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International Journal of Gynaecology... Jul 2019Intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) is recommended for preventing maternal and fetal effects of malaria in pregnancy. Increasing... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) is recommended for preventing maternal and fetal effects of malaria in pregnancy. Increasing parasite resistance to SP has necessitated the search for an alternative medication.
OBJECTIVE
To compare dihydroartemisinin-piperaquine (DP) and sulphadoxine-pyrimethamine in preventing malaria during pregnancy.
SEARCH STRATEGY
Databases including CENTRAL, MEDLINE, and ICTRP were searched until August 2018.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials that compared DP with SP given to pregnant women to prevent adverse maternal or fetal effects of malaria were included.
DATA COLLECTION AND ANALYSIS
Quality of evidence was determined with GRADE criteria. Effectiveness measures were calculated using odds ratios at 95% confidence intervals.
RESULTS
Three randomized controlled trials were included. Compared with IPT-SP, moderate certainty evidence indicated that women who received IPT-DP had significantly lower risks of clinical malaria during pregnancy. High certainty evidence showed intermittent screening and treatment with DP did not reduce placental malaria or maternal parasitemia at delivery. Effect of DP on low birth weight and adverse birth outcomes was minimal.
CONCLUSIONS
Moderate certainty evidence suggests that IPT-DP may reduce maternal and placental malaria compared with IPT-SP, and monthly DP is more effective than SP in reducing placental malaria.
PROSPERO ID
CRD42018084651.
Topics: Adult; Female; Humans; Pregnancy; Antimalarials; Artemisinins; Drug Combinations; Drug Therapy, Combination; Malaria; Parasitemia; Pregnancy Complications, Parasitic; Prenatal Care; Pyrimethamine; Quinolines; Randomized Controlled Trials as Topic; Sulfadoxine
PubMed: 31050803
DOI: 10.1002/ijgo.12835 -
BMC Medicine Nov 2018Several quinoline and structurally related antimalarial drugs are associated with cardiovascular side effects, particularly hypotension and electrocardiographic QT...
BACKGROUND
Several quinoline and structurally related antimalarial drugs are associated with cardiovascular side effects, particularly hypotension and electrocardiographic QT interval prolongation. A prolonged QT interval is a sensitive but not specific risk marker for the development of Torsade de Pointes-a potentially lethal polymorphic ventricular tachyarrhythmia. The increasing use of quinoline and structurally related antimalarials in mass treatments to eliminate malaria rapidly highlights the need to review their cardiovascular safety profiles.
METHODS
The primary objective of this systematic review was to describe the documented clinical and electrocardiographic cardiovascular side effects of quinine, mefloquine, lumefantrine, piperaquine, halofantrine, chloroquine, sulfadoxine-pyrimethamine, amodiaquine, and primaquine. Trials in healthy subjects or patients with Plasmodium falciparum or P. vivax infection were included if at least two ECGs were conducted during the trial. All trial designs were included except case reports and pooled analyses. Secondary outcomes were the methods adopted by trials for measuring and reporting the QT interval.
RESULTS
Data from trials published between 1982 and July 2016 were included. A total of 177 trials met the inclusion criteria. 35,448 participants received quinoline antimalarials in these trials, of which 18,436 participants underwent ECG evaluation. Subjects with co-medication use or comorbidities including cardiovascular disease were excluded from the majority of trials. Dihydroartemisinin-piperaquine was the drug most studied (5083 participants). Despite enormous use over the past 60 years, only 1076, 452, and 150 patients had ECG recordings reported in studies of chloroquine, amodiaquine, and primaquine respectively. Transiently high concentrations of quinine, quinidine, and chloroquine following parenteral administration have all been associated with hypotension, but there were no documented reports of death or syncope attributable to a cardiovascular cause, nor of electrocardiographic recordings of ventricular arrhythmia in these trials. The large volume of missing outcome information and the heterogeneity of ECG interval reporting and measurement methodology did not allow pooled quantitative analysis of QT interval changes.
CONCLUSIONS
No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation. While these findings provide further evidence of the rarity of serious cardiovascular events after treatment with these drugs, they also underscore the need for continued strengthening of pharmacovigilance systems for robust detection of rare drug adverse events in real-world populations. A standardised approach to measurement and reporting of ECG data in malaria trials is also needed.
TRIAL REGISTRATION
PROSPERO CRD42016036678.
Topics: Adult; Antimalarials; Cardiotoxicity; Female; Humans; Malaria, Falciparum; Male; Quinolines; Young Adult
PubMed: 30400791
DOI: 10.1186/s12916-018-1188-2 -
International Journal of Gynaecology... May 2013Malaria in pregnancy is a significant contributor to adverse pregnancy outcome, especially in Sub-Saharan Africa. Prevention with sulfadoxine/pyrimethamine (SP) during... (Review)
Review
BACKGROUND
Malaria in pregnancy is a significant contributor to adverse pregnancy outcome, especially in Sub-Saharan Africa. Prevention with sulfadoxine/pyrimethamine (SP) during pregnancy has been recommended in malaria-endemic areas but concerns remain about its benefit.
OBJECTIVES
To evaluate the association between recommended preventative SP programs in pregnancy and low birth weight (LBW) and maternal anemia through available clinical trial, observational, and programmatic evaluation studies.
SEARCH STRATEGY
Systematic review of published studies on malaria in pregnancy and pregnancy outcomes.
SELECTION CRITERIA
Clinical studies from Sub-Saharan Africa from the past 10 years were included.
DATA COLLECTION AND ANALYSIS
English articles published since 2002 and listed in PubMed were identified using defined keywords, and their source documents were reviewed. Thirty-three studies involving malaria in pregnancy that recorded treatment rates and birth outcomes were included.
MAIN RESULTS
SP use among primigravidae was consistently associated with decreased LBW and anemia rates in clinical trials. Effects were less consistent in observational studies.
CONCLUSIONS
Although randomized trials have demonstrated the efficacy of SP, studies evaluating scale-up programs found less consistent reductions in LBW and maternal anemia. Additional strategies to improve SP coverage may reduce the LBW and maternal anemia associated with malaria in pregnancy.
Topics: Africa South of the Sahara; Anemia; Antimalarials; Drug Combinations; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Malaria; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pyrimethamine; Sulfadoxine
PubMed: 23490427
DOI: 10.1016/j.ijgo.2012.12.014 -
Frontiers in Pharmacology 2021The WHO recommends Artemisinin-based combination therapy (ACTs) as the first-line treatment for malaria. This meta-analysis aims to analyze the effects of artemisinin... (Review)
Review
The Effect of Artemisinin-Based Drugs vs Non-artemisinin-based Drugs on Gametophyte Carrying in the Body After the Treatment of Uncomplicated Falciparum Malaria: A Systematic Review and Meta-analysis.
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, < 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, < 0.05); there was no significant difference in treatment failure during follow-up (RD = -0.01, 95%CI: 0.04-0.03, < 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.
PubMed: 35069184
DOI: 10.3389/fphar.2021.707498 -
Malaria Journal Mar 2018Malaria is a major public health problem in endemic countries including Sudan, where about 75% of populations are at risk. Due to widespread of chloroquine-resistant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria is a major public health problem in endemic countries including Sudan, where about 75% of populations are at risk. Due to widespread of chloroquine-resistant strains of Plasmodium falciparum, artemisinin-based combination therapy (ACT) is currently treatment of choice for malaria in the vast majority of malaria-endemic countries. This systematic review and meta-analysis is performed to obtain an overall stronger evidence of the outcomes of ACT in the treatment of uncomplicated falciparum malaria from the existing literature in Sudan.
METHODS
The preferred reporting items for systematic review and meta-analysis statement were used to select studies to be included in this review. A computerized systematic strategy was adopted to search articles from PubMed, Google Scholar and Science Direct databases. Unpublished materials were also included. Open Meta-Analyst software was used to perform the meta-analysis. Random effects model was used to combine the included studies and the heterogeneity of studies was assessed using Cochrane Q and I (χ = 73.05, df (19), P < 0.001 and I = 73.99).
RESULTS
Twenty studies fulfilled the inclusion criteria (ACT in the treatment of uncomplicated falciparum malaria) and were included in the final analysis with a total number of 4070 participants. Malaria treatment outcome was assessed using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Treatment success of all combined studies was 98% [(95% CI 97.2-98.8%), P < 0.001]. Treatment success was higher in malaria patients treated with artemether + lumefantrine (AL) than patients treated with artesunate + sulfadoxine-pyrimethamine (AS + SP) (98.9% (95% CI 98.4-99.4%) vs 97.1% (95% CI 95.5-98.6%), P < 0.001). Eleven studies reported adverse drug reactions (ADRs) to ACT (184 participants out of 3957 (4.65%). The ADRs were mild and resolved spontaneously. There was no severe ADRs or deaths.
CONCLUSION
Based on this review, the overall malaria treatment success was high (98%). AL regimen showed higher efficacy compared to AS + SP. The overall regimens were associated with mild low rates ADRs.
Topics: Antimalarials; Artemisinins; Drug Therapy, Combination; Humans; Malaria, Falciparum; Sudan
PubMed: 29534720
DOI: 10.1186/s12936-018-2265-x -
Infection and Drug Resistance 2022The use of poor quality drugs will have multiple consequences with an extended hazard of growing drug-resistant strains. (Review)
Review
BACKGROUND
The use of poor quality drugs will have multiple consequences with an extended hazard of growing drug-resistant strains.
PURPOSE
The review aimed to provide the quality status of antimalarial drugs in East Africa.
DATA SOURCE
PubMed, Scopus, Web of Science, and Google Scholar were searched from September 5 to September 12, 2021.
STUDY SELECTION
The review included articles available as original research targeted at evaluating the quality of antimalarial drugs. For inclusion, data on at least one of the following quality control parameters were required: packaging and labeling, hardness, friability, weight variation/uniformity of weight, disintegration, dissolution, and assay/percentage purity. Mendeley citation manager version 1.19.4 was used to avoid duplication and organize references, and titles and abstracts were primarily used for screening.
DATA EXTRACTION
The sample collection site, drug name, and the quality control parameters tested were retrieved from the selected studies.
DATA SYNTHESIS
Totally, 300 antimalarial drug samples from Ethiopia, Kenya and Tanzania were included in this review. No antimalarial drug tested failed the identification and disintegration test. However, 15.93% (36/226), 5.00% (15/300), and 1.90% (3/158) of antimalarial samples failed the dissolution, assay and mass uniformity test, respectively. Moreover, amodiaquine and sulfadoxine/pyrimethamine samples failed dissolution and assay tests. In addition, amodiaquine samples failed the mass uniformity test. However, artemether/lumefantrine and quinine passed all quality control parameters tested. Overall, 19.67% (59/300) of antimalarial drug samples did not meet at least one quality control parameter. And the higher faller rate was reported for sulfadoxine/pyrimethamine accounting for 52.86% (37/70).
CONCLUSIONS
An unneglected amount of antimalarial drug failed to meet at least one quality control parameter. Strengthening pharmaceutical management systems, including post-marketing surveillance, and providing the resources required for medication quality assurance, are recommended.
PubMed: 36277242
DOI: 10.2147/IDR.S373059 -
Expert Review of Anti-infective Therapy Dec 2013The WHO recommends the administration of sulfadoxine-pyrimethamine (SP) to all pregnant women living in areas of moderate (stable) to high malaria transmission during... (Review)
Review
The WHO recommends the administration of sulfadoxine-pyrimethamine (SP) to all pregnant women living in areas of moderate (stable) to high malaria transmission during scheduled antenatal visits, beginning in the second trimester and continuing to delivery. Malaria parasites have lost sensitivity to SP in many endemic areas, prompting the investigation of alternatives that include azithromycin-based combination (ABC) therapies. Use of ABC therapies may also confer protection against curable sexually transmitted infections and reproductive tract infections (STIs/RTIs). The magnitude of protection at the population level would depend on the efficacy of the azithromycin-based regimen used and the underlying prevalence of curable STIs/RTIs among pregnant women who receive preventive treatment. This systematic review summarizes the efficacy data of azithromycin against curable STIs/RTIs.
Topics: Adult; Anti-Bacterial Agents; Azithromycin; Clinical Trials as Topic; Drug Combinations; Drug Resistance, Bacterial; Female; Humans; Malaria, Falciparum; Male; Pregnancy; Pregnancy Outcome; Pyrimethamine; Reproductive Tract Infections; Sexually Transmitted Diseases; Sulfadoxine; Treatment Outcome; Vaginosis, Bacterial
PubMed: 24191955
DOI: 10.1586/14787210.2013.851601 -
Tropical Medicine & International... Sep 2014Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa.
METHODS
We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses.
RESULTS
Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire.
CONCLUSIONS
Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.
Topics: Africa South of the Sahara; Antimalarials; Child; Drug Combinations; Drug Resistance; HIV Infections; Humans; Malaria; Mutation; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 25039469
DOI: 10.1111/tmi.12352 -
The Cochrane Database of Systematic... 2003Artemether-lumefantrine is being recommended by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority... (Review)
Review
BACKGROUND
Artemether-lumefantrine is being recommended by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens.
OBJECTIVES
To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group specialized trials register (February 2003), the Cochrane Controlled Trials Register (Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to February 2003), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine.
SELECTION CRITERIA
Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination).
DATA COLLECTION AND ANALYSIS
Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies.
MAIN RESULTS
Six trials (1698 participants) tested a four dose regimen. Failure rates for artemether-lumefantrine tended to be higher (comparisons included sulfadoxine-pyrimethamine, halofantrine, and mefloquine; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. Two trials (419 participants) tested a six dose regimen against mefloquine plus artesunate. Artemether-lumefantrine was associated with higher failure rates but the studies were small.
REVIEWER'S CONCLUSIONS
The four dose regimen of artemether-lumefantrine seems to be less effective than most other current antimalarial regimens. The six dose regimen is largely untested.
Topics: Antimalarials; Artemether; Artemisinins; Drug Combinations; Ethanolamines; Fluorenes; Humans; Lumefantrine; Malaria, Falciparum; Randomized Controlled Trials as Topic; Sesquiterpenes
PubMed: 12804451
DOI: 10.1002/14651858.CD003125 -
The Cochrane Database of Systematic... 2002Artemether-lumefantrine is being promoted by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority... (Review)
Review
BACKGROUND
Artemether-lumefantrine is being promoted by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens.
OBJECTIVES
To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group specialized trials register (April 2002), the Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (1966 to April 2002), EMBASE (1988 to April 2002), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine.
SELECTION CRITERIA
Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination).
DATA COLLECTION AND ANALYSIS
Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies.
MAIN RESULTS
Eight trials (2117 participants) met the inclusion criteria. In the four studies against single agents, failure rates for artemether-lumefantrine tended to be higher in comparisons against sulfadoxine-pyrimethamine, halofantrine, and mefloquine. This difference was statistically significant for mefloquine. When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. All single agent studies used four doses of artemether-lumefantrine. In comparisons against combination treatment, three trials tested artemether-lumefantrine against mefloquine-artesunate and showed that artemether-lumefantrine was inferior for day 28 cure (Relative Risk 6.33, 95% confidence interval 3.08 to 13.01). If this comparison is confined to the two trials where participants received six doses, artemether-lumefantrine was associated with higher cure rates, but this was not statistically significant (Relative Risk 4.20, 95% confidence interval 0.55 to 31.93).
REVIEWER'S CONCLUSIONS
Artemether-lumefantrine is more effective than chloroquine in chloroquine resistant areas. Artemether-lumefantrine is less effective than mefloquine or mefloquine combined with artesunate. We found no evidence to confirm or refute whether artemether-lumefantrine was better than sulfadoxine-pyrimethamine.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Drug Combinations; Ethanolamines; Fluorenes; Humans; Malaria, Falciparum; Randomized Controlled Trials as Topic; Sesquiterpenes
PubMed: 12137676
DOI: 10.1002/14651858.CD003125