Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa.

Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.

Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection.

T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2-specific (SARS-CoV-2-specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non-COVID-19 patients. We showed that SARS-CoV-2-specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1-mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis-specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.

Accuracy of plain radiographs in diagnosing biopsy-proven malignant bone lesions.

BACKGROUND: The diagnosis of primary bone tumours is a three-fold approach based on a combination of clinical, radiological and histopathological findings. Radiographs form an integral part in the initial diagnosis, staging and treatment planning for the management of aggressive/malignant bone lesions. Few studies have been performed where the radiologist's interpretation of radiographs is compared with the histopathological diagnosis. OBJECTIVES: The study aimed to determine the frequency of bone tumours at a tertiary hospital in South Africa, and, using a systematic approach, to determine the sensitivity and specificity of radiograph interpretation in the diagnosis of aggressive bone lesions, correlating with histopathology. We also determined the inter-observer agreement in radiograph interpretation, calculated the positive and negative predictive values for aggressive/malignant bone tumours and computed the cumulative effect of multiple radiological signs to determine the yield for malignant bone tumours. METHOD: A retrospective, descriptive and correlational study was performed, reviewing the histopathological reports of all biopsies performed on suspected aggressive bone lesions during a 3-year period from 2012 to 2014. The radiographs were interpreted by three radiologists using predetermined criteria. The sensitivity and specificity of the readers' interpretation of the radiograph as 'benign/non-aggressive' or 'aggressive/malignant' were calculated against the histology, and the inter-rater agreement of the readers was computed using the Fleiss kappa values. RESULTS: Of the 88 suspected 'aggressive or malignant' bone tumours that fulfilled the inclusion criteria, 43 were infective or malignant and 45 were benign lesions at histology. Reader sensitivity in the diagnosis of malignancy/infective bone lesions ranged from 93% to 98% with a specificity of 53% - 73%. The average kappa value of 0.43 showed moderate agreement between radiological interpretation and final histology results. The four radiological signs with the highest positive predictive values were an ill-defined border, wide zone of transition, cortical destruction and malignant periosteal reaction. The presence of all four signs on radiography had a 100% yield for a malignant bone tumour or infective lesion. CONCLUSION: The use of a systemic approach in the interpretation of bone lesions on radiographs yields high sensitivity but low specificity for malignancy and infection. The presence of benign bone lesions with an aggressive radiographic appearance necessitates continuation of the triple approach for the diagnosis of primary bone tumours.

Obstructive pulmonary disease in patients with previous tuberculosis: Pathophysiology of a community-based cohort.

BACKGROUND: An association between chronic airflow limitation (CAL) and a history of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies, but the mechanisms responsible for this association are unclear. It is debated whether CAL in this context should be viewed as chronic obstructive pulmonary disease (COPD) or a separate phenotype. OBJECTIVE: To compare lung physiology and high-resolution computed tomography (HRCT) findings in subjects with CAL and evidence of previous (healed) PTB with those in subjects with smoking-related COPD without evidence of previous PTB. METHODS: Subjects with CAL identified during a Burden of Obstructive Lung Disease (BOLD) study performed in South Africa were studied. Investigations included questionnaires, lung physiology (spirometry, body plethysmography and diffusing capacity) and quantitative HRCT scans to assess bronchial anatomy and the presence of emphysema (<-950 HU), gas trapping (<-860 HU) and fibrosis (>-200 HU). Findings in subjects with a past history and/or HRCT evidence of PTB were compared with those in subjects without these features. RESULTS: One hundred and seven of 196 eligible subjects (54.6%) were enrolled, 104 performed physiology tests and 94 had an HRCT scan. Based on history and HRCT findings, subjects were categorised as no previous PTB (NPTB, n=31), probable previous PTB (n=33) or definite previous PTB (DPTB, n=39). Subjects with DPTB had a lower diffusing capacity (Δ=-17.7%; p=0.001) and inspiratory capacity (Δ=-21.5%; p=0.001) than NPTB subjects, and higher gas-trapping and fibrosis but not emphysema scores (Δ=+6.2% (p=0.021), +0.36% (p=0.017) and +3.5% (p=0.098), respectively). CONCLUSIONS: The mechanisms of CAL associated with previous PTB appear to differ from those in the more common smoking-related COPD and warrant further study.

Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography.

Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers that are predictive of progression.

Testing a dual-modality system that combines full-field digital mammography and automated breast ultrasound.

PURPOSE: The aim of this study was to test a novel dual-modality imaging system that combines full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in a single platform. Our Aceso system, named after the Greek goddess of healing, was specifically designed for the early detection of cancer in women with dense breast tissue. MATERIALS AND METHODS: Aceso was first tested using two industry standards: a Contrast Detail Mammography (CDMAM) phantom as endorsed by European Reference Organisation for Quality Assured Breast Screening and Diagnostic Services was used to assess the FFDM images; and the CIRS 040GSE ultrasound phantom was imaged to evaluate the quality of the ABUS images. In addition, 58 women participated in a clinical trial: 51 were healthy volunteers aged between 40 and 65, while 7 were patients referred by the breast clinic, 6 of whom had biopsy-proven breast cancer. RESULTS: The CDMAM tests showed that the FFDM results were "acceptable" but fell short of "achievable" which was attributed to the low dose used. The ABUS images had good depth penetration (80 mm) and adequate axial resolution (0.5 mm), but the lateral resolution of 2 mm was judged to be too coarse. In a 42-year-old volunteer with extremely dense breast tissue, the ABUS modality detected a lesion (a benign cyst) that was mammographically occult in the FFDM image. For a 73-year-old patient with fatty breasts, a malignant lesion was successfully detected and co-registered in the FFDM and ABUS images. On average, each woman spent less than 11 min in the acquisition room. CONCLUSIONS: While there is room for improvement in the quality of both the FFDM and ABUS images, Aceso has demonstrated its ability to acquire clinically meaningful images for a range of women with varying breast densities and, therefore, has potential as a screening device.

Incidence of occupational latent tuberculosis infection in South African healthcare workers.

The test-specific incidence of latent tuberculosis infection (LTBI) in healthcare workers from sub-Saharan Africa is unknown. 505 healthcare workers from South Africa were screened at baseline, and after 12 months, with a questionnaire, the tuberculin skin test (TST), and two T-cell assays (T-SPOT.TB and QuantiFERON-TB Gold-In-Tube). Test-specific conversion rates were calculated. The prevalence of presumed LTBI at baseline was 84, 69 and 62% using the TST, QuantiFERON-TB Gold-In-Tube and T-SPOT.TB, respectively. The annual test-specific conversion rate, depending on the cut-off point used, was as follows: TST 38%; QuantiFERON-TB Gold-In-Tube 13-22%; and T-SPOT.TB 18-22%. Annual reversion rates were 4, 7 and 16%, respectively. The annual TST conversion rate was significantly higher than that derived from published local community-based data (IRR 3.53, 95% CI 1.81-6.88). Factors associated with conversion (any test) included healthcare sector of employment, counselling of tuberculosis patients, and a baseline positive TST (for T-SPOT.TB). The annual rate of tuberculosis infection in South African healthcare workers was very high, irrespective of the testing method used, and may be explained by occupational exposure, as the rate was considerably higher than non-healthcare workers from the same community. Collectively, these data support the need for implementation of tuberculosis-specific infection control measures in Africa.