T cells exhaustion, inflammatory and cellular activity markers in PBMCs predict treatment outcome in pulmonary tuberculosis patients.

BACKGROUND: Pulmonary tuberculosis (PTB) is a well-known disease caused by Mycobacterium tuberculosis. Its pathogenesis is premised on evasion of the immune system and dampened immune cells activity. METHODS: Here, the transcription pattern of immune cells exhaustion, inflammatory, and cellular activity markers were examined in peripheral blood mononuclear cells (PBMCs) from PTB patients at various stages of treatment. PBMCs were isolated, and RNA extracted. cDNA synthesis was performed, then amplification of genes of interest. RESULTS: The T cell exhaustion markers (PD-L1, CTLA4, CD244 and LAG3) showed varied levels of expressions when comparing 0 T and 1 T to the other treatment phases, suggesting their potential roles as markers for monitoring TB treatment. IL-2, IFN-g and TNF-a expression at the gene level returned to normal at completion of treatment, while granzyme B levels remained undetectable at the cured stage. At the cured stage, the cellular activity monitors Ki67, CD69, GATA-3, CD8 and CD4 expressions were comparable to the healthy controls. Correlation analysis revealed a significantly strong negative relationship with CD244 expression, particularly between 1 T and 2 T (r = -0.94; p = 0.018), and 3 T (r = -0.95; p = 0.013). Comparing 0 T and 3 T, a genitive correlation existed in PD-L1 (r = -0.74) but statistically not significant, as seen in CTLA4 and LAG-3 expressions. CONCLUSION: Collectively, the findings of the study suggest that T-cells exhaustion marker particularly CD244, inflammatory markers IL-2, IFN-g and TNF-a, and cellular activity indicators such as Ki67, CD69, GATA-3, CD8 and CD4 are promising markers in monitoring the progress of PTB patients during treatment.

Staphylococcus aureus Nasal Colonization among Children with Sickle Cell Disease at the Children's Hospital, Accra: Prevalence, Risk Factors, and Antibiotic Resistance.

The aim of this study was to investigate S. aureus carriage among children with sickle cell disease (SCD), including the prevalence, risk factors, and antibiotic resistance. The study was cross-sectional, and involved 120 children with SCD recruited at the Princess Marie Louise Children's Hospital (PML) in Accra and 100 apparently healthy children from environs of the hospital. Nasal swab samples were collected from the study participants and cultured for bacteria. Confirmation of S. aureus and methicillin-resistant Staphylococcus aureus (MRSA) isolates were done using the tube coagulase test and mecA polymerase chain reaction, respectively. All the S. aureus isolates were tested against standard antimicrobial agents using the Kirby-Bauer method. A structured questionnaire was used to obtain the socio-demographic and clinical data of the study participants. Binary logistic regression was used to identify determinants of S. aureus and MRSA carriage among the study participants. The nasal carriage prevalence of S. aureus was 33.3% (n = 40) and 10% (n = 10) among the participants of the SCD and control groups, respectively. As regards MRSA nasal carriage prevalence, the respective values were 3.33% (n = 4) and 0.00% (n = 0). SCD was significantly associated with S. aureus colonization (p < 0.0001, OR = 4.045), but not MRSA colonization (p = 0.128). In the SCD group, the significant predictors of S. aureus carriage were increasing age (p = 0.003; OR = 1.275) and living in self-contained apartments (p = 0.033; OR = 3.632), whereas male gender (p = 0.018; OR = 0.344) and the practice of self-medication (p = 0.039; OR = 0.233) were protective of S. aureus carriage. In the control group, a history of hospitalization in the past year was a risk factor for the carriage of S. aureus (p = 0.048; OR = 14.333). Among the participants of the SCD and control groups, respectively, the resistance prevalence recorded by S. aureus against the various antibiotics investigated were penicillin (100% each), cotrimoxazole (27.5% vs. 20%), tetracycline (25% vs. 50%), rifampicin (82.5% vs. 50%), erythromycin (30% vs. 20%), clindamycin (32.5% vs. 50%), gentamicin (7.5% vs. 20%), cefoxitin (27.5% vs. 20%), linezolid (30% vs. 40%), and fusidic acid (95% vs. 80%). The proportion of S. aureus isolates that were multidrug resistant (MDR) was 92.5% (37/40) in the SCD group and 100% (10/10) in the control group.