J. Korean Med Sci: Atypical Presentation Of A MERS Case In A Returning Traveler From Kuwait

Credit WHO

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Although the number of MERS-CoV infections confirmed each month on the Arabian peninsula remains low - often in the single digits - there remain serious questions over how effective surveillance, detection, and reporting really are, and how many cases go unidentified. 

Since the initial signs of MERS infection are often similar to a number of common viral infections, differentiating who is - and who isn't - infected can be a extremely difficult, even for doctors used to seeing cases (see Evaluation of a Visual Triage for the Screening of MERS-CoV Patients).

Complicating matters further, in AJIC: Intermittent Positive Testing For MERS-CoV, we looked at some of the limitations of laboratory testing for the virus, which generally requires two negative tests - 48 hours apart - to declare a patient free of the virus.

As the testing of asymptomatic contacts of known cases has increased, so have the number of mildly ill or asymptomatic confirmed infections. Essentially, the more thoroughly we look, the more we find. Last month, we looked at:

Asymptomatic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: Extent and implications for infection control: A systematic review

Jaffar A.Al-Tawfiq abc Philippe Gautretd

Asymptomatic infections - once believed to be rare - now appear to be fairly common.  What isn't known is how well asymptomatic cases can transmit the MERS virus to others.  While this review is unable to directly answer that question, the authors did write:

Conclusions

The proportion of asymptomatic MERS cases were detected with increasing frequency as the disease progressed overtime. Those patients were less likely to have comorbid disease and may contribute to the transmission of the virus.

Over the years, we've seen 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. 
•  A 016 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.

And just last October (see mBio: High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia) a new study found approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected.

The authors strongly suggested that MERS may be flying under the radar, with a significant number mild or asymptomatic cases going undetected, writing:

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.

Another complicating factor in the diagnosis of MERS infection are atypical presentations, something we looked at three months ago in JIDC: Atypical Presentation Of MERS-CoV In A Lebanese Patient.

In this 2017 confirmed case - diagnosed at the American University of Beirut Medical Center (AUBMC) -  the patient presented without respiratory symptoms, but instead with just fever and gastrointestinal symptoms.

Also of note, the patient - a gastroenterologist from Riyadh  - had no recent camel contact and may have contracted the virus from an undiagnosed, asymptomatic (or mildly symptomatic) patient he treated at his job in Saudi hospital.

In September of 2018, the South Korean CDC Confirmed An Imported MERS-CoV Case in a traveler who had recently returned from Kuwait - Korea's first confirmed case in more than 3 years.

Today we've a pair of journal articles appearing in the Journal of Korean Medical Science on the unusual presentation of this case, and its potential impact on rapidly diagnosing MERS cases.  

I've only posted a few excerpts from each open-access report, so follow the links to read them in their entirety. 

J Korean Med Sci. 2018 Dec 31;33(53):e348. English.
Published online Dec 20, 2018.  https://doi.org/10.3346/jkms.2018.33.e348
© 2018 The Korean Academy of Medical Sciences.
   
An Atypical Case of Middle East Respiratory Syndrome in a Returning Traveler to Korea from Kuwait, 2018
 
Song Lee Bak, Kang Il Jun, Jongtak Jung, Jeong-Han Kim, Chang Kyung Kang, Wan Beom Park, Nam-Joong Kim and Myoung-don Oh

Abstract

We report a case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in a 61-year-old businessman returning from Kuwait. The patient arrived there on August 16, 2018, developed watery diarrhea on August 28 (day 0), and came back to Korea on September 7 (day 10) as his condition worsened. 

Upon arrival, he complained of diarrhea and weakness, but denied any respiratory symptoms, and he directly went to visit an emergency room. Chest radiography revealed interstitial infiltrates in the lungs, and he was immediately transferred to an isolation unit. Quantitative real-time PCR analysis of sputum samples taken on day 11 returned positive for MERS-CoV. No secondary MERS-CoV infection was identified among people who had close contact with him. 

This case underscores the importance of a high index of suspicion of MERS-CoV infection in any febrile patients who present after a trip to the Middle East.

       (Continue . . . . )

Linked to the above report is the following article:

J Korean Med Sci. 2018 Dec 31;33(53):e344. English.
Published online Dec 14, 2018.  https://doi.org/10.3346/jkms.2018.33.e344
© 2018 The Korean Academy of Medical Sciences.
   
Considering Revision the Criteria for Patients under Investigations for MERS-CoV Infections: Diarrhea or Not

Mi-Na Kim,1 and Eui-Chong Kim2

(EXCERPT)

Although human-to-human transmission in Saudi Arabia is markedly decreasing,6 the current case clearly showed that MERS-CoV patients can be imported from countries other than Saudi Arabia with atypical presentation in Korea, which will make recognition of PUI more difficult. 

As we learned from the Korean MERS outbreak, it is an absolute necessity to detect any influx of the MERS-CoV infections at quarantine surveillance to prevent its outbreak. 

There is a concern of excessive testing and preemptive isolation if diarrhea is added to the criteria of PUI of MERS because traveler's diarrhea is common. During the “watch” period of the national MERS response against the current case in 2018, a tertiary care hospital in Seoul modified the criteria for testing MERS-CoV to include patients with diarrhea associated with traveling history of Middle East countries and total of 16 patients were tested for MERS-CoV but no one was tested because of diarrhea. Therefore, addition of diarrhea in clinical features indicating PUI possibly makes surveillance for MERS infections more thorough with an affordable burden. 

For 7 weeks during the 2015 outbreak, a total of 27,009 MERS-CoV real-time reverse transcription PCR tests were performed to confirm PUI in clinical laboratories in Korea,10 which would be much larger than the number of MERS tests future, regardless of PUI criteria if no more outbreak occurs. Considering the detrimental impact on the healthcare system if an index case is missed, better PUI criteria provide tighter guard in quarantine surveillance. Note again that PUI criteria are not a case definition but for testing and revision of national PUI criteria to include diarrhea as a clinical feature would be beneficial in Korea. 

        (Continue . . . . )


Not quite a year 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 gaining a better understanding of how - and how well - the MERS coronavirus continues to spread in the community a high priority.