Data on respiratory syncytial virus (RSV) incidence and household transmission are limited. To describe RSV incidence and transmission, we conducted a prospective cohort study in rural and urban communities in South Africa over two seasons during 2017-2018. Nasopharyngeal swabs were collected twice-weekly for 10 months annually and tested for RSV using PCR. We tested 81,430 samples from 1,116 participants in 225 households (follow-up 90%). 32% (359/1116) of individuals had ≥1 RSV infection; 10% (37/359) had repeat infection during the same season, 33% (132/396) of infections were symptomatic, and 2% (9/396) sought medical care. Incidence was 47.2 infections/100 person-years and highest in children <5 years (78.3). Symptoms were commonest in individuals aged 10 days were more likely to transmit; household contacts aged 1-4 years vs. ≥65 years were more likely to acquire infection. Within two South African communities, RSV attack rate was high, and most infections asymptomatic. Young children were more likely to introduce RSV into the home, and to be infected. Future studies should examine whether vaccines targeting children aged <12 years could reduce community transmission.

Background: Economic burden estimates are essential to guide policy‐making for influenza vaccination, especially in resource‐limited settings.Methods: We estimated the cost, absenteeism, and years of life lost (YLL) of medically and non‐medically attended influenza‐associated mild and severe respiratory, circulatory and non‐respiratory/non‐circulatory illness in South Africa during 2013‐2015 using a modified version of the World Health Organization (WHO) worksheet based tool for estimating the economic burden of seasonal influenza. Additionally, we restricted the analysis to influenza‐associated severe acute respiratory illness (SARI) and influenza‐like illness (ILI; subsets of all‐respiratory illnesses) as suggested in the WHO manual.Results: The estimated mean annual cost of influenza‐associated illness was $270.5 million, of which $111.3 million (41%) were government‐incurred costs, 40.7 million (15%) were out‐of‐pocket expenses, and $118.4 million (44%) were indirect costs. The cost of influenza‐associated medically attended mild illness ($107.9 million) was 2.3 times higher than that of severe illness ($47.1 million). Influenza‐associated respiratory illness costs ($251.4 million) accounted for 93% of the total cost. Estimated absenteeism and YLL were 13.2 million days and 304 867 years, respectively. Among patients with influenza‐associated WHO‐defined ILI or SARI, the costs ($95.3 million), absenteeism (4.5 million days), and YLL (65 697) were 35%, 34%, and 21% of the total economic and health burden of influenza.Conclusion: The economic burden of influenza‐associated illness was substantial from both a government and a societal perspective. Models that limit estimates to those obtained from patients with WHO‐defined ILI or SARI substantially underestimated the total economic and health burden of influenza‐associated illness.

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. Participants were sampled with nasopharyngeal swabs twice‐weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually.Findings to Date: There were 122 113 potential individual follow‐up visits over the 3 years, and participants were interviewed for 105 783 (87%) of these. Out of 105 683 nasopharyngeal swabs, 1258 (1%) and 1026 (1%) tested positive on polymerase chain reaction (PCR) for influenza viruses and RSV, respectively. Over one third of individuals had PCR‐confirmed influenza each year. Overall, there was influenza transmission to 10% of household contacts of an index case.Future Plans: Future planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016–2018 were eligible for inclusion in a study of SARS‐CoV‐2 transmission initiated in July 2020. This study uses similar testing frequency to assess the community burden of SARS‐CoV‐2 infection and the role of asymptomatic infection in virus transmission.

Enteroviruses can cause outbreaks of severe acute respiratory illness (SARI) and EV‐A, ‐B, ‐C, and ‐D species have different pathogenic profiles and circulation patterns. We aimed to characterize and determine the prevalence of enterovirus genotypes among South African patients with respiratory illness and controls during June 2012 to July 2014. Syndromic SARI and influenza‐like illness (ILI) surveillance was performed at two sentinel sites. At each site nasopharyngeal/oropharyngeal specimens were collected from SARI and ILI patients as well as controls. Specimens were tested for enterovirus by real‐time PCR. Positive specimens were further genotyped by sequencing a region of the VP1 gene. The prevalence of enterovirus was 5.8% (87/1494), 3.4% (103/3079), and 3.4% (46/1367) among SARI, ILI, and controls, respectively (SARI/controls, P = 0.002 and ILI/control, P = 0.973). Among the 101/236 (42.8%) enterovirus‐positive specimens that could be genotyped, we observed a high diversity of circulating enterovirus genotypes (a total of 33 genotypes) from all four human enterovirus species with high prevalence of Enterovirus‐B (60.4%; 61/101) and Enterovirus‐A (21.8%; 22/101) compared to Enterovirus‐C (10.9%; 11/101) and Enterovirus‐D (6.9%; 7/101) (P = 0.477). Of the enterovirus genotypes identified, Echovirus 30 (9.9%, 10/101), Coxsackie virus B5 (7.9%, 8/101) and Enterovirus‐D68 (6.9%, 7/101) were most prevalent. There was no difference in disease severity (SARI or ILI compared to controls) between the different enterovirus species (P = 0.167). We observed a high number of enterovirus genotypes in patients with respiratory illness and in controls from South Africa with no disease association of EV species with disease severity.

Aim: To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa.Methods: The study included 680 South African patients randomly selected in age‐defined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real‐time polymerase chain reaction assay was used to detect hBoV; hCoV‐OC43, hCoV‐229E, hCoV‐NL63, and hCoV‐HKU1; and Washington University hPyV (hPyV‐WU) and Karolinska Insitute hPyV (hPyV‐KI), in respiratory tract specimens collected from patients with SARI. All respiratory specimens from patients enrolled through SARI surveillance were also routinely tested by multiplex reverse transcription real‐time polymerase chain reaction for adenovirus; enterovirus; human metapneumovirus; parainfluenza virus types 1, 2, and 3; respiratory syncytial virus; rhinovirus; influenza A, and influenza B.Results: Human bocavirus, hCoV‐229E, and hPyV‐WU were detected in 3.7% (25/680), 4.1% (28/680), and 4.1% (28/680) of respiratory specimens, respectively. All other viruses were detected in <2% of specimens. Rhinovirus was the most common coinfecting virus (21.4%‐60.7%), followed by adenovirus (21.4%‐39.3%), and respiratory syncytial virus (10.7%‐24.0%). Testing for the additional viruses (hBoV, hCoV, and hPyV) decreased the number of specimens that initially tested negative by 2.9% (20/680).Conclusion: Inclusion of laboratory tests for hBoV, hCoV‐229E, and hPyV‐WU in differential testing algorithms for surveillance and diagnostics for suspected cases of respiratory illness of unknown cause may improve our understanding of the etiology of SARI, especially in a country like South Africa with a high number of immune compromised persons.

Background: The attributable fraction of influenza virus detection to illness (INF‐AF) and the duration of symptoms as a surveillance inclusion criterion could potentially have substantial effects on influenza disease burden estimates.Methods: We estimated rates of influenza‐associated influenza‐like illness (ILI) and severe acute (SARI‐10) or chronic (SCRI‐10) respiratory illness (using a symptom duration cutoff of ≤10 days) among HIV‐infected and HIV‐uninfected patients attending 3 hospitals and 2 affiliated clinics in South Africa during 2013‐2015. We calculated the unadjusted and INF‐AF‐adjusted rates and relative risk (RR) due to HIV infection. Rates were expressed per 100 000 population.Results: The estimated mean annual unadjusted rates of influenza‐associated illness were 1467.7, 50.3, and 27.4 among patients with ILI, SARI‐10, and SCRI‐10, respectively. After adjusting for the INF‐AF, the percent reduction in the estimated rates was 8.9% (rate: 1336.9), 11.0% (rate: 44.8), and 16.3% (rate: 22.9) among patients with ILI, SARI‐10, and SCRI‐10, respectively. HIV‐infected compared to HIV‐uninfected individuals experienced a 2.3 (95% CI: 2.2‐2.4)‐, 9.7 (95% CI: 8.0‐11.8)‐, and 10.0 (95% CI: 7.9‐12.7)‐fold increased risk of influenza‐associated illness among patients with ILI, SARI‐10, and SCRI‐10, respectively. Overall 34% of the estimated influenza‐associated hospitalizations had symptom duration of >10 days; 8% and 44% among individuals aged <5 and ≥5 years, respectively.Conclusion: The marginal differences between unadjusted and INF‐AF‐adjusted rates are unlikely to affect policies on prioritization of interventions. HIV‐infected individuals experienced an increased risk of influenza‐associated illness and may benefit more from annual influenza immunization. The use of a symptom duration cutoff of ≤10 days may underestimate influenza‐associated disease burden, especially in older individuals.