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Cleaveland, S.

Publications and source records attributed to Cleaveland, S..

14 recordsLinked to original sources

Rift Valley fever virus dynamics in a transhumant cattle system in The Gambia

Rift Valley fever (RVF) is a zoonotic disease of global concern, driven by environmental conditions, vector activity, and livestock mobility. Although RVF has been reported in The Gambia, its epidemiology remains poorly understood. This study developed a compartmental model to study RVF dynamics in the cattle population of the country. The model incorporated seasonally dynamic transmission parameters reflecting transhumant movement and ecological differences between two distinct ecoclimatic regions: the Sahelian area and the Gambia river. Parameterised using serological data linked to household survey data, the model predicted endemic RVF virus (RVFV) circulation within The Gambia, and captured temporal infection trends that closely match empirical data. Weak decay rates of seropositivity were required to match predicted and observed age-seroprevalence. Results indicated sustained RVFV transmission during the dry season in the Gambia river eco-region, with a high risk of seasonal virus introductions to the Sahelian eco-region at the start of the wet season via the returning transhumant cattle. Our study highlighted the role of livestock mobility in RVFV epidemiology in The Gambia and the need for targeted control strategies that might include, for example, targeted cattle vaccination or application of topical insecticide treatments for transhumant herds.

ecology↗

Sero-epidemiology of Rift Valley fever virus in ruminant livestock in The Gambia

Rift Valley fever (RVF) virus is a globally significant zoonotic pathogen primarily transmitted by mosquitoes, causing abortion storms and neonatal mortality in ruminant livestock and haemorrhagic encephalitis in humans. Although localized RVF outbreaks occur frequently in the West Africa Sahel, the complex interplay between vectors, ruminant hosts, human behaviours, and ecoclimatic factors driving these outbreaks remains unclear. In 2022, we conducted a cross-sectional study across The Gambia that collected serum samples linked to questionnaire data from 202 randomly selected livestock-owning households to estimate population-level seroprevalence, investigate the patterns of, and identify risk factors associated with RVFV seropositivity in ruminant livestock. Design adjusted seroprevalence estimates were 36.8% (95% Confidence Interval [CI]: 31.6-40.0) for cattle (n = 1416), 2.1% (95% CI: 0.5-3.7) for goats (n = 1101) and 4.3% (95% CI: 1.2-7.4) for sheep (n = 1085) using the IDScreen(R) RVF c-ELISA assay. The intracluster correlation coefficients for RVFV seropositivity at the herd level were 0.13 (95% CI: 0.09-0.18) in cattle and 0.22 (95% CI: 0.06-0.31) in small ruminants on the logit scale. Risk factors associated with RVFV seropositivity were investigated using a LASSO regression, with transhumant movement to the Gambia river valley, increasing age, introduction of new ruminants, and proximity to water identified as most strongly associated with seropositivity. By fitting the serologic data to a catalytic force of infection (FOI) model, age-independent FOI estimates of 0.12 (95% Credible Interval [CrI]: 0.10-0.16) for cattle and 0.013 (95% CrI: 0.01-0.02) for small ruminants were obtained. The observed patterns of RVFV seropositivity indicate widespread and endemic viral circulation, with livestock management practices and the Gambia river floodplains likely sustaining transmission. The high seroprevalence in cattle raises concerns that sporadic outbreaks may have occurred unnoticed or unreported, underscoring the critical need for comprehensive One Health surveillance to identify potential clinical cases.

ecology↗

A randomized controlled trial of the effectiveness of a community-based rabies vaccination strategy

BackgroundApproximately 60,000 people die from dog-mediated rabies annually. Low and heterogeneous coverage reduces the effectiveness of dog vaccination campaigns that can eliminate rabies. Campaigns typically involve teams travelling annually to villages to deliver cold chain stored vaccines from centralized headquarters. Thermotolerant vaccines enable novel decentralized delivery of locally-stored vaccines by communities throughout the year. We compared the effectiveness of annual team-based versus continuous community-based dog vaccination strategies. MethodsWe conducted a cluster randomized controlled trial across Mara region, Tanzania. Trial clusters were administrative wards (112, on average four villages each). For the team-based arm vaccinators hosted annual static-point clinics, whilst for the community-based arm, a ward-based animal health officer with a village community leader managed vaccinations using vaccines stored within the ward. We measured vaccination coverage, the primary outcome, twice annually per cluster (month 1 and 11) through household surveys over three years (November 2020 to October 2023) and examined spatial and temporal coverage variations as secondary outcomes. FindingsCommunity-based delivery achieved significantly higher coverage (49-62%) than team-based delivery (22-46%), and consistently exceeded the critical threshold for herd immunity (40%), Odds ratio (OR): 1.48-3.49. The lower less uniform coverage achieved through team-based delivery had a higher monthly probability of falling below the critical threshold (0.6, 95% CI: 0.38-0.81) vs 0.18 (95% CI: 0.04-0.40). Greater declines in coverage over the year were recorded in the team-based arm compared to the community-based ConclusionCommunity-based mass dog vaccination achieves higher more consistent coverage than team-based delivery across settings typical of many sub-Saharan African countries. This approach could play an important role in national rabies elimination programmes aiming to end human rabies deaths by 2030 as part of the global zero by 30 strategy. FundingDepartment of Health and Human Services of the National Institutes of Health (R01AI141712), Wellcome Trust (207569/Z/17/Z, 224520/Z/21/Z) and MSD Animal Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

immunology↗

Modelling resource-driven movements of livestock herds to predict the impact of climate change on network dynamics

In East Africa, climate change is likely to profoundly impact livestock management and the potential spread of infectious diseases. Here, we developed a network model to describe livestock movements to grazing and watering sites, fitted it to data from the Serengeti district of Tanzania, and used it to explore how projected changes in resource availability due to climate change could impact future network structures and therefore infectious disease risks, using 2050 and 2080 as exemplar scenarios. Our modelled networks show increased connections between villages in grazing and watering networks, with connectivity increasing further in the future in correspondence with changes in vegetation and water availability. Our analyses show that targeted interventions to efficiently control regional disease spread may become more difficult, as village connectivity increases and disease vulnerability becomes more evenly distributed. This analysis also provides proof of principle for a novel approach applicable to agropastoral settings across many developing countries, where livestock trade plays a crucial role in maintaining local livelihoods but also in spreading disease.

ecology↗

The value of livestock abortion surveillance in Tanzania: identifying disease priorities and informing interventions

BackgroundLack of reliable data on the aetiology of livestock diseases, especially in Africa, is a major factor constraining the design of effective livestock health interventions to improve livelihoods, food security and public health. RationaleLivestock abortion is an important disease syndrome that affects productivity and livestock economies, and poses risks to public health. Worldwide, several pathogens are associated with livestock abortions but across Africa livestock disease surveillance data rarely include information from abortion events, little is known about the aetiology and impacts of livestock abortions, and data are not available to inform prioritisation of disease interventions. MethodsThis paper describes outcomes from a surveillance platform that was set up in 15 wards in northern Tanzania spanning pastoral, agropastoral and smallholder agro-ecological systems to investigate the causes and impacts of livestock abortion. Abortion cases were reported by farmers to Ministry of Livestock and Fisheries livestock field officers and on to investigation teams. The abortion was eligible for inclusion if the research field team or livestock field officer could attend within 72 hours of the event occurring. If so, a field investigation was carried out to collect diagnostic samples from aborted materials and aborting dams and questionnaire data on herd/flock management. Laboratory diagnostic tests were carried out for a range of abortigenic pathogens, and laboratory and questionnaire data analysed to investigate a) determinants of attribution; b) patterns of investigated events, including species and breed affected, previous abortion history and recent stressful events, and the seasonality of cases; c) determinants of reporting, investigation and attribution; (d) cases in which zoonotic pathogens were detected. ResultsOver a two-year period (2017-2019), 215 abortion events in cattle (n=71), sheep (n=44) and goats (n=100) were investigated from 13 of the 15 wards. The number of investigated cases varied widely across wards, with three of the 15 field officers (20%) reporting 70% of investigated cases. Aetiological attribution, achieved for 19.5% of cases through PCR-based diagnostics, was significantly affected by delays in obtaining samples from field investigation. Histopathology proved less useful than PCR diagnostics due to rapid deterioration of field samples. Vaginal swabs from aborting dams provided a practical and sensitive source of diagnostic material for pathogen detection. Discussion / ConclusionLivestock abortion surveillance, even at a small scale and when capturing only a small proportion of events, can generate valuable information on causes of zoonotic disease outbreaks, livestock reproductive losses and can identify important pathogens that are not easily captured through other forms of livestock disease surveillance. This study demonstrated the feasibility of establishing an effective reporting and investigation system that could be implemented across a range of settings, including remote rural areas. This has been achieved through effective engagement of community-based field officers, establishment of practical sample collection protocols and application of molecular diagnostic platforms.

zoology↗

Localized Rift Valley Fever Virus Persistence Depends on a High Transovarial Transmission Fraction

Rift Valley fever virus (RVFV) has spread beyond continental Africa and threatens to follow West Nile, chikungunya and Zika viruses into the Americas. Its impact in new localities and the capacity to control future outbreaks, depends on whether and how RVFV persists at small spatial scales. Transovarial transmission (TOT) is hypothesized as an important mechanism for local persistence, yet its role in RVFV ecology remains poorly understood. We examine whether RVFV can persist locally via TOT while maintaining a realistic seroprevalence pattern of interepidemic and epidemic transmission. We developed a mechanistic, compartmental model of RVFV dynamics within a single host (sheep) and two vector (mosquito) populations, driven by temperate climatic factors. Decades-long persistence was possible in our simulations, which generally captured the observed outbreak patterns in central South Africa with a mean annual seroprevalence ([~]23%) within the range reported during interepidemic periods (5-40%). Persistence was only possible with a substantial TOT fraction and over a narrow range of parameters. The basic reproduction number (R0) was close to one at mean vector population sizes, suggesting a relatively limited expansion of the infected vector population during outbreaks. This limited expansion provides the system with the flexibility to support both low-level transmission and large outbreaks and, counterintuitively, large outbreaks resulted in smaller infected Aedes egg populations. This has important consequences for control: low-level vaccination may prevent large outbreaks without eliminating RVFV and local control efforts may be most effective immediately following an outbreak, suggesting elimination may be possible after emergence in temperate regions.

ecology↗

Modelling the effectiveness of targeting Rift Valley fever virus vaccination using imperfect network information

Livestock movements contribute to the spread of several infectious diseases. Data on livestock movements can therefore be harnessed to guide policy on targeted interventions for controlling infectious livestock diseases, including Rift Valley fever (RVF) -- a vaccine-preventable arboviral fever. While detailed livestock movement data are available in many countries, such data are generally lacking in others, including many in East Africa, where multiple RVF outbreaks have been reported in recent years. Available movement data are imperfect, and the impact of imperfect movement data on targeted vaccination is not fully understood. Here, we used a network simulation model to describe the spread of RVF within and between 398 wards in northern Tanzania connected by cattle movements, on which we evaluated the impact of targeting vaccination using imperfect movement data. We show that pre-emptive vaccination guided by only market movement permit data could prevent large outbreaks. Targeted control (either by the risk of RVF introduction or onward transmission) at any level of imperfect movement information is preferred over random vaccination, and any improvement in information reliability is advantageous to their effectiveness. Our modelling approach demonstrates how targeted interventions can be carefully applied to inform animal and public health policies on disease control planning in settings where detailed data on livestock movements are unavailable or imperfect due to a lack of data-gathering resources.

genetics↗

Development, feasibility and potential effectiveness of community-based continuous mass dog vaccination delivery strategies: lessons for optimization and replication

ObjectivesDog vaccination can eliminate rabies, but annual delivery strategies do not sustain vaccination coverage between campaigns. We describe the development of a community-based continuous mass dog vaccination (CBC-MDV) approach designed to improve and maintain vaccination coverage in Tanzania and examine the feasibility of delivering this approach as well as lessons for its optimization. MethodsWe developed three delivery strategies of CBC-MDV and tested them against the current annual vaccination strategy following the UK MRCs guidance: i) developing an evidence-based theoretical framework of intervention pathways and ii) piloting to test feasibility and inform optimization. For our process evaluation of CBC-MDV we collected data using non-participant observations, meeting reports and implementation audits and in-depth interviews, as well as household surveys of vaccination coverage to assess potential effectiveness. We analyzed qualitative data thematically and quantitative data descriptively. ResultsThe final design included delivery by veterinary teams supported by village-level one health champions. In terms of feasibility, we found that less than half of CBC-MDVs components were implemented as planned. Fidelity of delivery was influenced by the strategy design, implementer availability and appreciation of value intervention components, and local environmental and socioeconomic events (e.g. elections, funerals, school cycles). CBC-MDV activities decreased sharply after initial campaigns, partly due to lack of supervision. Community engagement and involvement was not strong. Nonetheless, the CBC-MDV approaches achieved vaccination coverage above the critical threshold (40%) all-year-round. CBC-MDV components such as identifying vaccinated dogs, which village members work as one health champions and how provision of continuous vaccination is implemented need further optimization prior to scale up. InterpretationCBC-MDV is feasible to deliver and can achieve good vaccination coverage. Community involvement in the development of CBC-MDV, to better tailor components to contextual situations, and improved supervision of activities are likely to improve vaccination coverage in future. AUTHOR SUMMARYAnnual mass dog vaccination campaigns that reach at least 70% of the dog population, should maintain sufficient herd immunity between campaigns to interrupt rabies transmission. However, it is often challenging to reach 70% of the dog population with annual vaccination campaigns. We hypothesized that a community-based continuous approach to dog vaccination could better maintain high levels of vaccination coverage all-year-round. We describe the development of a community-based continuous approach to dog vaccination in Tanzania, and assessed the feasibility of delivering its components, its potential effectiveness and lessons for its optimization. We found that the approach was well accepted, as its development involved key stakeholders. Although less than half of the components of the community-based continuous approach were delivered exactly as planned, over 70% of dogs were vaccinated and the approach maintained coverage above the critical vaccination threshold throughout the year. We conclude that it is feasible to deliver a community-based continuous approach to dog vaccination, but that some components need further improvement; more supervision and community involvement should lead to better outcomes.

immunology↗

Spatial scale of transmission explains how acute infections circulate at low prevalence

Fundamental questions remain about the regulation of acute pathogens in the absence of acquired immunity. This is especially true for canine rabies, a universally fatal zoonosis. From tracing rabies transmission in a population of 50,000 dogs in Tanzania between 2002-2016 we unravel the processes through which rabies is regulated and persists, fitting individual-based models to spatially-resolved data to investigate the mechanisms modulating transmission and the scale over which they operate. We find that while prevalence never exceeds 0.15%, we detect significant susceptible depletion at local scales commensurate with rabid dog movement, reducing transmission through clustering of rabies deaths and individuals incubating infection. Individual variation in rabid dog behaviour facilitates virus dispersal and co-circulation of lineages, enabling metapopulation persistence. These mechanisms likely operate in many pathogens circulating in spatially structured populations, with important implications for prediction and control, yet are unobservable unless the scale of host interactions is identified. One-Sentence SummaryIdentifying the spatial scale of contact reveals the mechanisms that limit the size of rabies outbreaks and that are critical for predicting transmission dynamics.

ecology↗

An outbreak of Rift Valley fever among peri-urban dairy cattle in northern Tanzania, 2018

Undetected Rift Valley fever (RVF) outbreaks are expected in endemic countries but little is known about their size or frequency. We describe a previously unreported RVF outbreak involving dairy cattle that appeared to be limited to the edge of the town of Moshi, Tanzania and occurred from May through August, 2018. The outbreak was detected retrospectively using samples collected as part of a cohort study investigating the causes of livestock abortion across northern Tanzania. A total of 14 RVF-associated cattle abortions were identified using a combination of serology and quantitative reverse transcription PCR (RT-qPCR). Milk samples from three (21%) of 14 cases were also RT-qPCR positive. Genotyping revealed circulation of RVF viruses from two lineages. The occurrence of an RVF outbreak among peri-urban dairy cattle, and evidence for RVF viral shedding in milk, highlights the potential for emerging zoonotic risks associated with the growth of urban and peri-urban livestock populations.

ecology↗

Prospective cohort study reveals unexpected aetiologies of livestock abortion in northern Tanzania

Livestock abortion is an important cause of productivity losses worldwide and many infectious causes of abortion are zoonotic pathogens that impact on human health. Little is known about the relative importance of infectious causes of livestock abortion in Africa, including in subsistence farming communities that are critically dependent on livestock for food, income, and wellbeing. We conducted a prospective cohort study of livestock abortion, supported by cross-sectional serosurveillance, to determine aetiologies of livestock abortions in livestock in Tanzania. This approach generated several important findings including detection of a Rift Valley fever virus outbreak in cattle; high prevalence of C. burnetii infection in livestock; and the first report of Neospora caninum, Toxoplasma gondii, and pestiviruses associated with livestock abortion in Tanzania. Our approach provides a model for abortion surveillance in resource-limited settings. Our findings add substantially to current knowledge in sub-Saharan Africa, providing important evidence from which to prioritise disease interventions.

systems biology↗

Classification and characterisation of livestock production systems in northern Tanzania

Livestock keepers in sub-Saharan Africa face a growing range of pressures, including climate change, land loss, restrictive policies, and population increase. Widespread adaptation in response to such pressures can lead to the emergence of new, non-traditional typologies of livestock production. We sought to characterise livestock production systems in northern Tanzania, a region undergoing rapid social, economic, and environmental change. Questionnaire and spatial data were collected from 404 livestock-keeping households in 21 villages in Arusha and Manyara Regions in 2016. Multiple factor analysis and hierarchical cluster analysis were used to classify households into livestock production systems based on household-level characteristics. Indicators of vulnerability, including household-level reports of hunger, illness, livestock loss, land loss and crop losses were compared between production systems. Three distinct clusters emerged through this process. The ethnic, environmental and livestock management characteristics of households in each cluster broadly mapped onto traditional definitions of pastoral, agro-pastoral and smallholder livestock production in the region, suggesting that this quantitative classification system is complementary to more qualitative classification methods. Our findings also suggest that traditional systems of livestock production continue to persist in northern Tanzania. Nonetheless, we found indicators of substantial change within livestock production systems, most notably the adoption of crop agriculture in the majority of pastoral households. Smallholder households were less likely than either pastoral or agro-pastoral households to report hunger, illness, and livestock, land or crop losses. Livelihoods that rely solely on livestock are relatively rare in northern Tanzania, which represents an important shift in production in the region, particularly among pastoralists. Policy initiatives to improve household and community well-being should recognise the continuing distinctiveness of traditional livestock production systems in the region.

systems biology↗

Identifying age cohorts responsible for Peste des petits ruminants virus transmission among sheep, goats, and cattle in northern Tanzania

Peste des petits ruminants virus (PPRV) causes a contagious disease of high morbidity and mortality in global sheep and goat populations and leads to approximately $2 billion USD in global annual losses. PPRV is currently targeted by the Food and Agricultural Organization and World Animal Health Organization for global eradication by 2030. To better control this disease and inform eradication strategies, an improved understanding of how PPRV risk varies by age is needed. Our study used a piece-wise catalytic model to estimate the age-specific force of infection (FOI, per capita infection rate of susceptible hosts) among sheep, goats, and cattle from a cross-sectional serosurvey dataset collected in 2016 in Tanzania. Apparent seroprevalence rose with age, as would be expected if PPRV is a fully-immunizing infection, reaching 53.6%, 46.8%, and 11.6% (true seroprevalence: 52.7%, 52.8%, 39.2%) for sheep, goats, and cattle, respectively. Seroprevalence was significantly higher among pastoral animals than agropastoral animals across all ages, with pastoral sheep and goat seroprevalence approaching 70% and 80%, respectively, suggesting endemicity in pastoral settings. The best fitting piece-wise catalytic models included merged age groups: two age groups for sheep, three age groups for goats, and four age groups for cattle. However, the signal of these age heterogeneities was weak, with overlapping confidence intervals around force of infection estimates from most models with the exception of a significant FOI peak among 2.5-3.5 year old pastoral cattle. Pastoral animals had a higher force of infection overall, and across a wider range of ages than agropastoral animals. The subtle age-specific force of infection heterogeneities identified in this study among sheep, goats, and cattle suggest that targeting control efforts by age may not be as effective as targeting by other risk factors, such as management system type. Further research should investigate how specific husbandry practices affect PPRV transmission. Author SummaryAge differences in transmission are important for many infections, and can help target control programs. We used an age-structured serosurvey of Tanzanian sheep, goats, and cattle to explore peste des petits ruminants virus transmission. We estimated rate at which susceptibles acquire infection (force of infection) to determine which age group(s) had the highest transmission rates. We hypothesized that an age-varying model with multiple age groups would better fit the data than an age constant model and that the highest transmission rates would appear in the youngest age groups. Furthermore, we hypothesized evidence of immunity would increase with age. The data supported our hypothesis at the species level and the best fitting models merged age groups: two, three, and four age group models were best for sheep, goats, and cattle, respectively. The highest rates occurred among younger age groups and evidence of immunity rose with age for all species. In most models, confidence interval estimates overlapped, but there was a significant FOI peak among 2.3-3.5 year old pastoral cattle. Importantly, these data indicate that there is not sufficient evidence to support targeted control by age group, and that targeted control based on production system should be more effective.

ecology↗

Surveillance to Establish Elimination of Transmission and Freedom from Dog-mediated Rabies

BackgroundWith a global target set for zero human deaths from dog-mediated rabies by 2030 and some regional programmes close to eliminating canine rabies, there is an urgent need for enhanced surveillance strategies suitable for declaring freedom from disease and elimination of transmission with known confidence.\n\nMethodsUsing exhaustive contact tracing across settings in Tanzania we generated detailed data on rabies incidence, rabid dog biting behaviour and health-seeking behaviour of bite victims. Using these data we compared case detection of sampling-based and enhanced surveillance methodologies and investigated elimination verification procedures.\n\nFindingsWe demonstrate that patients presenting to clinics with bite injuries are sensitive sentinels for identifying dog rabies cases. Triage of patients based on bite history criteria and investigation of suspicious incidents can confirm >10% of dog rabies cases and is an affordable approach that will enable validation of disease freedom following two years without case detection. Approaches based on sampling the dog population without using bite-injury follow-up were found to be neither sensitive nor cost-effective.\n\nInterpretationThe low prevalence of rabies, and short window in which disease can be detected, preclude sampling-based surveillance. Instead, active case finding guided by bite-patient triage is needed as elimination is approached. Our proposed methodology is affordable, practical and supports the goal of eliminating human rabies deaths by improving administration of lifesaving post-exposure prophylaxis for genuinely exposed but untreated contacts. Moreover, joint investigations by public health and veterinary workers will strengthen intersectoral partnerships and capacity for control of emerging zoonoses.

epidemiology↗