Epidemiology of bovine viral diarrhoea virus (BVDV) in Tanzanian smallholder dairy cattle | The epidemiology of bovine viral diarrhoea virus (BVDV) in Tanzanian smallholder dairy cattle

Smallholder dairy cattle are an important source of livelihood for many rural households in Tanzania providing power, food and income. The cattle and their farmers experience numerous challenges from infectious diseases such as bovine viral diarrhoea (BVD). BVD negatively impacts the livelihoods of the rural communities which make up about 70% of the Tanzanian population, affecting food security and economic stability. Understanding the epidemiology of BVD and its consequences is critical for both human and animal health, thereby making it a crucial public health concern. BVD caused by bovine viral diarrhoea virus (BVDV) is one of the most important diseases of cattle. It has a global relevance and negative impact on production, reproduction and overall herd health. It establishes an in-utero infection during the first trimester of gestation, resulting in the birth of a persistently infected (PI) animal. PI animals act as superspreaders in the herd, continuously shedding the virus via virtually all body secretions and excretions, including nasal discharges, saliva, semen, urine, tears, milk, and skin and ear notch. The challenges caused by BVDV include clinical signs such as gastrointestinal disorder, respiratory illnesses, foetal defects, stillbirths, abortion, decreased milk yields, and mucosal disease (MD). The virus causes immunosuppression, making infected animals more susceptible to other infections and allowing their effects to be more severe. Risk factors responsible for the transmission of the virus include larger herd size, animal age, introduction of new animals, and poor biosecurity on the farm. Diagnosis of BVDV can be done using a variety of antigen and antibody detection tests to help identify PI animals or transiently infected (TI) animals. Despite the high prevalence of BVDV in Tanzania, there is currently no national control or surveillance for the virus. Control is possible using interventions such as vaccinations, testand- cull, quarantine, and proper biosecurity measures on farms. A combination of these is more effective than any single intervention on its own in controlling BVDV. Modelling as a control tool can be done in the absence of interventions in a region as it allows researchers to simulate different control scenarios, estimate infection spread and investigate the best control strategy for a specific region. Economic consequences such as low birth rate, high death rate of PIs, low milk production and high costs of treatment are often associated with the virus. BVDV is poorly quantified in many countries but there is a complete lack of evidence about the economic and financial losses of the disease in Tanzania. This thesis highlights and addresses some of the knowledge gaps in the understanding of the epidemiology of BVDV in low-and middle-income countries (LMIC). It also investigates the epidemiology of BVDV in Tanzanian smallholder dairy farms, with a focus on seroprevalence, significant hotspots, risk factors, and control strategies relevant to the system in six key dairyproducing Regions of Tanzania. Several analytical methods are used to study the epidemiology of BVDV without control, the seroprevalence estimates, the most important risk factors driving the virus spread, models to study the transmission of the virus and the most feasible control methods to tackle the virus. Together, the results from the various chapters provide methods and recommendations for evidence-based policies for the control of the virus. We study the epidemiology of BVDV in Tanzanian smallholder dairy with the specific study objectives outlined below: Objective 1 - to synthesize existing knowledge on the prevalence, health impact, risk factors, and economic consequences of BVDV in low- and middle-income countries through a systematic review. Objective 2 - to estimate the seroprevalence and investigate the spatial distribution of BVDV in six key Regions of Tanzania. Objective 3 - to identify risk factors associated with BVDV seropositivity and estimate their strength of association with the outcome in smallholder dairy farms. Objective 4 - to model the potential impact of vaccination on susceptible animals and culling of PI animals on BVDV transmission within Tanzanian dairy herds. In the first analysis, Chapter 2, a systematic literature review and meta-analysis was conducted to identify current research gaps in literature in low- and middle-income countries (LMIC) for BVDV prevalence, risk factors, health and economic impacts. The study identified gaps in literature, particularly the scarcity of studies on the health and economic impact of BVDV in these settings. While there are few studies estimating the seroprevalence of BVDV in LMIC there are no studies for identifying BVDV risk factors driving the infection, and no models for controlling the virus in Tanzania. In Chapter 3, using the dataset available from the Centre for Tropical Livestock Genetics and Health (CTLGH), I conducted an antibody enzyme-linked immunosorbent assay (ELISA) test to obtain seroprevalence results and investigated the spatial pattern of BVDV in the six Regions studied. The results revealed a BVDV seroprevalence of 25.0% (95%CI:23.1-26.9), indicative of widespread exposure in smallholder dairy herds in the various Regions and identified the areas where the infection was significantly clustering. These results showed that higher seroprevalence was found in the Northern Regions and lower levels of seroprevalence were found in the Southern Regions. This suggests more virus circulation in the north compared to the south, and therefore targeting the northern areas first might be appropriate in terms of control if resources are limited. In Chapter 4, I identify the risk factors associated with BVDV seropositivity in Tanzanian smallholder dairy farms, using mixed-effect multivariable logistic regression (MMLR) models. The overall model identified herd size, management practices, animal age and prior vaccination for other diseases (foot-and-mouth disease (FMD), and contagious bovine pleuropneumonia (CBPP)) as significant risk factors for BVDV seropositivity in an overall model. The unusual association between BVDV and vaccination seemed interesting, and this led to the creation of Regional models to re-examine the seroprevalence by Region. Regional models identified possible endemic transmission in Kilimanjaro, and different drivers in the other Regions, which led to the conclusion that there was vaccine-related seropositivity in Arusha, Tanga and Iringa, while Kilimanjaro had more of an endemic transmission. The overall results show that BVDV is endemic, and the risk factors are mainly driven by animal age in Kilimanjaro, but by vaccinations in three of the other Regions. Among the possible explanation for this were: 1) vaccines contaminated with extraneous agents, or 2) poor biosecurity measures where there is unhygienic use of hypodermic needles between animals during vaccination. Finally, in Chapter 5, using mathematical modelling, I investigated the effectiveness of pulse vaccination on susceptible animals, and culling of persistently infected (PI) animals as interventions to reduce BVDV transmission. The results suggest that the virus reaches endemic equilibrium at twelve years following introduction into a naïve population, and the low prevalence of PI animals in the system will continue to maintain transmission in the absence of intervention. Strategic pulse vaccination, even with limited coverage at 20%, could limit the spread of BVDV, and coverage approaching 100% significantly reduces BVDV transmission. Pulse vaccination lowers the prevalence and mitigates disease impact within smallholder herds. Vaccination combined with culling PI animals would significantly reduce BVDV prevalence within herds. These provide policymakers with evidence for the best control methods for the Regions even in the absence of resources to implement systematic control. The analyses in this thesis highlight the complexity of BVDV circulation and the potential that (1) there are natural transmissions in Kilimanjaro, and (2) possibly some of the apparent patterns are due to vaccination in other Regions such as Arusha, Tanga and Iringa. These then raise critical concerns about vaccine contamination, biosecurity and safety at manufacturing points. For more successful control, effective vaccination protocols and biosecurity must be prioritised, and routine vaccine testing for BVDV contamination could be implemented. This will mitigate transmission and limit the consequences of BVDV such as calf deaths and other losses due to BVDV in the Tanzanian smallholder dairy system.