Lynsey Blair

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.

Do Hosts and Parasites Coevolve? Empirical Support from the Schistosoma System

Coevolution between host and parasite is, in principle, a powerful determinant of the biology and genetics of infection and disease. However, coevolution is difficult to demonstrate rigorously in practice and therefore has rarely been observed empirically, particularly in animal‐parasite systems. Research on host‐schistosome interactions has the potential for making an important contribution to the study of coevolution or reciprocal adaptation. This may be particularly pertinent because schistosomes represent an indirectly transmitted macroparasite, so often overlooked among both theoretical and empirical studies. Here we present ideas and experiments on host‐schistosome interactions, in part reviewed from published work but focusing in particular on preliminary novel data from our ongoing studies of potential host‐schistosome evolution and coevolution in the laboratory. The article is split into three main sections: we first focus on the evidence for evolution in the host, then in the parasite, before combining both to illustrate the gathering evidence of host‐parasite coevolution in the snail‐schistosome system. In particular, we demonstrate that genetic architecture, variability, and selective pressures are present for the evolution of resistance and susceptibility, virulence, and infectivity to occur, the mechanisms allowing such polymorphisms to be maintained, and that hosts and parasites appear to have reciprocal effects on each other’s phenotype and genotype.

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 studys 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.

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial

Background Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. Methodology In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. Principal Findings The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0–19.7%) and 2.7% (range: 0–26.5%) in Unguja, and 8.9% (range: 0–31.8%) and 5.5% (range: 0–23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03–2.03). Decreasing adult age (OR: 1.04; CI: 1.02–1.06), being born in Pemba (OR: 1.48; CI: 1.02–2.13) or Tanzania (OR: 2.36; CI: 1.16–4.78), and use of freshwater (OR: 2.15; CI: 1.53–3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. Conclusions/Significance The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved.

Parasitological and malacological surveys reveal urogenital schistosomiasis on Mafia Island, Tanzania to be an imported infection.

To confirm the local endemicity of Schistosoma haematobium on Mafia Island, Tanzania, conjoint parasitological and malacological surveys were undertaken in July 2006 with parasitological investigations supplemented with case-history questionnaires. A total of 238 children (125 girls and 113 boys, mean age of 13.9 years) across 9 primary schools were examined. The prevalence of micro-haematuria and egg-patent infection was 18.1% (CI95=9.6-33.6) and 4.2% (CI95=1.9-7.6), respectively but a strong female bias was observed for micro-haematuria (5.6F:1M) contrasting with a strong male bias for the presence of eggs (1F:4M). All egg-patent infections were of light-intensity (<10eggs/10ml). No clear associations between infection prevalence and local water-contact, by school, were found and all 10 of the egg-positive children had a travel history to the nearby mainland or Zanzibar. Inspection of community diagnostic registers at Kilindoni Hospital revealed a low proportion (<2%) of egg-patent infection for 20,306 samples tested in the 2000-2005 period. A total of 43 freshwater sites, a third of which were previously sampled in 1999 and 2002, were surveyed and 11 species of freshwater mollusc were found. Four species of Bulinus (B. nasutus, B. forskalii, B. barthi and B. sp.) were encountered across 13 sites with B. nasutus restricted to 3 of these towards the north of the island. No collected snail was observed to shed schistosome cercariae. Further characterisation of B. nasutus and S. haematobium included infection challenge on two occasions, with miracidia obtained from egg-patent children from Mafia and Unguja islands as well as DNA barcoding of snails and schistosomes. B. nasutus was shown refractory to infection. With the substantial travel to and from Mafia, the refractory nature of local snails and evidence from DNA barcoding in schistosomes and snails, we conclude that urogenital schistosomiasis is an imported infection.

Estimation of changes in the force of infection for intestinal and urogenital schistosomiasis in countries with Schistosomiasis Control Initiative-assisted programmes

BackgroundThe last decade has seen an expansion of national schistosomiasis control programmes in Africa based on large-scale preventative chemotherapy. In many areas this has resulted in considerable reductions in infection and morbidity levels in treated individuals. In this paper, we quantify changes in the force of infection (FOI), defined here as the per (human) host parasite establishment rate, to ascertain the impact on transmission of some of these programmes under the umbrella of the Schistosomiasis Control Initiative (SCI).MethodsA previous model for the transmission dynamics of Schistosoma mansoni was adapted here to S. haematobium. These models were fitted to longitudinal cohort (infection intensity) monitoring and evaluation data. Changes in the FOI following up to three annual rounds of praziquantel were estimated for Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia in sub-Saharan Africa (SSA) according to country, baseline endemicity and schistosome species. Since schistosomiasis transmission is known to be highly focal, changes in the FOI at a finer geographical scale (that of sentinel site) were also estimated for S. mansoni in Uganda.ResultsSubstantial and statistically significant reductions in the FOI relative to baseline were recorded in the majority of, but not all, combinations of country, parasite species, and endemicity areas. At the finer geographical scale assessed within Uganda, marked heterogeneity in the magnitude and direction of the relative changes in FOI was observed that would not have been appreciated by a coarser-scale analysis.ConclusionsReductions in the rate at which humans acquire schistosomes have been achieved in many areas of SSA countries assisted by the SCI, while challenges in effectively reducing transmission persist in others. Understanding the underlying heterogeneity in the impact and performance of the control intervention at the level of the transmission site will become increasingly important for programmes transitioning from morbidity reduction to elimination of infection. Such analyses will require a fine-scale approach. The lack of association found between programmatic variables, such as therapeutic treatment coverage (recorded at district level) and changes in FOI (at sentinel site level) is discussed and recommendations are made.

Mass drug administration with praziquantel reduces the prevalence of Schistosoma mansoni and improves liver morbidity in untreated preschool children

BACKGROUND The aim of this study was to investigate the effects of mass drug administration on Schistosoma mansoni prevalence and associated liver morbidity in treated school-aged children and untreated preschool children. METHODS In April 2008, parasitological (using the Kato-Katz method) and morbidity (determined by portal vein score) data were collected from 263 schoolchildren aged 6 and 7 years. The children had never received praziquantel. In March 2010, following two annual rounds of mass drug administration, 207 children aged 8 and 9 years old were examined to determine the effect of treatment. In addition, 158 untreated 6-year-olds were assessed to compare with the untreated children from 2008. RESULTS Treatment significantly decreased the prevalence of S. mansoni and associated morbidity in the treated groups. The untreated preschool children also showed a significant decrease in the prevalence of S. mansoni, from 21.1% (2008) to 6.3% (2010) (p<0.001). The percentage of untreated schoolchildren with a normal portal vein score increased significantly from 57.8% (2008) to 70.3% (2010) (p=0.029). CONCLUSION The significantly lower rates of S. mansoni and the decreased liver morbidity in untreated preschool children in 2010 suggest decreased environmental transmission rates and improved liver morbidity in untreated children following several rounds of mass drug administration.