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Trends and predictive factors for treatment failure following artemisinin-based combination therapy among children with uncomplicated malaria in Ghana: 2005-2018

December 23, 2021 - 10:02 -- Open Access
Abuaku B, Duah-Quashie NO, Quashie N, Gyasi A, Afriyie PO, Owusu-Antwi F, Ghansah A, Malm KL, Bart-Plange C, Koram KA
BMC Infect Dis. 2021 Dec 15;21(1):1255

Since the introduction of artemisinin-based combination therapy (ACT) in Ghana in 2005 there has been a surveillance system by the National Malaria Control Programme (NMCP) and the University of Ghana Noguchi Memorial Institute for Medical Research (UG-NMIMR) to monitor the therapeutic efficacy of ACTs for the treatment of uncomplicated malaria in the country. We report trends and determinants of failure following treatment of Ghanaian children with artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) combinations.

Triple artemisinin-based combination therapies for malaria: proceed with caution

December 23, 2021 - 09:58 -- Open Access
Wang J, Xu C, Wong YK, Ma N, Liao FL, Jiang T, Tu Y
Lancet. 2021 Dec 19;396(10267):1976

Artemisinin-based combination therapies (ACTs) serve as the front-line treatment against malaria. Substantial evidence indicates that treatment failure of the 3-day ACT course in the Greater Mekong subregion (southeast Asia) is strongly linked to partner drug failure rather than artemisinin itself.

Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum

December 17, 2021 - 21:24 -- Open Access
Afolabi Owoloye, Michael Olufemi, Emmanuel T. Idowu and Kolapo M. Oyebola
Malaria Journal 2021 20:451, 2 December 2021

The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance.

The Artemiside-Artemisox-Artemisone-M1 Tetrad: Efficacies against Blood Stage P. falciparum Parasites, DMPK Properties, and the Case for Artemiside

December 14, 2021 - 20:20 -- Open Access
Gibhard L, Coertzen D, Reader J, Van der Watt ME, Birkholtz L, Wong HN, Batty KT, Haynes RK, Wiesner L
Pharmaceutics 2021, 13(12), 2066

Because of the need to replace the current clinical artemisinins in artemisinin combination therapies, we are evaluating fitness of amino-artemisinins for this purpose. These include the thiomorpholine derivative artemiside obtained in one scalable synthetic step from dihydroartemisinin (DHA) and the derived sulfone artemisone. We have recently shown that artemiside undergoes facile metabolism via the sulfoxide artemisox into artemisone and thence into the unsaturated metabolite M1; DHA is not a metabolite.

Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites

December 11, 2021 - 21:47 -- Open Access
Ashraf K, Tajeri S, Mazier D, et al.
Life Sci Alliance. 2021 Dec 2;5(3):e202101237

Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions from Artemisia annua (from which artemisinin is obtained) or Artemisia afra (lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance.

NOT Open Access | Derivatives of Dictyostelium differentiation-inducing factors suppress the growth of Plasmodium parasites in vitro and in vivo

December 11, 2021 - 21:45 -- NOT Open Access
Mita T, Hirai M, Maki Y, Nahar S, Yoshida N, Oshima Y, Kikuchi H, Kubohara Y
Biochem Pharmacol. 2021 Dec;194:114834

Malaria, which is caused by protozoa of the genus Plasmodium, remains a major endemic public health problem worldwide. Since artemisinin combination therapies are used as a first-line treatment in all endemic regions, the emergence of parasites resistant to these regimens has become a serious problem. Differentiation-inducing factor 1 (DIF-1) is a chlorinated alkylphenone originally found in the cellular slime mold Dictyostelium discoideum.

NOT Open Access | The pharmacokinetic properties of the antimalarial combination therapy artemether-lumefantrine in normal weight, overweight and obese healthy male adults

December 4, 2021 - 20:40 -- NOT Open Access
Sugiarto SR, Page-Sharp M, Drinkwater JJ, Davis WA, Salman S, Davis TME
Int J Antimicrob Agents. 2021 Nov 21:106482

The component drugs in the widely-used antimalarial artemisinin combination therapy artemether-lumefantrine are lipophilic, with the possibility that recommended fixed doses in adults may lead to sub-therapeutic concentrations and consequent treatment failure in overweight/obese individuals with malaria. The aim of this study was to investigate the pharmacokinetic properties of artemether, lumefantrine and their active metabolites dihydroartemisinin and desbutyl-lumefantrine in 16 normal-weight, overweight or obese healthy male volunteers (body mass index [BMI] categories ≤25 kg/m², >25 to ≤30 kg/m², and >30 kg/m², respectively; absolute range 19.3 to 37.2 kg/m²).

Our Exciting Journey to ACT-451840

December 1, 2021 - 19:47 -- Open Access
Boss C, Wittlin S
Chimia (Aarau). 2021 Nov 24;75(11):916-922

We describe our work resulting in the selection of ACT-451840 ( 38 ) as a novel antimalarial drug with a novel mode of action. The compound was broadly characterized in vitro as well as in vivo in rat PK experiments as well as two different mouse malaria models.

Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria

November 20, 2021 - 14:24 -- Open Access
Moses Ikegbunam, Johnson A. Ojo, Kossiwa Kokou, Ugonna Morikwe, Chukwuemeka Nworu, Chibuzo Uba, Charles Esimone, Thirumalaisamy P. Velavan and Olusola Ojurongbe
Malaria Journal 2021 20:434, 10 November 2021

The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Regular surveillance is necessary to make a definite conclusion on the emergence and pattern of possible resistance to ART.


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