Mosquitoes that transmit malaria are attracted to individuals by the profile of their body odour. Differences in odour profile make some people more attractive to mosquitoes than others, thus mosquito biting is non-random. Malaria infections increase attractiveness, making it more likely that infected people are bitten and the parasites are passed on to others.
Parasitic infections often change the behaviour or physiology of their hosts in ways that will enhance the likelihood that the parasite can continue its life cycle; either in another host or as a free living stage in the environment. However, these changes will only benefit the parasite if it has reached the stage in its development during which it is mature enough to infect its next host, or survive in the environment. For the vertebrate phase of the malaria parasite’s life cycle, this stage is the gametocyte and malaria transmission will only occur when these sexual stages are present. They are produced from the asexual, red blood cell stages after a period of multiplication and reinfection of new red blood cells. If taken up by a mosquito with its blood meal, female gametocytes are fertilized by male gametocytes and development in the mosquito begins. Therefore, increased host-attractiveness to mosquitoes will only benefit the parasite if gametocytes are present in the blood.
In addition to early studies using rodent-malaria parasite, a field study, conducted in Kenya a decade ago, investigated how attracted the local mosquito vector, Anopheles gambiae, was to children sleeping in experimental huts. The study produced evidence that children infected with
Plasmodium falciparum, the major species of human malaria in Africa, were twice as attractive when gametocytes were present in their blood than were uninfected children, or those just infected with the asexual (non-infective) stages. Furthermore, this increased attractiveness disappeared after antimalarial treatment. The experimenters concluded that the increased attractiveness of human odour to a malaria vector may be specifically associated with the presence of gametocytes.
A short report, recently published in Parasites and Vectors, concludes that the presence of gametocytes of another important species of malaria that infects humans, Plasmodium vivax, also makes their host more attractive to mosquitoes. Unlike the Kenyan study, these experiments were conducted in the laboratory and measured the short-distance attractiveness response of Anopheles darlingi, the main vector of P. vivax in Brazil. The attractiveness of patients was tested after the original malaria diagnosis. Patients were then treated with an antimalarial drug, primaquine, and re-tested 7 days later, during the treatment period, and again after 24 days when treatment had finished. In addition to the effect of body odour, the temperature of each subject was taken during each test to assess whether this had any effect.
Six malaria patients completed all phases of the study; gametocytes were detected in the blood of some of them and just asexual stages in others. The tests were conducted using an olfactometer consisting of two chambers. Mosquitoes were released into the upper chamber and, after five minutes acclimatisation time, the patient’s foot was placed below the lower chamber and the number of mosquitoes moving into this chamber was recorded.
Before treatment, three times as many mosquitoes were attracted to people carrying gametocytes than to patients that were not. In addition, during the trial, symptomatic patients carrying gametocytes were twice as attractive to mosquitoes, whereas the attractiveness of patients with no detectable gametocytes did not change during the 14 days. Infection alone was thus not sufficient to increase the patient’s attractiveness to mosquitoes, but the presence of gametocytes did make patients more attractive. Once treatment was completed, no differences in attractiveness were found.
In addition to body odour, mosquitoes could have been responding to changes in foot temperature that may have been caused by fever.
However, the researchers found temperature alone did not affect attractiveness, though those with fever and gametocytes were more attractive. In this study mosquitoes were not able to access the skin directly so, although there was no correlation between temperature and attractiveness, it is possible that physical changes such as temperature elevation during fever may influence feeding choice at very short range. Interestingly, pregnant women have been found to be twice as attractive to mosquitoes, possibly due to increased heat and volatiles production. This may be one reason why they are particularly prone to malaria infection.
As it happens, a team from the US and Switzerland have today reported a study which found that components of the odour of malaria-infected mice enhanced mosquito attraction. These compounds were part of the increased volatile production that occurred after the acute symptoms of malaria had abated, but the presence of gametocytes at this time made the mice very infective.
The Brazilian study was conducted in the laboratory and only a few patients completed the trials. Furthermore, although primaquine, used in this study, is known to act rapidly against the most mature gametocyte stage, the authors did not examine the blood of patients at the end of the trial to confirm that gametocytes had been eliminated. Further studies with more participants whose infection status is monitored throughout the treatment period would be valuable, as would investigations conducted in field settings and designed to measure attractiveness over longer distances.
The finding that the presence of malaria gametocytes modify the odour profile of infected patients, making them more attractive to malaria vectors, have important bearings on our understanding of the epidemiology of the disease. They suggest that particular efforts should be made to identify gametocyte carriers and protect them from exposure to mosquitoes. Several studies, including in the Brazilian Amazon basin have shown that many asymptomatic people are actually gametocyte carriers. If these carriers are more attractive to mosquitoes, this could exacerbate the transmission of malaria, suggesting that the inclusion of asymptomatic gametocyte carriers in mass treatment campaigns aimed at malaria elimination should also be considered. In addition, the identification of specific compounds associated with human infection and attractiveness would pave the way for the development of baited traps to lure mosquitoes away from biting infected people.
Clearly the relationship between the presence of gametocytes and the odour given off by their hosts merits further study.