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A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control.

ABSTRACT: Models that accurately estimate the age-specific infection prevalence of Schistosoma mansoni can be useful for schistosomiasis control programmes, particularly with regard to whether mass drug administration or selected treatment should be employed. We developed a Bayesian formulation of an immigration-death model that has been previously proposed, which used maximum likelihood inference for estimating the age-specific S. mansoni prevalence in a dataset from Egypt. For comparative purposes, we first applied the Bayesian formulation of the immigration-death model to the dataset from Egypt. We further analysed data obtained from a cross-sectional parasitological survey that determined the infection prevalence of S. mansoni among 447 individuals in a village in Côte d'Ivoire. Three consecutive stool samples were collected from each participant and analysed by the Kato-Katz technique. In the Côte d'Ivoire study, the observed S. mansoni infection prevalence was 41.6% and varied with age. The immigration-death model was able to correctly predict 50% of the observed age group-specific point prevalences. The model presented here can be utilized to estimate S. mansoni community infection prevalences, which in turn helps in the strategic planning of schistosomiasis control.

SUBMITTER: Raso G

PROVIDER: S-EPMC2756495 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control.

Raso Giovanna G Vounatsou Penelope P McManus Donald P DP N'Goran Eliézer K EK Utzinger Jürg J

International journal for parasitology 20070521 13

Models that accurately estimate the age-specific infection prevalence of Schistosoma mansoni can be useful for schistosomiasis control programmes, particularly with regard to whether mass drug administration or selected treatment should be employed. We developed a Bayesian formulation of an immigration-death model that has been previously proposed, which used maximum likelihood inference for estimating the age-specific S. mansoni prevalence in a dataset from Egypt. For comparative purposes, we f ...[more]

PMID: 17583713

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Project description:BackgroundSchistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite's biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite's life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts.Methodology/principal findingsWe used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics.Conclusions/significanceWe describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection).

Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs. The perfused adult female worms were incubated with cold RNAlater solution (Ambion) and kept at 4 0C until RNA extraction. Total RNA was extracted using Trizol reagent (Invitrogen) according to the manufacture's instructions. RNA was quantified using Nanodrop ND-1000 UV/Vis spectrophotometer and its quality was assured with Agilent 2100 Bioanalyzer, a micro fluidics-based electrophoresis platform. 1 Î¼g total RNA from each sample was amplified using the T7-RNA polymerase based SuperScript Indirect RNA amplification system (Invitrogen) and subsequently 3 Î¼g of aminoallyl-modified amplified RNA was labeled using Cy3 or Cy5 by indirect labeling (General Electric). Amplification and labeling were done according to manufacturer specifications. The Cy3 and Cy5 labeled samples were then combined, dried and re-suspended in hybridization buffer (50 % formamide, 25 % RNase free water and 25 % Microarray Hybridization buffer 4x) (General Electric). Pools of RNA from worms treated with QN were hybridized against RNA from control worms. In order to ensure the uniformity of data, all experiments were performed using slides from the same printing batch and dyes from the same lot. The same washing protocol was used and immediately after washing we scanned the slides using the same parameters. Technical and biological replicates were performed. Dye swap was employed in order to account for dye biases. A total of eight different replicated data values were obtained for each probe on the array. The samples were hybridized overnight to cDNA microarray slides containing 4,000 elements in duplicate (GEO accession: GPL3929) using ASP hybridization chambers (GE, USA) at 42 Â°C. Slides were washed once for 3 minutes in low stringency wash solution at 45 Â°C (1 x SSC + 0.2 % SDS), followed by one wash for 5 minutes in medium stringency wash solution (0.1 x SSC + 0.2%SDS) and one wash of 1 minute in high stringency wash solution (0.1 x SSC). Moreover, slides were air dried and scanned using a microarray dual channel laser scanner (GenePix 4000B, Molecular Devices, USA) at 5 Î¼m resolution, 100 % laser power and PMT levels were adjusted in order to obtain similar average intensities of red and green signal. Data were extracted using Array Vision 8.0 program. To correct for systematic biases on the data originated from small differences in the labeling and/or detection efficiencies between the fluorescent dyes, expression ratios were logged (base 2) and normalized using a locally weighted linear regression (LOWESS) algorithm [60]. Normalized log2 (ratios) were further analyzed with the Significance Analysis of Microarrays tool (SAM) [61] using a 0.1 % false discovery rate (FDR) to find differentially expressed genes. The genes identified in the previous step were filtered using a 1.7 fold change cut-off in at least 4 out of the 8 data points. This step is critical in identifying more biological relevant changes. It is important to stress that the fold change filter was used after the identification of differentially expressed genes, and our results are not influenced by the potentially misleading effects caused by the use of arbitrary thresholds to trim data sets before significance testing .

Dataset Information

A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control.

Publications

A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control.

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