The transmission dynamics of Middle East Respiratory Syndrome Coronavirus in dromedary camels: implications for vaccination

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe disease in humans – with a reported case fatality ratio of 35% – and is capable of causing explosive nosocomial outbreaks. Sporadic outbreaks in the Arabian Peninsula are driven by recurring zoonotic spillover from dromedary camels (Camelus dromedarius), leading to demand for a dromedary vaccine to avert human cases. With two vaccine candidates shown to reduce viral shedding, there is an urgent need to assess the potential impact of dromedary vaccination. This is hindered, however, by poor understanding of the transmission of MERS-CoV in dromedaries and a lack of mathematical models of transmission dynamics. In this thesis, I use mathematical models to better characterise the dynamics of MERS-CoV in dromedary populations and to simulate the potential impact of vaccination. In Chapter 2, published measures of MERS-CoV infection prevalence and seroprevalence in dromedaries are systematically reviewed. In Chapter 3, age-stratified seroprevalence data from dromedary populations across Africa, the Middle East and South Asia are used to fit catalytic models of seroconversion, producing estimates of transmissibility and the rate of waning of maternally acquired antibodies. In Chapter 4, a stochastic, age-structured, dynamic transmission model of MERS-CoV in dromedaries is developed. The model is used to estimate key, epidemiological quantities including R0 and the critical community size, that give an insight into how controllable MERS-CoV is in different dromedary populations. Seasonal calving is also explored as a potential driver of peaks of infection. Finally, in Chapter 5, the dynamic model is extended to simulate vaccination under different efficacy scenarios. The potential impact of vaccination on transmission in dromedaries is evaluated, as well as the optimal age for vaccination. Alongside empirical studies, insights from dynamic models such as those developed in this thesis could contribute to informing an effective response to the zoonotic transmission of MERS-CoV.Open Acces