Of Cattle, Sand Flies and Men: A Systematic Review of Risk Factor Analyses for South Asian Visceral Leishmaniasis and Implications for Elimination

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Abstract
Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kala-azar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peri-domestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed. Visceral leishmaniasis (VL) is a potentially deadly parasitic disease that affects 200,000 to 300,000 people per year in the Indian subcontinent, where an effort is currently underway to eliminate the disease. Studies have identified fairly consistent patterns of risk factors for VL. This information can help to inform the elimination effort. Because humans form the sole source of infection, clustering of VL cases is a prominent feature, both at the household level and on a larger scale. Mud walls, dampness in houses, and peri-domestic vegetation increase infection risk by promoting the survival of the insect vector. Bed nets, sleeping on a cot and indoor residual spraying decrease risk. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting a complex effect on vector abundance and vector infection rates. Poverty is a major underlying factor increasing risk of VL infection and disease. A well-designed demonstration project is needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid return of disease when interventions are scaled back.