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Porphyria cutanea tarda (PCT) is the most common type of porphyria, presenting in middle-aged patients with a photodistributed vesiculobullous eruption, milia, and scars. Porphyria cutanea tarda occurs in relation to inhibition of uroporphyrinogen decarboxylase, a key enzyme in the heme biosynthesis pathway. A number of genetic and acquired factors increase susceptibility to PCT by reducing uroporphyrinogen decarboxylase activity. A handful of other vesiculobullous conditions may mimic PCT both clinically and histologically; therefore, both skin biopsy and laboratory evaluation are helpful in confirming the diagnosis. We report a case of PCT in the setting of cigarette usage and untreated hepatitis C infection.

A number of proposed explanations to observed phenomena predict new physics that will be directly observable at the LHC. Each new theory is manifested in the experiments as an experimental signature that sets it apart from the many well understood Standard Model processes. Presented here is a summary of a selection of such searches performed using 8 TeV center of mass energy data produced by the LHC and collected with the ATLAS detector. As no significant deviations from the standard model are observed in any search channel presented here, the results are interpreted in terms of constraints on new physics in a number of scenarios including dark matter, sequential standard model extensions, and model independent interpretations depending on the given search channel.

Tuberculosis (TB) is the leading infectious disease cause of death worldwide. In recent years, stringent measures to contain the spread of SARS-CoV-2 have led to considerable disruptions of healthcare services for TB in many countries. The extent to which these measures have affected TB testing, treatment initiation and outcomes has not been comprehensively assessed. We aimed to estimate TB healthcare service disruptions occurring during the COVID-19 pandemic in Brazil, India, and South Africa. We obtained country-level TB programme and laboratory data and used autoregressive integrated moving average (ARIMA) time-series models to estimate healthcare service disruptions with respect to TB testing, treatment initiation, and treatment outcomes. We quantified disruptions as the percentage difference between TB indicator data observed during the COVID-19 pandemic compared with values for a hypothetical no-COVID scenario, predicted through forecasting of trends during a three-year pre-pandemic period. Annual estimates for 2020-2022 were derived from aggregated monthly data. We estimated that in 2020, the number of bacteriological tests conducted for TB diagnosis was 24.3% (95% uncertainty interval: 8.4%;36.6%) lower in Brazil, 27.8% (19.8;3 4.8%) lower in India, and 32.0% (28.9%;34.9%) lower in South Africa compared with values predicted for the no-COVID scenario. TB treatment initiations were 17.4% (13.9%;20.6%) lower than predicted in Brazil, 43.3% (39.8%;46.4%) in India, and 27.0% (15.2%;36.3%) in South Africa. Reductions in 2021 were less severe compared with 2020. The percentage deaths during TB treatment were 13.7% (8.1%; 19.7%) higher than predicted in Brazil, 1.7% (-8.9%;14.0%) in India and 21.8% (7.4%;39.2%) in South Africa. Our analysis suggests considerable disruptions of TB healthcare services occurred during the early phase of the COVID-19 pandemic in Brazil, India, and South Africa, with at least partial recovery in the following years. Sustained efforts to mitigate the detrimental impact of COVID-19 on TB healthcare services are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 de Villiers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: None disclosed.

Background: High HIV viral loads (VL) are associated with increased morbidity, mortality, and on-going transmission. HIV controllers maintain low VLs in the absence of antiretroviral therapy (ART). We previously used a massively multiplexed antibody profiling assay (VirScan) to compare antibody profiles in HIV controllers and persons living with HIV (PWH) who were virally suppressed on ART. In this report, we used VirScan to evaluate whether antibody reactivity to specific HIV targets and broad reactivity across the HIV genome was associated with VL and controller status 1-2 years after infection., Methods: Samples were obtained from participants who acquired HIV infection in a community-randomized trial in Africa that evaluated an integrated strategy for HIV prevention (HPTN 071 PopART). Controller status was determined using VL and antiretroviral (ARV) drug data obtained at the seroconversion visit and 1 year later. Viremic controllers had VLs <2,000 copies/mL at both visits; non-controllers had VLs >2,000 copies/mL at both visits. Both groups had no ARV drugs detected at either visit. VirScan testing was performed at the second HIV-positive visit (1-2 years after HIV infection)., Results: The study cohort included 13 viremic controllers and 64 non-controllers. We identified ten clusters of homologous peptides that had high levels of antibody reactivity (three in gag, three in env, two in integrase, one in protease, and one in vpu). Reactivity to 43 peptides (eight unique epitopes) in six of these clusters was associated with lower VL; reactivity to six of the eight epitopes was associated with HIV controller status. Higher aggregate antibody reactivity across the eight epitopes (more epitopes targeted, higher mean reactivity across all epitopes) and across the HIV genome was also associated with lower VL and controller status., Conclusions: We identified HIV antibody targets associated with lower VL and HIV controller status 1-2 years after infection. Robust aggregate responses to these targets and broad antibody reactivity across the HIV genome were also associated with lower VL and controller status. These findings provide novel insights into the relationship between humoral immunity and viral containment that could help inform the design of antibody-based approaches for reducing HIV VL., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: H.B.L. is an inventor on an issued patent (US20160320406A) filed by Brigham and Women’s Hospital that covers the use of the VirScan technology, is a founder of Infinity Bio, Portal Bioscience and Alchemab, and is an advisor to TScan Therapeutics., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Coronavirus disease (COVID-19) negatively impacted tuberculosis (TB) programs which were already struggling to meet End-TB targets globally. We aimed to quantify and compare diagnosis, treatment initiation, treatment success, and losses along this TB care cascade for drug-susceptible TB in Cape Town, South Africa, prior to and during COVID-19., Methods: This observational study used routine TB data within two predefined cohorts: pre-COVID-19 (1 October 2018-30 September 2019) and during-COVID-19 (1 April 2020-31 March 2021). The numbers of people diagnosed, treated for TB and successfully treated were received from the Western Cape Provincial Health Data Centre. Pre and post treatment loss to follow up and cascade success rates (proportion of individuals diagnosed with an outcome of treatment success) were calculated and compared across cohorts, disaggregated by sex, age, HIV status, TB treatment history and mode of diagnosis., Results: There were 27,481 and 19,800 individuals diagnosed with drug-susceptible TB in the pre- and during-COVID-19 cohorts respectively, a relative reduction of 28% (95% CI [27.4% - 28.5%]). Initial loss to follow up increased from 13.4% to 15.2% (p<0.001), while post treatment loss increased from 25.2% to 26.1% (p < 0.033). The overall cascade success rate dropped by 2.1%, from 64.8% to 62.7% (p< 0.001). Pre- and during-COVID-19 cascade success rates were negatively associated with living with HIV and having recurrent TB., Conclusions: An already poorly performing TB program in Cape Town was negatively impacted by the COVID-19 pandemic. There was a substantial reduction in the number of individuals diagnosed with drug-susceptible. Increases in pre-and post-treatment losses resulted in a decline in TB cascade success rates. Strengthened implementation of TB recovery plans is vital, as health services now face an even greater gap between achievements and targets and will need to become more resilient to possible future public health disruptions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jennings et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.

Background: Tuberculosis (TB) remains a leading cause of mortality among women of childbearing age and a significant contributor to maternal mortality. Pregnant women with TB are at high risk of adverse pregnancy outcomes. This study aimed to determine risk factors for an adverse pregnancy outcome among pregnant women diagnosed with TB., Methods: Using TB programmatic data, this retrospective cohort analysis included all women who were routinely diagnosed with TB in the public sector between October 2018 and March 2020 in two health subdistricts of Cape Town, and who were documented to be pregnant during their TB episode. Adverse pregnancy outcome was defined as either a live birth of an infant weighing <2500 g and/or with a gestation period <37 weeks or as stillbirth, miscarriage, termination of pregnancy, maternal or early neonatal death. Demographics, TB and pregnancy characteristics were described by HIV status. Logistic regression was used to determine risk factors for adverse pregnancy outcome., Results: Of 248 pregnant women, half (52%) were living with HIV; all were on antiretroviral therapy at the time of their TB diagnosis. Pregnancy outcomes were documented in 215 (87%) women, of whom 74 (34%) had an adverse pregnancy outcome. Being older (35-44 years vs 25-34 years (adjusted OR (aOR): 3.99; 95% CI: 1.37 to 11.57), living with HIV (aOR: 2.72; 95% CI: 0.99 to 4.63), having an unfavourable TB outcome (aOR: 2.29; 95% CI: 1.03 to 5.08) and having presented to antenatal services ≤1 month prior to delivery (aOR: 10.57; 95% CI: 4.01 to 27.89) were associated with higher odds of an adverse pregnancy outcome., Conclusions: Pregnancy outcomes among women with TB were poor, irrespective of HIV status. Pregnant women with TB are a complex population who need additional support prior to, during and after TB treatment to improve TB treatment and pregnancy outcomes. Pregnancy status should be considered for inclusion in TB registries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Mucormycosis, also known as black fungus, is a rare but aggressive fungal disease with high morbidity and mortality rates that tends to affect patients who are severely immunocompromised. Early recognition of the infection and prompt intervention is critical for treatment success. In recent years the coronavirus disease of 2019 (COVID-19) pandemic has resulted in a surge in the number of cases of mucormycosis. This study aims to report an unfortunate event involving an immunocompromised elderly man with mucormycosis of the foot who died as a result of sepsis caused by COVID-19. It is important to have a high clinical suspicion for mucormycosis when a clinical lesion develops, and to appropriately perform biopsy the lesion in question, particularly in the context of COVID-19. Raising awareness of COVID-19-associated mucormycosis may allow for early detection of the disease, thus enabling the initiation of rapid treatment, ultimately saving lives.

Every person diagnosed with tuberculosis (TB) needs to initiate treatment. The World Health Organization estimated that 61% of people who developed TB in 2021 were included in a TB treatment registration system. Initial loss to follow-up (ILTFU) is the loss of persons to care between diagnosis and treatment initiation/registration. LINKEDin, a quasi-experimental study, evaluated the effect of 2 interventions (hospital recording and an alert-and-response patient management intervention) in 6 subdistricts across 3 high-TB burden provinces of South Africa. Using integrated electronic reports, we identified all persons diagnosed with TB (Xpert MTB/RIF positive) in the hospital and at primary health care facilities. We prospectively determined linkage to care at 30 days after TB diagnosis. We calculated the risk of ILTFU during the baseline and intervention periods and the relative risk reduction in ILTFU between these periods. We found a relative reduction in ILTFU of 42.4% (95% CI, 28.5%-53.7%) in KwaZulu Natal (KZN) and 22.3% (95% CI, 13.3%-30.4%) in the Western Cape (WC), with no significant change in Gauteng. In KZN and the WC, the relative reduction in ILTFU appeared greater in subdistricts where the alert-and-response patient management intervention was implemented (KZN: 49.3%; 95% CI, 32.4%-62%; vs 32.2%; 95% CI, 5.4%-51.4%; and WC: 34.2%; 95% CI, 20.9%-45.3%; vs 13.4%; 95% CI, 0.7%-24.4%). We reported a notable reduction in ILTFU in 2 provinces using existing routine health service data and applying a simple intervention to trace and recall those not linked to care. TB programs need to consider ILTFU a priority and develop interventions specific to their context to ensure improved linkage to care., Competing Interests: Potential conflicts of interest. All authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Brazil, India and South Africa are among the top 30 high TB burden countries globally and experienced high rates of SARS-CoV-2 infection and mortality. The COVID-19 response in each country was unprecedented and complex, informed by distinct political, economic, social and health systems contexts. While COVID-19 responses have set back TB control efforts, they also hold lessons to inform future TB programming and services., Methods: This was a qualitative exploratory study involving interviews with TB stakeholders ( n = 76) in Brazil, India and South Africa 2 years into the COVID-19 pandemic. Interview transcripts were analysed using an inductive coding strategy., Results: Political will - whether national or subnational - enabled implementation of widespread prevention measures during the COVID-19 response in each country and stimulated mobile and telehealth service delivery innovations. Participants in all three countries emphasised the importance of mobilising and engaging communities in public health responses and noted limited health education and information as barriers to implementing TB control efforts at the community level., Conclusions: Building political will and social mobilisation must become more central to TB programming. COVID-19 has shown this is possible. A similar level of investment and collaborative effort, if not greater, as that seen during the COVID-19 pandemic is needed for TB through multi-sectoral partnerships., Competing Interests: Conflicts of interest: none declared., (© 2023 The Union.)

Introduction: HIV controllers have low viral loads (VL) without antiretroviral treatment (ART). We evaluated viraemic control in a community-randomized trial conducted in Zambia and South Africa that evaluated the impact of a combination prevention intervention on HIV incidence (HPTN 071 [PopART]; 2013-2018)., Methods: VL and antiretroviral (ARV) drug testing were performed using plasma samples collected 2 years after enrolment for 4072 participants who were HIV positive at the start of the study intervention. ARV drug use was assessed using a qualitative laboratory assay that detects 22 ARV drugs in five drug classes. Participants were classified as non-controllers if they had a VL ≥2000 copies/ml with no ARV drugs detected at this visit. Additional VL and ARV drug testing was performed at a second annual study visit to confirm controller status. Participants were classified as controllers if they had VLs <2000 with no ARV drugs detected at both visits. Non-controllers who had ARV drugs detected at either visit were excluded from the analysis to minimize potential confounders associated with ARV drug access and uptake., Results: The final cohort included 126 viraemic controllers and 766 non-controllers who had no ARV drugs detected. The prevalence of controllers among the 4072 persons assessed was 3.1% (95% confidence interval [CI]: 2.6%, 3.6%). This should be considered a minimum estimate, since high rates of ARV drug use in the parent study limited the ability to identify controllers. Among the 892 participants in the final cohort, controller status was associated with biological sex (female > male, p = 0.027). There was no significant association between controller status and age, study country or herpes simplex virus type 2 (HSV-2) status at study enrolment., Conclusions: To our knowledge, this report presents the first large-scale, population-level study evaluating the prevalence of viraemic control and associated factors in Africa. A key advantage of this study was that a biomedical assessment was used to assess ARV drug use (vs. self-reported data). This study identified a large cohort of HIV controllers and non-controllers not taking ARV drugs, providing a unique repository of longitudinal samples for additional research. This cohort may be useful for further studies investigating the mechanisms of virologic control., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: The global COVID-19 pandemic has reversed many of the hard-won gains made in TB programmes and the associated reduction in the number of TB deaths, case notifications and incidence over the last three decades. Modelling estimates show that the impact will be lasting. There are global calls to recover the shortfalls along the TB care cascade that have resulted from COVID-19, with the recognition that the COVID-19 response holds lessons to inform more robust and comprehensive TB programmes and services., Objective: To explore lessons from response measures to the COVID-19 pandemic in two high TB burden South African provinces., Design: This was an exploratory qualitative study. We conducted interviews with TB programme stakeholders (managers and facility-level staff: n = 35) between February and June 2022., Results: We identified eight facilitators of the COVID-19 response, including political will, rapid policy development, multi-sectoral collaboration, patient-centred models of care delivery, community engagement, mHealth and telehealth technologies, rigorous contact tracing and widespread mask wearing. Political will was singled out as a critical driver of the response., Conclusion: Leveraging COVID-19 inspired collaborations, technologies and avenues for health service delivery is an opportunity to maximise benefits for the TB programme. Reinvestment in national TB programmes and political prioritisation of TB are critical., (© 2023 The Union.)

Background: High HIV viral load (VL) is associated with increased transmission risk and faster disease progression. HIV controllers achieve viral suppression without antiretroviral (ARV) treatment. We evaluated viremic control in a community-randomized trial with >48,000 participants., Methods: A massively multiplexed antibody profiling system, VirScan, was used to quantify pre- and post-infection antibody reactivity to HIV peptides in 664 samples from 429 participants (13 controllers, 135 viremic non-controllers, 64 other non-controllers, 217 uninfected persons). Controllers had VLs <2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit and one year later. Viremic non-controllers had VLs 2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit. Other non-controllers had either ARV drugs detected at the first HIV-positive visit (n=47) or VLs <2,000 copies/mL with no ARV drugs detected at only one HIV-positive visit (n=17)., Results: We identified pre-infection HIV antibody reactivities that correlated with post-infection VL. Pre-infection reactivity to an epitope in the HR2 domain of gp41 was associated with controller status and lower VL. Pre-infection reactivity to an epitope in the C2 domain of gp120 was associated with non-controller status and higher VL. Different patterns of antibody reactivity were observed over time for these two epitopes., Conclusion: These studies suggest that pre-infection HIV antibodies are associated with controller status and modulation of HIV VL. These findings may inform research on antibody-based interventions for HIV treatment., Competing Interests: Author HBL is an inventor on an issued patent US20160320406A filed by Brigham and Women’s Hospital that covers the use of the VirScan technology, is a founder of ImmuneID, Portal Bioscience and Alchemab, and is an advisor to TScan Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Grant-McAuley, Morgenlander, Hudelson, Thakar, Piwowar-Manning, Clarke, Breaud, Blankson, Wilson, Ayles, Bock, Moore, Kosloff, Shanaube, Meehan, van Deventer, Fidler, Hayes, Ruczinski, Kammers, Laeyendecker, Larman and Eshleman.)

Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.

Background: Tuberculosis (TB)-associated mortality in South Africa remains high. This review aimed to systematically assess risk factors associated with death during TB treatment in South African patients., Methods: We conducted a systematic review of TB research articles published between 2010 and 2018. We searched BioMed Central (BMC), PubMed®, EBSCOhost, Cochrane, and SCOPUS for publications between January 2010 and December 2018. Searches were conducted between August 2019 and October 2019. We included randomised control trials (RCTs), case control, cross sectional, retrospective, and prospective cohort studies where TB mortality was a primary endpoint and effect measure estimates were provided for risk factors for TB mortality during TB treatment. Due to heterogeneity in effect measures and risk factors evaluated, a formal meta-analysis of risk factors for TB mortality was not appropriate. A random effects meta-analysis was used to estimate case fatality ratios (CFRs) for all studies and for specific subgroups so that these could be compared. Quality assessments were performed using the Newcastle-Ottawa scale or the Cochrane Risk of Bias Tool., Results: We identified 1995 titles for screening, 24 publications met our inclusion criteria (one cross-sectional study, 2 RCTs, and 21 cohort studies). Twenty-two studies reported on adults (n = 12561) and two were restricted to children < 15 years of age (n = 696). The CFR estimated for all studies was 26.4% (CI 18.1-34.7, n = 13257 ); 37.5% (CI 24.8-50.3, n = 5149) for drug-resistant (DR) TB; 12.5% (CI 1.1-23.9, n = 1935) for drug-susceptible (DS) TB; 15.6% (CI 8.1-23.2, n = 6173) for studies in which drug susceptibility was mixed or not specified; 21.3% (CI 15.3-27.3, n = 7375) for people living with HIV/AIDS (PLHIV); 19.2% (CI 7.7-30.7, n = 1691) in HIV-negative TB patients; and 6.8% (CI 4.9-8.7, n = 696) in paediatric studies. The main risk factors associated with TB mortality were HIV infection, prior TB treatment, DR-TB, and lower body weight at TB diagnosis., Conclusions: In South Africa, overall mortality during TB treatment remains high, people with DR-TB have an elevated risk of mortality during TB treatment and interventions to mitigate high mortality are needed. In addition, better prospective data on TB mortality are needed, especially amongst vulnerable sub-populations including young children, adolescents, pregnant women, and people with co-morbidities other than HIV. Limitations included a lack of prospective studies and RCTs and a high degree of heterogeneity in risk factors and comparator variables., Systematic Review Registration: The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42018108622. This study was funded by the Bill and Melinda Gates Foundation (Investment ID OPP1173131) via the South African TB Think Tank., (© 2023. The Author(s).)

Although drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with antiretrovirals, there are no published reports of bictegravir-induced DRESS. Bictegravir is recommended as first-line treatment for patients with human immunodeficiency virus (HIV). Recognition of DRESS, its skin manifestations, and potential complications is vital for appropriate care and management of acute HIV., Competing Interests: Potential conflicts of interest. MAD holds individual stocks in Abbvie, Abiomed Inc., Amgen Inc, Becton Dickinson, BioMarin Pharmaceutical Inc., Bristol-Myers Squibb, CVS Health Corporation, Gilead Sciences, Inc., Henry Schein, Inc., Hologic, Jazz Pharmaceuticals, Merck & Co., Inc., Quest Diagnostics, Vertex Pharmaceuticals, and West Pharmaceuticals. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Tuberculosis (TB) is a leading cause of death globally. In 2015, the World Health Organization hailed patient-centred care as the first of three pillars in the End TB strategy. Few examples of how to deliver patient-centred care in TB programmes exist in practice; TB control efforts have historically prioritised health systems structures and processes, with little consideration for the experiences of people affected by TB. We aimed to describe how patient-centred care interventions have been implemented for TB, highlighting gaps and opportunities. We conducted a scoping review of the published peer-reviewed research literature and grey literature on patient-centred TB care interventions between January 2005 and March 2020. We found limited information on implementing patient-centred care for TB programmes (13 research articles, 7 project reports, and 19 conference abstracts). Patient-centred TB care was implemented primarily as a means to improve adherence, reduce loss to follow-up, and improve treatment outcomes. Interventions focused on education and information for people affected by TB, and psychosocial, and socioeconomic support. Few patient-centred TB care interventions focused on screening, diagnosis, or treatment initiation. Patient-centred TB care has to go beyond programmatic improvements and requires recognition of the diverse needs of people affected by TB to provide holistic care in all aspects of TB prevention, care, and treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Myburgh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We investigated psychological distress in a South African childhood cancer survivor (CCS) cohort., Methods: Adult CCSs treated at Tygerberg Hospital, Cape Town, completed the Brief Symptom Inventory-18. Internal consistency was acceptable: Cronbach's alpha values were 0.91 (Global Severity Index (GSI)), 0.85 (depression), 0.83 (somatization), and 0.75 (anxiety). We compared results utilizing different case rules (GSI T scores of ≥50, ≥57, and ≥63) for the identification of psychological distress., Results: Forty CCSs (median age 24 years; median follow-up period 16 years) participated. Most (58%; 23 out of 40) completed school or tertiary education, were unmarried (90%; 36 out of 40), and unemployed (59.5%; 22 out of 37). The diagnoses included hematological malignancies (65%; 26 out of 40) and solid tumors (35%; 14 out of 40). The GSI T scores of ≥63, ≥57, and ≥50 identified 10% (four out of 40), 32.5% (13 out of 40), and 45% (18 out of 40) of survivors with psychological distress, respectively. Radiotherapy (odds ratio (OR) 4.6; p = .035), presence of ≥six late effects (OR 7.5; p = .026), and severe late effects (OR 6.6; p = .024) were significant risk factors (GSI T score ≥57). Follow-up period of 11-20 years (OR 7.3; p = .034) was significant for a GSI T score ≥50., Conclusion: This South African CCS cohort had higher levels of psychological distress utilizing the GSI T score ≥50 and ≥57 case rules than reported in the literature. Most were unmarried or unemployed. Significant contributing factors were radiotherapy, number and severity of late effects, and follow-up period. CCSs must be screened for psychological distress., (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Competing Interests: None disclosed.

Background: In South Africa, failure to link individuals diagnosed with TB to care remains an important gap in the TB care cascade. Compared to people diagnosed at primary healthcare (PHC) facilities, people diagnosed in hospitals are more likely to require additional support to be linked with PHC TB treatment services. We describe a patient interaction process to support linkage to TB care., Methods: We implemented a step-by-step early patient interaction process with 84 adults newly diagnosed with TB in one district hospital in Khayelitsha, Cape Town, South Africa (August 2020-March 2021). We confirmed patient contact details, provided TB and health information, shared information on accessing care at PHC facilities and answered patients' questions in their home language., Results: Most patients (54/84, 64%) provided updated telephone numbers, and 19/84 (23%) reported changes in their physical address. Patients welcomed practical and health information in their home language. The majority (74/84, 88%) were linked to care after hospital discharge., Conclusions: A simple early patient interaction process implemented as part of routine care is a feasible strategy to facilitate early TB treatment initiation and registration., Competing Interests: Conflicts of interest: none declared.

Together, SARS-CoV-2 and M. tuberculosis have killed approximately 5.7 million people worldwide over the past 2 years. The COVID-19 pandemic, and the non-pharmaceutical interventions to mitigate COVID-19 transmission (including social distancing regulations, partial lockdowns and quarantines), have disrupted healthcare services and led to a reallocation of resources to COVID-19 care. There has also been a tragic loss of healthcare workers who succumbed to the disease. This has had consequences for TB services, and the fear of contracting COVID-19 may also have contributed to reduced access to TB services. Altogether, this is projected to have resulted in a 5-year setback in terms of mortality from TB and a 9-year setback in terms of TB detection. In addition, past and present TB disease has been reported to increase both COVID-19 fatality and incidence. Similarly, COVID-19 may adversely affect TB outcomes. From a more positive perspective, the pandemic has also created opportunities to improve TB care. In this review, we highlight similarities and differences between these two infectious diseases, describe gaps in our knowledge and discuss solutions and priorities for future research.

Competing Interests: None disclosed.

OBJECTIVE: To investigate the uptake and usage of a WhatsApp-based interactive communication strategy to avert pre-diagnosis loss to follow-up (LTFU) from TB care in a high-incidence setting. METHODS: We enrolled adults (≥18 years) who underwent routine sputum TB testing in two primary healthcare clinics in Khayelitsha, Cape Town, South Africa. The intervention consisted of structured WhatsApp-based reminders (prompts) sent prior to a routine clinic appointment scheduled 2-3 days after the diagnostic visit. Pre-diagnosis LTFU was defined as failure to return for the scheduled appointment and within 10 days. RESULTS: We approached 332 adults with presumptive TB, of whom 103 (31%) were successfully enrolled; 213 (64%) did not own a WhatsApp-compatible phone. Of 103 participants, 74 (72%) actively responded to WhatsApp prompts; 69 (67%) opted to include a close contact in group communication to co-receive reminders. Pre-diagnosis LTFU was low overall ( n = 7, 6.8%) and was not associated with failure to respond to WhatsApp prompts. CONCLUSION: In this high-incidence setting, enrolment in a WhatsApp-based communication intervention among adults with presumptive TB was low, mainly due to low availability of WhatsApp-compatible phones. Among participants, we observed high message response rates and low LTFU, suggesting potential for interactive messaging services to support pre-diagnosis TB care.

Background: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge., Methods: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review., Results: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases., Conclusions: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reported barriers to HIV testing over the last 15 years have remained consistent, despite improved service offerings. We aimed to probe deeper by exploring how people who have never tested construct HIV testing in their talk. We used this to suggest underlying psychosocial barriers to testing even when there is high availability. We enrolled 14 participants who reported that they had never tested for HIV and conducted individual, open-ended interviews. The data were organised thematically with theory-generative interpretations informed by discourse analysis. Reasons for not testing reported reflect similar barriers identified in previous research. Deeper probing identified three discursive processes by which participants explained why they had never tested for HIV, suggesting that the way participants used 'reasons' in their talk is an indicator that the participants were repeating 'tropes'. While aware of HIV testing facilities, participants still chose not to test. Influences on the choice to test or not were positioned as outside of the person's control. These findings suggest that there are deeper reasons why some people have not tested and that these will not be resolved through merely increasing accessibility to testing services. We recommend increased consideration of the psychosocial implications of testing in service delivery.

Background: Delayed linkage to tuberculosis (TB) treatment leads to poor patient outcomes and increased onward transmission. Between 12% and 25% of people diagnosed with TB are never linked to a primary health care facility for continued care. The TB health program is for creating processes that promote and facilitates easy access to care. We explored how TB patients experience TB services and how this influenced their choices around linkage to TB care and treatment., Methods: We enrolled 20 participants routinely diagnosed with TB in hospital or at primary health care facilities (PHC) in a high TB/HIV burdened peri-urban community in South Africa. Using the Western Cape Provincial Health Data centre (PHDC) which consolidates person-level clinical data, we used dates of diagnosis and treatment initiation to select participants who had been linked (immediately, after a delay, or never). Between June 2019 and January 2020, we facilitated in-depth discussions to explore both the participants' experience of their TB diagnosis and their journey around linking to TB care at a primary health care facility. We analysed the data using case descriptions., Results: Twelve of twenty (12/20) participants interviewed who experienced a delay linking were diagnosed at the hospital. Participants who experienced delays in linking or never linked explained this as a result of lack of information and support from health care providers. Unpleasant previous TB treatment episodes made it difficult to 'face' TB again and being uncertain of their TB diagnosis. In contrast, participants said the main motivator for linking was a personal will to get better., Conclusion: The health care system, especially in hospitals, should focus on strengthening patient-centred care. Communication and clear messaging on TB processes is key, to prepare patients in transitioning from a hospital setting to PHC facilities for continuation of care. This should not just include a thorough explanation of their TB diagnosis but ensure that patients understand treatment processes. Former TB patients may require additional counselling and support to re-engage in care., Competing Interests: The authors have declared that no competing interests exist.

In South Africa, low tuberculosis (TB) treatment coverage and high TB case fatality remain important challenges. Following TB diagnosis, patients must link with a primary health care (PHC) facility for initiation or continuation of antituberculosis treatment and TB registration. We aimed to evaluate mortality among TB patients who did not link to a TB treatment facility for TB treatment within 30 days of their TB diagnosis, i.e. who were "initial loss to follow-up (ILTFU)" in Cape Town, South Africa. We prospectively included all patients with a routine laboratory or clinical diagnosis of TB made at PHC or hospital level in Khayelitsha and Tygerberg sub-districts in Cape Town, using routine TB data from an integrated provincial health data centre between October 2018 and March 2020. Overall, 74% (10,208/13,736) of TB patients were diagnosed at PHC facilities and ILTFU was 20.0% (2,742/13,736). Of ILTFU patients, 17.1% (468/2,742) died, with 69.7% (326/468) of deaths occurring within 30 days of diagnosis. Most ILTFU deaths (85.5%; 400/468) occurred in patients diagnosed in hospital. Multivariable logistic regression identified increasing age, HIV positive status, and hospital-based TB diagnosis (higher in the absence of TB treatment initiation and being ILTFU) as predictors of mortality. Although hospitals account for a modest proportion of diagnosed TB patients they have high TB-associated mortality. A hospital-based TB diagnosis is a critical opportunity to identify those at high risk of early and overall mortality. Interventions to diagnose TB before hospital admission, improve linkage to TB treatment following diagnosis, and reduce mortality in hospital-diagnosed TB patients should be prioritised., Competing Interests: The authors have declared that no competing interests exist.

Background: Hyaluronic acid filler reactions have been increasingly observed in recent years. Our study investigates whether the increased number of filler reactions observed since 2014 is associated with a specific histopathologic inflammatory pattern and type of filler., Methods: The institution's dermatopathology electronic database was retrospectively searched for histopathologic reactions to hyaluronic acid from January 2014 to December 2019. The age, sex, type of filler, procedure, location, and histopathologic patterns were recorded., Results: From 2014 to 2019, there were 15 cases of granulomatous reactions to hyaluronic acid filler. In 10 of these cases, there was a characteristic inflammatory pattern characterized by tightly cuffed palisades of histiocytes with varying numbers of eosinophils. Of the 11 cases in which the type of filler was known, all used Vycross technology, a novel manufacturing process in the production of hyaluronic acid filler., Conclusion: A characteristic histopathologic pattern of discrete foci of tightly cuffed palisaded granulomas with eosinophils is associated with fillers manufactured using Vycross technology., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Tuberculosis (TB) is a major public health concern in South Africa and TB-related mortality remains unacceptably high. Numerous clinical studies have examined the direct causes of TB-related mortality, but its wider, systemic drivers are less well understood. Applying systems thinking, we aimed to identify factors underlying TB mortality in South Africa and describe their relationships. At a meeting organised by the 'Optimising TB Treatment Outcomes' task team of the National TB Think Tank, we drew on the wide expertise of attendees to identify factors underlying TB mortality in South Africa. We generated a causal loop diagram to illustrate how these factors relate to each other., Results: Meeting attendees identified nine key variables: three 'drivers' (adequacy & availability of tools, implementation of guidelines, and the burden of bureaucracy); three 'links' (integration of health services, integration of data systems, and utilisation of prevention strategies); and three 'outcomes' (accessibility of services, patient empowerment, and socio-economic status). Through the development and refinement of the causal loop diagram, additional explanatory and linking variables were added and three important reinforcing loops identified. Loop 1, 'Leadership and management for outcomes' illustrated that poor leadership led to increased bureaucracy and reduced the accessibility of TB services, which increased TB-related mortality and reinforced poor leadership through patient empowerment. Loop 2, 'Prevention and structural determinants' describes the complex reinforcing loop between socio-economic status, patient empowerment, the poor uptake of TB and HIV prevention strategies and increasing TB mortality. Loop 3, 'System capacity' describes how fragmented leadership and limited resources compromise the workforce and the performance and accessibility of TB services, and how this negatively affects the demand for higher levels of stewardship., Conclusions: Strengthening leadership, reducing bureaucracy, improving integration across all levels of the system, increasing health care worker support, and using windows of opportunity to target points of leverage within the South African health system are needed to both strengthen the system and reduce TB mortality. Further refinement of this model may allow for the identification of additional areas of intervention.

Background/objective: Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity., Methods: In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded., Results: We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas., Conclusion: We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color., (© 2020 Wiley Periodicals LLC.)

Infectious panniculitis from hematogenous spread is uncommon and usually occurs in immunocompromised patients. Dissemination of gram-positive organisms to the subcutaneous tissue is rare with only several reports of disseminated panniculitis caused by Streptococcal species. We report a case of an immunocompetent 2-year-old boy presenting with diffuse neutrophilic panniculitis arising from methicillin-resistant Staphylococcus aureus septicemia. This case represents a highly atypical manifestation of severe MRSA infection and serves as a reminder to consider MRSA as a cause of disseminated neutrophilic panniculitis, particularly in high-risk populations., (© 2020 Wiley Periodicals, Inc.)

Background: Mobile HIV testing services (HTS) are effective at reaching undiagnosed people living with HIV. However, linkage to HIV care from mobile HTS is often poor, ranging from 10 to 60%. Point-of-care (POC) CD4 testing has shown to increase retention in health facilities, but little evidence exists about their use in mobile HTS. This study assessed the feasibility of POC CD4 test implementation and investigated linkage to HIV care among clients accepting a POC test at community-based mobile HTS., Methods: This retrospective study used routinely collected data from clients who utilized community-based mobile HTS in the City of Cape Town Metropolitan district, South Africa between December 2014 and September 2016. A POC CD4 test was offered to all clients with an HIV positive diagnosis during this period, and a CD4 cell count was provided to clients accepting a POC CD4 test. Random effects logistic regression was used to assess factors associated with POC CD4 test uptake and self-reported linkage to care among clients accepting a POC test. Models were adjusted for sex, age, previous HIV test done, tuberculosis status and year of HIV diagnosis., Results: One thousand three hundred twenty-five of Thirty-nine thousand seven hundred ninety clients utilizing mobile HTS tested HIV positive (3%). 51% (679/1325) accepted a POC test. The age group with the highest proportion accepting a POC test was 50+ years (60%). Females were less likely to accept a POC test than males (odds ratio = 0.7, 95%CI = 0.6-0.8). Median CD4 count was 429 cells/μl (interquartile range = 290-584). Among 679 clients who accepted a POC CD4 test, 491 (72%) linked to HIV care. CD4 cell count was not associated with linkage to care., Conclusion: Our findings suggest that mobile HTS can identify early HIV infection, and show that a high proportion of clients with a POC test result linked to care. Future research should assess factors associated with POC test acceptance and assess the impact of POC CD4 testing in comparison to alternative strategies to engage HIV positive people in care.

BACKGROUND: With the advent of digital microscopy, learning analytics can be leveraged to advance teaching of dermatopathology in dermatology residency. OBJECTIVE: To analyze the acquisition and decay of dermatopathology visual recognition skills and areas of diagnostic confusion amongst residents using learning metrics generated by a web-based learning tool. METHODS: This was a prospective, longitudinal study of dermatology residents who studied digital photomicrographs of 18 routine diagnostic entities using an online software platform. Residents at different years of training were given 60 minutes to complete assessments on three occasions (initial test with follow-ups at one and three months). RESULTS: 4,938 responses were analyzed. Accuracy and time to diagnosis improved within each assessment and between the first and second assessments. First year residents showed knowledge decay when tested at three months (67% vs 64%; P=0.002) while third year residents retained knowledge and continued to improve upon their accuracy after three months (83% to 91%, <0.001). Learning analytics highlighted diagnostically challenging cases for residents that contradicted experts’ predictions (R=0.48). CONCLUSIONS: The use of learning analytics and interactive digital platforms enhances dermatopathology curriculum development by identifying challenging diagnostic entities, assessing mastery of subject material, and optimizing review schedules. J Drugs Dermatol. 2019;18(12):1231-1236.

Introduction: Differentiated models of care that include referral of antiretroviral treatment (ART) clients to adherence clubs are an important strategy to help clinics manage increased number of clients living with HIV in resource-constrained settings. This study reported on (i) clinical outcomes among ART clients attending community-based adherence clubs and (ii) experiences of adherence clubs and perceptions of factors key to successful adherence club implementation among clients and healthcare workers., Methods: A retrospective cohort analysis of routine data and a descriptive analysis of data collected through self-administered surveys completed by clients and healthcare workers were completed. Clients starting ART at the study clinic, between January 2014 and December 2015, were included in the cohort analysis and followed up until December 2016. The survey data were collected from August to September 2017. The primary outcome for the cohort analysis was a comparison of loss to follow-up (LTFU) between clients staying in clinic care and those referred to adherence clubs. Survey data reported on client experiences of and healthcare worker perceptions of adherence club care., Results: Cohort analysis reported on 465 participants, median baseline CD4 count 374 (IQR: 234 to 532) cells/μl and median follow-up time 20.7 (IQR 14.1 to 27.7) months. Overall, 202 (43.4%) participants were referred to an adherence club. LTFU was lower in those attending an adherence club (aHR =0.25, 95% CI: 0.11 to 0.56). This finding was confirmed on analysis restricted to those eligible for adherence club referral (aHR =0.28, 95% CI: 0.12 to 0.65). Factors highlighted as associated with successful adherence club implementation included: (i) referral of stable clients to the club, (ii) an ideal club size of ≥20 members, (iii) club services led by a counsellor (iv) using churches or community halls as venues (v) effective communication between all parties, and (vi) timely delivery of prepacked medication., Conclusions: This study showed good clinical outcomes, positive patient experiences and healthcare worker perceptions of the adherence club model. Factors associated with successful adherence club implementation, highlighted in this study, can be used to guide implementers in the scale-up of adherence club services across varied high-burden settings., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)