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Tropical Medicine & International... Dec 2015To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G.
METHODS
We conducted a systematic review and meta-analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp-SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta-regression models to these data and conducted sensitivity analysis of the 581G mutation.
RESULTS
Variation in the protective effect of IPTp-SP against LBW could not be explained by malaria transmission intensity. Among primi- and secundigravidae, IPTp-SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = <0.01] and 581G was >10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.03). Random-effects models among multigravidae showed that IPTp-SP protects against LBW where 581G was ≤10.1% (OR = 0.56; 95% CI: 0.37, 0.86; P = 0.07), a finding of borderline statistical significance. No evidence of protection against LBW was observed where 581G was >10.1% (OR = 0.96; 95% CI: 0.70, 1.34; P = 0.47).
CONCLUSION
There appears to be a prevalence of 581G above which IPTp-SP no longer protects against LBW. Pregnancy studies are urgently needed where 581G is >10.1% to define the specific prevalence threshold where new strategies should be deployed.
Topics: Africa South of the Sahara; Antimalarials; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Female; Gravidity; Humans; Infant, Low Birth Weight; Malaria, Falciparum; Mutation; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine
PubMed: 26325263
DOI: 10.1111/tmi.12595 -
The Cochrane Database of Systematic... Jul 2007Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite... (Review)
Review
BACKGROUND
Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite stages), have been tested in randomized controlled trials in endemic areas.
OBJECTIVES
To assess malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae and P ovale in preventing infection, disease and death.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (April 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to April 2004), Science Citation Index (1981 to April 2004), and reference lists of articles. We also contacted organizations and researchers in the field.
SELECTION CRITERIA
Randomized controlled trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale with placebo or routine antimalarial control measures in people of any age receiving a challenge malaria infection.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data.
MAIN RESULTS
Eighteen efficacy trials involving 10,971 participants were included. There were ten trials of SPf66 vaccine, four trials of CS-NANP vaccines, two trials of RTS,S vaccine, and two of MSP/RESA vaccine. Results with SPf66 in reducing new malaria infections (P. falciparum) were heterogeneous: it was not effective in four African trials (Peto odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81 to 1.14), but in five trials outside Africa the number of first attacks was reduced (Peto OR 0.77, 95% CI 0.67 to 0.88). Trials to date have not indicated any serious adverse events with SPf66 vaccine. In three trials of CS-NANP vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (Peto OR 1.12, 95% CI 0.64 to 1.93). In a small trial in non-immune adults in the USA, RTS,S gave strong protection against experimental infection with P. falciparum. In a trial in an endemic area of the Gambia in semi-immune people, there was a reduction in clinical malaria episodes in the second year of follow up, corresponding to a vaccine efficacy of 66% (CI 14% to 85%). In a trial in Papua New Guinea, MSP/RESA had no protective effect against episodes of clinical malaria. There was evidence of an effect on parasite density, but this differed according to whether the participants had been pretreated with sulfadoxine/pyrimethamine or not. The prevalence of infections with the parasite subtype of MSP2 in the vaccine was reduced compared with the other subtype (Peto OR 0.35, CI 0.23 to 0.53).
AUTHORS' CONCLUSIONS
There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified. There was not enough evidence to evaluate the use of CS-NANP vaccines. The RTS,S vaccine showed promising result, as did the MSP/RESA vaccine, but it should include the other main allelic form of MSP2. The MSP/RESA trial demonstrated that chemotherapy during a vaccine trial may reduce vaccine efficacy, and trials should consider very carefully whether this practice is justified.
Topics: Adult; Antigens, Protozoan; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Protozoan Proteins; Randomized Controlled Trials as Topic; Recombinant Proteins; Vaccines, Synthetic
PubMed: 17636596
DOI: 10.1002/14651858.CD000129.pub2 -
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 -
BMJ Clinical Evidence Oct 2007Malaria is a major health problem in the tropics, with 300-500 million new clinical cases annually, most of them cases of uncomplicated malaria. An estimated 1.1-2.7... (Review)
Review
INTRODUCTION
Malaria is a major health problem in the tropics, with 300-500 million new clinical cases annually, most of them cases of uncomplicated malaria. An estimated 1.1-2.7 million deaths occur annually as a result of severe falciparum malaria. Uncomplicated malaria can progress to severe malaria, become chronic, or resolve, depending on host immunity and prompt access to appropriate treatment.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: Are artemisinin combination treatments more effective than non-artemisinin combination treatments in people living in endemic areas (excluding South East Asia)? Which artemisinin combination treatment is most effective in people living in endemic areas? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, artesunate plus mefloquine, artesunate plus amodiaquine, and artesunate plus sulfadoxine.
Topics: Antimalarials; Drug Therapy, Combination; Ethanolamines; Fluorenes; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum
PubMed: 19450360
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2005Chloroquine (CQ), amodiaquine (AQ), and sulfadoxine-pyrimethamine (SP) are inexpensive drugs, but treatment failure is a problem. Combination therapy may reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chloroquine (CQ), amodiaquine (AQ), and sulfadoxine-pyrimethamine (SP) are inexpensive drugs, but treatment failure is a problem. Combination therapy may reduce treatment failure. CQ or AQ plus SP are affordable options of combination treatment, but there is debate about their effectiveness.
OBJECTIVES
To assess the combination of CQ or AQ plus SP compared with SP alone for first-line treatment of uncomplicated falciparum malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1981 to April 2005), African Index Medicus (1993 to 1998), and reference lists. We also contacted researchers at relevant organizations and a pharmaceutical company.
SELECTION CRITERIA
Randomized controlled trials in adults or children with uncomplicated Plasmodium falciparum malaria were eligible for inclusion. The main outcomes of interest were total and clinical failure at day 28 follow up and serious adverse events.
DATA COLLECTION AND ANALYSIS
Two people independently applied the inclusion criteria. One author extracted data and another checked them independently. We used relative risk (RR) and 95% confidence intervals (CI).
MAIN RESULTS
Twelve trials (2107 participants) met the inclusion criteria. A meta-analysis of five AQ trials (461 participants) showed a statistically significant reduction in total failure at day 28 with the combination therapy (RR 0.64, 95% CI 0.46 to 0.91), and meta-analysis of three trials (384 participants) showed a significant reduction in clinical failure at day 28 (RR 0.23, 95% CI 0.11 to 0.49). The statistical significance in the total failure analysis was sensitive to losses to follow up. Data from two CQ trials showed no advantage for total failure with combination therapy at day 28. There was no evidence from the included trials of serious adverse events.
AUTHORS' CONCLUSIONS
The evidence base is not strong enough to support firm conclusions. The available evidence suggests that AQ plus SP can achieve less treatment failure than SP, but this might depend on existing levels of parasite resistance to the individual drugs.
Topics: Adult; Amodiaquine; Chloroquine; Drug Combinations; Drug Therapy, Combination; Humans; Malaria; Malaria, Falciparum; Pyrimethamine; Sulfadoxine
PubMed: 16235276
DOI: 10.1002/14651858.CD000386.pub2 -
The Cochrane Database of Systematic... Jul 2021Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited.
OBJECTIVES
To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas.
SEARCH METHODS
We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas.
DATA COLLECTION AND ANALYSIS
The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 30% reduction (rate ratio 0.70, 0.62 to 0.80; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.78, 0.69 to 0.88; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence).
AUTHORS' CONCLUSIONS
In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi.
Topics: Africa South of the Sahara; Amodiaquine; Antimalarials; Artemisinins; Bias; Confidence Intervals; Disease Eradication; Drug Combinations; Endemic Diseases; Hospitalization; Humans; Infant; Malaria; Parasitemia; Pyrimethamine; Quinolines; Randomized Controlled Trials as Topic; Sulfadoxine
PubMed: 34273901
DOI: 10.1002/14651858.CD011525.pub3 -
The Lancet. Infectious Diseases Jan 2011After the launch of the National Malaria Control Programme in 1953, the number of malaria cases reported in India fell to an all-time low of 0·1 million in 1965.... (Review)
Review
After the launch of the National Malaria Control Programme in 1953, the number of malaria cases reported in India fell to an all-time low of 0·1 million in 1965. However, the initial success could not be maintained and a resurgence of malaria began in the late 1960s. Resistance of Plasmodium falciparum to chloroquine was first reported in 1973 and increases in antimalarial resistance, along with rapid urbanisation and labour migration, complicated the challenge that India's large geographical area and population size already pose for malaria control. Although several institutions have done drug-resistance monitoring in India, a complete analysis of countrywide data across institutions does not exist. We did a systematic review of P falciparum malaria drug-efficacy studies in India to summarise drug-resistance data and describe changes over the past 30 years to inform future policy. Continued use of chloroquine for treatment of P falciparum malaria in India will likely be ineffective. Resistance to sulfa-pyrimethamine should be closely monitored to protect the effectiveness of treatment with artesunate plus sulfadoxine-pyrimethamine, which is the new first-line treatment for P falciparum malaria. Strategies to reduce the emergence and spread of future drug resistance need to be proactive and supported by intensive monitoring.
Topics: Antimalarials; Artemisinins; Artesunate; Chloroquine; Drug Combinations; Drug Resistance; Geography; Humans; India; Malaria, Falciparum; Plasmodium falciparum; Pyrimethamine; Sulfadoxine; Time Factors; Treatment Outcome
PubMed: 21183147
DOI: 10.1016/S1473-3099(10)70214-0 -
The Cochrane Database of Systematic... Feb 2018The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas. Whether this approach, and at this dose, is effective in reducing transmission is not clear.
OBJECTIVES
To assess the effects of single dose or short-course PQ (or an alternative 8AQ) alongside treatment for people with P. falciparum malaria.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; and the WHO International Clinical Trials Registry Platform (ICRTP) portal using 'malaria*', 'falciparum', 'primaquine', '8-aminoquinoline', and eight 8AQ drug names as search terms. We checked reference lists of included trials, and contacted researchers and organizations. Date of last search: 21 July 2017.
SELECTION CRITERIA
Randomized controlled trials (RCTs) or quasi-RCTs in children or adults, adding PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria.
DATA COLLECTION AND ANALYSIS
Two authors screened abstracts, applied inclusion criteria, and extracted data. We sought evidence on transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures assessed by microscopy or polymerase chain reaction [PCR]). We grouped trials into artemisinin and non-artemisinin treatments, and stratified by PQ dose (low, 0.2 to 0.25 mg/kg; moderate, 0.4 to 0.5 mg/kg; high, 0.75 mg/kg). We used GRADE, and absolute effects of infectiousness using trial control groups.
MAIN RESULTS
We included 24 RCTs and one quasi-RCT, comprising 43 arms. Fourteen trials evaluated artemisinin treatments (23 arms), nine trials evaluated non-artemisinin treatments (13 arms), and two trials included both artemisinin and non-artemisinin arms (three and two arms, respectively). Two trial arms used bulaquine. Seven PQ arms used low dose (six with artemisinin), 11 arms used moderate dose (seven with artemisinin), and the remaining arms used high dose. Fifteen trials tested for G6PD status: 11 excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and three included all, irrespective of status. The remaining 10 trials either did not test or did not report on testing.No cluster trials evaluating community effects on malaria transmission met the inclusion criteria.With artemisinin treatmentLow dose PQInfectiousness (participants infectious to mosquitoes) was reduced (day 3 or 4: RR 0.12, 95% CI 0.02 to 0.88, 3 trials, 105 participants; day 8: RR 0.34, 95% CI 0.07 to 1.58, 4 trials, 243 participants; low certainty evidence). This translates to a reduction in percentage of people infectious on day 3 or 4 from 14% to 2%, and, for day 8, from 4% to 1%; the waning infectiousness in the control group by day 8 making the absolute effect smaller by day 8. For gametocytes detected by PCR, there was little or no effect of PQ at day 3 or 4 (RR 1.02, 95% CI 0.87 to 1.21; 3 trials, 414 participants; moderate certainty evidence); with reduction at day 8 (RR 0.52, 95% CI 0.41 to 0.65; 4 trials, 532 participants; high certainty evidence). Severe haemolysis was infrequent, with or without PQ, in these groups with few G6PD-deficient individuals (RR 0.98, 95% CI 0.69 to 1.39; 4 trials, 752 participants, moderate certainty evidence).Moderate dose PQInfectiousness was reduced (day 3 or 4: RR 0.13, 95% CI 0.02 to 0.94; 3 trials, 109 participants; day 8 RR 0.33, 95% CI 0.07 to 1.57; 4 trials, 246 participants; low certainty evidence). Illustrative risk estimates for moderate dose were the same as low dose. The pattern and level of certainty of evidence with gametocytes detected by PCR was the same as low dose, and severe haemolysis was infrequent in both groups.High dose PQInfectiousness was reduced (day 4: RR 0.2, 95% CI 0.02 to 1.68, 1 trial, 101 participants; day 8: RR 0.18, 95% CI 0.02 to 1.41, 2 trials, 181 participants, low certainty evidence). The effects on gametocyte prevalence showed a similar pattern to moderate and low dose PQ. Trials did not systematically report evidence of haemolysis.With non-artemisinin treatmentTrials with non-artemisinin treatment have been conducted only for moderate and high dose PQ. With high dose, infectiousness appeared markedly reduced on day 5 (RR 0.09, 95% CI 0.01 to 0.62; 30 participants, very low certainty evidence), with similar reductions at day 8. For both moderate dose (two trials with 221 people) and high dose (two trials with 30 people), reduction in gametocytes (detected by microscopy) showed similar patterns as for artemisinin treatments, with little or no effect at day 4 or 5, and larger effects by day 8. No trials with non-artemisinin partner drugs systematically sought evidence of severe haemolysis.Two trials comparing bulaquine with PQ suggest bulaquine may have larger effects on gametocytes by microscopy on day 8 (RR 0.41, 95% CI 0.26 to 0.66; 2 trials, 112 participants).
AUTHORS' CONCLUSIONS
A single low dose of PQ (0.25 mg/kg) added to artemisinin-based combination therapy for malaria reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. The effect on infectiousness precedes the effect of PQ on gametocyte prevalence. We do not know whether single dose PQ could reduce malaria transmission at community level.
Topics: Adult; Antimalarials; Artemisinins; Child; Chloroquine; Drug Combinations; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Falciparum; Mefloquine; Non-Randomized Controlled Trials as Topic; Plasmodium falciparum; Primaquine; Pyrimethamine; Quinine; Randomized Controlled Trials as Topic; Sulfadoxine; Time Factors
PubMed: 29393511
DOI: 10.1002/14651858.CD008152.pub5 -
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 Lancet. Infectious Diseases Aug 2020Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum... (Meta-Analysis)
Meta-Analysis
Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis.
BACKGROUND
Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women.
METHODS
We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013.
FINDINGS
Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57-14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14-0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34-0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18-0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29-23·82).
INTERPRETATION
Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation.
FUNDING
The Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund.
Topics: Amodiaquine; Anti-Bacterial Agents; Antimalarials; Artemisinins; Artesunate; Atovaquone; Clindamycin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Malaria, Falciparum; Mefloquine; Pregnancy; Pregnancy Complications, Parasitic; Proguanil; Pyrimethamine; Quinine; Quinolines; Sulfadoxine
PubMed: 32530424
DOI: 10.1016/S1473-3099(20)30064-5