Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali.
BACKGROUND
Seasonal malaria chemoprevention (SMC) with sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ) is being scaled up in Sahelian countries of West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern.


METHODS
Two cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3-59 months received 7 rounds of curative doses of SP plus AQ over two malaria seasons. Genotypes of P. falciparum Pfdhfr codons 51, 59 and 108; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1codon 86 were analyzed by PCR on DNA from samples collected before and after SMC, and in non-SMC patient population as controls (November 2014).


RESULTS
In the SMC population 191/662 (28.9%) and 85/670 (12.7%) of children were P. falciparum positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the non-SMC patient population 220/310 (71%) were successfully PCR analyzed. In the SMC children, the prevalence of all molecular markers of SP resistance increased significantly after SMC including the Pfdhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p = 0.02). The prevalence of Pfmdr1-86Y significantly decreased from 26.7% to 15.3% (p = 0.04) while no significant change was seen for Pfcrt 76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC population patient (p < 0.01). No Pfdhfr-164 mutation was found neither at baseline nor post SMC.


CONCLUSIONS
SMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant increase of these markers of resistance in the general parasite population after 2 years and 7 rounds of SMC.
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Hamma
H
Maiga
Médecins Sans Frontières (MSF), New York, New York, United States of America.
Estrella
E
Lasry
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Modibo
M
Diarra
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Issaka
I
Sagara
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Amadou
A
Bamadio
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Aliou
A
Traore
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Samba
S
Coumare
Médecins Sans Frontières (MSF) Bamako, Mali.
Soma
S
Bahonan
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Boubou
B
Sangare
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Yeyia
Y
Dicko
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Nouhoum
N
Diallo
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Aly
A
Tembely
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Djibril
D
Traore
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Hamidou
H
Niangaly
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
François
F
Dao
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Aboubecrine
A
Haidara
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Alassane
A
Dicko
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Ogobara K
OK
Doumbo
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Abdoulaye A
AA
Djimde
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