Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

Abstract

BackgroundAs Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission.Methodology/ Principal FindingWe reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting.Conclusion/ SignificanceThere is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection.

Towards elimination of visceral leishmaniasis in the Indian subcontinent—Translating research to practice to public health

“…TDR-supported research showed a more than 8-fold underestimation of disease burden [83, 84], an annual VL incidence that was up to 22 times higher than the elimination target [85], a 6% case fatality rate (Table 3) [86], and established a baseline for the attack phase of the VL elimination programme. Furthermore, TDR-supported epidemiological research defines and corroborates the role of poverty, caste, literacy, housing condition, proximity to vegetation, water bodies, livestock, and sleeping habits in influencing exposure to the risk of VL, which helped understanding of human–vector transmission and to inform vector-control strategies for VL elimination [87–92]. …”

“…The strategy needs a paradigm shift from preventing disease to preventing infection and interrupting transmission. The infectiousness of asymptomatic individuals infected with Leishmania , markers for progression to VL disease, the role of domestic animals in transmission, and the potential of PKDL as a reservoir for infection need to be better understood [92, 125–127]. The implications of HIV coinfection with VL for treatment failure and relapse, transmission dynamics, and development of parasite resistance to drugs need to be studied further, and strategies need to be developed and tested as appropriate [42].…”

Housing structure including the surrounding environment as a risk factor for visceral leishmaniasis transmission in Nepal

“…We calculated the sample size taking into account only one explanatory variable, therefore the statistical power for detecting significant associations could be lower when analyzing multiple variables simultaneously. One particular challenge in VL field studies is the unknown number of asymptomatic cases [33]. However, as the ratio between clinical VL cases and asymptomatic cases is fairly constant, we can take the socio-economically more important clinical VL cases as an indicator of VL transmission.…”

“…In general terms, this and related studies on preventive measures are important for the maintenance of the VL elimination achievements [33,34] which are not only threatened by the decrease of Public Health activities after reaching the elimination goal (abandoning vector control and early case detection and treatment) but also the challenges of environmental and climate change which contribute to the spread of VL [16].…”

Intensely clustered outbreak of visceral leishmaniasis (kala-azar) in a setting of seasonal migration in a village of Bihar, India

“…Spleen becomes palpable only after being enlarged twice to thrice [40]. Therefore, transmission potential of such cases should also be considered [41,42]. Ultrasonographic detection of sub-palpable splenomegaly and bone marrow/ intercostal splenic parasitology has been found to provide additional yield of kala-azar cases [43].…”