Browsing by Author "Cohen, Cheryl"

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Cultureconfirmed neonatal bloodstream infections and meningitis in South Africa 201419 a crosssectional study
Mashau, Rudzani C.; Meiring, Susan ; Dramowski, Angela; Magobo, Rindidzani E.; Quan, Vanessa C. ; Von Gottberg, Anne ; Cohen, Cheryl ; Velaphi, Sithembiso ; Govender, Nelesh; Perovic, Olga
Background: Few population-level estimates of invasive neonatal infections have been reported from sub-Saharan Africa. We estimated the national incidence risk, aetiology, and pathogen antimicrobial susceptibility for cultureconfirmed neonatal bloodstream infections and meningitis in South Africa. Methods: We conducted a cross-sectional study of neonates (<28 days of life) admitted to neonatal or paediatric wards of 256 public sector health facilities in South Africa during 2014–19. Diagnostic pathology records from Jan 1, 2014, to Dec 31, 2019, were extracted from a national pathology data warehouse. A case was defined as a neonate with at least one positive blood or cerebrospinal fluid culture during a 14-day period. Incidence risk was calculated using annual numbers of registered livebirths. Among the causative pathogens identified, we calculated the proportion of cases attributed to each of them, as well as the rates of antibiotic susceptibility of Gram-positive and Gram-negative bacteria. Findings: Among 43 438 records of positive cultures, there were 37 631 incident cases of neonatal infection with at least one pathogen isolated. The overall incidence risk of culture-confirmed infections was 6·0 per 1000 livebirths (95% CI 6·0–6·1). The incidence risk of late-onset sepsis (days 3–27 of life) was 4·9 per 1000 livebirths (4·9–5·0) and that of early-onset sepsis (days 0–2 of life) was 1·1 per 1000 livebirths (1·1–1·1); risk ratio 4·4 (95% CI 4·3–4·5). The cause of infection differed by syndrome, timing of infection onset, facility, and province, although Klebsiella pneumoniae (26%), Acinetobacter baumannii (13%), and Staphylococcus aureus (12%) were the dominant pathogens overall. Gram-negative bacteria had declining susceptibility to most antibiotics over the study period. Interpretation We found a high incidence risk of late-onset sepsis with provincial variations, predominance of K pneumoniae, and declining antibiotic susceptibility among Gram-negative bacteria. This national surveillance in an upper-middle-income country provides a baseline burden of neonatal infections against which the impact of future clinical and public health interventions can be measured.
Influenza-associated morbidity and mortality in South Africa
(2015-04-21) Cohen, Cheryl
Introduction Data on the burden of influenza-associated hospitalisation and mortality in relation to other aetiologies of pneumonia as well as risk groups for severe and complicated disease are important to guide influenza prevention policy. Materials and methods We estimated influenza-related deaths as excess mortality above a model baseline during influenza epidemic periods from monthly age-specific mortality data using Serfling regression models. For individuals aged ≥65 years from South Africa and the United States of America (US) we evaluated influenza-related deaths due to all causes, pneumonia and influenza (P&I) and other influenza-associated diagnoses for 1998-2005. For adults with acquired immune deficiency syndrome (AIDS) aged 25-54 years in South Africa (1998-2005) and the US (pre-highly active antiretroviral therapy (HAART) era: 1987-1994; HAART era: 1997-2005) we estimated deaths due to all-causes and P&I. We prospectively enrolled individuals with severe acute respiratory illness (SARI) at six hospitals in four provinces of South Africa from 2009-2012. Using polymerase chain reaction, respiratory samples were tested for ten respiratory viruses and blood for pneumococcal DNA. Cumulative annual SARI incidence was estimated at one site with available population denominators. Results Age-standardised excess mortality rates amongst seniors were higher in South Africa than in the US (545 vs. 133 per 100,000 for all-causes, p<0.001; 63 vs. 21 for P&I, p=0.03). The mean percent of winter deaths attributable to influenza was 16% in South Africa and 6% in the US, p<0.001. For all respiratory causes, cerebrovascular disease and diabetes age-standardised excess death rates were 4- to 8-fold greater in South Africa than in the US, and the percent increase in winter deaths attributable to influenza was 2- to 4-fold higher. In the US pre-HAART, influenza-related mortality rates in adults with AIDS were 150- (95% confidence interval (CI) 49-460) and 208- (95% CI 74-583) times greater than in the general population for all-cause and P&I respectively and 2.5- (95% CI 0.9-7.2) and 4.1- (95% CI 1.4-13) times higher than in seniors. Following HAART introduction, influenza-related mortality in adults with AIDS dropped 3-6 fold but remained elevated compared to the general population (all cause relative risk (RR) 44, 95% CI 16-12); P&I RR 73, 95% CI 47-113). Influenza-related mortality in South African adults with AIDS was similar to that in the US in the pre-HAART era. From 2009-2012 we enrolled 8723 children age <5 years with SARI. The human immunodeficiency virus (HIV) prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), which included 26% (n=2216) respiratory syncytial virus (RSV) and 7% (n=613) influenza. The annual incidence of SARI hospitalisation in children age <5 years ranged from 2530-3173 per 100,000 and was 1.1-3-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to be hospitalised >7 days (odds ratio (OR) 3.6, 95% CI 2.8-5.0) and had a 4.2-fold (95% CI 2.6-6.8) higher case-fatality ratio. From 2009-2012, we enrolled 7193 individuals aged ≥5 years with SARI. HIV-prevalence was 74% (4663/6334) and 9% (621/7067) tested influenza positive. The annual incidence of SARI hospitalisation in individuals age ≥5 years ranged from 325-617 per 100,000 population and was 13 to 19-fold greater in HIV-infected individuals (p<0.001). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals were more likely to be receiving tuberculosis treatment (OR 2.1, 95% CI 1.3-3.2), have pneumococcal infection (OR 2.2, 95% CI 1.6-2.9), be hospitalised for longer (>7 days rather than <2 days OR 2.4, 95% CI 1.8-3.2) and had a higher case-fatality ratio (8% vs. 5%; OR 1.6, 95% CI 1.2-2.2), but were less likely to be infected with influenza (OR 0.6, 95% CI 0.5-0.8). Influenza was identified in 9% (1056/11925) of patients of all ages enrolled in SARI surveillance from 2009-2011. Among influenza case-patients, 44% (358/819) were HIV-infected. Age-adjusted influenza-associated SARI incidence was 4-8 times greater in HIV-infected (186-228 per 100,000 population) than HIV-uninfected (26-54 per 100,000 population). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals with influenza-associated SARI were more likely to have pneumococcal co-infection (OR 2.3, 95% CI 1.0-5.0), influenza type B than type A (OR 1.6, 95% CI 1.0-2.4), be hospitalised for 2-7 days (OR 2.8 95% CI 1.5-5.5) or >7 days (OR 4.5, 95% CI 2.1-9.5) and more likely to die (OR 3.9, 95% CI 1.1-14.1). Discussion and conclusions The mortality impact of seasonal influenza in the South African elderly may be substantially higher in an African setting compared to the US. Adults with AIDS in South Africa and the US experience substantially elevated influenza-associated mortality rates, which although lessened by widespread HAART treatment does not completely abrogate the heightened risk for influenza illness. HIV-infected children and adults also experience substantially elevated incidence of hospitalisation for influenza-associated SARI and have higher case-fatality ratios. Influenza is commonly detected amongst children (7%) and adults (9%) with SARI. Less frequent identification of influenza amongst HIV-infected than -uninfected individuals aged ≥5 years likely reflects increased relative burden and role of other opportunistic pathogens such as pnuemococcus and Pneumocystis jirovecii. Improved access to HAART for HIV-infected individuals and vaccination against influenza virus amongst HIV-infected individuals, young children and the elderly, where the influenza burden is great may reduce the high burden of hospitalisations and mortality associated with influenza.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission dynamics and social contact patterns
(University of the Witwatersrand, Johannesburg, 2023-03) Kleynhans, Jacoba Wilhelmina; Cohen, Cheryl; Tempia, Stefano
Background: Understanding the community burden and transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can assist to make informed decisions for prevention policies. Methods: From August through October 2018, before the SARS-CoV-2 pandemic, we performed a cross-sectional contact survey nested in a prospective household cohort in an urban (Jouberton, North West Province) and a rural community (Agincourt, Mpumalanga Province) in South Africa to measure contact rates in 535 study participants. Participants were interviewed to collect details on all contact events (within and outside of the household). During the SARS-CoV-2 pandemic we enrolled 1211 individuals from 232 randomly selected households in the same urban and rural community, and followed the cohort prospectively for 16 months (July 2020 through November 2021), collecting blood every two months to test for SARS-CoV-2 antibodies. Using these longitudinal SARS-CoV-2 seroprevalence estimates and comparing these with reported laboratory-confirmed cases, hospitalizations and deaths, we investigated the community burden and severity of SARS-CoV-2. We also performed a case-ascertained household transmission study of symptomatic SARS-CoV-2 index cases living with HIV (LWH) and not LWH (NLWH) in two urban communities (Jouberton, North West Province and Soweto, Gauteng Province) from October 2020 through September 2021. We enrolled 131 SARS-CoV-2 index cases at primary healthcare clinics. The index cases and their 457 household contacts were followed up for six weeks with thrice weekly visits to collect nasal swabs for SARS-CoV-2 testing on reverse transcription real-time polymerase chain reaction (rRT-PCR), irrespective of symptoms. We assessed household cumulative infection risk (HCIR), duration of virus detection and the interval between index and contact symptom onset (serial interval). By collecting high-resolution household contact patterns in these households using wearable sensors, we assessed the association between contact patterns and SARS-CoV-2 household transmission. Results: During the contact survey, we observed an overall contact rate of 14 (95% confidence interval (CI), 13-15) contacts per day, with higher contact rates in children aged 14-18 years (22, 95%CI 8-35) compared to children <7 years (15, 95%CI 12-17). We found higher contact rates in the rural site (21, 95%CI 14-28) compared to the urban site (12, 95%CI 11-13). When comparing the household cohort seroprevalence estimates to district SARS-CoV-2 laboratory-confirmed infections, we saw that only 5% of SARS-CoV-2 infections were reported to surveillance. Three percent of infections resulted in hospitalization and 0.7% in death. People LWH were not more likely to be seropositive for SARS-CoV-2 (odds ratio [OR] 1.0, 95%CI 0.7–1.5), although the sample size for people LWH was small (159/1131 LWH). During the case-ascertained household transmission study for SARS-CoV-2, we estimated a HCIR of 59% (220/373) in susceptible household members, with similar rates in households with an index LWH and NLWH (60% LWH vs 58% NLWH). We observed a higher risk of transmission from index cases aged 35–59 years (adjusted OR [aOR] 3.4, 95%CI 1.5–7.8) and ≥60 years (aOR 3.1, 95% CI 1.0–10.1) compared with those aged 18–34 years, and index cases with a high SARS-CoV-2 viral load (using cycle threshold values (Ct) <25 as a proxy, aOR 5.3, 95%CI 1.6–17.6). HCIR was also higher in contacts aged 13–17 years (aOR 7.1, 95%CI 1.5–33.9) and 18–34 years (aOR 4.4, 95% CI 1.0–18.4) compared with <5 years. Through the deployment of wearable sensors, we were able to measure high-resolution within-household contact patterns in the same households. We did not find an association between duration (aOR 1.0 95%CI 1.0-1.0) and frequency (aOR 1.0 95%CI 1.0-1.0) of close-proximity contact with SARS CoV-2 index cases and household members and transmission. Conclusion: We found high contact rates in school-going children, and higher contact rates in the rural community compared to the urban community. These contact rates add to the limited literature on measured contact patterns in South Africa. The burden of SARS-CoV-2 is underestimated in national surveillance, highlighting the importance of serological surveys to determine the true burden. Under-ascertainment of cases can hinder containment efforts through isolation and contact tracing. Based on seroprevalence estimates in our study, people LWH did not have higher SARS-CoV-2 community attack rates. In the household transmission study, we observed a high HCIR in households with symptomatic index cases, and that index cases LWH did not infect more household members compared to people NLWH. We found a correlation between age and SARS-CoV-2 transmission and acquisition, as well as between age and contact rates. Although we did not observe an association between household contact patterns and SARS-CoV-2 transmission, we generated SARS-CoV-2 transmission parameters and community and household contact data that can be used to parametrize infectious disease models for both SARS-CoV-2 and other pathogens to assist with forecasting and intervention assessments. The availability of robust data is important in the face of a pandemic where intervention strategies have to be adapted continuously.