Inter-epidemic Rift Valley fever virus infection incidence and risks for zoonotic spillover in northern Tanzania.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that has caused epidemics involving people and animals across Africa and the Arabian Peninsula. A number of studies have found evidence for the circulation of RVFV among livestock between these epidemics but the population-level incidence of infection during this inter-epidemic period (IEP) is rarely reported. General force of infection (FOI) models were applied to age-adjusted cross-sectional serological data to reconstruct the annual FOI and population-level incidence of RVFV infection among cattle, goats, and sheep in northern Tanzania from 2009 through 2015, a period without reported Rift Valley fever (RVF) cases in people or animals. To evaluate the potential for zoonotic RVFV spillover during this period, the relationship between village-level livestock RVFV FOI and human RVFV seropositivity was quantified using multi-level logistic regression. The predicted average annual incidence was 72 (95% Credible Interval [CrI] 63, 81) RVFV infections per 10,000 animals and 96 (95% CrI 81, 113), 79 (95% CrI 62, 98), and 39 (95% CrI 28, 52) per 10,000 cattle, sheep, and goats, respectively. There was variation in transmission intensity between study villages, with the highest estimated village-level FOI 2.49% (95% CrI 1.89, 3.23) and the lowest 0.12% (95% CrI 0.02, 0.43). The human RVFV seroprevalence was 8.2% (95% Confidence Interval 6.2, 10.9). Human seropositivity was strongly associated with the village-level FOI in livestock, with the odds of seropositivity in an individual person increasing by around 1.2 times (95% CrI 1.1, 1.3) for each additional annual RVFV seroconversion per 1,000 animals. A history of raw milk consumption was also positively associated with human seropositivity. RVFV has circulated at apparently low levels among livestock in northern Tanzania in the period since the last reported epidemic. Although our data do not allow us to confirm human RVFV infections during the IEP, a strong association between human seropositivity and the FOI in cattle, goats, and sheep supports the hypothesis that RVFV circulation among livestock during the IEP poses a risk for undetected zoonotic spillover in northern Tanzania. We provide further evidence for the likely role of raw milk consumption in RVFV transmission from animals to people. Author summary: Rift Valley fever outbreaks are reported in Tanzania every 10 to 15 years. Human and animal cases are not typically reported in the period between outbreaks, but the RVF virus (RVFV) is known to circulate among livestock during these periods. The last officially reported outbreak of RVF in Tanzania was in 2008. The incidence of RVFV infection among livestock in the period since this large epidemic in the country is not known. We used a general force of infection model to quantify the annual incidence of RVFV infection among livestock in northern Tanzania between 2009 and 2015, a period without reported RVF cases in people or animals. Using a sample of over 9,000 animals from 43 villages across northern Tanzania, we estimated a moderately low average annual incidence of 96, 39, and 79 RVFV infections per 10,000 cattle, goats, and sheep, respectively. There was considerable heterogeneity in the intensity of transmission between villages, highlighting important spatial differences in inter-epidemic RVFV transmission among livestock in this region. We also found that human seropositivity was strongly positively associated with the village-level force of RVFV infection among livestock. All people with seropositive results in this study were born before 2008. We therefore cannot be certain that these people were infected in the period since the last outbreak. However, the very strong positive association we find between inter-epidemic circulation of RVFV among livestock and human seropositivity provides support to the hypothesis that zoonotic RVFV spillover may be occuring during the period between large-scale outbreaks in northern Tanzania. Further studies are required to confirm this. We also found a strong positive association between a history of raw milk consumption and human RVFV seropositivity, providing further evidence for the importance of milk as a likely route for zoonotic RVFV transmission. [ABSTRACT FROM AUTHOR]