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Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy preserves the bladder after resection of high-risk non–muscle-invasive bladder cancer (NMIBC). About 30% of patients experience treatment failure, which cannot be predicted a priori and carries a high risk of disease progression. We examined the in vitro tuberculin responsiveness of CD4+ T cells before BCG immunotherapy in 42 patients with high-risk NMIBC. The frequencies and functionalities of cytokine-expressing CD4+ T cells immediately before and after BCG immunotherapy induction were assessed by flow cytometry after overnight tuberculin stimulation. Tuberculin-induced secreted mediators were measured by electrochemiluminescence. We correlated the results with recurrence-free patient survival 6 months after induction. A tuberculin-induced, secreted, IL2 concentration > 250 pg/mL was the best predictor of recurrence-free survival, providing 79% sensitivity, 86% specificity (AUC = 0.852, P = 0.000), and overall correct classification in 78.6% of cases. In 50% of patients later experiencing recurrence, but not in any of the recurrence-free survivors, IL2 secretion was < 120 pg/mL. Other parameters predicting recurrence-free survival included secreted IFNγ (AUC = 0.796, P = 0.002) and the frequencies of TNF-producing (TNF+) CD4+ T cells (AUC = 0.745, P = 0.010). “Polyfunctional” CD4+ T cells (IFNγ+/IL2+/TNF+) were significantly associated with recurrence-free survival (AUC = 0.801, P = 0.002). Thus, the amount of IL2 secretion from CD4+ T cells after overnight in vitro incubation with tuberculin predicted the outcome of BCG immunotherapy. As many as half of potential BCG failures could be identified before induction therapy is begun, enabling better choices regarding treatment. Cancer Immunol Res; 6(10); 1212–9. ©2018 AACR.

Urine cytokines before and after BCG induction therapy

Effect of BCG vaccination on secreted cytokines

Polyfunctional T-cell profiles

Kassu Desta,1,2 Eleni Aklillu,3 Yirgu Gebrehiwot,4 Fikre Enquselassie5 ,†Daire Cantillon,6 Leena Al-Hassan,6 James R Price,6 Melanie J Newport,6 Gail Davey,5,6 Yimtubezenash Woldeamanuel1 1Department of Microbiology, Immunology, and Parasitology, School of Medicine, College of Health Sciences (CHS), Addis Ababa University (AAU), Addis Ababa, Ethiopia; 2Department of Medical Laboratory Sciences, CHS, AAU, Addis Ababa, Ethiopia; 3Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, Karolinska, Sweden; 4Department of Obstetrics and Gynecology, School of Medicine, CHS, AAU, Addis Ababa, Ethiopia; 5School of Public Health, CHS, AAU, Addis Ababa, Ethiopia; 6Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton, UK†Fikre Enquselassie passed away on October 27, 2019Correspondence: Kassu Desta, Tel +251 911107099, Email kassudesta2020@gmail.comBackground: Staphylococcus aureus is a major human pathogen and causes healthcare and community-acquired infection. Data on the extent of MRSA colonization among health-care workers (HCWs) in sub-Saharan Africa are limited. Hence, we determined the burden of MRSA colonisation among HCWs and administrative staff in Tikur Anbessa Specialised Hospital (TASH), College of Health Sciences (CHS), Addis Ababa University, Ethiopia.Methods: Using a cross-sectional study design, participants were screened for MRSA colonisation between June 2018 and August 2019 using nasal swabs. The swabs were analysed using standard laboratory methods including antibiotic resistance gene, mecA. Anonymised sociodemographic data were collected by pretested questionnaires to evaluate HCWs factors associated with MRSA carriage.Results: A total of 588 HCWs and 468 administrative staff were screened for MRSA. Women were over-represented. Overall, 49.1% (289/588) of HCWs were nurses and 25% (117/468) of the administrative staff were cleaners or laundry workers. Overall, 138 S. aureus isolates were retrieved from the nasal swabs of both groups (16.3%, 96/588 from HCWs). The burden of MRSA colonisation was 4.8% (28/580, 95% CI: 3.1– 6.5%) among HCWs compared to 0.2% (1/468, 95% CI: 0.18– 0.6%) of administrative staff (p value < 0.05). The majority of S. aureus and all MRSA isolates were resistant to penicillin. Isolates from HCWs were more resistant to tested antibiotics than administrative staff (P-value < 0.05).Conclusion: This is the first report in Ethiopia on MRSA colonization using mecA and revealed that; (i) overall carriage rates of MRSA in HCWs are comparable with observations reported in some other countries and (ii) HCWs exhibit a higher burden of MRSA carriage than administrative staff. Our data support strategic screening of MRSA and antimicrobial stewardship for better intervention measures.Keywords: MRSA, HCWs, administrative staff, mecA, TASH, Ethiopia

Background Mycetoma is a chronic, progressively destructive disease of subcutaneous tissues and bones caused by certain species of bacteria or fungi. We conducted a cross-sectional community-based study alongside mapping of mycetoma in five administrative units with high mycetoma endemicity in the Eastern Sennar Locality, Sennar State, Sudan. Methods A household survey was administered which included questions about the household members, household characteristics, economic activity and history of mycetoma. A clinical examination was conducted on all members of the household. If mycetoma was suspected, an individual questionnaire was completed collecting demographic, clinical and epidemiological data as well as information on the use of health care and associated costs. Geographical coordinates and photos of the lesions were taken, and the affected persons were referred to the medical centre for confirmation of the diagnosis and treatment. We compared the characteristics of households with confirmed cases of mycetoma with those without confirmed cases, and individuals with confirmed mycetoma with those in whom mycetoma was not confirmed. Results In total 7,798 households in 60 villages were surveyed; 515 suspected cases were identified and 359 cases of mycetoma were confirmed. Approximately 15% of households with mycetoma had more than one household member affected by this disease. Households with mycetoma were worse off with respect to water supply, toilet facilities, electricity and electrical appliances compared to the survey households. Only 23% of study participants with mycetoma had sought professional help. Of these, 77% of patients travelled an average of six hours to visit a medical facility. More than half of patients had to pay towards their treatment. The estimated average cost of treatment was 26,957 Sudanese pounds per year (566 US dollars, exchange rate 2018). Conclusions Results of this survey suggest that agricultural practices and reduced access to sanitation and clean water can be risk factors in developing mycetoma. Poor access to health care and substantial financial costs were barriers to seeking treatment for mycetoma.