Changes in Prevalence and Seasonality of Pathogens Identified in Acute Respiratory Tract Infections in Hospitalised Individuals in Rural and Urban Settings in South Africa; 2018-2022.

Severe acute respiratory tract infections (SARIs) has been well described in South Africa with seasonal patterns described for influenza and respiratory syncytial virus (RSV), while others occur year-round (rhinovirus and adenovirus). This prospective syndromic hospital-based surveillance study describes the prevalence and impact of public interventions on the seasonality of other respiratory pathogens during the coronavirus disease-19 (COVID-19) pandemic. This occurred from August 2018 to April 2022, with 2595 patients who met the SARS case definition and 442 controls, from three sentinel urban and rural hospital sites in South Africa. Naso/oro-pharyngeal (NP/OP) swabs were tested using the FastTrack Diagnostics® Respiratory pathogens 33 (RUO) kit. Descriptive statistics, odds ratios, and univariate/multivariate analyses were used. Rhinovirus (14.80%, 228/1540) and Streptococcus pneumoniae (28.50%, 439/1540) were most frequently detected in NP/OP swabs and in children <1 years old (35%, 648/1876). Among others, pathogens associated with SARI cases causing disease were influenza A&B, HRV, RSV, hCoV 229e, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. Pre-COVID-19, seasonal trends of these pathogens correlated with previous years, with RSV and influenza A seasons only resuming after the national lockdown (2021). It is evident that stringent lockdown conditions have severe impacts on the prevalence of respiratory tract infections.

West Nile Virus, an Underdiagnosed Cause of Acute Fever of Unknown Origin and Neurological Disease among Hospitalized Patients in South Africa.

West Nile virus (WNV), a mosquito-borne flavivirus, is endemic to South Africa. However, its contribution to acute febrile and neurological disease in hospitalized patients in South Africa is unknown. This study examined two patient cohorts for WNV using molecular testing and IgM serology with confirmation of serological results by viral neutralization tests (VNT) to address this knowledge gap. Univariate analysis was performed using collected demographic and clinical information to identify risk factors. In the first cohort, 219 cerebrospinal fluid (CSF) specimens from patients with acute neurological disease in Gauteng hospitals collected in January to June 2017 were tested for WNV. The study identified WNV in 8/219 (3.65%, 95.00% CI (1.59-7.07)) patients with unsolved neurological infections. The second cohort, from 2019 to 2021, included 441 patients enrolled between January and June with acute febrile or neurological disease from urban and rural sites in Gauteng and Mpumalanga provinces. West Nile virus was diagnosed in 40/441 (9.07%, 95.00% CI (6.73-12.12)) of patients, of which 29/40 (72.50%, 95.00% CI (56.11-85.40)) had neurological signs, including headaches, encephalitis, meningitis, and acute flaccid paralysis (AFP). Notably, most of the cases were identified in children although adolescents and senior adults had a significantly higher risk of testing WNV positive. This suggests a previously underestimated disease burden and that WNV might be underrecognized as a cause of febrile and neurological diseases in hospitalized patients in South Africa, especially in children. This emphasizes the importance of further research and awareness regarding arboviruses of public health concern.

Epidemiology and aetiology of moderate to severe diarrhoea in hospitalised patients ≥5 years old living with HIV in South Africa, 2018-2021: A case-control analysis.

Diarrhoea is a recognised complication of HIV-infection, yet there are limited local aetiological data in this high-risk group. These data are important for informing public health interventions and updating diagnostic and treatment guidelines. This study aimed to determine the pathogenic causes of diarrhoeal admissions in people living with HIV (PLHIV) compared to hospital controls between July 2018 and November 2021. Admitted diarrhoeal cases (n = 243) and non-diarrhoeal hospital controls (n = 101) ≥5 years of age were enrolled at Kalafong, Mapulaneng and Matikwana hospitals. Stool specimens/rectal swabs were collected and pathogen screening was performed on multiple platforms. Differences in pathogen detections between cases and controls, stratified by HIV status, were investigated. The majority (n = 164, 67.5%) of enrolled diarrhoeal cases with known HIV status were HIV-infected. Pathogens could be detected in 66.3% (n = 228) of specimens, with significantly higher detection in cases compared to controls (72.8% versus 50.5%, p<0.001). Amongst PLHIV, prevalence of Cystoisospora spp. was significantly higher in cases than controls (17.7% versus 0.0%, p = 0.028), while Schistosoma was detected more often in controls than cases (17.4% versus 2.4%, p = 0.009). Amongst the HIV-uninfected participants, prevalence of Shigella spp., Salmonella spp. and Helicobacter pylori was significantly higher in cases compared to controls (36.7% versus 12.0%, p = 0.002; 11.4% versus 0.0%, p = 0.012; 10.1% versus 0.0%, p = 0.023). Diarrhoeal aetiology differed by HIV status, with Shigella spp. (36.7%) and Salmonella spp. (11.4%) having the highest prevalence amongst HIV-uninfected cases and Shigella spp. (18.3%), Cystoisospora (17.7%), and Cryptosporidium spp. (15.9%) having the highest prevalence in cases amongst PLHIV. These differences should be considered for the development of diagnostic and treatment guidelines.

Flow cytometry as an analytical method of drug-induced apoptosis in 3D bioprinted melanoma cells.

Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to its inherent advantages in providing more physiologically relevant information and more predictive data forin vivotests. Along with the development of more physiologically relevant 3D cell culture models, researchers bear the responsibility to validate new cell assay techniques capable of measuring and evaluating constructs that are physically larger and more complex compared to two-dimensional cell cultures. It is important to note that assays based on monolayer cultures may be insufficient for the use in 3D cell cultures models. In this study we firstly fabricated a 3D bioprinted hydrogel melanoma scaffold. This was used to validate a flow cytometry-based analytical method as a tool for 3D bioprinted structures to assess drug-induced apoptosis. The results indicated high robustness, reproducibility and sensitivity of the flow cytometric method established on the 3D cell-laden A375 melanoma hydrogel scaffolds. Over and above this, it was possible to determine the effect of etoposide on A375 melanoma cells using Annexin V and propidium iodide apoptosis assay.

Late-onset efavirenz toxicity: A descriptive study from Pretoria, South Africa.

Background: The neuropsychiatric side effects of efavirenz occur mainly early during treatment and are usually mild. A lesser-known and serious complication is late-onset efavirenz toxicity causing ataxia and encephalopathy. Data regarding this condition are limited. Objectives: We describe the clinical picture of late-onset efavirenz toxicity, investigate co-morbidities and report outcomes. Method: This descriptive study of all patients with late-onset efavirenz toxicity was conducted over three years at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa. Results: Forty consecutive patients were identified. Mean age was 42.1 years, three patients (7.5%) were male and the mean efavirenz level was 49.0 µg/mL (standard deviation [s.d.]: 24.8). Cerebellar ataxia (82.5%) and encephalopathy (47.5%) were the most common presenting features (40.0% had both); four patients presented with psychosis. Presence of encephalopathy and/or cerebellar ataxia was associated with higher efavirenz levels compared with psychosis (52.1 µg/mL, s.d.: 24.1 vs 25.0 µg/mL, s.d.: 17.1). In most patients, symptoms resolved, but four patients (10.0%) died, and one patient remained ataxic. Conclusion: Late-onset efavirenz toxicity typically presented with ataxia and encephalopathy, but psychosis can be the presenting feature. The outcome after withdrawal was good, but the mortality of 10.0% is concerning. Recent changes in guidelines favour dolutegravir, but many patients remain on efavirenz, and awareness of the condition is vital. What this study adds: This large, single-centre study contributes to the limited data of HIV-positive patients with late-onset efavirenz toxicity and emphasises its ongoing relevance in clinical practice.

Association between pheochromocytoma and neurofibromatosis type I: a rare entity in the African population.

The association of pheochromocytoma in patients with neurofibromatosis type I has rarely been reported in low-income countries, especially on the African continent. A 43-year-old woman with neurofibromatosis type I was diagnosed with a right adrenal pheochromocytoma in Pretoria, South Africa. To our knowledge, this report is the first case to be published of a patient with neurofibromatosis type I diagnosed with a pheochromocytoma in Pretoria, and one of three cases on the African continent. The rarity may be due to the two associated conditions being under-reported, undiagnosed, misdiagnosed or possibly the association is rare on the African continent. The clinician dealing with these two conditions should be aware of the association.