HIV-1 subtype C Envelope function becomes less sensitive to N-glycosylation deletion during disease progression

Objective As part of a larger study to understand how Envelope N-glycosylation influences HIV-1 pathogenesis, we selected a participant infected with a single Subtype C variant and determined whether deletion of specific potential N-glycan sites (PNGs) impacted Envelope function longitudinally. Results We deleted five PNGs previously linked to HIV-1 transmission of two matched Envelope clones representing variants at 5 and 173 weeks post-infection. The transmitted founder (TF) had significantly better pseudovirus entry efficiency than the chronic infection (CI) variant. Deletion of all PNGs significantly reduced TF entry efficiency, binding to dendritic cell-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) receptor and trans-infection. However, mutational analysis did not affect the phenotype of the CI Envelope to the same extent. Notably, deletion of the PNGs at N241 and N448 had no effect on CI Envelope function, suggesting that some PNGs might only be important during acute infection. Therefore, vaccines that elicit antibodies against N-glycans important for TF Envelope function could drive the loss of PNGs during immune escape, abrogating viral replication. Conversely, changes in N-glycosylation might have no effect on some variants, reducing vaccine efficacy. This finding highlights the need for further investigation into the role of Envelope N-glycosylation in HIV-1 pathogenesis

Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa

INTRODUCTION : We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and positive admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. METHODS : Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and whose death was judged SARS-CoV-2 related by attending physician. FINDINGS : 315 570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3 548 738 tests and 1.6% of all children in the country. Of children tested, 46 137 (14.6%) were positive. Children made up 2.9% (n = 2007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals [CI] 1.08–4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08–15.54)], age 10–14 years [aOR 4.20 (95% CI1.07–16.44)], age 15–17 years [aOR 4.86 (95% 1.28–18.51)] vs age 1–4 years; admission to a public hospital [aOR 5.07(95% 2.01–12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19–34.89)] vs none. CONCLUSIONS : Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years, those in certain provinces and those with underlying conditions should be considered for increased testing and vaccination.SUPPORTING INFORMATION : TABLE S1: Description of SARS-CoV-2 rRT-PCR positive children <18 years in South Africa, 1 March 2020–19 September 2020 (N = 45 609). TABLE S2: Description of SARS-CoV-2 rRT-PCR positive hospital admissions among children <18 years in South Africa by province, 1 March 2020–19 September 2020 (N = 2007). TABLE S3: Distribution of non-missing variables among children with complete follow up and included in multivariable model (N = 1817). TABLE S4: Factors associated with in-hospital death among SARS-CoV-2 rRT-PCR positive admissions in children <18 years, South Africa, 1 March 2020–19 September 2020. FIGURE S1: Number of SARS-CoV-2 rRT-PCR tests*, percent positive tests and associated- hospital admissions among children <18 years by province and epidemiology week, South Africa, 1 March 2020–19 September 2020.National Department of Health, Republic of South Africahttp://wileyonlinelibrary.com/journal/irvhj2022School of Health Systems and Public Health (SHSPH

Hospital-associated methicillin-resistant Staphylococcus aureus: A cross-sectional analysis of risk factors in South African tertiary public hospitals.

Hospital-associated methicillin-resistant S. aureus (HA-MRSA) remains a significant cause of morbidity and mortality worldwide. We conducted a study to determine risk factors for HA-MRSA in order to inform control strategies in South Africa.We used surveillance data collected from five tertiary hospitals in Gauteng and Western Cape provinces during 2014 for analysis. A case of HA-MRSA was defined as isolation of MRSA from a blood culture 48 hours after admission and/or if the patient was hospitalised in the six months prior to the current culture. Multivariable logistic regression modelling was used to determine risk factors for HA-MRSA.Of the 9971 patients with positive blood cultures, 7.7% (772) had S. aureus bacteraemia (SAB). The overall prevalence of MRSA among those with SAB was 30.9% (231/747; 95% confidence interval [CI] 27.6%- 34.3%). HA-MRSA infections accounted for 28.3% of patients with SAB (207/731; 95% CI 25.1%- 31.7%). Burns (adjusted odds ratio [aOR] 12.7; 95% CI 4.7-34.4), age ≤1 month (aOR 8.7; 95% CI 3.0-24.6), residency at a long-term care facility (aOR 5.2; 95% CI, 1.5-17.4), antibiotic use within two months of the current SAB episode (aOR 5.1; 95% CI 2.8-9.1), hospital stay of 13 days or more (aOR 2.8; 95% CI 1.3-5.6) and mechanical ventilation (aOR 2.2; 95% CI 1.07-4.6), were independent risk factors for HA-MRSA infection.The prevalence of MRSA remains high in South African tertiary public hospitals. Several identified risk factors of HA-MRSA infections should be considered when instituting infection and prevention strategies in public-sector hospitals, including intensifying the implementation of antimicrobial stewardship programmes. There is an urgent need to strengthen infection prevention and control in burn wards, neonatal wards, and intensive care units which house mechanically ventilated patients

Selective transmission of some HIV-1 subtype C variants might depend on Envelope stimulating dendritic cells to secrete IL-10.

Envelope (Env) phenotype(s) that provide transmitted founders (TF) with a selective advantage during HIV-1 transmission would be the ideal target for preventative therapy. We generated Env clones from four individuals infected with a single virus and one participant infected with multiple variants at transmission and compared phenotype with matched Envs from chronic infection (CI). When we determined whether pseudovirus (PSV) of the five TF and thirteen matched CI Env clones differed in their ability to 1) enter TZM-bl cells, 2) bind DC-SIGN, and 3) trans-infect CD4+ cells there was no association between time post-infection and variation in Env phenotype. However, when we compared the ability of PSV to induce monocyte-derived dendritic cells (MDDCs) to secrete Interleukin-10 (IL-10), we found that only TF Envs from single variant transmission cases induced MDDCs to secrete either higher or similar levels of IL-10 as the CI clones. Furthermore, interaction between MDDC DC-SIGN and Env was required for secretion of IL-10. When variants were grouped according to time post-infection, TF PSV induced the release of higher levels of IL-10 than their CI counterparts although this relationship varied across MDDC donors. The selection of variants during transmission is therefore likely a complex event dependent on both virus and host genetics. Our findings suggest that, potentially due to overall variation in N-glycosylation across variants, nuanced differences in binding of TF Env to DC-SIGN might trigger alternative DC immune responses (IRs) in the female genital tract (FGT) that favour HIV-1 survival and facilitate transmission

Candida auris Clinical Isolates Associated with Outbreak in Neonatal Unit of Tertiary Academic Hospital, South Africa

Candida auris was first detected at a university-affiliated hospital in Johannesburg, South Africa, in 2009. We used whole-genome sequencing to describe the molecular epidemiology of C. auris in the same hospital during 2016–2020; the neonatal unit had a persistent outbreak beginning in June 2019. Of 287 cases with culture-confirmed C. auris infection identified through laboratory surveillance, 207 (72%) had viable isolates and 188 (66%) were processed for whole-genome sequencing. Clade III (118/188, 63%) and IV (70/188, 37%) isolates co-circulated in the hospital. All 181/188 isolates that had a fluconazole MIC >32 µg/mL had ERG11 mutations; clade III isolates had VF125AL substitutions, and clade IV isolates had K177R/N335S/E343D substitutions. Dominated by clade III, the neonatal unit outbreak accounted for 32% (91/287) of all cases during the study period. The outbreak may have originated through transmission from infected or colonized patients, colonized healthcare workers, or contaminated equipment/environment

The number of SAB cases at five hospitals in Gauteng and Western Cape during 2014.

<p>AST, antimicrobial susceptibility testing results; SAB, <i>S</i>. <i>aureus</i> bacteraemia; CA, community-associated; HA, hospital-associated; MSSA, methicillin sensitive <i>S</i>. <i>aureus</i>; MRSA, methicillin-resistant <i>S</i>. <i>aureus</i>.</p

Multivariable analysis of risk factors for HA-MRSA infection in comparison to HA-MSSA infection among hospitalised patients in Gauteng and Western Cape during 2014.

<p>Multivariable analysis of risk factors for HA-MRSA infection in comparison to HA-MSSA infection among hospitalised patients in Gauteng and Western Cape during 2014.</p

Rates of SAB at five hospitals in Gauteng and Western Cape during 2014.

<p>Rates of SAB at five hospitals in Gauteng and Western Cape during 2014.</p

Univariate analysis of risk factors for HA-MRSA infection in comparison to HA-MSSA infection among hospitalised patients in Gauteng and Western Cape during 2014.

<p>Univariate analysis of risk factors for HA-MRSA infection in comparison to HA-MSSA infection among hospitalised patients in Gauteng and Western Cape during 2014.</p

High Prevalence of Candida auris Colonization during Protracted Neonatal Unit Outbreak, South Africa

One third of patients were colonized by Candida auris during a point-prevalence survey in a neonatal unit during an outbreak in South Africa. The sensitivity of a direct PCR for rapid colonization detection was 44% compared with culture. The infection incidence rate decreased by 85% after the survey and implementation of isolation/cohorting