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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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