Why bacteria are being recruited in the fight against dengue fever
April 16, 2013
It can be lethal, it makes patients ill for weeks and there’s no vaccine against it. Cases of dengue fever, the symptoms of which include high temperature, an aching body, and fatigue, have increased 30-fold in the last 50 years. The World Health Organization estimates that around 50 to 100 million people are infected yearly and 2.5 billion people live in risk areas. The mosquito-borne viral disease thrives in tropical and sub-tropical climates and has endemic status in the Americas, Southeast Asia, the Western Pacific, Africa and the Eastern Mediterranean, mostly in urban and semi-urban areas.
The main vector of the disease is a mosquito called Aedes aegypti. There are four variations of the dengue virus, hence the difficulty in developing a vaccine. There’s no specific medication either, and patients are usually treated with painkillers, fluid and rest. Although there are vaccine trials being conducted at present, a great deal of research is focused on preventing the mosquito from infecting people in the first place.
Dengue in Brazil
Brazil is one of the most affected countries in the world. Government data shows that in the first 12 weeks of 2013 alone, 635,100 Brazilians were infected. Out of this total, 108 people have died of the more severe, if rarer, manifestation of the disease known as dengue hemorrhagic fever. For that reason, one of the most promising developments in dengue prevention research is about to be tried out in that country by the Oswaldo Cruz Foundation (Fiocruz), one of Brazil’s most respected science institutions.
Fiocruz will apply the method developed by Eliminate Dengue: Our Challenge, an international cooperation led by Monash University in Australia, with branches in Indonesia, China and Vietnam. The project is funded by several organizations, including the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill & Melinda Gates Foundation.
The method involves introducing Wolbachia, a natural bacteria found in 70 percent of insects, into the Aedes aegypti mosquito via micro-injection. The bacteria stops the virus from growing and, consequently, it can’t be transmitted to people.
The first field trials of the Wolbachia dengue control method in Brazil are scheduled for May 2014. “Our hope, following extensive laboratory and field studies, approval from regulatory authorities and support from residents, is that we will be ready for the first field trials with Wolbachia Aedes aegypti mosquitoes in Rio de Janeiro in 2014,” Dr. Luciano Moreira, the Brazilian scientific partner of the Eliminate Dengue project, said in a press release.
In lab conditions, Wolbachia appears to be a great little helper to fight dengue. Besides blocking the virus in the Aedes aegypti mosquito, the Australian field trials showed that once Wolbachia is transmitted from generation to generation through the mosquito eggs and have reproductive advantages, in a few weeks the mosquitoes with Wolbachia became predominant in local populations of Aedes aegypti.
The Australian field trials kicked off in 2011, when researchers released Wolbachia mosquitoes in Yorkeys Knob and Gordonvale, two suburbs in Cairns, Queensland. In addition to Brazil, further trials are also planned for Vietnam and Indonesia.
“With this project, we are taking a leading role in an innovative, natural and economical approach against dengue, one of the greatest public health burdens in Brazil,” said Paulo Gadelha, Fiocruz’s president.
Once the mosquitoes are released, the researchers will monitor and assess the viability of the project. Currently, the project in Brazil is focused on rearing colony systems of mosquitoes with Wolbachia. These are then crossed with local mosquitoes that are genetically similar to their parents so they produce a genetically similar offspring through a process known as backcrossing. They are also constructing large cages to rear and trial the mosquitoes before the field releasing begins. Besides, the locations are being selected for the field trials next year, which includes collecting entomological data on the local mosquito populations.
“The Eliminate Dengue method is a long-term approach to control the spread of dengue and we must reinforce the message the project is still in the research phase," said Dr. Moreira. "The best strategy to combat the dengue vector at this time and in the future is still the manual removal of breeding sites around homes. It would be fully compatible with a vaccine, once developed.”
In fact, removing breeding sites around the house is a routine that most Brazilians have grown accustomed to, with televised public announcements constantly reminding them of the chore. However, if some stagnant water is unavoidable, those looking to keep Aedes aegypti at bay can turn to another ally in nature. Recently, the Instituto de Nacional de Pesquisas da Amazônia, an Amazon-based research center, discovered that a substance called Eugenol, which is found in clove (Syzygium aromaticum), can kill the larva of the dengue mosquito in 24 hours.
The formula is undergoing patenting, but it’s simple and can be prepared at home by blending 60 clove buds and a cup of water. No sieving is required and the solution can be kept in a fridge for up to one year. In terms of dosage, three drops suffice for a 15-cm vase (popular targets for dengue mosquitoes) or other types of containers that retain water. The blend will remain effective for about 14 days.
The researchers highlight that the clove solution is no substitute for other preventive measures, but it can drastically reduce reproduction of the mosquito. Like the Wolbachia bacteria method and the genetic modification of the mosquitoes, the clove-based remedy is harmless to the environment. Most importantly, it is readily available.
Another possible means of preventing dengue recently emerged from the labs of the Massachusetts Institute of Technology, where researchers have created a method to develop a therapy that uses mutated antibodies that target the more potent “A” strand region of the virus protein. They’ve chosen as their model an antibody known as 4E11, which had been shown in tests to neutralize dengue 1, 2 and 3, though not dengue 4.
The researchers then used a statistical approach to produce a final list of 10 mutations of the antibody in order to improve its dengue 4 neutralizing ability. Tests showed it had a 450-fold increase in binding to dengue 4, a 20-fold increase in binding for dengue 2, and lesser improvements in binding for dengue 1 and 3. Now they are preparing for preclinical trials and hope that the antibodies could be tested in humans in the next two or three years.
The video below explains Eliminate Dengue's work in more detail.
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