Investments in Research and Surveillance Are Needed to Go Beyond Elimination and Stop Transmission of Leishmania in the Indian Subcontinent

Olliaro, Piero; Shamsuzzaman, Tushar A. K. M.; Marasini, Baburam; Dhariwal, A C; Ahmed, Be-Nazir; Mondal, Dinesh; Banjara, Megha Raj; Das, Pradeep; Sundar, Shyam; Rijal, Suman; Arana, Byron; Alvar, Jorge; Argaw, Daniel; Peeling, Rosanna W.; Kroeger, Axel; Matlashewski, Greg

doi:10.1371/journal.pntd.0005190

Cited by 32 publications

(35 citation statements)

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Younis¹,

Kroeger

Joshi³

et al. 2020

PLoS Negl Trop Dis

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Visceral leishmaniasis (VL) in Nepal is found in 61 out of 75 districts including areas previously listed as non-endemic. This study focused on the role of housing conditions and its immediate environment in VL transmission, to limit future transmissions, ensure sustainable vector control and support the VL elimination program. The objective was to explore the risk factors in rural housing-and land lot typologies contributing to clinical VL occurrence and transmission. Housing structures and land lots were examined based on characteristics as risk factors of VL transmission in a case-control analysis. VL cases from 2013-2017 were identified based on the existing database from the Epidemiology and Disease Control Division and District Public Health Office from the plain Terai area (Morang, and Saptari districts) and hilly area (Palpa district) of Nepal. Two hundred and three built environments were analyzed (66 cases and 137 controls). Inferential statistics and logistic regression analysis were performed to determine the association of risk factors with VL. The risk factors with the highest odds of VL were: bamboo walls (adjusted odds ratio (AOR)-8.1, 95% CI 2.40-27.63, p = 0.001), walls made of leaves/branches (AOR-3.0, 95% CI 0.84-10.93, p = 0.090), cracks in bedroom walls (AOR-2.9, 95% CI 0.93-9.19, p = 0.065), and placing sacks near sleeping areas (AOR-19.2, 95% CI 4.06-90.46, p <0.001). Significant outdoor factors were: lots with Kadam trees (AOR-12.7, 95% CI 3.28-49.09, p <0.001), open ground-outdoor toilets (AOR-9.3, 95% CI 2.14-369.85, p = 0.003), moisture in outdoor toilet sheds (AOR-18.09, 95% CI 7.25-451.01, p = 0.002), nearby-open land (AOR-36.8, 95% CI 3.14-430.98, p = 0.004), moisture inside animal sheds (AOR-6.9, 95% CI 1.82-26.66, p = 0.005), and surrounding animals/animals wastes particularly goats (AOR-3.5, 95% CI 1.09-10.94, p = 0.036). Certain housing and surrounding environmental conditions and characteristics are risk factors for VL. Hence, elimination and educational programs should include the focus on housing improvement and avoidance of risk factors. Longitudinal interventional studies are required to document temporal relationships and whether interventions on these factors will have an impact on Leishmania transmission or burden.Visceral leishmaniasis (VL) is a fatal disease if not treated in time. It is the disease of the poorest people. Poor housing and sanitation around the house are considered as the risk factors for the occurrence of VL. The main objective of our research was to explore multiple risk factors from different housing and land lot-typologies for VL occurrence and transmission through a case-control study. Some of our results reveal that inside the dwelling the likelihood of having clinical VL was substantially enhanced by providing suitable breeding sites for the insect vectors; as an example: the probability of getting VL disease was about ten times higher when there were sacks (empty or filled) near sleeping areas. Also cracks in walls and floors were found to contr...

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Section: Discussionmentioning

confidence: 99%

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

Younis¹,

Kroeger

Joshi³

et al. 2020

PLoS Negl Trop Dis

Self Cite

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“…As countries in the Indian subcontinent progress towards the elimination goal in the affected regions, the concern is that elimination may be mistaken for eradication, and both donor fatigue and programme complacency may drift attention to the next unfinished agenda [122]. Limitations of the current programme and the need to maintain and consolidate gains has already been highlighted elsewhere by us, and TDR remains committed to supporting operational and implementation research to achieve the elimination goal [122, 123].…”

Section: Discussionmentioning

confidence: 99%

“…Limitations of the current programme and the need to maintain and consolidate gains has already been highlighted elsewhere by us, and TDR remains committed to supporting operational and implementation research to achieve the elimination goal [122, 123]. The challenge now is to ensure that the disease does not reemerge or is not reintroduced and that disease and vector surveillance are reinforced during the postelimination phase [124].…”

Section: Discussionmentioning

confidence: 99%

“…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]. The development of innovative approaches to impair infection through early case detection and treatment, particularly in remote or previously nonendemic areas, as well as vector surveillance systems, new methods to measure transmission, mathematical transmission modelling to measure progress post elimination, xenodiagnostic studies to measure reservoir potential, new noninvasive antigen-based diagnostic tools [41], better treatment of PKDL, and surveillance for drug resistance are some of the urgent research priorities for the immediate future [122, 128]. DWL as an option for vector control needs to be further explored, as well as other alternatives that can be applied by communities themselves, such as insecticidal paint or LLIN combined with other affordable “do-it-yourself” measures with appropriate support.…”

Section: Discussionmentioning

confidence: 99%

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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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“…In VL endemic areas self-resolving infection has also been observed by developing parasite-specific antibodies and/or T cell response [13,14]. Furthermore, patients who have recovered from kala-azar are usually immune to reinfection, which suggests that vaccination against leishmaniasis should be feasible [15,16].…”

Section: Development Of Rk39mentioning

confidence: 99%

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

Ejazi

Ghosh

Bhattacharyya

et al. 2020

Preprint

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Background: Visceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods: In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins. Results: We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions: The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell mediated immune response suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access long-term immune response.

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Investments in Research and Surveillance Are Needed to Go Beyond Elimination and Stop Transmission of Leishmania in the Indian Subcontinent

Cited by 32 publications

References 13 publications

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

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

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

Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

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