Dataset Information

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India.

ABSTRACT:

Background

Visceral Leishmaniasis (VL) is a neglected tropical disease that afflicts some of the poorest populations in the world including people living in the Bihar state of India. Due to efforts from local governments, NGOs and international organizations, the number of VL cases has declined in recent years. Despite this progress, the reservoir for transmission remains to be clearly defined since it is unknown what role post kala-azar dermal leishmaniasis (PKDL) and asymptomatic infections play in transmission. This information is vital to establish effective surveillance and monitoring to sustainably eliminate VL.

Methodology/principal findings

We performed a longitudinal study over a 24-month period to examine VL transmission and seroconversion in households with VL, PKDL and asymptomatic infections in the Saran and Muzaffarpur districts of Bihar. During the initial screening of 5,144 people in 16 highly endemic villages, 195 cases of recently treated VL, 116 healthy rK39 positive cases and 31 PKDL cases were identified. Approximately half of the rK39-positive healthy cases identified during the initial 6-month screening period were from households (HHs) where a VL case had been identified. During the 18-month follow-up period, seroconversion of family members in the HHs with VL cases, PKDL cases, and rK39-positive individuals was similar to control HHs. Therefore, seroconversion was highest in HHs closest to the time of VL disease of a household member and there was no evidence of higher transmission in households with PKDL or healthy rK39-positive HHs. Moreover, within the PKDL HHs, (the initial 31 PKDL cases plus an additional 66 PKDL cases), there were no cases of VL identified during the initial screen or the 18-month follow-up. Notably, 23% of the PKDL cases had no prior history of VL suggesting that infection resulting directly in PKDL is more common than previously estimated.

Conclusions/significance

These observations argue that acute VL cases represent the major reservoir for transmission in these villages and early identification and treatment of VL cases should remain a priority for VL elimination. We were unable to obtain evidence that transmission occurs in HHs with a PKDL case.

SUBMITTER: Das VN

PROVIDER: S-EPMC5156552 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India.

Das Vidya Nand Ravi VN Pandey Ravindra Nath RN Siddiqui Niyamat Ali NA Chapman Lloyd A C LA Kumar Vijay V Pandey Krishna K Matlashewski Greg G Das Pradeep P

PLoS neglected tropical diseases 20161214 12

<h4>Background</h4>Visceral Leishmaniasis (VL) is a neglected tropical disease that afflicts some of the poorest populations in the world including people living in the Bihar state of India. Due to efforts from local governments, NGOs and international organizations, the number of VL cases has declined in recent years. Despite this progress, the reservoir for transmission remains to be clearly defined since it is unknown what role post kala-azar dermal leishmaniasis (PKDL) and asymptomatic infec ...[more]

PMID: 27974858

Similar Datasets

Project description:People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen's Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33-46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts <100 (OR 3.1; 95% CI 1.2-7.6) and CD4 counts 100-199 (OR = 2.1;95% CI:1.1-4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR = 1.9;95% CI:1.1-3.1). A total of 2.2% (n = 28) participants were positive by Leishmania antigen ELISA, detecting 20 additional participants to the asymptomatic cohort. Prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. Using the Leishmania antigen ELISA, prevalence increased to 9.0%. Patients with low CD4 counts and larger household size were found to have significantly higher risk of ALI. Trial Registration: Clinical Trial Registration CTRI/2017/03/008120.

Project description:BackgroundVisceral leishmaniasis, also known on the Indian subcontinent as kala-azar, is a fatal form of leishmaniasis caused by the protozoan parasite Leishmania donovani and transmitted by the bites of the vector sandfly Phlebotomus argentipes. To achieve and sustain elimination of visceral leishmaniasis, the transmission potential of individuals exposed to L donovani from across the infection spectrum needs to be elucidated. The aim of this study was to evaluate the relative infectiousness to the sandfly vector of patients with visceral leishmaniasis or post-kala-azar dermal leishmaniasis, before and after treatment, and individuals with asymptomatic infection.MethodsIn this prospective xenodiagnosis study done in Muzaffarpur district of Bihar, India, we included patients with clinically confirmed active visceral leishmaniasis or post-kala-azar dermal leishmaniasis who presented to the Kala-Azar Medical Research Center. These participants received treatment for L donovani infection. We also included asymptomatic individuals identified through a serosurvey of 17 254 people living in 26 high-transmission clusters. Eligible participants were aged 12-64 years, were HIV negative, and had clinically or serologically confirmed L donovani infection. During xenodiagnosis, the forearms or lower legs of participants were exposed to 30-35 female P argentipes sandflies for 30 min. Blood-engorged flies were held in an environmental cabinet at 28°C and 85% humidity for 60-72 h, after which flies were dissected and evaluated for L donovani infection by microscopy and quantitative PCR (qPCR). The primary endpoint was the proportion of participants with visceral leishmaniasis or post-kala-azar dermal leishmaniasis, before and after treatment, as well as asymptomatic individuals, who were infectious to sandflies, with a participant considered infectious if promastigotes were observed in one or more individual flies by microscopy, or if one or more of the pools of flies tested positive by qPCR.FindingsBetween July 12, 2016, and March 19, 2019, we recruited 287 individuals, including 77 with active visceral leishmaniasis, 26 with post-kala-azar dermal leishmaniasis, and 184 with asymptomatic infection. Of the patients with active visceral leishmaniasis, 42 (55%) were deemed infectious to sandflies by microscopy and 60 (78%) by qPCR before treatment. No patient with visceral leishmaniasis was found to be infectious by microscopy at 30 days after treatment, although six (8%) were still positive by qPCR. Before treatment, 11 (42%) of 26 patients with post-kala-azar dermal leishmaniasis were deemed infectious to sandflies by microscopy and 23 (88%) by qPCR. Of 23 patients who were available for xenodiagnosis after treatment, one remained infectious to flies by qPCR on the pooled flies, but none remained positive by microscopy. None of the 184 asymptomatic participants were infectious to sandflies.InterpretationThese findings confirm that patients with active visceral leishmaniasis and patients with post-kala-azar dermal leishmaniasis can transmit L donovani to the sandfly vector and suggest that early diagnosis and treatment could effectively remove these individuals as infection reservoirs. An important role for asymptomatic individuals in the maintenance of the transmission cycle is not supported by these data.FundingBill & Melinda Gates Foundation.

Project description:Background: Visceral leishmaniasis (VL) is a vector-borne disease of public health importance in India, with the highest burden of disease in the states of Bihar, Jharkhand, West Bengal and Uttar Pradesh. The disease is currently targeted for elimination (annual incidence to less than one per 10,000 population) using indoor residual spraying, active case detection and treatment. Historically the disease trend in India has been regarded as cyclical with case resurgence characteristically occurring every 15 years. Understanding this pattern is essential if the VL elimination gains are to be sustained. To better understand the cyclical trends, annual climatic indicators including rainfall, temperature and humidity over time were compared with annual VL case incidence data. Methods: Annual climate data (rainfall, average and maximum temperature and specific humidity) from 1956-2004 were used to identify potential factors influencing VL incidence. Months relevant to the VL life-cycle were identified and defined (Monsoon, Sand-fly Peak, Pre-Sand-fly Peak and Annual) for analysis. The Kruskall-Wallis test was used to determine significant difference between categorical rainfall and VL incidence, whilst univariate negative binomial regression models were used to determine predictors of disease incidence. Results: The negative binomial regression model showed statistically significant associations (p <0.05) for VL incidence and maximum temperature, and average temperature, when considering annual and pre-sand fly peak time periods. No other associations between humidity, rainfall or temperature and VL incidence were detected (all values p >0.05). Conclusion: The VL programme in Bihar has made significant progress in adopting best practices for improved treatment and vector control, with the aim to achieve VL elimination. However, open access granular programme data for indoor residual spray activities and case detection is required to fully understand the role of climate in disease transmission and potential resurgence.

Project description:BACKGROUND:Despite the overall decrease in visceral leishmaniasis (VL) incidence on the Indian subcontinent, there remain spatiotemporal clusters or 'hotspots' of new cases. The characteristics of these hotspots, underlying transmission dynamics, and their importance for shaping control strategies are not yet fully understood and are investigated in this study for a VL endemic area of ~100,000 inhabitants in Bihar, India between 2007-2015. METHODOLOGY/PRINCIPAL FINDINGS:VL incidence (cases/10,000/year) dropped from 12.3 in 2007 to 0.9 in 2015, which is just below the World Health Organizations' threshold for elimination as a public health problem. Clustering of VL was assessed between subvillages (hamlets), using multiple geospatial and (spatio)temporal autocorrelation and hotspot analyses. One to three hotspots were identified each year, often persisting for 1-5 successive years with a modal radius of ~500m. The relative risk of having VL was 5-86 times higher for inhabitants of hotspots, compared to those living outside hotspots. Hotspots harbour significantly more households from the two lowest asset quintiles (as proxy for socio-economic status). Overall, children and young adelescents (5-14 years) have the highest risk for VL, but within hotspots and at the start of outbreaks, older age groups (35+ years) show a comparable high risk. CONCLUSIONS/SIGNIFICANCE:This study demonstrates significant spatiotemporal heterogeneity in VL incidence at subdistrict level. The association between poverty and hotspots confirms that VL is a disease of 'the poorest of the poor' and age patterns suggest a potential role of waning immunity as underlying driver of hotspots. The recommended insecticide spraying radius of 500m around detected VL cases corresponds to the modal hotspot radius found in this study. Additional data on immunity and asymptomatic infection, and the development of spatiotemporally explicit transmission models that simulate hotspot dynamics and predict the impact of interventions at the smaller geographical scale will be crucial tools in sustaining elimination.

Dataset Information

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India.

Background

Methodology/principal findings

Conclusions/significance

Publications

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets