High therapeutic efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Somalia

Warsame, Marian; Hassan, Abdillahi Mohamed; Hassan, Abdikarim Hussein; Jibril, Ali Mohamed; Khim, Nimol; Arale, Abdulkadir Mohamed; Gomey, Ahamed Hassan; Nur, Zainab Said; Osman, Said Mohamed; Mohamed, Marian Said; Ali, Abid; Yusuf, Fahmi; Amran, Jamal Ghilan Hefzullah; Witkowski, Benoît; Ringwald, Pascal

doi:10.1186/s12936-019-2864-1

Cited by 27 publications

(29 citation statements)

References 46 publications

(46 reference statements)

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“…This mutation was previously reported in the same locale in 2016 but at a lower frequency (19). This mutant has been recorded imported cases to China between 2016 to 2018 (27), along with isolates from Eritrea (28), and Somalia (29). Our data clearly demonstrates an increase of this mutant in northwest Ethiopia, although no association with in vivo artemisinin resistance could be established.…”

Section: Discussionsupporting

confidence: 69%

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Expansion of the Plasmodium falciparum Kelch 13 R622I mutation in Northwest Ethiopia

Alemayehu

Castañeda-Mogollón

Tesfa

et al. 2021

Preprint

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According to the WHO, almost two thirds of the Ethiopian population are at risk of contracting malaria, where infection with Plasmodium falciparum accounts for approximately 60% of cases today. The risk of artemisinin resistance spreading from SE Asia to Africa is a major concern. We conducted a 28-day in vivo efficacy trial of Artemether-Lumefantrine (Co-Artem) for treatment of uncomplicated malaria (n = 97) in the Gondar Region, North West Ethiopia in 2017–2018. Our results confirmed 100% adequate clinical and parasitological response (ACPR) with no parasites observed at day 3 by microscopy. Further analysis of day 0 samples showed the expansion of a kelch13 mutation R622I to 9.5% from 2.4% of isolates reported three years earlier. Closer examination of the R622I mutation in vitro is warranted.

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Section: Discussionsupporting

confidence: 69%

“…This mutant has been recorded by Chinese imported cases between 2016 to 2018 (27), along with isolates from Eritrea (28), and Somalia (29). Capillary sequencing was performed bidirectionally across all the isolates.…”

Section: Resultsmentioning

confidence: 99%

Expansion of the Plasmodium falciparum Kelch 13 R622I mutation in Northwest Ethiopia

Alemayehu

Castañeda-Mogollón

Tesfa

et al. 2021

Preprint

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“…The observed high efficacy of DHA–PQ was similar to that of other studies conducted in Africa [ 43 , 44 ] and a high transmission setting in Indonesia [ 45 ]. However, in a study done in Somalia, the recurrence of parasitaemia was lower in DHA–PQ as compared to AL arm [ 46 ] and after day 3, in both treatment groups none of the participants were parasitaemic. However, Pfk13 non-synonymous mutations (R622I) with unknown impact on the parasite resistance phenotype have been seen at a very low rate.…”

Section: Discussionmentioning

confidence: 98%

Efficacy and safety of dihydroartemisinin–piperaquine versus artemether–lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ugandan children: a systematic review and meta-analysis of randomized control trials

Assefa

Zeleke

Bekele

et al. 2021

Malar J

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Background The emergence of artemisinin resistance in Southeast Asia and Plasmodium falciparum kelch13 propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria. This is a critical concern in Uganda, where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum. The objective of this study was to compare the efficacy and safety of dihydroartemisinin–piperaquine (DHA–PQ) and artemether–lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Ugandan children. Methods A search of PubMed and the Cochrane Central Register of Controlled Trials for retrieving randomized controlled trials comparing the efficacy and safety of DHA–PQ and AL for treatment of uncomplicated falciparum malaria in Ugandan children was done. The search was performed up to 31 August 2020. The data extracted from eligible studies and pooled as risk ratio (RR) with a 95% confidence interval (CI), using Rev Man Software (5.4). The protocol was registered in PROSPERO, ID: CRD42020182354. Results Eleven trials were included in this review and two of them only included under safety outcome. Total 3798 participants were enrolled. The PCR unadjusted treatment failure was significantly lower with DHA–PQ at day 28 (RR 0.30, 95% CI 0.19–0.49; participants = 7863; studies = 5; I2 = 93%, low quality evidence) and at day 42 (RR 0.53, 95% CI 0.38–0.76; participants = 1618; studies = 4; I2 = 79%, moderate quality of evidence). The PCR adjusted treatment failure at day 42 was significantly lower with DHA–PQ treatment group (RR 0.45, 95% CI 0.28 to 0.72; participants = 1370; studies = 5, high quality of evidence), and it was below 5% in both arms at day 28 (moderate quality of evidence). AL showed a longer prophylactic effect on new infections which may last for up to 63 days (PCR-adjusted treatment failure: RR 2.04, 95% CI 1.13–3.70; participants = 1311; studies = 2, moderate quality of evidence). Compared to AL, DHA–PQ was associated with a slightly higher frequency of cough (RR 1.07, 95% CI 1.01 to 1.13; 2575 participants; six studies; high quality of evidence). In both treatment groups, the risk of recurrent parasitaemia due to possible recrudescence was less than 5% at day 28. The appearance of gametocyte between 29 and 42 days was also significantly lower in DHA–PQ than AL (RR 0.26, 95% CI 0.12 to 0.56; participants = 623; studies = 2; I2 = 0%). Conclusion Compared to AL, DHA–PQ appeared to reduce treatment failure and gametocyte carriage in Ugandan children. This may trigger DHA–PQ to become the first-line treatment option. Both treatments were safe and well-tolerated.

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“…As a result of widespread increasing reports of SP efficacy being compromised in Kenya especially at the coast [32,34], prompted another policy change in the treatment of malaria by introducing Coartem TM, an artemether-lumefantrine in government hospitals in the year 2006. A number of studies have observe that artemisinin-based combination therapy (ACT) is still efficacious for the treatment of uncomplicated falciparum malaria especially in Africa, and is the recommended antimalarial drug for the treatment of uncomplicated malaria caused by P. falciparum [10,[34][35]. However, as with other drugs, the curative effect of ACT has declined gradually along with its use within vivo P. falciparum susceptibility studies showing reduction over time [36].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade of its use in Kenya

Kishoyian

Njagi

Orinda

et al. 2020

Preprint

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Background: Plasmodium falciparum resistance to antimalarial drugs remains to be a major threat to the control of malaria globally. After the deployment of artemisinin-based combination therapy (ACT), there have been reports of reduced sensitivity of the drug to parasite clearance. In Kenya, artemisinin-lumefantrine (AL) is the recommended first-line drug in the treatment of uncomplicated malaria. This study sought to assess the efficacy of AL after its reintroduction in Kenya, a decade later. In this study, we assessed clinical and parasitological responses of children under five years in May and November 2015 in Chulaimbo sub-County, Kisumu, Kenya.Method: Patients of ≥6 and ≤60 months of age with confirmed Plasmodium falciparum mono-infection were enrolled in the study. The patients were treated with a standard dose of AL and followed up for 28 days. During which period we monitored treatment responses and follow-up adherence.Results: Of the 90 patients enrolled, fourteen (14) were lost to follow-up, with 76 completing the study period. Seventy-five patients 75 (98.7%) cleared, parasitemia within 48 hours while one (1.3%) cleared on day 3. There was 100% clinical and parasitological parasite clearance. Conclusion: Artemisinin lumefantrine was found to be highly efficacious to plasmodium falciparum parasites in children aged ≥6 and ≤60 months. Based on this, the drug can be used to treat uncomplicated malaria in the study population. However, there is need for continued monitoring of its effectiveness in children and adults to counter the threat of resistance.

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High therapeutic efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Somalia

Cited by 27 publications

References 46 publications

Expansion of the Plasmodium falciparum Kelch 13 R622I mutation in Northwest Ethiopia

Expansion of the Plasmodium falciparum Kelch 13 R622I mutation in Northwest Ethiopia

Efficacy and safety of dihydroartemisinin–piperaquine versus artemether–lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ugandan children: a systematic review and meta-analysis of randomized control trials

Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade of its use in Kenya

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