Asymptomatic Leishmania infections in northern India: a threat for the elimination programme?

Das, Sushmita; Matlashewski, Greg; Bhunia, Gouri Sankar; Kesari, Shreekant; Das, Pradeep

doi:10.1093/trstmh/tru146

Cited by 29 publications

(31 citation statements)

References 38 publications

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“…The role of asymptomatic infections and post kala-azar dermal leishmaniasis (PKDL) in transmission and maintenance of the human reservoir remains poorly understood. Asymptomatic infections include a positive result from serological assays, polymerase chain reaction (PCR), leishmanin skin test (LST) or IFN-γ release assay (IGRA) [5, 6]. It is difficult to know how many asymptomatic carriers there are in the Indian subcontinent because of the different study designs and assays used to identify asymptomatic carriers, but it has been estimated to be in the range of 5–10 asymptomatic cases for each active VL case [5, 6, 7].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India

et al. 2016

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BackgroundVisceral Leishmaniasis (VL) is a neglected tropical disease that afflicts some of the poorest populations in the world including people living in the Bihar state of India. Due to efforts from local governments, NGOs and international organizations, the number of VL cases has declined in recent years. Despite this progress, the reservoir for transmission remains to be clearly defined since it is unknown what role post kala-azar dermal leishmaniasis (PKDL) and asymptomatic infections play in transmission. This information is vital to establish effective surveillance and monitoring to sustainably eliminate VL.Methodology/Principal FindingsWe performed a longitudinal study over a 24-month period to examine VL transmission and seroconversion in households with VL, PKDL and asymptomatic infections in the Saran and Muzaffarpur districts of Bihar. During the initial screening of 5,144 people in 16 highly endemic villages, 195 cases of recently treated VL, 116 healthy rK39 positive cases and 31 PKDL cases were identified. Approximately half of the rK39-positive healthy cases identified during the initial 6-month screening period were from households (HHs) where a VL case had been identified. During the 18-month follow-up period, seroconversion of family members in the HHs with VL cases, PKDL cases, and rK39-positive individuals was similar to control HHs. Therefore, seroconversion was highest in HHs closest to the time of VL disease of a household member and there was no evidence of higher transmission in households with PKDL or healthy rK39-positive HHs. Moreover, within the PKDL HHs, (the initial 31 PKDL cases plus an additional 66 PKDL cases), there were no cases of VL identified during the initial screen or the 18-month follow-up. Notably, 23% of the PKDL cases had no prior history of VL suggesting that infection resulting directly in PKDL is more common than previously estimated.Conclusions/SignificanceThese observations argue that acute VL cases represent the major reservoir for transmission in these villages and early identification and treatment of VL cases should remain a priority for VL elimination. We were unable to obtain evidence that transmission occurs in HHs with a PKDL case.

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Section: Introductionmentioning

confidence: 99%

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India

et al. 2016

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“…Most infected people are asymptomatic, but may still contribute to transmission at low levels 7 . Patients with post-kala-azar dermal leishmaniasis (PKDL) are known to harbour parasites, often in the dermal region, and are assumed to be infectious to sand flies 8 .…”

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confidence: 99%

Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent

Medley

Hollingsworth

Olliaro

et al. 2015

Nature

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Countries in the Indian subcontinent have committed to reducing the incidence of kala-azar, a clinical manifestation of visceral leishmaniasis, to below 1 in 10,000 by 2020. We address the role of timing of use and accuracy of diagnostics in kala-azar control and elimination. We use empirical data on health-seeking behaviour and health-system performance from the Indian state of Bihar, Bangladesh and Nepal to parameterize a mathematical model. Diagnosis of cases is key to case management, control and surveillance. Treatment of cases prevents onward transmission, and we show that the differences in time to diagnosis in these three settings explain the observed differences in incidence. Shortening the time from health-care seeking to diagnosis is likely to lead to dramatic reductions in incidence in Bihar, bringing the incidence down to the levels seen in Bangladesh and Nepal. The results emphasize the importance of maintaining population and health-system awareness, particularly as transmission and disease incidence decline. We explore the possibility of diagnosing patients before the onset of clinical kala-azar (before 14 days fever), and show that this could have a marked impact on incidence, even for a moderately sensitive test. However, limited specificity (that results in false positives) is a major barrier to such a strategy. Diagnostic tests of high specificity used at an early stage of active infection, even if sensitivity is only moderate, could have a key role in the control of kala-azar, and prevent its resurgence when paired with the passive health-care system and tests of high sensitivity, such as the test for rK39 antibody response.

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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BackgroundThe decade following the Regional Strategic Framework for Visceral Leishmaniasis (VL) elimination in 2005 has shown compelling progress in the reduction of VL burden in the Indian subcontinent. The Special Programme for Research and Training in Tropical Diseases (TDR), hosted by the World Health Organization (WHO) and other stakeholders, has coordinated and financed research for the development of new innovative tools and strategies to support the regional VL elimination initiative. This paper describes the process of the TDR’s engagement and contribution to this initiative.Methodology/principal findingsMultiple databases were searched to identify 152 scientific papers and reports with WHO funding or authorship affiliation around the following 3 framework strategies: detection of new cases, morbidity reduction, and prevention of infection. TDR has played a critical role in the evaluation and subsequent use of the 39-aminoacid–recombinant kinesin antigen (rK39) rapid diagnostic test (RDT) as a confirmatory test for VL in the national program. TDR has supported the clinical research and development of miltefosine and single-dose liposomal amphotericin B as a first-line treatment against VL. TDR has engaged with in-country researchers, national programme managers, and partners to generate evidence-based interventions for early detection and treatment of VL patients. TDR evaluated the quality, community acceptance, and cost effectiveness of indoor residual spraying, insecticide-treated bed nets, insecticide-impregnated durable wall linings, insecticidal paint, and environmental management as tools for integrated vector management in reducing sandfly density.Conclusions/significanceTDR’s engagement with country policy makers, scientists, and clinicians in the development of effective diagnosis, treatment, case detection, and vector control represents an important example of TDR’s stewardship toward the elimination of VL in the Indian subcontinent.

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Asymptomatic Leishmania infections in northern India: a threat for the elimination programme?

Cited by 29 publications

References 38 publications

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India

Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India

Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent

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

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