Previous reports have highlighted the high prevalence of blood culture negative endocarditis (BCNE) in South Africa. The Tygerberg Endocarditis Cohort (TEC) study is an ongoing prospective cohort ...study of patients with confirmed or suspected IE presenting to Tygerberg Academic Hospital, Cape Town, South Africa. Current analysis includes patients that presented between November 2019 and August 2020. Forty four (44) patients have been included in this ongoing study. Fourteen of the 44 patients (31.8%) had BCNE. Further analysis of the patients with BCNE identified
Bartonella
species as the most common causative organism (
n
=6; 43%). Other causes included
Mycoplasma
species (
n
=2). No cause could be identified in 4 of the 44 patients (9%).
Bartonella quintana
was identified with PCR of valvular tissue as the causative organism in 4 of the 5 patients that underwent urgent surgery. The patients with Bartonella IE (
n
=6) had an average age of 39 years with equal gender distribution. The common clinical features were clubbing (
n
=5; 83%), anemia (
n
=4; 66.6%), haematuria (
n
=3; 50%), acute on chronic severe regurgitant lesion (
n
=3; 50%) and acute severe regurgitant lesion (
n
=2; 33.3%).The aortic valve was involved in 5 of 6 patients. During a mean follow-up period of 251 days after diagnosis, no major adverse events occurred. Bartonella-associated IE is an important cause of BCNE in the Western Cape of South Africa. Imaging findings (in patients with BCNE) of significant valvular destruction with large vegetations on the aortic valve not affected by congenital or rheumatic valve disease should raise the suspicion of Bartonella-associated IE.
The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care ...unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied.
We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO.
The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (PaO2/FiO2) was 68 (54–92) in 293 enroled patients. Of these, 137/293 (47%) of patients PaO2/FiO2 76 (63–93) were successfully weaned from HFNO. The median duration of HFNO was 6 (3–9) in those successfully treated versus 2 (1–5) days in those who failed (p<0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31–0.60), as was use of steroids (AHR 0.35, 95%CI 0.19–0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%).
In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.
Abstract
Background
The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is ...primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS.
Methods
Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography–tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described.
Results
Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0–65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07–0.15) µg/mL.
Conclusions
Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentration >12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.
In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B ...patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5-20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting.
Summary Objectives Hepatitis B virus (HBV), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are endemic in Africa. However, hepatitis co-infection rates among HIV-infected ...individuals remain controversial. The aim of this review was to determine the prevalence of HBV and HCV in HIV-infected patients in sub-Saharan Africa and to analyze whether HIV is associated with a higher HBV/HCV prevalence in that region. Design and methods We performed a systematic review and meta-analysis. Studies reporting HBV and HCV prevalence data amongst HIV-infected patients in sub-Saharan Africa were included. Weighted means and medians across studies were calculated. Studies including an HIV-negative control group were used for meta-analysis. Risk ratios (RRs) were calculated using a random effects model. Results Sixty studies were included. Among HIV-infected individuals, mean HBsAg and anti-HCV prevalence rates were 15% and 7%, respectively. RRs for a positive HBsAg and a positive anti-HCV were 1.40 (95% confidence interval (CI) 1.16–1.69) and 1.60 (95% CI 1.05–2.45) for HIV-infected, as compared to HIV-uninfected, patients. Conclusions Many HIV-positive individuals in sub-Saharan Africa are HBV or HCV co-infected. HIV is associated with a higher prevalence of both HBV and HCV in this region. However, this association is less evident than that observed in Western countries and varies between studies.
Over 130 million people have been diagnosed with Coronavirus disease 2019 (COVID-19), and more than one million fatalities have been reported worldwide. South Africa is unique in having a quadruple ...disease burden of type 2 diabetes, hypertension, human immunodeficiency virus (HIV) and tuberculosis, making COVID-19-related mortality of particular interest in the country. The aim of this study was to investigate the clinical characteristics and associated mortality of COVID-19 patients admitted to an intensive care unit (ICU) in a South African setting.
We performed a prospective observational study of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to the ICU of a South African tertiary hospital in Cape Town. The mortality and discharge rates were the primary outcomes. Demographic, clinical and laboratory data were analysed, and multivariable robust Poisson regression model was used to identify risk factors for mortality. Furthermore, Cox proportional hazards regression model was performed to assess the association between time to death and the predictor variables. Factors associated with death (time to death) at p-value < 0.05 were considered statistically significant. Of the 402 patients admitted to the ICU, 250 (62%) died, and another 12 (3%) died in the hospital after being discharged from the ICU. The median age of the study population was 54.1 years (IQR: 46.0-61.6). The mortality rate among those who were intubated was significantly higher at 201/221 (91%). After adjusting for confounding, multivariable robust Poisson regression analysis revealed that age more than 48 years, requiring invasive mechanical ventilation, HIV status, procalcitonin (PCT), Troponin T, Aspartate Aminotransferase (AST), and a low pH on admission all significantly predicted mortality. Three main risk factors predictive of mortality were identified in the analysis using Cox regression Cox proportional hazards regression model. HIV positive status, myalgia, and intubated in the ICU were identified as independent prognostic factors.
In this study, the mortality rate in COVID-19 patients admitted to the ICU was high. Older age, the need for invasive mechanical ventilation, HIV status, and metabolic acidosis were found to be significant predictors of mortality in patients admitted to the ICU.
There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for ...over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB.
Coronavirus disease 2019 (COVID‐19) and pneumocystis pneumonia (PCP) share many overlapping features and may be clinically indistinguishable on initial presentation in people living with HIV. We ...present the case of co‐infection with COVID‐19 and PCP in a patient with progressive respiratory failure admitted to our intensive care unit where the dominant disease was uncertain. This case highlights the difficulty in differentiating between the two diseases, especially in a high HIV prevalence setting where PCP is frequently diagnosed using case definitions and clinical experience due to limited access to bronchoscopy, appropriate laboratory testing, and computed tomography scans. In addition, diagnostic testing may yield false‐negative results in both diseases, and clinician awareness to the overlap and pitfalls is essential if COVID‐19 becomes endemic in such settings.
We present the case of a 54‐year‐old male with newly diagnosed advanced HIV who presented with clinical, biochemical, and radiological features that were consistent with both pneumocystis pneumonia (PCP) and coronavirus disease 2019 (COVID‐19). He subsequently tested positive for both diseases; however, the contribution of each disease to his progressive respiratory failure is unclear.
Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably ...the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection.
We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa. All HIV-infected patients were on antiretroviral therapy for ≥3 months. Liver stiffness measurements were assessed using the Fibroscan (Fibroscan 402, Echosens). Cell-based immunomarkers were measured by flow cytometry. Soluble serum/plasma immunomarkers were measured by Luminex technology and enzyme immunoassays. HIV (COBAS/Ampliprep TaqMan HIV-1) and HBV viral loads (in-house assay) were also performed.
HBV/HIV co-infected patients showed significantly higher levels of immune activation %CD8+/HLA-DR+/CD38+ (median 30%, interquartile range: 17-53) and %CD8+/PD-1 (median 22%, interquartile range: 15-33), p ≤ 0.01 compared to all other study groups. Despite this, the HBV-mono-infected group had the highest proportion of patients with advanced liver fibrosis (≥13 kPa) as measured by Fibroscan (18%). HBV mono-infected patients showed highest expression of most cytokines including IL-17 and basic fibroblastic growth factor. There was significant positive correlation between detectable HIV and HBV viral replication and liver fibrosis but not immune activation or gut translocation.
Highly-active antiretroviral therapy, including tenofovir, is effective against both HIV and HBV. Earlier therapy in the co-infected patients may therefore have controlled viral replication leading to better fibrosis scores when compared to HBV mono-infection in this study. On-going HBV and HIV viraemia, rather than microbial translocation or immune activation, appear to be the drivers of liver fibrosis. Moderate to advanced liver fibrosis in HBV-mono-infection may well indicate poor access to screening and treatment of HBV infection.
Subacute thyroiditis is a granulomatous inflammatory disorder often triggered by a preceding viral infection. Patients typically present with complaints of anterior neck pain associated with a tender ...enlarged thyroid gland. The coronaviruses have never before been implicated in the aetiology of subacute thyroiditis. It is postulated that the pathogenesis related to thyroid disease in Coronavirus disease 2019 (COVID-19) is multifactorial. Contributory factors include effects of the virus-related cytokine storm and direct action of the virus on SARS-CoV-2 receptors in the thyroid. This article further reviews the association between thyroiditis and COVID-19. The clinical characteristics, diagnostic workup and management of a patient who presented with subacute thyroiditis following COVID-19 are discussed. Furthermore, complications are entertained and suggestions for the management of thyroiditis following COVID-19 are provided.
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