A Potential Platform for Future Vaccine Trials Identifies a High Incidence of Symptomatic and Asymptomatic Influenza Infection Among Children Aged 6 to 23 Months in South Africa.

Background: Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both are important for developing improved vaccines. We estimated influenza infection incidence and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design.

Methods: We conducted a prospective cohort study among children aged 6 to 23 months from May to October 2022.

Characteristics of infections with ancestral, Beta and Delta variants of SARS-CoV-2 in the PHIRST-C community cohort study, South Africa, 2020-2021.

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.

An external quality assessment feasibility study; cross laboratory comparison of haemagglutination inhibition assay and microneutralization assay performance for seasonal influenza serology testing: A FLUCOP study.

Introduction: External Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods.

Risk Factors for Severe Coronavirus Disease 2019 Among Human Immunodeficiency Virus-Infected and -Uninfected Individuals in South Africa, April 2020-March 2022: Data From Sentinel Surveillance.

Background: Data on risk factors for coronavirus disease 2019 (COVID-19)-associated hospitalization and mortality in high human immunodeficiency virus (HIV) prevalence settings are limited.

Methods: Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalization and mortality.

Results: From April 2020 through March 2022, severe acute respiratory syndrome coronavirus 2 was detected in 24.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 From Adult Index Cases With and Without Human Immunodeficiency Virus in South Africa, 2020-2021: A Case-Ascertained, Prospective, Observational Household Transmission Study.

Background: In South Africa, 19% of adults are living with human immunodeficiency virus (HIV; LWH). Few data on the influence of HIV on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission are available.

Methods: We performed a case-ascertained, prospective household transmission study of symptomatic adult index SARS-CoV-2 cases LWH and not living with HIV (NLWH) and their contacts from October 2020 to September 2021.

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

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.

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

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.

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.

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.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 After the Second Wave in South Africa in Human Immunodeficiency Virus-Infected and Uninfected Persons: A Cross-Sectional Household Survey.

Background: Seroprevalence studies are important for quantifying the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in resource-constrained countries.

Methods: We conducted a cross-sectional household survey spanning the second pandemic wave (November 2020 to April 2021) in 3 communities. Blood was collected for SARS-CoV-2 antibody (2 enzyme-linked immunosorbent assays targeting spike and nucleocapsid) and human immunodeficiency virus (HIV) testing.

Prolonged Shedding of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at High Viral Loads Among Hospitalized Immunocompromised Persons Living With Human Immunodeficiency Virus (HIV), South Africa.

Background: We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding duration and magnitude among persons living with human immunodeficiency virus (HIV, PLHIV).

Methods: From May through December 2020, we conducted a prospective cohort study at 20 hospitals in South Africa. Adults hospitalized with symptomatic coronavirus disease 2019 (COVID-19) were enrolled and followed every 2 days with nasopharyngeal/oropharyngeal (NP/OP) swabs until documentation of cessation of SARS-CoV-2 shedding (2 consecutive negative NP/OP swabs).

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.

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).

SARS-CoV-2 Seroprevalence in a Rural and Urban Household Cohort during First and Second Waves of Infections, South Africa, July 2020-March 2021.

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.

Cohort profile: A Prospective Household cohort study of Influenza, Respiratory syncytial virus and other respiratory pathogens community burden and Transmission dynamics in South Africa, 2016-2018.

Purpose: The PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and to assess household transmission.

Participants: We enrolled 1684 individuals in 327 randomly selected households in a rural and an urban site over three consecutive influenza and two RSV seasons. A new cohort of households was enrolled each year.

Impact of Maternal HIV Infection and Placental Malaria on the Transplacental Transfer of Influenza Antibodies in Mother-Infant Pairs in Malawi, 2013-2014.

Background: Maternal influenza vaccination protects infants against influenza virus infection. Impaired transplacental transfer of influenza antibodies may reduce this protection.

Methods: We conducted a cross-sectional study of influenza vaccine-naïve pregnant women recruited at delivery from Blantyre (urban, low malaria transmission) and Chikwawa (rural, high malaria transmission) in Southern Malawi.

Sequencing and analysis of globally obtained human parainfluenza viruses 1 and 3 genomes.

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections.

Replacement of neuraminidase inhibitor-susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.

Background: Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done.

Objectives: We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa.

Patients/methods: We enrolled participants through national influenza-like illness surveillance, 2007-2013.

Risk of Human Infections With Highly Pathogenic H5N2 and Low Pathogenic H7N1 Avian Influenza Strains During Outbreaks in Ostriches in South Africa.

Background: Risk factors for human infection with highly pathogenic (HP) and low-pathogenic (LP) avian influenza (AI) H5N2 and H7N1 were investigated during outbreaks in ostriches in the Western Cape province, South Africa.

Methods: Serum surveys were conducted for veterinarians, farmworkers, and laboratory and abattoir workers involved in 2 AI outbreaks in the Western Cape province: (1) controlling and culling of 42000 ostriches during (HPAI)H5N2 outbreaks in ostriches (2011) (n = 207); (2) movement control during (LPAI)H7N1 outbreaks in 2012 (n = 66). A third serosurvey was conducted on state veterinarians from across the country in 2012 tasked with disease control in general (n = 37).

Epidemiology of influenza B/Yamagata and B/Victoria lineages in South Africa, 2005-2014.

Background: Studies describing the epidemiology of influenza B lineages in South Africa are lacking.

Methods: We conducted a prospective study to describe the circulation of influenza B/Victoria and B/Yamagata lineages among patients of all ages enrolled in South Africa through three respiratory illness surveillance systems between 2005 and 2014: (i) the Viral Watch (VW) program enrolled outpatients with influenza-like illness (ILI) from private healthcare facilities during 2005-2014; (ii) the influenza-like illnesses program enrolled outpatients in public healthcare clinics (ILI/PHC) during 2012-2014; and (iii) the severe acute respiratory illnesses (SARI) program enrolled inpatients from public hospitals during 2009-2014. Influenza B viruses were detected by virus isolation during 2005 to 2009 and by real-time reverse transcription polymerase chain reaction from 2009-2014.

Effectiveness and knowledge, attitudes and practices of seasonal influenza vaccine in primary healthcare settings in South Africa, 2010-2013.

Objectives: Influenza vaccine effectiveness (VE) and coverage data for sub-Saharan Africa are scarce. Using a test-negative case-control design, we estimated influenza VE annually among individuals with influenza-like illness presenting to an outpatient sentinel surveillance programme in South Africa from 2010 to 2013. A knowledge, attitudes and practices (KAP) influenza vaccine survey of programme clinicians was conducted in 2013.

Influenza epidemiology and vaccine effectiveness among patients with influenza-like illness, viral watch sentinel sites, South Africa, 2005-2009.

Background: There is limited data on the epidemiology of influenza and few published estimates of influenza vaccine effectiveness (VE) from Africa. In April 2009, a new influenza virus strain infecting humans was identified and rapidly spread globally. We compared the characteristics of patients ill with influenza A(H1N1)pdm09 virus to those ill with seasonal influenza and estimated influenza vaccine effectiveness during five influenza seasons (2005-2009) in South Africa.

Evolutionary dynamics of 2009 pandemic influenza A virus subtype H1N1 in South Africa during 2009-2010.

Background: The 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) was first detected in June 2009 in South Africa and later resulted in extensive transmission throughout Africa. Established routine surveillance programs and collaboration between private and public sector laboratories allowed for comprehensive molecular epidemiological and antigenic investigation of the first and second waves of 2009-2010 pandemic influenza in South Africa.

Methods: We used reverse-transcription polymerase chain reaction to screen for influenza virus in 9792 specimens recovered during 2009 and 6915 specimens recovered during 2010 from inpatients and outpatients with influenza-like illness or severe acute respiratory illness symptoms identified by surveillance programs.

Respiratory viral coinfections identified by a 10-plex real-time reverse-transcription polymerase chain reaction assay in patients hospitalized with severe acute respiratory illness--South Africa, 2009-2010.

Background: Data about respiratory coinfections with 2009 pandemic influenza A virus subtype H1N1 during the 2009-2010 influenza pandemic in Africa are limited. We used an existing surveillance program for severe acute respiratory illness to evaluate a new multiplex real-time polymerase chain reaction assay and investigate the role of influenza virus and other respiratory viruses in pneumonia hospitalizations during and after the influenza pandemic in South Africa.

Methods: The multiplex assay was developed to detect 10 respiratory viruses, including influenza A and B viruses, parainfluenza virus types 1-3, respiratory syncytial virus (RSV), enterovirus, human metapneumovirus (hMPV), adenovirus (AdV), and rhinovirus (RV), followed by influenza virus subtyping.

Twenty-five years of outpatient influenza surveillance in South Africa, 1984-2008.

Introduction: Understanding the seasonality of influenza can help inform prevention and clinical treatment strategies. The aim of this manuscript is to describe the trends and epidemiology of outpatient influenza in South Africa prior to the influenza A(H1N1) pandemic.

Methods: Throughout each year, participating healthcare practitioners sent throat swabs from patients with influenza-like illness (ILI) to the National Institute for Communicable Diseases for influenza testing by immunofluorescence and viral culture through the Viral Watch influenza surveillance program.

Setting up a platform for plant-based influenza virus vaccine production in South Africa.

Background: During a global influenza pandemic, the vaccine requirements of developing countries can surpass their supply capabilities, if these exist at all, compelling them to rely on developed countries for stocks that may not be available in time. There is thus a need for developing countries in general to produce their own pandemic and possibly seasonal influenza vaccines. Here we describe the development of a plant-based platform for producing influenza vaccines locally, in South Africa.