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Diagnostics (Basel, Switzerland) Mar 2021Rapid diagnostic tests (RDTs) have become a mainstay of malaria diagnosis in endemic countries since their implementation in the 1990s. We conducted a 30-year systematic... (Review)
Review
Rapid diagnostic tests (RDTs) have become a mainstay of malaria diagnosis in endemic countries since their implementation in the 1990s. We conducted a 30-year systematic review and meta-analysis on malaria RDTs performance in India. Outcomes of interest were sensitivity (Se), specificity (Sp), positive/negative likelihood ratio (PLR/NLR), and diagnostic odd ratio (DOR). Among the 75 studies included, most of the studies were cross-sectional (65.3%), hospital-based (77.3%), and targeted febrile patients (90.6%). Nearly half of RDTs were designed for detecting only (47.5%) while the rest were for and (11.9%), and /Pan- except for (32.3%). When compared to light microscopy (gold standard), pooled estimates of performances were: Se = 97.0%, Sp = 96.0%, PLR = 22.4, NLR = 0.02 and DOR = 1080. In comparison to polymerase chain reaction, the RDTs showed Se = 89.0% and Sp = 99.0%. Performance outcomes (Se and Sp) were similar for RDT targeting only, but decreased for mixed and non-falciparum infections. Performances of malaria RDTs are still high India. However, there is a need for developing RDTs with regard to targeting minor malarial species, individuals carrying only mature gametocytes, and -deleted parasites.
PubMed: 33806066
DOI: 10.3390/diagnostics11040590 -
Malaria Journal Apr 2021The emergence of artemisinin resistance in Southeast Asia and Plasmodium falciparum kelch13 propeller gene mutations in sub-Saharan African pose the greatest threat to... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of dihydroartemisinin-piperaquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ugandan children: a systematic review and meta-analysis of randomized control trials.
BACKGROUND
The emergence of artemisinin resistance in Southeast Asia and Plasmodium falciparum kelch13 propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria. This is a critical concern in Uganda, where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum. The objective of this study was to compare the efficacy and safety of dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Ugandan children.
METHODS
A search of PubMed and the Cochrane Central Register of Controlled Trials for retrieving randomized controlled trials comparing the efficacy and safety of DHA-PQ and AL for treatment of uncomplicated falciparum malaria in Ugandan children was done. The search was performed up to 31 August 2020. The data extracted from eligible studies and pooled as risk ratio (RR) with a 95% confidence interval (CI), using Rev Man Software (5.4). The protocol was registered in PROSPERO, ID: CRD42020182354.
RESULTS
Eleven trials were included in this review and two of them only included under safety outcome. Total 3798 participants were enrolled. The PCR unadjusted treatment failure was significantly lower with DHA-PQ at day 28 (RR 0.30, 95% CI 0.19-0.49; participants = 7863; studies = 5; I = 93%, low quality evidence) and at day 42 (RR 0.53, 95% CI 0.38-0.76; participants = 1618; studies = 4; I = 79%, moderate quality of evidence). The PCR adjusted treatment failure at day 42 was significantly lower with DHA-PQ treatment group (RR 0.45, 95% CI 0.28 to 0.72; participants = 1370; studies = 5, high quality of evidence), and it was below 5% in both arms at day 28 (moderate quality of evidence). AL showed a longer prophylactic effect on new infections which may last for up to 63 days (PCR-adjusted treatment failure: RR 2.04, 95% CI 1.13-3.70; participants = 1311; studies = 2, moderate quality of evidence). Compared to AL, DHA-PQ was associated with a slightly higher frequency of cough (RR 1.07, 95% CI 1.01 to 1.13; 2575 participants; six studies; high quality of evidence). In both treatment groups, the risk of recurrent parasitaemia due to possible recrudescence was less than 5% at day 28. The appearance of gametocyte between 29 and 42 days was also significantly lower in DHA-PQ than AL (RR 0.26, 95% CI 0.12 to 0.56; participants = 623; studies = 2; I = 0%).
CONCLUSION
Compared to AL, DHA-PQ appeared to reduce treatment failure and gametocyte carriage in Ugandan children. This may trigger DHA-PQ to become the first-line treatment option. Both treatments were safe and well-tolerated.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Child, Preschool; Drug Combinations; Humans; Infant; Malaria, Falciparum; Quinolines; Randomized Controlled Trials as Topic; Uganda
PubMed: 33794897
DOI: 10.1186/s12936-021-03711-4 -
PloS One 2021In Sub-Saharan Africa (SSA), where malaria transmission is stable, malaria infection in pregnancy adversely affects pregnant women, fetuses, and newborns and is often... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In Sub-Saharan Africa (SSA), where malaria transmission is stable, malaria infection in pregnancy adversely affects pregnant women, fetuses, and newborns and is often asymptomatic. So far, a plethora of primary studies have been carried out on asymptomatic malaria infection in pregnant women in SSA. Nevertheless, no meta-analysis estimated the burden of asymptomatic malaria infection in pregnant women in SSA, so this meta-analysis was carried out to bridge this gap.
METHODS
PubMed, Web of Science, Scopus, Embase, and ProQuest were systematically searched for relevant studies published until 4 August 2020, and also the expansion of the search was performed by October 24, 2020. We assessed heterogeneity among included studies using I-squared statistics (I2). Publication bias was assessed by visual inspection of the funnel plot and further quantitatively validated by Egger's and Begg's tests. The pooled prevalence and pooled odds ratio (OR) and their corresponding 95% Confidence Interval (CI) were estimated using the random-effects model in Stata 15 software.
RESULTS
For this meta-analysis, we included 35 eligible studies. The overall prevalence estimate of asymptomatic Plasmodium infection prevalence was 26.1%% (95%CI: 21-31.2%, I2 = 99.0%). According to species-specific pooled prevalence estimate, Plasmodium falciparum was dominant species (22.1%, 95%CI: 17.1-27.2%, I2 = 98.6%), followed by Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, respectively, found to be 3% (95%CI: 0-5%, I2 = 88.3%), 0.8% (95%CI: 0.3-0.13%, I2 = 60.5%), and 0.2% (95%CI: -0.01-0.5%, I2 = 31.5%). Asymptomatic malaria-infected pregnant women were 2.28 times more likely anemic (OR = 2.28, 95%CI: 1.66-3.13, I2 = 56.3%) than in non-infected pregnant women. Asymptomatic malaria infection was 1.54 times higher (OR = 1.54, 95%CI: 1.28-1.85, I2 = 11.5%) in primigravida women compared to multigravida women.
CONCLUSION
In SSA, asymptomatic malaria infection in pregnant women is prevalent, and it is associated with an increased likelihood of anemia compared to non-infected pregnant women. Thus, screening of asymptomatic pregnant women for malaria and anemia should be included as part of antenatal care.
Topics: Africa South of the Sahara; Asymptomatic Infections; Coinfection; Female; Humans; Malaria; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Prenatal Care; Prevalence
PubMed: 33793584
DOI: 10.1371/journal.pone.0248245 -
The American Journal of Tropical... Mar 2021Recent studies have suggested that malaria may affect the cardiovascular system. The aim of this systematic review and meta-analysis was to determine the prevalence of... (Meta-Analysis)
Meta-Analysis
Recent studies have suggested that malaria may affect the cardiovascular system. The aim of this systematic review and meta-analysis was to determine the prevalence of cardiovascular complications in symptomatic malaria patients. We searched databases such as Pubmed, Embase, Cochrane, and Web of Science (January 1950-April 2020) for studies reporting on cardiovascular complications in adults and children with malaria. Cardiovascular complications were defined as abnormalities in electrocardiogram (ECG), cardiac biomarkers, and echocardiography on admission or during outpatient examination. Studies of patients with known heart disease or cardiovascular evaluation performed after the start of intravenous antimalarial medication were excluded. The study was registered in International Prospective Register of Systematic Reviews (PROSPERO) (No.: CRD42020167672). The literature search yielded 1,243 studies, and a total of 43 studies with symptomatic malaria patients were included. Clinical studies (n = 12 adults; n = 5 children) comprised 3,117 patients, of which a majority had Plasmodium falciparum (n = 15) and were diagnosed with severe malaria (n = 13). In random-effects models of adults, the pooled prevalence estimate for any cardiovascular complication was 7% (95% CI: 5-9). No meta-analysis was conducted in children, but the range of abnormal ECG was 0-8%, cardiac biomarkers 0-57%, and echocardiography 4-9%. We analyzed 33 cases (n = 10 postmortem), in which the most common cardiovascular pathologies were myocarditis and acute coronary syndrome. All histopathological studies found evidence of parasitized red blood cells in the myocardium. Cardiovascular complications are not uncommon in symptomatic adults and children with malaria. Additional studies investigating malaria and cardiovascular disease are encouraged.
Topics: Acute Coronary Syndrome; Adult; Child; Electrocardiography; Erythrocytes; Humans; Malaria, Falciparum; Malaria, Vivax; Myocarditis; Myocardium; Plasmodium falciparum; Plasmodium vivax; Prevalence; Severity of Illness Index
PubMed: 33724926
DOI: 10.4269/ajtmh.20-1414 -
The American Journal of Tropical... Mar 2021Antimalarials, in particular artemisinin-based combination therapies (ACTs), are critical tools in reducing the global burden of malaria, which is concentrated in...
Antimalarials, in particular artemisinin-based combination therapies (ACTs), are critical tools in reducing the global burden of malaria, which is concentrated in sub-Saharan Africa. Performing and reporting antimalarial efficacy studies in a transparent and standardized fashion permit comparison of efficacy outcomes across countries and time periods. This systematic review summarizes study compliance with WHO laboratory and reporting guidance pertaining to antimalarial therapeutic efficacy studies and evaluates how well studies from sub-Saharan Africa adhered to these guidelines. We included all published studies (January 2020 or before) performed in sub-Saharan Africa where ACT efficacy for treatment of uncomplicated Plasmodium falciparum infection was reported. The primary outcome was a composite indicator for study methodology consistent with WHO guidelines for statistical analysis of corrected efficacy, defined as an article presenting a Kaplan-Meier survival analysis of corrected efficacy or reporting a per-protocol analysis where new infections were excluded from the numerator and denominator. Of 581 articles screened, we identified 279 for the review. Molecular correction was used in 83% (232/279) to distinguish new infections from recrudescences in subjects experiencing recurrent parasitemia. Only 45% (99/221) of articles with therapeutic efficacy as a primary outcome and performing molecular correction reported corrected efficacy outcomes calculated in a way consistent with WHO recommendations. These results indicate a widespread lack of compliance with WHO-recommended methods of analysis, which may result in biases in how antimalarial effectiveness is being measured and reported from sub-Saharan Africa.
Topics: Africa South of the Sahara; Analysis of Variance; Antimalarials; Artemisinins; Data Interpretation, Statistical; Drug Resistance; Guideline Adherence; Guidelines as Topic; Humans; Kaplan-Meier Estimate; Malaria, Falciparum; Plasmodium falciparum; Recurrence; Treatment Outcome
PubMed: 33724925
DOI: 10.4269/ajtmh.20-1481 -
Marine Drugs Feb 2021Malaria is an infectious disease caused by protozoan parasites of the genus through the bite of female Anopheles mosquitoes, affecting 228 million people and causing...
Malaria is an infectious disease caused by protozoan parasites of the genus through the bite of female Anopheles mosquitoes, affecting 228 million people and causing 415 thousand deaths in 2018. Artemisinin-based combination therapies (ACTs) are the most recommended treatment for malaria; however, the emergence of multidrug resistance has unfortunately limited their effects and challenged the field. In this context, the ocean and its rich biodiversity have emerged as a very promising resource of bioactive compounds and secondary metabolites from different marine organisms. This systematic review of the literature focuses on the advances achieved in the search for new antimalarials from marine sponges, which are ancient organisms that developed defense mechanisms in a hostile environment. The principal inclusion criterion for analysis was articles with compounds with IC below 10 µM or 10 µg/mL against culture. The secondary metabolites identified include alkaloids, terpenoids, polyketides endoperoxides and glycosphingolipids. The structural features of active compounds selected in this review may be an interesting scaffold to inspire synthetic development of new antimalarials for selectively targeting parasite cell metabolism.
Topics: Animals; Antimalarials; Drug Development; Drug Resistance, Multiple; Humans; Inhibitory Concentration 50; Malaria, Falciparum; Plasmodium falciparum; Porifera; Secondary Metabolism
PubMed: 33670878
DOI: 10.3390/md19030134 -
Journal of the American College of... Mar 2021As one of the tropical diseases, malaria is endemic in developing countries. Severe malaria, mainly caused by the Plasmodium falciparum parasite, can result in...
As one of the tropical diseases, malaria is endemic in developing countries. Severe malaria, mainly caused by the Plasmodium falciparum parasite, can result in life-threatening complications. Traditionally, cardiac involvement has not been included as a frequent cause of morbidity and mortality. This could be due to under-reporting or underdiagnosing. Specific cardiovascular (CV) complications include electrocardiogram abnormalities, myocarditis, pericarditis, pericardial effusion, ischemic disease, and heart failure. According to the data analyzed, CV manifestations can lead to severe consequences. Possible theories related to the pathophysiological mechanisms related to CV compromise include an imbalanced pro-inflammatory cytokine response and/or erythrocyte sequestration by increased cytoadherence to endothelium. Although there is a paucity of data regarding cardiac manifestations of malaria, an algorithm for appropriate use of diagnostic tools to assess cardiac involvement has been developed in this paper. Furthermore, it is important to note that typical antimalarial treatment regimens can have fatal cardiac side-effects.
Topics: Algorithms; Anemia; Antimalarials; Cytokines; Heart Diseases; Humans; Incidence; Malaria; Prevalence
PubMed: 33632486
DOI: 10.1016/j.jacc.2020.12.042 -
PLoS Neglected Tropical Diseases Feb 2021Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries.
METHODOLOGY/PRINCIPAL FINDINGS
We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in endemic countries. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane's Q and evaluated the severity of heterogeneity using I2 statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger's test (bias if p<0.1). Fifty-five of the 3,507 citations screened were eligible, 28 of which had sufficient data for meta-analysis. The 28 studies enrolled 22, 114 children in 13 countries across sub-Saharan Africa, Southeast Asia and South America. Overall, the pooled estimates showed a prevalence of Plasmodium-helminth co-infections of 17.7% (95% CI 12.7-23.2%). Summary estimates from 14 studies showed a lower odds of P. falciparum infection in children co-infected with Schistosoma spp (OR: 0.65; 95%CI: 0.37-1.16). Similar lower odds of P. falciparum infection were observed from the summary estimates of 24 studies in children co-infected with soil transmitted helminths (STH) (OR: 0.42; 95%CI: 0.28-0.64). When adjusted for age, gender, socio-economic status, nutritional status and geographic location of the children, the risk of P. falciparum infection in children co-infected with STH was higher compared with children who did not have STH infection (OR = 1.3; 95% CI 1.03-1.65). A subset of 16 studies showed that the odds of anaemia were higher in children co-infected with Plasmodium and STH than in children with Plasmodium infection alone (OR = 1.20; 95% CI: 0.59-2.45), and were almost equal in children co-infected with Plasmodium-Schistosoma spp or Plasmodium infection alone (OR = 0.97, 95% CI: 0.30-3.14).
CONCLUSIONS/SIGNIFICANCE
The current review suggests that prevalence of malaria-helminth co-infection is high in children living in endemic countries. The nature of the interactions between malaria and helminth infection and the impact of the co-infection on anaemia remain inconclusive and may be modulated by the immune responses of the affected children.
Topics: Adolescent; Anemia; Animals; Child; Child, Preschool; Coinfection; Female; Helminthiasis; Helminths; Humans; Infant; Malaria; Male; Plasmodium; Prevalence; Soil
PubMed: 33600494
DOI: 10.1371/journal.pntd.0009138 -
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 -
International Journal of Environmental... Jan 2021Coinfection of malaria and intestinal helminths affects one third of the global population, largely among communities with severe poverty. The spread of these parasitic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Coinfection of malaria and intestinal helminths affects one third of the global population, largely among communities with severe poverty. The spread of these parasitic infections overlays in several epidemiological locations and the host shows different outcomes. This systematic review and meta-analysis determine the pooled prevalence of malaria and intestinal helminthiases coinfections among malaria suspected patients in Ethiopia.
METHODS
Primary studies published in English language were retrieved using appropriate search terms on Google Scholar, PubMed/MEDLINE, CINHAL, Scopus, and Embase. The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used for critical appraisal of studies. A pooled statistical meta-analysis was conducted using STATA Version 14.0 software. The heterogeneity and publication bias were assessed using the I2 statistics and Egger's test, respectively. Duval and Tweedie's nonparametric trim and fill analysis using the random-effect analysis. The Random effects model was used to estimate the summary prevalence of comorbidity of malaria and soil transmitted helminthiases and the corresponding 95% confidence intervals (CI). The review protocol has registered in PROSPERO number CRD42019144803.
RESULTS
We identified ten studies ( = 6633 participants) in this study. The overall pooled result showed 13% of the ambulatory patients infected by malaria and intestinal helminths concurrently in Ethiopia. The pooled prevalence of and , and mixed infections were 12, 30, and 6%, respectively. The most common intestinal helminth parasites detected were , , and .
CONCLUSIONS
The comorbidity of malaria and intestinal helminths causes lower hemoglobin level leading to maternal anemia, preterm delivery, and still birth in pregnant women and lactating mother. School-aged children and neonates coinfected by plasmodium species and soil transmitted helminths develop cognitive impairment, protein energy malnutrition, low birth weight, small for gestational age, and gross motor delay. The Ministry of Health of Ethiopia and its international partners working on malaria elimination programs should give more emphasis to the effect of the interface of malaria and soil transmitted helminths, which calls for an integrated disease control and prevention.
Topics: Animals; Child; Comorbidity; Ethiopia; Female; Health Facilities; Helminths; Humans; Infant, Newborn; Lactation; Malaria; Outpatients; Pregnancy; Prevalence
PubMed: 33498343
DOI: 10.3390/ijerph18030862