Emergencies preparedness, response

Update 71 - Status of diagnostic tests, training course in China

2 June 2003

Status of diagnostic tests
The development of commercial diagnostic tests for SARS has progressed more slowly than initially hoped. Part of the problem arises from certain unusual features of SARS that make this disease an especially difficult scientific challenge.

For many viral diseases, the greatest quantities of the causative agent are excreted during the initial phase of illness, usually in the first few days following the onset of symptoms. This is often the period during which patients pose the greatest risk of infecting others.

SARS, however, follows a different pattern. During the initial phase of illness, virus shedding is comparatively low. Virus shedding peaks in respiratory specimens and in stools at around 10 days after onset of clinical illness. In effect, this unusual behaviour creates the need for tests having a particularly high sensitivity.

Such tests do not yet exist. Because small quantities of the virus are initially shed, available tests, though developed with impressive speed, are unable reliably to detect SARS virus or its genetic material, during the earliest days of illness. The low sensitivity of current virus detection tests is a particular challenge for SARS control, as patients are capable of infecting others during the initial phase and therefore need to be reliably detected and quickly isolated.

In SARS patients, detectable immune responses do not begin until day 5 or 6. Reliable antibody tests can detect virus only by around day 10 following the onset of symptoms.

WHO continues to recommend use of its case definitions, based on clinical presentation, distinct chest X-rays, and history of possible contact with SARS patients, to detect suspect and probable cases and make management decisions.

To expedite the development of better diagnostic tests, laboratories in the WHO collaborating network have made critical biological materials and reagents available to any laboratory having a sustained interest in the development of diagnostic tests, including the commercial sector. A comprehensive bank of clinical specimens, including respiratory specimens and samples of blood, urine, and faeces from SARS patients, has been established. The bank holds specimens representing all stages of the disease, ranging from the onset of symptoms to recovery.

During the development of diagnostic tests, such specimens are needed to assess how well a test will perform with real patients specimens, as opposed to under the artificial conditions of a laboratory.

Specimens from the bank, which was set up by the Hong Kong Department of Health and the Hospital Authority, are being supplied by a collaborating laboratory, at no charge, to developers of diagnostic tests. As a sample from a single specimen can be subdivided into 6 to 8 identical sub-samples, laboratories can work in parallel on identical specimens, which will further facilitate the assessment of comparative performance. Identical samples also support standardization of diagnostic tests to ensure consistent accuracy.

Laboratories in the WHO network have also made available standardizing reagents for virus and antibody tests. These reagents, which include samples of the inactivated virus and blood from patients in both acute and convalescent stages of illness, will allow uniform assessment of diagnostic results around the world against a “gold standard”.

Sera have been made available by collaborating laboratories in the United Kingdom and Hong Kong. Inactivated virus was prepared by the Bernard-Nocht Institute in Germany. Distribution of these reagents will be the responsibility of the Robert-Koch Institute, also in Germany. In return for the supply of these exclusive materials, recipients of WHO support have agreed to offer test kits, once available, at preferential prices to developing countries.

Training course in China
WHO is currently coordinating a series of training courses in Beijing aimed at establishing an efficient laboratory infrastructure for SARS diagnosis in all provinces throughout China. Work of the WHO laboratory network has made it possible to support the training courses with test materials and reagents.

Training in the use of currently available tests is being provided by representatives of the labs where they were developed – thus ensuring that Chinese professionals benefit from the best first-hand experience the world can offer. Trainers come from laboratories in China, Hong Kong, the UK and the USA.

China has already developed a highly promising ELISA diagnostic test. For early detection of SARS virus, the PCR molecular test offers the greatest potential under average hospital conditions. The Singapore Genomic Institute has made its PCR test available, at no cost, to support SARS diagnosis in China.

Although the number of new cases and deaths has declined considerably in mainland China, WHO and Chinese authorities remain concerned about the situation in some of the remote provinces which lack a sufficiently strong health infrastructure, including surveillance and reporting systems and hospital facilities, for responding to the magnitude of the SARS problem.

Update on cases and countries
As of today, a cumulative total of 8384 probable cases and 770 deaths has been reported from 29 countries. This represents an increase of 27 new cases and deaths compared with the last report on Saturday. The new deaths were reported in China (2) and Hong Kong (4).