Factors contributing to anaemia after uncomplicated Plasmodiumfalciparum malaria in children.

The factors contributing to anaemia in falciparum malaria were characterized in 1261 prospectively studied children in an endemic area of southwestern Nigeria. Of these, 487 (39%) presented with anaemia (haematocrit <30%). The following were found to be independent risk factors for anaemia at presentation: age <5 years, history of illness >3 days before presentation, presence of fever, a palpable liver, >parasitaemia 10,000/microl blood, and gametocytaemia. The mean maximum fractional fall in haematocrit (FFH) after treatment was 13.8% (95% confidence interval [CI] 13-14.6) of the baseline value. This occurred 3 days after treatment began and correlated positively with enrolment haematocrit. In children whose haematocrit was >30% at enrolment, the following were found to be independent risk factors associated with subsequent development of anaemia during follow-up: age <5 years and parasitaemia > or =100,000 parasites/microl. Haematological recovery was usually complete by 4-5 weeks, but was slower in children who were anaemic at enrolment and in those with recrudescence of their infections. Half of the children with recrudescence were still anaemic at 4 weeks. These findings have implications for the control of the burden of malarial anaemia in children in sub-Saharan African countries.

Therapeutic efficacy and effects of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine on gametocyte carriage in children with uncomplicated Plasmodium falciparum malaria in southwestern Nigeria.

The treatment efficacy and effects of artemether-lumefantrine (AL) and amodiaquine-sulfalene-pyrimethamine (ASP) on gametocyte carriage were evaluated in 181 children < or = 10 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive either drug combination. All children recovered clinically. Fever clearance times were similar. The rate of P. falciparum reappearance (recrudescence or re-infection) between two and six weeks after the start of therapy was significantly higher in AL-treated children (P = 0.01). Parasite clearance was significantly faster in children treated with AL (mean +/- SD = 1.7 +/- 0.6 days, 95% confidence interval = 1.58 - 1.83, P = 0.0001) but the polymerase chain reaction-corrected cure rate (90 of 91 versus 84 of 90) and the rate of resolution of malaria-related anemia two weeks after treatment began (45 of 50 versus 33 of 46) were higher in children treated with ASP. Gametocyte carriage rates were similar. Both regimens were well tolerated. Artemether-lumefantrine clears parasitemia more rapidly than ASP but both combinations are effective in treatment of uncomplicated P. falciparum malaria in Nigerian children.

Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo.

Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical application of the reversal phenomenon.

Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo

Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical appliation of the reversal phenomenon.

Effects of acute Plasmodium falciparum malaria on body weight in children in an endemic area.

The impacts of acute falciparum malaria on body weight and the host and parasite factors predictive of change in body weight were characterized in 465 prospectively studied children in an endemic area of southwest Nigeria. Pre-treatment weights were significantly lower than the 14 to 28-day post-treatment weights (P = 0.0001). In 187 children, fractional fall in body weight (FFBW) exceeded 4.9%. FFBW correlated negatively with age and body weight (P = 0.014 and 0.0001, respectively), but not with enrollment parasitaemia. In a multiple regression model, an age < or =5 years (AOR = 2.03, 95% CI 1.2-3.2, P = 0.003), a hematocrit < or =29% (AOR = 1.6, 95% CI 1.0-2.3, P = 0.037), and a body weight < or =9.6 kg (AOR = 5.4, 95% CI 1.7-20, P = 0.003) were independent predictors of FFBW > or =5% at presentation. Children who, after initial clearance, had recurrence of their parasitaemia within 28 days had a significantly higher propensity not to gain weight than children who were aparasitaemic after treatment (log-rank statistic 6.76, df = 1, P = 0.009). These results indicate that acute malaria contribute to sub-optimal growth in young children and may have implications for malaria control efforts in sub-Saharan Africa.