ResearchPad - kala-azar https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Kala-azar elimination in a highly-endemic district of Bihar, India: A success story]]> https://www.researchpad.co/article/elastic_article_14634 The World Health Organization (WHO) has set a target to eliminate visceral leishmaniasis (VL), commonly known as “Kala-azar,” as a public health problem in India by 2020. The elimination target is defined as achieving less than 1 case per 10,000 people at the block level. Although India has made substantial progress in the elimination of the disease since 2012, VL remains a stable public health problem in four middle-eastern states including Bihar. Bihar contributes >61% of the total Indian cases annually, and a few districts of the state have reported more than 600 cases annually. In this study, the results indicate that an intensive integrated VL control strategy including epidemiological analysis based on a geographical information system (GIS), hot-spot mapping, active case detection, vector control using the indoor residual spraying (IRS) of chemical insecticides, awareness campaigns, human resource development, the close monitoring of control activities, and active epidemiological surveillance and entomological monitoring can achieve the elimination target in the highly endemic region of Bihar. The elimination of VL from highly endemic zones is urgently required to control any new outbreak. Therefore, the implementation of the Vaishali VL control strategy is strongly recommended in all highly endemic districts of Bihar, India.

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<![CDATA[IgG1 as a Potential Biomarker of Post-chemotherapeutic Relapse in Visceral Leishmaniasis, and Adaptation to a Rapid Diagnostic Test]]> https://www.researchpad.co/article/5989daecab0ee8fa60bbfa51

Background

Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care.

Methodology/Principal Findings

All IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001).

Conclusions/Significance

Six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse.

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<![CDATA[The Challenges of Conducting Clinical Research on Neglected Tropical Diseases in Remote Endemic Areas in Sudan]]> https://www.researchpad.co/article/5989dac2ab0ee8fa60bb0fcc ]]> <![CDATA[Studies on sand fly fauna and ecological analysis of Phlebotomus orientalis in the highland and lowland foci of kala-azar in northwestern Ethiopia]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc508

Background

Visceral leishmaniasis (VL) also known as kala-azar is a growing health problem in Ethiopia with an estimated annual VL incidence between 3700 and 7400. The disease is mainly endemic in northwestern parts of the country. The aim of the current study was to determine the sand fly fauna and ecology of Phlebotomus orientalis in two endemic and ecologically distinct areas of northwestern Ethiopia.

Methods

Sand flies were collected using CDC light traps, sticky traps and pyrethrum spray catches from peri-domestic, mixed forest, farm field and indoor habitats from both Libo-Kemkem (May 2011-April 2012) and Metema (October 2012-September 2013) districts.

Results

A total of 51,411 sand fly specimens were collected and identified (10,776 from highland and 40, 635 from the lowland areas). Seven species were found in the highland area: two Phlebotomus spp. (P. orientalis and P. rodhaini) and five Sergentomyia species. Whereas 19 species were found in the lowland area: six Phlebotomus (P. orientalis, P. rodhaini, P. bergeroti, P. duboscqi, P. papatasi and P. martini) and 13 Sergentomyia species. Of the Phlebotomus spp., P. orientalis was the predominant species in both the highland (99.9%) and lowland (93.7%) areas. Indoor collections using pyrethrum spray catches and sticky traps indicated that P. orientalis has a strong exophilic and exophagic behaviors in both districts. In both areas, this species showed seasonal occurrence and showing abundance during the dry months (March-May/June) of the year and increasing in numbers till the rain season, when numbers dropped dramatically. Mean density of P. orientalis in the two areas had positive and significant correlation with mean temperature in light trap collections (P<0.05). However, mean density of P. orientalis in the two areas in sticky trap collections had positive and insignificant association with the temperature (P>0.05). Regarding the rainfall pattern, density of P. orientalis had negative and statistically insignificant correlation (for light trap collections for both areas) and significant correlation (for sticky trap collections for lowland area).

Conclusions

The current study indicated the variation in sand fly fauna between the highland and lowland districts, wherein, P. orientalis was found to be the most abundant Phlebotomus species. The study also determined that P. orientalis exhibits distinct seasonality, where its abundance increases during the dry season and disappears when the rainy period starts in both study areas. This entomological observation on the bionomics of P. orientalis provides significant evidence for considering vector control or preventive measures in the areas studied.

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<![CDATA[Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study]]> https://www.researchpad.co/article/5989dae3ab0ee8fa60bbc9a2

Background

Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients.

Methods

In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient’s house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development.

Results

Out of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1–200 μg/L and 200.1–432.0 μg/L were 1.85 (1.13–3.03) and 2.31 (1.39–3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02–2.7; p = 0.04).

Conclusion

Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.

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<![CDATA[Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients]]> https://www.researchpad.co/article/5989dad3ab0ee8fa60bb71f0

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

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<![CDATA[Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial]]> https://www.researchpad.co/article/5989da1aab0ee8fa60b7ca93

Background

SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa.

Methods

A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments.

Results

In sequential analyses with 49–51 patients per arm, initial cure was 85% (95% CI: 73–92) in all arms. At D210, definitive cure was 87% (95% CI: 77–97) for AmBisome + SSG, 77% (95% CI 64–90) for AmBisome + miltefosine and 72% (95% CI 60–85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults.

Conclusion

No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated.

Trial Registration

The study was registered with ClinicalTrials.gov, number NCT01067443

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<![CDATA[Disruption of Splenic Lymphoid Tissue and Plasmacytosis in Canine Visceral Leishmaniasis: Changes in Homing and Survival of Plasma Cells]]> https://www.researchpad.co/article/5989da5bab0ee8fa60b90036

Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum, which is transmitted by phlebotomine sandflies. Dogs are the main urban reservoir of this parasite and the disease presents similar characteristics in both humans and dogs. In this paper, we investigated the potential pathways involved in plasma cell replacement of normal cell populations in the spleen, with respect to disease severity in dogs from an endemic area for visceral leishmaniasis. To this end, canine spleen samples were grouped into three categories: TYPE1SC- (non-infected dogs or without active infection with organized white pulp), TYPE1SC+ (infected dogs with organized white pulp) or TYPE3SC+ (infected animals with disorganized white pulp). We analyzed the distribution of different plasma cell isotypes (IgA, IgG and IgM) in the spleen. The expression of cytokines and chemokines involved in plasma cell homing and survival were assessed by real time RT-PCR. Polyclonal B cell activation and hypergammaglobulinemia were also evaluated. The proportion of animals with moderate or intense plasmacytosis was higher in the TYPE3SC+ group than in the other groups (Fisher test, P<0.05). This was mainly due to a higher density of IgG+ plasma cells in the red pulp of this group. The albumin/globulin ratio was lower in the TYPE3SC+ animals than in the TYPE1SC- or TYPE1SC+ animals, which evidences VL-associated dysproteinemia. Interestingly, TYPE3SC+ animals showed increased expression of the BAFF and APRIL cytokines, as well as chemokine CXCL12. Aberrant expression of BAFF, APRIL and CXCL12, together with amplified extrafollicular B cell activation, lead to plasma cell homing and the extended survival of these cells in the splenic red pulp compartment. These changes in the distribution of immunocompetent cells in the spleen may contribute to the progression of VL, and impair the spleen’s ability to protect against blood borne pathogens.

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<![CDATA[Multi-modal Analysis of Courtship Behaviour in the Old World Leishmaniasis Vector Phlebotomus argentipes]]> https://www.researchpad.co/article/5989d9f8ab0ee8fa60b71197

Background

The sand fly Phlebotomus argentipes is arguably the most important vector of leishmaniasis worldwide. As there is no vaccine against the parasites that cause leishmaniasis, disease prevention focuses on control of the insect vector. Understanding reproductive behaviour will be essential to controlling populations of P. argentipes, and developing new strategies for reducing leishmaniasis transmission. Through statistical analysis of male-female interactions, this study provides a detailed description of P. argentipes courtship, and behaviours critical to mating success are highlighted. The potential for a role of cuticular hydrocarbons in P. argentipes courtship is also investigated, by comparing chemicals extracted from the surface of male and female flies.

Principal Findings

P. argentipes courtship shared many similarities with that of both Phlebotomus papatasi and the New World leishmaniasis vector Lutzomyia longipalpis. Male wing-flapping while approaching the female during courtship predicted mating success, and touching between males and females was a common and frequent occurrence. Both sexes were able to reject a potential partner. Significant differences were found in the profile of chemicals extracted from the surface of males and females. Results of GC analysis indicate that female extracts contained a number of peaks with relatively short retention times not present in males. Extracts from males had higher peaks for chemicals with relatively long retention times.

Conclusions

The importance of male approach flapping suggests that production of audio signals through wing beating, or dispersal of sex pheromones, are important to mating in this species. Frequent touching as a means of communication, and the differences in the chemical profiles extracted from males and females, may also indicate a role for cuticular hydrocarbons in P. argentipes courtship. Comparing characteristics of successful and unsuccessful mates could aid in identifying the modality of signals involved in P. argentipes courtship, and their potential for use in developing new strategies for vector control.

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<![CDATA[Optimal control and cost-effective analysis of malaria/visceral leishmaniasis co-infection]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdba10

In this paper, a deterministic model involving the transmission dynamics of malaria/visceral leishmaniasis co-infection is presented and studied. Optimal control theory is then applied to investigate the optimal strategies for curtailing the spread of the diseases using the use of personal protection, indoor residual spraying and culling of infected reservoirs as the system control variables. Various combination strategies were examined so as to investigate the impact of the controls on the spread of the disease. And we investigated the most cost-effective strategy of all the control strategies using three approaches, the infection averted ratio (IAR), the average cost-effectiveness ratio (ACER) and incremental cost-effectiveness ratio (ICER). Our results show that the implementation of the strategy combining all the time dependent control variables is the most cost-effective control strategy. This result is further emphasized by using the results obtained from the cost objective functional, the ACER, and the ICER.

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<![CDATA[Neglected tropical diseases: A DFID perspective]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf40d ]]> <![CDATA[Asymptomatic leishmaniasis in kala-azar endemic areas of Malda district, West Bengal, India]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcea5

Asymptomatic leishmaniasis may drive the epidemic and an important challenge to reach the goal of joint Visceral Leishmaniasis (VL) elimination initiative taken by three Asian countries. The role of these asymptomatic carriers in disease transmission, prognosis at individual level and rate of transformation to symptomatic VL/Post Kala-azar Dermal Leishmaniasis (PKDL) needs to be evaluated. Asymptomatic cases were diagnosed by active mass survey in eight tribal villages by detecting antileishmanial antibody using rK39 based rapid diagnostic kits and followed up for three years to observe the pattern of sero-conversion and disease transformation. Out of 2890 total population, 2603 were screened. Antileishmanial antibody was detected in 185 individuals of them 96 had a history of VL/PKDL and 89 without such history. Seventy nine such individuals were classified as asymptomatic leishmaniasis and ten as active VL with a ratio of 7.9:1. Out of 79 asymptomatic cases 2 were lost to follow up as they moved to other places. Amongst asymptomatically infected persons, disease transformation in 8/77 (10.39%) and sero-conversion in 62/77 (80.52%) cases were noted. Seven (9.09%) remained sero-positive even after three years. Progression to clinical disease among asymptomatic individuals was taking place at any time up to three years after the baseline survey. If there are no VL /PKDL cases for two or more years, it does not mean that the area is free from leishmaniasis as symptomatic VL or PKDL may appear even after three years, if there are such asymptomatic cases. So, asymptomatic infected individuals need much attention for VL elimination programme that has been initiated by three adjoining endemic countries.

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<![CDATA[Monthly Distribution of Phlebotomine Sand Flies, and Biotic and Abiotic Factors Related to Their Abundance, in an Urban Area to Which Visceral Leishmaniasis Is Endemic in Corumbá, Brazil]]> https://www.researchpad.co/article/5989da8eab0ee8fa60b9f1d8

The monthly distribution and abundance of sand flies are influenced by both biotic and abiotic factors. The present study aimed to evaluate the seasonal distribution of sand flies and the relation between their abundance and environmental parameters, including vegetation and climate. This study was conducted over a 2-year period (April 2012 to March 2014). Monthly distribution was evaluated through the weekly deployment of CDC light traps in the peridomicile area of 5 residences in an urban area of the municipality of Corumbá in the State of Mato Grosso do Sul, Brazil. Meteorological data were obtained from the Mato Grosso do Sul Center for Weather, Climate, and Water Resources. The spectral indices were calculated based on spatial resolution images (GeoEye) and the percentage of vegetal coverage. Differences in the abundance of sand flies among the collection sites were assessed using the Kruskal-Wallis test, and the strength of correlations between environmental variables was determined by calculating Spearman’s correlation coefficients. Lutzomyia cruzi, Lu. forattinii, and Evandromyia corumbaensis were the most frequently found species. Although no significant association was found among these sand fly species and the tested environmental variables (vegetation and climate), high population peaks were found during the rainy season, whereas low peaks were observed in the dry season. The monthly distribution of sand flies was primarily determined by Lu. cruzi, which accounted for 93.94% of the specimens collected each month throughout the experimental period. The fact that sand flies were detected year-round indicates a continuous risk of infection to humans, demonstrating the need for targeted management and education programs.

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<![CDATA[In Vitro and In Vivo Miltefosine Susceptibility of a Leishmania amazonensis Isolate from a Patient with Diffuse Cutaneous Leishmaniasis: Follow-Up]]> https://www.researchpad.co/article/5989d9e7ab0ee8fa60b6b8be ]]> <![CDATA[Visceral leishmaniasis in Somalia: A review of epidemiology and access to care]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd04d

Somalia, ravaged by conflict since 1991, has areas endemic for visceral leishmaniasis (VL), a deadly parasitic disease affecting the rural poor, internally displaced, and pastoralists. Very little is known about VL burden in Somalia, where the protracted crisis hampers access to health care. We reviewed evidence about VL epidemiology in Somalia and appraised control options within the context of this fragile state’s health system. VL has been reported in Somalia since 1934 and has persisted ever since in foci in the southern parts of the country. The only feasible VL control option is early diagnosis and treatment, currently mostly provided by nonstate actors. The availability of VL care in Somalia is limited and insufficient at best, both in coverage and quality. Precarious security remains a major obstacle to reach VL patients in the endemic areas, and the true VL burden and its impact remain unknown. Locally adjusted, innovative approaches in VL care provision should be explored, without undermining ongoing health system development in Somalia. Ensuring VL care is accessible is a moral imperative, and the limitations of the current VL diagnostic and treatment tools in Somalia and other endemic settings affected by conflict should be overcome.

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<![CDATA[Optimal combinations of control strategies and cost-effective analysis for visceral leishmaniasis disease transmission]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdba6a

Visceral leishmaniasis (VL) is a deadly neglected tropical disease that poses a serious problem in various countries all over the world. Implementation of various intervention strategies fail in controlling the spread of this disease due to issues of parasite drug resistance and resistance of sandfly vectors to insecticide sprays. Due to this, policy makers need to develop novel strategies or resort to a combination of multiple intervention strategies to control the spread of the disease. To address this issue, we propose an extensive SIR-type model for anthroponotic visceral leishmaniasis transmission with seasonal fluctuations modeled in the form of periodic sandfly biting rate. Fitting the model for real data reported in South Sudan, we estimate the model parameters and compare the model predictions with known VL cases. Using optimal control theory, we study the effects of popular control strategies namely, drug-based treatment of symptomatic and PKDL-infected individuals, insecticide treated bednets and spray of insecticides on the dynamics of infected human and vector populations. We propose that the strategies remain ineffective in curbing the disease individually, as opposed to the use of optimal combinations of the mentioned strategies. Testing the model for different optimal combinations while considering periodic seasonal fluctuations, we find that the optimal combination of treatment of individuals and insecticide sprays perform well in controlling the disease for the time period of intervention introduced. Performing a cost-effective analysis we identify that the same strategy also proves to be efficacious and cost-effective. Finally, we suggest that our model would be helpful for policy makers to predict the best intervention strategies for specific time periods and their appropriate implementation for elimination of visceral leishmaniasis.

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<![CDATA[Noninvasive Diagnosis of Visceral Leishmaniasis: Development and Evaluation of Two Urine-Based Immunoassays for Detection of Leishmania donovani Infection in India]]> https://www.researchpad.co/article/5989db16ab0ee8fa60bcd34e

Background

Visceral Leishmaniasis (VL), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. Post kala-azar dermal leishmaniasis (PKDL), a skin related outcome, is a potential reservoir for the spread of VL. Diagnostic tests available for VL such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. Serological tests although less invasive than tissue aspiration are incompetent to assess cure. Parasitological examination of slit-skin smear along with the clinical symptoms is routinely used for diagnosis of PKDL. Therefore, a noninvasive test with acceptable sensitivity and competency, additionally, to decide cure would be an asset in disease management and control.

Methodology/principal findings

We describe here, the development of antibody-capture ELISA and field adaptable dipstick test as noninvasive diagnostic tools for VL and PKDL and as a test of cure in VL treatment. Sensitivity and specificity of urine-ELISA were 97.94% (95/97) and 100% (75/75) respectively, for VL. Importantly, dipstick test demonstrated 100% sensitivity (97/97) and specificity (75/75) in VL diagnosis. Degree of agreement of the two methods with tissue aspiration was 98.83% (κ = 0.97) and 100% (κ = 1), for ELISA and dipstick test, respectively. Both the tests had 100% positivity for PKDL (14/14) cases. ELISA and dipstick test illustrated treatment efficacy in about 90% (16/18) VL cases when eventually turned negative after six months of treatment.

Conclusions/significance

ELISA and dipstick test found immensely effective for diagnosis of VL and PKDL through urine samples thus, may substitute the existing invasive diagnostics. Utility of these tests as indirect methods of monitoring parasite clearance can define infected versus cured. Urine-based dipstick test is simple, sensitive and above all noninvasive method that may help not only in active VL case detection but also to ascertain treatment response. It can therefore, be deployed widely for interventions in disease management of VL particularly in poor resource outskirts.

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<![CDATA[Single locus genotyping to track Leishmania donovani in the Indian subcontinent: Application in Nepal]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdcf76

Background

We designed a straightforward method for discriminating circulating Leishmania populations in the Indian subcontinent (ISC). Research on transmission dynamics of visceral leishmaniasis (VL, or Kala-azar) was recently identified as one of the key research priorities for elimination of the disease in the ISC. VL in Bangladesh, India, and Nepal is caused by genetically homogeneous populations of Leishmania donovani parasites, transmitted by female sandflies. Classical methods to study diversity of these protozoa in other regions of the world, such as microsatellite typing, have proven of little use in the area, as they are not able to discriminate most genotypes. Recently, whole genome sequencing (WGS) so far identified 10 different populations termed ISC001-ISC010.

Methodology / Principle findings

As an alternative to WGS for epidemiological or clinical studies, we designed assays based on PCR amplification followed by dideoxynucleotide sequencing for identification of the non-recombinant genotypes ISC001 up to ISC007. These assays were applied on 106 parasite isolates collected in Nepal between 2011 and 2014. Combined with data from WGS on strains collected in the period 2002–2011, we provide a proof-of-principle for the application of genotyping to study treatment outcome, and differential geographic distribution.

Conclusions / Significance

Our method can aid in epidemiological follow-up of visceral leishmaniasis in the Indian subcontinent, a necessity in the frame of the Kala-azar elimination initiative in the region.

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<![CDATA[Snowball Vs. House-to-House Technique for Measuring Annual Incidence of Kala-azar in the Higher Endemic Blocks of Bihar, India: A Comparison]]> https://www.researchpad.co/article/5989d9e5ab0ee8fa60b6aee4

Background

Visceral Leishmaniasis, commonly known as kala-azar, is widely prevalent in Bihar. The National Kala-azar Control Program has applied house-to-house survey approach several times for estimating Kala-azar incidence in the past. However, this approach includes huge logistics and operational cost, as occurrence of kala-azar is clustered in nature. The present study aims to compare efficiency, cost and feasibility of snowball sampling approach to house-to-house survey approach in capturing kala-azar cases in two endemic districts of Bihar, India.

Methodology/Principal findings

A community based cross-sectional study was conducted in two highly endemic Primary Health Centre (PHC) areas, each from two endemic districts of Bihar, India. Snowball technique (used to locate potential subjects with help of key informants where subjects are hard to locate) and house-to-house survey technique were applied to detect all the new cases of Kala-azar during a defined reference period of one year i.e. June, 2010 to May, 2011. The study covered a total of 105,035 households with 537,153 populations. Out of total 561 cases and 17 deaths probably due to kala-azar, identified by the study, snowball sampling approach captured only 221 cases and 13 deaths, whereas 489 cases and 17 deaths were detected by house-to-house survey approach. Higher value of McNemar’s χ² statistics (64; p<0.0001) for house-to-house survey approach than snowball sampling and relative difference (>1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to-house approach with 13% of omission.

Conclusion/Significance

Snowball sampling was not found sensitive enough as it captured only about 50% of VL cases. However, it captured about 77% of the deaths probably due to kala-azar and was found more cost-effective than house-to-house approach. Standardization of snowball approach with improved procedure, training and logistics may enhance the sensitivity of snowball sampling and its application in national Kala-azar elimination programme as cost-effective approach for estimation of kala-azar burden.

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<![CDATA[Investments in Research and Surveillance Are Needed to Go Beyond Elimination and Stop Transmission of Leishmania in the Indian Subcontinent]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcd81 ]]>