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Malaria Journal Dec 2017There is no agreed standard method to assess the efficacy of anti-malarials for uncomplicated falciparum in pregnancy despite an increased risk of adverse outcomes for... (Meta-Analysis)
Meta-Analysis Review
Systematic literature review and meta-analysis of the efficacy of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: methodological challenges.
BACKGROUND
There is no agreed standard method to assess the efficacy of anti-malarials for uncomplicated falciparum in pregnancy despite an increased risk of adverse outcomes for the mother and the fetus. The aim of this review is to present the currently available evidence from both observational and interventional cohort studies on anti-malarial efficacy in pregnancy and summarize the variability of assessment and reporting found in the review process.
METHODS
Efficacy methodology and assessment of artemisinin-based treatments (ABT) and quinine-based treatments (QBT) were reviewed systematically using seven databases and two clinical trial registries (protocol registration-PROSPERO: CRD42017054808). Pregnant women in all trimesters with parasitologically confirmed uncomplicated falciparum malaria were included irrespective of symptoms. This review attempted to re-calculate proportions of treatment success applying the same definition as the standard WHO methodology for non-pregnant populations. Aggregated data meta-analyses using data from randomized control trials (RCTs) comparing different treatments were performed by random effects model.
RESULTS
A total of 48 eligible efficacy studies were identified including 7279 treated Plasmodium falciparum episodes. While polymerase chain reaction (PCR) was used in 24 studies for differentiating recurrence, the assessment and reporting of treatment efficacy was heterogeneous. When the same definition could be applied, PCR-corrected treatment failure of ≥ 10% at any time points was observed in 3/30 ABT and 3/7 QBT arms. Ten RCTs compared different combinations of ABT but there was a maximum of two published RCTs with PCR-corrected outcomes for each comparison. Five RCTs compared ABT and QBT. Overall, the risk of treatment failure was significantly lower in ABT than in QBT (risk ratio 0.22, 95% confidence interval 0.07-0.63), although the actual drug combinations and outcome endpoints were different. First trimester women were included in 12 studies none of which were RCTs of ABT.
CONCLUSIONS
Efficacy studies in pregnancy are not only limited in number but use varied methodological assessments. In five RCTs with comparable methodology, ABT resulted in higher efficacy than QBT in the second and third trimester of pregnancy. Individual patient data meta-analysis can include data from observational cohort studies and could overcome some of the limitations of the current assessment given the paucity of data in this vulnerable group.
Topics: Antimalarials; Artemisinins; Drug Therapy, Combination; Female; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Quinine
PubMed: 29237461
DOI: 10.1186/s12936-017-2135-y -
The Cochrane Database of Systematic... Jan 2021Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has plateaued for the first time since the turn of the century. Researchers and policymakers are therefore exploring alternative and supplementary malaria vector control tools. Research in 1900 indicated that modification of houses may be effective in reducing malaria: this is now being revisited, with new research now examining blocking house mosquito entry points or modifying house construction materials to reduce exposure of inhabitants to infectious bites.
OBJECTIVES
To assess the effects of house modifications on malaria disease and transmission.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS), up to 1 November 2019. We also searched the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en/), ClinicalTrials.gov (www.clinicaltrials.gov), and the ISRCTN registry (www.isrctn.com/) to identify ongoing trials up to the same date.
SELECTION CRITERIA
Randomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies. We only considered studies reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We also summarised qualitative studies conducted alongside included studies.
DATA COLLECTION AND ANALYSIS
Two review authors selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS
Six cRCTs met our inclusion criteria, all conducted in sub-Saharan Africa; three randomized by household, two by village, and one at the community level. All trials assessed screening of windows, doors, eaves, ceilings or any combination of these; this was either alone, or in combination with eave closure, roof modification or eave tube installation (a "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In two trials, the interventions were insecticide-based. In five trials, the researchers implemented the interventions. The community implemented the interventions in the sixth trial. At the time of writing the review, two of the six trials had published results, both of which compared screened houses (without insecticide) to unscreened houses. One trial in Ethiopia assessed screening of windows and doors. Another trial in the Gambia assessed full screening (screening of eaves, doors and windows), as well as screening of ceilings only. Screening may reduce clinical malaria incidence caused by Plasmodium falciparum (rate ratio 0.38, 95% CI 0.18 to 0.82; 1 trial, 184 participants, 219.3 person-years; low-certainty evidence; Ethiopian study). For malaria parasite prevalence, the point estimate, derived from The Gambia study, was smaller (RR 0.84, 95% CI 0.60 to 1.17; 713 participants, 1 trial; low-certainty evidence), and showed an effect on anaemia (RR 0.61, 95% CI 0.42, 0.89; 705 participants; 1 trial, moderate-certainty evidence). Screening may reduce the entomological inoculation rate (EIR): both trials showed lower estimates in the intervention arm. In the Gambian trial, there was a mean difference in EIR between the control houses and treatment houses ranging from 0.45 to 1.50 (CIs ranged from -0.46 to 2.41; low-certainty evidence), depending on the study year and treatment arm. The Ethiopian trial reported a mean difference in EIR of 4.57, favouring screening (95% CI 3.81 to 5.33; low-certainty evidence). Pooled analysis of the trials showed that individuals living in fully screened houses were slightly less likely to sleep under a bed net (RR 0.84, 95% CI 0.65 to 1.09; 2 trials, 203 participants). In one trial, bed net usage was also lower in individuals living in houses with screened ceilings (RR 0.69, 95% CI 0.50 to 0.95; 1 trial, 135 participants).
AUTHORS' CONCLUSIONS
Based on the two trials published to date, there is some evidence that screening may reduce malaria transmission and malaria infection in people living in the house. The four trials awaiting publication are likely to enrich the current evidence base, and we will add these to this review when they become available.
Topics: Adolescent; Adult; Africa South of the Sahara; Anemia; Animals; Architecture; Child; Child, Preschool; Construction Materials; Female; Housing; Humans; Incidence; Infant; Insecticides; Malaria, Falciparum; Male; Mosquito Nets; Mosquito Vectors; Plasmodium falciparum; Pregnancy; Prevalence; Randomized Controlled Trials as Topic
PubMed: 33471371
DOI: 10.1002/14651858.CD013398.pub3 -
Parasites & Vectors Sep 2022Malaria in human immunodeficiency virus (HIV)-positive patients is an ever-increasing global burden for human health. The present meta-analysis summarizes published... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malaria in human immunodeficiency virus (HIV)-positive patients is an ever-increasing global burden for human health. The present meta-analysis summarizes published literature on the prevalence of malaria infection in HIV-positive children, pregnant women and adults.
METHODS
This study followed the PRISMA guideline. The PubMed, Science Direct, Google Scholar, Scopus and Cochrane databases were searched for relevant entries published between 1 January 1983 and 1 March 2020. All peer-reviewed original papers evaluating the prevalence of malaria among HIV-positive patients were included. Incoherence and heterogeneity between studies were quantified by the I index and Cochran's Q test. Publication and population biases were assessed with funnel plots, and Egger's regression asymmetry test.
RESULTS
A total of 106 studies were included in this systematic review. The average prevalence of malaria among HIV-positive children, HIV-positive pregnant women and HIV-positive adults was 39.4% (95% confidence interval [CI]: 26.6-52.9), 32.3% (95% CI = 26.3-38.6) and 27.3% (95% CI = 20.1-35.1), respectively. In adult patients with HIV, CD4 (cluster of differentiation 4) < 200 cells/µl and age < 40 years were associated with a significant increase in the odds of malaria infection (odds ratio [OR] = 1.5, 95% CI = 1.2-1.7 and OR = 1.1, 95% CI = 1-1.3, respectively). Antiretroviral therapy (ART) and being male were associated with a significant decrease in the chance of malaria infection in HIV-positive adults (OR = 0.8, 95% CI = 0.7-0.9 and OR = 0.2, 95% CI = 0.2-0.3, respectively). In pregnant women with HIV, CD4 count < 200 cells/µl was related to a higher risk for malaria infection (OR = 1.5, 95% CI = 1.1-1.9).
CONCLUSIONS
This systematic review demonstrates that malaria infection is concerningly common among HIV-positive children, pregnant women and adults. Among HIV-positive adults, ART medication and being male were associated with a substantial decrease in infection with malaria. For pregnant women, CD4 count of < 200 cells/µl was a considerable risk factor for malaria infection.
Topics: Adult; Child; Female; HIV Infections; Humans; Malaria; Male; Pregnancy; Pregnant Women; Prevalence; Risk Factors
PubMed: 36104731
DOI: 10.1186/s13071-022-05432-2 -
Malaria Journal Dec 2022In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those... (Review)
Review
BACKGROUND
In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those performing forest-related work. Furthermore, asymptomatic cases of P. knowlesi malaria have been reported including among women and children.
METHODS
Pubmed, Scopus and the Web of Science databases for literature describing asymptomatic P. knowlesi malaria published between 2010 and 2020 were searched. A systematic literature review was conducted to identify studies reporting the prevalence and incidence of laboratory confirmed asymptomatic P. knowlesi cases in humans, their clinical and demographic characteristics, and methods used to diagnose these cases.
RESULTS
By analysing over 102 papers, thirteen were eligible for this review. Asymptomatic P. knowlesi infections have been detected in 0.03%-4.0% of the population depending on region, and infections have been described in children as young as 2 years old. Various different diagnostic methods were used to detect P. knowlesi cases and there were differing definitions of asymptomatic cases in these studies. The literature indicates that regionally-differing immune-related mechanisms may play a part on the prevalence of asymptomatic P. knowlesi.
CONCLUSION
Differing epidemiological characteristics of asymptomatic P. knowlesi malaria in different regions reinforces the need to further investigate disease transmission mechanics. Effective public health responses to changes in P. knowlesi epidemiology require proactive intervention and multisectoral collaboration.
Topics: Child; Humans; Female; Child, Preschool; Plasmodium knowlesi; Communicable Diseases, Emerging
PubMed: 36474243
DOI: 10.1186/s12936-022-04339-8 -
Malaria Journal Dec 2016Reliable and comprehensive information on the burden of malaria is critical for guiding national and international efforts in malaria control. The purpose of this review... (Review)
Review
BACKGROUND
Reliable and comprehensive information on the burden of malaria is critical for guiding national and international efforts in malaria control. The purpose of this review is to provide an overview of published data and available information on malaria resulting from field studies/investigations conducted in the Republic of Congo (RoC) from 1992 to 2015, as baseline for assisting public health authorities and researchers to define future research priorities as well as interventions.
METHODS
This review considers data from peer-reviewed articles and information from the National Malaria Control Programme reports, based on field investigations or samples collected from 1992 to 2015. Peer-reviewed papers were searched throughout online bibliographic databases PubMed, HINARI and Google Scholar using the following terms: "malaria", "Congo", "Brazzaville", "prevalence", "antimalarial", "efficacy", "falciparum", "genetic", "diversity". Original articles and reviews were included and selection of relevant papers was made.
RESULTS
Twenty-eight published articles were included in this review and two additional records from the National Malaria Control Programme were also considered. The majority of studies were conducted in Brazzaville and Pointe-Noire.
CONCLUSION
The present systematic review reveals that number of studies have been conducted in the RoC with regard to malaria. However, their results cannot formally be generalized at the country level. This suggests a need for implementing regular multisite investigations and surveys that may be representative of the country, calling for the support and lead of the Ministry of Health.
Topics: Biomedical Research; Congo; Disease Transmission, Infectious; Health Policy; Humans; Malaria; Research
PubMed: 28010728
DOI: 10.1186/s12936-016-1617-7 -
Therapeutics and Clinical Risk... 2021Malaria is one of the infectious diseases with substantial risks for pregnant women, the fetus and the newborn child. Thus, prevention and treatment of malaria with safe... (Review)
Review
INTRODUCTION
Malaria is one of the infectious diseases with substantial risks for pregnant women, the fetus and the newborn child. Thus, prevention and treatment of malaria with safe and effective drugs is of paramount importance. Pregnant women are mostly excluded from clinical trials, and systematic approaches of pharmacovigilance in pregnancy are limited. This means the safety and efficacy of antimalarial agents during pregnancy are unclear.
PURPOSE
This study was designed to carry out a systematic review and aggregate data meta-analysis of literature published on efficacy and safety of artemisinin-based combination therapy (ACT) for uncomplicated malaria in pregnant women.
METHODS
A search of literature published between 1998 to 2020 on efficacy and safety of artemisinin-based combination therapy (ACT) in pregnant women was made using Cochrane Library, Medline and the Malaria in Pregnancy Consortium Library. Data were extracted independently by two reviewers, and any discrepancies were resolved by consensus. Meta-analysis was carried out using Open Meta-Analyst software. Random effects model was applied, and the heterogeneity of studies was evaluated using Higgins I.
RESULTS
Twenty-four studies that fulfilled the inclusion criteria were included in the final assessment. Overall, days 28 to 63 malaria treatment success rate was 96.1%. Overall days 28 to 63 cure rates for AL, AS+AQ, AS+MQ, DHA+PQ, AS+ATQ+PG and AS+SP were 95.1%, 92.2%, 97.0%,94.3%, 96.5% and 97.4%, respectively. Comparison of ACTs with non-ACTs revealed that the risk of treatment failure was substantially lower in patients treated with ACTs than with non-ACTs (risk ratio 0.20, 95% C.I. 0.09-0.43). The overall prevalences of miscarriage, stillbirth and congenital anomalies were 0.3%, 2.1% and 1.0%, respectively, and found to be comparable among various ACTs. There was comparable tolerability across ACTs during pregnancy.
CONCLUSION
ACTs demonstrated a high cure rate, safety and tolerability against infection in pregnant women. The higher treatment success and comparable tolerability could be used as an input for decision makers to support the continued usage of ACTs for treatment of uncomplicated falciparum malaria in pregnant women.
PubMed: 35221688
DOI: 10.2147/TCRM.S336771 -
PloS One 2020Plasmodium ovale can infect humans, causing malaria disease. We aimed to investigate the severity and mortality of severe P. ovale infection to increase the awareness of... (Meta-Analysis)
Meta-Analysis
Plasmodium ovale can infect humans, causing malaria disease. We aimed to investigate the severity and mortality of severe P. ovale infection to increase the awareness of physicians regarding the prognosis of this severe disease and outcome-related deaths in countries in which this disease is endemic. Articles that were published in the PubMed, Scopus, and ISI Web of Science databases prior to January 5, 2020 and reported the prevalence of severe P. ovale infection were systematically searched and reviewed. Studies that mainly reported severe P. ovale infection according to the 2014 WHO criteria for the treatment of malaria were included. Two reviewers selected, identified, assessed, and extracted data from studies independently. The pooled prevalence of severe P. ovale mono-infections was estimated using the command "metaprop case population, random/fixed", which yielded the pooled estimate, 95% confidence interval (CI) and the I2 value, indicating the level of heterogeneity. Meta-analyses of the proportions were performed using a random-effects model to explore the different proportions of severity between patients with P. ovale and those with other Plasmodium species infections. Among the eight studies that were included and had a total of 1,365 ovale malaria cases, the pooled prevalence of severe P. ovale was 0.03 (95% CI = 0.03-0.05%, I2 = 54.4%). Jaundice (1.1%), severe anemia (0.88%), and pulmonary impairments (0.59%) were the most common severe complications found in patients infected with P. ovale. The meta-analysis demonstrated that a smaller proportion of patients with P. ovale than of patients with P. falciparum had severe infections (P-value = 0.01, OR = 0.36, 95% CI = 0.16-0.81, I2 = 72%). The mortality rate of severe P. ovale infections was 0.15% (2/1,365 cases). Although severe complications of P. ovale infections in patients are rare, it is very important to increase the awareness of physicians regarding the prognosis of severe P. ovale infections in patients, especially in a high-risk population.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Malaria; Male; Middle Aged; Plasmodium falciparum; Plasmodium ovale; Prevalence
PubMed: 32559238
DOI: 10.1371/journal.pone.0235014 -
Malaria Journal Sep 2015Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in... (Review)
Review
BACKGROUND
Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has "strongly seasonal" transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized.
METHODS
The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts.
RESULTS AND DISCUSSION
152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both).
DISCUSSION
Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location.
CONCLUSIONS
The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales.
Topics: Animals; Anopheles; Climate; Humans; Incidence; Malaria, Falciparum; Plasmodium falciparum; Seasons; Weather
PubMed: 26370142
DOI: 10.1186/s12936-015-0849-2 -
Clinical Infectious Diseases : An... Jan 2022The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests...
BACKGROUND
The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests (RDTs) prompted the World Health Organization and other global health stakeholders to prioritize the discovery of novel diagnostic biomarkers for malaria.
METHODS
To address this pressing need, we adopted a dual, systematic approach by conducting a systematic review of the literature for publications on diagnostic biomarkers for uncomplicated malaria and a systematic in silico analysis of P. falciparum proteomics data for Plasmodium proteins with favorable diagnostic features.
RESULTS
Our complementary analyses led us to 2 novel malaria diagnostic biomarkers compatible for use in an RDT format: glyceraldehyde 3-phosphate dehydrogenase and dihydrofolate reductase-thymidylate synthase.
CONCLUSIONS
Overall, our results pave the way for the development of next-generation malaria RDTs based on new antigens by identifying 2 lead candidates with favorable diagnostic features and partially de-risked product development prospects.
Topics: Antigens, Protozoan; Biomarkers; Diagnostic Tests, Routine; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins; Sensitivity and Specificity
PubMed: 34718455
DOI: 10.1093/cid/ciab251 -
European Journal of Pharmaceutical... Apr 2023Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the... (Review)
Review
Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the development of drug resistance in malaria parasites. The standard treatment for malaria is artemisinin-combination therapy (ACT). Nevertheless, the Plasmodium parasite's extensive resistance to prior drugs and reduced ACT efficiency necessitates novel drug discovery. The progress in discovering novel, affordable, and effective antimalarial agents is significant in combating drug resistance, and the hybrid drug concept can be used to covalently link two or more active pharmacophores that may act on multiple targets. Pyrazole and pyrazoline derivatives are considered pharmacologically necessary active heterocyclic scaffolds that possess almost all types of pharmacological activities. This review summarized recent progress in antimalarial activities of synthesized pyrazole and pyrazoline derivatives. The studies published since 2000 are included in this systematic review. This review is anticipated to be beneficial for future study and new ideas in searching for rational development strategies for more effective pyrazole and pyrazoline derivatives as antimalarial drugs.
Topics: Humans; Antimalarials; Malaria; Pyrazoles; Drug Resistance; Folic Acid Antagonists; Plasmodium falciparum
PubMed: 36563914
DOI: 10.1016/j.ejps.2022.106365