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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.

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.

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.