The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique.

We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protective antigens. The study was carried out in the Escola Primária de Lingamo, a primary school in a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12 years) was randomly allocated to two equal groups, one receiving chemoprophylaxis with dapsone/pyrimethamine (Maloprim), the other receiving placebo every week from December 1989 to November 1990. The groups were then followed until November 1991 without chemoprophylaxis. Cellular responses to immunodominant epitopes from Pf155/RESA and GLURP, and to non malaria antigens C. albicans and PPD, were assessed by lymphocyte proliferation assays in vitro. Anti-GLURP and anti-Pf155/RESA antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and erythrocyte membrane immunofluorescence (EMIF), and total anti-P. falciparum antibodies were measured by indirect fluorescent antibody test (IFAT). Immunological reactivities were evaluated every six months, at the end of the rainy season and at the end of the dry season, both during the period of chemoprophylaxis and during the follow-up. The antibody response rate to the GLURP was lower in the Maloprim group than in the placebo group during the intervention phase. The lymphoproliferative response rate to the malaria antigens was significantly lower at the end of the rainy season than at the end of the dry season, but the difference between the experimental group and the control group of schoolchildren was not statistically significant. These results suggest that the antibody responses to the GLURP molecule and partly to the Pf155/RESA antigen in this study population were shortlived and dependent on frequent boostering, but whether these antigens play a role in the development of natural clinical immunity remains open. In the experimental group of schoolchildren weekly chemoprophylaxis successfully reduced the parasite rate during the rainy season from 43% to 4%, and during the dry season from 18% to 0%. Chemoprophylaxis may therefore have a useful role in combination with another partially effective malaria control measure such as insecticide-impregnated bed nets or a malaria vaccine.

Comparison of intramuscular and intravenous quinine for the treatment of severe and complicated malaria in children.

To compare the efficacy and side effects of intramuscular (i.m.) and intravenous (i.v.) quinine, children in Mozambique with severe and complicated malaria between 6 months and 7 years were randomized to treatment with i.m. or i.v. quinine, both in a dosage of quinine dihydrochloride 20 mg/kg followed by 10 mg/kg every 8 h. Of 57 children treated with i.m. quinine, 4 died, 3 had neurological sequelae and 2 had sterile intramuscular abscesses. Of 47 children treated with i.v. quinine, 6 died and 1 had neurological sequelae. The mean parasite clearance time was 58.6 h in the i.m. group and 59.3 h in the i.v. group. Mean temperature clearance times were 56.1 and 51.8 h, and mean coma clearance times 40.4 and 38.7 h, respectively. None of these differences was statistically significant. Mean trough and peak concentrations of quinine were almost identical in the 2 groups, ranging from 10.5 to 12.6 mg/L, which is in the therapeutic non-toxic range. It is concluded that i.m. quinine is as effective as quinine by i.v. infusion in children with severe and complicated malaria; that minor local side effects can probably be avoided by using diluted quinine for i.m. injection; and that the optimal dose regimen for children with severe and complicated malaria in Africa at present is probably quinine salt 20 mg/kg followed by 10 mg/kg every 12 h.

Efficacy of dapsone with pyrimethamine (Maloprim) for malaria prophylaxis in Maputo, Mozambique.

In a randomized controlled study of malaria prophylaxis, dapsone-pyrimethamine at a weekly dosage of dapsone 50-100 mg with pyrimethamine 6.25-12.5 mg or placebo was administered to 166 school children for 17 weeks. Fortnightly parasitological controls revealed 28 infections in the placebo group and none in the dapsone-pyrimethamine group. It is concluded that weekly dapsone-pyrimethamine is effective for the prophylaxis of falciparum malaria in Mozambique.

PIP: A randomized, blinded comparison of malaria prophylaxis with dapsone-pyrimethamine vs. placebo was conducted in 166 schoolchildren from Maputo, Mozambique, from February to June 1989. The children, aged 7-12, received 1 tablet of Maloprim (Wellcome, 100 mg dapsone and 12.5 mg pyrimethamine), or half a tablet if they weighed 30 kg. After being tested for malaria parasites, children were started on Maloprim the next day, or if infected, after treatment with sulfadoxine-primethamine for 2 weeks. Drugs were administered weekly, and capillary blood was checked by-weekly. There were 28 Plasmodium falciparum infections among children taking placebos, and none in those given prophylaxis. Hematocrits were unchanged. This is the 1st study of dapsone-pyrimethamine for prophylaxis in a chloroquine-resistant malaria area. Since use of this agent on a massive scale could result in resistance, it is recommended that its use be restricted to target groups such as primigravidas or to narrow time periods such as early stage of epidemics.