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Mathematical modelling of the use of insecticide-treated nets for elimination of visceral leishmaniasis in Bihar, India.

ABSTRACT: Visceral leishmaniasis (VL) is a deadly neglected tropical disease caused by a parasite Leishmania donovani and spread by female sand flies Phlebotomus argentipes. There is conflicting evidence regarding the role of insecticide-treated nets (ITNs) on the prevention of VL. Numerous studies demonstrated the effectiveness of ITNs. However, KalaNet, a large trial in Nepal and India did not support those findings. The purpose of this paper is to gain insight into the situation by mathematical modelling. We expand a mathematical model of VL transmission based on the KalaNet trial and incorporate the use of ITNs explicitly into the model. One of the major contributions of this work is that we calibrate the model based on the available epidemiological data, generally independent of the KalaNet trial. We validate the model on data collected during the KalaNet trial. We conclude that in order to eliminate VL, the ITN usage would have to stay above 96%. This is higher than the 91% ITNs use at the end of the trial which may explain why the trial did not show a positive effect from ITNs. At the same time, our model indicates that asymptomatic individuals play a crucial role in VL transmission.

SUBMITTER: Fortunato AK

PROVIDER: S-EPMC8242840 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Mathematical modelling of the use of insecticide-treated nets for elimination of visceral leishmaniasis in Bihar, India.

Fortunato Anna K AK Glasser Casey P CP Watson Joy A JA Lu Yongjin Y Rychtář Jan J Taylor Dewey D

Royal Society open science 20210630 6

Visceral leishmaniasis (VL) is a deadly neglected tropical disease caused by a parasite <i>Leishmania donovani</i> and spread by female sand flies <i>Phlebotomus argentipes</i>. There is conflicting evidence regarding the role of insecticide-treated nets (ITNs) on the prevention of VL. Numerous studies demonstrated the effectiveness of ITNs. However, KalaNet, a large trial in Nepal and India did not support those findings. The purpose of this paper is to gain insight into the situation by mathem ...[more]

PMID: 34234949

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Project description:Background: Visceral leishmaniasis (VL) is a vector-borne disease of public health importance in India, with the highest burden of disease in the states of Bihar, Jharkhand, West Bengal and Uttar Pradesh. The disease is currently targeted for elimination (annual incidence to less than one per 10,000 population) using indoor residual spraying, active case detection and treatment. Historically the disease trend in India has been regarded as cyclical with case resurgence characteristically occurring every 15 years. Understanding this pattern is essential if the VL elimination gains are to be sustained. To better understand the cyclical trends, annual climatic indicators including rainfall, temperature and humidity over time were compared with annual VL case incidence data. Methods: Annual climate data (rainfall, average and maximum temperature and specific humidity) from 1956-2004 were used to identify potential factors influencing VL incidence. Months relevant to the VL life-cycle were identified and defined (Monsoon, Sand-fly Peak, Pre-Sand-fly Peak and Annual) for analysis. The Kruskall-Wallis test was used to determine significant difference between categorical rainfall and VL incidence, whilst univariate negative binomial regression models were used to determine predictors of disease incidence. Results: The negative binomial regression model showed statistically significant associations (p <0.05) for VL incidence and maximum temperature, and average temperature, when considering annual and pre-sand fly peak time periods. No other associations between humidity, rainfall or temperature and VL incidence were detected (all values p >0.05). Conclusion: The VL programme in Bihar has made significant progress in adopting best practices for improved treatment and vector control, with the aim to achieve VL elimination. However, open access granular programme data for indoor residual spray activities and case detection is required to fully understand the role of climate in disease transmission and potential resurgence.

Project description:Visceral leishmaniasis (VL) has been targeted for elimination from Southeast Asia (SEA). The disease has been endemic in SEA, and in other parts of the world involving both humans and animals. One of the key strategies for combating VL is controlling for the vector sandfly. There are a few vector control strategies that are currently in practice. We sought to assess the efficacy and community effectiveness of insecticide treated nets (ITNs) in controlling the burden of sandfly and the occurrence of VL among humans. We conducted a systematic review following a study protocol and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. 6331 initial hits were retrieved from Google Scholar, Lilacs, PubMed, Science Direct, WHOlis, WHOiris and PAHOiris. 25 met the full inclusion criteria. Findings show that the insecticide impregnated bednets and the commercially treated long lasting insecticidal nets (LLINs) are effective in controlling sandflies, with mortalities as high as 75% lasting over a year; although their role in controlling VL in the community was not extensively studied, since effectiveness was usually measured with sandflies densities. Findings also show that insecticide impregnated bednets are low cost and well accepted in the community, however, early erosion of insecticides from nets could occur. Some studies also showed that killing of sandflies may not translate into reduction of VL, therefore sandfly knock down and killing data needs to be interpreted with caution. Conclusions of this review are (1) combining insecticide impregnated bednets, as targeted interventions, with another vector control measure, particularly indoor residual spraying, and in conjunction with case detection, could be the way forward to controlling VL in resource limited settings. (2) Given the current low incidence of VL in SEA, it can be difficult to further research the community effectiveness of those control measures in reducing VL.

Project description:Molecular surveillance of resistance is an increasingly important part of vector borne disease control programmes that utilise insecticides. The visceral leishmaniasis (VL) elimination programme in India uses indoor residual spraying (IRS) with the pyrethroid, alpha-cypermethrin to control Phlebotomus argentipes the vector of Leishmania donovani, the causative agent of VL. Prior long-term use of DDT may have selected for knockdown resistance (kdr) mutants (1014F and S) at the shared DDT and pyrethroid target site, which are common in India and can also cause pyrethroid cross-resistance. We monitored the frequency of these marker mutations over five years from 2017-2021 in sentinel sites in eight districts of north-eastern India covered by IRS. Frequencies varied markedly among the districts, though finer scale variation, among villages within districts, was limited. A pronounced and highly significant increase in resistance-associated genotypes occurred between 2017 and 2018, but with relative stability thereafter, and some reversion toward more susceptible genotypes in 2021. Analyses linked IRS with mutant frequencies suggesting an advantage to more resistant genotypes, especially when pyrethroid was under-sprayed in IRS. However, this advantage did not translate into sustained allele frequency changes over the study period, potentially because of a relatively greater net advantage under field conditions for a wild-type/mutant genotype than projected from laboratory studies and/or high costs of the most resistant genotype. Further work is required to improve calibration of each 1014 genotype with resistance, preferably using operationally relevant measures. The lack of change in resistance mechanism over the span of the study period, coupled with available bioassay data suggesting susceptibility, suggests that resistance has yet to emerge despite intensive IRS. Nevertheless, the advantage of resistance-associated genotypes with IRS and under spraying, suggest that measures to continue monitoring and improvement of spray quality are vital, and consideration of future alternatives to pyrethroids for IRS would be advisable.

Project description:BackgroundDespite the overall decrease in visceral leishmaniasis (VL) incidence on the Indian subcontinent, there remain spatiotemporal clusters or 'hotspots' of new cases. The characteristics of these hotspots, underlying transmission dynamics, and their importance for shaping control strategies are not yet fully understood and are investigated in this study for a VL endemic area of ~100,000 inhabitants in Bihar, India between 2007-2015.Methodology/principal findingsVL incidence (cases/10,000/year) dropped from 12.3 in 2007 to 0.9 in 2015, which is just below the World Health Organizations' threshold for elimination as a public health problem. Clustering of VL was assessed between subvillages (hamlets), using multiple geospatial and (spatio)temporal autocorrelation and hotspot analyses. One to three hotspots were identified each year, often persisting for 1-5 successive years with a modal radius of ~500m. The relative risk of having VL was 5-86 times higher for inhabitants of hotspots, compared to those living outside hotspots. Hotspots harbour significantly more households from the two lowest asset quintiles (as proxy for socio-economic status). Overall, children and young adelescents (5-14 years) have the highest risk for VL, but within hotspots and at the start of outbreaks, older age groups (35+ years) show a comparable high risk.Conclusions/significanceThis study demonstrates significant spatiotemporal heterogeneity in VL incidence at subdistrict level. The association between poverty and hotspots confirms that VL is a disease of 'the poorest of the poor' and age patterns suggest a potential role of waning immunity as underlying driver of hotspots. The recommended insecticide spraying radius of 500m around detected VL cases corresponds to the modal hotspot radius found in this study. Additional data on immunity and asymptomatic infection, and the development of spatiotemporally explicit transmission models that simulate hotspot dynamics and predict the impact of interventions at the smaller geographical scale will be crucial tools in sustaining elimination.

Project description:BackgroundVisceral leishmaniasis (VL) has been targeted by the WHO for elimination as a public health problem (< 1 case/10,000 people/year) in the Indian sub-continent (ISC) by 2020. Bihar State in India, which accounts for the majority of cases in the ISC, remains a major target for this elimination effort. However, there is considerable spatial, temporal and sub-population variation in occurrence of the disease and the pathway to care, which is largely unexplored and a threat to achieving the target.MethodsData from 6081 suspected VL patients who reported being clinically diagnosed during 2012-2013 across eight districts in Bihar were analysed. Graphical comparisons and Chi-square tests were used to determine differences in the burden of identified cases by season, district, age and sex. Log-linear regression models were fitted to onset (of symptoms)-to-diagnosis and onset-to-treatment waiting times to estimate their associations with age, sex, district and various socio-economic factors (SEFs). Logistic regression models were used to identify factors associated with mortality.ResultsComparisons of VL caseloads suggested an annual cycle peaking in January-March. A 17-fold variation in the burden of identified cases across districts and under-representation of young children (0-5 years) relative to age-specific populations in Bihar were observed. Women accounted for a significantly lower proportion of the reported cases than men (41 vs 59%, P < 0.0001). Age, district of residence, house wall materials, caste, treatment cost, travelling for diagnosis and the number of treatments for symptoms before diagnosis were identified as correlates of waiting times. Mortality was associated with age, district of residence, onset-to-treatment waiting time, treatment duration, cattle ownership and cost of diagnosis.ConclusionsThe distribution of VL in Bihar is highly heterogeneous, and reported caseloads and associated mortality vary significantly across different districts, posing different challenges to the elimination campaign. Socio-economic factors are important correlates of these differences, suggesting that elimination will require tailoring to population and sub-population circumstances.

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Mathematical modelling of the use of insecticide-treated nets for elimination of visceral leishmaniasis in Bihar, India.

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Mathematical modelling of the use of insecticide-treated nets for elimination of visceral leishmaniasis in Bihar, India.

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