Parasite clearance following treatment with sulphadoxine-pyrimethamine for intermittent preventive treatment in Burkina-Faso and Mali: 42-day in vivo follow-up study.
BACKGROUND
Intermittent Preventive Treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is widely used for the control of malaria in pregnancy in Africa. The emergence of resistance to SP is a concern requiring monitoring the effectiveness of SP for IPTp.


METHODS
This was an in-vivo efficacy study to determine the parasitological treatment response and the duration of post-treatment prophylaxis among asymptomatic pregnant women receiving SP as part of IPTp in Mali and Burkina-Faso. The primary outcome was the PCR-unadjusted % of patients with parasites recurrence by day 42 defined as a positive diagnostic test by malaria smear at any visit between days 4 and 42. Treatment failure was based on the standard World Health Organization criteria. The therapeutic response was estimated using the Kaplan-Meier curve.


RESULTS
A total of 580 women were enrolled in Mali (N=268) and Burkina-Faso (N=312) and followed weekly for 42 days. Among these, 94.3% completed the follow-up. The PCR-unadjusted cumulative risk of recurrence by day 42 was 4.9% overall, and 3.2% and 6.5% in Mali and Burkina Faso respectively (Hazard Ratio [HR] =2.14, 95%, CI [0.93-4.90]; P=0.070), and higher among the primi- and secundigravida (6.4%) than multigravida (2.2%, HR=3.01 [1.04-8.69]; P=0.042). The PCR-adjusted failure risk was 1.1% overall (Mali 0.8%, Burkina-Faso 1.4%). The frequencies (95% CI) of the dhfr double and triple mutant and dhps 437 and 540 alleles mutant genotype at enrolment were 24.2% (23.7-25.0), 4.7% (4.4-5.0), and 21.4% (20.8-22.0) and 0.37% (0.29-0.44) in Mali, and 7.1% (6.5-7.7), 44.9% (43.8-46.0) and 75.3% (74.5-76.2) and 0% in Burkina-Faso, respectively. There were no dhfr 164L or dhps 581G mutations.


CONCLUSIONS
SP remains effective at clearing existing infections when provided as IPTp to asymptomatic pregnant women in Mali and Burkina. Continued monitoring of IPTp-SP effectiveness, including of the impact on birth parameters in this region is essential.
Sheick O
SO
Coulibaly
Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Center, Faculty of Medicine and Odonto-stomatology of Bamako, University of Sciences, Technics and Technologies, BP: 1805, Bamako, Mali. kayentao@icermali.org.
Kassoum
K
Kayentao
Steve
S
Taylor
Etienne A
EA
Guirou
Carole
C
Khairallah
Nouhoun
N
Guindo
Moussa
M
Djimde
Richard
R
Bationo
Alamissa
A
Soulama
Edgar
E
Dabira
Binta
B
Barry
Moussa
M
Niangaly
Hammadoun
H
Diakite
Sidiki
S
Konate
Mohamed
M
Keita
Boubacar
B
Traore
Steve R
SR
Meshnick
Pascal
P
Magnussen
Ogobara K
OK
Doumbo
Feiko O
FO
ter Kuile
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D058345:Asymptomatic Infections / Q000453:epidemiology / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D002050:Burkina Faso / Q000453:epidemiology; D059788:Dried Blood Spot Testing; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008288:Malaria / Q000188:drug therapy* / Q000453:epidemiology; D008302:Mali / Q000453:epidemiology; D059208:Parasite Load; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D055815:Young Adult
D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine