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Malaria Journal Feb 2014Control of malaria in pregnant women is still a major challenge as it constitutes an important cause of maternal and neonatal mortality. Mefloquine (MQ) has been used... (Review)
Review
BACKGROUND
Control of malaria in pregnant women is still a major challenge as it constitutes an important cause of maternal and neonatal mortality. Mefloquine (MQ) has been used for malaria chemoprophylaxis in non-immune travellers for several decades and it constitutes a potential candidate for intermittent preventive treatment in pregnant women (IPTp).
METHODS
The safety of MQ, including its safety in pregnancy, is controversial and a continuing subject of debate. Published studies which evaluated the use of MQ for malaria prevention or treatment in pregnant women and which reported data on drug tolerability and/or pregnancy outcomes have been reviewed systematically.
RESULTS
Eighteen articles fitted the inclusion criteria, only one study was double-blind and placebo controlled. No differences were found in the risk of adverse pregnancy outcomes in women exposed to MQ compared to those exposed to other anti-malarials or to the general population. MQ combined with artesunate seems to be better tolerated than standard quinine therapy for treatment of non-severe falciparum malaria, but a MQ loading dose (10 mg/kg) is associated with more dizziness compared with placebo. When used for IPTp, MQ (15 mg/kg) may have more side effects than sulphadoxine- pyrimethamine.
CONCLUSIONS
In the published literature there are no indications that MQ use during pregnancy carries an increased risk for the foetus. Ideally, the use of MQ to prevent malaria should be based on a risk-benefit analysis of adverse effects against the risk of acquiring the infection. For this purpose double-blinded randomized controlled trials in African pregnant women are much needed.
Topics: Antimalarials; Chemoprevention; Female; Humans; Malaria; Mefloquine; Pregnancy; Pregnancy Complications, Infectious
PubMed: 24581338
DOI: 10.1186/1475-2875-13-75 -
International Journal For Parasitology.... Apr 2021Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at... (Review)
Review
Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.
Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at presenting the current scenario of drug resistance molecular markers, either selected or involved in treatment failures (TF) during in vivo ACT efficacy studies from sub-Saharan Africa (sSA) and India. Eight electronic databases were comprehensively used to search relevant articles and finally a total of 28 studies were included in the review, 21 from sSA and seven from India. On analysis, Artemether + lumefantrine (AL) and artesunate + sulfadoxine-pyrimethamine (AS + SP) are the main ACT in African and Indian regions with a 28-day efficacy range of 54.3-100% for AL and 63-100% for AS + SP respectively. It was observed that mutations in the Pfcrt (76T), Pfdhfr (51I, 59R, 108N), Pfdhps (437G) and Pfmdr1 (86Y, 184F, 1246Y) genes were involved in TF, which varied with respect to ACTs. Based on studies that have genotyped the Pfk13 gene, the reported TF cases, were mainly linked with mutations in genes associated with resistance to ACT partner drugs; indicating that the protection of the partner drug efficacy is crucial for maintaining the efficacy of ACT. This review reveals that ACT are largely efficacious in India and sSA despite the fact that some clinical efficacy and epidemiological studies have reported some validated mutations (i.e., 476I, 539T and 561H) in circulation in these two regions. Also, the role of PfATPase6 in ART resistance is controversial still, while P. falciparum plasmepsin 2 (Pfpm2) in piperaquine (PPQ) resistance and dihydroartemisinin (DHA) + PPQ failures is well documented in Southeast Asian countries but studied less in sSA. Hence, there is a need for continuous molecular surveillance of Pfk13 mutations for emergence of artemisinin (ART) resistance in these countries.
Topics: Africa South of the Sahara; Antimalarials; Artemisinins; Drug Resistance; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum
PubMed: 33556786
DOI: 10.1016/j.ijpddr.2020.11.006 -
The Cochrane Database of Systematic... Oct 2005The World Health Organization recommends artemether-lumefantrine for treating uncomplicated malaria. We sought evidence of superiority of the six-dose regimen over... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The World Health Organization recommends artemether-lumefantrine for treating uncomplicated malaria. We sought evidence of superiority of the six-dose regimen over existing treatment regimens as well as its effectiveness in clinical situations.
OBJECTIVES
To evaluate the six-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine.
SELECTION CRITERIA
Randomized controlled trials comparing six doses of artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination), or supervised with unsupervised treatment, for uncomplicated falciparum malaria.
DATA COLLECTION AND ANALYSIS
Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome.
MAIN RESULTS
Nine trials (4547 participants) tested the six-dose regimen. Total failure at day 28 for artemether-lumefantrine was lower when compared with amodiaquine (270 participants, 1 trial), amodiaquine plus sulfadoxine-pyrimethamine (507 participants, 1 trial), but not with chloroquine plus sulfadoxine-pyrimethamine (201 participants, 2 trials). In comparisons with artemisinin derivative combinations, artemether-lumefantrine performed better than amodiaquine plus artesunate (668 participants, 2 trials), worse than mefloquine plus artesunate (270 participants, 4 trials), and no differently to dihydroartemisinin-napthoquine-trimethoprim (89 participants, 1 trial).
AUTHORS' CONCLUSIONS
The six-dose regimen of artemether-lumefantrine appears more effective than antimalarial regimens not containing artemisinin derivatives.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Drug Combinations; Ethanolamines; Fluorenes; Humans; Malaria, Falciparum; Randomized Controlled Trials as Topic; Sesquiterpenes
PubMed: 16235412
DOI: 10.1002/14651858.CD005564 -
Malaria Journal May 2009An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by Plasmodium falciparum. The purpose of this systematic review was to determine the risk of treatment failure associated with specific polymorphisms in the parasite genome or gene copy number.
METHODS
Clinical studies of non-severe malaria reporting on target genetic markers (SNPs for pfmdr1, pfcrt, dhfr, dhps, gene copy number for pfmdr1) providing complete information on inclusion criteria, outcome, follow up and genotyping, were included. Three investigators independently extracted data from articles. Results were stratified by gene, codon, drug and duration of follow-up. For each study and aggregate data the random effect odds ratio (OR) with 95%CIs was estimated and presented as Forest plots. An OR with a lower 95th confidence interval > 1 was considered consistent with a failure being associated to a given gene mutation.
RESULTS
92 studies were eligible among the selection from computerized search, with information on pfcrt (25/159 studies), pfmdr1 (29/236 studies), dhfr (18/373 studies), dhps (20/195 studies). The risk of therapeutic failure after chloroquine was increased by the presence of pfcrt K76T (Day 28, OR = 7.2 [95%CI: 4.5-11.5]), pfmdr1 N86Y was associated with both chloroquine (Day 28, OR = 1.8 [95%CI: 1.3-2.4]) and amodiaquine failures (OR = 5.4 [95%CI: 2.6-11.3, p < 0.001]). For sulphadoxine-pyrimethamine the dhfr single (S108N) (Day 28, OR = 3.5 [95%CI: 1.9-6.3]) and triple mutants (S108N, N51I, C59R) (Day 28, OR = 3.1 [95%CI: 2.0-4.9]) and dhfr-dhps quintuple mutants (Day 28, OR = 5.2 [95%CI: 3.2-8.8]) also increased the risk of treatment failure. Increased pfmdr1 copy number was correlated with treatment failure following mefloquine (OR = 8.6 [95%CI: 3.3-22.9]).
CONCLUSION
When applying the selection procedure for comparative analysis, few studies fulfilled all inclusion criteria compared to the large number of papers identified, but heterogeneity was limited. Genetic molecular markers were related to an increased risk of therapeutic failure. Guidelines are discussed and a checklist for further studies is proposed.
Topics: Animals; Antimalarials; Drug Resistance; Gene Dosage; Genes, Protozoan; Genetic Markers; Humans; Malaria, Falciparum; Plasmodium falciparum; Polymorphism, Genetic; Treatment Failure
PubMed: 19413906
DOI: 10.1186/1475-2875-8-89 -
The Cochrane Database of Systematic... Oct 2008Women are more vulnerable to malaria during pregnancy, and malaria infection may have adverse consequences for the fetus. Identifying safe and effective treatments is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Women are more vulnerable to malaria during pregnancy, and malaria infection may have adverse consequences for the fetus. Identifying safe and effective treatments is important.
OBJECTIVES
To compare the effects of drug regimens for treating uncomplicated falciparum malaria in pregnant women.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (February 2008), CENTRAL (The Cochrane Library 2008, Issue 1), MEDLINE (1966 to February 2008), EMBASE (1974 to February 2008), LILACS (February 2008), mRCT (February 2008), reference lists, and conference abstracts. We also contacted researchers in the field, organizations, and pharmaceutical companies.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials of antimalarial drugs for treating uncomplicated malaria in pregnant women.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial eligibility and risk of bias, and extracted data. We performed a quantitative analysis only where we could combine the data. We combined dichotomous data using the risk ratio (RR) and presented each result with a 95% confidence interval (CI).
MAIN RESULTS
Ten trials (1805 participants) met the inclusion criteria. Two were quasi-randomized, seven did not describe allocation concealment, and all adjusted treatment failure to exclude new infections. One trial reported fewer treatment failures at day 63 with artesunate plus mefloquine compared with quinine (RR 0.09, 95% CI 0.02 to 0.38; 106 participants). One trial reported fewer treatment failures at day 63 with artesunate plus atovaquone-proguanil compared with quinine (RR 0.14, 95% CI 0.03 to 0.57; 80 participants). One trial reported fewer treatment failures at day 28 when amodiaquine was compared with chloroquine (RR 0.20, 95% CI 0.08 to 0.46; 420 participants) and when amodiaquine plus sulfadoxine-pyrimethamine was compared with chloroquine (RR 0.02, 95% CI 0.00 to 0.26; 418 participants). Compared with sulfadoxine-pyrimethamine given alone, one trial reported fewer treatment failures at delivery (or day 40) with artesunate plus sulfadoxine-pyrimethamine (RR 0.15, 95% CI 0.04 to 0.59; 79 participants) and azithromycin plus sulfadoxine-pyrimethamine (RR 0.27, 95% CI 0.10 to 0.76; 82 participants).
AUTHORS' CONCLUSIONS
Data are scant. Some combination treatments appear to be effective at treating malaria in pregnancy; however, safety data are limited.
Topics: Antimalarials; Female; Humans; Malaria; Mefloquine; Pregnancy; Pregnancy Complications, Parasitic; Randomized Controlled Trials as Topic; Stillbirth
PubMed: 18843672
DOI: 10.1002/14651858.CD004912.pub3 -
Malaria Journal Jan 2014Increasing access to and targeting of artemisinin-based combination therapy (ACT) is a key component of malaria control programmes. To maximize efficacy of ACT and... (Review)
Review
BACKGROUND
Increasing access to and targeting of artemisinin-based combination therapy (ACT) is a key component of malaria control programmes. To maximize efficacy of ACT and ensure adequate treatment outcomes, patient and caregiver adherence to treatment guidelines is essential. This review summarizes the current evidence base on ACT adherence, including definitions, measurement methods, and associated factors.
METHODS
A systematic search of the published literature was undertaken in November 2012 and updated in April 2013. Bibliographies of manuscripts were also searched and additional references identified. Studies were included if they involved at least one form of ACT and reported an adherence measurement.
RESULTS
The search yielded 1,412 records, 37 of which were found to measure adherence to ACT. Methods to measure adherence focused on self-report, pill counts and bioassays with varying definitions for adherence. Most studies only reported whether medication regimens were completed, but did not assess how the treatment was taken by the patient (i.e. timing, frequency and dose). Adherence data were available for four different ACT formulations: artemether-lumefantrine (AL) (range 39-100%), amodiaquine plus artesunate (AQ + AS) (range 48-94%), artesunate plus sulphadoxine-pyrimethamine (AS + SP) (range 39-75%) and artesunate plus mefloquine (AS + MQ) (range 77-95%). Association between demographic factors, such as age, gender, education and socio-economic status and adherence to ACT regimens was not consistent. Some evidence of positive association between adherence and patient age, caregiver education levels, drug preferences, health worker instructions, patient/caregiver knowledge and drug packaging were also observed.
CONCLUSIONS
This review highlights the weak evidence base on ACT adherence. Results suggest that ACT adherence levels varied substantially between study populations, but comparison between studies was challenging due to differences in study design, definitions, and methods used to measure adherence. Standardising methodologies for both self-report and bioassays used for evaluating adherence of different formulations across diverse contexts would improve the evidence base on ACT adherence and effectiveness; namely, specific and measurable definitions for adherence are needed for both methodologies. Additionally, further studies of the individual factors and barriers associated with non-adherence to ACT are needed in order to make informed policy choices and to improve the delivery of effective malaria treatment.
Topics: Antimalarials; Artemisinins; Drug Combinations; Drug Therapy, Combination; Humans; Malaria; Medication Adherence
PubMed: 24386988
DOI: 10.1186/1475-2875-13-7 -
The Cochrane Database of Systematic... Oct 2011Intermittent preventive treatment is recommended for pregnant women living in malaria endemic countries due to benefits for both mother and baby. However, the impact may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intermittent preventive treatment is recommended for pregnant women living in malaria endemic countries due to benefits for both mother and baby. However, the impact may not be the same in HIV-positive pregnant women, as HIV infection impairs a woman's immunity.
OBJECTIVES
To compare intermittent preventive treatment regimens for malaria in HIV-positive pregnant women living in malaria-endemic areas.
SEARCH STRATEGY
In June 2011, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE; EMBASE; LILACS, the metaRegister of Controlled Trials (mRCT), reference lists and conference abstracts. We also contacted researchers and organizations for information on relevant trials.
SELECTION CRITERIA
Randomized controlled trials comparing different intermittent preventive treatment regimens for preventing malaria in HIV-positive pregnant women in malaria-endemic areas.
DATA COLLECTION AND ANALYSIS
Two authors extracted data and assessed risk bias. Dichotomous variables were combined using risk ratios (RR) and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI).
MAIN RESULTS
Two randomized trials with 722 HIV-positive pregnant women were included, comparing monthly regimens of sulfadoxine-pyrimethamine (SP) to the standard 2-dose regimen in the second and third trimesters. There were no statistically significant differences between monthly SP and 2-dose SP in rates of maternal anaemia, low birth weight, and neonatal mortality. In primigravidae and secondigravidiae, the monthly regimen was associated with less placental parasitaemia (RR 0.38, 95% CI 0.21 to 0.70, two trials) and less peripheral parasitaemia (RR 0.25, 95% CI 0.14 to 0.43, two trials), but no effect was demonstrated in multigravid women. Babies born to primigravidae and secundigravida women on monthly SP had a higher mean birth weight (weighted mean difference (WMD) 130 g; 95% CI 120 g to 150 g, two trials) than babies born to mothers on 2-dose SP. Multigravidae women treated with monthly SP had significant higher haemoglobin level than those treated with treated 2 dose SP (WMD 0.21 g/dL, 95% CI 0.15 g/dL to 0.27 g/dL, one trial). There were no trials that assessed other treatment regimens for intermittent preventive treatment in HIV-positive pregnant women.
AUTHORS' CONCLUSIONS
Three or more doses of SP is superior to the standard two doses in HIV-positive pregnant women. However, since SP cannot be administered concurrently with co-trimoxazole - a drug often recommended for infection prophylaxis in HIV-positive pregnant women, new drugs and research is needed to address needs of HIV-positive pregnant women.
Topics: Antimalarials; Drug Combinations; Female; HIV Seropositivity; Humans; Malaria; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadoxine
PubMed: 21975756
DOI: 10.1002/14651858.CD006689.pub2 -
Malaria Journal May 2012Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive... (Comparative Study)
Comparative Study Review
Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL) in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the WHO recommendation to treat uncomplicated falciparum malaria with quinine plus clindamycin in early pregnancy and ACT in later pregnancy.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Quinine; Sulfadoxine; Treatment Outcome
PubMed: 22548983
DOI: 10.1186/1475-2875-11-141 -
The Cochrane Database of Systematic... Mar 2016Malaria causes ill health and death in Africa. Treating illness promptly with artemisinin-based combination therapy (ACT) is likely to cure people and avoid the disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malaria causes ill health and death in Africa. Treating illness promptly with artemisinin-based combination therapy (ACT) is likely to cure people and avoid the disease progressing to more severe forms and death. In many countries, ACT use remains low. Part of the problem is that most people seek treatment from the retail sector where ACTs are expensive; this expense is a barrier to their use.The Global Fund and other international organisations are subsidising the cost of ACTs for private retail providers to improve access to ACTs. The subsidy was initially organised through a stand-alone initiative, called the Affordable Medicines Facility-malaria (AMFm), but has since been integrated into the Global Fund core grant management and financial processes.
OBJECTIVES
To assess the effect of programmes that include ACT price subsidies for private retailers on ACT use, availability, price and market share.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1, The Cochrane Library, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EbscoHost), EconLit (ProQuest), Global Health (OvidSP), Regional Indexes (Global Health Library, WHO), LILACS (Global Health Library, WHO), Science Citation Index and Social Sciences Citation Index (ISI Web of Science) and Health Management (ProQuest). All databases were searched February 2015, except for Health Management which was searched November 2013, without any date, language or publication status restrictions. We also searched the International Clinical Trials Registry Platform (ICTRP; WHO), ClinicalTrials.gov (NIH) and various grey literature sources. We also conducted a cited reference search for all included studies in ISI Web of Knowledge, checked references of identified articles and contacted authors to identify additional studies.
SELECTION CRITERIA
Randomised trials, non-randomised trials, controlled before-after studies and interrupted-time-series studies that compared the effects of ACT price subsidies for private retailers to no subsidies or alternative ACT financing mechanisms were eligible for inclusion. Two authors independently screened and selected studies for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed study risk of bias and confidence in effect estimates (certainty of evidence) using Grading of Recommendations, Assessment, Development and Evaluation (GRADE).
MAIN RESULTS
We included four trials (two cluster-randomised trials reported in three articles and two non-randomised cluster trials). Three trials assessed retail sector ACT subsidies combined with supportive interventions (retail outlet provider training, community awareness and mass media campaigns). One trial assessed vouchers provided to households to purchase subsidised ACTs. Price subsidies ranged from 80% to 95%. One trial enrolled children under five years of age; the other three trials studied people of all age groups. The studies were done in rural districts in East Africa (Kenya, Uganda and Tanzania).In this East Africa setting, these ACT subsidy programmes increased the percentage of children under five years of age receiving ACTs on the day, or following day, of fever onset by 25 percentage points (95% confidence interval (CI) 14.1 to 35.9 percentage points; 1 study, high certainty evidence). This suggests that in practice, among febrile children under five years of age with an ACT usage rate of 5% without a subsidy, subsidy programmes would increase usage by between 19% and 41% over a one year period.The ACT subsidy programmes increased the percentage of retail outlets stocking ACTs for children under five years of age by 31.9 percentage points (95% CI 26.3 to 37.5 percentage points; 1 study, high certainty evidence). Effects on ACT stocking for patients of any age is unknown because the certainty of evidence was very low.The ACT subsidy programmes decreased the median cost of ACTs for children under five years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence).The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence).The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence).None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria.Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence).
AUTHORS' CONCLUSIONS
Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health.
Topics: Africa, Eastern; Antimalarials; Artemisinins; Child, Preschool; Drug Costs; Financial Support; Humans; Infant; Malaria; Private Sector; Program Evaluation; Randomized Controlled Trials as Topic
PubMed: 26954551
DOI: 10.1002/14651858.CD009926.pub2 -
The Cochrane Database of Systematic... Jan 2006Artemisinin-based combination treatments are strongly advocated, but supplies are limited. Sulfadoxine combined with amodiaquine is an alternative non-artemisinin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Artemisinin-based combination treatments are strongly advocated, but supplies are limited. Sulfadoxine combined with amodiaquine is an alternative non-artemisinin combination.
OBJECTIVES
To compare sulfadoxine-pyrimethamine plus amodiaquine (SP plus AQ) with sulfadoxine-pyrimethamine plus artesunate (SP plus AS) for treating uncomplicated Plasmodium falciparum malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to October 2005), EMBASE (1988 to October 2005), LILACS (October 2005), and reference lists. We also contacted researchers and organizations working in this field.
SELECTION CRITERIA
Randomized controlled trials comparing SP plus AS with SP plus AQ for treating uncomplicated P. falciparum malaria.
DATA COLLECTION AND ANALYSIS
Two authors independently applied the inclusion criteria, extracted data, and assessed methodological quality. The primary outcome measure was treatment failure (parasitological or clinical evidence of treatment failure between start of treatment and day 28). We calculated the relative risk (RR) with 95% confidence intervals (CI) for dichotomous data.
MAIN RESULTS
Four trials (775 participants) met the inclusion criteria. All were from areas of high and seasonal malaria transmission in Africa. Fewer participants using SP plus AQ failed treatment by day 28 (RR 0.59, 95% CI 0.42 to 0.83; 652 participants, 3 trials). Even excluding new infections, SP plus AQ performed better (RR 0.62, 95% CI 0.40 to 0.96; 649 participants, 3 trials). There was no statistically significant difference between the two treatments for treatment failure at day 14 (RR 1.14, 95% CI 0.47 to 2.78; 775 participants, 4 trials). SP plus AS was more effective at reducing gametocyte carriage at day seven (RR 2.31, 95% CI 1.36 to 3.92; 220 participants, 1 trial). One trial reported that one person - in the SP plus AQ group - developed severe malaria. Adverse events were poorly reported, but did not seem to differ in type and number between the two treatment combinations.
AUTHORS' CONCLUSIONS
SP plus AQ performed better at controlling treatment failure at day 28, but was not as good as SP plus AS at reducing gametocyte carriage at day seven. Careful consideration of local resistance patterns is required because resistance to sulfadoxine-pyrimethamine and amodiaquine are high in many areas. In order to delay development of resistance to artesunate, the combination with sulfadoxine-pyrimethamine should only be considered where both drugs are known to be effective. Data on adverse events are still lacking.
Topics: Amodiaquine; Artemisinins; Artesunate; Drug Combinations; Drug Therapy, Combination; Humans; Malaria, Falciparum; Pyrimethamine; Randomized Controlled Trials as Topic; Sesquiterpenes; Sulfadoxine
PubMed: 16437507
DOI: 10.1002/14651858.CD004966.pub2