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Risk factors for gametocyte carriage in Gambian children
L von Seidlein1, C Drakeley, B Greenwood
1Medical Research Council Laboratories, Fajara, The Gambia. lseidlein@ivi.int
Insights
Reducing Plasmodium falciparum gametocyte prevalence can lower malaria transmission. Effective antimalarial drugs, especially those combining pyrimethamine-sulfadoxine with multiple artesunate doses, significantly suppress gametocyte carriage.
Area of Science:
- Medical Research
- Infectious Diseases
- Parasitology
Background:
- Plasmodium falciparum gametocyte carriage is variable after infection.
- Gametocyte prevalence reduction is key to decreasing malaria transmission.
- Understanding risk factors for gametocytemia is crucial for effective treatment strategies.
Purpose of the Study:
- To analyze risk factors associated with gametocytemia at presentation and 7 days post-treatment.
- To evaluate the impact of different antimalarial drug regimens on gametocyte carriage.
- To determine optimal treatment strategies for suppressing gametocytemia and reducing malaria transmission.
Main Methods:
- Enrollment of 1,198 children in two antimalarial drug trials.
- Assignment to four treatment groups: chloroquine, pyrimethamine-sulfadoxine (PSD) alone, PSD + 1 dose artesunate, PSD + 3 doses artesunate.
- Assessment of gametocytemia at enrollment and 7 days post-treatment.
Main Results:
- At enrollment, 17% of children were gametocyte carriers. Anemia was linked to higher gametocyte prevalence, while fever and high parasite density were linked to lower prevalence.
- Seven days post-treatment, 37% of assessable children carried gametocytes. Pyrimethamine-sulfadoxine (PSD) alone resulted in significantly higher gametocytemia compared to other groups.
- Treatment with PSD + 3 doses of artesunate markedly reduced gametocytemia, with only 10% of children becoming carriers compared to 57% on PSD alone.
Conclusions:
- Early and effective antimalarial therapy is critical for preventing gametocytemia.
- The choice of first-line antimalarial drugs should consider both asexual parasite clearance and gametocyte suppression.
- Combination therapy, particularly PSD with multiple artesunate doses, shows significant potential in reducing gametocyte carriage and malaria transmission.
Abstract:
A widespread reduction in Plasmodium falciparum gametocyte prevalence could reduce malaria transmission. After infection with P. falciparum, a variable proportion of people are found to be gametocytemic. We analyzed risk factors associated with gametocytemia at presentation and 7 days later. We enrolled 1,198 children in 2 antimalarial drug trials between September and December 1998. The children were assigned to 1 of 4 treatment groups: chloroquine only; pyrimethamine-sulfadoxine (PSD) only; PSD combined with 1 dose of artesunate; and PSD combined with 3 doses of artesunate. By the time of enrollment, 200 (17%) of 1,198 children were gametocyte carriers. Three independent risk factors were associated with gametocytemia at enrollment. Children with anemia were more likely to carry gametocytes, whereas children with fever (> 37.4 degrees C) or high parasite densities (> 100,000 parasites/microL) were less frequently gametocyte carriers. Children with at least 2 of the risk factors were 4 times more likely to be gametocytemic than children with < 2 risk factors (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.7-7.1). Seven days after the start of treatment, 355 (37%) of 466 assessable children were found to be gametocyte carriers. Children treated with PSD alone had a significantly higher risk of being gametocytemic by Day 7 compared with children in the other 3 treatment groups. In the subgroup of children who had no detectable gametocytes on enrollment, the effect of treatment with PSD + 3 doses of artesunate was most marked. Nineteen (10%) of 198 children treated with PSD + 3 doses of artesunate became gametocytemic, in contrast to 184 (57%) of 321 children treated with PSD alone (OR, 12.7; 95% CI, 7.3-22.1). Early treatment with highly effective antimalarial therapy has the greatest chance of preventing gametocytemia. The choice of a first-line antimalarial drug for uncomplicated malaria should not only take into consideration the ablation asexual parasitemia but also the suppression of gametocytemia.