Plasmodium Falciparum - Causative Agent of Severe Malaria - Research Paper Example

Plasmodium Falciparum - Causative Agent of Severe Malaria Abstract The research paper revolves around the parasite Plasmodium falciparum which is the causative agent of severe Malaria. In 1976, William Trager and James Jensen developed continuous in vitro cultivation of Plasmodium falciparum which paved way for future research and development in malariology and enabled complete identification of P. falciparum genome. Since decades, P. falciparum has been the foci of attention and subjected to intense study throughout the world. Some aspects of this study include biochemistry of P. falciparum, development of effective vaccines and successful immunization of susceptible individuals. Even in today’s medically advanced world, malaria remains one of the primary concerns of researchers and health practitioners in areas where the disease is endemic. Despite immense research and availability of advanced health care facilities, malaria has a high mortality rate causing a million deaths each year and infecting a total of 300 million people around the world. The purpose of this research paper is to provide information on structure, etiology and other aspects of malaria caused by Plasmodium falciparum. Plasmodium Falciparum Mode of transmission The female Anopheles mosquito serves as a vector and a definitive host for Plasmodium falciparum. The two phases in the lifecycle of plasmodia are the sexual cycle and asexual cycle. The sexual phase occurs in female mosquito and asexual phase is completed in Humans. Due to the production of sporozoites, the sexual cycle is known as sporogony while on the other hand, the asexual cycle is known as schizogony because of the production of schizonts. Plasmodium sporozoites are introduced into intermediate host i.e. humans, through the saliva of infected mosquito when it bites an individual. Within 30 minutes, the sporozoites enter the hepatocytes where multiplication and differentiation is initiated resulting in the conversion sporozoites into merozoites (Levinson et al 1999). Physiology and lifecycle The merozoites produced in the liver are released into the peripheral circulation. Once released, the merozoites enter the red blood cells in order to mediate the erythrocytic phase of the disease. In erythrocytic phase, merozoites transform into a ring shaped trophozoite. Later, the trophozoite develops into an amoeboid form which further grows into a schizont. Each schizont is filled with several merozoites. The red blood cells burst and release the merozoites into general circulation where they infect other red blood cells in a similar manner. The release of merozoites into the blood is the cause of recurrent typical symptoms seen in malaria caused by Plasmodium falciparum. The development of male and female gametocytes leads to the initiation of sexual cycle of P. falciparum in the human red blood cells. When a female Anopheles mosquito takes a blood meal the gametocytes are sucked up and lead to the production of female macrogamete and eight male micro gametes which have an appearance similar to that of sperm cells. The male and female gametes undergo fertilization to form a diploid zygote. The process of differentiation occurs and converts the diploid zygote into a motile ookinete. The ookinete forms a hole in the gut wall and converts into many haploid sporozoites. The sporozoites leave the gut wall and enter the salivary glands of the Anopheles mosquito. Once, the sporozoites enter the salivary glands their sexual cycle is completed and they are now ready to cause malaria when the mosquito bites a human (Levinson et al 1999). Diagnosis Thick and thin Giemsa stain smears are observed under the microscope in order to determine the presence of parasite in the blood. To determine the presence of parasite, thick Giemsa smear is used while on the other hand thin smears are used for the identification of parasite species. Blood sample from an individual suffering from malaria show characteristic ring shaped trophozoites residing within the erythrocytes. The gametocytes of Plasmodium falciparum are easily distinguished from the gametocytes of other plasmodia species because its gametocytes have a characteristic crescent shape while others have spherical gametocytes. In addition to blood smears, other diagnostic methods such as PCR and ELISA are used (Levinson et al 1999). Pathogenesis and Epidemiology The erythrocyte schizogony leads to the destruction of red blood cells which is the major reason for development of typical malarial symptoms such as chills, recurrent fever and severe pain in joints. Once, plasmodium falciparum enters the red blood cells, it starts to feed on host hemoglobin and consumes more than 80% of it during the process of erythrocyte schizogony. In malaria, destruction of red blood cells occur in two ways; first, when merozoites are released and second, when spleen is stimulated to release and then subsequently lyse the red blood cells due to damage caused by the parasite. The congestion of sinusoids leads to the enlargement of spleen. The hyperplasia of immune cells and erythrocytes is responsible for the congestion of sinusoids. Plasmodium falciparum causes a several fold increased destruction of erythrocytes than caused by other plasmodia species. Furthermore, malaria caused by P. falciparum leads to the obstruction of capillaries with infected erythrocytes which may cause brain necrosis and hemorrhage. Extensive destruction of erythrocytes leads kidney damage due to the blockage of kidney tubules because of excess hemoglobin in the blood. The characteristic feature of Plasmodium falciparum is that it is responsible for causing a very high level of parasitemia. Individuals that have sickle cell anemia and glucose-6-phosphate dehydrogenase deficiency have a very low chance of being infected with malaria. In pregnant women, Plasmodium falciparum crosses human placenta and affects the fetus. Malarial parasite is also transmitted by transfusion of blood contaminated with parasite (Levinson et al 1999; Rasti et al 2004). Each year more than 300 million people are infected with malaria around the world and it claims a million deaths each year. Plasmodium falciparum is endemic in tropical and subtropical areas such as Central and South America and Asia (Levinson et al 1999). Cerebral malaria Plasmodium falciparum causes severe and fatal malaria. The infected individuals may die due to the development of a range of syndromes including cardiovascular shock and renal failure. However, the major cause of death in patients with malaria caused by P. falciparum is Cerebral Malaria. The pattern of cerebral malaria is dependent upon age and is different in children from that which occurs in adults. The process of sequestration occurs during which some of the parasites leave the erythrocytes and colonize in the vascular beds of brain, kidneys and lungs. The vital organ dysfunction characteristic of malaria caused by Plasmodium falciparum occurs because of the release of certain cytokines and chemical mediators. The cytokines such as tumor necrosis factor alpha have a generalized effect while on the other hand; chemical mediators such as nitric oxide have a local effect. Microscopic examination of specimens from individuals who died as a result of cerebral malaria exhibits a high level of cerebral sequestration which proved to be fatal. However, histological examination of specimens from certain patients of non cerebral malaria also shows significant levels of sequestration. In order to determine the viability of a link between cerebral micro vascular sequestration, coma and sequestration index, and investigators have used electron microscopy to evaluate the level of parasite sequestration. The levels of sequestration were then compared with blood samples collected from peripheral circulation from several patients that died of cerebral malaria. The results show a definitive link between cerebral sequestration and coma and indicate that there is a strong correlation between the two (Pongponratn et al 2003) Splenic complications A malarial splenic complication such as splenomegaly and rupture in most cases proves to be fatal. However, in most cases of Plasmodium falciparum malaria, splenic complications are not significant. This serves as an important differentiating factor between malaria caused by Plasmodium falciparum and vivax. Plasmodium vivax causes pronounced enlargement of the spleen (Ozsoy et al 2004) Treatment The drug of choice for the treatment of acute malaria is chloroquine. However only those strains of P. falciparum are susceptible to Chloroquine which have not developed resistance. Chloroquine resistance develops as a result of mutation of a gene which is responsible for encoding a cell membrane transporter for chloroquine. Malarial endemic areas such as Africa and India have chloroquine resistant strains of Plasmodium falciparum. Therefore, other drugs such as mefloquine are used. In severe malarial cases, a combination of two drugs is used which are quinine and an antibiotic doxycycline. Atovaquone and proguanil are used in combination for the treatment of malaria caused by chloroquine resistant strains of Plasmodium falciparum. In Thailand, new strains of Plasmodium falciparum have been discovered which are resistant to chloroquine and mefloquine as well and thus have posed a serious challenge for researchers and health care practitioners around the world. In severe P. falciparum malaria, intravenous administration of quinidine and doxycycline is employed. In certain parts of the world, artemisinins such as artesunate and artemether are used together with clindamycin and quinidine. Artemisinins are quite popular because of their low cost and lower incidence of side effects (Lalloo et al 2007; Levinson et al 1999). Chemoprophylaxis Individuals travelling to malaria endemic areas are advised to use mefloquine and doxycycline in an effort of preventing infection caused by Chloroquine resistant P. falciparum. Moreover, a combination of two anti malarial drugs such as atovaquone and Malarone can also be used. Furthermore, mosquito repellents should be used on exposed body parts in order to prevent being bitten by a mosquito. Insecticides such as DDT and organophosphates should be used in order to decrease mosquito population (Levinson et al 1999). Works Cited Lalloo, DG, D Shingadia, G Pasvol, PL Chiodini, CJ Whitty, NJ Beeching, DR Hill, DA Warrell, and BA Bannister. "Uk Malaria Treatment Guidelines." The Journal of Infection. 54.2 (2007): 111-21. Print. Levinson, Warren. Review of Medical Microbiology and Immunology. New York: McGraw-Hill Medical, 2008. Print. Ozsoy, M F, O Oncul, Z Pekkafali, A Pahsa, and O S. Yenen. "Splenic Complications in Malaria: Report of Two Cases from Turkey." Journal of Medical Microbiology. 53 (2004): 1255-1258. Print. Pongponratn, E, GD Turner, NP Day, NH Phu, JA Simpson, K Stepniewska, NT Mai, P Viriyavejakul, S Looareesuwan, TT Hien, DJ Ferguson, and NJ White. "An Ultrastructural Study of the Brain in Fatal Plasmodium Falciparum Malaria." The American Journal of Tropical Medicine and Hygiene. 69.4 (2003): 345-59. Print. Rasti, N, M Wahlgren, and Q Chen. "Molecular Aspects of Malaria Pathogenesis." Fems Immunology and Medical Microbiology. 41.1 (2004): 9-26. Print. Read More