Comparative study of the efficacy and tolerability of dihydroartemisinin - piperaquine - trimethoprim versus artemether - lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal

Menan, Hervé; Faye, Oumar; Same-Ekobo, A.; Oga, A.S.S.; Faye, Babacar; Barro, C.; Kueté, Thomas; Ndiaye, Jean-Louis; Vicky, Ama-Moor; Tine, Roger; Yavo, William; Kane, Dieynaba; Kassi, K.; Koné, Moussa

doi:10.1186/1475-2875-10-185

Cited by 25 publications

(27 citation statements)

References 14 publications

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“…In adults in Thailand, the protective efficacy of DHAPQ was 98% when DHAPQ was administered monthly and 86% when it was administered bimonthly (11). Despite extensive clinical evaluation and use of DHAPQ in Southeast Asia (12,13) and Africa (14)(15)(16), few studies have addressed pharmacokinetics of PQ in children (17)(18)(19). However, one of these studies suggested that children are underdosed with current regimens (17), which was also supported by a recent meta-analysis (20).…”

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confidence: 86%

Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso

Zongo

Milligan

Compaoré

et al. 2015

Antimicrob Agents Chemother

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fThe WHO recommends that children living in areas of highly seasonal malaria transmission in the Sahel subregion should receive seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). We evaluated the use of dihydroartemisinin-piperaquine (DHAPQ) as an alternative drug that could be used if SPAQ starts to lose efficacy. A total of 1,499 children 3 to 59 months old were randomized to receive SMC with SPAQ or DHAPQ over 3 months. The primary outcome measure was the risk of clinical malaria (fever or a history of fever with a parasite density of at least 3,000/l). A cohort of 250 children outside the trial was followed up as a control group. Molecular markers of drug resistance were assessed. The risk of a malaria attack was 0.19 in the DHAPQ group and 0.15 in the SPAQ group, an odds ratio of 1.33 (95% confidence interval [CI], 1.02 to 1.72). Efficacy of SMC compared to the control group was 77% (67% to 84%) for DHAPQ and 83% (74% to 89%) for SPAQ. pfdhfr and pfdhps mutations associated with antifolate resistance were more prevalent in parasites from children who received SPAQ than in children who received DHAPQ. Both regimens were highly efficacious and well tolerated. DHAPQ is a potential alternative drug for SMC. (This trial is registered at ClinicalTrials.gov under registration no. NCT00941785.) S ubstantial progress has been made in the control of malaria (1), but in most of sub-Saharan Africa, the disease remains a major public health problem. In Burkina Faso, malaria is still a leading cause of severe illness and mortality, accounting for 63% of hospital admissions and 71% of all deaths in hospital among children under 5 years of age in 2011 (2). Results from research studies indicate that the burden remains very high. In Boussé, in the Sahelian zone of the country, in 2011, 1,232 episodes of malaria were recorded over one transmission season in 1,500 children under 5 years of age who were using an insecticide-treated net (3). In such areas, new strategies for malaria control are needed. The WHO now recommends seasonal malaria chemoprevention (SMC) with sulfadoxine pyrimethamine plus amodiaquine (SPAQ) as a new strategy for malaria control in children in areas of highly seasonal transmission (4, 5), defined as areas where at least 60% of malaria cases occur during 4 months of the year and where SP and AQ retain good efficacy. Most parts of Burkina Faso fit these criteria, and implementation of SMC in Burkina Faso started in 2014 in seven districts.Resistance to both SP and AQ is common in much of Africa, but in most areas of seasonal transmission in the Sahel these drugs retain their antimalarial efficacy (5). However, alternative drug regimens may be needed in these areas in the future, and they are needed now if SMC is to be deployed in areas of eastern or southern Africa where antifolate resistance makes SP an unsuitable drug for SMC. Dihydroartemisinin-piperaquine (DHAPQ) is a potential alternative. Piperaquine (PQ) is a long-acting antimalarial; administration dail...

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confidence: 86%

Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso

Zongo

Milligan

Compaoré

et al. 2015

Antimicrob Agents Chemother

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“…Combinations of MQ and artesunic acid with ciprofloxacin, which are experimentally active in vitro against P. falciparum-iRBCs, appear promising ). The derivatisation of the fluoroquinolone ciprofloxacin enhanced the in vitro activity and yielded compounds that were 10-100-fold more active than ciprofloxacin (Dubar et al 2009); chalcones combined with ART (Bhattacharya et al 2009) and pyronaridine combined with artesunate (AS) (Tshefu et al 2010) and dihydroartemisinin-piperaquine (Menan et al 2011) showed intense activity, with the latter exhibiting advantages over artemether-lumefantrine in human malaria.…”

Section: Drug Combinations and Hybrids Used In Antimalarial Chemothermentioning

confidence: 99%

New approaches in antimalarial drug discovery and development: a review

Aguiar

Rocha

Souza

et al. 2012

Mem. Inst. Oswaldo Cruz

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Malaria remains a major world health problem following the emergence and spread of Plasmodium falciparum that is resistant to the majority of antimalarial drugs. This problem has since been aggravated by a decreased sensitivity of Plasmodium vivax to chloroquine. This review discusses strategies for evaluating the antimalarial activity of new compounds in vitro and in animal models ranging from conventional tests to the latest high-throughput screening technologies. Antimalarial discovery approaches include the following: the discovery of antimalarials from natural sources, chemical modifications of existing antimalarials, the development of hybrid compounds, testing of commercially available drugs that have been approved for human use for other diseases and molecular modelling using virtual screening technology and docking. Using these approaches, thousands of new drugs with known molecular specificity and active against P. falciparum have been selected. The inhibition of haemozoin formation in vitro, an indirect test that does not require P. falciparum cultures, has been described and this test is believed to improve antimalarial drug discovery. Clinical trials conducted with new funds from international agencies and the participation of several industries committed to the eradication of malaria should accelerate the discovery of drugs that are as effective as artemisinin derivatives, thus providing new hope for the control of malaria

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“…The indicator for treatment success was adequate clinical and parasitological response (ACPR). ACPR was de ned as absence of parasitaemia by the end of treatment (days 14, 28, 42, 63) irrespective of axillary temperature without previously meeting any of the criteria for early treatment failure or late clinical failure or late parasitological failure (17)(18)(19)(20). The treatment success was de ned based on PCR genotyping according to current World Health Organisation (WHO) recommendation.…”

Section: Assessment Of Treatment Outcomesmentioning

confidence: 99%

“…A total of 39 studies from 16 records with the same or different ACTs ful lled the inclusion criteria and were included in this systematic review and meta-analysis with a total sample size of 3,747 participants that ranged from a minimum of 48 patients [22] to a maximum of 255 patients [30]. Treatment outcomes in all studies were evaluated by adopting clinical and parasitological criteria based on WHO guidelines [17][18][19][20].…”

Section: Qualitative Synthesismentioning

confidence: 99%

Clinical Efficacy and Safety of Artemisinin-based Combination Therapies in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Cameroon: A Systematic Review and Meta-Analysis from Individual Patient Data (2004-2020)

Nji¹,

Niba²,

Netongo³

et al. 2020

Preprint

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Background: Cameroon remains a high malaria endemic country. The rapid emergence and spread of Plasmodium falciparum resistant parasites compelled the World Health Organisation (WHO) to recommend the change from monotherapies to artemisinin-based combination therapies (ACTs). This study aimed to assess the clinical efficacy and safety of artemisinin-based combination therapies in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon from 2004 to 2020.Methods: The preferred reporting items for systematic review and meta-analysis (PRISMA) statement were adopted for the selection of studies. The heterogeneity of the included studies was determined using Cochrane Q and the I2. The random effects model was used as standard to combine studies showing heterogeneity of Cochrane Q with P < 0.10 and I2 > 50.Results: Out of the 4,920 articles and unpublished datasets screened, 16 records with a sample size of 3,737 participants on 8 generic ACTs fulfilled the inclusion criteria. The per protocol (PP) analysis pooled efficacy of the ACTs was 97.9 % (95 % CI, 97.2-98.7, P<0.01). Sub-group analyses were performed for ASAQ, AL and DHAP. The aggregated efficacies of ASAQ, AL and DHAP were 97.5 % (95 % CI, 96.3-98.8, P<0.01), 99.4 % (95 % CI, 98.6-100.0, P=0.39), 98.0 % (95 % CI, 96.3-99.7, P=0.28) respectively. The pooled efficacies were above the WHO minimum benchmark of 90.0%. The ACTs are well tolerated and common adverse events reported were asthenia, diarrhoea, abdominal pain, anorexia, nausea and vomiting, headache and dizziness.Conclusion: This study reported a high pooled efficacy for all ACTs. AL and DHAP were found to have higher cumulative efficacies than ASAQ. The ACTs are still efficacious and well tolerated for the treatment of malaria in Cameroon. However, there is need for continuous monitoring of efficacy of ACTs despite the high cure rates as resistance seems inevitable.

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Comparative study of the efficacy and tolerability of dihydroartemisinin - piperaquine - trimethoprim versus artemether - lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal

Cited by 25 publications

References 14 publications

Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso

Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso

New approaches in antimalarial drug discovery and development: a review

Clinical Efficacy and Safety of Artemisinin-based Combination Therapies in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Cameroon: A Systematic Review and Meta-Analysis from Individual Patient Data (2004-2020)

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