Search

Background: Identifying risk factors for respiratory syncytial virus (RSV)–associated severe acute respiratory illness (SARI) will assist with targeting vaccine interventions. Methods: Using surveillance data from South Africa (2012–2018), we compared the characteristics of individuals with RSV-associated influenza-like illness (ILI) (reference group) to those with RSV-associated SARI to describe factors associated with SARI using a multivariable analysis. Results: RSV was detected in 6% (483/7792) of ILI cases and 15% (844/5672) of SARI cases. Factors associated with SARI in children included age < 2 months, compared to age 2–4 years (adjusted odds ratio (aOR) 54.4; 95% confidence interval (CI) 23.5–125.8), malnutrition (aOR 1.9; 95% CI 1.2–3.2), prematurity (aOR 2.4; 95% CI 1.3–4.6) and living with HIV (LWH) (aOR 22.5; 95% CI 2.9–174.3). In individuals ≥ 5 years, factors associated with SARI included age ≥ 65 years compared to age 5–24 years (aOR 10.7; 95% CI 1.1–107.5), symptom duration ≥ 5 days (aOR 2.7; 95% CI 1.1–6.3), underlying illness (aOR 2.7; 95% CI 1.5–26.1) and LWH (aOR 16.8, 95% CI: 4.8–58.2). Conclusion: Individuals at the extremes of age and those with identified risk factors might benefit most from RSV prevention interventions. Clinical trial number: Not applicable, this is not a clinical trial. [ABSTRACT FROM AUTHOR]

Purpose: Recent observational studies have indicated the efficacy of stent retriever devices for the treatment of posthemorrhagic cerebral vasospasm (CVS), both by deployment and on-site withdrawal into the microcatheter (stent angioplasty, SA) and deployment followed by retraction through the target vessel similar to thrombectomy (StentRetraction to reLieve Arterial Cerebral vaSospasm caused by SAH, Stent-ReLACSS). This article reports the findings with each application of pRESET and pRELAX in the treatment of CVS. Methods: We retrospectively enrolled 25 patients with severe CVS following aneurysmal subarachnoid hemorrhage. For the SA group, a stent retriever or a pRELAX was temporarily deployed into a narrow vessel segment and retrieved into the microcatheter after 3 min. For the Stent-ReLACSS group, a pRELAX was temporarily deployed into a narrow vessel and pulled back unfolded into the internal carotid artery. If intra-arterial vasodilators were administered, they were given exclusively after mechanical vasospasmolysis to maximize the effectiveness of the stent treatment. Results: In this study fifteen patients and 49 vessels were treated with SA. All were technically successful without periprocedural complications; however, 8/15 patients (53.3%) required additional treatment of the CVS. A total of 10 patients and 23 vessel segments were treated with Stent-ReLACSS. All maneuvers were technically successful without periprocedural complications and all vessels showed significant angiographic improvement. No recurrent CVS requiring further endovascular treatment occurred in-hospital, and neither territorial ischemia in the treated vessels nor vascular injury were observed in follow-up angiography. Conclusion: Based on the presented data it appears that Stent-ReLACSS with pRELAX does not pose any additional risks when used to treat CVS and might be superior to SA, especially concerning mid-term and long-term efficacy. The mechanism of action may be an effect on the endothelium rather than mechanical vasodilation. As many patients with CVS are diagnosed too late, prophylactic treatment of high-risk patients (e.g., poor grade, young, female) is potentially viable. [ABSTRACT FROM AUTHOR]

A globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www. gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale. [ABSTRACT FROM AUTHOR]

There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of >2 million adults during 2020–2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57–94 and 49–95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity. [ABSTRACT FROM AUTHOR]

Background: Identifying children at risk for severe COVID‐19 disease from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) may guide future mitigation interventions. Using sentinel surveillance data, we aimed to identify risk factors for SARS‐CoV‐2–associated hospitalisation among patients aged ≤ 18 years with respiratory illness. Methods: From April 2020 to March 2022, patients meeting study case definitions were enrolled at four outpatient influenza‐like illness (ILI) and five inpatient severe respiratory infection (SRI) surveillance sites and tested for SARS‐CoV‐2 infection using polymerase chain reaction (PCR). Each ILI clinic shared a catchment area with its corresponding SRI hospital. Potential risk factors for SARS‐CoV‐2–associated hospitalisation were analysed using multivariable logistic regression by comparing inpatient versus outpatient SARS‐CoV‐2 cases. Results: Of 4688 participants aged ≤ 18 years, 4556 (97%) with complete PCR and HIV data were included in the analysis. Among patients with ILI and SRI, 92/1145 (8%) and 154/3411 (5%) tested SARS‐CoV‐2 positive, respectively. Compared to outpatients, hospitalised SARS‐CoV‐2 cases were associated with age < 6 months ([adjusted odds ratio (aOR) 8.0, 95% confidence interval (CI) 2.7–24.0] versus 1–4 years); underlying medical condition other than HIV [aOR 5.8, 95% CI 2.3–14.6]; laboratory‐confirmed Omicron BA.1/BA.2 or Delta variant ([aOR 4.9, 95% CI 1.7–14.2] or [aOR 2.8, 95% CI 1.1–7.3] compared to ancestral SARS‐CoV‐2); and respiratory syncytial virus coinfection [aOR 6.2, 95% CI 1.0–38.5]. Conclusion: Aligning with previous research, we identified age < 6 months or having an underlying condition as risk factors for SARS‐CoV‐2–associated SRI hospitalisation and demonstrated the potential of sentinel surveillance to monitor COVID‐19 in children. [ABSTRACT FROM AUTHOR]

Purpose: Flow-diverter (FD) stents have become an established treatment for intracranial aneurysms in recent years, but their use for aneurysms in distal cerebral vessels with small carrier vessel diameters remains controversial. This study describes the method and mid- and long-term outcomes of FD treatment of distal anterior cerebral artery aneurysms (DACAAs) at two neurointerventional centers, to elucidate this topic and provide more in-depth data. Methods: Data for all patients at two neurointerventional centers who were treated with FDs for DACAAs in the pericallosal and supracallosal segment of the anterior cerebral artery were retrospectively analyzed. Data on periprocedural complications, and short-, mid- and long-term follow-up findings were recorded. Results: Forty-one patients were eligible for inclusion in the study. Three FD models were used, one of which had an anti-thrombotic coating. Two periprocedural complications (5%) occurred but did not cause a change in the mRS. In the long-term follow-up, at 29 months and beyond, 83% of assessable patients showed complete occlusion of the aneurysms without new neurological deficits. Conclusion: FDs are a safe and effective treatment approach for DACAAs. This study indicated a low risk of complications, and high closure rates in short-, mid- and long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Data on the characteristics of individuals with mild and asymptomatic infections with different SARS-CoV-2 variants are limited. We therefore compared the characteristics of individuals infected with ancestral, Beta and Delta SARS-CoV-2 variants in South Africa. Methods: We conducted a prospective cohort study in a rural and an urban site during July 2020-August 2021. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Differences in demographic and clinical characteristics, shedding and cycle threshold (Ct) value of infection episodes by variant were evaluated using multinomial regression. Overall and age-specific incidence rates of infection were compared by variant. Results: We included 1200 individuals from 222 households and 648 rRT-PCR-confirmed infection episodes (66, 10% ancestral, 260, 40% Beta, 322, 50% Delta). Symptomatic proportion was similar for ancestral (7, 11%), Beta (44, 17%), and Delta (46, 14%) infections (p=0.4). After accounting for previous infection, peak incidence shifted to younger age groups in successive waves (40-59 years ancestral, 19-39 years Beta, 13-18 years Delta). On multivariable analysis, compared to ancestral, Beta infection was more common in individuals aged 5-12 years (vs 19-39)(adjusted odds ratio (aOR) 2.6, 95% confidence interval (CI)1.1-6.6) and PCR cycle threshold (Ct) value <30 (vs >35)(aOR 3.2, 95%CI 1.3-7.9), while Delta was more common in individuals aged <5 (aOR 6.7, 95%CI1.4-31.2) and 5-12 years (aOR 6.6 95%CI2.6-16.7)(vs 19-39) and Ct value <30 (aOR 4.5, 95%CI 1.3-15.5) and 30-35 (aOR 6.0, 95%CI 2.3-15.7)(vs >35). Conclusions: Consecutive SARS-CoV-2 waves with Beta and Delta variants were associated with a shift to younger individuals. Beta and Delta infections were associated with higher peak viral loads, potentially increasing infectiousness. [ABSTRACT FROM AUTHOR]

Background Acute stroke treatment with intracranial thrombectomy and treatment of ipsilateral carotid artery stenosis/occlusion (“tandem lesion”, TL) in one session is considered safe. However, the risk of stent restenosis after TL treatment is high, and antiplatelet therapy (APT) preventing restenosis must be well balanced to avoid intracranial hemorrhage. We investigated the safety and 90-day outcome of patients receiving TL treatment under triple-APT, focused on stent-patency and possible disadvantageous comorbidities. Methods Patients receiving TL treatment in the setting of acute stroke between 2013 and 2022 were analyzed regarding peri-/postprocedural safety and stent patency after 90 days. All patients received intravenous eptifibatide and acetylsalicylic acid and one of the three drugs prasugrel, clopidogrel, or ticagrelor. Duplex imaging was performed 24 h after treatment, at discharge and 90 days, and digital subtraction angiography was performed if restenosis was suspected. Results 176 patients were included. Periprocedural complications occurred in 2.3% of the patients at no periprocedural death, and in-hospital death in 13.6%. Discharge mRS score was maintained or improved at the 90-day follow-up in 86%, 4.54% had an in-stent restenosis requiring treatment at 90 days. No recorded comorbidity considered disadvantageous for stent patency showed statistical significance, the duration of the endovascular procedure had no significant effect on outcome. Conclusion In our data, TL treatment with triple APT resulted in a low restenosis rate, low rates of sICH and a comparably high number of patients with favorable outcome. Aggressive APT in the initial phase may therefore have the potential to prevent recurrent stroke better than restrained platelet inhibition. Comorbidities did not influence stent patency. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.There is limited data on immune factors contributing to SARS-CoV-2 viral clearance in people living with HIV. Here, the authors show that re-emergence of the neutralizing antibody response may be key to clearing persistent SARS-CoV-2 infection in ART-mediated recovery from immunosuppression in advanced HIV disease. [ABSTRACT FROM AUTHOR]

Purpose: Endovascular and surgical treatments of stenosis of the extracranial internal carotid artery (ICA) are common procedures, yet both introduce a risk of restenosis due to endothelial hyperplasia. Drug-coated balloons (DCBs) are designed to decrease neointimal hyperplasia, however rarely used in the neurovascular setting. This study retrospectively analyzes mid-term results of DCB-treated in-stent restenosis (ISR) of the ICA. Materials and Methods: The medical history, comorbidities, and periprocedural data of patients receiving DCB treatment for > 50% ISR of the ICA after carotid artery stenting were analyzed. Follow-up after DCB treatment was performed with Doppler ultrasound. Suspicious cases were checked with CT- or MR-angiography and—if there was agreement between the modalities—validated with digital subtraction angiography. Potential risk factors for restenosis and differences in outcomes after PTA with three types of DCB balloons were evaluated. Results: DCB treatment was performed in 109 cases, 0.9% of which involved in-hospital major stroke; no minor strokes occurred. A total of 17 patients (15.6%) had recurrent ISR after DCB treatment, after a mean time of 30.2 months (7–85 months). Tobacco use was significantly associated with a higher incidence of recurrent ISR. Conclusion: DCB angioplasty for ISR is an effective treatment that may delay and decrease restenosis. Treating comorbidities and adopting lifestyle changes may additionally help prevent ISR. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate long-term outcomes in patients who underwent carotid artery stenting (CAS) for symptomatic or asymptomatic high-grade stenosis. Methods: A total of 1158 patients (asymptomatic, n = 636; symptomatic, n = 522) underwent CAS at our center between 2009 and 2020. A total of 560 patients or contacts (asymptomatic, n = 316; symptomatic, n = 244) were interviewed by telephone to evaluate long-term outcomes with a mean follow-up of 5 years. Mortality from all causes, myocardial infarction, and stroke, as well as comorbidities influencing their occurrence, including overall survival and stroke-free survival, were examined. Results: The overall survival rate for all-cause mortality was 91.6% at 1 year, 77.1% at 5 years, and 55.7% at 10 years. A total of 39 (6.9%) patients had an ischemic stroke during long-term follow-up. The stroke-free survival rates at 1 year, 5 years, and 10 years were 97.9%, 92.7%, and 86.6%, respectively. Stroke-free survival and overall survival did not differ significantly between the symptomatic and asymptomatic groups (overall survival, p = 0.304; stroke-free survival, p = 0.336). Regular physical activity reduced the risk of stroke and death and was associated with better long-term clinical outcomes. Age at treatment and diabetes mellitus were statistically significantly associated with death during follow-up. Conclusion: Long-term follow-up data confirmed the effectiveness and durability of CAS as a therapy option for both symptomatic and asymptomatic patients. In patient selection for CAS, special consideration should be paid to patient age, ability to engage in physical activity, and diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: The South African government employed various nonpharmaceutical interventions (NPIs) to reduce the spread of SARS‐CoV‐2. Surveillance data from South Africa indicates reduced circulation of respiratory syncytial virus (RSV) throughout the 2020–2021 seasons. Here, we use a mechanistic transmission model to project the rebound of RSV in the two subsequent seasons. Methods: We fit an age‐structured epidemiological model to hospitalization data from national RSV surveillance in South Africa, allowing for time‐varying reduction in RSV transmission during periods of COVID‐19 circulation. We apply the model to project the rebound of RSV in the 2022 and 2023 seasons. Results: We projected an early and intense outbreak of RSV in April 2022, with an age shift to older infants (6–23 months old) experiencing a larger portion of severe disease burden than typical. In March 2022, government alerts were issued to prepare the hospital system for this potentially intense outbreak. We then assess the 2022 predictions and project the 2023 season. Model predictions for 2023 indicate that RSV activity has not fully returned to normal, with a projected early and moderately intense wave. We estimate that NPIs reduced RSV transmission between 15% and 50% during periods of COVID‐19 circulation. Conclusions: A wide range of NPIs impacted the dynamics of the RSV outbreaks throughout 2020–2023 in regard to timing, magnitude, and age structure, with important implications in a low‐ and middle‐income countries (LMICs) setting where RSV interventions remain limited. More efforts should focus on adapting RSV models to LMIC data to project the impact of upcoming medical interventions for this disease. [ABSTRACT FROM AUTHOR]

Background: Large-scale prevention of respiratory syncytial virus (RSV) infection may have ecological consequences for co-circulating pathogens, including influenza. We assessed if and for how long RSV infection alters the risk for subsequent influenza infection. Methods: We analysed a prospective longitudinal cohort study conducted in South Africa between 2016 and 2018. For participating households, nasopharyngeal samples were taken twice weekly, irrespective of symptoms, across three respiratory virus seasons, and real-time polymerase chain reaction (PCR) was used to identify infection with RSV and/or influenza. We fitted an individual-level hidden Markov transmission model in order to estimate RSV and influenza infection rates and their interdependence. Results: Of a total of 122,113 samples collected, 1265 (1.0%) were positive for influenza and 1002 (0.8%) positive for RSV, with 15 (0.01%) samples from 12 individuals positive for both influenza and RSV. We observed a 2.25-fold higher incidence of co-infection than expected if assuming infections were unrelated. We estimated that infection with influenza is 2.13 (95% CI 0.97–4.69) times more likely when already infected with, and for a week following, RSV infection, adjusted for age. This equates to 1.4% of influenza infections that may be attributable to RSV in this population. Due to the local seasonality (RSV season precedes the influenza season), we were unable to estimate changes in RSV infection risk following influenza infection. Conclusions: We find no evidence to suggest that RSV was associated with a subsequent reduced risk of influenza infection. Instead, we observed an increased risk for influenza infection for a short period after infection. However, the impact on population-level transmission dynamics of this individual-level synergistic effect was not measurable in this setting. [ABSTRACT FROM AUTHOR]

As global SARS-CoV-2 burden and testing frequency have decreased, wastewater surveillance has emerged as a key tool to support clinical surveillance efforts. The aims of this study were to identify and characterize SARS-CoV-2 variants in wastewater samples collected from urban centers across South Africa. Here we show that wastewater sequencing analyses are temporally concordant with clinical genomic surveillance and reveal the presence of multiple lineages not detected by clinical surveillance. We show that wastewater genomics can support SARS-CoV-2 epidemiological investigations by reliably recovering the prevalence of local circulating variants, even when clinical samples are not available. Further, we find that analysis of mutations observed in wastewater can provide a signal of upcoming lineage transitions. Our study demonstrates the utility of wastewater genomics to monitor evolution and spread of endemic viruses. SARS-CoV-2 wastewater surveillance could provide an important means of monitoring population trends as clinical testing decreases. Here, the authors demonstrate the use of wastewater to track variants of concern through a sentinel wastewater surveillance system in South Africa. [ABSTRACT FROM AUTHOR]

Healthcare utilization surveys contextualize facility-based surveillance data for burden estimates. We describe healthcare utilization in the catchment areas for sentinel site healthcare facilities during the first year of the COVID-19 pandemic. We conducted a cross-sectional healthcare utilization survey in households in three communities from three provinces (KwaZulu-Natal, Western Cape and North West). Field workers administered structured questionnaires electronically with the household members reporting influenza-like illness (ILI) in the past 30 days or severe respiratory illness (SRI) since March 2020. Multivariable logistic regression was used to identify factors associated with healthcare utilization among individuals that reported illness. From November 2020 through April 2021, we enrolled 5804 households and 23,003 individuals. Any respiratory illness was reported by 1.6% of individuals; 0.7% reported ILI only, 0.8% reported SRI only, and 0.1% reported both ILI and SRI. Any form of medical care was sought by 40.8% (95% CI 32.9% - 49.6%) and 71.3% (95% CI 63.2% - 78.6%) of individuals with ILI and SRI, respectively. On multivariable analysis, respiratory illness was more likely to be medically attended for individuals at the Pietermaritzburg site (aOR 3.2, 95% CI 1.1–9.5, compared to Klerksdorp), that were underweight (aOR 11.5, 95% CI 1.5–90.2, compared to normal weight), with underlying illness (aOR 3.2, 95%CI 1.2–8.5), that experienced severe illness (aOR 4.8, 95% CI 1.6–14.3) and those with symptom duration of ≥10 days (aOR 7.9, 95% CI 2.1–30.2, compared to <5 days). Less than half of ILI episodes and only 71% of SRI episodes were medically attended during the first two COVID-19 waves in South Africa. Facility-based data may underestimate disease burden during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae bacteria cause life-threatening invasive pneumococcal disease (IPD), including meningitis. Pneumococci are classified into serotypes, determined by differences in capsular polysaccharide and both serotype and pneumolysin toxin are associated with disease severity. Strains of serotype 8, ST 53, are increasing in prevalence in IPD in several countries. Methods: Here we tested the virulence of such an isolate in a rat model of meningitis in comparison with a serotype 15B and a serotype 14 isolate. All three were isolated from meningitis patients in South Africa in 2019, where serotype 8 is currently the most common serotype in IPD. Introduction: Streptococcus pneumoniae bacteria cause life-threatening invasive pneumococcal disease (IPD), including meningitis. Pneumococci are classified into serotypes, determined by differences in capsular polysaccharide and both serotype and pneumolysin toxin are associated with disease severity. Strains of serotype 8, ST 53, are increasing in prevalence in IPD in several countries. Methods: Here we tested the virulence of such an isolate in a rat model of meningitis in comparison with a serotype 15B and a serotype 14 isolate. All three were isolated from meningitis patients in South Africa in 2019, where serotype 8 is currently the most common serotype in IPD. Results and Discussion: Only the serotype 8 isolate was hypervirulent causing brain injury and a high mortality rate. It induced a greater inflammatory cytokine response than either the serotype 15B or 14 strain in the rat model and from primary mixed-glia cells isolated from mouse brains. It had the thickest capsule of the three strains and produced non-haemolytic pneumolysin. Pneumolysin-sequestering liposomes reduced the neuroinflammatory cytokine response in vitro indicating that liposomes have the potential to be an effective adjuvant therapy even for hypervirulent pneumococcal strains with non-haemolytic pneumolysin. [ABSTRACT FROM AUTHOR]

Purpose: In elective carotid artery stenting (CAS), antiplatelet therapy (APT) is crucial. Several international societies have provided guidelines for loading time and dosage in endovascular treatment; however, no recommendations have been made for urgent, nonthrombectomy-associated CAS without adequate loading time. Here, we investigated the short-term outcomes for APT-naïve patients receiving "crash loading" (CL) on the day of intervention, compared with those for patients wi APT onset 3–5 days (semi-CL) or more than 5 days before CAS (EL). Methods: Outcomes of patients 30 days after CAS were evaluated in terms of the rates of in-stent thrombus, re-stenosis, stroke, hemorrhagic and thrombotic events, other periprocedural occurrences, in-hospital death and CAS-associated death. Patients' biological, pathological and hemostatic factors were recorded and compared. Results: A total of 1158 patients who received CAS at the authors' neuroradiology institution were analyzed: 275 EL, 846 semi-CL, and 37 CL. The patients receiving CL had the lowest rate of stroke, but the highest rates of CAS-associated and in-hospital deaths, although the deaths were not necessarily associated with APT. In-stent thrombosis was the highest in the semi-CL group. The rates and types of periprocedural occurrences favored the CL group. Conclusion: With the medical regimen used in this study, urgent CAS with CL APT did not produce more ischemic, thrombotic and hemorrhagic complications than longer loading times. However, careful patient selection might be crucial and adequate loading times should remain the standard of care. [ABSTRACT FROM AUTHOR]

Introduction: South Africa has the largest number of confirmed cases of COVID-19 in Africa. Data to inform public health strategies to mitigate the spread of new variants and severity of disease is needed, including information on knowledge, attitudes and practices (KAP) regarding COVID-19, factors associated with intention to get vaccinated, and viewpoints on reliable sources of data. Methods: we investigated these topics as part of the COVID-19 healthcare utilization and seroprevalence (HUTS) cross-sectional survey in three communities in South Africa: Mitchell's Plain (Western Cape Province), Pietermaritzburg (KwaZulu-Natal Province) and Klerksdorp (North West Province) during and after the second wave of COVID-19 prior to vaccine availability. Results: primary caregivers from 5799 households participated in the study, 41.1% from Pietermaritzburg, 34.2% from Klerksdorp and 24.7% from Mitchells Plain. Two-thirds and 94.7% of respondents had correct knowledge on the cause and spread of COVID-19, respectively. Knowledge measures were significantly associated with age less than 65 years, the highest level of education and site (Mitchells Plain). Desired preventive behaviors were associated with higher socio-economic status. While 64.7% of people intended to get vaccinated, those over 64 years of age were more likely to intend to vaccinate (aOR: 1.25, 95% CI: 1.06-1.47). Vaccine intention related to protection of self (58.4%) and family (40.0%). The most trusted source of COVID-19 information was television (59.3%) followed by radio (20.0%). Conclusion: these data can be used to design targeted public health campaigns for the current COVID-19 and future epidemics, ensuring that socio-economic constraints and preference for trusted information are considered. [ABSTRACT FROM AUTHOR]

Background: Data on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated the cost of RSV-associated illness in fine age bands to allow more accurate cost-effectiveness models to account for a limited duration of protection conferred by short- or long-acting interventions. Methods: We conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests, and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalizations or clinic visits; the PDE was multiplied by the number of days of care to provide a case cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged < 1 year and as a single group for children aged 1–4 years. We then applied our data to a modified version of the World Health Organization tool for estimating the mean annual national cost burden, including medically and non-medically attended RSV-associated illness. Results: The estimated mean annual cost of RSV-associated illness in children aged < 5 years was US dollars ($)137,204,393, of which 76% ($111,742,713) were healthcare system incurred, 6% ($8,881,612) were out-of-pocket expenses and 13% ($28,225,.801) were indirect costs. Thirty-three percent ($45,652,677/$137,204,393) of the total cost in children aged < 5 years was in the < 3-month age group, of which 52% ($71,654,002/$137,204,393) were healthcare system incurred. The costs of non-medically attended cases increased with age from $3,307,218 in the < 3-month age group to $8,603,377 in the 9–11-month age group. Conclusions: Among children < 5 years of age with RSV in South Africa, the highest cost burden was in the youngest infants; therefore, interventions against RSV targeting this age group are important to reduce the health and cost burden of RSV-associated illness. [ABSTRACT FROM AUTHOR]

Background: Vaccines and monoclonal antibodies to protect the very young infant against the respiratory syncytial virus (RSV)-associated illness are effective for limited time periods. We aimed to estimate age-specific burden to guide implementation strategies and cost-effectiveness analyses. Methods: We combined case-based surveillance and ecological data to generate a national estimate of the burden of RSV-associated acute respiratory illness (ARI) and severe acute respiratory illness (SARI) in South African children aged < 5 years (2011–2016), including adjustment for attributable fraction. We estimated the RSV burden by month of life in the < 1-year age group, by 3-month intervals until 2 years, and then 12 monthly intervals to < 5 years for medically and non-medically attended illness. Results: We estimated a mean annual total (medically and non-medically attended) of 264,112 (95% confidence interval (CI) 134,357–437,187) cases of RSV-associated ARI and 96,220 (95% CI 66,470–132,844) cases of RSV-associated SARI (4.7% and 1.7% of the population aged < 5 years, respectively). RSV-associated ARI incidence was highest in 2-month-old infants (18,361/100,000 population, 95% CI 9336–28,466). The highest incidence of RSV-associated SARI was in the < 1-month age group 14,674/100,000 (95% CI 11,175–19,645). RSV-associated deaths were highest in the first and second month of life (110.8 (95% CI 74.8–144.5) and 111.3 (86.0–135.8), respectively). Conclusions: Due to the high burden of RSV-associated illness, specifically SARI cases in young infants, maternal vaccination and monoclonal antibody products delivered at birth could prevent significant RSV-associated disease burden. [ABSTRACT FROM AUTHOR]

We conducted 3 prospective cohort studies (2016-2018), enrolling persons from 2 communities in South Africa. Nasopharyngeal swab specimens were collected twice a week from participants. Factors associated with Bordetella pertussis incidence, episode duration, and household transmission were determined by using Poisson regression, Weibull accelerated time-failure, and logistic regression hierarchical models, respectively. Among 1,684 participants, 118 episodes of infection were detected in 107 participants (incidence 0.21, 95% CI 0.17-0.25 infections/100 person-weeks). Children <5 years of age who had incomplete vaccination were more likely to have pertussis infection. Episode duration was longer for participants who had higher bacterial loads. Transmission was more likely to occur from male index case-patients and persons who had >7 days infection duration. In both communities, there was high incidence of B. pertussis infection and most cases were colonized. [ABSTRACT FROM AUTHOR]

South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. However, the size of its Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. We found that the Omicron BA.1/2 wave infected more than half of the cohort population, with reinfections and vaccine breakthroughs accounting for > 60% of all infections in both rural and urban sites. After the Omicron BA.1/2 wave, we found few (< 6%) remained naïve to SARS-CoV-2 and the population immunologic landscape is fragmented with diverse infection/immunization histories. Prior infection with the ancestral strain, Beta, and Delta variants provided 13%, 34%, and 51% protection against Omicron BA.1/2 infection, respectively. Hybrid immunity and repeated prior infections reduced the risks of Omicron BA.1/2 infection by 60% and 85% respectively. Our study sheds light on a rapidly shifting landscape of population immunity in the Omicron era and provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus. Emergence of the Omicron BA.1/2 SARS-CoV-2 subvariants led to a wave of infection South Africa. Here, the authors use serological data from a prospective household study to characterise infection rates in the context of diverse immune histories following vaccination and exposure to different variants. [ABSTRACT FROM AUTHOR]

Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019–2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV‐A and RSV‐B. This manuscript describes the preparation, distribution, and analysis of the 2019–2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in‐house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019–2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets. [ABSTRACT FROM AUTHOR]

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa's response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA--a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities. [ABSTRACT FROM AUTHOR]

Background: Drug-coated balloons (DCB) are an established tool in the prevention and treatment of coronary and peripheral artery restenosis. The underlying effects of restenosis resemble those in the neurovascular field, yet data on the use of DCB in cervical and intracranial arteries is rare. Methods: Medline, and international and major national guidelines and recommendations were systematically searched for data addressing the use of DCB in the neurovascular setting. Results: Of the 1448 relevant records found in Medline, 166 publications were considered for this review. Conclusions: Data on the use of DCB in the neurovascular setting show a possible benefit over preceding alternatives, such as self-expanding stents, and balloon-mounted or drug-eluting stents. Nonetheless, the role of DCB remains under-researched, and publications remain lacking. [ABSTRACT FROM AUTHOR]

Since the COVID-19 outbreak emerged, SARS-CoV-2 has continuously evolved into variants with underlying mutations associated with increased transmissibility, potential escape from neutralizing antibodies, and disease severity. The SARS-CoV-2 pandemic in South Africa has been characterized by periods of infections with four major epidemic waves. To determine whether the variants driving the epidemic waves at the national level were also driving the epidemic waves at the local level, we performed analysis of a total of 1287 samples from qPCR confirmed SARS-CoV-2 positive individuals. The samples were subjected to viral RNA extraction, genomic amplification, and sequencing. Variant assignment of the viral sequences and mutation identification were conducted using PANGOLIN and SARS-CoV-2 genome annotator, respectively. Our analysis revealed that during the initial part of the first wave, B.1, B.1.1, B.1.1.53, B.1.1.448 and B.1.237 circulated in the Free State province, followed by Beta variant, B.1.351 later in the wave. Although most of the initially detected variants disappeared during the second wave, the Beta variant, B.1.351, persisted. Early in the third wave, the Beta variant, B.1.351, predominated but was replaced by the Delta sub-lineage, AY.45. The fourth wave was characterized by unique emergence of the Omicron sub-variant, BA.1. The data further indicates that SARS-CoV-2 variants driving the epidemic waves in the Free State at the local level correlated with the ones driving the epidemic waves at the national level. Findings from this study highlight the importance of continued genomic surveillance and monitoring of the circulating SARS-CoV-2 variants to inform public health efforts and ensure adequate control of the ongoing pandemic. [ABSTRACT FROM AUTHOR]

Background: Core temperature monitoring is indispensable to prevent children from perioperative thermal perturbations. Although nasopharyngeal measurements are commonly used in anesthesia and considered to reflect core temperature accurately, standardized target depths for probe insertion are unknown in children. Aims: Our primary goal was to determine a target depth of nasopharyngeal temperature probe insertion in children by measuring distances on magnetic resonance imaging (MRI). Secondary aims were to correlate these measurements with biometric variables and facial landmark‐distances to derive formulas estimating target depth. Methods: We conducted a prospective observational study in children ≤12 years undergoing cranial MRI with anesthesia. We documented patient characteristics and measured the landmark‐distances nostril‐mandible, nostril‐tragus, and philtrum‐tragus on patient's faces. On MRI, the target point for the probe tip was considered to be the site of the nasopharyngeal mucosa with the closest proximity to the internal carotid artery. After its determination in the transverse axis and triangulation to the sagittal axis, we measured the distance to the nostril. This distance, defined as target insertion depth, was correlated with the patient characteristics and used for univariate and multiple linear regression analysis. Results: One hundred twenty children with a mean age of 4.5 years were included. The target insertion depth ranged from 61.8 mm in infants to 89.8 mm in 12‐year‐old children. Height correlated best (ρ = 0.685, 95%‐CI: [0.57–0.77]). The best‐fit estimation in millimeters, "40.8 + height [cm] × 0.32,″ would lead to a placement in the target position in 67% of cases. A simplified approach by categories of 50–80, 80–110, 110–130, and >130 cm height with target insertion depths of 60, 70, 80, and 85 mm, respectively, achieved similar probabilities. Conclusions: Height‐based formulas could be a valuable proxy for the insertion depth of nasopharyngeal temperature probes. Further clinical trials are necessary to investigate their measurement accuracy. [ABSTRACT FROM AUTHOR]

Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the history of past exposures to different SARS-CoV-2 variants and vaccination in the cohort most representative of South Africa's high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modeling suggests that the Omicron wave likely infected a large fraction (44 to 81%) of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. We project that future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection. SARS-CoV-2 in South Africa: Emerging SARS-CoV-2 variants bring questions as to their potential spread in populations. To analyze the spread of SARS-CoV-2 in South Africa, Sun et al. made use of detailed data from two household cohorts, one rural and one urban, who had longitudinal SARS-CoV-2 infection tests and serology assessments from July 2020 to August 2021. Their epidemiological analysis provides insights into the transmission dynamics of pre-Omicron SARS-CoV-2 variants and the population immunity landscape, and an additional modeling study evaluated the fitness advantage–fueled spread of Omicron and hypothetical future variants in this population. [ABSTRACT FROM AUTHOR]

Background: Estimates of the disease burden associated with different respiratory viruses are severely limited in low‐ and middle‐income countries, especially in Africa. Methods: We estimated age‐specific numbers and rates of medically and non‐medically attended influenza‐like illness (ILI) and severe respiratory illness (SRI) that were associated with influenza, respiratory syncytial virus (RSV), rhinovirus, human metapneumovirus, adenovirus, enterovirus and parainfluenza virus types 1–3 after adjusting for the attributable fraction (AF) of virus detection to illness in South Africa during 2013–2015. The base rates were estimated from five surveillance sites and extrapolated nationally. Results: The mean annual rates per 100,000 population were 51,383 and 4196 for ILI and SRI, respectively. Of these, 26% (for ILI) and 46% (for SRI) were medically attended. Among outpatients with ILI, rhinovirus had the highest AF‐adjusted rate (7221), followed by influenza (6443) and adenovirus (1364); whereas, among inpatients with SRI, rhinovirus had the highest AF‐adjusted rate (400), followed by RSV (247) and influenza (130). Rhinovirus (9424) and RSV (2026) had the highest AF‐adjusted rates among children aged <5 years with ILI or SRI, respectively, whereas rhinovirus (757) and influenza (306) had the highest AF‐adjusted rates among individuals aged ≥65 years with ILI or SRI, respectively. Conclusions: There was a substantial burden of ILI and SRI in South Africa during 2013–2015. Rhinovirus and influenza had a prominent disease burden among patients with ILI. RSV and influenza were the most prominent causes of SRI in children and the elderly, respectively. [ABSTRACT FROM AUTHOR]

By November 2021, after the third wave of severe acute respiratory syndrome coronavirus 2 infections in South Africa, seroprevalence was 60% in a rural community and 70% in an urban community. High seroprevalence before the Omicron variant emerged may have contributed to reduced illness severity observed in the fourth wave. [ABSTRACT FROM AUTHOR]

Background: Carotid artery stenting (CAS) is a minimally invasive and proven percutaneous procedure that is widely used to treat patients with symptomatic and asymptomatic carotid artery stenosis. The purpose of this study was to characterize the in-hospital outcomes of symptomatic and asymptomatic patients undergoing CAS at a single neurovascular center. Methods: The study was conducted as a retrospective analysis of 1158 patients (asymptomatic, n = 636; symptomatic, n = 522; male, n = 816; median age, 71 years; NASCET method, 70–99% stenosis, n = 830) who underwent CAS between May 2009 and December 2020. In-hospital neurological outcomes, adverse reactions to iodinated contrast media, acute myocardial infarction, intraprocedural complications, and access-site issues were evaluated. The primary endpoints were disabling stroke (including disabling cerebral hyperperfusion syndrome [CHS]) and all in-hospital deaths. Results: A carotid stent could not be deployed in one patient due to calcified plaques (technical failure rate of 0.09%). Four patients (0.3%) experienced in-hospital, stroke-associated death, while five patients (0.4%) died from non-stroke-related causes. All stroke-associated deaths occurred in the symptomatic group and were due to CHS. The disabling stroke rate was 0.9% overall (n = 10; 0.5% versus 1.3% in asymptomatic versus symptomatic patients, respectively). Nineteen patients (1.6%) reached the in-hospital primary endpoint. More patients in the symptomatic group achieved this endpoint than in the asymptomatic group (2.5% versus 0.9%, respectively; p = 0.060). Conclusions: An evaluation was conducted on the in-hospital outcomes of 1158 patients at a single center who underwent CAS and was performed by trained physicians who were supervised by a senior neurovascular interventionist with over 20 years of experience, confirming the excellent safety profile of this procedure with a low rate of complications. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe the prevalence of human respiratory syncytial virus (HRSV) and evaluate associations between HRSV subgroups and/or genotypes and epidemiologic characteristics and clinical outcomes in patients hospitalized with severe respiratory illness (SRI). Methods: Between January 2012 and December 2015, we enrolled patients of all ages admitted to two South African hospitals with SRI in prospective hospital‐based syndromic surveillance. We collected respiratory specimens and clinical and epidemiological data. Unconditional random effect multivariable logistic regression was used to assess factors associated with HRSV infection. Results: HRSV was detected in 11.2% (772/6908) of enrolled patients of which 47.0% (363/772) were under the age of 6 months. There were no differences in clinical outcomes of HRSV subgroup A‐infected patients compared with HRSV subgroup B‐infected patients but among patients aged <5 years, children with HRSV subgroup A were more likely be coinfected with Streptococcus pneumoniae (23/208, 11.0% vs. 2/90, 2.0%; adjusted odds ratio 5.7). No significant associations of HRSV A genotypes NA1 and ON1 with specific clinical outcomes were observed. Conclusions: While HRSV subgroup and genotype dominance shifted between seasons, we showed similar genotype diversity as noted worldwide. We found no association between clinical outcomes and HRSV subgroups or genotypes. [ABSTRACT FROM AUTHOR]

The Streptococcus pneumoniae polysaccharide capsule plays a role in disease severity. We assessed the association of serotype with case-fatality ratio (CFR) in invasive pneumococcal disease (IPD) and meningitis in South Africa, 2012-2018 (vaccine era), using multivariable logistic regression by manual backward elimination. The most common serotypes causing IPD were 8 and 19A. In patients <15 years of age, serotypes associated with increased CFR in IPD, compared with serotype 8 and controlling for confounding factors, were 11A, 13, 19F, 15A, and 6A. None of these serotypes were associated with increased CFR in meningitis. Among IPD patients >15 years of age, serotype 15B/C was associated with increased CFR. Among meningitis patients of all ages, serotype 1 was associated with increased CFR. PCV13 serotypes 1, 3, 6A, 19A, and 19F should be monitored, and serotypes 8, 12F, 15A, and 15B/C should be considered for inclusion in vaccines to reduce deaths caused by S. pneumoniae. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may be underestimated because of limited access to testing. We measured SARS-CoV-2 seroprevalence in South Africa every 2 months during July 2020-March 2021 in randomly selected household cohorts in 2 communities. We compared seroprevalence to reported laboratory-confirmed infections, hospitalizations, and deaths to calculate infection-case, infection-hospitalization, and infection-fatality ratios in 2 waves of infection. Post-second wave seroprevalence ranged from 18% in the rural community children <5 years of age, to 59% in urban community adults 35-59 years of age. The second wave saw a shift in age distribution of case-patients in the urban community (from persons 35-59 years of age to persons at the extremes of age), higher attack rates in the rural community, and a higher infection-fatality ratio in the urban community. Approximately 95% of SARS-CoV-2 infections were not reported to national surveillance. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018–2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host–pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study. [ABSTRACT FROM AUTHOR]

Background: A group of Victoria lineage influenza B viruses with a two amino acid deletion in the hemagglutinin (HA) at residues K162 and N163, was detected during the 2016 to 2017 Northern Hemisphere influenza season and continues to spread geographically. We describe the first identification of viruses with these deletions from South Africa in 2018. Methods: Nasopharyngeal samples were obtained from the syndromic surveillance programs. Real‐time reverse transcription‐polymerase chain reaction was used for virus detection and lineage determination. Influenza genetic characterization was done using next‐generation sequencing on the MiSeq platform. The duration of virus circulation was determined using thresholds calculated using the Moving Epidemic Method; duration was used as an indicator of disease transmissibility and impact. Results: In 2018, 42% (426/1015) of influenza‐positive specimens were influenza B viruses. Of 426 influenza B‐positive samples, 376 (88%) had the lineage determined of which 75% (283/376) were Victoria lineage. The transmissibility of the 2018 South African influenza season was high for a few weeks, although the severity remained moderate through most of the season. The sequenced 2018 South African Victoria lineage influenza B viruses clustered in sub‐clade V1A.1 with the 162‐163 deletions. Conclusions: We report the first detection of the 162‐163 deletion variant of influenza B/Victoria viruses from South Africa in 2018, and suggest that this deletion variant replaced the previous circulating influenza B/Victoria viruses. These deletions putatively affect the antigenic properties of the viruses because they border an immune‐dominant region at the tip of the HA. Therefore, close monitoring of these newly emerging viruses is essential. [ABSTRACT FROM AUTHOR]

Purpose: There is ample evidence that experiencing a criminal victimization is associated with lasting emotional problems among victims. To date, the mechanisms behind this association are not well understood. Based on the theoretical assumptions derived from a transactional stress-appraisal and coping model this study analyses the role of cognitive social capital (SC) in the association between criminal victimization (CV) and victims' mental health. Methods: A cross-sectional, computer-aided telephone survey including a representative sample of 3005 persons from three German cities was conducted. Respondents were asked about CV during their lifetime, cognitive SC, perceived victimization risk, perceived safety and perceived ability to prevent victimization. The PHQ-4 was used as a measure of anxiety and depression. The data were analyzed by means of logistic regression models and a path model controlled for sociodemographic characteristics. Results: Lifetime CV with any type of crime was associated with a clinically relevant increased risk of mental disorder (PHQ-4 ≥ 9; OR 1.8, p ≤ 0.05). Path analyses revealed that the direct association between CV and PHQ-4 (β = 0.454; p ≤ 0.01) was significantly diminished by cognitive SC (β = − 0.373; p ≤ 0.05). Conclusion: Our results suggest that cognitive SC is an individual resilience factor against negative experiences related to CV and that it holds the potential to diminish negative mental health consequences of CV. Further research should explore to what extent an enhancement of cognitive SC can help to prevent anxiety and depression among crime victims. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory illness (SARI) is an important cause of mortality in young children, especially in children living with HIV infection. Disparities in SARI death in children aged <5 years exist in urban and rural areas. Objective: To compare the factors associated with in-hospital death among children aged <5 years hospitalized with SARI in an urban vs. a rural setting in South Africa from 2009–2013. Methods: Data were collected from hospitalized children with SARI in one urban and two rural sentinel surveillance hospitals. Nasopharyngeal aspirates were tested for ten respiratory viruses and blood for pneumococcal DNA using polymerase chain reaction. We used multivariable logistic regression to identify patient and clinical characteristics associated with in-hospital death. Results: From 2009 through 2013, 5,297 children aged <5 years with SARI-associated hospital admission were enrolled; 3,811 (72%) in the urban and 1,486 (28%) in the rural hospitals. In-hospital case-fatality proportion (CFP) was higher in the rural hospitals (6.9%) than the urban hospital (1.3%, p<0.001), and among HIV-infected than the HIV-uninfected children (9.6% vs. 1.6%, p<0.001). In the urban hospital, HIV infection (odds ratio (OR):11.4, 95% confidence interval (CI):5.4–24.1) and presence of any other underlying illness (OR: 3.0, 95% CI: 1.0–9.2) were the only factors independently associated with death. In the rural hospitals, HIV infection (OR: 4.1, 95% CI: 2.3–7.1) and age <1 year (OR: 3.7, 95% CI: 1.9–7.2) were independently associated with death, whereas duration of hospitalization ≥5 days (OR: 0.5, 95% CI: 0.3–0.8) and any respiratory virus detection (OR: 0.4, 95% CI: 0.3–0.8) were negatively associated with death. Conclusion: We found that the case-fatality proportion was substantially higher among children admitted to rural hospitals and HIV infected children with SARI in South Africa. While efforts to prevent and treat HIV infections in children may reduce SARI deaths, further efforts to address health care inequality in rural populations are needed. [ABSTRACT FROM AUTHOR]

Background: Describing contact patterns is crucial to understanding infectious disease transmission dynamics and guiding targeted transmission mitigation interventions. Data on contact patterns in Africa, especially South Africa, are limited. We measured and compared contact patterns in a rural and urban community, South Africa. We assessed participant and contact characteristics associated with differences in contact rates.Methods: We conducted a cross-sectional study nested in a prospective household cohort study. We interviewed participants to collect information on persons in contact with for one day. We described self-reported contact rates as median number people contacted per day, assessed differences in contact rates based on participant characteristics using quantile regression, and used a Poisson model to assess differences in contact rates based on contact characteristics within age groups. We also calculated cumulative person hours in contact within age groups at different locations.Results: We conducted 535 interviews (269 rural, 266 urban), with 17,252 contacts reported. The overall contact rate was 14 (interquartile range (IQR) 9-33) contacts per day. Those ≤18 years had higher contact rates at the rural site (coefficient 17, 95% confidence interval (95%CI) 10-23) compared to the urban site, for those aged 14-18 years (13, 95%CI 3-23) compared to < 7 years. No differences were observed for adults. There was a strong age-based mixing, with age groups interacting more with similar age groups, but also interaction of participants of all ages with adults. Children aged 14-18 years had the highest cumulative person hours in contact (116.3 rural and 76.4 urban).Conclusions: Age played an important role in the number and duration of contact events, with children at the rural site having almost double the contact rate compared to the urban site. These contact rates can be utilized in mathematical models to assess transmission dynamics of infectious diseases in similar communities. [ABSTRACT FROM AUTHOR]

Background: Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions.Methods and Findings: We used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged <1 month. We created a composite (synthetic) control using Bayesian variable selection of nondiarrheal, nonpneumonia, and nonpneumococcal deaths to estimate the number of expected all-cause pneumonia deaths in the absence of PCV introduction post 2009. We compared all-cause pneumonia deaths from the death registry to the expected deaths in 2012 to 2016. We also estimated the number of prevented deaths during 2009 to 2016. Of the 9,324,638 deaths reported in South Africa from 1999 to 2016, 12·6% were pneumonia-related. Compared to number of deaths expected, we estimated a 33% (95% credible interval (CrI) 26% to 43%), 23% (95%CrI 17% to 29%), 25% (95%CrI 19% to 32%), and 23% (95%CrI 11% to 32%) reduction in pneumonia mortality in children aged 1 to 11 months, 1 to 4 years, 5 to 7 years, and 8 to 18 years in 2012 to 2016, respectively. In total, an estimated 18,422 (95%CrI 12,388 to 26,978) pneumonia-related deaths were prevented from 2009 to 2016 in children aged <19 years. No declines were estimated observed among adults following PCV introduction. This study was mainly limited by coding errors in original data that could have led to a lower impact estimate, and unmeasured factors could also have confounded estimates.Conclusions: This study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to <19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children. [ABSTRACT FROM AUTHOR]

Fingolimod represents a highly effective disease-modifying drug in patients with active relapsing-remitting multiple sclerosis (RRMS). Its immunosuppressive effects can mediate adverse events like increased risk of cancer development or appearance of opportunistic infections. Progressive multifocal leukoencephalopathy (PML)–representing a severe opportunistic infection–has been only infrequently described during Fingolimod treatment. Here, we present a case of a 63-year-old women with pre-diagnosed RRMS who presented with new multiple cerebral lesions in a routine MRI scan, also including a tumefactive lesion in the left parietal lobe, eventually leading to the diagnosis of brain metastases derived by an adenocarcinoma of the lung. Additionally, a JCV-DNA-PCR in the cerebrospinal fluid revealed positive results, corresponding to a paraclinical progressive multifocal leukoencephalopathy. In conclusion, adverse events potentially associated with immunosuppression can occur during Fingolimod treatment. In this context, the occurrence of cancer and opportunistic infections should be carefully monitored. Here, we report a case in which JCV-DNA-PCR in the cerebrospinal fluid suggests asymptomatic PML and simultaneously lung cancer brain metastases developed. While it is rather unlikely that either event occurred as an adverse event of fingolimod treatment, a contributing effect cannot be formally excluded. [ABSTRACT FROM AUTHOR]

Background: Modern genetics have in many ways revolutionized clinical routine and have, for instance, shown that formerly distinct disease entities relate to common pathogenic mutations. One such example is the connection between dementia and amyotrophic lateral sclerosis (ALS) in a continuous disease spectrum affirmed by the discovery of shared mutations. Case Report: We describe a new variant in the FIG4 gene in a patient with slowly progressing frontotemporal dementia (FTD) and probable primary lateral sclerosis (PLS). The patient initially showed depressive symptoms and global cognitive deficits. Severe difficulties with language and hallucinations became clearer as the disease progressed. Nuclear medicine imaging and cerebrospinal fluid (CSF) biomarkers were not specific for defined categories of dementia, but neuropsychological testing and clinical features finally led to an allocation of the syndrome to the non-fluent variant of primary progressive aphasia (nfv PPA). Because of increasing limb weakness and bulbar symptoms, motoneuron disease in the form of PLS was diagnosed, strongly supported by elevated CSF neurofilament and electrophysiologic assessments. The detected variant in the FIG4 gene is described as pathogenic or likely pathogenic in common databases and reported once in the literature. While the phenotype of our patient fits the description of FIG4 -associated disease in literature, we consider the present variant as VUS in this case. Conclusion: We describe a variant in the FIG4 gene in a patient with slowly progressing FTD and PLS. Mutations in the FIG4 gene have been associated with ALS and PLS; however, this exact mutation was not reported in ALS or PLS patients before. The case illustrates generic diagnostic challenges in patients presenting with genetic variants that offer an explanation for otherwise uncommon symptom combinations but yet are of unknown significance. [ABSTRACT FROM AUTHOR]

We evaluated pneumococcal colonization in children and adults between the time of 7-valent pneumococcal conjugate vaccine (PCV) introduction in the immunization program in 2009 to two years after transitioning to PCV13 in 2011. Community-based carriage surveillance was undertaken between May-November 2013 (Period-3), with similar surveys in 2009 (Period-1) and 2011 (Period-2). Households with children below two years had a similar probability of being sampled in all surveys. Nasopharyngeal swabs were processed using standard methods and serotyped by Quellung. In children>9-59 months old, overall pneumococcal colonization prevalence declined from 81.8% in Period-1 to 65.0% in Period-3 (p<0.001). Reductions of 70% (41.2% vs. 13.6%) in PCV7-serotypes colonization and 66% (15.3% vs. 4.4%) for the six additional PCV13-serotypes (PCV13-add6VT) were observed. There was, however, high residual colonization by PCV7-serotypes 19F (14.9% vs. 6.3%) and 23F (8.5% vs. 4.1%), despite reduction of 57% and 52%, respectively. Among individuals>12 years of age, there was 61% reduction in PCV7-serotype colonization (3.1% vs. 1.3%) and 75% decrease for PCV13-add6VT (2.1% vs. 0.6%) between Period-1 and Period-3. The residual prevalence of serotypes 19F and 23F, four years after introducing PCV in the South Africa, suggests ongoing community transmission and transient vaccine effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The polysaccharide capsule is a major virulence factor of S. pneumoniae in diseases such as meningitis. While some capsular serotypes are more often found in invasive disease, high case fatality rates are associated with those serotypes more commonly found in asymptomatic colonization. We tested whether growth patterns and capsule size in human cerebrospinal fluid depends on serotype using a clinical isolate of S. pneumoniae and its capsule switch mutants. Results: We found that the growth pattern differed markedly from that in culture medium by lacking the exponential and lysis phases. Growth in human cerebrospinal fluid was reduced when strains lost their capsules. When a capsule was present, growth was serotype-specific: high carriage serotypes (6B, 9 V, 19F and 23F) grew better than low carriage serotypes (7F, 14, 15B/C and 18C). Growth correlated with the case-fatality rates of serotypes reported in the literature. Capsule size in human cerebrospinal fluid also depended on serotype. Conclusions: We propose that serotype-specific differences in disease severity observed in meningitis patients may, at least in part, be explained by differences in growth and capsule size in human cerebrospinal fluid. This information could be useful to guide future vaccine design. [ABSTRACT FROM AUTHOR]