“Throwing a wrench into the works” is a common colloquial phrase used to describe how a complex plan can be disrupted by one simple action. This is most often the approach that scientists use when developing treatment strategies for debilitating disorders and could be the key to preventing the transmission of parasitic infections like malaria. Malaria is a disease that spreads incredibly efficiently, and current antimalarial medicines cannot do much to stop this since parasites remain in the patient's blood for a long time after treatment—allowing them to be taken up by feeding mosquitoes and spread to different human hosts. Now, a team of investigators, led by scientists at Radboud University Medical Center in Nijmegen, The Netherlands, believe they have deciphered the human immune signature during parasite infections that could be exploited to prevent parasite transmission.
Findings from the new study—released today in Nature Communications in an article entitled “Unravelling the Immune Signature of Plasmodium falciparum Transmission-Reducing Immunity”—describes how 1 in 25 malaria patients can stop the spread of malaria through antibodies their immune systems created, which end up destroying the parasites in the mosquito's stomach or prevent fertilization. Moreover, the research team found that missionaries who had been infected with malaria dozens of times during their missionary work, immunity was even more common.
“This is the first time that we have been able to produce direct evidence that human antibodies against malaria parasite proteins are able to prevent the spread of malaria,” explained co-senior study investigator Teun Bousema, Ph.D., a researcher at Radboud University and senior lecturer at the London School of Hygiene and Tropical Medicine.
Male and female parasites are fertilized in the mosquito's stomach; the offspring are transferred back to humans when they are bitten by a mosquito, and the cycle starts again. In this way, just one malaria patient can cause more than 100 new malaria infections. In the fight against malaria, it is therefore very important to make sure that people are not able to infect other mosquitos. Interestingly, malaria-infected individuals produce antibodies that can provide protection from further infection, but they can also prevent the spread of malaria as the antibodies destroy the parasites in the mosquito's stomach or prevent fertilization. In that case, it is not the patient who benefits from the antibodies that he or she produces, but other people who are bitten by the mosquito—creating an interesting form of altruistic immunity.
“Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito when they are ingested in an infectious blood meal,” the authors wrote. “Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays.”
Traditionally, research into whether people can stop the spread of malaria is incredibly labor intensive. For each patient, dozens of mosquitos need to be investigated to see whether they have been infected after sucking up the blood of the malaria patient. Until recently, all these mosquitos needed to be dissected. Luckily, however, this problem has now been solved.
“We have developed a malaria parasite that expresses a firefly gene,” Dr. Bousema added. “Allowing us to see just by looking at the mosquito whether or not it has been infected.” This has sped up the research considerably.
The research team studied patient’s immune response to over 300 malaria proteins to determine which, if any, were detrimental to the parasite's survival. “We saw that our test subjects produced antibodies that can slow the spread of malaria in response to 45 of these proteins,” noted lead study investigator William Stone, a doctoral candidate at Radboud University. “People with these antibodies were ten times less likely to infect mosquitos.”
The researchers are continuing their work to determine if any of the identified proteins would be good candidates for vaccine development.
“This research enables us to better understand which patients prevent the spread of malaria,” Dr. Bousema concluded. “We are now looking at whether it is possible to develop a malaria vaccine using some of these proteins. A vaccine that prevents the spread of malaria would help reduce the disease burden of malaria worldwide.”