Prevention of malaria.

Malaria is one of the most prevalent infectious diseases worldwide; it is transmitted in over 100 countries, and it is a major cause of serious morbidity and mortality in travelers. Clinicians should inform travelers of their risk, teach them the principles of personal protection, and offer individualized chemoprophylaxis regimens. The increasing prevalence of multiple drug-resistant Plasmodium falciparum in many parts of the world makes nonpharmacologic methods of malaria prevention important.     

Neurological complications of malaria.

This paper reviews the neurological complications of malaria. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red blood cells causing blood sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes a nonspecific, immune-mediated, inflammatory response with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations in malaria remains unexplored, but offers excellent perspectives for research at clinical as well as experimental level.     

Thrombocytopenia in malaria.

The relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with Plasmodium falciparum malaria and 12 patients with P. vivax malaria. Platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- SD) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes in counts and either indirect or direct platelet antibody levels. These findings suggest that a non-immunologically mediated mechanism is involved in the pathogenesis of thrombocytopenia in malaria.     

Case-control studies of severe malaria.

The majority of children infected with Plasmodium falciparum in areas of stable endemicity do not develop severe, life-threatening disease. It is important to identify risk factors for the minority who do. Case-control studies in which children with severe disease are compared with children with non-severe disease and with community controls, avoid some of the ethical and logistical problems inherent in such an undertaking. This paper discusses methodological aspects of case-control studies of severe malaria including case and control definitions, selection of cases and controls, potential risk factors, sample size calculations and analysis. Although specifically concerned with malaria, many of these issues are equally relevant to case-control studies of other infectious and parasitic diseases in a tropical environment.     

Chloroquine-resistant malaria in Burma.

Two field trials to detect chloroquine-resistant malaria were conducted according to WHO recommendations in a malaria free area near Rangoon. Peripheral blood smears were examined for asexual forms of P. falciparum on day one through to day seven, on day 14, 21, and 28 after a standard dose of 1500 mg. of chloroquine base. Haskins test to detect chloroquine in urine was done on all cases and plasma chloroquine levels were measured in some. Out of 105 patients tested RI resistance was detected in 66, RII in 19 and RIII in three. Subsequent trials with other anti-malarial drugs indicated that the chloroquine-resistant P. falciparum were also resistant to one day therapy with pyrimethamine 50 mg. or sulphamethoxypyridazine 1 G given singly; and resistant to one day therapy with combinations of pyrimethamine 50 mg. plus sulphamethoxy pyridazine 1 G, pyrimethamine 13 mg. plus dapsone 100 mg., and trimethoprim 320 mg. plus sulphamethoxazole 1600 mg. All those tested were sensitive to quinine sulphate, 0-6 G given three times a day for 10 days, and were also sensitive to one day therapy with combinations of trimethoprim 500 mg. plus sulphalene 1 G, and pyrimethamine 50 mg. plus sulphamethoxine 1 G. Pyrimethamine 12-5 mg. plus dapsone 100 mg. in weekly doses was shown to be an effective chemoprophylaxis. Quinine was tested on 38 subjects while other drug schedule were tested on six to eight subjects.     

Falciparum malaria and pregnancy.

Falciparum malaria in pregnancy is a significant health problem in India. Pregnant women constitute an important high risk group for malaria infection which may cause abortion, still births, intra uterine growth retardation (IUGR), and pre-mature labour. Two hundred eighty-eight admitted female patients of falciparum malaria were included in the study out of which 45 were pregnant. The mortality rate was highly significant in pregnant females (37.77%) in comparison to non-pregnant females (14.81%); (p < 0.001). The incidence of various pernicious syndromes including cerebral malaria, severe anaemia (Hb < 5 g%) hepatic and renal failure were more in pregnant females in comparison to non-pregnant females. The incidence of infection was higher among primigravida and second gravida 30/45 (66.66%) as compared to multigravida 15/45 (33.33%) and the greater incidence of infection was seen during 14-28 wk of gestation 23/45 (51.11%). Pregnancy related complications in the form of preterm live birth (20%). Intra uterine death (IUD 31.11%), still births (13.33%) and abortions (11.11%) were more pronounced in primiparous women as compared to multiparous. Weight of placenta in majority of patients ranged between 200-400 g (22/31; 70.96%). Normal pregnancy continued in only 11 out of 45 pregnant females, out of which seven had low birth weight body (63.63%). As the pregnancy is associated with increased incidence and adverse outcome of falciparum malaria infection, chemoprophylaxis should be made an integral part of antenatal care along with antianaemic therapy to reduce the risk of serious maternal and fetal complications.     

The antibody response to well-defined malaria antigens after acute malaria in individuals living under continuous malaria transmission.

The IgG and IgM antibody responses to the C-terminal 783 amino acids of the P. falciparum glutamate-rich protein, GLURP489-1271, expressed as an E. coli fusion protein, the IgG response to a 18-mer synthetic peptide EDKNEKGQHEIVEVEEIL (GLURP899-916) representing the C-terminal repeats of GLURP, and a synthetic peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria transmission. Some subjects did not recognize the antigens after malaria infection, and in subjects recognizing the antigens, the responses were often short-lived. In adults, the antibody responses to the GLURP489-1271 fusion protein and the (EENV)6 peptide peaked after 2 weeks, and not all individuals responded to all antigens. The antibody response, even against large fragments of conserved antigens, is not uniformly elicited by natural malaria infection in previously primed donors.     

Fading of malaria immunity in mice.

Fading of immunity in Swiss and C3H/StZ mice was progressive, and related to both, the interval elapsed since the last challenge infection and survival of parasites. In both mouse strains the proportion of mice that remained immune to challenge decreased with increasing fading periods. Moreover, a shift from delayed mortality to a normal course of infection as seen in non-immune controls was observed in C3H/StZ mice. Early parameters of fading were increasing peak parasitaemias after challenge in an increasing proportion of mice, and lethal infections instead of transient parasitaemias. Fading was also reflected by changes in the host cells preferentially infected early after reinfection: with increasing fading periods host cell preference shifted from predominantly polychromatophilic erythrocytes to mixed infections and finally to predominantly oxyphilic cells, especially in Swiss mice. The results of isodiagnosis indicated a positive correlation between persistence of parasites and immunity; whereas the absence of parasites was related to various phases of a fading immune response.     

Self-testing for falciparum malaria with antigen-capture cards by travelers with symptoms of malaria.

Kits for self-diagnosis of malaria by travelers in remote areas have been advocated. Antigen-capture test cards work reliably in the laboratory, but there is limited data regarding self-testing by ill patients. One hundred and fifty-three symptomatic patients presenting for a malaria test attempted self-diagnosis using these kits. Nine percent failed to perform a valid test. Against blood-film proven malaria, specificity was 97% (95% confidence intervals [CI] 93-99%) and sensitivity 95% (95% CI 74-99%). Although these results are encouraging, technical problems need to be addressed and test sensitivity proven by additional field-testing before this technology can be marketed to travelers.     

Pathology of falciparum malaria in Vietnam.

Autopsy samples from the brains of 20 patients who died of falciparum malaria were examined by light microscopy and by an immunohistologic method. Particular attention was paid to a comparison of the pathologic features of the white matter and the cortex. In the high-sequestration (greater than 50%) group (n = 8), the mean +/- SD percentage of cerebral microvessels that showed parasitized red blood cell (PRBC) sequestration was 71.2 +/- 8.1% in the cortex and 84.0 +/- 6.7% in the white matter. The difference in the PRBC sequestration rate between cortex and white matter was statistically significant (P less than 0.01). Perivascular and ring hemorrhages were seen more frequently in the white matter than in the cortex. Deposition of IgG and Plasmodium falciparum antigen in the cerebral microvessels was more highly significant in the white matter than in the cortex (P less than 0.01). Our study demonstrated that the localized concentration of PRBC sequestration in the brain correlated with the marked immunohistologic differences in the microvessels of cortex and white matter.     

Paternal investment affects prevalence of malaria.

Both reproduction and parasite defense can be costly, and an animal may face a trade-off between investing in offspring or in parasite defense. In contrast to the findings from nonexperimental studies that the poorly reproducing individuals are often the ones with high parasite loads, this life-history view predicts that individuals with high reproductive investment will show high parasite prevalence. Here we provide an experimental confirmation of a positive association between parental investment levels of male great tits Parus major and the prevalence of Plasmodium spp, a hematozoa causing malaria in various bird species. We manipulated brood size, measured feeding effort of both males and females, and assessed the prevalence of the hemoparasite from blood smears. In enlarged broods the males, but not the females, showed significantly higher rates of food provisioning to the chicks, and the rate of malarial infection was found to be more than double in male, but not female, parents of enlarged broods. The findings show that there may be a trade-off between reproductive effort and parasite defense of the host and also suggest a mechanism for the well documented trade-off between current reproductive effort and parental survival.     

Hepatic changes in P. falciparum malaria.

Liver function tests were performed in 165 hospitalized patients suffering from P. falciparum malaria with complications. Serum bilirubin was found increased in 33 patients, and 22 of them had unconjugated hyperbilirubinaemia. Serum alanine aminotransferase was increased in 5 patients, but only to mild to moderate levels. Serum alkaline phosphatase was increased in 11 patients, gamma-glutamyl transpeptidase in 3 patients. Serum total protein and albumin were significantly decreased but these were considered more as indicator of acute phase response. Liver cell necrosis was observed in one patient, and oedema and mononuclear cell infiltration in two patients. Though hepatomegaly and mild elevation of enzymes can be observed in a significant proportion of patients, involvement of liver leading to acute hepatitis or liver cell necrosis is a relatively uncommon complication in P. falciparum malaria.