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Indian Journal of Public Health 2023Seasonal malaria chemoprevention (SMC) is an important public health intervention that is being used to reduce the burden of malaria in sub-Saharan Africa. (Review)
Review
BACKGROUND
Seasonal malaria chemoprevention (SMC) is an important public health intervention that is being used to reduce the burden of malaria in sub-Saharan Africa.
OBJECTIVES
This study aimed to evaluate the implementation of SMC and pharmacovigilance practices in under-five children in Kebbi State, Nigeria.
MATERIALS AND METHODS
The methodology involved a comprehensive review of tools for managing SMC commodities, training data collectors, and fieldwork to evaluate all local government area (LGA) stores, the central medical store (CMS), and selected health facilities based on the sample size determined. Data were collected using SurveyCTO software and analyzed using MS Excel. Twenty-one data reviewers visited the CMS, 21 LGA stores, and 315 health facilities.
RESULTS
Our study uncovered significant inaccuracies in documentation, which led to many commodities needing to be more effectively accounted for regarding sources. Data triangulation showed inconsistencies between tools and physical counts that do not match the quantities on inventory control cards. Most primary health-care (PHC) staff in charge of SMC have been formally trained in pharmacovigilance. About 75% (237) of PHCs referred cases of adverse drug reactions (ADRs) to a secondary health-care facility, while 14% (45) treated the symptoms of the ADR with another drug, and 7% (21) took no action, and the reaction resolved on its own.
CONCLUSIONS
This study provides insight into the challenges and opportunities for improving the implementation of SMC and pharmacovigilance practices in Kebbi State, Nigeria, and has important implications for other settings with similar challenges.
Topics: Child, Preschool; Humans; Infant; Antimalarials; Chemoprevention; India; Malaria; Nigeria; Pharmacovigilance; Seasons
PubMed: 37929374
DOI: 10.4103/ijph.ijph_577_23 -
Wellcome Open Research 2017Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a...
Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans. We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques. Of the 2,349 records identified in the initial search, 51 human studies met the eligibility criteria. The median pooled prevalence range of mental and neurological manifestations associated with antimalarial drugs ranged from 0.7% (dapsone) to 48.3% (minocycline) across all studies, while it ranged from 0.6% (pyrimethamine) to 42.7% (amodiaquine) during treatment of acute malaria, and 0.7% (primaquine/dapsone) to 55.0% (sulfadoxine) during prophylaxis. Pooled prevalence of mental and neurological manifestations across all studies was associated with an increased number of antimalarial drugs (prevalence ratio= 5.51 (95%CI, 1.05-29.04); P=0.045) in a meta-regression analysis. Headaches (15%) and dizziness (14%) were the most common mental and neurological manifestations across all studies. Of individual antimalarial drugs still on the market, mental and neurological manifestations were most common with the use of sulphadoxine (55%) for prophylaxis studies and amodiaquine (42.7%) for acute malaria studies. Mefloquine affected more domains of mental and neurological manifestations than any other antimalarial drug. Antimalarial drugs, particularly those used for prophylaxis, may be associated with mental and neurological manifestations, and the number of antimalarial drugs taken determines the association. Mental and neurological manifestations should be assessed following the use of antimalarial drugs.
PubMed: 28630942
DOI: 10.12688/wellcomeopenres.10658.2 -
Frontiers in Pharmacology 2020The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria to improve the therapeutic efficacy...
OBJECTIVE
The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria to improve the therapeutic efficacy and limit the choice of drug-resistant parasites. This systematic review and meta-analysis aimed to evaluate the comparative efficacy and safety of artemisinin-piperaquine (AP) in the treatment of uncomplicated malaria relative to other commonly used ACTs.
METHODS
As per the PRISMA guidelines, the EMBASE, MEDLINE, the Google Scholar Library, and Cochrane library databases were systematically searched from inception until July 2020 with the following terms: "artemisinin-piperaquine" or "AP." Only randomized controlled trials (RCTs) were included. The competing interventions included dihydroartemisinin-piperaquine (DHA-PPQ), artemether-lumefantrine (AL, Coartem), artesunate-melfloquine (ASAM) and artesunate-amodiaquine (ASAQ, Artekin). Single-arm clinical trial on AP was also assessed. The reported outcomes, including the overall response, cure rate, fever and parasite clearance time, hematology, biochemistry, electrocardiogram (ECG), adverse events, recurrence rate, and sensitivity analyses, were systematically investigated. All data were analyzed using the Review Manager 5.3.
RESULTS
A total of seven studies were reviewed, including five RCTs and two single-arm studies. A pooled analysis of 5 RCTs (n = 772) revealed a comparable efficacy on polymerase chain reaction (PCR)-confirmed cure rate between AP and competing interventions in treating uncomplicated malaria. As for the fever and parasite clearance time, due to the lack of complete data in some studies, only 3 studies' data could be used. The patients showed good tolerance to all drugs, and some side-effects (such as headache, anoxia, vomiting, nausea, and dizziness) were reported for every group, but they were self-limited and showed no significant difference.
CONCLUSIONS
AP appeared to show similar efficacy and safety, with a simpler mode of administration and easier compliance when compared with other ACTs used in the treatment of uncomplicated malaria. Considering that the potential evolution of drug resistance is of a great concern, additional RCTs with high-quality and more rigorous design are warranted to substantiate the efficacy and safety in different populations and epidemiological regions.
PubMed: 33013398
DOI: 10.3389/fphar.2020.562363 -
PloS One 2016The adoption of Artemisinin based combination therapies (ACT) constitutes a basic strategy for malaria control in sub-Saharan Africa. Moreover, since cases of ACT...
The adoption of Artemisinin based combination therapies (ACT) constitutes a basic strategy for malaria control in sub-Saharan Africa. Moreover, since cases of ACT resistance have been reported in South-East Asia, the need to understand P. falciparum resistance mechanism to ACT has become a global research goal. The selective pressure of ACT and the possibility that some specific Pfcrt and Pfmdr1 alleles are associated with treatment failures was assessed in a clinical trial comparing ASAQ to AL in Nanoro. Dried blood spots collected on Day 0 and on the day of recurrent parasitaemia during the 28-day follow-up were analyzed using the restriction fragments length polymorphism (PCR-RFLP) method to detect single nucleotide polymorphisms (SNPs) in Pfcrt (codon76) and Pfmdr1 (codons 86, 184, 1034, 1042, and 1246) genes. Multivariate analysis of the relationship between the presence of Pfcrt and Pfmdr1 alleles and treatment outcome was performed. AL and ASAQ exerted opposite trends in selecting Pfcrt K76T and Pfmdr1-N86Y alleles, raising the potential beneficial effect of using diverse ACT at the same time as first line treatments to reduce the selective pressure by each treatment regimen. No clear association between the presence of Pfcrt and Pfmdr1 alleles carried at baseline and treatment failure was observed.
Topics: Adult; Aged; Alleles; Amodiaquine; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Burkina Faso; Child; Drug Combinations; Ethanolamines; Female; Fluorenes; Gene Frequency; Genotype; Host-Parasite Interactions; Humans; Malaria, Falciparum; Male; Membrane Transport Proteins; Middle Aged; Multidrug Resistance-Associated Proteins; Multivariate Analysis; Parasitemia; Plasmodium falciparum; Polymorphism, Single Nucleotide; Protozoan Proteins; Treatment Outcome
PubMed: 27031231
DOI: 10.1371/journal.pone.0151565 -
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 -
Scientific Reports Jun 2018We investigated the effects of chloroquine (CQ) and amodiaquine (AQ) on AMPK phosphorylation in renal tubular cells in a diabetic environment in vivo and in vitro. We...
We investigated the effects of chloroquine (CQ) and amodiaquine (AQ) on AMPK phosphorylation in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether CQ- or AQ-mediated AMPK activity restoration attenuated diabetic tubulopathy by normalizing mitochondrial fragmentation. Human renal proximal epithelial cells (HKC8) were incubated in high-glucose conditions. Diabetes was induced with streptozotocin in male C57/BL6J mice. Treatment with CQ or AQ abolished high-glucose-induced phospho-AMPK and phosph-PGC1α down-regulation in HKC8 cells. Improvements in functional mitochondrial mass and balanced fusion/fission protein expression were observed in HKC8 cells after treatment with CQ or AQ in high-glucose conditions. Moreover, decreased mitochondrial ROS production and reduced apoptotic and fibrotic protein expression were noted in HKC8 cells after treatment with CQ or AQ, even in high-glucose conditions. CQ and AQ treatment effectively mitigated albuminuria and renal histopathologic changes and increased AMPK activity in the kidneys of diabetic mice. Electron microscopy analysis showed that mitochondrial fragmentation was decreased, and 8-OHdG content was low in the renal tubular cells of the CQ and AQ treatment groups compared with those of the diabetic control group. Our results suggest that CQ and AQ may be useful treatments for patients with diabetic kidney disease.
Topics: AMP-Activated Protein Kinases; Amodiaquine; Animals; Antimalarials; Cell Line; Chloroquine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Enzyme Activators; Glucose; Humans; Kidney Tubules; Male; Mice, Inbred C57BL; Mitochondria; Phosphorylation
PubMed: 29884802
DOI: 10.1038/s41598-018-26858-8 -
BMC Medicine Feb 2020The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and... (Meta-Analysis)
Meta-Analysis
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data.
BACKGROUND
The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas.
METHODS
We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment.
RESULTS
We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission.
CONCLUSION
Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.
Topics: Amodiaquine; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child, Preschool; Drug Combinations; Female; Humans; Infant; Malaria, Falciparum; Male; Plasmodium falciparum
PubMed: 32098634
DOI: 10.1186/s12916-020-1494-3 -
BMC Infectious Diseases Feb 2022Many studies have reported high efficacy and safety of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) when administered under direct observation in... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness and safety of artesunate-amodiaquine versus artemether-lumefantrine for home-based treatment of uncomplicated Plasmodium falciparum malaria among children 6-120 months in Yaoundé, Cameroon: a randomized trial.
BACKGROUND
Many studies have reported high efficacy and safety of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) when administered under direct observation in Cameroon. There is paucity of data to support their continuous use in home-based treatment of uncomplicated Plasmodium falciparum malaria in Cameroon. Hence, this study aimed to assess the effectiveness and safety of AS-AQ versus AL for home-based treatment of uncomplicated P. falciparum malaria among children 6-120 months in Yaoundé, Cameroon.
METHODS
A two-arm, open-label, randomized, controlled trial comparing the equivalence of AS-AQ (experimental group) and AL (control group) was carried out from May 2019 to April 2020 at two secondary hospitals in Yaoundé. Participants were randomized to receive either AS-AQ or AL. After the first dose, antimalarial drugs were given at home, rather than under direct observation by a study staff. The conventional on-treatment and post-treatment laboratory and clinical evaluations were not done until day 3 of the full antimalarial treatment course. The evaluation of effectiveness was mainly based on per protocol polymerase chain reaction adjusted adequate clinical and parasitological response (PP PCR adjusted ACPR) on day 28 post-treatment. Safety was based on assessment of adverse events (AEs) and severe adverse events (SAEs) from day 1 to day 28.
RESULTS
A total of 242 children were randomized to receive AS-AQ (n = 114) and AL (n = 128). The PP PCR adjusted day 28 cure rates were [AS-AQ = 96.9% (95% CI, 91.2-99.4) versus AL = 95.5% (95% CI, 89.9-98.5), P = 0.797]. Expected mild to moderate adverse events were reported in both arms [AS-AQ = 83 (84.7%) versus AL = 99 (86.1%), P = 0.774]. The most common adverse events included: transient changes of hematologic indices and fever.
CONCLUSIONS
This study demonstrated that AS-AQ and AL are effective and safe for home management of malaria in Yaoundé. The evidence from this study supports the parallel use of the two drugs in routine practice. However, the findings from this study do not describe the likely duration of antimalarial effectiveness in holoendemic areas where multiple courses of treatment might be required.
TRIAL REGISTRATION
This study is a randomized controlled trial and it was retrospectively registered on 23/09/2020 at ClinicalTrials.gov with registration number NCT04565184.
Topics: Amodiaquine; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Artemisinins; Artesunate; Cameroon; Child; Drug Combinations; Ethanolamines; Humans; Infant; Malaria, Falciparum; Plasmodium falciparum; Treatment Outcome
PubMed: 35189818
DOI: 10.1186/s12879-022-07101-2 -
The Lancet. Infectious Diseases Feb 2017Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP.
METHODS
Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: "human" AND "dihydroartemisinin-piperaquine" OR "DHA-PPQ". Studies were eligible if they were randomised controlled trials (RCTs) or prospective cohort studies involving repeat exposures to standard 3-day courses of DP for either seasonal malaria chemoprevention, mass drug administration, or treatment of clinical malaria, conducted at any time and in any geographic location. Random-effects meta-analysis was used to generate pooled incidence rate ratios and relative risks, or risk differences.
FINDINGS
11 studies were included: two repeat treatment studies (one in children younger than 5 years and one in pregnant women), and nine IPT trials (five in children younger than 5 years, one in schoolchildren, one in adults, two in pregnant women). Comparator interventions included placebo, artemether-lumefantrine, sulfadoxine-pyrimethamine (SP), SP+amodiaquine, SP+piperaquine, SP+chloroquine, and co-trimoxazole. Of 14 628 participants, 3935 received multiple DP courses (2-18). Monthly IPT-DP was associated with an 84% reduction in the incidence of malaria parasitaemia measured by microscopy compared with placebo. Monthly IPT-DP was associated with fewer serious adverse events than placebo, daily co-trimoxazole, or monthly SP. Among 56 IPT-DP recipients (26 children, 30 pregnant women) with cardiac parameters, all QTc intervals were within normal limits, with no significant increase in QTc prolongation with increasing courses of DP.
INTERPRETATION
Monthly DP appears well tolerated and effective for IPT. Additional data are needed in pregnancy and to further explore the cardiac safety with monthly dosing.
FUNDING
Bill & Melinda Gates Foundation and NIH.
Topics: Antimalarials; Artemisinins; Drug Combinations; Drug Therapy, Combination; Humans; Malaria; Pyrimethamine; Quinolines; Randomized Controlled Trials as Topic; Sulfadoxine
PubMed: 27865890
DOI: 10.1016/S1473-3099(16)30378-4 -
Malaria Journal Nov 2017Seasonal malaria chemoprevention (SMC) was recommended in 2012 for young children in the Sahel during the peak malaria transmission season. Children are given a single...
Seasonal malaria chemoprevention (SMC) was recommended in 2012 for young children in the Sahel during the peak malaria transmission season. Children are given a single dose of sulfadoxine/pyrimethamine combined with a 3-day course of amodiaquine, once a month for up to 4 months. Roll-out and scale-up of SMC has been impressive, with 12 million children receiving the intervention in 2016. There is evidence of its overall benefit in routine implementation settings, and a meta-analysis of clinical trial data showed a 75% decrease in clinical malaria compared to placebo. SMC is not free of shortcomings. Its target zone includes many hard-to-reach areas, both because of poor infrastructure and because of political instability. Treatment adherence to a 3-day course of preventive treatment has not been fully documented, and could prove challenging. As SMC is scaled up, integration into a broader, community-based paradigm which includes other preventive and curative activities may prove beneficial, both for health systems and for recipients.
Topics: Africa South of the Sahara; Amodiaquine; Antimalarials; Chemoprevention; Child, Preschool; Drug Combinations; Humans; Infant; Malaria; Pyrimethamine; Seasons; Sulfadoxine
PubMed: 29183327
DOI: 10.1186/s12936-017-2132-1