Alteration of prothrombin time in Plasmodium falciparum and Plasmodium vivax infections with different levels of severity: a systematic review and 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, I2: 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, I2: 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, I2: 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.

Albumin levels in malaria patients: a systematic review and meta-analysis of their association with disease severity.

Albumin, a key protein in human blood plasma, has been linked to various health conditions. However, its association with malaria, particularly in assessing disease severity, remains inadequately understood. This comprehensive systematic review and meta-analysis aimed to elucidate the relationship between albumin levels and malaria severity. A comprehensive literature search was conducted across multiple databases, including Embase, Scopus, PubMed, MEDLINE, Ovid, and Google Scholar, to identify studies examining albumin levels in malaria patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Data were pooled using a random-effects model, and heterogeneity was assessed using I2 statistics. Subgroup and meta-regression analyses were performed based on publication year, study location, and Plasmodium species. A total of 37 studies were included in this review. The thematic synthesis indicated that albumin levels in malaria patients varied significantly based on geographical location. A meta-analysis of 28 studies found that albumin levels were significantly lower in malaria patients compared with non-malarial controls (P < 0.001, standardized mean differences [SMD] = -2.23, 95% CI - 3.25 to - 1.20, I2: 98%, random effects model, 28 studies). Additionally, subgroup analysis revealed variations in albumin levels based on geographical location and Plasmodium species. Regarding the association with disease severity, thematic synthesis showed that severe malaria cases generally had decreased albumin levels across various regions. However, one Brazilian study reported higher albumin levels in severe cases. A separate meta-analysis of five studies found significantly lower albumin levels in patients experiencing severe malaria relative to those with less severe forms of the disease (P < 0.001, SMD = -0.66, 95% CI - 1.07 to - 0.25), I2: 73%, random effects model, 5 studies). This study underscores the clinical significance of albumin as a potential biomarker for Plasmodium infection and the severity of malaria. The findings suggest that albumin level monitoring could be crucial in managing malaria patients, especially in assessing disease severity and tailoring treatment approaches. Additional studies are required to investigate the underlying mechanisms driving these associations and validate the clinical utility of albumin levels in malaria patient management.

Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity.

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, I2 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, I2 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.

A systematic review and meta-analysis of the relationship between magnesium levels and malaria severity.

Magnesium is associated with Plasmodium infections and malaria severity. This systematic review and meta-analysis was conducted to synthesize the link between Plasmodium infections and magnesium levels for improved clinical guidance and therapeutic interventions in malaria-affected regions. A systematic literature search was conducted across multiple databases, including ProQuest, Scopus, Embase, Ovid, MEDLINE, PubMed, and Google Scholar. The risk of bias in the selected studies was assessed using the Joanna Briggs Institute critical appraisal tools. A thematic synthesis was employed to demonstrate the magnesium levels across selected studies, for analyzing and grouping based on geographic regions, age demographics, and clinical manifestations of malaria. Meta-analyses determined differences in magnesium levels between individuals with malaria, uninfected controls, and patients with different clinical severities of malaria. The effect sizes from individual studies were pooled using the random-effects model. Out of 2533 records identified, 13 studies were included in the review. The thematic synthesis revealed complex and varied results, with studies showing different magnesium levels in malaria patients across different geographies, age groups, and clinical presentations. The meta-analysis indicated elevated magnesium levels in malaria patients compared with uninfected controls (P < 0.01, Hedges' g: 1.94, 95% CI 0.86-3.03, I2: 98.38%, 9 studies). No statistically significant difference was observed in magnesium levels between patients with severe and nonsevere malaria (P: 0.34, Hedges' g: 0.62, 95% CI - 0.64-1.88, I2: 91.46%, 2 studies). A significant increase in magnesium levels was seen in patients with malaria who died compared with those who survived (P < 0.01, Hedges' g: 0.39, 95% CI 0.13-0.64, I2: 3.39%, 3 studies). This systematic review and meta-analysis presented relationship between magnesium levels and malaria. While the meta-analysis indicated a general trend of increased magnesium levels in patients with malaria, the substantial heterogeneity and instability of the results hint toward a rich yet uncharted territory requiring more research depth. The intricate interplay between magnesium levels and malaria beckons a multidimensional approach in future studies.

Status of Blood Levels of Superoxide Dismutase in Patients with Malaria: A Systematic Review and Meta-Analysis.

Aims: The evidence of superoxide dismutase (SOD) in the pathogenesis of malaria is inconsistent. This study aimed to synthesize the evidence of blood levels of SOD in patients with malaria and determine the association of blood levels of SOD with the severity of malaria. Results: A total of 1874 articles were retrieved from database searches and 28 studies were included in the review. The blood levels of SOD were lower in individuals with malaria compared with those without malaria infection (p < 0.01, Cohen's d: -2.06, 95% CI: -2.99 to -1.14), I2: 98.96%, 2181 malaria cases/1186 uninfected cases). There were no differences in blood levels of SOD between severe and nonsevere malaria patients (p = 0.09, Cohen's d: -1.57, 95% CI: -3.39 to 0.26), I2: 96.02%, 69 severe malaria cases/256 nonsevere malaria cases). Innovation and Conclusion: The blood levels of SOD were lower in malaria patients compared with those without malaria infection. Further studies will be required to determine the extent to which SOD might prevent Plasmodium infections during pregnancy. Antioxid. Redox Signal. 40, 222-235.

Malaria Is Associated with Diminished Levels of Ascorbic Acid: A Systematic Review and Meta-Analysis.

Background: 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 Plasmodium species. Methods: 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 d) with 95% confidence intervals (CIs) was calculated using the random-effects model. Results: 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 (p < 0.01, Cohen's d = -3.71, 95% CI = -4.44 to -2.98, I2 = 98.87%, 30 studies). Comparable levels of ascorbic acid were observed between patients with severe malaria and those with nonsevere malaria (p = 0.06, Cohen's d = -1.39, 95% CI = -2.85 to 0.07, I2 = 96.58%, 4 studies). Similarly, levels of ascorbic acid were comparable between patients with Plasmodium falciparum and Plasmodium vivax malaria (p = 0.34, Cohen's d = -1.06, 95% CI = -3.23 to 1.12, I2 = 97.30%, 3 studies). Conclusions: 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. Antioxid. Redox Signal. 40, 460-469.

Evidence of malarial chemoprophylaxis among travellers who died from malaria: a systematic review and meta-analysis.

BACKGROUND: Chemoprophylaxis is a prevention method for malaria during travel in malaria-endemic countries. This study aimed to collate and synthesize the evidence of malarial chemoprophylaxis among malaria death cases. METHODS: Studies documenting malarial chemoprophylaxis related to malaria deaths were searched in PubMed, Scopus, MEDLINE, Embase, and CENTRAL until 3 July 2022. The pooled proportion of malarial chemoprophylaxis among death cases was synthesized using logit transformation and back transformation to a proportion performed using generalized linear mixed models. The pooled log odds ratio (log-OR) with a 95% confidence interval (CI) of malarial chemoprophylaxis in death cases compared to survivors were synthesized. RESULTS: Fifty-eight studies were included in the systematic review and the meta-analysis. Of 602 pooled malaria death cases, the number of patients who took chemoprophylaxis was 187 (30%) (95% CI 22-40, P < 0.01, 58 studies), and those who took adequate chemoprophylaxis were 24 (5%) (95% CI 2-13, P < 0.01, 42 studies). A comparable log-OR of underwent chemoprophylaxis was observed between malaria death cases and survivors (P = 0.94, pooled log-OR: - 0.02, 95% CI - 0.46-0.42, I2: 0%, 17 studies). Similarly, a comparable log-OR of adequate chemoprophylaxis was identified between malaria death cases and survivors (P = 0.15, pooled log-OR: 0.83, 95% CI - 0.30-1.97, I2: 47.08%, 11 studies). CONCLUSIONS: Among the studies where malarial chemoprophylaxis was reported, approximately 30% of malaria death cases had taken such prophylaxis. Notably, only 5% of these cases adhered fully or adequately to the recommended chemoprophylactic regimen. However, the analysis did not reveal a significant difference in the odds of malarial chemoprophylaxis between malaria death cases and survivors.

Regional and Age-Related Variations in Blood Calcium Levels among Patients with Plasmodium falciparum and P. vivax malaria: A Systematic Review and 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) p = 0.15, Hedge's g: -1.00, 95% CI: -2.37-0.38, I2: 98.97, 9 studies; (2) p = 0.35, Hedge's g: -0.33, 95% CI: -1.02-0.36, I2: 81.61, 3 studies; and (3) p = 0.71, Hedge's g: -0.14, 95% CI: -0.91-0.62, I2: 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.

A Systematic Review and Meta-Analysis Exploring Variations in Copper Levels between Individuals with Malaria and Uninfected Controls.

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 (p = 0.39; Hedges' g, 0.38; 95% CI, -0.48 to 1.25; I2, 98.73%). Subgroup analysis showed a significant difference in copper levels between patients with malaria and uninfected controls among studies conducted in Asia (p < 0.01; Hedges' g, 1.74; 95% CI, 1.04 to 2.44; I2, 90.88%; five studies) and studies employing plasma blood samples (p < 0.01; Hedges' g, 1.13; 95% CI, 0.60 to 2.07; I2, 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.

Association between Plasmodium Infection and Nitric Oxide Levels: A Systematic Review and Meta-Analysis.

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 (p = 0.25, Hedge's g: 0.35, 95% confidence interval (CI): -0.25-0.96, I2: 97.39%) or between severe and non-severe malaria cases (p = 0.09, Hedge's g: 0.71, 95% CI: -0.11-1.54, I2: 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.

Differences in catalase levels between malaria-infected individuals and uninfected controls: a systematic review and meta-analysis.

Inconsistent catalase (CAT) research necessitates a comprehensive review of CAT levels among patients with malaria to achieve better therapeutic strategies. This study aimed to systematically review and meta-analyze available literature on CAT levels in nonpregnant and pregnant individuals with malaria compared with those in uninfected controls, with the goal of providing a robust evidence base for future research and potential interventions. Following PRISMA guidelines, a systematic literature search across six databases was conducted to examine CAT levels in patients with malaria. Data was extracted independently by two reviewers, and study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. The standardized mean difference of CAT levels was calculated with heterogeneity assessment. Subgroup and sensitivity analyses were conducted to explore heterogeneity and assess the robustness of the findings. Publication bias was visually and statistically assessed and corrected, if necessary. Statistical analyses were performed using Stata software, with a significance level set at P < 0.05. Nineteen studies were included in the review. These studies, published from before 2000 to 2023, primarily from Africa and Asia, focused on different Plasmodium species and age groups. Results of qualitative synthesis among nonpregnant individuals consistently showed lower CAT levels in malaria-infected individuals, although some studies reported higher levels. No significant differences in CAT levels were found between malaria-infected and uninfected individuals, as demonstrated by a meta-analysis overall (P = 0.05, Hedges' g: - 0.78, 95% confidence interval (CI): (- 1.56)-0.01, I2: 98.47, 15 studies), but subgroup analyses showed significant differences in CAT levels in studies conducted in Africa (P = 0.02, Hedges' g: - 0.57, 95% CI: - 1.02-(0.11), I2: 91.81, 7 studies), and in studies that specifically focused on children (P = 0.03, Hedges' g: - 0.57, 95% CI: - 1.07-(- 0.07), I2: 87.52, 4 studies). Pregnant women showed variations in CAT levels across trimesters. This study provides valuable insights into the association between malaria infection and CAT enzyme levels, particularly in nonpregnant individuals. Furthermore, well-designed studies are essential to decoding the intricacies of this relationship, which could have significant implications for understanding disease processes and improving patient care.

Association of uric acid levels with severity of Plasmodium infections: a systematic review and meta-analysis.

Elevated uric acid (UA) levels have been reported in malaria patients and are particularly prominent in severe malaria cases. This study aims to synthesize the difference in UA levels between malaria patients and uninfected controls, and between patients with severe and non-severe malaria. A comprehensive literature search was carried out across databases such as Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar to identify relevant studies for inclusion. The methodological quality of the included studies was evaluated independently by two reviewers using the JBI critical appraisal tool for observational studies. A meta-analysis was performed to calculate the pooled effect sizes, expressed as Hedges' g, with 95% confidence intervals (CIs). The Hedges' g was pooled using the random-effects model. An initial search yielding a total of 1122 articles, and a final total of 19 studies being included in the review. Elevated UA levels were observed more prominently in malaria patients, especially those with severe manifestations, when compared to uninfected controls. The conducted meta-analysis demonstrated a significant elevation in UA levels in patients suffering from malaria as compared to uninfected controls (P < 0.01, Hedges's g = 1.40, 95% CI 0.84-1.95, I2 = 95.81, 16 studies). The conducted meta-analysis demonstrated a significant elevation in UA levels in patients suffering from severe malaria as compared to non-severe malaria (P < 0.01, Hedges's g = 3.45, 95% CI 1.06-5.83, I2 = 98.73, 6 studies). In summary, these findings provide valuable insights into the potential use of UA as a biomarker for malaria infection and determination of its severity. Further research is needed to validate these findings and to explore the underlying mechanisms that contribute to the elevation of UA levels during malaria infection.

The Association between Malaria and ß-Carotene Levels: A Systematic Review and Meta-Analysis.

BACKGROUND: ß-Carotene, which is a prominent carotenoid with notable antioxidant properties, may play a role in countering the oxidative stresses induced by malaria. The association between ß-carotene levels and malaria is not yet fully understood, prompting this systematic review and meta-analysis. METHODS: A rigorous search of databases, including Nursing and Allied Health Premium, EMBASE, MEDLINE, Ovid, PubMed, Scopus, and Google Scholar, was undertaken to collate studies that focused on ß-carotene levels in malaria patients. The selected studies underwent critical appraisal, followed by data extraction for a meta-analysis. RESULTS: Of the 2498 records initially identified, 10 were deemed suitable for synthesis. A considerable number of these studies indicated a pronounced reduction in ß-carotene levels among malaria patients in contrast with uninfected individuals. The meta-analysis, encompassing 421 malaria patients and 240 uninfected controls, revealed a significant correlation between reduced ß-carotene levels and malaria (p < 0.01, Hedges's g: -1.26, 95% CI: -2.00-(-0.53), I2: 93.86%, seven studies). CONCLUSIONS: The conducted systematic review and meta-analysis corroborated the correlation between lower ß-carotene levels and malaria. The intricate relationship between malaria and ß-carotene merits deeper exploration. A comprehensive understanding of this association might pave the way for innovative therapeutic approaches leveraging the antioxidant attributes of ß-carotene to combat malaria-induced oxidative stress.

Impact of malaria on glutathione peroxidase levels: a systematic review and meta-analysis.

The primary antioxidant, glutathione peroxidase (GPx), is hypothesized to contribute to the pathophysiology of malaria. This current study conducted a meta-analysis to examine variations in GPx blood levels in malaria patients. Seven electronic databases-ProQuest, Scopus, Embase, MEDLINE, PubMed, Ovid, and Google Scholar-were searched for relevant studies with no limitations to publication language or publication date. The Joanna Briggs Institute critical appraisal tools were used to appraise the risk of bias among the included studies critically. The meta-analysis was conducted by pooling the effect estimates and Hedges's g using a random-effects model. Search results returned 1253 articles, of which 16 studies were used for syntheses. Results of the meta-analysis indicated that malaria patients had decreased blood levels of GPx compared to uninfected individuals (P < 0.01, Hedges' g: - 4.06, 95% CI - 5.49-(- 2.63), I2: 99.07%, 1278 malaria patients/627 uninfected individuals, 15 studies). Subgroup analyses indicated that peripheral levels of GPx were significantly diminished in patients with P. falciparum malaria compared to uninfected controls (P < 0.01, Hedges' g: - 3.06, 95% CI - 4.46-(- 1.65), I2: 98.39%, 9 studies) but not in patients with P. vivax malaria (P = 0.15, Hedges' g: - 2.05, 95% CI - 4.83-0.74), I2: 98.64%, 2 studies) Overall, malaria is associated with declined levels of GPx, particularly in patients with P. falciparum malaria. The finding provides valuable insights that prompt the need to investigate the role of GPx depletion in malaria pathogenesis.

Interleukin-5 levels in relation to malaria severity: a systematic review.

BACKGROUND: The role of cytokines such as interleukin-5 (IL-5) in the pathogenesis of malaria remains unclear. This systematic review sought to synthesize variations in IL-5 levels between severe and uncomplicated malaria, as well as between malaria and controls not afflicted with the disease. METHODS: This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022368773). Searches for studies that reported IL-5 levels in patients with malaria (any severity) and/or uninfected individuals were performed in Web of Science, PubMed, EMBASE, Scopus, CENTRAL, and MEDLINE, between 1st and 10th October, 2022. The risk of bias among all included studies was minimized using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies. The differences in IL-5 levels between malaria and uninfected controls, and between severe and uncomplicated malaria were synthesized by narrative synthesis. RESULTS: Among 1177 articles identified in the databases, 23 matched the eligibility criteria and were included in this systematic review. Qualitative syntheses showed the heterogeneity of IL-5 levels between different severities of clinical malaria and uninfected controls. The majority of the included studies (12/15 studies, 80%) found no change in IL-5 levels between malaria cases and uninfected controls. Similarly, most studies found no difference in IL-5 levels between severe (regardless of complications) and uncomplicated malaria (4/8 studies, 50%). The qualitative syntheses revealed that most studies found no difference in IL-5 levels between severe and non-severe malaria. CONCLUSIONS: The comprehensive review suggests that IL-5 levels are unchanged in patients with different levels of clinical severity of malaria and uninfected controls. Given the limited number of published studies on IL-5 levels in malaria, there is a need for additional research to determine the function of this cytokine in the pathogenesis of malaria.

Effect of Malaria on Blood Levels of Vitamin E: A Systematic Review and Meta-Analysis.

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 (p < 0.01, Cohen's d: -2.74, 95% CI: -3.72-(-1.76), I2: 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 (p < 0.01, Cohen's d: -0.56, 95% CI: -0.85-(-0.26), I2: 0%, 2 studies), but no variation in blood levels of vitamin E among patients suffering from either P. falciparum or P. vivax malaria (p = 0.13, Cohen's d: -1.15, 95% CI: -2.62-0.33, I2: 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 P. falciparum or P. vivax, 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.

Effects of Daily Zinc Alone or in Combination with Other Nutrient Supplements on the Risk of Malaria Parasitaemia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Zinc supplementation has been explored as a potential intervention to reduce the risk of malaria parasitaemia in randomised controlled trials (RCTs). However, inconsistent evidence has been obtained regarding the efficacy of zinc supplementation in the context of malaria prevention. This systematic review was implemented to survey the existing literature to determine the effects of the daily oral administration of zinc, either alone or in combination with other nutrient supplements, on the risk of malaria parasitaemia. The systematic review was prospectively registered in the PROSPERO database CRD42023424345 and followed PRISMA protocols. A comprehensive search was conducted across multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar, from their inception until 6 May 2023. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool 2 (RoB 2). The effect sizes, represented as risk ratios (RRs) with 95% confidence intervals (CIs), were standardised by transforming them into log RRs and then pooling them using a fixed-effects or random-effects model depending on the heterogeneity across studies. Comparisons were made between individuals who received zinc alone or zinc in combination with other micronutrient supplements and those who did not receive zinc. A total of 1339 articles were identified through the database searches, and after the screening and selection process, 10 studies were included in the final synthesis. The meta-analysis revealed that zinc supplementation alone did not significantly affect the risk of malaria parasitaemia compared with placebo (p = 0.30, log RR = 0.05, 95% CI: -0.05-0.15, I2 = 0.00%, with 566 malaria cases in the zinc intake group and 521 malaria cases in the placebo group). However, the analysis demonstrated a borderline significant effect of zinc supplementation in combination with other micronutrients on the risk of malaria parasitaemia compared with placebo (p = 0.05, log RR = 1.31, 95% CI: 0.03-2.59, I2 = 99.22%, with 8904 malaria cases in the zinc intake group and 522 malaria cases in the placebo group). The findings of this systematic review indicate that zinc supplementation, either alone or combined with the supplementation of other micronutrients such as vitamin A, iron, or multiple nutrients, does not significantly alter the risk of malaria parasitaemia. Further research with larger sample sizes is warranted to explore the potential effects of multi-nutrient supplementation and to identify more specific micronutrients and additional factors associated with the risk of malaria, rather than just zinc alone, among individuals in different malaria-endemic areas.

Prevalence and proportion estimate of asymptomatic Plasmodium infection in Asia: a systematic review and 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.

Association between ovalocytosis and Plasmodium infection: a systematic review and meta-analysis.

Reports of an association between ovalocytosis and protection against Plasmodium infection are inconsistent. Therefore, we aimed to synthesise the overall evidence of the association between ovalocytosis and malaria infection using a meta-analysis approach. The systematic review protocol was registered with PROSPERO (CRD42023393778). A systematic literature search of the MEDLINE, Embase, Scopus, PubMed, Ovid, and ProQuest databases, from inception to 30 December 2022, was performed to retrieve studies documenting the association between ovalocytosis and Plasmodium infection. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Data synthesis included a narrative synthesis and a meta-analysis to calculate the pooled effect estimate (log odds ratios [ORs]) and 95% confidence intervals (CIs) using the random-effects model. Our database search retrieved 905 articles, 16 of which were included for data synthesis. Qualitative synthesis revealed that over half of the studies showed no association between ovalocytosis and malaria infections or severity. Furthermore, our meta-analysis demonstrated no association between ovalocytosis and Plasmodium infection (P = 0.81, log OR = 0.06, 95% CI - 0.44 to 0.19, I2: 86.20%; 11 studies). In conclusion, the meta-analysis results demonstrated no association between ovalocytosis and Plasmodium infection. Hence, the role of ovalocytosis in relation to protection against Plasmodium infection or disease severity should be further investigated in larger prospective studies.

Relation between Increased IL-10 Levels and Malaria Severity: A Systematic Review and Meta-Analysis.

The roles of anti-inflammatory cytokines in the pathogenesis of severe malaria have been widely studied, and the role of IL-10 in the pathogenesis of severe malaria remains unclear. Therefore, we performed a systematic review and meta-analysis to determine the difference in IL-10 levels between patients with severe malaria and those with non-severe malaria. The search for relevant studies was performed using PubMed, Scopus, and Embase from 1 February 2022 to 12 February 2022. The quality of the included studies was assessed according to the guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology. The random-effects model was used to estimate the pooled effect. In all, 1215 studies were identified, and 19 were included in the quantitative syntheses. The results showed that patients with severe malaria had a higher IL-10 level than those with non-severe malaria (p = 0.03, pooled standardized mean difference: 0.74, 95% CI: 0.08-1.40, I2: 97.22%, 19 studies/21 sub studies). The meta-analysis results demonstrated increased IL-10 levels in patients with severe malaria compared with those with non-severe malaria. However, with the heterogeneity of the meta-analysis results, further studies are required to confirm the changes in the IL-10 levels according to the severity of malaria and to investigate whether a combination of other severity parameters with IL-10 levels could be an alternative marker for severe malaria.