Age and gender effects in self-reported urinary schistosomiasis in Tanzania.

OBJECTIVES: To characterize age-gender prevalence profiles of urinary schistosomiasis according to the questionnaire responses, compare the profiles to field survey data from selected regions, and determine if the profiles varied spatially throughout Tanzania. METHODS: In 2004, a national school-based questionnaire survey for self-reported schistosomiasis and blood in urine (BIU) was conducted in all regions of mainland Tanzania, to assist targeted mass distribution of praziquantel. Field survey data were collected in six north-western and five coastal regions using microscopic examination of urine samples for the presence of Schistosoma haematobium eggs and assessment of micro-haematuria with chemical reagent strips. Bayesian logistic regression models were created to calculate age-gender profiles adjusted for demographic and ecological covariates and spatial correlation in the questionnaire data. Separate odds ratios (OR) for age-gender effects were calculated in each administrative area. RESULTS: Data were obtained from > 2.5 million schoolchildren. Boys had higher prevalence of self-reported schistosomiasis and BIU than girls. In boys, prevalence according to the questionnaire and field surveys followed similar age profiles. However, in girls, prevalence according to the field surveys increased in older age groups, but flattened out or decreased according to the questionnaire, indicating the latter underestimated prevalence in older girls. In the models, little spatial correlation was evident in the OR for the age-gender effects, suggesting that these did not vary spatially. CONCLUSION: Age-gender patterns of urinary schistosomiasis were consistent in different geographical areas of Tanzania. Because the questionnaire underestimated prevalence in older girls, we propose that upward calibration of observed prevalence is done for older females only.

Schistosoma mansoni in pregnancy and associations with anaemia in northwest Tanzania.

Schistosomiasis among pregnant women has been inadequately investigated. In order to determine the importance of Schistosoma mansoni in this subgroup, we conducted a cross-sectional survey of 972 women in Tanzania and investigated the prevalence of Schistosoma mansoni, hookworm and malaria and their associations with anaemia. Overall, 63.5% of women were infected with S. mansoni, with prevalence highest among younger women and decreasing with increasing age. The prevalence of hookworm was 56.3%, and 16.4% of women had malaria parasitaemia. Overall, 66.4% of women were anaemic. Increased risk of anaemia was associated with heavy infection with S. mansoni but not hookworm or Plasmodium falciparum parasitaemia.

First report of a natural hybrid between Schistosoma mansoni and S. rodhaini.

Experimental crosses between Schistosoma mansoni and S. rodhaini have shown that hybrid offspring are viable, yet, until now, no naturally occurring hybrid has been identified. A collection of freshwater snails from Nyamlebi-Ngoma, Ukerewe Island, Lake Victoria, Tanzania, yielded a mixed infection within a single Biomphalaria sudanica of S. mansoni females and S. mansoni-S. rodhaini hybrid males. The hybrids were identified using deoxyribonucleic acid (DNA) sequences. Mitochondrial DNA 16S and 12S sequences of the hybrids match those of S. mansoni, whereas their nuclear ribosomal DNA ITS1 and ITS2 sequences match those of S. rodhaini. The identification of hybrids in Tanzania highlights the possibility that the genetic identity of either parasite species might be modified by introgression.

Pre- and post-intervention perceptions and water contact behaviour related to schistosomiasis in north-western Tanzania.

Schistosomiasis is a widespread disease of public health importance in Tanzania requiring concerted efforts to control it. A study on schistosomiasis-related perceptions and water contact behaviour was undertaken in one community population of Hamuyebe village in Ukerewe district, north-western Tanzania, where intestinal schistosomiasis is endemic before and 2 years after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention. Data were obtained from baseline and post-intervention knowledge, attitudes and practices (KAP) questionnaire surveys conducted between 2008 and 2010 among 157 individuals aged 15 years and above. The surveys were further complemented by structured observations of human-water contact activities. We found significant increases in respondents' knowledge of the cause, transmission, symptoms and health consequences of schistosomiasis after the intervention. The reported treatment seeking and preventive practices were congruous with the actual (observed) behaviour. Frequency, duration and timing of water contacts also decreased significantly after the intervention and took into consideration the fact that those activities which need larger body surface exposure, for a long period and at an appropriate time when cercarial densities are high (i.e. around noon) are important for the transmission of schistosomiasis. We conclude that PHAST intervention has succeeded in effecting positive changes in peoples' perceptions and attitudes towards water. As a result, knowledge obtained from the said intervention was translated into actions to prevent schistosomiasis. Studies on knowledge, attitudes and practices coupled with structured observations should be part of the integrated approach for the control of schistosomiasis.

Dynamics of people's socio-economic status in the face of schistosomiasis control interventions in Ukerewe district, Tanzania.

There is a paucity of research on micro-level assessment of the dynamics of socio-economic status following health interventions. The use of household asset data to determine wealth indices is a common procedure for estimating socio-economic position in low-income countries. Indeed, in such settings information about income is usually lacking and the collection of individual consumption or expenditure data would require in-depth interviews, posing a considerable risk of bias. In this study, we determined the socio-economic status of 159 households in a village in north-western Tanzania before and 1 year after participatory hygiene and sanitation transformation (PHAST) intervention to control schistosomiasis. We constructed a household 'wealth index' based on durable assets ownership (e.g. bicycle and radio) and household characteristics dealing with ownership of land and house construction features (e.g. type of walls and roof). We employed principal components analysis and classified households into wealth quintiles. The study revealed that asset variables with positive factor scores were associated with higher socio-economic status, whereas asset variables with negative factor scores were associated with lower socio-economic status. Overall, households which were rated as the poorest and very poor were on the decrease, whereas those rated as poor, less poor and the least poor were on the increase after PHAST intervention. This decrease/increase was significant. The median shifted from -0.761 to -0.448, and the mean from -0.204 (standard deviation (SD) 1.924) to 0.193 (SD 2.079) between pre- and post-intervention phases. The difference in socio-economic status of the people comparing the pre- and post-intervention phases was highly statistically significant (p<0.001). This observation was confirmed by a multinomial model with a random effect on the households. We argue that significant changes in the socio-economic status observed in our study are attributable to the PHAST intervention, despite other sporadic interventions against schistosomiasis.

Reductions in genetic diversity of Schistosoma mansoni populations under chemotherapeutic pressure: the effect of sampling approach and parasite population definition.

Detecting potential changes in genetic diversity in schistosome populations following chemotherapy with praziquantel (PZQ) is crucial if we are to fully understand the impact of such chemotherapy with respect to the potential emergence of resistance and/or other evolutionary outcomes of interventions. Doing so by implementing effective, and cost-efficient sampling protocols will help to optimise time and financial resources, particularly relevant to a disease such as schistosomiasis currently reliant on a single available drug. Here we explore the effect on measures of parasite genetic diversity of applying various field sampling approaches, both in terms of the number of (human) hosts sampled and the number of transmission stages (miracidia) sampled per host for a Schistosoma mansoni population in Tanzania pre- and post-treatment with PZQ. In addition, we explore population structuring within and between hosts by comparing the estimates of genetic diversity obtained assuming a 'component population' approach with those using an 'infrapopulation' approach. We found that increasing the number of hosts sampled, rather than the number of miracidia per host, gives more robust estimates of genetic diversity. We also found statistically significant population structuring (using Wright's F-statistics) and significant differences in the measures of genetic diversity depending on the parasite population definition. The relative advantages, disadvantages and, hence, subsequent reliability of these metrics for parasites with complex life-cycles are discussed, both for the specific epidemiological and ecological scenario under study here and for their future application to other areas and schistosome species.

DNA 'barcoding' of Schistosoma mansoni across sub-Saharan Africa supports substantial within locality diversity and geographical separation of genotypes.

Schistosoma mansoni is a widespread human helminth and causes intestinal schistosomiasis in 54 countries, mainly across Africa but also in Madagascar, the Arabian Peninsula and the neotropics. The geographical range of this parasite relies on the distribution of certain species of freshwater pulmonate snails of the genus Biomphalaria. Whilst S. mansoni is known to exhibit high population diversity the true extent of this diversity is still to be fully elucidated as sampling of this taxon progressively accrues. Here a DNA 'barcoding' approach is taken using sequence analysis of a 450bp region within the mitochondrial cox1 gene to assess the genetic diversity within a large number of S. mansoni larval stages collected from their natural human hosts across sub-Saharan Africa. Five hundred and sixty one individual parasite samples were examined from 22 localities and 14 countries. Considerable within-species diversity was found with 120 unique haplotypes splitting geographically into five discrete lineages. The highest diversity was found in East Africa with samples forming three of the five lineages. Less diversity was found in the Far and Central Western regions of Africa with haplotypes from the New World showing a close affinity to the Far Western African S. mansoni populations supporting the hypothesis of a colonisation of South America via the West African slave trade. The data are discussed in relation to parasite diversity and disease epidemiology.

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.

A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil.

BACKGROUND: Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. METHODOLOGY/PRINCIPAL FINDINGS: Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n  =  428) or 60 mg/kg (n  =  428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR  =  0.78, 95% CI  = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). CONCLUSION: A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries.

Genetic consequences of mass human chemotherapy for Schistosoma mansoni: population structure pre- and post-praziquantel treatment in Tanzania.

Recent shifts in global health policy have led to the implementation of mass drug administration (MDA) for neglected tropical diseases. Here we show how population genetic analyses can provide vital insights into the impact of such MDA on endemic parasite populations. We show that even a single round of MDA produced a genetic bottleneck with reductions in a range of measures of genetic diversity of Schistosoma mansoni. Phylogenetic analyses and indices of population differentiation indicated that schistosomes collected in the same schools in different years were more dissimilar than those from different schools collected within either of the study's 2 years, in addition to distinguishing re-infection from non-clearance (that might indicate putatively resistant parasites) from within those children infected at both baseline and follow-up. Such unique results illustrate the importance of genetic monitoring and examination of long lived multi-cellular parasites such as these under novel or increased chemotherapeutic selective pressures.

Bayesian spatial analysis and disease mapping: tools to enhance planning and implementation of a schistosomiasis control programme in Tanzania.

OBJECTIVE: To predict the spatial distributions of Schistosoma haematobium and S. mansoni infections to assist planning the implementation of mass distribution of praziquantel as part of an on-going national control programme in Tanzania. METHODS: Bayesian geostatistical models were developed using parasitological data from 143 schools. RESULTS: In the S. haematobium models, although land surface temperature and rainfall were significant predictors of prevalence, they became non-significant when spatial correlation was taken into account. In the S. mansoni models, distance to water bodies and annual minimum temperature were significant predictors, even when adjusting for spatial correlation. Spatial correlation occurred over greater distances for S. haematobium than for S. mansoni. Uncertainties in predictions were examined to identify areas requiring further data collection before programme implementation. CONCLUSION: Bayesian geostatistical analysis is a powerful and statistically robust tool for identifying high prevalence areas in a heterogeneous and imperfectly known environment.

Origin and diversification of the human parasite Schistosoma mansoni.

Schistosoma mansoni is the most widespread of the human-infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult-stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasite's geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within-species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30-0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country.