Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1

Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia:a descriptive genomic study

BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85-95%, and four 30-50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre

Meningococcal disease during the Hajj and Umrah mass gatherings

The Hajj and Umrah religious mass gatherings hosted by the Kingdom of Saudi Arabia can facilitate the transmission of infectious diseases. The pilgrimages have been associated with a number of local and international outbreaks of meningococcal disease. These include serogroup A disease outbreaks in 1987 and throughout the 1990s and two international serogroup W135 outbreaks in 2000 and 2001. The implementation of strict preventative measures including mandatory quadrivalent meningococcal vaccination and antibiotic chemoprophylaxis for pilgrims from the African meningitis belt has prevented pilgrimage-associated meningococcal outbreaks since 2001. However, the fluid epidemiology of the disease and the possibility of outbreaks caused by serogroups not covered by the vaccine or emerging hyper-virulent strains, mean that the disease remains a serious public health threat during these events. Continuous surveillance of carriage state and the epidemiology of the disease in the Kingdom and globally and the introduction of preventative measures that provide broad and long-lasting immunity and impact carriage are warranted

Is the epidemiology of alkhurma hemorrhagic fever changing?: A three-year overview in Saudi Arabia.

BACKGROUND: The epidemiology of Alkhurma hemorrhagic fever disease is yet to be fully understood since the virus was isolated in 1994 in the Kingdom of Saudi Arabia. SETTING: Preventive Medicine department, Ministry of Health, Kingdom of Saudi Arabia. DESIGN: Retrospective analysis of all laboratory confirmed cases of Alkhurma hemorrhagic fever disease collected through active and passive surveillance from 1(st)-January 2009 to December, 31, 2011. RESULTS: Alkhurma hemorrhagic fever (AHFV) disease increased from 59 cases in 2009 to 93 cases in 2011. Cases are being discovered outside of the region where it was initially diagnosed in Saudi Arabia. About a third of cases had no direct contact with animals or its products. Almost all cases had gastro-intestinal symptoms. Case fatality rate was less than 1%. CONCLUSIONS: Findings in this study showed the mode of transmission of AHFV virus may not be limited to direct contact with animals or its products. Gastro-intestinal symptoms were not previously documented. Observed low case fatality rate contradicted earlier reports. Close monitoring of the epidemiology of AHFV is recommended to aid appropriate diagnosis. Housewives are advised to wear gloves when handling animals and animal products as a preventive measure

The monthly distribution of Alkhurma disease over a three year period in Saudi Arabia (2009–2011).

<p>The monthly distribution of Alkhurma disease over a three year period in Saudi Arabia (2009–2011).</p

Clinical Signs and Symptoms of Patients with Laboratory-Confirmed AHFV infected patients, 2009–2011.

<p>Clinical Signs and Symptoms of Patients with Laboratory-Confirmed AHFV infected patients, 2009–2011.</p

Some Demographic Characteristics of Patients with Alkhurma disease in Saudi Arabia (2009–2011).

<p>Some Demographic Characteristics of Patients with Alkhurma disease in Saudi Arabia (2009–2011).</p

Hajj: infectious disease surveillance and control.

Religious festivals attract a large number of pilgrims from worldwide and are a potential risk for the transmission of infectious diseases between pilgrims, and to the indigenous population. The gathering of a large number of pilgrims could compromise the health system of the host country. The threat to global health security posed by infectious diseases with epidemic potential shows the importance of advanced planning of public health surveillance and response at these religious events. Saudi Arabia has extensive experience of providing health care at mass gatherings acquired through decades of managing millions of pilgrims at the Hajj. In this report, we describe the extensive public health planning, surveillance systems used to monitor public health risks, and health services provided and accessed during Hajj 2012 and Hajj 2013 that together attracted more than 5 million pilgrims from 184 countries. We also describe the recent establishment of the Global Center for Mass Gathering Medicine, a Saudi Government partnership with the WHO Collaborating Centre for Mass Gatherings Medicine, Gulf Co-operation Council states, UK universities, and public health institutions globally

Seroprevalence of Alkhurma and Other Hemorrhagic Fever Viruses, Saudi Arabia

A 2009 deployment of military units from several Saudi Arabian provinces to Jazan Province, Saudi Arabia, enabled us to evaluate exposure to Alkhurma, Crimean-Congo, dengue, and Rift Valley hemorrhagic fever viruses. Seroprevalence to all viruses was low; however, Alkhurma virus seroprevalence was higher (1.3%) and less geographically restricted than previously thought