Although the WHO has declared India `SARS free', the various pronouncements made by the Health Ministry have caused considerable confusion in the public mind about whether the country is really free of the virus.
AFTER the first "confirmed case" of SARS, or Severe Acute Respiratory Syndrome, in India came to light in Goa on April 16, followed by two weeks of reports of "cases of SARS" from various parts of the country, the Union Health Ministry made a startling announcement on May 1 that India was "SARS free". The announcement came after the World Health Organisation (WHO) removed India from its list of countries with "Cumulative Number of Reported Probable Cases of SARS". Until then, the WHO had reported that India had one "probable case" of SARS, which had recovered. The one case was that of a marine engineer from Goa, who had travelled from Hong Kong via Singapore and Mumbai.
It is not clear why the WHO removed India from its list. A footnote to the list says: "As SARS is a diagnosis of exclusion, the status of a reported case may change over time. This means that previously reported cases may be discarded after further investigation and follow-up." The WHO guidelines clarify the grounds for discarding: "A case initially classified as `suspect' or `probable' for whom an alternative diagnosis can fully explain the illness, should be discarded after carefully considering the possibility of co-infection." Neither the WHO website nor the Health Ministry has offered any explanation for this. Indeed, the inclusion of the case in the list of "probable cases" was itself a dubious action as the patient, whose chest X-ray showed no signs of a patch in the lungs or symptoms of pneumonia or respiratory distress syndrome (RDS), did not fit the WHO's definition of a "probable case" (Frontline, May 9).
The WHO does not report the cases unilaterally, instead it relies on reports from member-countries. Perhaps the Health Ministry realised its mistake in communicating even the first case and had it removed after presenting the case history to the WHO. According to informed sources in the Health Ministry, in its over-zealousness to prove the efficiency of the Indian surveillance system, the Ministry might have bungled up its report to the WHO. The remarks made by Health Minister Sushma Swaraj and other officials about the efficient manner in which the system was able to pick up suspected cases and their contacts and then confirm them quickly through laboratory tests indicate that this might have been the case. But the subsequent announcements by the Ministry of "confirmed cases of SARS" being reported from different parts of the country caused panic among people in places such as Kolkata and Pune.
Even as Sushma Swaraj announced that India was "SARS free", the May 1 update by the Directorate-General of Health Services (DGHS) said the following: "In India, as on 1st May, 20 laboratory positive persons - 7 cases, 13 contacts (3 symptomatic and 10 asymptomatic contacts) - have been reported... A cumulative total of 71 clinical samples (41 cases and 30 contacts) have been received in the laboratories of the National Institute of Communicable Diseases (NICD), Delhi, and the National Institute of Virology (NIV), Pune. Reports of 14 cases are awaited." The trouble lies in the fact that the Ministry officials did not think it fit to clarify to the media and to the public in general, what they meant by "cases", "contacts", "symptomatic" and "asymptomatic". They have not issued a clarification that although the country is "SARS free", it is not "SARS virus free". The disease has to be distinguished from the infection and it has to be clarified that the latter does not always lead to the former. While laboratory diagnostics reveal infection, the WHO's case definition of March 16 was based on the spectrum of clinical symptoms of the disease.
In an emerging disease, and that too of unknown origin, this is the only rational approach. The initial identification of cases and their management has to be based on clinical symptoms alone. As the disease begins to be understood better and its causative agent is identified - in this case it is a new coronavirus, now called SARS-CoV - laboratory diagnostics that are specific to the causative agent and whose specificity and sensitivity to the infection improves with time are evolved.
By the time the infection arrived in India, the genetic sequences of the virus had been unravelled and the highly specific method known as the Reverse Transcription Polymerase Chain Reaction (RT-PCR), which was being used by Indian laboratories to test "suspect" cases and their contacts, had become possible. As such techniques improve and get validated, case definitions would gradually begin to rely on laboratory diagnostics more than on clinical symptoms. Indeed, with the increasing use of laboratory tests to exclude SARS cases, the WHO's case definition underwent a change as of May 1; and so did the definition in use by the Centres for Disease Control and Prevention (CDC) of the United States.
Although the WHO's case definition is intended to facilitate the reporting of cases by member-countries, the organisation has recommended individual countries to adapt case definitions depending on their own disease situation. It is being claimed that India's expertise in developing modern molecular diagnostic tools based on genetic sequences such as RT-PCR is as good as that of developed countries. Laboratories such as the NIV could, therefore, rise to the challenge of developing tests for SARS; the surveillance method could include a laboratory-test-based approach. However, the DGHS does not seem to have evolved a proper case definition that is in consonance with the surveillance methodology. Updates issued by the DGHS mention figures of laboratory-positive cases without clarifying whether they are clinically `suspect' or `probable' as per the WHO criteria. It is perhaps this administrative confusion that led to the classification of the Goa case, which was at best a `suspect' case, as `probable'.
This error could also have occurred owing to the confusion caused by the WHO's constantly evolving format of listing cases. It was perhaps compounded by the manner in which the U.S. was reporting its cases to the WHO. But unlike India, the CDC's guidelines and case definitions are clear about the surveillance procedures that are followed there. Following its global alert on March 12, the WHO put out its record of "Cumulative Number of Reported Suspect and Probable Cases" for the first time on March 16. The U.S. appeared on the list on March 19 with 11 cases. On March 24, the header of the WHO's table was changed to "Cumulative Number of Reported Cases (SARS)", under which the U.S. had 37 cases. It had the following footnote: "Due to differences in the case definitions being used at a national level, `probable' cases are reported by all countries except the U.S., which is reporting `suspect' cases under investigation."
On April 9, the title of the list was changed to "Cumulative Number of Reported Probable Cases of SARS". On April 17, India entered the list with one case, which was reported as cured on April 18. According to Kumara Rai, director of communicable diseases at the Regional Office of the WHO in New Delhi, although the case belonged to the `suspect' category, the list recorded it without the footnote, as was done in the case of the U.S. The situation changed for the U.S. on April 20, when it started reporting `probable' cases to the WHO and this began to be reflected in the list from April 21. On that date, from a total of 220 `suspect' cases earlier, the WHO record showed the U.S. as having 39 `probable' cases. From then on, only `probable' cases are being shown for the U.S. As of April 30, of a total of 289 `suspect cases', the U.S. had 56 `probable' cases. The difference between the U.S., or even Hong Kong or Singapore, and India is that in the former, complete clinical and epidemiological profiles of the cases are available in the public domain. In India, except for the 10 persons who are stated to be asymptomatic, there is no information on the clinical status of the seven "cases" and three "contacts" both categories have not been defined by the DGHS in clinical/epidemiological terms.
If the Health Ministry is following the WHO's criteria, then nine of the 10 symptomatic cases that have been reported belong to the `suspect' category, assuming that the DGHS figures include the Goa case, which was reported as a `probable' case and later removed. However, according to the revised case definition of May 1, all `suspect' cases that have tested positive in laboratory assays should be reported as "probable" cases (see nos. 3 and 4 in the box) "only if the testing procedures use appropriate quality control procedures". The WHO's rationale for retaining a clinical and epidemiological basis for the case definition despite the wide availability of diagnostic tools following the complete sequencing of the SARS-coronavirus is that "at present there is no validated, widely and consistently available test for infection with the SARS-CoV."
The Indian Council of Medical Research (ICMR), under which the NIV functions, is confident about the RT-PCR tests that it has developed using the sequence data of SARS-CoV. N.K. Ganguly, Director-General of the ICMR, said: "We have used separate sets of primers (for virus amplification) from three different sources and we verify our results with all of them. We have applied all the requisite positive and negative controls. We are also getting our test validated by other laboratories". He added: "We repeat the tests at the institute as well as at its Microbial Containment Centre, separated by 15 km. We have also been able to observe the virus particle morphologically using the electron microscope as well as the immuno-fluorescent assay. We have isolated the virus and have begun their culture".
So, if the health officials are confident of the PCR tests and the reporting authorities follow the WHO guidelines and reporting criteria strictly, there should be nine `probable' cases in India. "The DGHS is the national reporting authority to the WHO. What reporting system will be followed henceforth, I cannot say," Ganguly said. According to Kumara Rai, it is not clear whether and when the new reporting system will become effective, as it has not been accepted by all countries. "What matters ultimately is the manner in which the cases are managed and the spread of infection is controlled. Whether the WHO shows in its list or not is not so important. From that perspective, the quarantine procedures adopted by India for all the symptomatic cases that have tested positive for SARS virus is the same," he said.
One peculiar, but medically important, feature of the Indian situation is the existence of `asymptomatic' instances of SARS-CoV infection. The CDC has included `asymptomatic' and `mild infection' as clinical criteria in the surveillance system for healthcare workers and others exposed to SARS patients, it has not recorded any case of asymptomatic infection owing to SARS-CoV. The current system of the WHO does not require the reporting of cases of clinically fit persons who test positive for SARS-CoV. While the infection has arrived in the country, not a single case has been reported where the clinical symptoms are associated with the WHO's `probable' classification. It seems that in India, at best, we are seeing only a very mild manifestation of the infection. It remains to be seen whether this is a reflection of any innate immunity of the Indian population.
But the cases of asymptomatic infection point to a serious situation in terms of healthcare because we have in our midst persons who are silent carriers and potential transmitters of the virus. Therefore, the tracing of `suspect' cases becomes important and at the same time quite difficult. The performance of the system in this respect has not been encouraging. Persons suspected of carrying the virus have been allowed to mix with the general population even as laboratory results are awaited.
In this context, the May 2 press release of the Health Ministry defies all logic. According to it, the Ministry will not send for testing samples from people who do not conform to the WHO case definition. This means that asymptomatic contacts of cases will not be tested at all even though there is ample evidence to suggest that Indians are potential silent carriers and shedders of the virus. Clearly, the surveillance system is not responding to the emerging pattern of spread of SARS-CoV infection in the country. Ganguly refused to comment on the press statement and merely said: "We will carry out only what the Ministry wants us to do."Defining surveillance
The following are the World Health Organisation's (WHO) case definitions for the surveillance of SARS, as on March 16, 2003:Suspect case*
A person presenting after February 1, 2003 with a history of high fever (>38oC) (100.4oF) and one or more respiratory symptoms, including cough, shortness of breath, difficulty breathing and one or more of the following:
Close contact*, within 10 days of onset of symptoms, with a person who has been diagnosed with SARS;
History of travel, within 10 days of onset of symptoms, to an area in which there are reported foci of transmission of SARS.Probable case
A `suspect' case with chest x-ray findings of pneumonia or Respiratory Distress Syndrome (RDS), or a person with an unexplained respiratory illness resulting in death, with an autopsy examination demonstrating the pathology of RDS without an identifiable cause.
(In addition to fever and respiratory symptoms, SARS may be associated with other symptoms, including headache, muscular stiffness, loss of appetite, malaise, confusion, rash and diarrhoea.)
On May 1, the above specifications were revised to incorporate data from surveillance based on laboratory tests that are beginning to be adopted widely in many countries, including India. The key changes that were made are:
1. The beginning of the surveillance period was pushed back to November 1, 2002, in the light of the confirmation that the outbreak in Guangdong, China, in November was indeed that of SARS.
2. A `suspect' case in whom recovery is adequate but whose illness cannot be explained fully by an alternative diagnosis should remain as `suspect'.
3. A `suspect' case of SARS that has proved positive for SARS-coronavirus (SARS-CoV) in one or more laboratory assays should be reported as a `probable' case.
4. `Suspect' cases with positive laboratory results will be reclassified as `probable' cases for notification purposes only if the testing laboratories use appropriate quality control procedures.
5. No distinction will be made between `probable' cases with or without a positive laboratory result and `suspect' cases with a positive result for the purposes of global surveillance.
6. Cases that meet the surveillance case definition for SARS should not be discarded on the basis of negative laboratory tests at this time.
* Close contact means having cared for, having lived with, or having had direct contact with respiratory secretions and body fluids of a person with SARS.