Cohort Profile: a Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa (PHIRST), 2016-2018
Authors: Cohen Cheryl , McMorrow Meredith L. , Martinson Neil A. , Kahn Kathleen , Treurnicht Florette K. , Moyes Jocelyn , Mkhencele Thulisa , Hellferscee Orienka , Lebina Limakatso , Moroe Matebejane , Motlhaoleng Katlego , Gómez-Olivé F. Xavier , Wagner Ryan , Tollman Stephen , Wafawanaka Floidy , Ngobeni Sizzy , Kleynhans Jackie , Mathunjwa Azwifari , Buys Amelia , Maake Lorens , Wolter Nicole , Carrim Maimuna , Piketh Stuart , Language Brigitte , Mathee Angela , Gottberg Anne von , Tempia Stefano ,   for the PHIRST group
Published: January 2021

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 disease severity, and to assess household transmission. We further aimed to estimate the impact of HIV infection and age on disease burden and transmission, and to assess the burden of Bordetella pertussis and Streptococcus pneumoniae.

Participants

We enrolled 1684 individuals in 327 randomly selected households in two sites (rural Agincourt subdistrict, Mpumalanga Province and urban Jouberton Township, North West Province) over 3 consecutive influenza and RSV seasons. A new cohort of households was enrolled each year. Eligible households included those with >2 household members where ≥80% of household members provided consent (and assent for children aged 7-17 years). Enrolled household members 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 from follow-up visits, 1,258 (1%), 1,026 (1%), 273 (<1%), 38,829 (37%) tested positive on PCR for influenza viruses, respiratory syncytial virus, pertussis and pneumococcus respectively.

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 and household selection methods to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.

Registration

Clinical trials.gov NCT02519803

Article summary

Strengths and limitations of this study

PHIRST was conducted in urban and rural African settings with high HIV prevalence, allowing assessment of the effect of HIV on community burden and transmission dynamics of respiratory pathogens.

Households were selected randomly to provide a representative sample of the community. Twice weekly sampling from each cohort of individuals for 6-10 months irrespective of symptoms allows estimation of community burden, household secondary infection risk, and serial interval including asymptomatic or paucisymptomatic episodes.

Polymerase chain reaction testing of >100,000 nasopharyngeal swab samples for multiple pathogens (influenza, respiratory syncytial virus, pertussis and Streptoccocus pneumonia) allows detailed examination of disease burden and transmission and pathogen interactions

PHIRST was not powered to assess severe outcomes (i.e. hospitalisation and death).

We only examined four pathogens, but other micro-organisms may be important. Samples have been stored which could allow us to implement broader multi-pathogen testing in the future.