High-throughput analysis of T cell–monocyte interaction in human tuberculosis

The lack of efficient tools for identifying immunological correlates of tuberculosis (TB) protection or risk of disease progression impedes the development of improved control strategies. To more clearly understand the host response in TB, we recently established an imaging flow cytometer-based in-vitro assay, which assesses multiple aspects of T cell–monocyte interaction. Here, we extended our previous work and characterized communication between T cells and monocytes using clinical samples from individuals with different TB infection status and healthy controls from a TB endemic setting. To identify T cell–monocyte conjugates, peripheral blood mononuclear cells (PBMC) were stimulated with ds-Red-expressing Mycobacterium bovis bacille Calmette–Guérin or 6-kDa early secreted antigenic target (ESAT 6) peptides for 6 h, and analyzed by imaging flow cytometer (IFC). We then enumerated T cell–monocyte conjugates using polarization of T cell receptor (TCR) and F-actin as markers for synapse formation, and nuclear factor kappa B (NF-κB) nuclear translocation in the T cells. We observed a reduced frequency of T cell–monocyte conjugates in cells from patients with active pulmonary tuberculosis (pTB) compared to latent TB-infected (LTBI) and healthy controls. When we monitored NF-κB nuclear translocation in T cells interacting with monocytes, the proportion of responding cells was significantly higher in active pTB compared with LTBI and controls. Overall, these data underscore the need to consider multiple immunological parameters against TB, where IFC could be a valuable tool.     

Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3

In this study, we explored the local cytokine/chemokine profiles in patients with active pulmonary or pleural tuberculosis (TB) using multiplex protein analysis of bronchoalveolar lavage and pleural fluid samples. Despite increased pro-inflammation compared to the uninfected controls; there was no up-regulation of IFN-γ or the T cell chemoattractant CCL5 in the lung of patients with pulmonary TB. Instead, elevated levels of IL-4 and CCL4 were associated with high mycobacteria-specific IgG titres as well as SOCS3 (suppressors of cytokine signaling) mRNA and progression of moderate-to-severe disease. Contrary, IL-4, CCL4 and SOCS3 remained low in patients with extrapulmonary pleural TB, while IFN-γ, CCL5 and SOCS1 were up-regulated. Both SOCS molecules were induced in human macrophages infected with Mycobacterium tuberculosis in vitro. The Th2 immune response signature found in patients with progressive pulmonary TB could result from inappropriate cytokine/chemokine responses and excessive SOCS3 expression that may represent potential targets for clinical TB management.     

Prevalence and Associated Factors of Suicidal Ideation and Attempt among Prisoners in Ethiopia: A cross-sectional study

BackgroundSuicide is a serious cause of mortality worldwide and the single most common cause of death in the prison population. Studies on suicidal ideation and attempt among prison people in Ethiopia are limited. Therefore, the objective of this study was to assess the prevalence and associated factors of suicidal ideation and attempt among prisoners in Debre Markos Correctional Center, northwest, Ethiopia, 2019.MethodAn institution-based cross-sectional study was conducted using the simple random sampling technique; a total of 640 participants was recruited. Suicidal ideation and attempts were assessed using the suicidality module of the World Mental Health (WMH) survey initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI).ResultsThe prevalence of suicidal ideation and attempt were 21.9% and 13.1% with 95% CI (18.40, 25.20) and (10.60, 15.80) respectively. The study revealed that female sex (AOR=2.60, 95%CI: 1.39, 8.20) and family history of mental illness (AOR=2.08, 95%CI: 1.11, 3.90) were significantly associated with both suicidal ideation and attempt. Whereas divorced/widowed (AOR=3.67, 95%CI: 2.05, 6.58), common mental disorder (AOR=1.98, 95%CI: 1.25, 3.16) and poor social support (AOR=2.68, 95%CI: 1.42, 5.06) were statistically associated with suicidal ideation, and previous incarceration (AOR=2.38, 95%CI: 1.20, 5.16) was significantly associated with a suicide attempt.ConclusionThe result shows that the prevalence of suicidal ideation and attempt were serious problems among prisoners. As a result, inmate people need greater attention and interventions for suicidal behaviors.     

Perinatal Survival and Predictors of Mortality among Mothers with Hypertensive Disorders of Pregnancy at Antenatal care Clinics in Gamo Zone Public Hospitals

BackgroundPregnancy induced hypertension represents a significant public health problem throughout the world, which may complicate 0.5%–10% of all pregnancies. It is the leading cause of maternal as well perinatal mortality and morbidity worldwide. Pregnancy induced hypertension is a multisystem disorder unique to pregnancy and results in high perinatal mortality. The objective of this study was to determine the survival status, incidence and predictors of perinatal mortality among mothers with pregnancy induced hypertension at antenatal clinics of Gamo Zone public hospitals.MethodsFacility-based retrospective cohort study was conducted among selected 576(192 exposed and 384 unexposed) antenatal care attendants'' record at Gamo Zone public hospitals from 1^st January 2018 to 31^st December 2018. Data were entered into Epi data version 3.02 and exported to SPSS V 25 for analysis. Kaplan Meier survival curve together with log rank test was fitted to test the survival time. Statistical significance was declared at P-value ≤0.05 using cox proportional hazard model.ResultThe incidence of perinatal mortality was 124/1000 births. The cumulative proportion of surviving at the end of 4^th, 8^th, 12^th and 16^th weeks of follow-up among the exposed groups was 96.9%, 93.5%, 82.1% and 61.6% respectively whereas it was 99.5%, 98.9% and 98.5% at the end of 4^th, 8^th and 12^th weeks of follow-up for the non-exposed groups respectively. Parity of ≥5(AHR: 6.3; 95%CI: 1.36,10.55), mothers who delivered at <34 weeks of gestation(AHR:7.8; 95%CI: 2.6,23.1), being preterm(AHR:6; 95%CI: 5.3,19.2), perinatal birth weight ≤2500gm(AHR:6.1; 95&CI: 1.01,37.9), vaginal deliveryn(AHR:2.7; 95%CI:1.13,6.84), maternal highest systolic blood pressure level ≥160mmHg (AHR: 2.3; 95%CI: 1.02,5.55) and prepartum onset of pregnancy induced hypertension (AHR: 6; 95%CI: 5.3,19.2) were statistically significant in multivariable analysis.ConclusionThe risk of perinatal mortality was high among the mothers with pregnancy induced hypertension compared to those of pregnancy induced hypertension free mother,s and the perinatal mortality rate was high. High parity, low gestational age, low number of antenatal care visits, low birth weight, vaginal delivery, antepartum onset of pregnancy induced hypertension and highest maternal systolic blood pressure level were the independent predictors of perinatal mortality.