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      Immunological disturbances associated with malarial infection

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          Malaria is a reemerging disease in the countries where it was eradicated previously, whereas it is endemic in many countries including tropical countries. In India, malarial infection is on rise due to rapid urbanization and overcrowding in all major metropolitan cities. The incidence of morbidity and mortality due to malaria infection is increasing and could be attributed to drug resistance in strains of malarial parasite. Combining immune modulation strategies with anti-malarial drugs has a beneficial effect in an attempt to improve treatment for malaria. Along with clinical presentation and outcome of this parasitic infection, it is important to understand immunological disturbances associated with biological mechanisms underlying these actions in better understanding of pathogenesis of malarial infection. Immune and inflammatory responses in malarial infection are controlled and co-ordinated by various cytokines and chemokines. This review focuses on commonly seen immunological disturbances associated with malarial infection resulting in related humoral and cell mediated immune functions primarily with innate to subsequent adaptive immunity in tackling this parasitic infection.

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          Most cited references 17

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          Clinical review: Severe malaria

          Malaria represents a medical emergency because it may rapidly progress to complications and death without prompt and appropriate treatment. Severe malaria is almost exclusively caused by Plasmodium falciparum. The incidence of imported malaria is increasing and the case fatality rate remains high despite progress in intensive care and antimalarial treatment. Clinical deterioration usually appears 3–7 days after onset of fever. Complications involve the nervous, respiratory, renal, and/or hematopoietic systems. Metabolic acidosis and hypoglycemia are common systemic complications. Intravenous quinine and quinidine are the most widely used drugs in the initial treatment of severe falciparum malaria, whereas artemisinin derivatives are currently recommended for quinine-resistant cases. As soon as the patient is clinically stable and able to swallow, oral treatment should be given. The intravascular volume should be maintained at the lowest level sufficient for adequate systemic perfusion to prevent development of acute respiratory distress syndrome. Renal replacement therapy should be initiated early. Exchange blood transfusion has been suggested for the treatment of patients with severe malaria and high parasitemia. For early diagnosis, it is paramount to consider malaria in every febrile patient with a history of travel in an area endemic for malaria.
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            Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study.

            An association between HIV-1 and malaria is expected in theory, but has not been convincingly shown in practice. We studied the effects of HIV-1 infection and advancing immunosuppression on falciparum parasitaemia and clinical malaria. HIV-1-positive and HIV-1-negative adults selected from a population-based cohort in rural Uganda were invited to attend a clinic every 3 months (routine visits) and whenever they were sick (interim visits). At each visit, information was collected on recent fever, body temperature, and malaria parasites. Participants were assigned a clinical stage at each routine visit and had regular CD4-cell measurements. 484 participants made 7220 routine clinic visits between 1990 and 1998. Parasitaemia was more common at visits by HIV-1-positive individuals (328 of 2788 [11.8%] vs 231 of 3688 [6.3%], p<0.0001). At HIV-1-positive visits, lower CD4-cell counts were associated with higher parasite densities, compared with HIV-1-negative visits (p=0.0076). Clinical malaria was significantly more common at HIV-1-positive visits (55 of 2788 [2.0%] vs 26 of 3688 [0.7%], p=0.0003) and the odds of having clinical malaria increased with falling CD4-cell count (p=0.0002) and advancing clinical stage (p=0.0024). Participants made 3377 interim visits. The risk of clinical malaria was significantly higher at visits by HIV-1-positive individuals than HIV-1-negative individuals (4.0% vs 1.9%, p=0.009). The risk of clinical malaria tended to increase with falling CD4-cell counts (p=0.052). HIV-1 infection is associated with an increased frequency of clinical malaria and parasitaemia. This association tends to become more pronounced with advancing immunosuppression, and could have important public-health implications for sub-Saharan Africa.
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              Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection.

              A fever case management (CM) approach using sulfadoxine-pyrimethamine (SP) was compared with two presumptive intertmittent SP treatment regimens in the second and third trimesters in pregnant primigravidae and secundigravidae in an area of intense Plasmodium falciparum malaria transmission in western Kenya. The investigation evaluated efficacy of the antimalarial regimens for prevention of placental malaria and examined the effect of human immunodeficiency virus (HIV) infection on antimalarial drug efficacy and adverse drug reactions. Twenty-seven percent (93 of 343) of pregnant women in the CM group had placental malaria compared with 12% (38 of 330; P < 0.001) of women who received two doses of SP and compared with 9% (28 of 316; P < 0.001) of women who received monthly SP. Fourteen percent (49 of 341) of women in the CM group delivered low birth weight (LBW) infants compared with 8% (27 of 325; P=0.118) of women who received two doses of SP and compared with 8% (26 of 331; P=0.078) of women who received monthly SP. Seven percent (7 of 99) of the HIV-negative women on the two-dose SP regimen had placental malaria compared with 25% (10 of 39; P=0.007) of HIV-positive women on the same regimen; the rate of placental malaria in HIV-positive women was reduced to 7% (2 of 28; P=-0.051) for women on the monthly SP regimen. Less than 2% of women reported adverse drug reactions, with no statistically significant differences between HIV-positive and HIV-negative women. Intermittent treatment with SP is safe and efficacious for the prevention of placental malaria in pregnant primigravidae and secundigravidae in sub-Saharan Africa. While a two-dose SP regimen may be effective in areas with low HIV seroprevalence, administration of SP monthly during the second and third trimesters of pregnancy should be considered in areas of high HIV seroprevalence to prevent the effects of maternal malaria on the newborn.

                Author and article information

                J Parasit Dis
                J Parasit Dis
                Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
                Springer-Verlag (India )
                27 September 2012
                April 2013
                : 37
                : 1
                : 11-15
                Department of Clinical and Experimental Immunology, National Institute of Immunohaematology, Indian Council of Medical Research, New Multistoryed Building, 13th Floor, King Edward Memorial Hospital Campus, Parel, Mumbai, 400012 India
                © Indian Society for Parasitology 2012
                Review Article
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                © Indian Society for Parasitology 2013


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