RECIPIENT / PROFILE

Some members of the Nipah Encephalitis Team.

The courage shown by the Team was exemplary in dealing with an unknown disease that was infectious, rapidly fatal and with no known treatment then.
Tan Sri Augustine Ong,
Member of the nomination committee,
Health, Science & Technology category

Profile

In 1998, during the height of the financial crisis gripping Malaysia, a mysterious disease started to spread across the country. Beginning in pig farms in Perak, the disease soon spread to the States of Negeri Sembilan and Selangor. Young and healthy men working on pig farms started to succumb, collapsing with fever and delirium. Rendered comatose, the victims started to die. With entire villages being abandoned, the army stepping in to slaughter livestock and reducing farms to rubble, a state of panic began to grip the nation. All methods attempting to control the spread of the disease failed. At that point in time, a team of intrepid doctors and scientists from the University of Malaya's Faculty of Medicine came to the rescue. The Team, led by Professor Dr Tan Chong Tin, a neurologist, was comprised of members with all of the different specialisations necessary to study and combat the disease.

Dr Patrick Tan and Professor CT Tan in an ICU unit, where they spent much time monitoring Nipah Encephalitis patients.

These doctors rose above their disparate backgrounds and specialisations, and came together as academicians and professionals to tackle a disease which was rapidly threatening to become a pandemic. They succeeded beyond expectations.

The team's radiologists imaged and studied the virus' effects on patients.

Tracking A New Disease
In the initial stages of the outbreak, the disease was thought to be Japanese Encephalitis (JE), where the virus would use pigs as incubators and spread to humans via an insect vector. Accordingly, measures were taken to combat JE, such asthe vaccination of the pigs and villagers, and insecticide fogging of pig farms and neighbouring villages. However, these measures failed to halt the spread of the outbreak.

While the symptoms were superficially similar, there were differences between JE and this perplexing disease. For one, the victims did not fit the JE profile. JE tended to attack the very young and the very old, with no discernible pattern of infection. This disease, however, attacked healthy young men, with the infection confined to those who had been in contact with infected pigs. The pigs themselves exhibited signs of illness, whilst a pig infected with JE would not manifest any symptoms of the disease. In addition, many of the victims had been inoculated against JE, with the infection confined to those who had been in close contact with pigs, and the geographical clustering of the victim cannot be explained by a disease spread via mosquito.

A colony of Pteropus fruit bats. The team discovered that these wild fruitbats are the reservoir hosts of the virus.

These discrepancies necessitated further investigation. Already there were suspicions that the epidemic was not typical of JE; however, the prevailing opinion was so strong that objections were generally subdued. The Team tried to persuade families of deceased victims to allow further examination of the bodies. While many were understandably reluctant, several consented, and the first samples arrived in the testing laboratory in March 1999. Dr Chua started to receive the first samples of the cerebrospinal fluid in the laboratory in March 1999. He locked himself in the laboratory for a week, while conducting various tests on the samples.

He found something unusual in the culture. After coming up with negative results against a plethora of known viruses, Dr Chua was convinced that this was a previously unknown virus. The virus sample was taken to the Centers for Disease Control and Prevention in the United States for further identification. The virus was subsequently found to be related to the Hendra virus, which caused outbreaks of pneumonia and encephalitis in Australia. The novel virus was later named Nipah, the name being derived from Kampong Sungai Nipah, which was one of the villages affected by the outbreak.

Team members also served as WHO consultants for the Nipah outbreak in Bangladesh in 2004. Dr KB Chua and Prof CT Tan are standing on the right.

Further studies by the team helped to show that the large Pteropus fruit bats was the reservoir of the Nipah virus. The El Niño weather phenomenon which hit Malaysia hard during the 1997-1998 period, had driven the Pteropus bats from their natural habitat to fruit trees situated in the vicinity of the pig farms in Perak. Half eaten fruits by the bats were then fed to the pigs, where the virus multiplied and spread from pig-to-pig and subsequently to humans.

In the meantime, hospitals were inundated with patients infected by the Nipah virus, stretching hospital capabilities almost to breaking point. When the Seremban hospital, which was the nearest major hospital to the outbreak, could not cope with the sudden influx, many patients also sought treatment at the University of Malaya's Teaching Hospital.

An electron microspic image of the Nipah virus.

Management of patients was very much a team effort, with the neurologists as chief physicians. The radiologists were learning to identify the telltale signs of infection from the MRI scans, and pathogenesis, pathology, serology and EEG studies being conducted. Intensive Care Unit (ICU) equipment, ventilators and nurses were assembled, and surgeries postponed to accommodate the increasing number of patients requiring ventilation. As the risk of infection spreading from the patients to the health care workers were unknown, precautionary measures were formulated to prevent the spread of infection to medical staff and relatives. It was later discovered that humanto-human transmission of the Nipah virus was indeed possible and was an important mode of transmission during the Nipah encephalitis outbreaks in Bangladesh and India.

Having no other option, it was decided that ribavarin, an expensive antiviral medication for a therapeutic trial. To the delight of the Team, ribavarin treatment proved to be successful in reducing the mortality rates by 36% as compared to patients who had not been treated with the drug.

With the identification of the new virus, new strategies were devised to combat the continuing outbreak. Vaccination and insecticide fogging were stopped and pigs were culled. With this the outbreak came to a halt, and the epidemic was finally contained. In the meantime, the meticulous observations and investigations of the patients and elatedworks gave rise to many papers published in peer review medical journals, such as Science, the Lancet and New England Journal of Medicine. Team members were also offered lecture invitations and given awards in recognition of their efforts.

Since the outbreak in Malaysia, Bangladesh and India have experienced ten Nipah encephalitis outbreaks from 2001. The knowledge accumulated and experienced gained by the Team in the Malaysian outbreak have helped to cope with the outbreaks in the Indian sub-continent. Some members of the Team were also invited by the World Health Organization to help investigate the 2004 outbreak in Bangladesh. As the habitat of the Pteropus bats extends across most of the Old World's tropical zone, and increasing number of countries have found bats to be reservoirs of the Nipah virus, Nipah encephalitis has become an important emerging encephalitis.

Prof KT Wong visiting a village in Bangladesh with Nipah Encephalitis outbreak.

Concluding Remarks

The Nipah Viral Encephalitis Investigation Team displayed heroic courage in dealing with the epidemic. Risking infection to themselves and their families, this group of dedicated and passionate doctors selflessly sought to combat this disease, feeling that their professional duty overrode any personal considerations. Their achievement is also a great source of pride for Malaysia, as an entirely Malaysian team was instrumental in researching and combating a previously unknown virus, and in doing so made a significant contribution to the corpus of global medical knowledge.