The long road to schistosomiasis elimination in Zanzibar: A systematic review covering 100 years of research, interventions and control milestones.

Zanzibar is among the few places in sub-Saharan Africa where interruption of Schistosoma transmission seems an achievable goal. Our systematic review identifies and discusses milestones in schistosomiasis research, control and elimination efforts in Zanzibar over the past 100 years. The search in online databases, libraries, and the World Health Organization Archives revealed 153 records published between May 1928 and August 2022. The content of records was summarised to highlight the pivotal work leading towards urogenital schistosomiasis elimination and remaining research gaps. The greatest achievement following 100 years of schistosomiasis interventions and research is undoubtedly the improved health of Zanzibaris, exemplified by the reduction in Schistosoma haematobium prevalence from>50% historically down to<5% in 2020, and the absence of severe morbidities. Experiences from Zanzibar have contributed to global schistosomiasis guidelines, whilst also revealing challenges that impede progression towards elimination. Challenges include: transmission heterogeneity requiring micro-targeting of interventions, post-treatment recrudescence of infections in transmission hotspots, biological complexity of intermediate host snails, emergence of livestock Schistosoma species complicating surveillance whilst creating the risk for interspecies hybridisation, insufficient diagnostics performance for light intensity infections and female genital schistosomiasis, and a lack of acceptable sanitary alternatives to freshwater bodies. Our analysis of the past revealed that much can be achieved in the future with practical implementation of integrated interventions, alongside operational research. With continuing national and international commitments, interruption of S. haematobium transmission across both islands is within reach by 2030, signposting the future demise of urogenital schistosomiasis across other parts of sub-Saharan Africa.

How well do coverage surveys and programmatically reported mass drug administration coverage match? Results from 214 mass drug administration campaigns in 15 countries, 2008-2017.

INTRODUCTION: Delivering preventive chemotherapy through mass drug administration (MDA) is a central approach in controlling or eliminating several neglected tropical diseases (NTDs). Treatment coverage, a primary indicator of MDA performance, can be measured through routinely reported programmatic data or population-based coverage evaluation surveys. Reported coverage is often the easiest and least expensive way to estimate coverage; however, it is prone to inaccuracies due to errors in data compilation and imprecise denominators, and in some cases measures treatments offered as opposed to treatments swallowed. OBJECTIVE: Analyses presented here aimed to understand (1) how often coverage calculated using routinely reported data and survey data would lead programme managers to make the same programmatic decisions; (2) the magnitude and direction of the difference between these two estimates, and (3) whether there is meaningful variation by region, age group or country. METHODS: We analysed and compared reported and surveyed treatment coverage data from 214 MDAs implemented between 2008 and 2017 in 15 countries in Africa, Asia and the Caribbean. Routinely reported treatment coverage was compiled using data reported by national NTD programmes to donors, either directly or via NTD implementing partners, following the implementation of a district-level MDA campaign; coverage was calculated by dividing the number of individuals treated by a population value, which is typically based on national census projections and occasionally community registers. Surveyed treatment coverage came from post-MDA community-based coverage evaluation surveys, which were conducted as per standardised WHO recommended methodology. RESULTS: Coverage estimates using routine reporting and surveys gave the same result in terms of whether the minimum coverage threshold was reached in 72% of the MDAs surveyed in the Africa region and in 52% in the Asia region. The reported coverage value was within ±10 percentage points of the surveyed coverage value in 58/124 of the surveyed MDAs in the Africa region and 19/77 in the Asia region. Concordance between routinely reported and surveyed coverage estimates was 64% for the total population and 72% for school-age children. The study data showed variation across countries in the number of surveys conducted as well as the frequency with which there was concordance between the two coverage estimates. CONCLUSIONS: Programme managers must grapple with making decisions based on imperfect information, balancing needs for accuracy with cost and available capacity. The study shows that for many of the MDAs surveyed, based on the concordance with respect to reaching the minimum coverage thresholds, the routinely reported data were accurate enough to make programmatic decisions. Where coverage surveys do show a need to improve accuracy of routinely reported results, NTD programme managers should use various tools and approaches to strengthen data quality in order to use data for decision-making to achieve NTD control and elimination goals.

Praziquantel coverage in schools and communities targeted for the elimination of urogenital schistosomiasis in Zanzibar: a cross-sectional survey.

BACKGROUND: Biannual mass drug administration (MDA) with praziquantel and additional interventions to eliminate urogenital schistosomiasis has been implemented on the Zanzibar islands, United Republic of Tanzania, since 2012. We aimed to assess the coverage of school-based treatment (SBT) and community-wide treatment (CWT), to validate the coverage reported by the Zanzibar Ministry of Health (MoH) and to identify reasons for non-compliance. METHODS: We conducted a post-MDA cross-sectional survey in 93 schools and 92 communities on Pemba and Unguja islands in early 2014, 3-5 months after the last MDA round. Pupils and adults were asked whether they had received and taken the praziquantel treatment provided in the last SBT or CWT, respectively, and the observed and reported coverage were compared. Reasons for non-compliance were recorded in a pretested questionnaire and assessed in qualitative interviews. Urine samples of participants were examined for Schistosoma haematobium eggs with a single urine filtration. RESULTS: Around 8000 pupils and 4000 adults were included in the analysis. Our survey revealed a SBT coverage of 85.2% in Pemba and of 86.9% in Unguja, which was in line with MoH reports from Pemba (84.3%) and higher than reports from Unguja (63.9%). However, 15 among the 48 schools surveyed in Unguja had not received SBT. Among the interviewed adults, 53.6% in Pemba and 64.9% in Unguja had received praziquantel during CWT, which was less than the 59.0% and 67.7%, respectively, indicated by MoH reports. Moreover, only 43.8% and 54.0% of adults in Pemba and Unguja, respectively, had taken all the tablets as recommended. The main reasons for not receiving or taking praziquantel were absence during CWT, no drug distributor coming, being busy, fear of adverse events, pregnancy, breastfeeding or feeling healthy. CONCLUSION: To increase coverage and compliance in Zanzibar, SBT should target all schools and mobilization, sensitization and implementation of the CWT need to be improved. To reach elimination of urogenital schistosomiasis transmission in Zanzibar and elsewhere, a very high treatment coverage and compliance at national and local level is key and additional control measures such as snail control and behaviour change interventions will need to be implemented area wide. TRIAL REGISTRATION: ISRCTN48837681.

Estimation of changes in the force of infection for intestinal and urogenital schistosomiasis in countries with schistosomiasis control initiative-assisted programmes.

BACKGROUND: The 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). METHODS: A 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. RESULTS: Substantial 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. CONCLUSIONS: Reductions 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.

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.

Mapping helminth co-infection and co-intensity: geostatistical prediction in ghana.

BACKGROUND: Morbidity due to Schistosoma haematobium and hookworm infections is marked in those with intense co-infections by these parasites. The development of a spatial predictive decision-support tool is crucial for targeting the delivery of integrated mass drug administration (MDA) to those most in need. We investigated the co-distribution of S. haematobium and hookworm infection, plus the spatial overlap of infection intensity of both parasites, in Ghana. The aim was to produce maps to assist the planning and evaluation of national parasitic disease control programs. METHODOLOGY/PRINCIPAL FINDINGS: A national cross-sectional school-based parasitological survey was conducted in Ghana in 2008, using standardized sampling and parasitological methods. Bayesian geostatistical models were built, including a multinomial regression model for S. haematobium and hookworm mono- and co-infections and zero-inflated Poisson regression models for S. haematobium and hookworm infection intensity as measured by egg counts in urine and stool respectively. The resulting infection intensity maps were overlaid to determine the extent of geographical overlap of S. haematobium and hookworm infection intensity. In Ghana, prevalence of S. haematobium mono-infection was 14.4%, hookworm mono-infection was 3.2%, and S. haematobium and hookworm co-infection was 0.7%. Distance to water bodies was negatively associated with S. haematobium and hookworm co-infections, hookworm mono-infections and S. haematobium infection intensity. Land surface temperature was positively associated with hookworm mono-infections and S. haematobium infection intensity. While high-risk (prevalence >10-20%) of co-infection was predicted in an area around Lake Volta, co-intensity was predicted to be highest in foci within that area. CONCLUSIONS/SIGNIFICANCE: Our approach, based on the combination of co-infection and co-intensity maps allows the identification of communities at increased risk of severe morbidity and environmental contamination and provides a platform to evaluate progress of control efforts.

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.

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.

Is host-schistosome coevolution going anywhere?

BACKGROUND: That pathogens and hosts coevolve is a powerful concept with broad theoretical and applied implications spanning from genetic theory to the medical and veterinary sciences, particularly in the context of infectious disease epidemiology. A substantial body of theory has been developed to explore the likelihood and consequences of coevolution, but few empirical studies have been conducted to test these theories, particularly for indirectly-transmitted pathogen-host systems. We initiated replicate longitudinal host-schistosome co-selection trials under different host genotype combinations: Schistosoma mansoni parasite lines were co-selected with populations of either previously resistant-selected Biomphalaria glabrata host genotypes, or unselected susceptible B. glabrata genotypes, or a mixed population of the two. All parasite lines were also passaged through their obligatory mammalian definitive host at each generation. RESULTS: We demonstrated variation in, and a reciprocal impact on, the fitness of both host and pathogen phenotype and genotype, an outcome dependent on the combinations of genotypes involved, and evidence of change over time. Most apparent was the observation that parasites appeared to rapidly adapt to those intermediate hosts previously selected for resistance. CONCLUSION: Our results illustrate the potential for host-schistosome coevolution and, in particular, suggest that host resistance may be a temporary phenomenon in nature due, in part, to rapid counter-adaptations by parasites.

The control of schistosomiasis and soil-transmitted helminths in East Africa.

As a result of support from the Bill and Melinda Gates Foundation, schistosomiasis and intestinal or soil-transmitted helminth infections have been the subject of national control programmes in three Eastern and Southern African countries: Uganda, the United Republic of Tanzania and Zambia. Here, we review the significant progress made in their control efforts and highlight the different approaches being adopted to ensure programme effectiveness and sustainability. Although a positive start has been made to reduce morbidity resulting from schistosomiasis and soil-transmitted helminth infections in these countries, it is imperative that support is identified to sustain the programmes until these infections are no longer a public health problem and children can therefore be given a healthy start to life.

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.

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.