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Nutrients Nov 2023Micronutrient insufficiency has been implicated in malaria pathogenesis. However, the role of copper in malaria remains inconclusive. This study aimed to investigate the... (Meta-Analysis)
Meta-Analysis
Micronutrient insufficiency has been implicated in malaria pathogenesis. However, the role of copper in malaria remains inconclusive. This study aimed to investigate the association between copper levels and malaria pathogenesis, providing a deeper understanding of copper's role in the disease. A systematic review was conducted following the registered protocol in PROSPERO (CRD42023439732). Multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, and Google Scholar, were searched for relevant studies reporting blood copper levels in patients with malaria. The Joanna Briggs Institute critical appraisal checklist was used for assessing methodological quality. Qualitative and quantitative syntheses were employed, organizing, and summarizing the findings of the included studies. To calculate the standardized mean difference (Hedge's g) and 95% confidence intervals (CIs), a random-effects model was used. After screening the databases, 16 studies were included. Most studies (52.9%) reported that individuals with malaria had significantly higher copper levels than uninfected controls. The meta-analysis, based on 16 studies, showed no significant difference in copper levels between patients with malaria and uninfected controls overall ( = 0.39; Hedges' g, 0.38; 95% CI, -0.48 to 1.25; , 98.73%). Subgroup analysis showed a significant difference in copper levels between patients with malaria and uninfected controls among studies conducted in Asia ( < 0.01; Hedges' g, 1.74; 95% CI, 1.04 to 2.44; , 90.88%; five studies) and studies employing plasma blood samples ( < 0.01; Hedges' g, 1.13; 95% CI, 0.60 to 2.07; , 93.11%; four studies). The qualitative synthesis of the reviewed studies suggests a complex relationship between copper levels and malaria. The meta-analysis results showed no significant difference in copper levels between patients with malaria and uninfected controls overall. However, subgroup analyses based on various factors, including continent and blood sample type, showed copper level variations. These findings highlight the need for further research to better understand the role of copper in malaria pathogenesis by considering geographical factors and the blood sample type used for copper level measurement.
Topics: Humans; Copper; Malaria; Asia
PubMed: 38004142
DOI: 10.3390/nu15224749 -
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 -
Nutrients Oct 2023Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to... (Meta-Analysis)
Meta-Analysis
Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to synthesize the evidence on the association between blood calcium levels and malaria severity. A systematic literature search was conducted in the Embase, Scopus, PubMed, Ovid, and Google Scholar databases. The studies that investigated calcium levels in participants with malaria were reviewed and included for synthesis. The quality of included studies was assessed based on a standardized checklist by the Joanna Briggs Institute (JBI) critical appraisal checklists. The thematic synthesis had been used for qualitative synthesis. For the quantitative synthesis, the meta-analysis was performed to estimate the pooled effect sizes for differences in calcium levels between groups of participants using a random effect model using Hedge's g as a measure of effect size. Out of the 4574 identified records, 14 studies were reviewed. The thematic synthesis across these studies noted a consistent theme: reduced calcium levels in malaria patients compared to uninfected controls. However, the meta-analysis encompassing three specific analyses-comparing calcium levels between malaria patients and controls, severe and non-severe malaria cases, and fatal cases versus survivors-showed no significant difference in calcium levels. The statistics were as follows: (1) = 0.15, Hedge's g: -1.00, 95% CI: -2.37-0.38, : 98.97, 9 studies; (2) = 0.35, Hedge's g: -0.33, 95% CI: -1.02-0.36, : 81.61, 3 studies; and (3) = 0.71, Hedge's g: -0.14, 95% CI: -0.91-0.62, : 87.05, 3 studies. Subgroup analyses indicated that regional disparities, especially between Africa and Asia, and participant age groups may influence these outcomes. While a trend of decreased calcium levels in malaria patients was observed, the meta-analytical results suggest regional and age-related variations. Further investigations should emphasize these differences to better guide clinical management, prognostic applications, and the crafting of policies concerning malaria's metabolic effects.
Topics: Humans; Malaria, Vivax; Plasmodium falciparum; Calcium; Malaria; Africa
PubMed: 37960176
DOI: 10.3390/nu15214522 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
Frontiers in Public Health 2023In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data... (Review)
Review
INTRODUCTION
In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data published on malaria in pregnancy (MiP) in India.
METHODS
Epidemiological, clinical, parasitological, preventive and therapeutic aspects of MiP and its consequences on both mother and child were reviewed and critically analyzed. Knowledge gaps and solution ways are also presented and discussed. Several electronic databases including Google scholar, Google, PubMed, Scopus, Wiley Online library, the Malaria in Pregnancy Consortium library, the World Malaria Report, The WHO regional websites, and ClinicalTrials.gov were used to identify articles dealing with MiP in India. The archives of local scientific associations/journals and website of national programs were also consulted.
RESULTS
Malaria in pregnancy is mainly due to () and (), and on rare occasions to spp. and too. The overall prevalence of MiP is ~0.1-57.7% for peripheral malaria and ~ 0-29.3% for placental malaria. Peripheral infection at antenatal care (ANC) visits decreased from ~13% in 1991 to ~7% in 1995-1996 in Madhya Pradesh, while placental infection at delivery unit slightly decreased from ~1.5% in 2006-2007 to ~1% in 2012-2015 in Jharkhand. In contrast, the prevalence of peripheral infection at ANC increased from ~1% in 2006-2007 to ~5% in 2015 in Jharkhand, and from ~0.5% in 1984-1985 to ~1.5% in 2007-2008 in Chhattisgarh. Clinical presentation of MiP is diverse ranging from asymptomatic carriage of parasites to severe malaria, and associated with comorbidities and concurrent infections such as malnutrition, COVID-19, dengue, and cardiovascular disorders. Severe anemia, cerebral malaria, severe thrombocytopenia, and hypoglycemia are commonly seen in severe MiP, and are strongly associated with tragic consequences such as abortion and stillbirth. Congenital malaria is seen at prevalence of ~0-12.9%. Infected babies are generally small-for-gestational age, premature with low birthweight, and suffer mainly from anemia, thrombocytopenia, leucopenia and clinical jaundice. Main challenges and knowledge gaps to MiP control included diagnosis, relapsing malaria, mixed infection treatment, self-medication, low density infections and utility of artemisinin-based combination therapies.
CONCLUSION
All taken together, the findings could be immensely helpful to control MiP in malaria endemic areas.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; Anemia; India; Malaria; Malaria, Vivax; Placenta; Thrombocytopenia
PubMed: 37927870
DOI: 10.3389/fpubh.2023.1150466 -
Antioxidants (Basel, Switzerland) Oct 2023Nitric oxide (NO) has been implicated in the pathology of malaria. This systematic review and meta-analysis describe the association between NO levels and malaria.... (Review)
Review
Nitric oxide (NO) has been implicated in the pathology of malaria. This systematic review and meta-analysis describe the association between NO levels and malaria. Embase, Ovid, PubMed, Scopus, and Google Scholar were searched to identify studies evaluating NO levels in malaria patients and uninfected controls. Meta-regression and subgroup analyses were conducted to discern differences in NO levels between the groups. Of the 4517 records identified, 21 studies were included in the systematic review and meta-analysis. The findings illustrated significant disparities in NO levels based on geographic location and study time frames. Despite the fluctuations, such as higher NO levels in adults compared to children, no significant differences in mean NO levels between patients and uninfected controls ( = 0.25, Hedge's g: 0.35, 95% confidence interval (CI): -0.25-0.96, : 97.39%) or between severe and non-severe malaria cases ( = 0.09, Hedge's g: 0.71, 95% CI: -0.11-1.54, : 96.07%) were detected. The systematic review and meta-analysis highlighted inconsistencies in NO levels in malaria patients. Given the high heterogeneity of the results, further studies using standardized metrics for NO measurements and focusing on biochemical pathways dictating NO responses in malaria are imperative to understand the association between NO and malaria.
PubMed: 37891947
DOI: 10.3390/antiox12101868 -
Tropical Medicine and Infectious Disease Sep 2023The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy... (Review)
Review
The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical variability worldwide. Traditionally, researchers have described the Duffy negative genotype as a protective factor against infection. However, recent studies suggest that this microorganism's evolution could potentially diminish this protective effect. Nevertheless, there is currently insufficient global data to demonstrate this phenomenon. This study aimed to evaluate the relationship between the Duffy genotype/phenotype and the prevalence of infection. The protocol for the systematic review was registered in PROSPERO as CRD42022353427 and involved reviewing published studies from 2012 to 2022. The Medline/PubMed, Web of Science, Scopus, and SciELO databases were consulted. Assessments of study quality were conducted using the STROBE and GRADE tools. A total of 34 studies were included, with Africa accounting for the majority of recorded studies. The results varied significantly regarding the relationship between the Duffy genotype/phenotype and invasion. Some studies predominantly featured the negative Duffy genotype yet reported no malaria cases. Other studies identified minor percentages of infections. Conversely, certain studies observed a higher prevalence (99%) of Duffy-negative individuals infected with In conclusion, this systematic review found that the homozygous Duffy genotype positive for the A allele (FY*A/*A) is associated with a higher incidence of infection. Furthermore, the negative Duffy genotype does not confer protection against vivax malaria.
PubMed: 37888591
DOI: 10.3390/tropicalmed8100463 -
Tropical Medicine and Infectious Disease Sep 2023mosquitoes are the vectors of , the etiological agent of malaria. In addition, and are the main vectors of the O'nyong-nyong virus. However, research on the viruses... (Review)
Review
mosquitoes are the vectors of , the etiological agent of malaria. In addition, and are the main vectors of the O'nyong-nyong virus. However, research on the viruses carried by is scarce; thus, the possible transmission of viruses by is still unexplored. This systematic review was carried out to identify studies that report viruses in natural populations of or virus infection and transmission in laboratory-reared mosquitoes. The databases reviewed were EBSCO-Host, Google Scholar, Science Direct, Scopus and PubMed. After the identification and screening of candidate articles, a total of 203 original studies were included that reported on a variety of viruses detected in natural populations. In total, 161 viruses in 54 species from 41 countries worldwide were registered. In laboratory studies, 28 viruses in 15 species were evaluated for mosquito viral transmission capacity or viral infection. The viruses reported in encompassed 25 viral families and included arboviruses, probable arboviruses and Insect-Specific Viruses (ISVs). Insights after performing this review include the need for (1) a better understanding of -viral interactions, (2) characterizing the virome-considering the public health importance of the viruses potentially transmitted by and the significance of finding viruses with biological control activity-and (3) performing virological surveillance in natural populations of , especially in the current context of environmental modifications that may potentiate the expansion of the species distribution.
PubMed: 37888587
DOI: 10.3390/tropicalmed8100459 -
F1000Research 2022: Climatic change is an inescapable fact that implies alterations in seasons where weather occurrences have their schedules shift from the regular and magnitudes...
: Climatic change is an inescapable fact that implies alterations in seasons where weather occurrences have their schedules shift from the regular and magnitudes intensify to more extreme variations over a multi-year period. Southeast Asia is one of the many regions experiencing changes in climate and concurrently still has endemicities of malaria. Given that previous studies have suggested the influence of climate on malaria's vector the mosquitoes and parasite the Plasmodium group, this study was conducted to review the evidence of associations made between malaria cases and climatic variables in Southeast Asia throughout a multi-year period. : Our systematic literature review was informed by the PRISMA guidelines and registered in PROSPERO: CRD42022301826 on 5 February 2022. We searched for original articles in English and Indonesian that focused on the associations between climatic variables and malaria cases. : The initial identification stage resulted in 535 records of possible relevance and after abstract screening and eligibility assessment we included 19 research articles for the systematic review. Based on the reviewed articles, changing temperatures, precipitation, humidity and windspeed were considered for statistical association across a multi-year period and are correlated with malaria cases in various regions throughout Southeast Asia. : According to the review of evidence, climatic variables that exhibited a statistically significant correlation with malaria cases include temperatures, precipitation, and humidity. The strength of each climatic variable varies across studies. Our systematic review of the limited evidence indicates that further research for the Southeast Asia region remains to be explored.
Topics: Animals; Climate Change; Mosquito Vectors; Malaria; Anopheles; Asia, Southeastern; Asia, Eastern
PubMed: 37867624
DOI: 10.12688/f1000research.125294.2 -
Malaria Journal Oct 2023Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of... (Meta-Analysis)
Meta-Analysis
Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.
BACKGROUND
Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence.
METHODS
Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis.
RESULTS
Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1-16.1] in patients with poor adherence compared to 5.8% [5.0-6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8-2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3-15.2] in patients with poor adherence and 4.9% [4.1-5.8] in patients with full adherence; p < 0.001.
CONCLUSION
Reduced adherence, including less supervision, increases the risk of vivax recurrence.
Topics: Humans; Primaquine; Antimalarials; Plasmodium vivax; Recurrence; Malaria, Vivax; Folic Acid Antagonists
PubMed: 37817240
DOI: 10.1186/s12936-023-04725-w