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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 -
Parasite Epidemiology and Control Nov 2020The preferred treatment for management of toxoplasmosis is the combined use of pyrimethamine and sulfadiazine. However, there are a wide number of adverse side effects... (Review)
Review
BACKGROUND
The preferred treatment for management of toxoplasmosis is the combined use of pyrimethamine and sulfadiazine. However, there are a wide number of adverse side effects with these medications. Recent research has focused on the use of chitosan for the treatment of infections. This review was performed to obtain a better understanding of the and effects of chitosan on strains.
METHODS
The current study was carried out according to the PRISMA guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-analysis Facility (SyRF) database. The search was performed in five scientific databases, including Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, with date limits of 1992 to December 2019. The search was restricted to articles published in the English language. The words and terms searched were "", "Chitosan", "nanoparticles" and "anti-toxoplasmosis" with AND or OR.
RESULTS
Of 2500 manuscripts, 9 met the eligibility criteria for review. All studies used the RH strain of , with Me49 and PRU each included in one study. Five studies (56%) were performed , one study and 3 studies included and tests.
CONCLUSION
Considering the low toxicity and the high inhibitory potency of chitosan against , chitosan nanoparticles show potential as an alternative treatment for .
PubMed: 33163635
DOI: 10.1016/j.parepi.2020.e00189 -
Heliyon Jul 2020Pregnancy-associated malaria (PAM) is a health problem with serious clinical, epidemiological and economic effects. (Review)
Review
INTRODUCTION
Pregnancy-associated malaria (PAM) is a health problem with serious clinical, epidemiological and economic effects.
PURPOSE
To analyze the microeconomic evaluations of PAM reported in the world scientific literature.
METHODS
Systematic review with 15 different search strategies in PubMed, ScienceDirect, Scielo, Google Scholar and Malaria in Pregnancy (MiP) Library. A search, selection and extraction protocol was applied, which guaranteed completeness and reproducibility in accordance with preferred reporting items for systematic reviews and meta-analysis guidelines. The methodological quality was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guide. The analysis were based on frequencies, costs and average and incremental cost-effectiveness ratios in 2018 US dollars adjusted for purchasing power parity.
RESULTS
Twenty-two evaluations published between 1990 and 2018 were analyzed, of which 82% addressed cost-effectiveness in Africa. Twelve interventions were studied; of these, intermittent preventive treatment in pregnant women with sulfadoxine-pyrimethamine (IPTp-SP) was the most frequent strategy. The main outcomes were low birth weight, anaemia and DALYs avoided. The best average cost-effectiveness ratio was reported in IPTp-SP with a cost of US$ 2 per DALY avoided, followed by the administration of IPTp-SP in pregnant women with HIV (US$ 14.2).
CONCLUSIONS
The studies focus on Africa with a high heterogeneity in the interventions, outcomes, resources and populations studied. All the interventions were highly cost-effective, which demonstrates the importance of including prevention, care and control resources for PAM as a priority in health sector budgets. This is especially true considering the importance of its intervention for social progress and overcoming poverty in endemic areas.
PubMed: 32775727
DOI: 10.1016/j.heliyon.2020.e04558 -
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 -
The British Journal of Dermatology Dec 2020Pityriasis lichenoides (PL) is a papulosquamous dermatosis affecting both children and adults, for which no standard treatment currently exists.
BACKGROUND
Pityriasis lichenoides (PL) is a papulosquamous dermatosis affecting both children and adults, for which no standard treatment currently exists.
OBJECTIVES
To characterize different treatment options and develop an evidence-based treatment algorithm for PL.
METHODS
A systematic search of published literature on PL treatments was performed on 23 December 2017 via the MEDLINE, Embase, CINAHL, CENTRAL, ClinicalTrials.gov and the EU Clinical Trials Register databases.
RESULTS
Of 1090 abstracts retrieved, 27 full-text articles with 502 participants were included for analysis. Seventeen of the full-text articles were retrospective cohort studies and two were randomized controlled studies. Treatment modalities included in these articles were phototherapy, antibiotics, methotrexate, pyrimethamine and trisulfapyrimidine, corticosteroids and conservative treatment. Of these treatments, phototherapy led to complete remission in the highest proportion of patients, and topical corticosteroids were found to have been trialled in the highest number of patients.
CONCLUSIONS
The current literature consists almost entirely of uncontrolled studies, and none provides compelling data to support an evidence-based approach to PL treatment. Pityriasis lichenoides chronica and pityriasis lichenoides et varioliformis acuta should be distinguished in response to treatment, and definitions of response to treatment must be standardized. Additional randomized control studies with longer follow-up will help better differentiate between treatment efficacies and adverse effects.
Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Humans; Phototherapy; Pityriasis Lichenoides; Retrospective Studies
PubMed: 32112390
DOI: 10.1111/bjd.18977 -
PloS One 2019The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that assessed comparisons of ACTs for treating uncomplicated falciparum malaria reported conflicting results in treatment efficacy. A network meta-analysis is an extension of pairwise meta-analysis that can synthesize evidence simultaneously from both direct and indirect treatment comparisons. The objective was to synthesize evidence on the comparative efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region.
METHODS
Relevant randomized trials that assessed efficacy of antimalarial drugs for patients having uncomplicated falciparum malaria in Asian region were searched in health-related databases. We evaluated the methodological quality of the included studies with the Cochrane risk of bias tool. Main outcome was treatment success at day 28 as determined by the absence of parasiteamia. We performed network meta-analysis of the interventions in the trials, and assessed the overall quality of evidence using the GRADE approach.
RESULTS
Seventeen randomized trials (n = 5043) were included in this network meta-analysis study. A network geometry was formed with 14 antimalarial treatment options such as artemether-lumefantrine (AL), artemisinin-piperaquine, artesunate-amodiaquine, artesunate-mefloquine (ASMQ), artesunate-chloroquine, artesunate-mefloquine home treatment, artesunate-mefloquine 2-day course, artesunate plus sulfadoxine-pyrimethamine, chloroquine, dihydroartemisinin-piperaquine (DHP), dihydroartemisinin-piperaquine home treatment, dihydroartemisinin-piperaquine 4-day course, dihydroartemisinin-piperaquine and added artesunate, sulfadoxine-pyrimethamine. A maximum number of trials included was DHP compared to ASMQ (n = 5). In general, DHP had better efficacy than AL at day 28 (DHP vs AL: OR 2.5, 95%CI:1.08-5.8). There is low certainty evidence due to limited number of studies and small trials.
DISCUSSION/ CONCLUSIONS
The findings suggest the superiority of DHP (3-day course) to AL and other comparator ACTs are with the overall low/very low quality of evidence judgements. Moreover, one drug regimen is better than another is only if current drug-resistance patterns are at play. For example, the AL might be better than DHP in areas where both artemisinin and piperaquine resistance patterns are prevalent. For substantiation, well-designed larger trials from endemic countries are needed. In the light of benefit versus harm concept, future analysis with safety information is recommended.
Topics: Antimalarials; Asia; Databases, Factual; Drug Resistance; Humans; Malaria, Falciparum; Randomized Controlled Trials as Topic
PubMed: 31856172
DOI: 10.1371/journal.pone.0225882 -
The Cochrane Database of Systematic... Dec 2019Intermittent 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 27% reduction (rate ratio 0.73, 0.65 to 0.82; 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 0.79, 0.74 to 0.85; 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. 2 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (3 Dec, 2018) were included.
Topics: Africa South of the Sahara; Antimalarials; Disease Eradication; Drug Combinations; Endemic Diseases; Humans; Infant; Malaria; Parasitemia; Randomized Controlled Trials as Topic
PubMed: 31792925
DOI: 10.1002/14651858.CD011525.pub2 -
Pharmacological Research Aug 2019Malaria affects 200 million people worldwide. Today, the most successful treatments are artemisinin-based combination therapies (ACT). Resistance has already been...
Malaria affects 200 million people worldwide. Today, the most successful treatments are artemisinin-based combination therapies (ACT). Resistance has already been described for the elder anti-malarials chloroquine, sulfadoxine-pyrimethamine and mefloquine. Unfortunately, over the last few years there has also been an emerging resistance to the successfully used drug artemisinin, especially in African and Asian countries. A systematic PubMed literature research was conducted for studies published between January 2002 and December 2018. Despite ACTs continue to be first line treatment, the number of studies is rising reporting on artemisinin resistance mutations. Most publications reported on kelch13 mutations (45 studies), the second most frequent mutations were found in pfmdr1 (32 studies). PfATPase6 mutations have been mainly studied in Asian countries (4 of 6 studies). Bearing this in mind, there is a pressing need to further examine the role and spread of mutations conferring artemisinin resistance. A further decline of treatment efficacy could result in increased rates of malaria-related deaths.
Topics: Animals; Antimalarials; Artemisinins; Drug Resistance; Humans; Malaria; Mutation; Polymorphism, Genetic
PubMed: 31100335
DOI: 10.1016/j.phrs.2019.104275 -
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 -
The Lancet. Infectious Diseases May 2019Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) in... (Meta-Analysis)
Meta-Analysis
Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis.
BACKGROUND
Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) in sub-Saharan Africa. We aimed to assess the associations between markers of sulfadoxine-pyrimethamine resistance in P falciparum and the effectiveness of sulfadoxine-pyrimethamine IPTp for malaria-associated outcomes.
METHODS
For this systematic review and meta-analysis, we searched databases (from Jan 1, 1990 to March 1, 2018) for clinical studies (aggregated data) or surveys (individual participant data) that reported data on low birthweight (primary outcome) and malaria by sulfadoxine-pyrimethamine IPTp dose, and for studies that reported on molecular markers of sulfadoxine-pyrimethamine resistance. Studies that involved only HIV-infected women or combined interventions were excluded. We did a random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarised dose-response data (relative risk reduction [RRR]) and multivariate meta-regression to explore the modifying effects of sulfadoxine-pyrimethamine resistance (as indicated by Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene). This study is registered with PROSPERO, number 42016035540.
FINDINGS
Of 1097 records screened, 57 studies were included in the aggregated-data meta-analysis (including 59 457 births). The RRR for low birthweight declined with increasing prevalence of dhps Lys540Glu (p=0·0060) but not Ala437Gly (p=0·35). The RRR was 7% (95% CI 0 to 13) in areas of high resistance to sulfadoxine-pyrimethamine (Lys540Glu ≥90% in east and southern Africa; n=11), 21% (14 to 29) in moderate-resistance areas (Ala437Gly ≥90% [central and west Africa], or Lys540Glu ≥30% to <90% [east and southern Africa]; n=16), and 27% (21 to 33) in low-resistance areas (Ala437Gly <90% [central and west Africa], or Lys540Glu <30% [east and southern Africa]; n=30; p=0·0054 [univariate], I=69·5%). The overall RRR in all resistance strata was 21% (17 to 25). In the analysis of individual participant data from 13 surveys (42 394 births), sulfadoxine-pyrimethamine IPTp was associated with reduced prevalence of low birthweight in areas with a Lys540Glu prevalence of more than 90% and Ala581Gly prevalence of less than 10% (RRR 10% [7 to 12]), but not in those with an Ala581Gly prevalence of 10% or higher (pooled Ala581Gly prevalence 37% [range 29 to 46]; RRR 0·5% [-16 to 14]; 2326 births).
INTERPRETATION
The effectiveness of sulfadoxine-pyrimethamine IPTp is reduced in areas with high resistance to sulfadoxine-pyrimethamine among P falciparum parasites, but remains associated with reductions in low birthweight even in areas where dhps Lys540Glu prevalence exceeds 90% but where the sextuple-mutant parasite (harbouring the additional dhps Ala581Gly mutation) is uncommon. Therapeutic alternatives to sulfadoxine-pyrimethamine IPTp are needed in areas where the prevalence of the sextuple-mutant parasite exceeds 37%.
FUNDING
US Centers for Disease Control and Prevention, the Malaria in Pregnancy Consortium (funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine), Worldwide Antimalarial Resistance Network, European and Developing Countries Clinical Trials Partnership.
Topics: Africa; Antimalarials; Drug Combinations; Drug Resistance; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Malaria, Falciparum; Mutation; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine
PubMed: 30922818
DOI: 10.1016/S1473-3099(18)30732-1