Latent Infection with Leishmania donovani in Highly Endemic Villages in Bihar, India

Hasker, Epco; Kansal, Sangeeta; Malaviya, Paritosh; Gidwani, Kamlesh; Picado, Albert; Singh, Rudra Pratap; Chourasia, Ankita; Singh, Abhishek Kumar; Shankar, Ravi; Menten, Joris; Wilson, Mary E.; Boelaert, Marleen; Sundar, Shyam

doi:10.1371/journal.pntd.0002053

Cited by 59 publications

(88 citation statements)

References 38 publications

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“…These observations are consistent with a previous study reporting that within one year about 80% of healthy rK39-positive cases became seronegative [16] and one out of 50 direct agglutination test (DAT)-positive cases developed VL [7]. …”

Section: Discussionsupporting

confidence: 93%

“…Cumulative incidence of rK39 seroconversion in each of the cohorts over the course of the study was used as the measure of transmission. Sample size was calculated based on the assumption that at least 6% of the population in the highly endemic regions would become asymptomatically infected and seroconvert over 2 years [7,16,18]. In order to detect an odds ratio of 3.0 in the difference in seroconversion risk between any pair of cohorts, with a significance of 0.05 and a power of 0.8, at least 151 people were required in each cohort.…”

Section: Methodsmentioning

confidence: 99%

“…Although this assay is not sensitive enough to identify all asymptomatic infected cases, it does have the same sensitivity and specificity for each group and thus provides an accurate comparison of relative seroconversion between groups. Individuals with higher rK39 or DAT antibody titers have been reported to be associated with higher conversion rates to VL than people with low antibody titers [15,16,17]. We therefore believe that the rK39 RDT was an appropriate assay for comparing transmission between different cohorts in this longitudinal study.…”

Section: Introductionmentioning

confidence: 94%

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

et al. 2016

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BackgroundVisceral 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 FindingsWe 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/SignificanceThese 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.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

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

et al. 2016

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“…This might be contributed to a boosting effect in asymptomatic infected subjects upon repeated exposure. Similar observation has been reported in Hasker et al (2013) study.…”

Section: Discussionsupporting

confidence: 92%

Seroprevalence of Leishmania infection among the healthy blood donors in kala-azar endemic areas of Iran

et al. 2013

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Visceral leishmaniasis (VL) is a serious health problem in Iran. The disease is mainly transmitted by sand fly bites, but its transmission through transfusion in endemic areas may also occur. The current study aimed to determine the prevalence of Leishmania infection among blood donors in VL-endemic areas in south of Iran. A total of 2003 healthy blood donors from blood service centers in five VL-endemic districts in Fars province, southern Iran, were enrolled in the study. The blood samples were assessed for antibodies against Leishmania infantum by direct agglutination test (DAT). Seropositive subjects were tested for the presence of L. infantum DNA in their buffy coat by the molecular method. Socio-demographic features of the subjects were also documented during sample collecting. The mean age of participants was 36.3 (SD = 10.7 years). Male constituted 94.7 % of the subjects while only 5.3 % of donors were female. Twenty-eight blood donors (1.4 %) were positive for Leishmania infection by DAT. Only one of these seropositive donors was positive for Leishmania infection by polymerase chain reaction. A significant correlation was found between age, the place of residence and seropositivity to Leishmania (P \ 0.05). Findings of this study revealed that the prevalence of Leishmania infection among blood donors in transfusion centers in the VL-endemic areas in Iran is relatively high. These asymptomatic blood donors may constitute a risk of transmitting of VL to susceptible recipients.

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“…The interactions between exposure and disease can be inferred from the age distributions of KA cases. KA due to L. infantum (also known as "infantile VL") typically affects children <10 years (Badaro et al, 1986a;Davies and Mazloumi Gavgani, 1999), whereas KA due to L. donovani tends to be in older children and young adults <30 years in some locations, or older in others (Hailu et al, 2009;Mueller et al, 2012;Burza et al, 2014;Hasker et al, 2013). The age distribution will depend upon the exposure history of the population and will likely vary over the course of an epidemic cycle which is thought to be about 10-15 years on the ISC (Dye and Wolpert, 1988).…”

Section: Natural History Of Vl Diseasementioning

confidence: 99%

Progress in the Mathematical Modelling of Visceral Leishmaniasis

Rock¹,

Quinnell²,

Medley³

et al. 2016

Advances in Parasitology

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The leishmaniases comprise a complex of diseases characterised by clinical outcomes that range from self-limiting to chronic, disfiguring and stigmatising, to life-threatening. Diagnostic methods, treatments, and vector and reservoir control options exist, but deciding the most effective interventions requires a quantitative understanding of the population level infection and disease dynamics. The effectiveness of any set of interventions has to be determined within the context of operational conditions, including economic and political commitment. Mathematical models are the best available tools for studying quantitative systems crossing disciplinary spheres (biology, medicine, economics) within environmental and societal constraints.In 2005, the World Health Assembly and government health ministers of India, Nepal, and Bangladesh signed a Memorandum of Understanding to eliminate the life threatening form of leishmaniasis, visceral leishmaniasis (VL), on the Indian subcontinent by 2015 through a combination of early case detection, improved treatments, and vector control. The elimination target is <1/10,000 population at the district or subdistrict level compared to the current 20/10,000 in the regions of highest transmission.Towards this goal, this chapter focuses on mathematical models of VL, and the biology driving those models, to enable realistic predictions of the * Corresponding author Email address: orin.courtenay@warwick.ac.uk (Orin Courtenay)Preprint submitted to Advances in Parasitology July 18, 2016 best combination of interventions. Several key issues will be discussed which have affected previous modelling of VL and the direction future modelling may take. Current understanding of the natural history of disease, immunity (and loss of immunity), as well as stages of infection and their durations are considered particularly for humans, but also for dogs. Asymptomatic and clinical infection are discussed in the context of their relative roles in Leishmania transmission, as well as key components of the parasite-sandfly-vector interaction and intervention strategies including diagnosis, treatment and vector control. Gaps in current biological knowledge and potential avenues to improve model structures and mathematical predictions are identified. Underpinning the marriage between biology and mathematical modelling, the content of this chapter represents the first step towards developing the next generation of models for VL.

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Latent Infection with Leishmania donovani in Highly Endemic Villages in Bihar, India

Cited by 59 publications

References 38 publications

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

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

Seroprevalence of Leishmania infection among the healthy blood donors in kala-azar endemic areas of Iran

Progress in the Mathematical Modelling of Visceral Leishmaniasis

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