The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study.

BACKGROUND: Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies. METHODS AND FINDINGS: We developed a system of epidemiological and economic models, calibrated to demographic, epidemiological, and health service data in 105 LMICs. For each country, we assessed the likely future course of TB-related outcomes under several vaccine introduction scenarios, compared to a "no-new-vaccine" counterfactual. Vaccine scenarios considered 2 vaccine product profiles (1 targeted at infants, 1 at adolescents/adults), both assumed to prevent progression to active TB. Key economic inputs were derived from the Global Health Cost Consortium, World Health Organization (WHO) patient cost surveys, and the published literature. We estimated the incremental impact of vaccine introduction for a range of health and economic outcomes. In the base-case, we assumed a vaccine price of $4.60 and used a 1× per-capita gross domestic product (GDP) cost-effectiveness threshold (both varied in sensitivity analyses). Vaccine introduction was estimated to require substantial near-term resources, offset by future cost-savings from averted TB burden. From a health system perspective, adolescent/adult vaccination was cost-effective in 64 of 105 LMICs. From a societal perspective (including productivity gains and averted patient costs), adolescent/adult vaccination was projected to be cost-effective in 73 of 105 LMICs and cost-saving in 58 of 105 LMICs, including 96% of countries with higher TB burden. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult vaccine could produce $283 to 474 billion in economic benefits by 2050. Limited data availability required assumptions and extrapolations that may omit important country-level heterogeneity in epidemiology and costs. CONCLUSIONS: TB vaccination would be highly impactful and cost-effective in most LMICs. Further efforts are needed for future development, adoption, and implementation of novel TB vaccines.

Schistosomiasis - Assessing Progress toward the 2020 and 2025 Global Goals.

BACKGROUND: With the vision of "a world free of schistosomiasis," the World Health Organization (WHO) set ambitious goals of control of this debilitating disease and its elimination as a public health problem by 2020 and 2025, respectively. As these milestones become imminent, and if programs are to succeed, it is important to evaluate the WHO programmatic guidelines empirically. METHODS: We collated and analyzed multiyear cross-sectional data from nine national schistosomiasis control programs (in eight countries in sub-Saharan Africa and in Yemen). Data were analyzed according to schistosome species (Schistosoma mansoni or S. haematobium), number of treatment rounds, overall prevalence, and prevalence of heavy-intensity infection. Disease control was defined as a prevalence of heavy-intensity infection of less than 5% aggregated across sentinel sites, and the elimination target was defined as a prevalence of heavy-intensity infection of less than 1% in all sentinel sites. Heavy-intensity infection was defined as at least 400 eggs per gram of feces for S. mansoni infection or as more than 50 eggs per 10 ml of urine for S. haematobium infection. RESULTS: All but one country program (Niger) reached the disease-control target by two treatment rounds or less, which is earlier than projected by current WHO guidelines (5 to 10 years). Programs in areas with low endemicity levels at baseline were more likely to reach both the control and elimination targets than were programs in areas with moderate and high endemicity levels at baseline, although the elimination target was reached only for S. mansoni infection (in Burkina Faso, Burundi, and Rwanda within three treatment rounds). Intracountry variation was evident in the relationships between overall prevalence and heavy-intensity infection (stratified according to treatment rounds), a finding that highlights the challenges of using one metric to define control or elimination across all epidemiologic settings. CONCLUSIONS: These data suggest the need to reevaluate progress and treatment strategies in national schistosomiasis control programs more frequently, with local epidemiologic data taken into consideration, in order to determine the treatment effect and appropriate resource allocations and move closer to achieving the global goals. (Funded by the Children's Investment Fund Foundation and others.).

An early evaluation of clinical and economic costs and benefits of implementing point of care NAAT tests for Chlamydia trachomatis and Neisseria gonorrhoea in genitourinary medicine clinics in England.

OBJECTIVES: To estimate the costs and benefits of clinical pathways incorporating a point of care (POC) nucleic acid amplification test (NAAT) for chlamydia and gonorrhoea in genitourinary medicine (GUM) clinics compared with standard off-site laboratory testing. METHOD: We simulated 1.2 million GUM clinic attendees in England. A simulation in Microsoft Excel was developed to compare existing standard pathways of management for chlamydia and gonorrhoea with a POC NAAT. We conducted scenario analyses to evaluate the robustness of the model findings. The primary outcome was the incremental cost-effectiveness ratio. Secondary outcomes included the number of inappropriate treatments, complications and transmissions averted. RESULTS: The baseline cost of using the point of POC NAAT was £103.9 million compared with £115.6 million for standard care. The POC NAAT was also associated with a small increase of 46 quality adjusted life years, making the new test both more effective and cheaper. Over 95 000 inappropriate treatments might be avoided by using a POC NAAT. Patients receive diagnosis and treatment on the same day as testing, which may also prevent 189 cases of pelvic inflammatory disease and 17 561 onward transmissions annually. DISCUSSION: Replacing standard laboratory tests for chlamydia and gonorrhoea with a POC test could be cost saving and patients would benefit from more accurate diagnosis and less unnecessary treatment. Overtreatment currently accounts for about a tenth of the reported treatments for chlamydia and gonorrhoea and POC NAATs would effectively eliminate the need for presumptive treatment.

Strategic considerations on developing a CHIKV vaccine and ensuring equitable access for countries in need.

Chikungunya is an arboviral disease caused by the chikungunya virus (CHIKV) afflicting tropical and sub-tropical countries worldwide. It has been identified as a priority pathogen by the Coalition for Epidemics Preparedness Innovations (CEPI) and as an emerging infectious disease (EID) necessitating further action as soon as possible by the World Health Organization (WHO). Recent studies suggest that disability-adjusted life years (DALYs) due to CHIKV infection are as high as 106,089 DALYs lost globally. Significant progress has been made in the development of several vaccines, aimed at preventing CHIKV infections. This perspective article summarizes CEPI's efforts and strategic considerations for developing a CHIKV vaccine and ensuring equitable access for CHIKV endemic countries.

Demonstrating multi-country calibration of a tuberculosis model using new history matching and emulation package - hmer.

Infectious disease models are widely used by epidemiologists to improve the understanding of transmission dynamics and disease natural history, and to predict the possible effects of interventions. As the complexity of such models increases, however, it becomes increasingly challenging to robustly calibrate them to empirical data. History matching with emulation is a calibration method that has been successfully applied to such models, but has not been widely used in epidemiology partly due to the lack of available software. To address this issue, we developed a new, user-friendly R package hmer to simply and efficiently perform history matching with emulation. In this paper, we demonstrate the first use of hmer for calibrating a complex deterministic model for the country-level implementation of tuberculosis vaccines to 115 low- and middle-income countries. The model was fit to 9-13 target measures, by varying 19-22 input parameters. Overall, 105 countries were successfully calibrated. Among the remaining countries, hmer visualisation tools, combined with derivative emulation methods, provided strong evidence that the models were misspecified and could not be calibrated to the target ranges. This work shows that hmer can be used to simply and rapidly calibrate a complex model to data from over 100 countries, making it a useful addition to the epidemiologist's calibration tool-kit.

The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study.

BACKGROUND: Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks resulting from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low-income and middle-income countries (LMICs) in several delivery scenarios. METHODS: We calibrated a tuberculosis model to 105 LMICs (accounting for 93% of global incidence). Vaccine scenarios were implemented as the base-case (routine vaccination of those aged 9 years and one-off vaccination for those aged 10 years and older, with country-specific introduction between 2028 and 2047, and 5-year scale-up to target coverage); accelerated scale-up similar to the base-case, but with all countries introducing vaccines in 2025, with instant scale-up; and routine-only (similar to the base-case, but including routine vaccination only). Vaccines were assumed to protect against disease for 10 years, with 50% efficacy. FINDINGS: The base-case scenario would prevent 44·0 million (95% uncertainty range 37·2-51·6) tuberculosis cases and 5·0 million (4·6-5·4) tuberculosis deaths before 2050, compared with equivalent estimates of cases and deaths that would be predicted to occur before 2050 with no new vaccine introduction (the baseline scenario). The accelerated scale-up scenario would prevent 65·5 million (55·6-76·0) cases and 7·9 million (7·3-8·5) deaths before 2050, relative to baseline. The routine-only scenario would prevent 8·8 million (95% uncertainty range 7·6-10·1) cases and 1·1 million (0·9-1·2) deaths before 2050, relative to baseline. INTERPRETATION: Our results suggest novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a one-off vaccination campaign will be crucial for rapid impact. Accelerated introduction-at a pace similar to that seen for COVID-19 vaccines-would increase the number of lives saved before 2050 by around 60%. Investment is required to support vaccine development, manufacturing, prompt introduction, and scale-up. FUNDING: WHO (2020/985800-0). TRANSLATIONS: For the French, Spanish, Italian and Dutch translations of the abstract see Supplementary Materials section.

Direct estimates of absolute ventilation and estimated Mycobacterium tuberculosis transmission risk in clinics in South Africa.

Healthcare facilities are important sites for the transmission of pathogens spread via bioaerosols, such as Mycobacterium tuberculosis. Natural ventilation can play an important role in reducing this transmission. We aimed to measure rates of natural ventilation in clinics in KwaZulu-Natal and Western Cape provinces, South Africa, then use these measurements to estimate Mycobacterium tuberculosis transmission risk. We measured ventilation in clinic spaces using a tracer-gas release method. In spaces where this was not possible, we estimated ventilation using data on indoor and outdoor carbon dioxide levels. Ventilation was measured i) under usual conditions and ii) with all windows and doors fully open. Under various assumptions about infectiousness and duration of exposure, measured absolute ventilation rates were related to risk of Mycobacterium tuberculosis transmission using the Wells-Riley Equation. In 2019, we obtained ventilation measurements in 33 clinical spaces in 10 clinics: 13 consultation rooms, 16 waiting areas and 4 other clinical spaces. Under usual conditions, the absolute ventilation rate was much higher in waiting rooms (median 1769 m3/hr, range 338-4815 m3/hr) than in consultation rooms (median 197 m3/hr, range 0-1451 m3/hr). When compared with usual conditions, fully opening existing doors and windows resulted in a median two-fold increase in ventilation. Using standard assumptions about infectiousness, we estimated that a health worker would have a 24.8% annual risk of becoming infected with Mycobacterium tuberculosis, and that a patient would have an 0.1% risk of becoming infected per visit. Opening existing doors and windows and rearranging patient pathways to preferentially use better ventilated clinic spaces result in important reductions in Mycobacterium tuberculosis transmission risk. However, unless combined with other tuberculosis infection prevention and control interventions, these changes are insufficient to reduce risk to health workers, and other highly exposed individuals, to acceptable levels.

Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoni.

BACKGROUND: World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children. METHODOLOGY: A total of 22,488 children aged 6-15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003-2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data. PRINCIPAL FINDINGS: S. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed. CONCLUSIONS/SIGNIFICANCE: Current status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual's intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.

Estimating ventilation rates in rooms with varying occupancy levels: Relevance for reducing transmission risk of airborne pathogens.

BACKGROUND: In light of the role that airborne transmission plays in the spread of SARS-CoV-2, as well as the ongoing high global mortality from well-known airborne diseases such as tuberculosis and measles, there is an urgent need for practical ways of identifying congregate spaces where low ventilation levels contribute to high transmission risk. Poorly ventilated clinic spaces in particular may be high risk, due to the presence of both infectious and susceptible people. While relatively simple approaches to estimating ventilation rates exist, the approaches most frequently used in epidemiology cannot be used where occupancy varies, and so cannot be reliably applied in many of the types of spaces where they are most needed. METHODS: The aim of this study was to demonstrate the use of a non-steady state method to estimate the absolute ventilation rate, which can be applied in rooms where occupancy levels vary. We used data from a room in a primary healthcare clinic in a high TB and HIV prevalence setting, comprising indoor and outdoor carbon dioxide measurements and head counts (by age), taken over time. Two approaches were compared: approach 1 using a simple linear regression model and approach 2 using an ordinary differential equation model. RESULTS: The absolute ventilation rate, Q, using approach 1 was 2407 l/s [95% CI: 1632-3181] and Q from approach 2 was 2743 l/s [95% CI: 2139-4429]. CONCLUSIONS: We demonstrate two methods that can be used to estimate ventilation rate in busy congregate settings, such as clinic waiting rooms. Both approaches produced comparable results, however the simple linear regression method has the advantage of not requiring room volume measurements. These methods can be used to identify poorly-ventilated spaces, allowing measures to be taken to reduce the airborne transmission of pathogens such as Mycobacterium tuberculosis, measles, and SARS-CoV-2.

Modelling the effect of infection prevention and control measures on rate of Mycobacterium tuberculosis transmission to clinic attendees in primary health clinics in South Africa.

BACKGROUND: Elevated rates of tuberculosis in healthcare workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high-burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees. METHODS: An individual-based model of patient movements through clinics, ventilation in waiting areas, and Mtb transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions-codeveloped with health professionals and policy-makers-were simulated: (1) queue management systems with outdoor waiting areas, (2) ultraviolet germicidal irradiation (UVGI) systems, (3) appointment systems, (4) opening windows and doors, (5) surgical mask wearing by clinic attendees, (6) simple clinic retrofits and (7) increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the Central Chronic Medicine Dispensing and Distribution (CCMDD) service. RESULTS: In the model, (1) outdoor waiting areas reduced the transmission to clinic attendees by 83% (IQR 76%-88%), (2) UVGI by 77% (IQR 64%-85%), (3) appointment systems by 62% (IQR 45%-75%), (4) opening windows and doors by 55% (IQR 25%-72%), (5) masks by 47% (IQR 42%-50%), (6) clinic retrofits by 45% (IQR 16%-64%) and (7) increasing the coverage of CCMDD by 22% (IQR 12%-32%). CONCLUSIONS: The majority of the interventions achieved median reductions in the rate of transmission to clinic attendees of at least 45%, meaning that a range of highly effective intervention options are available, that can be tailored to the local context. Measures that are not traditionally considered to be IPC interventions, such as appointment systems, may be as effective as more traditional IPC measures, such as mask wearing.

Urogenital schistosomiasis in Cabo Delgado, northern Mozambique: baseline findings from the SCORE study.

BACKGROUND: The results presented here are part of a five-year cluster-randomised intervention trial that was implemented to understand how best to gain and sustain control of schistosomiasis through different preventive chemotherapy strategies. This paper presents baseline data that were collected in ten districts of Cabo Delgado province, northern Mozambique, before treatment. METHODS: A cross-sectional study of 19,039 individuals was sampled from 144 villages from May to September 2011. In each village prevalence and intensity of S. haematobium were investigated in 100 children first-year students (aged 5-8 years), 100 school children aged 9-12 years (from classes 2 to 7) and 50 adults (20-55 years). Prevalence and intensity of S. haematobium infection were evaluated microscopically by two filtrations, each of 10 ml, from a single urine specimen. Given that individual and community perceptions of schistosomiasis influence control efforts, community knowledge and environmental risk factors were collected using a face-to-face interview. Data were entered onto mobile phones using EpiCollect. Data summary was made using descriptive statistics. Chi-square and logistic regression were used to determine the association between dependent and independent variables. RESULTS: The overall prevalence of urogenital schistosomiasis was 60.4% with an arithmetic mean intensity of infection of 55.8 eggs/10 ml of urine. Heavy infections were detected in 17.7%, of which 235 individuals (6.97%) had an egg count of 1000 eggs/10 ml or more. There was a significantly higher likelihood of males being infected than females across all ages (62% vs 58%; P < 0.0005). Adolescents aged 9-12 years had a higher prevalence (66.6%) and mean infection intensity (71.9 eggs/10 ml) than first-year students (63.1%; 58.2 eggs/10 ml). This is the first study in Mozambique looking at infection rates among adults. Although children had higher levels of infection, it was found here that adults had a high average prevalence and intensity of infection (44.5%; 23.9 eggs/10 ml). Awareness of schistosomiasis was relatively high (68.6%); however, correct knowledge of how schistosomiasis is acquired was low (23.2%) among those who had heard of the disease. Schistosomiasis risk behaviour such as washing (91.3%) and bathing (86.7%) in open water sources likely to be infested with host snails was high. CONCLUSIONS: Urogenital schistosomiasis is widespread in Cabo Delgado. In addition, poor community knowledge about the causes of schistosomiasis and how to prevent it increases the significant public health challenge for the national control program. This was the first study in Mozambique that examined infection levels among adults, where results showed that S. haematobium infection was also extremely high. Given that this controlled trial aims to understand the impact of different combinations of schistosomiasis control through treatment of communities, schools, and treatment holidays over a five-year period, these findings highlight the importance of examining the impact of different treatment approaches also in adults. TRIAL REGISTRATION: The trials have been registered with the International Standard Randomised Controlled Trial registry under ISRCT 14117624 Mozambique (14 December 2015).

Evaluating the variation in the projected benefit of community-wide mass treatment for schistosomiasis: Implications for future economic evaluations.

BACKGROUND: The majority of schistosomiasis control programmes focus on targeting school-aged children. Expanding the use of community-wide mass treatment to reach more adults is under consideration. However, it should be noted that this would require a further increase in programmatic resources, international aid, and commitment for the provision of praziquantel. Consequently, it is important to understand (i) where a change of strategy would have the greatest benefit, and (ii) how generalisable the conclusions of field trials and analytical studies based on mathematical models investigating the impact of community-wide mass treatment, are to a broad range of settings. METHODS: In this paper, we employ a previously described deterministic fully age-structured schistosomiasis transmission model and evaluate the benefit of community-wide mass treatment both in terms of controlling morbidity and eliminating transmission for Schistosoma mansoni, across a wide range of epidemiological settings and programmatic scenarios. This included variation in the baseline relative worm pre-control burden in adults, the overall level of transmission in defined settings, choice of effectiveness metric (basing morbidity calculations on prevalence or intensity), the level of school enrolment and treatment compliance. RESULTS: Community-wide mass treatment was found to be more effective for controlling the transmission of schistosome parasites than using a school-based programme only targeting school-aged children. However, in the context of morbidity control, the potential benefit of switching to community-wide mass treatment was highly variable across the different scenarios analysed. In contrast, for areas where the goal is to eliminate transmission, the projected benefit of community-wide mass treatment was more consistent. CONCLUSION: Whether community-wide mass treatment is appropriate will depend on the local epidemiological setting (i.e. the relative pre-control burden in adults and transmission intensity), and whether the goal is morbidity control or eliminating transmission. This has important implications regarding the generalisability of cost-effectiveness analyses of schistosomiasis interventions. Our results indicate that areas with poor school-enrolment/coverage could benefit more from community-wide treatment of praziquantel and should potentially be prioritised for any change in strategy. This work highlights the importance of not over-generalising conclusions and policy in this area, but of basing decisions on high quality epidemiological data and quantitative analyses of the impact of interventions in a range of settings.

Markov Model Predicts Changes in STH Prevalence during Control Activities Even with a Reduced Amount of Baseline Information.

BACKGROUND: Estimating the reduction in levels of infection during implementation of soil-transmitted helminth (STH) control programmes is important to measure their performance and to plan interventions. Markov modelling techniques have been used with some success to predict changes in STH prevalence following treatment in Viet Nam. The model is stationary and to date, the prediction has been obtained by calculating the transition probabilities between the different classes of intensity following the first year of drug distribution and assuming that these remain constant in subsequent years. However, to run this model longitudinal parasitological data (including intensity of infection) are required for two consecutive years from at least 200 individuals. Since this amount of data is not often available from STH control programmes, the possible application of the model in control programme is limited. The present study aimed to address this issue by adapting the existing Markov model to allow its application when a more limited amount of data is available and to test the predictive capacities of these simplified models. METHOD: We analysed data from field studies conducted with different combination of three parameters: (i) the frequency of drug administration; (ii) the drug distributed; and (iii) the target treatment population (entire population or school-aged children only). This analysis allowed us to define 10 sets of standard transition probabilities to be used to predict prevalence changes when only baseline data are available (simplified model 1). We also formulated three equations (one for each STH parasite) to calculate the predicted prevalence of the different classes of intensity from the total prevalence. These equations allowed us to design a simplified model (SM2) to obtain predictions when the classes of intensity at baseline were not known. To evaluate the performance of the simplified models, we collected data from the scientific literature on changes in STH prevalence during the implementation of 26 control programmes in 16 countries. Using the baseline data observed, we applied the simplified models and predicted the onward prevalence of STH infection at each time-point for which programme data were available. We then compared the output from the model with the observed data from the programme. RESULTS: The comparison between the model-predicted prevalence and the observed values demonstrated a good accuracy of the predictions. In 77% of cases the original model predicted a prevalence within five absolute percentage points from the observed figure, for the simplified model one in 69% of cases and for the simplified model two in 60% of cases. We consider that the STH Markov model described here could be an important tool for programme managers to monitor the progress of their control programmes and to select the appropriate intervention. We also developed, and made freely available online, a software tool to enable the use of the STH Markov model by personnel with limited knowledge of mathematical models.

Development and evaluation of a Markov model to predict changes in schistosomiasis prevalence in response to praziquantel treatment: a case study of Schistosoma mansoni in Uganda and Mali.

BACKGROUND: Understanding whether schistosomiasis control programmes are on course to control morbidity and potentially switch towards elimination interventions would benefit from user-friendly quantitative tools that facilitate analysis of progress and highlight areas not responding to treatment. This study aimed to develop and evaluate such a tool using large datasets collected during Schistosomiasis Control Initiative-supported control programmes. METHODS: A discrete-time Markov model was developed using transition probability matrices parameterized with control programme longitudinal data on Schistosoma mansoni obtained from Uganda and Mali. Four matrix variants (A-D) were used to compare different data types for parameterization: A-C from Uganda and D from Mali. Matrix A used data at baseline and year 1 of the control programme; B used year 1 and year 2; C used baseline and year 1 from selected districts, and D used baseline and year 1 Mali data. Model predictions were tested against 3 subsets of the Uganda dataset: dataset 1, the full 4-year longitudinal cohort; dataset 2, from districts not used to parameterize matrix C; dataset 3, cross-sectional data, and dataset 4, from Mali as an independent dataset. RESULTS: The model parameterized using matrices A, B and D predicted similar infection dynamics (overall and when stratified by infection intensity). Matrices A-D successfully predicted prevalence in each follow-up year for low and high intensity categories in dataset 1 followed by dataset 2. Matrices A, B and D yielded similar and close matches to dataset 1 with marginal discrepancies when comparing model outputs against datasets 2 and 3. Matrix C produced more variable results, correctly estimating fewer data points. CONCLUSION: Model outputs closely matched observed values and were a useful predictor of the infection dynamics of S. mansoni when using longitudinal and cross-sectional data from Uganda. This also held when the model was tested with data from Mali. This was most apparent when modelling overall infection and in low and high infection intensity areas. Our results indicate the applicability of this Markov model approach as countries aim at reaching their control targets and potentially move towards the elimination of schistosomiasis.

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.