Four Artemisinin-Based Treatments in African Pregnant Women with Malaria

 

Flora Le, Mercer University College of Pharmacy

A meta-analysis comparing efficacy, safety and tolerability of artemisinin-based combination therapies (ACTs) versus quinine and other non-ACT antimalarial therapies suggested that artemisinin-based combination therapies are better than quinine in the second and third trimesters.  [1]

A review of 16 studies concluded that the use of artemether-lumefantrine (AL) for the treatment of uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy is largely supported by the large body of evidence and safety data.  [2]

Title: Four Artemisinin-Based Treatments in African Pregnant Women with Malaria
Design Multicenter, randomized, open-label trial; N= 3,428
Objective To measure the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa
Study Groups Artemether–lumefantrine (n= 880); amodiaquine–artesunate (n= 842); mefloquine–artesunate (n= 853); dihydroartemisinin–piperaquine (n= 848)
Methods A total of 3,428 pregnant women in the second or third trimester who had falciparum malaria at any parasite density, regardless of symptoms, were treated with artemether–lumefantrine, amodiaquine–artesunate, mefloquine–artesunate, or dihydroartemisinin–piperaquine.
Duration June 2010 through August 2013
Primary Outcome Measure Polymerase-chain reaction (PCR)–adjusted cure rates at day 63 and safety outcomes
Baseline Characteristics  

 

 

Artemether–lumefantrine
(n= 880)
Amodiaquin –artesunate
(n= 842)
Mefloquine–artesunate (n= 853) Dihydroartmisinin–piperaquine
(n= 848)
Country, (no.)
Burkina Faso 290 291 0 288
Ghana 0 261 265 260
Malawi 290 290 288 0
Zambia 300 0 300 300
Age, (yr.) 22.6 +/- 5.6 23.4 +/- 5.9 22.3 +/- 5.4 23.5 +/- 5.9
Symptomatic malaria, (%) 37.2 34.9 37.4 43.8
Fever, (%) 6.5 6.8 3.2 8.0
Parasite density > 2,000/ mm3 (%) 30.6 25.3 29.1 32.1
³ Three symptoms, (%) 7.2 9.3 11.8 14.3
Hemoglobin, (g/dL)
Median 10.2 10.1 10.1 10.1
Trimester gestation, (%)
Second 71.8 75.0 68.5 65.8
Third 28.2 24.9 31.5 34.2
Bed net use before trial entry, (%) 34.4 34.6 27.9 37.5
Use of intermittent preventative treatment before day zero, (%) 9.9 10.9 13.7 16.4
Results Per protocol analysis
PCR adjusted, (no. of patients) 789 729 707 716
PCR adjusted rate, %
(95% [CI])
94.8 (93.0-96.1) 98.5 (97.3- 99.2) 99.2 (98.2-99.6) 96.8 (95.2- 97.9)
PCR unadjusted (no. of patients) 810 742 720 728
PCR unadjusted, %
(95% [CI])
52.5 (49.0- 55.9) 82.3 (79.4- 84.9) 86.9 (84.3- 89.2) 73.8 (70.4- 76.8)
Intent to treat analysis
PCR adjusted, (no. of patients) 807 776 744 753
PCR adjusted rate, %
(95% [CI])
94.2 (92.3- 95.6) 96.9 (95.4- 97.9) 98.0 (96.7-98.8) 95.5 (93.8- 96.8)
PCR unadjusted (no. of patients) 830 791 759 770
PCR unadjusted, %
(95% [CI])
52.5 (49.1- 55.9) 81.2 (78.3- 83.7) 86.0 (83.4- 88.3) 72.3 (69.1- 73.4)
Adverse Events Common Adverse Events: drug related event: artemether–lumefantrine (11.5%), amodiaquine– artesunate (48.5%), dihydroartemisinin–piperaquine (20.6%), mefloquine–artesunate (50.6%)
Serious Adverse Events: blood disorder: artemether–lumefantrine (0%), amodiaquine– artesunate (0.7%), dihydroartemisinin–piperaquine (0.2%), mefloquine–artesunate (0%); moderate abdominal pain: artemether–lumefantrine (0%), amodiaquine– artesunate (0.2%), dihydroartemisinin–piperaquine (0%), mefloquine–artesunate (0.1%)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Artemether–lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-treatment prophylaxis, whereas dihydroartemisinin–piperaquine had the best efficacy and an acceptable safety profile.

The results from this study are consistent with prior studies indicating that the use of artemether–lumefantrine in the second and third trimester is safe and provides acceptable cure rates in treating P. falciparum malaria.  A limitation of this study was that the trial was open-label, which could introduce some bias between the researchers and participants since they know which treatment is being given.  For future studies, the safety and effectiveness of the four treatment groups (artemether–lumefantrine; amodiaquine–artesunate; mefloquine–artesunate; dihydroartemisinin–piperaquine) should evaluated in in the first trimester to determine if these treatment options could be used early on for the treatment or prevention of P. falciparum malaria.

References

  1. Burger RJ, Van eijk AM, Bussink M, Hill J, Ter kuile FO. Artemisinin-Based Combination Therapy Versus Quinine or Other Combinations for Treatment of Uncomplicated Plasmodium falciparum Malaria in the Second and Third Trimester of Pregnancy: A Systematic Review and Meta-Analysis. Open Forum Infect Dis. 2016;3(1):ofv170.
  2. Manyando C, Kayentao K, D’Alessandro U, Okafor HU, Juma E, Hamed K. A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicatedPlasmodium falciparummalaria during pregnancy. Malaria Journal. 2012;11:141. doi:10.1186/1475-2875-11-141.
  3. Pekyi D, Ampromfi AA, Tinto H, et al. Four Artemisinin-Based Treatments in African Pregnant Women with Malaria. N Engl J Med. 2016;374(10):913-27.

 

 

 

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s