ABSTRACT
Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine.However,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at bay.There is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement.This review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.
ABSTRACT
Background: Resistance of Plasmodium falciparum to antimalarial drugs is common in India. World Health Organization (WHO) recommends artemisinin based combination therapy (ACT) to counter the development of resistance in P. falciparum. WHO recommends that ideally antimalarial drug treatment policy or guidelines should be reviewed regularly and updated at least once every 24 months. In consideration to the above recommendation, we planned to conduct the following study. The objective was to determine the efficacy and safety of artesunate + sulphadoxine pyrimethamine (AS + SP) in patients with uncomplicated P. falciparum malaria. Methods: The study included 60 patients of uncomplicated P. falciparum. Each patient received AS + SP as per WHO guidelines. Diagnosis was confirmed by peripheral blood film. All patients were followed up on days 1, 3, 14, and 28 for detailed clinical and parasitological examination. Results: Of a total 60 patients, 55 patients were followed up for 28 days. Remaining 5 patients were lost in follow up. As per protocol analysis, 91% (50) of patients had demonstrated adequate clinical and parasitological response. Remaining 9% (5) had treatment failure in which 5.5% (3) had late parasitological failure and 3.6% (2) had late clinical failure. In our study, mean parasite clearance time was 45.2 ± 4.2 hrs. Conclusion: AS + SP is safe and effective drug for the treatment of uncomplicated falciparum malaria. However, the efficacy of this ACT needs to be carefully monitored periodically since treatment failure can occur due to resistance.
ABSTRACT
Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.
Subject(s)
Adult , Female , Humans , Middle Aged , Antimalarials/administration & dosage , Artemisinins/administration & dosage , Malaria, Falciparum/drug therapy , Quinine/administration & dosage , Antimalarials/adverse effects , Artemisinins/adverse effects , Drug Resistance , Drug Therapy, Combination/methods , Nigeria , Treatment FailureABSTRACT
Background & objectives: The artemisinin-based antimalarial medicines are first line medicines in the treatment of severe and uncomplicated falciparum malaria. Numerous brands of these medicines manufactured in various countries are available in the Ghanaian market. The study was aimed at evaluating the authenticity and quality of selected brands of artemisinin-based antimalarial medicines marketed in Ghana. Methods: In all, 14 artemisinin-based antimalarial medicines were purchased from pharmacies (P) and licensed chemical shops (LCSs) in the Kumasi metropolis, Ghana. Simple field tests based on colorimetry and thin layer chromatography were employed in determining the authenticity of the samples. Important quality assessment tests, namely uniformity of mass, crushing strength, disintegration time, and the percentage content of active pharmaceutical ingredients (APIs) were determined. Results: All the brands tested contained the stipulated APIs. Artesunate tablet AT2 failed the uniformity of mass test while artesunate tablets AT3 & AT4 as well as amodiaquine tablets AM4 & AM6 failed the crushing strength test. All the six artemether-lumefantrine tablet brands passed the uniformity of mass, crushing strength and disintegration tests. Only artemether-lumefantrine tablet brand AL1 contained the correct amount of the drugs. The other 13 artemisinin products contained either a lower (underdose) or higher (overdose) amount of the specified drug. Artesunate monotherapy tablets were readily available in pharmacies and licensed chemical shops. Interpretation & conclusion: All the artemisinin-based medicines tested (except AL1) were of substandard quality. The results demonstrate the need for continuous monitoring and evaluation of the quality of artemisininbased antimalarials in the Ghanaian market. Also, the practice of artemisinin antimalarial monotherapy is prevalent in Ghana. Determined efforts should, therefore, be made to eradicate the practice to prevent the development of resistance to the artemisinins.
ABSTRACT
Background & objectives: Artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (ACTs). However, ACTs are expensive and some of the non-artemisinin components are not well-tolerated by patients. There are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. Mature leaves of Carica papaya is widely used to treat malaria in several African countries. An ACT involving a medicinal herb extract or its active constituent(s) will provide an indigenous alternative/herbal ACT. Methods: Mature fresh leaves of Carica papaya were grounded and macerated in cold distilled water for 24 h and the extract (PCE) was stored in the refrigerator for seven days. Fresh extracts were made as needed. The antiplasmodial activity of PCE and/or artesunic acid were determined by using the Peter’s 4-day suppressive test in Plasmodium berghei-infected mice. The ED50 and ED90 were calculated from the dose-response relationships. Results: The combination of 50 mg/kg of PCE and 15 mg/kg of artesunic acid produced a significant reduction of parasitemia (81.25%), compared to 50 mg/kg PCE alone (37.7%). The mean survival time of the combinations of PCE and 15 mg/kg of artesunic acid, and PCE alone followed a dose-dependent manner. The ED50 of PCE showed that it has a very good activity. The isobolar equivalent (IE) calculated from the ED90 of PCE in combination with artesunic acid showed that the interaction was antagonistic. Interpretation & conclusion: Although pawpaw alone was found to have a very good activity, its combination with artesunic acid is antagonistic. Combinations of artemisinins and pawpaw show little promise for combination therapy development.
ABSTRACT
Artemisinin-based combination therapy (ACT) is currently promoted as a strategy for treating both uncomplicated and severe falciparum malaria, targeting asexual blood-stage Plasmodium falciparum parasites. However, the effect of ACT on sexual-stage parasites remains controversial. To determine the clearance of sexual-stage P. falciparum parasites from 342 uncomplicated, and 217 severe, adult malaria cases, we reviewed and followed peripheral blood sexualstage parasites for 4 wk after starting ACT. All patients presented with both asexual and sexual stage parasites on admission, and were treated with artesunate-mefloquine as the standard regimen. The results showed that all patients were asymptomatic and negative for asexual forms before discharge from hospital. The percentages of uncomplicated malaria patients positive for gametocytes on days 3, 7, 14, 21, and 28 were 41.5, 13.1, 3.8, 2.0, and 2.0%, while the percentages of gametocyte positive severe malaria patients on days 3, 7, 14, 21, and 28 were 33.6, 8.2, 2.7, 0.9, and 0.9%, respectively. Although all patients were negative for asexual parasites by day 7 after completion of the artesunate-mefloquine course, gametocytemia persisted in some patients. Thus, a gametocytocidal drug, e.g., primaquine, may be useful in combination with an artesunate-mefloquine regimen to clear gametocytes, so blocking transmission more effectively than artesunate alone, in malaria transmission areas.