Browsing by Author "Marck, Eric Van"
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Item Efficacy of sulphadoxine–pyrimethamine alone or combined with amodiaquine or chloroquine for the treatment of uncomplicated falciparum malaria in Ugandan children(Tropical medicine & international health, 2004) Talisun, Ambrose O.; Nalunkuma-Kazibwe, Anne; Bakyaita, Nathan; Langi, Peter; Mutabingwa, Theonest K.; Watkins, William W.; Marck, Eric Van; D’Alessandro, UmbertoThe rapid development of falciparum resistance to sulphadoxine–pyrimethamine (SP) in East and Central Africa has raised concerns as to the efficacy of combining it with another drug. In 2002, we assessed the efficacy of SP alone and combined with amodiaquine (AQ/SP) or chloroquine (CQ/SP) in Ugandan children with uncomplicated falciparum malaria. At day 14, adequate clinical response was 100% (84/84) for AQ/SP, 93% (92/101) for CQ/SP and 91% (73/80) for SP. At day 28, parasitological failure (RI–RIII) occurred in 16% (13/80) of children treated with AQ/SP, in 48% (48/100) of those treated with CQ/SP and in 61% (48/79) of those treated with SP alone. Compared with the AQ/SP arm, the odds for parasitological failure at day 28 were five times higher (95% CI, 2–10) in the CQ/SP group and sevenfold higher (95% CI, 3–17) in that of SP alone. CQ/SP does not offer any significant added benefit over SP alone while AQ/SP is an efficacious low-cost combination. These findings have important policy implications for Uganda and other resource-constrained African countries faced with the problematic choice of a new first-line antimalarial treatment in a context of high CQ resistance.Item Role of the pfcrt codon 76 mutation as a molecular marker for population-based surveillance of chloroquine (CC&resistant Plasmodium falciparum malaria in Ugandan sentinel sites with high CQ resistance(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2002) Talisuna, Ambrose O.; Kyosiimire-Lugemwa, Jackie; Langi, Peter; Mutabingwa, Theonest K.; Watkins, William; Marck, Eric Van; Egwang, Thomas; D'Alessandro, UmbertoThe mutant genotype at codon 76 of the pfcrt gene (T76) has been proposed as a molecular marker for surveillance of chloroquine (CQ)-resistant Plasmodium falciparum malaria but this proposal has not been validated by population-based surveys. In 1998–1999, in 6 Ugandan sentinel sites, the prevalence of P. falciparum infections with the T76 genotype and the level of CQ use were measured by community surveys, and CQ resistance was determined by in-vivo tests on 6–59-month-old children with clinical malaria. The prevalence of T76 was not related to the overall clinical (early and late treatment failure: ETF+LTF; r = 0 · 14, P = 0 · 78) or parasitological (RI+RII+RIII; r = 0 · 17, P = 0 · 73) CQ resistance. However, the percentage of individuals carrying only infections with the T76 genotype (T76 alone) increased with increasing ETF (r = 0 · 76, P = 0 · 07) and type RIII parasitological failure (r = 0 · 69, P = 0 · 12). Similarly, the ratio between T76 and K76 (the wild type) prevalences () was strongly and positively correlated with ETF (r = 0 · 85, P = 0 · 03) and RIII (r = 0 · 82, P = 0 · 04). Moreover, T76 alone (r = 0 · 90, P = 0 · 01) as well as (r = 0 · 90, P = 0 · 01) significantly increased with increasing community CQ use. T76 alone and can be useful markers to estimate the ETF and RIII prevalence as well as the amount of CQ use in the community.