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.

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.

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.

Molecular identification of Pentatrichomonas hominis in animals in central and western Thailand.

BACKGROUND: Pentatrichomonas hominis inhabits the digestive tracts of several vertebrates, such as humans, monkeys, pigs, dogs, cats and rats. This protozoan was originally considered a commensal of the digestive tract but has subsequently been identified as a potential zoonotic parasite and a causative agent of diarrhoea. Molecular techniques are considered more sensitive and specific to detect P. hominis. This study aimed to determine the presence and genetic diversity of P. hominis in animals in Thailand. A total of 403 faecal samples were collected from 119 cats, 55 dogs, 73 goats, 35 monkeys, 55 cattle and 66 pigs, and the presence of P. hominis was determined using the nested polymerase chain reaction method. Sequence analysis of small-subunit ribosomal RNA genes was used to determine the genotype of the organism. RESULTS: Twenty-six samples (26/403, 6.45%) were positive for P. hominis. The highest prevalence was found in cats (21/119; 17.65%), followed by cattle (3/55; 5.45%) and dogs (2/55; 3.64%). Seven out of 26 nucleotides demonstrated 100% sequence identity with existing sequences; additionally, 16 novel sequence patterns were identified. All nucleotide sequences of P. hominis-positive samples were shown in the same branch with the previously described P. hominis sequences found in humans, dogs and goat. CONCLUSION: This is the first study on P. hominis infections in animals in Thailand. Our findings revealed that the prevalence of P. hominis was significantly higher in cats than in cattle and dogs. Cats were the main reservoir host; however, P. hominis can infect several kinds of animals. Therefore, the proper waste management of animals is necessary to reduce and prevent infection in the community.

Molecular detection of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in school children at the Thai-Myanmar border.

Few data are available on the genetic identity of enteric protists Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in humans in Thailand. In this study, 254 stool samples were collected from primary school children from Ratchaburi Province at the Thai-Myanmar border and examined for Cryptosporidium spp., G. duodenalis, E. bieneusi and Cyclospora cayetanensis using PCR techniques. The genotype identity of the pathogens was determined by DNA sequence analysis of the PCR products. Cryptosporidium felis was found in 1 stool sample, G. duodenalis in 19 stool samples, and E. bieneusi in 4 stool samples. For G. duodenalis, sub-assemblage AII was the dominant genotype, but one infection with assemblage F was found. The E. bieneusi genotypes found included known genotypes D and J, and one novel genotype (HPTM1). Cyclospora cayetanensis was not detected in any samples. Results of the preliminary study indicate that children at the Thai-Myanmar border from Ratchaburi Province, Thailand are infected with diverse zoonotic genotypes of Cryptosporidium spp., G. duodenalis, and E. bieneusi.

"Enterocytozoon bieneusi and Cryptosporidium: a cross-sectional study conducted throughout Thailand".

BACKGROUND: Enterocytozoon bieneusi and Cryptosporidium spp. are prevalent zoonotic parasites associated with a high burden among children. To date only limited molecular epidemiological data on E. bieneusi and Cryptosporidium spp. in humans living in Thailand has been published. METHODS: PCR-based tools were used to detect and characterize E. bieneusi and Cryptosporidium spp. The internal transcribed spacer (ITS) region of the rRNA gene was used to investigate E. bieneusi, and the small subunit (SSU) rRNA gene was used to investigate Cryptosporidium spp., and 697 fecal samples from villagers and school children in rural areas in Thailand were analyzed. RESULTS: The infection rates were 2.15% (15/697) for E. bieneusi and 0.14% (1/697) for Cryptosporidium spp. The prevalence of E. bieneusi was significantly high in Loei province. Sequence analysis indicated that the Cryptosporidium isolate was C. parvum. Nine E. bieneusi genotypes were identified, EbpC, Peru12, TMH6, TMH3, TMH7, H, D, and two novel genotypes TMLH1 and TMLH2. E. bieneusi prevalence was significantly higher in male participants than in female participants, and in children aged 3-15 years than in participants aged > 15 years. CONCLUSIONS: The prevalence, genotypes, and zoonotic potential of E. bieneusi were found to vary significantly high even in one country. Transmission routes and key animal carriers of E. bieneusi may be associated with differences in hygiene, sanitation, and cultural behaviors. Further molecular studies including longitudinal studies will be required to unveil epidemiological characteristics of these opportunistic intestinal protozoa in all over the countries.

Identification of Enterocytozoon bieneusi in goats and cattle in Thailand.

BACKGROUND: Enterocytozoon bieneusi has been increasingly reported to infect domestic animals and humans, with human infections primarily reported as zoonotic in origin. The aim of the present study was to determine the presence and genotype of E. bieneusi in humans and domestic animals in central Thailand by testing stool samples of 200 apparently healthy humans, 73 goats, 60 cattle and 65 pigs using nested-PCR/ sequence analysis based on the ITS region of SSU rRNA genes. RESULTS: E. bieneusi tested positive in 2 (1%) of the 200 stool samples collected from humans and 56 (28.3%) of the 198 stool samples collected from domestic animals. The highest prevalence of E. bieneusi was observed in pigs (39/65, 60%), followed by goats (14/73, 19.2%) and cattle (3/60, 5%). Seven novel E. bieneusi genotypes were identified, which were named GoatAYE1-4 and PigAYE1-3 and clustered in either zoonotic Group 1 or Group 2. Moreover, eleven previously described E. bieneusi genotypes were also identified (O, D, H, SX1, CHC8, CHG3, CS-10, SHZC1, LW1, WildBoar5, and EbpC). All novel genotypes exhibited zoonotic potential from a phylogenetic analysis of ITS region. CONCLUSION: Our data showed that the prevalence of E. bieneusi is low in apparently healthy individuals and higher in pigs than cattle and goats. This study provides baseline data useful for controlling and preventing E. bieneusi infection in farm communities, where pigs and goats appear to be the major reservoir of E. bieneusi. The results of our study support the view that E. bieneusi is a zoonotic pathogen that should be considered a potential public health threat.

Mass spectrometry-based identification and whole-genome characterisation of the first pteropine orthoreovirus isolated from monkey faeces in Thailand.

BACKGROUND: The pteropine orthoreovirus (PRV) was isolated from monkey (Macaca fascicularis) faecal samples collected from human-inhabited areas in Lopburi Province, Thailand. These samples were initially obtained to survey for the presence of hepatitis E virus (HEV). RESULTS: Two virus isolates were retrieved by virus culture of 55 monkey faecal samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was successfully used to identify the viruses as the segmented dsRNA orthoreovirus. Phylogenetic analysis of the Lopburi orthoreovirus whole-genomes revealed relationships with the well-characterised PRVs Pulau (segment L1), Cangyuan (segments L2, M3 and S3), Melaka (segments L3 and M2), Kampar (segments M1 and S2) and Sikamat (segments S1 and S4) of Southeast Asia and China with nucleotide sequence identities of 93.5-98.9%. RT-PCR showed that PRV was detected in 10.9% (6/55) and HEV was detected in 25.5% (14/55) of the monkey faecal samples. CONCLUSIONS: PRV was isolated from monkey faeces for the first time in Thailand via viral culture and LC-MS/MS. The genetic diversity of the virus genome segments suggested a re-assortment within the PRV species group. The overall findings emphasise that monkey faeces can be sources of zoonotic viruses, including PRV and HEV, and suggest the need for active virus surveillance in areas of human and monkey co-habitation to prevent and control emerging zoonotic diseases in the future.

Knowledge, Behavior, and Free-Living Amoebae Contamination of Cosmetic Contact Lens Among University Wearers in Thailand: A Cross-Sectional Study.

OBJECTIVE: To assess the general knowledge, behavior, and presence of potentially pathogenic amoebae in cosmetic contact lens (CCL) wearers. METHODS: One hundred CCL asymptomatic wearers were randomly selected. A questionnaire regarding their lens use, and a pair of their CCL was obtained. Identification of free-living amoeba (FLA) strains was based on morphological diagnosis, enflagellation tests (for non-Acanthamoeba strains), and sequencing of the small-subunit rRNA gene fragments. RESULTS: Most (92%) of the participants surveyed were women, and the average age of the participants was 21.5±0.2 years. The CCL wearers generally showed a moderate (47%) or good (35%) level of knowledge, and good (51%) or excellent (40%) use of CCL. Two CCL samples were positive for Acanthamoeba genotype T3 or Vahlkampfia. The Acanthamoeba-contaminated CCL was from a wearer who used saline for treating lenses, and the Vahlkampfia-contaminated CCL was from a wearer who used CCL while swimming. CONCLUSIONS: This is the first report of the presence of potentially pathogenic FLA in used CCL from asymptomatic wearers in Thailand. Although there was satisfactory knowledge and practice of lens care use, the public should be aware of CCL contaminated with potentially pathogenic FLA that can directly or indirectly cause keratitis.

Subtype Distribution of Blastocystis in Communities along the Chao Phraya River, Thailand.

Blastocystis is a common zoonotic enteric protozoan that has been classified into 17 distinct subtypes (STs). A cross-sectional study was conducted to determine the prevalence and subtype distributions of Blastocystis in villagers living along the Chao Phraya River, Ayutthaya Province, Thailand, and to assess the risk of zoonotic infection. In total, 220 stool samples were collected, and DNA was extracted. PCR and sequencing were performed with primers targeting the small-subunit ribosomal RNA (SSU rRNA) genes. Blastocystis was present in 5.9% (13/220) of samples, and ST3 (5.0%; 11/220) was the predominant subtype, followed by ST2 (0.45%; 1/220) and ST6 (0.45%; 1/220). Phylogenetic trees were constructed with the maximum-likelihood method based on the Hasegawa-Kishino-Yano + G + I model, neighbor-joining, and maximum parsimony methods. The percentage of bootstrapped trees in which the associated taxa clustered together was relatively high. All the sequences of the Blastocystis-positive samples (KU051524-KU051536) were closely related to those from animals (pig, cattle, and chicken), indicating a zoonotic risk. Therefore, the villagers require proper health education, especially regarding the prevention of parasitic infection, to improve their personal hygiene and community health. Further studies are required to investigate the Blastocystis STs in the animals living in these villages.

Subtype distribution of Blastocystis in Thai-Myanmar border, Thailand.

Blastocystis sp. is a common zoonotic intestinal protozoa which has been classified into 17 subtypes (STs). A cross-sectional study was conducted to determine the prevalence and subtype distribution of Blastocystis in villagers living on the Thai-Myanmar border, where the risk of parasitic infection is high. A total of 207 stool samples were collected and DNA was extracted. PCR and sequencing using primers targeting small-subunit ribosomal RNA (SSU rRNA) gene were performed. The prevalence of Blastocystis infection was 37.2% (77/207). ST3 (19.8%; 41/207) was the predominant subtype, followed by ST1 (11.6%; 24/207), ST2 (5.3%; 11/207), and ST4 (0.5%; 1/207). A phylogenetic tree was reconstructed using the maximum likelihood (ML) method based on the Hasegawa-Kishino-Yano + G + I model. The percentage of bootstrapped trees in which the associated taxa clustered together was relatively high. Some sequences of Blastocystis positive samples (TK18, 39, 46, 71, and 90) were closely related to animals (pig and cattle) indicating zoonotic risks. Therefore, proper health education in parasitic prevention for the villagers should be promoted to improve their personal hygiene. Further longitudinal studies are required to monitor the prevalence of parasitic infections after providing health education and to investigate Blastocystis ST in animals living in these villages.

ANTIOXIDANT ENZYME ACTIVITY AMONG ORPHANS INFECTED WITH INTESTINAL PARASITES IN PATHUM THANI PROVINCE, THAILAND.

Intestinal parasitic infections can negatively impact growth and nutrition in children. The infections can induce oxidative stress, resulting in a variety of illnesses. We measured antioxidant enzyme levels in orphan children infected with intestinal parasites to investigate the influence of nutritional status on antioxidant enzymes. This cross sectional study was conducted at an orphanage in Thailand. Stool samples were obtained from each subject and examined for intestinal parasites. Anthropometric measurements, complete blood count and biochemical parameters, including serum superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, were obtained from studied subjects. One hundred twenty-eight children were included in the study. Intestinal parasites were found on microscopic examination of the stools in 36.7% (47/128); 18% (23/128) had a mixed parasite infection. Intestinal protozoa were found in 34.4% of subjects and intestinal helminthes were found in 2.3%. The median GPx level in children infected with intestinal parasites (2.3 ng/ml) was significantly lower than in non-infected children (7.7 ng/ml) (p < 0.05). However, there was no significant difference in SOD levels between the two groups. When comparing GPx levels in children with 1) pathogenic parasites, 2) non-pathogenic parasites and 3) no intestinal parasite infection, GPx levels differed significantly among three groups (2.2 ng/ml, 2.4 ng/ml and 7.7 ng/ml, respectively) (p < 0.05). When separating children by BMI and type of infection, the median SOD level in underweight children infected with pathogenic parasites (107.2 ng/ml) was significantly higher than in underweight children infected with non-pathogenic parasites (68.6 ng/ml) and without intestinal parasite infections (72.2 ng/ml). The present study identified two key findings: low GPx levels in children with intestinal parasitic infections, and the potential impact of malnutrition on some antioxidants.

Gastrointestinal parasites of dogs and cats in a refuge in Nakhon Nayok, Thailand.

We collected fecal samples from 500 dogs and 300 cats from an animal refuge in Nakhon Nayok Province, Thailand to test for gastrointestinal protozoa and helminths using a formalin-ether concentration technique. The overall prevalence of parasites in stool from dogs was 36.2% (181/500), 35.7% (177/500) had helminths and 2.8% (14/500) had protozoa. The helminths were: hookworm (30.6%), Trichuris vulpis (16.0%), Toxocara canis (6.6%), Hymenolepis diminuta (1.2%), Spirometra mansoni (0.6%), and Dipylidium caninum (0.2%). Giardia duodenalis (2.8%) was found in the stool of dogs. The overall prevalence of parasites in stool from cats was 44.3% (133/300), 43.3% (130/300) were helminths and 6.0% (18/300) were protozoa. The helminths were hookworm (34.7%), T. cati (9.7%), S. mansoni (4.0%), Platynosomum fastosum (2.7%), Strongyloides sp (0.7%), and Echinostoma sp (0.3%). Two species of protozoa, Isospora sp (5.7%) and G. duodenalis (0.3%) were found in the stool of cats. Two percent of dogs and 5.0% of cats had mixed protozoan and helminthic infections. Dogs with double, triple, and quadruple helminthic infections were found at rates of 22.0%, 2.8%, and 0.2%, respectively. Cats with double and triple helminthic infections were found at rates of 9.7% and 1.0%, respectively. Quadruple helminthic infections were not found in cats, and double protozoan infections were not found in either dogs or cats.

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.

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.

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.

Cats and dogs as hosts of Blastocystis - What is the evidence?

Blastocystis is one of the most common intestinal parasites observed in human and non-human hosts. Recent meta-analyses have indicated a potential role for pets such as dogs and cats as reservoir hosts of Blastocystis, but the data underpinning this hypothesis are of mixed quality. Reviewing data for 45,894 samples tested for Blastocystis by DNA-based methods and 11,908 subtype observations, a model was developed for calculating indices that could be used for evaluating individual species as natural hosts of Blastocystis, based on weighted products of positivity rates and subtype distributions. Data from cats and dogs were analysed, using other well-sampled hosts (pig, cattle, sheep, goat, and human) as references. Data from cats and dogs meeting the inclusion criteria were entered into the model. The overall positivity rates for pigs, cattle, sheep, goats, humans, dogs, and cats were 40 %, 40 %, 35 %, 28 %, 25 %, 6 %, and 5 %, respectively, with statistically significant lower positivity rates in cats and dogs (p < 0.0001). Indices indicating Blastocystis specificity to host ranged between 0.16 (humans) and 0.49 (cattle) for the reference hosts, whereas indices for cats and dogs were only 0.01 and 0.02, respectively. Finally, indices for ST specificity to host were higher for reference hosts (range, 0.66-0.93) than for cats (0.62) and dogs (0.56). Taken together, the analyses indicate that cats and dogs are not natural or reservoir hosts of Blastocystis and that the sporadic subtype pattern observed in these hosts might indicate exposure to Blastocystis through contaminated water/feed, including Blastocystis colonizing prey animals.

A systematic review and meta-analysis of cortisol levels in Plasmodium infections.

Malaria has complex interactions with host physiology, including alterations in cortisol levels. Cortisol, a key hormone in the stress response, is known to be dysregulated in various infectious diseases. This systematic review and meta-analysis aimed to elucidate the relationship between Plasmodium infection and cortisol levels, shedding light on the intricate interplay between the parasite and the host's endocrine system. The methodological protocol for assessing cortisol levels in malaria patients was registered in PROSPERO (CRD42024496578), a widely recognized international prospective register of systematic reviews. This registration ensures transparency and minimizes the risk of bias in our research. A comprehensive search strategy was employed across major databases, including Embase, PubMed, Scopus, and Medline, to include studies that reported cortisol levels in infected patients. The qualitative synthesis was undertaken to synthesize the difference in cortisol levels between malaria-infected and uninfected individuals. The meta-analysis employed the random effects model in the quantitative synthesis to calculate the effect estimate. The review included a total of 20 studies, with a substantial number conducted in Africa, followed by Asia and South America. Most included studies (13/20, 65%) reported higher cortisol levels in infected patients than in uninfected patients. The meta-analysis confirmed significantly higher cortisol levels in infected patients compared to uninfected individuals (P < 0.0001, standardized mean difference (SMD): 1.354, 95% confidence interval: 0.913 to 1.795, I2: 88.3%, across 15 studies). Notably, the method for cortisol measurement and the type of blood sample used (serum or plasma) were significant moderators in the analysis, indicating that these factors may influence the observed relationship between Plasmodium infection and cortisol levels. The systematic review and meta-analysis confirmed that Plasmodium infection is associated with increased cortisol levels, highlighting the intricate relationship between the disease and the host stress response. These findings underscore the potential of cortisol as a supplementary biomarker for understanding the pathophysiological impact of malaria. By providing insights into the stress-related mechanisms of malaria, this comprehensive understanding can inform future research and potentially enhance disease management and treatment strategies, particularly in regions heavily burdened by malaria.