Effect of diabetes and HIV on radiographic manifestations of pulmonary tuberculosis

Due to the epidemiological transition, diabetes prevalence in South Africa is increasing, while HIV prevalence remains high. Diabetes, along with HIV, has been found to be a significant risk factor for the development of tuberculosis. Early detection and treatment of tuberculosis is essential to prevent unwarranted morbidity and mortality. This hinges on efficient diagnostic methods and tools. The chest radiograph remains a cornerstone in pulmonary tuberculosis diagnosis, especially in those where microbiological evidence of disease is lacking. A study was conducted to investigate the chest radiographic presentation of pulmonary tuberculosis in patients with diabetes, as well as to analyse the effect of HIV comorbidity on this association. The study was conducted in Khayelitsha, Cape Town, an area with a high tuberculosis, HIV and diabetes burden. A literature review was conducted to identify the key features of pulmonary tuberculosis on chest radiograph for patients with diabetes and HIV. We found that patients with diabetes were more likely to have lower lung field infiltrates and increased cavitation, with glycaemic control affecting the presence of these findings. Patients with HIV presented more often with features of primary tuberculosis on chest radiograph, namely hilar and/or mediastinal adenopathy, diffuse reticulonodular infiltrate, and lower lung field (LLF) infiltrates and cavities. These features were influenced by degree of immunosuppression. This review also found that there was no literature describing the influence of HIV on the chest radiographic features of tuberculosis in patients with diabetes. This study was conducted between June 2013 - October 2015, where 377 patients with pulmonary tuberculosis, from Ubuntu and Site B primary care clinics in Khayelitsha, underwent posterior-anterior chest radiography. Chest radiographs were read using a CRRS tool. Participants with diabetes and tuberculosis (TBDM) had a higher proportion of lower lung field opacification (76,2%: 95% CI: 56,3 – 96,1) and were 3,92 times more likely to have LLF cavitations than patients with TB only. TBDM participants with HbA1c levels over 10% had more frequent LLF involvement overall (90,9% vs 61,9% p=0,052) and isolated LLF involvement (27,3% vs 3,6%; p= 0,019) than TB only participants. Both TBDM and TBDM participants with HIV (TBDMHIV) had higher proportions of isolated LLF lesions as compared to TB only participants (14,3% vs 3,6%; p=0,093 and 15,2% vs 3,6%; p = 0,039, respectively). As CD4 counts increased, there was an upward trend towards an increase in the proportion of cavitations for TBDMHIV participants, but this was not evident in participants with TB and HIV (TBHIV). This study confirms the atypical nature of chest radiograph in persons with TBDM, TBHIV and TBDMHIV, with diabetes driving the presence of lower lung field involvement. These findings can be used in bi-directional screening algorithms for patients with diabetes, with or without HIV and highlights the important role of radiographic examination in pulmonary tuberculosis

Treatment outcomes among adults with HIV/non-communicable disease multimorbidity attending integrated care clubs in Cape Town, South Africa.

Funder: Wellcome TrustBackgroundThe growing burden of the HIV and non-communicable disease (NCD) syndemic in Sub- Saharan Africa has necessitated introduction of integrated models of care in order to leverage existing HIV care infrastructure for NCDs. However, there is paucity of literature on treatment outcomes for multimorbid patients attending integrated care. We describe 12-month treatment outcomes among multimorbid patients attending integrated antiretroviral treatment (ART) and NCD clubs in Cape Town, South Africa.MethodsAs part of an integrated clubs (IC) model pilot implemented in 2016 by the local government at two primary health care clinics in Cape Town, we identified all multimorbid patients who were enrolled for IC for at least 12 months by August 2017. Mean adherence percentages (using proxy of medication collection and attendance of club visits) and optimal disease control (defined as the proportion of participants achieving optimal blood pressure, glycosylated haemoglobin control and HIV viral load suppression where appropriate) were calculated at 12 months before, at the point of IC enrolment and 12 months after IC enrolment. Predictors of NCD control 12 months post IC enrolment were investigated using multivariable logistic regression.ResultsAs of 31 August 2017, 247 HIV-infected patients in total had been enrolled into IC for at least 12 months. Of these, 221 (89.5%) had hypertension, 4 (1.6%) had diabetes mellitus and 22 (8.9%) had both diseases. Adherence was maintained before and after IC enrolment with mean adherence percentages of 92.2% and 94.2% respectively. HIV viral suppression rates were 98.6%, 99.5% and 99.4% at the three time points respectively. Retention in care was high with 6.9% lost to follow up at 12 months post IC enrolment. Across the 3 time-points, optimal blood pressure control was achieved in 43.1%, 58.9% and 49.4% of participants while optimal glycaemic control was achieved in 47.4%, 87.5% and 53.3% of participants with diabetes respectively. Multivariable logistic analyses showed no independent variables significantly associated with NCD control.ConclusionMultimorbid adults living with HIV achieved high levels of HIV control in integrated HIV and NCD clubs. However, intensified interventions are needed to maintain NCD control in the long term

Tuberculosis, Human Immunodeficiency Virus, and the Association With Transient Hyperglycemia in Periurban South Africa

Abstract Background Diabetes mellitus (DM) increases tuberculosis (TB) risk. We assessed the prevalence of hyperglycemia (DM and impaired glucose regulation [IGR]) in persons with TB and the association between hyperglycemia and TB at enrollment and 3 months after TB treatment in the context of human immunodeficiency virus (HIV) infection. Methods Adults presenting at a Cape Town TB clinic were enrolled. TB cases were defined by South African guidelines, while non-TB participants were those who presented with respiratory symptoms, negative TB tests, and resolution of symptoms 3 months later without TB treatment. HIV status was ascertained through medical records or HIV testing. All participants were screened for DM using glycated hemoglobin and fasting plasma glucose at TB treatment and after 3 months. The association between TB and DM was assessed. Results Overall DM prevalence was 11.9% (95% confidence interval [CI], 9.1%–15.4%) at enrollment and 9.3% (95% CI, 6.4%–13%) at follow-up; IGR prevalence was 46.9% (95% CI, 42.2%–51.8%) and 21.5% (95% CI, 16.9%–26.3%) at enrollment and follow-up. TB/DM association was significant at enrollment (odds ratio [OR], 2.41 [95% CI, 1.3–4.3]) and follow-up (OR, 3.3 [95% CI, 1.5–7.3]), whereas TB/IGR association was only positive at enrollment (OR, 2.3 [95% CI, 1.6–3.3]). The TB/DM association was significant at enrollment in both new and preexisting DM, but only persisted at follow-up in preexisting DM in patients with HIV-1 infection. Conclusions Our study demonstrated high prevalence of transient hyperglycemia and a significant TB/DM and TB/IGR association at enrollment in newly diagnosed DM, but persistent hyperglycemia and TB/DM association in patients with HIV-1 infection and preexisting DM, despite TB therapy. This work was supported by the Wellcome Trust (grant numbers 084323, 104873, and 203135), a Carnegie Corporation Postdoctoral Fellowship, and a Harry Crossley Senior Clinical Fellowship. R. J. W. is supported by the Francis Crick Institute, which receives funding from Cancer Research UK (grant number FC001010218), Research Councils UK (grant number FC0010218), and the Wellcome Trust (grant number FC0010218). He also receives support from the National Institutes of Health (NIH) (grant number U1 AI115940), NIH (grant number WILK116PTB), and European and Developing Countries Clinical Trials Partnership (grant number SRIA 2015–1065). M. K. is supported by the South African Centre for Epidemiological Modelling and Analysis, the International Epidemiology Databases to Evaluate AIDS, and the NIH (grant number U01AI069924)

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Analysis of the Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells to Discriminate Latent from Active Tuberculosis in HIV-Uninfected and HIV-Infected Individuals

Several immune-based assays have been suggested to differentiate latent from active tuberculosis (TB). However, their relative performance as well as their efficacy in HIV-infected persons, a highly at-risk population, remains unclear. In a study of 81 individuals, divided into four groups based on their HIV-1 status and TB disease activity, we compared the differentiation (CD27 and KLRG1), activation (HLA-DR), homing potential (CCR4, CCR6, CXCR3, and CD161) and functional profiles (IFNγ, IL-2, and TNFα) of Mycobacterium tuberculosis (Mtb)-specific CD4+ T cells using flow cytometry. Active TB disease induced major changes within the Mtb-responding CD4+ T cell population, promoting memory maturation, elevated activation and increased inflammatory potential when compared to individuals with latent TB infection. Moreover, the functional profile of Mtb-specific CD4+ T cells appeared to be inherently related to their degree of differentiation. While these specific cell features were all capable of discriminating latent from active TB, irrespective of HIV status, HLA-DR expression showed the best performance for TB diagnosis [area-under-the-curve (AUC) = 0.92, 95% CI: 0.82–1.01, specificity: 82%, sensitivity: 84% for HIV− and AUC = 0.99, 95% CI: 0.98–1.01, specificity: 94%, sensitivity: 93% for HIV+]. In conclusion, these data support the idea that analysis of T cell phenotype can be diagnostically useful in TB

Spatial and temporal trends of SARS-CoV-2 RNA from wastewater treatment plants over 6 weeks in Cape Town, South Africa

CITATION: Street, R. et al. 2021. Spatial and temporal trends of SARS-CoV-2 RNA from wastewater treatment plants over 6 weeks in Cape Town, South Africa. International Journal of Environmental Research and Public Health, 18(22):12085, doi:10.3390/ijerph182212085.The original publication is available at www.mdpi.comRecent scientific trends have revealed that the collection and analysis of data on the occurrence and fate of SARS-CoV-2 in wastewater may serve as an early warning system for COVID-19. In South Africa, the first COVID-19 epicenter emerged in the Western Cape Province. The City of Cape Town, located in the Western Cape Province, has approximately 4 million inhabitants. This study reports on the monitoring of SARS-CoV-2 RNA in the wastewater of the City of Cape Town’s wastewater treatment plants (WWTPs) during the peak of the epidemic. During this period, the highest overall median viral RNA signal was observed in week 1 (9200 RNA copies/mL) and declined to 127 copies/mL in week 6. The overall decrease in the amount of detected viral SARS-CoV-2 RNA over the 6-week study period was associated with a declining number of newly identified COVID-19 cases in the city. The SARS-CoV-2 early warning system has now been established to detect future waves of COVID-19.https://www.mdpi.com/1660-4601/18/22/12085Publisher's versio