Xenodiagnosis leads the way: elimination of visceral leishmaniasis from the Indian subcontinent is feasible and sustainable
Authors: Richard Reithinger
Journal: The Lancet Microbe (2021)

Visceral leishmaniasis is a neglected tropical disease caused by parasites of the Leishmania donovani complex and transmitted to humans by the bite of female phlebotomine sandflies.1Burza S Croft SL Boelaert M Leishmaniasis.Lancet. 2018; 392: 951-970Summary Full Text Full Text PDF PubMed Scopus (582) Google Scholar Globally, 17 082 cases were reported to WHO in 2018, although this number is probably an underestimate. If left untreated, visceral leishmaniasis is fatal.1Burza S Croft SL Boelaert M Leishmaniasis.Lancet. 2018; 392: 951-970Summary Full Text Full Text PDF PubMed Scopus (582) Google Scholar In endemic areas, visceral leishmaniasis has a substantial economic impact, with affected households potentially having out-of-pocket expenditures that equal or exceed their annual household income.2Ozaki M Islam S Rahman KM Rahman A Luby SP Bern C Economic consequences of post-kalaazar dermal leishmaniasis in a rural Bangladeshi community.Am J Trop Med Hyg. 2011; 85: 528-534Crossref Scopus (8) Google Scholar In the past decade, substantial progress has been made in controlling visceral leishmaniasis: indeed, on the Indian subcontinent, visceral leishmaniasis elimination is now within reach, with both Bangladesh and Nepal having already met, and India coming close to, the set elimination threshold of less than one detected visceral leishmaniasis case per 10 000 population per year at the subdistrict or district level.3WHO Regional Office for South-East AsiaProcess of validation of elimination of kala-azar as a public health problem in south-east Asia.https://www.who.int/leishmaniasis/resources/Process_of_validation_of_VL_elimination_SEA_CD_321.pdf?ua=1&ua=1Date: July 5, 2016Date accessed: November 20, 2020Google Scholar For years, key questions asked when implementing visceral leishmaniasis control and elimination efforts and determining whether reductions in incidence, and eventual elimination, are sustainable have been: what is the relative infectiousness of people with asymptomatic infection, patients with active visceral leishmaniasis, patients with visceral leishmaniasis that has been successfully treated, and patients with post-kala-azar dermal leishmaniasis (a complication of visceral leishmaniasis)? And how do any differences in infectiousness affect visceral leishmaniasis transmission dynamics? In The Lancet Microbe, Om Prakash Singh and colleagues4Singh OP Tiwary P Kushwaha AK et al.Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics study.Lancet Microbe. 2021; 2: e23-e31Google Scholar address these questions through use of direct xenodiagnosis (ie, determining the presence of a pathogen by exposing possibly infected tissue to an insect vector and then examining the vector for the presence of the pathogen it might have ingested), and find that control and elimination efforts on the Indian subcontinent will probably have to focus only on individuals with active disease. In what is the largest study of its kind to date, the authors exposed 287 individuals with varying clinical status (asymptomatic infection, active visceral leishmaniasis or post-kala-azar dermal leishmaniasis, or treated visceral leishmaniasis or post-kala-azar dermal leishmaniasis) to 16 087 female Phlebotomus argentipes sandflies, the primary vector of visceral leishmaniasis in South Asia. Their findings show that patients with active visceral leishmaniasis or post-kala-azar dermal leishmaniasis were highly infectious to P argentipes, with 42 (55%) or 60 (78%) of 77 patients with active visceral leishmaniasis (as assessed by microscopy or quantitative PCR, respectively) and 11 (42%) or 23 (88%) of 26 patients with active post-kala-azar dermal leishmaniasis transmitting parasites to sandflies. By contrast, individuals with asymptomatic infection, as well as treated and cured patients, were not, or were barely, infectious. Singh and colleagues' study confirms previous xenodiagnoses studies in human and reservoir hosts, which showed that infectiousness of L donovani complex parasites to sandflies increases as a function of disease severity.5Quinnell RJ Courtenay O Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis.Parasitology. 2009; 136: 1915-1934Crossref PubMed Scopus (303) Google Scholar In the study by Singh and colleagues, infectiousness of patients with visceral leishmaniasis was associated with increasing splenic score and parasite burden in the blood, and in patients with post-kala-azar dermal leishmaniasis with parasite burden in the skin. The study also confirms that visceral leishmaniasis treatment with liposomal amphotericin B is highly effective and results in parasitological cure.1Burza S Croft SL Boelaert M Leishmaniasis.Lancet. 2018; 392: 951-970Summary Full Text Full Text PDF PubMed Scopus (582) Google Scholar Interestingly, the study seems to indicate that if sandflies become infected only when biting people with active disease, then the elusive quest for markers of infectiousness might not be as important as previously thought.5Quinnell RJ Courtenay O Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis.Parasitology. 2009; 136: 1915-1934Crossref PubMed Scopus (303) Google Scholar, 6Le Rutte EA Coffeng LE Bontje DM et al.Feasibility of eliminating visceral leishmaniasis from the Indian subcontinent: explorations with a set of deterministic age-structured transmission models.Parasit Vectors. 2016; 9: 24Crossref PubMed Scopus (32) Google Scholar For example, a study in 1993–95 in dogs, the natural reservoir host for L donovani complex parasites in Brazil, showed that 17% of infectious dogs accounted for more than 80% of sandfly infections, implying that infectiousness followed Pareto principles and that some individuals could act as superspreaders—identifying those superspreaders was therefore seen as important.5Quinnell RJ Courtenay O Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis.Parasitology. 2009; 136: 1915-1934Crossref PubMed Scopus (303) Google Scholar From a public health perspective, what is highly encouraging for visceral leishmaniasis control and elimination efforts is the seemingly negligible importance of asymptomatic infections, as well as of treated and cured patients, for L donovani complex transmission dynamics. Although these findings confirm results of earlier, smaller studies,7Costa CH Gomes RB Silva MR et al.Competence of the human host as a reservoir for Leishmania chagasi.J Infect Dis. 2000; 182: 997-1000Crossref PubMed Scopus (74) Google Scholar they are in contrast with concerns stemming from some modelling work, which implied that asymptomatic infections could contribute to up to 82% of new infections.6Le Rutte EA Coffeng LE Bontje DM et al.Feasibility of eliminating visceral leishmaniasis from the Indian subcontinent: explorations with a set of deterministic age-structured transmission models.Parasit Vectors. 2016; 9: 24Crossref PubMed Scopus (32) Google Scholar Singh and colleagues' findings mean that visceral leishmaniasis elimination on the Indian subcontinent, as outlined in the regional elimination strategy,8WHO Regional Office for South-East AsiaRegional strategic framework for elimination of kala-azar from the south-east Asia region (2011–2015).https://apps.who.int/iris/handle/10665/205826Date: 2012Date accessed: November 20, 2020Google Scholar and re-stipulated in the 2012–30 roadmap for neglected tropical diseases,9WHOEnding the neglect to attain the Sustainable Development Goals. A road map for neglected tropical diseases 2021–2030.https://apps.who.int/iris/rest/bitstreams/1277958/retrieveDate accessed: November 20, 2020Google Scholar could be achieved by early and prompt diagnosis and treatment of visceral leishmaniasis and post-kala-azar dermal leishmaniasis, complemented by targeted vector control (eg, insecticide-treated bednets or indoor residual spraying of households with insecticide) and enhanced surveillance, including reactive case-finding and follow-up. Such an approach has been applied for years in the malaria field and is starting to yield dividends, with several countries having been certified as malaria-free in the past 5 years.10WHOA framework for malaria elimination. World Health Organization, Geneva2017http://apps.who.int/iris/bitstream/10665/254761/1/9789241511988-eng.pdf?ua=1Date accessed: November 20, 2020Google Scholar The global leishmaniasis community must take this opportunity to close the deal on what is now truly within reach: the elimination of visceral leishmaniasis from the Indian subcontinent. I declare no competing interests. Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics studyThese 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. Full-Text PDF Open Access