Pediatric tuberculosis: clinical and epidemiological reflections from a highly endemic setting

Pediatric TB provides unique opportunities to study TB disease epidemiology. Improved diagnostics are of key importance in order to address many of the challenges posed by TB in children. In the Western Cape Province in South Africa, the TB notification rate was more than 600 out of 100,000 for children aged 0-14 years in 2007; the maternal HIV prevalence was 15%, with a good vertical preventative program. The HIV transmission rate was 4-5%; 99% of neonates routinely receive BCG vaccination at birth. Isoniazid prophylaxis, shown to be effective in the prevention of TB in young children, is seldom initiated and many missed opportunities for preventive therapy exist. In children admitted to hospital, mycobacterial culture is routinely done for TB in children less than five years of age through gastric aspiration of stomach contents in this setting; the culture yield is 30-40% in children with clinically suspected TB.Peer Reviewe

Pediatric tuberculosis : clinical and epidemiological reflections from a highly endemic setting

Pediatric TB provides unique opportunities to study TB disease epidemiology. Improved diagnostics are of key importance in order to address many of the challenges posed by TB in children. In the Western Cape Province in South Africa, the TB notification rate was more than 600 out of 100,000 for children aged 0-14 years in 2007; the maternal HIV prevalence was 15%, with a good vertical preventative program. The HIV transmission rate was 4-5%; 99% of neonates routinely receive BCG vaccination at birth. Isoniazid prophylaxis, shown to be effective in the prevention of TB in young children, is seldom initiated and many missed opportunities for preventive therapy exist. In children admitted to hospital, mycobacterial culture is routinely done for TB in children less than five years of age through gastric aspiration of stomach contents in this setting; the culture yield is 30-40% in children with clinically suspected TB.Peer Reviewe

Retooling existing tuberculosis drugs for children.

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Assessing the impact of multidrug-resistant tuberculosis in children : an exploratory qualitative study

Please cite as follows: Franck, C. et al. 2014. Assessing the impact of multidrug-resistant tuberculosis in children: an exploratory qualitative study. BMC Infectious Diseases, 14(1):426, doi:10.1186/1471-2334-14-426.The original publication is available at http://www.biomedcentral.com/1471-2334/14/426Publication of this article was funded by the Stellenbosch University Open Access Fund.Background: While the prevalence of multidrug-resistant (MDR) tuberculosis (TB) is high among children in the Western Cape of South Africa, the psychosocial implications of treatment for children with MDR-TB remain poorly understood. We sought to explore how MDR-TB and its treatment impact children on an individual, familial, and social level. Methods: Semi-structured interviews were conducted with 20 children and caregivers purposively sampled from a prospective clinical cohort of children. The sample was stratified by age at the start of treatment (children >10 years, and 5-10 years). Caregiver proxy interviews were conducted with younger children, supplemented with child interviews; older children were interviewed directly, supplemented with caregiver proxy interviews. Data were analysed using grounded theory. Results: Findings revealed pill volume and adverse effects produced significant physical, psychological and academic disturbances in children. Adverse effects related to the medication were important obstacles to treatment adherence. While there appear to be no long-lasting effects in younger children, a few older children showed evidence of persisting internalised stigma. Caregivers suffered important treatment-related financial and psychological costs. Community support, notably through the continued involvement of children in strong social networks, promoted resilience among children and their families. Conclusions: We found that the current treatment regimen for childhood MDR-TB has significant psychological, academic, and financial impacts on children and their families. There is a need for psychosocial support of children and caregivers to mitigate the negative effects of community stigma, and to manage the stressors associated with chronic illness.Publishers’ versio

Morbidity and mortality up to 5 years post tuberculosis treatment in South Africa: a pilot study

Background A high risk of tuberculosis (TB), chronic lung disease, and mortality have been reported among people with a history of previous TB treatment, but data from high-incidence settings remain limited. The aim of this study was to characterize general morbidity and mortality among adults who had successfully completed TB treatment in the past 5 years in a high-incidence setting in South Africa. Methods Adults (≥18 years) who had completed treatment for pulmonary TB between 2013 and 2017 were randomly selected from TB treatment registers. Household visits were conducted to locate and interview former TB (FTB) patients, and bacteriological testing for TB was offered. Additional data sources were used to ascertain the vitality status of FTB patients who could not be located. Results Addresses were located for 200 of the 223 FTB patients sampled and 89 FTB patients were contacted of whom 51 agreed to be interviewed. Approximately half reported persistent respiratory symptoms, such as shortness of breath and wheezing, and repeated lung infections. One (3.6%) of 28 patients who provided a sputum sample had culture-positive TB and another two were currently on re-treatment for TB. Fifteen deaths post treatment were ascertained, resulting in a standardized mortality ratio of 3.8 (95% confidence interval 2.3–6.3) after successful TB treatment relative to the general population. Conclusions In this high-incidence setting, locating and interviewing FTB patients was challenging. The study findings are consistent with a high rate of respiratory disease, including recurrent TB, and substantially elevated mortality among FTB patients

The PREVENT study to evaluate the effectiveness and acceptability of a community-based intervention to prevent childhood tuberculosis in Lesotho: study protocol for a cluster randomized controlled trial

Background Effective, evidence-based interventions to prevent childhood tuberculosis (TB) in high TB/HIV-burden, resource-limited settings are urgently needed. There is limited implementation of evidence-based contact management strategies, including isoniazid preventive therapy (IPT), for child contacts of TB cases in Lesotho. Methods/design This mixed-methods implementation science study utilizes a two-arm cluster-randomized trial design with randomization at the health facility level. The study aims to evaluate the effectiveness and acceptability of a combination community-based intervention (CBI) versus standard of care (SOC) for the management of child TB contacts. The study includes three phases: (I) exploratory phase; (II) intervention implementation and testing phase; (III) post-intervention explanatory phase. Healthcare provider interviews to inform intervention refinement (phase I) were completed in December 2015. In phase II, 10 health facilities were randomized to deliver the CBI or SOC, with stratification by facility type (i.e., hospital vs. health center). CBI holistically addresses the complex provider-related, patient-related, and caregiver-related barriers to prevention of childhood TB through nurse training and mentorship; health education for caregivers and patients by village health workers; adherence support using text messaging and village health workers; and multidisciplinary team meetings, where programmatic data are reviewed and challenges and solutions are discussed. SOC sites follow country guidelines for child TB contact management. Routine TB program data will be abstracted for all adult TB cases newly registered during the study period and their child contacts from TB registers and cards. The anticipated sample size is 1080 child contacts. Primary outcomes are yield (number) of child contacts, including children < 5 years of age and HIV-positive children < 15 years of age; IPT initiation; and IPT completion. Secondary outcomes include HIV testing; yield of active prevalent TB among child contacts; and acceptability and utilization of CBI components. Intervention implementation began in February 2016 and is ongoing. Post-intervention interviews with healthcare providers and caregivers (phase III) commenced in February 2017. Discussion The PREVENT study tests the effectiveness and acceptability of a novel combination CBI for child TB contact management in Lesotho. If effective, CBI will have important implications for addressing childhood TB in Lesotho and elsewhere. Trial registration ClinicalTrials.gov, NCT02662829 . Registered on 15 January 2016

Delayed BCG immunization does not alter antibody responses to EPI vaccines in HIV-exposed and -unexposed South African infants.

BACKGROUND: Bacille Calmette-Guérin (BCG) is routinely given at birth in tuberculosis-endemic settings due to its protective effect against disseminated tuberculosis in infants. BCG is however contraindicated in HIV-infected infants. We investigated whether delaying BCG vaccination to 14 weeks of age affected vaccine-induced antibody responses to Haemophilus influenzae type b (Hib)-conjugate, pertussis, tetanus and Hepatitis B (HBV) vaccines, in HIV-exposed uninfected (HEU) and -unexposed uninfected (HUU) infants. METHODS: Infants were randomized to receive BCG at birth or at 14 weeks of age. Blood was taken at 14, 24, and 52 weeks of age and analyzed for Hib, pertussis, tetanus and HBV specific antibodies. RESULTS: BCG was given either at birth (106 infants, 51 HEU) or at 14 weeks of age (74 infants, 50 HEU). The timing of BCG vaccination did not influence the antibody response to any antigen studied. However, in a non-randomized comparison, HEU infants had higher Hib antibody concentrations at weeks 14 and 24 (p=0.001 and <0.001, respectively) and pertussis at week 24 (p=0.003). Conversely, HEU infants had lower antibody concentrations to HBV at 14 and 52 weeks (p=0.032 and p=0.031) with no differences in tetanus titres. CONCLUSIONS: HIV exposure, but not the timing of BCG vaccination, was associated with antibody concentrations to Hib, pertussis, HBV and tetanus primary immunization. CLINICAL TRIAL REGISTRATION: DOH-27-1106-1520

A scoping review of patient-centred tuberculosis care interventions: gaps and opportunities

Tuberculosis (TB) is a leading cause of death globally. In 2015, the World Health Organization hailed patient-centred care as the first of three pillars in the End TB strategy. Few examples of how to deliver patient-centred care in TB programmes exist in practice; TB control efforts have historically prioritised health systems structures and processes, with little consideration for the experiences of people affected by TB. We aimed to describe how patient-centred care interventions have been implemented for TB, highlighting gaps and opportunities. We conducted a scoping review of the published peer-reviewed research literature and grey literature on patient-centred TB care interventions between January 2005 and March 2020. We found limited information on implementing patient-centred care for TB programmes (13 research articles, 7 project reports, and 19 conference abstracts). Patient-centred TB care was implemented primarily as a means to improve adherence, reduce loss to follow-up, and improve treatment outcomes. Interventions focused on education and information for people affected by TB, and psychosocial, and socioeconomic support. Few patient-centred TB care interventions focused on screening, diagnosis, or treatment initiation. Patient-centred TB care has to go beyond programmatic improvements and requires recognition of the diverse needs of people affected by TB to provide holistic care in all aspects of TB prevention, care, and treatment