Trends in COVID-19 admissions and deaths among people living with HIV in South Africa: analysis of national surveillance data.

BACKGROUND: In 2021, the HIV prevalence among South African adults was 18% and more than 2 million people had uncontrolled HIV and, therefore, had increased risk of poor outcomes with SARS-CoV-2 infection. We investigated trends in COVID-19 admissions and factors associated with in-hospital COVID-19 mortality among people living with HIV and people without HIV. METHODS: In this analysis of national surveillance data, we linked and analysed data collected between March 5, 2020, and May 28, 2022, from the DATCOV South African national COVID-19 hospital surveillance system, the SARS-CoV-2 case line list, and the Electronic Vaccination Data System. All analyses included patients hospitalised with SARS-CoV-2 with known in-hospital outcomes (ie, who were discharged alive or had died) at the time of data extraction. We used descriptive statistics for admissions and mortality trends. Using post-imputation random-effect multivariable logistic regression models, we compared characteristics and the case fatality ratio of people with HIV and people without HIV. Using modified Poisson regression models, we compared factors associated with mortality among all people with COVID-19 admitted to hospital and factors associated with mortality among people with HIV. FINDINGS: Among 397 082 people with COVID-19 admitted to hospital, 301 407 (75·9%) were discharged alive, 89 565 (22·6%) died, and 6110 (1·5%) had no recorded outcome. 270 737 (68·2%) people with COVID-19 had documented HIV status (22 858 with HIV and 247 879 without). Comparing characteristics of people without HIV and people with HIV in each COVID-19 wave, people with HIV had increased odds of mortality in the D614G (adjusted odds ratio 1·19, 95% CI 1·09-1·29), beta (1·08, 1·01-1·16), delta (1·10, 1·03-1·18), omicron BA.1 and BA.2 (1·71, 1·54-1·90), and omicron BA.4 and BA.5 (1·81, 1·41-2·33) waves. Among all COVID-19 admissions, mortality was lower among people with previous SARS-CoV-2 infection (adjusted incident rate ratio 0·32, 95% CI 0·29-0·34) and with partial (0·93, 0·90-0·96), full (0·70, 0·67-0·73), or boosted (0·50, 0·41-0·62) COVID-19 vaccination. Compared with people without HIV who were unvaccinated, people without HIV who were vaccinated had lower risk of mortality (0·68, 0·65-0·71) but people with HIV who were vaccinated did not have any difference in mortality risk (1·08, 0·96-1·23). In-hospital mortality was higher for people with HIV with CD4 counts less than 200 cells per µL, irrespective of viral load and vaccination status. INTERPRETATION: HIV and immunosuppression might be important risk factors for mortality as COVID-19 becomes endemic. FUNDING: South African National Institute for Communicable Diseases, the South African National Government, and the United States Agency for International Development.

Placental histopathology, maternal characteristics and neonatal outcome in cases of preterm birth in a high risk population in South Africa.

BACKGROUND: Preterm birth remains a global health concern and is one of the most common pregnancy complications associated with perinatal morbidity and mortality.   Objective. This study investigated placental pathology and its associations with obstetric, maternal and neonatal outcomes in the Eastern Cape region of South Africa in order to help understand its associations with preterm birth in that region.   Methods. In this prospective study, placentas were collected consecutively from patients attending a public tertiary referral hospital in South Africa, delivering preterm (n=100; 28-34 weeks gestational age) and term (n=20; >36 weeks gestational age). Placentas were submitted for histopathology, and comparisons with maternal characteristics and neonatal outcomes in preterm birth were undertaken.   Results. Histological analysis revealed pathology in all preterm placentas (100%), with maternal vascular malperfusion (47%) and abruptio placentae (41%) most commonly identified. Acute chorioamnionitis (21%) was associated with term births (p=0.002). Maternal characteristics and neonatal outcomes significantly associated with preterm birth included preeclampsia (p=0.006), neonatal respiratory distress syndrome (p=0.004) and neonatal jaundice (p=0.003). Intrauterine demise (p=0.004), and alcohol abuse (p≤0.005) were significantly associated with term delivery. The number of mothers delivering preterm who were HIV positive was high (41%).  Conclusion. The pathology identified in all preterm placentas supports the need to update institutional policies for submission of placentas from all preterm births for histopathology, particularly in countries with a high burden of preterm birth.

Trends in Cases, Hospitalizations, and Mortality Related to the Omicron BA.4/BA.5 Subvariants in South Africa.

BACKGROUND: In this study, we compared admission incidence risk and the risk of mortality in the Omicron BA.4/BA.5 wave to previous waves. METHODS: Data from South Africa's SARS-CoV-2 case linelist, national COVID-19 hospital surveillance system, and Electronic Vaccine Data System were linked and analyzed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100 000 population. In-hospital case fatality ratios (CFRs) during the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves were compared using post-imputation random effect multivariable logistic regression models. RESULTS: The CFR was 25.9% (N = 37 538 of 144 778), 10.9% (N = 6123 of 56 384), and 8.2% (N = 1212 of 14 879) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves, respectively. After adjusting for age, sex, race, comorbidities, health sector, and province, compared with the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR], 1.3; 95% confidence interval [CI]: 1.2-1.4) and Delta wave (aOR, 3.0; 95% CI: 2.8-3.2). Being partially vaccinated (aOR, 0.9; 95% CI: .9-.9), fully vaccinated (aOR, 0.6; 95% CI: .6-.7), and boosted (aOR, 0.4; 95% CI: .4-.5) and having prior laboratory-confirmed infection (aOR, 0.4; 95% CI: .3-.4) were associated with reduced risks of mortality. CONCLUSIONS: Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa's first 3 waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.

Digital Chest X-Ray with Computer-aided Detection for Tuberculosis Screening within Correctional Facilities.

Rationale: Realizing the Global Plan to End Tuberculosis (TB) will require reaching at least 90% of people in key populations, such as inmates, through optimizing case-finding approaches. Objectives: To evaluate the value of adding digital chest X-ray (d-CXR) with computer-aided detection (CAD) to symptom-based screening on TB yield among inmates. Methods: Consecutive adult inmates from four correctional facilities in South Africa were screened for TB using symptoms and d-CXR. Any person with at least one symptom or CAD score of ⩾50 provided two sputa for liquid culture and GeneXpert MTB/RIF Ultra (Xpert Ultra) testing. In a sample of 800 symptom-negative inmates with CAD score <50, Xpert Ultra testing was also conducted. TB yield was defined as the proportion of new patients with bacteriologically confirmed TB who were identified. Results: We enrolled 3,576 participants: 99.6% male, median age of 34 years (interquartile range, 28-41), and 584 (16.3%) with positive test results for human immunodeficiency virus. Of those screened, 867 (24.2%) participants required investigation (394 [11.2%] symptomatic, 685 [19.1%] with abnormal CAD results, and 867 [24.2%] with either). Sputum was taken in 747 (86.2%) participants, with 28 (7.8 per 1,000 population) new TB cases diagnosed. On the basis of hypothesized screening modalities, yield would have been 3.6 per 1,000 population on the basis of symptoms alone and 7.0 per 1,000 population on the basis of d-CXR alone. Among an additional 800 inmates tested who initially screened symptom negative and had a CAD score <50, five TB cases were diagnosed. There was no difference in TB yield when comparing Xpert Ultra against culture (5.6 vs. 4.8 per 1,000 population; P = 0.21). Conclusions: The addition of d-CXR identified two times more patients with undiagnosed TB than did investigation of symptoms alone. Complementary use of d-CXR may potentially overcome the subjectivity inherent in symptom screening alone for identifying TB in this population.

Spectrum of Bacterial Colonization in Patients Hospitalized for Treatment of Multidrug-Resistant Tuberculosis.

This study investigated the bacterial colonization in patients admitted for treatment of drug-resistant tuberculosis in a specialized TB hospital. Identification and antimicrobial susceptibility testing of bacterial isolates (n = 62) from nasal, groin, and rectal swabs [patient cohort (n = 37)] were determined by the VITEK-MS system. Resistance gene analysis was by PCR and DNA sequencing. Molecular typing of Klebsiella pneumoniae isolates was by Multilocus Sequencing Typing (MLST). Patients (n = 13/37; 35%) were colonized by multidrug-resistant (MDR) bacteria (ESBL and MRSA) on admission. Of the 24 patients who were not colonized by MDR bacteria on admission, 46% (17/37) became colonized by MDR bacteria within 1 month of admission, mostly with ESBL-producing Enterobacteriales and resistance to aminoglycosides and fluoroquinolones. ESBL Escherichia coli (41/62; 66%) and K. pneumoniae (14/62; 23%) predominated. Genes encoding for ESBLs (blaCTX-M-14, blaCTX-M-15, blaSHV-28, blaOXA-1, and blaOXY-2) and plasmid-mediated quinolone resistant genes (qnrB1, qnrB4, and qnrB10) were detected. MLST revealed genetic diversity among the K. pneumoniae isolates from hospitalized patients. This study provides insight into bacterial pathogen colonization in hospitalized TB patients with the first occurrence of the qnrB4 and qnrB10 genes and co-expression of genes: qnrB4+aac(6')-lb-cr, qnrB10+aac(6')-lb-cr, qnrB4+qnrS1, and qnrB10+qnrS1 in fluoroquinolone-resistant E. coli isolates within South Africa. However, the source and colonization routes of these isolates could not be determined.

Ureaplasma species and preterm birth: current perspectives.

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide, and the human Ureaplasma species are most frequently isolated from the amniotic fluid and placenta in these cases. Ureaplasma colonisation is associated with infertility, stillbirth, histologic chorioamnionitis, and neonatal morbidities, including congenital pneumonia, bronchopulmonary dysplasia, meningitis and perinatal death. The human Ureaplasma spp. are separated into Ureaplasma urealyticum and Ureaplasma parvum with 14 known serotypes. The small genome has several genes, which code for surface proteins; most significantly the Multiple Banded Antigen (MBA) where an antigenic C-terminal domain elicits a host antibody response. Other genes code for various virulence factors such as IgA protease and urease. Ureaplasma spp. infection is diagnosed by culture and polymerase chain reaction (PCR) and commercial assays are available to improve turnaround time. Microbroth dilution assays are routinely used to test antimicrobial susceptibility of clinical Ureaplasma spp. especially against doxycycline, azithromycin, ofloxacin and josamycin. Resistance to macrolides, fluoroquinolones and tetracyclines has been reported. A concise review of Ureaplasma spp. and their role in pregnancy outcomes, especially preterm birth, offers insight into the early diagnosis and appropriate antibiotic therapy to prevent long-term complications of Ureaplasma spp. infections.

Wild-Type Zebrafish (Danio rerio) Larvae as a Vertebrate Model for Diabetes and Comorbidities: A Review.

Zebrafish have become a popular alternative to higher animals in biomedical and pharmaceutical research. The development of stable mutant lines to model target specific aspects of many diseases, including diabetes, is well reported. However, these mutant lines are much more costly and challenging to maintain than wild-type zebrafish and are simply not an option for many research facilities. As an alternative to address the disadvantages of advanced mutant lines, wild-type larvae may represent a suitable option. In this review, we evaluate organ development in zebrafish larvae and discuss established methods that use wild-type zebrafish larvae up to seven days post fertilization to test for potential drug candidates for diabetes and its commonly associated conditions of oxidative stress and inflammation. This provides an up to date overview of the relevance of wild-type zebrafish larvae as a vertebrate antidiabetic model and confidence as an alternative tool for preclinical studies. We highlight the advantages and disadvantages of established methods and suggest recommendations for future developments to promote the use of zebrafish, specifically larvae, rather than higher animals in the early phase of antidiabetic drug discovery.

Characterization of ESBL-producing Escherichia coli ST131 isolates from Port Elizabeth.

This study investigated resistance determinants and genetic relatedness in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates. PCR and DNA sequencing were used for screening isolates for blaCTX-M, blaTEM, and blaSHV (qnrA, qnrB, qnrC, qnrD, qnrS, aac(6)-lb-cr, and qepA) resistance genes and the sequence type 131 (ST131) clone. Genetic relatedness of E. coli ST131 isolates was determined by pulsed-field gel electrophoresis. Twelve isolates belonged to the ST131 clonal complex, while 8 were positive for aac(6')-lb-cr with qnrB1 also detected in 1 isolate. This study describes the first occurrence of CTX-M-9, qnrB1+aac(6')-lb-cr and CTX-M-3+qnrS1 among E. coli ST131 isolates from South Africa and illustrates their genetic diversity.

Molecular detection and characterization of resistant genes in Mycobacterium tuberculosis complex from DNA isolated from tuberculosis patients in the Eastern Cape province South Africa.

BACKGROUND: Tuberculosis (TB) in both animals and humans is caused by Mycobacterium tuberculosis complex (MTBC) primarily transmitted by inhalation of aerosolized droplets containing the organism. Multi-drug resistance (MDR) and extensive drug resistance (XDR) are evolutionary features of Mycobacterium tuberculosis to subvert the antibiotic regimes in place. The heavy burden of TB worsened by HIV endemic in South Africa motivated for the investigation of MTBC prevalence among TB patients in Port Elizabeth and the amplification and sequencing of the DNA amplicons known to confer resistance to TB drugs. METHODS: Three thousand eight hundred and ten (3810) sputum specimens were processed and DNA was isolated from sputum specimens collected from different hospitals and health care places in the Eastern Cape Province, South Africa. DNA was amplified using the Seeplex® MTB Nested ACE detection assay. The agar-dilution proportion method was used to perform drug-sensitivity testing using 7H10 Middlebrook medium. Target genes known to confer resistance to first and second-line drugs were amplified and the amplicons sequenced. RESULTS: One hundred and ninety (5%) DNA samples tested positive for MTBC and from the resistant profiles of the 190 positive samples, we noted that multidrug-resistant TB was identified in 189 (99.5%) with 190 (100%) patients infected with MTB resistant to isoniazid and 189 (99.5%) having MTB resistant to rifampicin. Other percentages of drug resistance observed including 40% pre-XDR and 60% of XDR. CONCLUSION: This study provides valuable data on the different kinds of mutations occurring at various target loci in resistant MTBC strains isolated from samples obtained from the Eastern Cape Province. The results obtained reveal a high incidence of MDR amongst the positive samples from Eastern Cape Province, South Africa.

Heterologous expression and purification of biologically active domains 3 and 4 of human polymeric immunoglobulin receptor and its interaction with choline binding protein A of Streptococcus pneumoniae.

Streptococcus pneumoniae, one of the common causes of pneumonia, colonises the epithelium via the interaction between a choline binding protein of S. pneumoniae and the human polymeric immunoglobulin receptor (pIgR). One of the functions of pIgR is to mediate the transcytosis of polymeric immunoglobulins from the basolateral to the apical surface of epithelial cells. S. pneumoniae invades human epithelial cells by exploiting the transcytosis machinery. Due to an increase in the prevalence of antibiotic resistant strains of S. pneumoniae, and the limitations and expense of the vaccines available, extensive research may provide insights into the potential of new therapeutic regimes. This study investigated the potential of pIgR domains as an alternative non-antibiotic immune therapy for treating pneumonia. The aim was to determine the binding affinity of recombinant D3D4 protein, the domains of pIgR responsible for binding S. pneumoniae, to recombinant R1R2 repeat domains of choline binding protein A of S. pneumoniae. Biologically active recombinant D3D4 was produced in Escherichia coli using a gel filtration chromatography refolding method, a novel approach for the refolding of pIgR domains, after the purification of inclusion bodies using nickel affinity chromatography. Surface Plasmon resonance (SPR) spectroscopy showed that purified recombinant D3D4 binds recombinant R1R2 with an equilibrium dissociation constant (KD) of 3.36×10(-7)M.

Tetracycline Resistance Genes of Ureaplasmas

There is limited information in the medical setting on antimicrobial susceptibilities and resistance development in ureaplasmas. The study investigated tetracycline and doxycycline resistance in clinical isolates of Ureaplasma parvum and Ureaplasma urealyticum. Culture with species PCR confirmatory techniques were applied to 191 endocervical specimens collected during the period January-March 2006. MIC determinations were performed by microbroth dilution with tetM resistance and int-Tn genes characterised employing PCR and sequencing. Sixty-six Ureaplasma cultures (35 U. parvum; 9 U. urealyticum; 22 U. parvum + U. urealyticum) were obtained. On screening the Ureaplasma cultures; tetM gene regions were demonstrated from both tetracycline-susceptible and -resistant ureaplasmas. Seven isolates [U. parvum (6); U. urealyticum (1)] were resistant to tetracycline with dual doxycycline resistance observed in three strains. Int-Tn gene characterisation of the seven tetracycline-resistant strains revealed three types were present indicating transposons from different origins had integrated into Ureaplasma genomes. TetM sequences of five tetracycline-resistant strains were seen to be highly mosaic in structure. The finding of transposon and/or tetM regions in all Ureaplasma cultures investigated with or without full expression of tetracycline resistance; in conjunction with tetM and int-Tn gene mosaic/diversity; verifies that ureaplasmas undergo extensive genetic exchange of transposon/resistance genes with concomitant genomic remodelling

Neurocysticercosis in patients presenting with epilepsy at St Elizabeth's Hospital, Lusikisiki.

OBJECTIVE: To survey the prevalence of neurocysticercosis in patients treated for epilepsy in Lusikisiki, E Cape. DESIGN: This was a descriptive study. Variables considered were age, gender, symptoms and type of seizure, serological data, electroencephalogram and computed tomography (CT) findings, treatment, and ownership of pigs. Prevalence and risk assessment were determined by statistical analysis. SUBJECTS AND SETTING: 113 patients presenting with epilepsy at St Elizabeth's Hospital, Lusikisiki, E Cape. OUTCOME MEASURES: Prevalence of neurocysticercosis in patients presenting with epilepsy. RESULTS: CT scans indicated that 61.1% of the patients had neurocysticercosis-associated epilepsy, the prevalence being highest in the 10 - 19-year-old age group (12.4% of the total). Neuro-imaging studies showed that calcified lesions were frequent, while active lesions were often associated with positive serological results. Non-commercial pig farming was not a significant risk factor for neurocysticercosis in the sample studied. CONCLUSION: Neurocysticercosis was common in patients presenting with and undergoing treatment for epilepsy.

An investigation of the role of vitamin E in the protection of mice against microcystin toxicity.

The presence of cyanobacterial toxins in drinking and recreational waters represents a potential public health risk. Microcystin-LR (MC-LR) is a potent cyclic heptapeptide hepatotoxin produced by the blue-green alga Microcystis aeruginosa. Chemoprotectant studies have indicated that membrane-active antioxidants such as vitamin E may offer protection against microcystin toxicity. This study investigated the effect of vitamin E supplementation on microcystin toxicity in mouse liver. Groups of mice were fed vitamin E supplements (8.33 or 33.3 U/mouse/day) for 4 weeks, with intraperitoneal doses of MC-LR extract (70% LD(50)) every 3 days from day 8. The potential benefits of vitamin E were evaluated based on lipid peroxidation, alanine transaminase (ALT), and glutathione S-transferase (GST) levels. Vitamin E supplementation at 33.3 U/mouse/day offered some protection against lipid peroxidation induced by repeated exposure to MC-LR extract and limited both the toxin-induced increase in ALT leakage and decrease in GST activity. Vitamin E supplementation at 66.6 U/mouse/day significantly increased the time to death and reduced the increase in liver percentage body weight induced in mice given a lethal dose challenge of MC-LR extract. Therefore, vitamin E, taken as a dietary supplement, may have a protective effect against chronic exposure to MC-LR.