First Malaria Vaccine Trial In Humans

Plasmodium virax parasites inside red blood cells. Kateryna Kon/Shutterstock

Two new developments in the battle against malaria, one of the world's biggest killers, have been announced. For the first time, a vaccine has been trialed in humans that might offer protection against the most common malaria parasite, Plasmodium vivax, although results so far are modest. Meanwhile, evidence has emerged that the most effective existing control method may have more life in it than expected.

In the journal PLOS Neglected Tropical Diseases, a team from the Walter Reed Institute of Research announced that 30 volunteers had been given three doses of a trial vaccine and bitten by Plasmodium vivax-carrying mosquitoes 14 days after the final dose.

P. vivax is not as frequently deadly as its fellow malaria-causing relative, Plasmodium falciparum, against which vaccine development is more advanced. Nevertheless, it can make untreated patients very sick, and return multiple times. These two Plasmodium species were responsible for more than 400,000 deaths in 2015, mostly children.

None of the participants in the trial suffered serious ill effects from the vaccine itself, although headaches and fatigue were common, and all showed a strong immune response. However, inoculation did not prevent any of them from catching malaria, although the disease's development was delayed compared to six unvaccinated controls, particularly for the ten participants who received the highest dose.

An anopheles mosquito drinking blood. Amir Ridhwan/Shutterstock

As unpleasant as the trial must have been for those infected, it was also a challenge for the research team, who had to arrange for mosquitoes to feed on the blood of a Thai patient infected with P. vivax since, unlike P. facliparum, P. vivax cannot currently be grown in the lab.

"This study represents the first vaccine study to test the effectiveness of a P. vivax vaccine candidate in humans using controlled human malaria infection," said first author Lt. Col. Jason W. Bennett in a statement.

The researchers made an unexpected discovery in the process of their research. The only FDA-approved drug to treat the dormant stages of P. vivax is primaquine, without which relapses are common. Primaquine is known to not work for some people. Bennett's team are the first to provide an explanation, showing that individuals who for genetic reasons have low levels of the liver enzyme 2D6 (CYP2D6) cannot convert primaquine to the active drug that kills the dormant parasite.

Given the vaccine's limited success it's encouraging that insecticide-treated bed nets, currently the most cost-effective way of fighting mosquito-borne diseases, may have more of a future than some have feared.

Mosquitoes are masters at developing resistance to insecticides, most notably becoming immune to DDT in many areas, rendering what was once a wonder-chemical useless. There are fears that the same would occur with the pyrethroid insecticides with which the bed nets are treated.

In the journal Parasites and Vectors, PhD student Mojca Kristan of the London School of Hygiene and Tropical Medicine revealed that even when mosquitoes are resistant to the insecticide deltamethrin, the malarial parasite is not.

“Both prevalence and intensity of infection were significantly reduced in delta-methrin-exposed mosquites compared to those exposed to untreated nets,” the paper reported. People sleeping under the nets might get bitten once resistance develops, but Kristan's work suggests they are unlikely to get sick. Nevertheless, Kristan warned in a statement that the work needs to be extended to see if more limited contact with the nets has the same effect.

Image in text: A woman sleeping under a bed net, designed to protect against malaria. Milkovasa/Shutterstock

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