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Background: It was hypothesized that glucose-6-phosphate dehydrogenase (G6PD) deficiency confers a protective effect against malaria infection, however, safety concerns have been raised regarding haemolytic toxicity caused by radical cure with 8-aminoquinolines in G6PD-deficient individuals. Malaria elimination and control are also complicated by the high prevalence of G6PD deficiency in malaria-endemic areas. Hence, accurate identification of G6PD deficiency is required to identify those who are eligible for malaria treatment using 8-aminoquinolines., Methods: The prevalence of G6PD deficiency among 408 Thai participants diagnosed with malaria by microscopy (71), and malaria-negative controls (337), was assessed using a phenotypic test based on water-soluble tetrazolium salts. High-resolution melting (HRM) curve analysis was developed from a previous study to enable the detection of 15 common missense, synonymous and intronic G6PD mutations in Asian populations. The identified mutations were subjected to biochemical and structural characterisation to understand the molecular mechanisms underlying enzyme deficiency., Results: Based on phenotypic testing, the prevalence of G6PD deficiency (< 30% activity) was 6.13% (25/408) and intermediate deficiency (30-70% activity) was found in 15.20% (62/408) of participants. Several G6PD genotypes with newly discovered double missense variants were identified by HRM assays, including G6PD Gaohe + Viangchan, G6PD Valladolid + Viangchan and G6PD Canton + Viangchan. A significantly high frequency of synonymous (c.1311C>T) and intronic (c.1365-13T>C and c.486-34delT) mutations was detected with intermediate to normal enzyme activity. The double missense mutations were less catalytically active than their corresponding single missense mutations, resulting in severe enzyme deficiency. While the mutations had a minor effect on binding affinity, structural instability was a key contributor to the enzyme deficiency observed in G6PD-deficient individuals., Conclusions: With varying degrees of enzyme deficiency, G6PD genotyping can be used as a complement to phenotypic screening to identify those who are eligible for 8-aminoquinolines. The information gained from this study could be useful for management and treatment of malaria, as well as for the prevention of unanticipated reactions to certain medications and foods in the studied population., (© 2024. The Author(s).)

Malaria disease is a public health problem especially in tropical countries, 445.000 of malaria-related deaths have been reported in 2017. MicroRNAs (miRNAs) are small non-coding RNAs with 18-24 nucleotides in length, which have been demonstrated to regulate gene expression of several biological processes. The dysregulation of host immune-related gene expressions during the transcriptional process by microRNA has been extensively reported in malaria parasite invasion of erythrocytes infection. The candidate's miRNAs would be used as potential biomarkers in the future and perspective. A systematic review on miRNAs as candidate clinical biomarkers in malaria infection has been established in this study. Electronic databases (Medline, EMBASE, CINAHL and Cochrane data bases) were screened and articles were included as per established selection criteria. We comprehensively searched to identify publications related to malaria and miRNA. PRISMA guidelines were followed, 262 articles were searched, duplicates and unconnected papers were excluded. Nineteen articles were included in the study. It was found that malaria parasite infected liver or tissue produce tissue-specific miRNAs and release to the blood stream. The association of miRNAs including miR-16, miR-155, miR-150, miR-451 and miR-223 with the dysregulations of immune-related genes expression such as PfEMP-1, IFN-γ, AGO- 1 AGO-2; IL4, CD80, CD86, CD36, ANG-1 and ANG-2 during early, severe and/or cerebral malaria infections indicate the potential use of those miRNAs as biomarkers for malaria infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Severe malaria has a poor prognosis with a morbidity rate of 80% in tropical areas. The early parasite detection is one of the effective means to prevent severe malaria of which specific treatment strategies are limited. Many clinical characteristics and laboratory testings have been used for the early diagnosis and prediction of severe disease. However, a few of these factors could be applied to clinical practice. MicroRNAs (miRNAs) were demonstrated as useful biomarkers in many diseases such as malignant diseases and cardiovascular diseases. Recently it was found that plasma miR-451 and miR-16 were downregulated in malaria infection at parasitic stages or with multi-organ failure involvement. MiR-125b, -27a, -23a, -150, 17-92 and -24 are deregulated in malaria patients with multiple organ failures. Here, the current findings of miRNAs were reviewed in relation to clinical severity of malaria infection and emphasized that miRNAs are potential biomarkers for severe malaria infection.

Abtract Malaria is a common parasitic disease in tropical countries, causing one to two million deaths every year. To establish the new biomarker, we analyzed plasma miRNAs obtained from 19 malaria patients and 19 normal subjects, using reverse transcription-based quantitative polymerase chain reaction (RT-qPCR). The average levels of plasma miR-451 and miR-16 were significantly lower in malaria patients, (8.9-fold; p  <   0.001 and 10.4-fold; p  = 0.01, respectively). The levels of other abundant miRNAs in plasma (miR-223, miR-226-3p) did not change significantly in malaria patients. Our data suggest that plasma miR-451 and miR-16 are relevant biomarkers for malaria infection. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU) admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases) and 151 patients with non-severe malaria (controls). Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1) referrals, (2) no prior history of malaria, (3) body temperature of >38.5°C, (4) white blood cell counts >10×109/µL, (5) presence of schizonts in peripheral blood smears, and (6) albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05). Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1) ethnicity of Thai [odds ratio (OR) = 3.601, 95% confidence interval (CI) = 1.011–12.822] or Myanmar [OR = 3.610, 95% CI = 1.138–11.445]; (2) referrals [OR = 3.571, 95% CI = 1.306–9.762]; (3) no prior history of malaria [OR = 5.887, 95% CI = 1.354–25.594]; and (4) albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802–28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could develop severe malaria and require ICU admission. Early identification and the timely initiation of appropriate treatments may well improve the outcomes and reduce the mortality of these patients. [ABSTRACT FROM AUTHOR]