Discussion
Our findings indicate that several proximal, medial and distal factors in a child’s ecosystem may impact on the risk of childhood PTB and nutritional status. Proximal risk factors for childhood TB included sex and previous hospitalization. Consistent with this, young male South African children have been reported to be at higher risk for tuberculin skin test conversion, TB disease and LRTI, which may reflect a biological susceptibility due to hormonal or other factors25. Medial risk factors included caregiver tobacco use. While caregiver tobacco use was not associated with childhood PTB beyond univariate analyses, caregiver tobacco use is a known risk factor for PTB. Tuberculosis and second-hand smoke exposure have a severe negative impact on the respiratory system. A meta-analysis conducted on second hand smoke (SHS) exposure and TB risk has shown that children have more than 3-fold increased risk of SHS-associated active TB compared to those not exposed to SHS26. Similarly, caregiver psychological distress was not associated with childhood PTB. However, severe psychological distress among caregivers was common. This may reflect the burden of caring for a child with illness and environmental stressors inherent in living in poverty1; 3. The high number of caregivers surviving on a subsistence budget in our study may compound the elevated levels of psychological distress. This is consistent with the literature, that has found an association between caregiver psychological distress and socioeconomic status8.
Finally, we examined distal factors linked to childhood TB. Caregivers with less than 10 years of schooling, a monthly income of less than <$68 per month were distal determinants associated with childhood TB. As evidenced through the outcome of mycobacteriologically confirmed TB limited monetary resources and educational attainment underscore the structural barriers some caregivers experience when caring for a child with TB.
Malnutrition is a known risk factor for childhood TB5; however, this link was only evidenced by our findings that low-weight or low-height for age were associated with childhood TB in the univariate analyses. This may also reflect that our control group were children sick with non-TB respiratory illnesses, for which malnutrition may also be a risk factor. Medial factors observed for the outcome of TB diagnostic category and TB treatment related to caregiver characteristics were also associated with childhood malnutrition at baseline. Caregiver smoking was an important risk factor for childhood malnutrition with a 3-fold increased risk for childhood malnutrition. Malnutrition, was more than twice as likely to be present in children of caregivers who suffered from severe psychological distress. Given the nuanced links between childhood TB and proximal, medial and distal risk factors in our data, child malnutrition appears to be a distal risk factor for childhood TB that needs further exploration. Additional studies using a child ecosystem approach are needed to confirm our findings in relation to child nutrition.
The proximal, medial and distal factors identified in our ecosystem analysis help to provide an important context to the high prevalence of TB among children in this population. Promisingly, adherence in this study was extremely high. Despite the high adherence rates, rates of lost-to-follow-up shed light on a subpopulation in our study that could benefit from family-ecosystem oriented interventions. Of the 6% of children that did not attend the 3-month visit, loss-to-follow-up was associated with proximal, medial and distal factors associated with childhood TB and childhood malnutrition that we identified using a childhood ecosystem framework. These findings indicate that caregivers with less schooling and suboptimal mental health may need additional support from healthcare systems to ensure that adherence for their children’s TB treatment stays high.
The high rates of psychological distress among caregivers is concerning. These data are consistent with reported rates of psychological distress in studies of adult TB patients in South Africa9-11, and how this may relate to childhood TB including adherence to follow-up visits is an avenue that warrants further exploration.
Limitations include that questionnaires were self-completed by caregivers. As such, prevalence of smoking, alcohol use or psychological distress may have been underestimated.That notwithstanding, a strong association was shown between these risk factors as organized through the childhood ecosystem approach and TB diagnosis, TB treatment and childhood malnutrition. Second, only 69% of the caregivers of children consented to completing the questionnaires. Caregivers that elected to not participate in this study may have been less healthy [Supplemental Table VII]. Our reported prevalence rates represent the minimum prevalence for psychological distress or substance use. Reasons for not consenting were not recorded. No differences in age, level of schooling or gender between those that consented and those that did not consent were found.
Despite these limitations, the findings emerging from this study provide a clearer picture of risks for childhood TB. Our findings highlight the need for broad interventions to provide appropriate support protection strategies to reduce this burden, such as labor market supports such as job training or temporary subsidies to families in need. Additional research is required to explore the impact of the child ecosystem during transitional points in the development trajectory. For example, the role of family, peers, and individuals in the educational ecosystem may have varying points of prominence depending on what stage of development the child is in. Interventions should consider developmental milestones that may be leveraged for maximum intervention effect. Such studies may provide a more nuanced understanding and approach to risk reduction of transmission, diagnosis or management of TB.