Visceral Leishmaniasis Elimination Program Research Articles

NEWER DRUGS FOR VISCERAL LEISHMANIASIS: A REVIEW

Visceral Leishmaniasis (VL) is one of the most neglected tropical diseases worldwide. The diagnosis and treatment of this disease is quite complex. Sodium Antimony Gluconate (SAG) which used to be a very effective treatment has now developed resistance and is potentially a cardio-toxic drug. Pentamidine has now been discarded because of adverse effect of diabetes mellitus. Amphotericin-B is an effective drug but can cause nephrotoxicity. Miltefosine is a new oral effective drug which has recently been introduced in the kala-azar elimination program in the Indian subcontinent. Paromomycin is an injectable aminoglycoside which is quite cheap but can cause ototoxicity and nephrotoxicity. Sitamaquine, an oral antimalarial drug is still in phase-II trial stage. Combination Therapy is been tried with good results. Single dose Ambisome (liposomal Amphotericin-B) though costly is a very good alternative.

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?

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.

Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: a feasibility study.

To rapidly reduce the burden of visceral leishmaniasis for national elimination programmes, an acceptable, safe, and effective treatment is needed that can be delivered at primary health-care centres. We aimed to assess the tolerability, safety, and cure rate of single-dose liposomal amphotericin B (AmBisome, Gilead, USA) for visceral leishmaniasis treatment in such a setting in Bangladesh. We enrolled patients who had been diagnosed with visceral leishmaniasis at Muktagacha upazila (subdistrict) hospital, Bangladesh. Eligible participants were at least 5 years old and had a history of fever for more than 2 weeks, splenomegaly, rK39 rapid test positivity, and haemoglobin concentrations of at least 50 g/L. Participants were provided a one-off intravenous infusion of liposomal amphotericin B (10 mg/kg bodyweight). Clinical assessments were done during treatment, before hospital discharge, and on days 30 and 180 after treatment. Cure was defined as resolution of fever, decrease in spleen size, and an increase in haemoglobin by 10% compared with baseline or to at least 100 g/L. We estimated efficacy in terms of initial cure (at day 30) and final cure (at 6 months), and safety in all patients who were enrolled (intention-to-treat analysis). We also assessed efficacy in all patients who completed treatment and 6 month follow-up after treatment with or without visceral leishmaniasis relapse (per protocol analysis). We assessed acceptability in terms of proportion of patients who consented to treatment. This study was registered with the Australian New Zealand Clinical Trial Registry, number CTRN12612000367842. Between March 5, and Aug 14, 2012, 329 (55%) of 594 cases of suspected visceral leishmaniasis were confirmed. Of these cases, five patients did not consent to treatment and 24 were ineligible for treatment. In the intention-to-treat analysis, 261 (87%) of 300 patients achieved initial cure and 290 (97%) achieved final cure. In the per-protocol analysis, 260 (88%) of 296 patients achieved initial cure and 289 (98%) achieved final cure. One patient did not start treatment owing to an allergic reaction to liposomal amphotericin B. During treatment or within 2 h afterwards, 79 (26%) patients developed fever, 109 (36%) had fever with rigor, and 56 (19%) had hypotension. No patients needed referral to a tertiary hospital for management of adverse events. Treatment of visceral leishmaniasis in a primary health-care facility with single-dose liposomal amphotericin B could safely and effectively be adopted by the national visceral leishmaniasis elimination programme in Bangladesh. Neglected Tropical Diseases (WHO), Agencia Española de Cooperación Internacional.

Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting Leishmania donovani Strain

ABSTRACTLeishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. Miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the Indian subcontinent. This relapse rate of up to 20% within 12 months after treatment was shown not to be related to reinfection, drug quality, drug exposure, or drug-resistant parasites. We therefore aimed to assess other phenotypes of the parasite that may affect treatment outcome and found a significant association between the number of metacyclic parasites, parasite infectivity, and patient treatment outcome in the Indian subcontinent. Together with previous studies on resistance of L. donovani against pentavalent antimonials, these data suggest that the infectivity of the parasite, or related phenotypes, might be a more determinant factor for treatment failure in visceral leishmaniasis than drug susceptibility, warranting a reassessment of our current view on treatment failure and drug resistance in leishmaniasis and beyond.

Increasing Failure of Miltefosine in the Treatment of Kala-azar in Nepal and the Potential Role of Parasite Drug Resistance, Reinfection, or Noncompliance

Miltefosine (MIL), the only oral drug for visceral leishmaniasis (VL), is currently the first-line therapy in the VL elimination program of the Indian subcontinent. Given the paucity of anti-VL drugs and the looming threat of resistance, there is an obvious need for close monitoring of clinical efficacy of MIL. In a cohort study of 120 VL patients treated with MIL in Nepal, we monitored the clinical outcomes up to 12 months after completion of therapy and explored the potential role of drug compliance, parasite drug resistance, and reinfection. The initial cure rate was 95.8% (95% confidence interval [CI], 92.2-99.4) and the relapse rate at 6 and 12 months was 10.8% (95% CI, 5.2-16.4) and 20.0% (95% CI, 12.8-27.2) , respectively. No significant clinical risk factors of relapse apart from age <12 years were found. Parasite fingerprints of pretreatment and relapse bone marrow isolates within 8 patients were similar, suggesting that clinical relapses were not due to reinfection with a new strain. The mean promastigote MIL susceptibility (50% inhibitory concentration) of isolates from definite cures was similar to that of relapses. Although more tolerant strains were observed, parasite resistance, as currently measured, is thus not likely involved in MIL treatment failure. Moreover, MIL blood levels at the end of treatment were similar in cured and relapsed patients. Relapse in one-fifth of the MIL-treated patients observed in our study is an alarming signal for the VL elimination campaign, urging for further review and cohort monitoring.

Active case detection in national visceral leishmaniasis elimination programs in Bangladesh, India, and Nepal: feasibility, performance and costs

BackgroundActive case detection (ACD) significantly contributes to early detection and treatment of visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) cases and is cost effective. This paper evaluates the performance and feasibility of adapting ACD strategies into national programs for VL elimination in Bangladesh, India and Nepal.MethodsThe camp search and index case search strategies were piloted in 2010-11 by national programs in high and moderate endemic districts / sub-districts respectively. Researchers independently assessed the performance and feasibility of these strategies through direct observation of activities and review of records. Program costs were estimated using an ingredients costing method.ResultsAltogether 48 camps (Bangladesh-27, India-19, Nepal-2) and 81 index case searches (India-36, Nepal-45) were conducted by the health services across 50 health center areas (Bangladesh-4 Upazillas, India-9 PHCs, Nepal-37 VDCs). The mean number of new case detected per camp was 1.3 and it varied from 0.32 in India to 2.0 in Bangladesh. The cost (excluding training costs) of detecting one new VL case per camp varied from USD 22 in Bangladesh, USD 199 in Nepal to USD 320 in India. The camp search strategy detected a substantive number of new PKDL cases. The major challenges faced by the programs were inadequate preparation, time and resources spent on promoting camp awareness through IEC activities in the community. Incorrectly diagnosed splenic enlargement at camps probably due to poor clinical examination skills resulted in a high proportion of patients being subjected to rK39 testing.ConclusionNational programs can adapt ACD strategies for detection of new VL/PKDL cases. However adequate time and resources are required for training, planning and strengthening referral services to overcome challenges faced by the programs in conducting ACD.

847 An Epidemiological Study to Assess the Prevalence of Pkdl in Pediatric Age Group in Endemic Areas of Bihar

Post Kala-azar Dermal Leishmaniasis (PKDL) is a dermatosis usually occurs as a sequel of Visceral Leishmaniasis (VL), commonly known as kala-azar (KA), caused by L. donovani (L.d.) and characterized by...

Drug Susceptibility in Leishmania Isolates Following Miltefosine Treatment in Cases of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis

BackgroundWith widespread resistance to antimonials in Visceral Leishmaniasis (VL) in the Indian subcontinent, Miltefosine (MIL) has been introduced as the first line therapy. Surveillance of MIL susceptibility in natural populations of Leishmania donovani is vital to preserve it and support the VL elimination program.Methodology and Principal FindingsWe measured in vitro susceptibility towards MIL and paromomycin (PMM) in L. donovani isolated from VL and PKDL, pre- and post-treatment cases, using an amastigote-macrophage model. MIL susceptibility of post-treatment isolates from cured VL cases (n = 13, mean IC50±SD = 2.43±1.44 µM), was comparable (p>0.05) whereas that from relapses (n = 3, mean IC50 = 4.72±1.99 µM) was significantly higher (p = 0.04) to that of the pre-treatment group (n = 6, mean IC50 = 1.86±0.75 µM). In PKDL, post-treatment isolates (n = 3, mean IC50 = 16.13±2.64 µM) exhibited significantly lower susceptibility (p = 0.03) than pre-treatment isolates (n = 5, mean IC50 = 8.63±0.94 µM). Overall, PKDL isolates (n = 8, mean IC50 = 11.45±4.19 µM) exhibited significantly higher tolerance (p<0.0001) to MIL than VL isolates (n = 22, mean IC50 = 2.58±1.58 µM). Point mutations in the miltefosine transporter (LdMT) and its beta subunit (LdRos3) genes previously reported in parasites with experimentally induced MIL resistance were not present in the clinical isolates. Further, the mRNA expression profile of these genes was comparable in the pre- and post-treatment isolates. Parasite isolates from VL and PKDL cases were uniformly susceptible to PMM with respective mean IC50 = 7.05±2.24 µM and 6.18±1.51 µM.ConclusionThe in vitro susceptibility of VL isolates remained unchanged at the end of MIL treatment; however, isolates from relapsed VL and PKDL cases had lower susceptibility than the pre-treatment isolates. PKDL isolates were more tolerant towards MIL in comparison with VL isolates. All parasite isolates were uniformly susceptible to PMM. Mutations in the LdMT and LdRos3 genes as well as changes in the expression of these genes previously correlated with experimental resistance to MIL could not be verified for the field isolates.

Visceral Leishmaniasis Eradication is a Reality: Data from a Community-based Active Surveillance in Bangladesh

More than 20 million people in Bangladesh are considered at risk of developing visceral leishmaniasis (VL). A community-based active surveillance was conducted in eight randomly selected villages in a highly endemic area of Bangladesh from 2006 to 2008. A total of 6,761 individuals living in 1,550 mud-walled houses were included in the active surveillance. Rapid rK39 dipstick tests were conducted throughout the study period to facilitate the case diagnosis. Individuals with previous or current clinical leishmaniasis were identified on the basis of the case definition of the VL elimination program. Untreated cases of suspected VL were referred to the hospital for treatment. Socioeconomic and environmental information including bed net use was also collected. In 2006, the annual incidence of clinical leishmaniasis in the study area was 141.9 cases per 10,000 population, which was significantly increased by the following year owing to community-based active surveillance for case detection and reporting. However, early case detection and early referral for treatment led to a significant decrease in incidence in 2008. This study suggests that community-based active surveillance using a simple diagnostic tool might play a role in achieving the goal of the VL elimination program.

PCR-Based Detection of Leishmania DNA in Skin Samples of Post Kala-Azar Dermal Leishmaniasis Patients from an Endemic Area of Bangladesh

Post kala-azar dermal leishmaniasis (PKDL) is a sequel of visceral leishmaniasis (VL) and PKDL patients are an important reservoir for anthroponotic transmission of VL. Therefore, diagnosis and treatment of PKDL is important for the kala-azar elimination program in South Asia, including Bangladesh. While definitive diagnosis of PKDL is still based on microscopy, despite the low sensitivity of this method of diagnosis, PCR for identification of kinetoplast DNA (kDNA) from Leishmania parasites is expected to be a rapid and sensitive diagnostic method. We attempted PCR-based diagnosis from skin biopsy specimens and compared PCR to other available detection methods in order to determine the acceptability and feasibility of the PCR diagnostic method in an endemic area of VL in Bangladesh. Both skin biopsy specimens and blood samples were collected from 110 patients suspected to have PKDL from 6 subdistrict health complexes in Mymensingh, Bangladesh. Using microscopy, we identified 32 samples (29.1%) that were positive for Leishmania. Immunochromatography tests indicated that 85 samples (77.3%) were positive for Leishmania. In contrast, a total of 104 (94.5%) samples tested positive using nested PCR, while unaffected portions of skin from PKDL patients tested negative. Sequencing analysis of the PCR products indicated that the amplified portion had more than 98% nucleotide sequence identity to the Leishmania donovani reference strain, D10. These findings indicate that the PCR method using a skin biopsy is highly sensitive and useful for confirmatory diagnosis of PKDL.

Visceral Leishmaniasis in the Indian Subcontinent: Modelling Epidemiology and Control

BackgroundIn the Indian subcontinent, about 200 million people are at risk of developing visceral leishmaniasis (VL). In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. This model was used to predict the effects of different intervention strategies.Methods and FindingsParameters on the natural history of Leishmania infection were estimated based on a literature review and expert opinion or drawn from a community intervention trial (the KALANET project). The transmission dynamic of Leishmania donovani is rather slow, mainly due to its long incubation period and the potentially long persistence of parasites in infected humans. Cellular immunity as measured by the Leishmanin skin test (LST) lasts on average for roughly one year, and re-infection occurs in intervals of about two years, with variation not specified. The model suggests that transmission of L. donovani is predominantly maintained by asymptomatically infected hosts. Only patients with symptomatic disease were eligible for treatment; thus, in contrast to vector control, the treatment of cases had almost no effect on the overall intensity of transmission.ConclusionsTreatment of Kala-azar is necessary on the level of the individual patient but may have little effect on transmission of parasites. In contrast, vector control or exposure prophylaxis has the potential to efficiently reduce transmission of parasites. Based on these findings, control of VL should pay more attention to vector-related interventions. Cases of PKDL may appear after years and may initiate a new outbreak of disease; interventions should therefore be long enough, combined with an active case detection and include effective treatment.

Antimonial Resistance in Leishmania donovani Is Associated with Increased In Vivo Parasite Burden

Leishmania donovani is an intracellular protozoan parasite that causes visceral leishmaniasis (VL). Antimonials (SSG) have long been the first-line treatment against VL, but have now been replaced by miltefosine (MIL) in the Indian subcontinent due to the emergence of SSG-resistance. Our previous study hypothesised that SSG-resistant L. donovani might have increased in vivo survival skills which could affect the efficacy of other treatments such as MIL. The present study attempts to validate these hypotheses. Fourteen strains derived from Nepalese clinical isolates with documented SSG-susceptibility were infected in BALB/c mice to study their survival capacity in drug free conditions (non-treated mice) and in MIL-treated mice. SSG-resistant parasites caused a significant higher in vivo parasite load compared to SSG-sensitive parasites. However, this did not seem to affect the strains' response to MIL-treatment since parasites from both phenotypes responded equally well to in vivo MIL exposure. We conclude that there is a positive association between SSG-resistance and in vivo survival skills in our sample of L. donovani strains which could suggest a higher virulence of SSG-R strains compared to SSG-S strains. These greater in vivo survival skills of SSG-R parasites do not seem to directly affect their susceptibility to MIL. However, it cannot be excluded that repeated MIL exposure will elicit different adaptations in these SSG-R parasites with superior survival skills compared to the SSG-S parasites. Our results therefore highlight the need to closely monitor drug efficacy in the field, especially in the context of the Kala-azar elimination programme ongoing in the Indian subcontinent.

Short communication: evaluation of a new rapid diagnostic test for quality assurance by kala azar elimination programme in bangladesh.

In Bangladesh, serological tests have been widely used for the primary screening of visceral leishmaniasis (VL). Several serologic tests are available for the diagnosis of VL. Selection of the best test is important to permit diagnostic differentiation between symptomatic and asymptomatic patients and to reduce cross-reactivity. We evaluated the effectiveness of a new serological test “Onsite Leishmania Ab Rapid Test” as a part of “quality assurance” activities for the kala azar elimination programme of the Government of Bangladesh. Plasma samples of 100 parasitologically confirmed cases of VL along with 101 healthy controls were tested, and “Onsite Leishmania Ab Rapid Test” strip tests were positive in 94 out of 100 confirmed VL cases, whereas four out of 51 healthy subjects from the VL endemic areas also tested positive. All the 50 healthy volunteers tested negative. Thus, the sensitivity and specificity of “Onsite Leishmania Ab Rapid Test” strip test were found to be 94% (95% CI: 87–98) and 96% (95% CI: 90–99), respectively. This study showed that the performance of the “Onsite Leishmania Ab Rapid Test” strip tests was up to the recommended level.

Insecticide-treated bed nets in rural Bangladesh: their potential role in the visceral leishmaniasis elimination programme

To analyse the feasibility, acceptability and effectiveness of insecticide-treated bed nets with slow-release insecticides (KO Tab 123) as an option for kala-azar vector management in Bangladesh. Intervention study involving an insecticide dipping programme through village health workers supervised by public health officers covering 6967 households in Mymensingh and 8287 in Rajshahi district. In a subsample of households, sandfly densities at baseline, 1, 12 and 18 months were measured with CDC light traps both in intervention and control areas. Bioassays were performed for determining the bioavailability of the insecticide and tests of chemical residues in the treated bed nets were undertaken. Satisfaction surveys and direct observation of use of treated bed net use were conducted. The dipping programme was feasible with the help of communities and public health staff, was well accepted, reached a coverage of 98.2% and 96.2% in the two study sites within 4 weeks and was effective in terms of a significant reduction in sandfly densities (approximately 60%) for a period of 18 months. Bioassay results were satisfactory (>80% sandfly mortality) and the average chemical content of the treated bed nets was sufficient for killing sand flies at the end of the observation period. Bed nets treated with slow-release insecticides can be an important complementary measure for sandfly control in the visceral leishmaniasis elimination programme.

Enhanced case detection and improved diagnosis of PKDL in a Kala-azar-endemic area of Bangladesh.

ObjectivesTo support the Bangladesh National Kala-azar Elimination Programme (NKEP), we investigated the feasibility of using trained village volunteers for detecting post-kala-azar dermal leishmaniasis (PKDL) cases, using polymerase chain reaction (PCR) for confirmation of diagnosis and treatment compliance by PKDL patients in Kanthal union of Trishal sub-district, Mymensingh, Bangladesh.MethodsIn this cross-sectional study, Field Research Assistants (FRAs) conducted census in the study area, and the research team trained village volunteers on how to look for PKDL suspects. The trained village volunteers (TVVs) visited each household in the study area for PKDL suspects and referred the suspected PKDL cases to the study clinic. The suspected cases underwent physical examinations by a qualified doctor and rK39 strip testing by the FRAs and, if positive, slit skin examination (SSE), culture, and PCR of skin specimens and peripheral buffy coat were done. Those with evidence of Leishmania donovani (LD) were referred for treatment. All the cases were followed for one year.ResultsThe total population of the study area was 29,226 from 6,566 households. The TVVs referred 52 PKDL suspects. Probable PKDL was diagnosed in 18 of the 52 PKDL suspect cases, and PKDL was confirmed in 9 of the 18 probable PKDL cases. The prevalence of probable PKDL was 6.2 per 10,000 people in the study area. Thirteen PKDL suspects self-reported from outside the study area, and probable and confirmed PKDL was diagnosed in 10 of the 13 suspects and in 5 of 10 probable PKDL cases respectively. All probable PKDL cases had hypopigmented macules. The median time for PKDL development was 36 months (IQR, 24–48). Evidence of the LD parasite was documented by SSE and PCR in 3.6% and 64.3% of the cases, respectively. PCR positivity was associated with gender and severity of disease. Those who were untreated had an increased risk (odds ratio = 3.33, 95%CI 1.29–8.59) of having persistent skin lesions compared to those who were treated. Patients' treatment-seeking behavior and treatment compliance were poor.ConclusionImproved detection of PKDL cases by TVVs is feasible and useful. The NKEP should promote PCR for the diagnosis of PKDL and should find ways for improving treatment compliance by patients.

Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial

BackgroundVisceral leishmaniasis (VL) control in the Indian subcontinent is currently based on case detection and treatment, and on vector control using indoor residual spraying (IRS). The use of long-lasting insecticidal nets (LN) has been postulated as an alternative or complement to IRS. Here we tested the impact of comprehensive distribution of LN on the density of Phlebotomus argentipes in VL-endemic villages.MethodsA cluster-randomized controlled trial with household P. argentipes density as outcome was designed. Twelve clusters from an ongoing LN clinical trial—three intervention and three control clusters in both India and Nepal—were selected on the basis of accessibility and VL incidence. Ten houses per cluster selected on the basis of high pre-intervention P. argentipes density were monitored monthly for 12 months after distribution of LN using CDC light traps (LT) and mouth aspiration methods. Ten cattle sheds per cluster were also monitored by aspiration.FindingsA random effect linear regression model showed that the cluster-wide distribution of LNs significantly reduced the P. argentipes density/house by 24.9% (95% CI 1.80%–42.5%) as measured by means of LTs.InterpretationThe ongoing clinical trial, designed to measure the impact of LNs on VL incidence, will confirm whether LNs should be adopted as a control strategy in the regional VL elimination programs. The entomological evidence described here provides some evidence that LNs could be usefully deployed as part of the VL control program.Trial registrationClinicalTrials.gov CT-2005-015374

Chemical and environmental vector control as a contribution to the elimination of visceral leishmaniasis on the Indian subcontinent: cluster randomized controlled trials in Bangladesh, India and Nepal

BackgroundBangladesh, India and Nepal are working towards the elimination of visceral leishmaniasis (VL) by 2015. In 2005 the World Health Organization/Training in Tropical Diseases launched an implementation research programme to support integrated vector management for the elimination of VL from Bangladesh, India and Nepal. The programme is conducted in different phases, from proof-of-concept to scaling up intervention. This study was designed in order to evaluate the efficacy of the three different interventions for VL vector management: indoor residual spraying (IRS); long-lasting insecticide treated nets (LLIN); and environmental modification (EVM) through plastering of walls with lime or mud.MethodsUsing a cluster randomized controlled trial we compared three vector control interventions with a control arm in 96 clusters (hamlets or neighbourhoods) in each of the 4 study sites: Bangladesh (one), India (one) and Nepal (two). In each site four villages with high reported VL incidences were included. In each village six clusters and in each cluster five households were randomly selected for sand fly collection on two consecutive nights. Control and intervention clusters were matched with average pre-intervention vector densities.In each site six clusters were randomly assigned to each of the following interventions: indoor residual spraying (IRS); long-lasting insecticide treated nets (LLIN); environmental management (EVM) or control. All the houses (50-100) in each intervention cluster underwent the intervention measures. A reduction of intra-domestic sand fly densities measured in the study households by overnight US Centres for Disease Prevention and Control light trap captures (that is the number of sand flies per trap per night) was the main outcome measure.ResultsIRS, and to a lesser extent EVM and LLINs, significantly reduced sand fly densities for at least 5 months in the study households irrespective of type of walls or whether or not people shared their house with cattle. IRS was effective in all sites but LLINs were only effective in Bangladesh and India. Mud plastering did not reduce sand fly density (Bangladesh study); lime plastering in India and one Nepali site, resulted in a significant reduction of sand fly density but not in the second Nepali site.ConclusionSand fly control can contribute to the regional VL elimination programme; IRS should be strengthened in India and Nepal but in Bangladesh, where vector control has largely been abandoned during the last decades, the insecticide treatment of existing bed nets (coverage above 90% in VL endemic districts) could bring about an immediate reduction of vector populations; operational research to inform policy makers about the efficacious options for VL vector control and programme performance should be strengthened in the three countries.

Novel Noninvasive Method for Diagnosis of Visceral Leishmaniasis by rK39 Testing of Sputum Samples

Novel Noninvasive Method for Diagnosis of Visceral Leishmaniasis by rK39 Testing of Sputum Samples

Visceral leishmaniasis elimination programme in India, Bangladesh, and Nepal: reshaping the case finding/case management strategy.

ObjectiveWe sought to estimate visceral leishmaniasis (VL) burden in Bangladesh, India, and Nepal and document care-seeking behaviour for VL to provide baseline information for monitoring the VL elimination program and identify options for improved case finding and management.DesignA cross-sectional study using cluster sampling (clusters being villages) of 4 VL endemic districts was used in order to document all current and existing VL cases over the preceding 12 mo. Extended (in-depth) interviews were conducted in a subsample of households to explore (a) VL-related knowledge, attitudes, and practices of the population; (b) use of VL care by patients; and (c) delay between onset of symptoms, diagnosis, and start of treatment, as well as treatment interruption. Findings were discussed with national program managers and policy makers to develop improved strategies.ResultsScreening for VL was done in 18,933 households (106,425 inhabitants). The estimated annual incidence of VL in the endemic districts was on average 22 times higher than the elimination target of less than one case per 10,000 inhabitants in 2015. This incidence varied widely between study sites, from 9.0 to 29.8 per 10,000 inhabitants. The percentage of newly detected cases through the household screening was high in the districts least covered by health-care services (particularly Rajshahi, Bangladesh, 49%; and to a lesser extent Vaishali in Bihar, India, 32.5%), and much lower in districts with greater availability of VL care (Muzaffarpur, India, 3.8%). On average 267 houses had to be visited, i.e., at least three to four working days per health worker, to identify a new VL (ranging from 1,432 houses in Muzaffarpur, India to only 166 houses in Rajshahi, Bangladesh). Knowledge of the disease and its vectors was good in India and Nepal but poor in Bangladesh (Rajshahi) where very little attention has been given to VL over the last decades. Although all socio-demographic indicators showed high levels of poverty, people in India preferred private medical practitioners for the treatment of VL, whereas in Nepal, and even more in Bangladesh, the public health-care sector was preferred. Delays between onset of symptoms and diagnosis as well as start of treatment was high. Reported non-adherence to treatment was particularly high in the more under-served districts and was mainly due to lack of resources.DiscussionThe findings suggest that (a) house-to-house screening may be useful in highly endemic districts with a poor passive case detection system, but further evidence on case finding adapted to local conditions has to be collected; (b) strengthening the quality of the public health sector is imperative in the three countries, especially in India, with its largely unregulated private-sector provision of VL care.