Plasmodium falciparum malaria:
Background: Antibody responses to malaria antigens are known to mediate protection from clinical malaria. This study aimed to measure antibody response of a randomly selected cohort of children to two Plasmodium falciparum MSP1 and GLURP antigens considered as vaccine candidates
Methods: The study was conducted in two villages: Kajara and Daraweesh, in the central part of Gadaref State in eastern Sudan. Thearea is characterized by seasonal unstable malaria transmission. A cohort of 510 children of both sexes was randomly selected and followed for two years. Clinical examination, finger prick blood smears and blood samples were collected during three surveys conducted before and after the rainy season. Standardized ELISA protocols were used to measure IgM, IgG and IgG subclass levels to Merozoite Surface Protein 1–19 (MSP119) and Glutamate Rich Protein (GLURP) antigens. Plasmodium falciparum parasites detected in clinical cases during the survey were characterized using PCR.
Results: The incidence of malaria was 2.5%. High levels of IgG1 and IgG3 to MSP1-19 were detected in sera of children who didn’t develop clinical malaria during the study. The detected IgG1 and IgG3 are known cytophilic antibodies , The level of total IgG to GLURP and MSP1-19 was strongly associated with reduced malaria incidence (P=0.009 and P=0.003) respectively.. IgG3 and IgG1 against MSP1-19 were associated with reduced risk of clinical malaria. There was a significant increase in the levels of IgG antibodies to MSP1 and GLURP in the elder age groups who are known to be at lower risk for developing clinical malaria There was no evidence of association between antibody responses to MSP1-19 and baseline parasitemia.
Conclusion: Although children are known to be more vulnerable to clinical malaria, in areas of seasonal unstable transmission, children who produce high level of IgM, IgG1 and IgG3 antibodies to MSP1 and GLURP are protected from clinical malaria. Similar findings were reported in other studies (Dodooet al., 2012). In conclusion Plasmodium falciparum MSP1 and GLURP antigens induce protective antibody responses in children living in areas of season unstable transmission.
Malaria life cycle is complex, of which the asexual stages are responsible for the clinical symptoms while sexual stages (gametocytes) are necessary for transmission of the parasite from man to mosquito, but the process of gametocytogenesis and maturation has not been elucidated yet.
In recent years knowledge on the malaria sexual phase has benefited. As a result a number of new sexual stage antigens have been identified, and progress has been made in the identification and functional characterization of enzymes and regulatory proteins that are involved in gametocyte differentiation and fertilization .
Different studies showed that Gametocytogenesis influenced by different environmental factors leading to influence in gametocyte rate, one of these factor including stress, There is a belief that exposure to ‘stress’ causes P. falciprumto commit to sexual development.
Although evidence from in vitro studies suggests that an immune response stimulateshost immunity to rising asexual parasitaemia has been correlated withboth increased and decreased gametocytaemia.
Treatment with antifolate drugs,such as pyrimethamine and the sulfa-drugs, as well asthe combination also accelerate gametocytogensis. Fansidar, has been reported to raisethe proportion of gametocytes detected in blood smearsof P. falciprum-infected patients. Similarly,sub curative doses of chloriquine administered to infected mice resulted in an increased rateand an earlier peak of gametocyte production. In contrast,the use of artemisinin derivatives to treat acuteuncomplicated falciparum malaria in western Thailandresulted in greatly decreased gametocyte carriage,when compared to mefloquine-treated individuals.
Host hormones, including insulin, progesterone, 17-b-oestradiol,testosterone and corticosteroids have all been shownto enhance gametocyte conversion of P. falciprum in vitro; although only insulin increased the overall parasitaemia. Neither the mechanism of hormone action northe signaling pathways activated has been investigated.
The presence of a second genotype of plasmodium repressed the asexual population density of the first genotype ( measured on Day 10 after infection) and stimulated resultant transmissibility However, in another experiment, asexual parasitaemia was stimulated initially by the presence of a second genotype.
Gene expression in gametocytogensis
The entire growth period of the gametocyte has been divided into five stages (I-V) spanning a period of 8-17 days following erythrocyte invasion of a sexually committed merozoite (Hawking et al., 1971). Development of gametocytes is accompanied by a coordinated expression of sexual stage-specific genes, in addition to the many genes whose expression is up- or down regulated (Janse and Waters, 2004). The analysis of the parasite genome using a high density microarray, Le Roch et al. (2003) identified 152 genes showing elevated levels of expression in gametocytes, and 218 genes expressed uniquely in sexual stages. Of these 370 genes, approximately 84% were identified only as hypothetical proteins. Because the expression of many of the sexual-stage specific genes, especially the surface antigens, is not essential for asexual proliferation, they provide a good target for gene disruption studies.
Malaria drug resistance: