Monday, February 24, 2014

MERS Case Definition and Confirmation Standards

When an ill person arrives at a hospital emergency room, how does staff determine if the patient could be carrying a dangerous new disease, like the Middle East Respiratory Syndrome (MERS), rather than a common form of influenza?

Public health agencies use 'Case Definitions' to establish a uniform set of criteria which can be applied consistently across international boundaries and in a variety of health care settings. These commonly applied standards allow public health agencies to reliably count and classify suspected cases.

The Center for Disease Control and Prevention (CDC) and The World Health Organization (WHO) have issued guidelines for the identification and reporting of suspected MERS infections. A suspected case or, 'Patient Under Investigation' (PIU) would include:
  • A fever of 38°C/100.4°F or higher with pneumonia or severe respiratory distress
    plus one of the following risk factors:
  • Residence or travel to the Arabian Peninsula or neighboring countries within 14 days before the onset of symptoms or close contact with someone who has recently traveled there.
  • Members of a suspected cluster of patients with severe and acute respiratory illness of unknown origin, especially for clusters involving health care providers. These patients should be evaluated for MERS and state or local health departments should be consulted. 
Testing for a variety of respiratory illnesses can be conducted simultaneously and positive results for a different illness should not preclude also testing for MERS.

Countries which are at risk for exposure to MERS include Bahrain, Iraq, Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestinian territories, Qatar, Saudi Arabia, Syria, UAE and Yemen.

A Close Contact is defined by the CDC as a family member, health professional or anyone else who cared or worked closely with a suspected or confirmed MERS patient. It also includes other household members or visitors while the patient was sick.

WHO considers a wider group to be close contacts, including individuals who work together, students attending the same classroom or persons traveling together in any type of vehicle.

Detailed guidelines from WHO for investigating suspected MERS cases, including a patient questionnaire, testing procedures, infection control and reporting information is available here (pdf).

Laboratory Confirmation vs. Probable Cases
Polymerase Chain Reaction (PCR) and sequencing are used to genetically verify the presence of the MERS corona virus and produce a laboratory confirmation of the disease

These techniques allow small fragments of DNA to be replicated thousands of times, enabling researchers to target and study specific regions of the gene. PCR replicates both strands of DNA whereas Sanger sequencing duplicates only one.

This technique is extremely sensitive and highly useful in identifying the virus, but samples can be easily cross-contaminated with a minuscule amount of foreign material or the wrong DNA fragment may be amplified. Therefore, two positive tests are required for confirmation.

Laboratory Confirmation of MERS requires genetic testing of the virus and must produce two positive targets, either through a positive PCR on a minimum of two specific genomic targets or a single positive target with sequencing on a second.

Asymptomatic cases are held to a higher standard of proof and should be verified by re-extracting the RNA and testing for different target genes and, if possible, at an independent lab.

Probable cases of MERS are also defined by a specific set of factors, involving clinical, epidemiological and laboratory criteria. The probable MERS patient will fit one of the following scenarios:
  • A patient with symptoms of pneumonia or acute respiratory distress with a direct epidemiological link to a confirmed MERS patient. MERS testing must be unavailable or produces a negative result when using a single and inadequate sample.
  • A patient with symptoms of pneumonia or acute respiratory distress who is a resident or visitor to a region where the disease is known to be present. In addition, there must have been an inconclusive laboratory test, such as a positive initial screening without confirmation.
  • Finally, a patient with respiratory illness of any severity who also is a close contact of a confirmed MERS case, combined with an inconclusive laboratory test, such as a positive initial screening without confirmation. 
WHO recommends re-testing inconclusive patients to definitively determine if MERS is present.

Public Health Agencies have developed a detailed Case Definition for identifying and reporting suspected MERS cases. These standards, though imperfect, provide researchers and health professionals with a set of common standards for reliably identifying and tracking the disease through a wide variety of health care facilities around the world.

No comments:

Post a Comment