HEALTH: Cuba Making Progress towards Dengue Vaccine

By Patricia Grogg Reprint | | Print |

Patricia Grogg

HAVANA, Jul 19 2002 (IPS) - Researchers in Cuba continue making progress towards a vaccine against dengue, although without losing sight of the fact that for now, prevention measures are the only answer to the spread of the potentially fatal disease.

“When I started to work on this question, in the early 1980s, we used to say that in 10 years we would have a vaccine. We still say that today, but now we are closer to actually achieving it,” Guadalupe Guzmán, director of the Pedro Kouri Institute of Tropical Medicine (IPK) virology department, told IPS.

The IPK is spearheading Cuba’s efforts to come up with a vaccine, in which the Centre for Genetic Engineering and Research and the Finlay Institute are also involved, Guzmán explained. All three institutions are based in Havana.

The group is carrying out recombinant research, which is based on genetic engineering techniques.

“At this time, studies are being carried out on monkeys, basically, and they’re going very well so far,” said Guzmán, who also works with one of the World Health Organisation’s (WHO) collaborative centres for studies on viral diseases.

The most advanced research in the world on dengue is being conducted by Aventis Pasteur in France, which obtained the licence for a live attenuated vaccine from the University of Thailand. The institute has already carried out phase I and II trials, and is preparing the third and final stage of research.

At the same time, the U.S.-based pharmaceutical company Glaxo- SmithKline is working on its own live attenuated vaccine, similar to that being developed by Aventis Pasteur, and reportedly already has a group of adults immune to the dengue virus.

The first reported epidemics of dengue fever, which is transmitted by the Aedes aegypti mosquito, occurred in 1779-1780 in Asia, Africa, and the Americas.

In the Americas, the disease was virtually eradicated by efforts against yellow fever, which is transmitted by the same mosquito. But major outbreaks occurred in the 1960s in tropical areas in the region, and dengue is now making inroads in subtropical areas.

Hemorrhagic dengue, the most virulent form of the disease, killed 158 people – including 101 children – in Cuba in 1981, and claimed 74 lives in Venezuela in 1989.

The first symptoms of the disease are flu-like – fever, headache, loss of appetite and joint and stomach pain – which stands in the way of early diagnosis, essential to providing the necessary supportive treatment in the form of rest, abundant fluids, pain-killers and hospitalisation if hemorrhagic fever or dengue shock syndrome develop.

There is no cure for dengue, which makes the search for a vaccine even more urgent.

The process of developing vaccines against dengue begins with lab research, and then testing on lab animals. The innoculations that provide the strongest immunological response are later tested on human beings in clinical trials.

The clinical trials are broken down into three phases. In phase I, the vaccine is tested on 20 to 40 volunteers to confirm that it is immunogenic and does not have undesireable side-effects.

Phase II trials are then carried out among a bigger pool of volunteers, usually from 100 to 300 people.

In phase III testing, researchers measure the effectiveness of the vaccine, using thousands of volunteers who are exposed to a high risk of infection by all four types or serotypes of dengue.

Dr. Guzmán explained that “a vaccine should be low-cost and provide long-lasting immunity to each of the four serotypes of dengue. It must be tested in southeast Asia as well as the Americas, because the different serotypes do not necessarily respond in the same manner.”

The trials must also involve children, the hardest hit segment of the population, among whom the risks are even greater, said the researcher.

But “when we test it, we don’t know if the vaccine itself will infect the subject with dengue. That is something we must watch out for,” she added.

Guzmán stressed that it is indispensable to set up the infrastructure needed to monitor the health of the minors involved in testing the vaccine – infrastructure that tends to be lacking in the poor, tropical countries where dengue epidemics occur.

Another aspect compounding the complexity of the research is that each serotype has different strains. “For example, there are strains of the number 2 virus that come from southeast Asia and are capable of producing hemorrhagic dengue, the most dangerous form of the disease,” she explained.

Guzmán also reported that researchers are attempting to evaluate possible changes in the serotypes as the epidemics advance. “We think that the virus gradually changes as time goes on, although not as much as the AIDS virus,” she said.

Getting a second dengue infection, particularly with type 2, leads to an even worse infection, with the risk of hemorrhagic fever or dengue shock syndrome, which can be fatal. There is no “cross-protective immunity”, which means that people can potentially be reinfected four times in their lifetime, by each of the four different serotypes.

Guzmán also said the danger is much greater in children than in adults. And contrary to what was long believed, the patient remains at risk of reinfection for 20 years after the first bout of illness.

Dengue has a short incubation period, usually less than a week. The symptoms include a sudden, rapidly climbing fever, severe headache, nausea and vomiting, loss of appetite, rash and deep muscle and joint pains. The disease has been dubbed “breakbone fever” due to the last two symptoms.

If hemorrhagic fever develops, the patient starts bleeding – from the nose, the mouth, the gums, the skin, the intestinal tract. And when shock syndrome occurs, blood pressure plunges.

Hemorrhagic dengue was first reported in southeast Asia, where all four types of the virus circulate, and where epidemics break out every year.

“The situation in the Americas is beginning to look like the situation in southeast Asia. All four viruses can now be found in this region, some countries have two or three different serotypes at the same time, and the Aedes aegypti mosquito is occurring in high density,” said Guzmán.

She noted that the density of mosquitos is growing as urban poverty expands, because the conditions in overcrowded city slums that lack clean water, sewerage and garbage collection services create an ideal breeding-ground for the mosquitos, which need standing water – which can be found in empty tires, flower pots, or any kind of empty container – in which to lay their eggs.

“Until a vaccine appears, it is indispensable to put into practice ongoing programmes aimed at controlling dengue and the mosquito which transmits it. For now, there is no other option by prevention,” Guzmán underlined.