Xenodiagnosis to address key questions in visceral leishmaniasis control and elimination

Singh, Om Prakash; Hasker, Epco; Boelaert, Marleen; Sacks, David L.; Sundar, Shyam

doi:10.1371/journal.pntd.0008363

Cited by 28 publications

(24 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Visceral leishmaniasis in the Indian subcontinent is believed to have an anthroponotic transmission cycle as there is no direct evidence that non-human hosts can transmit infection to the sandfly vector. 9 , 10 With a decreasing number of active visceral leishmaniasis cases in the community, the relative importance of other infectious groups in the transmission dynamics is increasing. 11 Both patients with post-kala-azar dermal leishmaniasis, who have skin eruptions as sequelae of treated visceral leishmaniasis, and those with HIV co-infection, who can have repeated clinical visceral leishmaniasis episodes, have been shown to be infectious to sandflies.…”

Section: Introductionmentioning

confidence: 99%

“… 10 , 14 Xenodiagnosis is the most direct way to determine the infectiousness of an infected host to vector sandflies and can be used to investigate the role of potential reservoir populations in the shifting ecology of L donovani transmission. 9 The aim of this study was to use xenodiagnosis to evaluate the relative infectiousness to sandflies of patients with visceral leishmaniasis or post-kala-azar dermal leishmaniasis, before and after treatment, and asymptomatic individuals, so to provide missing information about L donovani transmission dynamics for timely incorporation into the visceral leishmaniasis elimination programme in India.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics study

et al. 2021

Self Cite

View full text Add to dashboard Cite

Summary Background Visceral 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. Methods In 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. Findings Between 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 ...

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics study

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Xenodiagnosis is the classical approach for quantifying transmissibility from a host to an insect species with a view to distinguish infectious from non-infectious hosts ( Singh et al., 2020 ). This method when applied can help define the characteristics of L. donovani transmission and provide key epidemiological evidence to guide the program.…”

Section: Resultsmentioning

confidence: 99%

“…It was further expanded to larger cohorts in Bangladesh wherein the infectiousness was higher in the polymorphic variant (17/21 81%) vs. macular (9/35, 35%) cases ( Mondal et al., 2019 ); similarly, a substantial proportion of VL cases (10/15, 67%) were also able to transmit to sandflies ( Mondal et al., 2019 ). Taken together, as tracking of the Leishmania parasite in sandflies provides key information regarding the infectiousness of VL and PKDL cases ( Singh et al., 2020 ), application of molecular tools could provide information regarding the reservoir competence.…”

Section: Resultsmentioning

confidence: 99%

Molecular Tracking of the Leishmania Parasite

Moulik¹,

Sengupta²,

Chatterjee³

2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

With the Visceral Leishmaniasis/Kala-azar Elimination Program in South Asia in its consolidation phase, the focus is mainly on case detection, vector control, and identifying potential sources of infection. Accordingly, emphasis is presently on curbing transmission, which is potentially achievable by identification and elimination of potential reservoirs. The strongest contenders for being the disease reservoir are cases of Post Kala-azar Dermal Leishmaniasis (PKDL) which occurs in a minor proportion of individuals apparently cured of Visceral Leishmaniasis (VL). The demonstration of parasites in tissue aspirates despite being a risky and invasive process is the gold standard for diagnosis of VL, but is now being replaced by serological tests e.g., rK39 strip test and direct agglutination test. However, these antibody based tests are limited in their ability to diagnose relapses, detect cases of PKDL, and monitor effectiveness of treatment. Accordingly, detection of antigen or nucleic acids by polymerase chain reaction has been successfully applied for monitoring of parasite kinetics. This review article provides updated information on recent developments regarding the available antibody or antigen/nucleic acid based biomarkers for longitudinal monitoring of patients with VL or PKDL and emphasizes the need for availability of studies pertaining to quantification of treatment response or relapse.

show abstract

“…A recent xenodiagnosis study on asymptomatic VL subjects in the Mediterranean basin (Molina et al, 2020) and India (Singh et al, 2020b) indicated serologically positive asymptomatic people were not the cause for ongoing transmission (Figure 3) , suggesting that there could be an alternative non-human host sustaining transmission. These models conclude that xenodiagnosis experiments and more clinical data are necessary to predict the role of asymptomatic infection, PKDL, and domestic animals as infection reservoirs on the ISC (Tiwary et al, 2017, Le Rutte et al, 2016, Singh et al, 2020a.…”

Section: Challenges Of Elimination and Possible Infection Sources On mentioning

confidence: 99%

Domestic Mammals as Reservoirs for Leishmania donovani on the Indian Subcontinent: Possibility and Consequences on Elimination

Kushwaha

Scorza

Singh

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Leishmania donovani is the causative agent of historically anthroponotic visceral leishmaniasis (VL) on the Indian subcontinent (ISC). L. donovani is transmitted by the sand fly species Phlebotomus argentipes. Our collaborative group and others have shown that sand flies trapped outside in endemic villages have fed on cattle and dogs in addition to people. Domestic animals are reservoirs for L. donovani complex spp., particularly L. infantum, in other endemic areas. Multiple studies using quantitative PCR or serological detection methods have demonstrated that goats, cattle, rats and dogs were diagnostically positive for L. donovani infection or exposure in eastern Africa, Bangladesh, Nepal and India. There is a limited understanding of the extent to which L. donovani infection of domestic animals drives transmission to other animals or humans on the ISC. Evidence from other vector-borne disease elimination strategies indicated that emerging infections in domestic species hindered eradication. The predominant lesson learned from these other situations is that non-human reservoirs must be identified, controlled and/or prevented. Massive efforts are underway for VL elimination on the Indian subcontinent. Despite these herculean efforts, residual VL incidence persists. The specter of an animal reservoir complicating elimination efforts haunts the final push toward full VL control. Better understanding of L. donovani transmission on the Indian subcontinent and rigorous consideration of how non-human reservoirs alter VL ecology are critical to sustain elimination goals.

show abstract

Xenodiagnosis to address key questions in visceral leishmaniasis control and elimination

Cited by 28 publications

References 88 publications

Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics study

Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics study

Molecular Tracking of the Leishmania Parasite

Domestic Mammals as Reservoirs for Leishmania donovani on the Indian Subcontinent: Possibility and Consequences on Elimination

Contact Info

Product

Resources

About