The effect of beta-blockers on foetal birth weight in pregnancies in women with structural heart disease: a prospective cohort study

Objective: To examine whether treatment with beta-blockers (BBs) in pregnant women with structural heart disease (SHD) resulted in a decrease in foetal birth weight (FBW) in a South African cohort. Methods: This was a prospective cohort study conducted in a tertiary-level hospital in Cape Town from 2010 to 2016. Of the 178 pregnant women with SHD, 24.2% received BBs for a minimum of two weeks. Adverse foetal outcomes and mean FBW were compared between the BB groups and subgroups (congenital, valvular, cardiomyopathy and other). Adverse foetal outcome was defined as: low birth weight (LBW) < 2 500 g, Apgar score < 7, premature birth (< 37 weeks) and small for gestational age (SGA). Results: BB exposure during pregnancy was found to be associated with a non-significant increased FBW (2 912 vs 2 807 g, p = 0.347). A significant decrease (p = 0.009) was noted in FBW for valvular SHD pregnancies using BBs, while a significant increase (p = 0.049) was observed for the same outcome in the cardiomyopathy subgroup using BBs. A significant increase was observed for SGA (p = 0.010) and LBW (p = 0.003) pregnancies within the valvular subgroup when exposed to BBs. Conclusion: BB use in pregnant women with SHD in a South African cohort showed no association with a decrease in FBW or an increase in adverse foetal outcomes when compared to non-BB usage

HIV-1 RNA testing of pooled dried blood spots is feasible to diagnose acute HIV infection in resource limited settings

CITATION: Dowling, W., et al. 2018. HIV-1 RNA testing of pooled dried blood spots is feasible to diagnose acute HIV infection in resource limited settings. Southern African Journal of Infectious Diseases, 33(2):50-53, doi:10.1080/23120053.2017.1393247.The original publication is available at https://www.tandfonline.comObjectives: Rapid human immunodeficiency virus (HIV) antibody tests, routinely used for diagnosis in adults and older children in resource-limited settings (RLS), do not detect early HIV infections prior to seroconversion or when antibody levels are still low. Nucleic acid amplification to detect HIV-1 RNA is the most sensitive method for acute HIV infection diagnosis, but is costly. We therefore investigated HIV- 1 RNA testing of pooled dried blood spots (DBS) to diagnose acute HIV infection. Design: Laboratory-based investigation. Methods: DBS were collected from HIV-1 Voluntary Counselling and Testing (HVCT) clients who tested negative on the Advanced QualityTM HIV antibody rapid test. DBS samples from five participants were pooled and tested on the COBAS AmpliPrep/COBAS TaqMan HIV-1 (CAP/CTM) Test v2. Individual DBS were tested when pools tested positive (> 200 RNA copies/ml). Acute infection was confirmed by HIV viral load testing, two fourth-generation HIV serological assays, and Geenius™ HIV 1/2 Assay for antibody band identification. Results: Of 482 participants who were tested, one (0.2%) had acute HIV infection: Fourth generation serology was low-level positive, the plasma HIV viral load was 15 929 HIV-1 RNA copies/ml, gp160 and gp41 antibody bands were positive and the p31 band was negative, indicating a Fiebig Stage 5 infection. Conclusions: Pooled DBS HIV-1 RNA testing is efficient compared to individual testing for acute HIV infection diagnosis. Early identification of participants with acute HIV infection facilitates immediate initiation of antiretroviral therapy to improve immune recovery and prevent transmission to others.https://www.tandfonline.com/doi/full/10.1080/23120053.2017.1393247Publisher's versio

Outcome in German and South African peripartum cardiomyopathy cohorts associates with medical therapy and fibrosis markers

Aims This study aims to compare the clinical course of peripartum cardiomyopathy (PPCM) cohorts from Germany (G‐PPCM) and South Africa (SA‐PPCM) with fibrosis‐related markers to get insights into novel pathomechanisms of PPCM. Methods and results G‐PPCM (n = 79) and SA‐PPCM (n = 72) patients and healthy pregnancy‐matched women from Germany (n = 56) and South Africa (n = 40) were enrolled. Circulating levels of procollagen type‐I (PINP) and type‐III (PIIINP) N‐terminal propeptides, soluble ST2, galectin‐3, and full‐length and cleaved osteopontin (OPN) were measured at diagnosis (baseline) and 6 months of follow‐up. Both cohorts received standard heart failure therapy while anticoagulation therapy was applied in 100% of G‐PPCM but only in 7% of SA‐PPCM patients. In G‐PPCM patients, baseline left ventricular ejection fraction (LVEF) was lower, and outcome was better (baseline LVEF, 24 ± 8%, full recovery: 52%, mortality: 0%) compared with SA‐PPCM patients (baseline LVEF: 30 ± 9%, full recovery: 32%, mortality: 11%; P < 0.05). At baseline, PINP/PIIINP ratio was lower in SA‐PPCM and higher in G‐PPCM compared with respective controls, whereas total OPN was elevated in both collectives. Cleaved OPN, which increases PIIINP levels, is generated by thrombin and was reduced in patients receiving anticoagulation therapy. High baseline galectin‐3, soluble ST2, and OPN levels were associated with poor outcome in all PPCM patients. Conclusions SA‐PPCM patients displayed a more profibrotic biomarker profile, which was associated with a less favourable outcome despite better cardiac function at baseline, compared with G‐PPCM patients. Use of bromocriptine and anticoagulation therapy in G‐PPCM may counteract fibrosis and may in part be responsible for their better outcome

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial

Background: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. Methods: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. Discussion: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. Trial registration: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986