title: Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent - A Systematic Literature Review.
abstract: BACKGROUND
  As 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.
  We 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.
  There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection.
authors.affiliation: Global Influenza Programme, World Health Organization, Geneva, Switzerland.
authors.forename: Siddhivinayak
authors.identifier: http://orcid.org/0000-0002-9651-7789
authors.initials: S
authors.lastname: Hirve
authors.affiliation: Epidemiology and Control of Tropical Diseases, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Boelaert
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Matlashewski
authors.affiliation: Nutrition and Clinical Services Division, International Center for Diarrheal Disease Research, Dhaka, Bangladesh.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Mondal
authors.affiliation: Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
authors.forename: Byron
authors.initials: B
authors.lastname: Arana
authors.affiliation: Special Programme on Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Kroeger
authors.affiliation: Special Programme on Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
mesh_terms: D000818:Animals; D058345:Asymptomatic Infections / Q000453:epidemiology*; D001459:Bangladesh / Q000453:epidemiology; D060085:Coinfection; D006801:Humans; D007194:India / Q000453:epidemiology; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000453:epidemiology* / Q000635:transmission*; D009390:Nepal / Q000453:epidemiology; D011576:Psychodidae / Q000469:parasitology*; D012008:Recurrence; D012307:Risk Factors