Skin lesions are reservoirs for Kala-azar infection
doi:10.1038/nindia.2019.93 Published online 22 July 2019
People treated for visceral leishmaniasis (VL) can act as a reservoir for infection after treatment if they develop a skin condition known as post-kala azar dermal leishmaniasis (PKDL), a new study confirms1.
Patients can develop PKDL, lesions in the form of rashes and boils, usually six months to a year after completing treatment for visceral leishmaniasis, a deadly parasitic disease transmitted by sandflies, also known as kala-azar, or black fever.
PKDL’s role as a reservoir poses a major challenge for those who aim to eliminate visceral leishmaniasis across South Asia by 2020.
According to the World Health Organisation(WHO), VL is fatal in more than 95% of cases if left untreated. It is characterized by irregular bouts of fever, weight loss, enlargement of the spleen and liver, and anaemia. Most cases occur in Brazil, East Africa and in South-East Asia. PKDL usually follows visceral leishmaniasis, and appears as macular, papular or nodular rash usually on face, upper arms, torso and other parts of the body.
In April 2017, countries in the WHO south-east Asian region, including India, had resolved to fast-track efforts to eradicate and eliminate neglected tropical diseases (NTD) such as leprosy, lymphatic filariasis and kala-azar by 2020.
“This study positions PKDL as one of the central challenges to VL elimination on the Indian subcontinent. Our data provide proof and quantification of the infectious potential of nodular and macular PKDL patients,” the authors from the non-profit research and development organisation Drugs for Neglected Diseases initiative (DNDi) and its partner, International Centre for Diarrhoeal Disease Research, Bangladesh, say.
In 2018, a total of 4,380 cases of kala-azar were reported in India, of which 3,423 were in Bihar alone. Until June 2019, 1,741 cases have been reported, of which 1374 are from Bihar. In 2018, the total number of PKDL cases in India was 1245. Almost all the cases of PKDL are confined to four states, Bihar, Jharkhand, West Bengal and Uttar Pradesh.
The study attempted to assess whether people infected with PKDL could transmit the parasite responsible for VL to uninfected laboratory-reared sandflies. The researchers used xenodiagnoses which is the most accurate approach to evaluate infectivity to sandflies. Around 57.4% of the 47 PKDL patients in the study were found to infect the sand flies. Patients who infected sandflies had a significantly higher parasite load in the skin. In addition, patients with nodular PKDL were more likely to be infective than those with macular PKDL.
As part of the trial, the PKDL patients were bitten by laboratory-reared, infection-free sandflies by placing their hands in a cage of male and female sandflies for 15 minutes. For patients without hand lesions, the sandflies were placed in a tube and held against a single lesion for the flies to feed on. The sandflies were then analysed for the parasites that cause kala-azar.
The authors claim that this is the largest study to date – fully characterizing 47 cases – to assess infectivity of PKDL patients to sand flies. “Until now, information on the infectivity of PKDL was scarce and scattered across decades, with only nine cases studied so far since 1928,” says Jorge Alvar, the co-principal investigator and senior leishmaniasis advisor at DNDi. They show that these patients – regardless of the clinical form macular or nodular — can play a pivotal role in “maintaining” the transmission of the disease in between epidemics.
Since PKDL is an important reservoir for transmission, “we must also engage in identifying PKDL and provide prompt treatment,” says Suman Rijal, director of DNDi in India.
The study proves earlier hypotheses that PKDL patients can act as reservoirs of infection, says Shyam Sundar, distinguished professor of medicine at the Institute of Medical Science, Benaras Hindu University in Varanasi. "It should be broadened to include asymptomatic infected subjects, active kala azar patients, cured patients and kala azar-HIV co-infected patients to see whether they can be a source of infection," he says.
1. Mondal. D. et al. Quantifying the infectiousness of Post-Kala-Azar Dermal Leishmaniasis toward sand flies. Clin. Infect. Dis. 69, 251–258 (2019) doi: 10.1093/cid/ciy891