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      Policy Recommendations From Transmission Modeling for the Elimination of Visceral Leishmaniasis in the Indian Subcontinent

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          Abstract

          Background

          Visceral leishmaniasis (VL) has been targeted by the World Health Organization (WHO) and 5 countries in the Indian subcontinent for elimination as a public health problem. To achieve this target, the WHO has developed guidelines consisting of 4 phases of different levels of interventions, based on vector control through indoor residual spraying of insecticide (IRS) and active case detection (ACD). Mathematical transmission models of VL are increasingly used for planning and assessing the efficacy of interventions and evaluating the intensity and timescale required to achieve the elimination target.

          Methods

          This paper draws together the key policy-relevant conclusions from recent transmission modeling of VL, and presents new predictions for VL incidence under the interventions recommended by the WHO using the latest transmission models.

          Results

          The model predictions suggest that the current WHO guidelines should be sufficient to reach the elimination target in areas that had medium VL endemicities (up to 5 VL cases per 10000 population per year) prior to the start of interventions. However, additional interventions, such as extending the WHO attack phase (intensive IRS and ACD), may be required to bring forward elimination in regions with high precontrol endemicities, depending on the relative infectiousness of different disease stages.

          Conclusions

          The potential hurdle that asymptomatic and, in particular, post-kala-azar dermal leishmaniasis cases may pose to reaching and sustaining the target needs to be addressed. As VL incidence decreases, the pool of immunologically naive individuals will grow, creating the potential for new outbreaks.

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          Most cited references27

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          Post-kala-azar dermal leishmaniasis.

          Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.
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            Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis.

            Zoonotic visceral leishmaniasis (ZVL) caused by Leishmania infantum is an important disease of humans and dogs. Here we review aspects of the transmission and control of ZVL. Whilst there is clear evidence that ZVL is maintained by sandfly transmission, transmission may also occur by non-sandfly routes, such as congenital and sexual transmission. Dogs are the only confirmed primary reservoir of infection. Meta-analysis of dog studies confirms that infectiousness is higher in symptomatic infection; infectiousness is also higher in European than South American studies. A high prevalence of infection has been reported from an increasing number of domestic and wild mammals; updated host ranges are provided. The crab-eating fox Cerdocyon thous, opossums Didelphis spp., domestic cat Felis cattus, black rat Rattus rattus and humans can infect sandflies, but confirmation of these hosts as primary or secondary reservoirs requires further xenodiagnosis studies at the population level. Thus the putative sylvatic reservoir(s) of ZVL remains unknown. Review of intervention studies examining the effectiveness of current control methods highlights the lack of randomized controlled trials of both dog culling and residual insecticide spraying. Topical insecticides (deltamethrin-impregnated collars and pour-ons) have been shown to provide a high level of individual protection to treated dogs, but further community-level studies are needed.
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              The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village.

              We examined the epidemiology of kala-azar and asymptomatic leishmanial infection measured by serologic and leishmanin skin test results in a Bangladeshi community. In a subset, we measured serum retinol, zinc and C-reactive protein (CRP). Kala-azar and seroconversion incidence were 15.6 and 63.1 per 1,000 person-years, respectively. Proximity to a previous kala-azar case increased the likelihood of both kala-azar and asymptomatic infection. Bed net use protected against kala-azar (rate ratio = 0.35, P < 0.01), but not subclinical infection (rate ratio = 1.1, P = 0.82). Kala-azar patients were younger (P < 0.001) and reported lower red meat consumption (P < 0.01) than asymptomatic seropositive individuals. Retinol and zinc levels were lower in current kala-azar patients and those who later developed kala-azar compared with uninfected and asymptomatically infected subjects. The CRP levels were higher in kala-azar patients compared with the other two groups. Low red meat intake and poor zinc and retinol status may characterize a group at higher risk of symptomatic disease.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                15 June 2018
                01 June 2018
                : 66
                : Suppl 4 , Reaching the 2020 Goals for Nine Neglected Tropical Diseases
                : S301-S308
                Affiliations
                [1 ]Department of Public Health, Erasmus MC, University Medical Center Rotterdam, The Netherlands
                [2 ]Zeeman Institute, University of Warwick, Coventry, United Kingdom
                [3 ]London School of Hygiene and Tropical Medicine, United Kingdom
                [4 ]Department of Control of Neglected Tropical Diseases
                [5 ]Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland
                [6 ]Liverpool School of Tropical Medicine, United Kingdom
                [7 ]Institute of Tropical Medicine, Antwerp, Belgium
                [8 ]Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford
                Author notes

                E. A. L. and L. A. C. C. contributed equally to this work.

                T. D. H., G. F. M., and S. J. d. V. contributed equally to this work.

                Correspondence: L. A. C. Chapman, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, Kings Cross, London, WC1H 9SH, United Kingdom ( Lloyd.Chapman@ 123456lshtm.ac.uk ).
                Article
                ciy007
                10.1093/cid/ciy007
                5982727
                29860292
                e620ac4c-ed77-416a-83b2-82dcc32dda34
                © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 IGO (CC BY 3.0 IGO) License ( https://creativecommons.org/licenses/by/3.0/igo/) which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Pages: 8
                Funding
                Funded by: Neglected Tropical Disease Modelling Consortium
                Award ID: OPP1053230
                Categories
                Supplement Articles

                Infectious disease & Microbiology
                visceral leishmaniasis,indian subcontinent,transmission modeling,who guidelines,elimination

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