Browsing by Author "Hesseling, Anneke"

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    Open Access
    Culture-confirmed childhood tuberculosis in Cape Town, South Africa: a review of 596 cases
    (Biomed Central Ltd, 2007) Schaaf, H Simon; Marais, Ben; Whitelaw, Andrew; Hesseling, Anneke; Eley, Brian; Hussey, Gregory; Donald, Peter
    BACKGROUND:The clinical, radiological and microbiological features of culture-confirmed childhood tuberculosis diagnosed at two referral hospitals are described. METHODS: Cultures of Mycobacterium tuberculosis from children less than 13 years of age at Tygerberg and Red Cross Children's Hospitals, Cape Town, South Africa, were collected from March 2003 through February 2005. Folder review and chest radiography were performed and drug susceptibility tests done. RESULTS: Of 596 children (median age 31 months), 330 (55.4%) were males. Of all children, 281 (47.1%) were HIV-uninfected, 133 (22.3%) HIV-infected and 182 (30.5%) not tested. Contact with infectious tuberculosis adults was recorded in 295 (49.5%) children. Missed opportunities for chemoprophylaxis were present in 117/182 (64.3%) children less than 5 years of age.Extrathoracic TB was less common in HIV-infected than in HIV-uninfected children (49/133 vs. 156/281; odds ratio 0.50, 95% confidence interval 0.32-0.78). Alveolar opacification (84/126 vs. 128/274; OR 1.85, 95%CI 1.08-3.19) and cavitation (33/126 vs. 44/274; OR 2.28, 95%CI 1.44-3.63) were more common in HIV-infected than in HIV-uninfected children. Microscopy for acid-fast bacilli on gastric aspirates and sputum was positive in 29/142 (20.4%) and 40/125 (32.0%) children, respectively. Sixty-seven of 592 (11.3%) children's isolates showed resistance to isoniazid and/or rifampicin; 43 (7.3%) were isoniazid-monoresistant, 2 (0.3%) rifampicin-monoresistant and 22 (3.7%) multidrug-resistant. Death in 41 children (6.9%) was more common in HIV-infected children and very young infants. CONCLUSION: HIV infection and missed opportunities for chemoprophylaxis were common in children with culture-confirmed TB. With cavitating disease and sputum or gastric aspirates positive for acid-fast bacilli, children may be infectious. Transmission of drug-resistant TB is high in this setting.
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    Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial
    (BioMed Central, 2018-04-19) Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M
    Background: Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. Methods/design: SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Discussion: Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smearnegative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. Trial registration: International Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.
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    Tuberculosis treatment delay in adults and household transmission to children: a community-based study in a setting with high burden of tuberculosis and HIV
    (2015) Rose, Penelope Cathryn; Hesseling, Anneke; Myer, Landon
    Background: Tuberculosis (TB) control depends on interrupting transmission through rapid diagnosis and treatment initiation of infectious TB cases. With increasing delay in the diagnosis and treatment of pulmonary TB, disease is likely to progress, leading to progressive lung cavitation and increased sputum bacillary load, likely increasing TB transmission. This study investigated the effect of treatment delay in adult TB patients on the risk of TB infection and disease in child household contacts. Methodology: Secondary analysis was performed using data from a community-based household contact investigation study. Cross-sectional analysis was conducted of baseline data collected at enrolment. Children aged three months to fifteen years with documented household exposure to an adult with TB were enrolled between December 2007 and June 2012. These children were screened for TB infection (Mantoux tuberculin skin test [TST] and two interferon-gamma release assays [IGRA]) and disease. Total treatment delay was measured in adult TB source cases as the time from cough onset until treatment initiation, with those reporting no cough serving as the reference category. Logistic regression models were used to evaluate the effect of total treatment delay in adults on the risk of TB infection in child household contacts, with TB disease evaluated as a secondary endpoint. Results In total 671 children were enrolled as household contacts of 290 adult TB source cases. In multivariate analysis, the odds of TST positivity increased with cough duration ≥4 weeks prior to TB treatment initiation (odds ratio (OR) = 1.77 [95% CI 1.02-3.09] for cough <4 weeks; OR = 2.74 [95% confidence interval ( CI ) = 1.39-5.40] for cough 4-12 weeks; OR = 2.39 [95% CI = 1.19-4.82] for cough >12 weeks, compared to non-coughing adult TB patients), child's age ≥5 years (OR = 4.51, [95% CI = 2.60-7.83]), sharing the same bedroom (OR = 2.17, [95% CI = 1.43-3.31]), more than one household TB contact (OR = 2.70, [95% CI = 1.35- 2 5.42]) and with household tobacco smoke exposure (OR = 2.10, [95% CI = 1.22-3.61]). Adult TB source case HIV status did not modify the association between cough duration and risk of infection in children. Results of analyses of TB infection indicated by IGRA positivity were consistent with TST results. Prevalent TB disease in child contacts was associated with source case sputum smear and culture positivity, additional household TB contacts and decreasing age of the child. Conclusions: Delays of longer than four weeks from cough onset until TB treatment initiation were associated with increased risk of TB infection in child household contacts. These findings confirm the importance of reducing delays in TB diagnosis and treatment in adults to reduce transmission, ideally to less than four weeks. Although HIV co -infected TB patients are often considered less infectious, delayed treatment initiation remained associated with TB transmission, even amongst HIV co-infected adults with TB. In addition to the traditional risk factors for developing TB disease after infection, source case exposure factors also increased the risk of exposed children developing TB disease.