Malaria is a life-threatening – but treatable and preventable – mosquito-borne disease, typically characterized by fevers, chills, and vomiting. Malaria is caused by five species of parasites of the genus Plasmodium: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale (including two subspecies, P. ovale curtisi and P. ovale wallikeri), and Plasmodium knowlesi. Of these, P. falciparum is the most deadly, and together with P. vivax makes up the vast majority of cases of malaria. Infected mosquitoes (of the genus Anopheles) transmit these parasites to human hosts, who remain symptomless for a latent period of varying lengths, after which they can experience sudden, severe symptoms often resulting in death.
Scientists have been studying malaria for over 100 years, but there is still much to learn. We know the general form of the parasite life cycle but still do not fully understand how parasites perform some of the functions researchers have seen, or how the human immune response works. Indeed, there is not even a consensus on why the Global Malaria Elimination Program was successful in eliminating the disease from many countries (generally outside sub-Saharan Africa), and why malaria returned in only a few of those countries. In short, malaria transmission is incredibly complex, depending on both physical and built environments as well as the interactions and behavior of human, parasite, and mosquito populations and ever changing based on these factors.
The aim of the Malaria Modeling Consortium’s work is to synthesize the results of different studies in order to have as comprehensive an understanding of malaria transmission as is currently possible, identify areas requiring further research, and make policy recommendations for malaria control and elimination.
Plasmodium parasites enter the body when an infected mosquito bites a human and injects sporozoites into the bloodstream. Sporozoites do not remain in the blood long, quickly migrating to the liver and invading liver cells. There they undergo asexual reproduction until the liver cell bursts, releasing the newly formed merozoites into the bloodstream. The duration of asexual reproduction in the liver varies with parasite species, but for some species (notably P. vivax), some parasites remain in the liver and can cause a relapse months after the initial infection. Additionally, detection is generally difficult during this stage due to the absence of symptoms and a lack of parasites in the blood.
Once merozoites enter the bloodstream, they invade red blood cells (RBC), beginning the blood stage of the infection. Once a parasite infects a RBC, it grows by ingesting and breaking down the host RBC’s hemoglobin, in the process releasing a byproduct, hemozoin, which has long been recognized as ‘malarial pigment.’ Once the parasite has matured within the RBC, it begins another stage of asexual reproduction, producing more merozoites, which will invade more RBCs, continuing the infection. After a period of asexual reproduction (for P. falciparum, generally 24-72 hours), the host RBC bursts and releases the merozoites into the bloodstream. It is this bursting of RBCs that causes the symptoms of malaria, and the synchronization of reproduction of many parasites within RBCs that causes symptoms to occur in cycles. In addition, rather than producing more merozoites in the RBC, some parasites initiate the sexual stage of the life cycle, producing gametocytes, which do not cause additional symptoms but are the only form of the parasite that can infect a mosquito.
When a mosquito ingests gametocytes of both sexes in its blood meal, the gametocytes mature, begin sexual reproduction and migrate to the lining of the mosquito’s gut, and eventually produce sporozoites. The time required for maturation and production of sporozoites depends on several factors, including species and temperature, and is an important consideration in understanding transmission. Once sporozoites have been produced, they migrate to the salivary glands, where they can be injected into a human (or animal) host when the mosquito bites, starting the cycle of infection again.