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.