Search

Background: RegiSCAR validation criteria for drug reaction with eosinophilia and systemic symptoms (DRESS) includes lymphadenopathy, a frequent feature of both tuberculosis (TB) and human immunodeficiency virus (HIV). TB is the most common HIV-associated coinfection. Advanced HIV is associated with lymph node (LN) fibrosis. It is not clear if this negatively affects case validation in HIV-associated DRESS. To answer this question, we designed a prospective descriptive study to assess lymphadenopathy in various combinations of comorbid HIV, TB, and DRESS. Objectives: We sought to describe the prevalence of DRESS-associated lymphadenopathy and characterize LN quality, size, and distribution in a high HIV-TB burden setting over time. Methods: We prospectively and systematically examined LN in 25 consecutive acute DRESS cases hospitalized at a South African tertiary-care center and 10 hospitalized non-DRESS HIV-TB coinfected controls. Results: Fourteen (56%) of 25 patients were HIV infected, with a median (interquartile range) CD4 count of 254 (66-478) cells/mm³, and 7 of 14 were coinfected with TB. Using RegiSCAR criteria, 12 (46%) of 25 were definite DRESS cases, 8 (31%) of 25 probable, and 5 (23%) of 25 possible. Possible cases were excluded in the analysis. Fifteen (75%) of 20 subjects had LN in ≥2 anatomic sites, including all 7 patients with HIV-TB coinfection. In contrast, 1 (20%) of 5 hospitalized non-DRESS HIV-TB coinfected controls had LN. Cervical LN, in 15 (88%) of 17, was most common, followed by axillary (76%) and inguinal (59%). Cervical LN ranged between 1 and 2 cm in size. Among the 8 (32%) of 25 subjects with follow-up data, LN had regressed in all within 6 weeks of stopping the offending drug and initiating TB treatment. There was no correlation with CD4 cell count and LN. Conclusion: Lymphadenopathy is a common feature of acute DRESS, even among HIV-TB–coinfected patients with advanced immunosuppression.

Abstract South Africa’s urban population is increasing, and in parallel, urban green infrastructure has shown an increase in alien tree species, e.g., mulberry (Morus sp.), oak (Quercus spp.) and plane trees (Platanus spp.) to name a few. This causes ecological problems since alien trees are often more water-demanding and competitive than indigenous trees, but they also increase the abundance of respiratory diseases often triggered by an allergic reaction towards the pollen of those alien taxa. In the current study, utilizing 7-day volumetric spore traps, we illustrate that the most abundant tree pollen in the two largest cities of South Africa, Cape Town and Johannesburg, is produced by alien trees with a high risk of allergenicity. This adds another aspect related to public health when evaluating plant species composition in urban forestry and urban ecology, which underlines the urgency of more intense monitoring. More importantly, this—for South Africa—newly emphasized risk for public health underlines the applicability of current directives [i.e., Spatial Development Frameworks (SDFs), localized Precinct Plans, Land Use Schemes (LUSs)] and implementation options in urban planning. Here, we present ideas that may be implemented in such a framework. From both a public health and an ecological perspective, it is recommended to plant indigenous trees like Combretum erythrophyllum, Vachellia and Senegalia spp. that have fewer ecosystem disservices, like a lower impact on public health due to lower allergenicity/lower pollen occurrence and providing more ecosystem services such as lower water needs.

Abstract Background Pollen monitoring has been discontinuously undertaken in South Africa, a country with high biodiversity, a seasonal rainfall gradient, and nine biomes from arid to subtropical. The South African Pollen Monitoring Network was set up in 2019 to conduct the first long‐term national aerospora monitoring across multiple biomes, providing weekly reports to allergy sufferers and healthcare providers. Methods Daily airborne pollen concentrations were measured from August 2019 to August 2021 in seven cities across South Africa. Updated pollen calendars were created for the major pollen types (>3%), the average Annual Pollen Index over 12 months was calculated, and the results were compared to available historical data. Results The main pollen types were from exotic vegetation. The most abundant taxa were Poaceae, Cupressaceae, Moraceae and Buddleja. The pollen season start, peak and end varied widely according to the biome and suite of pollen taxa. The main tree season started in the last week of August, peaked in September and ended in early December. Grass seasons followed rainfall patterns: September–January and January–April for summer and winter rainfall areas, respectively. Major urban centres, for example, Johannesburg and Pretoria in the same biome with similar rainfall, showed substantive differences in pollen taxa and abundance. Some major differences in pollen spectra were detected compared with historical data. However, we are cognisant that we are describing only 2 years of data that may be skewed by short‐term weather patterns. Conclusions Differences in pollen spectra and concentrations were noted across biomes and between geographically close urban centres. Comparison with historical data suggests pollen spectra and seasons may be changing due to anthropogenic climate change and landscaping. These data stress the importance of regional and continuous pollen monitoring for informed care of pollinosis.

Background: Chronic spontaneous urticaria (CSU) is defined as the spontaneous occurrence of hives, angioedema, or both for more than 6 weeks; several inciting triggers including vaccines have been implicated. Coronavirus disease 2019 (COVID-19) vaccinations have been well tolerated by patients with CSU. However, reports have emerged of CSU triggered by COVID-19 vaccination and this study describes a South African case series. Objective: To provide details of the first case series of new-onset CSU post–COVID-19 vaccination in Africa and summarize the global literature of reported cases to date. Methods: All patients referred to our Urticaria Center of Excellence in Cape Town from the initiation of the COVID-19 vaccine rollout in South Africa (from February 2021 to August 2022) were reviewed to identify patients who developed new-onset CSU within 12 weeks of receiving a COVID-19 vaccine. Medical history, physical examinations, and laboratory investigations were reviewed. Results: More than 20 million adults received COVID-19 vaccinations in South Africa during the study period. Eight patients had new-onset chronic urticaria post–COVID-19 vaccination; 6 of the 8 patients were female, the median age was 41 years (interquartile range [IQR], 38-44), and all had a history of atopy. Only 1 reported COVID-19 infection post vaccination. Chronic urticaria occurred following Pfizer-BioNTech, AstraZeneca, and Janssen Ad26.COV2.S vaccination in 6, 1, and 1 patient, respectively, with a median of 12 days (IQR, 3-38) from vaccination to symptoms onset. The baseline median score for Urticarial Activity Score 7 was 34 (IQR, 29-40), and 5 of the 8 patients (63%) had a total IgE level of more than 43 IU/L. All patients received high-dose antihistamines, with only 3 patients controlled. Conclusions: New-onset CSU can rarely be triggered by COVID-19 vaccinations, most commonly mRNA vaccines. COVID-19 vaccine–triggered CSU appears to have a phenotype similar to that triggered by other inciting agents and across populations.

Abstract Introduction The integrated care pathways for atopic dermatitis (AD‐ICPs) aim to bridge the gap between existing AD treatment evidence‐based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co‐ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD‐ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results The AD‐ICPs outline the diagnostic procedures, possible co‐morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion The AD‐ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Objective To assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population.Design Open label, single arm, phase 3B study.Setting Sisonke study, South Africa, 17 February to 15 June 2021.Participants The Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine.Main outcome measures Observed rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software).Results Most of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population.Conclusions Vaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates.Trial registration ClinicalTrials.gov NCT04838795.

Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the role of viral infection and vaccination in acute and chronic urticaria improved as a result of the COVID-19 pandemic but it has also highlighted knowledge gaps. Viral infections, especially respiratory tract infections like COVID-19, can trigger the onset of acute urticaria (AU) and the exacerbation of chronic urticaria (CU). Less frequently, vaccination against viruses including SARS-CoV-2 can also lead to new onset urticaria as well as worsening of CU in minority. Here, with a particular focus on COVID-19, we review what is known about the role of viral infections and vaccinations as triggers and causes of acute and chronic urticaria. We also discuss possible mechanistic pathways and outline the unmet needs in our knowledge. Although the underlying mechanisms are not clearly understood, it is believed that viral signals, medications, and stress can activate skin mast cells (MCs). Further studies are needed to fully understand the relevance of viral infections and vaccinations in acute and chronic urticaria and to better clarify causal pathways.

Abstract Background Timely identification of people who are at risk of dying is an important first component of end-of-life care. Clinicians often fail to identify such patients, thus trigger tools have been developed to assist in this process. We aimed to evaluate the performance of a identification tool (based on the Gold Standards Framework Prognostic Indicator Guidance) to predict death at 12 months in a population of hospitalised patients in South Africa. Methods Patients admitted to the acute medical services in two public hospitals in Cape Town, South Africa were enrolled in a prospective observational study. Demographic data were collected from patients and patient notes. Patients were assessed within two days of admission by two trained clinicians who were not the primary care givers, using the identification tool. Outcome mortality data were obtained from patient folders, the hospital electronic patient management system and the Western Cape Provincial death registry which links a unique patient identification number with national death certificate records and system wide electronic records. Results 822 patients (median age of 52 years), admitted with a variety of medical conditions were assessed during their admission. 22% of the cohort were HIV-infected. 218 patients were identified using the screening tool as being in the last year of their lives. Mortality in this group was 56% at 12 months, compared with 7% for those not meeting any criteria. The specific indicator component of the tool performed best in predicting death in both HIV-infected and HIV-uninfected patients, with a sensitivity of 74% (68–81%), specificity of 85% (83–88%), a positive predictive value of 56% (49–63%) and a negative predictive value of 93% (91–95%). The hazard ratio of 12-month mortality for those identified vs not was 11.52 (7.87–16.9, p

Abstract Background Berotralstat (BCX7353) is an oral, once‐daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long‐term safety study of berotralstat in patients with HAE. Methods APeX‐S is an ongoing, phase 2, open‐label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE‐C1‐INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long‐term safety and the secondary objective was to evaluate effectiveness. Results Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11–540) and 307 (14–429) days for the 150‐mg and 110‐mg groups, respectively. Treatment‐emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug‐related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug‐related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline. Conclusions In this analysis, both berotralstat doses, 150 and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE. Trial registration The study is registered with ClinicalTrials.gov (NCT03472040).

Pollen and fungal spores (aerospora) are the major atmospheric bioaerosols. Aerospora occurrence and concentration vary by geographical region and blossoming period, and with meteorological factors. Allergic respiratory diseases affect about 20 million South Africans, with pollen and fungal allergens amongst the leading triggers. Asthma triggered by aerospora can be life threatening; allergic rhinitis causes considerable morbidity and carries financial implications for individuals and health systems. Thus, knowledge about geographical variation, seasonal timing and intensity, as well as annual aerospora fluctuations in South Africa, where climate and vegetation are exceptionally diverse, is essential for effective diagnosis and treatment of allergies. Unfortunately, there is a lack of continuous aeropalynological data from South Africa. The longest annual monitoring exists for Cape Town (~20 years), with almost no data out of the Cape since the 1990s, and many parts of South Africa have never been monitored. In this brief review, we highlight the cross-disciplinary need for strengthened and expanded continuous aeropalynological study in South Africa, the history of efforts to date, and the introduction of the interdisciplinary South African Pollen Network (SAPNET). SAPNET was launched in seven major cities in August 2019 in order to monitor weekly variations of aerospora, and provide online data for allergy sufferers and health-care providers (www.pollencount.co.za) with the aim to establish regional pollen calendars. Significance: • The significance of aerobiology as the study of airborne organic particles which include pollen, spores of fungi and cryptogams, plant hair, insect remains etc. especially as agents of allergic rhinitis (commonly known as hay fever) is outlined. Cases of allergic rhinitis are globally increasing due to current climate change. • Very limited pollen monitoring data are available for South Africa; such data are a prerequisite for establishing pollen calendars to help medical practitioners and allergy sufferers. SAPNET (South African Pollen Network) addresses this lack of data. Since August 2019, seven 7-day volumetric spore traps have been operating in South Africa in major cities, and are continuously gathering data about the pollen and spore contents in a country which is highly affected by allergic rhinitis.

Summary: Background: Rapid on-site diagnosis facilitates tuberculosis control. Performing Xpert MTB/RIF (Xpert) at point of care is feasible, even when performed by minimally trained health-care workers, and when compared with point-of-care smear microscopy, reduces time to diagnosis and pretreatment loss to follow-up. However, whether Xpert is cost-effective at point of care remains unclear. Methods: We empirically collected cost (US$, 2014) and clinical outcome data from participants presenting to primary health-care facilities in four African countries (South Africa, Zambia, Zimbabwe, and Tanzania) during the TB-NEAT trial. Costs were determined using an bottom-up ingredients approach. Effectiveness measures from the trial included number of cases diagnosed, initiated on treatment, and completing treatment. The primary outcome was the incremental cost-effectiveness of point-of-care Xpert relative to smear microscopy. The study was performed from the perspective of the health-care provider. Findings: Using data from 1502 patients, we calculated that the mean Xpert unit cost was lower when performed at a centralised laboratory (Lab Xpert) rather than at point of care ($23·00 [95% CI 22·12–23·88] vs $28·03 [26·19–29·87]). Per 1000 patients screened, and relative to smear microscopy, point-of-care Xpert cost an additional $35 529 (27 054–40 025) and was associated with an additional 24·3 treatment initiations ([–20·0 to 68·5]; $1464 per treatment), 63·4 same-day treatment initiations ([27·3–99·4]; $511 per same-day treatment), and 29·4 treatment completions ([–6·9 to 65·6]; $1211 per completion). Xpert costs were most sensitive to test volume, whereas incremental outcomes were most sensitive to the number of patients initiating and completing treatment. The probability of point-of-care Xpert being cost-effective was 90% at a willingness to pay of $3820 per treatment completion. Interpretation: In southern Africa, although point-of-care Xpert unit cost is higher than Lab Xpert, it is likely to offer good value for money relative to smear microscopy. With the current availability of point-of-care nucleic acid amplification platforms (eg, Xpert Edge), these data inform much needed investment and resource allocation strategies in tuberculosis endemic settings. Funding: European Union European and Developing Countries Clinical Trials Partnership.

BackgroundThe prevalence of and mortality from HIV-associated tuberculosis (HIV/TB) in hospital inpatients in Africa remains unacceptably high. Currently, there is a lack of tools to identify those at high risk of early mortality who may benefit from adjunctive interventions. We therefore aimed to develop and validate a simple clinical risk score to predict mortality in high-burden, low-resource settings.Methods and findingsA cohort of HIV-positive adults with laboratory-confirmed TB from the STAMP TB screening trial (Malawi and South Africa) was used to derive a clinical risk score using multivariable predictive modelling, considering factors at hospital admission (including urine lipoarabinomannan [LAM] detection) thought to be associated with 2-month mortality. Performance was evaluated internally and then externally validated using independent cohorts from 2 other studies (LAM-RCT and a Médecins Sans Frontières [MSF] cohort) from South Africa, Zambia, Zimbabwe, Tanzania, and Kenya. The derivation cohort included 315 patients enrolled from October 2015 and September 2017. Their median age was 36 years (IQR 30-43), 45.4% were female, median CD4 cell count at admission was 76 cells/μl (IQR 23-206), and 80.2% (210/262) of those who knew they were HIV-positive at hospital admission were taking antiretroviral therapy (ART). Two-month mortality was 30% (94/315), and mortality was associated with the following factors included in the score: age 55 years or older, male sex, being ART experienced, having severe anaemia (haemoglobin < 80 g/l), being unable to walk unaided, and having a positive urinary Determine TB LAM Ag test (Alere). The score identified patients with a 46.4% (95% CI 37.8%-55.2%) mortality risk in the high-risk group compared to 12.5% (95% CI 5.7%-25.4%) in the low-risk group (p < 0.001). The odds ratio (OR) for mortality was 6.1 (95% CI 2.4-15.2) in high-risk patients compared to low-risk patients (p < 0.001). Discrimination (c-statistic 0.70, 95% CI 0.63-0.76) and calibration (Hosmer-Lemeshow statistic, p = 0.78) were good in the derivation cohort, and similar in the external validation cohort (complete cases n = 372, c-statistic 0.68 [95% CI 0.61-0.74]). The validation cohort included 644 patients between January 2013 and August 2015. Median age was 36 years, 48.9% were female, and median CD4 count at admission was 61 (IQR 21-145). OR for mortality was 5.3 (95% CI 2.2-9.5) for high compared to low-risk patients (complete cases n = 372, p < 0.001). The score also predicted patients at higher risk of death both pre- and post-discharge. A simplified score (any 3 or more of the predictors) performed equally well. The main limitations of the scores were their imperfect accuracy, the need for access to urine LAM testing, modest study size, and not measuring all potential predictors of mortality (e.g., tuberculosis drug resistance).ConclusionsThis risk score is capable of identifying patients who could benefit from enhanced clinical care, follow-up, and/or adjunctive interventions, although further prospective validation studies are necessary. Given the scale of HIV/TB morbidity and mortality in African hospitals, better prognostic tools along with interventions could contribute towards global targets to reduce tuberculosis mortality.

There are limited data about the epidemiology and treatment-related outcomes associated with capreomycin resistance in patients with XDR-TB. Capreomycin achieves high serum concentrations relative to MIC but whether capreomycin has therapeutic benefit despite microbiological resistance remains unclear.We reviewed the susceptibility profiles and outcomes associated with capreomycin usage in patients diagnosed with XDR-TB between August 2002 and October 2012 in two provinces of South Africa. Patients whose isolates were genotypically tested for capreomycin resistance were included in the analysis.Of 178 XDR-TB patients 41% were HIV-infected. 87% (154/178) isolates contained a capreomycin resistance-conferring mutation [80% (143/178) rrs A1401G and 6% (11/178) were heteroresistant (containing both the rrs A1401G mutation and wild-type sequences)]. Previous MDR-TB treatment, prior usage of kanamycin, or strain type was not associated with capreomycin resistance. 92% (163/178) of XDR-TB patients were empirically treated with capreomycin. Capreomycin resistance decreased the odds of sputum culture conversion. In capreomycin sensitive and resistant persons combined weight at diagnosis was the only independent predictor for survival (p=

Measures of bacillary load in patients with tuberculosis (TB) may be useful for predicting and monitoring response to treatment. The relationship between quantitative T-cell responses and mycobacterial load remains unclear. We hypothesised that, in a HIV-prevalent high burden setting, the magnitude of mycobacterial antigen-specific and non-specific T-cell IFN-γ responses would correlate with (a) bacterial load and (b) culture conversion in patients undergoing treatment.We compared baseline (n = 147), 2 (n = 35) and 6 month (n = 13) purified-protein-derivative (PPD) and RD1-specific (TSPOT.TB and QFT-GIT) blood RD1-specific (TSPOT.TB; QFT-GIT) responses with associates of sputum bacillary load in patients with culture-confirmed TB in Cape Town, South Africa.IFN-γ responses were not associated with liquid culture time-to-positivity, smear-grade, Xpert MTB/RIF-generated cycle threshold values or the presence of cavities on the chest radiograph in patients with culture-confirmed TB and irrespective of HIV-status. 2-month IGRA conversion rates (positive-to-negative) were negligible [