Child contact management in high tuberculosis burden countries: A mixed-methods systematic review

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Considering the World Health Organization recommendation to implement child contact management (CCM) for TB, we conducted a mixed-methods systematic review to summarize CCM implementation, challenges, predictors, and recommendations. We searched the electronic databases of PubMed/MEDLINE, Scopus, and Web of Science for studies published between 1996–2017 that reported CCM data from high TB-burden countries. Protocol details for this systematic review were registered on PROSPERO: International prospective register of systematic reviews (#CRD42016038105). We formulated a search strategy to identify all available studies, published in English that specifically targeted a) population: child contacts (<15 years) exposed to TB in the household from programmatic settings in high burden countries (HBCs), b) interventions: CCM strategies implemented within the CCM cascade, c) comparisons: CCM strategies studied and compared in HBCs, and d) outcomes: monitoring and evaluation of CCM outcomes reported in the literature for each CCM cascade step. We included any quantitative, qualitative, mixed-methods study design except for randomized-controlled trials, editorials or commentaries. Thirty-seven studies were reviewed. Child contact losses varied greatly for screening, isoniazid preventive therapy initiation, and completion. CCM challenges included: infrastructure, knowledge, attitudes, stigma, access, competing priorities, and treatment. CCM recommendations included: health system strengthening, health education, and improved preventive therapy. Identified predictors included: index case and clinic characteristics, perceptions of barriers and risk, costs, and treatment characteristics. CCM lacks standardization resulting in common challenges and losses throughout the CCM cascade. Prioritization of a CCM-friendly healthcare environment with improved CCM processes and tools; health education; and active, evidence-based strategies can decrease barriers. A focused approach toward every aspect of the CCM cascade will likely diminish losses throughout the CCM cascade and ultimately decrease TB related morbidity and mortality in children

Community-Based Tuberculosis Contact Management: Caregiver Experience and Factors Promoting Adherence to Preventive Therapy

Delivery of tuberculosis preventive therapy (TPT) for children with household exposure to tuberculosis is a globally supported intervention to reduce the impact of tuberculosis disease (TB) in vulnerable children; however, it is sub-optimally implemented in most high-burden settings. As part of a community-based household contact management program, we evaluated predictors of adherence to community based TPT in children and performed qualitative assessments of caregiver experiences. The Vikela Ekhaya (Protect the Home) project was a community-based household contact management program implemented between 2019 and 2020 in the Hhohho Region of Eswatini. At home visits, contact management teams screened children for TB, initiated TPT when indicated and performed follow-up assessments reviewing TPT adherence. TPT non-adherence was defined as either two self-reported missed doses or a pill count indicating at least two missed doses, and risk factors were evaluated using multivariate clustered Cox regression models. Semi-structured interviews were performed with caregivers to assess acceptability of home visits for TPT administration. In total, 278 children under 15 years initiated TPT and 96% completed TPT through the Vikela Ekhaya project. Risk factors for TPT non-adherence among children initiating 3HR included low family income (adjusted hazard ratio (aHR) 2.3, 95%CI 1.2-4.4), female gender of the child (aHR 2.5, 95% CI 1.4-5.0) and an urban living environment (aHR 3.1, 95%CI 1.6-6.0). Children with non-adherence at the first follow-up visit were 9.1 fold more likely not to complete therapy. Caregivers indicated an appreciation for community services, citing increased comfort, reduced cost, and support from community members. Our results are supportive of recent World Health Organization (WHO) recommendations for decentralization of TB preventive services. Here, we identify populations that may benefit from additional support to promote TPT adherence, but overall demonstrate a clear preference for and excellent outcomes with community based TPT delivery

Screening tests for active pulmonary tuberculosis in children

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To determine the sensitivity, specificity, and positive and negative predictive value of 1) the presence of one or more tuberculosis symptoms, or symptom combinations; 2) chest radiography; 3) Xpert MTB/RIF; 4) Xpert Ultra; and 5) combinations of the aforementioned tests as screening tests for detecting active pulmonary tuberculosis in children in the following groups. Household contacts of a person with active tuberculosis; School contacts of a person with active tuberculosis; Other close contacts of a person with active tuberculosis; Children living with HIV; Children with pneumonia; Other risk groups (e.g. children with a history of previous tuberculosis, malnourished children); Children in the general population in high burden settings Secondary objectives To compare the accuracy of the different index tests, including different applications of tests (e.g. CXR with any abnormality versus, more specifically, CXR with abnormality suggestive of tuberculosis); we are interested in the accuracy of the index tests in any setting (i.e. community, outpatient, and inpatient). To investigate potential sources of heterogeneity in accuracy estimates in relation to age group, HIV status, whether the study was conducted in a high tuberculosis burden country, and whether the child received a single screening or more than one screening

Vikela Ekhaya: A Novel, Community-Based, Tuberculosis Contact Management Program in a High Burden Setting

BACKGROUND: The prevention of tuberculosis (TB) in child contacts of TB cases and people living with human immunodeficiency virus (HIV) is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT. METHODS: Vikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases by using mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants\u27 homes. RESULTS: In total, 945 contacts from 244 households were screened for TB symptoms; 72 (8%) contacts reported TB symptoms, and 5 contacts (0.5%) were diagnosed with prevalent TB. A total of 322 of 330 (98%) eligible asymptomatic household contacts initiated TPT. Of 322 contacts initiating TPT, 248 children initiated 3 months of isoniazid and rifampicin and 74 children and adults living with HIV initiated 6 months of isoniazid; 298 (93%) completed TPT. In clustered logistic regression analyses, unknown HIV status (adjusted odds ratio [aOR] 5.7, P = .023), positive HIV status (aOR 21.1, P = .001), urban setting (aOR 5.6, P = .006), and low income (aOR 5.9, P = .001) predicted loss from the cascade of care among TPT-eligible contacts. CONCLUSION: Vikela Ekhaya demonstrated that community-based TB household contact management is a feasible, acceptable, and successful strategy for TB screening and TPT delivery. The results of this study support the development of novel, differentiated, community-based interventions for TB prevention and control

Screening tests for active pulmonary tuberculosis in children

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To determine the sensitivity, specificity, and positive and negative predictive value of 1) the presence of one or more tuberculosis symptoms, or symptom combinations; 2) chest radiography; 3) Xpert MTB/RIF; 4) Xpert Ultra; and 5) combinations of the aforementioned tests as screening tests for detecting active pulmonary tuberculosis in children in the following groups. Household contacts of a person with active tuberculosis; School contacts of a person with active tuberculosis; Other close contacts of a person with active tuberculosis; Children living with HIV; Children with pneumonia; Other risk groups (e.g. children with a history of previous tuberculosis, malnourished children); Children in the general population in high burden settings Secondary objectives To compare the accuracy of the different index tests, including different applications of tests (e.g. CXR with any abnormality versus, more specifically, CXR with abnormality suggestive of tuberculosis); we are interested in the accuracy of the index tests in any setting (i.e. community, outpatient, and inpatient). To investigate potential sources of heterogeneity in accuracy estimates in relation to age group, HIV status, whether the study was conducted in a high tuberculosis burden country, and whether the child received a single screening or more than one screening

Perspectives for systems biology in the management of tuberculosis

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.Publisher PDFPeer reviewe

West Nile Virus Epidemic, Northeast Ohio, 2002

Serum samples and sociodemographic data were obtained from 1,209 Ohio residents. West Nile virus immunoglobulin M (IgM) and IgG antibodies were detected by enzyme-linked immunosorbent assay and confirmed. Children were 4.5 times more likely to become infected yet 110× less likely to have neuroinvasive disease develop

Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected childre