Monday, April 30, 2018

The Lancet Inf. Dis.: MERS-CoV Risk Factors & Determinants Of Primary, Household, & Nosocomial Transmission

Credit WHO












#13,297


We first learned that a novel coronavirus was circulating in Saudi Arabia from a September 2012 letter posted in ProMed Mail (NOVEL CORONAVIRUS - SAUDI ARABIA: HUMAN ISOLATE) by Dr. Ali Mohamed Zaki - an Egyptian Virologist working In Saudi Arabia.
Retrospective analysis, however, revealed the MERS coronavirus to have been involved in a pneumonia outbreak at a hospital in Jordan in April of that year (see Serological Testing Of 2012 Jordanian MERS Outbreak).
Although the source, and mode of transmission remained unknown, by the end of 2012, the World Health Organization reported:
Thus far, the laboratory confirmed cases have been reported by Qatar (two cases), Saudi Arabia (five cases) and Jordan (two cases). All patients were severely ill, and five have died.
As the number of human infections slowly climbed, in August of 2013 the first evidence was presented (see Lancet: Camels Found With Antibodies To MERS-CoV-Like Virus), that some camels on the Arabian peninsula had been exposed to – and likely carried - a MERS-like virus.

By December, researchers led by Marion Koopmans, DVM, PhD, head of virology at the Laboratory for Infectious Diseases at the RIVM in the Netherlands, determined that the human viruses and the camel viruses collected from a Qatari farm were almost an identical match (see The Lancet: Identification Of MERS Virus In Camels).
So close, in fact, that they were unable to determine whether the humans or the camels were infected first.
Acceptance of this MERS-camel connection in Saudi Arabia and the Middle East was slow at first, resulting in a huge backlash (see Saudi Camel Owners Threaten Over MERS `Slander’) and back peddling by officials (see Saudi MOA Spokesman: Camel Link Unproven).

After large nosocomial outbreaks erupted in Jeddah in the spring of 2014 (see chart below), the tide slowly turned, and warnings about camel contact and consumption of raw camel products were intensified.



By the summer of 2014, more than 700 cases had been reported, with the vast majority coming out of Saudi Arabia. While camel contact was considered a factor in many of these infections, it certainly wasn't responsible for all - or even most - of the cases.
Limited human-to-human transmission - particularly in households and health care facilities - was responsible for at least half of all known cases.
Additionally, a substantial number of `primary' community acquired cases - with no known exposure - were also reported, raising the possibility that mild or asymptomatic cases were flying under the surveillance radar, and occasionally transmitting the virus.

Some early blogs on that possibility include:
Study: Possible Transmission From Asymptomatic MERS-CoV Case
EID Journal: Asymptomatic MERS Infections Possibly Linked to Infected Camels

WHO Guidance On The Management Of Asymptomatic MERS Cases
EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016

Despite these concerns, asymptomatic MERS infections were practically ignored in Saudi Arabia, at least until the summer of 2015, when the WHO Statement On The 10th Meeting Of the IHR Emergency Committee On MERS - without specifically naming the Saudis – chastised the response to MERS in unusually blunt terms, stating: 
The Committee further noted that its advice has not been completely followed. Asymptomatic cases that have tested positive for the virus are not always being reported as required.
Timely sharing of detailed information of public health importance, including from research studies conducted in the affected countries, and virological surveillance, remains limited and has fallen short of expectations.
Inadequate progress has been made, for example, in understanding how the virus is transmitted from animals to people, and between people, in a variety of settings. The Committee was disappointed at the lack of information from the animal sector.
Despite a substantial increase in the flow of information on MERS since then, nearly three years later a great many questions on how the virus is transmitted  - particularly in the community - remain unanswered.
What we know, what is strongly suspected, and a long list of what we still need to learn is well summarized in the following (lengthy) Lancet Infectious Diseases review, which I'm pleased to note contains a section devoted to Transmission of MERS-CoV by asymptomatic individuals.
Follow the link to read the full review.

Review
Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission

Prof David S Hui, FRCP, Prof Esam I Azhar, PhD, Yae-Jean Kim, MD, Prof Ziad A Memish, FRCP, Prof Myoung-don Oh, MD, Prof Sir Alimuddin Zumla, FRCP
Published: 18 April 2018

DOI: https://doi.org/10.1016/S1473-3099(18)30127-0

Summary

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonosis that causes death in 35·7% of cases. As of Feb 28, 2018, 2182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide, with most being reported in Saudi Arabia (1807 cases with 705 deaths). MERS-CoV features prominently in the WHO blueprint list of priority pathogens that threaten global health security. Although primary transmission of MERS-CoV to human beings is linked to exposure to dromedary camels (Camelus dromedarius), the exact mode by which MERS-CoV infection is acquired remains undefined. 

Up to 50% of MERS-CoV cases in Saudi Arabia have been classified as secondary, occurring from human-to-human transmission through contact with asymptomatic or symptomatic individuals infected with MERS-CoV. 

Hospital outbreaks of MERS-CoV are a hallmark of MERS-CoV infection. The clinical features associated with MERS-CoV infection are not MERS-specific and are similar to other respiratory tract infections. Thus, the diagnosis of MERS can easily be missed, unless the doctor or health-care worker has a high degree of clinical awareness and the patient undergoes specific testing for MERS-CoV. 

The largest outbreak of MERS-CoV outside the Arabian Peninsula occurred in South Korea in May, 2015, resulting in 186 cases with 38 deaths. This outbreak was caused by a traveller with undiagnosed MERS-CoV infection who became ill after returning to Seoul from a trip to the Middle East. The traveller visited several health facilities in South Korea, transmitting the virus to many other individuals long before a diagnosis was made.
With 10 million pilgrims visiting Saudi Arabia each year from 182 countries, watchful surveillance by public health systems, and a high degree of clinical awareness of the possibility of MERS-CoV infection is essential. 

In this Review, we provide a comprehensive update and synthesis of the latest available data on the epidemiology, determinants, and risk factors of primary, household, and nosocomial transmission of MERS-CoV, and suggest measures to reduce risk of transmission.
        (Continue . . . )


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While MERS-CoV hasn't taken off the way that SARS did in 2003, we've seen analyses (see Study: A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia) suggesting the virus doesn't have all that far to evolve before it could pose a genuine global threat.

Seven weeks ago, in the WHO List Of Blueprint Priority Diseases, we saw MERS-CoV listed among the 8 disease threat in need of urgent accelerated research and development. 
List of Blueprint priority diseases
(SNIP)
The second annual review occurred 6-7 February, 2018. Experts consider that given their potential to cause a public health emergency and the absence of efficacious drugs and/or vaccines, there is an urgent need for accelerated research and development for*:
  • Crimean-Congo haemorrhagic fever (CCHF)
  • Ebola virus disease and Marburg virus disease
  • Lassa fever
  • Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)
  • Nipah and henipaviral diseases
  • Rift Valley fever (RVF)
  • Zika
  • Disease X

All of which makes the filling in of our substantial knowledge gaps on the MERS coronavirus a high priority.

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