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.