Massive doubts about dengue fever vaccine effect

Dengue fever vaccine did not appear to be the celebrated breakthrough

15/09/2012

After a study on a possible vaccine against dengue fever was published in the journal "The Lancet", the French pharmaceutical company Sanofi Pasteur is already celebrating its development as a breakthrough. However, numerous media reports point to the weaknesses of the vaccine and the study authors have only found an effectiveness of up to 30 percent. Obviously, the sale should be made possible by the misinterpretation of the results of the study by the Group.

The dengue virus has been spreading worldwide since the 1970s. The originally only spatially limited occurring four different dengue virus types are now widespread in large parts of South Africa, Southeast Asia, India and South and Central America Also in the south of the US and the north of Australia people are getting more and more people with dengue fever. The cause of the growing virus spread is global travel and climate change, which allows the tropical carrier mosquitoes of the dengue virus to develop larger habitats. The possibilities of treatment and prevention are so far extremely limited. Special drugs for dengue fever or a vaccine do not exist. For prevention is only an efficient mosquito repellent, with mosquito nets, body-covering clothing and anti-mosquito repellents. For years, the major pharmaceutical companies such as GlaxoSmithKline, Inviragen, Merck or Sanofi Pasteur are working on the development of a vaccine - so far without success. Also the Sanofi Pasteur currently acclaimed study ultimately comes to no other result.

Up to 100 million dengue fever diseases per year
According to World Health Organization (WHO) estimates, up to 100 million people worldwide contract dengue fever each year. In the past decade, the number of diseases has doubled, according to WHO. The infection takes place via mosquito bites, with the Egyptian and Asian tiger mosquito being the most frequent carriers. After a maximum of two weeks incubation, the dengue fever manifests itself in symptoms such as fever, chills, severe headache, muscle and limb pain. Not infrequently, the disease is also accompanied by an itchy skin rash (rash). Normally they will return symptoms after one week at the latest. In rare cases, however, the dengue fever takes a much more difficult course. It threatens a hemorrhagic fever, with internal bleeding, vomiting blood, tarry, cerebral seizures and circulatory collapse (shock). Such a course of dengue fever can also lead to coma or, in the worst case, death of the patient.

Serious disease progression in a secondary infection
The risk of a serious illness is particularly high in a secondary infection with the dengue virus. Although the organism has developed antibodies against the type of virus in which the patients were already ill, but a new infection is usually from one of the other three dengue virus types. The immune defense or the antibodies from the first infection are overwhelmed by the altered form of the virus. It threatens misguided reactions and particularly severe disease. On the one hand, this aspect is particularly critical for children who carry antibodies given by their mothers, but it also makes it more difficult to find a suitable vaccine. Because the vaccine would have to act against all known dengue virus types equally, so as not to provoke particularly severe disease courses. Otherwise, vaccinated people may become more ill than people who have no dengue antibodies at all. Sanofi Pasteur's allegedly positive news that serum was first developed to protect against three out of four dengue virus types is actually an argument against the vaccine. Because before the fourth virus type, the vaccine offered no protection.

Dubious effectiveness of dengue fever vaccine
Also, the testimony on the efficacy of the vaccine is more than daring, given a protective effect of no more than 30 per cent found in the current study. Other vaccines have already been withdrawn from the market with significantly higher efficacy because they did not provide adequate protection. To test Sanofi Pasteur's vaccine, researchers from Thailand, France, and the United States injected more than 4,000 voluntary Thai schoolchildren between the ages of four and eleven years of age with the serum or placebo, and then watched over two years how frequent the subjects were on dengue Fever fell ill. 2,669 study participants received the vaccine, 1,333 served as a control group.

45 children fall ill despite a vaccination
According to the authors of the study, a total of 134 children fell ill with Prof. Arunee Sabchareon from the Institute of Pediatrics at the Mahidol University Bangkok. Derek Wallace, working for Sanofi Pasteur in Singapore, while studying dengue fever. Four study participants suffered a dangerous secondary infection. 45 diseases accounted for the vaccine group. This results in an efficiency of up to 30 percent according to the researchers. The vaccine was well tolerated and did not show any serious side effects, Wallace and colleagues continued. "These data show for the first time that a safe vaccine against dengue fever is possible," scientists write in the latest article.

Criticism of the success stories of the pharmaceutical company
The Head of Diagnostics of Viral Diseases at the Hamburg Bernhard Nocht Institute for Tropical Medicine, Dr. med. med. Jonas Schmidt-Chanasit, expressed his skepticism towards "ZEIT Online", in view of the current success stories of the pharmaceutical company Sanofi Pasteur. "In reality, there was no significant difference between the vaccinated children and the control group," criticized Schmidt-Chanasit. Other vaccines have been withdrawn from the market with an efficacy of 40 to 60 percent, as the protective effect did not meet the applicable standard. In addition, even with a higher effect against all four dengue virus types would remain a residual risk, as more virus variants can occur. Only recently has been "researching more closely, which dengue viruses among monkeys are in circulation," said Schmidt-Chanasit. These could also be transmitted by mosquitoes to humans, which could trigger the risky effect of a second infection with extreme immune responses of the vaccinees.

Mosquito repellent the best dengue fever prevention
The study authors were not only concerned with demonstrating the effectiveness of the dengue fever vaccine, but also with the safety of the vaccine. They considered it a significant success that the vaccine was well tolerated and no vaccinated child had the effect of a dangerous second infection. According to the researchers, the vaccine group did not show any more severe disease progression or increased hospital stays. The vaccine will now be tested in a large phase 3 trial of 30,000 volunteers in South America and Asia to gain more data. The long-term risk of side effects would also have to be scrutinized more closely, since a two-year trial period hardly provides any information on the long-term consequences of the vaccine, the critics say. Dr. Schmidt-Chanasit, who specializes in the rapid diagnosis of dengue fever as a motion sickness and researches the transmission risk of native mosquito species, said mosquito repellent remained the best prevention against dengue fever. Here are also the current research in Australia, to control the carrier mosquitoes with infested bacteria "a very important approach, without which you can not stem Dengue," the expert told "TIME Online".

Distribution of dengue fever in Germany
Although diseases of dengue fever in Germany are currently an exception, the number of infections has increased significantly in Germany over the past ten years. The Robert Koch Institute in Berlin reports about 400 diseases in 2010. In 2001, the number was still 60 infections. Most of the dengue fever is still brought as a motion sickness, but also the carrier mosquitoes have spread in recent years increasingly in Germany. As long as the dengue viruses are not yet widespread in the population, they can not be transmitted by the mosquitoes. However, Dr. Schmidt-Chanasit to consider that the pathogens, once they have settled once in the mosquito population, will be passed through the eggs to the offspring. Accordingly, a further increase in dengue fever infections is likely in the coming years. For the pharmaceutical companies, a rewarding business beckons here, so that premature success stories must also be evaluated against this background. (Fp)

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