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Restructured Mitochondrial-Nuclear Interaction in Plasmodium falciparum Dormancy and Persister Survival after Artemisinin Exposure

June 1, 2021 - 15:38 -- Open Access
Connelly SV, Manzella-Lapeira J, Levine ZC, Brzostowski J, Krymskaya L, Rahman RS, Ellis AC, Amin SN, Sá JM, Wellems TE
mBio. 2021 May 28:e0075321

Artemisinin and its semisynthetic derivatives (ART) are fast acting, potent antimalarials; however, their use in malaria treatment is frequently confounded by recrudescences from bloodstream Plasmodium parasites that enter into and later reactivate from a dormant persister state. Here, we provide evidence that the mitochondria of dihydroartemisinin (DHA)-exposed persisters are dramatically altered and enlarged relative to the mitochondria of young, actively replicating ring forms. Restructured mitochondrial-nuclear associations and an altered metabolic state are consistent with stress from reactive oxygen species.

Not Open Access | Dihydroartemisinin alleviates skin fibrosis and endothelial dysfunction in bleomycin-induced skin fibrosis models

May 25, 2021 - 14:59 -- NOT Open Access
Li R, Yin H, Wang J, He D, Yan Q, Lu L
Clin Rheumatol. 2021 May 19

The present study was to investigate whether dihydroartemisinin (DHA), which is a highly effective and safe drug in the treatment of malaria, could be repurposed for the treatment of skin fibrosis and vascular dysfunction in systemic sclerosis (SSc).

NOT Open Access | In Vitro Susceptibility of Plasmodium falciparum Isolates from the China-Myanmar Border Area to Piperaquine and Association with Candidate Markers

March 13, 2021 - 16:31 -- NOT Open Access
Si Y, Zeng W, Cui L, et al.
Antimicrob Agents Chemother. 2021 Mar 8:AAC.02305-20

Plasmodium falciparum from the Greater Mekong subregion has evolved resistance to the artemisinin-based combination therapy dihydroartemisinin and the partner drug piperaquine. To monitor the potential westward spread or independent evolution of piperaquine resistance, we evaluated the in vitro susceptibility of 120 P. falciparum isolates collected at the China-Myanmar border during 2007-2016.

Artesunate and Dihydroartemisinin Inhibit Rabies Virus Replication

March 10, 2021 - 13:29 -- Open Access
Luo J, Zhang Y, Wang Y, Liu Q, Li J, He H, Luo Y, Huang S, Guo X
Virol Sin. 2021 Mar 4:1-9

Rabies is caused by infection of rabies virus (RABV) and remains a serious threat to the global public health. Except for the requirement for cold chain and high cost of human rabies immune globulin, no small molecule drugs are currently available for clinical treatment of rabies. So, it is of great importance to identify novel compounds that can effectively inhibit RABV infection. Artesunate (ART) and dihydroartemisinin (DHA), two derivatives of artemisinin, are widely used for treatment of malaria in adults and children, showing high safety. In this study, we found that both ART and DHA were able to inhibit RABV replication in host cells at a low concentration (0.1 μmol/L).

Effect of Body Weight and Age on the Pharmacokinetics of Dihydroartemisinin: FDA Basis for Dose Determination of Artesunate for Injection in Pediatric Patients with Severe Malaria

February 23, 2021 - 12:48 -- Open Access
Kitabi E, Bensman TJ, Earp JC, Chilukuri DM, Smith H, Ball L, O'Shaughnessy E, Yasinskaya Y, Colangelo PM, Reynolds KS
Clin Infect Dis. 2021 Feb 19:ciab149

For treatment of severe malaria, the WHO recommends 3 mg/kg intravenous artesunate in pediatric patients weighing less than 20 kg.

NOT Open Access | Dihydroartemisinin, an active metabolite of artemisinin, interferes with Leishmania braziliensis mitochondrial bioenergetics and survival

January 12, 2021 - 14:55 -- NOT Open Access
Grazzia N, Boaventura S Jr, Garcia VL, Gadelha FR, Miguel DC
Parasitol Res. 2021 Jan 8

Leishmaniasis is one of the most neglected parasitic infections of the world and current therapeutic options show several limitations. In the search for more effective drugs, plant compounds represent a powerful natural source. Artemisinin is a sesquiterpene lactone extracted from Artemisia annua L. leaves, from which dihydroartemisinin (DQHS) and artesunic acid (AA)/artesunate are examples of active derivatives.

NOT Open Access | Predicting the Disposition of the Antimalarial Drug Artesunate and its Active Metabolite Dihydroartemisinin Using Physiologically-Based Pharmacokinetic Modeling

December 29, 2020 - 15:33 -- NOT Open Access
Arey R, Reisfeld B
Antimicrob Agents Chemother. 2020 Dec 23:AAC.02280-20

Artemisinin-based combination therapies (ACTs) have proven to be effective in helping to combat the global malaria epidemic. To optimally apply these drugs, information about their tissue-specific disposition is required, and one approach to predict these pharmacokinetic characteristics is physiologically-based pharmacokinetic (PBPK) modeling. In this study, a whole-body PBPK model was developed to simulate the time-dependent tissue concentrations of artesunate (AS) and its active metabolite, dihydroartemisinin (DHA).

Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial

November 25, 2020 - 12:10 -- Open Access
Dabira ED, Soumare HM, D'Alessandro U, et al.
JMIR Res Protoc. 2020 Nov 19;9(11):e20904

With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission.

NOT Open Access | Artemisinin-type drugs for the treatment of hematological malignancies

November 4, 2020 - 15:11 -- NOT Open Access
Mancuso RI, Foglio MA, Olalla Saad ST
Cancer Chemother Pharmacol. 2020 Nov 3

Qinghaosu, known as artemisinin (ARS), has been for over two millennia, one of the most common herbs prescribed in traditional Chinese medicine (TCM). ARS was developed as an antimalarial drug and currently belongs to the established standard treatments of malaria as a combination therapy worldwide. In addition to the antimalarial bioactivity of ARS, anticancer activities have been shown both in vitro and in vivo.

Artemisinin exposure at the ring or trophozoite stage impacts Plasmodium falciparum sexual conversion differently

October 22, 2020 - 15:52 -- Open Access
Portugaliza HP, Miyazaki S, Geurten FJ, Pell C, Rosanas-Urgell A, Janse CJ, Cortés A
Elife. 2020 Oct 21;9:e60058

Malaria transmission is dependent on the formation of gametocytes in the human blood. The sexual conversion rate, the proportion of asexual parasites that convert into gametocytes at each multiplication cycle, is variable and reflects the relative parasite investment between transmission and maintaining the infection. The impact of environmental factors such as drugs on sexual conversion rates is not well understood.


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