Immune complex levels in children with severe Plasmodium falciparum malaria

Malaria infection leads to the formation of circulating immune complexes. However, it is unclear whether these complexes play a role in the pathogenesis of complicated Plasmodium falciparum malaria. This study aimed at determining if there are differences in the levels of immune complexes between children with severe malaria-associated anemia and cerebral malaria and between each of these two groups and their respective uncomplicated symptomatic malaria or healthy asymptomatic controls. Children with severe malaria-associated anemia and cerebral malaria had significantly higher immune complex levels than their respective controls, but there were no significant differences in the levels between the two severe malaria groups. In addition, there was an inverse relationship between the hemoglobin levels and immune complex levels in the severe anemia controls, suggesting that immune complexes may contribute to erythrocyte destruction in these children. These results suggest that immune complex levels alone cannot account for the differences in the distinct clinical presentation between severe malaria-associated anemia and cerebral malaria.     

Thrombopoietin in Plasmodium falciparum malaria

Thrombopoietin (TPO) is the key growth factor for platelet production and is elevated in states of platelet depletion. As thrombocytopenia is a common finding in malaria, we analysed TPO regulation before, during and after antimalarial treatment. Before treatment, TPO serum levels were significantly higher in patients with severe malaria (n = 35) than in patients with uncomplicated malaria (n = 44; P = 0.024), normalizing within 14-21 d of therapy. The rapid normalization of TPO levels and increase in low peripheral platelet counts after treatment indicate that the biosynthesis of TPO and its regulation in malaria patients are normal.     

Immune responses to Plasmodium falciparum antigens during a malaria vaccine trial in Tanzanian children

Among Tanzanian children living in an area of intense and perennial malaria transmission, prevalence of naturally acquired IgG antibodies that recognize SPf66, NANP, p190 and a 19 kDa fragment of the merozoite surface protein-1 (MSP-1) is high and increases with age. This possibly reflects the high level of natural exposure of the children to P. falciparum. The prevalences of IgG antibodies that recognize the three putative merozoite derived sequences contained in the malaria vaccine SPf66 (83.1, 55.1 and 35.1) is low but also show some age dependence. Three doses of the SPf66 vaccine induce a strong IgG antibody response against both the SPf66 construct, NANP and the three individual peptides. Vaccination with SPf66 did not result in an increase of anti19 kDa fragment antibodies. This reflects the specificity of the humoral immune response induced by the SPf66 construct. Among vaccinated children, antibody titres against SPf66 decreased over time following the third dose. However, 18 months after the third dose, SPf66 recipients still had significantly higher IgG titres and stimulation indices of peripheral blood mononuclear cells (PBMC) than placebo recipients. Within the vaccine group, there is a trend for increasing anti-SPf66 IgG titre to be associated with decreasing risk of clinical malaria but this was not statistically significant. Results also show the difficulties of establishing whether antibody responses are related to protection in field trials in endemic areas .     

Antimalarial activity of a riboflavin analog against Plasmodium vinckei in vivo and Plasmodium falciparum in vitro

The riboflavin analog 10-(4'-chlorophenyl)-3-methylflavin was found to have significant activity against Plasmodium vinckei vinckei when administered orally and parenterally; it was active against P. falciparum in culture. It inhibited mouse erythrocyte glutathione reductase in a dose-dependent manner. When administered orally, 5-deazariboflavin was not active in vivo although it has been shown to have activity against P. falciparum in vitro.     

Drug resistance in Plasmodium falciparum malaria

Four classes of drugs are reviewed: blood schizontocides acting only on the hemoglobin-digesting blood stages, the antifolates which attack tetrahydrofolate synthesis in all the growing stages, antimitochondrials affecting synthesis and electron transport, and 8-aminoquinolines which interfere with redox processes. Drug efflux via a multidrug resistance membrane protein, and the production of a protein competing with the drug for the target hemin are thought to be responsible for resistance to blood schizontocides. Structural changes in target enzymes are responsible for easily-developed resistance to antifolates and antimitochondrials. The judicious use of drug combinations can help to avoid development of resistance and combat resistant infections, but new drugs are urgently needed.     

RII-RIII chloroquine resistant Plasmodium falciparum malaria from East Africa: studies of the in vivo and in vitro response to chloroquine

A case is reported of Plasmodium falciparum malaria from East Africa resistant to chloroquine in the in vivo test at the RII level. Serum chloroquine concentrations and the in vitro test indicated RIII resistance. The need for further comparative studies of parasitaemia, serum chloroquine concentration and in vitro chloroquine sensitivity assessment is emphasized.     

Age as a risk factor for severe Plasmodium falciparum malaria in nonimmune patients.

In this nationwide, cross-sectional study, we evaluated the influence of age and other factors that affect clinical outcome of Plasmodium falciparum malaria in nonimmune patients. Of 135 patients with P. falciparum malaria, 84 (62%) were < 40 years old, and only 5% of the patients in this age group developed severe malaria, compared with 18% of the subjects who were > or =40 years of age (odds ratio, 4.29); moreover, all deaths occurred in the latter group. Male subjects did not differ from female subjects with regard to severity of disease.     

Immunization against malaria with antigen from Plasmodium falciparum cultivated in vitro.

Aotus monkeys, which are generally killed when infected with the human malaria parasite Plasmodium falciparum, have been identified and grouped by karyotype. These animals were immunized with parasite material obtained from P. falciparum cultivated in vitro which had been maintained in culture for over a year. When sufficient amounts of this antigenic material were used with a synthetic muramyl dipeptide (MDP), protective immunity was induced without presenting the antigen in complete Freund's adjuvant.     

Plasmodium falciparum in Madagascar: in vivo and in vitro sensitivity to seven drugs

The sensitivity level of Plasmodium falciparum isolates to chloroquine and the activity of six other antimalarials were studied in the different climatic zones of Madagascar in 1983. In vivo tests were done with 10 and 25 mg kg-1 of chloroquine and amodiaquine. Early recrudescence or RII resistance was observed after treatment with 10 mg kg-1 of these drugs in 34% of the cases for chloroquine and 6.5% for amodiaquine, and after the 25 mg kg-1 dose in 7% and 0% of the cases respectively. In vitro sensitivity of 84 P. falciparum isolates to seven drugs were studied with a semi-microtest. For chloroquine, 9% of the isolates had an IC50 above 250 nM, indicating resistance. In vitro activity of piperaquine was high for all isolates except two. In vitro activity of amodiaquine, dichlorquinazine, quinine, mefloquine and halofantrine was good against all isolates (maximum IC50 was 76, 92, 560, less than or equal to 20 and less than or equal to 12 nM, respectively). Correlation between the WHO standard field test and the in vitro semi-microtest was good. Resistance of P. falciparum to chloroquine was observed in the six survey areas, but the other tested drugs showed good activity. Since no cross-resistance to 4-aminoquinolines seems to exist in Madagascar, amodiaquine (the only one available at present) should be studied as an alternative to chloroquine in the prevention and treatment of falciparum malaria in this area.     

Leukocyte alkaline phosphatase in Plasmodium falciparum malaria

We studied leukocyte alkaline phosphatase in malaria to assess leukocyte defence mechanisms. Twenty-seven patients with malaria were stratified into two classes on the basis of disease severity. Fifteen malaria negative patients were taken as controls. Data showed mild polymorphonucleated cell activation, in the absence of correlation with the severity of the malaria.     

In vivo efficacy of quinine treatment for Plasmodium falciparum malaria in Malawian children

Twenty-five Malwaian children with Plasmodium falciparum infection were studied for response to quinine in an eight-hourly dosage of 10 mg salt kg-1 body weight. The mean parasite clearance time, defined as the time after initiation of treatment when the first of two consecutive 12-hourly smears was negative for P. falciparum parasites, was 67 hours. The mean fever clearance time, defined as the time after initiation of treatment when the axillary temperature first fell below 37.5 degrees C and remained below this level for 48 hours, was 36 hours. Twenty-four hours after the first dose of quinine, the geometric mean parasite density among the children studied had decreased by 84%, from 41 357-6586 parasites mm-3, and all children cleared their parasitaemia within 108 hours. Results of this study confirm that quinine remains effective in rapidly controlling P. falciparum parasitaemias in Malawi, where resistance to the 4-aminoquinolines is highly prevalent.