Avian Flu Diary: mBio: High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia

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MERS continues to simmer in the Middle East with the latest WHO EMRO report showing 118 cases reported (through Sept 30th) in 2018. Since 2012, 2260 conﬁrmed cases of MERS - including 803 fatalities - have been reported globally.

Saudi Arabia appears to have finally gotten a handle on MERS infection control in their hospitals, and while smaller nosocomial outbreaks continue to be reported, the truly large outbreaks (100+ cases) have been absent the past couple of years.

Community acquired cases - some with direct camel contact, but most without - continue to be reported sporadically throughout the region, with illnesses that range from mild to severe and/or fatal.

The source of most of these infections remains unknown, sparking legitimate concerns that the virus may be spreading at low levels via mildly symptomatic or asymptomatic carriers in the community.

In recent months we've looked at reports of Atypical Presentation Of MERS-CoV, and apparent deficits in the Saudi's Visual Triage for the Screening of MERS-CoV Patients, both of which suggest some (perhaps, many) cases go unidentified.

Over the years, we've seen other analyses that have concluded that only a fraction of MERS cases are likely diagnosed, including:

In November of 2013, we looked at a study published in The Lancet Infectious Diseases, that estimated for every case identified, there are likely 5 to 10 that go undetected.
In 2015, when Saudi Arabia had recorded fewer than 1200 MERS cases, a seroprevalence study (see Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study by Drosten & Memish et al.,) suggested nearly 45,000 might have been infected.
And a 2016 study (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016) suggested that as much as 60% of severe Saudi MERS cases go undiagnosed.

Serological testing for past MERS infection has previously returned only low levels of exposure in the general population of Saudi Arabia, and slightly elevated levels in camel workers.

But we know that mild or asymptomatic cases tend to mount a weak, short term, immune response, and may therefore not test positive within a few months of their illness.

In April of 2016, in EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors, a study tested 9 health care workers who were infected during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic), found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.
A year later (May 2017) a report in the EID Journal: MERS-CoV Antibody Response After 1 Year, followed and tested 11 survivors of South Korea's 2015 MERS outbreak at 6 and 12 months, and like earlier studies, found that those with mild illness saw significant reduction in antibody titers over a year's time.

All of which brings us to a new report, published today in mBio, which suggests there may be considerably more undiagnosed MERS cases in the region than previously known.

Using an array of tests, researchers found a much higher incidence of MERS antibodies in camel workers (CW) - roughly 50% - which far exceeds earlier studies.

This a long, detailed study, and I've only posted a few excerpts. Follow the link to read it in its entirety.

High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia

Abeer N. Alshukairi, Jian Zheng, Jingxian Zhao, Atef Nehdi, Salim A. Baharoon, Laila Layqah, Ahmad Bokhari, Sameera M. Al Johani, Nosaibah Samman, Mohamad Boudjelal, Patrick Ten Eyck, Maha A. Al-Mozaini, Jincun Zhao, Stanley Perlman, Abdulaziz N. Alagaili

Mark R. Denison, Editor

DOI: 10.1128/mBio.01985-18

ABSTRACT

Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development.

While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear.

Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses.

Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood.

Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.

IMPORTANCE

The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure.

Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease.

Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.

(Continue . . . )

There are (as always) some limitations to this study, and some important caveats regarding their conclusions. The authors caution:

Our results will need to be confirmed with larger numbers of CWs in prevalence studies and in longitudinal studies, in order to identify additional factors that contribute to transmission and to determine whether CWs are repeatedly infected.

Also, camels are infected with other alphacoronaviruses and betacoronaviruses, including one that is related to HCoV-OC43 (32, 33). It will be important to determine whether these viruses infect humans, especially CWs, and if so, and while unlikely, whether these viruses induce a T cell response that is cross-reactive with that of MERS-CoV-specific T cells.

Finally, it will be paramount to directly demonstrate infection of CW contacts to validate the notion that CWs are a source for spread within the community and to determine whether CWs are contagious after repeated exposure to the virus.

Despite these reservations, the authors strongly suggest that MERS may be flying under the radar, with a significant number mild or asymptomatic cases going undetected.

Our results indicate that a high proportion of CWs are infected, and this, combined with data demonstrating that patients with subclinical MERS are contagious (31), suggests a plausible mechanism for how patients without documented camel exposure become infected.

It is possible that some healthy contacts of CWs are subclinically infected, while exposed individuals with underlying comorbidities or who are otherwise more susceptible develop clinical disease.

For more background on serological testing for MERS, you may wish to visit: