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We conducted a study on the Trobriand Islands of Papua New Guinea (PNG) in 2018 to verify the safety and efficacy of the artemisinin-piperaquine (AP) mass drug administration (MDA) campaign in regions with moderate to high mixed malaria transmission. Based on the natural topography of the Trobriand Islands, 44,855 residents from 92 villages on the islands were enrolled and divided into the main and outer islands. Three rounds of MDA were conducted using grid-based management. The primary endpoint was the coverage rate. Adverse reactions, parasitemia, and malaria morbidity were the secondary endpoints. There were 36,716 people living in 75 villages on the main island, and the MDA coverage rate was 92.58-95.68%. Furthermore, 8,139 people living in 17 villages on the outer islands had a coverage rate of 94.93-96.11%. The adverse reactions were mild in both groups, and parasitemia decreased by 87.2% after one year of surveillance. The average annual malaria morbidity has decreased by 89.3% after the program for four years. High compliance and mild adverse reactions indicated that the MDA campaign with AP was safe. The short-term effect is relatively ideal, but the evidence for long-term effect evaluation is insufficient.
RESUMO
The WHO recommends Artemisinin-based combination therapy (ACTs) as the first-line treatment for malaria. This meta-analysis aims to analyze the effects of artemisinin and its derivatives as well as non-artemisinin drugs on the gametophytes in the host during the treatment of falciparum malaria. Fourteen studies were included in this analysis, and the artemisinin combination drugs involved were: artemether-lumefantrine (AL), artemisinin (AST), artemether-benflumetol (AB), dihydroartemisinin-piperaquine + trimethoprim + primaquine (CV8), amodiaquine + sulfadoxine-pyrimethamine (ASP), pyronaridine-phosphate + dihydroartemisinin (PP-DHA), dihydroartemisinin (DHA), and mefloquine + artesunate (MA), with 1702 patients. The control intervention measures involved the following: sulfadoxine-pyrimethamine (SP), mefloquine (MQ), atovaquone-proguanil (AT-PG), chloroquine + sulfadoxine-pyrimethamine (C-SP), quinine (Q), pyronaridine-phosphate (PP), pyronaridine (PN), and mefloquine + primaquine (MP), with 833 patients. The effect of ACTs was more obvious (OR = 0.37, 95%CI: 0.22-0.62, p < 0.05). In the control group of second malaria attacks, the difference between the two groups was not statistically significant (RD = 1.16, 95%CI: 0.81-1.66, p < 0.05); there was no significant difference in treatment failure during follow-up (RD = -0.01, 95%CI: 0.04-0.03, p < 0.05). There were also very few serious adverse events in both groups. ACTs showed good therapeutic effects in preventing gametocythemia but did not control the recrudescence rate and overall cure, which indicated the effectiveness of the combination of antimalarial drugs. Further research is required to explore which compatibility method is most conducive to the development of clinical malaria control.
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Objective: The purpose of this meta-analysis of longitudinal studies is to determine the safety and efficacy of artesunate combined with other forms of adjunctive therapies for severe malaria. Methods: Following the PRISMA guidelines, we searched multiple databases with the search terms "artesunate" and "adjunctive therapy" and "severe malaria" in July 2020. If the search showed a randomized controlled trial, the study was included in this meta-analysis. The random-effects model was used to calculate the combined incidence rate and relative risk or risk difference. Results: This meta-analysis included nine longitudinal studies with 724 participants. We found that the mortality rates in the artesunate monotherapy group and the artesunate + adjuvant therapy group are similar (RD = -0.02, 95% confidence interval: -0.06-0.02). The incidence of adverse reactions in the artesunate monotherapy group and the artesunate + adjuvant therapy group was also similar. Conclusion: No significant differences in safety and efficacy were observed between the artesunate monotherapy group and the artesunate + adjuvant therapy group. Higher quality and rigorously designed randomized controlled studies are needed to validate our findings.
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OBJECTIVE: The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria to improve the therapeutic efficacy and limit the choice of drug-resistant parasites. This systematic review and meta-analysis aimed to evaluate the comparative efficacy and safety of artemisinin-piperaquine (AP) in the treatment of uncomplicated malaria relative to other commonly used ACTs. METHODS: As per the PRISMA guidelines, the EMBASE, MEDLINE, the Google Scholar Library, and Cochrane library databases were systematically searched from inception until July 2020 with the following terms: "artemisinin-piperaquine" or "AP." Only randomized controlled trials (RCTs) were included. The competing interventions included dihydroartemisinin-piperaquine (DHA-PPQ), artemether-lumefantrine (AL, Coartem), artesunate-melfloquine (ASAM) and artesunate-amodiaquine (ASAQ, Artekin). Single-arm clinical trial on AP was also assessed. The reported outcomes, including the overall response, cure rate, fever and parasite clearance time, hematology, biochemistry, electrocardiogram (ECG), adverse events, recurrence rate, and sensitivity analyses, were systematically investigated. All data were analyzed using the Review Manager 5.3. RESULTS: A total of seven studies were reviewed, including five RCTs and two single-arm studies. A pooled analysis of 5 RCTs (n = 772) revealed a comparable efficacy on polymerase chain reaction (PCR)-confirmed cure rate between AP and competing interventions in treating uncomplicated malaria. As for the fever and parasite clearance time, due to the lack of complete data in some studies, only 3 studies' data could be used. The patients showed good tolerance to all drugs, and some side-effects (such as headache, anoxia, vomiting, nausea, and dizziness) were reported for every group, but they were self-limited and showed no significant difference. CONCLUSIONS: AP appeared to show similar efficacy and safety, with a simpler mode of administration and easier compliance when compared with other ACTs used in the treatment of uncomplicated malaria. Considering that the potential evolution of drug resistance is of a great concern, additional RCTs with high-quality and more rigorous design are warranted to substantiate the efficacy and safety in different populations and epidemiological regions.
RESUMO
BACKGROUND: Malaria is a major public health concern in Togo. The Est-Mono district of Togo has a population of 150,000. Accordingly, the Guangzhou University of Chinese Medicine, China and the Ministry of Health and Social Security, Togo launched a nationwide Mass Drug Administration Project with artemisinin-piperaquine (AP) in Est-Mono. Before launching this project, the sensitivity test of AP was conducted in a general clinic in Elawagnon, Togo. With this background, we evaluated the efficacy and safety of AP for the treatment of uncomplicated falciparum malaria in children under the age of 5 years. METHODS: Children aged 6-59 months with uncomplicated falciparum malaria were enrolled in this study. The selected patients were treated with a combination regime of artemisinin-piperaquine. The patients were followed up for 28 days, during which signs of the following were observed for: the duration for fever clearance, parasitemia density, gametophyte generation, cure rate, hemoglobin level, and merozoite surface protein-2 (msp-2) polymorphism. The primary end point was a 28-day cure rate and polymerase chain reaction (PCR)-corrected reinfection and recrudescence. This research followed the standardized World Health Organization (WHO) protocol for the assessment of the efficacy of antimalarial drugs. RESULTS: A total of 91 children with uncomplicated falciparum malaria were enrolled in this study. Adequate clinical and parasitological responses (ACPRs) before and after PCR-correction were 66 (73%) and 90 (99%), respectively. The average hemoglobin level in the patient increased by 0.05 g/dl per day (p < 0.0001) after the treatment. The gametophyte generation did not decline at the beginning of the treatment; however, after 14 days, it declined (day 21: p < 0.05; day 28: p < 0.01). In the msp-2 polymorphism study of 24 children treated for parasite infection, one case of msp-2 with 3D7 haplotype and FC27 haplotype was noted, indicating its recrudescence, with a frequency of 4%. The remaining 23 cases could have been of reinfection, with a frequency of 96%. No serious adverse reactions occurred, and AP was well-tolerated by all patients. CONCLUSION: Artemisinin-piperaquine was found to be an effective combination for treating uncomplicated falciparum malaria in children aged <5 years in Togo, and the drugs were well-tolerated. In Togo, Plasmodium falciparum remains sensitive to artemisinin-piperaquine, necessitating its trial in this region. CLINICAL TRIAL REGISTRATION: Trial registration: ECGPHCM No. B2017-054-01; MHSST AVIS N° 0001/2016/CBRS du 07 janvier 2016. Registered 17 March 2014, http://www.chinadrugtrials.org.cn/eap/main.
