T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases. We characterized blood samples from tuberculosis patients (n=28) and healthy contacts (n=28) from Ghana for M. tuberculosis-specific T-cell responses, constitutive cytokine production, and SOCS3 and pSTAT3 expression. Lentiviral modulation of primary CD4 T-cells was performed to determine the effects of SOCS3 on T-cell functions. T-cells from tuberculosis patients expressed higher levels of IL-10 and IL-6 and lower levels of T helper type (T)17 cytokines after M. tuberculosis-specific stimulation compared to healthy contacts. In addition, tuberculosis patients had higher IL-10 and IL-6 levels in the supernatants of non-stimulated immune cells and plasma samples compared to healthy contacts. Notably, aberrant cytokine expression was accompanied by high constitutive pSTAT3 levels and SOCS3 expression in T-cells. Multivariate analysis identified an IL-6/IL-10 co-expression-based principal component in tuberculosis patients that correlated with high pSTAT3 levels. SOCS3 contributed to a regulatory component, and tuberculosis patients with high SOCS3 expression showed decreased T1 cytokine expression and impaired IL-2-induced STAT5 phosphorylation. SOCS3 over-expression in primary CD4 T-cells confirmed the SOCS3 inhibitory function on IL-2-induced STAT5 phosphorylation. We conclude that constitutive pSTAT3 and high SOCS3 expression are influential factors that indicate impaired T-cell functions in tuberculosis patients.Cellular and Molecular Immunology advance online publication, 19 March 2018; doi:10.1038/cmi.2018.5.

T-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 (IL-7) availability and receptivity. Regulation of IL-7 receptor (IL-7R) expression and signalling are key for IL-7-modulated T-cell functions. Aberrant expression of soluble (s) and membrane-associated (m) IL-7R molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (AIDS) patients. Here we investigated the role of IL-7/IL-7R on T-cell immunity in human tuberculosis. We performed two independent case-control studies comparing tuberculosis patients and healthy contacts. This was combined with follow-up examinations for a subgroup of tuberculosis patients under therapy and recovery. Blood plasma and T cells were characterised for IL-7/sIL-7R and mIL-7R expression, respectively. IL-7-dependent T-cell functions were determined by analysing STAT5 phosphorylation, antigen-specific cytokine release and by analysing markers of T-cell exhaustion and inflammation. Tuberculosis patients had lower soluble IL-7R (p < 0.001) and higher IL-7 (p < 0.001) plasma concentrations as compared to healthy contacts. Both markers were largely independent and aberrant expression normalised during therapy and recovery. Furthermore, tuberculosis patients had lower levels of mIL-7R in T cells caused by post-transcriptional mechanisms. Functional in vitro tests indicated diminished IL-7-induced STAT5 phosphorylation and impaired IL-7-promoted cytokine release of Mycobacterium tuberculosis-specific CD4+ T cells from tuberculosis patients. Finally, we determined T-cell exhaustion markers PD-1 and SOCS3 and detected increased SOCS3 expression during therapy. Only moderate correlation of PD-1 and SOCS3 with IL-7 expression was observed. We conclude that diminished soluble IL-7R and increased IL-7 plasma concentrations, as well as decreased membrane-associated IL-7R expression in T cells, reflect impaired T-cell sensitivity to IL-7 in tuberculosis patients. These findings show similarities to pathognomonic features of impaired T-cell functions and immune failure described in AIDS patients.

Introduction. Surgical treatment of perforated peptic ulcer (PPU) is a challenge for surgeons in Africa. Aim. To determine risk factors of postoperative complications or mortality among black Ivoirian patients with PPU. Methods. All 161 patients (median age = 34 years, 90.7 male) operated on for PPU in the visceral and general surgery unit were enrolled in a retrospective cohort study. Variables were studied with Kaplan Meier and Cox proportional hazard models. Results. Among 161 patients operated on for PPU, 36 (27.5%) experienced complications and 31 (19.3%) died. Follow-up results were the incidence of complications and mortality of 6.4 (95% CI: 4.9–8.0) per 100 person-days and 3.0 (95% CI: 1.9–4.0) per 100 person-days for incidence of mortality. In multivariate analysis, risk factors of postoperative complications or mortality were comorbidities (HR = 2.1, P = 0.03), tachycardia (pulse rate > 100/minutes) (HR = 2.4, P = 0.02), purulent intra-abdominal fluid collection (HR = 2.1, P = 0.04), hyponatremia (median value ≤ 134 mEq/L) (HR = 2.3, P = 0.01), delayed time of hospital admission > 72 hours (HR = 2.6, P < 0.0001), and delayed time of surgical intervention between 24 and 48 hours (HR = 3.8, P < 0.0001). Conclusion. The delayed hospital admission or surgical intervention and hyponatremia may be considered as additional risk of postoperative complications or mortality in Black African patients with PPU.

Summary Background The WHO Regional Office for the Africa Regional Immunization Technical Advisory Group, in 2011, adopted the measles control and elimination goals for all countries of the African region to achieve in 2015 and 2020 respectively. Our aim was to track the current status of progress towards measles control and elimination milestones across 15 west African countries between 2001 and 2019. Methods We did a retrospective multicountry series analysis of national immunisation coverage and case surveillance data from Jan 1, 2001, to Dec 31, 2019. Our analysis focused on the 15 west African countries that constitute the Economic Community of West African States. We tracked progress in the coverage of measles-containing vaccines (MCVs), measles supplementary immunisation activities, and measles incidence rates. We developed a country-level measles summary scorecard using eight indicators to track progress towards measles elimination as of the end of 2019. The summary indicators were tracked against measles control and elimination milestones. Findings The weighted average regional first-dose MCV coverage in 2019 was 66% compared with 45% in 2001. 73% (11 of 15) of the west African countries had introduced second-dose MCV as of December, 2019. An estimated 4 588 040 children (aged 12–23 months) did not receive first-dose MCV in 2019, the majority (71%) of whom lived in Nigeria. Based on the scorecard, 12 (80%) countries are off-track to achieving measles elimination milestones; however, Cape Verde, The Gambia, and Ghana have made substantial progress. Interpretation Measles will continue to be endemic in west Africa after 2020. The regional measles incidence rate in 2019 was 33 times the 2020 elimination target of less than 1 case per million population. However, some hope exists as countries can look at the efforts made by Cape Verde, The Gambia, and Ghana and learn from them. Funding None.