Search

Malaria-associated anaemia is a major public-health problem. Although the treatment of uncomplicated, Plasmodium falciparum malaria aims to clear the parasites, relieve the symptoms and permit haematological recovery, data on the impact of antimalarial treatment on haematological recovery are few. Haematological recovery and the prevalence of anaemia were therefore evaluated in 600 Kenyan children with uncomplicated malaria who were randomly assigned to one of three treatment groups. The children were given sulfadoxine-pyrimethamine (SP) on day 0, SP plus artesunate on day 0 (AS1), or SP on day 0 and artesunate on each of days 0-2 (AS3). Haemoglobin (Hb) concentrations were measured on days 0, 7, 14, 21 and 28, with haematological recovery defined as a day-28 Hb concentration of at least 11 g/dl. Only 96 (18%) of the 543 children who were anaemic (i.e. with <11.0 g Hb/dl) at enrolment achieved haematological recovery. The prevalence of anaemia fell from 91% on day 0 to 74% (252/340) by day 28 (P=0.065). Compared with SP alone, neither artesunate regimen resulted in higher Hb concentrations on day 28 (with means of 10.2, 9.9 and 10.2 g/dl for AS3, AS1 and SP, respectively; P=0.254), a higher frequency of haematological recovery (19%, 14% and 20% for AS3, AS1 and SP, respectively; P=0.301) or a greater reduction in the prevalence of anaemia (prevalences in the AS3, AS1 and SP arms falling from 90%, 89% and 93%, respectively, on day 0, to corresponding values of 71%, 82% and 69% on day 28; P=0.40). In fact, between days 0 and 7, the children in the AS3 arm showed a larger drop in mean Hb than the children in the other two treatment arms. In general, haematological recovery was most likely in older children who had mild anaemia at presentation and were parasitologically cured. Overall, the frequencies of haematological recovery were modest and not influenced by the artesunate treatments. Other factors contributing to anaemia need to be explored more fully.

Although erythromycin has been reported to be active against Plasmodium falciparum in vitro and P. berghei in vivo and in vitro when given alone or with chloroquine, it has been difficult to demonstrate a beneficial effect for the combination of erythromycin and chloroquine when used for the treatment of P. falciparum infections in humans. We developed a seven-day test of parasite sensitivity to a 4-aminoquinoline and erythromycin combination in vitro. Eight isolates of P. falciparum from the Kenyan coast were culture-adapted and exposed to erythromycin with chloroquine or with amodiaquine. The interaction of the drugs was evaluated by plotting the concentration of each drug needed to inhibit parasite growth. In seven isolates the combination of chloroquine and erythromycin was antagonistic; one isolate showed slight synergy The combination of amodiaquine and erythromycin was synergistic in three isolates but antagonistic in five. An antagonistic interaction may explain why erythromycin does not enhance chloroquine treatment of malaria in vivo in Kenya.

The association of pruritus and ingestion of chloroquine phosphate in Saradidi, Kenya, was determined by randomly giving 437 children (less than 18 years) and 182 adults either 10 mg base kg-1 of regular chloroquine, 10 mg base kg-1 of enteric-coated chloroquine, 10 mg base kg-1 of amodiaquine, or one 300 mg tablet of enteric-coated ferrous sulphate. Before treatment, a blood smear was taken. Paired urine samples were tested for 4-aminoquinolines to exclude prior drug ingestion, to document drug absorption, and to exclude chloroquine or amodiaquine intake in persons who received iron. The following day, the incidence of itching was ascertained. More adults (20.3%) reported itching than did children (12.8%) (P less than 0.05); no significant difference between males and females was noted. A history of itching 24 hours after treatment was not significantly more common in persons with malaria parasitaemia. Pruritus was more frequent in those receiving regular chloroquine (21.5% of 186) and enteric-coated chloroquine (17.8% of 118) than after amodiaquine (11.6% of 173) or iron (8.5% of 142) (P less than 0.005). Amodiaquine which is a 4-aminoquinoline like chloroquine did not appear to cause significant pruritus in this population. These results demonstrate that chloroquine-associated pruritus is experienced frequently in Saradidi. This side effect of malaria treatment could influence usage of chloroquine phosphate provided by village health workers.

From 1981 through 1984, the response of Plasmodium falciparum to chloroquine was monitored in Saradidi, Kenya, as a part of a community-based health programme to provide treatment for malaria in each village. Before 1983, all 71 infections treated with chloroquine were sensitive in vivo; parasitaemia cleared by day 3 and remained absent to day 7. In June 1983, 23.1% of 26 infections treated with chloroquine base 10 mg kg-1 either recrudesced in seven days (RI resistance, five infections) or decreased but failed to clear (RII resistance, one infection). In September 1983, 16.2% of 68 and in February 1984, 13.2% of 53 infections were resistant in vivo after treatment with chloroquine base 10 mg kg-1. A course of chloroquine base 25 mg kg-1 over three days remained effective; only two (1.6%) of 129 infections examined were resistant in vivo; in both, parasitaemia cleared then recurred (RI). In September 1984, however, nine (10.2%) infections were resistant after treatment with chloroquine base 25 mg kg-1; in four of these parasitaemia decreased but never cleared (RII). Similar results were observed in vitro. In the Rieckmann macro in vitro test, 63.3% of 30 P. falciparum isolates tested were resistant to chloroquine (minimal inhibitory concentration (MIC) greater than or equal to 1.25 X 10(-6) mol 1(-1) blood) in June 1983, as were 61.8% of 34 isolates in the Rieckmann micro test (MIC greater than or equal to 1.14 X 10(-6) mol 1(-1) blood).(ABSTRACT TRUNCATED AT 250 WORDS)