Biology subjects

Lugelo, A.

Publications and source records attributed to Lugelo, A..

6 recordsLinked to original sources

bioRxiv2024

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↗

bioRxiv2024

Reducing spatial heterogeneity in coverage improves the effectiveness of dog vaccination against rabies

Vaccination programs are the mainstay of control for many infectious diseases. Heterogeneous coverage is hypothesised to reduce vaccination programme effectiveness, but this impact has not been quantified in real systems. We address this gap using fine-scale data from two decades of rabies contact tracing and dog vaccination campaigns in Serengeti district, Tanzania. We also aimed to identify drivers of continued circulation of rabies in the district despite annual vaccination campaigns. Using generalised linear mixed models, we find that current focal (village-level) dog rabies incidence decreases with increasing recent focal vaccination coverage. However, current focal incidence depends most on recent incidence, both focally and in the wider district, consistent with high population connectivity. Removing the masking effects of prior non-focal incidence shows that, for the same average prior non-focal (wider-district) vaccination coverage, increased heterogeneity in coverage among the non-focal villages leads to increased focal incidence. These effects led to outbreaks following years when vaccination campaigns missed many villages, whereas when heterogeneity in coverage was reduced, incidence declined to low levels (<0.4 cases/1,000 dogs annually and no human deaths) and short vaccination lapses thereafter did not lead to resurgence. Through transmission-tree reconstruction, we inferred frequent incursions into the district each year (mean of 7). Inferred incursions substantially increased as a percentage of all cases in recent years, reaching 50% in 2022, suggesting regional connectivity is driving residual transmission. Overall, we empirically demonstrate how population connectivity and spatial heterogeneity in vaccination can impact disease outcomes, highlighting the importance of fine-scale monitoring in managing vaccination programs.

ecology↗

bioRxiv2023

Examining the molecular clock hypothesis for the contemporary evolution of the rabies virus

The molecular clock hypothesis assumes that mutations accumulate on an organisms genome at a constant rate over time, but this assumption does not always hold true. While modelling approaches exist to accommodate deviations from a strict molecular clock, assumptions about rate variation may not fully represent the underlying evolutionary processes. There is considerable variability in rabies virus (RABV) incubation periods, ranging from days to over a year, during which viral replication may be reduced. This prompts the question of whether modelling RABV on a per infection generation basis might be more appropriate. We investigate how variable incubation periods affect root-to-tip divergence under per-unit time and per-generation models of mutation. Additionally, we assess how well these models represent root-to-tip divergence in time-stamped RABV sequences. We find that at low substitution rates (<1 substitution per genome per generation) divergence patterns between these models are difficult to distinguish, while above this threshold differences become apparent across a range of sampling rates. Using a Tanzanian RABV dataset, we calculate the mean substitution rate to be 0.17 substitutions per genome per generation. At RABVs substitution rate, the per-generation substitution model is unlikely to represent rabies evolution substantially differently than the molecular clock model when examining contemporary outbreaks; over enough generations for any divergence to accumulate, extreme incubation periods average out. However, measuring substitution rates per-generation holds potential in applications such as inferring transmission trees and predicting lineage emergence. Author SummaryRabies is a neglected disease that kills around 60,000 people each year. After entering the body, the incubation period of the virus is usually less than one month, but can sometimes span months to years. While we normally assume a virus accumulates mutations at a constant rate, it is possible that rabies occasional long incubation periods mean that mutations accumulate at varying rates if the virus replicates (and thus mutates) more slowly during the incubation period. We compared how the rabies virus evolves over time using two simulation models where mutations either occur per unit time or per infection generation. We also calculated the mean substitution rate per infection generation, which can be useful for inferring linkage between related rabies cases. We found that at realistic substitution rates for the rabies virus, we could not distinguish between the two models. Our calculations show that in most generations no mutations are expected to occur. Thus, over a time period long enough to observe genetic divergence, occasional long incubation periods would be "cancelled out" by shorter than average incubation periods, meaning that the two models are almost equivalent. However our work suggests that modelling substitution rates per generation may be useful for epidemiological inference.

microbiology↗

bioRxiv2022

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↗

bioRxiv2021

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↗

bioRxiv2016

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↗