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Wednesday, August 13, 2003
Dengue vaccine: Now in the offing?
By Henrylito D. Tacio
RESEARCHERS from Thailand, using sophisticated techniques once the exclusive domain of Western scientists, have developed a vaccine against dengue, a mosquito-borne disease that infects more than 100 million people a year.
The vaccine, developed at Mahidol University with grant support from the World Health Organization (WHO), has just finished its so-called "Phase 2" clinical trial in the said country.
"Now, we are waiting for Phase 3 trial where the vaccine will be tested against a large number of subjects may be as many as 20,000 children and to see that it could protect the disease by comparing with placebo group," said Dr. Natth Bhamarapravati, a pathology professor of the university and head of the on-going study.
A placebo is an inactive substance given as if it were a real dose of a needed drug.
Placebos are used in drug studies to compare the effects of the inactive substance with those of an experimental drug.
"The two groups will have to be blinded to determine the effect of the dengue vaccine," Dr. Bhamarapravati said.
The dengue vaccine, initial findings of the trials showed, appears to be the best bet to tackle a disease that has spread alarmingly over the past three decades.
About 2.5 billion people are believed to be at risk of the viral infection.
By 1975, dengue had become a leading cause of hospitalization and death among children in many countries, especially in Southeast Asia.
"Dengue is now one of the leading causes of death among children in such countries as Thailand, Indonesia, the Philippines and Vietnam," says Dr. Allan Schapira, an epidemiologist who used to work with the WHO regional office in Manila.
"The problem is increasing" and "the epidemics are dramatic."
That is how Dr. Schapira, who is now with the WHO headquarters in Geneva, describes the dengue crisis in the region.
In Asia, the number of recorded cases per year is about 200,000 to 400,000. "But this figure is just the tip of the iceberg," the WHO officer warns, adding that "the real number of infections is probably about 10 times as high."
The increase in dengue cases is the result of the expanding geographical distribution of the mosquitoes that carry the virus, especially the "Aedes aegypti" species, which is mainly found in urban areas.
At the same time, the rapid rise in urban populations has increased the number of people exposed to the virus.
Dengue is characterized by an abrupt onset of high fever lasting from three to five days, severe headache, pain behind the eyes, muscle and joint pains, nausea and vomiting, and a measles-like rash on the chest and upper limbs.
These characteristics vary according to the age and general health of the patient.
This is why the Department of Health (DOH) is advising people to immediately see a doctor if they suspect they have dengue.
It is up to the doctor to determine whether the patient should be hospitalized or could be treated at home.
Dengue hemorrhagic fever (DHF) is the fatal stage. It is characterized by high continuous fever lasting two to seven days that may be accompanied by loss of appetite, nausea, vomiting, abdominal pain and subsequent evidence of bleeding like persistent red spots on the skin, nose or gum bleeding, coffee-ground vomit, and dark stools.
The patient can go into shock. "After a dengue patient has gone into shock, it's usually a matter of time before multi-organ failure occurs and death becomes inevitable," says Dr. Lulu C. Bravo, chief of pediatric infectious disease section at the Philippine General Hospital.
Some five percent of DHF cases are fatal; without proper treatment, the rate rises to 15 per cent.
Dengue is caused by one of four dengue viruses. Recovery from infections ensures lifelong immunity against the particular virus involved, but not against the other three. Even worse, if subsequent infection with a different serotype or variant occurs, it is believed to increase susceptibility to DHF.
"This is what is called antibody enhancement phenomenon," explains Dr. Malik Peiris, an American microbiologist.
It's why a vaccine has so far eluded scientists. "The worry is that if you immunize someone without immunizing them against all four types, it might actually be worse," he said.
However, hope is on the horizon.
"Many biotechnological approaches have been used in attempts to develop dengue vaccine candidates, including live attenuated vaccines, infectious clone-derived vaccines, recombinant live vector systems, subunit vaccines and nucleic acid vaccines," reports the State of the World's Vaccines and Immunization.
Major projects to fight dengue are being undertaken by private and academic researchers in the United States, France, and Australia.
The Thai project, initiated in 1976, chose to make a live attenuated virus vaccine, an approach used successfully against poliomyelitis, measles, and mumps.
Under this method, the virus loses its disease-causing properties while retaining the ability to stimulate the production of antibodies.
(August 13, 2003 issue)
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