Biology subjects

Sikana, L.

Publications and source records attributed to Sikana, L..

3 recordsLinked to original sources

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↗

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↗