and trigonometric function. Microdots structure array with cell adhesion effect was designed by computer-assisted design software according to the adhesive and non-adhesive components of dermal tissue. Four sizes (8 microm x 3 microm, space 6 microm; 16 microm x 3 microm, space 6 microm; 16 microm x 5 microm, space 8 microm; 20 microm x 3 microm, space 2 microm) of micropier grid used for cell culture (MPGCC) with cell-adhesive microdots, built up with micro-pattern printing and molecule self-assembly method were used to culture dermal Fb. Fb cultured with cell culture matrix without micropier grid was set up as control. The expression of skeleton protein (alpha-SMA) of Fb, cell viability and cell secretion were detected with immunohistochemistry, fluorescent immunohistochemistry, MTT test and the hydroxyproline content assay. The three-dimensional structure of dermal tissue could be simulated by MPGCC as shown in arithmetic analysis. Compared with those of control group [(12 +/- 3)% and (0.53 +/- 0.03) microg/mg, (0.35 +/- 0.04)], the expression of alpha-SMA [(49 +/- 3)%, (61 +/- 3)%, (47 +/- 4)%, (51 +/- 3)%] and the content of hydroxyproline [(0.95 +/- 0.04), (0.87 +/- 0.03), (0.81 +/- 0.03), (0.77 +/- 0.03) microg/mg] were increased significantly (P < 0.05), the cell viability of Fb (0.12 +/- 0.03, 0.13 +/- 0.04, 0.14 +/- 0.03, 0.19 +/- 0.03) cultured in MPGCC was decreased significantly (P < 0.05). When the parameters of micropier grid were changed, the expression of alpha-SMA, the cell viability and the content of hydroxyproline of Fb cultured in four sizes of MPGCC were also significantly changed as compared with one another (P < 0.05). MPGCC may be the basic functional unit of dermal template, or unit of dermal template to call

The Impact of Micro-Teaching on the Teaching Practice Performance of Undergraduate Agricultural Education Students in College of Education, Azare

ERIC Educational Resources Information Center

Sa'ad, Tata Umar; Sabo, Shehu; Abdullahi, Aliyu Dahuwa

2015-01-01

Micro-teaching and teaching practices are two integral parts of teacher education programme. Therefore, this study investigated the impact of micro-teaching on the teaching practice of the undergraduate Agricultural Education Students admitted in 2012/2013 Academic session in College of Education, Azare, Bauchi State, Nigeria. The 400 level…

Standardization of intralesional meglumine antimoniate treatment for cutaneous leishmaniasis.

PubMed

Duque, Maria Cristina de Oliveira; Vasconcellos, Érica de Camargo Ferreira E; Pimentel, Maria Inês Fernandes; Lyra, Marcelo Rosandiski; Pacheco, Sandro Javier Bedoya; Marzochi, Mauro Celio de Almeida; Rosalino, Cláudia Maria Valete; Schubach, Armando de Oliveira

2016-01-01

Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. The technique is described in detail sufficient to enable replication. The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.

Comparison of dermal and inhalation routes of entry for organic chemicals

NASA Technical Reports Server (NTRS)

Jepson, Gary W.; Mcdougal, James N.; Clewell, Harvey J., III

1992-01-01

The quantitative comparison of the chemical concentration inside the body as the result of a dermal exposure versus an inhalation exposure is useful for assessing human health risks and deciding on an appropriate protective posture. In order to describe the relationship between dermal and inhalation routes of exposure, a variety of organic chemicals were evaluated. The types of chemicals chosen for the study were halogenated hydrocarbons, aromatic compounds, non-polar hydrocarbons and inhalation anesthetics. Both dermal and inhalation exposures were conducted in rats and the chemicals were in the form of vapors. Prior to the dermal exposure, rat fur was closely clipped and during the exposure rats were provided fresh breathing air through latex masks. Blood samples were taken during 4-hour exposures and analyzed for the chemical of interest. A physiologically based pharmacokinetic model was used to predict permeability constants (cm/hr) consistent with the observed blood concentrations of the chemical. The ratio of dermal exposure to inhalation exposure required to achieve the same internal dose of chemical was calculated for each test chemical. The calculated ratio in humans ranged from 18 for styrene to 1180 for isoflurane. This methodology can be used to estimate the dermal exposure required to reach the internal dose achieved by a specific inhalation exposure. Such extrapolation is important since allowable exposure standards are often set for inhalation exposures, but occupational exposures may be dermal.

Epidemiological aspects of human and canine visceral leishmaniasis in State of Alagoas, Northeast, Brazil.

PubMed

Rocha, M A N; Matos-Rocha, T J; Ribeiro, C M B; Abreu, S R O

2018-02-05

Zoonotic visceral leishmaniasis (ZVL), caused by protozoans of the genus Leishmania, it is a worldwide of great importance disease. In the northeast region of Brazil, the state of Alagoas has an endemic status for ZVL. Thus, this work aimed to analyze the epidemiological situation of human and canine visceral leishmaniasis in Alagoas, Northeast, Brazil, from 2007 to 2013. We conducted a descriptive, observational, retrospective study using secondary data from the Notifiable Diseases Information System, the Center of Zoonosis Control of Maceió, and the Central Laboratory of Public Health of Alagoas. During the studied period, it was observed that the highest incidence of human visceral leishmaniasis was in 2011 and the lowest in 2013. On the other hand, canine visceral leishmaniasis had its highest incidence in 2007 and its lowest in 2012. Of the 55 municipalities in the State of Alagoas that showed human visceral leishmaniasis (HVL), São José da Tapera presented an average of 4.4 cases over the past five years, being classified as of intense transmission. Regarding canine visceral leishmaniasis, in the same studied period, 45,112 dogs were examined in the State, of which 4,466 were positive. It resulted, thus, in a 9.9% positivity rate. Our data are important because canine infection is an important risk factor for the human disease.

Vibration anesthesia for the reduction of pain with facial dermal filler injections.

PubMed

Mally, Pooja; Czyz, Craig N; Chan, Norman J; Wulc, Allan E

2014-04-01

Vibration anesthesia is an effective pain-reduction technique for facial cosmetic injections. The analgesic effect of this method was tested in this study during facial dermal filler injections. The study aimed to evaluate the safety and efficacy of vibration anesthesia for these facial injections. This prospective study analyzed 41 patients who received dermal filler injections to the nasolabial folds, tear troughs, cheeks, and other facial sites. The injections were administered in a randomly assigned split-face design. One side of the patient's face received vibration together with dermal filler injections, whereas the other side received dermal filler injections alone. The patients completed a posttreatment questionnaire pertaining to injection pain, adverse effects, and preference for vibration with future dermal filler injections. The patients experienced both clinically and statistically significant pain reduction when a vibration stimulus was co-administered with the dermal filler injections. No adverse events were reported. The majority of the patients (95 %) reported a preference for vibration anesthesia with subsequent dermal filler injections. Vibration is a safe and effective method of achieving anesthesia during facial dermal filler injections. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Rural campaign to diagnose and treat mucocutaneous leishmaniasis in Bolivia.

PubMed Central

Dedet, J. P.; Melogno, R.; Cardenas, F.; Valda, L.; David, C.; Fernandez, V.; Torrez, M. E.; Dimier-David, L.; Lyevre, P.; Villareal, M. E.

1995-01-01

Mucocutaneous leishmaniasis (MCL) is endemic in the tropical Amazonian lowlands of Bolivia, an area that regularly receives influxes of migratory populations. In these new agricultural development areas, a campaign to diagnose and treat the disease was carried out between 1989 and 1992, in order to provide direct access to MCL treatment in the endemic areas at a standard equivalent to that offered in the urban centres in Bolivia. The campaign led to the creation of decentralized local centres for diagnosis and treatment of the disease. A campaign to inform the population about leishmaniasis was also undertaken and courses were run to educate medical and paramedical personnel. As a result of the campaign, 3285 cases of leishmaniasis were diagnosed, including 2152 cutaneous and 326 mucosal forms. Also, a total of 1888 cases were treated, 1677 of which cutaneous and 211, mucosal. Images Fig. 2 PMID:7614666

The relationship between dermal papillary structure and skin surface properties, color, and elasticity.

PubMed

Mizukoshi, K; Nakamura, T; Oba, A

2016-08-01

The skin contains an undulating structure called the dermal papillary structure between the border of the epidermis and dermis. The physiological importance of the dermal papillary structures has been discussed, however, the dermal papillary structures have never been evaluated for their contribution to skin appearance. In this study, we investigated the correlation between the dermal papillary structure and skin color and elasticity. In addition, the relationship was validated with skin model experiments. The dermal papillary structures in the skin of the female cheek were quantitatively measured by in vivo confocal laser scanning microscopy images. In addition, the skin color and elasticity were measured at the same site. A skin model with dermal papilla-like structures was created by referring to the optical and shape properties of the skin using agar gel and a scattering sheet. Correlations were found between the dermal papillary structures and skin color irregularity and skin elasticity. These relationships were verified by the experiments employing a skin model. The results of this study indicated that the dermal papillary structure is also an important factor for skin appearance such as color and elasticity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tegumentary leishmaniasis and coinfections other than HIV

PubMed Central

Kaye, Paul M.; Adaui, Vanessa; Polman, Katja; Llanos-Cuentas, Alejandro; Dujardin, Jean-Claude; Boelaert, Marleen

2018-01-01

Background Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by Leishmania parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL. Methodology and principal findings This review focuses on the frequency of TL coinfections in human populations, interactions between Leishmania and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of Trypanosoma cruzi coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., Leishmania and Sporothrix schenckii), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects. Conclusions and significance In patients with TL, coinfection

Lipid based delivery and immuno-stimulatory systems: Master tools to combat leishmaniasis.

PubMed

Sabur, Abdus; Asad, Mohammad; Ali, Nahid

2016-11-01

Disease management of leishmaniasis is appalling due to lack of a human vaccine and the toxicity and resistance concerns with limited therapeutic drugs. The challenges in development of a safe vaccine for generation and maintenance of robust antileishmanial protective immunity through a human administrable route of immunization can be addressed through immunomodulation and targeted delivery. The versatility of lipid based particulate system for deliberate delivery of diverse range of molecules including immunomodulators, antigens and drugs have essentially found pivotal role in design of proficient vaccination and therapeutic strategies against leishmaniasis. The prospects of lipid based preventive and curative formulations for leishmaniasis have been highlighted in this review. Copyright © 2016. Published by Elsevier Inc.

Is leishmaniasis widespread in Spain? First data on canine leishmaniasis in the province of Lleida, Catalonia, northeast Spain.

PubMed

Ballart, C; Alcover, M M; Portús, M; Gállego, M

2012-02-01

Canine leishmaniasis (CanL) is a widespread disease present in 42 countries. It is considered of epidemiological importance because of its role as a reservoir of human leishmaniasis. Knowledge of the real distribution of CanL and its emergence and/or re-emergence is of great importance in order to determine the extension of the disease. This work reports the detection of CanL in a farm dog located in a Pyrenean area of northwest Catalonia (Spain) where the disease was previously unknown. Since the dog had never left the region and sandfly vectors, Phlebotomus ariasi and P. perniciosus, were present in the farm the case is considered as autochthonous and is the first to be published in this region of Spain. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

New perspectives for leishmaniasis chemotherapy over current anti-leishmanial drugs: a patent landscape.

PubMed

Machado-Silva, Alice; Guimarães, Pedro Pires Goulart; Tavares, Carlos Alberto Pereira; Sinisterra, Rubén Dario

2015-03-01

Although leishmaniasis is estimated to cause the ninth largest disease burden among individual infectious diseases, it is still one of the most neglected diseases in terms of drug development. Current drugs are highly toxic, resistance is common and compliance of patients to treatment is low, as treatment is long and drug price is high. In this review, the authors carried out a patent landscape in search for new perspectives for leishmaniasis therapy. This search encompassed patent documents having priority date between 1994 and 2014. Selected compounds were compared to current anti-leishmanial drugs regarding efficacy and toxicity, when experimental data were available. Most patents related to drugs for leishmaniasis have not been produced by the pharmaceutical industry but rather by public research institutes or by universities, and the majority of the inventions disclosed are still in preclinical phase. There is an urgent need to find new ways of funding research for leishmaniasis drugs, incentivizing product development partnerships and pushing forward innovation.

The development and clinical evaluation of second-generation leishmaniasis vaccines.

PubMed

Duthie, Malcolm S; Raman, Vanitha S; Piazza, Franco M; Reed, Steven G

2012-01-05

Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1+MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Development and Clinical Evaluation of Second-Generation Leishmaniasis Vaccines

PubMed Central

Duthie, Malcolm S.; Raman, Vanitha S.; Piazza, Franco M.; Reed, Steven G.

2011-01-01

Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1 + MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed. PMID:22085553

Visceral leishmaniasis in captive wild canids in Brazil.

PubMed

Luppi, Marcela M; Malta, Marcelo C C; Silva, Teane M A; Silva, Fabiana L; Motta, Rafael O C; Miranda, Ildikó; Ecco, Roselene; Santos, Renato L

2008-08-01

Visceral leishmaniasis (VL) is endemic in Belo Horizonte (State of Minas Gerais, Brazil). Leishmania sp. can naturally infect several species of mammals, and the domestic dog is the most important reservoir of the disease in South America. This report describes five cases of visceral leishmaniasis in Brazilian canids. Among 15 animals kept in captivity in a zoo in Belo Horizonte (State of Minas Gerais, Brazil), two animals, a bush dog (Spheotos venaticos) and a hoary zorro (Lycalopex vetulus) were serologically positive and developed clinical signs of VL, whereas three other canids, including a crab-eating fox (Cerdocyon thous), a maned wolf (Chrysocyon brachyurus), and a hoary zorro (Lycalopex vetulus) had positive serological results without clinical signs.

Validation of in vitro assays in three-dimensional human dermal constructs.

PubMed

Idrees, Ayesha; Chiono, Valeria; Ciardelli, Gianluca; Shah, Siegfried; Viebahn, Richard; Zhang, Xiang; Salber, Jochen

2018-05-01

Three-dimensional cell culture systems are urgently needed for cytocompatibility testing of biomaterials. This work aimed at the development of three-dimensional in vitro dermal skin models and their optimization for cytocompatibility evaluation. Initially "murine in vitro dermal construct" based on L929 cells was generated, leading to the development of "human in vitro dermal construct" consisting of normal human dermal fibroblasts in rat tail tendon collagen type I. To assess the viability of the cells, different assays CellTiter-Blue ® , RealTime-Glo ™ MT, and CellTiter-Glo ® (Promega) were evaluated to optimize the best-suited assay to the respective cell type and three-dimensional system. Z-stack imaging (Live/Dead and Phalloidin/DAPI-Promokine) was performed to visualize normal human dermal fibroblasts inside matrix revealing filopodia-like morphology and a uniform distribution of normal human dermal fibroblasts in matrix. CellTiter-Glo was found to be the optimal cell viability assay among those analyzed. CellTiter-Blue reagent affected the cell morphology of normal human dermal fibroblasts (unlike L929), suggesting an interference with cell biological activity, resulting in less reliable viability data. On the other hand, RealTime-Glo provided a linear signal only with a very low cell density, which made this assay unsuitable for this system. CellTiter-Glo adapted to three-dimensional dermal construct by optimizing the "shaking time" to enhance the reagent penetration and maximum adenosine triphosphate release, indicating 2.4 times higher viability value by shaking for 60 min than for 5 min. In addition, viability results showed that cells were viable inside the matrix. This model would be further advanced with more layers of skin to make a full thickness model.

Intestinal leishmaniasis in acquired immunodeficiency syndrome.

PubMed

Molaei, M; Minakari, M; Pejhan, Sh; Mashayekhi, R; Modaress Fatthi, A R; Zali, M R

2011-05-01

In endemic regions, visceral leishmaniasis is one of the most common opportunistic infections in HIV positive patients. Simultaneous infection with Leishmania and HIV has been reported in some countries but this is the first report of such a case in Iran. Our patient was a 27 years old man with intermittent night fever, abdominal pain, loss of appetite, vomiting, watery diarrhea and severe weight loss for 6 months. He had low socio-economic status with an imprisonment history. The patient was quite cachectic and had low grade fever. Physical exam and upper GI endoscopy revealed oropharyngeal candidiasis. Microscopic evaluation of duodenal biopsy material showed Leishmania amastigotes in macrophages of lamina propria. Leishman bodies were also observed in bone marrow aspiration specimen. Serologic tests were positive for Leishmania infantum. HIV antibody was also positive with a CD4+cell count of 80/μl. The diagnosis was acquired immunodeficiency syndrome with simultaneous visceral leishmaniasis involving intestinal mucosa.

Spatial modeling of cutaneous leishmaniasis in Iran from 1983 to 2013.

PubMed

Holakouie-Naieni, Kourosh; Mostafavi, Ehsan; Boloorani, Ali Darvishi; Mohebali, Mehdi; Pakzad, Reza

2017-02-01

Cutaneous Leshmaniasis (CL), a parasitic skin infection caused by Leishmania species, is endemic in some regions of Iran. In this study, the effect of location on the incidence and distribution of CL in Iran was studied. We collected datas including the number of Cutaneous Leishmaniasis cases and populations at-risk of disease in Iran's different provinces reported by the Iranian ministry of health and the National Bureau of Statistics, respectively. Spatial modeling was performed using Arc GIS software. Descriptive maps, hotspot analysis, and high/low clustering analysis were used to demonstrate distribution of the cutaneous leishmaniasis, to determine regions at risk of disease's incidence, and to reach the most appropriate method for clustering of disease. The total number of cases of cutaneous leishmaniasis reported through the study period was 589,913. The annual incidence of CL was estimated to be 30.9 per 100,000 in Iranian population. We also demonstrated that Cutaneous leishmaniasis most prominently occurs in regions with dry and desert climates as well as in central parts of Iran. It affected the southwest of Iran between 1983 and 1997, and subsequently developed towards the center and the eastern between 1998 and 2013. Disease hotspots were focused in the provinces of Yazd, Khozestan and Kohgiloyeh-Boyer-Ahmad (p<0.05). No pattern of spatial clustering was observed. Cutaneous leishmaniasis is a major health problem which could be a serious threat for inhabitants who live in high-risk provinces of Iran; much more resources need to be allocated in these areas, to warrant the prevention as well as effectively management of this disease. Copyright © 2016 Elsevier B.V. All rights reserved.

In silico search of energy metabolism inhibitors for alternative leishmaniasis treatments.

PubMed

Silva, Lourival A; Vinaud, Marina C; Castro, Ana Maria; Cravo, Pedro Vítor L; Bezerra, José Clecildo B

2015-01-01

Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genus Leishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways of Leishmania include several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes in Leishmania could be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93 Leishmania energy metabolism targets. Using each gene's designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis.

Recent advances in phlebotomine sand fly research related to leishmaniasis control.

PubMed

Bates, Paul A; Depaquit, Jerôme; Galati, Eunice A B; Kamhawi, Shaden; Maroli, Michele; McDowell, Mary Ann; Picado, Albert; Ready, Paul D; Salomón, O Daniel; Shaw, Jeffrey J; Traub-Csekö, Yara M; Warburg, Alon

2015-02-27

Phlebotomine sand flies are the subject of much research because of the role of their females as the only proven natural vectors of Leishmania species, the parasitic protozoans that are the causative agents of the neglected tropical disease leishmaniasis. Activity in this field was highlighted by the eighth International Symposium on Phlebotomine Sand flies (ISOPS) held in September 2014, which prompted this review focusing on vector control. Topics reviewed include: Taxonomy and phylogenetics, Vector competence, Genetics, genomics and transcriptomics, Eco-epidemiology, and Vector control. Research on sand flies as leishmaniasis vectors has revealed a diverse array of zoonotic and anthroponotic transmission cycles, mostly in subtropical and tropical regions of Africa, Asia and Latin America, but also in Mediterranean Europe. The challenge is to progress beyond descriptive eco-epidemiology, in order to separate vectors of biomedical importance from the sand fly species that are competent vectors but lack the vectorial capacity to cause much human disease. Transmission modelling is required to identify the vectors that are a public health priority, the ones that must be controlled as part of the integrated control of leishmaniasis. Effective modelling of transmission will require the use of entomological indices more precise than those usually reported in the leishmaniasis literature.

Imaging host-Leishmania interactions: significance in visceral leishmaniasis.

PubMed

Forestier, C-L

2013-01-01

Leishmaniasis is a neglected disease that is associated with a spectrum of clinical manifestations ranging from self-healing cutaneous lesions to fatal visceral infections, which primarily depends on the parasite species. In visceral leishmaniasis (VL), as opposed to cutaneous leishmaniasis (CL), parasites that infect host cells at the sand fly bite site have the striking ability to disseminate to visceral organs where they proliferate and persist for long periods of time. Imaging the dynamics of the host-Leishmania interaction in VL provides a powerful approach to understanding the mechanisms underlying host cell invasion, Leishmania dissemination and persistence within visceral organs and, to dissecting the immune responses to infection. Therefore, by allowing the visualization of the critical steps involved in the pathogenesis of VL, state-of-the-art microscopy technologies have the great potential to aid in the identification of better intervention strategies for this devastating disease. In this review, we emphasize the current knowledge and the potential significance of imaging technologies in understanding the infection process of visceralizing Leishmania species. Then, we discuss how application of innovative microscopy technologies to the study of VL will provide rich opportunities for investigating host-parasite interactions at a previously unexplored level and elucidating visceral disease-promoting mechanisms. © 2013 John Wiley & Sons Ltd.

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

PubMed Central

Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho

2016-01-01

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. PMID:27067332

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--PESTICIDES IN DERMAL ANALYTICAL RESULTS

EPA Science Inventory

The Pesticides in Dermal Wipes data set contains analytical results for measurements of up to 8 pesticides in 86 dermal wipe samples over 86 households. Each sample was collected from the primary respondent within each household. The Dermal/Pesticide hand wipe was collected 7 d...

Histological study of cell migration in the dermis of hamsters after immunisation with two different vaccines against visceral leishmaniasis.

PubMed

Moreira, Nádia das Dores; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Vitoriano-Souza, Juliana; Roatt, Bruno Mendes; Malaquias, Luiz Cosme Cotta; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

2009-04-15

Vaccine candidates, including live and/or killed parasites, Leishmania-purified fractions, defined recombinant antigens and antigen-encoding DNA-plasmids have been proposed to use as vaccine anti-Leishmania. More recently, the hamsters have been used to pre-selection of antigens candidate to apply in further experiments using canine model. In this report we evaluated the kinetics of cell migration in dermal inflammatory infiltrate, circulating leukocytes and the presence of nitric oxide (NO)/induced nitric oxide synthase during the early (1-24h) and late (48-168h) periods following inoculation of hamsters with antigenic components of anti-canine visceral leishmaniasis vaccines Leishmune and Leishmania braziliensis antigen (LB) with and without saponin (Sap) adjuvant. Our results show that LB caused an early reduction of lymphocytes in the dermis while Sap and LBSap triggered a late recruitment, suggesting the role of the adjuvant in the traffic of antigen-presenting cells and the induction of lymphocyte migration. In that manner our results suggest that the kinetics of cell migration on hamster model may be of value in the selection of vaccine antigens prior the tests in dogs particularly in respect of the toxicity of the preparations.

Dermal uptake of phthalates from clothing: Comparison of model to human participant results.

PubMed

Morrison, G C; Weschler, C J; Bekö, G

2017-05-01

In this research, we extend a model of transdermal uptake of phthalates to include a layer of clothing. When compared with experimental results, this model better estimates dermal uptake of diethylphthalate and di-n-butylphthalate (DnBP) than a previous model. The model predictions are consistent with the observation that previously exposed clothing can increase dermal uptake over that observed in bare-skin participants for the same exposure air concentrations. The model predicts that dermal uptake from clothing of DnBP is a substantial fraction of total uptake from all sources of exposure. For compounds that have high dermal permeability coefficients, dermal uptake is increased for (i) thinner clothing, (ii) a narrower gap between clothing and skin, and (iii) longer time intervals between laundering and wearing. Enhanced dermal uptake is most pronounced for compounds with clothing-air partition coefficients between 10 4 and 10 7 . In the absence of direct measurements of cotton cloth-air partition coefficients, dermal exposure may be predicted using equilibrium data for compounds in equilibrium with cellulose and water, in combination with computational methods of predicting partition coefficients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Current and future ecological niche of Leishmaniasis (Kinetoplastida: Trypanosomatidae) in the Neotropical region].

PubMed

Moo-Llanes, David A

2016-09-01

The leishmaniasis is a complex disease system, caused by the protozoan parasite Leishmania and transmitted to humans by the vector Lutzomyia spp. Since it is listed as a neglected disease according to the World Health Organization, the aim of this study was to determine the current and future niche of cutaneous and visceral leishmaniasis in the Neotropical region. We built the ecological niche model (ENM) of cutaneous (N= 2 910 occurrences) and visceral (N= 851 occurrences) leishmaniasis using MaxEnt algorithm. Nine bioclimatic variables (BIO1, BIO4, BIO5, BIO6, BIO7, BIO12, BIO13, BIO14, BIO15 (downloaded from the Worldclim) and disease occurrences data were used for the construction of ENM for three periods (current, 2050 and 2070) and four climate change scenarios (RCP 2.6, 4.5, 6.0 y 8.5). We analyzed the number of pixels occupied, identity niche, modified niche (stable, loss, and gain) and seasonality. Our analyses indicated the expansion for cutaneous leishmaniasis (CL), a comparison for visceral leishmaniasis (VL). We rejected the null hypothesis of niche identity between CL and VL with Hellinger’s index = 0.91 (0.92-0.98) and Schoener’s Index = 0.67 (0.85-1.00) but with an overlap niche of 56.3 %. The differences between the two leishmaniasis types were detected in relation to RCP scenarios and niche shifts (area gained / loss). Seasonality was more important for CL. We provided a current picture of CL and VL distributions and the predicted distributional changes associated to different climate change scenarios for the Neotropical region. We can anticipate that increasing range is likely although it will depend locally on the future trends in weather seasonality.

Detection of Leishmania parasites in the blood of patients with isolated cutaneous leishmaniasis.

PubMed

Nakkash-Chmaisse, Hania; Makki, Raja; Nahhas, Georges; Knio, Khouzama; Nuwayri-Salti, Nuha

2011-07-01

The consequences of the spread of Leishmania parasites to the blood from lesions in patients with cutaneous leishmaniasis are numerous. To assess the magnitude of this invasion we conducted the present study on patients referred to the American University of Beirut Medical Center for cutaneous leishmaniasis. Patients referred for the management of cutaneous leishmaniasis were included in the study. Skin and blood cultures for Leishmania were taken from these patients. One hundred sixty-two patients were proven to have cutaneous leishmaniasis by pathology; 52% were males and 44% females (gender information was missing for 4%). Patient age ranged from 5 months to 70 years. None of the patients had received treatment for Leishmania. We obtained parasite isolates from 85 patients (52.5%), proven by cultures from skin and blood/blood components. Interestingly, the parasite was isolated in the blood and blood components of 50 patients (30.9%). Isoenzyme analysis confirmed the fact that the organisms in blood and skin were the same; from the 28 isolates that were positive in both skin and blood, eight isolates were Leishmania major and two were Leishmania tropica. The remaining isolates, whether positive in both blood and skin or in either of these tissues, skin or blood and its products, were Leishmania infantum sensu lato. In the current study, the detection rate of parasites in the blood of patients with cutaneous leishmaniasis was high. This illustrates the invasive characteristic of the parasite that has escaped the skin. Testing should be considered in areas other than Lebanon, especially around the Mediterranean basin. Whether these findings support the administration of systemic treatment for cutaneous leishmaniasis or not needs to be confirmed in larger prospective studies. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Treatment of canine leishmaniasis with marbofloxacin in dogs with renal disease.

PubMed

Pineda, Carmen; Aguilera-Tejero, Escolastico; Morales, Maria C; Belinchon-Lorenzo, Silvia; Gomez-Nieto, Luis C; Garcia, Pablo; Martinez-Moreno, Julio M; Rodriguez-Ortiz, Maria E; Lopez, Ignacio

2017-01-01

Treatment of canine leishmaniasis (CanL) represents a challenge. Due to the high prevalence of renal disease associated to CanL, it is important to find an effective drug that does not damage the kidneys. Marbofloxacin has been shown to be effective and well tolerated in non-azotemic dogs with leishmaniasis. To evaluate the safety and efficacy of marbofloxacin in dogs with leishmaniasis and decreased renal function, 28 dogs suffering from leishmaniasis and chronic kidney disease (CKD) were treated with oral marbofloxacin at 2 mg/Kg/day for 28 days. During treatment dogs were assessed by performing weekly physical exams, measuring blood pressure and evaluating blood and urine parameters. Lymph node aspirations were also obtained at days 0 and 28. The global clinical score decreased significantly, from 6.2±3.4 to 4.7±3.1 (p = 0.0001), after treatment. Marbofloxacin also decreased parasitic load in 72% of the dogs. No significant differences in plasma creatinine, urine specific gravity, urinary concentrations of cystatin C, ferritin and urinary protein loss were detected during treatment. A transient but significant decrease in blood pressure was detected up to day 14 (from 180.1±36.6 to 166.0±32.7 mmHg; p = 0.016). Moreover, dogs showed a significant increase in plasma albumin concentration (from 15.0±5.2 to 16.6±3.9 g/L; p = 0.014) and a significant decrease in globulin concentration (from 59.0±18.1 to 54.1±18.0 g/L; p = 0.005). The results demonstrate that, in addition to being effective for treatment of CanL, marbofloxacin is a very safe drug in dogs with CKD and leishmaniasis.

Treatment of canine leishmaniasis with marbofloxacin in dogs with renal disease

PubMed Central

Pineda, Carmen; Aguilera-Tejero, Escolastico; Morales, Maria C.; Belinchon-Lorenzo, Silvia; Gomez-Nieto, Luis C.; Garcia, Pablo; Martinez-Moreno, Julio M.; Rodriguez-Ortiz, Maria E.

2017-01-01

Treatment of canine leishmaniasis (CanL) represents a challenge. Due to the high prevalence of renal disease associated to CanL, it is important to find an effective drug that does not damage the kidneys. Marbofloxacin has been shown to be effective and well tolerated in non-azotemic dogs with leishmaniasis. To evaluate the safety and efficacy of marbofloxacin in dogs with leishmaniasis and decreased renal function, 28 dogs suffering from leishmaniasis and chronic kidney disease (CKD) were treated with oral marbofloxacin at 2 mg/Kg/day for 28 days. During treatment dogs were assessed by performing weekly physical exams, measuring blood pressure and evaluating blood and urine parameters. Lymph node aspirations were also obtained at days 0 and 28. The global clinical score decreased significantly, from 6.2±3.4 to 4.7±3.1 (p = 0.0001), after treatment. Marbofloxacin also decreased parasitic load in 72% of the dogs. No significant differences in plasma creatinine, urine specific gravity, urinary concentrations of cystatin C, ferritin and urinary protein loss were detected during treatment. A transient but significant decrease in blood pressure was detected up to day 14 (from 180.1±36.6 to 166.0±32.7 mmHg; p = 0.016). Moreover, dogs showed a significant increase in plasma albumin concentration (from 15.0±5.2 to 16.6±3.9 g/L; p = 0.014) and a significant decrease in globulin concentration (from 59.0±18.1 to 54.1±18.0 g/L; p = 0.005). The results demonstrate that, in addition to being effective for treatment of CanL, marbofloxacin is a very safe drug in dogs with CKD and leishmaniasis. PMID:28982165

Establishment of dermal sheath cell line from Cashmere goat and characterizing cytokeratin 13 as its novel biomarker.

PubMed

Zhu, Bing; Guo, Zhili; Jin, Muzi; Bai, Yujuan; Yang, Wenliang; Hui, Lihua

2018-05-01

To establish a dermal sheath cell line, a dermal papilla cell line and a outer root sheath cell line from Cashmere goat and clarify the similarities and differences among them. We established a dermal sheath cell line, a dermal papilla cell line and a outer root sheath cell line from the pelage skin hair follicles of Cashmere goat. The growth rate of dermal sheath cells was intermediate between that of dermal papilla cells and outer root sheath cells. Immunofluorescence experiments and reverse transcription-polymerase chain reaction analysis showed that at both the transcriptional and translational levels, the dermal sheath cells were alpha-smooth muscle actin (α-SMA) + /cytokeratin 13 + , while the dermal papilla cells were α-SMA + /cytokeratin 13 - and the outer root sheath cells were α-SMA - /cytokeratin 13 + . Patterns of cytokeratin 13 expression could distinguish the dermal sheath cells from the dermal papilla cells. These results suggest that cytokeratin 13 could serve as a novel biomarker for dermal sheath cells of Cashmere goat, and should prove useful for researchers investigating dermal stem cells or interaction of different types of cells during hair cycle.

The cost effectiveness of acellular dermal matrix in expander-implant immediate breast reconstruction.

PubMed

Krishnan, Naveen M; Chatterjee, Abhishek; Rosenkranz, Kari M; Powell, Stephen G; Nigriny, John F; Vidal, Dale C

2014-04-01

Expander-implant breast reconstruction is often supplemented with acellular dermal matrix (ADM). The use of acellular dermal matrix has allowed for faster, less painful expansions and improved aesthetics, but with increased cost. Our goal was to provide the first cost utility analysis of using acellular dermal matrix in two-stage, expander-implant immediate breast reconstruction following mastectomy. A comprehensive literature review was conducted to identify complication rates for two-stage, expander-implant immediate breast reconstruction with and without acellular dermal matrix. The probabilities of the most common complications were combined with Medicare Current Procedural Terminology reimbursement codes and expert utility estimates to fit into a decision model. The decision model evaluated the cost effectiveness of acellular dermal matrix relative to reconstructions without it. Retail costs for ADM were derived from the LifeCell 2012 company catalogue for Alloderm. The overall complication rates were 30% and 34.5% with and without ADM. The decision model revealed a baseline cost increase of $361.96 when acellular dermal matrix is used. The increase in Quality-Adjusted Life Years (QALYs) is 1.37 in the population with acellular dermal matrix. This yields a cost effective incremental cost-utility ratio (ICUR) of $264.20/QALY. Univariate sensitivity analysis confirmed that using acellular dermal matrix is cost effective even when using retail costs for unilateral and bilateral reconstructions. Our study shows that, despite an increased cost, acellular dermal matrix is a cost effective technology for patients undergoing two-stage, expander-implant immediate breast reconstruction due to its increased utility in successful procedures. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Evaluation of Serum Levels of Zinc, Copper, Iron, and Zinc/Copper Ratio in Cutaneous Leishmaniasis

PubMed Central

Pourfallah, F; Javadian, S; Zamani, Z; Saghiri, R; Sadeghi, S; Zarea, B; Faiaz, Sh; Mirkhani, F; Fatemi, N

2009-01-01

Background: The purpose of this study was to evaluate the levels of zinc (Zn), copper (Cu), iron (Fe) and zinc/ copper ratio in the serum of patients with cutaneous leishmaniasis in Qom Province, center of Iran. Methods: Serum levels of zinc and copper were determined by flame atomic absorption spectrophotometer and serum iron concentration was measured by using an Auto Analyzer. The study group consisted of 60 patients with cutaneous leishmaniasis and the control group of 100 healthy volunteers from the same area who were not exposed to cutaneous leishmaniasis. Result: There were no statistically significant differences in age and body mass index between the two groups. Serum Zn (P< 0.001) and Fe (P< 0.05) levels were lower in patients with cutaneous leishmaniasis than the control group. We also found serum Cu concentration (P< 0.05) in the patient group was significantly higher than that of the control group. However, zinc/ copper ratio (P< 0.001) was lower in patients with cutaneous leishmaniasis than in the control group. Conclusion: Our data indicated that Zn/Cu ratio was significantly lower in patients with CL as compared to the controls. Earlier reports suggest that, this ratio imbalance could be a useful marker for immune dysfunction in leishmaniasis. There was also strong association of Zn, Cu and Fe with CL. It suggests the use of blood zinc, copper, iron concentration and the copper/zinc ratio (Zn/Cu), as a means for estimating the prognosis of CL. PMID:22808376

A Novel Field-Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0195 TITLE: A Novel Field-Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis PRINCIPAL INVESTIGATOR...Field-Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Month % completion Aim 1: To use simulated field conditions to optimize and produce the established RPA lateral flow diagnostic test for POC

A Novel Field-Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis

DTIC Science & Technology

2016-10-01

14. ABSTRACT Leishmaniasis is caused by the protozoan Leishmania and is generally transmitted by the bite of sand flies of the genus Lutzomyia or...INTRODUCTION: Leishmaniasis is caused by the protozoan Leishmania and is generally transmitted by the bite of sand flies of the genus Lutzomyia or...and requires minimal training, will improve the quality of life of populations living in endemic areas. The availability of RPA-LF in economically

LINKING DERMAL MODELING AND LOADING DATA TO PREDICT LONG-TERM DOSES FROM INTERMITTENT DERMAL CONTACT

EPA Science Inventory

In this paper we assess dermal exposure and dose resulting from intermittent contact with residue-contaminated surfaces. These estimates require an understanding of (1) the quantitative relationship between exposure and absorbed dose; (2) the impact of intermittent exposure on ...

Etiologic agent of an epidemic of cutaneous leishmaniasis in Tolima, Colombia.

PubMed

Rodríguez-Barraquer, Isabel; Góngora, Rafael; Prager, Martín; Pacheco, Robinson; Montero, Luz Mery; Navas, Adriana; Ferro, Cristina; Miranda, Maria Consuelo; Saravia, Nancy G

2008-02-01

American cutaneous leishmaniasis (ACL) has been characterized as a zoonotic disease. However, peridomestic and domestic transmission have been recorded in at least nine countries in Central and South America. The present study was undertaken to identify the etiologic agent of a peridomestic epidemic of ACL in the Department of Tolima, Colombia. Leishmania isolates were obtained during the diagnosis of 56 patients with ACL who consulted the local leishmaniasis control program in three municipalities in Tolima. Species were identified using monoclonal antibodies and isoenzyme electrophoresis. A total of 53 (94.6%) of 56 isolates were identified as Leishmania (Viannia) guyanensis. Three isolates (5.4%) were identified as L. (V.) panamensis. Leishmania (V.) guyanensis is the probable etiologic agent of the largest epidemic of cutaneous leishmaniasis recorded in Colombia. This species has not previously been reported outside the Amazon and southeastern regions of Colombia, and has not been described in the peridomestic setting or linked with an epidemic.

Cost-effectiveness of prevention strategies for American tegumentary leishmaniasis in Argentina.

PubMed

Orellano, Pablo Wenceslao; Vazquez, Nestor; Salomon, Oscar Daniel

2013-12-01

The aim of this study was to estimate the cost-effectiveness of reducing tegumentary leishmaniasis transmission using insecticide-impregnated clothing and curtains, and implementing training programs for early diagnosis. A societal perspective was adopted, with outcomes assessed in terms of costs per disability adjusted life years (DALY). Simulation was structured as a Markov model and costs were expressed in American dollars (US$). The incremental cost-effectiveness ratio of each strategy was calculated. One-way and multivariate sensitivity analyses were performed. The incremental cost-effectiveness ratio for early diagnosis strategy was estimated at US$ 156.46 per DALY averted, while that of prevention of transmission with insecticide-impregnated curtains and clothing was US$ 13,155.52 per DALY averted. Both strategies were more sensitive to the natural incidence of leishmaniasis, to the effectiveness of mucocutaneous leishmaniasis treatment and to the cost of each strategy. Prevention of vectorial transmission and early diagnosis have proved to be cost-effective measures.

Pediatric Old World cutaneous leishmaniasis treated with oral fluconazole: A case series.

PubMed

Michelerio, Andrea; Barruscotti, Stefania; Bossi, Grazia; Brazzelli, Valeria

2018-05-01

Cutaneous leishmaniasis has an incidence of 0.7-1.2 million cases per year and represents a growing concern in the outpatient dermatologic practice in Europe because of imported cases due to increased travel to risk areas and to immigration phenomena. When dealing with children, the treatment can be challenging because of side effects and pain of classic antimonial therapy leading to poor rates of course completion and requirement of sedation for several children. We retrospectively studied three cases of cutaneous leishmaniasis in pediatric patients, between the ages of 3 and 6 years of age, treated with oral fluconazole. We examined the efficacy, the tolerability, the safety profile and the cosmetic result of fluconazole at a dose of 6 mg/kg/daily for 6 weeks. The patients had a complete resolution of their lesions with minimal scarring. No adverse effect was reported. The leishmaniasis species identified were L. major or L. tropica. Considering sides effects and the parents' and the clinician's concern for systemic treatment in the pediatric population, fluconazole represents a valid, safe and easily manageable option for Old World cutaneous leishmaniasis in pediatric outpatients caused by L. major or L. tropica. © 2018 Wiley Periodicals, Inc.

Leishmania proteophosphoglycans regurgitated from infected sand flies accelerate dermal wound repair and exacerbate leishmaniasis via insulin-like growth factor 1-dependent signalling

PubMed Central

Giraud, Emilie; Martin, Oihane; Dillon, Rod J.; Műller, Ingrid

2018-01-01

Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts. These transcripts were transiently up-regulated during the first 6 hours post-wound and enriched for pathways involved in inflammation, cell proliferation, fibrosis, epithelial cell differentiation and wound remodelling. We found that PSG significantly accelerated wound healing in vitro and in mice; which was associated with an early up-regulation of transcripts involved in inflammation (IL-1β, IL-6, IL-10, TNFα) and inflammatory cell recruitment (CCL2, CCL3, CCL4, CXCL2), followed 6 days later by enhanced expression of transcripts associated with epithelial cell proliferation, fibroplasia and fibrosis (FGFR2, EGF, EGFR, IGF1). Dermal expression of IGF1 was enhanced following an infected sand fly bite and was acutely responsive to the deposition of PSG but not the inoculation of parasites or sand fly saliva. Antibody blockade of IGF1 ablated the gel’s ability to promote wound closure in mouse ears and significantly reduced the virulence of Leishmania mexicana infection delivered by an individual sand fly bite. Dermal macrophages recruited to air-pouches on the backs of mice revealed that IGF1 was pivotal to the PSG’s ability to promote macrophage alternative activation and Leishmania infection. Our data demonstrate that through the regurgitation of PSG Leishmania exploit the wound healing response of the host to the vector bite by promoting

IL-1β Production by Intermediate Monocytes Is Associated with Immunopathology in Cutaneous Leishmaniasis.

PubMed

Santos, Daniela; Campos, Taís M; Saldanha, Maíra; Oliveira, Sergio C; Nascimento, Mauricio; Zamboni, Dario S; Machado, Paulo R; Arruda, Sérgio; Scott, Phillip; Carvalho, Edgar M; Carvalho, Lucas P

2018-05-01

Cutaneous leishmaniasis due to Leishmania braziliensis infection is an inflammatory disease in which skin ulcer development is associated with mononuclear cell infiltrate and high levels of inflammatory cytokine production. Recently, NLRP3 inflammasome activation and IL-1β production have been associated with increased pathology in murine cutaneous leishmaniasis. We hypothesized that cutaneous leishmaniasis patients have increased expression of NLRP3, leading to high levels of IL-1β production. In this article we show high production of IL-1β in biopsy samples and Leishmania antigen-stimulated peripheral blood mononuclear cells from patients infected with L. braziliensis and reduced IL-1β levels after cure. IL-1β production positively correlated with the area of necrosis in lesions and duration of the lesions. The main source of IL-1β was intermediate monocytes (CD14 ++ CD16 + ). Furthermore, our murine experiments show that IL-1β production in response to L. braziliensis was dependent on NLRP3, caspase-1, and caspase-recruiting domain (ASC). Additionally, we observed an increased expression of the NLRP3 gene in macrophages and the NLRP3 protein in intermediate monocytes from cutaneous leishmaniasis patients. These results identify an important role for human intermediate monocytes in the production of IL-1β, which contributes to the immunopathology observed in cutaneous leishmaniasis patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Dermal bioavailability of benzo[a]pyrene on lampblack: implications for risk assessment.

PubMed

Stroo, Hans F; Roy, Timothy A; Liban, Cris B; Kreitinger, Joseph P

2005-06-01

Lampblack is the principal source of contamination in soils at manufactured gas plant (MGP) sites where oil was used as the feedstock. Risks and cleanup criteria at these sites are determined primarily by the total carcinogenic polynuclear aromatic hydrocarbon (PAH) content, particularly the concentration of benzo[a]pyrene (BaP). Dermal contact with soils at oil-gas MGP sites is a significant component of the overall risks. Seven samples were collected from oil-gas MGP sites and the steady-state dermal fluxes were measured over 96 h in vitro. The standard dermal bioassay technique (in which 3H-BaP is added to the soil matrix) was modified to allow direct measurement of the dermal absorption of the native BaP in the samples. The experimentally derived dermal absorption factors for BaP were 14 to 107 times lower than the default assumption of 15% over 24 h (55-fold lower on average). The dermal fluxes were correlated positively to the total BaP and total carbon concentrations. The measured dermal absorption factors were compared to the default risk-assessment calculations for all seven samples. The calculated excess cancer risk was reduced as a result of using the measured absorption factors by 97% on average (with reductions ranging from 93 to 99%). This work indicates the risks at oil-gas MGP sites currently are overestimated by one to two orders of magnitude, and provides a protocol for the testing and data analysis needed to generate site-specific cleanup levels.

Leishmania donovani tyrosyl-tRNA synthetase structure in complex with a tyrosyl adenylate analog and comparisons with human and protozoan counterparts.

PubMed

Barros-Álvarez, Ximena; Kerchner, Keshia M; Koh, Cho Yeow; Turley, Stewart; Pardon, Els; Steyaert, Jan; Ranade, Ranae M; Gillespie, J Robert; Zhang, Zhongsheng; Verlinde, Christophe L M J; Fan, Erkang; Buckner, Frederick S; Hol, Wim G J

2017-07-01

The crystal structure of Leishmania donovani tyrosyl-tRNA synthetase (LdTyrRS) in complex with a nanobody and the tyrosyl adenylate analog TyrSA was determined at 2.75 Å resolution. Nanobodies are the variable domains of camelid heavy chain-only antibodies. The nanobody makes numerous crystal contacts and in addition reduces the flexibility of a loop of LdTyrRS. TyrSA is engaged in many interactions with active site residues occupying the tyrosine and adenine binding pockets. The LdTyrRS polypeptide chain consists of two pseudo-monomers, each consisting of two domains. Comparing the two independent chains in the asymmetric unit reveals that the two pseudo-monomers of LdTyrRS can bend with respect to each other essentially as rigid bodies. This flexibility might be useful in the positioning of tRNA for catalysis since both pseudo-monomers in the LdTyrRS chain are needed for charging tRNA Tyr . An "extra pocket" (EP) appears to be present near the adenine binding region of LdTyrRS. Since this pocket is absent in the two human homologous enzymes, the EP provides interesting opportunities for obtaining selective drugs for treating infections caused by L. donovani, a unicellular parasite causing visceral leishmaniasis, or kala azar, which claims 20,000 to 30,000 deaths per year. Sequence and structural comparisons indicate that the EP is a characteristic which also occurs in the active site of several other important pathogenic protozoa. Therefore, the structure of LdTyrRS could inspire the design of compounds useful for treating several different parasitic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis.

PubMed

Nilforoushzadeh, Mohammad Ali; Jaffary, Fariba; Moradi, Shahram; Derakhshan, Roya; Haftbaradaran, Elaheh

2007-04-27

Leishmaniasis is an endemic disease in Iran. Although many treatments have been suggested for this disease, there hasn't been an effective and safe treatment yet. Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis, we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar. In a prospective clinical trial, 100 patients with confirmed cutaneous leishmaniasis were selected and randomized into 2 groups. Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks. Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks, too. The patients were followed for 4 months. The collected data were analyzed statistically using statistical tests including Chi-square, Mann Whitney and Kaplan-Mayer tests. In this study, 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime. Ten patients left out the study. In the glucantime alone treated group, 32 patients (71.1%) had complete cure whereas in the group treated with both glucantime & topical honey, 23 patients (51.1%) achieved complete cure. This difference was significant statistically (p = 0.04). Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed. We suggest that in another study, the efficacy of honey with standardized level of antibacterial activity is evaluated against cutaneous leishmaniasis.

Endemic Transmission of Visceral Leishmaniasis in Bhutan

PubMed Central

Yangzom, Thinley; Cruz, Israel; Bern, Caryn; Argaw, Daniel; den Boer, Margriet; Vélez, Iván Dario; Bhattacharya, Sujit K.; Molina, Ricardo; Alvar, Jorge

2012-01-01

Visceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated. PMID:23091191

Natural Products: Insights into Leishmaniasis Inflammatory Response

PubMed Central

Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

2015-01-01

Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

Dermal Filler Injection: A Novel Approach for Limiting Infarct Expansion

PubMed Central

Ryan, Liam P.; Matsuzaki, Kanji; Noma, Mio; Jackson, Benjamin M.; Eperjesi, Thomas J.; Plappert, Theodore J.; St. John-Sutton, Martin G.; Gorman, Joseph H.; Gorman, Robert C.

2011-01-01

Background Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. Methods Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite–based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. Results All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 ± 3.6 mL versus 44.5 ± 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 ± 0.016 versus 0.373 ± 0.017; p < 0.05) at 4 weeks after infarction. Conclusions Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling. PMID:19101288

Presence of American cutaneous Leishmaniasis vectors surrounding the city of Medellín, Colombia.

PubMed

Agudelo, Luz A; Uribe, Jaime; Sierra, Diana; Ruiz, Fredy; Velez, Iván D

2002-07-01

The presence of Lutzomyia (Helcocyrtomyia) hartmanni, as a vector of Leishmania colombiensis and L. columbiana (Verrucarum group), recently incriminated in the transmission of leishmaniasis, and L. pia (Verrucarum group) are reported for the first time in a periurban area of Medellín city. There is thus a risk of leishmaniasis transmission in this town.

South American collaboration in scientific publications on leishmaniasis: bibliometric analysis in SCOPUS (2000-2011).

PubMed

Huamaní, Charles; Romaní, Franco; González-Alcaide, Gregorio; Mejia, Miluska O; Ramos, José Manuel; Espinoza, Manuel; Cabezas, César

2014-01-01

Evaluate the production and the research collaborative network on Leishmaniasis in South America. A bibliometric research was carried out using SCOPUS database. The analysis unit was original research articles published from 2000 to 2011, that dealt with leishmaniasis and that included at least one South American author. The following items were obtained for each article: journal name, language, year of publication, number of authors, institutions, countries, and others variables. 3,174 articles were published, 2,272 of them were original articles. 1,160 different institutional signatures, 58 different countries and 398 scientific journals were identified. Brazil was the country with more articles (60.7%) and Oswaldo Cruz Foundation (FIOCRUZ) had 18% of Brazilian production, which is the South American nucleus of the major scientific network in Leishmaniasis. South American scientific production on Leishmaniasis published in journals indexed in SCOPUS is focused on Brazilian research activity. It is necessary to strengthen the collaboration networks. The first step is to identify the institutions with higher production, in order to perform collaborative research according to the priorities of each country.

SOUTH AMERICAN COLLABORATION IN SCIENTIFIC PUBLICATIONS ON LEISHMANIASIS: BIBLIOMETRIC ANALYSIS IN SCOPUS (2000-2011)

PubMed Central

Huamaní, Charles; Romaní, Franco; González-Alcaide, Gregorio; Mejia, Miluska O.; Ramos, José Manuel; Espinoza, Manuel; Cabezas, César

2014-01-01

Objectives: Evaluate the production and the research collaborative network on Leishmaniasis in South America. Methods: A bibliometric research was carried out using SCOPUS database. The analysis unit was original research articles published from 2000 to 2011, that dealt with leishmaniasis and that included at least one South American author. The following items were obtained for each article: journal name, language, year of publication, number of authors, institutions, countries, and others variables. Results: 3,174 articles were published, 2,272 of them were original articles. 1,160 different institutional signatures, 58 different countries and 398 scientific journals were identified. Brazil was the country with more articles (60.7%) and Oswaldo Cruz Foundation (FIOCRUZ) had 18% of Brazilian production, which is the South American nucleus of the major scientific network in Leishmaniasis. Conclusions: South American scientific production on Leishmaniasis published in journals indexed in SCOPUS is focused on Brazilian research activity. It is necessary to strengthen the collaboration networks. The first step is to identify the institutions with higher production, in order to perform collaborative research according to the priorities of each country. PMID:25229217

Insecticidal effect of plant extracts on Phlebotomus argentipes (Diptera: Psychodidae) in Bihar, India

PubMed Central

Dinesh, Diwakar Singh; Kumari, Seema; Pandit, Vibhishan; Kumar, Jainendra; Kumari, Nisha; Kumar, Prahlad; Hassan, Faizan; Kumar, Vijay; Das, Pradeep

2015-01-01

Background & objectives: Phlebotomus argentipes (Diptera: Psychodidae), the established vector for kala-azar is presently being controlled by indoor residual spray of DDT in kala-azar endemic areas in India. Search for non-hazardous and non-toxic biodegradable active molecules from botanicals may provide cost-effective and eco-friendly alternatives to synthetic insecticides. The present study was aimed at evaluating various plant extracts from endemic and non-endemic areas of Bihar for their insecticidal activity against sandfly to identify the most effective plant extract. Methods: Bio-assay test was conducted with larvae and adult of P. argentipes with different plant extracts collected in distilled water, hexane, ethyl acetate, acetone and methanol. Thin layer chromatography (TLC), column chromatography and high performance liquid chromatography (HPLC) were conducted for detection of active molecules. Results: Adults and larvae of sandflies exposed to the aqueous extract of Nicotiana tabacum resulted in 100 per cent mortality. The hexane extract of Clerodendrum infortunatum was found to kill 77 per cent adults but was ineffective against larvae. Bio-assay test of the ninth fraction (hexane extract-methanol phase) separated by column chromatography was found to be 63 per cent effective. The purple spot on the TLC of this fraction indicated the presence of a diterpenoid. HPLC of this fraction detected nine compounds with two peaks covering 20.44 and 56.52 per cent areas with retention time of 2.439 and 5.182 min, respectively supporting the TLC results. Interpretation & conclusions: The column separated 9th fraction of C. infortunatum extract was found to be effective in killing 63 per cent of adult P. argentipes. Compounds of this fraction need to be evaluated further for identification and characterization of the active molecule by conducting individual bio-assay tests followed by further fractionation and HPLC. Once the structure of the active molecule is

Leishmaniasis in Turkey: Visceral and cutaneous leishmaniasis caused by Leishmania donovani in Turkey.

PubMed

Özbilgin, Ahmet; Harman, Mehmet; Karakuş, Mehmet; Bart, Aldert; Töz, Seray; Kurt, Özgür; Çavuş, İbrahim; Polat, Erdal; Gündüz, Cumhur; Van Gool, Tom; Özbel, Yusuf

2017-09-01

In Turkey, the main causative agents are Leishmania tropica (L. tropica) and Leishmania infantum (L. infantum) for cutaneous leishmaniasis (CL) and L. infantum for visceral leishmaniasis (VL). In this study, we investigated leishmaniasis cases caused by L. donovani and established animal models for understanding its tropism in in vivo conditions. Clinical samples (lesion aspirations and bone marrow) obtained from CL/VL patients were investigated using parasitological (smear/NNN) and DNA-based techniques. For species identification, a real time ITS1-PCR was performed using isolates and results were confirmed by hsp70 PCR-N/sequencing and cpb gene PCR/sequencing in order to reveal Leishmania donovani and Leishmania infantum discrimination. Clinical materials from CL and VL patients were also inoculated into two experimental groups (Group CL and Group VL) of Balb/C mice intraperitoneally for creating clinical picture of Turkish L. donovani strains. After 45days, the samples from visible sores of the skin were taken, and spleens and livers were removed. Measurements of the internal organs were done and touch preparations were prepared for checking the presence of amastigotes. The strains were isolated from all patients and amastigotes were seen in all smears of the patients, and then isolates were immediately stored in liquid nitrogen. In real time ITS1-PCR, the melting temperatures of all samples were out of range of L. infantum, L. tropica and L. major. Sequencing of hsp70 PCR-N showed that all isolates highly identical to previously submitted L. donovani sequences in GenBank, and cpb gene sequencing showed five isolates had longer cpbF allele, whereas one isolate contained a mixed sequence of both cpbF and cpbE. All mice in both experimental groups became infected. Compared to controls, the length and width of both liver and spleen were significantly elevated (p<0.001) in both groups of mice. However, the weight of the liver increased significantly in all mice

Wnt/β-catenin signaling in dermal condensates is required for hair follicle formation

PubMed Central

Tsai, Su-Yi; Sennett, Rachel; Rezza, Amélie; Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Najam, Sara; Rendl, Michael

2014-01-01

Broad dermal Wnt signaling is required for patterned induction of hair follicle placodes and subsequent Wnt signaling in placode stem cells is essential for induction of dermal condensates, cell clusters of precursors for the hair follicle dermal papilla (DP). Progression of hair follicle formation then requires coordinated signal exchange between dermal condensates and placode stem cells. However, it remains unknown whether continued Wnt signaling in DP precursor cells plays a role in this process, largely due to the long-standing inability to specifically target dermal condensates for gene ablation. Here we use the Tbx18Cre knockin mouse line to ablate the Wnt-responsive transcription factor β-catenin specifically in these cells at E14.5 during the first wave of guard hair follicle formation. In the absence of β-catenin, canonical Wnt signaling is effectively abolished in these cells. Sox2+ dermal condensates initiate normally, however by E16.5 guard hair follicle numbers are strongly reduced and by E18.5 most whiskers and guard hair follicles are absent, suggesting that active Wnt signaling in dermal condensates is important for hair follicle formation to proceed after induction. To explore the molecular mechanisms by which Wnt signaling in dermal condensates regulates hair follicle formation, we analyze genome-wide the gene expression changes in embryonic β-catenin null DP precursor cells. We find altered expression of several signaling pathway genes, including Fgfs and Activin, both previously implicated in hair follicle formation. In summary, these data reveal a functional role of Wnt signaling in DP precursors for embryonic hair follicle formation and identify Fgf and Activin signaling as potential effectors of Wnt signaling-regulated events. PMID:24309208

American cutaneous leishmaniasis: use of a skin test as a predictor of relapse after treatment.

PubMed Central

Passos, V. M.; Barreto, S. M.; Romanha, A. J.; Krettli, A. U.; Volpini, A. C.; Lima e Costa, M. F.

2000-01-01

While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test has been described until now to predict such relapses. A cohort of 318 American cutaneous leishmaniasis patients was followed up for two years after treatment with meglumine antimoniate, during which time 32 relapses occurred, 30 in the first year and two in the second (accumulated risk: 10.5%). No association was found between these relapses and the parasite-specific antibody response before and after treatment, or between the relapses and stratification by sociodemographic and clinical characteristics. However when Leishmania was used as antigen, patients with a negative skin test at the time of diagnosis presented a 3.4-fold higher risk (hazard risk = 3.4; 95% confidence interval, 1.7-7.0) of American cutaneous leishmaniasis relapse, compared with patients with a positive response. This result shows that the skin test can be a predictor of American cutaneous leishmaniasis relapse after treatment. PMID:10994280

Estimating dermal transfer from PCB-contaminated porous surfaces.

PubMed

Slayton, T M; Valberg, P A; Wait, A D

1998-06-01

Health risks posed by dermal contact with PCB-contaminated porous surfaces have not been directly demonstrated and are difficult to estimate indirectly. Surface contamination by organic compounds is commonly assessed by collecting wipe samples with hexane as the solvent. However, for porous surfaces, hexane wipe characterization is of limited direct use when estimating potential human exposure. Particularly for porous surfaces, the relationship between the amount of organic material collected by hexane and the amount actually picked up by, for example, a person's hand touch is unknown. To better mimic PCB pickup by casual hand contact with contaminated concrete surfaces, we used alternate solvents and wipe application methods that more closely mimic casual dermal contact. Our sampling results were compared to PCB pickup using hexane-wetted wipes and the standard rubbing protocol. Dry and oil-wetted samples, applied without rubbing, picked up less than 1% of the PCBs picked up by the standard hexane procedure; with rubbing, they picked up about 2%. Without rubbing, saline-wetted wipes picked up 2.5%; with rubbing, they picked up about 12%. While the nature of dermal contact with a contaminated surface cannot be perfectly reproduced with a wipe sample, our results with alternate wiping solvents and rubbing methods more closely mimic hand contact than the standard hexane wipe protocol. The relative pickup estimates presented in this paper can be used in conjunction with site-specific PCB hexane wipe results to estimate dermal pickup rates at sites with PCB-contaminated concrete.

NHEXAS PHASE I ARIZONA STUDY--PESTICIDES IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Pesticides in Dermal Wipes data set contains analytical results for measurements of up to 3 pesticides in 177 dermal wipe samples over 177 households. Each sample was collected from the primary respondent within each household during Stage III of the NHEXAS study. The Derma...

NHEXAS PHASE I MARYLAND STUDY--PESTICIDES IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Pesticides in Dermal Wipe Samples data set contains analytical results for measurements of up to 8 pesticides in 40 dermal wipe samples over 40 households. Each sample was collected from the primary respondent within each household. The sampling period occurred on the last ...

Hydrocortisone effect on hyaluronate synthesis in a self-assembled human dermal equivalent.

PubMed

Deshpande, Madhura; Papp, Suzanne; Schaffer, Lana; Pouyani, Tara

2016-10-01

Human dermal matrix is a 'self-assembled' dermal equivalent containing large amounts of the glycosaminoglycan hyaluronic acid (hyaluronate, hyaluronan, HA). We sought to investigate the actions of the hormone hydrocortisone on hyaluronate synthesis in the human dermal matrix. To this end, human dermal fibroblasts were cultured under serum-free conditions, and in the absence of a three-dimensional matrix, in the presence of varying amounts of hydrocortisone. The resultant human dermal matrices were characterized. We report that low concentrations of hydrocortisone enhance hyaluronate synthesis in the human dermal equivalent and higher concentrations cause inhibition of hyaluronate synthesis. Other glycosaminoglycan (chondroitin sulphate) synthesis is not affected by changing hydrocortisone concentrations up to 500× (200 µg/ml) of the base value. In order to gain preliminary insight into the molecular mechanism of hyaluronate inhibition, a differential gene array analysis was conducted of human dermal matrix grown in the presence of 200 µg/ml hydrocortisone and in a physiological concentration (0.4 µg/ml, normal conditions). The results of these experiments demonstrate the differential expression of 43 genes in the 500× (200 µg/ml) hydrocortisone construct as compared to the construct grown under normal conditions (0.4 µg/ml hydrocortisone). These preliminary experiments suggest that hydrocortisone at higher concentrations may exert its inhibitory effect on hyaluronate synthesis early in the glycolytic pathway, leading to HA biosynthesis by downregulation of phosphoglucomutase and glucose phosphate isomerase, possibly leading to depletion of the cellular pool of UDP-sugar precursors necessary for HA synthesis. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Detection of Leishmania in Unaffected Mucosal Tissues of Patients with Cutaneous Leishmaniasis Caused by Leishmania (Viannia) Species

PubMed Central

Figueroa, Roger Adrian; Lozano, Leyder Elena; Romero, Ibeth Cristina; Cardona, Maria Teresa; Prager, Martin; Pacheco, Robinson; Diaz, Yira Rosalba; Tellez, Jair Alexander; Saravia, Nancy Gore

2016-01-01

Background Leishmania (Viannia) species are the principal cause of mucosal leishmaniasis. The natural history and pathogenesis of mucosal disease are enigmatic. Parasitological evaluation of mucosal tissues has been constrained by the invasiveness of conventional sampling methods. Methods We evaluated the presence ofLeishmania in the mucosa of 26 patients with cutaneous leishmaniasis and 2 patients with mucocutaneous leishmaniasis. Swab samples of the nasal mucosa, tonsils, and conjunctiva were analyzed using polymerase chain reaction with LV-B1 primers and Southern blot hybridization. Results Two patients with mucocutaneous leishmaniasis and 21 (81%) of 26 patients with cutaneous leishmaniasis had Leishmania kinetoplast minicircle DNA (kDNA) in mucosal tissues. kDNA was amplified from swab samples of nasal mucosa from 14 (58%) of 24 patients, tonsils from 13 (46%) of 28 patients, and conjunctiva from 6 (25%) of 24 patients. kDNA was detected in the mucosa of patients with cutaneous disease caused by Leishmania panamensis, Leishmania guyanensis, and Leishmania braziliensis. Conclusion The asymptomatic presence of parasites in mucosal tissues may be common in patients with Leishmania (Viannia) infection. PMID:19569974

Crosslinked hyaluronic acid dermal fillers: a comparison of rheological properties.

PubMed

Falcone, Samuel J; Berg, Richard A

2008-10-01

Temporary dermal fillers composed of crosslinked hyaluronic acid (XLHA) are space filling gels that are readily available in the United States and Europe. Several families of dermal fillers based on XLHA are now available and here we compare the physical and rheological properties of these fillers to the clinical effectiveness. The XLHA fillers are prepared with different crosslinkers, using HA isolated from different sources, have different particle sizes, and differ substantially in rheological properties. For these fillers, the magnitude of the complex viscosity, |eta*|, varies by a factor of 20, the magnitude of the complex rigidity modulus, |G*|, and the magnitude of the complex compliance, |J*| vary by a factor of 10, the percent elasticity varies from 58% to 89.9%, and the tan delta varies from 0.11 to 0.70. The available clinical data cannot be correlated with either the oscillatory dynamic or steady flow rotational rheological properties of the various fillers. However, the clinical data appear to correlate strongly with the total concentration of XLHA in the products and to a lesser extent with percent elasticity. Hence, our data suggest the following correlation: dermal filler persistence = [polymer] x [% elasticity] and the clinical persistence of a dermal filler composed of XLHA is dominated by the mass and elasticity of the material implanted. This work predicts that the development of future XLHA dermal filler formulations should focus on increasing the polymer concentration and elasticity to improve the clinical persistence.

Safety Evaluation of Silk Protein Film (A Novel Wound Healing Agent) in Terms of Acute Dermal Toxicity, Acute Dermal Irritation and Skin Sensitization

PubMed Central

Padol, Amol R.; Jayakumar, K.; Shridhar, N. B.; Narayana Swamy, H. D.; Narayana Swamy, M.; Mohan, K.

2011-01-01

Acute dermal toxicity study was conducted in rats. The parameters studied were body weight, serum biochemistry and gross pathology. The animals were also observed for clinical signs and mortality after the application of test film. The dermal irritation potential of silk protein film was examined using Draize test. In the initial test, three test patches were applied sequentially for 3 min, 1 and 4 hours, respectively, and skin reaction was graded. The irritant or negative response was confirmed using two additional animals, each with one patch, for an exposure period of 4 hours. The responses were scored at 1, 24, 48 and 72 hours after the patch removal. Skin sensitization study was conducted according to Buehler test in guinea pigs, in which on day 0, 7 and 14, the animals were exposed to test material for 6 hours (Induction phase) and on day 28, the animals were exposed for a period of 24 hours (Challenge phase). The skin was observed and recorded at 24 and 48 hours after the patch removal. In acute dermal toxicity study, the rats dermally treated with silk film did not show any abnormal clinical signs and the body weight, biochemical parameters and gross pathological observations were not significantly different from the control group. In acute dermal irritation study, the treated rabbits showed no signs of erythema, edema and eschar, and the scoring was given as “0” for all time points of observations according to Draize scoring system. In skin sensitization study, there were no skin reactions 24 and 48 hours after the removal of challenge patch, which was scored “0” based on Magnusson/Kligman grading scale. PMID:21430915

Treatment of Linear Scleroderma (en Coup de Sabre) With Dermal Fat Grafting.

PubMed

Barin, Ensar Zafer; Cinal, Hakan; Cakmak, Mehmet Akif; Tan, Onder

2016-05-01

Linear scleroderma, also known as "en coup de sabre," is a subtype of localized scleroderma that warrants aesthetic correction because it appears on the forehead region in children. To report dermal fat grafting as a novel and effective surgical treatment option in linear scleroderma. Under local anesthesia, a dermal fat graft was successfully placed into a subcutaneous pocket that was prepared underneath the depressed scar. The donor site was closed primarily. No early or late complications developed postoperatively. After 1-year follow-up, the dermal fat graft was viable, the depressed scar was adequately augmented, and a good aesthetic result and patient satisfaction were obtained. We believe that dermal fat grafting is a cost-effective option and provides a long-lasting aesthetic outcome in the management of linear scleroderma. © The Author(s) 2015.

NHEXAS PHASE I ARIZONA STUDY--METALS IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Metals in Dermal Wipes data set contains analytical results for measurements of up to 11 metals in 179 dermal wipe samples over 179 households. Each sample was collected from the primary respondent within each household during Stage III of the NHEXAS study. The sampling per...

NHEXAS PHASE I MARYLAND STUDY--METALS IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Metals in Dermal Wipe Samples data set contains analytical results for measurements of up to 4 metals in 343 dermal wipe samples over 80 households. Each sample was collected from the primary respondent within each household. The sampling period occurred on the first day of...

Induction of IL-10 and TGFβ from CD4+CD25+FoxP3+ T Cells Correlates with Parasite Load in Indian Kala-azar Patients Infected with Leishmania donovani

PubMed Central

Bhattacharya, Pradyot; Ghosh, Smriti; Ejazi, Sarfaraz Ahmad; Rahaman, Mehebubar; Pandey, Krishna; Ravi Das, Vidya Nand; Das, Pradeep; Goswami, Rama Prosad; Saha, Bibhuti; Ali, Nahid

2016-01-01

Background Visceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown. Methodology/Principal Findings We examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGFβ and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGFβ and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGFβ to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGFβ respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4+CD25+ (r = 0.55), CD4+CD25hi (r = 0.61) as well as percentages of CD4+CD25+FoxP3+ T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4+CD25+ and CD4+CD25+FoxP3+ Treg cells to secrete significantly (p<0.05) higher amounts of not only IL-10 but also TGFβ in comparison to corresponding CD25- T cells. Conclusions/Significance Our findings shed some light on source(s) of TGFβ and suggest an association between these disease promoting cytokines and Treg cells with parasite load during active disease. Moreover, the direct evidence of CD4+CD25+FoxP3+ Treg cells as a source of IL-10 and TGFβ during active VL could open new avenues for immunotherapy towards cure of this potentially fatal disease. PMID:26829554

Systemic Meglumine Antimoniate in Cutaneous Leishmaniasis of Children: Clinical and Laboratory Complications.

PubMed

Layegh, Pouran; Khademi, Zeinab; Afzal Aghaee, Monavar; Moghiman, Toktam

2015-12-01

Children account for 7%-20% of cutaneous leishmaniasis cases in Iran, but there are few safety data to guide pediatric antiparasitic therapy. We evaluated the clinical and laboratory tolerance of the systemic pentavalent antimonial compound meglumine antimoniate, in 70 Iranian children with cutaneous leishmaniasis. Adverse effects were similar to those seen in adults. © The Author 2014. 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.

Porcine dermal lesions produced by 1540-nm laser radiation pulses

NASA Astrophysics Data System (ADS)

Roach, William P.; Johnson, Thomas E.

2001-07-01

Completion of recent studies within our group indicates a breed-based difference in dermal response to 1540 nm 0.8 millisecond laser pulses. Laser exposure to Yucatan Mini- Pigs (highly pigmented skin) and Yorkshire pigs (lightly pigmented skin) demonstrate statistical differences between the ED50's of the two breeds. Laser delivery is accomplished using an Er:Glass system producing 1540 nm of light at millisecond exposure times and in the range of 5 to 95 J/cm2. Dermal lesion development was evaluated for acute, 1 hour, and 24-hour post exposure presentation. Our data contradicts the theory that water absorption is the sole mechanism of dermal tissue damage observed from 1540 nm laser exposures, as skin chromophores appear to play a role in lesion development.

Immunologic memory in cutaneous leishmaniasis.

PubMed

Scott, Phillip

2005-12-01

Leishmania major infections induce solid immunity to reinfection. Experimental studies in mice indicate that the CD4+ T cells responsible for this immunity include two populations: parasite-dependent T effector cells and parasite-independent central memory T (Tcm) cells. While there currently is no vaccine for leishmaniasis, the existence of a long-lived population of Tcm cells that does not require the continued presence of live parasites suggests that a vaccine that expands these cells might be efficacious.

Reprint of "Spatial modeling of Cutaneous Leishmaniasis in Iran from 1983 to 2013".

PubMed

Holakouie-Naieni, Kourosh; Mostafavi, Ehsan; Boloorani, Ali Darvishi; Mohebali, Mehdi; Pakzad, Reza

2017-01-01

Cutaneous Leshmaniasis (CL), a parasitic skin infection caused by Leishmania species, is endemic in some regions of Iran. In this study, the effect of location on the incidence and distribution of CL in Iran was studied. We collected datas including the number of Cutaneous Leishmaniasis cases and populations at-risk of disease in Iran's different provinces reported by the Iranian ministry of health and the National Bureau of Statistics, respectively. Spatial modeling was performed using Arc GIS software. Descriptive maps, hotspot analysis, and high/low clustering analysis were used to demonstrate distribution of the cutaneous leishmaniasis, to determine regions at risk of disease's incidence, and to reach the most appropriate method for clustering of disease. The total number of cases of cutaneous leishmaniasis reported through the study period was 589,913. The annual incidence of CL was estimated to be 30.9 per 100,000 in Iranian population. We also demonstrated that Cutaneous leishmaniasis most prominently occurs in regions with dry and desert climates as well as in central parts of Iran. It affected the southwest of Iran between 1983 and 1997, and subsequently developed towards the center and the eastern between 1998 and 2013. Disease hotspots were focused in the provinces of Yazd, Khozestan and Kohgiloyeh-Boyer-Ahmad (p<0.05). No pattern of spatial clustering was observed. Cutaneous leishmaniasis is a major health problem which could be a serious threat for inhabitants who live in high-risk provinces of Iran; much more resources need to be allocated in these areas, to warrant the prevention as well as effectively management of this disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Dermal insecticide residues from birds inhabiting an orchard

USGS Publications Warehouse

Vyas, N.B.; Spann, J.W.; Hulse, C.S.; Gentry, S.; Borges, S.L.

2007-01-01

The US Environmental Protection Agency conducts risk assessments of insecticide applications to wild birds using a model that is limited to the dietary route of exposure. However, free-flying birds are also exposed to insecticides via the inhalation and dermal routes. We measured azinphos-methyl residues on the skin plus feathers and the feet of brown-headed cowbirds (Molothrus ater) in order to quantify dermal exposure to songbirds that entered and inhabited an apple (Malus x domestica) orchard following an insecticide application. Exposure to azinphos-methyl was measured by sampling birds from an aviary that was built around an apple tree. Birds sampled at 36 h and 7-day post-application were placed in the aviary within 1 h after the application whereas birds exposed for 3 days were released into the aviary 4-day post-application. Residues on vegetation and soil were also measured. Azinphos-methyl residues were detected from the skin plus feathers and the feet from all exposure periods. Our results underscore the importance of incorporating dermal exposure into avian pesticide risk assessments.

[Contribution of Achille Breda to the understanding of American mucocutaneous leishmaniasis].

PubMed

Pampiglione, S

1979-12-01

The majority of Parasitology textbooks and reference lists on Leishmaniasis do not quote the name of Achille Breda. This Italian dermatologist (1850-1934) however must be considered the first who clinically identified and carefully described the American muco-cutaneous Leishmaniasis, a disease for which some scientists proposed the name of "Breda's disease" (Jeanselme, 1910). Breda studied at the University of Padua, attending as postgraduate the famous Hebra's school of Wien. He became professor of "Syphilodermatopathology" in 1878 and during 47 years taught in Padua. He never was in South or Central America, but studied the illness in Padua itself, in 18 Italian emigrants who had come back ill from the São Paulo region, Brazil. At that time the agents of yaws, cutaneous and muco-cutaneous leishmaniasis and syphilis had not yet discovered and there was great confusion about the granulomatous lesions of the skin and mucosae seen in tropical areas. In this situation he exactly differentiated the condition from syphilis, yaws and lupus and could affirm, with the security of a highly skilled observer that it was an autonomous, different illness, peculiar to some rural areas of Brazil, non contagious directly, appearing in determinate season of the year but lasting for years and often conducting the subjects to the cachexia. His description of the symptomatology, post-morten anatomy, histology and his epidemiological observations, even nowadays represent one of the most accurate and complete pictures of this illesss. Breda's life and works are here reviewed and some passages of his papers on mucocutaneous leishmaniasis reported.

Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells.

PubMed

Kiratipaiboon, Chayanin; Tengamnuay, Parkpoom; Chanvorachote, Pithi

2015-12-15

Although the growth of unwanted hair or hirsutism is a harmless condition, many people find it bothersome and embarrassing. Maintaining stem cell features of dermal papilla cells is a critical biological process that keeps the high rate of hair growth. Glycyrrhizic acid has been reported to impair hair growth in some studies; however, its underlying mechanism has not yet been investigated. This study aimed to explore the effect and underlying mechanism of glycyrrhizic acid on stemness of human dermal papilla cells. The stem cell molecular markers, epithelial to mesenchymal markers and Wnt/β-catenin-associated proteins of human dermal papilla cell line and primary human dermal papilla cells were analysed by western blot analysis and immunocytochemistry. The present study demonstrated that glycyrrhizic acid significantly depressed the stemness of dermal papilla cells in dose- and time-dependent manners. Clonogenicity and stem cell markers in the glycyrrhizic acid-treated cells were found to gradually decrease in the culture in a time-dependent manner. Our results demonstrated that glycyrrhizic acid exerted the stem cell suppressing effects through the interruption of ATP-dependent tyrosine kinase/glycogen synthase kinase3β-dependent mechanism which in turn down-regulated the β-catenin signalling pathway, coupled with decreased its down-stream epithelial-mesenchymal transition and self-renewal transcription factors, namely, Oct-4, Nanog, Sox2, ZEB1 and Snail. The effect of glycyrrhizic acid on the reduction of stem cell features was also observed in the primary dermal papilla cells directly obtained from human hair follicles. These results revealed a novel molecular mechanism of glycyrrhizic acid in regulation of dermal papilla cells and provided the evidence supporting the use of this compound in suppressing the growth of unwanted hair. Copyright © 2015 Elsevier GmbH. All rights reserved.

Optical coherence tomography for image-guided dermal filler injection and biomechanical evaluation

NASA Astrophysics Data System (ADS)

Singh, Manmohan; Wang, Shang; Yee, Richard W.; Han, Zhaolong; Aglyamov, Salavat R.; Larin, Kirill V.

2017-02-01

Dermal fillers are a very popular anti-ag ing treatment with estimated sales in the billions of dollars and millions of procedures performed. As the aging population continues to grow, these figures are only e xpected to increase. Dermal fillers have various compositions depending on their intended applicati on. Reactions to dermal fillers can be severe, such as ischemic events and filler migration to the eyes. Howe ver, these adverse reactions are rare. Nevertheless, the capability to perform imag e-guided filler injections would minimize th e risk of such reacti ons. In addition, the biomechanical properties of various fillers have been evalua ted, but there has been no investigation on the effects of filler on the biomechanical properties of skin. In this work, we utilize optical cohe rence tomography (OCT) for visualizing dermal filler injections with micrometer-scale sp atial resolution. In addition, we utilize noncontact optical coherence elastography (OCE) to quantify the changes in the biomechan ical properties of pig skin after the dermal filler injections. OCT was successfully able to visualize the dermal filler injecti on process, and OCE showed that the viscoelasticity of the pig skin was increased locally at the filler injection sites. OCT may be able to provide real-time image guidance in 3D, and when combined with functional OCT techniques such as optical microangiography, could be used to avoid blood vessels during the injection.

[Penile augmentation and elongation using autologous dermal-fat strip grafting].

PubMed

Yang, Zhe; Li, Yang-qun; Tang, Yong; Chen, Wen; Li, Qiang; Zhou, Chuan-de; Zhao, Mu-xin; Hu, Chun-mei

2012-05-01

To investigate the effect of autologous dermal-fat strip grafting in penile augmentation and elongation. From May 2004 to December 2010, 24 patients underwent penile enhancement with free dermal-fat strip grafting. Through suprapubic incision, the superior suspensory ligament and part deep suspensory ligament are cutted off to lengthen the penis. The resulted dead space is filled with the autologous dermal-fat strip (6.0-9.5 cm in length, 1.2-1.5 cm in width and 0.6-0.8 cm in depth) to enhance the penis. Primary healing was achieved in 23 cases. Incisional fat liquefaction happened in one case which healed after dressing change. The penile appearance was satisfactory both at rest or erection. The penile length and circumference increased by 2.5-4.8 cm (average, 3.2 cm) and 1.8-3.0 cm (average, 2.4 cm), respectively. 18 patients were followed up for 3 months to 5 years. All the patients were satisfactory on the cosmetic and functional results. No complication happened. It is safe and effective for penile augmention and elongation with autologous dermal-fat strip grafting and disconnection of penile suspensory ligament.

[American integumentary leishmaniasis associated with AIDS in Argentina].

PubMed

Romero, Héctor D; Taranto, Néstor J; Malchiodi, Emilio L

2004-01-01

Migration of HIV infected individuals from cities to small towns and rural areas spreads AIDS among non urban population, superimposing HIV with other endemic or epidemic infections as parasitoses. This situation is a big challenge to public health because in most cases the association between these infections worsens both prognoses. We present here the first case in Argentina of AIDS associated to a mucocutaneous form of American tegumentary leishmaniasis. The patient was from Orán, an area where in the middle eighties, an epidemic outbreak took place. By now more than 2000 cases have been parasitologically confirmed in our Institute and the causing species were identified as Leishmania (V.) braziliensis and L. (L.) amasonensis. Considering the existence of co-infection of HIV and Leishmania, it is recommended that in patients from endemic areas with records of cutaneous or mucocutaneous ulcers, even healed, leishmaniasis must be investigated, among other diseases.

Epidemiology of visceral leishmaniasis in Georgia.

PubMed

Babuadze, Giorgi; Alvar, Jorge; Argaw, Daniel; de Koning, Harry P; Iosava, Merab; Kekelidze, Merab; Tsertsvadze, Nikoloz; Tsereteli, David; Chakhunashvili, Giorgi; Mamatsashvili, Tamar; Beria, Nino; Kalandadze, Irine; Ejov, Mikhail; Imnadze, Paata

2014-03-01

This study investigated the transmission and prevalence of Leishmania parasite infection of humans in two foci of Visceral Leishmaniasis (VL) in Georgia, the well known focus in Tbilisi in the East, and in Kutaisi, a new focus in the West of the country. The seroprevalence of canine leishmaniasis was investigated in order to understand the zoonotic transmission. Blood samples of 1575 dogs (stray and pet) and 77 wild canids were tested for VL by Kalazar Detect rK39 rapid diagnostic tests. Three districts were investigated in Tbilisi and one in Kutaisi. The highest proportions of seropositive pet dogs were present in District #2 (28.1%, 82/292) and District #1 (26.9%, 24/89) in Tbilisi, compared to 17.3% (26/150) of pet dogs in Kutaisi. The percentage of seropositive stray dogs was also twice as high in Tbilisi (16.1%, n = 670) than in Kutaisi (8%, n = 50); only 2/58 wild animals screened were seropositive (2. 6%). A total of 873 Phlebotomine sand flies were collected, with 5 different species identified in Tbilisi and 3 species in Kutaisi; 2.3% of the females were positive for Leishmania parasites. The Leishmanin Skin Test (LST) was performed on 981 human subjects in VL foci in urban areas in Tbilisi and Kutaisi. A particularly high prevalence of LST positives was observed in Tbilisi District #1 (22.2%, 37.5% and 19.5% for ages 5-9, 15-24 and 25-59, respectively); lower prevalence was observed in Kutaisi (0%, 3.2% and 5.2%, respectively; P<0.05). This study shows that Tbilisi is an active focus for leishmaniasis and that the infection prevalence is very high in dogs and in humans. Although exposure is as yet not as high in Kutaisi, this is a new VL focus. The overall situation in the country is alarming and new control measures are urgently needed.

Posterior repair with perforated porcine dermal graft.

PubMed

Taylor, G Bernard; Moore, Robert D; Miklos, John R; Mattox, T Fleming

2008-01-01

To compare postoperative vaginal incision separation and healing in patients undergoing posterior repair with perforated porcine dermal grafts with those that received grafts without perforations. Secondarily, the tensile properties of the perforated and non-perforated grafts were measured and compared. This was a non-randomized retrospective cohort analysis of women with stage II or greater rectoceles who underwent posterior repair with perforated and non-perforated porcine dermal grafts (Pelvicol(TM) CR Bard Covington, GA USA). The incidence of postoperative vaginal incision separation (dehiscence) was compared. A secondary analysis to assess graft tensile strength, suture pull out strength, and flexibility after perforation was performed using standard test method TM 0133 and ASTM bending and resistance protocols. Seventeen percent of patients (21/127) who received grafts without perforations developed vaginal incision dehiscence compared to 7% (5/71) of patients who received perforated grafts (p = 0.078). Four patients with vaginal incision dehiscence with non-perforated grafts required surgical revision to facilitate healing. Neither tensile strength or suture pull out strength were significantly different between perforated and non-perforated grafts (p = 0.81, p = 0.29, respectively). There was no difference in the flexibility of the two grafts (p = 0.20). Perforated porcine dermal grafts retain their tensile properties and are associated with fewer vaginal incision dehiscences.

Hydroquinone PBPK model refinement and application to dermal exposure.

PubMed

Poet, Torka S; Carlton, Betsy D; Deyo, James A; Hinderliter, Paul M

2010-11-01

A physiologically based pharmacokinetic (PBPK) model for hydroquinone (HQ) was refined to include an expanded description of HQ-glucuronide metabolites and a description of dermal exposures to support route-to-route and cross-species extrapolation. Total urinary excretion of metabolites from in vivo rat dermal exposures was used to estimate a percutaneous permeability coefficient (K(p); 3.6×10(-5) cm/h). The human in vivo K(p) was estimated to be 1.62×10(-4) cm/h, based on in vitro skin permeability data in rats and humans and rat in vivo values. The projected total multi-substituted glutathione (which was used as an internal dose surrogate for the toxic glutathione metabolites) was modeled following an exposure scenario based on submersion of both hands in a 5% aqueous solution of HQ (similar to black and white photographic developing solution) for 2 h, a worst-case exposure scenario. Total multi-substituted glutathione following this human dermal exposure scenario was several orders of magnitude lower than the internal total glutathione conjugates in rats following an oral exposure to the rat NOEL of 20 mg/kg. Thus, under more realistic human dermal exposure conditions, it is unlikely that toxic glutathione conjugates (primarily the di- and, to a lesser degree, the tri-glutathione conjugate) will reach significant levels in target tissues. Copyright © 2010. Published by Elsevier Ltd.

Dermal Sensitization Potential of Triethyleneglycol Dinitrate (TEGDN) in Guinea Pigs

DTIC Science & Technology

1989-01-01

mutagenicity assay, acute oral toxicity tests in rats and mice, acute dermal toxicity in rabbits, dermal and ocular irritation studies in rabbits, and...conditions: 85E0102 had diffuse tracheitis, mild endocarditis , mild hepatitis, and diffuse pigment granules in the small intestine; 85E0103 had mild...severe ulceration progressing to necrosis. Sensitization is manifested as indirect inflammation mediated by components of the immune system in

Canine susceptibility to visceral leishmaniasis: A systematic review upon genetic aspects, considering breed factors and immunological concepts.

PubMed

de Vasconcelos, Tassia Cristina Bello; Furtado, Marina Carvalho; Belo, Vínicus Silva; Morgado, Fernanda Nazaré; Figueiredo, Fabiano Borges

2017-10-05

Dogs have different susceptibility degrees to leishmaniasis; however, genetic research on this theme is scarce, manly on visceral form. The aims of this systematic review were to describe and discuss the existing scientific findings on genetic susceptibility to canine leishmaniasis, as well as to show the gaps of the existing knowledge. Twelve articles were selected, including breed immunological studies, genome wide associations or other gene polymorphism or gene sequencing studies, and transcription approaches. As main results of literature, there was a suggestion of genetic clinical resistance background for Ibizan Hound dogs, and alleles associated with protection or susceptibility to visceral leishmaniasis in Boxer dogs. Genetic markers can explain phenotypic variance in both pro- and anti-inflammatory cytokines and in cellular immune responses, including antigen presentation. Many gene segments are involved in canine visceral leishmaniasis phenotype, with Natural Resistance Associated Macrophage Protein 1 (NRAMP1) as the most studied. This was related to both protection and susceptibility. In comparison with murine and human genetic approaches, lack of knowledge in dogs is notorious, with many possibilities for new studies, revealing a wide field to be assessed on canine leishmaniasis susceptibility research. Copyright © 2017 Elsevier B.V. All rights reserved.

[Epidemiological, clinical and parasitological data about canine leishmaniasis in Tunisia].

PubMed

Bouratbine, A; Aoun, K; Gharbi, M; Haouas, N; Zaroui, J; Harrat, Z; Baba, H; Darghouth, M A

2005-12-01

Epidemiological, clinical and parasitological data concerning canine leishmaniasis were collected in two Tunisian populations of dogs, different in breed and life style: 23 rural dogs and 26 dogs of European breeds. All were symptomatic and lived in the north of Tunisia where human visceral and cutaneous leishmaniasis caused by Leishmania infantum are endemic. Leishmaniasis has been confirmed in all dogs by serology or/and by parasitic identification. Significant differences concerning age and symptoms suggest a higher susceptibility to infection in European imported breeds. In fact individuals of this population were significantly younger; 81% were less than 5 years old whereas 57% of the autochthonous rural dogs were more than 5 years old with 31% of them being older than 9 (p = 0.014). In spite of their young age, 75% of imported breeds presented an affection of their general state with more frequent cutaneous symptoms than the rural dogs (96% versus 69%, p = 0.02). Isoenzyme typing of 31 strains, obtained from the two populations, from different sites (blood, lymph nodes, spleen) has only identified the zymodeme Leishmania infantum MON-1. This stresses the need of more investigations to determine reservoirs of the other enzymatic variants identified in humans in Tunisia and Mediterranean basin.

Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

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

Abou-Elwafa Abdallah, Mohamed, E-mail: mae_abdallah@yahoo.co.uk; Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut; Pawar, Gopal

Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm{sup 2}, finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPPmore » and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K{sub p}, cm/h) showed a significant negative correlation with log K{sub ow} for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K{sub ow} of PFRs. • Skin washing reduced the overall dermal

Minipigs as an Animal Model for Dermal Vaccine Delivery

PubMed Central

Ploemen, Ivo HJ; Hirschberg, Hoang JHB; Kraan, Heleen; Zeltner, Adrian; van Kuijk, Sandra; Lankveld, Danielle PK; Royals, Michael; Kersten, Gideon FA; Amorij, Jean-Pierre

2014-01-01

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg). Intradermal vaccine delivery by needle and syringe and by needle-free jet injection induced humoral antiHBsAg responses. Priming immunization by using the disposable syringe jet injector (DSJI) resulted in a higher antibody titer than did conventional intradermal immunization and a titer comparable to that after intramuscular vaccination with HBsAg and Al(OH)3 adjuvant. This study highlights the utility of the minipig model in vaccine studies assessing the efficacy of conventional and novel methods of dermal delivery. Moreover, we include suggestions regarding working with minipigs during dermal vaccine delivery studies, thereby fostering future work in this area of vaccinology. PMID:24512961

Environmental Factors as Key Determinants for Visceral Leishmaniasis in Solid Organ Transplant Recipients, Madrid, Spain

PubMed Central

López-Medrano, Francisco; Fernández-Ruiz, Mario; Carrillo, Eugenia; Moreno, Javier; García-Reyne, Ana; Pérez-Ayala, Ana; Rodríguez-Ferrero, María Luisa; Lumbreras, Carlos; San-Juan, Rafael; Alvar, Jorge; Aguado, José María

2017-01-01

During a visceral leishmaniasis outbreak in an area of Madrid, Spain, the incidence of disease among solid organ transplant recipients was 10.3% (7/68). Being a black person from sub-Saharan Africa, undergoing transplantation during the outbreak, and residing <1,000 m from the epidemic focus were risk factors for posttransplant visceral leishmaniasis. PMID:28628447

Characterization of dermal plates from armored catfish Pterygoplichthys pardalis reveals sandwich-like nanocomposite structure.

PubMed

Ebenstein, Donna; Calderon, Carlos; Troncoso, Omar P; Torres, Fernando G

2015-05-01

Dermal plates from armored catfish are bony structures that cover their body. In this paper we characterized structural, chemical, and nanomechanical properties of the dermal plates from the Amazonian fish Pterygoplichthys pardalis. Analysis of the morphology of the plates using scanning electron microscopy (SEM) revealed that the dermal plates have a sandwich-like structure composed of an inner porous matrix surrounded by two external dense layers. This is different from the plywood-like laminated structure of elasmoid fish scales but similar to the structure of osteoderms found in the dermal armour of some reptiles and mammals. Chemical analysis performed using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed similarities between the composition of P. pardalis plates and the elasmoid fish scales of Arapaima gigas. Reduced moduli of P. pardalis plates measured using nanoindentation were also consistent with reported values for A. gigas scales, but further revealed that the dermal plate is an anisotropic and heterogeneous material, similar to many other fish scales and osteoderms. It is postulated that the sandwich-like structure of the dermal plates provides a lightweight and tough protective layer. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vitro dermal absorption of pyrethroid pesticides in human and rat skin

EPA Science Inventory

Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flowthrough diffusi...

Non-cross-linked porcine acellular dermal matrices for abdominal wall reconstruction.

PubMed

Burns, Nadja K; Jaffari, Mona V; Rios, Carmen N; Mathur, Anshu B; Butler, Charles E

2010-01-01

Non-cross-linked porcine acellular dermal matrices have been used clinically for abdominal wall repair; however, their biologic and mechanical properties and propensity to form visceral adhesions have not been studied. The authors hypothesized that their use would result in fewer, weaker visceral adhesions than polypropylene mesh when used to repair ventral hernias and form a strong interface with the surrounding musculofascia. Thirty-four guinea pigs underwent inlay repair of surgically created ventral hernias using polypropylene mesh, porcine acellular dermal matrix, or a composite of the two. The animals were killed at 4 weeks, and the adhesion tenacity grade and surface area of the repair site involved by adhesions were measured. Sections of the repair sites, including the implant-musculofascia interface, underwent histologic analysis and uniaxial mechanical testing. The incidence of bowel adhesions to the repair site was significantly lower with the dermal matrix (8 percent, p < 0.01) and the matrix/mesh combination (0 percent, p < 0.001) than with polypropylene mesh alone (70 percent). The repairs made with the matrix or the matrix/mesh combination, compared with the polypropylene mesh repairs, had significantly lower mean adhesion surface areas [12.8 percent (p < 0.001), 9.2 percent (p < 0.001), and 79.9 percent] and grades [0.6 (p < 0.001), 0.6 (p < 0.001), and 2.9]. The dermal matrix underwent robust cellular and vascular infiltration. The ultimate tensile strength at the implant-musculofascia interface was similar in all groups. Porcine acellular dermal matrix becomes incorporated into the host tissue and causes fewer adhesions to repair sites than does polypropylene mesh, with similar implant-musculofascia interface strength. It also inhibits adhesions to adjacent dermal matrix in the combination repairs. It has distinct advantages over polypropylene mesh for complex abdominal wall repairs, particularly when material placement directly over bowel is

Complex torso reconstruction with human acellular dermal matrix: long-term clinical follow-up.

PubMed

Nemeth, Nicole L; Butler, Charles E

2009-01-01

Although reports have demonstrated good early outcomes with human acellular dermal matrix even when used for complex, contaminated defects, no long-term outcomes have been reported. The authors reviewed the long-term outcomes of 13 patients who had complex torso reconstructions that included human acellular dermal matrix. All patients were at increased risk for mesh-related complications. Eight patients died as a result of progression of their oncologic disease at a mean of 258 days postoperatively. The mean follow-up for the remaining five patients was 43.7 months. Six patients had early complications (none were human acellular dermal matrix-related) and were reported on previously. Two patients had developed complications since the initial report. One patient developed a flap donor-site seroma remote from the reconstruction site, and another developed a recurrent ventral hernia. No patients have required additional surgery for human acellular dermal matrix-related complications. This follow-up report indicates that human acellular dermal matrix repair of large, complex torso defects can result in good long-term outcomes even when patients are at high risk for mesh-related complications.

Immunopathological characterization of human cutaneous leishmaniasis lesions caused by Leishmania (Viannia) spp. in Amazonian Brazil.

PubMed

Castro Gomes, Cláudia Maria; Sousa, Maria Gloria Teixeira; Menezes, Joyce Prieto Bezerra; Batista, Marliane Campos; Lima, Ana Carolina Stocco; Belda, Walter; Bradshaw, Daniel; Gama, Monica Elinor Alves; Laurenti, Márcia Dalastra; Silveira, Fernando Tobias; Corbett, Carlos Eduardo Pereira

2017-05-01

American cutaneous leishmaniasis (ACL) is a chronic infectious disease caused by different protozoan species of Leishmania, and it is endemic in both tropical and subtropical countries. Using immunohistochemistry, we investigate the density of CD68 + , lysozyme + , CD1a + , factor XIIIa + , CD4 + , CD8 + , CD56 + , interferon (IFN)-γ + , and inducible NO synthase (iNOS + ) cells. These cells were analyzed from 22 biopsy samples obtained from the lesions of ACL patients, whose infection was caused by Leishmania (Viannia) spp. Histopathological analysis showed dense mononuclear inflammatory infiltration in the dermis, which was composed of lymphocytes, macrophages, plasma cells, and discrete tissue parasitism. Granulomatous reactions were also present in the majority of cases. The density of the activated macrophages was higher than that of inactivated macrophages in the lesions. The density of Langerhans cells (CD1a + ) was lower than that of dermal dendrocytes (factor XIIIa + ). The density of CD8 + T lymphocytes was higher than that of CD4 + T lymphocytes. The cellular density of these immunological markers in relation to the species of Leishmania demonstrated that L. (Viannia) sp. lesions had higher IFN-γ expression than that Leishmania (Viania) braziliensis lesions. The evaluation of these markers, according to disease progression, did not reveal any significant differences. L. (Viannia) sp. infection leads to a favorable immune response in the host, as predominantly represented by lysozyme + , factor XIIIa + , CD8 + T cells, and the expression of (IFN)-γ + at the lesion site.

Chitosan solutions as injectable systems for dermal filler applications: Rheological characterization and biological evidence.

PubMed

Halimi, C; Montembault, A; Guerry, A; Delair, T; Viguier, E; Fulchiron, R; David, L

2015-01-01

A new generation of dermal filler for wrinkle filler based on chitosan was compared to current hyaluronic acid-based dermal fillers by using a new rheological performance criterion based on viscosity during injection related to Newtonian viscosity. In addition an in vivo evaluation was performed for preclinical evidence of chitosan use as dermal filler. In this way, biocompatibility and dermis reconstruction was evaluated on a pig model.

Characterization and evolution of dermal filaments from patients with Morgellons disease

PubMed Central

Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process. PMID:23326202

Characterization and evolution of dermal filaments from patients with Morgellons disease.

PubMed

Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process.

In vivo study of dermal collagen of striae distensae by confocal Raman spectroscopy.

PubMed

Lung, Pam Wen; Tippavajhala, Vamshi Krishna; de Oliveira Mendes, Thiago; Téllez-Soto, Claudio A; Schuck, Desirée Cigaran; Brohem, Carla Abdo; Lorencini, Marcio; Martin, Airton Abrahão

2018-04-01

This research work mainly deals with studying qualitatively the changes in the dermal collagen of two forms of striae distensae (SD) namely striae rubrae (SR) and striae albae (SA) when compared to normal skin (NS) using confocal Raman spectroscopy. The methodology includes an in vivo human skin study for the comparison of confocal Raman spectra of dermis region of SR, SA, and NS by supervised multivariate analysis using partial least squares discriminant analysis (PLS-DA) to determine qualitatively the changes in dermal collagen. These groups are further analyzed for the extent of hydration of dermal collagen by studying the changes in the water content bound to it. PLS-DA score plot showed good separation of the confocal Raman spectra of dermis region into SR, SA, and NS data groups. Further analysis using loading plot and S-plot indicated the participation of various components of dermal collagen in the separation of these groups. Bound water content analysis showed that the extent of hydration of collagen is more in SD when compared to NS. Based on the results obtained, this study confirms the active involvement of dermal collagen in the formation of SD. It also emphasizes the need to study quantitatively the role of these various biochemical changes in the dermal collagen responsible for the variance between SR, SA, and NS.

[Leishmaniasis: a preliminary epidemiological study in a locality of the endemic area in the state of the Tabasco].

PubMed

Córdova-Uscanga, C; Albertos-Alpuche, N E; Andrade-Narváez, F J; Canto-Lara, S B

1993-01-01

The state of Tabasco is localized in the endemic area of cutaneous leishmaniasis where both diffuse cutaneous leishmaniasis and mucocutaneous leishmaniasis have recently been reported. The objective of the present study was to obtain reliable information of the situation of this disease--which has a great relevance as a worldwide public health problem--through determination of the allergic index in a randomized sample from Ranchería Miguel Hidalgo, Comalcalco Municipality, Tabasco, Mexico. We found an allergic index of 56 per cent. Farmers and housewives had the highest positive responses to the Montenegro skin test. We found no statistical differences between males and females. Moreover, 3 patients with active lesions and people with scars suggestive of prior leishmaniasis were detected during the study. This village should be considered a high endemic focus.

Predictors of dermal exposures to polycyclic aromatic compounds among hot-mix asphalt paving workers.

PubMed

Cavallari, Jennifer M; Osborn, Linda V; Snawder, John E; Kriech, Anthony J; Olsen, Larry D; Herrick, Robert F; McClean, Michael D

2012-03-01

The primary objective of this study was to identify the source and work practices that affect dermal exposure to polycyclic aromatic compounds (PACs) among hot-mix asphalt (HMA) paving workers. Four workers were recruited from each of three asphalt paving crews (12 workers) and were monitored for three consecutive days over 4 weeks for a total of 12 sampling days per worker (144 worker days). Two sampling weeks were conducted under standard conditions for dermal exposures. The third week included the substitution of biodiesel for diesel oil used to clean tools and equipment and the fourth week included dermal protection through the use of gloves, hat and neck cloth, clean pants, and long-sleeved shirts. Dermal exposure to PACs was quantified using two methods: a passive organic dermal (POD) sampler specifically developed for this study and a sunflower oil hand wash technique. Linear mixed-effects models were used to evaluate predictors of PAC exposures. Dermal exposures measured under all conditions via POD and hand wash were low with most samples for each analyte being below the limit of the detection with the exception of phenanthrene and pyrene. The geometric mean (GM) concentrations of phenanthrene were 0.69 ng cm(-2) on the polypropylene layer of the POD sampler and 1.37 ng cm(-2) in the hand wash sample. The GM concentrations of pyrene were 0.30 ng cm(-2) on the polypropylene layer of the POD sampler and 0.29 ng cm(-2) in the hand wash sample. Both the biodiesel substitution and dermal protection scenarios were effective in reducing dermal exposures. Based on the results of multivariate linear mixed-effects models, increasing frequency of glove use was associated with significant (P < 0.0001) reductions for hand wash and POD phenanthrene and pyrene concentrations; percent reductions ranged from 40 to 90%. Similar reductions in hand wash concentrations of phenanthrene (P = 0.01) and pyrene (P = 0.003) were observed when biodiesel was substituted for diesel oil

Arnica Tincture Cures Cutaneous Leishmaniasis in Golden Hamsters.

PubMed

Robledo, Sara M; Vélez, Ivan D; Schmidt, Thomas J

2018-01-12

In search for potential therapeutic alternatives to existing treatments for cutaneous Leishmaniasis, we have investigated the effect of Arnica tincture Ph. Eur. (a 70% hydroethanolic tincture prepared from flowerheads of Arnica montana L.) on the lesions caused by infection with Leishmania braziliensis in a model with golden hamsters. The animals were treated topically with a daily single dose of the preparation for 28 days. Subsequently, the healing process was monitored by recording the lesion size in intervals of 15 days up to day 90. As a result, Arnica tincture fully cured three out of five hamsters while one animal showed an improvement and another one suffered from a relapse. This result was slightly better than that obtained with the positive control, meglumine antimonate, which cured two of five hamsters while the other three showed a relapse after 90 days. This result encourages us to further investigate the potential of Arnica tincture in the treatment of cutaneous Leishmaniasis.

Penile Reconstruction with Skin Grafts and Dermal Matrices: Indications and Management

PubMed Central

Triana Junco, Paloma; Dore, Mariela; Nuñez Cerezo, Vanesa; Jimenez Gomez, Javier; Miguel Ferrero, Miriam; Díaz González, Mercedes; Lopez-Pereira, Pedro; Lopez-Gutierrez, Juan Carlos

2017-01-01

Introduction  The penis eventually needs specific cutaneous coverage in the context of reconstructive procedures following trauma or congenital anomalies. Local flaps are the first choice but are not always available after multiple previous procedures. In these cases, skin graft and dermal matrices should be considered. Materials and Methods  This study was a retrospective review of the past 4 years of four patients with severe loss of penile shaft skin who underwent skin reconstruction. Dermal matrices and skin grafts were utilized. Dermal matrices were placed for a median of 4.5 weeks (3.0–6.0 weeks). The skin graft was harvested from the inner thigh region for split-thickness skin graft (STSG) and the inguinal region for full-thickness skin graft (FTSG). Results  The four patients presented with complete loss of skin in the penile shaft. One patient had a vesical exstrophy, one had a buried penis with only one corpus cavernosum, one had a wide congenital lymphedema of the genitalia, and one had a lack of skin following circumcision at home. They underwent reconstruction with three patients undergoing split-thickness skin graft; two dermal matrices; and one full-thickness graft, respectively, thereby achieving a good cosmetic and functional result. There were no complications, and all the patients successfully accepted the graft. Conclusion  Dermal matrices and skin grafts may serve as effective tools in the management of severe penile skin defects unable to be covered with local flaps. PMID:28868232

Dynamic interactions between dermal macrophages and Staphylococcus aureus.

PubMed

Feuerstein, Reinhild; Kolter, Julia; Henneke, Philipp

2017-01-01

The dermis, a major reservoir of immune cells in immediate vicinity to the colonizing skin microflora, serves as an important site of host-pathogen interactions. Macrophages (Mϕ) are the most frequent resident immune cell type in the dermis. They protect the host from invasive infections by highly adapted bacteria, such as staphylococci via pattern recognition of bacterial effectors, phagocytosis, and recruitment of other myeloid cells from the blood. Already under homeostatic conditions, the dermal Mϕ population receives a dynamic input of monocytes invading from the bloodstream. This quantitative renewal is promoted further at the beginning of life, when prenatally seeded cells are rapidly replaced and in healing phases after injuries or infections. Here, we discuss the potential implications of the dynamic dermal Mϕ biology on the establishment and maintenance of immunity against Staphylococcus aureus, which can either be a harmless colonizer or an invasive pathogen. The understanding of the heterogeneity of the "mature" dermal Mϕ compartment driven both by the influx of differentiating monocytes and by a bone marrow-independent Mϕ persistence and expansion may help to explain failing immunity and immunopathology originating from the skin, the important interface between host and environment. © Society for Leukocyte Biology.

Inhalational and dermal exposures during spray application of biocides.

PubMed

Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

2005-01-01

Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

IN VITRO DERMAL ABSORPTION OF PYRETHROID PESTICIDES IN RAT AND HUMAN SKIN

EPA Science Inventory

Pyrethriods are a class of neurotoxic pesticides and their use may lead to dermal exposure. This study examined the in vitro dermal absorption of pyrethroids in rat and human skin. Dorsal skin removed from adult male LD rats (hair clipped 24 h previously) was dermatomed and mou...

Liposomal amphotericin B treatment of Old World cutaneous and mucosal leishmaniasis: A literature review.

PubMed

Mosimann, Vincent; Neumayr, Andreas; Paris, Daniel H; Blum, Johannes

2018-06-01

Old World cutaneous and mucosal leishmaniasis is a potentially serious disease. Systemic treatment approaches with pentavalent antimonials, liposomal amphotericin B, fluconazole and miltefosine are increasingly used despite the absence of supportive evidence - to date, no prospective clinical trials have been conducted for systemic treatment of these diseases. We performed a literature search to delineate the contemporary evidence for the use of liposomal amphotericin B, and found that although cure rates of 17/20 (85%) were achieved in immune competent patients with Old World cutaneous leishmaniasis and cure rates of 10/13 (77%) for Old World mucosal leishmaniasis due to L. infantum, the available data is highly limited with high variation in total treatment dosages. The presented findings reflect a lack of consensus on the optimal treatment dosage and on the schedule of application. Copyright © 2018 Elsevier B.V. All rights reserved.

DERMAL DRUG LEVELS OF ANTIBIOTIC (CEPHALEXIN) DETERMINED BY ELECTROPORATION AND TRANSCUTANEOUS SAMPLING (ETS) TECHNIQUE

PubMed Central

Sammeta, SM; Vaka, SRK; Murthy, S. Narasimha

2009-01-01

The purpose of this project was to assess the validity of a novel “Electroporation and transcutaneous sampling (ETS)” technique for sampling cephalexin from the dermal extracellular fluid (ECF). This work also investigated the plausibility of using cephalexin levels in the dermal ECF as a surrogate for the drug level in the synovial fluid. In vitro and in vivo studies were carried out using hair less rats to assess the workability of ETS. Cephalexin (20mg/kg) was administered i.v. through tail vein and the time course of drug concentration in the plasma was determined. In the same rats, cephalexin concentration in the dermal ECF was determined by ETS and microdialysis techniques. In a separate set of rats, only intraarticular microdialysis was carried out determine the time course of cephalexin concentration in synovial fluid. The drug concentration in the dermal ECF determined by ETS and microdialysis did not differ significantly from each other and so as were the pharmacokinetic parameters. The results provide validity to the ETS technique. Further, there was a good correlation (~0.9) between synovial fluid and dermal ECF levels of cephalexin indicating that dermal ECF levels could be used as a potential surrogate for cephalexin concentration in the synovial fluid. PMID:19067398

Heterogeneity of Environments Associated with Transmission of Visceral Leishmaniasis in South-Eastern France and Implication for Control Strategies

PubMed Central

Faucher, Benoit; Gaudart, Jean; Faraut, Francoise; Pomares, Christelle; Mary, Charles; Marty, Pierre; Piarroux, Renaud

2012-01-01

Background Visceral leishmaniasis due to Leishmania infantum is currently spreading into new foci across Europe. Leishmania infantum transmission in the Old World was reported to be strongly associated with a few specific environments. Environmental changes due to global warming or human activity were therefore incriminated in the spread of the disease. However, comprehensive studies were lacking to reliably identify all the environments at risk and thereby optimize monitoring and control strategy. Methodology/Findings We exhaustively collected 328 cases of autochthonous visceral leishmaniasis from 1993 to 2009 in South-Eastern France. Leishmaniasis incidence decreased from 31 yearly cases between 1993 and 1997 to 12 yearly cases between 2005 and 2009 mostly because Leishmania/HIV coinfection were less frequent. No spread of human visceral leishmaniasis was observed in the studied region. Two major foci were identified, associated with opposite environments: whereas one involved semi-rural hillside environments partly made of mixed forests, the other involved urban and peri-urban areas in and around the region main town, Marseille. The two neighboring foci were related to differing environments despite similar vectors (P. perniciosus), canine reservoir, parasite (L. infantum zymodeme MON-1), and human host. Conclusions/Significance This unprecedented collection of cases highlighted the occurrence of protracted urban transmission of L. infantum in France, a worrisome finding as the disease is currently spreading in other areas around the Mediterranean. These results complete previous studies about more widespread canine leishmaniasis or human asymptomatic carriage. This first application of systematic geostatistical methods to European human visceral leishmaniasis demonstrated an unsuspected heterogeneity of environments associated with the transmission of the disease. These findings modify the current view of leishmaniasis epidemiology. They notably stress the need

Heterogeneity of environments associated with transmission of visceral leishmaniasis in South-Eastern France and implication for control strategies.

PubMed

Faucher, Benoit; Gaudart, Jean; Faraut, Francoise; Pomares, Christelle; Mary, Charles; Marty, Pierre; Piarroux, Renaud

2012-01-01

Visceral leishmaniasis due to Leishmania infantum is currently spreading into new foci across Europe. Leishmania infantum transmission in the Old World was reported to be strongly associated with a few specific environments. Environmental changes due to global warming or human activity were therefore incriminated in the spread of the disease. However, comprehensive studies were lacking to reliably identify all the environments at risk and thereby optimize monitoring and control strategy. We exhaustively collected 328 cases of autochthonous visceral leishmaniasis from 1993 to 2009 in South-Eastern France. Leishmaniasis incidence decreased from 31 yearly cases between 1993 and 1997 to 12 yearly cases between 2005 and 2009 mostly because Leishmania/HIV coinfection were less frequent. No spread of human visceral leishmaniasis was observed in the studied region. Two major foci were identified, associated with opposite environments: whereas one involved semi-rural hillside environments partly made of mixed forests, the other involved urban and peri-urban areas in and around the region main town, Marseille. The two neighboring foci were related to differing environments despite similar vectors (P. perniciosus), canine reservoir, parasite (L. infantum zymodeme MON-1), and human host. This unprecedented collection of cases highlighted the occurrence of protracted urban transmission of L. infantum in France, a worrisome finding as the disease is currently spreading in other areas around the Mediterranean. These results complete previous studies about more widespread canine leishmaniasis or human asymptomatic carriage. This first application of systematic geostatistical methods to European human visceral leishmaniasis demonstrated an unsuspected heterogeneity of environments associated with the transmission of the disease. These findings modify the current view of leishmaniasis epidemiology. They notably stress the need for locally defined control strategies and extensive

Plasma levels of interlukin-4 and Interferon-γ in patients with chronic or healed cutaneous leishmaniasis

PubMed Central

Taheri, Ahmad Reza; Mashayekhi Goyonlo, Vahid; Nahidi, Yalda; Moheghi, Nasrin; Tavakkol Afshari, Jalil

2014-01-01

Objective(s): In this study, the serum level of interferon-γ (IFN- γ) and interlukin-4 (IL-4) was evaluated as a marker of Th1 and Th2 immune response that influence the clinical course of cutaneous leishmaniasis . Materials and Methods: This cross-sectional study was conducted on 44 cases of cutaneous leishmaniasis (21 cases with healed lesions and 23 cases with chronic non-healing lesions. Thirty-two non-infected persons living in the area were considered as controls. Serum levels of IFN- γ and IL-4 were determined using ELISA, and the results along with clinical data were analyzed using SPSS 11.5. Results: Serum IFN-γ level was not significantly different between various patient groups and control (P=0.27), but the serum level of IL-4 in patient groups was higher than in healthy subjects, and it was higher in patients with non-healed chronic cutaneous leishmaniasis than those with healed lesions (P<0.01). Conclusion: Serum IL-4 level is a good marker for evaluation of the clinical course of cutaneous leishmaniasis. PMID:24847425

Report of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in a cutaneous-leishmaniasis-endemic area of Panama.

PubMed

Valderrama, Anayansi; Tavares, Mara Garcia; Andrade Filho, José Dilermando

2011-12-01

Lutzomyia longipalpis is the primary vector of the parasite responsible for visceral leishmaniasis in the Americas. In the present study, Lu. longipalpis was found in a domiciliary area in Limón, a district in Capira, a region in which cutaneous leishmaniasis is endemic in Panama. Previously, this species has been found in a humid forest in this same region. Finding Lu. longipalpis in domiciliary areas indicates that this species may be adapting to new habitats and that it may play a role in the transmission of leishmaniasis in Panama.

Estimating terrestrial amphibian pesticide body burden through dermal exposure.

PubMed

Van Meter, Robin J; Glinski, Donna A; Hong, Tao; Cyterski, Mike; Henderson, W Matthew; Purucker, S Thomas

2014-10-01

Dermal exposure presents a potentially significant but understudied route for pesticide uptake in terrestrial amphibians. Our study measured dermal uptake of pesticides of varying hydrophobicity (logKow) in frogs. Amphibians were indirectly exposed to one of five pesticide active ingredients through contact with contaminated soil: imidacloprid (logKow = 0.57), atrazine (logKow = 2.5), triadimefon (logKow = 3.0), fipronil (logKow = 4.11) or pendimethalin (logKow = 5.18). All amphibians had measurable body burdens at the end of the exposure in concentrations ranging from 0.019 to 14.562 μg/g across the pesticides tested. Atrazine produced the greatest body burdens and bioconcentration factors, but fipronil was more permeable to amphibian skin when application rate was considered. Soil partition coefficient and water solubility were much better predictors of pesticide body burden, bioconcentration factor, and skin permeability than logKow. Dermal uptake data can be used to improve risk estimates of pesticide exposure among amphibians as non-target organisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Possible implication of the genetic composition of the Lutzomyia longipalpis (Diptera: Psychodidae) populations in the epidemiology of the visceral leishmaniasis.

PubMed

Rocha, Leonardo de Souza; Falqueto, Aloisio; Dos Santos, Claudiney Biral; Grimaldi, Gabriel Júnior; Cupolillo, Elisa

2011-09-01

Lutzomyia longipalpis (Diptera: Psychodidae) is the principal vector of American visceral leishmaniasis. Several studies have indicated that the Lu. longipalpis population structure is complex. It has been suggested that genetic divergence caused by genetic drift, selection, or both may affect the vectorial capacity of Lu. longipalpis. However, it remains unclear whether genetic differences among Lu. longipalpis populations are directly implicated in the transmission features of visceral leishmaniasis. We evaluated the genetic composition and the patterns of genetic differentiation among Lu. longipalpis populations collected from regions with different patterns of transmission of visceral leishmaniasis by analyzing the sequence variation in the mitochondrial cytochrome b gene. Furthermore, we investigated the temporal distribution of haplotypes and compared our results with those obtained in a previous study. Our data indicate that there are differences in the haplotype composition and that there has been significant differentiation between the analyzed populations. Our results reveal that measures used to control visceral leishmaniasis might have influenced the genetic composition of the vector population. This finding raises important questions concerning the epidemiology of visceral leishmaniasis, because these differences in the genetic structures among populations of Lu. longipalpis may have implications with respect to their efficiency as vectors for visceral leishmaniasis.

Differential Apoptosis in Mucosal and Dermal Wound Healing

PubMed Central

Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

2014-01-01

Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; p<0.05), Casp7 (at D5; p<0.05), Trp53 (at 24 h and D5; p<0.05), Tnfrsf1b (at 24 h; p<0.05), FasR (at 24 h, D5, and D7; p<0.05), and Casp8 (at 24 h; p<0.05) and significantly lower gene expression of Tradd (at 24 h; p<0.05). Innovation: Our observations indicate differential execution of apoptosis in oral wound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

[Mediterranean visceral leishmaniasis].

PubMed

Marty, Pierre; Pomares, Christelle; Michel, Grégory; Delaunay, Pascal; Ferrua, Bernard; Rosenthal, Eric

2011-01-01

Mediterranean visceral leishmaniasis is a parasitic zoonosis due to Leishmania infantum. The dog is the reservoir species and also the main victim. The vector is the female Phlebotomus sand fly. In the southern Mediterranean region the disease is most frequent in children, whereas in Europe, and particularly in France, it is mostly an opportunistic infection associated with immunosuppression. Frequent asymptomatic carriage has been detected in southern Europe. The classic symptom triad consists of fever, pallor and splenomegaly. Biological signs include low cell blood counts (anemia, leukoneutropenia, and thrombocytopenia) and an inflammatory syndrome. Commercial serologic tests such as those based on immunoblotting are very useful. The gold standard for diagnosis is parasite detection in bone marrow or blood. PCR is useful for therapeutic follow-up. Treatment is currently based on liposomal amphotericin B (AmBisome).

Plant-derived compounds in treatment of leishmaniasis

PubMed Central

Oryan, A

2015-01-01

Leishmaniasis is a neglected public health problem caused by the protozoan species belonging to the genus Leishmania affecting mostly the poor populations of developing countries. The causative organism is transmitted by female sandflies. Cutaneous, mucocutaneous, and visceral clinical manifestations are the most frequent forms of leishmaniasis. Chemotherapy still relies on the use of pentavalent antimonials, amphotericin B, paromomycin, miltefosin and liposomal amphotericin B. However, the application of these drugs is limited due to low efficacy, life-threatening side effects, high toxicity, induction of parasite resistance, length of treatment and high cost. Given the fact that antileishmanial vaccines may not become available in the near future, the search for better drugs should be continued. Natural products may offer an unlimited source of chemical diversity to identify new drug modules. New medicines should be less toxic or non-toxic, safe, more efficient, less expensive and readily available antileishmanial agents, especially for low-income populations. In the present review, special focus is on medicinal plants used against leishmanaiasis. The bioactive phytocompounds present in the plant derivatives including the crude extracts, essential oils, and other useful compounds can be a good source for discovering and producing new antileishmanial medicines. PMID:27175144

Assessment of anti-protozoal activity of plants traditionally used in Ecuador in the treatment of leishmaniasis.

PubMed

Gachet, María Salomé; Lecaro, Javier Salazar; Kaiser, Marcel; Brun, Reto; Navarrete, Hugo; Muñoz, Ricardo A; Bauer, Rudolf; Schühly, Wolfgang

2010-03-02

For the assessment of the in vitro anti-protozoal potential of plants traditionally used in Ecuador in the treatment of leishmaniasis, a combined approach based on interviews with healers as well as a literature search was carried out. From three regions of Ecuador, 256 local healers called "Agents of Traditional Medicine" (ATMs) were interviewed about their knowledge of the use of plants to treat and heal the illness recognized by the ATMs as leishmaniasis. From literature sources, 14 plants were identified as being used in the treatment of leishmaniasis. Subsequently, plant material was collected from a representative selection of 39 species. A total of 140 extracts were screened in vitro against Leishmania donovani, Plasmodium falciparum, Trypanosoma brucei rhodesiense and Trypanosoma cruzi. Additionally, these extracts were evaluated for their anti-microbial activities using five gram-positive and -negative bacteria as well as Candida albicans. The survey resulted in 431 use-records for 145 plant-taxa used for the treatment of leishmaniasis. The 10 most frequently reported taxa accounted for 37.7% of all records. In the case of leishmaniasis, activity was observed for Elephantopus mollis, Minquartia guianensis, Bocconia integrifolia, Gouania lupuloides, Scoparia dulcis, an as-yet-unidentified species of Piper and Brugmansia. For the leaves of M. guianensis and the twigs and bark of G. lupuloides a good selectivity index (SI) was found. IC(50) values and the SI of active plant extracts are presented. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Clinical and epidemiological features of leishmaniasis in northwestern-Argentina through a retrospective analysis of recent cases.

PubMed

García Bustos, María F; González-Prieto, Gabriela; Ramos, Federico; Mora, María C; Hashiguchi, Yoshihisa; Parodi, Cecilia; Basombrío, Miguel A; Moreno, Sonia; Monroig, Sibila; Beckar, Josefina; Jaime, Daniela; Sajama, Jesús; Yeo, Matthew; Marco, Jorge D; Locatelli, Fabricio M; Barrio, Alejandra

2016-02-01

Leishmaniasis is a parasitic disease caused by hemoflagellates of the genus Leishmania and is transmitted to humans by the bite of infected phlebotomine sandflies. Depending on the Leishmania species, the disease has different clinical forms including cutaneous, mucocutaneous, and visceral manifestations. Previous studies performed in endemic zones of northwestern-Argentina, during epidemic outbreaks, have been important for detecting patients suffering from the acute phase of the disease, but have not given a complete representation of the clinical and epidemiological features in the region. Furthermore, due to the resurgence of leishmaniasis worldwide and in particular the large increase of international tourism to the region, it seems pertinent to update the current epidemiological and clinical profile of leishmaniasis in northwestern-Argentina. Here we present a retrospective analysis of 95 Leishmania positive cases, presenting between 2000 and 2014. Patients were derived from hospitals and diagnosed in our lab at the University of Salta, located in a non-endemic area in Salta, Argentina. We detected numerous extensive mucocutaneous cases (34/95, 35.8%) distinct from mucosal affected patients, some instances originating in locations with no previously reported human cases. Additionally patients suffering from concomitant diseases, besides leishmaniasis, were assessed. These included Chagas disease, syphilis, deep mycoses, tuberculosis, toxoplasmosis and intestinal parasitosis. This study updates the clinical and epidemiological features of leishmaniasis in northwestern-Argentina, and discusses the implications and management strategy for patients who acquire the disease in this region. Copyright © 2015 Elsevier B.V. All rights reserved.

Polypoid dermal hemangiopericytoma: a case report.

PubMed

Pollock, A M; Sweeney, E C

1998-10-01

A polypoid dermal lesion with histologic, immunohistochemical, and ultrastructural features of hemangiopericytoma is described. Such tumors, arising in the dermis, are exceptionally rare, and whereas the tumor bears some resemblance to meningioma-like tumors of the skin and the well-recognized animal counterpart, canine hemangiopericytoma, it is histologically distinct.

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2014 CFR

2014-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2012 CFR

2012-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2013 CFR

2013-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2011 CFR

2011-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

PubMed Central

Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

2014-01-01

Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration. PMID:25383178

Cleft Palate Fistula Closure Utilizing Acellular Dermal Matrix.

PubMed

Emodi, Omri; Ginini, Jiriys George; van Aalst, John A; Shilo, Dekel; Naddaf, Raja; Aizenbud, Dror; Rachmiel, Adi

2018-03-01

Fistulas represent failure of cleft palate repair. Secondary and tertiary fistula repair is challenging, with high recurrence rates. In the present retrospective study, we review the efficacy of using acellular dermal matrix as an interposition layer for cleft palate fistula closure in 20 consecutive patients between 2013 and 2016. Complete fistula closure was obtained in 16 patients; 1 patient had asymptomatic recurrent fistula; 2 patients had partial closure with reduction of fistula size and minimal nasal regurgitation; 1 patient developed a recurrent fistula without changes in symptoms (success rate of 85%). We conclude that utilizing acellular dermal matrix for cleft palate fistula repair is safe and simple with a high success rate.

Cleft Palate Fistula Closure Utilizing Acellular Dermal Matrix

PubMed Central

Emodi, Omri; van Aalst, John A.; Shilo, Dekel; Naddaf, Raja; Aizenbud, Dror; Rachmiel, Adi

2018-01-01

Summary: Fistulas represent failure of cleft palate repair. Secondary and tertiary fistula repair is challenging, with high recurrence rates. In the present retrospective study, we review the efficacy of using acellular dermal matrix as an interposition layer for cleft palate fistula closure in 20 consecutive patients between 2013 and 2016. Complete fistula closure was obtained in 16 patients; 1 patient had asymptomatic recurrent fistula; 2 patients had partial closure with reduction of fistula size and minimal nasal regurgitation; 1 patient developed a recurrent fistula without changes in symptoms (success rate of 85%). We conclude that utilizing acellular dermal matrix for cleft palate fistula repair is safe and simple with a high success rate. PMID:29707449

The Use of Meshed Dermal Autograft in Breast Reconstruction.

PubMed

Zingaretti, Nicola; Guarneri, Gianni Franco; De Biasio, Fabrizio; Shoeib, Mohamed A; Parodi, Pier Camillo

2018-02-01

The advantages and disadvantages of acellular dermal matrix (ADM) in breast reconstruction have been well documented. ADM is commonly used in breast reconstruction, but it adds cost to the procedure and has been associated with an increased risk of seroma, flap necrosis and infectious complications. A dermal autograft may be a useful alternative to matrices, and it has a lot of advantages: more biocompatible and more likely to be retained as a free graft, low cost, well tolerated, readily available and integrated. This report discusses a new surgical technique that uses an autologous dermis, which was harvested from the controlateral breast in patients having simultaneous breast reduction/mastopexy. Before the insertion, the autologous dermal matrix was meshed at a ratio of 3:1 to increase the graft surface area, to provide additional draining and to improve the engraftment of the autologous dermal matrix. Consequently, the resulting meshed graft allows for the cover of the inferior pole of a larger breast size implant and decreases the complication rate. In our clinic, this method was used on five women; there was one limited necrosis of the mastectomy flaps. The described technique is straightforward and reliable, it adds minimally to the operative time, and it eliminates costs and covers a bigger part of the prosthesis and promises good results. No Level Assigned This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dermis, acellular dermal matrix, and fibroblasts from different layers of pig skin exhibit different profibrotic characteristics: evidence from in vivo study

PubMed Central

Zuo, Yanhai; Lu, Shuliang

2017-01-01

To explore the profibrotic characteristics of the autografted dermis, acellular dermal matrix, and dermal fibroblasts from superficial/deep layers of pig skin, 93 wounds were established on the dorsa of 7 pigs. 72 wounds autografted with the superficial/deep dermis and acellular dermal matrix served as the superficial/deep dermis and acellular dermal matrix group, respectively, and were sampled at 2, 4, and 8 weeks post-wounding. 21 wounds autografted with/without superficial/deep dermal fibroblasts served as the superficial/deep dermal fibroblast group and the control group, respectively, and were sampled at 2 weeks post-wounding. The hematoxylin and eosin staining showed that the wounded skin thicknesses in the deep dermis group (superficial acellular dermal matrix group) were significantly greater than those in the superficial dermis group (deep acellular dermal matrix group) at each time point, the thickness of the cutting plane in the deep dermal fibroblast group was significantly greater than that in the superficial dermal fibroblast group and the control group. The western blots showed that the α-smooth muscle actin expression in the deep dermis group (superficial acellular dermal matrix group) was significantly greater than that in the superficial dermis group (deep acellular dermal matrix group) at each time point. In summary, the deep dermis and dermal fibroblasts exhibited more profibrotic characteristics than the superficial ones, on the contrary, the deep acellular dermal matrix exhibited less profibrotic characteristics than the superficial one. PMID:28423561

The effects of carbon nanotubes on lung and dermal cellular behaviors

PubMed Central

Luanpitpong, Sudjit; Wang, Liying; Rojanasakul, Yon

2016-01-01

Carbon nanotubes (CNTs) hold great promise to create new and better products, but their adverse health effect is a major concern. Human exposure to CNTs is primarily through inhalation and dermal contact, especially during the manufacturing and handling processes. Numerous animal studies have demonstrated the potential pulmonary and dermal hazards associated with CNT exposure, while in vitro studies have assessed the effects of CNT exposure on various cellular behaviors and have been used to perform mechanistic studies. In this review, we provide an overview of the pathological effects of CNTs and examine the acute and chronic effects of CNT exposure on lung and dermal cellular behaviors, beyond the generally discussed cytotoxicity. We then examine the linkage of cellular behaviors and disease pathogenesis, and discuss the pertinent mechanisms. PMID:24981653

Pharmacokinetics of Miltefosine in Old World Cutaneous Leishmaniasis Patients▿

PubMed Central

Dorlo, Thomas P. C.; van Thiel, Pieter P. A. M.; Huitema, Alwin D. R.; Keizer, Ron J.; de Vries, Henry J. C.; Beijnen, Jos H.; de Vries, Peter J.

2008-01-01

The pharmacokinetics of miltefosine in leishmaniasis patients are, to a great extent, unknown. We examined and characterized the pharmacokinetics of miltefosine in a group of patients with Old World (Leishmania major) cutaneous leishmaniasis. Miltefosine plasma concentrations were determined in samples taken during and up to 5 months after the end of treatment from 31 Dutch military personnel who contracted cutaneous leishmaniasis in Afghanistan and were treated with 150 mg miltefosine/day for 28 days. Samples were analyzed with a validated liquid chromatography-tandem mass spectrometry assay with a lower limit of quantification (LLOQ) of 4 ng/ml. Population pharmacokinetic modeling was performed with nonlinear mixed-effect modeling, using NONMEM. The pharmacokinetics of miltefosine could best be described by an open two-compartment disposition model, with a first elimination half-life of 7.05 days and a terminal elimination half-life of 30.9 days. The median concentration in the last week of treatment (days 22 to 28) was 30,800 ng/ml. The maximum duration of follow-up was 202 days after the start of treatment. All analyzed samples contained a concentration above the LLOQ. Miltefosine is eliminated from the body much slower than previously thought and is therefore still detectable in human plasma samples taken 5 to 6 months after the end of treatment. The presence of subtherapeutic miltefosine concentrations in the blood beyond 5 months after treatment might contribute to the selection of resistant parasites, and moreover, the measures for preventing the teratogenic risks of miltefosine treatment should be reconsidered. PMID:18519729

Human acellular dermal wound matrix: evidence and experience.

PubMed

Kirsner, Robert S; Bohn, Greg; Driver, Vickie R; Mills, Joseph L; Nanney, Lillian B; Williams, Marie L; Wu, Stephanie C

2015-12-01

A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma.

PubMed

Kim, Nan-Hyung; Choi, Soo-Hyun; Lee, Tae Ryong; Lee, Chang-Hoon; Lee, Ai-Young

2016-06-15

Basement membrane (BM) disruption and dermal changes (elastosis, collagenolysis, vascular ectasia) have been reported in melasma. Although ultraviolet (UV) irradiation can induce these changes, UV is not always necessary for melasma development. Cadherin 11 (CDH11), which is upregulated in some melasma patients, has previously been shown to stimulate melanogenesis. Because CDH11 action requires cell-cell adhesion between fibroblasts and melanocytes, BM disruption in vivo should facilitate this. The aim of this study was to examine whether CDH11 overexpression leads to BM disruption and dermal changes, independent of UV irradiation. Immunohistochemistry/immunofluorescence, real-time PCR, Western blotting, and zymography suggested that BM disruption/dermal changes and related factors were present in the hyperpigmented skin of CDH11-upregulated melasma patients and in CDH11-overexpressing fibroblasts/keratinocytes. The opposite was seen in CDH11-knockdown cells. UV irradiation of the cultured cells did not increase CDH11 expression. Collectively, these data demonstrate that CDH11 overexpression could induce BM disruption and dermal changes in melasma, regardless of UV exposure.

Cutaneous leishmaniasis in Cuban immigrants to Texas who traveled through the Darién Jungle, Panama.

PubMed

Barry, Meagan A; Koshelev, Misha V; Sun, Grace S; Grekin, Sarah J; Stager, Charles E; Diwan, A Hafeez; Wasko, Carina A; Murray, Kristy O; Woc-Colburn, Laila

2014-08-01

Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis. © The American Society of Tropical Medicine and Hygiene.

[Canine visceral leishmaniasis in northeast Brazil: epidemiological aspects].

PubMed

Silva, O A; Silva, P B; Silva, O V; Braga, G M; Albuquerque Júnior, A; Queiros Neto, V; Rocha, M E; Silva, E F

2007-02-01

In a rural area of Northeast Brazil, the relatively high serological infection by Leishmania in dogs, the lack of classical vector Lutzomyia longipalpis and of American Visceral Leishmaniasis cases in human beings and the observation of Leishmania in ticks collected in infected dogs suggest that ticks may be responsible for the transmission between dogs.

Potential Challenges of Controlling Leishmaniasis in Sri Lanka at a Disease Outbreak

PubMed Central

Gunawardana, Kithsiri; Rodrigo, Wasana

2017-01-01

The present works reviewed the existing information on leishmaniasis in Sri Lanka and in other countries, focusing on challenges of controlling leishmaniasis in the country, in an outbreak. Evidence from recent studies suggests that there is a possibility of a leishmaniasis outbreak in Sri Lanka in the near future. Difficulty of early diagnosis due to lack of awareness and unavailability or inadequacy of sensitive tests are two of the main challenges for effective case management. Furthermore, the absence of a proper drug for treatment and lack of knowledge about vector biology, distribution, taxonomy and bionomics, and reservoir hosts make the problem serious. The evident potential for visceralization in the cutaneous variant of L. donovani in Sri Lanka may also complicate the issue. Lack of knowledge among local communities also reduces the effectiveness of vector and reservoir host control programs. Immediate actions need to be taken in order to increase scientific knowledge about the disease and a higher effectiveness of the patient management and control programs must be achieved through increased awareness about the disease among general public and active participation of local community in control activities. PMID:28630867

Canine visceral leishmaniasis as a systemic fibrotic disease

PubMed Central

Silva, Lucelia C; Castro, Rodrigo S; Figueiredo, Maria M; Michalick, Marilene S M; Tafuri, Washington L; Tafuri, Wagner L

2013-01-01

We propose that canine visceral leishmaniasis (CVL) is a systemic fibrotic disease, as evidenced by the wide distribution of fibrosis that we have found in the dogs suffering from chronic condition. The inflammatory cells apparently direct fibrosis formation. Twenty-four cases (symptomatic dogs) were identified from a total of one hundred and five cases that had been naturally infected with Leishmania chagasi and had been documented during an epidemiological survey of CVL carried out by the metropolitan area of the municipality of Belo Horizonte, MG, Brazil. The histological criterion was intralobular liver fibrosis, as has been described previously in dogs with visceral leishmaniasis. In addition to the findings in the liver, here we describe and quantify conspicuous and systemic deposition of collagen in other organs, including spleen, cervical lymph nodes, lung and kidney of all the infected symptomatic dogs. Thus we report that there is a systematic fibrotic picture in these animals, where inflammatory cells appear to direct fibrosis in all organs that have been studied. Therefore we propose that CVL is a systemic fibrotic disease. PMID:23419132

Geographic and ecological features of phlebotomine sand flies (Diptera: Psychodidae) as leishmaniasis in Central Iran.

PubMed

Vatandoost, Hassan; Nejati, Jalil; Saghafipour, Abedin; Zahraei-Ramazani, Alireza

2018-03-01

Phlebotomine sand flies occur throughout the tropics and subtropics, as well as in temperate regions of the world. They are vectors of human and canine leishmaniasis and sand fly fevers caused by phleboviruses. This study was aimed to determine the geographic and ecological characteristics of phlebotomine sand flies as vectors of leishmaniasis and to prepare a checklist of phlebotomine sand flies. The study was conducted in Qom province, central Iran, between April and November 2016. Qom is located in latitude 34.6399°N and longitude 50.8759°E with average annual minimum and maximum temperatures of 16.5 and 49 °C, annual rainfall of 150 mm and relative humidity of 84 and 28%, respectively. Sand flies were collected by sticky paper traps from Qom city and its six districts. The sand flies collected were separated from the sticky paper traps using an insulin syringe and kept in 70% ethanol for species identification using taxonomic keys. Also, a literature review was performed using all published reports on phlebotomine sand flies in this province during 1999-2015. A total of 28,410 sand flies from two genera and 14 species were collected. Phlebotomus papatasi, the main vector of zoonotic cutaneous leishmaniasis and arboviruses, and Phlebotomus sergenti , the vector of anthroponotic cutaneous leishmaniasis, were the predominant species followed by Phlebotomus kandelakii , P. major and P. alexandri . Fourteen species from two genera mostly from wet and mountainous areas were identified in the study area. Kahak and Markazi districts were identified as high-risk foci with numerous leishmaniasis vectors species; we recommend intensifying and strengthening of vector control programme in the area of study.

Ecological Niche Modeling for the Prediction of the Geographic Distribution of Cutaneous Leishmaniasis in Tunisia

PubMed Central

Chalghaf, Bilel; Chlif, Sadok; Mayala, Benjamin; Ghawar, Wissem; Bettaieb, Jihène; Harrabi, Myriam; Benie, Goze Bertin; Michael, Edwin; Salah, Afif Ben

2016-01-01

Cutaneous leishmaniasis is a very complex disease involving multiple factors that limit its emergence and spatial distribution. Prediction of cutaneous leishmaniasis epidemics in Tunisia remains difficult because most of the epidemiological tools used so far are descriptive in nature and mainly focus on a time dimension. The purpose of this work is to predict the potential geographic distribution of Phlebotomus papatasi and zoonotic cutaneous leishmaniasis caused by Leishmania major in Tunisia using Grinnellian ecological niche modeling. We attempted to assess the importance of environmental factors influencing the potential distribution of P. papatasi and cutaneous leishmaniasis caused by L. major. Vectors were trapped in central Tunisia during the transmission season using CDC light traps (John W. Hock Co., Gainesville, FL). A global positioning system was used to record the geographical coordinates of vector occurrence points and households tested positive for cutaneous leishmaniasis caused by L. major. Nine environmental layers were used as predictor variables to model the P. papatasi geographical distribution and five variables were used to model the L. major potential distribution. Ecological niche modeling was used to relate known species' occurrence points to values of environmental factors for these same points to predict the presence of the species in unsampled regions based on the value of the predictor variables. Rainfall and temperature contributed the most as predictors for sand flies and human case distributions. Ecological niche modeling anticipated the current distribution of P. papatasi with the highest suitability for species occurrence in the central and southeastern part of Tunisian. Furthermore, our study demonstrated that governorates of Gafsa, Sidi Bouzid, and Kairouan are at highest epidemic risk. PMID:26856914

Ecological Niche Modeling for the Prediction of the Geographic Distribution of Cutaneous Leishmaniasis in Tunisia.

PubMed

Chalghaf, Bilel; Chlif, Sadok; Mayala, Benjamin; Ghawar, Wissem; Bettaieb, Jihène; Harrabi, Myriam; Benie, Goze Bertin; Michael, Edwin; Salah, Afif Ben

2016-04-01

Cutaneous leishmaniasis is a very complex disease involving multiple factors that limit its emergence and spatial distribution. Prediction of cutaneous leishmaniasis epidemics in Tunisia remains difficult because most of the epidemiological tools used so far are descriptive in nature and mainly focus on a time dimension. The purpose of this work is to predict the potential geographic distribution of Phlebotomus papatasi and zoonotic cutaneous leishmaniasis caused by Leishmania major in Tunisia using Grinnellian ecological niche modeling. We attempted to assess the importance of environmental factors influencing the potential distribution of P. papatasi and cutaneous leishmaniasis caused by L. major. Vectors were trapped in central Tunisia during the transmission season using CDC light traps (John W. Hock Co., Gainesville, FL). A global positioning system was used to record the geographical coordinates of vector occurrence points and households tested positive for cutaneous leishmaniasis caused by L. major. Nine environmental layers were used as predictor variables to model the P. papatasi geographical distribution and five variables were used to model the L. major potential distribution. Ecological niche modeling was used to relate known species' occurrence points to values of environmental factors for these same points to predict the presence of the species in unsampled regions based on the value of the predictor variables. Rainfall and temperature contributed the most as predictors for sand flies and human case distributions. Ecological niche modeling anticipated the current distribution of P. papatasi with the highest suitability for species occurrence in the central and southeastern part of Tunisian. Furthermore, our study demonstrated that governorates of Gafsa, Sidi Bouzid, and Kairouan are at highest epidemic risk. © The American Society of Tropical Medicine and Hygiene.

Liposome-containing Hibiscus sabdariffa calyx extract formulations with increased antioxidant activity, improved dermal penetration and reduced dermal toxicity.

PubMed

Pinsuwan, Sirirat; Amnuaikit, Thanaporn; Ungphaiboon, Suwipa; Itharat, Arunporn

2010-12-01

Hibiscus sabdariffa Linn, or Roselle, is a medicinal plant used extensively in traditional Thai medicine since ancient times. The extracts of Roselle calyces possess antioxidant activity and have potential for development as active ingredients in cosmetic products. However the limitations of using Roselle extracts in cosmetics are its low skin permeation and dermal irritation. Liposome technology is an obvious approach that might overcome these problems. Liposome formulations of standardized Roselle extracts were developed with various lipid components. The formulation showing the highest entrapment efficiency was selected for stability, skin permeation and dermal irritability studies. The liposome formulation with the highest entrapment efficiency (83%) and smalôlest particle size (332 mm) was formulated with phosphatidylcholine from soybean (SPC): Tween 80: deoxycholic acid (DA); 84:16:2.5 weight ratio, total lipid of 200 g/mL and 10% w/v Roselle extract in final liposomal preparation. This liposome formulation was found to be stable after storage at 4 degrees C, protected from light, for 2 months. The in vitro skin permeation studies, using freshly excised pig skin and modified Franz-diffusion cells, showed that the liposome formulation was able to considerably increased the rate of permeation of active compounds in Roselle extracts compared to the Roselle extract solution. The in vivo dermal irritability testing on rabbit skin showed that the liposome formulation dramatically decreased skin irritability compared to the unformulated extract. These results showed that the liposomes containing Roselle extracts had good stability, high entrapment efficacy, increased skin permeation and low skin irritation.

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--METALS IN DERMAL ANALYTICAL RESULTS

EPA Science Inventory

The Metals in Dermal Wipes data set contains analytical results for measurements of up to 11 metals in 86 dermal wipe samples over 86 households. Each sample was collected from the primary respondent within each household. The sampling period occurred on the first day of the fi...

In vitro Dermal Absorption of Hydroquinone: Protocol Validation and Applicability on Illegal Skin-Whitening Cosmetics.

PubMed

Desmedt, Bart; Ates, Gamze; Courselle, Patricia; De Beer, Jacques O; Rogiers, Vera; Hendrickx, Benoit; Deconinck, Eric; De Paepe, Kristien

2016-01-01

In Europe, hydroquinone is a forbidden cosmetic ingredient. It is, however, still abundantly used because of its effective skin-whitening properties. The question arises as to whether the quantities of hydroquinone used become systemically available and may cause damage to human health. Dermal absorption studies can provide this information. In the EU, dermal absorption has to be assessed in vitro since the Cosmetic Regulation 1223/2009/EC forbids the use of animals. To obtain human-relevant data, a Franz diffusion cell protocol was validated using human skin. The results obtained were comparable to those from a multicentre validation study. The protocol was applied to hydroquinone and the dermal absorption ranged between 31 and 44%, which is within the range of published in vivo human values. This shows that a well-validated in vitro dermal absorption study using human skin provides relevant human data. The validated protocol was used to determine the dermal absorption of illegal skin-whitening cosmetics containing hydroquinone. All samples gave high dermal absorption values, rendering them all unsafe for human health. These results add to our knowledge of illegal cosmetics on the EU market, namely that they exhibit a negative toxicological profile and are likely to induce health problems. © 2017 S. Karger AG, Basel.

The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Xiang, W. Z.; Xu, A. E.; Xu, J.; Bi, Z. G.; Shang, Y. B.; Ren, Q. S.

2010-08-01

Confocal laser scanning microscopy (CLSM) allows noninvasive visualization of human skin in vivo, without needing to fix or section the tissue. Melanocytes and pigmented keratinocytes at the level of the basal layer form bright dermal papillary rings which are readily amenable to identify in confocal images. Our purpose was to explore the role of dermal papillary rings in assessment of lesion location, the diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. Seventy-one patients were imaged with the VivaScope 1500 reflectance confocal microscope provided by Lucid, Inc. The results indicate that dermal papillary rings can assess the location of lesion; the application of dermal papillary rings can provide diagnostic support and differential diagnosis for vitiligo, nevus depigmentosus, tinea versicolor, halo nevus, common nevi, and assess the therapeutic efficacy of NBUVB phototherapy plus topical 0.1 percent tacrolimus ointment for vitiligo. In conclusion, our findings indicate that the dermal papillary rings play an important role in the assessment the location of lesion, diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. CLSM may be a promising tool for noninvasive examination in dermatology. However, larger studies are needed to expand the application of dermal papillary rings in dermatology.

Two cases of cutaneous leishmaniasis in Dutch military personnel treated with oral miltefosine.

PubMed

van der Snoek, Eric Martin; Couwenberg, S M; Stijnis, C; Kortbeek, L M; Schadd, E M

2017-02-01

In the Netherlands, cutaneous leishmaniasis is most commonly seen in military personnel deployed on a mission or training abroad. The treatment of two Dutch soldiers who acquired cutaneous leishmaniasis with oral miltefosine was evaluated. Adverse effects were monitored and the improvement of skin lesions was assessed. A military nurse with a painless Chiclero's ulcer due to Leishmania (Viannia) braziliensis acquired in Belize and a military physical training instructor with itchy swelling and small ulcer of the back of his left elbow due to L. donovani/infantum complex acquired in Ibiza were treated with oral miltefosine 50 mg three times a day for 28 days. Both patients responded well to oral miltefosine. Adverse effects were mild. Increase of creatinine levels was seen while liver transaminase levels were unremarkable. Miltefosine proved to be a convenient, effective and well-tolerated treatment option in the treatment of cutaneous leishmaniasis in Dutch military personnel. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The first record of American visceral leishmaniasis in domestic cats from Rio de Janeiro, Brazil.

PubMed

da Silva, Alba Valéria Machado; de Souza Cândido, Claudia Dias; de Pita Pereira, Daniela; Brazil, Reginaldo Peçanha; Carreira, João Carlos Araujo

2008-01-01

This paper is the first to report visceral leishmaniasis in domestic cats (Felis catus domesticus) from an endemic area in Rio de Janeiro state, Brazil. A relatively high seroprevalence of 25% was observed although none of them have presented any symptom. Our results support the observation of previous authors, suggesting that cats may be considered as alternative domestic hosts of visceral leishmaniasis and should be included in serological investigations performed in endemic areas.

Cutaneous leishmaniasis in subtropical Ecuador: popular perceptions, knowledge, and treatment.

PubMed

Weigel, M M; Armijos, R X; Racines, R J; Zurita, C; Izurieta, R; Herrera, E; Hinojsa, E

1994-06-01

Popular perceptions and knowledge about cutaneous leishmaniasis and its treatment were studied in an endemic area of subtropical Northwest Ecuador. Although most of the adults surveyed were familiar with the disease, the vector, and traditional treatments, many showed a lack of knowledge about transmission of the disease, ulcer healing, and conventional treatment. Gender was found to have a significant impact on disease risk, perceptions, and treatment knowledge. Males experienced a risk of contracting cutaneous leishmaniasis that was almost triple that of women. Men were also more likely to perceive that the disease seriously diminished the victim's capacity to work. Women, on the other hand, were more prone to perceive that cutaneous leishmaniasis was a serious disease that significantly decreased self-esteem. Although 80% of the subjects knew at least one method of treating the disease, women tended to know more methods than men. Most of 150 different therapies reported involved the use of indigenous plants, chemicals, acids, antibiotics, heat treatments, or petroleum by-products. Some of these treatments could have clinical value. However, only 7% of the subjects knew about pentavalent antimonials. Almost 70% of the subjects with a past or present infection history were treated solely by traditional methods; only 12% received a full course of Glucantime, while 7.5% got an incomplete course. The findings indicate that it will be important to consider the identified gaps in knowledge and gender perceptions regarding the disease and its treatment when planning future control programs.

SIRT-1 regulates TGF-β-induced dermal fibroblast migration via modulation of Cyr61 expression.

PubMed

Kwon, Eun-Jeong; Park, Eun-Jung; Yu, Hyeran; Huh, Jung-Sik; Kim, Jinseok; Cho, Moonjae

2018-05-01

SIRT1 is a NAD-dependent protein deacetylase that participates in cellular regulation. The increased migration of fibroblasts is an important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial as to whether SIRT1 acts as an activator or suppressor of cell migration. Therefore, we have established the role of SIRT1 in the migration of human dermal fibroblasts and explored targets of SIRT1 during dermal fibroblast migration. SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation with TGF-β further induced their expression. Treatment with resveratrol (RSV), a SIRT1 agonist, or overexpression of SIRT1 also promoted the expression Cyr61 in human dermal fibroblasts, whereas the inhibition of SIRT1 activity by nicotinamide or knockdown of SIRT1 decreased the level of Cyr61, as well as TGF-β or RSV-induced Cyr61 expression. Blocking of ERK signaling by PD98509 reduced the expression of Cyr61 induced by TGF-β or RSV. TGF-β, RSV, or SIRT1 overexpression enhanced β-catenin as well as Cyr61 expression. This stimulation was reduced by the Wnt inhibitor XAV939. RSV increased migration and nicotinamide attenuated RSV-induced migration of human dermal fibroblasts. Furthermore, SIRT1 overexpression promoted cell migration, whereas blocking Cyr61 attenuated SIRT1-stimulated migration of human dermal fibroblasts. SIRT1 increased cell migration by stimulating Cyr61 expression and the ERK and Wnt/β-catenin signaling. SIRT1-induced Cyr61 activity is very important for human dermal fibroblasts migration.

Successful treatment of complex traumatic and surgical wounds with a foetal bovine dermal matrix.

PubMed

Hayn, Ernesto

2014-12-01

A foetal bovine dermal repair scaffold (PriMatrix, TEI Biosciences) was used to treat complex surgical or traumatic wounds where the clinical need was to avoid skin flaps and to build new tissue in the wound that could be reepithelialised from the wound margins or closed with a subsequent application of a split-thickness skin graft (STSG). Forty-three consecutive cases were reviewed having an average size of 79·3 cm(2) , 50% of which had exposed tendon and/or bone. In a subset of wounds (44·7%), the implantation of the foetal dermal collagen scaffold was also augmented with negative pressure wound therapy (NPWT). Complete wound healing was documented in over 80% of the wounds treated, whether the wound was treated with the foetal bovine dermal scaffold alone (95·2%) or when supplemented with NPWT (82·4%). The scaffold successfully incorporated into wounds with exposed tendon and/or bone to build vascularised, dermal-like tissue. The new tissue in the wound supported STSGs however, in the majority of the cases (88·3%); wound closure was achieved through reepithelialisation of the incorporated dermal scaffold by endogenous wound keratinocytes. The foetal bovine dermal repair scaffold was found to offer an effective alternative treatment strategy for definitive closure of challenging traumatic or surgical wounds on patients who were not suitable candidates for tissue flaps. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Hair Follicle Generation by Injections of Adult Human Follicular Epithelial and Dermal Papilla Cells into Nude Mice

PubMed Central

Nilforoushzadeh, Mohammadali; Rahimi Jameh, Elham; Jaffary, Fariba; Abolhasani, Ehsan; Keshtmand, Gelavizh; Zarkob, Hajar; Mohammadi, Parvaneh; Aghdami, Nasser

2017-01-01

Objective Dermal papilla and hair epithelial stem cells regulate hair formation and the growth cycle. Damage to or loss of these cells can cause hair loss. Although several studies claim to reconstitute hairs using rodent cells in an animal model, additional research is needed to develop a stable human hair follicle reconstitution protocol. In this study, we have evaluated hair induction by injecting adult cultured human dermal papilla cells and a mixture of hair epithelial and dermal papilla cells in a mouse model. Materials and Methods In this experimental study, discarded human scalp skins were used to obtain dermal papilla and hair epithelial cells. After separation, cells were cultured and assessed for their characteristics. We randomly allocated 15 C57BL/6 nude mice into three groups that received injections in their dorsal skin. The first group received cultured dermal papilla cells, the second group received a mixture of cultured epithelial and dermal papilla cells, and the third group (control) received a placebo [phosphate-buffered saline (PBS-)]. Results Histopathologic examination of the injection sites showed evidence of hair growth in samples that received cells compared with the control group. However, the group that received epithelial and dermal papilla cells had visible evidence of hair growth. PKH tracing confirmed the presence of transplanted cells in the new hair. Conclusion Our data showed that injection of a combination of adult human cultured dermal papilla and epithelial cells could induce hair growth in nude mice. This study emphasized that the combination of human adult cultured dermal papilla and epithelial cells could induce new hair in nude mice. PMID:28670518

Respiratory and dermal symptoms in Thai nurses using latex products.

PubMed

Supapvanich, C; Povey, A C; de Vocht, F

2013-09-01

Despite known health risks related to the use of powdered latex gloves (PLGs), they are still widely used in hospitals in developing countries due to the high cost of alternatives. To determine the prevalence of dermal and respiratory symptoms associated with latex glove use in nurses in Thailand and evaluate the influence of previously reported occupational risk factors in this population. A cross-sectional study in female nurses working in three Thai hospitals. Participants completed a questionnaire on demographics, occupational and personal history, use of latex products at work and dermal and respiratory symptoms attributed to occupational use of latex gloves. Of 899 nurses, 18% reported health effects attributed to the use of latex products. After adjustment for confounding, occupational risk factors associated with increased reporting of dermal symptoms included wearing more than 15 pairs of PLG per day (odds ratio (OR): 2.10, 95% confidence interval (CI): [1.32-3.34]), using chlorhexidine (OR: 2.07, 95% CI: [1.22-3.52]) and being an operating theatre nurse (OR: 2.46, 95% CI: [1.47-4.12]). Being a labour ward nurse (OR: 3.52, 95% CI: [1.26-9.85]) was the only factor associated with increased reporting of respiratory symptoms. Continuing use of PLGs in Thai nurses is associated with increased prevalence of dermal symptoms compared with data from developed countries. Measures to reduce such health effects are well established and should be considered. Additionally, replacement of chlorhexidine with an alternative detergent seems advisable.

Rheological properties of cross-linked hyaluronic acid dermal fillers.

PubMed

Santoro, Stefano; Russo, Luisa; Argenzio, Vincenzo; Borzacchiello, Assunta

2011-01-01

Ha based dermal fillers in recent years aroused big interest in the area of cosmetic surgery for the rejuvenation of the dermis. There is not a ideal dermal filler (DF) for all applications and in commerce there are many types of DF that differ for their chemical-physical properties. So the aim of this paper is to correlate the rheological and physical properties of different DF to their clinical effectiveness. In this frame the samples have been subjected to oscillation dynamic rheological and steady shear measurements. Our results demonstrate that the viscoelastic properties of different DF varie strongly also considering fillers of the same family. Furthermore it was found that the materials physical properties influence significantly the performance of dermal filler. In particular the clinical data appear to correlate with the concentration of the polymer and with the product between the concentration and the percent elasticity, so these should be crucial parameters for the clinical performance of DF. So rheological data can be a tool to have an indication on the efficacy and longevity of DF but it has to be considered that production technology, in-vivo-conditions, injector skills and experience influence them also significantly.

Dermal Stem Cells Can Differentiate Down an Endothelial Lineage

PubMed Central

Bell, Emma; Richardson, Gavin D.; Jahoda, Colin A.; Gledhill, Karl; Phillips, Helen M.; Henderson, Deborah; Owens, W. Andrew

2012-01-01

In this study, we have demonstrated that cells of neural crest origin located in the dermal papilla (DP) exhibit endothelial marker expression and a functional activity. When grown in endothelial growth media, DP primary cultures upregulate expression of vascular endothelial growth factor receptor 1 (FLT1) mRNA and downregulate expression of the dermal stem cell marker α-smooth muscle actin. DP cells have demonstrated functional characteristics of endothelial cells, including the ability to form capillary-like structures on Matrigel, increase uptake of low-density lipoprotein and upregulate ICAM1 (CD54) in response to tumour necrosis factor alpha (TNF-α) stimulation. We confirmed that these observations were not due to contaminating endothelial cells, by using DP clones. We have also used the WNT1cre/ROSA26R and WNT1cre/YFP lineage-tracing mouse models to identify a population of neural crest-derived cells in DP cultures that express the endothelial marker PECAM (CD31); these cells also form capillary-like structures on Matrigel. Importantly, cells of neural crest origin that express markers of endothelial and mesenchymal lineages exist within the dermal sheath of the vibrissae follicle. PMID:22571645

Pedestrian injuries resulting from road traffic accidents: the Azare experience.

PubMed

Umaru, H; Ahidjo, A; Dogo, H

2007-01-01

Road traffic accident (RTA) is a leading cause of serious morbidity and mortality world wide. The pedestrians are not spared from this epidemic. The aim of this study is to identify factors that puts the pedestrian at risk of injuries from RTA and the anatomical regions most commonly involved in our environment and suggest ways of curbing them. This was a one-year retrospective study of 122 pedestrian casualties resulting from road traffic accident attending the Accident and Emergency (A/E) Unit of the Federal Medical Centre, Azare. Majority of the patients (72%) were males with a male to female ratio of 2.6:1. Children and adolescents constitute 54.1% of the casualties. Motorcycles were responsible for most of the pedestrian injuries (73%). The head and neck was the most frequently injured anatomical region of the body (43.4%), followed by the extremities (37%). The months of August and January were the peak periods of injuries. The safety of pedestrian is seriously threatened by the growing popularity of commercial motorcycles on our roads. Preventive measures are advocated to ensure only licensed cyclists are allowed on the roads. Adequate personnel training to manage head injury in our centers is also advised. More patrol by the road safety agents is advised in the months of January and August.

DERMAL, ORAL, AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation ki...

The Dermal Apron Technique for Immediate Implant Socket Management: A Novel Technique.

PubMed

Levin, Barry P

2016-01-01

With immediate implant placement and provisionalization (IIP) in the esthetic zone, measures to counter hard and soft tissue loss are frequently necessary. To reduce the morbidity associated with bone and connective tissue procurement, various exogenous materials are utilized. The "Dermal Apron Technique" presented in this article demonstrates the use of a composite bone particulate (allograft/xenograft) plus a dermal allograft, adapted around screw-retained temporary crowns and secured within a subperiosteal pouch. The purpose is to augment the thickness of peri-implant mucosa for the purpose of preserving ridge dimensions and preventing mucosal recession. Controlled studies are required to further support its use. Clinical significance: Soft tissue health and harmony are critical for successful implant therapy in the esthetic regions of the dentition. Often, autogenous soft tissue grafts are used to augment peri-implant soft tissues. The Dermal Apron Technique is a method, that in specific situations, obviates the need for autogenous grafting. This reduces treatment time and morbidity associated with procurement of these grafts. The Dermal Apron Technique is used simultaneous with immediate placement and provisionalization and can improve long-term esthetic outcomes for patients. © 2016 Wiley Periodicals, Inc.

Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators

PubMed Central

Sirimahachaiyakul, Pornthep; Sood, Ravi F.; Muffley, Lara A.; Seaton, Max; Lin, Cheng-Ta; Qiao, Liang; Armaly, Jeffrey S.; Hocking, Anne M.; Gibran, Nicole S.

2015-01-01

Introduction Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses. Methods and Materials Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium. Results Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium. Discussion Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring. PMID:26418010

Dermal exposure to monoterpenes during wood work.

PubMed

Eriksson, Kare; Wiklund, Leif

2004-06-01

The dermal exposure to the suspected allergenic monoterpenes [small alpha]-pinene, [small beta]-pinene and [capital Delta](3)-carene was assessed with a patch sampling technique. The patch used was made of activated charcoal sandwiched between two layers of cotton cloth. Patches were fastened at 12 different spots on a sampling overall and at the front of a cap to estimate the potential exposure of the body. Fastening two patches on a cotton glove, one patch representing the dorsal side and one patch representing the palm of the hand respectively, assessed the exposure on the hands. Sampling was carried out during collecting of pine and spruce boards in sawmills and during sawing of pine wood pieces in joinery shops respectively. The potential dermal exposure of the total body was 29.0-1 890 mg h(-1) with a geometric mean (GM) of 238 mg h(-1) during sawing. During collecting the GM was estimated to 100 mg h(-1) with a range of 12.2-959 mg h(-1). The hands had a mean exposure of 9.24 mg h(-1) during sawing and 3.25 mg h(-1) during collecting respectively. The good correlation between the mass of contamination on the individual body parts and the potential body exposure indicates that sampling can be performed on one body part to give a good estimation of the potential body exposure. Monoterpenes were detected at patches fastened underneath the protective clothing indicating a contamination of the skin of the worker. The patch used may overestimate the dermal exposure.

MALDI MS imaging investigation of the host response to visceral leishmaniasis.

PubMed

Jaegger, C F; Negrão, F; Assis, D M; Belaz, K R A; Angolini, C F F; Fernandes, A M A P; Santos, V G; Pimentel, A; Abánades, D R; Giorgio, S; Eberlin, M N; Rocha, D F O

2017-09-26

Mass spectrometry imaging (MSI) of animal tissues has become an important tool for in situ molecular analyses and biomarker studies in several clinical areas, but there are few applications in parasitological studies. Leishmaniasis is a neglected tropical disease, and experimental mouse models have been essential to evaluate pathological and immunological processes and to develop diagnostic methods. Herein we have employed MALDI MSI to examine peptides and low molecular weight proteins (2 to 20 kDa) differentially expressed in the liver during visceral leishmaniasis in mice models. We analyzed liver sections of Balb/c mice infected with Leishmania infantum using the SCiLS Lab software for statistical analysis, which facilitated data interpretation and thus highlighted several key proteins and/or peptides. We proposed a decision tree classification for visceral leishmaniasis with distinct phases of the disease, which are named here as healthy, acute infection and chronic infection. Among others, the ion of m/z 4963 was the most important to identify acute infection and was tentatively identified as Thymosin β4. This peptide was previously established as a recovery factor in the human liver and might participate in the response of mice to Leishmania infection. This preliminary investigation shows the potential of MALDI MSI to complement classical compound selective imaging techniques and to explore new features not yet recognized by these approaches.

Insights into reptile dermal contaminant exposure: Reptile skin permeability to pesticides.

PubMed

Weir, Scott M; Talent, Larry G; Anderson, Todd A; Salice, Christopher J

2016-07-01

There is growing interest in improving ecological risk assessment exposure estimation, specifically by incorporating dermal exposure. At the same time, there is a growing interest in amphibians and reptiles as receptors in ecological risk assessment, despite generally receiving less research than more traditional receptors. Previous research has suggested that dermal exposure may be more important than previously considered for reptiles. We measured reptile skin permeability to four pesticides (thiamethoxam, malathion, tebuthiuron, trifluralin) using ventral skin samples. All four pesticides penetrated the skin but generally had low permeability. There was no apparent relationship between physicochemical properties and permeability coefficients. Malathion had a significantly greater permeability rate at all time points compared to the other pesticides. Tebuthiuron had a greater permeability than thiamethoxam. Reptiles and mammals appear to have similar skin permeability suggesting that dermal exposure estimates for mammals may be representative of reptiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Management of gingival recession with acellular dermal matrix graft: A clinical study

PubMed Central

Balaji, V. R.; Ramakrishnan, T.; Manikandan, D.; Lambodharan, R.; Karthikeyan, B.; Niazi, Thanvir Mohammed; Ulaganathan, G.

2016-01-01

Aims and Objectives: Obtaining root coverage has become an important part of periodontal therapy. The aims of this studyare to evaluate the clinical efficacy of acellular dermal matrix graft in the coverage of denuded roots and also to examine the change in the width of keratinized gingiva. Materials and Methods: A total of 20 sites with more than or equal to 2 mm of recession depth were taken into the study, for treatment with acellular dermal matrix graft. The clinical parameters such as recession depth, recession width, width of keratinized gingiva, probing pocket depth (PD), and clinical attachment level (CAL) were measured at the baseline, 8th week, and at the end of the study (16th week). The defects were treated with a coronally positioned pedicle graft combined with acellular dermal matrix graft. Results: Out of 20 sites treated with acellular dermal matrix graft, seven sites showed complete root coverage (100%), and the mean root coverage obtained was 73.39%. There was a statistically significant reduction in recession depth, recession width, and probing PD. There was also a statistically significant increase in width of keratinized gingiva and also gain in CAL. The postoperative results were both clinically and statistically significant (P < 0.0001). Conclusion: The results of this study were esthetically acceptable to the patients and clinically acceptable in all cases. From this study, it may be concluded that acellular dermal matrix graft is an excellent substitute for autogenous graft in coverage of denuded roots. PMID:27829749

A systematic review of dermal fillers for age-related lines and wrinkles.

PubMed

Sturm, Lana P; Cooter, Rodney D; Mutimer, Keith L; Graham, John C; Maddern, Guy J

2011-01-01

Dermal fillers are gaining popularity for rapid aesthetic improvement. Long-term efficacy and safety have not been well documented. The aim of this systematic review was to assess the safety and efficacy of injectable dermal fillers compared with other facial augmentation techniques for the management of age-related lines and wrinkles. Studies including patients receiving injectable semi-permanent or permanent dermal fillers for age-related lines and wrinkles were included in this review. Efficacy outcomes (including changes in skin thickness and patient satisfaction) and safety outcomes (including mortality, lumps and infections) were examined. Three randomized control trials and six case series were included. Permanent and semi-permanent dermal fillers improved subjective ratings of appearance and resulted in higher patient satisfaction than temporary fillers. Long-term efficacy appeared good in the few studies that reported it. Short-term safety appeared favourable. Lumps were reported in all but one study but received little follow-up. Long-term safety data were limited. The treatment of age-related lines and wrinkles with permanent and semi-permanent dermal fillers is more efficacious compared with temporary fillers in those studies that compared them. Case series evidence suggests that these fillers achieve their objective, which is to decrease the visible effects of age-related changes. These fillers appear at least as safe as temporary fillers in the short term in those studies that compared them. Long-term safety could not be determined. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Absorption, distribution, metabolism and excretion of loxoprofen after dermal application of loxoprofen gel to rats.

PubMed

Sawamura, Ryoko; Kazui, Miho; Kurihara, Atsushi; Izumi, Takashi

2014-11-01

1. Loxoprofen (LX), is a prodrug of the pharmacologically active form, trans-alcohol metabolite (trans-OH form), which shows very potent analgesic effect. In this study, the pharmacokinetics and metabolism of [(14)C]LX-derived radioactivity after dermal application of [(14)C]LX gel (LX-G) to rats were evaluated. 2. The area under concentration-time curve (AUC0-∞) of radioactivity in the plasma after the dermal application was 13.6% of that of the oral administration (p < 0.05). 3. After the dermal application, the radioactivity remained in the skin and skeletal muscle at the treated site for 168 h, whereas the AUC0-168 h of the radioactivity concentration in every tissue examined except the treated site was statistically lower than that after the oral administration (p < 0.05). 4. The trans-OH form was observed at high levels in the treated skin site at 0.5 h. Metabolite profiles in plasma, non-treated skin site and urine after the dermal application were comparable with those after the oral administration. 5. Renal excretion was the main route of elimination after the dermal application. 6. In conclusion, compared to the oral administration, the dermal application of [(14)C]LX-G showed lower systemic and tissue exposure with higher exposure in the therapeutic target site. The radioactivity revealed similar metabolite profiles in both administration routes.

DERMAL, ORAL AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhal...

Nutritional status in patients with cutaneous leishmaniasis and a study of the effects of zinc supplementation together with antimony treatment.

PubMed

Guzman-Rivero, Miguel; Rojas, Ernesto; Verduguez-Orellana, Aleida; Pardo, Henry; Torrico, Mary Cruz; Cloetens, Lieselotte; Akesson, Björn; Sejas, Edgar

2014-01-01

The role of micronutrient status for the incidence and clinical course of cutaneous leishmaniasis is not much studied. Still zinc supplementation in leishmaniasis has shown some effect on the clinical recovery, but the evidence in humans is limited. To compare biochemical nutritional status in cutaneous leishmaniasis patients with that in controls and to study the effects of zinc supplementation for 60 days. Twenty-nine patients with cutaneous leishmaniasis were treated with antimony for 20 days. Fourteen of them got 45 mg zinc daily and 15 of them got placebo. Biomarkers of nutritional and inflammatory status and changes in size and characteristics of skin lesions were measured. The level of transferrin receptor was higher in patients than in controls but otherwise no differences in nutritional status were found between patients and controls. No significant effects of zinc supplementation on the clinical recovery were observed as assessed by lesion area reduction and characteristics or on biochemical parameters. It is concluded that nutritional status was essentially unaffected in cutaneous leishmaniasis and that oral zinc supplementation administered together with intramuscular injection of antimony had no additional clinical benefit.

Case Report: Cutaneous Leishmaniasis in Cuban Immigrants to Texas who Traveled through the Darién Jungle, Panama

PubMed Central

Barry, Meagan A.; Koshelev, Misha V.; Sun, Grace S.; Grekin, Sarah J.; Stager, Charles E.; Diwan, A. Hafeez; Wasko, Carina A.; Murray, Kristy O.; Woc-Colburn, Laila

2014-01-01

Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis. PMID:24865687

Interventions for American Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review Update

PubMed Central

Reveiz, Ludovic; Maia-Elkhoury, Ana Nilce Silveira; Nicholls, Rubén Santiago; Sierra Romero, Gustavo Adolfo; Yadon, Zaida E.

2013-01-01

Introduction Leishmaniasis is an important public health problem in the Americas. A Cochrane review published in 2009 analyzed 38 randomized controlled trials (RCT). We conducted a systematic review to evaluate the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis. Methods All studies were extracted from PubMed, Embase, Lilacs (2009 to July, 2012 respectively), the Cochrane Central Register of Controlled Trials (6-2012) and references of identified publications. RCTs’ risk of bias was assessed. Results We identified 1865 references of interest; we finally included 10 new RCTs. The risk of bias scored low or unclear for most domains. Miltefosine was not significantly different from meglumine antimoniate in the complete cure rate at 6 months (4 RCT; 584 participants; ITT; RR: 1.12; 95%CI: 0.85 to 1.47; I2 78%). However a significant difference in the rate of complete cure favoring miltefosine at 6 months was found in L. panamensis and L. guyanensis (2 RCTs, 206 participants; ITT; RR: 1.22; 95%CI: 1.02 to 1.46; I2 0%). One RCT found that meglumine antimoniate was superior to pentamidine in the rate of complete cure for L. braziliensis (80 participants, ITT; RR: 2.21; 95%CI: 1.41 to 3.49), while another RCT assessing L. guyanensis did not find any significant difference. Although meta-analysis of three studies found a significant difference in the rate of complete cure at 3 months favoring imiquimod versus placebo (134 participants; ITT; RR: 1.45; 95%CI: 1.12 to 1.88; I2 0%), no significant differences were found at 6 and 12 months. Thermotherapy and nitric oxide were not superior to meglumine antimoniate. Conclusion Therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis are varied and should be decided according to the context. Since mucosal disease is the more neglected form of leishmaniasis a multicentric trial should be urgently considered. PMID:23637917

Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.

PubMed

Modepalli, Naresh; Shivakumar, H Nanjappa; McCrudden, Maeliosa T C; Donnelly, Ryan F; Banga, Ajay; Murthy, S Narasimha

2016-03-01

Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Identification of Cadherin 11 as a Mediator of Dermal Fibrosis and Possible Role in Systemic Sclerosis

PubMed Central

Wu, Minghua; Pedroza, Mesias; Lafyatis, Robert; George, Anuh-Teresa; Mayes, Maureen D.; Assassi, Shervin; Tan, Filemon K.; Brenner, Michael B.; Agarwal, Sandeep K.

2014-01-01

Objective Systemic sclerosis (SSc) is a chronic autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Recent microarray studies demonstrated that cadherin 11 (Cad-11) expression is increased in the affected skin of patients with SSc. The purpose of this study was to examine our hypothesis that Cad-11 is a mediator of dermal fibrosis. Methods Biopsy samples of skin from SSc patients and healthy control subjects were used for real-time quantitative polymerase chain reaction analysis to assess Cad-11 expression and for immunohistochemistry to determine the expression pattern of Cad-11. To determine whether Cad-11 is a mediator of dermal fibrosis, Cad-11–deficient mice and anti–Cad-11 monoclonal antibodies (mAb) were used in the bleomycin-induced dermal fibrosis model. In vitro studies with dermal fibroblasts and bone marrow–derived macrophages were used to determine the mechanisms by which Cad-11 contributes to the development of tissue fibrosis. Results Levels of messenger RNA for Cad-11 were increased in skin biopsy samples from patients with SSc and correlated with the modified Rodnan skin thickness scores. Cad-11 expression was localized to dermal fibroblasts and macrophages in SSc skin. Cad-11–knockout mice injected with bleomycin had markedly attenuated dermal fibrosis, as quantified by measurements of skin thickness, collagen levels, myofibroblast accumulation, and profibrotic gene expression, in lesional skin as compared to the skin of wild-type mice. In addition, anti–Cad-11 mAb decreased fibrosis at various time points in the bleomycin-induced dermal fibrosis model. In vitro studies demonstrated that Cad-11 regulated the production of transforming growth factor β (TGFβ) by macrophages and the migration of fibroblasts. Conclusion These data demonstrate that Cad-11 is a mediator of dermal fibrosis and TGFβ production and suggest that Cad-11 may be a therapeutic target in SSc. PMID:24757152

Efficacy of fractional CO2 laser in treatment of atrophic scar of cutaneous leishmaniasis.

PubMed

Banihashemi, Mahnaz; Nahidi, Yalda; Maleki, Masoud; Esmaily, Habibollah; Moghimi, Hamid Reza

2016-05-01

Cutaneous leishmaniasis is an endemic disease in Iran. Unfortunately, it can lead to unsightly atrophic scars with limited treatment options. Fractional CO2 laser is accepted for treatment of atrophic acne scars and recently has been used to treat cutaneous leishmaniasis, so we planned to use fractional CO2 laser on leishmaniasis scar. We conducted this study on 60 leishmaniasis scars on the face of 40 patients. The lesions were treated by a fractional CO2 laser with beam size of 120 μm, with energy of 50-90 mJ, and 50-100 spots/cm(2) density with two passes in three monthly sessions. Evaluation was done in the first and second months after the first treatment and 3 and 6 months after the last treatment. Digital photography was performed at each visit. Assessment of improvement rate by patient and physician was rated separately as follows: no improvement (0%), mild (<25%), moderate (25-50%), good (51-75%), and excellent (76-100%). Based on patients' opinion, in the first and second follow-up, 48.3 and 90% of them reported moderate to excellent healing, respectively (p < 0.001). In 3 and 6 months follow-up after the end of the experiment, most of the patients (88.3 and 95%, respectively) reported moderate to excellent healing of scars. Based on two observers' opinion, healing in the first follow-up in most of the patients (65%) was mild to moderate and 33% were reported as having no healing. In the second follow-up, only 5% of the patients were reported with no healing and 60% were reported as having moderate healing (p < 0.001). In 3 and 6 months follow-up, most of the patients (95 and 96.6%) were reported as having moderate to excellent healing (p = <0.001). Our results underlined the high efficacy of fractional CO2 laser for leishmaniasis scar. No significant adverse effects were noted.

Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types.

PubMed

Villani, Rehan; Hodgson, Samantha; Legrand, Julien; Greaney, Jessica; Wong, Ho Yi; Pichol-Thievend, Cathy; Adolphe, Christelle; Wainwight, Brandon; Francois, Mathias; Khosrotehrani, Kiarash

2017-05-15

SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type; however, the role they play during development remains unclear. Here, we demonstrate that Sox18 regulates the normal differentiation of the dermal papilla of all hair types. In guard (primary) hair dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types. © 2017. Published by The Company of Biologists Ltd.

Phlebotomine sand flies (Diptera: Psychodidae) associated with the appearance of urban Leishmaniasis in the city of Sincelejo, Colombia.

PubMed

Bejarano, Eduar Elías; Uribe, Sandra; Rojas, Winston; Dario Velez, Iván

2002-07-01

Although once associated only with rural areas, the American leishmaniasis vectors now appear to be associated also with urban and suburban areas of the Neotropics. Following the appearance of the first autochthonous visceral and cutaneous leishmaniasis cases in the urban area of the city of Sincelejo, Colombia, a preliminary entomological survey of the sand fly species composition was performed using Shannon and CDC light traps. A total of 486 sand flies representing six Lutzomyia species were collected. L. evansi, L. panamensis and L. gomezi, known vectors of Leishmania spp. were the predominant sand fly species around dwellings. The finding of these species in relation to the appearance of the first cases of leishmaniasis in the city mentioned is discussed.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment.

PubMed

Chávez-Fumagalli, Miguel Angel; Ribeiro, Tatiana Gomes; Castilho, Rachel Oliveira; Fernandes, Simone Odília Antunes; Cardoso, Valbert Nascimento; Coelho, Cecília Steinberg Perilo; Mendonça, Débora Vasconcelos Costa; Soto, Manuel; Tavares, Carlos Alberto Pereira; Faraco, André Augusto Gomes; Coelho, Eduardo Antonio Ferraz

2015-01-01

Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.

Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity.

PubMed Central

Davies, C. R.; Llanos-Cuentas, E. A.; Pyke, S. D.; Dye, C.

1995-01-01

A prospective longitudinal survey of cutaneous leishmaniasis (Leishmania peruviana) was carried out in Peru on a study population of 4716 persons living in 38 villages (Departments of Lima, Ancash and Piura). Demographic and clinical data were collected from all individuals, and a Montenegro skin test (MST) was carried out on 72% (3418) of the study population. Each household was revisited at 3-monthly intervals for up to 2 years to detect new leishmaniasis cases; 497 people received a second MST at the end of the study. Analysis of the epidemiological data indicated that (i) 17% (16/94) of all infections were subclinical, (ii) this percentage increased significantly with age, (iii) clinical infections led to 73.9% protective immunity (95% C.I. 53.0-85.5%) and relatively permanent MST responsiveness (recovery rate = 0.0098/year; 95% C.I. 0.000-0.020/year), (iv) sub-clinical infections led to protective immunity, which was positively correlated with their MST induration size (increasing by 17.9% per mm; P < 0.0001), and a mean MST recovery rate of 0.114/year (4/421 man-months), and (v) recurrent leishmaniasis was dominated by reactivations, not by reinfections. PMID:7705493

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: a review.

PubMed

Abdallah, Mohamed Abou-Elwafa; Pawar, Gopal; Harrad, Stuart

2015-01-01

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunohaematological and rheological parameters in canine visceral leishmaniasis.

PubMed

Silva, José Nivaldo da; Cotrim, Aron Carlos; Conceição, Luciana Auxiliadora Viebrantz da; Marins, Camila Moreira Ferreira; Marchi, Patricia Gelli Feres de; Honorio-França, Adenilda Cristina; Almeida, Arleana do Bom Parto Ferreira de; França, Eduardo Luzía; Sousa, Valéria Régia Franco

2018-05-24

The aim of this study was to find correlations between haematological and rheological parameters in canine visceral leishmaniasis (CLV). Enrolled dogs with CVL (n=31) had a confirmed diagnosis using the rapid test Dual Path Platform (TR DPP®) kit and Polymerase Chain Reaction (PCR) assay. A control group (n=31) comprised healthy dogs with negative results for the TR DPP® kit and PCR assay. Haematological parameters and total protein, albumin, globulin, and antibody were assessed. The rheological properties of the blood samples were also determined. Erythrocytes, haematocrit and platelet values of dogs in the CVL group were found to be lower than those of the control group. The total protein, globulin and IgG concentrations were higher in serum samples from the CVL group. The blood flow curve demonstrated increased shear rates in the CVL group. The viscosity of the blood from the infected animals was lower than in the healthy dogs. A positive correlation was found between erythrocyte numbers and blood viscosity. These data suggest that changes in the flow curve and viscosity of blood as well as the erythrocyte values may be a viable low-cost alternative for the monitoring of dogs with visceral leishmaniasis.

Immune Regulation during Chronic Visceral Leishmaniasis

PubMed Central

Faleiro, Rebecca J.; Kumar, Rajiv; Hafner, Louise M.; Engwerda, Christian R.

2014-01-01

Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed. PMID:25010815

Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs.

PubMed

Morrison, Glenn C; Weschler, Charles J; Bekö, Gabriel; Koch, Holger M; Salthammer, Tunga; Schripp, Tobias; Toftum, Jørn; Clausen, Geo

2016-01-01

To assess the influence of clothing on dermal uptake of semi-volatile organic compounds (SVOCs), we measured uptake of selected airborne phthalates for an individual wearing clean clothes or air-exposed clothes and compared these results with dermal uptake for bare-skinned individuals under otherwise identical experimental conditions. Using a breathing hood to isolate dermal from inhalation uptake, we measured urinary metabolites of diethylphthalate (DEP) and di-n-butylphthalate (DnBP) from an individual exposed to known concentrations of these compounds for 6 h in an experimental chamber. The individual wore either clean (fresh) cotton clothes or cotton clothes that had been exposed to the same chamber air concentrations for 9 days. For a 6-h exposure, the net amounts of DEP and DnBP absorbed when wearing fresh clothes were, respectively, 0.017 and 0.007 μg/kg/(μg/m(3)); for exposed clothes the results were 0.178 and 0.261 μg/kg/(μg/m(3)), respectively (values normalized by air concentration and body mass). When compared against the average results for bare-skinned participants, clean clothes were protective, whereas exposed clothes increased dermal uptake for DEP and DnBP by factors of 3.3 and 6.5, respectively. Even for non-occupational environments, wearing clothing that has adsorbed/absorbed indoor air pollutants can increase dermal uptake of SVOCs by substantial amounts relative to bare skin.

Pharmacokinetics of loxoprofen and its active metabolite after dermal application of loxoprofen gel to rats.

PubMed

Sawamura, R; Kazui, M; Kurihara, A; Izumi, T

2015-02-01

This study was conducted to evaluate the pharmacokinetics of loxoprofen (LX) and its active metabolite (trans-OH form) after a single dermal application of LX gel (LX-G) to rats. In the skin at the treated site, generation of the trans-OH form was detected and both LX and the trans-OH form remained at high concentrations for 24 h after dermal application. Furthermore, both LX and the trans-OH form also remained in the skeletal muscle over 24 h after the single dermal application, while they eliminated rapidly after the single oral administration. The area under the curve up to the last measurable point (AUC(0-t)) for plasma concentrations of LX or the trans-OH form after dermal application of LX-G was less than 11% of that after oral administration of LX. In addition, C(max) and AUC(0-t) increased in a saturable manner while increasing the dose. Overall, these results demonstrated that the trans-OH form was generated at the treated site with the process of dermal absorption of LX and it remained at the target site for a long period with low systemic exposure compared to oral administration.

Spatial patterns and secular trends in human leishmaniasis incidence in Morocco between 2003 and 2013.

PubMed

Sadeq, Mina

2016-05-11

Few studies on spatial patterns or secular trends in human leishmanias have been conducted in Morocco. This study aimed to examine spatial patterns and trends associated with the human leishmaniasis incidence rate (HLIR) at the province/prefecture level between 2003 and 2013 in Morocco. Only the available published country data on the HLIR between 2003 and 2013, from the open access files of the Ministry of Health, were used. Secular trends were examined using Kendall's rank correlation. An exploratory spatial data analysis was also conducted to examine the spatial autocorrelation (Global Moran's I and local indicator of spatial association [LISA]), and spatial diffusion at the province/prefecture level. The influence of various covariates (poverty rate, vulnerability rate, population density, and urbanization) on the HLIR was tested via spatial regression (ordinary least squares regression). At the country level, no secular variation was observed. Poisson annual incidence rate estimates were 13 per 100 000 population (95 % CI = 12.9-13.1) for cutaneous leishmaniasis (CL) and 0.4 per 100 000 population (95 % CI = 0.4-0.5) for visceral leishmaniasis (VL). The available data on HLIR were based on combined CL and VL cases, however, as the CL cases totally outnumbered the VL ones, HLIR may be considered as CL incidence rate. At the provincial level, a secular increase in the incidence rate was observed in Al Hoceima (P = 0.008), Taounate (P = 0.04), Larache (P = 0.002), Tétouan (P = 0.0003), Khenifra (P = 0.008), Meknes (P = 0.03), and El Kelaa (P = 0.0007), whereas a secular decrease was observed only in the Chichaoua province (P = 0.006). Even though increased or decreased rate was evident in these provinces, none of them showed clustering of leishmaniasis incidence. Significant spatial clusters of high leishmaniasis incidence were located in the northeastern part of Morocco, while spatial clusters of low leishmaniasis

Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian urban area.

PubMed

Toledo, Celina Roma Sánchez de; Almeida, Andréa Sobral de; Chaves, Sergio Augusto de Miranda; Sabroza, Paulo Chagastelles; Toledo, Luciano Medeiros; Caldas, Jefferson Pereira

2017-05-15

To analyze the determinants for the occurrence of human visceral leishmaniasis linked to the conditions of vulnerability. This is an ecological study, whose spatial analysis unit was the Territorial Analysis Unit in Araguaína, State of Tocantins, Brazil, from 2007 to 2012. We have carried out an analysis of the sociodemographic and urban infrastructure situation of the municipality. Normalized primary indicators were calculated and used to construct the indicators of vulnerability of the social structure, household structure, and urban infrastructure. From them, we have composed a vulnerability index. Kernel density estimation was used to evaluate the density of cases of human visceral leishmaniasis, based on the coordinates of the cases. Bivariate global Moran's I was used to verify the existence of spatial autocorrelation between the incidence of human visceral leishmaniasis and the indicators and index of vulnerability. Bivariate local Moran's I was used to identify spatial clusters. We have observed a pattern of centrifugal spread of human visceral leishmaniasis in the municipality, where outbreaks of the disease have progressively reached central and peri-urban areas. There has been no correlation between higher incidences of human visceral leishmaniasis and worse living conditions. Statistically significant clusters have been observed between the incidences of human visceral leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012) and the indicators and index of vulnerability. The environment in circumscribed areas helps as protection factor or increases the local vulnerability to the occurrence of human visceral leishmaniasis. The use of methodology that analyzes the conditions of life of the population and the spatial distribution of human visceral leishmaniasis is essential to identify the most vulnerable areas to the spread/maintenance of the disease. Analisar determinantes para a ocorrência da leishmaniose visceral humana vinculados �

Murine cutaneous leishmaniasis investigated by MALDI mass spectrometry imaging.

PubMed

Negrão, Fernanda; de O Rocha, Daniele F; Jaeeger, Caroline F; Rocha, Francisca J S; Eberlin, Marcos N; Giorgio, Selma

2017-09-26

Imaging mass spectrometry (IMS) is recognized as a powerful tool to investigate the spatial distribution of untargeted or targeted molecules of a wide variety of samples including tissue sections. Leishmania is a protozoan parasite that causes different clinical manifestations in mammalian hosts. Leishmaniasis is a major public health risk in different continents and represents one of the most important neglected diseases. Cutaneous lesions from mice experimentally infected with Leishmania spp. were investigated by matrix-assisted laser desorption ionization MS using the SCiLS Lab software for statistical analysis. Being applied to cutaneous leishmaniasis (CL) for the first time, MALDI-IMS was used to search for peptides and low molecular weight proteins (2-10 kDa) as candidates for potential biomarkers. Footpad sections of Balb/c mice infected with (i) Leishmania amazonensis or (ii) Leishmania major were imaged. The comparison between healthy and infected skin highlighted a set of twelve possible biomarker proteins for L. amazonenis and four proteins for L. major. Further characterization of these proteins could reveal how these proteins act in pathology progression and confirm their values as biomarkers.

Novel low-cost thermotherapy for cutaneous leishmaniasis in Peru.

PubMed

Valencia, Braulio M; Miller, David; Witzig, Richard S; Boggild, Andrea K; Llanos-Cuentas, Alejandro

2013-01-01

Thermotherapy is an accepted alternative therapy for new-world cutaneous leishmaniasis, but current heat-delivery modalities are too costly to be made widely available to endemic populations. We adapted a low-cost heat pack named the HECT-CL device that delivers safe, reliable, and renewable conduction heat. 25 patients with cutaneous leishmaniasis completed treatment with the device at an initial temperature of 52°C ± 2°C for 3 minutes to each lesion, repeated daily for 7 days, and were followed up for 6 months by direct observation. The overall definitive clinical cure rate was 60%. Concurrently, 13 patients meeting minimally significant exclusion criteria received identical compassionate use treatment with a cumulative definitive cure rate of 68.4%, 75% for those who had experienced CL relapse after prior antimonial treatment. Therapy was well tolerated. Reversible second-degree burns occurred in two patients and no bacterial super-infections were observed. HECT-CL is a promising treatment and deserves further study to verify its safety and efficacy as adjuvant and mono- therapy.

Novel Low-Cost Thermotherapy for Cutaneous Leishmaniasis in Peru

PubMed Central

Witzig, Richard S.; Boggild, Andrea K.; Llanos-Cuentas, Alejandro

2013-01-01

Thermotherapy is an accepted alternative therapy for new-world cutaneous leishmaniasis, but current heat-delivery modalities are too costly to be made widely available to endemic populations. We adapted a low-cost heat pack named the HECT-CL device that delivers safe, reliable, and renewable conduction heat. 25 patients with cutaneous leishmaniasis completed treatment with the device at an initial temperature of 52°C±2°C for 3 minutes to each lesion, repeated daily for 7 days, and were followed up for 6 months by direct observation. The overall definitive clinical cure rate was 60%. Concurrently, 13 patients meeting minimally significant exclusion criteria received identical compassionate use treatment with a cumulative definitive cure rate of 68.4%, 75% for those who had experienced CL relapse after prior antimonial treatment. Therapy was well tolerated. Reversible second-degree burns occurred in two patients and no bacterial super-infections were observed. HECT-CL is a promising treatment and deserves further study to verify its safety and efficacy as adjuvant and mono- therapy. PMID:23658851

Use of porcine acellular dermal matrix following early dermabrasion reduces length of stay in extensive deep dermal burns.

PubMed

Guo, Zhi-Qian; Qiu, Le; Gao, You; Li, Jin-Hu; Zhang, Xin-He; Yang, Xin-Lei; Peszel, April; Chen, Xu-Lin

2016-05-01

Extensive deep partial-thickness burns still seriously challenge the surgeon's abilities. This study aimed to assess the impact of early dermabrasion combined with porcine acellular dermal matrix (ADM) in extensive deep dermal burns. From September 2009 to September 2013, a total of 60 adult patients sustained greater than 50% total body surface area (TBSA) burn by hot water or gas explosion were divided into three groups based on dermabrasion: group A (early dermabrasion and porcine ADM), group B (early dermabrasion and nano-silver dressings), and group C (conservative group). The wound healing time and length of hospital stay were analyzed. Scar assessment was performed at 3 and 12 months after the injury with a modified Vancouver Scar Scale linked with TBSA (mVSS-TBSA). No significant difference was found in mean burn size, burn depth, age, male-to-female ratio, or incidence of inhalation injury between the patients in the three groups (p>0.05). Compared with groups B and C, the patients that received early dermabrasion combined with porcine ADM had a shorter wound healing time (p<0.01). The burn patients treated with early dermabrasion and porcine ADM coverage had a mean length of hospital stay of 28.3 days (±7.2), which was significantly shorter than that of groups B and C (p<0.05-0.01). The mVSS-TBSA of patients in group A was significantly improved in comparison with groups B and C at 3 and 12 months after the injury. There was no significant difference in the mortality rate between the three groups (p>0.05). Early dermabrasion combined with porcine ADM coverage facilitates wound healing, reduces the length of hospital stay, and improves esthetic and functional results in extensive deep dermal burns with burn size over 50% TBSA. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

The relationship between inadvertent ingestion and dermal exposure pathways: a new integrated conceptual model and a database of dermal and oral transfer efficiencies.

PubMed

Gorman Ng, Melanie; Semple, Sean; Cherrie, John W; Christopher, Yvette; Northage, Christine; Tielemans, Erik; Veroughstraete, Violaine; Van Tongeren, Martie

2012-11-01

Occupational inadvertent ingestion exposure is ingestion exposure due to contact between the mouth and contaminated hands or objects. Although individuals are typically oblivious to their exposure by this route, it is a potentially significant source of occupational exposure for some substances. Due to the continual flux of saliva through the oral cavity and the non-specificity of biological monitoring to routes of exposure, direct measurement of exposure by the inadvertent ingestion route is challenging; predictive models may be required to assess exposure. The work described in this manuscript has been carried out as part of a project to develop a predictive model for estimating inadvertent ingestion exposure in the workplace. As inadvertent ingestion exposure mainly arises from hand-to-mouth contact, it is closely linked to dermal exposure. We present a new integrated conceptual model for dermal and inadvertent ingestion exposure that should help to increase our understanding of ingestion exposure and our ability to simultaneously estimate exposure by the dermal and ingestion routes. The conceptual model consists of eight compartments (source, air, surface contaminant layer, outer clothing contaminant layer, inner clothing contaminant layer, hands and arms layer, perioral layer, and oral cavity) and nine mass transport processes (emission, deposition, resuspension or evaporation, transfer, removal, redistribution, decontamination, penetration and/or permeation, and swallowing) that describe event-based movement of substances between compartments (e.g. emission, deposition, etc.). This conceptual model is intended to guide the development of predictive exposure models that estimate exposure from both the dermal and the inadvertent ingestion pathways. For exposure by these pathways the efficiency of transfer of materials between compartments (for example from surfaces to hands, or from hands to the mouth) are important determinants of exposure. A database of

The quest for canine leishmaniasis in Romania: the presence of an autochthonous focus with subclinical infections in an area where disease occurred.

PubMed

Dumitrache, Mirabela Oana; Nachum-Biala, Yaarit; Gilad, Matan; Mircean, Viorica; Cazan, Cristina Daniela; Mihalca, Andrei Daniel; Baneth, Gad

2016-05-21

Canine leishmaniasis is a severe, potentially life-threatening, systemic vector-borne disease of dogs caused by protozoan parasites of the genus Leishmania. Romania has been traditionally regarded as a non-endemic country for leishmaniasis with sporadic human disease cases. However, the recent report of an autochthonous canine leishmaniasis case (the first in the last 80 years) suggested the presence of an infection focus in the area of Râmnicu Vâlcea. The present study describes a survey of canine leishmaniasis in this geographical area with comparison to a georeferenced dataset of sand fly distribution based on historical literature records. The study was carried out in Râmnicu Vâlcea and included samples (serum, blood and conjunctival swabs) collected from 80 dogs including client-owned dogs from two local practices and dogs from two public shelters. Serum anti-leishmanial antibodies were assessed by ELISA. All blood and conjunctival samples were assessed by real-time quantitative PCR, targeting the leishmanial kinetoplast minicircle DNA. Three dogs (3.7 %) were seropositive and another four (5.0 %) showed borderline results indicative of exposure or infection. TaqMan PCR was performed for all dogs, on both blood and conjunctival swabs. Seven dogs (8.7 %) were positive by conjunctival swab PCR and one dog (1.2 %) by blood PCR. None of the positive dogs presented clinical signs compatible with canine leishmaniasis. This is the first study evaluating canine leishmaniasis in a dog population in Romania by both highly sensitive PCR and serology. Although the prevalence was relatively low compared to other endemic regions, our results clearly demonstrate the presence of a canine leishmaniasis focus in Romania.

Dermal changes in superficial basal cell carcinoma, melanoma in situ and actinic keratosis and their implications

PubMed Central

Kazlouskaya, Viktoryia; Malhotra, Saurabh; Navarro, Raquel; Wu, Karen Nguyen; Shvartsbeyn, Marianna; Shengli, Chen; Gui, Jiang; Elston, Dirk M.

2018-01-01

Background Basal cell carcinoma (BCC) has a characteristic stroma, but less is known about the dermal characteristics associated with melanoma in situ (MIS) and actinic keratosis (AK). Materials and methods Dermal changes were studied in 301 specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from 90 randomly selected cases of those entities were used to assess the predictive value of the dermal changes. Agreement with the final diagnosis was calculated using kappa coefficient (κ). Results Fibromyxoid stroma was present in 82% of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK specimens (p <0.05). A lichenoid inflammatory infiltrate was frequently associated with AK and a perifollicular infiltrate with periadnexal fibrosis with MIS. Blinded evaluation of images of the dermal changes associated with the tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by the three appraisers. Coefficient of agreement in blinded imaged evaluation with the actual diagnosis was higher in the BCC and MIS compared with AK (κ = 0.37, p = 0.0001; κ = 0.2, p = 0.0005 and κ = −0.06, p = 0.84, respectively). Conclusion Dermal features may be helpful in predicting the correct diagnosis when tumor is not visible. PMID:24117926

PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

EPA Science Inventory

PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

M.J.K. Selgrade, E.H. Boykin, N.H. Coates, D.L. Doerfler, S.H. Gavett
Experimental Toxicology Div., National Health and Environmental Research Laboratory, Office of Research and Developmen...

Tricho-odonto-onycho-dermal dysplasia and WNT10A mutations.

PubMed

Kantaputra, P; Kaewgahya, M; Jotikasthira, D; Kantaputra, W

2014-04-01

We report on three novel (IVS2+1G>A splice site, c.1066G>T, and c.1039G>T, and one previously reported (c.637G>A) WNT10A mutations in three patients affected with odonto-onycho-dermal dysplasia (OODD; OMIM 275980). OODD is a rare form of autosomal recessive ectodermal dysplasia involving hair, teeth, nails, and skin, characterized by hypodontia (tooth agenesis), smooth tongue with marked reduction of filiform and fungiform papillae, nail dysplasia, dry skin, palmoplantar keratoderma, and hyperhidrosis of palms and soles. The novel IVS+1G>A splice site mutation is predicted to cause significant protein alteration. The other novel mutations we found including c.1066G>T and c.1039G>T are predicted to cause p.Gly356Cys and p.Glu347X, respectively. Barrel-shaped mandibular incisors and severe hypodontia appear to be associated with homozygous or compound heterozygous mutations of WNT10A. The name "tricho-odonto-onycho-dermal dysplasia" is suggested to replace "odonto-onycho-dermal dysplasia" because hair anomalies including hypotrichosis and slow-growing hair have been reported in numerous reported patients with this syndrome. © 2014 Wiley Periodicals, Inc.

Dermal absorption and urinary elimination of N-methyl-2-pyrrolidone.

PubMed

Bader, Michael; Keener, Stephen A; Wrbitzky, Renate

2005-09-01

The dermal absorption of the solvent N-methyl-2-pyrrolidone (NMP) and its elimination in urine was investigated in an experimental study. Seven volunteers were exposed to 1045 mg of liquid NMP under occlusive conditions for 2 h. Urine was collected before, during and up to 72 h after the exposure and analysed for NMP by GC/MS after liquid-liquid extraction. Additionally, the remaining NMP in the pads was determined to estimate the total dermal uptake. The concentration of NMP in urine increased rapidly after beginning of the exposure up to 1 h after the exposure was completed. A peak concentration of 1,836+/-863 microg/l was observed, the half-life in urine was 3.2 h. About 0.5% of the absorbed dose was excreted metabolically unchanged. An average dermal absorption of 5.5 mg cm(-2) h(-1) was calculated. The results of this study show that the percutaneous absorption of NMP may contribute significantly to the overall uptake of the solvent, e.g. in the workplace. Therefore, a biological monitoring of NMP exposed workers is essential for occupational-medical surveillance.

Hydrocortisone and triiodothyronine regulate hyaluronate synthesis in a tissue-engineered human dermal equivalent through independent pathways.

PubMed

Deshpande, Madhura; Papp, Suzanne; Schaffer, Lana; Pouyani, Tara

2015-02-01

Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix). We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in the tissue engineered human dermal matrix. To this end, neonatal human dermal fibroblasts were cultured in defined serum-free medium for 21 days in the presence of each hormone alone, or in combination, in varying concentrations. Through a process of self-assembly, a substantial dermal extracellular matrix formed that was characterized. The results of these studies demonstrate that combinations of the hormones T3 and hydrocortisone showed significantly higher levels of hyaluronate inhibition as compared to each hormone alone in the human dermal matrix. In order to gain preliminary insight into the genes regulating HA synthesis in this system, a differential gene array analysis was conducted in which the construct prepared in the presence of 200 μg/mL HC and 0.2 nM T3 was compared to the normal construct (0.4 μg/mL HC and 20 pM T3). Using a GLYCOv4 gene chip containing approximately 1260 human genes, we observed differential expression of 131 genes. These data suggest that when these two hormones are used in concert a different mechanism of inhibition prevails and a combination of degradation and inhibition of HA synthesis may be responsible for HA regulation in the human dermal matrix. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Functional trade-off between strength and thermal capacity of dermal armor: Insights from girdled lizards.

PubMed

Broeckhoven, Chris; du Plessis, Anton; Hui, Cang

2017-10-01

The presence of dermal armor is often unambiguously considered the result of an evolutionary predator-prey arms-race. Recent studies focusing predominantly on osteoderms - mineralized elements embedded in the dermis layer of various extant and extinct vertebrates - have instead proposed that dermal armor might exhibit additional functionalities besides protection. Multiple divergent functionalities could impose conflicting demands on a phenotype, yet, functional trade-offs in dermal armor have rarely been investigated. Here, we use high-resolution micro-computed tomography and voxel-based simulations to test for a trade-off between the strength and thermal capacity of osteoderms using two armored cordylid lizards as model organisms. We demonstrate that high vascularization, associated with improved thermal capacity might limit the strength of osteoderms. These results call for a holistic, cautionary future approach to studies investigating dermal armor, especially those aiming to inspire artificial protective materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimation of intake and uptake of bisphenols and triclosan from personal care products by dermal contact.

PubMed

Lu, Shaoyou; Yu, Yuling; Ren, Lu; Zhang, Xiaolan; Liu, Guihua; Yu, Yingxin

2018-04-15

Increasing concern has been raised in respect of exposure to bisphenols and triclosan (TCS) due to their widespread use. However, little is known about their occurrence in personal care products (PCPs) or, particularly, their dermal uptake following daily application. It is therefore necessary to evaluate the human health risk of bisphenols and TCS via dermal absorption. In this study, 150 PCPs, covering 11 different categories, were collected in China. The concentrations of seven bisphenol analogues and TCS were measured, and the associated human health risks by dermal contact were estimated. High detection frequencies of TCS (46.7%) and bisphenol AF (38.7%) were found in the PCPs. The highest mean concentration of Σ 7 BPs (sum concentration of all seven bisphenols) was 77.8ngg -1 found in masks, and the highest mean concentration of TCS was 86.7ngg -1 in hand sanitizers. The bisphenol composition profiles varied among different categories. Bisphenol A and bisphenol F generally showed higher concentrations. Combining the concentrations of the target substances with the daily usage quantities of PCPs and other parameters, the total estimated dermal intakes and uptakes of Σ 7 BPs and TCS were calculated. The results showed that the former (12.1 and 1.06ng·kg -1 bw day -1 ) were markedly higher than the latter (1.21 and 9.58×10 -2 ng·kg -1 bw day -1 ), which included dermal absorption rates of the chemicals in the estimation. Although diet is the main source, and oral ingestion is the main route, for human BPA exposure, the results of the estimated dermal uptakes of BPA in the present study combined with those from a European study show that dermal contact is the main route with thermal paper being the main contributor when both unconjugated and conjugated BPA in the human body are considered. The present study also showed that exposure to BPA in PCPs following dermal contact should not be ignored. Copyright © 2017 Elsevier B.V. All rights reserved.

Parasitological and biochemical studies on cutaneous leishmaniasis in Shara'b District, Taiz, Yemen.

PubMed

Asmaa, Qhtan; Al-Shamerii, Salwa; Al-Tag, Mohammed; Al-Shamerii, Adam; Li, Yiping; Osman, Bashir H

2017-07-04

The leishmaniasis is a group of diseases caused by intracellular haemoflagellate protozoan parasites of the genus Leishmania. Leishmaniasis has diverse clinical manifestations; cutaneous leishmaniasis (CL) is the most common form of leishmaniasis which is responsible for 60% of disability-adjusted life years. CL is endemic in Yemen. In Shara'b there is no reference study available to identify the prevalence of endemic diseases and no investigation has been conducted for diagnosing the diseases. This study was conducted in villages for CL which collected randomly. The study aimed at investigating the epidemiological factors of CL in Shara'b by using questioner. Symptoms of lesions in patients suffering from CL, confirmed by laboratory tests, gave a new evidence of biochemical diagnosis in 525 villagers aged between 1 and 60 years old. Venous bloods were collected from 99 patients as well as from 51 control after an overnight fast. The percentage prevalence of CL was found 18.8%. The prevalence rate of infection among males (19.3%) was higher than females (18.40%). Younger age group (1-15) had a higher prevalence rate (20.3%) than the other age groups. Furthermore, the population with no formal education had the higher rate of infection (61% of the total). A significant increase of serum malondialdehyde (P < 0.001) in CL patients was obtained. The highest level of MDA may be due to over production of ROS and RNS results in oxidative stress and the acceleration of lipid peroxidation in CL patients. There were high prevalence rates of CL in Shara'b. The patient who had CL has been found with many changes in some biochemical levels. This study provides a clear indication on the role of MDA as an early biochemical marker of peroxidation damage occurring during CL. Increased uric acid, and catalase activity was provided of free radical.

Leishmania tropica-induced cutaneous and presumptive concomitant viscerotropic leishmaniasis with prolonged incubation.

PubMed

Weiss, Francesca; Vogenthaler, Nicholas; Franco-Paredes, Carlos; Parker, Sareeta R S

2009-09-01

Leishmaniasis includes a spectrum of diseases caused by protozoan parasites belonging to the genus Leishmania. The disease is traditionally classified into visceral, cutaneous, or mucocutaneous leishmaniasis, depending on clinical characteristics as well as the species involved. Leishmania tropica is one of the causative agents of cutaneous leishmaniasis, with a typical incubation period of weeks to months. Observation We describe a 17-year-old Afghani girl who had lived in the United States for 4 years and who presented with a 6-month history of pretibial ulcerations, 9.1-kg weight loss, abdominal pain, splenomegaly, and extreme fatigue. Histopathologic examination and culture with isoenzyme electrophoresis speciation of her skin lesions confirmed the presence of L tropica. In addition, results of serum laboratory and serological studies were highly suggestive of concomitant visceral involvement. The patient was treated with a 28-day course of intravenous pentavalent antimonial compound sodium stibogluconate with complete resolution of her systemic signs and symptoms and improvement of her pretibial ulcerations. This is an exceptional case in that our patient presented with disease after an incubation period of years rather than the more typical weeks to months. In addition, this patient had confirmed cutaneous involvement, as well as strong evidence of viscerotropic disease caused by L tropica, a species that characteristically displays dermotropism, not viscerotropism.

Cutaneous Leishmaniasis in Pediatric Patients in a Single Tertiary Hospital in Ankara.

PubMed

Kaman, Ayşe; Tanır, Gönül; Gayretli Aydın, Zeynep Gökçe; Metin, Özge; Aydın Teke, Türkan; Öz, Fatma Nur; Mungan, Mesut

2017-12-01

Leishmaniasis is an infectious disease that is caused by a protozoan parasite of the Leishmania genus and that occurs worldwide. Leishmaniasis is endemic in southeastern Turkey and the neighboring Middle Eastern countries. The purpose of this study was to describe the clinical characteristics of patients admitted to our hospital with a diagnosis of cutaneous leishmaniasis (CL). A total of 16 CL patients [11 (69%) boys and five (31%) girls] were admitted between January 2014 and December 2015. The data of the patients were retrospectively recorded from their medical records. Their mean age was 74.3±32.3 months (range: 1-10.5 years). Double lesions were most commonly seen in eight (50%) patients. The face and neck was the most commonly involved site (87.5% of the patients). Skin smears for a parasitological examination were positive in nine (56%) patients. Two patients (12.5%) with limb lesions were treated with intralesional meglumine antimoniate. Fourteen patients were treated with systemic agents. We felt that the increase in human movement that include travels and forced migration due to the war might make it possible for CL to appear in non-endemic provinces such as Ankara. In particular, in patients with painless cutaneous lesion(s) who came from endemic areas such as Syria, CL should be kept in mind by the clinicians that residing in even non-endemic areas .

Studies on African Trypanosomiasis and Leishmaniasis. Volume 2.

DTIC Science & Technology

1984-07-01

8217 flies with heavy infections in their anterior midguts transmit parasites when they feed is not known, but the biting behavior of such insects is not the...of cutaneous leishmaniasis by contaminated mouthparts of the 4 hamsters developed a culture-positive nose lesion of both biting and nonbiting insects ...the cibarium, an experiment predicated on the hypothesis that such infections interfer with cibarial blood meal-sensing receptors , thereby changing

[Multiple digestive involvement in visceral leishmaniasis in a patient with HIV infection: favourable course with itraconazole].

PubMed

Béchade, D; Seurat, L; Discamps, G; Tanière, P H; Du Bourguet, F

1996-01-01

We report a case of visceral leishmaniasis due to Leishmania infantum in a 35 year-old patient with acquired immunodeficiency syndrome who complained of chronic diarrhea. Biopsy specimens of gastric and duodenal mucosa and bone marrow aspirate led to the diagnosis. Enterocytozoon bieneusi, fortuitously found in the duodenal mucosa, did not seem to be the causative agent of diarrhea in this case, but its association with visceral leishmaniasis is rare. A treatment with itraconazole brought about a sustained clinical remission.

American tegumentary leishmaniasis: correlations among immunological, histopathological and clinical parameters.

PubMed

Martins, Ana Luiza Grizzo Peres; Barreto, Jaison Antonio; Lauris, José Roberto Pereira; Martins, Ana Claudia Grizzo Peres

2014-01-01

American tegumentary leishmaniasis has an annual incidence of 1 to 1.5 million cases. In some cases, the patient's immune response can eliminate the parasite, and the lesion spontaneously resolves. However, when this does not occur, patients develop the disseminated form of the disease. To investigate the association between clinical, laboratory and pathological findings in cases of American tegumentary leishmaniasis. A retrospective study of the medical records of 47 patients with American cutaneous leishmaniasis. Clinical, laboratory and epidemiological data were collected, and semi-quantitative histopathological analyses were performed using the Spearman correlation coefficient (p <0.05). Mean patient age was 40.5 years. A total of 29.7% individuals were female and 70.2% were male, and 40.4% of the patients were farmers. The ulcerative form was found in 53.2% of patients, of whom 59.6% had lesions in the limbs. The average time to diagnosis was 22.3 months. The following positive correlations were significant: age and duration of the disease, Montenegro reaction, degree of granulomatous transformation and epithelioid cell count; duration of disease, Montenegro reaction and number of lymphocytes; epithelial hyperplasia and edema, hemorrhaging, and epithelial aggression; number of plasmocytes and number of parasites. The main negative correlations found were as follows: age and serology; time and parasite load; epithelial hyperplasia and degree of granulomatous transformation. The long duration of the disease could be explained by the fact that lesions were relatively asymptomatic, and therefore ignored by patients with low literacy levels. Individuals may have simply waited for spontaneous healing, which proved to be dependent on the activation of hypersensitivity mechanisms.

Quantitative dermal measurements following treatment with AirGent.

PubMed

Kobus, Kazimierz F; Dydymski, Tomasz

2010-09-01

As an alternative to other minimally-invasive approaches to facial rejuvenation, enhancement and treatment of the dermis with a compressed air molecule of hyaluronic acid (HA) is a promising method in that it lacks some of the drawbacks of other procedures. The novelty of these systems, one of which is tested in this study, is based on the supposition that jet lateral dispersion of HA produces both instant dermal augmentation and specific wound-healing processes, leading to its long-term dermal thickening. The authors report on the efficacy and safety of the AirGent system (PerfAction, Rehovot, Israel), which is a renewal system designed to initiate a wound-healing process in the dermal layer. It is a computer-guided system that delivers treatment through compressed air molecules of HA to the dermal layer of the skin. The authors treated 20 patients (a total of 105 treatment sessions) with the AirGent system between May 2008 and November 2008. Each patient received three treatments at three- to four-week intervals. Each patient's skin thickness was measured with ultrasonography pretreatment, immediately after each session, and at six months posttreatment. Seven days after the last procedure, an increase in skin thickness was observed in all patients. The most significant differences were noted in the upper lip area, where the thickness had increased by an average of 1.3 mm. Six months after the last session, an increase in skin thickness was still noted in most patients, at which time the biggest difference was noted around the eyes, where the skin remained thicker by an average of 0.77 mm over baseline. According to the results of the Global Improvement Assessment questionnaire, at the six-month follow-up to evaluate their satisfaction with the long-term results, at least 59.9% of patients still noted at least a slight improvement in their appearance. Although a small group of patients and a relatively short period of observation limit the scope of our conclusions

Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis.

PubMed

Carvalho, Augusto M; Magalhães, Andréa; Carvalho, Lucas P; Bacellar, Olívia; Scott, Phillip; Carvalho, Edgar M

2013-11-09

The main clinical forms of tegumentary leishmaniasis are cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). L.braziliensis infection is characterized by an exaggerated production of IFN-gamma and TNF-alpha, cytokines involved in parasite destruction, but also in the pathology. Maintenance of an antigen-specific immune response may be important for resistance to re-infection and will contribute for vaccine development. In the present work we investigated the immune response in CL and ML cured individuals. Participants in the present study included 20 CL and 20 ML patients, who were evaluated prior to, as well as 2 to 15 years after therapy. IFN-gamma, IL-2 and TNF-alpha production were determined by ELISA in supernatants of mononuclear cells stimulated with soluble L.braziliensis antigen (SLA). The frequency of memory CD4+ T cell populations was determined by FACS. Here we show that the majority of CL and ML patients did not produce in vitro IFN-gamma in response to SLA after cure. In the cured individuals who responded to SLA, effector memory (CD45RA-CCR7-) CD4+ T cells were the ones producing IFN-gamma. Because a large percent of CL and ML cured patients lost SLA-induced IFN-gamma production in peripheral blood, we performed Leishmania skin test (LST). A positive LST was found in 87.5% and 100% of CL and ML cured individuals, respectively, who did not produce IFN-gamma or IL-2 in vitro. This study shows that in spite of losing in vitro antigen-specific response to Leishmania, cured CL and ML subjects retain the ability to respond to SLA in vivo. These findings indicate that LST, rather than IFN-gamma production, may be a better assessment of lasting immunity to leishmaniasis in human studies, and thus a better tool for assessing immunization after vaccine. Furthermore, in cured individuals which maintains Leishmania-specific IFN-gamma production, effector memory CD4+ T cells were the main source of this cytokine.

Epidemiology of Imported Leishmaniasis in Italy: Implications for a European Endemic Country

PubMed Central

Di Muccio, Trentina; Scalone, Aldo; Bruno, Antonella; Marangi, Massimo; Grande, Romualdo; Armignacco, Orlando; Gradoni, Luigi; Gramiccia, Marina

2015-01-01

In the past decade, the number of imported leishmaniasis cases has increased in countries of Western Europe. The trend is associated with increasing travels, ecotourism activity, military operations and immigration. While in endemic countries leishmaniasis is usually well diagnosed, accurate patient history and parasite identification are necessary to distinguish between autochthonous and imported cases. This is particularly important, as new Leishmania species/genotypes may be introduced and transmitted by local phlebotomine vectors without appropriate surveillance, with unpredictable consequences. We report on the surveillance of imported leishmaniasis performed by the Leishmania Identification Reference Centre of Rome from 1986 through 2012, involving health care centres from 16/20 Italian regions. Suspected imported cases were analyzed and conclusions were based on clinical, epidemiological and diagnostic findings. Over the years, different parasite identification methods were employed, including MultiLocus Enzyme Electrophoresis and molecular techniques combining disease diagnosis (SSU rDNA nested-PCR) and Leishmania typing (nuclear repetitive sequence and ITS-1 PCR-RFLPs). A total of 105 imported cases were recorded (annual range: 0-20) of which 36 were visceral (VL) (16 HIV-coinfections) and 69 cutaneous (CL) cases; 85 cases (52 CL) were from the Old World and 20 (17 CL) from the New World. Eight Leishmania species were identified, of which 7 were exotic to Italy. VL importation until 1995 was associated with the spread of Mediterranean Leishmania-HIV co-infections in early 1990s. Following the introduction of HAART treatment, such cases became occasional in Italians but relatively frequent among immigrants. In contrast, a steady increase of CL cases was observed from different areas of the Old and New Worlds, that in recent years included mainly immigrants ‘visiting friends and relatives’ and Italian tourists. This positive trend likely depends on

Electrical, structural and thermal studies of carbon nanotubes from natural legume seeds: kala chana

NASA Astrophysics Data System (ADS)

Ranu, Rachana; Chauhan, Yatishwar; Singh, Pramod K.; Bhattacharya, B.; Tomar, S. K.

2016-12-01

Carbon nanotubes (CNTs) are the carbon materials measured at nanoscale level and they are defined in two types according to the number of concentric layers, i.e. single-layer tube is single-walled nanotubes, while multi-layer tube structure is called multi-walled nanotubes. The green method synthesis for the preparation of CNTs begins with the smashing of legume seeds kala chana, and then they form complex with cobalt salt. Desiccation of the complex compound forms cobalt salt and seed protein. The complex is then decomposed at 625 °C in muffle furnace for 20 min. Purification of the decomposed sample is done through acid wash treatment and dried in vacuum oven. The confirmations of CNTs are done by nuclear magnetic resonance and Fourier transform infrared, which analyzes the denatured protein, reacted to the metal salt. X-Ray diffraction determines the MWNTs with transmission electron microscope (TEM) reports the network structure of CNTs. thermal gravimetric analysis (TGA)-differential thermal analysis (DTA)-thermogravimetric analysis (DTG) tests the amount of sample under thermal treatment. Vibrating sample magnetometer determines the paramagnetic nature of CNTs. CNTs thus prepared can be used in mechanical fields, in solar cells, in electronics fields, etc. because of their multidisciplinary properties. The synthesized CNTs are eco-friendly in nature, prepared by the legume seed natural precursor.

Nitrotyrosine localization to dermal nerves in borderline leprosy.

PubMed

Schön, T; Hernández-Pando, R; Baquera-Heredia, J; Negesse, Y; Becerril-Villanueva, L E; Eon-Contreras, J C L; Sundqvist, T; Britton, S

2004-03-01

Nerve damage is a common and disabling feature of leprosy, with unclear aetiology. It has been reported that the peroxidizing agents of myelin lipids-nitric oxide (NO) and peroxynitrite-are produced in leprosy skin lesions. To investigate the localization of nitrotyrosine (NT)-a local end-product of peroxynitrite-in leprosy lesions where dermal nerves are affected by a granulomatous reaction. We investigated by immunohistochemistry and immunoelectron microscopy the localization of the inducible NO synthase (iNOS) and NT in biopsies exhibiting dermal nerves from patients with untreated leprosy. There were abundant NT-positive and iNOS-positive macrophages in the borderline leprosy granulomas infiltrating peripheral nerves identified by light microscopy, S-100 and neurofilament immunostaining. Immunoelectron microscopy showed NT reactivity in neurofilament aggregates and in the cell wall of Mycobacterium leprae. Our results suggest that NO and peroxynitrite could be involved in the nerve damage following borderline leprosy.

Visceral leishmaniasis in the state of Sao Paulo, Brazil: spatial and space-time analysis

PubMed Central

Cardim, Marisa Furtado Mozini; Guirado, Marluci Monteiro; Dibo, Margareth Regina; Chiaravalloti, Francisco

2016-01-01

ABSTRACT OBJECTIVE To perform both space and space-time evaluations of visceral leishmaniasis in humans in the state of Sao Paulo, Brazil. METHODS The population considered in the study comprised autochthonous cases of visceral leishmaniasis and deaths resulting from it in Sao Paulo, between 1999 and 2013. The analysis considered the western region of the state as its studied area. Thematic maps were created to show visceral leishmaniasis dissemination in humans in the municipality. Spatial analysis tools Kernel and Kernel ratio were used to respectively obtain the distribution of cases and deaths and the distribution of incidence and mortality. Scan statistics were used in order to identify spatial and space-time clusters of cases and deaths. RESULTS The visceral leishmaniasis cases in humans, during the studied period, were observed to occur in the western portion of Sao Paulo, and their territorial extension mainly followed the eastbound course of the Marechal Rondon highway. The incidences were characterized as two sequences of concentric ellipses of decreasing intensities. The first and more intense one was found to have its epicenter in the municipality of Castilho (where the Marechal Rondon highway crosses the border of the state of Mato Grosso do Sul) and the second one in Bauru. Mortality was found to have a similar behavior to incidence. The spatial and space-time clusters of cases were observed to coincide with the two areas of highest incidence. Both the space-time clusters identified, even without coinciding in time, were started three years after the human cases were detected and had the same duration, that is, six years. CONCLUSIONS The expansion of visceral leishmaniasis in Sao Paulo has been taking place in an eastbound direction, focusing on the role of highways, especially Marechal Rondon, in this process. The space-time analysis detected the disease occurred in cycles, in different spaces and time periods. These meetings, if considered, may

Why calpain inhibitors are interesting leading compounds to search for new therapeutic options to treat leishmaniasis?

PubMed

Ennes-Vidal, Vitor; Menna-Barreto, Rubem Figueiredo Sadock; Branquinha, Marta Helena; Dos Santos, André Luis Souza; D'Avila-Levy, Claudia Masini

2017-02-01

Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials. The deregulated activity of these enzymes is associated with several pathologies, such as strokes, diabetes and Parkinson's disease, to name a few. In Leishmania, calpain upregulation has been associated to drug resistance and virulence. Whereas the difficulties in developing new drugs for neglected diseases are more economical than biotechnological, repurposing approach with compounds already approved for clinical use by the regulatory agencies can be an interesting shortcut to a successful chemotherapeutic treatment for leishmaniasis.

Epidemiology and Control of Malaria, Leishmaniasis and Schistosomiasis in Brazil

DTIC Science & Technology

1991-02-15

using a 22 gauge needle. The aspirates were inoculated onto NNN media overlaid with 0.9% NaCl with Gentamyacin and . Penicillin /Streptomyosin, and...13-16. 2. Chulay JD, Oster CN, McGreevy PB, Hendricks LD, Kreutzer RD, 1988. American cutaneous leishmaniasis. Rev Soc Brasileira Med Trop 21 165-72

Risk factors for cutaneous leishmaniasis in the rainforest of Bolivia: a cross-sectional study.

PubMed

Eid, Daniel; Guzman-Rivero, Miguel; Rojas, Ernesto; Goicolea, Isabel; Hurtig, Anna-Karin; Illanes, Daniel; San Sebastian, Miguel

2018-01-01

Cutaneous leishmaniasis (CL) is an endemic disease in Bolivia, particularly in the rainforest of Cochabamba, in the municipality of Villa Tunari. The precarious, dispersed, and poorly accessible settlements in these farming communities make it difficult to study them, and there are no epidemiological studies in the area. The aim of the present study was to identify the risk factors associated with cutaneous leishmaniasis. A cross-sectional study was conducted in August 2015 and August 2016 in two communities of Villa Tunari, Cochabamba. The cases were diagnosed through clinical examinations, identification of the parasite by microscopic examination, and the Montenegro skin test. Risk factors were identified through logistic regression. A total of 274 participants (40.9% female and 59.1% male) were surveyed, of which 43% were CL positive. Sex was the only factor associated with CL with three times more risk for men than for women; this finding suggests a sylvatic mechanism of transmission in the area. It is advisable to focus on education and prevention policies at an early age for activities related to either leisure or work. Further research is needed to assess the influence of gender-associated behavior for the risk of cutaneous leishmaniasis.

Dermal in vitro penetration of methiocarb, paclobutrazol, and pirimicarb: effect of nonylphenolethoxylate and protective gloves.

PubMed Central

Nielsen, J B; Andersen, H R

2001-01-01

Dermal exposure has become the major route of human occupational exposure to pesticides. Detergents are used as part of formulated pesticide products and are known to change the barrier properties of human skin in vitro. However, studies on the influence of detergents as well as protective glove materials on dermal penetration of pesticides are scarce. In an experiment using in vitro static diffusion cells mounted with human skin, we evaluated the effect of nonylphenol-ethoxylate on dermal penetration of three extensively used pesticides--methiocarb, paclobutrazol, and pirimicarb--and the protection against dermal penetration offered by protective gloves made of latex or nitrile. There was a general tendency, though not statistically significant for all pesticides, for nonylphenolethoxylate to decrease the percutaneous penetration of the three pesticides. The nitrile generally offered better protection against percutaneous penetration of pesticides than did latex, but the degree of protection decreased over time and depended on the pesticides used. PMID:11266321

Evaluation of two recombinant Leishmania proteins identified by an immunoproteomic approach as tools for the serodiagnosis of canine visceral and human tegumentary leishmaniasis.

PubMed

Coelho, Eduardo Antonio Ferraz; Costa, Lourena Emanuele; Lage, Daniela Pagliara; Martins, Vívian Tamietti; Garde, Esther; de Jesus Pereira, Nathália Cristina; Lopes, Eliane Gonçalves Paiva; Borges, Luiz Felipe Nunes Menezes; Duarte, Mariana Costa; Menezes-Souza, Daniel; de Magalhães-Soares, Danielle Ferreira; Chávez-Fumagalli, Miguel Angel; Soto, Manuel; Tavares, Carlos Alberto Pereira

2016-01-15

Serological diagnostic tests for canine and human leishmaniasis present problems related with their sensitivity and/or specificity. Recently, an immunoproteomic approach performed with Leishmania infantum proteins identified new parasite antigens. In the present study, the diagnostic properties of two of these proteins, cytochrome c oxidase and IgE-dependent histamine-releasing factor, were evaluated for the serodiagnosis of canine visceral (CVL) and human tegumentary (HTL) leishmaniasis. For the CVL diagnosis, sera samples from non-infected dogs living in an endemic or non-endemic area of leishmaniasis, sera from asymptomatic or symptomatic visceral leishmaniasis (VL) dogs, from Leish-Tec(®)-vaccinated dogs, and sera from animals experimentally infected by Trypanosoma cruzi or Ehrlichia canis were used. For the HTL diagnosis, sera from non-infected subjects living in an endemic area of leishmaniasis, sera from active cutaneous or mucosal leishmaniasis patients, as well as those from T. cruzi-infected patients were employed. ELISA assays using the recombinant proteins showed both sensitivity and specificity values of 100% for the serodiagnosis of both forms of disease, with high positive and negative predictive values, showing better diagnostic properties than the parasite recombinant A2 protein or a soluble Leishmania antigen extract. In this context, the two new recombinant proteins could be considered to be used in the serodiagnosis of CVL and HTL. Copyright © 2015 Elsevier B.V. All rights reserved.

Function of Macrophage and Parasite Phosphatases in Leishmaniasis

PubMed Central

Soulat, Didier; Bogdan, Christian

2017-01-01

The kinetoplastid protozoan parasites belonging to the genus Leishmania are the causative agents of different clinical forms of leishmaniasis, a vector-borne infectious disease with worldwide prevalence. The protective host immune response against Leishmania parasites relies on myeloid cells such as dendritic cells and macrophages in which upon stimulation by cytokines (e.g., interferon-γ) a complex network of signaling pathways is switched on leading to strong antimicrobial activities directed against the intracellular parasite stage. The regulation of these pathways classically depends on post-translational modifications of proteins, with phosphorylation events playing a cardinal role. Leishmania parasites deactivate their phagocytic host cells by inducing specific mammalian phosphatases that are capable to impede signaling. On the other hand, there is now also evidence that Leishmania spp. themselves express phosphatases that might target host cell molecules and thereby facilitate the intracellular survival of the parasite. This review will present an overview on the modulation of host phosphatases by Leishmania parasites as well as on the known families of Leishmania phosphatases and their possible function as virulence factors. A more detailed understanding of the role of phosphatases in Leishmania–host cell interactions might open new avenues for the treatment of non-healing, progressive forms of leishmaniasis. PMID:29312331

Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

PubMed Central

Higgins, Claire A.; Chen, James C.; Cerise, Jane E.; Jahoda, Colin A. B.; Christiano, Angela M.

2013-01-01

De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

Urban Transmission of American Cutaneous Leishmaniasis in Argentina: Spatial Analysis Study

PubMed Central

Gil, José F.; Nasser, Julio R.; Cajal, Silvana P.; Juarez, Marisa; Acosta, Norma; Cimino, Rubén O.; Diosque, Patricio; Krolewiecki, Alejandro J.

2010-01-01

We used kernel density and scan statistics to examine the spatial distribution of cases of pediatric and adult American cutaneous leishmaniasis in an urban disease-endemic area in Salta Province, Argentina. Spatial analysis was used for the whole population and stratified by women > 14 years of age (n = 159), men > 14 years of age (n = 667), and children < 15 years of age (n = 213). Although kernel density for adults encompassed nearly the entire city, distribution in children was most prevalent in the peripheral areas of the city. Scan statistic analysis for adult males, adult females, and children found 11, 2, and 8 clusters, respectively. Clusters for children had the highest odds ratios (P < 0.05) and were located in proximity of plantations and secondary vegetation. The data from this study provide further evidence of the potential urban transmission of American cutaneous leishmaniasis in northern Argentina. PMID:20207869

Dermal exposure of applicators to chlorpyrifos on rice farms in Ghana.

PubMed

Atabila, Albert; Phung, Dung Tri; Hogarh, Jonathan N; Osei-Fosu, Paul; Sadler, Ross; Connell, Des; Chu, Cordia

2017-07-01

Studies evaluating dermal exposure to pesticides among applicators in tropical countries have largely been conducted using the patch dosimetry and hand wiping/washing techniques. This study used the more accurate whole-body dosimetry technique to evaluate dermal exposure to chlorpyrifos among applicators on rice farms in Ghana. The exposure levels were plotted as Cumulative Probability Distribution (CPD). Total Dermal Exposure (TDE) of chlorpyrifos among the median exposed and the 5% highly exposed groups during a spray event were 24 mg and 48 mg, respectively. When these were converted as a percentage of the quantity of active ingredient applied (Unit Exposure, UE), UE values of 0.03% and 0.06% were found among the median exposed and the 5% highly exposed groups, respectively. Overall, the hands were the most contaminated anatomical regions of the applicators, both in terms of proportion of TDE (39%) and skin loading (13 μg/cm 2 ). Also, the lower anatomical region was more contaminated (82% of TDE) compared to the upper anatomical region (18% of TDE). The levels of chlorpyrifos TDE among the applicators were found to be influenced by the quantity of insecticide applied and the height of the crops sprayed (p < 0.05). The pesticide UE data of the present study can be used to estimate the levels of dermal exposure under similar pesticide use scenarios among applicators. The findings of the present study suggest that protecting the hands and the lower anatomical regions with appropriate PPE may significantly reduce exposure among applicators. Copyright © 2017 Elsevier Ltd. All rights reserved.

Climate change and threat of vector-borne diseases in India: are we prepared?

PubMed

Dhiman, Ramesh C; Pahwa, Sharmila; Dhillon, G P S; Dash, Aditya P

2010-03-01

It is unequivocal that climate change is happening and is likely to expand the geographical distribution of several vector-borne diseases, including malaria and dengue etc. to higher altitudes and latitudes. India is endemic for six major vector-borne diseases (VBD) namely malaria, dengue, chikungunya, filariasis, Japanese encephalitis and visceral leishmaniasis. Over the years, there has been reduction in the incidence of almost all the diseases except chikungunya which has re-emerged since 2005. The upcoming issue of climate change has surfaced as a new threat and challenge for ongoing efforts to contain vector-borne diseases. There is greater awareness about the potential impacts of climate change on VBDs in India and research institutions and national authorities have initiated actions to assess the impacts. Studies undertaken in India on malaria in the context of climate change impact reveal that transmission windows in Punjab, Haryana, Jammu and Kashmir and north-eastern states are likely to extend temporally by 2-3 months and in Orissa, Andhra Pradesh and Tamil Nadu there may be reduction in transmission windows. Using PRECIS model (driven by HadRM2) at the resolution of 50 x 50 Km for daily temperature and relative humidity for year 2050, it was found that Orissa, West Bengal and southern parts of Assam will still remain malarious and transmission windows will open up in Himachal Pradesh and north-eastern states etc. Impact of climate change on dengue also reveals increase in transmission with 2 C rise in temperature in northern India. Re-emergence of kala-azar in northern parts of India and reappearance of chikungunya mainly in southern states of India has also been discussed. The possible need to address the threat and efforts made in India have also been highlighted. The paper concludes with a positive lead that with better preparedness threat of climate change on vector-borne diseases may be negated.

Pathogenicity of Leishmania donovani is associated with the high expression of a group low molecular weight proteins

PubMed Central

Mitra, Partha

2015-01-01

Background: With few exceptions, members of the Leishmania donovani complex such as L. donovani, L. infantum and L. chagashi are the etiological agents of visceral leishmaniasis or kala-azar. Promastigotes of Leishmania spp. lose their Pathogenicity; the ability to establish infection in a susceptible host, after prolonged culture. The molecular basis of this evolution of pathogenic to nonpathogenic culture has not been very well understood. It has been proposed that the loss of pathogenicity is associated with the gradual disappearance of selective parasite proteins. An alternative hypothesis is that during prolonged culture, the pathogenic clonal population of the parasite is deleted from the mixed population due to their selection pressure. This clonal deletion is proposed to be responsible for the emergence of the nonpathogenic population. Study Methodology and Results: We have a done a series of two-dimensional polyacrylamide gel electrophoresis followed by western blot experiments to study the antigenic profile of few L. donovani isolates of Indian origin. We observed a gradual and significant downregulation of expression of a group of low molecular weight proteins (LMW, molecular weight 20–30 kDa) which are associated with loss of pathogenicity. These proteins are recognized only by antiserum raised against the whole cell extract of one of the pathogenic Indian L. donovani isolates, Ag83, and remained undetected by antiserum raised against the nonpathogenic AG83 isolates. These LMW proteins were also present in the nonpathogenic extract in very low levels and remained undetected by the virulent serum, indicating a phenomenon of simultaneous downregulation of the expression and altered immunogenicity. LMW proteins were universally expressed in all early passage Indian isolate we tested and also detected in two clones obtained from pathogenic parasite culture. The antigenic patterns of none of the eight clones obtained from nonpathogenic culture were not

Pathogenicity of Leishmania donovani is associated with the high expression of a group low molecular weight proteins.

PubMed

Mitra, Partha

2015-01-01

With few exceptions, members of the Leishmania donovani complex such as L. donovani, L. infantum and L. chagashi are the etiological agents of visceral leishmaniasis or kala-azar. Promastigotes of Leishmania spp. lose their Pathogenicity; the ability to establish infection in a susceptible host, after prolonged culture. The molecular basis of this evolution of pathogenic to nonpathogenic culture has not been very well understood. It has been proposed that the loss of pathogenicity is associated with the gradual disappearance of selective parasite proteins. An alternative hypothesis is that during prolonged culture, the pathogenic clonal population of the parasite is deleted from the mixed population due to their selection pressure. This clonal deletion is proposed to be responsible for the emergence of the nonpathogenic population. We have a done a series of two-dimensional polyacrylamide gel electrophoresis followed by western blot experiments to study the antigenic profile of few L. donovani isolates of Indian origin. We observed a gradual and significant downregulation of expression of a group of low molecular weight proteins (LMW, molecular weight 20-30 kDa) which are associated with loss of pathogenicity. These proteins are recognized only by antiserum raised against the whole cell extract of one of the pathogenic Indian L. donovani isolates, Ag83, and remained undetected by antiserum raised against the nonpathogenic AG83 isolates. These LMW proteins were also present in the nonpathogenic extract in very low levels and remained undetected by the virulent serum, indicating a phenomenon of simultaneous downregulation of the expression and altered immunogenicity. LMW proteins were universally expressed in all early passage Indian isolate we tested and also detected in two clones obtained from pathogenic parasite culture. The antigenic patterns of none of the eight clones obtained from nonpathogenic culture were not exactly similar with the pathogenic clones

DERMAL EXPOSURE ASSESSMENT: A SUMMARY OF EPA APPROACHES

EPA Science Inventory

This final report presents a concise description and evaluation of the approaches used in the Agency for dermal exposure assessment including a discussion about harmonization and research needs in this area. The report is intended to be used by EPA program offices in their effort...

Interposition Ankle Arthroplasty Using Acellular Dermal Matrix: A Small Series.

PubMed

Carpenter, Brian; Duncan, Kyle; Ernst, Jordan; Ryba, Dalton; Suzuki, Sumihiro

Although ankle arthrodesis is the reference standard for end-stage ankle arthritis, loss of mobility and adjacent joint arthritis are consequences that alternatives to arthrodesis attempt to avoid. The purpose of the present study was to report the clinical results of interpositional arthroplasty using acellular dermal matrix in 4 patients (age 32 to 42 years) for the treatment of advanced ankle osteoarthritis. The primary findings included relief of pain, with improvement in tibiotalar joint range of motion from a mean of 16.5° (range 0° to 24°) preoperatively to a mean of 31° (range 25° to 40°) postoperatively. All 4 patients underwent open arthrotomy of the anterior and posterior tibiotalar capsule with plafond exostectomy and debridement of all deleterious tissue within the ankle capsule. The articular surface of the talar dome was denuded down to smooth subchondral bone, and microfracture was performed. Autologous calcaneal bone marrow aspirate was applied, and talar resurfacing was achieved using an acellular dermal matrix. Knotless anchors placed medially and laterally within the anterior and posterior dome were used to affix the dermal matrix. The follow-up period ranged from 12 to 18 (mean 14) months. The mean pre- and 12-month postoperative Association of Orthopaedic Foot and Ankle Society hindfoot-ankle scale scores were 35 and 88.5, respectively. These outcomes suggest that interpositional tibiotalar arthroplasty using an acellular dermal matrix is successful in improving function and range of motion and decreasing pain. As an alternative to tibiotalar arthrodesis, interpositional tibiotalar arthroplasty might be the procedure of choice for young patients with end-stage ankle arthritis. Longer follow-up periods, histologic testing, and arthroscopic evaluations would be advantageous to further assess the durability of this procedure. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Bio-artificial pleura using an autologous dermal fibroblast sheet

NASA Astrophysics Data System (ADS)

Kanzaki, Masato; Takagi, Ryo; Washio, Kaoru; Kokubo, Mami; Yamato, Masayuki

2017-10-01

Air leaks (ALs) are observed after pulmonary resections, and without proper treatment, can produce severe complications. AL prevention is a critical objective for managing patients after pulmonary resection. This study applied autologous dermal fibroblast sheets (DFS) to close ALs. For sealing ALs in a 44-year-old male human patient with multiple bullae, a 5 × 15-mm section of skin was surgically excised. From this skin specimen, primary dermal fibroblasts were isolated and cultured for 4 weeks to produce DFSs that were harvested after a 10-day culture. ALs were completely sealed using surgical placement of these autologous DFSs. DFS were found to be a durable long-term AL sealant, exhibiting requisite flexibility, elasticity, durability, biocompatibility, and usability, resulting reliable AL closure. DFS should prove to be an extremely useful tissue-engineered pleura substitute.

Prevalence of and Factors Associated with Negative Microscopic Diagnosis of Cutaneous Leishmaniasis in Rural Peru.

PubMed

Lamm, Ryan; Alves, Clark; Perrotta, Grace; Murphy, Meagan; Messina, Catherine; Sanchez, Juan F; Perez, Erika; Rosales, Luis Angel; Lescano, Andres G; Smith, Edward; Valdivia, Hugo; Fuhrer, Jack; Ballard, Sarah-Blythe

2018-06-04

Cutaneous leishmaniasis is endemic to South America where diagnosis is most commonly conducted via microscopy. Patients with suspected leishmaniasis were referred for enrollment by the Ministry of Health (MoH) in Lima, Iquitos, Puerto Maldonado, and several rural areas of Peru. A 43-question survey requesting age, gender, occupation, characterization of the lesion(s), history of leishmaniasis, and insect-deterrent behaviors was administered. Polymerase chain reaction (PCR) was conducted on lesion materials at the Naval Medical Research Unit No. 6 in Lima, and the results were compared with those obtained by the MoH using microscopy. Factors associated with negative microscopy and positive PCR results were identified using χ 2 test, t -test, and multivariate logistic regression analyses. Negative microscopy with positive PCR occurred in 31% (123/403) of the 403 cases. After adjusting for confounders, binary multivariate logistic regression analyses revealed that negative microscopy with positive PCR was associated with patients who were male (adjusted OR = 1.93 [1.06-3.53], P = 0.032), had previous leishmaniasis (adjusted OR = 2.93 [1.65-5.22], P < 0.0001), had larger lesions (adjusted OR = 1.02 [1.003-1.03], P = 0.016), and/or had a longer duration between lesion appearance and PCR testing (adjusted OR = 1.12 [1.02-1.22], P = 0.017). Future research should focus on further exploration of these underlying variables, discovery of other factors that may be associated with negative microscopy diagnosis, and the development and implementation of improved testing in endemic regions.

Drug search for leishmaniasis: a virtual screening approach by grid computing

NASA Astrophysics Data System (ADS)

Ochoa, Rodrigo; Watowich, Stanley J.; Flórez, Andrés; Mesa, Carol V.; Robledo, Sara M.; Muskus, Carlos

2016-07-01

The trypanosomatid protozoa Leishmania is endemic in 100 countries, with infections causing 2 million new cases of leishmaniasis annually. Disease symptoms can include severe skin and mucosal ulcers, fever, anemia, splenomegaly, and death. Unfortunately, therapeutics approved to treat leishmaniasis are associated with potentially severe side effects, including death. Furthermore, drug-resistant Leishmania parasites have developed in most endemic countries. To address an urgent need for new, safe and inexpensive anti-leishmanial drugs, we utilized the IBM World Community Grid to complete computer-based drug discovery screens (Drug Search for Leishmaniasis) using unique leishmanial proteins and a database of 600,000 drug-like small molecules. Protein structures from different Leishmania species were selected for molecular dynamics (MD) simulations, and a series of conformational "snapshots" were chosen from each MD trajectory to simulate the protein's flexibility. A Relaxed Complex Scheme methodology was used to screen 2000 MD conformations against the small molecule database, producing >1 billion protein-ligand structures. For each protein target, a binding spectrum was calculated to identify compounds predicted to bind with highest average affinity to all protein conformations. Significantly, four different Leishmania protein targets were predicted to strongly bind small molecules, with the strongest binding interactions predicted to occur for dihydroorotate dehydrogenase (LmDHODH; PDB:3MJY). A number of predicted tight-binding LmDHODH inhibitors were tested in vitro and potent selective inhibitors of Leishmania panamensis were identified. These promising small molecules are suitable for further development using iterative structure-based optimization and in vitro/in vivo validation assays.

Sustaining visceral leishmaniasis elimination in Bangladesh - Could a policy brief help?

PubMed

Fitzpatrick, Alyssa; Al-Kobaisi, Noor Saad M S; Beitman Maya, Jessica; Ren Chung, Yu; Duhan, Satyender; Elbegdorj, Erdene; Jain, Sushant; Kuhn, Edward; Nastase, Alexandra; Ahmed, Be-Nazir; Olliaro, Piero

2017-12-01

Bangladesh has made significant progress towards elimination of visceral leishmaniasis, and is on track to achieve its target of less than one case per 10,000 inhabitants in each subdistrict in 2017. As the incidence of disease falls, it is likely that the political capital and financial resources dedicated towards the elimination of visceral leishmaniasis may decrease, raising the prospect of disease resurgence. Policy memos may play a crucial role during the transition of the elimination plan from the 'attack' to the 'consolidation' and 'maintenance' phases, highlighting key stakeholders and areas where ongoing investment is crucial. An example of a policy brief is outlined in this paper. The background to the current elimination efforts is highlighted, with emphasis on remaining uncertainties including the impact of disease reservoirs and sustainable surveillance strategies. A stakeholder map is provided outlining the current and projected future activities of key bodies. Identification of key stakeholders subsequently frames the discussion of three key policy recommendations in the Bangladeshi context for the transition to the consolidation and maintenance phases of the elimination program. Recommendations include determining optimal vector control and surveillance strategies, shifting the emphasis towards horizontal integration of disease programs, and prioritising remaining research questions with a focus on operational and technical capacity. Achieving elimination is as much a political as a scientific question. Integrating the discussion of key stakeholders with policy priorities and the research agenda provides a novel insight into potential pathways forwards in the elimination of visceral leishmaniasis in Bangladesh and in the rest of the Indian subcontinent.

Noninferiority of Miltefosine Versus Meglumine Antimoniate for Cutaneous Leishmaniasis in Children

PubMed Central

Rubiano, Luisa Consuelo; Miranda, María Consuelo; Muvdi Arenas, Sandra; Montero, Luz Mery; Rodríguez-Barraquer, Isabel; Garcerant, Daniel; Prager, Martín; Osorio, Lyda; Rojas, Maria Ximena; Pérez, Mauricio; Nicholls, Ruben Santiago

2012-01-01

Background. Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. Methods. A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2–12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8–2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). Results. Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%–28.7%) for miltefosine and 31% (98% CI, 16.9%–45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, −4.5% to 32%) (P = .04). Adverse events were mild for both treatments. Conclusions. Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. Clinical Trial Registration. NCT00487253. PMID:22238470

Drug search for leishmaniasis: a virtual screening approach by grid computing.

PubMed

Ochoa, Rodrigo; Watowich, Stanley J; Flórez, Andrés; Mesa, Carol V; Robledo, Sara M; Muskus, Carlos

2016-07-01

The trypanosomatid protozoa Leishmania is endemic in ~100 countries, with infections causing ~2 million new cases of leishmaniasis annually. Disease symptoms can include severe skin and mucosal ulcers, fever, anemia, splenomegaly, and death. Unfortunately, therapeutics approved to treat leishmaniasis are associated with potentially severe side effects, including death. Furthermore, drug-resistant Leishmania parasites have developed in most endemic countries. To address an urgent need for new, safe and inexpensive anti-leishmanial drugs, we utilized the IBM World Community Grid to complete computer-based drug discovery screens (Drug Search for Leishmaniasis) using unique leishmanial proteins and a database of 600,000 drug-like small molecules. Protein structures from different Leishmania species were selected for molecular dynamics (MD) simulations, and a series of conformational "snapshots" were chosen from each MD trajectory to simulate the protein's flexibility. A Relaxed Complex Scheme methodology was used to screen ~2000 MD conformations against the small molecule database, producing >1 billion protein-ligand structures. For each protein target, a binding spectrum was calculated to identify compounds predicted to bind with highest average affinity to all protein conformations. Significantly, four different Leishmania protein targets were predicted to strongly bind small molecules, with the strongest binding interactions predicted to occur for dihydroorotate dehydrogenase (LmDHODH; PDB:3MJY). A number of predicted tight-binding LmDHODH inhibitors were tested in vitro and potent selective inhibitors of Leishmania panamensis were identified. These promising small molecules are suitable for further development using iterative structure-based optimization and in vitro/in vivo validation assays.

Visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis in a traveler returning from a pilgrimage to the Camino de Santiago.

PubMed

Watkins, Emily R; Shamasunder, Sriram; Cascino, Thomas; White, Kristie L; Katrak, Shereen; Bern, Caryn; Schwartz, Brian S

2014-01-01

We report the case of a 73-year-old American traveler who presented with 3 weeks of fatigue, fevers, chills, and pancytopenia. Clinical and laboratory findings were consistent with hemophagocytic lymphohystiocytosis (HLH) and bone marrow biopsy revealed amastigotes consistent with visceral leishmaniasis. The range of endemic visceral leishmaniasis transmission now extends into northern Spain and travelers to this region should use personal protective measures against sand fly exposure. © 2014 International Society of Travel Medicine.

A quantitative method for estimating dermal benzene absorption from benzene-containing hydrocarbon liquids.

PubMed

Petty, Stephen E; Nicas, Mark; Boiarski, Anthony A

2011-01-01

This study examines a method for estimating the dermal absorption of benzene contained in hydrocarbon liquids that contact the skin. This method applies to crude oil, gasoline, organic solvents, penetrants, and oils. The flux of benzene through occluded skin as a function of the percent vol/vol benzene in the liquid is derived by fitting a curve to experimental data; the function is supralinear at benzene concentrations < or = 5% vol/vol. When a liquid other than pure benzene is on nonoccluded skin, benzene may preferentially evaporate from the liquid, which thereby decreases the benzene flux. We present a time-averaging method here for estimating the reduced dermal flux during evaporation. Example calculations are presented for benzene at 2% vol/vol in gasoline, and for benzene at 0.1% vol/vol in a less volatile liquid. We also discuss other factors affecting dermal absorption.

[Differences between plaque-like variants of dermatofibrosarcoma protuberans and plaque-like dermal fibromatosis (dermatomyofibroma)].

PubMed

Hügel, H; Kutzner, H; Rütten, A; Biess, B

1994-05-01

On the basis of two cases the differences between the plaque-like variant of dermatofibrosarcoma protuberans (PDFSP) and the plaque-like dermal fibromatosis (synonym: dermatomyofibroma; PDF) are presented. PDFSP and PDF are two clinically very similar dermal fibrous proliferations, but differentiation is important because of their different therapy and prognosis. Histologically and immunohistochemically PDFSP and PDF can be recognized as separate entities.

Red light accelerates the formation of a human dermal equivalent.

PubMed

Oliveira, Anna Cb; Morais, Thayz Fl; Bernal, Claudia; Martins, Virginia Ca; Plepis, Ana Mg; Menezes, Priscila Fc; Perussi, Janice R

2018-04-01

Development of biomaterials' substitutes and/or equivalents to mimic normal tissue is a current challenge in tissue engineering. Thus, three-dimensional cell culture using type I collagen as a polymeric matrix cell support designed to promote cell proliferation and differentiation was employed to create a dermal equivalent in vitro, as well to evaluate the photobiomodulation using red light. Polymeric matrix cell support was prepared from porcine serous collagen (1.1%) hydrolyzed for 96 h. The biomaterial exhibited porosity of 95%, a median pore of 44 µm and channels with an average distance between the walls of 78 ± 14 µm. The absorption of culture medium was 95%, and the sponge showed no cytotoxicity to Vero cells, a non-tumor cell line. Additionally, it was observed that irradiation with light at 630 nm (fluency 30 J cm -2 ) leads to the cellular photobiomodulation in both monolayer and human dermal equivalent (three-dimensional cell culture system). It was also verified that the cells cultured in the presence of the polymeric matrix cell support, allows differentiation and extracellular matrix secretion. Therefore, the results showed that the collagen sponge used as polymeric matrix cell support and the photobiomodulation at 630 nm are efficient for the production of a reconstructed human dermal equivalent in vitro.

Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.

PubMed

Goodnough, L Henry; Dinuoscio, Gregg J; Ferguson, James W; Williams, Trevor; Lang, Richard A; Atit, Radhika P

2014-02-01

The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

Molecular identification of Leishmania spp. isolates causes cutaneous leishmaniasis (CL) in Sanliurfa Province, Turkey, where CL is highly endemic.

PubMed

Gurses, Gulcan; Ozaslan, Mehmet; Zeyrek, Fadile Yıldız; Kılıç, Ibrahim H; Doni, Nebiye Yentür; Karagöz, I Didem; Uluca, Nermin

2018-05-01

Cutaneous leishmaniasis (CL) is an important public health problem in Turkey. CL has been most frequently seen in Sanliurfa. There is an expectation of increase in the population of leishmaniasis cases with the influence of Syrian refugees arriving in Turkey. In this study we aimed to diagnosis of CL and identifying of parasite from Leishmania isolates by using ITS 1 PCR RFLP. Samples were collected from 135 CL patients in Sanliurfa. After the specimens were inoculated in medium NNN, the ones which were cultures positive were cultivated in RPMI 1640 followed by PCR-RFLP. Genomic DNA was extracted phenol-chloroform procedure. Samples were examined by using ITS 1 PCR followed by RFLP analysis. Our results indicated that two species, L. tropica (132 samples) and L. major (3 samples), are responsible for cutaneous leishmaniasis in Sanlıurfa. Our study is the first scientific study in which it is reported molecular analyses of cutaneous leishmaniasis cases caused by L. major in Sanliurfa in Southestern Anatolia Region. Because CL cases caused by L.major are detected in our study, it is considered that genotyping is important for diagnosis of Leishmania and following change of epidemiology.

Creeping attachment after 10 years of treatment of a gingival recession with acellular dermal matrix: a case report.

PubMed

Santos, Antonio; Goumenos, George; Pascual, Andrés; Nart, Jose

2011-02-01

Acellular dermal matrix grafts have become a good alternative to autogenous soft tissue grafts in root coverage. Until now, the literature has reported short- or medium-term data regarding the stability of the gingival margin after the use of acellular dermal matrix on root coverage. The aim of this article is to describe a case report with 10 years of evolution with creeping attachment that developed bucally on a moderate recession of a maxillary canine with an old composite restoration subsequent to an acellular dermal matrix. Long-term creeping attachment and complete root coverage on a restored tooth treated with acellular dermal matrix has not been previously reported in the dental literature.

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed

Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

2015-01-01

Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

Review of data on the dermal penetration of mineral oils and waxes used in cosmetic applications.

PubMed

Petry, T; Bury, D; Fautz, R; Hauser, M; Huber, B; Markowetz, A; Mishra, S; Rettinger, K; Schuh, W; Teichert, T

2017-10-05

Mineral oils and waxes used in cosmetic products, also referred to as "personal care products" outside the European Union, are mixtures of predominantly saturated hydrocarbons consisting of straight-chain, branched and ring structures with carbon chain lengths greater than C16. They are used in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. Recently, concerns have been raised regarding potential adverse health effects of mineral oils and waxes from dermal application of cosmetics. In order to be able to assess the risk for the consumer the dermal penetration potential of these ingredients has to be evaluated. The scope and objective of this review are to identify and summarize publicly available literature on the dermal penetration of mineral oils and waxes as used in cosmetic products. For this purpose, a comprehensive literature search was conducted. A total of 13 in vivo (human, animal) and in vitro studies investigating the dermal penetration of mineral oils and waxes has been identified and analysed. The majority of the substances were dermally adsorbed to the stratum corneum and only a minor fraction reached deeper skin layers. Overall, there is no evidence from the various studies that mineral oils and waxes are percutaneously absorbed and become systemically available. Thus, given the absence of dermal uptake, mineral oils and waxes as used in cosmetic products do not present a risk to the health of the consumer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Increasing Incidence of Zoonotic Visceral Leishmaniasis on Crete, Greece

PubMed Central

Antoniou, Maria; Messaritakis, Ippokratis; Christodoulou, Vasiliki; Ascoksilaki, Ioanna; Kanavakis, Nikos; Sutton, Andrew J.; Carson, Connor

2009-01-01

To determine whether the incidence of canine leishmaniasis has increased on Crete, Greece, we fitted infection models to serodiagnostic records of 8,848 dog samples for 1990–2006. Models predicted that seroprevalence has increased 2.4% (95% confidence interval 1.61%–3.51%) per year and that incidence has increased 2.2- to 3.8-fold over this 17-year period. PMID:19523295

Development of Novel Therapeutics for Neglected Tropical Disease Leishmaniasis

DTIC Science & Technology

2015-10-01

Approved for public release; distribution unlimited We undertook planning of kick off coordination meeting. A low dose infection model of CL was validated...A large scale synthesis of PEN optimized and in vitro studies were performed revealed that PEN alters parasite lipidome. Further studies were...Pentalinonsterol, Leishmania, cutaneous leishmaniasis, treatment Accomplishments • Undertook planning of kick off coordination meeting • Large scale synthesis of

Photochemistry-based immune modulation in the treatment of cutaneous leishmaniasis

NASA Astrophysics Data System (ADS)

Akilov, Oleg E.; Kosaka, Sachiko; Hasan, Tayyaba

2009-06-01

The destruction of infectious pathogens by photodynamic therapy (PDT) is an emerging modality. We demonstrated the efficacy of PDT for the management of cutaneous leishmaniasis in our previous studies. However, much remains to be done for the improvement of PDT regimens. The modulation of the immune response by photochemistry is an exciting but under-explored area of PDT research. The goal of this study is to understand the mechanisms of the augmentation of the host immune response after PDT of cutaneous leishmaniasis (CL). We found that PDT with phenoxiazine analogues was capable for induction of Th1 immune response due to stimulation of IL- 12 production by dendritic cells. Single PDT treatment facilitated fast healing of the CL lesions due to effective parasite eradication and augmentation of the immune system. Comparative study with different photosensitizers (PS) (porphyrins, pehnoxiazines) demonstrated different immunomodulating properties of PDT depending on chemical class of PS. Knowing the particular profiles and immunomodulating properties of the pertinent PSs allows us to select the optimal PS with regards to both the photodestructive and immunostimulating potential.

Natural compounds and extracts from Mexican medicinal plants with anti-leishmaniasis activity: An update.

PubMed

Gutiérrez-Rebolledo, Gabriel Alfonso; Drier-Jonas, Susan; Jiménez-Arellanes, María Adelina

2017-12-01

Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceral-type leishmaniasis are recorded and 60000 persons died from the disease. In Mexico, cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major, while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC 50  ≤ 30 μg/mL or μM have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Factors associated with the seroprevalence of leishmaniasis in dogs living around Atlantic Forest fragments.

PubMed

Curi, Nelson Henrique de Almeida; Paschoal, Ana Maria de Oliveira; Massara, Rodrigo Lima; Marcelino, Andreza Pain; Ribeiro, Adriana Aparecida; Passamani, Marcelo; Demétrio, Guilherme Ramos; Chiarello, Adriano Garcia

2014-01-01

Canine visceral leishmaniasis is an important zoonosis in Brazil. However, infection patterns are unknown in some scenarios such as rural settlements around Atlantic Forest fragments. Additionally, controversy remains over risk factors, and most identified patterns of infection in dogs have been found in urban areas. We conducted a cross-sectional epidemiological survey to assess the prevalence of leishmaniasis in dogs through three different serological tests, and interviews with owners to assess features of dogs and households around five Atlantic Forest remnants in southeastern Brazil. We used Generalized Linear Mixed Models and Chi-square tests to detect associations between prevalence and variables that might influence Leishmania infection, and a nearest neighbor dispersion analysis to assess clustering in the spatial distribution of seropositive dogs. Our findings showed an average prevalence of 20% (ranging from 10 to 32%) in dogs. Nearly 40% (ranging from 22 to 55%) of households had at least one seropositive dog. Some individual traits of dogs (height, sterilization, long fur, age class) were found to positively influence the prevalence, while some had negative influence (weight, body score, presence of ectoparasites). Environmental and management features (number of cats in the households, dogs with free-ranging behavior) also entered models as negative associations with seropositivity. Strong and consistent negative (protective) influences of the presence of chickens and pigs in dog seropositivity were detected. Spatial clustering of cases was detected in only one of the five study sites. The results showed that different risk factors than those found in urban areas may drive the prevalence of canine leishmaniasis in farm/forest interfaces, and that humans and wildlife risk infection in these areas. Domestic dog population limitation by gonadectomy, legal restriction of dog numbers per household and owner education are of the greatest importance for the

Multi-modal Analysis of Courtship Behaviour in the Old World Leishmaniasis Vector Phlebotomus argentipes

PubMed Central

Bray, Daniel P.; Yaman, Khatijah; Underhilll, Beryl A.; Mitchell, Fraser; Carter, Victoria; Hamilton, James G. C.

2014-01-01

Background The sand fly Phlebotomus argentipes is arguably the most important vector of leishmaniasis worldwide. As there is no vaccine against the parasites that cause leishmaniasis, disease prevention focuses on control of the insect vector. Understanding reproductive behaviour will be essential to controlling populations of P. argentipes, and developing new strategies for reducing leishmaniasis transmission. Through statistical analysis of male-female interactions, this study provides a detailed description of P. argentipes courtship, and behaviours critical to mating success are highlighted. The potential for a role of cuticular hydrocarbons in P. argentipes courtship is also investigated, by comparing chemicals extracted from the surface of male and female flies. Principal Findings P. argentipes courtship shared many similarities with that of both Phlebotomus papatasi and the New World leishmaniasis vector Lutzomyia longipalpis. Male wing-flapping while approaching the female during courtship predicted mating success, and touching between males and females was a common and frequent occurrence. Both sexes were able to reject a potential partner. Significant differences were found in the profile of chemicals extracted from the surface of males and females. Results of GC analysis indicate that female extracts contained a number of peaks with relatively short retention times not present in males. Extracts from males had higher peaks for chemicals with relatively long retention times. Conclusions The importance of male approach flapping suggests that production of audio signals through wing beating, or dispersal of sex pheromones, are important to mating in this species. Frequent touching as a means of communication, and the differences in the chemical profiles extracted from males and females, may also indicate a role for cuticular hydrocarbons in P. argentipes courtship. Comparing characteristics of successful and unsuccessful mates could aid in identifying the

Dermal morphological changes following salicylic acid peeling and microdermabrasion.

PubMed

Abdel-Motaleb, Amira A; Abu-Dief, Eman E; Hussein, Mahmoud Ra

2017-12-01

Microdermabrasion and chemical peeling are popular, inexpensive, and safe methods for treatment of some skin disorders and to rejuvenate skin. To study the alterations of the dermal connective tissue following salicylic acid peeling and microdermabrasion. Twenty patients were participated in our study. All participants underwent facial salicylic acid 30% peel or microdermabrasion (10 cases in each group) weekly for 6 weeks. Punch biopsies were obtained from the clinically normal skin of the right postauricular region 1 week before treatment (control group). Other punch skin biopsies were obtained 1 week after the end of the treatments from the left postauricular area. This region was treated in a similar way to the adjacent lesional skin (treated group). We used routine histological techniques (H&E stain), special stains (Masson trichrome and orcein stains), and image analyzer to study the alterations of the dermal connective tissues. Our study demonstrates variations in the morphological changes between the control and the treated groups, and between chemical peels and microdermabrasion. Both salicylic acid 30% and microdermabrasion were associated with thickened epidermal layer, shallow dermal papillae, dense collagen, and elastic fibers. There was a significant increase among those treated sites vs control regarding epidermal thickness and collagen thickness. Also, there was a highly statistically significant increase among those treated with salicylic acid vs microdermabrasion regarding the epidermal, collagen, and elastin thickness. Both methods stimulate the repair process. The mechanisms underlying these variations are open for further investigations. © 2017 Wiley Periodicals, Inc.

Recellularizing of human acellular dermal matrices imaged by high-definition optical coherence tomography.

PubMed

Boone, Marc A L M; Draye, Jean Pierre; Verween, Gunther; Aiti, Annalisa; Pirnay, Jean-Paul; Verbeken, Gilbert; De Vos, Daniel; Rose, Thomas; Jennes, Serge; Jemec, Gregor B E; Del Marmol, Veronique

2015-05-01

High-definition optical coherence tomography (HD-OCT) permits real-time 3D imaging of the impact of selected agents on human skin allografts. The real-time 3D HD-OCT assessment of (i) the impact on morphological and cellular characteristics of the processing of human acellular dermal matrices (HADMs) and (ii) repopulation of HADMs in vitro by human fibroblasts and remodelling of the extracellular matrix by these cells. Four different skin decellularization methods, Dispase II/Triton X-100, Dispase II/SDS (sodium dodecyl sulphate), NaCl/Triton X-100 and NaCl/SDS, were analysed by HD-OCT. HD-OCT features of epidermal removal, dermo-epidermal junction (DEJ) integrity, cellularity and dermal architecture were correlated with reflectance confocal microscopy (RCM), histopathology and immunohistochemistry. Human adult dermal fibroblasts were in vitro seeded on the NaCl/Triton X-100 processed HADMs, cultured up to 19 days and evaluated by HD-OCT in comparison with MTT proliferation test and histology. Epidermis was effectively removed by all treatments. DEJ was best preserved after NaCl/Triton X-100 treatment. Dispase II/SDS treatment seemed to remove all cellular debris in comparison with NaCl/Triton X-100 but disturbed the DEJ severely. The dermal micro-architectural structure and vascular spaces of (sub)papillary dermis were best preserved with the NaCl/Triton X-100. The impact on the 3D structure and vascular holes was detrimental with Dispase II/SDS. Elastic fibre fragmentation was only observed after Dispase II incubation. HD-OCT showed that NaCl/Triton X-100 processed matrices permitted in vitro repopulation by human dermal fibroblasts (confirmed by MTT test and histology) and underwent remodelling upon increasing incubation time. Care must be taken in choosing the appropriate processing steps to maintain selected properties of the extracellular matrix in HADMs. Processing HADMs with NaCl/Triton X-100 permits in vitro the proliferation and remodelling activity of

A new technique to assess dermal absorption of volatile chemicals in vitro by thermal gravimetric analysis.

PubMed

Rauma, Matias; Isaksson, Tina S; Johanson, Gunnar

2006-10-01

Potential health hazards of dermal exposure, variability in reported dermal absorption rates and potential losses from the skin by evaporation indicate a need for a simple, inexpensive and standardized procedure to measure dermal absorption and desorption of chemical substances. The aim of this study was to explore the possibility to measure dermal absorption and desorption of volatile chemicals using a new gravimetric technique, namely thermal gravimetric analysis (TGA), and trypsinated stratum corneum from pig. Changes in skin weight were readily detected before, during and after exposure to vapours of water, 2-propanol, methanol and toluene. The shape and height of the weight curves differed between the four chemicals, reflecting differences in diffusivity and partial pressure and skin:air partitioning, respectively. As the skin weight is highly sensitive to the partial pressure of volatile chemicals, including water, this technique requires carefully controlled conditions with respect to air flow, temperature, chemical vapour generation and humidity. This new technique may help in the assessment of dermal uptake of volatile chemicals. Only a small piece of skin is needed and skin integrity is not necessary, facilitating the use of human samples. The high resolution weight-time curves obtained may also help to elucidate the characteristics of absorption, desorption and diffusion of chemicals in skin.

Assessment of dermal exposure and histopathologic changes of different sized nano-silver in healthy adult rabbits

NASA Astrophysics Data System (ADS)

kazem Koohi, Mohammad; Hejazy, Marzie; Asadi, Farzad; Asadian, Peyman

2011-07-01

The purpose of this study is to evaluate the dermal toxicity (Irritation/Corrosion) of three sizes of nanosilver particles (10, 20 and 30 nm) during 3 min, 1 and 4 hours according to the OECD/OCDE guideline Histopathological effects in secondary organs from liver, kidney, heart, spleen and brain 14 day post dermal administration are also reported. 10 and 20 nm Ag nanoparticles treated group showed well defined dermal erythema and oedema. Histopathological findings of 10 and 20 nm (4 hours exposure) on 14-day post dermal administration showed hyperkeratosis, acanthosis, hair-filled follicles and papillomatosis in an irregular epidermis, fibrosis, hyperemia, erythema, intracellular oedema and hyalinisation of collagen in dermis of skin. Liver revealed midzonal and periacinar necrosis, portal mononuclear infiltration, liver fatty change, liver congestion and hyperemic central vein. Splenic red pulp congestion and white pulp hyperreactivity, splenic trabeculae and sinusoidal congestion and hyaline change were found in spleen. Fatty degeneration in some cardiovascular cells and subendocardial hemorrhage without inflammation was perceived. Picnotic appearance of pyramidal neurons in the brain cortex, gliosis and mild perineuronal oedema ischemic cell change and hyperemic meninges was observed in brain. Our research concluded that dermal exposure to lesser sizes of silver nanoparticles is more disastrous than greater ones.

Design of an elastin-layered dermal regeneration template.

PubMed

Mithieux, Suzanne M; Weiss, Anthony S

2017-04-01

We demonstrate a novel approach for the production of tunable quantities of elastic fibers. We also show that exogenous tropoelastin is rate-limiting for elastin synthesis regardless of the age of the dermal fibroblast donor. Additionally, we provide a strategy to further enhance synthesis by older cells through the application of conditioned media. We show that this approach delivers an elastin layer on one side of the leading dermal repair template for contact with the deep dermis in order to deliver prefabricated elastic fibers to a physiologically appropriate site during subsequent surgery. This system is attractive because it provides for the first time a viable path for sufficient, histologically detectable levels of patient elastin into full-thickness wound sites that have until now lacked this elastic underlayer. The scars of full thickness wounds typically lack elasticity. Elastin is essential for skin elasticity and is enriched in the deep dermis. This paper is significant because it shows that: (1) we can generate elastic fibers in tunable quantities, (2) tropoelastin is the rate-limiting component in elastin synthesis in vitro, (3) we can generate elastin fibers regardless of donor age, (4) we describe a novel approach to further increase the numbers and thickness of elastic fibers for older donors, (5) we improve on Integra Dermal Regeneration Template and generate a new hybrid biomaterial intended to subsequently surgically deliver these elastic fibers, (6) the elastic fiber layer is presented on the side of Integra that is intended for delivery into its physiologically appropriate site i.e. the deep dermis. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bovine versus porcine acellular dermal matrix for complex abdominal wall reconstruction.

PubMed

Clemens, Mark W; Selber, Jesse C; Liu, Jun; Adelman, David M; Baumann, Donald P; Garvey, Patrick B; Butler, Charles E

2013-01-01

Abdominal wall reconstruction with bioprosthetic mesh is associated with lower rates of mesh infection, fistula formation, and mesh explantation than reconstruction with synthetic mesh. The authors directly compared commonly used bioprosthetic meshes in terms of clinical outcomes and complications. A database of consecutive patients who underwent abdominal wall reconstruction with porcine or bovine acellular dermal matrix and midline musculofascial closure at their institution between January of 2008 and March of 2011 was reviewed. Surgical outcomes were compared. One hundred twenty patients were identified who underwent a nonbridged, inlay abdominal wall reconstruction with porcine [69 patients (57.5 percent)] or bovine acellular dermal matrix (51 patients (42.5 percent)]. The mean follow-up time was 21.0 ± 9.9 months. The overall complication rate was 36.6 percent; the porcine matrix group had a significantly higher complication rate (44.9 percent) than the bovine matrix group (25.5 percent; p = 0.04) and statistically equivalent surgical complications (29.2 percent versus 21.6 percent; p = 0.34). There were no significant differences in rates of recurrent hernia (2.9 percent versus 3.9 percent; p = 0.99) or bulge (7.2 percent versus 0 percent; p = 0.07). However, the rate of intraoperative adverse events in the porcine matrix group [seven events (10.1 percent)] was significantly higher than that in the bovine matrix group (0 percent; p = 0.02). In patients who undergo complex abdominal wall reconstruction, both bovine and porcine acellular dermal matrix are associated with similar rates of postoperative surgical complications and appear to result in similar outcomes. Porcine acellular dermal matrix may be prone to intraoperative device failure. Therapeutic, III.

PAF involvement in dermal extravasation in the reverse passive Arthus reaction

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

Deacon, R.W.; Melden, M.K.; Saunders, R.N.

The reverse passive erthus reaction (RPAR) is characterized by PMN infiltration, increased vascular permeability leading to plasma extravasation and vessel damage. In the skin RPAR is an inflammatory response initiated by deposition of immune complexes and attributed to complement activation. As PAF can elicit similar dermal reactions, they examined the PAF antagonist SRI 63-072 in the RPAR. Guinea pigs were given an i.v. injection of /sup 125/I-BSA (Ag-20 mg/kg with 20 mg/kg Evan's blue as a permeability tracer), followed by intradermal (i.d.) injections (0.1 ml/site) of anti-BSA antibodies (Ab). After 30 min, dermal sites (2 cm diam.) were removed, countedmore » and the ..mu..l plasma/site (over background counts) calculated from plasma radioactivity measurements. The plasma leakage (..mu..l plasma/site) was dose-dependent upon Ab dose (6-200 ..mu..g/site). At the ultrastructural level, the presence of neutrophils and eosinophils were observed in the extravascular spaces. The luminal endothelium exhibited cytotoxic characteristics and loss of junctional integrity. SRI 63-072 exhibited 50% maximal inhibition when given i.d. with the Ab (0.1 ..mu..g/site) but only 5-10% when given at 3.0 mg/kg i.v. with Ag. No further inhibition of dermal extravasation was observed using SRI 63-441, a competitive receptor antagonist with 3-30 fold the in vivo potency of SRI 63-072. As dermal extravasation in RPAR is only partially inhibited by a PAF antagonist, it appears that other vasoactive mediators, possibly histamine, may be influencing vessel permeability as well.« less

Immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-DNA vaccine of Leishmania donovani.

PubMed

Gamboa-León, R; Paraguai de Souza, E; Borja-Cabrera, G P; Santos, F N; Myashiro, L M; Pinheiro, R O; Dumonteil, E; Palatnik-de-Sousa, C B

2006-05-29

The nucleoside hydrolase (NH36) of Leishmania (L.) donovani is a vital enzyme which releases purines or pyrimidines of foreign DNA to be used in the synthesis of parasite DNA. As a bivalent DNA vaccine, the VR1012-NH36 was immunoprotective against visceral and cutaneous murine leishmaniasis. In this work we tested the immunotherapy against Leishmania (L.) chagasi infection, using two doses of 100 or 20 microg VR1012-NH36 vaccine (i.m. route), and, as a possible immunomodulator, aqueous garlic extract (8 mg/kg/day by the i.p. route), which was effective in immunotherapy of cutaneous murine leishmaniasis. Liver parasitic load was significantly reduced following treatment with 100 microg (91%) and 20 microg (77%) of the DNA vaccine, and by 20 microg DNA vaccine and garlic extract (76%) (p=0.023). Survival was 33% for saline controls, 100% for the 100 microg vaccine, and 83 and 67% for the 20 microg vaccine with and without garlic extract addition, respectively. Garlic treatment alone did not reduce parasite load (p>0.05), but increased survival (100%). The NH36-DNA vaccine was highly effective as a new tool for the therapy and control of visceral leishmaniasis, while the mild protective effect of garlic might be related to an unspecific enhancement of IFN-gamma secretion.

A short-term and long-term comparison of root coverage with an acellular dermal matrix and a subepithelial graft.

PubMed

Harris, Randall J

2004-05-01

Obtaining predictable and esthetic root coverage has become important. Unfortunately, there is only a limited amount of information available on the long-term results of root coverage procedures. The goal of this study was to evaluate the short-term and long-term root coverage results obtained with an acellular dermal matrix and a subepithelial graft. An a priori power analysis was done to determine that 25 was an adequate sample size for each group in this study. Twenty-five patients treated with either an acellular dermal matrix or a subepithelial graft for root coverage were included in this study. The short-term (mean 12.3 to 13.2 weeks) and long-term (mean 48.1 to 49.2 months) results were compared. Additionally, various factors were evaluated to determine whether they could affect the results. This study was a retrospective study of patients in a fee-for-service private periodontal practice. The patients were not randomly assigned to treatment groups. The mean root coverages for the short-term acellular dermal matrix (93.4%), short-term subepithelial graft (96.6%), and long-term subepithelial graft (97.0%) were statistically similar. All three were statistically greater than the long-term acellular dermal matrix mean root coverage (65.8%). Similar results were noted in the change in recession. There were smaller probing reductions and less of an increase in keratinized tissue with the acellular dermal matrix than the subepithelial graft. None of the factors evaluated resulted in the acellular dermal graft having a statistically significant better result than the subepithelial graft. However, in long-term cases where multiple defects were treated with an acellular dermal matrix, the mean root coverage (70.8%) was greater than the mean root coverage in long-term cases where a single defect was treated with an acellular dermal matrix (50.0%). The mean results with the subepithelial graft held up with time better than the mean results with an acellular dermal

FIRST CASE OF AUTOCHTHONOUS HUMAN VISCERAL LEISHMANIASIS IN THE URBAN CENTER OF RIO DE JANEIRO: CASE REPORT

PubMed Central

da Silva, Guilherme Almeida Rosa; Boechat, Thiago de Oliveira; Ferry, Fernando Raphael de Almeida; Pinto, Jorge Francisco da Cunha; de Azevedo, Marcelo Costa Velho Mendes; Carvalho, Ricardo de Souza; Motta, Rogerio Neves; Veras, Mariana Ferreira

2014-01-01

Visceral leishmaniasis is an anthropozoonosis that is caused by protozoa of the genus Leishmania, especially Leishmania (Leishmania) infantum, and is transmitted to humans by the bite of sandflies of the genus Lutzomyia, such as Lutzomyia longipalpis. There are many reservoirs, including Canis familiaris. It is a chronic infectious disease with systemic involvement that is characterized by three phases: the initial period, the state period and the final period. The main symptoms are fever, malnutrition, hepatosplenomegaly, and pancytopenia. This article reports a case of a patient diagnosed with visceral leishmaniasis in the final period following autochthonous transmission in the urban area of Rio de Janeiro. The case reported here is considered by the Municipal Civil Defense and Health Surveillance of Rio de Janeiro to be the first instance of autochthonous visceral leishmaniasis in humans in the urban area of this city. The patient was discharged and is undergoing a follow-up at the outpatient clinic, demonstrating clinical improvement. PMID:24553614

First case of autochthonous human visceral leishmaniasis in the urban center of Rio de Janeiro: case report.

PubMed

Silva, Guilherme Almeida Rosa da; Boechat, Thiago de Oliveira; Ferry, Fernando Raphael de Almeida; Pinto, Jorge Francisco da Cunha; Azevedo, Marcelo Costa Velho Mendes de; Carvalho, Ricardo de Souza; Motta, Rogerio Neves; Veras, Mariana Ferreira

2014-01-01

Visceral leishmaniasis is an anthropozoonosis that is caused by protozoa of the genus Leishmania, especially Leishmania (Leishmania) infantum, and is transmitted to humans by the bite of sandflies of the genus Lutzomyia, such as Lutzomyia longipalpis. There are many reservoirs, including Canis familiaris. It is a chronic infectious disease with systemic involvement that is characterized by three phases: the initial period, the state period and the final period. The main symptoms are fever, malnutrition, hepatosplenomegaly, and pancytopenia. This article reports a case of a patient diagnosed with visceral leishmaniasis in the final period following autochthonous transmission in the urban area of Rio de Janeiro. The case reported here is considered by the Municipal Civil Defense and Health Surveillance of Rio de Janeiro to be the first instance of autochthonous visceral leishmaniasis in humans in the urban area of this city. The patient was discharged and is undergoing a follow-up at the outpatient clinic, demonstrating clinical improvement.

Protective effect of crocin on ultraviolet B‑induced dermal fibroblast photoaging.

PubMed

Deng, Mingwu; Li, Dong; Zhang, Yichen; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wenjie

2018-06-11

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS), resulting in the aging of dermal fibroblasts. Crocin, a bioactive constituent of Crocus sativus, possesses anti‑oxidation effects. The purpose of the present study was to evaluate the protective effect of crocin on UVB‑induced dermal fibroblast photoaging. Human dermal fibroblasts were isolated and cultured with different concentrations of crocin prior to and following exposure to UVB irradiation. The senescent phenotypes of cells were evaluated, including cell proliferation, cell cycle, senescence‑associated β‑galactosidase (SA‑β‑gal) expression, intracellular ROS, expression of antioxidant protein glutathione peroxidase 1 (GPX‑1) and extracellular matrix protein collagen type 1 (Col‑1). Crocin rescued the cell proliferation inhibited by UVB irradiation, prevented cell cycle arrest and markedly decreased the number of SA‑β‑gal‑positive cells. In addition, crocin reduced UVB‑induced ROS by increasing GPX‑1 expression and other direct neutralization effects. Furthermore, crocin promoted the expression of the extracellular matrix protein Col‑1. Crocin could effectively prevent UVB‑induced cell damage via the reduction of intracellular ROS; thus, it could potentially be used in the prevention of skin photoaging.

Control of zoonotic cutaneous leishmaniasis vector, Phlebotomus papatasi, using attractive toxic sugar baits (ATSB).

PubMed

Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Rassi, Yavar; Karami Jooshin, Moharram; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad

2017-01-01

Attractive Toxic Sugar Baits (ATSB) is a new vector control method that meets Integrated Vector Management (IVM) goals. In an experimental design, this study aimed to determine effects of ATSB on control of Phlebotomus papatasi, as a main vector of Zoonotic Cutaneous Leishmaniasis (ZCL), in Qom Province, center of Iran. In a cross-sectional design, boric acid was mixed with brown sugar solution and tested as toxic baits for P. papatasi. Two methods were utilized to use the baits: (a) spraying ATSB on vegetation, bushes, and shrubs; and (b) setting ATSB-treated barrier fences in front of colonies at 500 m distance from the houses in outskirts of villages. In order to examine the residual efficacy rate of ATSB-treated barrier fences, the bioassay test was used. Density of P. papatasi sandflies was measured using sticky and light traps biweekly. For data analysis, Mann-Whitney U Test and Kruskal-Wallis were used. Results ATSB-treated barrier fences led to 3 times reduction in P. papatasi population. Besides that, ATSB spraying on plants led to more than 5 times reduction in P. papatasi population. Comparing the incidence of leishmaniasis in treated villages before and after the study showed that the incidence was statistically reduced. Therefore, ATSB is an effective method to control vectors and prevent leishmaniasis.

The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns.

PubMed

Parcells, Alexis Lanteri; Karcich, Jenika; Granick, Mark S; Marano, Michael A

2014-01-01

Management of full-thickness burn wounds represents a challenge when reconstructive options are not applicable. Fetal bovine dermal matrix is a bioactive collagen scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. We present the use of fetal bovine dermal scaffold PriMatrix in the treatment of a patient who sustained scald-immersion full-thickness burns of her bilateral hands that failed conventional wound therapy. A 71-year-old woman with advanced Parkinson's disease sustained self-induced 5% mixed second- and third-degree scald-immersion burns of her bilateral hands and fingers. The patient underwent extensive debridement that resulted in partially avascular wounds measuring 66 cm(2) and 72 cm(2) with exposed extensor tendons and no evidence of bleeding. Meshed homograft was applied, but her hands remained partly avascular. PriMatrix fetal bovine dermal scaffold was applied to provide tissue remodeling over the bones, which allowed successful skin grafting and complete wound healing. Our experience shows fetal bovine dermal scaffold to be an effective method in management of complicated burn wounds in selected cases. Further studies need to be implemented to confer this conclusion.

The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns

PubMed Central

Karcich, Jenika; Granick, Mark S.; Marano, Michael A.