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Intervention Packages for Early Visceral Leishmaniasis Case Detection and Sandfly Control in Bangladesh: A Comparative Analysis.

ABSTRACT: We compared the efficacy of three intervention packages for active case detection (ACD) of visceral leishmaniasis (VL)/post-kala-azar dermal leishmaniasis (PKDL) combined with sandfly control around an index case. The packages were 1) no kala-azar transmission activity involving indoor residual spraying (IRS) with deltamethrin, peri-domestic deployment of larvicide with temephos, and house-to-house search for cases; 2) fever camp (FC) plus durable wall lining (DWL) with deltamethrin; and 3) FC plus insecticide (deltamethrin) impregnated bed-nets (ITN) around an index case. Fever camp includes 1-day campaign at the village level to screen and diagnose VL, PKDL, leprosy, malaria, and tuberculosis among residents with chronic fever or skin disease. Efficacy was measured through yield of new cases, vector density reduction, and mortality at 1, 3, 6, 9, and 12 months following intervention. Fever camp + DWL was the most efficacious intervention package with 0.5 case detected per intervention, 79% reduction in vector density (incidence rate ratio [IRR] = 0.21, P = 0.010), and 95.1% (95% confidence interval: 93.4%, 96.8%) sandfly mortality at 12 months. No kala-azar transmission activity was efficacious for vector control (74% vector reduction, IRR = 0.26, P < 0.0001 at 9 months; and 84% sandfly mortality at 3 months), but not for case detection (0 case per intervention). Fever camp + ITN was efficacious in detection of VL/PKDL cases (0.43 case per intervention), but its efficacy for vector control was inconsistent. We recommend index case-based FC for ACD combined with DWL or IRS plus larvicide for sandfly control during the consolidation and maintenance phases of the VL elimination program of the Indian subcontinent.

SUBMITTER: Huda MM

PROVIDER: S-EPMC6335927 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Immune responses to sandfly saliva have been shown to protect animals against Leishmania infection. Yet very little is known about the molecular characteristics of salivary proteins from different sandflies, particularly from vectors transmitting visceral leishmaniasis, the fatal form of the disease. Further knowledge of the repertoire of these salivary proteins will give us insights into the molecular evolution of these proteins and will help us select relevant antigens for the development of a vector based anti-Leishmania vaccine. RESULTS:Two salivary gland cDNA libraries from female sandflies Phlebotomus argentipes and P. perniciosus were constructed, sequenced and proteomic analysis of the salivary proteins was performed. The majority of the sequenced transcripts from the two cDNA libraries coded for secreted proteins. In this analysis we identified transcripts coding for protein families not previously described in sandflies. A comparative sandfly salivary transcriptome analysis was performed by using these two cDNA libraries and two other sandfly salivary gland cDNA libraries from P. ariasi and Lutzomyia longipalpis, also vectors of visceral leishmaniasis. Full-length secreted proteins from each sandfly library were compared using a stand-alone version of BLAST, creating formatted protein databases of each sandfly library. Related groups of proteins from each sandfly species were combined into defined families of proteins. With this comparison, we identified families of salivary proteins common among all of the sandflies studied, proteins to be genus specific and proteins that appear to be species specific. The common proteins included apyrase, yellow-related protein, antigen-5, PpSP15 and PpSP32-related protein, a 33-kDa protein, D7-related protein, a 39- and a 16.1- kDa protein and an endonuclease-like protein. Some of these families contained multiple members, including PPSP15-like, yellow proteins and D7-related proteins suggesting gene expansion in these proteins. CONCLUSION:This comprehensive analysis allows us the identification of genus- specific proteins, species-specific proteins and, more importantly, proteins common among these different sandflies. These results give us insights into the repertoire of salivary proteins that are potential candidates for a vector-based vaccine.

Project description:BackgroundIn Brazil, the transmission of Leishmania infantum in urban settings is closely related to infection among dogs, with occasional transmission to humans. Serological screening of dogs for Leishmania spp. infection on requests of their owners (passive case detection) represents a frequent, but little studied, practice within the scope of Brazilian public health. This study identified factors associated with canine visceral leishmaniasis (CVL) diagnosis-seeking behavior of dog owners in Rondonópolis (236,000 inhabitants), a municipality in Central-Western Brazil where VL is endemic. Also, we evaluated the profile of dog owners and their animals screened on free demand.Methodology/principal findingsUsing mixed effects negative binomial regression, we modelled the number of dogs screened for Leishmania infection on free demand per neighborhood from 2011 to 2016 as a function of time-dependent predictors (current or recent canine seropositivity and human VL incidence), distance to the screening site, and demographic variables. We assessed potential delays in the effect of time-dependent predictors on the outcome. Among 12,536 dogs screened for Leishmania infection, 64.2% were tested during serosurveys and 35.8% were tested on free demand. Of these, 63.9% were positive. Uptake of screening under free demand was strongly associated with higher levels of canine seropositivity in the neighborhood (current or recent) and decreasing distance to the screening site. A subsample of dog owners (n = 93) who sought CVL screening between 2016 and 2017 were interviewed in more detail. Owners with better socioeconomic status and dogs with apparent CVL clinical manifestations prevailed among them.Conclusions/significanceTo support timely CVL management, passive case detection along with awareness activities aimed at dog owners should be encouraged in endemic areas. Screening sites should be prioritized in accessible zones, as well as in socio-economically disadvantage areas. In parallel, CVL active case detection should be continued as a surveillance tool to guide control actions.

Project description:BackgroundThe VL elimination strategy requires cost-effective tools for case detection and management. This intervention study tests the yield, feasibility and cost of 4 different active case detection (ACD) strategies (camp, index case, incentive and blanket approach) in VL endemic districts of India, Nepal and Bangladesh.Methodology/principal findingsFirst, VL screening (fever more than 14 days, splenomegaly, rK39 test) was performed in camps. This was followed by house to house screening (blanket approach). An analysis of secondary VL cases in the neighborhood of index cases was simulated (index case approach). A second screening round was repeated 4-6 months later. In another sub-district in India and Nepal, health workers received incentives for detecting new VL cases over a 4 month period (incentive approach). This was followed by house screening for undetected cases. A total of 28 new VL cases were identified by blanket approach in the 1(st) screening round, and used as ACD gold standard. Of these, the camp approach identified 22 (sensitivity 78.6%), index case approach identified 12 (sensitivity--42.9%), and incentive approach identified 23 new VL cases out of 29 cases detected by the house screening (sensitivity--79.3%). The effort required to detect a new VL case varied (blanket approach--1092 households, incentive approach--978 households; index case approach--788 households had to be screened). The cost per new case detected varied (camp approach $21 - $661; index case approach $149 - $200; incentive based approach $50 - $543; blanket screening $112 - $629). The 2(nd) screening round yielded 20 new VL cases. Sixty and nine new PKDL cases were detected in the first and second round respectively.Conclusions/significanceACD in the VL elimination campaign has a high yield of new cases at programme costs which vary according to the screening method chosen. Countries need the right mix of approaches according to the epidemiological profile, affordability and organizational feasibility.

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Intervention Packages for Early Visceral Leishmaniasis Case Detection and Sandfly Control in Bangladesh: A Comparative Analysis.

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