Institute of Tropical Medicine Antwerp

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    6320 research outputs found

    Complexities in using sentinel pigs to study Taenia solium transmission dynamics under field conditions

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    The transmission dynamics of the pork tapeworm, Taenia solium, remain a matter of research and debate. In a longitudinal field study performed in southeastern Nepal, 18 sentinel pigs were serologically monitored to study the field kinetics of Taenia antigens and anti-T. solium antibodies. At the end of the twelve months' study period, necropsy was performed and suspected lesions were subjected to molecular identification of the Taenia species. The study generated new hypotheses on the transmission dynamics of Taenia spp. and exposed crucial complexities in the use of sentinel pigs in longitudinal field studies. Sentinel pigs can be useful epidemiological tools, but their use should be thoroughly planned before initiating a study and carefully monitored throughout the course of the study. Important aspects to be considered are those affecting the pig's susceptibility to infection, such as passive immunity, age, hormonal levels, and infection with competing Taenia species. In addition, serological test results should be interpreted considering possible cross-reactions and with proper understanding of the significance of a positive test result

    An outbreak investigation of visceral leishmaniasis among residents of Dharan town, eastern Nepal, evidence for urban transmission of Leishmania donovani

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    BACKGROUND: Visceral leishmaniasis (VL) is a predominantly rural disease, common in the low lands of eastern Nepal. Since 1997 VL cases have also been reported among residents of the city of Dharan. Our main research objective was to find out whether there had been local transmission of VL inside the city. METHODS: We conducted an outbreak investigation including a case--control study; cases were all urban residents treated for VL between 2000 and 2008 at BP Koirala Institute of Health Sciences, a university hospital in the city. For each case, we selected four random controls, with no history of previous VL; frequency-matched for age. Cases and controls were subjected to a structured interview on the main exposures of interest and potential confounders; a binominal multilevel model was used to analyze the data. We also collected entomological data from all neighborhoods of the city. RESULTS: We enrolled 115 VL patients and 448 controls. Cases were strongly clustered, 70% residing in 3 out of 19 neighborhoods. We found a strong association with socio-economic status, the poorest being most at risk. Housing was a risk factor independent from socio-economic status, most at risk were those living in thatched houses without windows. 'Sleeping upstairs' and 'sleeping on a bed' were strongly protective, OR of 0.08 and 0.25 respectively; proximity to a case was a strong risk factor (OR 3.79). Sand flies were captured in all neighborhoods; in collections from several neighborhoods presence of L. donovani could be demonstrated by PCR. CONCLUSION: The evidence found in this study is consistent with transmission of anthroponotic VL within the city. The vector P. argentipes and the parasite L. donovani have both been identified inside the town. These findings are highly relevant for policy makers; in VL endemic areas appropriate surveillance and disease control measures must be adopted not only in rural areas but in urban areas as well

    Comparison of visceral leishmaniasis diagnostic antigens in African and Asian Leishmania donovani reveals extensive diversity and region-specific polymorphisms

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    BACKGROUND: Visceral leishmaniasis (VL), caused by infection with complex, remains a major public health problem in endemic regions of South Asia, East Africa, and Brazil. If untreated, symptomatic VL is usually fatal. Rapid field diagnosis relies principally on demonstration of anti- antibodies in clinically suspect cases. The rK39 immunochromatographic rapid diagnostic test (RDT) is based on rK39, encoded by a fragment of a kinesin-related gene derived from a Brazilian , now recognised as , originating from Europe. Despite its reliability in South Asia, the rK39 test is reported to have lower sensitivity in East Africa. A reason for this differential response may reside in the molecular diversity of the rK39 homologous sequences among East African strains. METHODOLOGYPRINCIPAL FINDINGS: Coding sequences of rK39 homologues from East African strains were amplified from genomic DNA, analysed for diversity from the rK39 sequence, and compared to South Asian sequences. East African sequences were revealed to display significant diversity from rK39. Most coding changes in the 5' half of repeats were non-conservative, with multiple substitutions involving charge changes, whereas amino acid substitutions in the 3' half of repeats were conservative. Specific polymorphisms were found between South Asian and East African strains. Diversity of HASPB1 and HASPB2 gene repeat sequences, used to flank sequences of a kinesin homologue in the synthetic antigen rK28 designed to reduce variable RDT performance, was also investigated. Non-canonical combination repeat arrangements were revealed for HASPB1 and HASPB2 gene products in strains producing unpredicted size amplicons. CONCLUSIONSSIGNIFICANCE: We demonstrate that there is extensive kinesin genetic diversity among strains in East Africa and between East Africa and South Asia, with ample scope for influencing performance of rK39 diagnostic assays. We also show the importance of targeted comparative genomics in guiding optimisation of recombinant/synthetic diagnostic antigens

    HIV-1 protease inhibitors for treatment of visceral leishmaniasis in HIV-co-infected individuals

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    The global prevalence of HIV is a major challenge for control of visceral leishmaniasis, a disseminated protozoan infection. In some east African regions, up to 40% of patients with visceral leishmaniasis are co-infected with HIV. Management of visceral leishmaniasis in such patients is complicated by treatment failures and relapses, even while patients are receiving standard antiretroviral therapy. In-vitro studies have consistently documented an inhibitory effect of specific HIV-1 protease inhibitors on leishmania parasites, and the underlying mechanism is partly explained. With the global scaling up of HIV treatment, HIV-1 protease inhibitors are increasingly becoming available for second-line HIV treatment in regions where visceral leishmaniasis and HIV are endemic. However, additional research is needed before HIV-1 protease inhibitors can be taken forward for clinical use against visceral leishmaniasis in HIV-infected patients. Since the effect of protease inhibitors against Leishmania species was generally observed at high drug concentrations, efficacy and dose-response relationships should be studied in animals before these drugs are used in clinical trials. More extensive studies of all available HIV protease inhibitors are needed, including investigation of drug interactions and emergence of drug-resistant parasites. In addition to exploring the full potential of current HIV-1 protease inhibitors against visceral leishmaniasis, leishmania-specific protease inhibitors should be developed

    Incidence and risk factors for tuberculosis in HIV-infected patients while on antiretroviral treatment in Cambodia

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    BACKGROUND: Given the lack of detailed studies on tuberculosis (TB) in patients on antiretroviral treatment (ART) in South-East Asia, we aimed to determine the incidence and risk factors for early (after 6 months of ART) incident TB in Cambodia. METHODS: We conducted a retrospective analysis of all patients started on ART at a non-governmental hospital in Phnom Penh (March 2003-December 2010). TB diagnosis was performed according to WHO algorithms. Risk factor analysis was performed using multivariate Cox regression modeling. RESULTS: Overall, 2984 patients started ART. The median baseline CD4 count was 89 cells microl(-1) (IQR 25-209), median age 34 years (IQR 29-40). Fifty-three percent of the patients were female. Median follow-up time on ART was 2.4 years. In addition to 932 (31.2%) patients already on TB treatment at ART initiation, 313 (10.5%) developed TB, with an overall incidence rate of 3.9/100 patient-years. Of those developing TB, 179 (6.0%) patients were diagnosed with early TB and 134 (4.5%) with late TB, corresponding with a rate of 13.5 and 2.0 per 100 patient-years respectively. Risk factors for early TB included low body mass index, low baseline CD4 count and low hemoglobin levels. Low on-treatment CD4 counts and hemoglobin levels, being underweight while on ART and prevalent TB were identified as risk factors for late TB. CONCLUSION: The incidence of early TB was high, and predominantly associated with advanced HIV progression markers. Earlier ART initiation and enhanced TB screening prior to and after ART initiation is warranted. Late TB amounts to almost half of the total TB burden, meriting specific preventive and diagnostic approaches

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