SUNScholar - Browsing by Author "Schaaf, H. Simon"

Browsing by Author "Schaaf, H. Simon"

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Adherence to isoniazid preventive chemotherapy: a prospective community based study
(BMJ Publishing Group, 2006-09) Marais, B. J.; Van Zyl, S.; Schaaf, H. Simon; Van Aardt, M. C.; Gie, R. P.; Beyers, Nulda
Background: Current international guidelines recommend 6–9 months of isoniazid (INH) preventive chemotherapy to prevent the development of active tuberculosis in children exposed to a susceptible strain of M tuberculosis. However, this is dependent on good adherence and retrospective studies have indicated that adherence to unsupervised INH preventive chemotherapy is poor. Aim: To prospectively document adherence to six months of unsupervised INH monotherapy and outcome in children with household exposure to an adult pulmonary tuberculosis index case. Methods: From February 2003 to January 2005 in two suburbs of Cape Town, South Africa, all children <5 years old in household contact with an adult pulmonary tuberculosis index case were screened for tuberculosis and given unsupervised INH preventive chemotherapy once active tuberculosis was excluded. Adherence and outcome were monitored. Results: In total, 217 index cases from 185 households were identified; 274 children <5 years old experienced household exposure, of whom 229 (84%) were fully evaluated. Thirty eight children were treated for tuberculosis and 180 received preventive chemotherapy. Of the children who received preventive chemotherapy, 36/180 (20%) completed ⩾5 months of unsupervised INH monotherapy. During the subsequent surveillance period six children developed tuberculosis: two received no preventive chemotherapy, and four had very poor adherence. Conclusion: Adherence to six months of unsupervised INH preventive chemotherapy was poor. Strategies to improve adherence, such as using shorter duration multidrug regimens and/or supervision of preventive treatment require further evaluation, particularly in children who are at high risk to progress to disease following exposure.
Aminoglycoside-induced hearing loss in HIV-positive and HIV-negtive multidrug-resistant tuberculosis patients
(Health and Medical Publishing Group (HMPG), 2012-06) Harris, Tashneem; Bardien, Soraya; Schaaf, H. Simon; Petersen, Lucretia; De Jong, Greetje; Fagan, Johannes J.
Background. Ototoxicity following aminoglycoside treatment for multidrug-resistant tuberculosis (MDR-TB), is a significant problem. This study documents the incidence of ototoxicity in HIVpositive and HIV-negative patients with MDR-TB and presents clinical guidelines relating to ototoxicity. Methods. A prospective cohort study of 153 MDR-TB patients with normal hearing and middle ear status at baseline controlling for 6 mitochondrial mutations associated with aminoglycosiderelated ototoxicity, at Brooklyn Chest Hospital in Cape Town. Pure tone audiometry was performed monthly for 3 months to determine hearing loss. HIV status was recorded, as was the presence of 6 mutations in the MT-RNR1 gene. Results. Fifty-seven per cent developed high-frequency hearing loss. HIV-positive patients (70%) were more likely to develop hearing loss than HIV-negative patients (42%). Of 115 patients who were genetically screened, none had MT-RNR1 mutations. Conclusion. Ototoxic hearing loss is common in MDR-TB patients treated with aminoglycosides. HIV-positive patients are at increased risk of ototoxicity. Auditory monitoring and auditory rehabilitation should be an integral part of the package of care of MDR-TB patients.
Assessing the impact of multidrug-resistant tuberculosis in children : an exploratory qualitative study
(BioMed Central, 2014-08) Franck, Caroline; Seddon, James A.; Hesseling, Anneke C.; Schaaf, H. Simon; Skinner, Donald; Reynolds, Lucy
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.
BCG vaccination in South African HIV-exposed infants : risks and benefits
(Health and Medical Publishing Group (HMPG), 2009-02) Hesseling, A. C.; Caldwell, J.; Cotton, M. F.; Eley, B. S.; Jaspan, H. B.; Jennings, K.; Marais, B. J.; Nuttall, J.; Rabie, H.; Roux, P.; Schaaf, H. Simon
Child abuse and neglect : social work experience at Tygerberg hospital
(Stellenbosch University. Department of Social Work, 1999) Louw, H. M.; Van Schalkwyk, H. J. S.; Barnes, J. M.; Dhansay, S.; Schaaf, H. Simon
Since the proclamation of the Child Care Act 74 of 1983 suspected cases of child abuse and neglect have been notifiable by medical personnel. This obligation to notify has recently been extended to include social workers and several other categories of people taking care of children. The objective of this study is to share the social work experience in a tertiary care hospital in response to the greater awareness of child abuse and the importance of a central register for every institution or district managing cases of child abuse. A comprehensive register of all suspected cases of abuse in children below 18 years of age and cases of severe malnutrition has been kept at the Social Work Department at Tygerberg Hospital (TBH) in the Western Cape Province since 1987. This register was surveyed for the period 1 April 1994 - 31 March 1995. Five hundred and eighty six children with suspected child abuse were referred to the Social Work Department during this time. Of these, 246 (42%) were evaluated for child sexual abuse, 213 (36%) for physical abuse and 127 (22%) for severe malnutrition and neglect. Social workers from TBH were involved for a median duration of 1-2 months for physically abused and malnourished children, and 2-3 months for sexual abuse cases. A total of 5545 hours were spent on interviews, arrangements of children's safety, completing notification and referral reports, and preparing evidence for court and preparing children for court proceedings during this period. The magnitude of serious child abuse is extensive and more than the present infrastructure can handle. More social workers functioning within well-trained and supervised teams and placed suitably in the service network, notably in the outlying areas, are urgently needed.
Clinical features and outcome in children admitted to a TB hospital in the Western Cape : the influence of HIV infection and drug resistance
(SAMJ, 2005-08) Soeters, M.; De Vries, Anne Martien; Kimpen, Jan L. L.; Donald, Peter R.; Schaaf, H. Simon
Background. The Western Cape has a high incidence of tuberculosis (TB) and a rising prevalence of HIV infection. Children form 15-20% of this TB burden. Objective. To document the clinical features and outcome of TB among children admitted to a regional TB hospital. Method. A retrospective, descriptive study was undertaken of children under 15 years of age admitted to Brooklyn Hospital for Chest Diseases from January 2000 to December 2001. Demographic and clinical details of children were recorded routinely in a register that formed the basis of this review. Results. Two hundred and thirty-eight of the 250 children admitted had TB, of whom 120 (50.4%) were boys. The median age was 25 months. Reasons for admission were disease severity in 99 cases, social reasons in 36, and a combination in 103. Adult source cases were identified in 138 instances; 9 had drug-resistant TB, 31 drug-susceptible TB and in 98 cases susceptibility was unknown. TB was confirmed by culture in 119 children. Of 79 in whom susceptibility testing was done, 10 had isoniazid-resistant TB and 8 multidrug-resistant TB. HIV serology was positive in 43 of 138 children tested (31%). Previous antituberculosis treatment, severe malnutrition and weight under the 3rd percentile for age, a negative Mantoux test, and mortality were significantly more common in the HIV-infected children. Twenty-two of 41 previously negative Mantoux tests (< 5 mm induration) were positive on retesting. Conclusions. HIV infection is common in children with TB and malnutrition, and mortality in this group is high. Repeat Mantoux tests may show an increased number of positive results.
Clinical presentation and outcome of tuberculosis in human immunodeficiency virus infected children on anti-retroviral therapy
(BioMed Central, 2008-01) Walters, Elisabetta; Cotton, Mark F.; Rabie, Helena; Schaaf, H. Simon; Walters, Lourens O.; Marais, Ben J.
Background: The tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics are poorly controlled in sub-Saharan Africa, where highly active antiretroviral treatment (HAART) has become more freely available. Little is known about the clinical presentation and outcome of TB in HIV-infected children on HAART. Methods: We performed a comprehensive file review of all children who commenced HAART at Tygerberg Children's Hospital from January 2003 through December 2005. Results: Data from 290 children were analyzed; 137 TB episodes were recorded in 136 children; 116 episodes occurred before and 21 after HAART initiation; 10 episodes were probably related to immune reconstitution inflammatory syndrome (IRIS). The number of TB cases per 100 patient years were 53.3 during the 9 months prior to HAART initiation, and 6.4 during post HAART follow-up [odds ratio (OR) 16.6; 95% confidence interval (CI) 12.5–22.4]. A positive outcome was achieved in 97/137 (71%) episodes, 6 (4%) cases experienced no improvement, 16 (12%) died and the outcome could not be established in 18 (13%). Mortality was less in children on HAART (1/21; 4.8%) compared to those not on HAART (15/116; 12.9%). Conclusion: We recorded an extremely high incidence of TB among HIV-infected children, especially prior to HAART initiation. Starting HAART at an earlier stage is likely to reduce morbidity and mortality related to TB, particularly in TB-endemic areas. Management frequently deviated from standard guidelines, but outcomes in general were good.
Complementary surveillance strategies are needed to better characterise the epidemiology, care pathways and treatment outcomes of tuberculosis in children
(BioMed Central, 2018-03-23) Du Preez, Karen; Schaaf, H. Simon; Dunbar, Rory; Walters, Elisabetta; Swartz, Alvera; Solomons, Regan; Hesseling, Anneke C.
Background: Tuberculosis (TB) in young and HIV-infected children is frequently diagnosed at hospital level. In settings where general hospitals do not function as TB reporting units, the burden and severity of childhood TB may not be accurately reflected in routine TB surveillance data. Given the paucibacillary nature of childhood TB, microbiological surveillance alone will miss the majority of hospital-managed children. The study objective was to combine complementary hospital-based surveillance strategies to accurately report the burden, spectrum and outcomes of childhood TB managed at referral hospital-level in a high TB burden setting. Methods: We conducted a prospective cohort study including all children (< 13 years) managed for TB at a large referral hospital in Cape Town, South Africa during 2012. Children were identified through newly implemented clinical surveillance in addition to existing laboratory surveillance. Data were collected from clinical patient records, the National Health Laboratory Service database, and provincial electronic TB registers. Descriptive statistics were used to report overall TB disease burden, spectrum, care pathways and treatment outcomes. Univariate analysis compared characteristics between children identified through the two hospital-based surveillance strategies to characterise the group of children missed by existing laboratory surveillance. Results: During 2012, 395 children (180 [45.6%] < 2 years) were managed for TB. Clinical surveillance identified 237 (60%) children in addition to laboratory surveillance. Ninety (24.3%) children were HIV co-infected; 113 (29.5%) had weight-for-age z-scores <− 3. Extra-pulmonary TB (EPTB) was diagnosed in 188 (47.6%); 77 (19.5%) with disseminated TB. Favourable TB treatment outcomes were reported in 300/344 (87.2%) children with drugsusceptible and 50/51 (98.0%) children with drug-resistant TB. Older children (OR 1.7; 95% CI 1.0–2.8), children with EPTB (OR 2.3; 95% CI 1.5–3.6) and in-hospital deaths (OR 5.4; 95% CI 1.1–26.9) were more frequently detected by laboratory surveillance. TB/HIV co-infected children were less likely to be identified through laboratory surveillance (OR 0.3; 95% CI 0.2–0.5). Conclusions: The burden and spectrum of childhood TB disease managed at referral hospital level in high burden settings is substantial. Hospital-based surveillance in addition to routine TB surveillance is essential to provide a complete picture of the burden, spectrum and impact of childhood TB in settings where hospitals are not TB reporting units.
Correction to : The impact of drug resistance on the risk of tuberculosis infection and disease in child household contacts : a cross sectional study
(BioMed Central, 2017-11-07) Golla, Vera; Snow, Kathryn; Mandalakas, Anna M.; Schaaf, H. Simon; Du Preez, Karen; Hesseling, Anneke C.; Seddon, James A.
Correction: After publication of the original article [1] the authors noted that the following errors had occurred: The name of the author H. Simon Schaaf had been incorrectly tagged as Simon H. Schaaf. This has been corrected in the author list above. The first p value below Table 1 is listed as p < 0.011, however it should be p < 0.01. An updated version of this table is included with this Correction. The original article has also been corrected.
Culture-confirmed childhood tuberculosis in Cape Town, South Africa : a review of 596 cases
(BioMed Central, 2007-11) Schaaf, H. Simon; Marais, Ben J.; Whitelaw, Andrew; Hesseling, Anneke C.; Eley, Brian; Hussey, Gregory D.; Donald, Peter R.
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.
Drug-resistant tuberculosis in children
(Health and Medical Publishing Group (HMPG), 2007-10) Schaaf, H. Simon
Hearing loss in patients on treatment for drug-resistant tuberculosis
(European Respiratory Society, 2012-06) Seddon, James A.; Godfrey-Faussett, Peter; Jacobs, Kayleen; Ebrahim, Adam; Hesseling, Anneke C.; Schaaf, H. Simon
The treatment of drug‐resistant (DR) tuberculosis (TB) necessitates the use of second‐line injectable anti‐TB drugs which are associated with hearing loss. Hearing loss affects communication and for children the development of language and social skills. This article describes the pathophysiology of hearing loss and the testing methodologies that can be employed. It is the first paper to systematically review the literature regarding hearing loss in those treated for DR‐TB. In the studies identified, the methodology used to test for and to classify hearing loss is inconsistent and children and those with HIV are poorly represented. The review describes existing guidelines and suggests management strategies when hearing loss is found. It describes the challenges of testing hearing in the developing world contexts where the majority of patients with DR‐TB are treated. Finally it makes the recommendation that a standardised testing methodology and classification system be used.
Infective endocarditis - The effect of liposomes as carrier substance for α1-antitrypsin and amicillin
(Health & Medical Publishing Group, 1991) Schaaf, H. Simon; Bates, W. D.; Hanekom, C.; Neiteler, B. F.; Kriegler, A. B.; Van der Merwe, P.-L.
Infective endocarditis has a high mortality and morbidity rate despite all available treatment. Little attention has been paid to the possible role of polymorphonuclear leucocytes in damage to the heart valves. It was postulated that if the elastases set free from these leucocytes could be neutralised, this would prevent damage to the heart valves. Alpha1-antitrypsin (α1-AT) in liposomes was used to neutralise elastases. This process on its own and in various combinations with ampicillin were compared in animal models. Evaluation was performed by measuring vegetation size, by blood and vegetation cultures, and by light microscopy of the damaged tissue. A statistically significant difference (t-test; P < 0,005, with Bonferroni's correction for multiple comparisons) was found in vegetation size in the groups receiving ampicillin in liposomes, but the hypothesis that α1-AT might reduce valvular damage was not proven.
Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis : study protocol for a phase III cluster randomised controlled trial (TB-CHAMP)
(BMC (part of Springer Nature), 2018-12-20) Seddon, James A.; Garcia-Prats, Anthony J.; Purchase, Susan E.; Osman, Muhammad; Demers, Anne-Marie; Hoddinott, Graeme; Crook, Angela M.; Owen-Powell, Ellen; Thomason, Margaret J.; Turkova, Anna; Gibb, Diana M.; Fairlie, Lee; Martinson, Neil; Schaaf, H. Simon; Hesseling, Anneke C.
Background: Multidrug-resistant (MDR) tuberculosis (TB) presents a challenge for global TB control. Treating individuals with MDR-TB infection to prevent progression to disease could be an effective public health strategy. Young children are at high risk of developing TB disease following infection and are commonly infected by an adult in their household. Identifying young children with household exposure to MDR-TB and providing them with MDR-TB preventive therapy could reduce the risk of disease progression. To date, no trials of MDR-TB preventive therapy have been completed and World Health Organization guidelines suggest close observation with no active treatment. Methods: The tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) trial is a phase III cluster randomised placebo-controlled trial to assess the efficacy of levofloxacin in young child contacts of MDR-TB cases. The trial is taking place at three sites in South Africa where adults with MDR-TB are identified. If a child aged < 5 years lives in their household, we assess the adult index case, screen all household members for TB disease and evaluate any child aged < 5 years for trial eligibility. Eligible children are randomised by household to receive daily levofloxacin (15–20 mg/kg) or matching placebo for six months. Children are closely monitored for disease development, drug tolerability and adverse events. The primary endpoint is incident TB disease or TB death by one year after recruitment. We will enrol 1556 children from approximately 778 households with an average of two eligible children per household. Recruitment will run for 18–24 months with all children followed for 18 months after treatment. Qualitative and health economic evaluations are embedded in the trial. Discussion: If the TB-CHAMP trial demonstrates that levofloxacin is effective in preventing TB disease in young children who have been exposed to MDR-TB and that it is safe, well tolerated, acceptable and cost-effective, we would expect that that this intervention would rapidly transfer into policy.
MDR/XDR-TB management of patients and contacts : challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network
(Elsevier, 2020-03) Migliori, Giovanni Battista; Tiberi, Simon; Zumla, Alimuddin; Petersen, Eskild; Chakaya, Jeremiah Muhwa; Wejse, Christian; Torrico, Marcela Munoz; Duarte, Raquel; Alffenaar, Jan Willem; Schaaf, H. Simon; Marais, Ben J.; Cirillo, Daniela Maria; Alagna, Riccardo; Rendon, Adrian; Pontali, Emanuele; Piubello, Alberto; Figueroa, Jose; Ferlazzo, Gabriella; García-Basteiro, Alberto; Centis, Rosella; Visca, Dina; D’Ambrosio, Lia; Sotgiu, Giovanni
The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.
Missed opportunities in the diagnosis of pulmonary tuberculosis in children
(Health & Medical Publishing Group, 1993) Gie, R. P.; Beyers, Nulda; Schaaf, H. Simon; Donald, P. R.
In 52% of children with confirmed and probable tuberculosis the diagnosis could have been made earlier than it was. The main clinical clues which should have led to suspicion of tuberculosis were close adult contacts and previous recurrent respiratory tract infections.
Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study
(International Union Against Tuberculosis and Lung Disease, 2015-04) Wiseman, C. A.; Mandalakas, A. M.; Kirchner, H. L.; Gie, R. P.; Schaaf, H. Simon; Walters, E.; Hesseling, A. C.; Paediatrics and Child Health
BACKGROUND: International (National Institutes of Health [NIH]) case definitions have been proposed for paediatric tuberculosis (TB) diagnostic studies. The relevance of these definitions for contact tracing studies is unknown. METHODS: We developed case definitions for a community-based contact tracing diagnostic study. We compare disease certainty using protocol-defined and NIH case definitions and describe TB disease spectrum and severity. RESULTS: There were 111 potential disease episodes in 109 (21% human immunodeficiency virus [HIV] infected) of 1093 children enrolled. Based on NIH definitions, there were 8 confirmed, 12 probable, 17 possible and 3 unlikely TB and 2 non-TB episodes. Using protocol case definitions, there were 23 episodes of confirmed, 36 probable, 27 possible and 0 unlikely TB and 21 non-TB. Of 111 potential episodes, 69 were unclassifiable using the NIH definition, while 4 were unclassifiable using the protocol definition. Agreement between definitions was 0.30 (95%CI 0.23-0.38). There were 62 episodes (72%) of non-severe and 24 (28%) of severe TB. CONCLUSIONS: The NIH definition had limited applicability to household contact studies, despite the wide spectrum of disease observed. Further research is needed to develop case definitions relevant to different research settings, including contact investigation to capture the wide spectrum of paediatric TB in clinical research.
Pharmacokinetics and drug-drug interactions of abacavir and lamuvudine co-administered with antituberculosis drugs in HIV-positive children treated for multidrug-resistant tuberculosis
(Frontiers Media S.A, 2021-10-08) Van der Laan, Louvina E.; Garcia-Prats, Anthony J.; Schaaf, H. Simon; Winckler, Jana L.; Draper, Heather; Norman, Jennifer; Wiesner, Lubbe; McIlleron, Helen; Denti, Paolo; Hesseling, Anneke C.
Given the high prevalence of multidrug-resistant (MDR)-TB in high HIV burden settings, it is important to identify potential drug-drug interactions between MDR-TB treatment and widely used nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-positive children. Population pharmacokinetic models were developed for lamivudine (n = 54) and abacavir (n = 50) in 54 HIV-positive children established on NRTIs; 27 with MDR-TB (combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, fluoroquinolones, and amikacin), and 27 controls without TB. Two-compartment models with first-order elimination and transit compartment absorption described both lamivudine and abacavir pharmacokinetics, respectively. Allometric scaling with body weight adjusted for the effect of body size. Clearance was predicted to reach half its mature value ∼2 (lamivudine) and ∼3 (abacavir) months after birth, with completion of maturation for both drugs at ∼2 years. No significant difference was found in key pharmacokinetic parameters of lamivudine and abacavir when co-administered with routine drugs used for MDR-TB in HIV-positive children.
Presentation and outcome of culture-confirmed isoniazid-resistant rifampicin-susceptible tuberculosis in children
(International Union Against Tuberculosis and Lung Disease, 2016) Garcia-Prats, Anthony J.; Du Plessis, L.; Draper, H. R.; Burger, A.; Seddon, J. A.; Zimri, K.; Hesseling, Anneke C.; Schaaf, H. Simon
Setting: Isoniazid-resistant rifampicin-susceptible (HRRS) tuberculosis (TB) is the most prevalent form of drug-resistant TB globally, and may be a risk factor for poor outcomes. HRRS-TB in children has been poorly described. Objective: To characterize the clinical presentation, treatment, and clinical and microbiological outcomes, and factors associated with poor outcomes among children with culture-confirmed HRRS-TB. Design: Retrospective hospital-based cohort study. Results: Of the 72 children included, median age 50.1 months (IQR 21.5-102.5), 42% were male. Forty-four (51%) had a potential source case; only 13 were confirmed HRRS-TB. Twelve of 66 tested (17%) were HIV-infected, and 36 of 60 (60%) with pulmonary TB had severe disease. Seventy had treatment data; median total duration was 11.3 months (IQR 9-12.3); 25 (36%) initiated treatment with a 3-drug intensive phase; 52 (74%) received a fluoroquinolone. Of 63 with known outcome, 55 (88%) had a favourable outcome; 1 died and 3 had treatment failure. Ten had positive follow-up cultures at ≥2 months after starting treatment (17% of all PTB and 27% of those with follow-up culture data); older age (p=0.008), previous TB treatment (p=0.023) and severe PTB (p=0.018) were associated with failure to culture-convert at ≥2 months. Conclusions: Although overall outcomes were good, prolonged culture positivity and cases of treatment failure emphasize the need for additional attention to clinical management of children with HRRS-TB.
The prevalence of symptoms associated with pulmonary tuberculosis in randomly selected children from a high burden community
(BMJ Publishing Group, 2005-11) Marais, B. J.; Obihara, C. C.; Gie, R. P.; Schaaf, H. Simon; Hesseling, A. C.; Lombard, C.; Enarson, D.; Bateman, E.; Beyers, Nulda
Background: Diagnosis of childhood tuberculosis is problematic and symptom based diagnostic approaches are often promoted in high burden settings. This study aimed (i) to document the prevalence of symptoms associated with tuberculosis among randomly selected children living in a high burden community, and (ii) to compare the prevalence of these symptoms in children without tuberculosis to those in children with newly diagnosed tuberculosis. Methods: A cross sectional, community based survey was performed on a 15% random sample of residential addresses. A symptom based questionnaire and tuberculin skin test (TST) were completed in all children. Chest radiographs were performed according to South African National Tuberculosis Control Program guidelines. Results: Results were available in 1415 children of whom 451 (31.9%) were TST positive. Tuberculosis was diagnosed in 18 (1.3%) children. Of the 1397 children without tuberculosis, 253 (26.4%) reported a cough during the preceding 3 months. Comparison of individual symptoms (cough, dyspnoea, chest pain, haemoptysis, anorexia, weight loss, fatigue, fever, night sweats) in children with and without tuberculosis revealed that only weight loss differed significantly (OR = 4.5, 95% CI 1.5 to 12.3), while the combination of cough and weight loss was most significant (OR = 5.4, 95% CI 1.7 to 16.9). Children with newly diagnosed tuberculosis reported no symptoms in 50% of cases. Conclusion: Children from this high burden community frequently reported symptoms associated with tuberculosis. These symptoms had limited value to differentiate children diagnosed with tuberculosis from those without tuberculosis. Improved case definitions and symptom characterisation are required when evaluating the diagnostic value of symptoms.

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