The epidemiology of Rift Valley fever in northern Tanzania

Rift Valley fever is a mosquito-borne viral disease of ruminants, camels and humans. In Tanzania, outbreaks have occurred at intervals of 10 - 20 years with major epidemics reported in 1977, 1997/98 and 2006/2007. Our ability to prevent future epidemics is limited by poor understanding of how the virus circulates between major epidemics. This study aimed to investigate the epidemiology of inter-epidemic RVFV infections in northern Tanzania. This study involved (a) collection and characterisation of mosquitoes; (b) RVFV serological analysis of serum samples from cattle (n=3582), sheep (n=2586), goats (n=3303) and human populations (n=565) collected through cross-sectional household surveys; (c) analysis of risk factors for livestock and human seropositivity; (d) molecular detection of RVFV in mosquitoes and diagnostic materials collected during investigation of 190 livestock abortion events. Generalised Linear Mixed-Effects Models (GLMMs) were used to examine predictors of vector mosquito abundance, and risk factors for RVFV exposure in livestock and humans. Maximum Entropy (MaxEnt) algorithm was used to model vector mosquito habitat suitability and spatial distribution. A total of 2224 mosquitoes were collected including Culex spp (n = 1123), Anopheles spp (n=1006), Mansonia spp (n=56), Aedes spp (n=34), and Coquillettidia spp (n=5) with significant variation in abundance with percentage difference in normalised difference vegetation index (NDVI). No RVFV infections were detected in any of the mosquitoes collected. RVFV seroprevalence was higher in cattle 4.4% (95% CI:3.7-5.1), than in sheep 2.6%, (95% CI: 2.0-3.3) and goats 1.4% (95%CI: 1.0-1.8), with seropositivity in young animals providing evidence of recent virus circulation. Seropositivity in livestock increased with age (OR=1.3, CI: 1.2 - 1.4, p<0.001) consistent with endemic circulation and was associated with a history of abortion in goats (OR=2.5, 95%CI: 1.1 - 5.4, P=0.023) and sheep (OR=2.7, 95%CI: 1.1 - 6.3, P=0.025). Human seroprevalence was 8.5% (95% CI: 6.4 - 11.2) and varied between villages and between households within villages. Handling of aborted material (OR=4.3, 95% CI: 1.7-10.8) and consumption of raw milk (OR=4.1, 95%CI: 1.8 - 9.3, P=0.001) were significant risk factors for human seropositivity. RVFV was detected in a cluster of 14 (7.4%) abortion cases including the milk of three aborting dams. This provides strong evidence for continuous RVFV circulation in livestock between major epidemics in Tanzania and that unboiled milk is an important potential source of infection for people

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

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

Enhanced immunosurveillance for animal morbilliviruses using vesicular stomatitis virus (VSV) pseudotypes

The measurement of virus-specific neutralising antibodies represents the “gold-standard” for diagnostic serology. For animal morbilliviruses, such as peste des petits ruminants (PPRV) or rinderpest virus (RPV), live virus-based neutralisation tests require high-level biocontainment to prevent the accidental escape of the infectious agents. In this study, we describe the adaptation of a replication-defective vesicular stomatitis virus (VSVΔG) based pseudotyping system for the measurement of neutralising antibodies against animal morbilliviruses. By expressing the haemagglutinin (H) and fusion (F) proteins of PPRV on VSVΔG pseudotypes bearing a luciferase marker gene, neutralising antibody titres could be measured rapidly and with high sensitivity. Serological responses against the four distinct lineages of PPRV could be measured simultaneously and cross-neutralising responses against other morbilliviruses compared. Using this approach, we observed that titres of neutralising antibodies induced by vaccination with live attenuated PPRV were lower than those induced by wild type virus infection and the level of cross-lineage neutralisation varied between vaccinates. By comparing neutralising responses from animals infected with either PPRV or RPV, we found that responses were highest against the homologous virus, indicating that retrospective analyses of serum samples could be used to confirm the nature of the original pathogen to which an animal had been exposed. Accordingly, when screening sera from domestic livestock and wild ruminants in Tanzania, we detected evidence of cross-species infection with PPRV, canine distemper virus (CDV) and a RPV-related bovine morbillivirus, suggesting that exposure to animal morbilliviruses may be more widespread than indicated previously using existing diagnostic techniques

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

Human and animal seroprevalence data collected in northern Tanzania between 2013 and 2015. Used for the analysis of the paper titled "Inter-epidemic Rift Valley fever virus infection in livestock and risks for zoonotic spillover in northern Tanzania"

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

Background: Human and animal cases of Rift Valley fever (RVF) are typically only reported during large outbreaks. The occurrence of RVF cases that go undetected by national surveillance systems in the period between these outbreaks is considered likely. The last reported cases of RVF in Tanzania occurred during a large outbreak in 2007–2008. Methods: Samples collected between 2017 and 2019 from livestock suffering abortion across northern Tanzania were retrospectively tested for evidence of RVF virus infection using serology and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: A total of 14 RVF-associated cattle abortions were identified among dairy cattle in a peri-urban area surrounding the town of Moshi. RVF cases occurred from May to August 2018 and were considered to represent an undetected, small-scale RVF outbreak. Milk samples from 3 of 14 cases (21%) were found to be RT-qPCR positive. Genotyping revealed circulation of RVF viruses from two distinct lineages. Conclusions: RVF outbreaks can occur more often in endemic settings than would be expected on the basis of detection by national surveillance. The occurrence of RVF cases among peri-urban dairy cattle and evidence for viral shedding in milk, also highlights potentially emerging risks for RVF associated with increasing urban and peri-urban livestock populations