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Science Translational Medicine: Antibiotics: A Natural Vaccine for Malaria?
People at high risk for malaria may benefit from swallowing a cocktail of antibiotics as a preventative measure, a new Science Translational Medicine study in mice suggests. The drugs may evoke natural immunity to malaria parasites in healthy but vulnerable populations, providing lifelong protection against future malaria infections.
This electron micrograph shows a Plasmodium sporozoite, the infectious stage transmitted upon a mosquito bite, upon entry into its first host cell in the human body, a liver cell. Antibiotic prophylaxis arrests the parasite life cycle only after maturation of parasite daughter cells and is a surrogate needle-free malaria immunization strategy that takes advantage of natural mosquito-born sporozoite injection.
In 2008, malaria caused nearly 1 million deaths—mostly among children living in Africa, where a child dies every 45 seconds of the disease, according to the World Health Organization. Malaria is caused by Plasmodium parasites, spread to people through the bites of infected Anopheles mosquitoes.
Preventative treatment with affordable and safe antibiotics in residents of regions with intense transmission has the potential to act as a "needle-free" natural vaccine against malaria and will likely provide relief in areas where repeated immunizations with expensive anti-malaria vaccines present a number of complex logistic challenges.
The authors believe that the benefits of using antibiotics against the disease outweigh the risks of growing bacterial resistance to malaria drugs, as these are not frequently used in resource-poor, malaria-endemic countries.
In the study, Johannes Friesen from the Heidelberg University School of Medicine and colleagues from the Max Planck Institute for Infection Biology, London School of Tropical Medicine and Hygiene, and Kenya Medical Research Institute gave healthy mice preventative antibiotics and subsequently infected the animals with malaria parasites.
This immunofluorescence picture shows an arrested, mature malaria parasite inside its first host cell in the human body, a liver cell. Despite antibiotic prophylaxis a sporozoite enters a liver cell and forms many daughter cells, each containing a nucleus (small blue dots). The essential organelle of red algal origin, termed apicoplast (red), is targeted by antibiotics and can no longer form the typical branched and extended structures. As a consequence, Plasmodium merozoites emerging from the liver cannot infect and reproduce within the next target cells, host erythrocytes.
Image courtesy of Johannes Friesen
The researchers found that the mice generated a vaccine-like immunity against re-infection. Moreover, even when given low doses of antibiotics, almost all mice were protected from the fatal brain complications associated with the most dangerous malaria parasite, Plasmodium falciparum.
The antibiotics work by causing a cellular defect in malaria parasites during their journey into the liver of the infected host. This action blocks the malaria parasite’s fatal conversion from the liver stage to the disease-causing blood stage. The developmentally arrested parasite inside the liver allows the body to mount a strong protective immunity to malaria, akin to a traditional vaccination.
Thereafter, new malaria parasites will be recognized and destroyed in the liver. Clinical trials are needed next to ensure this approach works as well in humans. If successful, periodic administration of antibiotics in high-risk population groups, such as young children, may prove to be a valuable tool for controlling and/or eliminating malaria in regions of high transmission.
Science Translational Medicine, the newest journal from Science, focuses on outstanding science with promise to improve human health and quality-of-life. Under the direction of Elias Zerhouni, chief scientific adviser and former director of the National Institutes of Health, and Editor Katrina Kelner, the journal aims to publish groundbreaking research from basic biology that will help make significant advances in medical care, along with commentary on the latest issues in translational medicine.
14 July 2010