Immunity to malaria

B7. Brown, K. N., and Brown, I. N., Immunity to malaria. Antigenic variation in chronic infections of Plasmodium knowlesi. Nature (London) 208, 1286-1288 (1965). 

Contraction of malaria, today known to be a protozoan infection caused by the bite of the Anopheles mosquito, does not accord immediate and/or universal immunity. Whereas those in geographical regions frequently exposed to malarial infection often exhibit no or attenuated symptoms, those less exposed can become severely and repeatedly ill. Even today the molecular mechanisms underlying natural immunity to malaria are not clearly understood. For details, see the Oxford Research on Childhood Disease Malaria at and WHO/TDR [World Health Organization/Tropical Disease Research] Database at (reviewed Feb. 6, 2001). Repeated attacks may even cause chronic malaria characterized by severe anemia, emaciation, enlargement of the spleen, weakness, edema of the ankles, and... 

The differential diagnosis in most areas of the world has malaria at the top of the list. However, the presence of parasitemia in patients partially immune to malaria does not prove that malaria is the cause of the symptoms (48). Other confounding infections include typhoid fever, rickettsial and leptospiral diseases, nontyphoidal salmonellosis, shigellosis, relapsing fever, fulminant hepatitis, and meningococ-cemia. In patients with DIG, the differential diagnosis includes acute leukemia, lupus erythematosus, idiopathic or thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (48). 

Topolska, A. E., Richie, T. L., Nhan, D. FI., and Coppel, R. L. (2004c). Associations between responses to the rhoptry-associated membrane antigen of Plasmodium falciparum and immunity to malaria infection. Infect. Immun. 72,3325-3330. 

It would be interesting to know whether there is any (say, epidemiologic) connection between malarial immunity and cancer immunity. Thus, many native inhabitants of the tropical areas fortunately develop immunity to malaria, which may or may not be related to the inhibition of the malarial enzyme lactate dehydrogenase or other critical malarial enzymes. 

Although acquired immunity to some parasitic diseases may lower the level of infection, absolute immunity as seen in bacterial and viral infections is seldom seen in parasitic diseases. Since parasitic infections produce a wide variety of antigens because of the many life cycle phases, it is more difficult to identify a constant antigenic protein against which specific antibodies are protective. However, malaria remains a likely candidate for a vaccine and there are ongoing studies to develop one. 

It now appears certain that destruction of malaria parasites in vivo depends in part, if not wholly, upon the presence of humoral antibodies, and this must explain the success achieved with the passive transfer experiments. The exact role of the T and B lymphocytes in immunity in malaria infection in man still needs clarification. In rats the ability to resist P. berghei infection seems to be thymus dependent, and higher parasitemias were encountered in the thymectomized rats, which also developed severe anemia (B6). 

C16. Cohen, S., McGregor, I. A., and Carrington, S., Gamma globulin and acquired immunity to human malaria. Nature (London) 192, 733-737 (1961). 

Two major diseases, malaria and AIDS, are still out of control vaccines are not available, while the malaria parasite and the HIV virus, responsible for AIDS, have developed resistance to current dmgs. Variability of the agent, lack of commercial interest, and perhaps also unconfessed political plans at population growth control, have been an obstacle to active immunization against malaria. The hope for an HIV vaccine is now from the engagement of Merck Co (Conference 2001). 

In addition to malaria, several other serious infections may occur in humans due to parasitic invasion by protozoa.2,44 Severe intestinal infections (dysentery) produced by various protozoa occur quite frequently, especially in areas where contaminated food and drinking water are prevalent. Infections in tissues such as the liver, heart, lungs, brain, and other organs may also occur because of protozoal infestation. As mentioned in this chapter s introduction, individuals with a compromised immune system may be especially susceptible to these intestinal and extraintestinal infections.2,70... 

Andrew K. Black has indicated that incidents of malaria among black were considerably lower than among whites due to the fact that nearly all had previous exposure to malaria and had acquired either natural immunity or exhibited attenuated symptoms. See Andrew K. Black, In the Service of the United States Comparative Mortality Among African-American and White Troops in the Union Army, Journal of Negro History 79 (1994) 324-325. 

In areas where malaria is endemic and ever-present, many individuals appear to be immune to the disease. In some populations, including those of India, Latin America, southern Europe, and especially Africa, the gene causing sickle-cell anemia is present. This gene is directly connected with malaria immunity a person possessing... 

Malarial infection does not produce immunity in patients, and active research has been initiated to develop a malaria vaccine. " A vaccine that blocks the entry of sporozoites into the liver cells will prevent malaria at this stage. However, immunity to sporozoites does not protect the host against parasites in the erythrocytic cycle. Infective sporozoites of P. falciparum are covered by a polypeptide, circumsporozoite protein. Isolatiou aud ideutification of the gene encoding for this circumsporozoite protein have led to the development of a monoclonal antibody by recombinant DNA technology P. falciparum sporozoite vaccine is now under investigation. ... 

Gupta, S., Snow, R., Donnelly, C., Marsh, K., and Newbold, C. (1997). Immunity to non-cerebral malaria is acquired after one or two infections. Nature Medicine 5,340-343. 

Wang R, Richie T L, Baraceros M F, et al. (2005). Boosting of DNA vaccine-elicited gamma interferon responses in humans by exposure to malaria parasites. Infect. Immun. 73 2863-2872. 

Burt RA, Baldwin TM, Marshall VM, Foote SJ 1999 Temporal expression of an H2-linked locus in host response to mouse malaria. Immunogenetics 50 278-285 Casanova JL, Abel L 2004 The human model a genetic dissection of immunity to infection in natural conditions. Nat Rev Immunol 4 55-66... 

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