Data sources
Data source 1: Respiratory viruses surveillance among patients with influenza-like-illness and severe respiratory illness
We conducted active prospective hospital-based surveillance among patients with SRI at 3 public hospitals in 2 provinces [Edendale Hospital in a peri-urban area of KwaZulu-Natal province, and Klerksdorp and Tshepong Hospitals (the Klerksdorp-Tshepong Hospital Complex, KTHC) in a peri-urban area of North West province] during 2013-2015. A case of SRI was defined as a hospitalized person with symptoms of any duration who met age-specific clinical inclusion criteria. A case in children aged 2 days to <3 months included any hospitalized patient with diagnosis of suspected sepsis or physician-diagnosed acute lower respiratory tract infection irrespective of signs and symptoms. A case in children aged 3 months to <5 years included any hospitalized patient with physician-diagnosed acute lower respiratory tract infection, including bronchitis, bronchiolitis, pneumonia and pleural effusion. A case in individuals aged ≥5 years included any hospitalized patient presenting with manifestation of acute lower respiratory tract infection with fever (≥38°C) or history of fever and cough.
In addition, we conducted prospective surveillance for patients presenting with ILI at two outpatient clinics (Edendale Gateway Clinic, KwaZulu-Natal province, and Jouberton Clinic, North West province) located in the same catchment area as the above-mentioned hospitals over the same study period. An ILI case was defined as an outpatient of any age presenting with either temperature ≥38°C or history of fever and cough of duration of ≤10 days.
We also enrolled persons presenting at the same outpatient clinics with no history of fever, respiratory or gastrointestinal symptoms during the 14 days preceding the visit (hereafter referred to as controls). These individuals commonly presented to the clinics for visits such as dental procedures, family planning, well baby visits, voluntary HIV counseling and testing or acute care for non-febrile illnesses. We aimed to enroll one HIV-infected and one HIV-uninfected control every week in each clinic within each of the following age categories: <1, 1-4, 5-24, 25-44, 45-64 and ≥65years.
The procedures of these surveillance programs have been previously described [11Cohen C, Moyes J, Tempia S, et al. Severe influenza-associated lower respiratory tract infection in a high HIV-Prevalence setting – South Africa, 2009-2011. Emerg Infec Dis.2013 ; 19(11):1766-74.,22Moyes J, Cohen C, Pretorius M, et al. Epidemiology of respiratory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV-infected and HIV-uninfected South African children, 2010-2011. J Infect Dis.2013 ; 208(S3):S217-26.,33Wolter N, Cohen C, Tempia S, et al. HIV and influenza virus infections are associated with increased blood pneumococcal load: a prospective hospital-based observational study in South Africa, 2009-2011. J Infcet Dis.2014 ; 209(1):56-65.]. In brief, study staff completed case report forms for all enrolled controls and ILI and SRI cases. Referral to hospital was recorded for all enrolled ILI cases. ILI cases that were referred to hospital were excluded from the analysis. Numbers of patients meeting the ILI and SRI case definitions and numbers enrolled were collected throughout the study period. Outpatient care prior to hospitalization was also recorded for enrolled SRI cases.
Respiratory specimens (i.e., nasopharyngeal aspirates for children aged <5 years and nasopharyngeal and oropharyngeal swabs from persons aged ≥5 years) were collected from all enrolled individuals (controls and ILI and SRI cases), placed in universal transport medium (Copan Diagnostics Inc., California, USA), stored at 4-8°C and transported to the National Institute for Communicable Diseases (NICD) for testing within 72 hours of collection. Specimens were tested for the presence of 10 respiratory viruses [influenza A and B viruses; parainfluenza virus (PIV) types 1, 2 and 3; respiratory syncytial virus (RSV); adenovirus; rhinovirus; human metapneumovirus (HMPV); and enterovirus] using a multiplex real-time reverse transcription polymerase chain reaction assay [44Pretorius MA, Tempia S, Walaza S, et al. The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa, 2012-2015. J Clin Virol.2016 ; 75:21-6.]. Influenza A-positive samples were further subtyped.
HIV results were obtained from a combination of two sources: (i) patient clinical records when available and (ii) for consenting patients, a dried blood spot was tested at NICD. Testing included HIV enzyme-linked immunosorbent assay (ELISA) for patients aged ≥18 months and PCR for children aged <18 months if the ELISA was reactive.
Data source 2: Healthcare utilization surveys
We obtained data on actual healthcare seeking behavior (including information on provider/institution where medical care was sought or not seeking medical care) among individuals with reported ILI and SRI from three healthcare utilization surveys (HUS) conducted in South Africa [55Wong KK, von Mollendorf C, Martinson NA, et al. Healthcare utilization for common infectious diseases syndromes in Soweto and Klerksdorp, South Africa.2017 .,66McAnerney JM, Cohen C, Cohen AL, et al. Healthcare utilization patterns for common syndromes in Msunduzi Municipality, Pietermaritzburg, KwaZulu-Natal Province, South Africa, 2013. 2017.].
Data source 3: Prevalence of risk factors for pneumonia and healthcare seeking behavior for acute respiratory infection
We obtained the provincial-level prevalence of known risk factors for pneumonia and the provincial data on healthcare seeking behavior among cases with acute respiratory infection (ARI) from the 2016 South Africa Demographic and Health Survey (DHS) [77South Africa Demographic and Health Survey, 2016. Available at: http://www.statssa.gov.za/publications/Report%2003-00-09/Report%2003-00-092016.pdf . Accessed on 11 June 2017.] and the THEMBISA model (specifically for the prevalence of HIV infection in the community) [88THEMBISA Model. Available at: http://www.thembisa.org/. Accessed on 25 July 2017.].
Data source 4: Population denominators
We obtained age- and year-specific population denominators for the catchment area of the surveillance sites described in data source 1 from projections of 2011 census data for South Africa [99Statistics South Africa – 2011 Census. Available at: http://www.statssa.gov.za/?page_id=3839. Accessed on 25 July 2017.]. We also obtained the provincial age- and year-specific population denominators from the same data source.