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Transactions of the Royal Society of... Feb 2024To provide a continuous update on the safety and efficacy of artesunate-mefloquine (ASMQ) compared with other artemisinin combination therapy (ACT) schemes used in the... (Meta-Analysis)
Meta-Analysis
To provide a continuous update on the safety and efficacy of artesunate-mefloquine (ASMQ) compared with other artemisinin combination therapy (ACT) schemes used in the treatment of uncomplicated malaria caused by Plasmodium falciparum, this study updated and expanded the results of the systematic literature review published in 2016. Only randomised controlled clinical trials published from 1 January 2001 to 12 June 2023 from five databases were included in this study. The results related to efficacy, expressed through RR, were summarized in meta-analyses, performed according to the compared ACTs and with the intention-to-treat and per-protocol analyses. The results related to safety were synthesized in a descriptive manner. Thirty-two studies were included, of which 24 had been analysed in the 2016 review and eight new ones were added. Although the methodological quality of most studies was considered moderate, the body of evidence gathered indicates that ASMQ continues to be safe and effective for the treatment of uncomplicated infections caused by P. falciparum compared with other ACTs. However, the inclusion of two new studies, which identified failure rates exceeding 10%, suggests a possible reduction in the efficacy of ASMQ in the analysed locations. The incidence of serious adverse effects, such as seizure, encephalopathy and cardiac arrhythmia, was infrequent in both the ASMQ group and the comparison groups. After including new evidence, ASMQ is still recommended as a first-line treatment of uncomplicated malaria caused by P. falciparum, although local aspects need to be considered.
Topics: Humans; Mefloquine; Artesunate; Antimalarials; Drug Therapy, Combination; Malaria, Falciparum; Malaria; Plasmodium falciparum
PubMed: 37772768
DOI: 10.1093/trstmh/trad069 -
Expert Review of Molecular Diagnostics 2023This review presents an overview of field findings on sequence variation of histidine-rich proteins 2/3 (HRP2/3) for which reference types (1-24) have been identified,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review presents an overview of field findings on sequence variation of histidine-rich proteins 2/3 (HRP2/3) for which reference types (1-24) have been identified, and its critical impact on HRP2-based rapid diagnostic test (RDT) detection.
RESEARCH DESIGN AND METHODS
This systematic review and meta-analysis was registered with PROSPERO, CRD42022316027, and conducted as per the PRISMA guidelines, and the methodological quality of studies was assessed.
RESULTS
Of the 2184 records identified, 34 studies were included mostly from Africa (47.1%) and Asia (35.3%). The reference HRP2 types 1, 2, 3, 6, and 7 are invariably found at proportions ≥ 80-100% in all areas with the exception of The Americas where their proportion is very low. The proteins exhibited high diversity of variants/unknown types, especially for types 1, 2, 4, and 7. Eleven major HRP2 epitopes were found at pooled proportion > 90%. The existing models to predict RDT detection are greatly limited by the impact of factors such as low (very low) parasitemia, RDT brand, and HRP3 cross-reactivity. HRP2 length and presence/number of a given reference repeat type/variant did not seem to impact RDT detection.
CONCLUSIONS
HRP2/3 are highly polymorphic and current findings are insufficient, conflicting and not convincing enough to conclude on the role of HRP2/3 sequence polymorphism in HRP2-based RDT detection.
Topics: Humans; Plasmodium falciparum; Histidine; Malaria, Falciparum; Rapid Diagnostic Tests; Protozoan Proteins; Antigens, Protozoan; Malaria; Diagnostic Tests, Routine
PubMed: 37698448
DOI: 10.1080/14737159.2023.2255136 -
Malaria Journal Sep 2023Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies.
METHODS
A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission.
RESULTS
A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively.
CONCLUSION
Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.
Topics: Humans; Malaria
PubMed: 37661286
DOI: 10.1186/s12936-023-04670-8 -
Antioxidants (Basel, Switzerland) Jul 2023Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and infections; however, the findings remain inconclusive. This study... (Review)
Review
Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and infections; however, the findings remain inconclusive. This study synthesized differences in MDA concentrations among patients with different levels of clinical severity, uninfected controls, and different species. The research protocol was registered in PROSPERO (CRD42023393540). Systematic literature searches for relevant studies were performed using the Embase, MEDLINE, Ovid, ProQuest, PubMed, Scopus, and Google Scholar databases. Qualitative and quantitative syntheses (meta-analyses) of distinct MDA concentrations between the disease groups were performed. Twenty-three studies met the eligibility criteria and were included in the systematic review. Overall, MDA concentrations were significantly elevated in participants with malaria relative to uninfected controls ( < 0.01, Cohen d: 2.51, 95% confidence interval (CI): 1.88-3.14, I: 96.22%, 14 studies). Increased MDA concentrations in participants with malaria compared with uninfected controls were found in studies that enrolled patients with malaria ( < 0.01, Cohen d: 2.50, 95% CI: 1.90-3.10, I: 89.7%, 7 studies) and malaria ( < 0.01, Cohen d: 3.70, 95% CI: 2.48-4.92, I: 90.11%, 3 studies). Our findings confirm that MDA concentrations increase during infection, indicating a rise in oxidative stress and lipid peroxidation. Thus, MDA levels can be a valuable biomarker for evaluating these processes in individuals with malaria. However, further research is necessary to fully elucidate the intricate relationship between malaria, antioxidants, oxidative stress, and the specific role of MDA in the progression of malaria.
PubMed: 37627497
DOI: 10.3390/antiox12081502 -
The Cochrane Database of Systematic... Aug 2023Insecticide-based interventions, such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS), remain the backbone of malaria vector control.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Insecticide-based interventions, such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS), remain the backbone of malaria vector control. These interventions target mosquitoes that prefer to feed and rest indoors, but have limited capacity to prevent transmission that occurs outdoors or outside regular sleeping hours. In low-endemicity areas, malaria elimination will require that these control gaps are addressed, and complementary tools are found. The use of topical repellents may be particularly useful for populations who may not benefit from programmatic malaria control measures, such as refugees, the military, or forest goers. This Cochrane Review aims to measure the effectiveness of topical repellents to prevent malaria infection among high- and non-high-risk populations living in malaria-endemic regions.
OBJECTIVES
To assess the effect of topical repellents alone or in combination with other background interventions (long-lasting insecticide-treated nets, or indoor residual spraying, or both) for reducing the incidence of malaria in high- and non-high-risk populations living in endemic areas.
SEARCH METHODS
We searched the following databases up to 11 January 2023: the Cochrane Infectious Diseases Group Specialised Register; CENTRAL (in the Cochrane Library); MEDLINE; Embase; CAB Abstracts; and LILACS. We also searched trial registration platforms and conference proceedings; and contacted organizations and companies for ongoing and unpublished trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and cluster-randomized controlled trials (cRCTs) of topical repellents proven to repel mosquitoes. We also included non-randomized studies that complied with pre-specified inclusion criteria: controlled before-after studies (CBA), controlled interrupted time series (ITS), and controlled cross-over trials.
DATA COLLECTION AND ANALYSIS
Four review authors independently assessed trials for inclusion, and extracted the data. Two authors independently assessed the risk of bias (RoB) using the Cochrane RoB 2 tool. A fifth review author resolved any disagreements. We analysed data by conducting a meta-analysis, stratified by whether studies included populations considered to be at high-risk of developing malaria infection (for example, refugees, forest goers, or deployed military troops). We combined results from cRCTs with RCTs by adjusting for clustering and presented results using forest plots. We used the GRADE framework to assess the certainty of the evidence. We only included data on Plasmodium falciparum infections in the meta-analysis.
MAIN RESULTS
Thirteen articles relating to eight trials met the inclusion criteria and were qualitatively described. We included six trials in the meta-analysis (five cRCTs and one RCT). Effect on malaria incidence Topical repellents may slightly reduce P falciparum infection and clinical incidence when both outcomes are considered together (incidence rate ratio (IRR) 0.74, 95% confidence interval (CI) 0.56 to 0.98; 3 cRCTs and 1 RCT, 61,651 participants; low-certainty evidence); but not when these two outcomes were considered independently. Two cRCTs and one RCT (12,813 participants) evaluated the effect of topical repellents on infection incidence (IRR 0.76, 95% CI 0.56 to 1.02; low-certainty evidence). One cRCT (48,838 participants) evaluated their effect on clinical case incidence (IRR 0.66, 95% CI 0.32 to 1.36; low-certainty evidence). Three studies (2 cRCTs and 1 RCT) included participants belonging to groups considered at high-risk of being infected, while only one cRCT did not include participants at high risk. Adverse events Topical repellents are considered safe. The prevalence of adverse events among participants who used topical repellents was very low (0.6%, 283/47,515) and limited to mild skin reactions. Effect on malaria prevalence Topical repellents may slightly reduce P falciparum prevalence (odds ratio (OR) 0.81, 95% CI 0.67 to 0.97; 3 cRCTs and 1 RCT; 55,366 participants; low-certainty evidence). Two of these studies (1 cRCT and 1 RCT) were carried out in refugee camps, and included exclusively high-risk populations that were not receiving any other background vector control intervention.
AUTHORS' CONCLUSIONS
There is insufficient evidence to conclude that topical repellents can prevent malaria in settings where other vector control interventions are in place. We found the certainty of evidence for all outcomes to be low, primarily due to the risk of bias. A protective effect was suggested among high-risk populations, specially refugees, who might not have access to other standard vector control measures. More adequately powered clinical trials carried out in refugee camps could provide further information on the potential benefit of topical repellents in this setting. Individually randomized studies are also likely necessary to understand whether topical repellents have an effect on personal protection, and the degree to which diversion to non-protected participants affects overall transmission dynamics. Despite this, the potential additional benefits of topical repellents are most likely limited in contexts where other interventions are available.
Topics: Animals; Humans; Insecticides; Mosquito Vectors; Malaria, Falciparum; Controlled Before-After Studies; Culicidae
PubMed: 37602418
DOI: 10.1002/14651858.CD015422.pub2 -
Nutrients Aug 2023Vitamin E has an antioxidant property and is associated with protection against malaria. The current study used systematic review and meta-analysis approaches examining... (Meta-Analysis)
Meta-Analysis Review
Vitamin E has an antioxidant property and is associated with protection against malaria. The current study used systematic review and meta-analysis approaches examining the variance in blood levels of vitamin E in malaria patients as compared with uninfected individuals. The protocol for the systematic review was registered with PROSPERO (CRD4202341481). Searches for pertinent studies were carried out on Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar. The combined effect estimate (Cohen's d) of the difference in vitamin E levels in malaria patients as compared with uninfected individuals was estimated using the random effects model. The searches yielded 2009 records, and 23 studies were included in the systematic review. The majority of the studies (80%) found that vitamin E levels were significantly lower in malaria patients than those who were not infected. Overall, the results revealed a significant reduction in blood levels of vitamin E in malaria patients when compared with uninfected individuals ( < 0.01, Cohen's d: -2.74, 95% CI: -3.72-(-1.76), I: 98.69%, 21 studies). There was a significant reduction in blood levels of vitamin E in patients suffering from severe malaria, in comparison with those experiencing less severe forms of the disease ( < 0.01, Cohen's d: -0.56, 95% CI: -0.85-(-0.26), I: 0%, 2 studies), but no variation in blood levels of vitamin E among patients suffering from either or malaria ( = 0.13, Cohen's d: -1.15, 95% CI: -2.62-0.33, I: 93.22%, 3 studies). In summary, the present study strongly suggests that vitamin E levels are significantly reduced in malaria patients, with a more pronounced decrease observed in cases of severe malaria. However, the type of malaria parasite, specifically or , did not appear to influence the levels of vitamin E. This study highlights the potential role of vitamin E in the pathogenesis of malaria and suggests that improved vitamin E status might be beneficial for improving disease outcomes.
Topics: Humans; Vitamin E; Malaria; Malaria, Vivax; Antioxidants
PubMed: 37571409
DOI: 10.3390/nu15153472 -
Scientific Reports Jun 2023Asymptomatic Plasmodium infection raises a problem for the persistent transmission of malaria in low-endemic areas such as Asia. This systematic review was undertaken to... (Meta-Analysis)
Meta-Analysis
Asymptomatic Plasmodium infection raises a problem for the persistent transmission of malaria in low-endemic areas such as Asia. This systematic review was undertaken to estimate the prevalence and proportion of asymptomatic Plasmodium infection in Asia. The systematic review was registered at PROSPERO (ID: CRD42022373664). The research followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A comprehensive search of five databases, Ovid, Scopus, MEDLINE, PubMed, and Embase, was conducted to identify studies of asymptomatic Plasmodium infection in Asian countries. The pooled prevalence of asymptomatic Plasmodium infection, the pooled proportion of asymptomatic Plasmodium infection among all parasitised individuals, and the associated 95% confidence intervals were estimated using a random-effects model. A total of 916 articles were retrieved, and 87 articles that met the criteria were included in the systematic review. The pooled prevalence of asymptomatic Plasmodium infection among enrolled participants in Southeast Asia, South Asia, and Western Asia was 5.8%, 9.4%, and 8.4%, respectively. The pooled proportion of asymptomatic Plasmodium infection among all parasitised individuals in Southeast Asia, South Asia, and Western Asia was 89.3%, 87.2%, and 64.8%, respectively. There was a low prevalence of asymptomatic Plasmodium infection, but there was a high proportion of asymptomatic Plasmodium infection per all parasitised individuals in different parts of Asia. These results may support and facilitate elimination and control programs for asymptomatic Plasmodium infection in Asia.
Topics: Humans; Malaria, Falciparum; Prevalence; Malaria; Plasmodium; Asia; Asymptomatic Infections
PubMed: 37369862
DOI: 10.1038/s41598-023-37439-9 -
Tropical Medicine and Infectious Disease May 2023Disseminated intravascular coagulation (DIC) is a potentially life-threatening condition that causes systemic coagulation to be turned on and coagulation factors to be... (Review)
Review
Disseminated intravascular coagulation (DIC) is a potentially life-threatening condition that causes systemic coagulation to be turned on and coagulation factors to be used up. However, the evidence for DIC in malaria patients is still not clear, and small case series and retrospective studies have shown varying results. This meta-analysis was intended for the evaluation of the evidence of DIC among malaria patients using a meta-analysis approach. The protocol for the systematic review was registered at PROSPERO as CRD42023392194. Studies that investigated DIC in patients with malaria were searched in Ovid, Scopus, Embase, PubMed, and MEDLINE. The pooled proportion with 95% confidence intervals (CI) of DIC among malaria patients was estimated using a random-effects model. A total of 1837 articles were identified, and 38 articles were included in the meta-analysis. The overall proportion of DIC in malaria was 11.6% (95% CI: 8.9%-14.3%, I: 93.2%, 38 studies). DIC in severe malaria and fatal malaria was 14.6% (95% CI: 5.0-24.3%, I: 95.5%, 11 studies) and 82.2% (95% CI: 56.2-100%, I: 87.3, 4 studies). The estimates of DIC among severe malaria patients who had multi-organ dysfunction with bleeding, cerebral malaria, acute renal failure, and ≥2 complications were 79.6% (95% CI: 67.1-88.2%, one study), 11.9% (95% CI: 7.9-17.6%, one study), 16.7% (95% CI: 10.2-23.3%, ten studies), and 4.8% (95% CI: 1.9-7.7%, nine studies), respectively. The proportion estimates of DIC among the patients with malaria depended on the species, clinical severity, and types of severe complications. The information from this study provided useful information to guide the management of malaria patients. Future studies are needed to investigate the association between infection and DIC and to understand the mechanism of malaria-induced DIC.
PubMed: 37368707
DOI: 10.3390/tropicalmed8060289 -
Antioxidants & Redox Signaling Mar 2024It is still unclear how ascorbic acid levels relate to the pathogenesis of malaria. This systematic review synthesized different ascorbic acid levels in malaria... (Meta-Analysis)
Meta-Analysis
It is still unclear how ascorbic acid levels relate to the pathogenesis of malaria. This systematic review synthesized different ascorbic acid levels in malaria patients with different severity levels of malaria and species. The systematic review protocol was registered in the PROSPERO database (CRD42023394849). A systematic search of PubMed, Embase, MEDLINE, Ovid, Scopus, and Google Scholar was conducted to identify studies that reported ascorbic acid and malaria. The pooled standardized mean difference (Cohen's ) with 95% confidence intervals (CIs) was calculated using the random-effects model. A total of 1480 articles were obtained from the searches of the databases, and 30 studies were included for syntheses. The meta-analysis revealed that patients with malaria had lower levels of ascorbic acid than those without malaria or uninfected controls ( < 0.01, Cohen's = -3.71, 95% CI = -4.44 to -2.98, = 98.87%, 30 studies). Comparable levels of ascorbic acid were observed between patients with severe malaria and those with nonsevere malaria ( = 0.06, Cohen's = -1.39, 95% CI = -2.85 to 0.07, = 96.58%, 4 studies). Similarly, levels of ascorbic acid were comparable between patients with and malaria ( = 0.34, Cohen's = -1.06, 95% CI = -3.23 to 1.12, = 97.30%, 3 studies). The meta-analysis reveals diminished levels of ascorbic acid in malaria cases. Manipulating the host's nutritional status, such as by supplementing it with ascorbic acid to restore reactive oxygen species balance, may alter the progression of malarial infection and prevention of disease severity. 40, 460-469.
Topics: Humans; Malaria; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Systematic Reviews as Topic; Ascorbic Acid
PubMed: 37337659
DOI: 10.1089/ars.2023.0306 -
The Lancet. Global Health Jul 2023Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD).
METHODS
For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342.
FINDINGS
The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection.
INTERPRETATION
During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections.
FUNDING
Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.
Topics: Female; Humans; Pregnancy; Adult; Prevalence; Malaria; Antimalarials; Malaria, Falciparum; Risk Factors
PubMed: 37276878
DOI: 10.1016/S2214-109X(23)00194-8