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Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial.

ABSTRACT: BACKGROUND AND OBJECTIVE:Prior small-scale clinical trials showed that Artemisia annua and Artemisia afra infusions, decoctions, capsules, or tablets were low cost, easy to use, and efficient in curing malaria infections. In a larger-scale trial in Kalima district, Democratic Republic of Congo, we aimed to show A. annua and/or A. afra infusions were superior or at least equivalent to artesunate-amodiaquine (ASAQ) against malaria. METHODS:A double blind, randomized clinical trial with 957 malaria-infected patients had two treatment arms: 472 patients for ASAQ and 471 for Artemisia (248 A. annua, 223 A. afra) remained at end of the trial. ASAQ-treated patients were treated per manufacturer posology, and Artemisia-treated patients received 1?l/d of dry leaf/twig infusions for 7 d; both arms had 28 d follow-up. Parasitemia and gametocytes were measured microscopically with results statistically compared among arms for age and gender. RESULTS:Artemisinin content of A. afra was negligible, but therapeutic responses of patients were similar to A. annua-treated patients; trophozoites cleared after 24? h, but took up to 14 d to clear in ASAQ-treated patients. D28 cure rates defined as absence of parasitemia were for pediatrics 82, 91, and 50% for A. afra, A. annua and ASAQ; while for adults cure rates were 91, 100, and 30%, respectively. Fever clearance took 48 ?h for ASAQ, but 24 ?h for Artemisia. From D14-28 no Artemisia-treated patients had microscopically detectable gametocytes, while 10 ASAQ-treated patients remained gametocyte carriers at D28. More females than males were gametocyte carriers in the ASAQ arm but were unaffected in the Artemisia arms. Hemoglobin remained constant at 11?g/dl for A. afra after D1, while for A. annua and ASAQ it decreased to 9-9.5? g/dl. Only 5.0% of Artemisia-treated patients reported adverse effects, vs. 42.8% for ASAQ. CONCLUSION:A. annua and A. afra infusions are polytherapies with better outcomes than ASAQ against malaria. In contrast to ASAQ, both Artemisias appeared to break the cycle of malaria by eliminating gametocytes. This study merits further investigation for possible inclusion of Artemisia tea infusions as an alternative for fighting and eradicating malaria.

SUBMITTER: Munyangi J

PROVIDER: S-EPMC6990969 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial.

Munyangi Jérôme J Cornet-Vernet Lucile L Idumbo Michel M Lu Chen C Lutgen Pierre P Perronne Christian C Ngombe Nadège N Bianga Jacques J Mupenda Bavon B Lalukala Paul P Mergeai Guy G Mumba Dieudonné D Towler Melissa M Weathers Pamela P

Phytomedicine : international journal of phytotherapy and phytopharmacology 20181205

<h4>Background and objective</h4>Prior small-scale clinical trials showed that Artemisia annua and Artemisia afra infusions, decoctions, capsules, or tablets were low cost, easy to use, and efficient in curing malaria infections. In a larger-scale trial in Kalima district, Democratic Republic of Congo, we aimed to show A. annua and/or A. afra infusions were superior or at least equivalent to artesunate-amodiaquine (ASAQ) against malaria.<h4>Methods</h4>A double blind, randomized clinical trial w ...[more]

PMID: 30668322

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Project description:Background and objectiveSchistosomiasis (bilharzia), a serious neglected tropical disease affecting millions, has few cost-effective treatments, so two Artemisia wormwood species, A. annua and A. afra, were compared with the current standard praziquantel (PZQ) treatment in an 800 patient clinical trial, August-November of 2015.MethodsThe double blind, randomized, superiority clinical trial had three treatment arms: 400 for PZQ, 200 for A. annua, and 200 for A. afra. PZQ-treated patients followed manufacturer posology. Artemisia-treated patients received 1 l/d of dry leaf/twig tea infusions divided into 3 aliquots daily, for 7 days with 28-day follow-up.ResultsOf 800 enrolled patients having an average of >700 Schistosoma mansoni eggs per fecal sample, 780 completed the trial. Within 14 days of treatment, all Artemisia-treated patients had no detectable eggs in fecal smears, a result sustained 28 days post treatment. Eggs in fecal smears of PZQ-treated patients were undetectable after D21. More males than females who entered the trial had melena, but both genders responded equally well to treatment; by D28 melena disappeared in all patients. In all arms, eosinophil levels declined by about 27% from D0 to D28. From D0 to D28 hemoglobin increases were greater in PZQ and A. afra-treated patients than in A. annua-treated patients. Hematocrit increases were greater from D0 to D28 for patients treated with either PZQ or A. annua compared to those treated with A. afra. Gender comparison showed that A. afra-treated males had significantly greater hemoglobin and hematocrit increases by D28 than either PZQ or A. annua-treated males. In contrast, PZQ and A. afra-treated females had greater hemoglobin and hematocrit increases than A. annua-treated females. Both adults and pediatric patients treated with A. annua responded better compared to PZQ treatment.ConclusionBoth A. annua and A. afra provided faster effective treatment of schistosomiasis and should be considered for implementation on a global scale.

Project description:Ethnopharmacological relevanceEmergence of drug-resistant and multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is a major barrier to tuberculosis (TB) eradication, as it leads to longer treatment regimens and in many cases treatment failure. Thus, there is an urgent need to explore new TB drugs and combinations, in order to shorten TB treatment and improve outcomes. Here, we evaluated the potential of two Asian and African traditional medicinal plants, Artemisia annua, a natural source of artemisinin (AN), and Artemisia afra, as sources of novel antitubercular agents.Aim of the studyOur goal was to measure the activity of A. annua and A. afra extracts against Mtb as potential natural and inexpensive therapies for TB treatment, or as sources of compounds that could be further developed into effective treatments.Materials and methodsThe minimum inhibitory concentrations (MICs) of A. annua and A. afra dichloromethane extracts were determined, and concentrations above the MICs were used to evaluate their ability to kill Mtb and Mycobacterium abscessus in vitro.ResultsPrevious studies showed that A. annua and A. afra inhibit Mtb growth. Here, we show for the first time that Artemisia extracts have a strong bactericidal activity against Mtb. The killing effect of A. annua was much stronger than equivalent concentrations of pure AN, suggesting that A. annua extracts kill Mtb through a combination of AN and additional compounds. A. afra, which produces very little AN, displayed bactericidal activity against Mtb that was substantial but weaker than that of A. annua. In addition, we measured the activity of Artemisia extracts against Mycobacterium abscessus. Interestingly, we observed that while A. annua is not bactericidal, it inhibits growth of M. abscessus, highlighting the potential of this plant in combinatory therapies to treat M. abscessus infections.ConclusionOur results indicate that Artemisia extracts have an enormous potential for treatment of TB and M. abscessus infections, and that these plants contain bactericidal compounds in addition to AN. Combination of extracts with existing antibiotics may not only improve treatment outcomes but also reduce the emergence of resistance to other drugs.

Project description:BackgroundPharmacokinetic (PK) and pharmacodynamic (PD) data are limited for artesunate (AS) and amodiaquine (AQ) in uncomplicated Plasmodium falciparum.MethodsFrom 2007-8, 54 P. falciparum-infected, Kenyan adults were assigned randomly fixed dose (FD) ASAQ (n?=?26) or non-fixed (NF) ASAQ (n?=?28). Total doses were 600 mg AS (both arms) + 1,620 mg (FD) or 1,836 mg (NF)AQ. Follow-up extended over 28 days. PK data were collected for AS, dihydroartemisinin (DHA), AS + DHA combined as DHA equivalents (DHAeq), AQ, desethylamodiaquine (DAQ),and their relationships assessed against the PD collected data consisting of parasitological efficacy, adverse events (AEs), and the Bazett's corrected QTinterval (QTcB).ResultsMean AUC 0-72 of dihydroartemisinin equivalents (DHAeq) when administered as a fixed dose (FD) compared to NF dose were similar: 24.2 ±4.6 vs 26.4±6.9 µmol*h/L (p?=?0.68) Parasite clearance rates were also similar after 24 hrs: 17/25 (68%) vs 18/28(64.3%) (p?=?0.86),as well as at 48 hrs: 25/8 (100%)vs 26 (92.9%)/28 (p?=?0.49). Mean FD vs NF DAQ AUC0-28 were 27.6±3.19 vs 32.7±5.53 mg*h/L (p?=?0.0005). Two PCR-proven new infections occurred on Day (D) 28 for estimated, in vivo, DAQ minimum inhibitory concentrations of 15.2 and 27.5 ng/mL. Combining the FD and NF arms, the mean QTcB at D2+4 hrs increased significantly (p?=?0.0059) vs baseline: 420 vs410 ms (??=?9.02 (95% confidence interval 2.72-15.31 ms), explained by falling heart rates, increasing DAQ concentrations and female sex in a general linear mixed effects model. Ten of 108 (9.26%) AEs (5/arm) reported by 37/54 (68.5%) patients were possibly or probably drug related. Severe, asymptomatic neutropaenia developed in 2/47 (4.25%) patients on D28: 574/µL (vsD0: 5,075/µL), and 777/µL (vsD0: 3,778/µL).ConclusionsTolerability of both formulations was good. For QTcB, a parameter for ECG modifications, increases were modest and due to rising DAQ concentrations and falling heart rates as malaria resolved. Rapid parasite clearance rates and no resistant infections suggest effective pharmacokinetics of both formulations.

Project description:BackgroundSince 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance.MethodsChildren aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000-100,000 parasites/µl determined by microscopy were enrolled from May-September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted.ResultsOf 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100-100) and 95% (95% CI 91-100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97-100) in Ankazomborona and 83% (95% CI 76-92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100-100) and 98% (95% CI 95-100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99-100) in Ankazomborona and 95% (95% CI 91-100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72-76.ConclusionPCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.

Dataset Information

Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial.

Publications

Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial.

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