Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria
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《英国医生杂志》
EDITOR—How to reconcile our article's report of a sustained 80% efficacy with White's assertion that we found cure rates of less than 40%? We used the World Health Organization's standard definition of antimalarial therapeutic efficacy in high transmission areas, which is based on follow up through 14 days after treatment.1 We also reported parasitaemia prevalences at 28 days after treatment, but these data do not provide cure rates in any accepted or standard sense. In high transmission settings, the "cure rate" declines as follow-up is extended from 14 days to 28 days or longer.
A longitudinal study compared the efficacy of sulfadoxine-pyrimethamine and chlorproguanil-dapsone in Malawi from 1997 to 1999.2 Chlorproguanil-dapsone, a short-acting antifolate combination, had 95% efficacy compared with 80% for sulfadoxine-pyrimethamine. Children treated with sulfadoxine-pyrimethamine for all episodes of malaria over a year had no more episodes of uncomplicated malaria, anaemia, or severe malaria than those treated with chlorproguanil-dapsone. Radical cure, which can be achieved with short-acting, highly efficacious combinations, should be the goal where the risk of reinfection is low, but this study demonstrates that over time, children in areas of high transmission may do as well or better with a longer acting drug with mediocre efficacy than with a highly curative short acting regimen. Assumptions that the best approach to malaria therapy in one setting can be extrapolated to all other settings are unwise.
Malawi introduced sulfadoxine-pyrimethamine as the first line antimalarial in 1993. This was accompanied by a 20% reduction in infant mortality and a 22% reduction in child mortality from 1990 through 2000,3 despite increasing rates of HIV mortality during this period, and in contrast to increasing infant and child mortality in the rest of the region, where other countries continued to use chloroquine. The continued use of chloroquine in the face of truly dismal efficacy rates was likely to be responsible for higher mortality among children in other countries of this region.
Subsequent to our study, both the protocol for monitoring antimalarial efficacy and the threshold for recommending switching malaria drugs were changed, as noted by Ringwald. Nevertheless, we agree with White and Ringwald that the observed degree of efficacy (however it is defined) reported in our study is less than satisfactory. Hence the statement in our paper that the efficacy levels we reported for sulfadoxine-pyrimethamine do not warrant complacency about seeking alternative treatments for its replacement. The situation is changing, and all countries must now seek to introduce optimal first line treatments and to monitor their effectiveness against malaria-attributable mortality in children.
Christopher V Plowe, associate professor
cplowe@medicine.umaryland.edu
James G Kublin, clinical instructor
Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF1-480, Baltimore, MD 21044, USA
Fraction K Dzinjalamala, research associate, Deborah S Kamwendo, research associate, Rabia A G Mukadam, research associate, Phillips Chimpeni, clinical officer
Blantyre Malaria Project, College of Medicine, University of Malawi, Blantyre, Malawi
Malcolm E Molyneux, professor
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
Terrie E Taylor, professor
College of Osteopathic Medicine, Michigan State University, Lansing, MI, USA
Competing interests: None declared.
References
World Health Organization. Assessment of therapeutic efficacy of antimalarial drugs for uncomplicated falciparum malaria in areas with intense transmission. Geneva, World Health Organization, Division of Control of Tropical Diseases, 1996.
Sulo J, Chimpeni P, Hatcher J, Kublin JG, Plowe CV, Molyneux ME, et al. Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial. Lancet 2002;360: 1136-43.
Statistics Division, World Health Organization. Millennium indicators database. http://unstats.un.org/unsd/mi/mi_goals.asp (accessed 6 May 2004).
A longitudinal study compared the efficacy of sulfadoxine-pyrimethamine and chlorproguanil-dapsone in Malawi from 1997 to 1999.2 Chlorproguanil-dapsone, a short-acting antifolate combination, had 95% efficacy compared with 80% for sulfadoxine-pyrimethamine. Children treated with sulfadoxine-pyrimethamine for all episodes of malaria over a year had no more episodes of uncomplicated malaria, anaemia, or severe malaria than those treated with chlorproguanil-dapsone. Radical cure, which can be achieved with short-acting, highly efficacious combinations, should be the goal where the risk of reinfection is low, but this study demonstrates that over time, children in areas of high transmission may do as well or better with a longer acting drug with mediocre efficacy than with a highly curative short acting regimen. Assumptions that the best approach to malaria therapy in one setting can be extrapolated to all other settings are unwise.
Malawi introduced sulfadoxine-pyrimethamine as the first line antimalarial in 1993. This was accompanied by a 20% reduction in infant mortality and a 22% reduction in child mortality from 1990 through 2000,3 despite increasing rates of HIV mortality during this period, and in contrast to increasing infant and child mortality in the rest of the region, where other countries continued to use chloroquine. The continued use of chloroquine in the face of truly dismal efficacy rates was likely to be responsible for higher mortality among children in other countries of this region.
Subsequent to our study, both the protocol for monitoring antimalarial efficacy and the threshold for recommending switching malaria drugs were changed, as noted by Ringwald. Nevertheless, we agree with White and Ringwald that the observed degree of efficacy (however it is defined) reported in our study is less than satisfactory. Hence the statement in our paper that the efficacy levels we reported for sulfadoxine-pyrimethamine do not warrant complacency about seeking alternative treatments for its replacement. The situation is changing, and all countries must now seek to introduce optimal first line treatments and to monitor their effectiveness against malaria-attributable mortality in children.
Christopher V Plowe, associate professor
cplowe@medicine.umaryland.edu
James G Kublin, clinical instructor
Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF1-480, Baltimore, MD 21044, USA
Fraction K Dzinjalamala, research associate, Deborah S Kamwendo, research associate, Rabia A G Mukadam, research associate, Phillips Chimpeni, clinical officer
Blantyre Malaria Project, College of Medicine, University of Malawi, Blantyre, Malawi
Malcolm E Molyneux, professor
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
Terrie E Taylor, professor
College of Osteopathic Medicine, Michigan State University, Lansing, MI, USA
Competing interests: None declared.
References
World Health Organization. Assessment of therapeutic efficacy of antimalarial drugs for uncomplicated falciparum malaria in areas with intense transmission. Geneva, World Health Organization, Division of Control of Tropical Diseases, 1996.
Sulo J, Chimpeni P, Hatcher J, Kublin JG, Plowe CV, Molyneux ME, et al. Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial. Lancet 2002;360: 1136-43.
Statistics Division, World Health Organization. Millennium indicators database. http://unstats.un.org/unsd/mi/mi_goals.asp (accessed 6 May 2004).