A systematic review and meta-analysis of the global prevalence and relationships among Burkholderia pseudomallei sequence types isolated from humans, animals, and the environment.

Background and Aim: Burkholderia pseudomallei, a highly pathogenic bacterium responsible for melioidosis, exhibits ecological ubiquity and thrives within soil and water reservoirs, posing significant infection risks to humans and animals through direct contact. The aim of this study was to elucidate the genetic diversity and prevalence patterns of B. pseudomallei sequence types (STs) across a global spectrum and to understand the relationships between strains isolated from different sources. Materials and Methods: We performed a systematic review and meta-analysis in this study. Extensive research was carried out across three comprehensive databases, including PubMed, Scopus, and ScienceDirect with data collected from 1924 to 2023. Results: A total of 40 carefully selected articles contributed 2737 B. pseudomallei isolates attributed to 729 distinct STs and were incorporated into the systematic review. Among these, ST46 emerged as the most prominent, featuring in 35% of the articles and demonstrating a dominant prevalence, particularly within Southeast Asia. Moreover, ST51 consistently appeared across human, animal, and environmental studies. Subsequently, we performed a meta-analysis, focusing on nine specific STs: ST46, ST51, ST54, ST70, ST84, ST109, ST289, ST325, and ST376. Surprisingly, no statistically significant differences in their pooled prevalence proportions were observed across these compartments for ST46, ST70, ST289, ST325, and ST376 (all p > 0.69). Conversely, the remaining STs, including ST51, ST54, ST84, and ST109, displayed notable variations in their prevalence among the three domains (all p < 0.04). Notably, the pooled prevalence of ST51 in animals and environmental samples surpassed that found in human isolates (p < 0.01). Conclusion: To the best of our knowledge, this study is the first systematic review and meta-analysis to investigate the intricate relationships between STs and their sources and contributes significantly to our understanding of B. pseudomallei diversity within the One Health framework.

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.

Increased Blood Concentrations of Malondialdehyde in Plasmodium Infection: A Systematic Review and Meta-Analysis.

Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and Plasmodium infections; however, the findings remain inconclusive. This study synthesized differences in MDA concentrations among patients with different levels of clinical severity, uninfected controls, and different Plasmodium species. The research protocol was registered in PROSPERO (CRD42023393540). Systematic literature searches for relevant studies were performed using the Embase, MEDLINE, Ovid, ProQuest, PubMed, Scopus, and Google Scholar databases. Qualitative and quantitative syntheses (meta-analyses) of distinct MDA concentrations between the disease groups were performed. Twenty-three studies met the eligibility criteria and were included in the systematic review. Overall, MDA concentrations were significantly elevated in participants with malaria relative to uninfected controls (p < 0.01, Cohen d: 2.51, 95% confidence interval (CI): 1.88-3.14, I2: 96.22%, 14 studies). Increased MDA concentrations in participants with malaria compared with uninfected controls were found in studies that enrolled patients with P. falciparum malaria (p < 0.01, Cohen d: 2.50, 95% CI: 1.90-3.10, I2: 89.7%, 7 studies) and P. vivax malaria (p < 0.01, Cohen d: 3.70, 95% CI: 2.48-4.92, I2: 90.11%, 3 studies). Our findings confirm that MDA concentrations increase during Plasmodium infection, indicating a rise in oxidative stress and lipid peroxidation. Thus, MDA levels can be a valuable biomarker for evaluating these processes in individuals with malaria. However, further research is necessary to fully elucidate the intricate relationship between malaria, antioxidants, oxidative stress, and the specific role of MDA in the progression of malaria.

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.

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.

Distinct cytokine profiles in malaria coinfections: A systematic review.

BACKGROUND: Few data exist on the distinct cytokine profiles of individuals with malaria coinfections and other diseases. This study focuses on data collation of distinct cytokine profiles between individuals with malaria coinfections and monoinfections to provide evidence for further diagnostic or prognostic studies. METHODS: We searched five medical databases, including Embase, MEDLINE, PubMed, Ovid, and Scopus, for articles on cytokines in malaria coinfections published from January 1, 1983 to May 3, 2022, after which the distinct cytokine patterns between malaria coinfection and monoinfection were illustrated in heat maps. RESULTS: Preliminary searches identified 2127 articles, of which 34 were included in the systematic review. Distinct cytokine profiles in malaria coinfections with bacteremia; HIV; HBV; dengue; filariasis; intestinal parasites; and schistosomiasis were tumor necrosis factor (TNF), interferon (IFN)-γ, IFN-α, interleukin (IL)-1, IL-1 receptor antagonist (Ra), IL-4, IL-7, IL-12, IL-15, IL-17; TNF, IL-1Ra, IL-4, IL-10, IL-12, IL-18, CCL3, CCL5, CXCL8, CXCL9, CXCL11, granulocyte colony-stimulating factor (G-CSF); TNF, IFN-γ, IL-4, IL-6, IL-10, IL-12, CCL2; IFN-γ, IL-1, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, CCL2, CCL3, CCL4, G-CSF; IL-1Ra, IL-10, CXCL5, CXCL8, CXCL10; TNF, IL-2, IL-4, IL-6, IL-10; and TNF, IFN-γ, IL-4, IL-5, IL-10, transforming growth factor-ß, CXCL8, respectively. CONCLUSION: This systematic review provides information on distinct cytokine profiles of malaria coinfections and malaria monoinfections. Further studies should investigate whether specific cytokines for each coinfection type could serve as essential diagnostic or prognostic biomarkers for malaria coinfections.

Increased interferon-γ levels and risk of severe malaria: a meta-analysis.

Interferon (IFN)-γ contributes to the pathogenesis of severe malaria; however, its mechanism remains unclear. Herein, differences in IFN-γ levels between patients with severe and uncomplicated malaria were evaluated using qualitative and quantitative (meta-analysis) approaches. The systematic review protocol was registered at PROSPERO (ID: CRD42022315213). The searches for relevant studies were performed in five databases, including PubMed, Scopus, Embase, MEDLINE and Web of Science, between 1 January and 10 July 2022. A meta-analysis was conducted to pool the mean difference (MD) of IFN-γ levels between patients with severe malaria and those with uncomplicated malaria using a random-effects model (DerSimonian and Laird method). Overall, qualitative synthesis indicated that most studies (14, 58.3%) reported no statistically significant difference in IFN-γ levels between patients with severe malaria and those with uncomplicated malaria. Meanwhile, remaining studies (9, 37.5%) reported that IFN-γ levels were significantly higher in patients with severe malaria than those in patients with uncomplicated malaria. Only one study (4.17%) reported that IFN-γ levels were significantly lower in patients with severe malaria than those in patients with uncomplicated malaria. The meta-analysis results indicated that patients with severe malaria had higher mean IFN-γ levels than those with uncomplicated malaria (p < 0.001, MD: 13.63 pg/mL, 95% confidence interval: 6.98-20.29 pg/mL, I2: 99.02%, 14 studies/15 study sites, 652 severe cases/1096 uncomplicated cases). In summary, patients with severe malaria exhibited higher IFN-γ levels than those with uncomplicated malaria, although the heterogeneity of the outcomes is yet to be elucidated. To confirm whether alteration in IFN-γ levels of patients with malaria may indicate disease severity and/or poor prognosis, further studies are warranted.

First isolation of verocytotoxin-producing Escherichia coli O157:H7 from sports animals in Southern Thailand.

Background and Aim: Escherichia coli O157:H7 is enterohemorrhagic E. coli, which produces verocytotoxin or Shiga toxin. It is a well-known cause of severe diseases in humans worldwide. Cattle and other ruminants are the main reservoirs of this organism. Sports animals, such as fighting bulls, riding horses, and fighting cocks, are economic animals in Southern Thailand. This study aimed to identify E. coli O157:H7 from the rectal swabs of these sports animals and determine the antimicrobial susceptibility patterns of isolated bacteria. Materials and Methods: The rectal swabs were collected from 34 fighting bulls, 32 riding horses, and 31 fighting cocks. The swabs were cultured on MacConkey (MAC) Agar; the suspected colonies were then identified by VITEK® 2 GN card, and the antimicrobial susceptibility was tested by VITEK® 2 AST N194 in VITEK® 2 Compact automation. Escherichia coli O157:H7 was confirmed by culturing on sorbitol MAC agar, the ability to grow at 44°C, and the presence of H7 antigen. In addition, the eaeA (E. coli attaching and effacing), along with stx1 and stx2 (Shiga cytotoxins) genes, were determined using polymerase chain reaction. Finally, the cytotoxicity of Shiga toxin was confirmed using the Vero cytotoxicity test. Results: Fifty-five suspected isolates (56.70%), which were collected from 19 fighting bulls (55.88%), 13 riding horses (40.63%), and 23 fighting cocks (71.13%), were identified as E. coli. However, one sample (Bull H9/1) from fighting bulls had an equal confidence level (50%) for E. coli and E. coli O157. The confirmation of this isolate demonstrated that it was sorbitol non-fermenter, could assimilate L-lactate, was unable to grow well at 44°C, and reacted with anti-serum to H7 antigen. In addition, it was positive with stx2 and eaeA genes, and the toxin affected Vero cells by a dose-dependent response. The antimicrobial susceptibility test revealed that five out of 55 (9.09%) E. coli isolates were resistant to antimicrobial agents. All five isolates (21.74%) were collected from fighting cocks. Escherichia coli Cock H4/3 was only one of the five isolates resistant to three antimicrobial agents (ciprofloxacin, moxifloxacin, and trimethoprim/sulfamethoxazole). Fortunately, it was not multidrug-resistant bacteria. Conclusion: This is the first report on detection of E. coli O157:H7 in fighting bulls and antibiotic-resistant characteristic of E. coli in fighting cocks in Southern Thailand. This research is beneficial in preventing the dissemination of E. coli O157:H7 or antimicrobial agent-resistant E. coli in sports animals and humans.

Evidence of and deaths from malaria and severe pneumonia co-infections in malaria-endemic areas: a systematic review and meta-analysis.

Malaria and pneumonia are the leading causes of childhood mortality in children under 5 years of age. Nevertheless, the proportions and deaths of malaria co-infection among patients with severe pneumonia, particularly in children under 5 years of age, and characteristics of co-infection remain poorly explored. Hence, the present study aimed to collate the evidence of malaria among patients with severe pneumonia, severe pneumonia among patients with malaria, and the proportion of deaths among patients with co-infections. Potentially relevant studies were searched in six databases including PubMed, Scopus, Web of Science, Embase, Ovid, and MEDLINE to identify studies on malaria and severe pneumonia co-infections that were published until 21 July 2022 with a restriction for the non-English language but no restriction for the publication year. The quality of the included studies was determined using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The pooled estimates, including the pooled proportion of malaria among patients with severe pneumonia, and the proportion of deaths among patients with co-infections, were estimated by the random-effects model. Of the 4094 studies examined, 11 studies that met the eligibility criteria were included in the review. Meta-analysis results showed that the proportion of malaria (2162 cases) among patients with severe pneumonia (9738 cases) was 19% (95% CI 12-26%, I2: 98.79%, 11 studies). The proportion of severe pneumonia (546 cases) among patients with malaria (10,325 cases) was 20% (95% CI 0-40%, I2: 99.48%, 4 studies). The proportion of deaths among patients with co-infection was 13% (95% CI 2-23%, I2: 85.1%, 3 studies). In conclusion, nearly one-fifth of patients with severe pneumonia have malaria, one-fifth of patients with malaria have severe pneumonia, and about 13% of co-infections lead to deaths. This information raised the clinical importance of diagnosis and management of concurrent infections. Patients with severe pneumonia should be investigated for malaria, and vice versa. Detection of co-infections might provide the information to inform the physician to manage and cure co-infected patients who live in areas where both diseases were endemic.

Prevalence, probability, and characteristics of malaria and filariasis co-infections: A systematic review and meta-analysis.

BACKGROUND: Malaria and filariasis are significant vector-borne diseases that are co-endemic in the same human populations. This study aims to collate the evidence, probability, and characteristics of malaria and filariasis co-infections in participants among studies reporting the co-occurrence of both diseases. METHODS: We searched for potentially relevant articles reporting the co-occurrence of malaria and filariasis in five electronic databases (Embase, PubMed, Scopus, Medline, and CENTRAL) from inception to May 22, 2022. We estimated the pooled prevalence and probability of malaria and filariasis co-infections among study participants using random-effects meta-analyses and synthesized the characteristics of patients with co-infections narratively. RESULTS: We identified 951 articles, 24 of which (96,838 participants) met eligibility criteria and were included in the systematic review. Results of the meta-analysis showed a pooled prevalence of malaria and filariasis co-infections among participants of 11%. The prevalence of co-infections was 2.3% in Africa, 0.2% in Asia, and 1.6% in South America. The pooled prevalences of malaria and Wuchereria bancrofti, malaria and Loa loa, malaria and Mansonella perstans co-infections were 0.7%, 1.2%, and 1.0%, respectively. The meta-analysis results showed that the co-infections between two parasites occurred by probability (P = 0.001). Patients with co-infections were at increased risk of having an enlarged spleen, a lower rate of severe anemia, lower parasite density, and more asymptomatic clinical status. Patients with co-infections had decreased levels of C-X-C motif chemokine 5, tumor necrosis factor-α, interleukin-4, c4 complement, and interleukin-10. In addition, patients with co-infections had a lower interleukin-10/tumor necrosis factor-α ratio and higher interleukin-10/interleukin-6 ratio. CONCLUSION: The present study showed that the prevalence of malaria and filariasis co-infections was low and varied between geographical areas in the selected articles. Co-infections tended to occur with a low probability. Further studies investigating the outcomes and characteristics of co-infections are needed.

Procalcitonin as a Candidate Biomarker for Malarial Infection and Severe Malaria: A Meta-Analysis.

Procalcitonin (PCT), as a marker of malaria severity, remains to be investigated. The present study collated and compared the levels of PCT between patients with severe malaria, uncomplicated malaria, and control participants to assess their role in predicting malaria infection and disease severity. The systematic review was registered at PROSPERO with registration number CRD42021297243. The search for relevant studies that reported PCT in patients with malaria was performed in PubMed, Scopus, and Web of Science. The following meta-analyses were conducted; (1) the pooled mean PCT levels in patients with severe and uncomplicated malaria, and (2) the pooled mean difference in PCT levels between patients with severe and uncomplicated malaria. Fifteen studies were included for qualitative and quantitative syntheses. The meta-analysis results show that the pooled mean PCT levels in patients with uncomplicated malaria were 3.92 ng/mL (95% CI: 2.26-5.58 ng/mL, I2: 96.5, five studies), whereas the pooled mean PCT levels in patients with severe malaria were 14.13 ng/mL (95% CI: 8.75-19.5 ng/mL, I2: 92.6, six studies). The meta-analysis showed that patients with severe malaria had an equal mean of PCT compared to those with uncomplicated malaria when the random-effects model was used (p: 0.055, weighted mean difference: 6.93, 95% CI: -0.16-14.02, I2: 84.6%, four studies). There were probable correlations between the level of parasitemia, immunity level, and possibly bacterial or other parasitic co-infection that could affect the PCT level among different clinical severities of malaria. Therefore, the PCT level alone does not seem to be a suitable biomarker to discriminate the severe/uncomplicated or infected/uninfected cases. Further studies should investigate the increased PCT levels in combination with other markers in association with malaria infection and severity.

The Prevalence of Malaria and Bacteremia Co-Infections among Febrile Patients: A Systematic Review and Meta-Analysis.

Comprehensive data on the relative contribution of bacteremia to malaria outcomes in a large number of participants are lacking. Therefore, we collated data on the co-existence of malaria and bacteremia in the literature to provide evidence-based information for future studies investigating the clinical significance of this co-infection. The study protocol was registered at PROSPERO (ID: CRD42021287971). Relevant studies were identified from PubMed, Web of Science, and Scopus. The pooled prevalence of (1) co-existent malaria and bacteremia among febrile patients, (2) the pooled prevalence of bacteremia among patients with malaria, (3) the probability of co-infection, and (4) the pooled prevalence of deaths were estimated by the random-effects model. Fifty-one studies involving 1583 cases of co-infection were included in the analyses. Typhoidal Salmonella spp. and Staphylococcus aureus were the most common Gram-negative and Gram-positive bacteria, respectively. The prevalence of co-existent malaria and bacteremia among febrile patients was 1.9% (95% confidence interval (CI) = 1.5-2.2%, I2 = 96.64%, 31 studies). The prevalence of bacteremia among patients with malaria was 7.6% (95% CI = 6.7-8.7%, and I2 = 96.68%, 43 studies). Co-infection by malaria and bacteremia did not occur by chance (p = 0.024, odds ratio = 0.64, 95% CI = 0.43-0.94, and I2 = 95.7%, 29 studies). The pooled prevalence of deaths among patients with co-infection was 15.0% (95% CI = 8.0-23.0%, I2 = 75.23%, 8 studies). On the basis of this study, we conclude that although the prevalence of co-infection was low, patients with malaria appear at greater risk of bacteremia and death.

Prevalence and Characteristics of Malaria and Influenza Co-Infection in Febrile Patients: A Systematic Review and Meta-Analysis.

Malaria and influenza are co-endemic in several geographical areas, and differentiation of their clinical features is difficult. The present study aimed to qualitatively and quantitatively analyze the prevalence and characteristics of malaria and influenza co-infection in febrile patients. The systematic review was registered at PROSPERO (CRD42021264525). Relevant literature that reported malaria and influenza co-infection in febrile patients were searched in PubMed, Web of Science, and Scopus from 20 June to 27 June 2021 and the risk of bias for each study was assessed. Quantitative analysis included pooled prevalence, and the odds of malaria and influenza virus co-infection among febrile patients were estimated using a random-effects model. Subgroup analyses were performed to summarize the effect estimate for each group. Funnel plot, Egger's test, and contour-enhanced funnel plot were used to demonstrate any publication bias among outcomes of included studies. Among 4253 studies retrieved, 10 studies that enrolled 22,066 febrile patients with 650 co-infected patients were included for qualitative and quantitative syntheses. The pooled prevalence of malaria and influenza virus co-infection among febrile patients was 31.0% in Nigeria, 1.0% in Tanzania, 1.0% in Uganda, 1.0% in Malawi, 1.0% in Ghana, 0% in Cambodia, 7.0% in the Central African Republic, and 7.0% in Kenya. Meta-analysis also showed co-infection occurrence by chance (p = 0.097, odds ratio 0.54, 95% CI 0.26-1.12, I2 94.9%). The prevalence of malaria and influenza virus co-infection among febrile patients was heterogeneous by country, characteristics of febrile participants, and diagnostic tests for influenza virus. Further studies should investigate severe clinical manifestations or differentiate clinical outcomes between mono-infected or co-infected individuals, whether the co-infection leads to severe disease outcome.

Prevalence of Plasmodium spp. in Anopheles mosquitoes in Thailand: a systematic review and meta-analysis.

BACKGROUND: The entomological inoculation rate (EIR) is one of the key indices used to evaluate malaria transmission and vector control interventions. One of the components of the EIR is the sporozoite rate in Anopheles vectors. A systematic review and meta-analysis was performed to identify the prevalence of Plasmodium spp. in field-collected Anopheles species across Thailand. METHODS: This systematic review was registered under the PROSPERO number CRD42021297255. Studies that focused on the identification of Plasmodium spp. in Anopheles mosquitoes were identified from the electronic databases PubMed, Web of Science, and Scopus. The quality of the identified studies was determined using the Strengthening the Reporting of Observational Studies in Epidemiology approach. The proportion of Anopheles mosquitoes collected, Anopheles vectors for Plasmodium species, and specificity of Anopheles vectors for Plasmodium species were analyzed. The pooled prevalence of Plasmodium species among the primary vectors (Anopheles dirus, Anopheles minimus, and Anopheles maculatus) was estimated using the random-effects model. RESULTS: Of the 1113 studies identified, 31 were included in the syntheses. Of the 100,910 Anopheles mosquitoes identified for species and sibling species, An. minimus (40.16%), An. maculatus (16.59%), and Anopheles epiroticus (9.18%) were the most prevalent Anopheles species. Of the 123,286 Anopheles mosquitoes identified, 566 (0.46%) were positive for Plasmodium species. The highest proportions of Plasmodium species were identified in Anopheles hodgkini (2/6, 33.3%), Anopheles nigerrimus (2/24, 8.33%), Anopheles balabacensis (4/84, 4.76%), An. dirus (114/4956, 2.3%), Anopheles annularis (16/852, 1.88%), Anopheles kochi (8/519, 1.54%), Anopheles vagus (3/215, 1.4%), and Anopheles baimaii (1/86, 1.16%). The pooled prevalence of Plasmodium species identified in the main Anopheles vectors was 0.4% of that of Plasmodium species identified in An. dirus was 2.1%, that of Plasmodium species identified in An. minimus was 0.4%, and that of Plasmodium species identified in An. maculatus was 0.4%. CONCLUSIONS: We found a low prevalence of Plasmodium infection in Anopheles mosquitoes across Thailand. Therefore, the use of EIR to determine the impact of vector control intervention on malaria parasite transmission and elimination in Thailand must be undertaken with caution, as a large number of Anopheles specimens may be required.

Prevalence, anti-malarial chemoprophylaxis and causes of deaths for severe imported malaria: A systematic review and meta-analysis.

BACKGROUND: There are limited data regarding prevalence, anti-malarial chemoprophylaxis, and causes of death for severe imported malaria. Thus, we conducted a systematic review and meta-analysis to characterise these variables. METHODS: We searched studies reporting deaths attributable to severe imported malaria. The following pooled prevalence rates were determined: 1) the pooled prevalence of severe malaria among patients with imported malaria, 2) the pooled prevalence of deaths among patients with severe imported malaria, 3) the pooled prevalence of anti-malarial chemoprophylaxis among patients with severe imported malaria, and 4) the causes of death among patients with severe imported malaria. RESULTS: The search identified 52 studies that were mainly conducted in Europe (25, 48.1%), North America (16, 30.8%) and Asia (7, 13.5%). The pooled prevalence of severe imported malaria was 12.5% (95% confidence interval [CI] = 10.3%-14.6%, I2 = 99.32%, 12393 severe cases/118325 imported cases). The pooled prevalence of deaths attributable to severe imported malaria was 5.1% (95% CI = 4.0%-6.2%, I2 = 91.72%, 721 deaths/16310 severe cases). The pooled prevalence of adequate anti-malarial chemoprophylaxis among patients with severe imported malaria was 9.7% (95% CI = 6.5%-13.0%, I2 = 89.9%, 203/2049 cases). The most common cause of death was multi-organ failure (12.3%). CONCLUSION: The results highlighted the need for education and preventative measures for travellers, immigrants, or workers who plan to visit malaria-endemic areas to minimize the risk of severe disease or death.

Tumour necrosis factor-α as a prognostic biomarker of severe malaria: a systematic review and meta-analysis.

BACKGROUND: Tumour necrosis factor-alpha (TNF-α) levels are reportedly altered during malaria. In this systematic review and meta-analysis, we aimed to collect and compare data on TNF-α levels between patients with malaria of varying severity and healthy asymptomatic positive controls. METHODS: We searched PubMed, Scopus and Web of Science for studies that reported TNF-α levels in malaria cases of different severity and healthy asymptomatic positive controls using a combination of search terms. The quality of the included studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. To compare the TNF-α levels among fatal cases, severe cases, uncomplicated cases and healthy asymptomatic positive controls, we applied the random-effects model that assumed the existence of variations between studies. The effect estimate was pooled mean difference (MD) with a 95% confidence interval (CI). RESULTS: From 1694 studies, we included 31 studies that met our eligibility criteria for systematic review and meta-analysis. Patients with severe malaria showed higher mean TNF-α levels than those with uncomplicated malaria (P < 0.001, pooled MD = 79.02 pg/ml, 95% CI: 63.68-94.35 pg/ml, I2: 99.5%, n = 26 studies). Furthermore, fatal cases had no difference in the mean TNF-α levels in comparison with survived cases (P = 0.055, pooled MD = 82.38 pg/ml, 95% CI: -1.93 to 166.69 pg/ml, I2: 99.54%, n = 5 studies). Finally, patients with uncomplicated malaria showed higher mean TNF-α levels than those with asymptomatic malaria (P < 0.001, pooled MD = 45.10 pg/ml, 95% CI: 18.45-71.76 pg/ml, I2: 97.09%, n = 5 studies). CONCLUSION: This systematic review and meta-analysis confirmed the increase of TNF-α levels in patients with severe malaria. Therefore, TNF-α may be alternatively used as a prognostic biomarker of severe malaria. TRIAL REGISTRATION: Not applicable.

Increased interleukin-6 levels associated with malaria infection and disease severity: a systematic review and meta-analysis.

Interleukin-6 (IL-6) is generated by immune cells during infection with malaria parasites and they are associated with the immunopathogenesis of malaria. The present systematic review and meta-analysis aimed to compare the differences in IL-6 levels between several groups of patients with malaria and healthy control groups. The systematic review was registered at PROSPERO with a registration number: CRD42021290753. Systematic literature searches were conducted in PubMed, Web of Science, and Scopus until November 7, 2021 to obtain studies that documented IL-6 levels in patients with malaria. The quality of the included studies was assessed using critical appraisal tools from the Joanna Briggs Institute. Differences in the mean IL-6 levels among patients with: (1) severe and non-severe malaria, (2) uncomplicated malaria and controls, (3) uncomplicated and asymptomatic malaria, (4) asymptomatic malaria and healthy controls, and (5) those that died or survived were estimated using a random-effects model. Forty-three of 1,969 studies were included in the systematic review. Results of the meta-analysis showed that patients with severe malaria had higher mean IL-6 levels than those with non-severe malaria [P = 0.04, weight mean difference (WMD) = 96.63 pg/mL, 95% confidence interval (CI) = 0.88 - 19.38 pg/mL, I2 = 99.9%, 13 studies]. Patients with uncomplicated malaria had higher mean IL-6 levels than the controls (P < 0.001, WMD = 42.86 pg/mL, 95% CI = 30.17 - 55.56 pg/mL, I2 = 100%, 17 studies). No differences in the mean levels of IL-6 were found between patients with uncomplicated malaria and those with asymptomatic malaria (P = 0.063, WMD = 42.07 pg/mL, 95% CI = - 2.23 pg/mL to - 86.37 pg/mL, I2 = 99.1%, 8 studies), or between patients with asymptomatic malaria and healthy controls (P = 0.45, WMD = 1.67 pg/mL, 95% CI = - 2.73 pg/mL to - 6.07 pg/mL, I2 = 98.1%, 2 studies). A higher mean level of IL-6 was observed in patients who died compared with the levels of those who survived (P = 0.007, WMD = 1,399.19 pg/mL, 95% CI = 384.16 - 2,414.2 pg/mL, I2 = 93.1%, 4 studies). Our meta-analysis of the pooled evidence can be used to guide future studies in which IL-6 levels are measured during malaria outbreaks to monitor malaria severity. Heterogeneity of the effect estimate among the included studies was the main limitation of this analysis. In conclusion, significantly increased levels of IL-6 were observed in patients with severe malaria compared with those in patients with non-severe malaria, which indicates that IL-6 is a candidate marker for severe malaria. Future studies should investigate the sensitivity and specificity of increased IL-6 levels to determine the effectiveness of assessments of IL-6 levels monitoring of malaria infection and severity.

Prevalence of Signs of Severity Identified in the Thai Population with Malaria: A Systematic Review and Meta-Analysis.

Understanding the prevalence of signs of severity identified in the Thai population with malaria could aid clinical management and disease control efforts, decrease mortality, and promote malaria elimination in Thailand. This systematic review aimed to collate the evidence regarding signs of severity identified in the Thai population with malaria. MEDLINE, Web of Science, and Scopus were searched for potentially relevant studies. The quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal tools. The pooled prevalence of signs of severity among patients with severe malaria and the pooled proportion of each sign of severity among all signs of severity were estimated using random-effects models. Heterogeneity among included studies was assessed using Cochran's Q test. A subgroup analysis was performed to evaluate whether differences in pooled estimates between different study sites. Publication bias was assessed by visualizing funnel plot asymmetry and using Egger's test. Among 741 studies identified by literature searching, 12 studies of a total of 2900 patients with severe malaria, in 7 Thai hospitals, met the eligibility criteria. Results of meta-analyses showed that the signs of the severity of malaria with the highest prevalence in Thailand were jaundice (54%), hyperparasitemia (47%), impaired consciousness/coma (21%), acidosis (18%), renal impairment (13%), shock (10%), convulsions (9%), severe anemia (8%), pulmonary edema/acute respiratory distress syndrome (ARDS) (8%), hypoglycemia (4%), and bleeding/disseminated intravascular coagulation (DIC) (2%). The signs of the severity of malaria that made up the highest proportion of all signs of severity identified in the Thai population with malaria were hyperparasitemia (33%), jaundice (33%), impaired consciousness/coma (12%), acidosis (9%), renal impairment (7%), severe anemia (6%), convulsions (5%), shock (5%), pulmonary edema/ARDS (3%), bleeding/DIC (1%), and hypoglycemia (1%). The present study revealed the prevalence of signs of severity identified in the Thai population with malaria. Jaundice, hyperparasitemia, and impaired consciousness/coma were the most common signs of severity identified. These results may inform the management of patients with severe malaria and promote malaria-elimination efforts in Thailand.

Alteration of Platelet Count in Patients with Severe Non-Plasmodium falciparum Malaria: A Systematic Review and Meta-Analysis.

The understanding of platelet biology under physiological and pathological conditions like malaria infection is critical importance in the context of the disease outcome or model systems used. The importance of severe thrombocytopenia (platelet count < 50,000 cells (µL) and profound thrombocytopenia (platelet count < 20,000 cells/µL) in malaria patients remains unclear. This study aimed to synthesize evidence regarding the risks of severe and profound thrombocytopenia in patients with severe non-Plasmodium falciparum malaria. Our overall aim was to identify potential indicators of severe non-P. falciparum malaria and the Plasmodium species that cause severe outcomes. This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under registration ID CRD42020196541. Studies were identified from previous systematic reviews (n = 5) and the MEDLINE, Scopus, and Web of Science databases from 9 June 2019 to 9 June 2020. Studies were included if they reported the outcome of severe non-Plasmodium species infection, as defined by the World Health Organization (WHO) criteria, in patients with known platelet counts and/or severe and profound thrombocytopenia. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Data were pooled, and pooled prevalence (PP) and pooled odds ratios (ORs) were calculated using random effects models. Of the 118 studies identified from previous meta-nalyses, 21 met the inclusion criteria. Of the 4807 studies identified from the databases, three met the inclusion criteria. Nine studies identified from reference lists and other sources also met the inclusion criteria. The results of 33 studies reporting the outcomes of patients with severe P. vivax and P. knowlesi infection were pooled for meta-analysis. The PP of severe thrombocytopenia (reported in 21 studies) was estimated at 47% (95% confidence interval (CI): 33-61%, I2: 96.5%), while that of profound thrombocytopenia (reported in 13 studies) was estimated at 20% (95% CI: 14-27%, 85.2%). The pooled weighted mean difference (WMD) in platelet counts between severe uncomplicated Plasmodium infections (reported in 11 studies) was estimated at -28.51% (95% CI: -40.35-61%, I2: 97.7%), while the pooled WMD in platelet counts between severe non-Plasmodium and severe P. falciparum infections (reported in eight studies) was estimated at -3.83% (95% CI: -13.90-6.25%, I2: 85.2%). The pooled OR for severe/profound thrombocytopenia comparing severe to uncomplicated Plasmodium infection was 2.92 (95% CI: 2.24-3.81, I2: 39.9%). The PP of death from severe and profound thrombocytopenia was estimated at 11% (95% CI: 0-22%). These results suggest that individuals with severe non-P. falciparum infection (particularly P. vivax and P. knowlesi) who exhibit severe or profound thrombocytopenia should be regarded as high risk, and should be treated for severe malaria according to current WHO guidelines. In addition, severe or profound thrombocytopenia coupled with other clinical and microscopic parameters can significantly improve malaria diagnosis, enhance the timely treatment of malaria infections, and reduce the morbidity and mortality of severe non-P. falciparum malaria.