Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

TB preventive therapy preferences among children and adolescents.

BACKGROUND: TB preventive therapy (TPT) is critical for ending TB, yet implementation remains poor. With new global guidelines expanding TPT eligibility and regimens, we aimed to understand TPT preferences among children, adolescents and caregivers.METHODS: We undertook a discrete choice experiment among 131 children, 170 adolescents and 173 caregivers, and conducted 17 in-depth interviews in 25 clinics in Cape Town, South Africa. The design included attributes for location, waiting time, treatment duration, dosing frequency, formulation/size, side effects, packaging and taste. Mixed-effects logistic regression models were used for analysis.RESULTS: Among children and caregivers, the number and size of pills, taste and side effects were important drivers of preferences. Among adolescents and caregivers, clinic waiting times and side effects were significant drivers of preferences. Adolescents expressed concerns about being stigmatised, and preferred services from local clinics to services delivered in the community. Dosing frequency and treatment duration were only significant drivers of choice among adolescents, and only if linked to fewer clinic visits.CONCLUSIONS: Introducing shorter TPT regimens in isolation without consideration of preferences and health services may not have the desired effect on uptake and completion. Developing TPT delivery models and formulations that align with preferences must be prioritised.

Post-TB health and wellbeing.

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

Reasons for poor uptake of TB preventive therapy in South Africa.

BACKGROUND: South Africa has one the highest TB and HIV burdens globally. TB preventive therapy (TPT) reduces the risk of TB disease and TB-related mortality in adults and children living with HIV and is indicated for use in TB-exposed HIV-negative individuals and children. TPT implementation in South Africa remains suboptimal. METHODS: We conducted a pragmatic review of TPT implementation using multiple data sources, including informant interviews (n = 134), semi-structured observations (n = 93) and TB patient folder reviews in 31 health facilities purposively selected across three high TB burden provinces. We used case descriptive analysis and thematic coding to identify barriers and facilitators to TPT implementation. RESULTS: TPT programme implementation was suboptimal, with inadequate monitoring even in health districts with well-functioning TB services. Health workers reported scepticism about TPT effectiveness, deprioritised TPT in practice and expressed divergent opinions about the cadres of staff responsible for implementation. Service- and facility-level barriers included ineffective contact tracing, resource shortages, lack of standardised reporting mechanisms and insufficient patient education on TPT. Patient-level barriers included socio-economic factors. CONCLUSIONS: Improving TPT implementation will require radically simplified and more feasible systems and training for all cadres of health workers. Partnership with communities to stimulate demand driven service uptake can potentially facilitate implementation.

CONTEXTE: L'Afrique du Sud a l'une des charges de TB et de VIH les plus élevées au monde. La thérapie préventive contre la TB (TPT) réduit le risque de TB maladie et de mortalité liée à la TB chez les adultes et les enfants vivant avec le VIH et est indiquée chez les personnes et les enfants séronégatifs exposés à la TB. La mise en œuvre du TPT en Afrique du Sud reste sous-optimale. MÉTHODES: Nous avons procédé à un examen pragmatique de la mise en œuvre du TPT à l'aide de plusieurs sources de données, notamment des entretiens avec des informateurs (n = 134), des observations semi-structurées (n = 93) et des examens de dossiers de patients atteints de TB dans 31 établissements de santé sélectionnés à dessein dans trois provinces fortement touchées par la TB. Nous avons utilisé une analyse descriptive des cas et un codage thématique pour identifier les obstacles et les facilitateurs de la mise en œuvre du programme TPT. RÉSULTATS: La mise en œuvre du programme TPT était sousoptimale, avec un suivi inadéquat, y compris dans les districts sanitaires où les services de lutte contre la TB fonctionnaient correctement. Les agents de santé ont fait part de leur scepticisme quant à l'efficacité de la TPT, n'ont pas accordé la priorité à la TPT dans la pratique et ont exprimé des opinions divergentes sur les cadres du personnel responsables de la mise en œuvre. Les obstacles au niveau des services et des établissements comprennent l'inefficacité de la recherche des contacts, la pénurie de ressources, l'absence de mécanismes de déclaration standardisés et l'insuffisance de l'éducation des patients sur la TPT. Les obstacles au niveau des patients comprenaient des facteurs socio-économiques. CONCLUSIONS: L'amélioration de la mise en œuvre des TPT nécessitera des systèmes radicalement simplifiés et plus réalisables ainsi qu'une formation pour tous les cadres du personnel de santé. Un partenariat avec les communautés pour stimuler l'adoption de services axés sur la demande peut potentiellement faciliter la mise en œuvre.

The clinical presentation and management of a naturally occuring Bluetongue virus infection in a pregnant Rottweiler dog.

Few reports of clinical Bluetongue virus (BTV) infections have been described in dogs. Most cases were linked to inoculation with a BTV-contaminated canine modified live vaccine. In dogs, cases have only been described in pregnant females with clinical signs of fever and abortion followed by severe dyspnoea and death. A pregnant Rottweiler dog was presented with a three-day history of progressive lethargy and anorexia. The patient was a guard dog living in an enclosure where sheep were kept at night. High mortalities had been experienced in the sheep but had not been investigated. On presentation, the major clinical findings were dyspnoea and hypoxia. Clinicopathological tests showed hypoxia and systemic inflammation. Radiological findings were consistent with non-cardiogenic pulmonary oedema. The patient was treated symptomatically and recovered but did not retain the pregnancy. Bluetongue virus was identified in the patient's blood using BTV RT-PCR (Ct value 24.7). At a follow-up farm visit, an ongoing BTV outbreak in the sheep was diagnosed with affected sheep testing positive for BTV on RT-PCR. This report describes the clinical presentation, diagnostic investigations and successful treatment of a dog with BTV infection. This is the first case report of a naturally occurring clinical BTV infection in a dog. Possible routes of infection were direct contact, midgeborne, or ingestion of infected afterbirth or abortus from sheep.

Closing the reporting gap for childhood tuberculosis in South Africa: improving hospital referrals and linkages.

SETTING: A referral hospital in Cape Town, Western Cape Province, Republic of South Africa. OBJECTIVE: To measure the impact of a hospital-based referral service (intervention) to reduce initial loss to follow-up among children with tuberculosis (TB) and ensure the completeness of routine TB surveillance data. DESIGN: A dedicated TB referral service was established in the paediatric wards at Tygerberg Hospital, Cape Town, in 2012. Allocated personnel provided TB education and counselling, TB referral support and weekly telephonic follow-up after hospital discharge. All children identified with TB were matched to electronic TB treatment registers (ETR.Net/EDRWeb). Multivariable logistic regression was used to compare reporting of culture-confirmed and drug-susceptible TB cases before (2007-2009) and during (2012) the intervention. RESULTS: Successful referral with linkage to care was confirmed in 267/272 (98%) and successful reporting in 227/272 (84%) children. Children with drug-susceptible, culture-confirmed TB were significantly more likely to be reported during the intervention period than in the pre-intervention period (OR 2.52, 95%CI 1.33-4.77). The intervention effect remained consistent in multivariable analysis (adjusted OR 2.62; 95%CI 1.31-5.25) after adjusting for age, sex, human immunodeficiency virus status and the presence of TB meningitis. CONCLUSIONS: A simple hospital-based TB referral service can reduce initial loss to follow-up and improve recording and reporting of childhood TB in settings with decentralised TB services.

Child and adult spinal tuberculosis at tertiary hospitals in the Western Cape, South Africa: 4-year burden and trend.

The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6-4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.

Burden, spectrum and outcomes of children with tuberculosis diagnosed at a district-level hospital in South Africa.

SETTING: The Khayelitsha subdistrict has the highest burden of reported tuberculosis (TB) cases in Cape Town, Western Cape Province, South Africa. OBJECTIVES: To characterise the TB burden, spectrum and treatment outcomes among children managed at a district-level hospital, the Khayelitsha District Hospital. DESIGN: Retrospective medical record review of all children (age <13 years) diagnosed with TB in January-July 2014. A lay health care worker completed daily surveillance and supported linkage to TB care. Symptoms and investigations at presentation, TB disease spectrum, referral pathways and outcomes were reported. RESULTS: Most children were aged 2 years (84/99, 85%), 18/96 (19%) were infected with the human immunodeficiency virus, 31/91 (34%) were malnourished and 80/99 (81%) had pulmonary TB only. The majority of the children (63/80, 79%) presented with cough of acute onset (<2 weeks). Only 5/36 (14%) eligible child contacts had documentation of receiving isoniazid preventive therapy. Twelve (13%) children had bacteriologically confirmed pulmonary TB. Overall, 93/97 (96%) children successfully continued TB care after hospital discharge. Favourable TB treatment outcomes were recorded in only 77 (78%) children. CONCLUSIONS: Children with TB managed at this district-level hospital were young, and frequently had acute symptoms and substantial comorbidities. Missed opportunities for TB prevention were identified. Linkage to care support resulted in excellent continuation of TB care; however, treatment outcomes could be further improved.

Timing of HIV diagnosis in children with tuberculosis managed at a referral hospital in Cape Town, South Africa.

SETTING: Tygerberg Hospital, Western Cape Province, Cape Town, South Africa. OBJECTIVE: To investigate the prevalence of and factors associated with simultaneous tuberculosis (TB) and human immunodeficiency virus (HIV) diagnoses in children. DESIGN: Retrospective cohort study in TB-HIV co-infected children aged <13 years admitted to Tygerberg Hospital in 2012. Data were collected from medical records, laboratory results and electronic TB treatment registers. A simultaneous TB-HIV diagnosis was defined as an HIV diagnosis made within 7 days before or after a diagnosis of TB. RESULTS: Of 88 children with TB-HIV co-infection, 37 (42%) had a simultaneous TB-HIV diagnosis; 51 children had been known to have HIV before their TB diagnosis. Interruption of antiretroviral therapy (ART) was reported in 9/32 (28%) children with known HIV infection at TB diagnosis, while missed opportunities for ART initiation were identified in 8/19 (42%) ART-naïve children. Simultaneous TB-HIV diagnosis was more likely if maternal HIV infection was unknown at the time of the child's birth (OR 2.7, 95%CI 1.0-7.2), and was associated with unfavourable TB treatment outcomes (OR 5.9, 95%CI 1.4-25.2). CONCLUSION: TB diagnosis provides an important opportunity to test children for HIV. Missed opportunities for HIV prevention, earlier diagnosis and ART initiation were identified.

Operational implementation and impact of The Union's online childhood TB training course in South Africa.

Novel, effective tuberculosis (TB) training strategies are needed in developing settings to scale up training and improve TB management at facility level. This study evaluated the feasibility of implementing an online childhood TB training course for community-based health-care workers in the Eastern Cape Province, South Africa, and measured its impact on knowledge. Training sessions were convened and participants completed the course independently. A total of 220 primary care participants completed pre- and post-training tests. The mean knowledge increase was 8% (95% confidence interval 7.0-8.8, P < 0.001). The course proved an acceptable, versatile option for decentralised training in childhood TB, provided that the technology requirements can be met.

De nouvelles stratégies efficaces de formation à la tuberculose (TB) sont requises dans les pays en développement afin d'accélérer la formation et d'améliorer la prise en charge de la TB au niveau des structures de santé. Cette étude a évalué la faisabilité de la mise en œuvre d'un cours de formation en ligne à la TB de l'enfant pour les travailleurs de santé en communauté dans la province du Cap Est, Afrique du Sud, et a mesuré l'impact sur les connaissances. Des séances de formation ont été organisées et les participants ont terminé le cours indépendamment. Un total de 220 participants travaillant en soins de santé primaires ont fait les tests avant et après la formation. L'augmentation moyenne des connaissances a été de 8% (intervalle de confiance 95% 7,0­8,8 ; P < 0,001). Le cours s'est avéré une option acceptable et souple pour une formation décentralisée à la TB de l'enfant si les exigences techniques le permettent.

En los entornos poco desarrollados se precisan estrategias de capacitación innovadoras y eficaces en materia de tuberculosis (TB) con el objeto de ampliar la escala de las iniciativas de formación y mejorar la coordinación asistencial de la TB en los establecimientos de salud. El objetivo del estudio fue evaluar la factibilidad de poner en práctica un curso de capacitación en línea sobre la TB en la niñez dirigido a los agentes de salud comunitarios en la Provincia Oriental del Cabo en Suráfrica y medir su repercusión sobre el nivel de conocimientos de los profesionales. Se convocaron sesiones de formación y luego los participantes completaron por su cuenta el curso. Doscientos veinte profesionales de atención primaria participantes completaron los cuestionarios antes y después de la capacitación. Se observó un progreso promedio de los conocimientos de 8% (intervalo de confianza del 95% 7,0­8,8; P < 0,001). Se demostró que el curso representa una opción aceptable y versátil de formación descentralizada sobre la TB en la niñez, siempre y cuando se puedan cumplir los requisitos tecnológicos.

Tuberculosis in adolescents and young adults: epidemiology and treatment outcomes in the Western Cape.

SETTING: Western Cape Province, South Africa. OBJECTIVES: To characterise tuberculosis (TB) epidemiology, disease presentation and treatment outcomes among adolescents (age 10-19 years) and young adults (age 20-24 years) in the Western Cape. DESIGN: A retrospective, cross-sectional review of routine patient-level data from the Electronic TB Register (ETR.Net) for 2013. Site of TB disease, human immunodeficiency virus (HIV) status and TB treatment outcomes were analysed by 5-year age groups (<5, 5-9, 10-14, 15-19, 20-24 and 25 years of age). TB notification rates were calculated using census data. RESULTS: Adolescents and young adults comprised 18.0% of all new TB notifications in 2013. The notification rate was 141 TB cases/100 000 person-years (py) among 10-14 year olds, 418/100 000 py among 15-19 year olds and 627/100 000 py among 20-24 year olds. HIV prevalence among TB patients was 10.9% in 10-14 year olds, 8.8% in 15-19 year olds and 27.2% in 20-24 year olds. Older adolescents (age 15-19 years) and young adults (age 20-24 years) with HIV co-infection had poor treatment outcomes: 15.6% discontinued treatment prematurely and 4.0% died. CONCLUSIONS: Young people in the Western Cape suffer a substantial burden of TB, and those with TB-HIV co-infection are at high risk of treatment discontinuation.

Surveillance provides insight into epidemiology and spectrum of culture-confirmed mycobacterial disease in children.

BACKGROUND: Longer-term tuberculosis (TB) drug resistance surveillance among children is rare. We determined the prevalence of drug resistance among children with culture-confirmed TB from 2011 to 2013, compared these results with four previous consecutive 2-year periods and documented other mycobacterial isolates identified. METHOD: Surveillance study of mycobacterial culture in all children aged <13 years conducted from March 2011 to February 2013 at the Tygerberg Children's Hospital, Cape Town, South Africa. Drug susceptibility testing against isoniazid (INH) and rifampicin (RMP) was performed using line-probe assay (GenoType(®) MTBDRplus). Clinical data were obtained through folder review. RESULTS: Of 381 children, 323 (84.8%; 324 episodes) had Mycobacterium tuberculosis, 46 (12.1%) had M. bovis bacille Calmette-Guérin and 12 (3.1%) had non-tuberculous mycobacteria isolated. Forty-one (12.7%) children had M. tuberculosis resistant to INH and/or RMP; 15 (4.7%) had multidrug-resistant TB (MDR-TB). The prevalence of INH mono- or polyresistance remained stable; however, RMP monoresistance increased (0/313 in 2003-2005 vs. 6/324, 1.9%, in 2011-2013; P = 0.041); MDR-TB prevalence has declined significantly, from 26/292 (8.9%) in 2007-2009 to 15/324 (4.7%) in 2011-2013 (OR 0.50, 95%CI 0.24-0.99). The prevalence of human immunodeficiency virus co-infection has decreased significantly, from a peak of 29% to 15.3%. CONCLUSIONS: There has been a significant reduction in bacteriologically confirmed MDR-TB cases. The increase in RMP monoresistance has important implications for treatment.

Determinants of tuberculosis treatment completion among newborns in a high-burden setting.

BACKGROUND: Newborns exposed to Mycobacterium tuberculosis are at high risk of progression to tuberculosis (TB) disease. DESIGN AND SETTING: A prospective cohort study conducted in Cape Town, South Africa, from January 2011 to June 2012. TB-exposed newborns requiring isoniazid preventive therapy (IPT) or anti-tuberculosis treatment were followed to 6 months of age. Appropriate tuberculosis treatment referral, maternal and socio-economic determinants were evaluated. The primary outcome, completion of treatment (6 months IPT, 3 months IPT with a negative tuberculin skin test, or 6 months' treatment for disease) was measured at 6 months. Data were collected from folders and care giver interviews. Cox regression was used to determine hazard ratios (HR) for non-completion of treatment. RESULTS: Fifty-six (63% human immunodeficiency virus [HIV] exposed) TB-exposed newborns were included; median gestational age and mean birth weight were respectively 36 weeks and 2242 g. Of the 56 newborns, 44 (79%) were followed to 6 months; 29/44 (66%) completed anti-tuberculosis treatment without study team intervention. Appropriate treatment referral was associated with a lower hazard of non-completion of treatment (unadjusted HR 0.34, 95%CI 0.12-0.93). This relationship was maintained in multivariable adjustment for maternal HIV status and type of care giver (adjusted HR 0.26, 95%CI 0.09-0.77). CONCLUSIONS: Appropriate anti-tuberculosis treatment referral improves completion of treatment in infants.

Completeness and accuracy of electronic recording of paediatric drug-resistant tuberculosis in Cape Town, South Africa.

SETTING: Cape Town, South Africa. OBJECTIVE: To assess the completeness and accuracy of electronic recording of drug-resistant tuberculosis (DR-TB) in children. DESIGN: Retrospective cohort study. All children aged <15 years treated for DR-TB during 2012 were included, with clinical data collected from routine health services. Matching was performed between clinical data and an extracted data set from an electronic register for DR-TB (EDR.web), and data sources were compared. RESULTS: Seventy-seven children were identified clinically, of whom only 49 (64%) were found in EDR.web. Most data in EDR.web were complete and accurate, but there were some internal inconsistencies for confirmed TB. Only 4.4% of all EDR.web entries were children. CONCLUSION: Only two thirds of children clinically treated for DR-TB were recorded in the electronic reporting system, suggesting under-reporting. We also found a lower than expected prevalence of childhood DR-TB, probably suggesting both under-diagnosis and under-recording of DR-TB in children. Clinicians at facility level should be able to access the electronic reporting system, and data transfer between clinical paper-based and electronic sources should be simplified. Cross-linking between electronic registers for drug-susceptible and DR-TB or consolidation of registers could improve the accuracy of recording. Improved recording and reporting of DR-TB in children is needed.

High tuberculosis exposure among neonates in a high tuberculosis and human immunodeficiency virus burden setting.

BACKGROUND: Maternal and neonatal tuberculosis (TB) are under-recognised, particularly in settings with a high burden of human immunodeficiency virus (HIV) infection. DESIGN AND SETTING: Retrospective audit of neonates routinely screened for TB in a South African hospital during 2009. Surveillance sources reviewed included routine clinical, laboratory and pharmacy records. RESULTS: Among 70 neonates (60% HIV-exposed) screened for TB, the median gestational age was 35.5 weeks (IQR 33-38), and the median birth weight was 2000 g (IQR 1530-2484). The neonates were grouped according to a history of documented TB exposure: maternal TB in 41/70 (59%), suspected maternal TB in 9/70 (13%), other documented household TB exposure in 5/70 (7%), and no known TB exposure 15/70 (21%). Of the 50 neonates exposed to confirmed or suspected maternal TB, 36 (72%) were initiated on TB chemoprophylaxis, 5 (10%) received TB treatment and 9 (18%) received no intervention. Eight (8/50, 16%) were diagnosed with TB, all of whom were born to mothers with suspected or proven TB. CONCLUSIONS: Maternal TB, primarily among HIV-infected women, was the main indication for TB screening of neonates. Routine TB screening of pregnant women and TB care in mothers and infants should be improved in settings with a high burden of TB and HIV.

Opportunities for chemoprophylaxis in children with culture-confirmed tuberculosis.

BACKGROUND AND OBJECTIVES: Chemoprophylaxis is an effective strategy to prevent progression of tuberculosis (TB) in vulnerable children who have had contact with an infectious source of TB. However, many operational gaps prevent implementation of routine chemoprophylaxis in high-burden settings. The TB exposure status and disease spectrum in children diagnosed with culture-confirmed TB are described and missed opportunities for chemoprophylaxis are highlighted. METHODS: All children <13 years of age diagnosed with culture-confirmed TB at a tertiary referral hospital between March 2003 and February 2007 were included. Clinical data were collected from retrospective review of files. TB was classified as pulmonary and extra-pulmonary; disseminated TB included miliary disease and TB meningitis. RESULTS: During the study period, 614 children (327, 53·3% boys, median age 32 months) were diagnosed with culture-confirmed TB. Contact with an infectious adult source case was documented in 333 (54·2%), 237 (71·2%) of whom were <5 years of age, and 24 (7·2%) were HIV-infected and ≥5 years of age. Of those eligible for chemoprophylaxis, missed opportunities were identified in 156/221 (70·6%) children; 127 (81·4%) were <3 years of age, 39 (25%) had disseminated TB and 8 (5·1%) died. The TB source case was the mother or father in 74/156 (47·4%) children. CONCLUSION: Opportunities for initiation of chemoprophylaxis in vulnerable children following TB exposure are often missed. Awareness should be increased among health-care workers and in the community at large regarding the importance of chemoprophylaxis in young and HIV-infected children. Health system strengthening is required to improve delivery of chemoprophylaxis to vulnerable children in close contact with newly diagnosed infectious TB cases.