MERS Coronavirus at the Human - Animal Interface

M. Elmoubashar Farag (2019)
Thèse doctorale soutenue au Centre Erasmus de Rotterdam (Qatar), 231p

Résumé (en anglais)

The reporting of human cases of MERS-CoV in Qatar during 2012 has sparked intensive investigative efforts to identify factors that might have influenced the emergence, transmission and spread of MERS-CoV. A “One Health” approach was found to be the most feasible and practical way to study the human and animal dynamics in relation to MERSCoV. Recognizing interconnection of human and veterinary health, “One Health” uses a multidisciplinary and cross-sectorial approach to address (re)emerging risks that originate at the animal-human-ecosystems interface. We explored the strengths and challenges faced by health system partners in preparing for and responding to the MERS-CoV epidemic. The objective of this thesis was to gain knowledge on the ecology and epidemiology of MERS-CoV in Qatar and to enable evidence-based prevention and intervention strategies to reduce the risk of infections at human-animal interface. Additionally, it reviews the current epidemiology and clinical presentation of MERS-CoV infection while describing the preparedness plans to combat the disease.
A comprehensive literature review was conducted in order to determine the gaps in knowledge about MERS-CoV infection at human-animal interface and to lay the foundation for the overall research studies conducted in this thesis (Chapter 1). To better understand the emergence and modes of transmission of MERS-CoV infection in Qatar, a descriptive epidemiological investigation of MERS human cases in Qatar was conducted (Chapter 2).
Camel workers were found seropositive for viral antibody in West Qatar (Chapter 3). The case-control study showed that participants who were found seropositive were more involved in camel training and herding, cleaning farm equipment, or milking camels. In addition, seropositive workers were less likely to wash their hands before and after animal contact and were more likely to handle camels that travelled abroad. Contact with camel excretions and subsequent touching of mucous membranes was likely an important source of infection. The identified risk factors can be used to establish infection prevention and control measures for MERS-CoV by introducing farm biosecurity system. (Chapter 3).
With the objective to design prevention measures as well as explaining the reportedly high MERS-COV mortality rate, a population-based serosurvey was conducted among camel-contact versus non-camel contact personnel (Chapter 4). Serum-neutralizing antibodies were only detected among camel-contact persons of the 498 randomly sampled sera, suggesting exposure to dromedary as a major risk factor for the infection. Further, upon studying exposure risk factors for MERS-CoV, a high risk was shown by not using personal protection equipment for workers at Doha slaughterhouse (Chapter 4). When investigating MERS-CoV shedding patterns, a high proportion of camels presented for slaughter in Qatar showed significant evidence for nasal MERS-CoV shedding compared to both fecal and oral shedding. This led to the conclusion that nasal swabs constitute the samples of choice for diagnosis and surveillance of MERS-CoV in camels (Chapter 5.2). Sequence analysis showed that at least five different virus strains were found to be circulating in Qatar, suggesting the slaughterhouse in Doha as a driver of MERS-CoV perpetuation as well as a high-risk area for human exposure. As no correlation was observed between RNA loads and the levels of neutralizing antibodies among examined camels, it was inferred that the immune protection is limited and the potential for reinfection is likely regardless previous exposure (Chapter 4 and Chapter 5.1). After MERS-CoV was first isolated from camels, the phylogenetic analysis of the complete genome clearly showed that MERS-CoV camel/Qatar_2_2014 was very similar to human MERS-CoV. It was also the closest relative to MERS-CoV England/Qatar1 2012 (Chapter 5.2). These data supported the hypothesis that dromedary camels are a reservoir for MERS-CoV and can transmit the infection to humans. The evidence for a possible role of food-borne of MERS-CoV infection was investigated. Camel milk and urine were collected form the high risk areas. We found MERS-CoV specific antibodies in urine samples while all camels showed such evidence for a (previous) MERSCoV infection in serum (Chapter 5.3). Raw milk samples were tested for anti-MERS-CoV antibodies using both protein microarray assay and virus neutralization with parallel testing of serum, nasal and rectal swabs for multiple genomic targets. All sera and milk samples were positive for MERS-CoV antibodies. Moreover, the presence of MERS-CoV RNA in milk of camels which actively shed the virus warrants measures to prevent putative food borne transmission of MERS-CoV (Chapter 5.4).
A case study describes how One Health approach was initiated and used to develop and establish surveillance and response to MERS-CoV in Qatar during 2012 (Chapter 6). Initial emergency response actions were identified through the Qatar national outbreak control task force including a joint national human-animal health investigation team. Requesting inputs from several international organizations, a comprehensive roadmap for MERSCoV surveillance and response on the human-animal interface for Qatar was generated. Research findings were used to provide national and international guidance for studies and prevention measures. A survey was conducted among the governmental health and veterinary authorities to monitor preparedness and response to MERS-CoV epidemic through ‘One-Health’ approach (Chapter 7). Nominating lack of political will as one of the key gaps to adopt ‘One-Health’, that was also mentioned in ‘Doha Declaration’ to take the epidemic as a chance to promote the inter-sectorial collaboration to contain MERS-CoV epidemic and to enhance preparedness to combat other possible future emerging zoonotic diseases.
To provide an overview of current knowledge on the distribution, spread and risk factors of infections in dromedary camels, a systematic review was carried out where published data MERS-CoV was compiled and analysed. (Chapter 8). Camels only show minor clinical signs of disease after being infected with MERS-CoV. Serological evidence of MERS-CoV in camels has been found in 20 countries, with molecular evidence for virus circulation in 13 countries. The seroprevalence of MERS-CoV antibodies increases with age in camels, while the prevalence of viral shedding MERS-CoV RNA detection in nasal swabs decreases as determined by. In several studies, camels that were sampled at animal markets or quarantine facilities were seropositive compared to those at farms as well as imported camels vs. locally bred camels. Some studies show a relatively higher seroprevalence and viral detection during the cooler winter months. Knowledge of the animal reservoir of MERS-CoV is essential to develop intervention and control measures to prevent human infections (Chapter 8).
To identify and quantify key possible drivers that might have contributed to the MERSCoV emergence and spread in Qatar (Chapter 9), a list of potential human, animal and environmental drivers for disease emergence were identified utilizing literature review, database analysis, and expert opinions. Observing that the discovery and subsequent exploitation of oil and gas has led to a fivefold increase of Qatar GDP and a seven-fold increase in the population in the past 30 years, the resulting increase in income has gradually transformed lifestyle from Bedouin life to urban sedentary life. The subsequent flourishing of the governmental-supported culturally embedded camel sector has led as early as 1990 to duplication of the camel numbers. Experiencing overgrazing and desertification, open grazing was banned in 2005. Replacing this with compact barn housing, camels, camel attendants and other animal species were forced to live in contact and significantly cross borders to seek new grazing areas. Such major habitual changes might have offered the virus the right circumstance to spill over from camels to humans and spread throughout Northern Africa and the Middle East (Chapter 9).
An integrated framework for One Health and camel farm Biosecurity was proposed as a practical strategy to prevent and control MERS-CoV and other zoonoses at the humananimal interface (Chapter 10).

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