Navigating complex care pathways-healthcare workers' perspectives on health system barriers for children with tuberculous meningitis in Cape Town, South Africa.

Tuberculous meningitis (TBM) occurs when tuberculosis (TB) bacilli disseminate and seed into the meninges, triggering a severe inflammatory response that often leads to brain infarction. It is the most severe and debilitating form of childhood TB with high mortality, and children who survive TBM often suffer lifelong physical and neuro-disability resulting in emotional, social, and economic burdens for families. In the early stages the symptoms may be non-specific and so the diagnosis is often made late when the patient already has significant brain injury. To facilitate earlier diagnosis, it is important to understand how patients are evaluated. This study aimed to chart health systems for paediatric TBM care at both primary healthcare (PHC) and hospital level in Cape Town, South Africa. We conducted fourteen in-depth interviews and eight days of semi-structured observations of patient flow across eight healthcare facilities. We found that children with TBM navigate multiple levels of care categorised into pre-admission and primary care, hospital admission and inpatient care, and post-discharge follow-up care. Healthcare workers identified the following health system barriers along the TBM care pathway for children: limited post-training and mentorship opportunities to manage TBM, overburdened facilities, time constraints, lack of recognition of TBM symptoms, delays in referral between PHC and hospital, lack of standardized diagnostic algorithms, limited diagnostic tests and a lack of child-friendly, easy-to-administer treatment. Regular and compulsory training on TB and TBM in children, including continuous mentoring and support to healthcare workers working in child health and TB services in high TB-burden settings, can facilitate early recognition of symptoms and rapid referral for diagnosis. Algorithms outlining referral criteria for patients with possible TBM at both PHC facilities and district level hospitals can guide healthcare providers and facilitate timely referral between different levels of healthcare services. An integrated data system and alert functions could flag multiple healthcare visits and improve communication between different healthcare facilities during diagnosis and treatment. Children and families affected by TBM are an especially vulnerable sub-population requiring high priority attention and support.

A systematic review of risk factors for mortality among tuberculosis patients in South Africa.

BACKGROUND: Tuberculosis (TB)-associated mortality in South Africa remains high. This review aimed to systematically assess risk factors associated with death during TB treatment in South African patients. METHODS: We conducted a systematic review of TB research articles published between 2010 and 2018. We searched BioMed Central (BMC), PubMed®, EBSCOhost, Cochrane, and SCOPUS for publications between January 2010 and December 2018. Searches were conducted between August 2019 and October 2019. We included randomised control trials (RCTs), case control, cross sectional, retrospective, and prospective cohort studies where TB mortality was a primary endpoint and effect measure estimates were provided for risk factors for TB mortality during TB treatment. Due to heterogeneity in effect measures and risk factors evaluated, a formal meta-analysis of risk factors for TB mortality was not appropriate. A random effects meta-analysis was used to estimate case fatality ratios (CFRs) for all studies and for specific subgroups so that these could be compared. Quality assessments were performed using the Newcastle-Ottawa scale or the Cochrane Risk of Bias Tool. RESULTS: We identified 1995 titles for screening, 24 publications met our inclusion criteria (one cross-sectional study, 2 RCTs, and 21 cohort studies). Twenty-two studies reported on adults (n = 12561) and two were restricted to children < 15 years of age (n = 696). The CFR estimated for all studies was 26.4% (CI 18.1-34.7, n = 13257 ); 37.5% (CI 24.8-50.3, n = 5149) for drug-resistant (DR) TB; 12.5% (CI 1.1-23.9, n = 1935) for drug-susceptible (DS) TB; 15.6% (CI 8.1-23.2, n = 6173) for studies in which drug susceptibility was mixed or not specified; 21.3% (CI 15.3-27.3, n = 7375) for people living with HIV/AIDS (PLHIV); 19.2% (CI 7.7-30.7, n = 1691) in HIV-negative TB patients; and 6.8% (CI 4.9-8.7, n = 696) in paediatric studies. The main risk factors associated with TB mortality were HIV infection, prior TB treatment, DR-TB, and lower body weight at TB diagnosis. CONCLUSIONS: In South Africa, overall mortality during TB treatment remains high, people with DR-TB have an elevated risk of mortality during TB treatment and interventions to mitigate high mortality are needed. In addition, better prospective data on TB mortality are needed, especially amongst vulnerable sub-populations including young children, adolescents, pregnant women, and people with co-morbidities other than HIV. Limitations included a lack of prospective studies and RCTs and a high degree of heterogeneity in risk factors and comparator variables. SYSTEMATIC REVIEW REGISTRATION: The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42018108622. This study was funded by the Bill and Melinda Gates Foundation (Investment ID OPP1173131) via the South African TB Think Tank.

Priority Activities in Child and Adolescent Tuberculosis to Close the Policy-Practice Gap in Low- and Middle-Income Countries.

Over the past 15 years, and despite many difficulties, significant progress has been made to advance child and adolescent tuberculosis (TB) care. Despite increasing availability of safe and effective treatment and prevention options, TB remains a global health priority as a major cause of child and adolescent morbidity and mortality-over one and a half million children and adolescents develop TB each year. A history of the global public health perspective on child and adolescent TB is followed by 12 narratives detailing challenges and progress in 19 TB endemic low and middle-income countries. Overarching challenges include: under-detection and under-reporting of child and adolescent TB; poor implementation and reporting of contact investigation and TB preventive treatment services; the need for health systems strengthening to deliver effective, decentralized services; and lack of integration between TB programs and child health services. The COVID-19 pandemic has had a significant negative impact on case detection and treatment outcomes. Child and adolescent TB working groups can address country-specific challenges to close the policy-practice gaps by developing and supporting decentral ized models of care, strengthening clinical and laboratory diagnosis, including of multidrug-resistant TB, providing recommended options for treatment of disease and infection, and forging strong collaborations across relevant health sectors.