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.

IFN-γ is crucial for protection against Mycobacterium tuberculosis. miR-29 was recently shown to non-redundantly inhibit IFN-γ. Here, we investigated IFN-γ and miR-29a expression dynamics of CD4(+) T cells from patients during active tuberculosis (TB) (n = 32) and in household contacts who were latently M. tuberculosis infected (n = 19) from Ghana. Whereas M. tuberculosis-specific IFN-γ expression was similar during TB chemotherapy, superantigen stimulation indicated generally impaired IFN-γ expression in TB patients. No interdependency between miR-29a and IFN-γ expression of T cells was observed. However, miR-29a was differentially expressed in T cells during chemotherapy. We concluded that differential miR-29a expression in active TB was not causative for impaired IFN-γ expression.

IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0-16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.

BackgroundA surge in pro-inflammatory markers, Il-6 and TNF-α, has been associated with type 2 diabetes mellitus (T2DM). However, there is no data on the dynamics of these markers in T2DM Ghanaian populations. The aim of this study was to determine variations in the levels of IL-6 and TNF-α in T2DM patients. This study also examined the associations of IL-6 and TNF-α with anthropometric measurement and the effect of co-morbidity with hypertension using rural and urban dwellers in the Ashanti region, Ghana.MethodsA nested case–control design using participants aged 25–70 years consisting of 77 T2DM ± hypertension patients and 112 controls were selected from a larger study on Research on Obesity and Diabetes among African Migrants (RODAM). Anthropometric measurements, blood pressure and body fat percentage were measured. Fasting blood samples were analyzed for glucose, IL-6 and TNF-α levels.ResultsThe median level of IL-6 was significantly higher (p < 0.0001) among rural dwellers compared to urban dwellers. Inversely, urban dwellers had significantly higher (p = 0.0424) median level of TNF-α compared to rural cases. No significant differences were observed in IL-6 (p = 0.3571) and TNF-α (p = 0.2581) among T2DM patients compared with T2DM ± hypertension patients. A weak negative correlation was found between IL-6 and BMI in urban T2DM.DiscussionThe average level of IL-6 was higher in rural T2DM participants compared with those in urban setting. However, higher levels of TNF-α was observed among the study participants with T2DM in urban settings compared to those of rural. In this study, we observed that co-morbidity of hypertension had no significant effect on the levels of IL-6 and TNF-α. We are of the opinion that higher physical activity levels among rural particpants and high obesity levels in urabn participants explain the observation but needs more numbers to validate.ConclusionThis study revealed that IL-6 levels were higher among rural dwellers than urban while TNF-α levels were higher in urban dwellers than rural in patients with T2DM. There was no association of body fat percentage and body mass index with IL-6 and TNF-α levels. Co-morbidity of hypertension with T2DM had no effect on IL-6 and TNF-α levels.

Background The current COVID-19 pandemic affects the entire world population and has serious health, economic and social consequences. Assessing the prevalence of COVID-19 through population-based serological surveys is essential to monitor the progression of the epidemic, especially in African countries where the extent of SARS-CoV-2 spread remains unclear. Methods A two-stage cluster population-based SARS-CoV-2 seroprevalence survey was conducted in Bobo-Dioulasso and in Ouagadougou, Burkina Faso, Fianarantsoa, Madagascar and Kumasi, Ghana between February and June 2021. IgG seropositivity was determined in 2,163 households with a specificity improved SARS-CoV-2 Enzyme-linked Immunosorbent Assay. Population seroprevalence was evaluated using a Bayesian logistic regression model that accounted for test performance and age, sex and neighbourhood of the participants. Results Seroprevalence adjusted for test performance and population characteristics were 55.7% [95% Credible Interval (CrI) 49·0; 62·8] in Bobo-Dioulasso, 37·4% [95% CrI 31·3; 43·5] in Ouagadougou, 41·5% [95% CrI 36·5; 47·2] in Fianarantsoa, and 41·2% [95% CrI 34·5; 49·0] in Kumasi. Within the study population, less than 6% of participants performed a test for acute SARS-CoV-2 infection since the onset of the pandemic. Conclusions High exposure to SARS-CoV-2 was found in the surveyed regions albeit below the herd immunity threshold and with a low rate of previous testing for acute infections. Despite the high seroprevalence in our study population, the duration of protection from naturally acquired immunity remains unclear and new virus variants continue to emerge. This highlights the importance of vaccine deployment and continued preventive measures to protect the population at risk.