Malaria pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Yazan Daaboul, Serge Korjian, Alison Leibowitz [2]
Overview
Malaria in humans develops in two phases: an exo-erythrocytic (hepatic) and an erythrocytic phase. When an infected mosquito pierces an individual's skin for blood, sporozoites in the mosquito's saliva enter the bloodstream and subsequently migrate to the liver.
Pathophysiology
Malaria is caused by protozoan parasites of the genus Plasmodium (phylum Apicomplexa). In humans, malaria is caused by P. falciparum, P. malariae, P. ovale, P. vivax and Plasmodium knowlesi. P. vivax is the most common cause of infection, responsible for about 80% of all malaria cases. P. falciparum, the most significant cause of disease, is responsible for about 15% of infections and 90% of deaths.[1][2]
Life Cycle
The life cycle of Plasmodium parasites begin when the sporozoite, a haploid form of the parasite, is injected into the human bloodstream by the female Anopheles mosquito.[3] The sporozoites travel in the bloodstream to the liver and invade human hepatocytes. Over 1-2 weeks later, in the exo-erythrocytic phase, the sporozoites grow into schizonts and produce thousands of merozoites in each hepatocyte. The merozoite is a haploid form of the parasite.[3] While some hepatocytes rupture and release the merozoites, other parasites remain dormant within the liver.[3] The release of merozoites, by the hepatocytes, into the bloodsteam results in the manifestation of the malarial symptoms. The latency of cell rupture between various hepatocytes and the consequent merozoite release into the bloodstream, is responsible for the characteristic periodic fever associated with malarial infections.[3]
As merozoites are released into the bloodstream, they infect erythrocytes and undergo asexual multiplication (mitosis). Some merozoites continue the cycle of asexual replication into mature trophozoites and schizonts, which rupture to re-release merozoites. Others develop into sexual forms, the gametocytes, which involve male (microgametocyte) and female (macrogametocyte) parasites.[3]
Though biting, Anopheles mosquitos ingest the gametocytes within the red blood cells, initiating the sporogonic cycle inside the mosquito. In the mosquito's gut, the cells burst and the gametocytes are then released, allowing their development into mature gametes. The fusion of male and female gametes forms diploid zygotes, which become ookinetes, motile and elongated forms of the parasites. Within the mosquito midgut wall, they develop into oocysts.[3] As oocysts continue to grow, they divide into active haploid forms, the sporozoites. Thousands of sporozoites are produced in each oocyst. When oocysts burst following 1-2 weeks, sporozoites travel to the mosquito's salivary glands, so that when the mosquito bites other humans they inject the sporozoites into their bloodstream, leading the cycle to restart.[3]
While parasites generally shift from sporozoites into merozoites as they invade red blood cells, some species, such as P. vivax and P. ovale are characterized by their ability to produce hypnozoites, an intermediate stage where the parasite remains dormant for a few months/years before reactivation into merozoites. The hypnozoite stage allows teh species to demonstrate late relapses and long incubation periods.[4]
Human Factors
Some human factors may provide a protective advantage against malarial infection. Individuals with sickle cell trait, defined as the heterozygous for the abnormal globin gene, HbS, are protected against P. falciparum. In individuals with sickle cell trait, red blood cells invaded by P. falciparum tend to sickle more readily than other red blood cells, leading them to be eliminated from the bloodstream by macrophages.[5] The preventative advantage demonstrated in heterozygous sickle cell patients is not observed in patients who have sickle cell anemia and carry a homozygous sickle gene. Contrarily, these patients are more susceptible to lethal complications of severe anemia.[5] Other similar hematological diseases that provide a protective effect against malaria are thalassemia, hemoglobin C, and G6PD deficiency.
Similarly, individuals who have a negative Duffy blood group are resistant to infection by P. vivax. These individuals are still susceptible to other species of malaria, especially P. ovale, which frequently infects individuals with negative Duffy blood group.[6]
References
- ↑ Mendis K, Sina B, Marchesini P, Carter R (2001). "The neglected burden of Plasmodium vivax malaria" (PDF). Am J Trop Med Hyg. 64 (1-2 Suppl): 97–106. PMID 11425182.
- ↑ Long CA, Zavala F (2017). "Immune Responses in Malaria". Cold Spring Harb Perspect Med. doi:10.1101/cshperspect.a025577. PMID 28389518.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Malaria". National Institute of Allergy and Infectious Diseases. NIH. Apr. 3 2012. Retrieved Jul 24 2014. Check date values in:
|accessdate=, |date=(help) - ↑ Cogswell F (1992). "The hypnozoite and relapse in primate malaria". Clin Microbiol Rev. 5 (1): 26–35. PMID 1735093.
- ↑ 5.0 5.1 Luzzatto L (2012). "Sickle cell anaemia and malaria". Mediterr J Hematol Infect Dis. 4 (1): e2012065. doi:10.4084/MJHID.2012.065. PMC 3499995. PMID 23170194.
- ↑ "Malaria". Centers for Disease Control and Prevention. CDC. Nov 9 2012. Retrieved Jul 24 2014. Check date values in:
|accessdate=, |date=(help)