Clinical spectrum of disease and outcomes in children with Omicron SARS-COV-2 infection in Cape Town, South Africa.

INTRODUCTION: Children with underlying comorbidities and infants are most severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including in low- and middle-income countries with a high prevalence of HIV and TB. We describe the clinical presentation of SARS-CoV-2 infection in children during the Omicron wave, in Cape Town, South Africa. METHODS: We analysed routine care data from a prospective cohort of children aged 0-13 years, with a positive SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) or SARS-CoV-2 antigen test, admitted to Tygerberg Hospital between 1 November 2021 until 1 March 2022. Risk factors for severity of disease were assessed. RESULTS: Ninety-five children tested positive for SARS-CoV-2, of whom 87 (91.6%) were symptomatic. Clinical data were available for 86 children. The median age was 11 months (IQR 3.0-60.0), 37 (43.0%) were females, 21 (24.7%) were HIV-exposed and 7 (8.1%) were living with HIV (CLHIV). In total, 44 (51.2%) children had at least one underlying comorbidity. TB co-infection was seen in 11 children, 6 children were newly diagnosed and 5 children were already on TB treatment at the time of admission. CONCLUSION: There was no evidence of more severe disease in children living with HIV or TB.

INTRODUCTION: Les enfants et les nourrissons présentant des comorbidités sous-jacentes sont les plus gravement touchés par l'infection par le coronavirus-2 du syndrome respiratoire aigu sévère (SARS-CoV-2), y compris dans les pays à revenu faible ou intermédiaire où la prévalence du VIH et de la TB est élevée. Nous décrivons la présentation clinique de l'infection par le SARS-CoV-2 chez les enfants pendant la vague Omicron, au Cap, en Afrique du Sud. MÉTHODES: Nous avons analysé les données de soins de routine d'une cohorte prospective d'enfants âgés de 0 à 13 ans, avec un test positif de réaction en chaîne de la polymérase de transcription inverse en temps réel (rRT-PCR) ou d'antigène du SARS-CoV-2, admis à l'hôpital Tygerberg entre le 1er novembre 2021 et le 1er mars 2022. Les facteurs de risque de gravité de la maladie ont été évalués. RÉSULTATS: Quatre-vingt-quinze enfants ont été testés positifs au SARS-CoV-2, dont 87 (91,6%) étaient symptomatiques. Des données cliniques étaient disponibles pour 86 enfants. L'âge médian était de 11 mois (IQR 3,0­60,0), 37 (43,0%) étaient des filles, 21 (24,7%) étaient exposés au VIH et 7 (8,1%) vivaient avec le VIH (CLHIV). Au total, 44 (51,2%) enfants présentaient au moins une comorbidité sous-jacente. La co-infection par la TB a été observée chez 11 enfants, 6 enfants ont été nouvellement diagnostiqués et 5 enfants étaient déjà sous traitement antituberculeux au moment de l'admission. CONCLUSION: Il n'y a pas de preuve d'une maladie plus grave chez les enfants vivant avec le VIH ou la TB.

The role of new hepatitis B vaccines in South Africa.

Vaccination is key to eliminating hepatitis B virus infection in South Africa (SA). Despite introducing immunisation in 1995, as part of the expanded programme of immunisation (EPI), hepatitis B virus infection remains endemic, and EPI vaccine coverage is incomplete. In addition to infants, non-immune adults at risk of infection through their occupation or with behavioural risk factors should receive vaccination. SA has many individuals with diabetes mellitus (a prevalence of almost 13%), obesity, HIV (8.45 million) or older age (5 million >60 years old), associated with a poorer vaccine response. Recently two new hepatitis B vaccines have been licensed: HEPLISAV-B includes an adjuvant that improves immunogenicity and has shown improved vaccine response in individuals with HIV, old age or diabetes mellitus. PreHevbrio, which includes three hepatitis B surface protein domains, instead of one, may also be more immunogenic, although clinical study data are still limited. These two novel vaccines have not yet been investigated in children and licensed in SA. Should HEPLISAV-B become available in SA, it may be particularly valuable to target high-risk groups in the country, such as people living with HIV, who show a poor response to the currently licensed vaccine.

High burden of viral respiratory co-infections in a cohort of children with suspected pulmonary tuberculosis.

BACKGROUND: The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up. METHODS: In an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8. RESULTS: Seventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0-48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8. CONCLUSIONS: We found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.

HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa.

BACKGROUND: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART. METHODS: A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to Stanford HIVdb v7.0.1. RESULTS: A total of 788 sequences were available for analysis. Most patients failed a tenofovir-based NRTI backbone (74.4%) in combination with efavirenz (82.1%) after median treatment duration of 36 months. K103N (48.9%) and V106M (34.9%) were the most common NNRTI mutations. Only one-third of patients retained full susceptibility to second-generation NNRTIs such as etravirine (36.5%) and rilpivirine (27.3%). After M184V/I (82.7%), K65R was the most common NRTI mutation (45.8%). The prevalence of K65R increased to 57.5% in patients failing a tenofovir regimen without prior stavudine exposure. Cross-resistance to NRTIs was often observed, but did not seem to affect the predicted activity of zidovudine as 82.9% of patients remained fully susceptible to this drug. CONCLUSIONS: The introduction of tenofovir-based first-line regimens has dramatically increased the prevalence of K65R mutations in the HIV-1-infected South African population. However, most patients failing tenofovir-based regimens remained fully susceptible to zidovudine. Based on these data, there is currently no need to change either the recommended first- or second-line ART regimens in South Africa.

Prevalence of Antiretroviral Drug Resistance in Patients Who Are Not Responding to Protease Inhibitor-Based Treatment: Results From the First National Survey in South Africa.

Limited data exist on human immunodeficiency virus type 1 (HIV-1) resistance in patients who are not responding to protease inhibitor (PI)-based regimens in resource-limited settings. This study assessed resistance profiles in adults across South Africa who were not responding to PI-based regimens. pol sequencing was undertaken and submitted to the Stanford HIV Drug Resistance Database. At least 1 major PI mutation was detected in 16.4% of 350 participants. A total of 53.4% showed intermediate resistance to darunavir/ritonavir, whereas high-level resistance was not observed. Only 5.2% and 32.8% of participants showed high-level and intermediate resistance to etravirine, respectively. Although the prevalence of major PI mutations was within previously reported ranges, most patients will likely experience virological suppression during receipt of currently available South African third-line regimens.

South African medical schools: Current state of selection criteria and medical students' demographic profile.

BACKGROUND: Selection of medical students at South African (SA) medical schools must promote equitable and fair access to students from all population groups, while ensuring optimal student throughput and success, and training future healthcare practitioners who will fulfil the needs of the local society. In keeping with international practices, a variety of academic and non-academic measures are used to select applicants for medical training programmes in SA medical schools. OBJECTIVES: To provide an overview of the selection procedures used by all eight medical schools in SA, and the student demographics (race and gender) at these medical schools, and to determine to what extent collective practices are achieving the goals of student diversity and inclusivity. METHODS: A retrospective, quantitative, descriptive study design was used. All eight medical schools in SA provided information regarding selection criteria, selection procedures, and student demographics (race and gender). Descriptive analysis of data was done by calculating frequencies and percentages of the variables measured. RESULTS: Medical schools in SA make use of academic and non-academic criteria in their selection processes. The latter include indices of socioeconomic disadvantage. Most undergraduate medical students in SA are black (38.7%), followed by white (33.0%), coloured (13.4%) and Indian/Asian (13.6%). The majority of students are female (62.2%). The number of black students is still proportionately lower than in the general population, while other groups are overrepresented. CONCLUSION: Selection policies for undergraduate medical programmes aimed at redress should be continued and further refined, along with the provision of support to ensure student success.

International Nurses Day and press coverage in South Africa.

BACKGROUND: In some countries, nursing's appeal as a profession is diminishing, partly due to poor press coverage and the media's portrayal of an over-loaded, poorly paid profession. The media is important for shaping public perceptions and raising policy issues. International Nurses Day gives nurses an opportunity to profile their critical contribution to quality health care. AIM: To determine the influence of this commemorative day on press coverage about nursing by examining whether there was a difference in the proportion of South African press articles on nursing between January-April and May-June 2010. METHODS: A quantitative content analysis was conducted of all press articles mentioning 'nursing' or 'nurse/s' in the South African lay press from 1 January-31 June 2010. Articles were coded for theme, slant and prominence, and inter-coder reliability was assessed. Descriptive statistics with chi square or Fisher's exact tests were used to compare the two time periods. RESULTS: We identified 242 articles in 95 publications. The month of May had almost double the press coverage of January. International Nurses Day articles were mainly positive, and appeared in May to June in weekly community publications rather than in daily national and regional newspapers. When they were excluded, most articles portrayed nursing negatively. LIMITATIONS: The 6-month period may not be representative of the entire year. Only the dominant topic was coded, which possibly influenced the analysis. CONCLUSION: International Nurses Day positively influenced the extent and slant of press coverage. Efforts to sustain coverage beyond the event through strategic partnerships and media engagement should be strengthened. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The media's portrayal of nurses and nursing may influence the choice of nursing as a career. International Nurses Day is an opportunity to portray nursing positively. Media training may help nurses to advocate for their profession in the media.

Academic hospital accreditation strengthens postgraduate training programmes: case study from Universitas Academic Hospital.

Benefits derived from the Council for Health Services Accreditation South Africa (COHSASA) accreditation of the Universitas Academic Hospital (UAH) in Bloemfontein are illustrated. Accreditation assessments were performed between 2001 and 2007, and full compliance with the COHSASA standards for Academic Hospitals was achieved. An initiative to develop thoracic surgery in central South Africa (SA) was launched by the Department of Cardiothoracic Surgery at UAH. The synergistic effects of quality improvements in healthcare provision owing to the accreditation process, and the project to increase service provision in thoracic surgery in central SA, have led to a qualitative and quantitative increase in thoracic surgical service provision. The importance of academic hospital accreditation in strengthening postgraduate training programmes is shown, and the accreditation process is recommended for all South African academic teaching hospitals to support, improve and sustain our training platforms.

Pooling strategies to reduce the cost of HIV-1 RNA load monitoring in a resource-limited setting.

BACKGROUND: Quantitative human immunodeficiency virus (HIV) RNA load testing surpasses CD4 cell count and clinical monitoring in detecting antiretroviral therapy (ART) failure; however, its cost can be prohibitive. Recently, the use of pooling strategies with a clinically appropriate viral load threshold was shown to be accurate and efficient for monitoring when the prevalence of virologic failure is low. METHODS: We used laboratory request form information to identify specimens with a low pretest probability of virologic failure. Patients aged ≥15 years who were receiving first-line ART had individual viral load results available were eligible. Blood plasma, dried blood spots, and dried plasma spots were evaluated. Two pooling strategies were compared: minipools of 5 samples and a 10 ×10 matrix platform (liquid plasma specimens only). A deconvolution algorithm was used to identify specimens(s) with detectable viral loads. RESULTS: The virologic failure rate in the study sample was <10%. Specimens included were liquid plasma specimens tested in minipools(n = 400), of which 300 were available for testing by matrix, and specimens tested with minipools only: dried blood spots (n = 100) and dried plasma spots (n = 185). Pooling methods resulted in 30.5%-60% fewer HIV RNA tests required to screen the study sample. For plasma pooling, the matrix strategy had the better efficiency, but minipools of 5 dried blood spots had the best efficiency overall and were accurate at a >95% negative predictive value with minimal technical requirements. CONCLUSIONS: In resource-constrained settings, a combination of preselection of patients with low pretest probability of virologic failure and pooled testing can reduce the cost of virologic monitoring without compromising accuracy.

Pleuro-pulmonary disease in central South Africa: A thoracic surgical deficiency.

We wished to estimate the performance gap between thoracic surgical service provision and the burden of thoracic surgical disease in central South Africa (SA). We compared burden of disease data to the number of thoracic operations performed for inflammatory pleuro-pulmonary disease and primary lung cancer. The performance gap was estimated to be a factor of 1:20 for lung cancer and 1:10 for thoracic surgery as a whole. The extent of under-provision of thoracic surgical services in central SA demonstrates that urgent major healthcare system reforms are required at all levels to address the significant performance gap between service provision by thoracic surgery and the burden of disease in central SA.

NucliSens EasyQ HIV-1 V1.2 system: Detection of human plasma-derived background signal.

Until recently the NucliSens EasyQ HIV-1 V1.2 system has been used throughout South Africa as part of the national antiretroviral roll-out programme for the monitoring of HIV-1 RNA load in patients on antiretroviral treatment. Shortly after changing to a new assay lot number an increased proportion of patient specimens, showing detectable but low viral loads, was observed (<200 IU/ml). The test runs remained valid as the lysis buffer-only no-template controls (NTCs) remained negative. Contamination with amplification product was excluded. Subsequently the same phenomenon was observed in at least three other South African laboratories across different assay lot numbers. When testing aliquots of plasma, freshly obtained from HIV-negative donors, at two of these laboratories, 33/134 aliquots showed detectable values (range 26-370, median: 64 IU/ml), while all NTCs remained negative. These findings emphasize the importance of appropriate specimen controls in all diagnostic assays. In this case HIV-negative human plasma should be included routinely in addition to NTCs, which would allow rapid detection of a background signal.

Fifty years of thoracic surgical research in South Africa.

AIM: To investigate the scope and trends in clinical research in South African thoracic surgery between 1955 and 2006 and to measure its impact on clinical practice. METHOD: A systematic review of all SA thoracic surgical publications was performed. RESULTS: There were 252 general thoracic publications and a marked decrease in publications was noted after the peak period of productivity of the 1980s. There was a shift toward the private sector as an origin of articles and toward a local, non-indexed journal. Inflammatory lung disease was the most frequent topic of publication. Case series and case reports were the most frequent type of article. CONCLUSION: The vulnerability of a small specialty in a developing country is illustrated by the clear trends that emerged. The study provides important indicators for future research, highlights the need for a national database of clinical experience, and emphasises the importance of rekindling interest and a culture of research in thoracic surgery.

Extraction buffer contaminated bacterially as a cause of invalid HIV-1 viral load results on the NucliSens EasyQ system.

Shortly after starting to use the NucliSens EasyQ HIV-1 V1.1 system for HIV-1 RNA load testing, the number of invalid tests per assay run gradually increased. Within five days, approximately 50% of tests showed a total lack of amplification of the calibrator and in most cases also of the HIV-1 template. According to the manufacturer's specifications, the lysis buffer and three extraction buffers remain on the automated NucliSens easyMAG extraction system between assay runs. Therefore possible microbial contamination of these buffers was investigated, after they had been on the automated system for approximately one week. The NucliSens easyMAG extraction buffer 2 yielded bacterial growth identified as Acinetobacter baumannii. After regular decontamination of the machine's tubing system with 70% alcohol and storage of the buffers at 4 degrees C between assay runs were commenced, invalid results due to failed internal calibrator signal occurred no longer. It is likely that bacterial contamination of the buffer was the cause of assay failure, probably due to ribonuclease (RNase) activity. Bacterial contamination of PCR systems should be added to the list of potential hazards in diagnostic virology. This experience underlines the necessity of state-of-the-art assay design incorporating adequate internal controls and calibrators.

Zidovudine with nevirapine for the prevention of HIV mother-to-child transmission reduces nevirapine resistance in mothers from the Western Cape, South Africa.

In the Western Cape province of South Africa, an intensified regimen for the prevention-of-mother-to-child-transmission-of-HIV consisting of zidovudine (AZT) from 34 weeks of pregnancy plus single dose (sd) nevirapine (NVP) during labor was instituted in 2004. The newborn baby receives a single dose of NVP and AZT for 7 days. Similar strategies in Thailand and Africa have been shown to be more effective in reducing transmission than NVP alone. The use of sd NVP only for the prevention-of-mother-to-child-transmission-of-HIV has a high risk of inducing resistance (25-69%) with an average of 35.7% by a recent meta-analysis and has been shown to adversely affect non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy when initiated within 6 months. In this study the prevalence of resistance to NVP and AZT in mothers who had received the intensified regimen was measured. Specimens collected from mothers were genotyped by in-house PCR and sequencing. In specimens obtained within 60 days of delivery, acquired NVP resistance mutations were detected in 13 of 76 patients (17.1%, 95% confidence interval: 8.7-25.6%), which appears to be lower than in studies with sd NVP alone (37.5%, 95% confidence interval: 23.0-50.6%).

Pitfalls with rapid HIV antibody testing in HIV-infected children in the Western Cape, South Africa.

BACKGROUND: Rapid HIV antibody tests are commonly used for HIV diagnosis in the developing world. These tests are generally reported as sensitive, despite paucity of evaluations in paediatric populations. OBJECTIVES: We tested specimens of paediatric patients, known to be HIV-infected, to detect any false negative tests and determine associations with such an outcome. STUDY DESIGN: One hundred and fifty-three specimens, from 109 patients, recorded to be HIV-infected by standard testing, were tested on the Capillustrade mark HIV-1/HIV-2 test (Trinity Biotech, Ireland); 150 specimens also had sufficient volume to be tested on Abbott Determinetrade mark HIV1/2 assay (Abbott GmbH, Wiesbaden, Germany). Treatment information, CD4 counts and HIV-1 viral load measurements were obtained from patient files and laboratory databases. RESULTS: Twenty-one of 153 specimens tested negative on the Capillus (sensitivity 86.3%). False negative results by Capillus were associated with antiretroviral treatment (ART) (p=0.0018) and lower HIV-1 viral load (p=0.013). Serial dilutions of some of the specimens indicated that both rapid tests, and the Capillus in particular, became negative at lower dilutions than an HIV enzyme immunoassay (EIA). CONCLUSIONS: The Capillus test had an unexpectedly low sensitivity in a South African population of HIV-infected children that had access to antiretroviral treatment, posing a risk of false negative HIV testing.

Clinical rotation in pathology: description of a case based approach.

BACKGROUND: The implementation of a system based, integrated curriculum at the Faculty of Health Sciences of Stellenbosch University, Western Cape, South Africa, resulted in less contact time for the pathology disciplines during theoretical modules, while a weekly rotation in pathology was introduced during clinical training in the fourth and fifth years. OBJECTIVE: To describe a problem based approach for this rotation. METHODS: Students are presented with a clinical "paper" case daily, integrating as many of the pathology disciplines as possible to demonstrate the interdependence of the various disciplines. They receive chemical pathology tutorials, visit the various laboratories, and receive practical training in fine needle aspiration biopsy. On the final day, the case studies are assessed and discussed. RESULTS: Most students appreciated all activities. This rotation enhanced student interactivity and autonomy and guaranteed immediate feedback. On evaluation of the rotation it was found that the students enjoyed the rotation, learnt something new, and realised the value of group work. CONCLUSIONS: This innovation integrates pathology with clinical practice and illustrates the use of laboratory medicine in the management of common diseases seen in this country. Students appreciate learning practical skills and having to request special investigations under a pathologist's supervision changes their approach to pathology requests. Familiarity with the pathology environment empowers the student to use pathology with greater ease. A bank of case studies that can be expanded to include all medical disciplines will facilitate the application of a problem based approach and enhance communication between the basic science disciplines and the clinical and pathology disciplines.