Battling Plagues – One after Another

Penang-born scientist Dr Mary Jane Cardosa’s commitment to public health is unwavering.

The Dr Wu Lien-Teh Society conducts annual public lectures to showcase contributions made by notable medical figures in the realm of public health. Now in its fourth edition, this year saw Dr Mary Jane Cardosa, the founder and chief scientific officer of Sentinext Therapeutics, speaking on the topic of “Virology in the Jungle: Pay Attention to What Matters to Local Communities” at Penang Institute.

President of the Dr Wu Lien-Teh Society Datuk Dr Anwar Fazal with Dr Mary Jane Cardosa.

For much of her career, Cardosa has been actively involved in disease surveillance activities, especially for dengue, Japanese encephalitis (JE), enterovirus 71 (EV71) and other emerging diseases, as well as outbreak control. Her laboratory was central in working with public health authorities to manage outbreaks of infectious diseases, particularly in Sarawak. Well-established as a leader in emerging infectious diseases, Cardosa was the first virologist to recognise the emergence of the EV71 virus in the region.

“Cardosa shares similar attributes as Dr Wu Lien-teh, who was a legend – he not only excelled in pioneering research, he also had the courage to challenge existing views,” says Datuk Dr Anwar Fazal, the society’s president. “(Similarly), Cardosa is a brilliant researcher and is always prepared to challenge medical misconceptions. Through these lectures and these outstanding champions, we hope that more and more people will be better informed, inspired, and will initiate new ideas and actions in the medical field. Malaysia can certainly then be a world leader in tropical medicines.”

Beginnings

In the 1990s, while lecturing at the School of Pharmaceutical Sciences in Universiti Sains Malaysia (USM), Cardosa was offered an exciting opportunity she couldn’t refuse: the chance to set up the first virology unit, the Institute of Health and Community Medicine (IHCM), in Borneo. The intent was to study tropical diseases in areas where they naturally occur. “In terms of building our research programme, we focused our study on the genetics of viruses. This we did by speaking to medical practitioners, as well as members from the public health arena, to ascertain the kinds of diseases they required our assistance with.”

Vector-borne diseases were top on the list, followed by faecal-oral and respiratory transmissions and diseases relating to the central nervous system (CNS). The research programme was built on three different platforms: Diagnosis, Prevention and Control; Pathogenesis and Basic Biology; and Therapeutics and Vaccine Design. “We actually ended up getting stuck at the first platform as there was very strong demand for us to continue conducting research in that area. It was only after I retired that the IHCM was able to move ahead to platform three – to develop the vaccines.”

The Politics of Medicine

In 1996 Cardosa and her team commenced their research on infectious diseases, in particular CNS-related viruses among children. “Children were being admitted to hospitals with neurological problems and at the time, the assumption was that it was JE, which we knew was prevalent in Sarawak owing to studies done by British and American researchers who previously spent a lot of time in the jungles of Sarawak.

“Though we were able to identify the occasional JE cases, by April 1997 it became apparent that we were dealing with a much deadlier disease – EV71, which is an associated hand, foot and mouth (HFM) disease. But nobody believed us. Twenty-nine children succumbed to the virus between April and June that year, and the institute was thrown into a big boiling pot of politics. The Minister of Health came to Sarawak; so did the Centers for Disease Control (CDC). Interestingly, our government also had a young medical trainee from the US CDC flown in to assess the situation. He had never encountered such a case before, but we were required to listen to him. I began to learn very quickly the politics of things.

“But in the end, we were proven right. The institute became well-known for the studies it conducted on the virus. This was no small feat considering we were a small lab based in the middle of nowhere, going head-to-head with the US CDC and coming out on top.”

The lab also had the backing of Datuk Dr Andrew Kiyu, the State Health Department consultant epidemiologist. “He understood that as a state, Sarawak had a large population and that a different approach must be taken with regards to public health control measures. He insisted on a three-way collaboration between clinicians, members from the public health department and the lab, which worked out very well.”

A prospective surveillance programme was created in 1998 to learn more about the EV71 virus. “We recruited the help of two paediatricians – we wanted to carefully study the trends rather than the absolute numbers. We discovered that between 1997 and 2003, three outbreak cases were reported within a three-year interval period, and the mean age of the infected children was around three years old. From mathematical algorithms and calculations, we were also able to trace the EV71 virus of 1997 to its first appearance in Sarawak, which was about two to three years prior. However, during the later plagues, the EV71 virus began evolving from one form to another.”

Cardosa and her team were likewise able to determine the kind of factors that influenced the epidemiological curves: “Associated phenomenon is one,” she explains. “When studying the curves separately, we noticed the government clinics were slower to pick up on the EV71 cases compared to the private ones. This may be because the patients were coming to the public clinics much later, when the situation had drastically worsened.

“The political factor comes into play as well: if KL announces that there are no outbreaks, then no one talks about it – the media included. We faced similar problems with the other outbreak cases. We were also able to see a peak in the epidemiological curve during June of the outbreak years, when everybody goes back to their longhouses to celebrate the Gawai Festival. And of course, there’s the question of health-seeking behaviours of different communities.”

Putting Out Fires

In 2003 Sarawak was beset with both the SARS and EV71 outbreaks. “Instructions were issued by the government and the World Health Organization to avoid public places and to frequently wash one’s hands. Interestingly, we discovered that when a disease affects the adult population more than the children, there’s more compliance to instructions,” says Cardosa. “I was told that it was because adults are more economically important than children. Concern for the children’s well-being is more familiar and immediate, while for adults, it’s more general.”

When the EV71 virus made its fourth appearance in 2006, Cardosa and her team were better prepared. “We started the public health messages early. After the first three cases were identified, kindergartens were ordered to close; at the time, it seemed that the outbreak was successfully contained. We were pleased because we thought we had finally done it.”

At the outset, the EV71 cases were primarily concentrated in Kuching, but the virus shifted to the Serian township later in the year. “Parents were sending their children off to their grandparents’ in the kampungs; this inadvertently sparked another outbreak. This is the kind of situation we have to grapple with all the time: are the interventions we’re doing effective, and are they enough? When preventative measures were focused on one place, we observed the epidemiological curve come down sharply, and we assumed the interventions were indeed effective. But we also unintentionally caused another outbreak in a different location. If we weren’t monitoring the area, we would never have known that.

“It was important to me that when the lab was first set up, it should be relevant to the local communities, whether they reside in the city or in the jungles.”

For her extensive work, among the awards Cardosa received was the Donald Mackay Medal from the American Society for Tropical Medicine and Hygiene for her outstanding works in tropical health, especially relating to improvements in the health of rural and urban workers in the tropics. Though retired, Cardosa is hard at work developing the first-ever vaccine against the EV71 virus. “It’s currently undergoing a phase one trial in Australia.”


Wu Lien-Teh – A Pioneer of Modern Medicine

Born in Penang in 1879 to a family of immigrants from Taishan, China, Dr Wu Lien-Teh received his primary and secondary education at Penang Free School. At 17, he was admitted to Emmanuel College, Cambridge under the prestigious Queen's Scholarship, where he completed his medical degree two years ahead of requirement, and virtually won all possible prizes and scholarships in a class of 135 students.

Wu successfully halted the pneumonic plague that swept through Manchuria in the winter of 1910. Dispatched by the Qing government to investigate the cause (the disease was traced to marmot-trappers and fur traders in Manzhouli) and to contain the outbreak, Wu and his medical team quickly set to work. Quarantine measures were put in place as was the invention of the “Wu mask” to discourage the infection’s spread by inhalation of plague bacilli in the sputum.

Going a step further and against tradition, Wu appealed to the Emperor for the cremation of the unburied infected corpses. The Imperial Edict arrived and in 1911, China witnessed its first mass cremation. Within six months, the epidemic, which had claimed a devastating total of 60,000 lives, was effectively brought under control.

Wu was conferred the positions of “Medical Jinshi”, “Imperial Army Major” and a string of other honours by the Qing government, and called to audience by the Regent, Dai Feng, at the Imperial Palace in Peking. He was honoured by the French and Russian governments as well.

His long illustrious life came to an end after he suffered a stroke. He passed away on January 20, 1960 at the age of 81, barely one week after returning to his new home at Chor Sin Kheng Road, Penang.

Regina Hoo is a Broadcasting and Journalism graduate from the University of Wolverhampton.



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