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Tropical Medicine and Health Nov 2023The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at... (Review)
Review
CONTEXT
The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveys of malaria parasites carrying molecular markers of drug-resistance across the country.
METHODS
A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science).
RESULTS
We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparum clinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime, but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine-pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRN-GE mutants (i.e., parasites carrying the PfDHFR N51I-C59R-S108N and PfDHPS A437G-K540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates.
CONCLUSIONS
Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidence for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.
PubMed: 37968745
DOI: 10.1186/s41182-023-00551-7 -
The American Journal of Tropical... May 2024Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of...
Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of resources. We conducted a systematic search and review of publications in seven databases to compile resistance marker data from studies in India. The sample collection from the studies identified from this search was conducted between 1994 and 2020, and these studies were published between 1994 and 2022. In all, Plasmodium falciparum Kelch13 (PfK13), P. falciparum dihydropteroate synthase, and P. falciparum dihydrofolate reductase (PfDHPS) genotype data from 2,953, 4,148, and 4,222 blood samples from patients with laboratory-confirmed malaria, respectively, were extracted from these publications and uploaded onto the WorldWide Antimalarial Resistance Network molecular surveyors. These data were fed into hierarchical geostatistical models to produce maps with a predicted prevalence of the PfK13 and PfDHPS markers, and of the associated uncertainty. Zones with a predicted PfDHPS 540E prevalence of >15% were identified in central, eastern, and northeastern India. The predicted prevalence of PfK13 mutants was nonzero at only a few locations, but were within or adjacent to the zones with >15% prevalence of PfDHPS 540E. There may be a greater probability of artesunate-sulfadoxine-pyrimethamine failures in these regions, but these predictions need confirmation. This work can be applied in India and elsewhere to help identify the treatments most likely to be effective for malaria elimination.
Topics: Plasmodium falciparum; Pyrimethamine; Sulfadoxine; India; Drug Resistance; Antimalarials; Drug Combinations; Humans; Malaria, Falciparum; Artemisinins; Tetrahydrofolate Dehydrogenase; Genetic Markers; Dihydropteroate Synthase; Protozoan Proteins
PubMed: 38574550
DOI: 10.4269/ajtmh.23-0631 -
Scientific Reports May 2024Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across... (Meta-Analysis)
Meta-Analysis
Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across different severities and between Plasmodium falciparum and P. vivax, this study aimed to synthesize available evidence on PT variations in clinical malaria. A systematic literature search was performed in PubMed, Embase, Scopus, Ovid, and Medline from 27 November 2021 to 2 March 2023 to obtain studies documenting PT in malaria. Study quality was evaluated using the Joanna Briggs Institute checklist, with data synthesized through both qualitative and quantitative methods, including meta-regression and subgroup analyses, to explore heterogeneity and publication bias. From 2767 articles, 21 studies were included. Most studies reported prolonged or increased PT in malaria patients compared to controls, a finding substantiated by the meta-analysis (P < 0.01, Mean difference: 8.86 s, 95% CI 5.32-12.40 s, I: 87.88%, 4 studies). Severe malaria cases also showed significantly higher PT than non-severe ones (P = 0.03, Hedges's g: 1.65, 95% CI 0.20-3.10, I: 97.91%, 7 studies). No significant PT difference was observed between P. falciparum and P. vivax infections (P = 0.88, Mean difference: 0.06, 95% CI - 0.691-0.8, I: 65.09%, 2 studies). The relationship between PT and malaria-related mortality remains unclear, underscoring the need for further studies. PT is typically prolonged or increased in malaria, particularly in severe cases, with no notable difference between P. falciparum and P. vivax infections. The inconsistency in PT findings between fatal and non-fatal cases highlights a gap in current understanding, emphasizing the need for future studies to inform therapeutic strategies.
Topics: Humans; Malaria, Vivax; Malaria, Falciparum; Plasmodium vivax; Plasmodium falciparum; Prothrombin Time; Severity of Illness Index
PubMed: 38698102
DOI: 10.1038/s41598-024-60170-y -
Scientific Reports Feb 2024Reports indicate that Plasmodium infections influence methemoglobin levels. However, findings have been inconclusive or have varied across different geographic and... (Meta-Analysis)
Meta-Analysis
Reports indicate that Plasmodium infections influence methemoglobin levels. However, findings have been inconclusive or have varied across different geographic and demographic contexts. This systematic review and meta-analysis aimed to consolidate existing data regarding the association between Plasmodium infections and alterations in methemoglobin levels related to the severity of the infection. A comprehensive literature search of several databases, including Ovid, ProQuest, Embase, Scopus, MEDLINE, and PubMed, was conducted to identify relevant studies that examined methemoglobin levels in patients with malaria. Qualitative synthesis and meta-analysis of the pooled standardized mean difference were conducted to synthesize the differences in methemoglobin levels between: (1) patients with malaria and those without malaria and (2) patients with severe malaria and those with uncomplicated malaria based on various themes including publication year, study design, study area, Plasmodium species, age group, symptomatic status, severity status, and method of malaria detection. Of the 1846 studies that were initially identified from the main databases and additional searches on Google Scholar, 10 studies met the eligibility criteria and were selected for this review. The systematic review distinctly highlighted an association between malaria and elevated methemoglobin levels, an observation consistent across diverse geographical regions and various Plasmodium species. Furthermore, the meta-analysis confirmed this by demonstrating increased methemoglobin levels in patients with malaria compared to those without malaria (P < 0.001, Hedges' g 2.32, 95% CI 1.36-3.29, I 97.27, 8 studies). Moreover, the meta-analysis found elevated methemoglobin levels in patients with severe malaria compared to those with uncomplicated malaria (P < 0.001, Hedges' g 2.20, 95% CI 0.82-3.58, I 96.20, 5 studies). This systematic review and meta-analysis revealed increased methemoglobin levels in patients with P. falciparum and P. vivax infections, with a notable association between elevated methemoglobin levels and severe malaria. Future research should focus on elucidating the specific mechanisms by which changes in methemoglobin levels are related to infections by P. falciparum and P. vivax, particularly in terms of severity, and how these alterations could potentially impact patient management and treatment outcomes.
Topics: Humans; Plasmodium falciparum; Plasmodium vivax; Methemoglobin; Malaria; Malaria, Vivax; Malaria, Falciparum; Plasmodium; Patient Acuity
PubMed: 38332023
DOI: 10.1038/s41598-024-53741-6 -
Parasite Epidemiology and Control Feb 2024Asymptomatic malaria during pregnancy is a significant public health concern in malaria-endemic regions, which worsens the various effects of malaria on the mother and... (Review)
Review
BACKGROUND
Asymptomatic malaria during pregnancy is a significant public health concern in malaria-endemic regions, which worsens the various effects of malaria on the mother and fetus and increases maternal and neonatal mortality. To date, no meta-analysis has been conducted on asymptomatic malaria in pregnant women in Ethiopia. Thus, we aimed to estimate the pooled prevalence of asymptomatic malaria and its associated factors in pregnant women in Ethiopia.
METHODS
PubMed/Medline, Google Scholar, Web of Science, Cochrane, AJOL, and Ethiopian University repositories were systematically searched to identify studies reporting the prevalence of asymptomatic malaria infection among pregnant women in Ethiopia. A random effects model was used to perform the analysis. The heterogeneity of the studies was assessed with the I-squared tests, and subgroup analyses were performed to identify the sources of heterogeneity.
RESULTS
Ten articles with 3277 study participants were included in this review. The pooled prevalence of asymptomatic malaria infection among pregnant women in Ethiopia was 7.03% (95% CI: 6.23-9.12); I = 81.2%). In the species-specific pooled prevalence estimate, Plasmodium falciparum prevalence was 5.34% (95%CI: 3.38-7.3; I2 = 87.8%), and Plasmodium vivax prevalence was 1.69% (95%CI: 1.2-5; I2 = 91.5%).Not using insecticide-treated bed nets [OR = 7.36, 95% CI (2.75, 19.73)], being primi-gravida [OR = 1.86, 95% CI (1.23, 2.82)]; lack of health education about malaria prevention [OR = 6.86, 95% CI (2.90, 11.44)] were predictors of asymptomatic malaria infection during pregnancy.
CONCLUSION
This study revealed that asymptomatic malaria was prevalent among pregnant women in Ethiopia. This suggests that relying merely on reported symptoms may result in missed malaria cases. Therefore, regular screening and treatment protocols for malaria are recommended in antenatal care. It is also crucial to ensure that pregnant women have access to insecticide-treated bed nets and other effective malaria prevention measures.
PubMed: 38323191
DOI: 10.1016/j.parepi.2024.e00339 -
PeerJ 2024COVID-19 and malaria cause significant morbidity and mortality globally. Co-infection of these diseases can worsen their impact on public health. This review aims to...
BACKGROUND
COVID-19 and malaria cause significant morbidity and mortality globally. Co-infection of these diseases can worsen their impact on public health. This review aims to synthesize literature on the clinical outcomes of COVID-19 and malaria co-infection to develop effective prevention and treatment strategies.
METHODS
A comprehensive literature search was conducted using MeSH terms and keywords from the start of the COVID-19 pandemic to January 2023. The review included original articles on COVID-19 and malaria co-infection, evaluating their methodological quality and certainty of evidence. It was registered in PROSPERO (CRD42023393562).
RESULTS
Out of 1,596 screened articles, 19 met the inclusion criteria. These studies involved 2,810 patients, 618 of whom had COVID-19 and malaria co-infection. Plasmodium falciparum and vivax were identified as causative organisms in six studies. Hospital admission ranged from three to 18 days. Nine studies associated co-infection with severe disease, ICU admission, assisted ventilation, and related complications. One study reported 6% ICU admission, and mortality rates of 3%, 9.4%, and 40.4% were observed in four studies. Estimated crude mortality rates were 10.71 and 5.87 per 1,000 person-days for patients with and without concurrent malaria, respectively. Common co-morbidities included Diabetes mellitus, hypertension, cardiovascular diseases, and respiratory disorders.
CONCLUSION
Most patients with COVID-19 and malaria co-infection experienced short-term hospitalization and mild to moderate disease severity. However, at presentation, co-morbidities and severe malaria were significantly associated with higher mortality or worse clinical outcomes. These findings emphasize the importance of early detection, prompt treatment, and close monitoring of patients with COVID-19 and malaria co-infection.
Topics: Humans; COVID-19; Coinfection; Malaria; SARS-CoV-2; Hospitalization; Comorbidity; Malaria, Falciparum
PubMed: 38646476
DOI: 10.7717/peerj.17160 -
Malaria Journal Oct 2023Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa.
METHODS
Relevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates.
RESULTS
Twenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide, Plasmodium falciparum and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008-2013 to 3.8% during 2014-2017 and to 5.5% during 2018-2021 (p = 0.0414).
CONCLUSION
There was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions. Protocol registration number: CRD42022311301.
Topics: Humans; Dengue Virus; Coinfection; Dengue; Cross-Sectional Studies; Prevalence; Malaria; Africa; Fever
PubMed: 37803381
DOI: 10.1186/s12936-023-04723-y -
Imported malaria in pregnancy in Europe: A systematic review of the literature of the last 25 years.Travel Medicine and Infectious Disease 2023Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases... (Review)
Review
BACKGROUND
Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases of malaria in pregnant women in Europe and evaluate which factors are associated with a non-favourable outcome.
METHODS
A computerized search of the literature was performed combining the terms plasmod*, malaria, pregnan*, maternal, gravid, parturient, expectant, and congenital, from January 1997 to July 2023.
RESULTS
28 articles reporting 57 cases of malaria in pregnant women immigrant in non-endemic areas were included. The patients mainly came from Sub-Saharan Africa. There were 10 asymptomatic cases, while the predominant clinical syndrome among the symptomatic women was fever associated with anaemia. The median latency period from permanence in endemic areas and diagnosis in European countries was 180 days (IQR 15-730). Pregnancy outcomes were favourable in 35 cases (61 %): all term pregnancies, no low-birth-weight newborns. There were 4 abortions; 1 child was delivered pre-term; 7 babies were reported to have a low birth weight; 10 cases of congenital malaria were documented. P. falciparum was found with a higher frequency in women with a favourable outcome, while P. vivax was, in all cases, associated with a worse prognosis.
CONCLUSIONS
Diagnosis of malaria in pregnant woman in non-endemic countries may be challenging and a delay in diagnosis may lead to an adverse outcome. Screening for malaria should be performed in pregnant women from endemic areas, especially if they present anaemia or fever.
Topics: Child; Female; Pregnancy; Infant, Newborn; Humans; Malaria; Malaria, Falciparum; Pregnancy Outcome; Malaria, Vivax; Anemia; Europe
PubMed: 38008239
DOI: 10.1016/j.tmaid.2023.102673 -
The American Journal of Tropical... Apr 2024Malaria remains a significant cause of morbidity and mortality, even in low-transmission settings. With the advent of longer acting, more effective, and well-tolerated... (Meta-Analysis)
Meta-Analysis
Malaria remains a significant cause of morbidity and mortality, even in low-transmission settings. With the advent of longer acting, more effective, and well-tolerated antimalarials, there is renewed interest in the efficacy of mass drug administration (MDA) to accelerate to elimination. We conducted a systematic review and meta-analysis to assess the efficacy of MDA to reduce the incidence and prevalence of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) infection. From 1,044 articles screened, 14 articles, including 10 randomized controlled trials (RCTs), were identified. Five included data on Pf only; five included Pf and Pv. Two of the Pf studies were conducted in areas of high-moderate transmission, the remainder were in areas of low-very low transmission. In higher transmission areas, MDA reduced incidence of Pf parasitemia (rate ratio = 0.61, 95% CI: 0.40-0.92; moderate certainty) 1 to 3 months after drug administration; no significant effect of MDA on Pf parasitemia prevalence was detected 1 to 3 months post-MDA (risk ratio [RR] = 1.76, 95% CI: 0.58-5.36; low certainty). In lower transmission settings, both incidence and prevalence of Pf parasitemia were reduced 1 to 3 months post-MDA (rate ratio = 0.37, 95% CI: 0.21-0.66; RR = 0.25, 95% CI: 0.15-0.41, respectively). Pv prevalence was reduced 1 to 3 months post-MDA (RR = 0.15, 95% CI: 0.10-0.24); there were no RCTs providing data on incidence of Pv. There was no significant effect of MDA at later time points. MDA may have short-term benefits; however, there was no evidence for longer term impact, although none of the trials assessed prolonged interventions.
Topics: Humans; Mass Drug Administration; Parasitemia; Antimalarials; Malaria; Malaria, Vivax; Plasmodium falciparum
PubMed: 38118174
DOI: 10.4269/ajtmh.22-0766 -
Tropical Medicine and Health Jan 2024Malaria remains a significant cause of morbidity and mortality globally and continues to disproportionately afflict the African population. We aimed to evaluate the...
BACKGROUND
Malaria remains a significant cause of morbidity and mortality globally and continues to disproportionately afflict the African population. We aimed to evaluate the effect of home management of malaria intervention on health outcomes.
METHODS
In our systematic review and meta-analysis, six databases (Pubmed, Cochrane CENTRAL, EMBASE, CAB Abstracts and Global Health, CINAHL Complete, and BIOSIS) were searched for studies of home management of malaria from inception until November 15, 2023. We included before-after studies, observational studies, and randomised controlled trials of home management intervention delivered in community settings. The primary outcomes were malaria mortality and all-cause mortality. The risk of bias in individual observational studies was assessed using the ROBINS-I tool, whilst randomised controlled trials were judged using a revised Cochrane risk of bias tool and cluster-randomised controlled trials were evaluated using an adapted Cochrane risk of bias tool for cluster-randomised trials. We computed risk ratios with accompanying 95% confidence intervals for health-related outcomes reported in the studies and subsequently pooled the results by using a random-effects model (DerSimonian-Laird method).
RESULTS
We identified 1203 citations through database and hand searches, from which 56 articles from 47 studies encompassing 234,002 participants were included in the systematic review. All studies were conducted in people living in sub-Saharan Africa and were rated to have a low or moderate risk of bias. Pooled analyses showed that mortality rates due to malaria (RR = 0.40, 95% CI = 0.29-0.54, P = 0.00001, I = 0%) and all-cause mortality rates (RR = 0.62, 95% CI = 0.53-0.72, P = 0.00001, I = 0%) were significantly lower among participants receiving home management intervention compared to the control group. However, in children under 5 years of age, there was no significant difference in mortality rates before and after implementation of home management of malaria. In terms of secondary outcomes, home management of malaria was associated with a reduction in the risk of febrile episodes (RR = 1.27, 95% CI = 1.09-1.47, P = 0.002, I = 97%) and higher effective rates of antimalarial treatments (RR = 2.72, 95% CI = 1.90-3.88, P < 0.00001, I = 96%) compared to standard care. Home malaria management combined with intermittent preventive treatment showed a significantly lower incidence risk of malaria than home management intervention that exclusively provided treatment to individuals with febrile illness suggestive of malaria. The risks for adverse events were found to be similar for home management intervention using different antimalarial drugs. Cost-effectiveness findings depicted that home malaria management merited special preferential scale-up.
CONCLUSIONS
Home management of malaria intervention was associated with significant reductions in malaria mortality and all-cause mortality. The intervention could help decrease health and economic burden attributable to malaria. Further clinical studies are warranted to enable more meaningful interpretations with regard to wide-scale implementation of the intervention, settings of differing transmission intensity, and new antimalarial drugs.
PubMed: 38191459
DOI: 10.1186/s41182-023-00572-2