The prevalence of pulmonary hypertension in post-tuberculosis and active tuberculosis populations: a systematic review and meta-analysis.

BACKGROUND: The prevalence of tuberculosis (TB)-associated pulmonary hypertension (PH) has not previously been quantified, resulting in an underappreciated burden of disease. We aimed to estimate the prevalence of PH in post-TB and active TB populations. METHODS: In this systematic review and meta-analysis, we searched PubMed/Medline, Cochrane Library, EBSCOhost, Scopus, African Journals Online and Google Scholar, with no language restriction, for available literature published after 1950. Eligible studies described adult participants (≥16 years), with documented evidence of active or prior TB, diagnosed with PH. Study quality was assessed using a risk of bias tool specifically developed for prevalence studies. Aggregate prevalence estimates with 95% confidence intervals were synthesised using a random-effects meta-analysis model, incorporating the Freeman-Tukey transformation. Subgroup analysis was conducted to ascertain prevalence estimates in specific patient populations. RESULTS: We identified 1452 unique records, of which 34 met our inclusion criteria. 23 studies, with an acceptable risk of bias and where PH was diagnosed at right heart catheterisation or echocardiography, were included in the meta-analysis. In post-TB studies (14/23), the prevalence of PH was 67.0% (95% CI 50.8-81.4) in patients with chronic respiratory failure, 42.4% (95% CI 31.3-54.0) in hospitalised or symptomatic patients and 6.3% (95% CI 2.3-11.8) in nonhealthcare-seeking outpatients (I2=96%). There was a lower estimated prevalence of PH in studies of populations with active TB (9.4%, 95% CI 6.3-13.0), I2=84%). CONCLUSION: Our results highlight the significant burden of PH in post-TB and active TB populations. We emphasise the need for increased recognition of TB-associated PH and additional high-quality prevalence data.

Scoping review of post-TB pulmonary vascular disease: Proceedings from the 2nd International Post-Tuberculosis Symposium.

Tuberculosis (TB) may cause significant long-term cardiorespiratory complications, of which pulmonary vascular disease is most under-recognized. TB is rarely listed as a cause of pulmonary hypertension (PH) in most PH guidelines, yet PH may develop at various stages in the time course of TB, from active infection through to the post-TB period. Predisposing risk factors for the development of PH are likely multifactorial, involving active TB disease and post-TB lung disease (PTLD), host-related and environment-related factors. Moreover, post-TB PH should likely be classified in Group 3 PH, with the pathogenesis similarly complex and multifactorial as other Group 3 PH causes. Identifying risk factors that predispose to post-TB PH may aid in developing risk stratification criteria for early identification and referral for confirmatory diagnostic tests. Given that universal screening for PH in TB survivors may be impractical and unfeasible, a targeted screening approach for high-risk individuals would be sensible. In this scoping review of post-TB PH, resulting from the proceedings of the 2nd International Post-Tuberculosis Symposium, we aim to describe the epidemiology, risk factors, and pathophysiology of post-TB PH. We emphasize diagnosing PH with an alternative set of diagnostic guidelines in resource-constrained settings where right heart catheterization may not be feasible. Research to describe the burden and distribution of post-TB PH should be prioritized as there is a current gap in knowledge regarding the prevalence and incidence of post-TB PH among persons with TB.

Relationship Between Tenofovir Diphosphate Concentrations in Dried Blood Spots and Virological Outcomes After Initiating Tenofovir-Lamivudine-Dolutegravir as First-Line or Second-Line Antiretroviral Therapy.

BACKGROUND: Tenofovir diphosphate (TFV-DP) concentration in dried blood spots is a marker of long-term adherence. We investigated the relationship between TFV-DP concentrations and virological outcomes in participants initiating tenofovir-lamivudine-dolutegravir (TLD) as first-line or second-line antiretroviral therapy. SETTING: Three primary care clinics in Khayelitsha, Cape Town, South Africa. METHODS: We conducted a post hoc analysis of 2 randomized controlled trials of participants initiating TLD. TFV-DP concentrations and viral loads were measured at 12, 24, and 48 weeks. Multivariable logistic regression was performed to assess the association with virological suppression (<50 copies/mL) per natural logarithm increase in TFV-DP concentration. Generalized estimating equations with logit link were used to assess associations with virological rebound. The Akaike Information Criterion and Quasi-likelihood Information Criteria were used to compare models built on continuous TFV-DP data to 4 previously defined concentration categories. RESULTS: We included 294 participants in the analysis, 188 (64%) of whom initiated TLD as second-line therapy. Adjusted odds ratios (95% CIs) of virological suppression were 2.12 (1.23, 3.75), 3.11 (1.84, 5.65), and 4.69 (2.81, 8.68) per natural logarithm increase in TFV-DP concentration at weeks 12, 24, and 48, respectively. In participants with virological suppression at week 12, the adjusted odds ratio for remaining virologically suppressed was 3.63 (95% CI: 2.21 to 5.69) per natural logarithm increase in TFV-DP concentration. Models using continuous TFV-DP data had lower Akaike Information Criterion and Quasi-likelihood Information Criteria values than those using categorical data for predicting virological outcomes. CONCLUSION: TFV-DP concentrations in dried blood spots exhibit a dose-response relationship with viral load. Analyzing TFV-DP concentrations as continuous variables rather than conventional categorization may be appropriate.

Cutaneous tuberculosis: An infrequent manifestation of a common pathogen in South Africa.

Cutaneous tuberculosis is an infrequent form of extra-pulmonary tuberculosis, even in high-prevalence settings. We present the case of a patient living with advanced HIV who developed extensive cutaneous tuberculosis. The polymorphic skin lesions were the most striking clinical manifestation of underlying disseminated tuberculosis. Contribution: This case report highlights an unusual presentation of tuberculosis. Cutaneous tuberculosis has a wide spectrum of clinical presentations and may be under-recognised by clinicians. We recommend early biopsy for microbiological diagnosis.

Childhood Cancers Misdiagnosed as Tuberculosis in a High Tuberculosis Burden Setting.

BACKGROUND: Tuberculosis (TB) and childhood cancers have overlapping presentations and malignancies may be misdiagnosed as TB in high TB-burden settings. METHODS: This retrospective study investigated the diagnosis of TB in children with cancer registered in the Tygerberg Hospital Childhood Tumor Registry from 2008 to 2018. We studied children on anti-tuberculosis treatment (ATT) at cancer diagnosis or diagnosed with TB within 1 month of cancer diagnosis. We describe the circumstances and extent of this misdiagnosis, quantify the delay in therapy and document the outcomes of these children. RESULTS: Twenty-seven of 539 (5%) children in the registry started ATT before cancer diagnosis. Both pulmonary and extrapulmonary TB complicated the cancer diagnosis. Of the 27 patients on ATT at cancer diagnosis, 22 (81%) had contact with a TB case and in 6 of 12 children (50%) a tuberculin skin test was positive. At cancer diagnosis, 16/27 (59%) children had chest radiograph changes interpreted as TB with 11/27 (41%) regarded as suggestive of TB on expert review. The median diagnostic delay between TB and cancer diagnoses was 25 days (interquartile range 3.5-58). Of 539 children with cancer, 204 (38%) died of cancer, including 18/30 (60%) children on ATT at cancer diagnosis or diagnosed with TB within 1 month of cancer diagnosis (odds ratio 2.6; 95% confidence interval: 1.2-5.4; P = 0.012). CONCLUSIONS: The clinical and radiologic overlap of TB and cancer causes diagnostic confusion in a significant number of children with cancer and may contribute to increased mortality.

Multisystem inflammatory syndrome (MIS): a multicentre retrospective review of adults and adolescents in South Africa.

OBJECTIVES: The aim of this study was to add to the descriptive data pertaining to the epidemiology, presentation, and clinical course of multisystem inflammatory syndrome (MIS) temporally associated with coronavirus disease 2019 in adults and adolescents from low- and middle-income countries. METHODS: Patients presenting to the adult wards (14 years and older) of three academic hospitals in South Africa, who were diagnosed with MIS between August 1, 2020 and May 31, 2021, were reviewed retrospectively. The presentation, laboratory and radiographic findings, and clinical course are described. RESULTS: Eleven cases of MIS were reported, four in adolescents (14-19 years) and seven in adults (≥19 years). Fever was universal. Gastrointestinal symptoms (90.9%), cardiorespiratory abnormalities (90.9%), and mucocutaneous findings (72.7%) were prominent. Echocardiography in 10/11 patients (90.9%) showed a median left ventricular ejection fraction of 26.3% (interquartile range 21.9-33.6%). All patients required high care admission and 72.7% required inotropic support. Glucocorticoids were initiated in all cases and 72.7% received intravenous immunoglobulin. CONCLUSIONS: This constitutes the largest multicentre review of adults and adolescents with MIS in Africa. MIS may be overlooked in resource-limited settings, and heightened suspicion is needed in patients with multi-organ dysfunction, especially where repeated investigations for other aetiologies are negative.