Modelling timelines to elimination of sleeping sickness in the Democratic Republic of Congo, accounting for possible cryptic human and animal transmission.

BACKGROUND: Sleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans. METHODS: Using modelling, we explore how cryptic (undetected) transmission impacts the monitoring of progress towards and the achievement of the EoT goal. We have developed gHAT models that include either asymptomatic or animal transmission, and compare these to a baseline gHAT model without either of these transmission routes, to explore the potential role of cryptic infections on the EoT goal. Each model was independently calibrated to five different health zones in the Democratic Republic of the Congo (DRC) using available historical human case data for 2000-2020 (obtained from the World Health Organization's HAT Atlas). We applied a novel Bayesian sequential updating approach for the asymptomatic model to enable us to combine statistical information about this type of transmission from each health zone. RESULTS: Our results suggest that, when matched to past case data, we estimated similar numbers of new human infections between model variants, although human infections were slightly higher in the models with cryptic infections. We simulated the continuation of screen-confirm-and-treat interventions, and found that forward projections from the animal and asymptomatic transmission models produced lower probabilities of EoT than the baseline model; however, cryptic infections did not prevent EoT from being achieved eventually under this approach. CONCLUSIONS: This study is the first to simulate an (as-yet-to-be available) screen-and-treat strategy and found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared with the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised.

Comparison of stochastic and deterministic models for gambiense sleeping sickness at different spatial scales: A health area analysis in the DRC.

The intensification of intervention activities against the fatal vector-borne disease gambiense human African trypanosomiasis (gHAT, sleeping sickness) in the last two decades has led to a large decline in the number of annually reported cases. However, while we move closer to achieving the ambitious target of elimination of transmission (EoT) to humans, pockets of infection remain, and it becomes increasingly important to quantitatively assess if different regions are on track for elimination, and where intervention efforts should be focused. We present a previously developed stochastic mathematical model for gHAT in the Democratic Republic of Congo (DRC) and show that this same formulation is able to capture the dynamics of gHAT observed at the health area level (approximately 10,000 people). This analysis was the first time any stochastic gHAT model has been fitted directly to case data and allows us to better quantify the uncertainty in our results. The analysis focuses on utilising a particle filter Markov chain Monte Carlo (MCMC) methodology to fit the model to the data from 16 health areas of Mosango health zone in Kwilu province as a case study. The spatial heterogeneity in cases is reflected in modelling results, where we predict that under the current intervention strategies, the health area of Kinzamba II, which has approximately one third of the health zone's cases, will have the latest expected year for EoT. We find that fitting the analogous deterministic version of the gHAT model using MCMC has substantially faster computation times than fitting the stochastic model using pMCMC, but produces virtually indistinguishable posterior parameterisation. This suggests that expanding health area fitting, to cover more of the DRC, should be done with deterministic fits for efficiency, but with stochastic projections used to capture both the parameter and stochastic variation in case reporting and elimination year estimations.

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Subnational Projections of Lymphatic Filariasis Elimination Targets in Ethiopia to Support National Level Policy.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. METHODS: Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. RESULTS: Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. CONCLUSIONS: The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.

Molecular-Scale Imaging Enables Direct Visualization of Molecular Defects and Chain Structure of Conjugated Polymers.

Conjugated polymers have become materials of choice for applications ranging from flexible optoelectronics to neuromorphic computing, but their polydispersity and tendency to aggregate pose severe challenges to their precise characterization. Here, the combination of vacuum electrospray deposition (ESD) with scanning tunneling microscopy (STM) is used to acquire, within the same experiment, assembly patterns, full mass distributions, exact sequencing, and quantification of polymerization defects. In a first step, the ESD-STM results are successfully benchmarked against NMR for low molecular mass polymers, where this technique is still applicable. Then, it is shown that ESD-STM is capable of reaching beyond its limits by characterizing, with the same accuracy, samples that are inaccessible to NMR. Finally, a recalibration procedure is proposed for size exclusion chromatography (SEC) mass distributions, using ESD-STM results as a reference. The distinctiveness of the molecular-scale information obtained by ESD-STM highlights its role as a crucial technique for the characterization of conjugated polymers.

Evaluating the effectiveness of a low fidelity, easily available simulator to teach basic arthroscopy skills to novice learners: A prospective cohort study.

BACKGROUND: Arthroscopy proficiency is key to being a competent orthopaedic surgeon and acquiring arthroscopic skills takes years of exposure and diligent practice. However, today's graduating consultants have had considerably less time in operating theatre than their senior colleagues at the same point of their careers. OBJECTIVES: To evaluate whether: (1) Students could improve their arthroscopic technique using a low fidelity arthroscopic training tool (2) students enjoyed the use of the simulator (3) If certain demographics correlate to performance on the simulator. METHODS: Medical students who have no previous training in arthroscopy were included. A combined left- and right-handed timed run with a low-fidelity arthroscopic triangulation simulator was recorded before and after 40-minutes of practice. RESULTS: 84 participants took part with an average improvement of was 66.8%. Students felt that their arthroscopic skills increased on average by 36.4%. 73 of the 84 participants gave the maximum score of 5 when asked if they enjoyed the session and 74 participants gave the maximum score of 5 as to whether they would be interested in participating in further sessions. Factors such as biological sex, video game play and sports were found to be statistically significant to performance. CONCLUSIONS: This study showed a statistically significant improvement in students' arthroscopic performance with a low-fidelity arthroscopic simulator. Students found the experience useful with the vast majority indicating interest in completing further training sessions to help improve practical surgical skills. Video gamers, sports players and males were found to have a correlation with performance on the simulator.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Patella Denervation With Circumferential Electrocautery in Primary Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: The aim of this study was to investigate the clinical effectiveness of patella rim electrocautery "denervation" versus no denervation in patients undergoing total knee arthroplasty (TKA). METHODS: We conducted a single-center, double-blind randomized controlled trial. Patients aged 40 years or older, due to undergo a TKA who did not have patella resurfacing (usual care) were randomized with or without circumferential patella electrocautery. This was undertaken according to a randomly generated sequence of treatment allocation that was placed into numbered, sealed opaque envelopes. Participants were blinded to treatment allocation. There was no crossover. The primary outcome was Oxford Knee Score at 1 year postoperatively. Secondary outcomes were Bartlett Patella Score, Western Ontario and McMaster Universities Arthritis Index (WOMAC), and 12-Item Short Form Survey. Linear regression analyses were performed with adjustments by age, sex, and baseline (preoperative) scores. There were 142 participants recruited, of which 49 (35%) were allocated to the denervation intervention. Recruitment was stopped early when interim statistical analyses confirmed adequate numbers in both groups despite an imbalance in early treatment allocation rates due to the randomization method. The mean patient age was 71 years (range, 50 to 85) and 51% (n = 74) were women. RESULTS: No difference in Oxford Knee Score was detected at 1 year (mean difference [MD] 1.87; 95% confidence interval [CI] -1.28 to 5.03). No difference was detected in Bartlett Patella Score (MD 0.490; 95% CI -1.61 to 2.59) or 12-Item Short Form Survey (MD 0.196; 95% CI -2.54 to 2.93). A statistically significant difference in WOMAC was detected, but at a level less than the minimal clinically important difference for WOMAC (MD 4.79; 95% CI 1.05 to 8.52). CONCLUSION: No clinically relevant benefit was detected from patella rim electrocautery in patients undergoing TKA who did not have patella resurfacing (including no benefit in terms of anterior knee pain). This treatment is therefore not recommended for clinical practice. LEVEL OF EVIDENCE: Level 1.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted, while HIV transmission to girls and women (aged 15-24 years) from older men declined by about one third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programs to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Year-round longitudinal health surveillance in UK Olympic Summer Sport Athletes 2016-2019.

OBJECTIVES: To identify the priority injury and illness types across UK summer Olympic World Class Programme sports to inform development, implementation and evaluation of associated injury risk mitigation and management initiatives. METHODS: Four years (2016-2019) of electronic medical records of 1247 athletes from 22 sports were analysed and reported using methods based on the 2020 International Olympic Committee consensus statement for epidemiological recording and reporting. RESULTS: 3562 injuries and 1218 illness were recorded, accounting for 146 156 and 27 442 time-loss days. Overall, 814 (65%) athletes reported at least one injury, while 517 (41%) reported at least one illness. There were 1.3 injuries per athlete year resulting in a mean burden of 54.1 days per athlete year. The lumbar/pelvis, knee, ankle and shoulder body regions had the highest incidence and burden. Athletes reported 0.5 illnesses per athlete year, resulting in a mean burden of 10.4 days per athlete year, with most composed of respiratory illness and gastroenteritis. Injuries within sport groups were representative of the injury risk profile for those sports (eg, knee, hand and head injuries had the highest incidence in combat sports), but respiratory illnesses were consistently the greatest problem for each sport group. CONCLUSIONS: To optimise availability for training and performance, systematic risk mitigation and management initiatives should target priority injury problems occurring in the lumbar/pelvis, knee, ankle and shoulder, and respiratory illness. Follow-up analysis should include identification of sport-specific priority health problems and associated risk factors.

Diagnosis of helminths depends on worm fecundity and the distribution of parasites within hosts.

Helminth transmission and morbidity are dependent on the number of mature parasites within a host; however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver fluke Opisthorchis viverrini, which infects approximately 10 million people across Southeast Asia, by analysing five epidemiological surveys (n = 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that greater than 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is nonlinear and strongly influenced by parasite aggregation.

Omitting age-dependent mosquito mortality in malaria models underestimates the effectiveness of insecticide-treated nets.

Mathematical models of vector-borne infections, including malaria, often assume age-independent mortality rates of vectors, despite evidence that many insects senesce. In this study we present survival data on insecticide-resistant Anopheles gambiae s.l. from experiments in Côte d'Ivoire. We fit a constant mortality function and two age-dependent functions (logistic and Gompertz) to the data from mosquitoes exposed (treated) and not exposed (control) to insecticide-treated nets (ITNs), to establish biologically realistic survival functions. This enables us to explore the effects of insecticide exposure on mosquito mortality rates, and the extent to which insecticide resistance might impact the effectiveness of ITNs. We investigate this by calculating the expected number of infectious bites a mosquito will take in its lifetime, and by extension the vectorial capacity. Our results show that the predicted vectorial capacity is substantially lower in mosquitoes exposed to ITNs, despite the mosquitoes in the experiment being highly insecticide-resistant. The more realistic age-dependent functions provide a better fit to the experimental data compared to a constant mortality function and, hence, influence the predicted impact of ITNs on malaria transmission potential. In models with age-independent mortality, there is a great reduction for the vectorial capacity under exposure compared to no exposure. However, the two age-dependent functions predicted an even larger reduction due to exposure, highlighting the impact of incorporating age in the mortality rates. These results further show that multiple exposures to ITNs had a considerable effect on the vectorial capacity. Overall, the study highlights the importance of including age dependency in mathematical models of vector-borne disease transmission and in fully understanding the impact of interventions.

Modelling to infer the role of animals in gambiense human African trypanosomiasis transmission and elimination in the DRC.

Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly approaching, there remain fundamental questions about the presence of non-human animal transmission cycles and their potential role in slowing progress towards, or even preventing, EoT. In this study we focus on the country with the most gHAT disease burden, the Democratic Republic of Congo (DRC), and use mathematical modelling to assess whether animals may contribute to transmission in specific regions, and if so, how their presence could impact the likelihood and timing of EoT. By fitting two model variants-one with, and one without animal transmission-to the human case data from 2000-2016 we estimate model parameters for 158 endemic health zones of the DRC. We evaluate the statistical support for each model variant in each health zone and infer the contribution of animals to overall transmission and how this could impact predicted time to EoT. We conclude that there are 24/158 health zones where there is substantial to decisive statistical support for some animal transmission. However-even in these regions-we estimate that animals would be extremely unlikely to maintain transmission on their own. Animal transmission could hamper progress towards EoT in some settings, with projections under continuing interventions indicating that the number of health zones expected to achieve EoT by 2030 reduces from 68/158 to 61/158 if animal transmission is included in the model. With supplementary vector control (at a modest 60% tsetse reduction) added to medical screening and treatment interventions, the predicted number of health zones meeting the goal increases to 147/158 for the model including animal transmission. This is due to the impact of vector reduction on transmission to and from all hosts.

Statistical methods for linking geostatistical maps and transmission models: Application to lymphatic filariasis in East Africa.

Infectious diseases remain one of the major causes of human mortality and suffering. Mathematical models have been established as an important tool for capturing the features that drive the spread of the disease, predicting the progression of an epidemic and hence guiding the development of strategies to control it. Another important area of epidemiological interest is the development of geostatistical methods for the analysis of data from spatially referenced prevalence surveys. Maps of prevalence are useful, not only for enabling a more precise disease risk stratification, but also for guiding the planning of more reliable spatial control programmes by identifying affected areas. Despite the methodological advances that have been made in each area independently, efforts to link transmission models and geostatistical maps have been limited. Motivated by this fact, we developed a Bayesian approach that combines fine-scale geostatistical maps of disease prevalence with transmission models to provide quantitative, spatially-explicit projections of the current and future impact of control programs against a disease. These estimates can then be used at a local level to identify the effectiveness of suggested intervention schemes and allow investigation of alternative strategies. The methodology has been applied to lymphatic filariasis in East Africa to provide estimates of the impact of different intervention strategies against the disease.

Revealing the Reactivity of Individual Chemical Entities in Complex Mixtures: the Chemistry Behind Bio-Oil Upgrading.

Bio-oils are precursors for biofuels but are highly corrosive necessitating further upgrading. Furthermore, bio-oil samples are highly complex and represent a broad range of chemistries. They are complex mixtures not simply because of the large number of poly-oxygenated compounds but because each composition can comprise many isomers with multiple functional groups. The use of hyphenated ultrahigh-resolution mass spectrometry affords the ability to separate isomeric species of complex mixtures. Here, we present for the first time, the use of this powerful analytical technique combined with chemical reactivity to gain greater insights into the reactivity of the individual isomeric species of bio-oils. A pyrolysis bio-oils and its esterified bio-oil were analyzed using gas chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry, and in-house software (KairosMS) was used for fast comparison of the hyphenated data sets. The data revealed a total of 10,368 isomers in the pyrolysis bio-oil and an increase to 18,827 isomers after esterification conditions. Furthermore, the comparison of the isomeric distribution before and after esterification provide new light on the reactivities within these complex mixtures; these reactivities would be expected to correspond with carboxylic acid, aldehyde, and ketone functional groups. Using this approach, it was possible to reveal the increased chemical complexity of bio-oils after upgrading and target detection of valuable compounds within the bio-oils. The combination of chemical reactions alongside with in-depth molecular characterization opens a new window for the understanding of the chemistry and reactivity of complex mixtures.

Identifying regions for enhanced control of gambiense sleeping sickness in the Democratic Republic of Congo.

Gambiense human African trypanosomiasis (sleeping sickness, gHAT) is a disease targeted for elimination of transmission by 2030. While annual new cases are at a historical minimum, the likelihood of achieving the target is unknown. We utilised modelling to study the impacts of four strategies using currently available interventions, including active and passive screening and vector control, on disease burden and transmission across 168 endemic health zones in the Democratic Republic of the Congo. Median projected years of elimination of transmission show only 98 health zones are on track despite significant reduction in disease burden under medical-only strategies (64 health zones if > 90% certainty required). Blanket coverage with vector control is impractical, but is predicted to reach the target in all heath zones. Utilising projected disease burden under the uniform medical-only strategy, we provide a priority list of health zones for consideration for supplementary vector control alongside medical interventions.

Medical care and first aid: an interassociation consensus framework for organised non-elite sport during the COVID-19 pandemic.

The cessation of amateur and recreational sport has had significant implications globally, impacting economic, social and health facets of population well-being. As a result, there is pressure to resume sport at all levels. The ongoing prevalence of SARS-CoV-2 and subsequent 'second waves' require urgent best practice guidelines to be developed to return recreational (non-elite) sports as quickly as possible while prioritising the well-being of the participants and support staff.This guidance document describes the need for such advice and the process of collating available evidence. Expert opinion is integrated into this document to provide uniform and pragmatic recommendations, thereby optimising on-field and field-side safety for all involved persons, including coaches, first responders and participants.The nature of SARS-CoV-2 transmission means that the use of some procedures performed during emergency care and resuscitation could potentially be hazardous, necessitating the need for guidance on the use of personal protective equipment, the allocation of predetermined areas to manage potentially infective cases and the governance and audit of the process.

Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo.

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to care.

Modelling the persistence and control of Rift Valley fever virus in a spatially heterogeneous landscape.

The persistence mechanisms of Rift Valley fever (RVF), a zoonotic arboviral haemorrhagic fever, at both local and broader geographical scales have yet to be fully understood and rigorously quantified. We developed a mathematical metapopulation model describing RVF virus transmission in livestock across the four islands of the Comoros archipelago, accounting for island-specific environments and inter-island animal movements. By fitting our model in a Bayesian framework to 2004-2015 surveillance data, we estimated the importance of environmental drivers and animal movements on disease persistence, and tested the impact of different control scenarios on reducing disease burden throughout the archipelago. Here we report that (i) the archipelago network was able to sustain viral transmission in the absence of explicit disease introduction events after early 2007, (ii) repeated outbreaks during 2004-2020 may have gone under-detected by local surveillance, and (iii) co-ordinated within-island control measures are more effective than between-island animal movement restrictions.