Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study.

BACKGROUND: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). METHODS: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. RESULTS: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels. CONCLUSION: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.

Masculinity and Suicide in Bangladesh.

Suicide is a serious but under-researched public health problem in Bangladesh. In light of this, we sought to explore the association between masculinities and suicide. We interviewed 20 family members/friends of men who died by suicide across 12 rural areas of the Jhenaidah district, Bangladesh. We found that male suicide was attributed to men's inability to fulfil hegemonic masculine demands such as financial provision and meeting the sexual needs of their spouses. Suicide was also linked to men's loss of self-respect and respect from others. Some participants mentioned that men committed suicide as an act of self-sacrifice, while others cited mental and physical illness. As a result of these findings, we propose that addressing socio-cultural and religious issues associated with men's troubles may help to prevent suicide. At the same time, changing the restrictive gender roles and masculinity-related ideals is also needed to counter the problem.

A dimorphic fungus causing disseminated infection in South Africa.

BACKGROUND: The genus emmonsia contains three species that are associated with human disease. Emmonsia crescens and Emmonsia parva are the agents that cause adiaspiromycosis, and one human case of Emmonsia pasteuriana infection has been described. We report a fungal pathogen within the genus emmonsia that is most closely related to E. pasteuriana in human immunodeficiency virus (HIV)-infected adults in South Africa. METHODS: Between July 2008 and July 2011, we conducted enhanced surveillance to identify the cause of systemic, dimorphic fungal infections in patients presenting to Groote Schuur Hospital and other hospitals affiliated with the University of Cape Town, Cape Town, South Africa. DNA sequencing was used to identify pathogenic fungi. RESULTS: A total of 24 cases of dimorphic fungal infection were diagnosed, 13 of which were caused by an emmonsia species. All 13 patients were HIV-infected, with a median CD4+ T-cell count of 16 cells per cubic millimeter (interquartile range, 10 to 44), and all had evidence of disseminated fungal disease. Three patients died soon after presentation, but the others had a good response to a variety of antifungal agents and antiretroviral therapy. Phylogenetic analysis of five genes (LSU, ITS1-2, and the genes encoding actin, ß-tubulin, and intein PRP8) revealed that this fungus belongs in the genus emmonsia and is most closely related to E. pasteuriana. CONCLUSIONS: The findings suggest that these isolates of an emmonsia species represent a new species of dimorphic fungus that is pathogenic to humans. The species appears to be an important cause of infections in Cape Town.

Race trouble: experiences of Black medical specialist trainees in South Africa.

BACKGROUND: This research aimed to identify and explore the experiences of Black registrars in their training in the Western Cape's academic hospitals in order to identify structures, practices, attitudes and ideologies that may promote or impede the advancement of Black doctors into specialist medicine. This is justified by the requirement for universities to work towards monitoring and evaluating efforts to create non-discriminatory and inclusive training environments. METHODS: This study employed qualitative research methods. Ten Black African medical specialists were interviewed about their training experiences in two university training hospitals in the Western Cape Province, South Africa. Interview data was collected using open-ended questions and coded and analysed using thematic and critical discursive analysis techniques. RESULTS: Four experiential themes emerged from the interview data, they included: 1) experiences of everyday racism during work hours, 2) the physical and psychological effects of tokenism and an increased need to perform, 3) institutional racism as a result of inconsistent and unclear methods of promotion and clinical competence building, and 4) an organisational culture that was experienced as having a race and gender bias. CONCLUSION: This is a pilot study and there are limits on the generalizability of the data due to the small sample. What is clear from our participants, though, is the strong experiential component of finding it challenging to be a Black trainee in a White-dominated profession. We are undertaking further research to explore the issues raised in more detail.

Clinical Characteristics, Diagnosis, Management, and Outcomes of Disseminated Emmonsiosis: A Retrospective Case Series.

BACKGROUND: We describe the geographic distribution, clinical characteristics, and management of patients with disease caused by Emmonsia sp., a novel dimorphic fungal pathogen recently described in South Africa. METHODS: We performed a multicenter, retrospective chart review of laboratory-confirmed cases of emmonsiosis diagnosed across South Africa from January 2008 through February 2015. RESULTS: Fifty-four patients were diagnosed in 5/9 provinces. Fifty-one patients (94%) were human immunodeficiency virus coinfected (median CD4 count 16 cells/µL [interquartile range, 6-40]). In 12 (24%) of these, antiretroviral therapy had been initiated in the preceding 2 months. All patients had disseminated disease, most commonly involving skin (n = 50/52, 96%) and lung (n = 42/48, 88%). Yeasts were visualized on histopathologic examination of skin (n = 34/37), respiratory tissue (n = 2/4), brain (n = 1/1), liver (n = 1/2), and bone marrow (n = 1/15). Emmonsia sp. was cultured from skin biopsy (n = 20/28), mycobacterial/fungal and aerobic blood culture (n = 15/25 and n = 9/37, respectively), bone marrow (n = 12/14), lung (n = 1/1), lymph node (n = 1/1), and brain (n = 1/1). Twenty-four of 34 patients (71%) treated with amphotericin B deoxycholate, 4/12 (33%) treated with a triazole alone, and none of 8 (0%) who received no antifungals survived. Twenty-six patients (48%) died, half undiagnosed. CONCLUSIONS: Disseminated emmonsiosis is more widespread in South Africa and carries a higher case fatality rate than previously appreciated. Cutaneous involvement is near universal, and skin biopsy can be used to diagnose the majority of patients.

Lack of cross-toxicity between isoniazid and ethionamide in severe cutaneous adverse drug reactions: a series of 25 consecutive confirmed cases.

BACKGROUND: Isoniazid and ethionamide are important first- and second-line anti-TB drugs (FLDs and SLDs), respectively. Ethionamide is a structural analogue of isoniazid and the two drugs share other similarities, including their metabolism, therapeutic targets, hepato-toxicity patterns and drug resistance. As a result, there has always been concern about possible cross-reactivity between them. METHODS: Among 69 patients with drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) to FLDs, FLDs were stopped and SLDs added when the skin and laboratory parameters had settled. This was followed by sequential and additive rechallenge with FLDs. We report 25 consecutive cases that developed confirmed cutaneous adverse drug reactions (CADRs) to isoniazid or ethionamide used as FLD and SLD, respectively. RESULTS: Sixty-nine participants who developed CADRs on FLDs were enrolled in the study. Twenty developed a rechallenge reaction to isoniazid and five reacted to ethionamide. Four of the 20 isoniazid cases were patch test positive, 3/20 were skin prick test positive and 13/20 reacted to oral rechallenge. All seven cases that were patch and skin prick test positive were associated with systemic reactions. Twenty of the 25 cases had DRESS and 5 had SJS/TEN. Twenty-three of the 25 cases with rechallenge reactions were HIV infected. Importantly, none of the cases that reacted to ethionamide during the rechallenge reacted to isoniazid and none who subsequently reacted to isoniazid reacted to ethionamide. CONCLUSIONS: Our findings strongly suggest that the risk of cross-reactivity of isoniazid and ethionamide in DRESS syndrome and SJS/TEN is low. These findings have implications for clinical management.

Why We Need to Change How We Talk About Infectious Disease.

This article builds a case for raising occupational consciousness by critically questioning ahistorical and apolitical uses of battle language, especially when referring to infectious diseases. Words such as invasion, colonization, and resistance are particularly ethically troubling, and this article considers why the social practices our language brings about matter in health care. Dynamic relationships among humans and microbes, as well as metaphor, are considered here in historical context and through the lens of Derrida's portmanteau hostipitality, which invites reconsideration of an infectious disease notion of host and how conceptions of hospitality have been institutionalized and commodified. This article argues that language used in infectious disease care settings should be informed by coexistence as a guiding value of clinical and ethical relevance.

Mentorship as an overlooked dimension of research capacity strengthening: how to embed value-driven practices in global health.

Mentorship in global health remains an overlooked dimension of research partnerships. Commitment to effective mentorship models requires value-driven approaches. This includes having an understanding of (1) what mentorship means across different cultural and hierarchical boundaries in the health research environment, and (2) addressing entrenched power asymmetries across different aspects including funding, leadership, data and outputs, and capacity strengthening. Existing guidance towards equity and sustainability fails to inform how to navigate complex relationships which hinder effective mentorship models. We focus this perspective piece on human capacity strengthening in research partnerships through mentorship. Using a case study of a research partnership, we describe the lessons learnt and the challenges faced in the mentor mentee relationship while maintaining an effective and sustainable partnership. Human capacity strengthening must research projects and collaborations, and recognise local leadership and ownership. To be transformative and effective, practices need to be driven by common values across research teams.

Annular erythema and photosensitivity as manifestations of efavirenz-induced cutaneous reactions: a review of five consecutive cases.

OBJECTIVES: In HIV-infected persons, a rash is the most common manifestation of drug hypersensitivity reactions. Non-nucleotide reverse transcriptase inhibitors are a major cause of cutaneous reactions. While the characteristics of nevirapine-associated cutaneous adverse drug reactions (CADRs) have been well described, there are limited data on efavirenz-associated CADRs. The objective of this study was to characterize the clinical features of consecutive cases of efavirenz-associated CADRs in a single referral centre diagnosed over a 3 year period. METHODS: We retrospectively reviewed the clinical records of 231 patients admitted with CADRs to a tertiary dermatology ward in Cape Town, South Africa. RESULTS: In 42/231(18%) cases, there had been exposure to efavirenz in the preceding 8 weeks. Of these, 5/42 (12%) patients were diagnosed with probable efavirenz-associated CADRs based on the Naranjo score. The median exposure to efavirenz before the onset of the rash was 12 days (range 2-48). All the patients were female, with a median age of 31 years and a median CD4 cell count of 300 cells/mm(3) (range 81-887). Four had a photo-distributed eruption and one had a confluent indurated erythema affecting the face, trunk and limbs. In three out of five cases, there were annular plaques with raised erythematous edges and dusky centres, which were photo-distributed. Two patients had a mild transaminitis and another a mild eosinophilia. Histological features were non-specific, with perivascular lymphocytes the only consistent feature. In all five cases, efavirenz was withdrawn and potent topical steroid was the only CADR-specific intervention. The eruptions resolved on discharge from hospital, with no sequelae except for residual post-inflammatory hyperpigmentation. CONCLUSIONS: Photo-distribution and annular erythema should alert clinicians to the possibility of efavirenz-associated CADRs.

Incidence and distribution of human leptospirosis in the Western Cape Province, South Africa (2010-2019): a retrospective study.

Introduction: leptospirosis is an emerging zoonosis of global importance. In South Africa, the infection is an underreported public health concern, with limited information on its incidence and distribution. This study investigated the incidence of human leptospirosis in Western Cape Province (WCP) between 2010 and 2019, and compared the incidence based on seasonal and demographic factors. Methods: a retrospective study was conducted with data on leptospirosis diagnoses in WCP obtained from the National Health Laboratory Services. With the provincial population sizes as the denominator, incidence of leptospirosis was estimated and expressed as cases per 100,000 population. Negative binomial regression was used to estimate the effect of sex, season, and year on the incidence of leptospirosis. Results: two hundred and fifty-four (254) cases of leptospirosis were reported between 2010 and 2019, with the highest number of cases being in 2015 and the annual incidence ranged between 0.15 and 0.66/100,000 population. Males had a higher incidence compared to females (0.55 vs. 0.25/ 100,000 population; incidence rate ratio (IRR) 2.2, 95% CI: 1.66,3.03). The 18-44 age cohort had the highest average incidence (0.56/100,000 population), while the ≤17 age cohort had the lowest incidence (0.07/100,000 population). The 18-44 (IRR 8.0, 95% CI: 4.65,15.15) and ≥45 (IRR 7.4, 95% CI: 4.17,14.17) age cohorts were more at risk of infection compared to ≤17 age cohort. Conclusion: leptospirosis is an important zoonosis in WCP disproportionately affecting males and the productive age demographic groups. These findings should enhance targeted prevention and provoke further investigation on the importance of environmental and socioeconomic factors on leptospirosis burden.

A case of pericardial schistosomiasis and non-Hodgkin high grade B-cell lymphoma.

Chronic schistosomiasis affects either the genitourinary or gastrointestinal tract. Rarely, schistosomes cause ectopic disease, such as in the case of a South African woman from a non-endemic province, who presented with suspected pericardial tamponade because of tuberculosis. However, histology and polymerase chain reaction from pericardial biopsy confirmed Schistosoma haematobium. A finding of mediastinal non-Hodgkin lymphoma came to light when our patient's clinical condition unexpectedly deteriorated. Contribution: This case highlights an unusual manifestation of schistosomiasis.

The COVID-19 Pandemic and Explaining Outcomes in Africa: Could Genomic Variation Add to the Debate?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, emanated from the Wuhan Province in China and rapidly spread across the globe causing extensive morbidity and mortality rate, and affecting the global economy and livelihoods. Contrary to early predictions of "body bags" across Africa, the African COVID-19 pandemic was marked by apparent low case numbers and an overall mortality rate when compared with the other geographical regions. Factors used to describe this unexpected pattern included a younger population, a swifter and more effective national health policy, limited testing capacities, and the possibility of inadequate reporting of the cases, among others. However, despite genomics contributing to interindividual variations in many diseases across the world, there are inadequate genomic and multiomics data on COVID-19 in Africa that prevent richer transdisciplinary discussions on the contribution of genomics to the spread of COVID-19 pandemic. To invite future debates on comparative studies of COVID-19 genomics and the pandemic spread around the world regions, this expert review evaluates the reported frequency distribution of genetic variants in candidate genes that are likely to affect COVID-19 infection dynamics/disease outcomes. We propose here that genomic variation should be considered among the many factors determining the COVID-19 infection and its outcomes in African populations and across the world.

Multisystem cytomegalovirus end-organ disease in a patient with advanced HIV.

Cytomegalovirus (CMV) infection is common in people living with HIV, but multisystem CMV end-organ disease (EOD) is rare following the introduction of effective antiretroviral therapy. We present the case of a patient with advanced HIV and multisystem manifestations of CMV EOD. Contributions: This case report highlights the potential morbidity and mortality associated with CMV disease in patients with advanced HIV. Clinicians should be vigilant in considering CMV EOD in patients with advanced HIV and visual, neurological and gastointestinal symptoms.

Adherence to a care bundle for Staphylococcus aureus bacteraemia: A retrospective cohort study.

Background: Staphylococcus aureus bacteraemia is associated with high hospital mortality. Improvements in outcome have been described with standardised bundles of care. Objectives: To study the adherence of a standardised bundle of care (BOC) recommendations using a consultation pro forma, for all patients admitted with S. aureus bacteraemia to Groote Schuur Hospital over a year. The study further aimed to describe the 90-day mortality in these patients and to assess for an association between adherence to the bundle of care and outcome. Method: A retrospective audit of all unsolicited infectious disease consultations for patients with S. aureus bacteraemia admitted to Groote Schuur Hospital during 2018. Adherence to recommendations of a standard bundle of care was audited. Results: A total of 86 patients were included in the study: 61 (71%) with hospital-associated infection and 25 (29%) with community-associated infection. Over 80% of adherence to treatment recommendations was achieved regarding antibiotic (including vancomycin) usage, source control and use of echocardiography as required. In-hospital mortality was 16%, while the overall 90-day mortality was 18%, with only age as an independent predictor of mortality. No association between adherence to the bundle of care and outcome was found. Conclusion: Adherence to a simple, structured bundle of care was good when using standardised pro forma as communication tools for advice and a structured antibiotic chart for vancomycin administration. Although adherence was not associated with outcome, the overall mortality for S. aureus bacteraemia was improving in the institution under study. Contribution: Our findings support feasibility and ongoing use of bundles of care for S. aureus bacteraemia in similar settings.

A comprehensive overview of pneumococcal vaccination recommendations for adults in South Africa, 2022.

Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data.

Patterns of detectable viral load in a cohort of HIV-positive adolescents on antiretroviral therapy in South Africa.

INTRODUCTION: Despite improved treatment and access to care, adolescent AIDS deaths are decreasing more slowly than in any other age group. There is lack of longitudinal data around adolescent adherence and the dynamics of viraemia over time. We aimed to describe patterns of detectable viral load (VL) in a cohort of adolescents attending an ARV clinic in Cape Town, South Africa. METHODS: We conducted a retrospective cohort study of all patients on antiretroviral therapy aged 10 to 19 years. Participants were included if they underwent at least two VL measurements and remained in care at the Groote Schuur Hospital HIV Clinic for at least 24 months between 2002 and 2016. The primary outcome was two consecutive HIV VL >100 copies/mL, in line with the lower limit of detection of assays in use over the follow-up period. RESULTS AND DISCUSSION: Of the 482 screened participants, 327 met inclusion criteria. Most participants had perinatally acquired HIV (n = 314; 96%), and 170 (52%) were males. Overall, there were 203 episodes of confirmed detectable VL involving 159 (49% (95% CI 43% to 54%)) participants during the follow-up period. Six participants had genotyped resistance to protease inhibitors. Four of these never suppressed, while two suppressed on salvage regimens. Total follow-up time was 1723 person years (PY), of which 880 (51%) were contributed by the 159 participants who experienced detectable VL. Overall time with detectable VL was 370 PY. This comprised 22% of total follow-up time, and 42% of the follow-up time contributed by those who experienced detectable VL. The rate of detectable VL was 11.8 (95% CI 10.3 to 13.5) episodes per 100 PY. The risk increased by 24% for each year of increasing age (Relative Risk 1.24 (95% CI 1.17 to 1.31); p < 0.0001). There was no sex difference with respect to duration (p = 0.4), prevalence (p = 0.46) and rate (p = 0.608) of detectable VL. CONCLUSIONS: Clinicians need to be alert to the high prevalence of detectable VL during adolescence so as to pre-empt it and act swiftly once it is diagnosed. This study helps to highlight the risk of detectable VL that is associated with increase in age as well the high proportion of time that poorly adherent adolescents spend in this state.

Blood culture contamination rates at different level healthcare institutions in the Western Cape, South Africa.

Sterile blood culture (BC) collection procedures are important to prevent the consequences of contamination, namely, prolonged patient hospitalisation, unnecessary antimicrobial exposure and an increase in hospital costs. Blood culture contamination rates were determined at different hospitals in the Cape Metropole over a 3-year period. Study findings showed that contaminated BCs have a financial impact on the healthcare system and contamination rates remain above accepted international standards, except in the presence of a phlebotomist team. High BC contamination rates might be reduced by the implementation of cost-effective educational intervention programmes, which reminds healthcare workers to collect BC samples aseptically.

The cost-effectiveness of using pneumococcal conjugate vaccine (PCV13) versus pneumococcal polysaccharide vaccine (PPSV23), in South African adults.

Streptococcus pneumoniae (pneumococcus) remains an important cause of morbidity and mortality. Pneumococcal vaccination is part of the South African pediatric public immunization program but the potential cost-effectiveness of such an intervention for adults is unknown. This study aimed to compare the cost-effectiveness of two widely used pneumococcal vaccines: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) in South African adults, 18 years and older. Four analyses were carried out in a) both the private and public health care sectors; and b) for the HIV-infected population alone and for the total mixed population (all HIV-infected and -uninfected people). A previously published global pharmacoeconomic model was adapted and populated to represent the South African adult population. The model utilized a Markov-type process to depict the lifetime clinical and economic outcomes of patients who acquire pneumococcal disease in 2015, from a societal perspective. Costs were sourced in South African rand and converted to US dollar (USD). The incremental cost divided by the incremental effectiveness (expressed as quality-adjusted life years gained) represented the incremental cost-effectiveness ratio for PCV13 compared to PPSV23. Results indicated that the use of PCV13 compared to PPSV23 is highly cost-effective in the public sector cohorts with incremental cost-effectiveness ratios of $771 (R11,106)/quality-adjusted life year and $956 (R13,773)/quality-adjusted life year for the HIV-infected and mixed populations, respectively. The private sector cohort showed similar highly cost-effective results for the mixed population (incremental cost-effectiveness ratio $626 (R9,013)/quality-adjusted life year) and the HIV-infected cohort (dominant). In sensitivity analysis, the model was sensitive to vaccine price and effectiveness. Probabilistic sensitivity analyses found predominantly cost-effective ICERs. From a societal perspective, these findings provide some guidance to policy makers for consideration and implementation of an immunization strategy for both the public and private sector and amongst different adult patient pools in South Africa.

The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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%). INTERPRETATION: 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.

Fingerstick test quantifying humoral and cellular biomarkers indicative for M. leprae infection.

OBJECTIVES: New user-friendly diagnostic tests for detection of individuals infected by Mycobacterium leprae (M. leprae), the causative pathogen of leprosy, can help guide therapeutic and prophylactic treatment, thus positively contributing to clinical outcome and reduction of transmission. To facilitate point-of-care testing without the presence of phlebotomists, the use of fingerstick blood (FSB) rather than whole blood-derived serum is preferred. This study is a first proof-of-principle validating that previously described rapid serum tests detecting antibodies and cytokines can also be used with FSB. METHODS: Quantitative detection of previously identified biomarkers for leprosy and M. leprae infection, anti-M. leprae PGL-I IgM antibodies (αPGL-I), IP-10 and CRP, was performed with lateral flow (LF) strips utilizing luminescent up-converting reporter particles (UCP) and a portable reader generating unbiased read-outs. Precise amounts of FSB samples were collected using disposable heparinized capillaries. Biomarker levels in paired FSB and serum samples were determined using UCP-LF test strips for leprosy patients and controls in Bangladesh, Brazil, South-Africa and the Netherlands. RESULTS: Correlations between serum and FSB from the same individuals for αPGL-I, CRP and IP-10 were highly significant (p < .0001) even after FSB samples had been frozen. The αPGL-I FSB test was able to correctly identify all multibacillary leprosy patients presenting a good quantitative correlation with the bacterial index. CONCLUSIONS: Reader-assisted, quantitative UCP-LF tests for the detection of humoral and cellular biomarkers for M. leprae infection, are compatible with FSB. This allows near-patient testing for M. leprae infection and immunomonitoring of treatment without highly trained staff. On site availability of test-result concedes immediate initiation of appropriate counselling and treatment. Alternatively, the UCP-LF format allows frozen storage of FSB samples compatible with deferred testing in central laboratories.