Methods
Study design and Setting
Data were derived from a prospective study of children enrolled with
suspected TB disease in a TB diagnostic study at two sites in Cape Town,
South Africa: 1) Nolungile Clinic, a primary health care clinic in an
urban low socioeconomic area, and 2) Red Cross War Memorial Children’s
Hospital, a tertiary care referral hospital13; 14.
Children with suspected pulmonary TB (PTB) were followed at 1, 3 and 6
months for response to treatment. Ethical approval for the study was
obtained from the Human Research Ethics Committee of the Faculty of
Health Sciences at University of Cape Town (UCT HREC:045/2008). Written
informed consent was obtained from a parent or legal guardian, and
verbal assent was obtained from children 7 years or older.
Enrollment and Participant Consent
Inclusion criteria were: 1) children less than 15 years old with
suspected TB based on cough of any duration and one of the following:
household TB contact; 2) recent weight loss; 3) positive tuberculin skin
test or a chest radiograph suggestive of PTB13; 14. TB
therapy was initiated at the discretion of the treating doctor.
Follow-up visits were done at 1, 3 and 6 months for children on TB
therapy and at 1 and 3 months for those not treated.
Outcome measures
Outcome measures used in our child-ecosystem framework include TB
diagnostic category and TB treatment. To look for patterns among TB
related determinants using the childhood ecosystem approach,
malnutrition was selected as an outcome measure for an additional
analysis given the known risk factors between malnutrition and childhood
TB. PTB diagnostic categorization was based on clinical and
microbiological investigations, in line with National Institute of
Health (NIH) consensus definitions as ‘confirmed PTB’ (microbiologically
confirmed), ‘unconfirmed TPB’ (microbiologically negative, clinically
diagnosed) and ‘unlikely PTB’ (lower respiratory disease not due to TB
with improvement on follow-up in the absence of TB
treatment)15. We also examined treatment for those
clinically diagnosed with PTB. Children falling in the category
‘unlikely’ served as controls compare to those children falling into the
categories of confirmed and likely (but unconfirmed) PTB.
Ecosystem Measures
Determinants of TB diagnostic category and TB treatment were organized
into proximal, medial and distal levels as part of our hierarchical
framework for understanding the childhood ecosystem for TB in South
Africa. Proximal determinants were understood as factors that were
specific to the individual child characteristics including demographic
factors that were hypothesised to impact child TB outcomes such as
gender and TB treatment. Medial determinants including factors relating
to interpersonal factors that might impact childhood TB. These factors
included aspects of caregiver health that might impact interactions with
the child (psychological health, substance use, stress) and other
interpersonal measures such as social support. Distal determinants
included macro-level determinants of disease such as socioeconomic
status (SES) and food insecurity.
Child-focused measures
Clinical diagnostics for children other than TB diagnosis and treatment
were operationalized as proximal measures in PTB consistent with how
they were operationalized in the chronic disease context by Egger and
Dixon6. Measures include gender and previous
hospitalization for TB.
Caregiver Questionnaire
To capture the medial and distal measures of the child-ecosystem,
caregivers completed a self-administered questionnaire at enrolment to
assess risk factors for TB. The questionnaires included assessment of
SES8, substance abuse, psychological distress,
perceived stress, social support and on caregiver health including
substance use was collected. Six measures were used to contextualize the
child ecosystem measuring health status for caregivers, including the
following.