New malaria treatments may not be ideal
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《英国医生杂志》
Combination therapy based on artemisinins, which forms the basis of a newer class of antimalarial drugs, has been advocated recently to improve efficacy and limit the spread of resistance. But these drugs may not be the ideal treatment for uncomplicated malaria, especially in highly endemic areas in Africa.
In the regions of Africa that have the highest transmission rates, cheaper combinations of older medicines, principally amodiaquine and sulfadoxine pyrimethamine, worked better. Patients on these drugs have at least as good a chance of preventing recurrent malarial infection (defined as either new infections or the previous infection returning) compared with patients treated with the newer, more expensive artemisinin based regimens. (PLoS Medicine 2005;2(7):e190).
The high endemic nature of malaria in Africa may impact on the efficacy of artemisinin based combination therapy. If used alone, artemisinins will cure falciparum malaria, which is the most severe kind of the disease, in seven days. The monotherapy also carries the highest risk of recurrence, however, and therefore needs to be combined with other antimalarial drugs to achieve maximum efficacy.
In a new study, authors led by Adoke Yeka of the Uganda Ministry of Health, compared artemisinin based with other combination therapies in four districts of Uganda that had varying transmission intensity.
A total of 2160 patients aged 6 months or more, drawn from the four different sites, all of whom had uncomplicated falciparum malaria, were enrolled in the study. They were randomised to receive one of three different regimens, based on either chloroquine plus sulfadoxine pyrimethamine; amodiaquine plus sulfadoxine pyrimethamine; or amodiaquine plus artesunate.
Of the patients who started the study and completed follow-up, 1749 (84%) were younger than 5 years. The primary endpoints were the 28 day risks of parasitological failure, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections
The results showed significant variability between the four sites, but, overall, the risk of recrudescence after treatment with chloroquine plus sulfadozine pyrimethamine was highest, ranging from 22% to 46% across the four sites. This risk was significantly lower (P<0.01) after amodiaquine plus sulfadozine pyrimethamine (between 7% and 18% at the four sites) and for amodiaquine plus artesunate (between 4% and 12% at the different sites).
The risk of recrudescence between the four sites seemed to correlate with measures of the density and intensity of the parasitic infection in those different regions.
Compared with amodiaquine plus sulfadozine pyrimethamine, amodiaquine plus artesunate was associated with a lower risk of recurrence but a higher risk of new infection.
"Considering endemicity, patients with symptomatic malaria from highly endemic areas such as Africa generally have higher pretreatment parasite densities compared to patients from lower endemic areas such as Southeast Asia, and higher pretreatment parasite densities have been associated with a higher risk of recrudescence after treatment with ," the authors write.
"Additionally, the increased risk of new infections in highly endemic areas may contribute greatly to treatment outcome."
These factors show that in Africa, more so than other areas, "it is critical that artemisinins be combined with other highly effective drugs. However, whether partner drug should be short- or long-acting remains unclear. Long-acting partner drugs offer an extended prophylactic effect; however, they may encourage the selection of drug resistance," they write.(New York Scott Gottlieb)
In the regions of Africa that have the highest transmission rates, cheaper combinations of older medicines, principally amodiaquine and sulfadoxine pyrimethamine, worked better. Patients on these drugs have at least as good a chance of preventing recurrent malarial infection (defined as either new infections or the previous infection returning) compared with patients treated with the newer, more expensive artemisinin based regimens. (PLoS Medicine 2005;2(7):e190).
The high endemic nature of malaria in Africa may impact on the efficacy of artemisinin based combination therapy. If used alone, artemisinins will cure falciparum malaria, which is the most severe kind of the disease, in seven days. The monotherapy also carries the highest risk of recurrence, however, and therefore needs to be combined with other antimalarial drugs to achieve maximum efficacy.
In a new study, authors led by Adoke Yeka of the Uganda Ministry of Health, compared artemisinin based with other combination therapies in four districts of Uganda that had varying transmission intensity.
A total of 2160 patients aged 6 months or more, drawn from the four different sites, all of whom had uncomplicated falciparum malaria, were enrolled in the study. They were randomised to receive one of three different regimens, based on either chloroquine plus sulfadoxine pyrimethamine; amodiaquine plus sulfadoxine pyrimethamine; or amodiaquine plus artesunate.
Of the patients who started the study and completed follow-up, 1749 (84%) were younger than 5 years. The primary endpoints were the 28 day risks of parasitological failure, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections
The results showed significant variability between the four sites, but, overall, the risk of recrudescence after treatment with chloroquine plus sulfadozine pyrimethamine was highest, ranging from 22% to 46% across the four sites. This risk was significantly lower (P<0.01) after amodiaquine plus sulfadozine pyrimethamine (between 7% and 18% at the four sites) and for amodiaquine plus artesunate (between 4% and 12% at the different sites).
The risk of recrudescence between the four sites seemed to correlate with measures of the density and intensity of the parasitic infection in those different regions.
Compared with amodiaquine plus sulfadozine pyrimethamine, amodiaquine plus artesunate was associated with a lower risk of recurrence but a higher risk of new infection.
"Considering endemicity, patients with symptomatic malaria from highly endemic areas such as Africa generally have higher pretreatment parasite densities compared to patients from lower endemic areas such as Southeast Asia, and higher pretreatment parasite densities have been associated with a higher risk of recrudescence after treatment with ," the authors write.
"Additionally, the increased risk of new infections in highly endemic areas may contribute greatly to treatment outcome."
These factors show that in Africa, more so than other areas, "it is critical that artemisinins be combined with other highly effective drugs. However, whether partner drug should be short- or long-acting remains unclear. Long-acting partner drugs offer an extended prophylactic effect; however, they may encourage the selection of drug resistance," they write.(New York Scott Gottlieb)