Browsing by Author "Epco Hasker"

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A global comparative evaluation of commercial immunochromatographic rapid diagnostic tests for visceral leishmaniasis
(Oxford University Press, 2012) Jane Cunningham; Epco Hasker; Pradeep Das; Sayda El Safi; Hiro Goto; Dinesh Mondal; Margaret Mbuchi; Maowia Mukhtar; Ana Rabello; Suman Rijal; Shyam Sundar; Monique Wasunna; Emily Adams; Joris Menten; Rosanna Peeling; Marleen Boelaert; Murari Das; Edward Oliveira; Tália Machado de Assis; Khondaker Rifathassan Bhaskar; M. Mamun Huda; Mukidul Hassan; Asim Osman Abdoun; Aymen Awad; Mohamed Osman; Dinesh Kumar Prajapati; Kamlesh Gidwani; Puja Tiwary; Anamaria Mello Miranda Paniago; Maria Carmen Arroyo Sanchez; Beatriz Julieta Celeste; Diane Jacquet; Charles Magiri; A. Muia; J. Kesusu; Al Farazdag Ageed; Nuha Galal; Osman Salih Osman; A.K. Gupta; Afrad S. Bimal; V.N.R. Das
Background. Poor access to diagnosis stymies control of visceral leishmaniasis (VL). Antibody-detecting rapid diagnostic tests (RDTs) can be performed in peripheral health settings. However, there are many brands available and published reports of variable accuracy. Methods. Commercial VL RDTs containing bound rK39 or rKE16 antigen were evaluated using archived human sera from confirmed VL cases (n = 750) and endemic non-VL controls (n = 754) in the Indian subcontinent (ISC), Brazil, and East Africa to assess sensitivity and specificity with 95 confidence intervals. A subset of RDTs were also evaluated after 60 days' heat incubation (37°C, 45°C). Interlot and interobserver variability was assessed. Results. All test brands performed well against ISC panels (sensitivity range, 92.8-100; specificity range, 96-100); however, sensitivity was lower against Brazil and East African panels (61.5-91 and 36.8-87.2, respectively). Specificity was consistently > 95 in Brazil and ranged between 90.8 and 98 in East Africa. Performance of some products was adversely affected by high temperatures. Agreement between lots and readers was good to excellent ( > 0.73-0.99). Conclusions. Diagnostic accuracy of VL RDTs varies between the major endemic regions. Many tests performed well and showed good heat stability in the ISC; however, reduced sensitivity against Brazilian and East African panels suggests that in these regions, used alone, several RDTs are inadequate for excluding a VL diagnosis. More research is needed to assess ease of use and to compare performance using whole blood instead of serum and in patients coinfected with human immunodeficiency virus. © 2012 The Author.
Assessing L. donovani Skin Parasite Load: A Proof of Concept Study of a Microbiopsy Device in an Indian Setting
(Frontiers Media S.A., 2021) Kristien Cloots; Om Prakash Singh; Abhishek Kumar Singh; Gert Van der Auwera; Prashant Kumar; Mallikarjuna Rao Gedda; Tulika Kumari Rai; Epco Hasker; Shyam Sundar; Marleen Boelaert
Background: In the endgame of the elimination initiative of visceral leishmaniasis (VL) on the Indian subcontinent, one of the main questions remaining is whether asymptomatically infected individuals also contribute to transmission. We piloted a minimally invasive microbiopsy device that could help answer this question. While the potential of this device has been previously illustrated in Ethiopia, no such information is available for the setting of the Indian subcontinent. In this proof of concept study we aimed to assess 1) to what extent skin parasite load obtained with the new microbiopsy device correlates with disease status, 2) to what extent skin parasite load correlates with blood parasite load in the same subject, and 3) to what extent the skin parasite load obtained from different sampling sites on the body correlates with one another. Methods: We performed a pilot study in Bihar, India, including 29 VL patients, 28 PKDL patients, 94 asymptomatically infected individuals, 22 endemic controls (EC), and 28 non-endemic controls (NEC). Presence of infection with L. donovani in the blood was assessed using Direct Agglutination Test, rK39 ELISA, Whole Blood Analysis measuring IFN-γ and qPCR. A skin sample was collected with the microbiopsy device on two different locations on the body. PKDL patients provided a third skin sample from the edge of a PKDL lesion. Parasite load in the skin was measured by qPCR. Findings: We found a clear correlation between the skin parasite load obtained with the microbiopsy device and disease status, with both higher skin parasite loads and higher proportions of positive skin samples in VL and PKDL patients compared to asymptomatics, EC, and NEC. No clear correlation between skin parasite load and blood parasite load was found, but a moderate correlation was present between the skin parasite load in arm and neck samples. In addition, we found four positive skin samples among asymptomatic individuals, and 85% of PKDL lesions tested positive using this microbiopsy device. Conclusions: In line with previous pilot studies, our results from an Indian setting suggest that the microbiopsy device provides a promising tool to measure skin parasite load, and – if validated by xenodiagnosis studies – could facilitate much needed larger scale studies on infectiousness of human subgroups. In addition, we advocate further evaluation of this device as a diagnostic tool for PKDL. © Copyright © 2021 Cloots, Singh, Singh, Van der Auwera, Kumar, Gedda, Rai, Hasker, Sundar and Boelaert.
Asymptomatic leishmania infection: A new challenge for leishmania control
(University of Chicago Press, 2014) Om Prakash Singh; Epco Hasker; David Sacks; Marleen Boelaert; Shyam Sundar
Visceral leishmaniasis (VL) is a serious parasitic disease, causing high morbidity and mortality in the developing world. The pathogenesis of VL is complex, and the clinical presentation ranges from asymptomatic infection to severe and fatal disease. Despite a wealth of research on the full-blown "clinical VL" syndrome, asymptomatic leishmania infections remain poorly understood. Asymptomatic infection could present a major challenge for control programs if its infectiousness is confirmed. In this viewpoint, we highlight the crucial knowledge gaps as well as the obstacles in research on asymptomatic leishmanial infection. Research in this area is essential for the development of more-effective VL control strategies. © 2014 The Author.
Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study
(Public Library of Science, 2018) Jaya Chakravarty; Epco Hasker; Sangeeta Kansal; Om Prakash Singh; Paritosh Malaviya; Abhishek Kumar Singh; Ankita Chourasia; Toolika Singh; Medhavi Sudarshan; Akhil Pratap Singh; Bhawana Singh; Rudra Pratap Singh; Bart Ostyn; Michaela Fakiola; Albert Picado; Joris Menten; Jenefer M. Blackwell; Mary E. Wilson; David Sacks; Marleen Boelaert; Shyam Sundar
Background: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). Methods: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6–12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. Results: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1–8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. Conclusion: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated. © 2018, Public Library of Science. All rights reserved. https://creativecommons.org/publicdomain/zero/1.0/.
Diagnosis of Visceral Leishmaniasis in an Elimination Setting: A Validation Study of the Diagnostic Algorithm in India
(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Kristien Cloots; Om Prakash Singh; Abhishek Kumar Singh; Anurag Kumar Kushwaha; Paritosh Malaviya; Sangeeta Kansal; Epco Hasker; Shyam Sundar
Visceral leishmaniasis (VL) is on the verge of elimination on the Indian subcontinent. Nonetheless, the currently low VL-incidence setting brings along new challenges, one of which is the validity of the diagnostic algorithm, based on a combination of suggestive clinical symptoms in combination with a positive rK39 Rapid Diagnostic Test (RDT). With this study, we aimed to assess the positive predictive value of the diagnostic algorithm in the current low-endemic setting in India by re-assessing newly diagnosed VL patients with a qPCR analysis on venous blood as the reference test. In addition, we evaluated the specificity of the rK39 RDT by testing non-VL cases with the rK39 RDT. Participants were recruited in Bihar and Uttar Pradesh, India. VL patients diagnosed based on the diagnostic algorithm were recruited through six primary health care centers (PHCs); non-VL cases were identified through a door-to-door survey in currently endemic, previously endemic, and non-endemic clusters, and tested with rK39 RDT, as well as—if positive—with qPCR on peripheral blood. We found that 95% (70/74; 95% CI 87–99%) of incident VL cases diagnosed at the PHC level using the current diagnostic algorithm were confirmed by qPCR. Among 15,422 non-VL cases, 39 were rK39 RDT positive, reflecting a specificity of the test of 99.7% (95% CI 99.7–99.8%). The current diagnostic algorithm combining suggestive clinical features with a positive rK39 RDT still seems valid in the current low-endemic setting in India. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Elimination of visceral leishmaniasis on the Indian subcontinent
(Lancet Publishing Group, 2016) Om Prakash Singh; Epco Hasker; Marleen Boelaert; Shyam Sundar
Visceral leishmaniasis is a serious public health problem on the Indian subcontinent, causing high morbidity and mortality. The governments in the region launched a visceral leishmaniasis elimination initiative in 2005. We review knowledge gaps and research priorities. Key challenges include low coverage of health services for those most at risk, drug resistance, the absence of a vaccine, and the complex biology of the sandfly–human host transmission cycle. Vector control is an essential component, but innovation in this field is insufficient. Substantial progress has been made in the area of diagnostic, therapeutic, and vaccine development, but there are still many hurdles to overcome. For visceral leishmaniasis elimination to become a reality, effective deployment of these existing and new tools is essential. A strong commitment at community level is imperative, and appropriate diagnostic and treatment services as well as effective epidemiological surveillance need to be ensured. © 2016 Elsevier Ltd
Exposure to phlebotomus argentipes (diptera, psychodidae, phlebotominae) sand flies in rural areas of Bihar, India: The role of housing conditions
(Public Library of Science, 2014) Paritosh Malaviya; Epco Hasker; Albert Picado; Mukesh Mishra; Jean-Pierre Van Geertruyden; Murari Lal Das; Marleen Boelaert; Shyam Sundar
Background: Visceral Leishmaniasis (VL) is a vector-borne infectious disease, caused by the protozoan Leishmania donovani, which is transmitted by phlebotomine sand flies. In an earlier study in Bihar, India, we found an association between incidence of VL and housing conditions. In the current study we investigated the influence of housing structure and conditions in and around the house on the indoor abundance of Phlebotomus argentipes, the vector of VL in this area. Methods: In each of 50 study villages in Muzaffarpur district, we randomly selected 10 houses. Light traps were installed in each house for one night during three annual peaks of sand fly density over two successive years. Sand flies captured were morphologically identified and segregated by species, sex and feeding status. Data on housing conditions and socioeconomic status were also collected. We fitted a linear mixed-effects regression model with log-transformed P. argentipes counts as outcome variable and village as random effect. Results: P. argentipes was found in all but four of the 500 households. There was considerable variability between the years and the seasons. On bivariate analysis, housing structure, dampness of the floor, keeping animals inside, presence of animal dung around the house, and socio-economic status were all significantly associated with sand fly density. Highest sand fly densities were observed in thatched houses. In the multivariate model only the housing structure and socio-economic status remained significant. Conclusions: Better housing conditions are associated with lower sand fly densities, independent of other socio-economic conditions. However, in this area in Bihar even in the better-built houses sand flies are present. © 2014 Malaviya et al.
Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia
(Public Library of Science, 2014) Bart Ostyn; Epco Hasker; Thomas P. C. Dorlo; Suman Rijal; Shyam Sundar; Jean-Claude Dujardin; Marleen Boelaert
Background: High frequency of relapse in miltefosine-treated visceral leishmaniasis (VL) patients in India and Nepal followed up for twelve months. Objective: To identify epidemiological and clinical risk factors for relapse of VL in patients recently treated with standard dosing of miltefosine in India and Nepal. Design: Prospective observational study in three Primary Health Centers and one reference center in Muzaffarpur district, Bihar, India; and two zonal hospitals and a university hospital in South-east Nepal; records of all consenting patients diagnosed with VL and treated with miltefosine according to the current treatment guidelines of the Kala azar elimination program between 2009 and 2011. Results: We compared the clinical records of 78 cases of relapse with those of 775 patients who had no record of subsequent relapse. Relapse was 2 times more common amongst male patients (IRR 2.14, 95% CI 1.27-3.61), and 2 to 3 times more frequent in the age groups below 15 compared to the over 25 year olds (age 10 to 14: IRR 2.53; 95% CI 1.37-4.65 and Age 2 to 9: IRR 3.19; 95% CI 1.77-5.77). History of earlier VL episodes, or specific clinical features at time of diagnosis such as duration of symptoms or spleen size were no predictors of relapse. Conclusions: Young age and male gender were associated with increased risk of VL relapse after miltefosine, suggesting that the mechanism of relapse is mainly host-related i.e. immunological factors and/or drug exposure (pharmacokinetics). The observed decrease in efficacy of miltefosine may be explained by the inclusion of younger patients compared to the earlier clinical trials, rather than by a decreased susceptibility of the parasite to miltefosine. Our findings highlight the importance of proper clinical trials in children, including pharmacokinetics, to determine the safety, efficacy, drug exposure and therapeutic response of new drugs in this age group. © 2014 Ostyn et al.
Field-friendly anti-PGL-I serosurvey in children to monitor Mycobacterium leprae transmission in Bihar, India
(Frontiers Media SA, 2023) Louise Pierneef; Paritosh Malaviya; Anouk van Hooij; Shyam Sundar; Abhishek Kumar Singh; Rajiv Kumar; Danielle de Jong; Maaike Meuldijk; Awnish Kumar; Zijie Zhou; Kristien Cloots; Paul Corstjens; Epco Hasker; Annemieke Geluk
Background: It has been amply described that levels of IgM antibodies against Mycobacterium leprae (M. leprae) phenolic glycolipid I (PGL-I) correlate strongly with the bacterial load in an infected individual. These findings have generated the concept of using seropositivity for antibodies against M. leprae PGL-I as an indicator of the proportion of the population that has been infected. Although anti-PGL-I IgM levels provide information on whether an individual has ever been infected, their presence cannot discriminate between recent and past infections. Since infection in (young) children by definition indicates recent transmission, we piloted the feasibility of assessment of anti-PGL-I IgM seroprevalence among children in a leprosy endemic area in India as a proxy for recent M. leprae transmission. Material and methods: A serosurvey for anti-PGL-I IgM antibodies among children in highly leprosy endemic villages in Bihar, India, was performed, applying the quantitative anti-PGL-I UCP-LFA cassette combined with low-invasive, small-volume fingerstick blood (FSB). Results: Local staff obtained FSB of 1,857 children (age 3–11 years) living in 12 leprosy endemic villages in Bihar; of these, 215 children (11.58%) were seropositive for anti-PGL-I IgM. Conclusion: The anti-PGL-I seroprevalence level of 11.58% among children corresponds with the seroprevalence levels described in studies in other leprosy endemic areas over the past decades where no prophylactic interventions have taken place. The anti-PGL-I UCP-LFA was found to be a low-complexity tool that could be practically combined with serosurveys and was well-accepted by both healthcare staff and the population. On route to leprosy elimination, quantitative anti-PGL-I serology in young children holds promise as a strategy to monitor recent M. leprae transmission in an area. Copyright © 2023 Pierneef, Malaviya, van Hooij, Sundar, Singh, Kumar, de Jong, Meuldijk, Kumar, Zhou, Cloots, Corstjens, Hasker and Geluk.
Health & demographic surveillance system profile: The muzaffarpur-tmrc health and demographic surveillance system
(Oxford University Press, 2014) Paritosh Malaviya; Albert Picado; Epco Hasker; Bart Ostyn; Sangeeta Kansal; Rudra Pratap Singh; Ravi Shankar; Marleen Boelaert; Shyam Sundar
The Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS), established in 2007, was developed as an enlargement of the scope of a research collaboration on the project Visceral Leishmaniasis in Bihar, which had been ongoing since 2005. The HDSS is located in a visceral leishmaniasis (VL)-endemic area in the Muzaffarpur district of Bihar state in India. It is the only HDSS conducting research on VL, which is a vectorborne infectious disease transmitted by female phlebotomine sandflies and is fatal if left untreated. Currently the HDSS serves a population of over 105 000 in 66 villages. The HDSS collects data on vital events including pregnancies, births, deaths, migration and marriages, as well as other socio-economic indicators, at regular intervals. Incident VL cases are identified. The HDSS team is experienced in conducting both qualitative and quantitative studies, sample collection and rapid diagnostic tests in the field. In each village, volunteers connect the HDSS team with the community members. The Muzaffarpur-TMRC HDSS provides opportunities for studies on VL and other neglected tropical diseases (NTDs) and their interaction with demographic events such as migration. © The Author 2014; all rights reserved.
Latent Infection with Leishmania donovani in Highly Endemic Villages in Bihar, India
(Public Library of Science, 2013) Epco Hasker; Sangeeta Kansal; Paritosh Malaviya; Kamlesh Gidwani; Albert Picado; Rudra Pratap Singh; Ankita Chourasia; Abhishek Kumar Singh; Ravi Shankar; Joris Menten; Mary Elizabeth Wilson; Marleen Boelaert; Shyam Sundar
Introduction: Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL) usually outnumber clinically apparent cases by a ratio of 4-10 to 1. We describe patterns of markers of Leishmania donovani infection and clinical VL in relation to age in Bihar, India. Methods: We selected eleven villages highly endemic for Leishmania donovani. During a 1-year interval we conducted two house to house surveys during which we collected blood samples on filter paper from all consenting individuals aged 2 years and above. Samples were tested for anti-leishmania serology by Direct Agglutination Test (DAT) and rK39 ELISA. Data collected during the surveys included information on episodes of clinical VL among study participants. Results: We enrolled 13,163 persons; 6.2% were reactive to DAT and 5.9% to rK39. Agreement between the tests was weak (kappa = 0.30). Among those who were negative on both tests at baseline, 3.6% had converted to sero-positive on either of the two tests one year later. Proportions of sero-positives and sero-converters increased steadily with age. Clinical VL occurred mainly among children and young adults (median age 19 years). Discussion: Although infection with L. donovani is assumed to be permanent, serological markers revert to negative. Most VL cases occur at younger ages, yet we observed a steady increase with age in the frequency of sero-positivity and sero-conversion. Our findings can be explained by a boosting effect upon repeated exposure to the parasite or by intermittent release of parasites in infected subjects from safe target cells. A certain proportion of sero-negative subjects could have been infected but below the threshold of antibody abundance for our serologic testing.
Long-lasting Insecticidal Nets to Prevent Visceral Leishmaniasis in the Indian Subcontinent; Methodological Lessons Learned from a Cluster Randomised Controlled Trial
(Public Library of Science, 2015) Albert Picado; Bart Ostyn; Suman Rijal; Shyam Sundar; Shri Prakash Singh; François Chappuis; Murari Lal Das; Basudha Khanal; Kamlesh Gidwani; Epco Hasker; Jean Claude Dujardin; Veerle Vanlerberghe; Joris Menten; Marc Coosemans; Marleen Boelaert
[No abstract available]
Male predominance in reported visceral leishmaniasis cases: Nature or nurture? A comparison of population-based with health facility-reported data
(Public Library of Science, 2020) Kristien Cloots; Sakib Burza; Paritosh Malaviya; Epco Hasker; Sangeeta Kansal; Guy Mollett; Jaya Chakravarty; Nurpur Roy; Bibek Kumar Lal; Suman Rijal; Shyam Sundar; Marleen Boelaert
Background Bangladesh, India, and Nepal aim for the elimination of Visceral Leishmaniasis (VL), a sys-temic parasitic infectious disease, as a public health problem by 2020. For decades, male patients have comprised the majority of reported VL cases in this region. By comparing this reported VL sex ratio to the one observed in population-based studies conducted in the Indian subcontinent, we tested the working hypothesis that mainly socio-cultural gender differences in healthcare-seeking behavior explain this gender imbalance. Methodology/Principal findings We compared the observed sex ratio of male versus female among all VL cases reported by the health system in Nepal and in the two most endemic states in India with that observed in population-based cohort studies in India and Nepal. Also, we assessed male sex as a poten-tial risk factor for seroprevalence at baseline, seroconversion, and VL incidence in the same population-based data. The male/female ratio among VL cases reported by the health systems was 1.40 (95% CI 1.37–1.43). In the population cohort data, the age-and study site-adjusted male to female risk ratio was 1.27 (95% CI 1.08–1.51). Also, males had a 19% higher chance of being seropositive at baseline in the population surveys (RR 1.19; 95% CI 1.11–1.27), while we observed no significant difference in seroconversion rate between both sexes at the DAT cut-off titer defined as the primary endpoint. Conclusions/Significance Our population-based data show that male sex is a risk factor for VL, and not only as a socio-cultural determinant. Biological sex-related differences likely play an important role in the pathogenesis of this disease. © 2020 Cloots et al.
Monitoring of Leishmania transmission in the postelimination phase: The potential of serological surveys
(Elsevier B.V., 2024) Kristien Cloots; Om Prakash Singh; Abhishek Kumar Singh; Tulika Kumari Rai; Vishwa Deepak Tiwari; Aziza Neyaz; Sundaram Pandey; Vivek Kumar Scholar; Paritosh Malaviya; Epco Hasker; Shyam Sundar
Objectives: Monitoring of Leishmania transmission is considered a strategic priority for sustaining elimination of visceral leishmaniasis as a public health problem in the Indian subcontinent. The objective of this study was to evaluate whether serological surveys can distinguish between communities with and without Leishmania transmission, and to assess which serological marker performs best. Methods: Seven villages were selected from Bihar and Uttar Pradesh state, India, and categorized as either currently endemic (CE), previously endemic (PE) or nonendemic (NE). Blood samples were analyzed with the rK39 RDT, direct agglutination test (DAT), and rK39 ELISA. Results: Contrary to the rK39 RDT and DAT, the rK39 ELISA showed a significant difference between all three categories of endemicity, with a seroprevalence of 5.21% in CE villages, 1.55% in PE villages, and 0.13% in NE villages. Even when only looking at the seroprevalence among children aged <10 years, the rK39 ELISA was still able to differentiate between villages with and without ongoing transmission. Conclusion: Our findings suggest the rK39 ELISA to be the most promising marker for monitoring of Leishmania transmission. Further validation is required, and practical, context-adapted recommendations need to be formulated in order to guide policymakers toward meaningful and sustainable surveillance strategies in the post-elimination phase. © 2024 The Author(s)
Post kala azar dermal leishmaniasis and leprosy prevalence and distribution in the Muzaffarpur health and demographic surveillance site
(Public Library of Science, 2019) Epco Hasker; Paritosh Malaviya; Vivek Kumar Scholar; Pieter de Koning; Om Prakash Singh; Sangeeta Kansal; Kristien Cloots; Marleen Boelaert; Shyam Sundar
Introduction Post-kala-azar dermal leishmaniasis (PKDL) is a skin manifestation that is a late clinical outcome of visceral leishmaniasis (VL). Its presentation is similar to leprosy, and the differential diagnosis is not always easy. In VL endemic rural areas of Bihar, India, both infectious diseases co-exist. This observational study aimed to determine the prevalence and distribution of both conditions in an area that had until recently been highly endemic for VL. Methods We conducted a door-to-door survey in an area that belongs to the Health and Demographic Surveillance Site (HDSS) of Muzaffarpur, Bihar, India. Within the HDSS we selected the villages that had reported the highest numbers of VL cases in preceding years. All consenting household members were screened for skin conditions, and minor conditions were treated on the spot. Upon completion of screening activities at the level of a few villages, a dermatology clinic (“skin camp”) was conducted to which suspect leprosy and PKDL patients and other patients with skin conditions requiring expert advice were referred. We studied the association between distance from an index case of leprosy and the probability of disease in the neighborhood by fitting a Poisson model. Results We recorded a population of 33,319, out of which 25,686 (77.1%) were clinically screened. Participation in skin camps was excellent. Most common conditions were fungal infections, eczema, and scabies. There were three PKDL patients and 44 active leprosy patients, equivalent to a prevalence rate of leprosy of 17.1 per 10,000. Two out of three PKDL patients had a history of VL. Leprosy patients were widely spread across villages, but within villages, we found strong spatial clustering, with incidence rate ratios of 6.3 (95% C.I. 1.9–21.0) for household members and 3.6 (95% C.I. 1.3–10.2) for neighbors within 25 meters, with those living at more than 100 meters as the reference category. Discussion Even in this previously highly VL endemic area, PKDL is a rare condition. Nevertheless, even a single case can trigger a new VL outbreak. Leprosy is also a rare disease, but current prevalence is over 17 times the elimination threshold proclaimed by WHO. Both diseases require continued surveillance. Active case finding for leprosy can be recommended among household members and close neighbors of leprosy patients but would not be feasible for entire populations. Periodic skin camps may be a feasible and affordable alternative. © 2019 Hasker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Post-kala-azar dermal leishmaniasis in visceral leishmaniasis-endemic communities in Bihar, India
(2012) Rudra Pratap Singh; Albert Picado; Shahnawaz Alam; Epco Hasker; Shri Prakash Singh; Bart Ostyn; François Chappuis; Shyam Sundar; Marleen Boelaert
We assessed the prevalence of post-kala-azar dermal leishmaniasis (PKDL), a late cutaneous manifestation of visceral leishmaniasis (VL), in 16 VL-endemic communities in Bihar, India. The prevalence of confirmed PKDL cases was 4.4 per 10000 individuals and 7.8 if probable cases were also considered. The clinical history and treatment of the post-kala-azar dermal leishmaniasis cases are discussed. © 2012 Blackwell Publishing Ltd.
Retrospective Quarterly Cohort Monitoring for patients with Visceral Leishmaniasis in the Indian subcontinent: Outcomes of a pilot project
(2013) Bart Ostyn; Paritosh Malaviya; Epco Hasker; Surendra Uranw; Rudra P. Singh; Suman Rijal; Shyam Sundar; Jean-Claude Dujardin; Marleen Boelaert
Objective: To evaluate a new tool for the monitoring of Visceral Leishmaniasis (VL) treatment outcomes in primary healthcare (PHC) settings, adapted from the standardised Retrospective Quarterly Cohort Monitoring done in tuberculosis control. Methods: We developed standard case definitions for early and late VL treatment outcomes, a single register allowing for one-line entry per patient as registration tool, and quarterly reporting formats for the clinical outcomes. We pilot-tested these tools in three Indian Primary Health Centres and two Nepalese district hospitals, as well as in a charity VL treatment centre and a university hospital. Results: Data collection for early treatment outcome was easily implemented but information on late treatment outcome was hard to obtain. Effectiveness of Miltefosine under routine care conditions was about 87% at end of treatment, and 76% at 6 months post-treatment related to the high number of patients lost to follow up at the latter end point. Conclusion: A retrospective cohort monitoring methodology is conceptually a good framework for monitoring clinical outcomes for chronic conditions as VL. The monitoring of early outcomes of VL treatment is perfectly feasible in Primary Care settings. The completeness of information on late outcomes can be improved by a number of strategies that remain to be field tested. Generally, clinical outcome monitoring should be strengthened in the VL control programmes. © 2013 John Wiley & Sons Ltd.
Risk factors for visceral leishmaniasis and asymptomatic Leishmania donovani infection in India and Nepal
(Public Library of Science, 2014) Albert Picado; Bart Ostyn; Shri Prakash Singh; Surendra Uranw; Epco Hasker; Suman Rijal; Shyam Sundar; Marleen Boelaert; François Chappuis
There is increasing interest in the role of asymptomatic infection in transmission of Visceral Leishmaniasis (VL). We studied the individual, household and environmental factors associated with asymptomatic Leishmania donovani infected individuals and VL. 7,538 individuals living in VL endemic villages in India and Nepal were divided into three mutually exclusive groups based on their VL history and Direct Agglutination Test (DAT) results in yearly serosurveys over a two-year period. The groups were (1) VL cases, (2) asymptomatically infected individuals (seroconverters) and (3) seronegative individuals. VL cases and seroconverters were compared to seronegative individuals in mixed logistic regression models. The risk of seroconversion and disease was significantly increased in individuals aged 14 to 24 years old and by the presence of other DAT-positive, asymptomatically infected individuals and VL cases in the house. The risk of seroconversion was higher in Indian than in Nepalese villages and it increased significantly with age, but not so for VL. This study demonstrates that, when risk factors for leishmanial infection and VL disease are evaluated in the same population, epidemiological determinants for asymptomatic infection and VL are largely similar. © 2014 Picado et al.
Strong Association between Serological Status and Probability of Progression to Clinical Visceral Leishmaniasis in Prospective Cohort Studies in India and Nepal
(Public Library of Science, 2014) Epco Hasker; Paritosh Malaviya; Kamlesh Gidwani; Albert Picado; Bart Ostyn; Sangeeta Kansal; Rudra Pratap Singh; Om Prakash Singh; Ankita Chourasia; Abhishek Kumar Singh; Ravi Shankar; Mary E. Wilson; Basudha Khanal; Suman Rijal; Marleen Boelaert; Shyam Sundar
Introduction:Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL) usually outnumber clinically apparent cases by a ratio of 4-10 to 1. We assessed the risk of progression from infection to disease as a function of DAT and rK39 serological titers.Methods:We used available data on four cohorts from villages in India and Nepal that are highly endemic for Leishmania donovani. In each cohort two serosurveys had been conducted. Based on results of initial surveys, subjects were classified as seronegative, moderately seropositive or strongly seropositive using both DAT and rK39. Based on the combination of first and second survey results we identified seroconvertors for both markers. Seroconvertors were subdivided in high and low titer convertors. Subjects were followed up for at least one year following the second survey. Incident VL cases were recorded and verified.Results:We assessed a total of 32,529 enrolled subjects, for a total follow-up time of 72,169 person years. Altogether 235 incident VL cases were documented. The probability of progression to disease was strongly associated with initial serostatus and with seroconversion; this was particularly the case for those with high titers and most prominently among seroconvertors. For high titer DAT convertors the hazard ratio reached as high as 97.4 when compared to non-convertors. The strengths of the associations varied between cohorts and between markers but similar trends were observed between the four cohorts and the two markers.Discussion:There is a strongly increased risk of progressing to disease among DAT and/or rK39 seropositives with high titers. The options for prophylactic treatment for this group merit further investigation, as it could be of clinical benefit if it prevents progression to disease. Prophylactic treatment might also have a public health benefit if it can be corroborated that these asymptomatically infected individuals are infectious for sand flies.
Visceral Leishmaniasis in Muzaffarpur district, Bihar, India from 1990 to 2008
(2011) Paritosh Malaviya; Albert Picado; Shri Prakash Singh; Epco Hasker; Rudra Pratap Singh; Marleen Boelaert; Shyam Sundar
Background:Visceral Leishmaniasis (VL) is a vector-borne disease transmitted by Phlebotomus argentipes. To understand the VL seasonality, annual and monthly variations of VL incidence and its relationship to meteorological variables, the numbers of VL cases reported in Muzaffarpur district, Bihar, India from 1990 to 2008 were studied.Methods:Annual VL incidence per 10,000 and the total number of annual VL cases reported at block Community Health Centres (CHC), Public Hospitals or Non-Governmental Organisations (NGO) and the number of VL cases per month from 2000 to 2008 as well as the monthly average of cases for 2000-08, 2000-04 and 2005-08 periods along with the monthly averages of temperature, rainfall and relative humidity were plotted. VL Standardised Incidence Ratios per block were computed for the periods of 1990-1993, 1994-1998, 1999-2004 and 2005-2008 and month wise from 2002 to 2008. A negative binomial regression model was used to evaluate the association between meteorological variables and the number of VL cases per month from 2000 to 2008.Results:A total of 68,358 VL cases were reported in Muzaffarpur district from 1990 to 2008, ranging from 1,2481 in 1992 to 1,161 in 2001. The blocks with the highest number of cases shifted from East (1990-98) to West (1999-2008). Monthly averages of cases ranged from 149 to 309, highest peak in March-April and another one in July. Monthly VL incidence was associated positively to rainfall and negatively to relative humidity and the numbers of VL cases in the previous month.Interpretation:The number of cases reported to the public health sector allowed the describing of the spatial distribution and temporal variations in the Muzaffarpur from 1990 to 2008. However, to assess the actual VL burden, as well as the efficacy of the control measures applied in the district, reporting from private practices and NGOs should be encouraged. © 2011 Malaviya et al.