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Introduction: While a large proportion of people with HIV (PWH) have experienced SARS‐CoV‐2 infections, there is uncertainty about the role of HIV disease severity on COVID‐19 outcomes, especially in lower‐income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH. Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS‐CoV‐2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID‐19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first‐diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions: Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID‐19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized. [ABSTRACT FROM AUTHOR]

Background: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB).Methods: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed.Results: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels.Conclusion: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population. [ABSTRACT FROM AUTHOR]

Background There are limited data on the etiology of respiratory infections in human immunodeficiency virus (HIV)–infected patients in resource-limited settings. Methods We performed quantitative multiplex real-time polymerase chain reaction (PCR) for Pneumocystis jirovecii and common bacterial and viral respiratory pathogens on sputum samples (spontaneous or induced) from a prospective cohort study of HIV-infected inpatients with World Health Organization danger signs and cough. Mycobacterial culture was done on 2 sputum samples, blood cultures, and relevant extrapulmonary samples. Results We enrolled 284 participants from 2 secondary-level hospitals in Cape Town, South Africa: median CD4 count was 97 cells/μL, 64% were women, and 38% were on antiretroviral therapy. One hundred forty-eight had culture-positive tuberculosis, 100 had community-acquired pneumonia (CAP), 26 had P. jirovecii pneumonia (PJP), and 64 had other diagnoses. Probable bacterial infection (>105 copies/mL) was detected in 133 participants; the prevalence was highest in those with CAP (52%). Haemophilus influenzae and Streptococcus pneumoniae were the commonest bacterial pathogens detected; atypical bacteria were uncommon. Viruses were detected in 203 participants; the prevalence was highest in those with PJP (85%). Human metapneumovirus was the commonest virus detected. Multiple coinfections were commonly detected. Conclusions Sputum multiplex PCR could become a useful diagnostic tool for bacterial respiratory infections in HIV-infected inpatients, but its value is limited as quantitative cutoffs have only been established for a few bacterial pathogens and validation has not been done in this patient population. We found a high prevalence of respiratory viruses, but it is unclear whether these viruses were causing infection as there are no accepted quantitative PCR cutoffs for diagnosing respiratory viral infections. [ABSTRACT FROM AUTHOR]

Background. The World Health Organization (WHO) algorithm for the diagnosis of tuberculosis in seriously ill human immunodeficiency virus (HIV)-infected patients lacks a firm evidence base. We aimed to develop a clinical prediction rule for the diagnosis of tuberculosis and to determine the diagnostic utility of the Xpert MTB/RIF assay in seriously ill HIV-infected patients. Methods. We conducted a prospective study among HIV-infected inpatients with any cough duration and WHO-defined danger signs. Culture-positive tuberculosis from any site was the reference standard. A priori selected variables were assessed for univariate associations with tuberculosis. The most predictive variables were assessed in a multivariate logistic regression model and used to establish a clinical prediction rule for diagnosing tuberculosis. Results. We enrolled 484 participants. The median age was 36 years, 65.5% were female, the median CD4 count was 89 cells/ μL and 35.3% were on antiretroviral therapy. Tuberculosis was diagnosed in 52.7% of participants. The c-statistic of our clinical prediction rule (variables: cough ≥14 days, unable to walk unaided, temperature >39°C, chest radiograph assessment, hemoglobin, and white cell count) was 0.811 (95% confidence interval, .802–.819). The classic tuberculosis symptoms (fever, night sweats, weight loss) added no discriminatory value in diagnosing tuberculosis. Xpert MTB/RIF assay sensitivity was 86.3% and specificity was 96.1%. Conclusions. Our clinical prediction rule had good diagnostic utility for tuberculosis among seriously ill HIV-infected inpatients. Xpert MTB/RIF assay, incorporated into the updated 2016 WHO algorithm, had high sensitivity and specificity in this population. Our findings could facilitate improved diagnosis of tuberculosis among seriously ill HIV-infected inpatients in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Background: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods: We pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher's exact test, multivariate logistic regression and Cox proportional hazards models. Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR 41.0-113.2). In 73/181 patients (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13-4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97-12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients. Conclusions: Around 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS. [ABSTRACT FROM AUTHOR]

The article presents a study which aimed to identify the cause of systemic dimorphic fungal infection in patients in South Africa. In the study, DNA sequencing was employed to determine pathogenic fungi. It cites the three species of the genus emmonsia that are linked with human disease, namely, the Emmonsia crescens, Emmonsia parva, and Emmonsia pasteuriana.

: Using a microarray-based approach, Michael Levin and colleagues develop a disease risk score to distinguish active from latent tuberculosis, as well as tuberculosis from other diseases, using whole blood samples. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. Methods: Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. Results: Between May 2009 and November 2010, 112 patients (60% female), with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm3 (IQR 31–106) and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68%) developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. Conclusions: High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1st three months following ART initiation. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis, bacterial community-acquired pneumonia (CAP), and Pneumocystis jirovecii pneumonia (PJP) are the three commonest causes of hospitalisation in HIV-infected adults. Prompt diagnosis and treatment initiation are important to reduce morbidity and mortality, but are hampered by limited diagnostic resources in resource poor settings. C-reactive protein (CRP) and procalcitonin have shown diagnostic utility for respiratory tract infections, however few studies have focussed on their ability to distinguish between tuberculosis, CAP, and PJP in HIV-infected inpatients.Methods: We evaluated the diagnostic accuracy of CRP and procalcitonin, compared with composite reference standards, to discriminate between the three target infections in adult HIV-infected inpatients in two district level hospitals in Cape Town, South Africa. Participants were admitted with current cough and danger signs in accordance with the WHO algorithm for tuberculosis in seriously ill HIV-infected patients. Study clinicians were blinded to CRP and procalcitonin results.Results: Two hundred forty-eight participants met study case definitions: 133 with tuberculosis, 61 with CAP, 16 with PJP, and 38 with mixed infection. In the 210 particpants with single infections the differences in median CRP and procalcitonin concentrations between the three infections were statistically significant, but distributions overlapped considerably. CRP and procalcitonin concentrations were highest in the CAP group and lowest in the PJP group. CRP and procalcitonin cut-offs with sensitivities of ≥90% were found for all three target infection pairs, but corresponding specificities were low. Highest receiver operating characteristic areas under the curve for CRP and procalcitonin were for PJP versus tuberculosis and PJP versus CAP (0.68 and 0.71, and 0.74 and 0.69 respectively).Conclusions: CRP and procalcitonin showed limited value in discriminating between the three target infections due to widely overlapping distributions, but diagnostic accuracy was higher for discriminating PJP from CAP or tuberculosis. Our findings show limitations for CRP and procalcitonin, particularly for discriminiation of tuberculosis form CAP, however they may have greater diagnostic utility as part of a panel of biomarkers or in clinical prediction rules. [ABSTRACT FROM AUTHOR]

Background: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS.Methods: We pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher's exact test, multivariate logistic regression and Cox proportional hazards models.Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR 41.0-113.2). In 73/181 patients (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13-4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97-12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients.Conclusions: Around 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS.Trial Registration: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548 on 17 August 2005. [ABSTRACT FROM AUTHOR]