In the wake of its recent conclusion that camels are probably fueling Middle East respiratory syndrome coronavirus (MERS-CoV) cases in humans, the World Health Organization (WHO) has revised its guidance for case-control studies to ascertain exactly how the virus is getting into people.
The 22-page guidance is designed to equip investigators to compare MERS case-patients with other people who don't have MERS, with the aim of identifying what factors might have caused exposure to the virus. The revision includes many questions about contact with animals, especially camels.
The lack of case-control studies has been cited by experts as a major gap in the response to MERS-CoV. It's not clear if any of the Middle Eastern countries most affected by MERS have launched a case-control study as yet.
In its Mar 27 summary of MERS developments, the WHO said, "Recent studies support the premise that camels serve as the primary source of the MERS-CoV infecting humans and that other livestock are not involved."
It said that available genetic data show the MERS-CoV isolates in camels and humans are closely linked and "suggest the current observed pattern of disease in humans is the result of repeated introductions into human populations from camels, with subsequent limited human-to-human transmission, rather than sustained community transmission among humans. As such, discovery of the route of transmission between camels and humans remains critical to stopping the initial introduction into human populations."
Multinational effort wanted
The case-control study guidance, dated Mar 28, was completed at a meeting in Riyadh on Mar 1 and 2 and was distributed to affected countries after the meeting, according to the WHO.
The stated goals of the guidance are to "identify modifiable non-human exposures that lead to human MERS-CoV infection" and describe other risk factors for infection, such as pre-existing medical conditions.
Investigation should focus on primary (index or sporadic) cases, meaning those in patients with no recent exposure to other confirmed or probable MERS patients, the document says.
"The study should be a multinational effort combining standardized data from all participating countries," it states. "Implementation will be supported by an international team of experts and national focal points that will jointly resolve issues and questions regarding implementation by consensus."
Anthony W. Mounts, MD, the WHO's MERS-CoV technical lead, recently told CIDRAP News that the agency would like to see the case-control study "include some retrospective cases but also enroll new cases as they occur."
He said the study would be carried out by the affected countries, with the WHO in a strictly advisory role.
Focus on privacy, animal contacts
The guidance calls for including only adults in the study. It envisions two types of controls: randomly selected residents of the case-patient's neighborhood, matched for age and sex, and randomly selected hospital patients matched for date of admission, age, and sex.
The WHO promises that data will be stored in a secure database in the country in which it is collected and that individuals' identities will be protected. Saudi Arabian officials have repeatedly cited privacy concerns as the reason for releasing very little information about MERS-CoV cases.
The guidance includes close to four pages of questions about contact with animals and their environments. For example, study subjects are asked if, during a visit to a farm with livestock, they fed animals, cleaned animal housing or farm equipment, slaughtered animals, assisted with the birth of animals, milked camels, or kissed or hugged camels.
Countries that have had indigenous MERS-CoV cases are Jordan, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates (UAE). Cases with links to the Middle East have been reported in France, Germany, Italy, the United Kingdom, and Tunisia.
Mar 28 WHO guidance on MERS case-control study
Mar 27 WHO MERS-CoV summary
Jul 3, 2013, CIDRAP News story on earlier case-control study guidance