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A spatio-temporal approach to short-term prediction of visceral leishmaniasis diagnoses in India.

ABSTRACT: BACKGROUND:The elimination programme for visceral leishmaniasis (VL) in India has seen great progress, with total cases decreasing by over 80% since 2010 and many blocks now reporting zero cases from year to year. Prompt diagnosis and treatment is critical to continue progress and avoid epidemics in the increasingly susceptible population. Short-term forecasts could be used to highlight anomalies in incidence and support health service logistics. The model which best fits the data is not necessarily most useful for prediction, yet little empirical work has been done to investigate the balance between fit and predictive performance. METHODOLOGY/PRINCIPAL FINDINGS:We developed statistical models of monthly VL case counts at block level. By evaluating a set of randomly-generated models, we found that fit and one-month-ahead prediction were strongly correlated and that rolling updates to model parameters as data accrued were not crucial for accurate prediction. The final model incorporated auto-regression over four months, spatial correlation between neighbouring blocks, and seasonality. Ninety-four percent of 10-90% prediction intervals from this model captured the observed count during a 24-month test period. Comparison of one-, three- and four-month-ahead predictions from the final model fit demonstrated that a longer time horizon yielded only a small sacrifice in predictive power for the vast majority of blocks. CONCLUSIONS/SIGNIFICANCE:The model developed is informed by routinely-collected surveillance data as it accumulates, and predictions are sufficiently accurate and precise to be useful. Such forecasts could, for example, be used to guide stock requirements for rapid diagnostic tests and drugs. More comprehensive data on factors thought to influence geographic variation in VL burden could be incorporated, and might better explain the heterogeneity between blocks and improve uniformity of predictive performance. Integration of the approach in the management of the VL programme would be an important step to ensuring continued successful control.

SUBMITTER: Nightingale ES

PROVIDER: S-EPMC7373294 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A spatio-temporal approach to short-term prediction of visceral leishmaniasis diagnoses in India.

Nightingale Emily S ES Chapman Lloyd A C LAC Srikantiah Sridhar S Subramanian Swaminathan S Jambulingam Purushothaman P Bracher Johannes J Cameron Mary M MM Medley Graham F GF

PLoS neglected tropical diseases 20200709 7

<h4>Background</h4>The elimination programme for visceral leishmaniasis (VL) in India has seen great progress, with total cases decreasing by over 80% since 2010 and many blocks now reporting zero cases from year to year. Prompt diagnosis and treatment is critical to continue progress and avoid epidemics in the increasingly susceptible population. Short-term forecasts could be used to highlight anomalies in incidence and support health service logistics. The model which best fits the data is not ...[more]

PMID: 32644989

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Project description:With several decades of concerted control efforts, visceral leishmaniasis(VL) eradication had almost been achieved in China. However, VL cases continue to be detected in parts of western China recent years. Using data of reported cases, this study aimed to investigate the epidemiology and spatio⁃temporal distribution, of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in China between the years 2015 and 2019. Epidemiological data pertaining to patients with visceral leishmaniasis (VL) were collected in Gansu, Shaanxi, Sichuan, Shanxi, Henan and Hebei provinces between the years 2015 and 2019. Joinpoint regression analysis was performed to determine changes in the epidemic trend of MT-ZVL within the time period during which data was collected. Spatial autocorrelation of infection was examined using the Global Moran's I statistic wand hotspot analysis was carried out using the Getis-Ord Gi* statistic. Spatio-temporal clustering analysis was conducted using the retrospective space-time permutation flexible spatial scanning statistics. A total of 529 cases of MT-ZVL were detected in the six provinces from which data were collected during the study time period, predominantly in Gansu (55.0%), Shanxi (21.7%), Shaanxi (12.5%) and Sichuan (8.9%) provinces. A decline in VL incidence in China was observed during the study period, whereas an increase in MT-ZVL incidence was observed in the six provinces from which data was obtained (t = 4.87, P < 0.05), with highest incidence in Shanxi province (t = 16.91, P < 0.05). Significant differences in the Moran's I statistic were observed during study time period (P < 0.05), indicating spatial autocorrelation in the spatial distribution of MT-ZVL. Hotspot and spatial autocorrelation analysis revealed clustering of infection cases in the Shaanxi-Shanxi border areas and in east of Shanxi province, where transmission increased rapidly over the study duration, as well as in well know high transmission areas in the south of Gansu province and the north of the Sichuan province. It indicates resurgence of MT-ZVL transmission over the latter three years of the study. Spatial clustering of infection was observed in localized areas, as well as sporadic outbreaks of infection.

Project description:In this study we set out to determine whole blood transcriptional profiles that might distinguish asymptomatic infection with Leishmania donovani from active disease, as well as to monitor the changes in transcriptional profiles that accompanied drug treatment. Amphotericin B provides improved therapy for visceral leishmaniasis (VL) caused by Leishmania donovani, with single dose liposomal-encapsulated Ambisome providing the best cure rates. The VL elimination program aims to reduce the incidence rate in the Indian subcontinent to <1/10,000 population/year. Ability to predict which asymptomatic individuals (e.g. anti-leishmanial IgG and/or Leishmania-specific modified Quantiferon positive) will progress to clinical VL would help in monitoring disease outbreaks. Here we examined whole blood transcriptional profiles associated with asymptomatic infection, active disease, and in treated cases. Two independent microarray experiments were performed, with analysis focussed primarily on differentially expressed genes (DEGs) concordant across both experiments. No DEGs were identified for IgG or Quantiferon positive asymptomatic groups compared to negative healthy endemic controls. We therefore concentrated on comparing concordant DEGs from active cases with all healthy controls, and in examining differences in the transcriptome following different regimens of drug treatment. In these comparisons 6 major themes emerged: (i) expression of genes and enrichment of gene sets associated with erythrocyte function in active cases; (ii) strong evidence for enrichment of gene sets involved in cell cycle in comparing active cases with healthy controls; (iii) identification of IFNG encoding interferon- as the major hub gene in concordant gene expression patterns across experiments comparing active cases with healthy controls or with treated cases; (iv) enrichment for interleukin signalling (IL-1/3/4/6/7/8) and a prominent role for CXCL10/9/11 and chemokine signalling pathways in comparing active cases with treated cases; (v) the novel identification of Aryl Hydrocarbon Receptor signalling as a significant canonical pathway when comparing active cases with healthy controls, and to a lesser extent with treated cases; and (vi) global expression profiling support for more effective cure at day 30 post-treatment with a single dose of liposomal encapsulated amphotericin B compared to multi-dose non-liposomal amphotericin B treatment over 30 days.

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A spatio-temporal approach to short-term prediction of visceral leishmaniasis diagnoses in India.

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A spatio-temporal approach to short-term prediction of visceral leishmaniasis diagnoses in India.

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