Browsing by Author "Bart Ostyn"

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Characterisation of antimony-resistant Leishmania donovani isolates: Biochemical and biophysical studies and interaction with host cells
(2011) Rupkatha Mukhopadhyay; Sandip Mukherjee; Budhaditya Mukherjee; Kshudiram Naskar; Dinesh Mondal; Saskia Decuypere; Bart Ostyn; Vijay Kumar Prajapati; Shyam Sundar; Jean Claude Dujardin; Syamal Roy
Recent clinical isolates of Leishmania donovani from the hyperendemic zone of Bihar were characterised in vitro in terms of their sensitivity towards sodium stibogluconate in a macrophage culture system. The resulting half maximal effective concentration (EC 50) values were compared with those of known sensitive isolates. Fifteen of the isolates showed decreased sensitivity towards SSG with an average EC 50 of 25.7±4.5μg/ml pentavalent antimony (defined as antimony resistant), whereas nine showed considerable sensitivity with an average EC 50 of 4.6±1.7μg/ml (defined as antimony sensitive). Out of those nine, seven were recent clinical isolates and the remaining two were known sensitive isolates. Compared with the antimony sensitive, resistant isolates showed enhanced expression of thiol metabolising enzymes in varying degrees coupled with increased intracellular non-protein thiol content, decreased fluorescence anisotropy (inversely proportional with membrane fluidity) and over-expression of the terminal glycoconjugates (N-acetyl-d-galactosaminyl residue). Macrophages infected with resistant but not with sensitive showed up-regulation of the ATP Binding Cassette transporter multidrug resistance protein 1 and permeability glycoprotein, while the supernatant contained abundant IL-10. The above results reinforce the notion that antimony resistant parasites have undergone a number of biochemical and biophysical changes as part of their adaptation to ensure their survival in the host. © 2011 Australian Society for Parasitology Inc.
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/.
Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use
(2012) Shyam Sundar; Anup Singh; Madhukar Rai; Vijay K. Prajapati; Avinash K. Singh; Bart Ostyn; Marleen Boelaert; Jean-Claude Dujardin; Jaya Chakravarty
Background. Miltefosine is the only oral drug available for treatment of Indian visceral leishmaniasis (VL), which was shown to have an efficacy of 94% in a phase III trial in the Indian subcontinent. Its unrestricted use has raised concern about its continued effectiveness. This study evaluates the efficacy and safety of miltefosine for the treatment of VL after a decade of use in India. Methods. An open-label, noncomparative study was performed in which 567 patients received oral miltefosine (50 mg for patients weighing <25 kg, 100 mg in divided doses for those weighing =25 kg, and 2.5 mg per kg for those aged <12 years, daily for 28 days) in a directly observed manner. Patients were followed up for 6 months to see the response to therapy. Results. At the end of treatment the initial cure rate was 97.5% (intention to treat), and 6 months after the end of treatment the final cure rate was 90.3%. The overall death rate was 0.9% (5 of 567), and 2 deaths were related to drug toxicity. Gastrointestinal intolerance was frequent (64.5%). The drug was interrupted in 9 patients (1.5%) because of drug-associated adverse events. Conclusions. As compared to the phase III trial that led to registration of the drug a decade ago, there is a substantial increase in the failure rate of oral miltefosine for treatment of VL in India. © The Author 2012.
Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent
(eLife Sciences Publications Ltd, 2016) Hideo Imamura; Tim Downing; Frederik van den Broeck; Mandy J. Sanders; Suman Rijal; Shyam Sundar; An Mannaert; Manu Vanaerschot; Maya Berg; Géraldine de Muylder; Franck Dumetz; Bart Cuypers; Ilse Maes; Malgorzata Domagalska; Saskia Decuypere; Keshav Rai; Surendra Uranw; Narayan Raj Bhattarai; Basudha Khanal; Vijay Kumar Prajapati; Smriti Sharma; Olivia Stark; Gabriele Schönian; Harry P. de Koning; Luca Settimo; Benoit Vanhollebeke; Syamal Roy; Bart Ostyn; Marleen Boelaert; Louis Maes; Matthew Berriman; Jean-Claude Dujardin; James A. Cotton
Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector- borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment. © Imamura 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.
Genetic markers for SSG resistance in leishmania donovani and SSG treatment failure in visceral leishmaniasis patients of the Indian subcontinent
(2012) Manu Vanaerschot; Saskia Decuypere; Tim Downing; Hideo Imamura; Olivia Stark; Simonne De Doncker; Syamal Roy; Bart Ostyn; Louis Maes; Basudha Khanal; Marleen Boelaert; Gabriele Schönian; Matthew Berriman; François Chappuis; Jean-Claude Dujardin; Shyam Sundar; Suman Rijal
The current standard to assess pentavalent antimonial (SSG) susceptibility of Leishmania is a laborious in vitro assay of which the result has little clinical value because SSG-resistant parasites are also found in SSG-cured patients. Candidate genetic markers for clinically relevant SSG-resistant parasites identified by full genome sequencing were here validated on a larger set of clinical strains. We show that 3 genomic locations suffice to specifically detect the SSG-resistant parasites found only in patients experiencing SSG treatment failure. This finding allows the development of rapid assays to monitor the emergence and spread of clinically relevant SSG-resistant Leishmania parasites. © The Author 2012.
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.
In vitro susceptibility of leishmania donovani to miltefosine in Indian visceral leishmaniasis
(2013) Vijay Kumar Prajapati; Smriti Sharma; Madhukar Rai; Bart Ostyn; Poonam Salotra; Manu Vanaerschot; Jean-Claude Dujardin; Shyam Sundar
Promastigote miltefosine (MIL) susceptibility was performed on Leishmania donovani isolates from Indian patients with visceral leishmaniasis treated with MIL. Isolates that were obtained before the onset of MIL treatment, after completion of treatment (29th day), or at the time of treatment failure, were screened using in vitro promastigote assay. The MIL susceptibility of the pre-treatment isolates (N = 24, mean IC50 ± SEM= 3.74 ± 0.38 mM) was significantly higher than that of the post-treatment group (N = 26, mean IC50 ± SEM = 6.15 ± 0.52 mM; P = 0.0006) but was similar in the cured patients (N = 22, mean IC50 ± SEM= 5.58 ± 0.56 mM) and those who failed treatment (N = 28, mean IC50 ± SEM= 4.53 ± 0.47 mM). The pre/post-treatment results thus showed a 2-fold difference, whereas isolated from cured versus failed patients showed a similar susceptibility, suggesting that this higher tolerance is not responsible forMIL-treatment failure. Our work highlights the need for careful monitoring of MIL susceptibility for implementation in national VL elimination programs. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene.
Incidence of symptomatic and asymptomatic Leishmania donovani infections in High-Endemic foci in India and Nepal: A prospective study
(2011) Bart Ostyn; Kamlesh Gidwani; Basudha Khanal; Albert Picado; François Chappuis; Shri Prakash Singh; Suman Rijal; Shyam Sundar; Marleen Boelaert
Incidence of Leishmania donovani infection and Visceral Leishmaniasis (VL) was assessed in a prospective study in Indian and Nepalese high-endemic villages. DAT-seroconversion was used as marker of incident infection in 3 yearly surveys. The study population was followed up to month 30 to identify incident clinical cases. In a cohort of 9034 DAT-negative individuals with neither active signs nor history of VL at baseline, 42 VL cases and 375 asymptomatic seroconversions were recorded in the first year, giving an infection:disease ratio of 8.9 to 1. In the 18 months' follow-up, 7 extra cases of VL were observed in the seroconverters group (N = 375), against 14 VL cases among the individuals who had not seroconverted in the first year (N = 8570) (RR = 11.5(4.5
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]
Longlasting insecticidal nets for prevention of Leishmania donovaniinfection in India and Nepal: Paired cluster randomised trial
(2011) Albert Picado; Shri Prakash Singh; Suman Rijal; Shyam Sundar; Bart Ostyn; François Chappuis; Surendra Uranw; Kamlesh Gidwani; Basudha Khanal; Madhukar Rai; Ishwari Sharma Paudel; Murari Lal Das; Rajiv Kumar; Pankaj Srivastava; Jean Claude Dujardin; Veerle Vanlerberghe; Elisabeth Wreford Andersen; Clive Richard Davies; Marleen Boelaert
Objective: To test the effectiveness of large scale distribution of longlasting nets treated with insecticide in reducing the incidence of visceral leishmaniasis in India and Nepal. Design: Paired cluster randomised controlled trial designed to detect a 50% reduction in incidence of Leishmania donovani infection. Setting: Villages in Muzaffarpur district in India and Saptari, Sunsari, and Morang districts in Nepal. Participants: 13 intervention and 13 control clusters. 12 691 people were included in the analysis of the main outcome (infection), and 19 810 were enrolled for the secondary (disease) end point. Intervention: Longlasting insecticidal nets (treated with deltamethrin) were distributed in the intervention clusters in December 2006. Main outcome measures: Infection was determined by direct agglutination test at 12 and 24 months after the intervention in those who had negative results (titre <1:1600) at baseline. The effect estimate was computed as the geometric mean of the risk ratios for seroconversion for each cluster pair (net/no net), with its 95% confidence interval. Formal tests of effect of no intervention were obtained with a paired t test. Results: There was no significant difference in the risk of seroconversion over 24 months in intervention (5.4%; 347/6372) compared with control (5.5%; 345/6319 people) clusters (risk ratio 0.90, 95% confidence interval 0.49 to 1.65) nor in the risk of clinical visceral leishmaniasis (0.99, 0.46 to 1.40). Adjustment for covariates did not alter these conclusions. Conclusions: There is no evidence that large scale distribution of longlasting insecticidal nets provides additional protection against visceral leishmaniasis compared with existing control practice in the Indian subcontinent. The observed effect was small and not significant, though the confidence intervals did not exclude a 50% change in either direction. Trial registration: Clinical Trials NCT 2005-015374.
Model-Based Investigations of Different Vector-Related Intervention Strategies to Eliminate Visceral Leishmaniasis on the Indian Subcontinent
(Public Library of Science, 2014) Anette Stauch; Hans-Peter Duerr; Albert Picado; Bart Ostyn; Shyam Sundar; Suman Rijal; Marleen Boelaert; Jean-Claude Dujardin; Martin Eichner
The elimination of infectious diseases requires reducing transmission below a certain threshold. The Visceral Leishmaniasis (VL) Elimination Initiative in Southeast Asia aims to reduce the annual VL incidence rate below 1 case per 10,000 inhabitants in endemic areas by 2015 via a combination of case management and vector control. Using a previously developed VL transmission model, we investigated transmission thresholds dependent on measures reducing the sand fly density either by killing sand flies (e.g., indoor residual spraying and long-lasting insecticidal nets) or by destroying breeding sites (e.g., environmental management).Model simulations suggest that elimination of VL is possible if the sand fly density can be reduced by 67% through killing sand flies, or if the number of breeding sites can be reduced by more than 79% through measures of environmental management.These results were compared to data from two recent cluster randomised controlled trials conducted in India, Nepal and Bangladesh showing a 72% reduction in sand fly density after indoor residual spraying, a 44% and 25% reduction through the use of long-lasting insecticidal nets and a 42% reduction after environmental management.Based on model predictions, we identified the parameters within the transmission cycle of VL that predominantly determine the prospects of intervention success. We suggest further research to refine model-based predictions into the elimination of VL. © 2014 Stauch et al.
Molecular and serological markers of Leishmania donovani infection in healthy individuals from endemic areas of Bihar, India
(2013) Pankaj Srivastava; Kamlesh Gidwani; Albert Picado; Gert Van der Auwera; Puja Tiwary; Bart Ostyn; Jean-Claude Dujardin; Marleen Boelaert; Shyam Sundar
Objectives: Recent epidemiological reports indicate that asymptomatic human infections with Leishmania donovani, the causative agent of visceral leishmaniasis or Kala-azar (KA), occur frequently in India. We explored markers of infection. Methods: Blood samples were collected from 286 healthy subjects from 16 villages in the Muzaffarpur district of Bihar. These individuals were classified into three groups: (i) persons with no history of KA and living in a house where no KA cases were previously reported, (ii) persons with no history of KA but living in a house where KA cases were diagnosed at the time of sampling or in the past, and (iii) successfully treated KA patients. Each sample was tested using a Leishmania-specific PCR to detect Leishmania DNA, and two serological tests to demonstrate anti-Leishmania antibodies: the Direct Agglutination Test and rK39 ELISA. Results: PCR positivity was similar among the three groups (20-25%). In contrast, among treated patients, the percentage of serologically positive individuals was roughly five times that of healthy individuals with no KA history, as measured with either test. Living in a house where KA had been reported did not affect seropositivity. Conclusion: A significant proportion of asymptomatic infections of Leishmania exist in endemic regions. Using a combination of molecular and serological tests increases the capacity to detect infections at different stages. Further work is required to understand the kinetics of the markers. © 2013 Blackwell Publishing Ltd.
Persistence of Leishmania donovani antibodies in past visceral leishmaniasis cases in India
(2011) Kamlesh Gidwani; Albert Picado; Bart Ostyn; Shri Prakash Singh; Rajiv Kumar; Basudha Khanal; Veerle Lejon; François Chappuis; Marleen Boelaert; Shyam Sundar
The persistence of anti-Leishmania donovani antibodies in past visceral leishmaniasis (VL) cases was retrospectively assessed by means of the direct agglutination test (DAT) and the rK39 enzyme-linked immunosorbent assay (ELISA). Antibody titers remained high for an extended period of time in past cases of VL. These results highlight the need to carefully elicit the history of patients with VL symptoms. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
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.
Residual activity and integrity of PermaNet® 2.0 after 24 months of household use in a community randomised trial of long lasting insecticidal nets against visceral leishmaniasis in India and Nepal
(2012) Albert Picado; Shri Prakash Singh; Veerle Vanlerberghe; Surendra Uranw; Bart Ostyn; Harparkash Kaur; Murari Lal Das; Shyam Sundar; Suman Rijal; Patrick Tungu; Marleen Boelaert; Mark Rowland
The World Health Organization (WHO) recommends several brands of long lasting insecticidal net (LN) for protection against insect vectors but also advises national programmes to monitor and evaluate performance under local conditions to help them select the most suitable LN for their setting. During the course of a community randomised trial of LNs against visceral leishmaniasis in northern India and Nepal, opportunity arose to assess the efficacy of PermaNet 2.0 (Vestergaard-Frandsen, Denmark) after two years of use against sandfly vectors. Between 63% (India) and 78% (Nepal) of LNs became holed over the course of two years, deltamethrin residues fell from 55mg/m2 to an average of 11.6mg/m2 (India) and 27.9mg/m2 (Nepal), but on the basis of bioassay criteria all LNs tested still met the WHO Pesticide Evaluation Scheme standard for LN effectiveness. Nets had on average only been washed 2.5 times (India) and 0.6 times (Nepal) by householders over the course of two years. The loss of insecticide was attributed to factors which had little or nothing to do with washing, such as handling, friction and torsion during daily use. Under conditions pertaining in this region of south Asia, and for two years at least, this brand of net continues to meet the criteria established by WHO for LNs. © 2011 Royal Society of Tropical Medicine and Hygiene.
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.
Serological markers for Leishmania donovani infection in Nepal: Agreement between direct agglutination test and rK39 ELISA
(2010) Basudha Khanal; Suman Rijal; Bart Ostyn; Albert Picado; Kamlesh Gidwani; Joris Menten; Diane Jacquet; Veerle Lejon; François Chappuis; Marleen Boelaert
Visceral leishmaniasis (VL) is an important vector-borne disease caused by Leishmania donovani in the Indian subcontinent. The actual incidence and role of asymptomatic infections in the region are not well known. We used the direct agglutination test (DAT) and the rK39 ELISA as L. donovani infection markers in 10 VL endemic villages in Nepal. DAT titre distribution showed two subgroups in the population (infected and non-infected individuals), while rK39 did not. The agreement between both tests was moderate (κ=0.53; 95% CI 0.49-0.57). More research is needed to develop validated markers for Leishmania infection. © 2010 Blackwell Publishing Ltd.
Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: A cluster-randomized trial
(2011) Kamlesh Gidwani; Albert Picado; Suman Rijal; Shri Prakash Singh; Lalita Roy; Vera Volfova; Elisabeth Wreford Andersen; Surendra Uranw; Bart Ostyn; Medhavi Sudarshan; Jaya Chakravarty; Petr Volf; Shyam Sundar; Marleen Boelaert; Matthew Edward Rogers
Background: Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial. Methods: As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention. Results: A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83-0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80-1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi. Conclusions: This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions. © 2011 Gidwani et al.