The association between child Schistosoma spp. infections and morbidity in an irrigated rice region in Mali: A localized study.

BACKGROUND: Schistosomiasis is one of the neglected tropical diseases endemic to Mali. There has been insufficient investigation of the morbidity burden in highly endemic irrigated rice areas with the ongoing mass drug administration with praziquantel. In February 2005, a year after an initial mass drug administration in 2004, we performed the first cross-sectional survey of schistosomiasis in the Kokry-Bozo village in the Office du Niger rice irrigation region. In the fourteen years since this survey, there has been almost no research into schistosomiasis morbidity in Mali due to lack of funding. Therefore, the 2005 survey supplies near-baseline data for any future research into the treatment impacts in the area. METHODS: One hundred and ninety-four children aged 6-14 years from two schools were assessed for bladder pathology by ultrasound, and for anaemia and micro-haematuria by laboratory tests. Schistosoma eggs were examined microscopically in fresh stool and urine samples. Multivariate logistic regression analysis quantified the association of Schistosoma infections with anaemia, bladder pathology and micro-haematuria. Akaike's information criterion was used to test the assumption of linear effects of infection intensity classes and used to compare across models. RESULTS: The overall prevalence of schistosomiasis in 189 school children was 97%; 17% (33/189) had a single infection (S. mansoni,13%, or S. haematobium, 4%) and 80% (156/189) were co-infected with S. mansoni and S. haematobium. The overall prevalence of S. mansoni with light infection was 27% (53/194), moderate infection was 24% (47/194) and heavy infection was 42% (81/194). Of the 194 of children investigated for S. haematobium 59% (114/194) had light infection and 26% (50/194) had heavy infection. No hookworm eggs were detected. The level of abnormal bladder pathology was 18% (35/189) with the highest found in 10-14 year old children. The prevalence of anaemia was 91% (172/189) and was twice as likely to be associated (OR 2.0, 95% CI 1.1-3.9) with S. mansoni infections than in children without infection. As infection intensity with S. mansoni increased the risk of anaemia (OR 2.0, 95% CI 1.1-3.9) also increased. As infection intensity with S. haematobium increased bladder pathology (OR 2.4, 95%CI 1.3-4.5), haematuria (OR 6.7, 95%CI 3.3-13.6) and micro-haematuria increased (OR 2.4, 95%CI 1.3-4.5). CONCLUSION: Our research contributes an important micro-geographical assessment of the heavy burden of schistosomiasis and associated morbidity in children who live in the rice irrigation regions. Our literature review found that there has been very limited research conducted on the impact of the treatment to control morbidity in the ON. Therefore, there is a need to do a comparable, but more extensive, study to identify any changes in morbidity and to indicate current requirements for the control programme. Our results from 2005 called for routine integration of iron supplementation, food fortification and diet diversification into the deworming program.

Population genetic structure of Schistosoma mansoni and Schistosoma haematobium from across six sub-Saharan African countries: implications for epidemiology, evolution and control.

We conducted the first meta-analysis of ten Schistosoma haematobium (one published and nine unpublished) and eight Schistosoma mansoni (two published and six unpublished) microsatellite datasets collected from individual schistosome-infected school-children across six sub-Saharan Africa countries. High levels of genetic diversity were documented in both S. haematobium and S. mansoni. In S. haematobium populations, allelic richness did not differ significantly between the ten schools, despite widely varying prevalences and intensities of infection, but higher levels of heterozygote deficiency were seen in East than in West Africa. In contrast, S. mansoni populations were more diverse in East than West African schools, but heterozygosity levels did not vary significantly with geography. Genetic structure in both S. haematobium and S. mansoni populations was documented, at both a regional and continental scale. Such structuring might be expected to slow the spread to new areas of anti-schistosomal drug resistance should it develop. There was, however, limited evidence of genetic structure at the individual host level, which might be predicted to promote the development or establishment of drug resistance, particularly if it were a recessive trait. Our results are discussed in terms of their potential implications for the epidemiology and evolution of schistosomes as well as their subsequent control across sub-Saharan Africa.

Significantly reduced intensity of infection but persistent prevalence of schistosomiasis in a highly endemic region in Mali after repeated treatment.

BACKGROUND: Preventive chemotherapy against schistosomiasis has been implemented since 2005 in Mali, targeting school-age children and adults at high risk. A cross-sectional survey was conducted in 2010 to evaluate the impact of repeated treatment among school-age children in the highly-endemic region of Segou. METHODOLOGY/PRINCIPAL FINDINGS: The survey was conducted in six sentinel schools in three highly-endemic districts, and 640 school children aged 7-14 years were examined. Infections with Schistosoma haematobium and S. mansoni were diagnosed with the urine filtration and the Kato-Katz method respectively. Overall prevalence of S. haematobium infection was 61.7%, a significant reduction of 30% from the baseline in 2004 (p<0.01), while overall prevalence of S. mansoni infection was 12.7% which was not significantly different from the baseline. Overall mean intensity of S. haematobium and S. mansoni infection was 180.4 eggs/10 ml of urine and 88.2 epg in 2004 respectively. These were reduced to 33.2 eggs/10 ml of urine and 43.2 epg in 2010 respectively, a significant reduction of 81.6% and 51% (p<0.001). The proportion of heavy S. haematobium infections was reduced from 48.8% in 2004 to 13.8% in 2010, and the proportion of moderate and heavy S. mansoni infection was reduced from 15.6% in 2004 to 9.4% in 2010, both significantly (p<0.01). Mathematical modelling suggests that the observed results were in line with the expected changes. CONCLUSIONS/SIGNIFICANCE: Significant reduction in intensity of infection on both infections and modest but significant reduction in S. haematobium prevalence were achieved in highly-endemic Segou region after repeated chemotherapy. However, persistent prevalence of both infections and relatively high level of intensity of S. mansoni infection suggest that more intensified control measures be implemented in order to achieve the goal of schistosomiasis elimination. In addition, closer monitoring and evaluation activities are needed in the programme to monitor the drug tolerance and to adjust treatment focus.

Implementing preventive chemotherapy through an integrated National Neglected Tropical Disease Control Program in Mali.

BACKGROUND: Mali is endemic for all five targeted major neglected tropical diseases (NTDs). As one of the five 'fast-track' countries supported with the United States Agency for International Development (USAID) funds, Mali started to integrate the activities of existing disease-specific national control programs on these diseases in 2007. The ultimate objectives are to eliminate lymphatic filariasis, onchocerciasis and trachoma as public health problems and to reduce morbidity caused by schistosomiasis and soil-transmitted helminthiasis through regular treatment to eligible populations, and the specific objectives were to achieve 80% program coverage and 100% geographical coverage yearly. The paper reports on the implementation of the integrated mass drug administration and the lessons learned. METHODOLOGY/PRINCIPAL FINDINGS: The integrated control program was led by the Ministry of Health and coordinated by the national NTD Control Program. The drug packages were designed according to the disease endemicity in each district and delivered through various platforms to eligible populations involving the primary health care system. Treatment data were recorded and reported by the community drug distributors. After a pilot implementation of integrated drug delivery in three regions in 2007, the treatment for all five targeted NTDs was steadily scaled up to 100% geographical coverage by 2009, and program coverage has since been maintained at a high level: over 85% for lymphatic filariasis, over 90% for onchocerciasis and soil-transmitted helminthiasis, around 90% in school-age children for schistosomiasis, and 76-97% for trachoma. Around 10 million people have received one or more drug packages each year since 2009. No severe cases of adverse effects were reported. CONCLUSIONS/SIGNIFICANCE: Mali has scaled up the drug treatment to national coverage through integrated drug delivery involving the primary health care system. The successes and lessons learned in Mali can be valuable assets to other countries starting up their own integrated national NTD control programs.

The impact of single versus mixed schistosome species infections on liver, spleen and bladder morbidity within Malian children pre- and post-praziquantel treatment.

BACKGROUND: In the developing world co-infections and polyparasitism within humans appear to be the rule rather than the exception, be it any combination of inter-specific and/or inter- and intra-Genera mixed infections. Mixed infections might generate synergistic or antagonistic interactions and thereby clinically affect individuals and/or impact parasite epidemiology. METHODS: The current study uniquely assesses both Schistosoma mansoni- and Schistosoma haematobium-related morbidity of the liver and the bladder as assessed by ultrasound as well as spleen and liver morbidity through clinical exams. The impact of praziquantel (PZQ) treatment on such potential inter-specific schistosome interactions and resulting morbidity using uniquely detailed longitudinal data (pre- and one year post-PZQ treatment) arising from the National Schistosomiasis Control Program in three areas of Mali: Ségou, Koulikoro and Bamako, is also evaluated. At baseline, data were collected from up to 2196 children (aged 7-14 years), 844 of which were infected with S. haematobium only, 124 with S. mansoni only and 477 with both. Follow-up data were collected from up to 1265 children. RESULTS: Results suggested lower liver morbidity in mixed compared to single S. mansoni infections and higher bladder morbidity in mixed compared to single S. haematobium infections. Single S. haematobium or S. mansoni infections were also associated with liver and spleen morbidity whilst only single S. haematobium infections were associated with bladder morbidity in these children (light S. haematobium infection OR: 4.3, p < 0.001 and heavy S. haematobium infection OR: 19, p < 0.001). PZQ treatment contributed to the regression of some of the forms of such morbidities. CONCLUSIONS: Whilst the precise biological mechanisms for these observations remain to be ascertained, the results illustrate the importance of considering mixed species infections in any analyses of parasite-induced morbidity, including that for the proposed Disability Adjusted Life Years (DALYs) revised estimates of schistosomiasis morbidity.

A comparative study of the spatial distribution of schistosomiasis in Mali in 1984-1989 and 2004-2006.

BACKGROUND: We investigated changes in the spatial distribution of schistosomiasis in Mali following a decade of donor-funded control and a further 12 years without control. METHODOLOGY/PRINCIPAL FINDINGS: National pre-intervention cross-sectional schistosomiasis surveys were conducted in Mali in 1984-1989 (in communities) and again in 2004-2006 (in schools). Bayesian geostatistical models were built separately for each time period and on the datasets combined across time periods. In the former, data from one period were used to predict prevalence of schistosome infections for the other period, and in the latter, the models were used to determine whether spatial autocorrelation and covariate effects were consistent across periods. Schistosoma haematobium prevalence was 25.7% in 1984-1989 and 38.3% in 2004-2006; S. mansoni prevalence was 7.4% in 1984-1989 and 6.7% in 2004-2006 (note the models showed no significant difference in mean prevalence of either infection between time periods). Prevalence of both infections showed a focal spatial pattern and negative associations with distance from perennial waterbodies, which was consistent across time periods. Spatial models developed using 1984-1989 data were able to predict the distributions of both schistosome species in 2004-2006 (area under the receiver operating characteristic curve was typically >0.7) and vice versa. CONCLUSIONS/SIGNIFICANCE: A decade after the apparently successful conclusion of a donor-funded schistosomiasis control programme from 1982-1992, national prevalence of schistosomiasis had rebounded to pre-intervention levels. Clusters of schistosome infections occurred in generally the same areas accross time periods, although the precise locations varied. To achieve long-term control, it is essential to plan for sustainability of ongoing interventions, including stengthening endemic country health systems.

Use of Bayesian geostatistical prediction to estimate local variations in Schistosoma haematobium infection in western Africa.

OBJECTIVE: To predict the subnational spatial variation in the number of people infected with Schistosoma haematobium in Burkina Faso, Mali and the Niger prior to national control programmes. METHODS: We used field survey data sets covering a contiguous area 2750 x 850 km and including 26,790 school-age children (5-14 years old) in 418 schools. The prevalence of high- and low-intensity infection and associated 95% credible intervals (CrIs) were predicted using Bayesian geostatistical models. The number infected was determined from the predicted prevalence and the number of school-age children in each km(2). FINDINGS: The predicted number of school-age children with a low-intensity infection was 433,268 in Burkina Faso, 872,328 in Mali and 580 286 in the Niger. The number with a high-intensity infection was 416,009, 511,845 and 254,150 in each country, respectively. The 95% CrIs were wide: e.g. the mean number of boys aged 10-14 years infected in Mali was 140,200 (95% CrI: 6200-512,100). CONCLUSION: National aggregate estimates of infection mask important local variations:: e.g. most S. haematobium infections in the Niger occur in the Niger River valley. High-intensity infection was strongly clustered in western and central Mali, north-eastern and northwestern Burkina Faso and the Niger River valley in the Niger. Populations in these foci will carry the bulk of the urinary schistosomiasis burden and should be prioritized for schistosomiasis control. Uncertainties in the predicted prevalence and the numbers infected should be acknowledged by control programme planners.

Mapping the probability of schistosomiasis and associated uncertainty, West Africa.

We aimed to map the probability of Schistosoma haematobium infection being >50%, a threshold for annual mass praziquantel distribution. Parasitologic surveys were conducted in Burkina Faso, Mali, and Niger, 2004-2006, and predictions were made by using Bayesian geostatistical models. Clusters with >50% probability of having >50% prevalence were delineated in each country.

Assessment of ultrasound morbidity indicators of schistosomiasis in the context of large-scale programs illustrated with experiences from Malian children.

We assessed morbidity indicators for both Schistosoma haematobium and Schistosoma mansoni infections and evaluated the appropriateness of the World Health Organization (WHO) guidelines for ultrasound in schistosomiasis in the context of large-scale control interventions. Abdominal and urinary tract ultrasonography was performed on 2,247 and 2,822 school children, respectively, from 29 randomly selected schools in Mali before the implementation of mass anthelminthic drug administration. Using two-level logistic regression models, we examined associations of potential factors with the risk of having a positive ultrasound global score (morbidity indicative of S. haematobium infection), abnormal image pattern scores, dilatation of the portal vein, and/or enlarged liver (morbidity indicative of S. mansoni infection). The WHO protocol was found useful for detection of S. haematobium pathology but overestimated the risk of portal vein dilatation and left liver lobe enlargement associated with S. mansoni infection. We conclude that ultrasonography should be included in large-scale control interventions, where logistics allow, but cautiously.

Implementation of national schistosomiasis control programmes in West Africa.

Burkina Faso, Mali and Niger are countries endemic for schistosomiasis, with a high predominance of Schistosoma haematobium. With the support of the Bill and Melinda Gates Foundation through the Schistosomiasis Control Initiative, national control programmes were launched in these countries in 2004. Here, we describe the progress of implementation for each programme and the challenges for maintaining sustainability for schistosomiasis control in these countries.