Publications by authors named "Cheryl Cohen"

218 Publications

Unmasking pneumococcal carriage in a high HIV prevalence population in two community cohorts with a high prevalence of HIV in South Africa, 2016-2018: the PHIRST study.

Clin Infect Dis 2022 Jun 19. Epub 2022 Jun 19.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Introduction: Longitudinal pneumococcus colonization data in high HIV prevalence settings following pneumococcal conjugate vaccine introduction are limited.

Methods: In 327 randomly selected households, 1,684 individuals were enrolled and followed-up for 6-10 months during 2016-2018 from two communities. Nasopharyngeal swabs were collected twice-weekly and tested for pneumococcus using quantitative lytA real-time PCR. A Markov model was fitted to the data to define the start and end of an episode of colonization. We assessed factors associated with colonization using logistic regression.

Results: During the study period, 98% (1,655/1,684) of participants were colonized with pneumococcus at least once. Younger age (<5 years: adjusted odds ratio (aOR) 14.1, 95% confidence (CI) 1.8-111.3 and 5-24 years: aOR 4.8, 95% CI 1.9-11.9, compared to 25-44 years) and HIV-infection (aOR 10.1; 95% CI 1.3-77.1) were associated with increased odds of colonization. Children aged <5 years had fewer colonization episodes (median 9) than individuals ≥5 years (median 18; P < 0.001) but had a longer episode duration (<5 years: 35.5 days (interquartile range (IQR): 17-88) vs. ≥5 years: 5.5 days (4-12)). High pneumococcal loads were associated with age (<1 year: aOR 25.4, 95% CI 7.4-87.6; 1-4 years: aOR 13.5, 95% CI 8.3-22.9; 5-14 years: aOR 3.1, 95% CI 2.1-4.4 vs. 45-65 year olds) and HIV infection (aOR 1.7; 95% CI 1.2-2.4).

Conclusions: We observed high levels of pneumococcus colonization across all age groups. Children and people living with HIV were more likely to be colonized and had higher pneumococcal loads. Carriage duration decreased with age highlighting that children remain important in pneumococcal transmission.
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http://dx.doi.org/10.1093/cid/ciac499DOI Listing
June 2022

Pathogens detected using a syndromic molecular diagnostic platform in patients hospitalized with severe respiratory illness in South Africa in 2017.

Int J Infect Dis 2022 Jun 11. Epub 2022 Jun 11.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Objectives: We describe the use of a multi-pathogen platform, TaqMan array card (TAC) real-time PCR, for the detection of pathogens in patients hospitalized with severe respiratory illness (SRI).

Methods: Prospective hospital-based syndromic surveillance for acute and chronic SRI was carried out at two sentinel sites in South Africa between January and December 2017. We tested respiratory specimens for 21 respiratory pathogens and blood samples for nine bacteria using TAC. Pathogen detection was compared by age group and HIV status using the chi-squared test.

Results: During 2017, 956 patients of all ages were enrolled in the SRI surveillance, and of these, 637 (67%) patients were included in this study (637 blood, 487 naso- and oro-pharyngeal swabs and 411 sputum specimens tested). At least one pathogen was detected in 83% (527/637) of patients. Common pathogens detected included H. influenzae (225/637; 35%), S. pneumoniae (224/637; 35%), rhinovirus (144/637; 23%), S. aureus (129/637; 20%), K. pneumoniae (85/637; 13%), M. tuberculosis (75/637; 12%), and respiratory syncytial virus (57/637; 9%). Multiple pathogens (≥2) were co-detected in 57% (364/637) of patients.

Conclusion: While use of a multi-pathogen platform improved pathogen yield, pathogen co-detections were common and would need clinical assessment for usefulness in individual-level treatment and management decisions.
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http://dx.doi.org/10.1016/j.ijid.2022.06.011DOI Listing
June 2022

SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron's impact in South African population cohorts.

Sci Transl Med 2022 May 31:eabo7081. Epub 2022 May 31.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, 2131, South Africa.

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 more representative urban cohort given South Africa's high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modelling suggests the Omicron wave likely infected a large fraction (44% - 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.
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http://dx.doi.org/10.1126/scitranslmed.abo7081DOI Listing
May 2022

SARS-CoV-2 cases reported from long-term residential facilities (care homes) in South Africa: a retrospective cohort study.

BMC Public Health 2022 May 24;22(1):1035. Epub 2022 May 24.

Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa.

Background: Globally, long-term care facilities (LTCFs) experienced a large burden of deaths during the COVID-19 pandemic. The study aimed to describe the temporal trends as well as the characteristics and risk factors for mortality among residents and staff who tested positive for SARS-CoV-2 in selected LTCFs across South Africa.

Method: We analysed data reported to the DATCOV sentinel surveillance system by 45 LTCFs. Outbreaks in LTCFs were defined as large if more than one-third of residents and staff had been infected or there were more than 20 epidemiologically linked cases. Multivariable logistic regression was used to assess risk factors for mortality amongst LTCF residents.

Results: A total of 2324 SARS-CoV-2 cases were reported from 5 March 2020 through 31 July 2021; 1504 (65%) were residents and 820 (35%) staff. Among LTCFs, 6 reported sporadic cases and 39 experienced outbreaks. Of those reporting outbreaks, 10 (26%) reported one and 29 (74%) reported more than one outbreak. There were 48 (66.7%) small outbreaks and 24 (33.3%) large outbreaks reported. There were 30 outbreaks reported in the first wave, 21 in the second wave and 15 in the third wave, with 6 outbreaks reporting between waves. There were 1259 cases during the first COVID-19 wave, 362 during the second wave, and 299 during the current third wave. The case fatality ratio was 9% (138/1504) among residents and 0.5% (4/820) among staff. On multivariable analysis, factors associated with SARS-CoV-2 mortality among LTCF residents were age 40-59 years, 60-79 years and ≥ 80 years compared to < 40 years and being a resident in a LTCF in Free State or Northern Cape compared to Western Cape. Compared to pre-wave 1, there was a decreased risk of mortality in wave 1, post-wave 1, wave 2, post-wave 2 and wave 3.

Conclusion: The analysis of SARS-CoV-2 cases in sentinel LTCFs in South Africa points to an encouraging trend of decreasing numbers of outbreaks, cases and risk for mortality since the first wave. LTCFs are likely to have learnt from international experience and adopted national protocols, which include improved measures to limit transmission and administer early and appropriate clinical care.
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http://dx.doi.org/10.1186/s12889-022-13403-6DOI Listing
May 2022

Clinical severity of COVID-19 in patients admitted to hospital during the omicron wave in South Africa: a retrospective observational study.

Lancet Glob Health 2022 Jul 18;10(7):e961-e969. Epub 2022 May 18.

National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.

Background: Up to the end of January, 2022, South Africa has had four recognisable COVID-19 pandemic waves, each predominantly dominated by one variant of concern: the ancestral strain with an Asp614Gly mutation during the first wave, the beta variant (B.1.351) during the second wave, the delta variant (B.1.617.2) during the third wave, and lastly, the omicron variant (B.1.1.529) during the fourth wave. We aimed to assess the clinical disease severity of patients admitted to hospital with SARS-CoV-2 infection during the omicron wave and compare the findings with those of the preceding three pandemic waves in South Africa.

Methods: We defined the start and end of each pandemic wave as the crossing of the threshold of weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases per 100 000 population. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. We compared disease severity across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of the following: acute respiratory distress, receipt of supplemental oxygen or mechanical ventilation, admission to intensive care, or death.

Findings: We analysed 335 219 laboratory-confirmed SARS-CoV-2 hospital admissions with a known outcome, constituting 10·4% of 3 216 179 cases recorded during the four waves. During the omicron wave, 52 038 (8·3%) of 629 617 cases were admitted to hospital, compared with 71 411 (12·9%) of 553 530 in the Asp614Gly wave, 91 843 (12·6%) of 726 772 in the beta wave, and 131 083 (10·0%) of 1 306 260 in the delta wave (p<0·0001). During the omicron wave, 15 421 (33·6%) of 45 927 patients admitted to hospital had severe disease, compared with 36 837 (52·3%) of 70 424 in the Asp614Gly wave, 57 247 (63·4%) of 90 310 in the beta wave, and 81 040 (63·0%) of 128 558 in the delta wave (p<0·0001). The in-hospital case-fatality ratio during the omicron wave was 10·7%, compared with 21·5% during the Asp614Gly wave, 28·8% during the beta wave, and 26·4% during the delta wave (p<0·0001). Compared with those admitted to hospital during the omicron wave, patients admitted during the other three waves had more severe clinical presentations (adjusted odds ratio 2·07 [95% CI 2·01-2·13] in the Asp614Gly wave, 3·59 [3·49-3·70] in the beta wave, and 3·47 [3·38-3·57] in the delta wave).

Interpretation: The trend of increasing cases and admissions across South Africa's first three waves shifted in the omicron wave, with a higher and quicker peak but fewer patients admitted to hospital, less clinically severe illness, and a lower case-fatality ratio compared with the preceding three waves. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile, and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and previous infection levels.

Funding: National Institute for Communicable Diseases.
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http://dx.doi.org/10.1016/S2214-109X(22)00114-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116895PMC
July 2022

COVID-19 vaccine hesitancy in rural South Africa: Deepening understanding to increase uptake and access.

J Glob Health 2022 May 14;12:05013. Epub 2022 May 14.

MRC/Wits Rural Public Health and Health Transitions Research Unit, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Background: To date, COVID-19 vaccine coverage in the African region falls far too short of global goals. Increasing vaccination rates requires understanding barriers to vaccination so that effective interventions that sensitively and effectively address barriers to vaccination can be implemented.

Methods: To assess COVID-19 vaccination levels and identify major barriers to vaccine uptake we conducted a population-based, cross-sectional survey among 1662 adults 18 and older from August 25 to October 29 2021 in the Agincourt Health and Socio-Demographic Surveillance System (AHDSS) area, Mpumalanga, South Africa.

Results: Half of participants reported receiving a COVID-19 vaccine (50.4%) with 41.1% being fully vaccinated and 9.3% being partially vaccinated; 49.6% were unvaccinated. More women than men were vaccinated (55.5% vs 42.8%, P < 0.001), and older age groups were more likely to be vaccinated than younger age groups (P < 0.001). Among the unvaccinated, 69.0% planned to get vaccinated as soon as possible, while 14.7% reported definitely not wanting the vaccine. Major barriers to vaccination included lacking information on eligibility (12.3%) or where to get vaccinated (13.0%), concerns about side effects (12.5%), and inconvenient hours and locations for vaccination (11.0%). Confidence in the safety and efficacy of COVID-19 vaccines was higher among those vaccinated than unvaccinated (75.3% vs 51.2%, 75.8% vs 51.0%, both P < 0.001, respectively).

Conclusions: Increasing vaccination in South Africa beyond current levels will require a concerted effort to address concerns around vaccine safety and increase confidence in vaccine efficacy. Clarifying eligibility and ensuring access to vaccines at times and places that are convenient to younger populations, men, and other vulnerable groups is necessary.
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http://dx.doi.org/10.7189/jogh.12.05013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107307PMC
May 2022

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.

Trop Med Int Health 2022 Jun 10;27(6):564-573. Epub 2022 May 10.

Groote Schuur Hospital, Western Cape Government: Health, Cape Town, South Africa.

Objectives: The objective was to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained.

Methods: In this cohort study, we included public sector patients aged ≥20 years with a laboratory-confirmed COVID-19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection.

Results: We included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58).

Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta-driven wave.
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http://dx.doi.org/10.1111/tmi.13752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115442PMC
June 2022

Costs of seasonal influenza vaccination in South Africa.

Influenza Other Respir Viruses 2022 Mar 30. Epub 2022 Mar 30.

SAMRC Centre for Health Economics and Decision Science-PRICELESS SA, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Background: Influenza accounts for a substantial number of deaths and hospitalisations annually in South Africa. To address this disease burden, the South African National Department of Health introduced a trivalent inactivated influenza vaccination programme in 2010.

Methods: We adapted and populated the WHO Seasonal Influenza Immunization Costing Tool (WHO SIICT) with country-specific data to estimate the cost of the influenza vaccination programme in South Africa. Data were obtained through key-informant interviews at different levels of the health system and through a review of existing secondary data sources. Costs were estimated from a public provider perspective and expressed in 2018 prices. We conducted scenario analyses to assess the impact of different levels of programme expansion and the use of quadrivalent vaccines on total programme costs.

Results: Total financial and economic costs were estimated at approximately USD 2.93 million and USD 7.91 million, respectively, while financial and economic cost per person immunised was estimated at USD 3.29 and USD 8.88, respectively. Expanding the programme by 5% and 10% increased economic cost per person immunised to USD 9.36 and USD 9.52 in the two scenarios, respectively. Finally, replacing trivalent inactivated influenza vaccine (TIV) with quadrivalent vaccine increased financial and economic costs to USD 4.89 and USD 10.48 per person immunised, respectively.

Conclusion: We adapted the WHO SIICT and provide estimates of the total costs of the seasonal influenza vaccination programme in South Africa. These estimates provide a basis for planning future programme expansion and may serve as inputs for cost-effectiveness analyses of seasonal influenza vaccination programmes.
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http://dx.doi.org/10.1111/irv.12987DOI Listing
March 2022

The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions.

Lancet Respir Med 2022 06 23;10(6):603-622. Epub 2022 Mar 23.

McGill International TB Centre, McGill University, Montreal, QC, Canada.

The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Here, we consider points of intersection between the tuberculosis and COVID-19 pandemics, identifying wide-ranging approaches that could be taken to reverse the devastating effects of COVID-19 on tuberculosis control. We review the impact of COVID-19 at the population level on tuberculosis case detection, morbidity and mortality, and the patient-level impact, including susceptibility to disease, clinical presentation, diagnosis, management, and prognosis. We propose strategies to reverse or mitigate the deleterious effects of COVID-19 and restore tuberculosis services. Finally, we highlight research priorities and major challenges and controversies that need to be addressed to restore and advance the global response to tuberculosis.
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http://dx.doi.org/10.1016/S2213-2600(22)00092-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942481PMC
June 2022

Effective surveillance of variants.

Science 2022 03 24;375(6587):1349-1350. Epub 2022 Mar 24.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Community testing studies can provide insights as SARS-CoV-2 evolves.
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http://dx.doi.org/10.1126/science.abo4257DOI Listing
March 2022

SARS-CoV-2 Seroprevalence after Third Wave of Infections, South Africa.

Emerg Infect Dis 2022 05 23;28(5):1055-1058. Epub 2022 Mar 23.

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.
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http://dx.doi.org/10.3201/eid2805.220278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045427PMC
May 2022

The impact of COVID-19 non-pharmaceutical interventions on future respiratory syncytial virus transmission in South Africa.

medRxiv 2022 Mar 13. Epub 2022 Mar 13.

In response to the COVID-19 pandemic, the South African government employed various nonpharmaceutical interventions (NPIs) in order to reduce the spread of SARS-CoV-2. In addition to mitigating transmission of SARS-CoV-2, these public health measures have also functioned in slowing the spread of other endemic respiratory pathogens. Surveillance data from South Africa indicates low circulation of respiratory syncytial virus (RSV) throughout the 2020-2021 Southern Hemisphere winter seasons. Here we fit age-structured epidemiological models to national surveillance data to predict the 2022 RSV outbreak following two suppressed seasons. We project a 32% increase in the peak number of monthly hospitalizations among infants ≤ 2 years, with older infants (6-23 month olds) experiencing a larger portion of severe disease burden than typical. Our results suggest that hospital system readiness should be prepared for an intense RSV season in early 2022.
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http://dx.doi.org/10.1101/2022.03.12.22271872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936096PMC
March 2022

Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study.

Lancet 2022 03;399(10330):1141-1153

National Department of Health, Pretoria, South Africa.

Background: We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic.

Methods: In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5 × 10 viral particles of the Ad26.COV2.S vaccine. Vaccinated participants were linked with their person-level data from one of two national medical insurance schemes (scheme A and scheme B) and matched for COVID-19 risk with an unvaccinated member of the general population. The primary outcome was vaccine effectiveness against severe COVID-19, defined as COVID-19-related admission to hospital, hospitalisation requiring critical or intensive care, or death, in health-care workers compared with the general population, ascertained 28 days or more after vaccination or matching, up to data cutoff. This study is registered with the South African National Clinical Trial Registry, DOH-27-022021-6844, ClinicalTrials.gov, NCT04838795, and the Pan African Clinical Trials Registry, PACTR202102855526180, and is closed to accrual.

Findings: Between Feb 17 and May 17, 2021, 477 102 health-care workers were enrolled and vaccinated, of whom 357 401 (74·9%) were female and 119 701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215 813 vaccinated individuals were matched with 215 813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89]).

Interpretation: The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally.

Funding: National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S0140-6736(22)00007-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930006PMC
March 2022

SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-21.

Lancet Infect Dis 2022 06 14;22(6):821-834. Epub 2022 Mar 14.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: By August, 2021, South Africa had been affected by three waves of SARS-CoV-2; the second associated with the beta variant and the third with the delta variant. Data on SARS-CoV-2 burden, transmission, and asymptomatic infections from Africa are scarce. We aimed to evaluate SARS-CoV-2 burden and transmission in one rural and one urban community in South Africa.

Methods: We conducted a prospective cohort study of households in Agincourt, Mpumalanga province (rural site) and Klerksdorp, North West province (urban site) from July, 2020 to August, 2021. We randomly selected households for the rural site from a health and sociodemographic surveillance system and for the urban site using GPS coordinates. Households with more than two members and where at least 75% of members consented to participate were eligible. Midturbinate nasal swabs were collected twice a week from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time RT-PCR (RT-rtPCR). Serum was collected every 2 months and tested for anti-SARS-CoV-2 antibodies. Main outcomes were the cumulative incidence of SARS-CoV-2 infection, frequency of reinfection, symptomatic fraction (percent of infected individuals with ≥1 symptom), the duration of viral RNA shedding (number of days of SARS-CoV-2 RT-rtPCR positivity), and the household cumulative infection risk (HCIR; number of infected household contacts divided by the number of susceptible household members).

Findings: 222 households (114 at the rural site and 108 at the urban site), and 1200 household members (643 at the rural site and 557 at the urban site) were included in the analysis. For 115 759 nasal specimens from 1200 household members (follow-up 92·5%), 1976 (1·7%) were SARS-CoV-2-positive on RT-rtPCR. By RT-rtPCR and serology combined, 749 of 1200 individuals (62·4% [95% CI 58·1-66·4]) had at least one SARS-CoV-2 infection episode, and 87 of 749 (11·6% [9·4-14·2]) were reinfected. The mean infection episode duration was 11·6 days (SD 9·0; range 4-137). Of 662 RT-rtPCR-confirmed episodes (>14 days after the start of follow-up) with available data, 97 (14·7% [11·9-17·9]) were symptomatic with at least one symptom (in individuals aged <19 years, 28 [7·5%] of 373 episodes symptomatic; in individuals aged ≥19 years, 69 [23·9%] of 289 episodes symptomatic). Among 222 households, 200 (90·1% [85·3-93·7]) had at least one SARS-CoV-2-positive individual on RT-rtPCR or serology. HCIR overall was 23·9% (195 of 817 susceptible household members infected [95% CI 19·8-28·4]). HCIR was 23·3% (20 of 86) for symptomatic index cases and 23·9% (175 of 731) for asymptomatic index cases (univariate odds ratio [OR] 1·0 [95% CI 0·5-2·0]). On multivariable analysis, accounting for age and sex, low minimum cycle threshold value (≤30 vs >30) of the index case (OR 5·3 [2·3-12·4]) and beta and delta variant infection (vs Wuhan-Hu-1, OR 3·3 [1·4-8·2] and 10·4 [4·1-26·7], respectively) were associated with increased HCIR. People living with HIV who were not virally supressed (≥400 viral load copies per mL) were more likely to develop symptomatic illness when infected with SAR-CoV-2 (OR 3·3 [1·3-8·4]), and shed SARS-CoV-2 for longer (hazard ratio 0·4 [95% CI 0·3-0·6]) compared with HIV-uninfected individuals.

Interpretation: In this study, 565 (85·3%) SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of beta and delta variants was likely to have contributed to successive waves of SARS-CoV-2 infection, with more than 60% of individuals infected by the end of follow-up.

Funding: US CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust.
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http://dx.doi.org/10.1016/S1473-3099(22)00069-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920516PMC
June 2022

Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa.

Science 2022 05 6;376(6593):eabn4947. Epub 2022 May 6.

National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg, South Africa.

We provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic to date. Although we found no evidence of increased reinfection risk associated with circulation of the Beta (B.1.351) or Delta (B.1.617.2) variants, we did find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 1 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021.
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http://dx.doi.org/10.1126/science.abn4947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995029PMC
May 2022

Seroprevalence of SARS-CoV-2 after the second wave in South Africa in HIV-infected and uninfected persons: a cross-sectional household survey.

Clin Infect Dis 2022 Mar 10. Epub 2022 Mar 10.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa.

Background: Seroprevalence studies are important for quantifying the burden of SARS-CoV-2 infections in resource-constrained countries.

Methods: We conducted a cross-sectional household survey spanning the second pandemic wave (November 2020 - April 2021) in three communities. Blood was collected for SARS-CoV-2 antibody (two ELISA assays targeting spike and nucleocapsid) and HIV testing. An individual was considered seropositive if testing positive on ≥1 assay. Factors associated with infection, and the age-standardised infection to case detection rate (ICR), infection hospitalisation rate (IHR) and infection fatality rate (IFR) were calculated.

Results: Overall 7959 participants were enrolled, with a median age of 34 years and HIV prevalence of 22.7%. SARS-CoV-2 seroprevalence was 45.2% (95% confidence interval 43.7% - 46.7%), and increased from 26.9% among individuals enrolled in December 2020 to 47.1% among individuals in April 2021. On multivariable analysis, seropositivity was associated with age, sex, race, being overweight/obese, having respiratory symptoms, and low socioeconomic status. Persons living with HIV (PLWHIV) with high viral load were less likely to be seropositive compared to HIV-uninfected individuals. The site-specific ICR, IHR and IFR ranged across sites from 4.4% to 8.2%, 1.2% to 2.5% and 0.3% to 0.6%, respectively.

Conclusions: South Africa has experienced a large burden of SARS-CoV-2 infections, with <10% of infections diagnosed. Lower seroprevalence among non-virally suppressed PLWHIV, likely as a result of inadequate antibody production, highlights the need to prioritise this group for intervention.
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http://dx.doi.org/10.1093/cid/ciac198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047164PMC
March 2022

Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections - a survival analysis.

Int J Infect Dis 2022 May 27;118:150-154. Epub 2022 Feb 27.

Division of Medical Virology, University of Cape Town, Cape Town, Western Cape, South Africa; National Health Laboratory Service, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.

Background: At present, it is unclear whether the extent of reduced risk of severe disease seen with SARS-Cov-2 Omicron variant infection is caused by a decrease in variant virulence or by higher levels of population immunity.

Methods: RdRp target delay (RTD) in the Seegene Allplex 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene Allplex assay from November 1 to December 14, 2021 in the Western Cape Province, South Africa, in the public sector. Adjustments were made for vaccination status and prior diagnosis of infection.

Results: A total of 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77).

Conclusion: Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.
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http://dx.doi.org/10.1016/j.ijid.2022.02.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882068PMC
May 2022

The national burden of influenza-like illness and severe respiratory illness overall and associated with nine respiratory viruses in South Africa, 2013-2015.

Influenza Other Respir Viruses 2022 05 11;16(3):438-451. Epub 2022 Feb 11.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

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.
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http://dx.doi.org/10.1111/irv.12949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983907PMC
May 2022

Study protocol for a population-based observational surveillance study of culture-confirmed neonatal bloodstream infections and meningitis in South Africa: Baby GERMS-SA.

BMJ Open 2022 Feb 8;12(2):e049070. Epub 2022 Feb 8.

National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa.

Introduction: Worldwide, neonatal mortality remains high accounting for 47% of childhood deaths in 2019 and including an estimated 500 000 deaths from neonatal infections. While 42% of global neonatal deaths occur in sub-Saharan Africa, there is limited understanding of population-level burden and aetiology of neonatal infections outside tertiary-level institutions.

Methods And Analysis: We aim to implement the first population-level surveillance for bloodstream infections and meningitis among neonates aged <28 days in South Africa. Tier 1 will include national surveillance of culture-confirmed neonatal infections at all public-sector hospitals describing infection incidence risk, pathogen profile and antimicrobial susceptibility by institution, province and healthcare level (2014-2021). Tier 2 (nested within tier 1) will be conducted at six regional neonatal units over 12 months, will compare the clinical characteristics of neonates with early-onset and late-onset infections and identify potentially modifiable risk factors for mortality. Through tier 2, we will determine the antimicrobial susceptibility of neonatal pathogens, evaluate the appropriateness of empiric antibiotic prescribing and determine the genomic epidemiology of multidrug resistant bacterial and fungal pathogens.

Ethics And Dissemination: Ethics clearance was obtained from the Human Research Ethics Committee of the University of the Witwatersrand (M190320). Funding for the study was obtained through a grant from the Bill and Melinda Gates Foundation (OPP1208882). Baby GERMS-SA aims to impact on national policy, resource allocation and neonatal guidelines by describing the national burden of neonatal infections in South Africa. In addition, end-users in neonatal units will benefit from a facility-level dashboard displaying key indicators of the surveillance findings.
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http://dx.doi.org/10.1136/bmjopen-2021-049070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830263PMC
February 2022

Prolonged shedding of SARS-CoV-2 at high viral loads amongst hospitalised immunocompromised persons living with HIV, South Africa.

Clin Infect Dis 2022 Feb 2. Epub 2022 Feb 2.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Johannesburg, South Africa.

Background: We assessed SARS-CoV-2 RNA shedding duration and magnitude amongst persons living with HIV (PLHIV).

Methods: From May through December 2020, we conducted a prospective cohort study at 20 hospitals in South Africa. Adults hospitalised with symptomatic COVID-19 were enrolled and followed every two days with nasopharyngeal/oropharyngeal (NP/OP) swabs until documentation of cessation of SARS-CoV-2 shedding (two consecutive negative NP/OP swabs). Real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2 was performed and Cycle-threshold (Ct) values <30 were considered a proxy for high SARS-CoV-2 viral load. Factors associated with prolonged shedding were assessed using accelerated time-failure Weibull regression models.

Results: Of 2,175 COVID-19 patients screened, 300 were enrolled and 257 individuals (155 HIV-uninfected and 102 PLHIV) had >1 swabbing visit (median 5 visits (range2-21)). Median time to cessation of shedding was 13 days (inter-quartile range (IQR)6-25) and did not differ significantly by HIV-infection.

Discussion: Amongst a subset of 94 patients (41 PLHIV and 53 HIV-uninfected) with initial respiratory sample Ct-value <30, median time of shedding at high SARS-CoV-2 viral load was 8 days (IQR4-17). This was significantly longer in PLHIV with CD4 count<200cells/µl, compared to HIV-uninfected persons (median 27 days (IQR8-43) versus 7 days (IQR 4-13); aHR 0.14, 95%CI 0.07-0.28, p<0.001), with similar results in unsuppressed-HIV versus HIV-uninfected persons.

Conclusion: Although SARS-CoV-2 shedding duration did not differ significantly by HIV-infection, amongst a subset with high initial SARS-CoV-2 viral loads, immunocompromised PLHIV shed SARS-CoV-2 at high viral loads for longer than HIV-uninfected persons. Better HIV control may potentially decrease transmission time of SARS-CoV-2.
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http://dx.doi.org/10.1093/cid/ciac077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903337PMC
February 2022

The direct and indirect effects of the COVID-19 pandemic on private healthcare utilization in South Africa, March 2020 - September 2021.

Clin Infect Dis 2022 Jan 27. Epub 2022 Jan 27.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Background: The COVID-19 pandemic caused severe disruptions to healthcare in many areas of the world, but data remain scarce for sub-Saharan Africa.

Methods: We evaluated trends in hospital admissions and outpatient emergency department (ED) and general practitioner (GP) visits to South Africa's largest private healthcare system during 2016 - 2021. We fit time series models to historical data and, from March 2020 to September 2021, quantified changes in encounters relative to baseline.

Results: The nationwide lockdown on 26 March 2020 led to sharp reductions in care-seeking behavior that persisted for 18 months after initial declines. For example, total admissions dropped 59.6% [95% confidence interval: 52.4, 66.8] during home confinement and were 33.2% [29, 37.4] below baseline in September 2021. We identified three waves of all-cause respiratory encounters consistent with COVID-19 activity. Intestinal infections and non-COVID-19 respiratory illnesses experienced the most pronounced declines, with some diagnoses reduced 80%, even as non-pharmaceutical interventions (NPIs) were relaxed. Non-respiratory hospitalizations, including injuries and acute illnesses (e.g., heart attack, stroke), were 20-60% below baseline throughout the pandemic and exhibited strong temporal associations with NPIs and mobility behavior. ED attendances exhibited similar trends to hospitalizations, while GP visits, particularly for chronic illnesses and HIV, were less impacted and have returned to pre-pandemic levels.

Conclusions: We find substantially reduced use of health services during the pandemic for a range of conditions unrelated to COVID-19. Persistent declines in hospitalizations and ED visits indicate that high-risk patients are still delaying seeking care, which could lead to morbidity or mortality increases in the future.
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http://dx.doi.org/10.1093/cid/ciac055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807275PMC
January 2022

Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.

Lancet 2022 01 19;399(10323):437-446. Epub 2022 Jan 19.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address:

Background: The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy.

Methods: We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021.

Findings: From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1-0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3-1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2-0·5), after controlling for factors associated with disease severity.

Interpretation: Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity.

Funding: The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.
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http://dx.doi.org/10.1016/S0140-6736(22)00017-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769664PMC
January 2022

Deaths from RSV in young infants-the hidden community burden.

Lancet Glob Health 2022 02;10(2):e169-e170

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, and SA-MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.

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http://dx.doi.org/10.1016/S2214-109X(21)00558-1DOI Listing
February 2022

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.

medRxiv 2022 Jan 12. Epub 2022 Jan 12.

Groote Schuur Hospital, Western Cape Government: Health.

Objectives: We aimed to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection, and whether protection against severe disease conferred by prior infection and/or vaccination was maintained.

Methods: In this cohort study, we included public sector patients aged ≥20 years with a laboratory confirmed COVID-19 diagnosis between 14 November-11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalization or death and any hospitalization or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection.

Results: We included 5,144 patients from wave four and 11,609 from prior waves. Risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted Hazard Ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR:0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58).

Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for an approximately 25% reduced risk of severe hospitalization or death compared to Delta.
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http://dx.doi.org/10.1101/2022.01.12.22269148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764730PMC
January 2022

Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016-2018: A hidden Markov modelling study.

PLoS Comput Biol 2021 12 23;17(12):e1009680. Epub 2021 Dec 23.

Centre for the Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant's age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9-80.5%) than older children (5-17 years-old) (31.7-50.0%) or adults (11.5-23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7-15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91-1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2-12.8 vs 6.0 days, 95%CI: 5.6-6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507-714 vs 389, 95%CI: 311.1-435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.
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http://dx.doi.org/10.1371/journal.pcbi.1009680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699682PMC
December 2021

Streptococcus pneumoniae Serotypes Associated with Death, South Africa, 2012-2018.

Emerg Infect Dis 2022 01;28(1):166-179

These authors contributed equally to this article.

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.
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http://dx.doi.org/10.3201/eid2801.210956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714227PMC
January 2022

SARS-CoV-2 incidence, transmission and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-2021.

medRxiv 2021 Dec 4. Epub 2021 Dec 4.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Background: By August 2021, South Africa experienced three SARS-CoV-2 waves; the second and third associated with emergence of Beta and Delta variants respectively.

Methods: We conducted a prospective cohort study during July 2020-August 2021 in one rural and one urban community. 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). Serum was collected every two months and tested for anti-SARS-CoV-2 antibodies.

Results: Among 115,759 nasal specimens from 1,200 members (follow-up rate 93%), 1976 (2%) were SARS-CoV-2-positive. By rRT-PCR and serology combined, 62% (749/1200) of individuals experienced ≥1 SARS-CoV-2 infection episode, and 12% (87/749) experienced reinfection. Of 662 PCR-confirmed episodes with available data, 15% (n=97) were associated with ≥1 symptom. Among 222 households, 200 (90%) had ≥1 SARS-CoV-2-positive individual. Household cumulative infection risk (HCIR) was 25% (213/856). On multivariable analysis, accounting for age and sex, index case lower cycle threshold value (OR 3.9, 95%CI 1.7-8.8), urban community (OR 2.0,95%CI 1.1-3.9), Beta (OR 4.2, 95%CI 1.7-10.1) and Delta (OR 14.6, 95%CI 5.7-37.5) variant infection were associated with increased HCIR. HCIR was similar for symptomatic (21/110, 19%) and asymptomatic (195/775, 25%) index cases (p=0.165). Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection. People living with HIV who were not virally supressed were more likely to develop symptomatic illness, and shed SARS-CoV-2 for longer compared to HIV-uninfected individuals.

Conclusions: In this study, 85% of SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of Beta and Delta variants, likely contributed to successive waves, with >60% of individuals infected by the end of follow-up.

Research In Context: Previous studies have generated wide-ranging estimates of the proportion of SARS-CoV-2 infections which are asymptomatic. A recent systematic review found that 20% (95% CI 3%-67%) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remained asymptomatic throughout infection and that transmission from asymptomatic individuals was reduced. A systematic review and meta-analysis of 87 household transmission studies of SARS-CoV-2 found an estimated secondary attack rate of 19% (95% CI 16-22). The review also found that household secondary attack rates were increased from symptomatic index cases and that adults were more likely to acquire infection. As of December 2021, South Africa experienced three waves of SARS-CoV-2 infections; the second and third waves were associated with circulation of Beta and Delta variants respectively. SARS-CoV-2 vaccines became available in February 2021, but uptake was low in study sites reaching 5% fully vaccinated at the end of follow up. Studies to quantify the burden of asymptomatic infections, symptomatic fraction, reinfection frequency, duration of shedding and household transmission of SARS-CoV-2 from asymptomatically infected individuals have mostly been conducted as part of outbreak investigations or in specific settings. Comprehensive systematic community studies of SARS-CoV-2 burden and transmission including for the Beta and Delta variants are lacking, especially in low vaccination settings. We conducted a unique detailed COVID-19 household cohort study over a 13 month period in South Africa, with real time reverse transcriptase polymerase chain reaction (rRT-PCR) testing twice a week irrespective of symptoms and bimonthly serology. By the end of the study in August 2021, 749 (62%) of 1200 individuals from 222 randomly sampled households in a rural and an urban community in South Africa had at least one confirmed SARS-CoV-2 infection, detected on rRT-PCR and/or serology, and 12% (87/749) experienced reinfection. Symptom data were analysed for 662 rRT-PCR-confirmed infection episodes that occurred >14 days after the start of follow-up (of a total of 718 rRT-PCR-confirmed episodes), of these, 15% (n=97) were associated with one or more symptoms. Among symptomatic indvidiausl, 9% (n=9) were hospitalised and 2% (n=2) died. Ninety percent (200/222) of included households, had one or more individual infected with SARS-CoV-2 on rRT-PCR and/or serology within the household. SARS-CoV-2 infected index cases transmitted the infection to 25% (213/856) of susceptible household contacts. Index case ribonucleic acid (RNA) viral load proxied by rRT-PCR cycle threshold value was strongly predictive of household transmission. Presence of symptoms in the index case was not associated with household transmission. Household transmission was four times greater from index cases infected with Beta variant and fifteen times greater from index cases infected with Delta variant compared to wild-type infection. Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection within households. People living with HIV (PLHIV) who were not virally supressed were more likely to develop symptomatic illness when infected with SARS-CoV-2, and shed SARS-CoV-2 for longer when compared to HIV-uninfected individuals. We found a high rate of SARS-CoV-2 infection in households in a rural community and an urban community in South Africa, with the majority of infections being asymptomatic in individuals of all ages. Asymptomatic individuals transmitted SARS-CoV-2 at similar levels to symptomatic individuals suggesting that interventions targeting symptomatic individuals such as symptom-based testing and contact tracing of individuals tested because they report symptoms may have a limited impact as control measures. Increased household transmission of Beta and Delta variants, likely contributed to recurrent waves of COVID-19, with >60% of individuals infected by the end of follow-up. Higher attack rates, reinfection and acquisition in adolescents and prolonged SARS-CoV-2 shedding in PLHIV who were not virally suppressed suggests that prioritised vaccination of individuals in these groups could impact community transmission.
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http://dx.doi.org/10.1101/2021.07.20.21260855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669861PMC
December 2021

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

Influenza Other Respir Viruses 2022 01 18;16(1):34-47. Epub 2021 Nov 18.

National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, 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.
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http://dx.doi.org/10.1111/irv.12916DOI Listing
January 2022

Detection of Victoria lineage influenza B viruses with K162 and N163 deletions in the hemagglutinin gene, South Africa, 2018.

Health Sci Rep 2021 Sep 17;4(3):e367. Epub 2021 Sep 17.

Centre for Respiratory Diseases and Meningitis National Institute for Communicable Diseases of the National Health Laboratory Service Johannesburg South Africa.

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.
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http://dx.doi.org/10.1002/hsr2.367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448392PMC
September 2021

Human respiratory syncytial virus diversity and epidemiology among patients hospitalized with severe respiratory illness in South Africa, 2012-2015.

Influenza Other Respir Viruses 2022 03 16;16(2):222-235. Epub 2021 Sep 16.

University of the Witwatersrand, Johannesburg, South Africa.

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.
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http://dx.doi.org/10.1111/irv.12905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818822PMC
March 2022
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