Abstrakt
Background- Artemisinin-based-combination
therapies (ACT), are the drugs of choice in the
treatment of malaria globally because of their good
tolerability and efficacy. Although Artemether
lumefantrine (AL) and Artesunate-amodiaquine are
the ACTs of choice in Nigeria, there are other ACTs
in the market of which artemisinin-piperaquine (AP)
is one. There is paucity of information about the
safety and efficacy of AP in Nigeria. In this study,
we evaluated the safety and efficacy of AP against
AL, the preferred ACT in Nigeria.
Methods- Children (114) aged 2-10 years with acute
uncomplicated malaria were enrolled and followed
up using the WHO antimalarial efficacy testing
protocol. Enrollees were randomized to receive AP
(56) or AL (58) at standard doses for three days.
Laboratory evaluations for hematological, liver and
renal functions were done at D0, D7 (and D28 if
necessary) as part of safety evaluation.
Results - Geometric mean parasite densities were
17,406/µL and 11,571/µL for AP and AL treated
children respectively. Response of infection to
treatment was prompt. Uncorrected adequate clinical
and parasitological response (ACPR) rate for AP was
96.1% and for 90.4% AL. while polymerase chain
reaction (PCR) corrected ACPR was 100% for both.
Parasite clearance time was significantly shorter for
AL (1.81±0.63 days) versus 2.34±0.70 days for AP
(ρ <0.001). Fever clearance times were 1.13±0.34
and 1.33±0.66 days (ρ=0.181) for AP and AL
respectively. Gametocyte clearance time was shorter
for AL than AP (3 versus 7 days). Both drugs were
well tolerated.
Conclusion- AP and AL was found to be safe and
efficacious for the treatment of uncomplicated
malaria in children in the study area.
Bibliografia
World Health Organization. Guidelines for the
treatment of malaria. Third edition. Geneva
http://www.who.int/malaria/publications/
atoz/9789241549127/en/
World Health Organization. Factsheet on the
World Malaria Report 2013.Geneva 2013. http:/
/ w w w . w h o . i n t / m a l a r i a / m e d i a /
world_malaria_report_2013/en/
World Malaria Report 2016. Geneva: World
Health Organization; 2016. Licence:CC BYNC-SA 3.0 IGO.
Malaria Consortium. Artemisinin-based
Combination Therapy (ACT) [Internet]. 2016
Available from: http://www.malaria
consortium.org/pages/112.htm
Federal Ministry of Health (FMOH). National
antimalarial treatment policy. National Malaria
and Vector Control Division Abuja-Nigeria.
Jianping S, Socheat D, Suon Seila BT, et al.
Randomized trials of artemisinin-piperaquine,
dihydroartemisinin-piperaquine phosphate and
artemether-lumefantrine for the treatment of
multi-drug resistant falciparum malaria in
Cambodia-Thailand border area. Malar J. 2011
Aug 10; 10:231. http://dx.doi.org/10.1186/1475-
-10-231
Xuan TN, Trung TN, Phong NC, et al. The
efficacy and tolerability of artemisininpiperaquine (Artequick®) versus artesunateamodiaquine (CoarsucamTM) for the
treatment of uncomplicated Plasmodium
falciparum malaria in south-central Vietnam.
Malar J. 2012 Jun 28; 11:217. https://doi.org/
1186/1475-2875-11-217
National Bureau of Statistics, Nigeria.
Population (states). 2006. [Internet]. Available
from:http://www.population.gov.ng/images/
Vol%2003%20Table%20DSx%20LGAPop%20
by%20SDistrict-PDF.pdf
Blackwelder WC. “Proving the null hypothesis”
in clinical trials. Control Clin Trials. 1982
Dec; 3(4):345–353.
World Health Organization. Basic malaria
microscopy –Learner’s guide. 2nd edition.
Feb. ISBN: 9241547820. http://
www.who.int/malaria/publications/atoz/
/en/
Trung TN, Tan B, Phuc DVand Song J. A
randomized, controlled trial of artemisininpiperaquine vs dihydroartemisinin-piperaquine
phosphate in treatment of falciparum malaria.
Chin J Integr Med. 2009 Jun 1; 15(3):189–92.
https://link.springer.com/article/10.1007/
s11655-009-0189-6
Falade C and Manyando C. Safety profile of
Coartem®: the evidence base. Malar J. 2009;
(1):1–14. http://dx.doi.org/10.1186/1475-
-8-S1-S6
Falade CO, Ogundele SO, Yusuf SM, Ladipo
SM and Ademowo OG. High Efficacy of Two
Artemisinin Based Combinations (ArtemetherLumefantrine and Artesunate Plus
Amodiaquine) For Acute Uncomplicated
Malaria in Ibadan, Nigeria. Tropical Medicine
& International Health , 2008; 13 (5): 635 -
http://onlinelibrary.wiley.com/doi/10.1111/
j.1365-3156.2008.02043.x/abstract
Makanga M, Bassat Q, Falade C. O, et al.
Efficacy and safety of artemetherlumefantrine in the treatment of acute,
uncomplicated falciparum malaria: a pooled
analysis. American Journal of Tropical
Medicine and Hygiene; 2011; 85(5):793-804.
http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3205621/
WWARN Parasite Clearance Study Group.
Baseline data of parasite clearance in patients
with falciparum malaria treated with an
artemisinin derivative: an individual patient data
meta analysis. Group Malar J (2015) 14:359.
DOI 10.1186/s12936-015-0874-1.
White NJ (2018). Anaemia and malaria.
malaria Journal. 17:371 https://doi.org/
1186/s12936-018-2509-9, 2018
Bousema T and Drakeley C. Epidemiology
and Infectivity of Plasmodium falciparum and
Plasmodium vivax Gametocytes in Relation to
Malaria Control and Elimination. Clin
Microbiol Rev. 2011 Apr 1; 24(2):377–410.
http://cmr.asm.org/content/24/2/377.
Price RN, Simpson JA, Nosten F, et al. Factors
contributing to anemia after uncomplicated
falciparum malaria. Am J Trop Med Hyg.2001
Nov; 65(5):614–22. https://www.ncbi.nlm.nih.
gov/pmc/articles/PMC4337986/
Aitken EH, Alemu A and Rogerson SJ.
Neutrophils and Malaria. Front Immunol
[Internet]. 2018 [cited 2019 Jan 7]; 9. Available
from: https://www.frontiersin.org/articles/
3389/fimmu.2018.03005/full
Cairns ME, Walker PGT, Okell LC, et al.
Seasonality in malaria transmission:
Implications for case-management with longacting artemisinin combination therapy in sub-
AP and AL antimalarial efficacy and safety in Southwest Nigeria 95
Saharan Africa. Malar J. 2015; 14(321). https:/
/doi.org/10.1186/s12936-015-0839-4.
Sowunmi A, Ntadom G, Akano K, et al.
Declining responsiveness of childhood
Plasmodium falciparum infections to
artemisinin-based combination treatments ten
years following deployment as first-line
antimalarials in Nigeria. Infect Dis Poverty.
Aug 6;8(1):69.
WWARN Gametocyte Study Group.
Gametocyte carriage in uncomplicated
Plasmodium falciparum malaria following
treatment with artemisinin combination therapy:
a systematic review and meta-analysis of
individual patient data, WWARN Gametocyte
Study Group BMC Medicine (2016) 14:79. DOI
1186/s12916-016-0621-7