Total antioxidant status levels in malaria: a systematic review and meta-analysis.

BACKGROUND: Malaria, a severe health threat, significantly affects total antioxidant status (TAS) levels, leading to considerable oxidative stress. This systematic review and meta-analysis aimed to delineate differences in TAS levels between malaria patients and healthy controls, and assess correlations between disease severity and parasite density. METHODS: The systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023448761. A comprehensive literature search was conducted in databases such as Embase, MEDLINE, Journals@Ovid, PubMed, Scopus, ProQuest, and Google Scholar to identify studies reporting data on TAS levels in malaria patients. Data from the included studies were analysed both qualitatively and quantitatively. Differences in TAS levels between malaria patients and controls were pooled using a random effects model, with Hedges' g as the effect size measure. RESULTS: Of 1796 identified records, 20 studies met the inclusion criteria. The qualitative synthesis of these studies revealed a marked decrease in TAS levels in patients with malaria compared to non-malaria cases. The meta-analysis results showed a significant decrease in TAS levels in patients with malaria compared to non-malaria cases (P < 0.01, Hedges' g: - 2.75, 95% CI - 3.72 to -1.78, I2: 98.16%, 13 studies), suggesting elevated oxidative stress in these patients. Subgroup analyses revealed that TAS level variations were significantly influenced by geographical region, age group, Plasmodium species, and method for measuring TAS. Notably, TAS levels were significantly lower in severe malaria cases and those with high parasite density, indicating a potential relationship between oxidative stress and disease severity. CONCLUSION: This study highlights the potential utility of TAS as a biomarker for disease risk and severity in malaria. The significant decrease in TAS levels in malaria patients compared to controls implies increased oxidative stress. Further well-designed, large-scale studies are warranted to validate these findings and elucidate the intricate mechanisms linking TAS and malaria.

A systematic review and meta-analysis of changes in interleukin-8 levels in malaria infection.

The roles of interleukin-8 (IL-8) in malaria are inconsistent and unclear. This study synthesised evidence for differences in IL-8 levels in patients with malaria of various levels of severity. Relevant studies were searched in Scopus, MEDLINE, Embase, CENTRAL and PubMed from inception to 22 April 2022. Pooled mean differences (MDs) and 95% confidence intervals (CIs) were estimated using the random effects model. Of 1083 articles retrieved from the databases, 34 were included for syntheses. The meta-analysis revealed increased IL-8 levels in individuals with uncomplicated malaria compared with those without malaria (P = 0.04; MD, 25.57 pg/mL; 95% CI, 1.70 to 49.43 pg/mL; I2, 99.53, 4 studies; 400 uncomplicated malaria, 204 uninfected controls). The meta-analysis revealed comparable levels of IL-8 between the two groups (P = 0.10; MD, 74.46 pg/mL; 95% CI, -15.08 to 164.0 pg/mL; I2, 9.03; 4 studies; 133 severe malaria cases, 568 uncomplicated malaria cases). The study found evidence of increased IL-8 levels in individuals with malaria compared with those without malaria. However, no differences were found in IL-8 levels between patients with severe and non-severe malaria. Further research is needed to investigate the IL-8 cytokine levels in patients with malaria of different levels of severity.

Association between NDRG1 protein expression and aggressive features of breast cancer: a systematic review and meta-analysis.

BACKGROUND: N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer. METHODS: The protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status. RESULTS: A total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13-1.05, I2: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32-(-0.20), I2: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41). CONCLUSION: The study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.

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.

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.

A systematic review and meta-analysis of blood interleukin-4 levels concerning malaria infection and severity.

BACKGROUND: Interleukin (IL)-4 had been linked to malaria severity, but the findings are controversial, and the evidence is inconsistent and imprecise. In the current investigation, data on IL-4 levels in patients with severe and uncomplicated malaria were compiled. METHODS: The systematic review was registered at PROSPERO (CRD42022323387). Searches for relevant articles on IL-4 levels in patients with severe malaria and studies that examined IL-4 levels in both uncomplicated malaria and healthy controls were performed in PubMed, Embase, and Scopus using the search strategy without limitation to publication years or language. The quality of all included studies was evaluated using The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: standards for reporting observational studies. Qualitative and quantitative data syntheses were performed. The random-effects model, which weights each study according to its between- and within-study variance, was used to pool the mean difference (MD) of individual studies. The degree of heterogeneity was determined using Cochran's Q and I2 statistics. Additionally, meta-regression and subgroup analyses were perfomed to investigate possible sources of heterogeneity. The outliers were identified using the leave-one-out method and assessed publication bias using funnel plots, Egger's test, and a contour-enhanced funnel plot. RESULTS: A total of 2300 studies were identified through database searches, and 36 were included for analyses. The meta-analysis results showed lower mean IL-4 levels in severe malaria (434 cases) than in uncomplicated malaria (611 cases) (P = 0.01, pooled MD: -3.36 pg/mL, 95% confidence intervals CI -5.55 to -1.16 pg/mL, I2: 98.15%, 11 studies). The meta-analysis results showed no difference in mean IL-4 levels between cerebral malaria (96 cases) and noncerebral severe malaria (108 cases) (P = 0.71, pooled MD: 0.86 pg/mL, 95% CI -3.60 to 5.32 pg/mL, I2 92.13%, four studies). Finally, no difference was found in mean IL-4 levels between uncomplicated malaria (635 cases) and healthy controls (674 cases) (P = 0.57, pooled MD: 0.79 pg/mL, 95% CI -1.92 to 3.50 pg/mL, I2: 99.89%, 11 studies). CONCLUSION: The meta-analysis revealed lower IL-4 levels in patients with severe malaria than in those with uncomplicated malaria, though a trend toward comparable IL-4 levels between both groups was more likely because several sources of heterogeneities were observed. Based on the limited number of studies included in the meta-analysis, until additional investigations have been conducted, IL-4 consideration as an alternative prognostic factor for malaria severity is not warranted.

Elevation of serum interleukin-1ß levels as a potential indicator for malarial infection and severe malaria: a meta-analysis.

BACKGROUND: Interleukin (IL)-1ß is a proinflammatory cytokine that has a role in disease-related inflammation, including malaria. However, reports on the effect of IL-1ß on malaria severity are inconsistent. Therefore, meta-analyses to compare differences in IL-1ß levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls were performed. METHODS: The PRISMA standards were used to perform a systematic review and meta-analysis. A search of PubMed, Scopus, EMBASE and reference lists was conducted for articles providing data on IL-1ß levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls between January 1988 and March 2022, using a combination of search terms. The quality of all studies included in this review was determined using the Strengthening the Reporting of Observational Studies in Epidemiology statement: guidelines for reporting observational studies. The evidence was synthesized quantitatively and qualitatively. The differences in IL-1 levels across participant groups were recounted narratively for qualitative synthesis. For quantitative synthesis, the mean difference in IL-1ß levels across groups of participants was calculated using a random effects meta-analysis. The publication bias was assessed using funnel plots, Egger's test and a contour-enhanced funnel plot. RESULTS: A total of 1281 articles were discovered, and the 17 that satisfied the inclusion criteria were included for syntheses. The meta-analysis results using data from 555 cases of severe malaria and 1059 cases of uncomplicated malaria showed that severe malaria had a higher mean of IL-1ß levels than uncomplicated malaria (P < 0.01, pooled mean difference: 1.92 pg/mL, 95% confidence interval: 0.60-3.25 pg/mL, I2: 90.41%, 6 studies). The meta-analysis results using data from 542 cases of uncomplicated malaria and 455 healthy controls showed no difference in mean IL-1ß levels between the two groups (P = 0.07, pooled mean difference: 1.42 pg/mL, 95% confidence interval: - 0.1-2.94 pg/mL, I2: 98.93%, 6 studies). CONCLUSION: The results from the meta-analysis revealed that IL-1ß levels were higher in patients with severe malaria than in patients with uncomplicated malaria; however, IL-1ß levels were similar in patients with uncomplicated malaria and healthy controls. Based on the limitations of the number of studies included in the meta-analysis and high levels of heterogeneity, further studies are needed to conclude that differences in IL-1ß levels can be useful for monitoring the malaria severity.

Quantification of the misidentification of Plasmodium knowlesi as Plasmodium malariae by microscopy: an analysis of 1569 P. knowlesi cases.

BACKGROUND: Plasmodium knowlesi is recognized as the fifth Plasmodium species causing malaria in humans. It is morphologically similar to the human malaria parasite Plasmodium malariae, so molecular detection should be used to clearly discriminate between these Plasmodium species. This study aimed to quantify the rate at which P. knowlesi is misidentified as P. malariae by microscopy in endemic and non-endemic areas. METHODS: The protocol of this systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID = CRD42020204770). Studies reporting the misidentification of P. knowlesi as P. malariae by microscopy and confirmation of this by molecular methods in MEDLINE, Web of Science and Scopus were reviewed. The risk of bias in the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). The pooled prevalence and 95% confidence interval (CI) of the misidentification of P. knowlesi as P. malariae by microscopy were estimated using a random effects model. Subgroup analysis of the study sites was performed to demonstrate any differences in the misidentification rates in different areas. Heterogeneity across the included studies was assessed and quantified using Cochran's Q and I2 statistics, respectively. Publication bias in the included studies was assessed using the funnel plot, Egger's test and contour-enhanced funnel plot. RESULTS: Among 375 reviewed studies, 11 studies with a total of 1569 confirmed P. knowlesi cases in humans were included. Overall, the pooled prevalence of the misidentification of P. knowlesi as P. malariae by microscopy was estimated at 57% (95% CI 37-77%, I2: 99.3%). Subgroup analysis demonstrated the highest rate of misidentification in Sawarak, Malaysia (87%, 95% CI 83-90%, I2: 95%), followed by Sabah, Malaysia (85%, 95% CI 79-92%, I2: 85.1%), Indonesia (16%, 95% CI 6-38%), and then Thailand (4%, 95% CI 2-9%, I2: 95%). CONCLUSION: Although the World Health Organization (WHO) recommends that all P. malariae-positive diagnoses made by microscopy in P. knowlesi endemic areas be reported as P. malariae/P. knowlesi malaria, the possibility of microscopists misidentifying P. knowlesi as P. malariae is a diagnostic challenge. The use of molecular techniques in cases with malariae-like Plasmodium with high parasite density as determined by microscopy could help identify human P. knowlesi cases in non-endemic countries.

Preliminary review on the prevalence, proportion, geographical distribution, and characteristics of naturally acquired Plasmodium cynomolgi infection in mosquitoes, macaques, and humans: a systematic review and meta-analysis.

BACKGROUND: Plasmodium cynomolgi is a simian malaria parasite that has been reported as a naturally acquired human infection. The present study aims to systematically review reports on naturally acquired P. cynomolgi in humans, mosquitoes, and macaques to provide relevant data for pre-emptive surveillance and preparation in the event of an outbreak of zoonotic malaria in Southeast Asia. METHODS: The protocol of the systematic review was registered at PROSPERO with approval ID CRD42020203046. Three databases (Web of Science, Scopus, and MEDLINE) were searched for studies reporting the prevalence of P. cynomolgi infections in Southeast Asian countries between 1946 and 2020. The pooled prevalence or pooled proportion of P. cynomolgi parasitemia in humans, mosquitoes, and macaques was estimated using a random-effects model. Differences in the clinical characteristics of P. cynomolgi infections were also estimated using a random-effects model and presented as pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Thirteen studies reporting on the prevalence of naturally acquired P. cynomolgi in humans (3 studies, 21 cases), mosquitoes (3 studies, 28 cases), and macaques (7 studies, 334 cases) were included. The results demonstrated that the pooled proportion of naturally acquired P. cynomolgi in humans was 1% (95% CI, 0.1%, I2, 0%), while the pooled proportion of P. cynomolgi infecting mosquitoes was 18% (95% CI, 10-26%, I2, 32.7%). The pooled prevalence of naturally acquired P. cynomolgi in macaques was 47% (95% CI, 27-67%, I2, 98.3%). Most of the cases of naturally acquired P. cynomolgi in humans were reported in Cambodia (62%) and Malaysia (38%), while cases of P. cynomolgi in macaques were reported in Malaysia (35.4%), Singapore (23.2%), Indonesia (17.3%), Philippines (8.5%), Laos (7.93%), and Cambodia (7.65%). Cases of P. cynomolgi in mosquitoes were reported in Vietnam (76.9%) and Malaysia (23.1%). CONCLUSIONS: This study demonstrated the occurrence of naturally acquired P. cynomolgi infection in humans, mosquitoes, and macaques. Further studies of P. cynomolgi in asymptomatic human cases in areas where vectors and natural hosts are endemic are extensively needed if human infections with P. cynomolgi do become public health problems.

Prevalence of and risk factors for Plasmodium spp. co-infection with hepatitis B virus: a systematic review and meta-analysis.

BACKGROUND: Plasmodium spp. and hepatitis B virus (HBV) are among the most common infectious diseases in underdeveloped countries. This study aimed to determine the prevalence of Plasmodium spp. and HBV co-infection in people living in endemic areas of both diseases and to assess the risk factors related to this co-infection. METHODS: The PubMed, Web of Science, and Scopus databases were searched. Observational cross-sectional studies and retrospective studies assessing the prevalence of Plasmodium species and HBV co-infection were examined. The methodological quality of the included studies was assessed with the Newcastle-Ottawa Scale (NOS), a tool for assessing the quality of nonrandomized studies in meta-analyses, and heterogeneity among the included studies was assessed with Cochran's Q test and the I2 (inconsistency) statistic. The pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effects model, depending on the amount of heterogeneity there was among the included studies. The pooled odds ratio (OR) represented the difference in qualitative variables, whereas the pooled mean difference (MD) represented the difference in quantitative variables. Meta-analyses of the potential risk factors for Plasmodium spp. and HBV co-infection, including patient age and gender, were identified and represented as pooled odds ratios (OR) and 95% CIs. Publication bias among the included studies was assessed by visual inspection of a funnel plot to search for asymmetry. RESULTS: Twenty-two studies were included in the present systematic review and meta-analysis. Overall, the pooled prevalence estimate of Plasmodium spp. and HBV co-infection was 6% (95% CI 4-7%, Cochran's Q statistic < 0.001, I2: 95.8%), with prevalences of 10% in Gambia (95% CI: 8-12%, weight: 4.95%), 8% in Italy (95% CI 5-12%, weight: 3.8%), 7% in Nigeria (95% CI 4-10%, weight: 53.5%), and 4% in Brazil (95% CI 2-5%, weight: 19.9%). The pooled prevalence estimate of Plasmodium spp. and HBV co-infection was higher in studies published before 2015 (7%, 95% CI 4-9%, Cochran's Q statistic < 0.001, I2: 96%) than in those published since 2015 (3%, 95% CI 1-5%, Cochran's Q statistic < 0.001, I2: 81.3%). No difference in age and risk of Plasmodium spp. and HBV co-infection group was found between the Plasmodium spp. and HBV co-infection and the Plasmodium monoinfection group (p: 0.48, OR: 1.33, 95% CI 0.60-2.96). No difference in gender and risk of Plasmodium spp. and HBV co-infection group was found between the Plasmodium spp. and HBV co-infection and HBV co-infection group and the Plasmodium monoinfection group (p: 0.09, OR: 2.79, 95% CI 0.86-9.10). No differences in mean aspartate aminotransferase (AST), mean alanine aminotransferase (ALT), or mean total bilirubin levels were found (p > 0.05) between the Plasmodium spp. and HBV co-infection group and the Plasmodium monoinfection group. CONCLUSIONS: The present study revealed the prevalence of Plasmodium spp. and HBV co-infection, which will help in understanding co-infection and designing treatment strategies. Future studies assessing the interaction between Plasmodium spp. and HBV are recommended.

Prevalence and proportion of Plasmodium spp. triple mixed infections compared with double mixed infections: a systematic review and meta-analysis.

BACKGROUND: Although mixed infection by two Plasmodium species has been recognized, mixed infection by three different Plasmodium species within one individual has not been clarified. This study sought to determine the pooled prevalence and proportion of triple mixed Plasmodium spp. infection compared with double mixed infection. METHODS: Articles from PubMed, Scopus, and Web of Science were searched for cross-sectional studies of triple mixed infection by Plasmodium species and then were retrieved and extracted. The pooled proportion and prevalence of triple mixed infection by Plasmodium species were subjected to random-effects analysis. The secondary outcomes were differences in the pooled proportion between triple mixed infection and double mixed infection by Plasmodium species reported in the included studies. RESULTS: Of 5621 identified studies, triple mixed infection data were available for 35 records, including 601 patients from 22 countries. The overall pooled prevalence of triple mixed infection was 4% (95% Confidence Interval (CI) 3-5%; I2 = 92.5%). The pooled proportion of triple mixed infection compared with double mixed infection was 12% (95% CI 9-18; I2 = 91%). Most of the included studies (29/35; 82.9%) presented a lower proportion of triple mixed infection than double mixed infection. Subgroup analysis demonstrated that the proportion of triple mixed infection was the highest in Oceania (23%; 95% CI 15-36%) and Europe (21%; 95% CI 5-86%), but the lowest in the USA (3%; 95% CI 2-4%). Moreover, the proportion of triple mixed infection was higher in residents (20%; 95% CI 14-29%) than in febrile patients (7%; 95% CI 4-13%), when compared with the proportion of double mixed infection. Subgroup analysis of the age groups demonstrated that, compared with the proportion of double mixed infection, triple mixed infection was lower in patients aged ≤ 5 years (OR = 0.27; 95% CI 0.13-0.56; I2 = 31%) and > 5 years (OR = 0.09; 95% CI 0.04-0.25, I2 = 78%). CONCLUSIONS: The present study suggested that, in areas where triple mixed infection were endemic, PCR or molecular diagnosis for all residents in communities where malaria is submicroscopic can provide prevalence data and intervention measures, as well as prevent disease transmission and enhance malaria elimination efforts.

Global prevalence and mortality of severe Plasmodium malariae infection: a systematic review and meta-analysis.

BACKGROUND: Severe complications among patients with Plasmodium malariae infection are rare. This is the first systematic review and meta-analysis demonstrating the global prevalence and mortality of severe P. malariae infection in humans. METHODS: The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All research articles published on the severity and mortality of P. malariae infection cases in humans were retrieved from three public databases: PubMed, Scopus, and ISI Web of Science. The pooled prevalence estimate and 95% confidence interval (CI) of complications in patients with P. malariae malaria was analysed using the random-effects model provided in Stata software. The pooled odds ratio (OR) and 95% CI of severe malaria for P. malariae infection and Plasmodium falciparum infection were analysed using Review Manager software. RESULTS: Six studies were used to estimate the pooled prevalence of severe P. malariae malaria. Out of 10,520 patients infected with P. malariae, the pooled prevalence estimate of severe P. malariae infection was 3% (95% CI 2-5%), with high heterogeneity (I2: 90.7%). Severe anaemia (3.32%), pulmonary complications (0.46%), and renal impairments (0.24%) were the most common severe complications found in patients with P. malariae infection. The pooled proportion of severe anaemia for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.74, 95% CI 0.22-2.45, I2 = 98%). The pooled proportion of pulmonary complications was comparable between patients with P. malariae infection and those with P. falciparum infection among the four included studies (OR: 1.44; 95% CI 0.17-12.31, I2: 92%). For renal complications, the funnel plot showed that the pooled proportion of renal complications for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.94, 95% CI 0.18-4.93, I2: 91%). The mortality rate of patients with P. malariae infection was 0.17% (18/10,502 cases). CONCLUSIONS: This systematic review demonstrated that approximately two percent of patients with P. malariae infection developed severe complications, with a low mortality rate. Severe anaemia, pulmonary involvement, and renal impairment were the most common complications found in patients with P. malariae infection. Although a low prevalence and low mortality of P. malariae infection have been reported, patients with P. malariae infection need to be investigated for severe anaemia and, if present, treated aggressively to prevent anaemia-related death.

Prevalence and risk factors related to poor outcome of patients with severe Plasmodium vivax infection: a systematic review, meta-analysis, and analysis of case reports.

BACKGROUND: Plasmodium vivax rarely develops severe complications when compared to severe falciparum malaria. However, severe vivax malaria also needs urgent, intensive care and treatment as severe falciparum malaria. This systematic review aimed to explore pooled prevalence of severe vivax malaria and to identify factors related to poor outcome of patients who developed severe manifestation. METHODS: The systematic review conducted by two reviewers independently through searching of research publications related to severe P. vivax malaria in three databases including MEDLINE, Web of Science (ISI), and Scopus until October, 22 2019. The pooled prevalence of severe vivax malaria was achieved using STATA and RevMan 5 Software. Factors related to poor outcome of patients with severe vivax malaria were analyzed using SPSS 11.5 Software. RESULTS: Among 2615 research publications retrieved from three databases, 49 articles reporting on 42,325 severity cases were selected for calculating pooled prevalence. Seventy-six patients from case reports, case series, letter to editors, and research communications were collected to identify factors related to poor outcome of patients with severe vivax malaria. The results showed that severe anemia, jaundice, respiratory distress, impaired consciousness, and renal failure were the most common major manifestations of severe malaria guided by the World Health Organization (WHO) criterion. The meta-analysis indicated that severe malaria was less frequent in patient with P. vivax compared to those with P. falciparum (P -value < 0.00001, OR = 0.38, 95% CI = 0.25-0.56, I2 = 87%). In addition, thrombocytopenia, anemia, hepatitis, and severe thrombocytopenia were the most common minor complications. Analysis of cases indicated that convulsion, respiratory distress, renal failure, jaundice, anuria/oliguria, and complication during treatment impacted on longer hospital stays compared to other severe complications (P-value < 0.05). Respiratory distress was frequently found after first treatment with anti-malarial drugs (P-value = 0.002). Renal failure was frequently found before treatment with anti-malarial drugs (P-value = 0.016). Mean days of fever and higher pulse rates at presentation were predictors of poor outcome among patients with severe vivax malaria (P-value < 0.05). CONCLUSIONS: Severe anemia was the most common major manifestation of P. vivax malaria guided by the WHO criterion. Severe anemia was found less frequently in patients with P. vivax than those with P. falciparum. Renal failure, jaundice, anuria/oliguria, and complication during treatment along with, mean days of fever and higher pulse rates at presentation might be predictors of poor outcome of patients with severe vivax malaria.

Detection of Acanthamoeba spp. in two major water reservoirs in the Philippines.

Water reservoirs are important manmade structures providing water security to deliver clean and safe water for drinking and other purposes to the community. Eighty water samples were collected from Magat and Ipo water reservoirs using purposive sampling between November 2018 and January 2019. Water samples were collected in sterile containers for testing. The samples were cultured in non-nutrient agar and lawned with Escherichia coli and incubated at 33 °C. Twelve out of the 80 (15%) water samples were positive for amoebic growth. Light and scanning electron microscopy (SEM) revealed double-walled cystic stages and were initially identified as Acanthamoeba spp. based on morphological characteristic in reference to Page's established criteria. Their extracted DNAs were used in polymerase chain reaction using JDP1 and JDP2 primers and confirmed the presence of Acanthamoeba DNA in agarose gel electrophoresis. Aligned sequences from PCR products were deposited in GenBank under accession numbers MK886460, MK909919, MK905437, MK910997, MK911021 and MK886514. The presence of potentially pathogenic Acanthamoeba spp. in water reservoirs is considered a potential risk for public health, requiring appropriate processing of water in treatment plants.

Acanthamoeba species isolated from Philippine freshwater systems: epidemiological and molecular aspects.

Free-living amoeba (FLA) research in the Philippines is still in its infancy but has, by far, demonstrated the presence of potentially pathogenic species. Acanthamoeba may cause sight-threatening and central nervous system infections to humans, yet its epidemiologic distribution from local environmental sources is yet to be defined. The present study aimed to provide a baseline epidemiologic distribution of Acanthamoeba spp. in freshwater systems in the Philippines and establish potential pathogenicity of isolates through thermo-tolerance assay. A total of 63 water samples were collected from 13 freshwater systems all over the Philippine archipelago. The low-volume (50 ml) water samples were processed and cultured on non-nutrient agar lawned with Escherichia coli and observed for amoebic growth using light microscopy. Amoebic culture demonstrated 14.28% (9/63) positivity while further molecular testing of culture-positive plates using Acanthamoeba-specific primers demonstrated 100% (9/9) confirmation of Acanthamoeba species. Genotyping of Acanthamoeba isolates revealed T1, T3, T4, T5, T7, T11, and T15 genotypes. Thermo-tolerance assay demonstrated that T5 and T7 genotypes were potentially pathogenic strains. The evidence of environmental distribution of Acanthamoeba spp. in the freshwater systems in the Philippines and thermo-tolerance profile of isolates are significant aspects of amoeba study in public health and calls for initiatives in the dissemination of relevant information and the expansion of knowledge, awareness, and policies on pathogenic waterborne amoeba to mitigate, prevent, detect, and report cases of human infections.

Occurrence and the first report of Naegleria australiensis presence in a major lake in the Philippines.

Laguna de Bay or Laguna Lake is one of the six major lakes in the Philippines to be in close contact with population activities due to the expansion of urban settlements in the immediate cities surrounding the lake, thus pushing the population to settle upon its shores. To date, there are no data showing the biodiversity of free-living amoebae (FLA) present in this lake. The present study aims to isolate and identify the FLA present in Laguna de Bay, Philippines. Thirty subsurface water samples were taken from Laguna De Bay using random purposive sampling in May 2018 and were examined for amoebic growth under light microscopy (LM). Results show that 8 out of 30 (26.6%) water samples were positive for amoebic growth and were further tested for more advanced data and genetic variation of the species. Initial molecular analysis using polymerase chain reaction (PCR) and sequencing showed the presence of potentially pathogenic FLA Naegleria australiensis (MK418954). The detection of potential pathogenic FLA in lakes and dams may prove useful in preventing and controlling possible human infections in the country. More data from this study will aid in public awareness and establishing safety guidelines and control programs.

Prevalence and laboratory analysis of malaria and dengue co-infection: a systematic review and meta-analysis.

BACKGROUND: A clear understanding of the epidemiology of malaria and dengue co-infection is essential for informed decisions on appropriate control strategies for dengue and malaria. This systematic review synthesized evidence on the relationship of malaria and dengue co-infection and related it to alterations in platelet, hemoglobin, hematocrit, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels when compared to malaria mono-infection. METHODS: A systematic review in accordance with PRISMA guidelines was conducted. All published articles available in PubMed and Web of Science (ISI) databases before October 21, 2017 were recruited. All epidemiological studies except case reports on the prevalence or incidence of malaria and dengue co-infection among patients visiting hospitals with febrile illness were included. Studies that involved conference abstracts, protocols, systematic reviews, only mono-dengue or mono-malaria infections, and only animal or in vitro studies were excluded after screening the titles, abstracts, and body texts. Studies were additionally excluded after full text review when they lacked epidemiologic data on malaria and dengue co-infection. Two reviewers independently screened, reviewed, and assessed all the studies. Cochrane Q (Chi-square) and Moran's I2 were used to assess heterogeneity, and the funnel plot was used to examine publication bias. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated using a fixed-effects model. Thirteen cross-sectional and two retrospective studies were eligible to be included in the systematic review and meta-analysis. RESULTS: Out of the 2269 citations screened, 15 articles were eligible to be included in the systematic review and meta-analysis. The 15 studies involved 13,798 (10,373 cases with malaria and 3425 with dengue) patients in 9 countries. Thirteen studies compared the incidence and odds of Plasmodium sp. infection, five studies compared the odds of mean platelet, three studies compared Plasmodium parasite density, and four studies compared the odds of hemoglobin, hematocrit, AST, and ALT levels among co-infected groups and single-malaria-infected groups. CONCLUSIONS: This study showed that dengue and malaria co-infection was associated with decreased odds of malaria infection, malaria parasitemia, AST, and ALT levels when compared to malaria mono-infection. However, malaria and dengue co-infection was associated with increased odds of platelet and hemoglobin levels when compared to malaria mono-infection.

Prevalence of malarial recurrence and hematological alteration following the initial drug regimen: a retrospective study in Western Thailand.

BACKGROUND: The hematological changes following the initial drug regimen has been poorly understood in Thailand. This study was designed to determine the prevalence of malaria parasite recurrence and hematological alteration of patients during the initial drug regimen. METHODS: A retrospective study was conducted at Phop Phra Hospital, Tak Province, located in northwestern Thailand. All data from patients who were diagnosed with Plasmodium spp. infection - including types of Plasmodium spp., clinical characteristics, and hematological parameters - were retrieved and analyzed. RESULTS: The results demonstrated that during years 2012-2018, 95 out of 971 patients (9.78%) were infected with malaria two or more times. The gender, nationality, symptom of headache, type of Plasmodium spp., and career of each patient were associated with recurrence (P-value< 0.05). Among patients treated with malarial drug, the leukocyte count and red cell distribution width (RDW) were significantly changed when compared to untreated patients with recurrence (P-value< 0.05). CONCLUSION: This study indicated the high prevalence of malarial recurrence in Tak Province, Western Thailand, and its relationship to certain characteristics of individuals. Patients who were treated with antimalarial drugs exhibited leukocyte and RDW changes following the initial drug regimen. This data could be useful for prompt detection, treatment, and prevention of malarial recurrence in endemic areas of Thailand.

Diet and risk of breast cancer.

Diet may play a role in both promoting and inhibiting human breast cancer development. In this review, nutritional risk factors such as consumption of dietary fat, meat, fiber, and alcohol, and intake of phytoestrogen, vitamin D, iron, and folate associated with breast cancer are reviewed. These nutritional factors have a variety of associations with breast cancer risk. Type of fat consumed has different effects on risk of breast cancer: consumption of meat is associated with heterocyclic amine (HCA) exposure; different types of plant fiber have various effects on breast cancer risk; alcohol consumption may increase the risk of breast cancer by producing acetaldehyde and reactive oxygen species (ROS); intake of phytoestrogen may reduce risk of breast cancer through genomic and non-genomic action; vitamin D can reduce the risk of breast cancer by inhibiting the process of cancer invasion and metastasis; intake of dietary iron may lead to oxidative stress, DNA damage, and lipid peroxidation; and lower intake of folate may be linked to a higher risk of breast cancer.

Differential expression of matrix metalloproteinase-13 in association with invasion of breast cancer.

Matrix metalloproteinase-13 (MMP-13) has a potential role in tumour invasion and metastasis. However, its relevance to the prognosis of human breast cancer is poorly understood. The aim of this study is to investigate the expression patterns of MMP-13 protein and to determine its prognostic value in breast cancer, and to define its relation to the clinicopathological features. Immunohistochemistry analysis of MMP-13 was performed on formalin-fixed, paraffin-embedded sections of cancerous breast tissue (n = 76) and normal breast tissue (n = 20), all of which had clinicopathological information available. Based on the principle of immunoreactivity, the detection of MMP-13 on breast tissue was conducted using monoclonal antibodies against MMP-13. A semi-quantitative scoring system was used to assess the presence of, as well as the cellular localisation of MMP-13. MMP-13 expression was significantly greater in the cancerous breast tissues in comparison to those of normal breast tissues. In addition, high levels of MMP-13 expression were also found to be related to the positive detection of breast cancer cells in lymph nodes-amongst breast cancer patients. The results of this study showed that MMP-13 was frequently present in breast tumours, especially when tumours were accompanied by positive breast cancer cell detection in lymph nodes. This suggests that MMP-13 plays a potentially significant role in breast cancer invasion and metastasis.