Plasma Galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV.

OBJECTIVE: Adolescents with perinatally-acquired HIV (AWH) are at an increased risk of poor cognitive development but the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multi-morbidity in adults with HIV despite anti-retroviral therapy (ART), however, relationship between Gal-9 in AWH and cognition remain unexplored. DESIGN: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART (n = 15), ART-naïve (n = 15), and adolescents without HIV (AWOH; n = 10)] and Myanmar [AWH on ART (n = 54) and AWOH (n = 22)] were studied. Adolescents from Myanmar underwent standardized cognitive tests. METHODS: Plasma Gal-9 and soluble mediators were measured by immunoassays and cellular immune markers by flow cytometry. We used Mann-Whitney U tests to determine group-wise differences, Spearman's correlation for associations and machine learning (ML) to identify a classifier of cognitive status (impaired vs. unimpaired) built from clinical (age, sex, HIV status) and immunological markers. RESULTS: Gal-9 levels were elevated in ART-treated AWH compared to AWOH in both cohorts (all p < 0.05). Higher Gal-9 in AWH correlated with increased levels of inflammatory mediators (sCD14, TNFα, MCP-1, IP-10, IL-10) and activated CD8 T cells (all p < 0.05). Irrespective of HIV status, higher Gal-9 levels correlated with lower cognitive test scores in multiple domains (verbal learning, visuospatial learning, memory, motor skills (all p < 0.05). ML classification identified Gal-9, CTLA-4, HVEM, and TIM-3 as significant predictors of cognitive deficits in adolescents (mean AUC = 0.837). CONCLUSION: Our results highlight a potential role of Gal-9 as a biomarker of inflammation and cognitive health among adolescents with perinatally acquired HIV.

Pathogen and Antibody Identification in Children with Encephalitis in Myanmar.

OBJECTIVE: Prospective studies of encephalitis are rare in regions where encephalitis is prevalent, such as low middle-income Southeast Asian countries. We compared the diagnostic yield of local and advanced tests in cases of pediatric encephalitis in Myanmar. METHODS: Children with suspected subacute or acute encephalitis at Yangon Children's Hospital, Yangon, Myanmar, were prospectively recruited from 2016-2018. Cohort 1 (n = 65) had locally available diagnostic testing, whereas cohort 2 (n = 38) had advanced tests for autoantibodies (ie, cell-based assays, tissue immunostaining, studies with cultured neurons) and infections (ie, BioFire FilmArray multiplex Meningitis/Encephalitis multiplex PCR panel, metagenomic sequencing, and pan-viral serologic testing [VirScan] of cerebrospinal fluid). RESULTS: A total of 20 cases (13 in cohort 1 and 7 in cohort 2) were found to have illnesses other than encephalitis. Of the 52 remaining cases in cohort 1, 43 (83%) had presumed infectious encephalitis, of which 2 cases (4%) had a confirmed infectious etiology. Nine cases (17%) had presumed autoimmune encephalitis. Of the 31 cases in cohort 2, 23 (74%) had presumed infectious encephalitis, of which one (3%) had confirmed infectious etiology using local tests only, whereas 8 (26%) had presumed autoimmune encephalitis. Advanced tests confirmed an additional 10 (32%) infections, 4 (13%) possible infections, and 5 (16%) cases of N-methyl-D-aspartate receptor antibody encephalitis. INTERPRETATION: Pediatric encephalitis is prevalent in Myanmar, and advanced technologies increase identification of treatable infectious and autoimmune causes. Developing affordable advanced tests to use globally represents a high clinical and research priority to improve the diagnosis and prognosis of encephalitis. ANN NEUROL 2023;93:615-628.

Virulence factors and genetic characteristics of methicillin-resistant and -susceptible Staphylococcus aureus isolates in Myanmar.

Staphylococcus aureus produces virulence factors, including various exotoxins and adhesins, which are associated with a variety of symptoms caused by its infections. In the present study, the prevalence of these virulence factors was analyzed for 23 S. aureus strains isolated from wound infections in hospitals, nasal swabs, or vomit from patients and cooks in a food poisoning case and from healthy adults in Yangon, Myanmar. Among these strains, five were methicillin-resistant S. aureus (MRSA) derived from pus (four strains, SCCmec III, ST239) and a healthy adult (one strain, SCCmec-IVa, ST5). The Panton-Valentine leukocidine (PVL) gene was detected in five methicillin-susceptible S. aureus (MSSA) clinical strains belonging to ST121 (CC121). The MRSA clinical strains had only a few or no staphylococcal enterotoxin (SE) genes, whereas PVL-positive MSSA and an MRSA strain from a healthy adult possessed an enterotoxin gene cluster (seg, sei, sem, sen, seo, and selu). Strains from the food poisoning case had either SE genes or only etd and edin-B. Adhesin genes, which are associated with binding to fibronectin, fibrinogen, and elastin, were detected in all the MRSA and most of the MSSA strains examined. However, the bone sialoprotein-binding protein gene (bbp) and the variant form of the elastin-binding protein gene (ebpS-v) with an internal 180 bp deletion were identified only in the MSSA strains harboring the PVL gene. These findings suggest that those genetic traits are characteristic of PVL-positive ST121 S. aureus strains in Myanmar.