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Efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria: revisiting molecular markers in an area of emerging AQ and SP resistance in Mali.

Tekete M, Djimde AA, Beavogui AH, Maiga H, Sagara I, Fofana B, Ouologuem D, Dama S, Kone A, Dembele D, Wele M, Dicko A, Doumbo OK - Malar. J. (2009)

Bottom Line: Amodiaquine was the most effective on fever.No infection with dhps 540E was found.The study demonstrated that sulphadoxine-pyrimethamine and amodiaquine were appropriate partner drugs that could be associated with artemisinin derivatives in an artemisinin-based combination therapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Malaria Research and Training Center, Bamako, Mali. mtekete@mrtcbko.org

ABSTRACT

Background: To update the National Malaria Control Programme of Mali on the efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria.

Methods: During the malaria transmission seasons of 2002 and 2003, 455 children--between six and 59 months of age, with uncomplicated malaria in Kolle, Mali, were randomly assigned to one of three treatment arms. In vivo outcomes were assessed using WHO standard protocols. Genotyping of msp1, msp2 and CA1 polymorphisms were used to distinguish reinfection from recrudescent parasites (molecular correction).

Results: Day 28 adequate clinical and parasitological responses (ACPR) were 14.1%, 62.3% and 88.9% in 2002 and 18.2%, 60% and 85.2% in 2003 for chloroquine, amodiaquine and sulphadoxine-pyrimethamine, respectively. After molecular correction, ACPRs (cACPR) were 63.2%, 88.5% and 98.0% in 2002 and 75.5%, 85.2% and 96.6% in 2003 for CQ, AQ and SP, respectively. Amodiaquine was the most effective on fever. Amodiaquine therapy selected molecular markers for chloroquine resistance, while in the sulphadoxine-pyrimethamine arm the level of dhfr triple mutant and dhfr/dhps quadruple mutant increased from 31.5% and 3.8% in 2002 to 42.9% and 8.9% in 2003, respectively. No infection with dhps 540E was found.

Conclusion: In this study, treatment with sulphadoxine-pyrimethamine emerged as the most efficacious on uncomplicated falciparum malaria followed by amodiaquine. The study demonstrated that sulphadoxine-pyrimethamine and amodiaquine were appropriate partner drugs that could be associated with artemisinin derivatives in an artemisinin-based combination therapy.

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Selection of molecular markers of CQ by AQ.
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Figure 4: Selection of molecular markers of CQ by AQ.

Mentions: The well-known selection effect of CQ treatment on pfcrt 76T and pfmdr-1 86Y was also seen in this study. When these markers were considered separately, treatment failure in the AQ arm was neither associated with mutations in pfcrt (rates of pfcrt 76T were 70%,(n = 10) in the failure group and 69% (n = 87) in the cured group; OR = 1.05, 95% CI = 0.22 – 5.60, p = 0.62) nor with pfmdr-1 (rates of pfmdr-1 86Y level were 63.6% (n = 11) in the failure group and 41.7% (n = 96) in the cured group, OR = 2.45, 95% CI = 0.59 – 10.80, p = 0.14). However, when the two mutations were considered together (pfcrt 76T and pfmdr-1 86Y), there was a trend toward a significant association between the presence of both mutations in an infection and treatment failure with AQ (rate of pfcrt 76T+pfmdr-1 86Y was 60% (n = 10) in the failure group and 32.2% (n = 87) in the cured group, OR = 3.16, 95% CI = 0.71–14.75, p = 0.08). Furthermore, each of these mutations was significantly selected in vivo by AQ monotherapy as was the combination of pfcrt 76T and pfmdr-1 86Y (Figure 4).


Efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria: revisiting molecular markers in an area of emerging AQ and SP resistance in Mali.

Tekete M, Djimde AA, Beavogui AH, Maiga H, Sagara I, Fofana B, Ouologuem D, Dama S, Kone A, Dembele D, Wele M, Dicko A, Doumbo OK - Malar. J. (2009)

Selection of molecular markers of CQ by AQ.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651187&req=5

Figure 4: Selection of molecular markers of CQ by AQ.
Mentions: The well-known selection effect of CQ treatment on pfcrt 76T and pfmdr-1 86Y was also seen in this study. When these markers were considered separately, treatment failure in the AQ arm was neither associated with mutations in pfcrt (rates of pfcrt 76T were 70%,(n = 10) in the failure group and 69% (n = 87) in the cured group; OR = 1.05, 95% CI = 0.22 – 5.60, p = 0.62) nor with pfmdr-1 (rates of pfmdr-1 86Y level were 63.6% (n = 11) in the failure group and 41.7% (n = 96) in the cured group, OR = 2.45, 95% CI = 0.59 – 10.80, p = 0.14). However, when the two mutations were considered together (pfcrt 76T and pfmdr-1 86Y), there was a trend toward a significant association between the presence of both mutations in an infection and treatment failure with AQ (rate of pfcrt 76T+pfmdr-1 86Y was 60% (n = 10) in the failure group and 32.2% (n = 87) in the cured group, OR = 3.16, 95% CI = 0.71–14.75, p = 0.08). Furthermore, each of these mutations was significantly selected in vivo by AQ monotherapy as was the combination of pfcrt 76T and pfmdr-1 86Y (Figure 4).

Bottom Line: Amodiaquine was the most effective on fever.No infection with dhps 540E was found.The study demonstrated that sulphadoxine-pyrimethamine and amodiaquine were appropriate partner drugs that could be associated with artemisinin derivatives in an artemisinin-based combination therapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Malaria Research and Training Center, Bamako, Mali. mtekete@mrtcbko.org

ABSTRACT

Background: To update the National Malaria Control Programme of Mali on the efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria.

Methods: During the malaria transmission seasons of 2002 and 2003, 455 children--between six and 59 months of age, with uncomplicated malaria in Kolle, Mali, were randomly assigned to one of three treatment arms. In vivo outcomes were assessed using WHO standard protocols. Genotyping of msp1, msp2 and CA1 polymorphisms were used to distinguish reinfection from recrudescent parasites (molecular correction).

Results: Day 28 adequate clinical and parasitological responses (ACPR) were 14.1%, 62.3% and 88.9% in 2002 and 18.2%, 60% and 85.2% in 2003 for chloroquine, amodiaquine and sulphadoxine-pyrimethamine, respectively. After molecular correction, ACPRs (cACPR) were 63.2%, 88.5% and 98.0% in 2002 and 75.5%, 85.2% and 96.6% in 2003 for CQ, AQ and SP, respectively. Amodiaquine was the most effective on fever. Amodiaquine therapy selected molecular markers for chloroquine resistance, while in the sulphadoxine-pyrimethamine arm the level of dhfr triple mutant and dhfr/dhps quadruple mutant increased from 31.5% and 3.8% in 2002 to 42.9% and 8.9% in 2003, respectively. No infection with dhps 540E was found.

Conclusion: In this study, treatment with sulphadoxine-pyrimethamine emerged as the most efficacious on uncomplicated falciparum malaria followed by amodiaquine. The study demonstrated that sulphadoxine-pyrimethamine and amodiaquine were appropriate partner drugs that could be associated with artemisinin derivatives in an artemisinin-based combination therapy.

Show MeSH
Related in: MedlinePlus