Research Articles (Paediatrics and Child Health)

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Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir
(2020-05) Rabie, Helena; Tikiso, Tjokosela; Lee, Janice
ABSTRACT In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopi-navir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interac-tions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing 15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of anti-tuberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treat-ment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with ﬁrst-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identiﬁed: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treat-ment with rifampin and LPV/r-4:4 but remained within the median adult recom-mended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure signiﬁcantly decreased dur-ing concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identiﬁer NCT02348177.)
Acquired neonatal bronchial stenosis after selective intubation : successful managed with balloon dilatation
(Wiley Open Access, 2019) Goussard, Pierre; Morrison, Julie; Bekker, Adrie; Fourie, Barend
ENGLISH ABSTRACT: Premature babies are prone to airway‐related complications. Selective intubation for the management of pulmonary interstitial emphysema may cause acquired bronchial stenosis. Balloon dilatation under fluoroscopy is a safe minimal invasive and successful intervention for acquired bronchial stenosis. Follow‐up bronchoscopy is needed due to risk of restenosis.
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.
Adolescent tuberculosis
(Health & Medical Publishing Group, 1996-3) Donald, P. R.; Beyers, Nulda; Rook, G. A. W.
INTRODUCTION: One of the most intriguing features of the epidemiology of tuberculosis is the well-known variation in the age incidence of disease and the variation in the nature of the disease with age. During infancy and early childhood, tuberculous disease is particularly liable to follow infection and high morbidity and mortality are experienced. Disseminated forms of disease, such as miliary tuberculosis and tuberculous meningitis, are particularly likely to develop.
Adrenal rest tumours in congenital adrenal hyperplasia
(Journal of Endocrinology, Metabolism and Diabetes of South Africa (JEMDSA), 2008-07) Zollner, Ekkehard W.; Pitcher, Richard
Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is rare, occurring approximately once in every 15 000 live births.1 At birth it is often suspected in girls because of ambiguous genitalia, whereas boys have normal genitalia. The salt-losing type of CAH presents with adrenal crisis a few weeks after birth, while the simple type manifests virilisation and rapid growth years later. The diagnosis is confirmed by an elevated plasma 17-hydroxyprogesterone (17- OHP) level. Additional features in the salt-losing variety are hyponatraemia, hyperkalaemia, metabolic acidosis and an elevated plasma renin level. The gluco- and mineralocorticoid insufficiency is corrected by providing hydrocortisone and fludrocortisone, respectively. It may be necessary to add sodium chloride to infant feeds. Treatment is lifelong. If compliance is poor, excess androgen production, accelerated growth, secondary central precocious puberty and, in boys, adrenal rest tumours can occur, as in the following case.
Age-disparity, sexual connectedness and HIV infection in disadvantaged communities around Cape Town, South Africa: A study protocol
(BioMed Central Ltd, 2011) Delva, Wim; Beauclair, Roxanne; Welte, Alex; Vansteelandt, Stijn; Hens, Niel; Aerts, Marc; Du Toit, Elizabeth; Beyers, Nulda; Temmerman, Marleen
Abstract: Background Crucial connections between sexual network structure and the distribution of HIV remain inadequately understood, especially in regard to the role of concurrency and age disparity in relationships, and how these network characteristics correlate with each other and other risk factors. Social desirability bias and inaccurate recall are obstacles to obtaining valid, detailed information about sexual behaviour and relationship histories. Therefore, this study aims to use novel research methods in order to determine whether HIV status is associated with age-disparity and sexual connectedness as well as establish the primary behavioural and socio-demographic predictors of the egocentric and community sexual network structures. Method/Design We will conduct a cross-sectional survey that uses a questionnaire exploring one-year sexual histories, with a focus on timing and age disparity of relationships, as well as other risk factors such as unprotected intercourse and the use of alcohol and recreational drugs. The questionnaire will be administered in a safe and confidential mobile interview space, using audio computer-assisted self-interview (ACASI) technology on touch screen computers. The ACASI features a choice of languages and visual feedback of temporal information. The survey will be administered in three peri-urban disadvantaged communities in the greater Cape Town area with a high burden of HIV. The study communities participated in a previous TB/HIV study, from which HIV test results will be anonymously linked to the survey dataset. Statistical analyses of the data will include descriptive statistics, linear mixed-effects models for the inter- and intra-subject variability in the age difference between sexual partners, survival analysis for correlated event times to model concurrency patterns, and logistic regression for association of HIV status with age disparity and sexual connectedness. Discussion This study design is intended to facilitate more accurate recall of sensitive sexual history data and has the potential to provide substantial insights into the relationship between key sexual network attributes and additional risk factors for HIV infection. This will help to inform the design of context-specific HIV prevention programmes.
Aggressive desmoid fibromatosis : first case in a Rwandan child
(Health & Medical Publishing Group, 2013-08-30) Kanyamuhunga, Aimable; McCall, Natalie; Tuyisenge, Lisine; Mumena, Crispus; Stefan, Daniela Cristina
Desmoid tumours are a rare group of locally aggressive, non-malignant tumours of fibroblastic origin that can result in significant morbidity due to local invasion. Facial involvement in children with aggressive fibromatosis is uncommon. We present the case of a 14-month-old Rwandan child with an aggressive desmoid tumour involving the left mid-facial region. The patient presented with severe stertor due to massive nasal obstruction. After intensive supportive care the diagnosis was confirmed histopathologically. Treatment consisted of eight courses of chemotherapy with vincristine, actinomycin-D and cyclophosphamide followed by surgical removal of the remaining mass. The outcome was impressive and encouraging.
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.
Annual risk of tuberculous infection using different methods in communities with a high prevalence of TB and HIV in Zambia and South Africa
(Public Library of Science (PLOS), 2009-11) Shanaube, Kwame; Sisminidis, Charalambos; Ayles, Helen; Beyers, Nulda; Schaap, Ab; Lawrence, Katherine-Anne; Barker, Annie; Godfrey-Faussett, Peter
Background: The annual risk of tuberculous infection (ARTI) is a key epidemiological indicator of the extent of transmission in a community. Several methods have been suggested to estimate the prevalence of tuberculous infection using tuberculin skin test data. This paper explores the implications of using different methods to estimate prevalence of infection and ARTI. The effect of BCG vaccination on these estimates is also investigated. Methodology/Principal Findings: Tuberculin surveys among school children in 16 communities in Zambia and 8 in South Africa (SA) were performed in 2005, as part of baseline data collection and for randomisation purposes of the ZAMSTAR study. Infection prevalence and ARTI estimates were calculated using five methods: different cut-offs with or without adjustments for sensitivity, the mirror method, and mixture analysis. A total of 49,835 children were registered for the surveys, of which 25,048 (50%) had skin tests done and 22,563 (90%) of those tested were read. Infection prevalence was higher in the combined SA than Zambian communities. The mirror method resulted in the least difference of 7.8%, whereas that estimated by the cut-off methods varied from 12.2% to 17.3%. The ARTI in the Zambian and SA communities was between 0.8% and 2.8% and 2.5% and 4.2% respectively, depending on the method used. In the SA communities, the ARTI was higher among the younger children. BCG vaccination had little effect on these estimates. Conclusions/Significance: ARTI estimates are dependent on the calculation method used. All methods agreed that there were substantial differences in infection prevalence across the communities, with higher rates in SA. Although TB notification rates have increased over the past decades, the difference in cumulative exposure between younger and older children is less dramatic and a rise in risk of infection in parallel with the estimated incidence of active tuberculosis cannot be excluded. © 2009 Shanaube et al.
Another phenocopy for chondrodysplasia punctata in addition to warfarin embryopathy?
(HMPG, 1978) Gericke G.S.; van der Walt A.; de Jong G.
[No abstract available]
Anti-Group B Streptococcus antibody in infants born to mothers with human immunodeficiency virus (HIV) infection
(Elsevier, 2015-01-29) Le Doare, Kirsty; Allen, Lauren; Kampmann, Beate; Heath, Paul Trafford; Taylor, Stephen; Hesseling, Anneke C.; Gorringe, Andrew; Jones, Christine Elizabeth
Background: HIV-exposed uninfected infants have increased infection risk and mortality compared to HIV-unexposed infants. HIV-exposed infants may be at increased risk of invasive GBS disease due to reduced maternal antibody against GBS. Methods: We quantified antibodies that bind to the surface of whole Group B Streptococcus (GBS) of serotypes Ia, Ib, II, III and V using novel flow cytometry assays in South African HIV-infected and non-infected mothers and their uninfected infants. Antibody-mediated complement C3b/iC3b deposition onto GBS of these serotypes was also quantified by a novel flow cytometry assay. Results: Geometric mean concentration (GMC) of both surface-binding anti-GBS antibody and antibody-mediated complement deposition onto GBS were reduced in HIV-infected women (n = 46) compared to HIV-uninfected women (n = 58) for ST1a (surface-binding: 19.3 vs 29.3; p = 0.003; complement deposition: 2.9 vs 5.3 SU/mL; p = 0.003), STIb (24.9 vs 47.6; p = 0.003; 2.6 vs 4.9 SU/mL; p = 0.003), STII (19.8 vs 50.0; p = 0.001; 3.1 vs 6.2 SU/mL; p = 0.001), STIII (27.8 vs 60.1; p = 0.001; 2.8 vs 5.3 SU/mL; p = 0.001) and STV (121.9 vs 185.6 SU/mL; p < 0.001) and in their infants for STIa (complement deposition 9.4 vs 27.0 SU/mL; p = 0.02), STIb (13.4 vs 24.5 SU/mL; p = 0.02), STII (14.6 vs 42.7 SU/mL; p = 0.03), STIII (26.6 vs 62.7 SU/mL; p = 0.03) and STV (90.4 vs 165.8 SU/mL; p = 0.04). Median transplacental transfer of antibody from HIV-infected women to their infants was reduced compared to HIV-uninfected women for GBS serotypes II (0.42 [IQR 0.22–0.59] vs 1.0 SU/mL [0.42–1.66]; p < 0.001), III (0.54 [0.31–1.03] vs 0.95 SU/mL [0.42–3.05], p = 0.05) and V (0.51 [0.28–0.79] vs 0.75 SU/mL [0.26–2.9], p = 0.04). The differences between infants remained significant at 16 weeks of age. Conclusions: Maternal HIV infection was associated with lower anti-GBS surface binding antibody concentration and antibody-mediated C3b/iC3b deposition onto GBS bacteria of serotypes Ia, Ib, II, III and V. This may render these infants more susceptible to early and late onset GBS disease.
Antiretroviral therapy for the management of HIV in children
(Health & Medical Publishing Group, 2014-12) Frigati, L.; Cotton, Mark F.; Rabie, H.
Since 2004, when antiretroviral therapy (ART) was first available to children through the National Department of Health, there has been significant progress in preventing and treating paediatric HIV. Large cohort studies and prospective trials confirmed that young children require early diagnosis with rapid access to ART regardless of CD4+ lymphocyte count. Studies also confirmed the importance of ritonavir-boosted protease inhibitors during therapy, regardless of prior nevirapine exposure. As prevention strengthens and the paediatric population ages, the goal posts are shifting towards even earlier diagnosis, targeting newborn infants on the first day of life and also the perinatally infected adolescent. There is an increasing focus on the long-term health, social, developmental and scholastic outcomes of HIV-infected children. Clinicians require new skills to assist children with transition into adulthood. In this article we focus on the care of infants and children.
Antiretroviral therapy in children - increased benefit from increased complexity
(Health & Medical Publishing Group, 2000-10) Cotton, Mark F.
Antiretroviral therapy (ART) started as monotherapy with significant short-term gains. With the advent of newer drugs management has become more complex, but with significant gains in quality and quantity of life. The evolution of ART in children lags behind that of adults for many reasons. These include an unwillingness to use new medications in children before efficacy has been established and also difficulty in developing suitable formulations for children. ART has progressed from monotherapy to dual, triple and even quadruple therapy, stimulated by insights into the rapidity of viral replication, development of resistance, and availability of new agents. The most pressing concern with ART is its lack of accessibility to the majority of patients that need it. Other important issues are how and when to use it in ways that promote durability of response but avoid unnecessary use. Most information is derived from studies with relatively short periods of follow-up. The long-term durability of therapy is not known, but with development of new agents should be sustained.
Approach to headaches in children
(Health & Medical Publishing Group, 2011) Solomons, Regan; Schoeman, Johan; Van Toorn, Ronald
Headache is a common problem in childhood – up to 25% of schoolchildren suffer from chronic, recurrent headaches. Although primary headaches are far more common than those with a secondary cause, it is the latter that result in the most anxiety for families.1 A logical approach to investigating and managing headaches is needed.
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.
Assessment of the delayed repair of uncomplicated inguinal hernias in infants
(Medpharm, 2020-03) Botes, S. N.; Edge, J.; Apffelstaedt, J. P.; Sidler, D.
BACKGROUND: Potential strangulation of infant inguinal hernias is the main indication for their urgent repair. Lack of theatre time delays repair and prolongs hospitalisation. We report a series of patients with uncomplicated hernias who were discharged home to have their elective surgery at a later stage and assessed the outcomes of this approach METHODS: A retrospective audit was performed of all infants with an inguinal hernia from January 2010 to June 2015. Incomplete records and infants operated after their first birthday were excluded. Two groups were identified; immediate surgery for infants with uncomplicated hernias, and delayed surgery for infants with uncomplicated hernias. Incarceration/ strangulation rates in the interim period were documented for the delayed group, and comparison made between the groups regarding perioperative and anaesthetic complications and length of postoperative hospital stay RESULTS: The mean time delay between diagnosis and repair was 8.78 weeks. None of the hernias in the delay group strangulated while awaiting repair. There was no significant difference in the perioperative complications between the two groups. Out ofthe 70 cases in the immediate repair group, there was 7 (10%) surgical and 4 (5.7%) anaesthetic complications. The delayed group (169 infants) had 8 (4.7%) surgical and 6 (3.6%) anaesthetic complications. The incarceration rate after being discharged home was 4.1%. This group of infants had no anaesthetic or surgical complications. Length of hospital stay postoperatively was 1.43 days in the immediate group and 1.3 in the delayed group (p = .485 CONCLUSION: Delayed repair, up to 2 months later, for uncomplicated infant hernia carries a small risk of incarceration but does not increase the rate of strangulation or other complications
The association between preterm labour, perinatal mortality and infant death (during the first year) in Bishop Lavis, Cape Town, South Africa
(Health & Medical Publishing Group, 2019) Brink, L. T.; Gebhardt, G. S.; Mason, D.; Groenewald, C. A.; Odendaal, H. J.
Background. We present further analyses from the Safe Passage Study, where the effect of alcohol exposure during pregnancy on sudden infant death syndrome and stillbirth was investigated. Objectives. To describe pregnancy and neonatal outcome in a large prospective study where information on the outcome of pregnancy was known in >98.3% of participants and ultrasound was used to determine gestational age (GA). Methods. As part of the Safe Passage Study of the PASS Network in Cape Town, South Africa, the outcomes of 6 866 singleton pregnancies were prospectively followed from recruitment in early pregnancy until the infant was 12 months old to assess pregnancy outcome. Fetal growth was assessed by z-scores of the birth weight, and GA at birth was derived from early ultrasound assessments. The effects of fetal growth restriction and preterm delivery on pregnancy outcome were determined. Results. There were 66 miscarriages, 107 stillbirths at ≥22 weeks’ gestation, 66 stillbirths at ≥28 weeks’ gestation, 29 and 18 neonatal deaths at ≥22 and ≥28 weeks’ gestation, respectively, and 54 post-neonatal deaths (28 days - 12 months). The miscarriage rate was 9.6/1 000 and the infant mortality rate 12.4/1 000. Of the births, 13.8% were preterm. For deliveries at ≥22 and ≥28 weeks, the stillbirth rates were 15.7 and 9.8/1 000 deliveries, respectively. For deliveries at ≥22 and ≥28 weeks, the neonatal death rates were 4.3 and 2.7/1 000 live births, respectively. For these pregnancies the perinatal mortality rates were 20.0/1 000 (≥22 weeks) and 12.5/1 000 (≥28 weeks), respectively. Only 15.9% of stillbirths occurred during labour (in 15.9% of cases it was uncertain whether death had occurred during labour). In the majority of cases (68.2%) fetal death occurred before labour, and 82.2% of stillbirths and 62.1% of neonatal deaths occurred in deliveries before 37 weeks. Including the miscarriages, stillbirths and infant deaths, there were 256 pregnancy losses; 77.3% were associated with deliveries before 37 weeks. Only 1.8% of all the women were HIV-positive, whereas the HIV-positive rate was 3.7% among those who had stillbirths. Birth weight was below the 10th centile in 25.6% of neonatal and post-neonatal deaths compared with 17.7% of survivors. Conclusions. Preterm birth and fetal growth restriction play significant roles in fetal, neonatal and infant losses.
The association between the ratio of monocytes : lymphocytes at age 3 months and risk of tuberculosis (TB) in the first two years of life
(BioMed Central, 2014-07-17) Naranbhai, Vivek; Kim, Soyeon; Fletcher, Helen; Cotton, Mark F.; Violari, Avy; Mitchell, Charles; Nachman, Sharon; McSherry, George; McShane, Helen; Hill, Adrian V. S.; Madhi, Shabir A.
Background: Recent transcriptomic studies revived a hypothesis suggested by historical studies in rabbits that the ratio of peripheral blood monocytes to lymphocytes (ML) is associated with risk of tuberculosis (TB) disease. Recent data confirmed the hypothesis in cattle and in adults infected with HIV. Methods: We tested this hypothesis in 1,336 infants (540 HIV-infected, 796 HIV-exposed, uninfected (HEU)) prospectively followed in a randomized controlled trial of isoniazid prophylaxis in Southern Africa, the IMPAACT P1041 study. We modeled the relationship between ML ratio at enrollment (91 to 120 days after birth) and TB disease or death in HIV-infected children and latent Mycobacterium tuberculosis (MTB) infection, TB disease or death in HEU children within 96 weeks (with 12 week window) of randomization. Infants were followed-up prospectively and routinely assessed for MTB exposure and outcomes. Cox proportional hazards models allowing for non-linear associations were used; in all cases linear models were the most parsimonious. Results: Increasing ML ratio at baseline was significantly associated with TB disease/death within two years (adjusted hazard ratio (HR) 1.17 per unit increase in ML ratio; 95% confidence interval (CI) 1.01 to 1.34; P = 0.03). Neither monocyte count nor lymphocyte counts alone were associated with TB disease. The association was not statistically dissimilar between HIV infected and HEU children. Baseline ML ratio was associated with composite endpoints of TB disease and death and/or TB infection. It was strongest when restricted to probable and definite TB disease (HR 1.50; 95% CI 1.19 to 1.89; P = 0.006). Therefore, per 0.1 unit increase in the ML ratio at three to four months of age, the hazard of probable or definite TB disease before two years was increased by roughly 4% (95% CI 1.7% to 6.6%). Conclusion: Elevated ML ratio at three- to four-months old is associated with increased hazards of TB disease before two years among children in Southern Africa. While significant, the modest effect size suggests that the ML ratio plays a modest role in predicting TB disease-free survival; its utility may, therefore, be limited to combination with existing tools to stratify TB risk, or to inform underlying pathophysiologic determinants of TB disease.
The association of hyperglycaemia with prevalent tuberculosis : a population-based cross-sectional study
(BioMed Central, 2016) Bailey, Sarah Lou; Ayles, Helen; Beyers, Nulda; Godfrey-Faussett, Peter; Muyoyeta, Monde; Du Toit, Elizabeth; Yudkin, John S.; Floyd, Sian
Background: Systematic reviews suggest that the incidence of diagnosed tuberculosis is two- to- three times higher in those with diabetes mellitus than in those without. Few studies have previously reported the association between diabetes or hyperglycaemia and the prevalence of active tuberculosis and none in a population-based study with microbiologically-defined tuberculosis. Most have instead concentrated on cases of diagnosed tuberculosis that present to health facilities. We had the opportunity to measure glycaemia alongside prevalent tuberculosis. A focus on prevalent tuberculosis enables estimation of the contribution of hyperglycaemia to the population prevalence of tuberculosis. Methods: A population-based cross-sectional study was conducted among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Prevalent tuberculosis was defined by the presence of a respiratory sample that was culture positive for M. tuberculosis. Glycaemia was measured by random blood glucose (RBG) concentration. Association with prevalent tuberculosis was explored across the whole spectrum of glycaemia. Results: Among 27,800 Zambian and 11,367 Western Cape participants, 4,431 (15.9%) and 1,835 (16.1%) respectively had a RBG concentration ≥7.0 mmol/L, and 405 (1.5%) and 322 (2.8%) respectively had a RBG concentration ≥11. 1 mmol/L. In Zambia, the prevalence of tuberculosis was 0 · 5% (142/27,395) among individuals with RBG concentration <11.1 mmol/L and also ≥11.1 mmol/L (2/405); corresponding figures for WC were 2 · 5% (272/11,045) and 4 · 0% (13/322). There was evidence for a positive linear association between hyperglycaemia and pulmonary prevalent tuberculosis. Taking a RBG cut-off 11.1 mmol/L, a combined analysis of data from Zambian and WC communities found evidence of association between hyperglycaemia and TB (adjusted odds ratio = 2 · 15, 95% CI [1 · 17–3 · 94]). The population attributable fraction of prevalent tuberculosis to hyperglycaemia for Zambia and WC combined was 0.99% (95% CI 0 · 12%–1.85%) for hyperglycaemia with a RBG cut-off of 11.1 mmol/L. Conclusions: This study demonstrates an association between hyperglycaemia and prevalent tuberculosis in a large population-based survey in Zambia and Western Cape. However, assuming causation, this association contributes little to the prevalence of TB in these populations.
Asthma treatment in children : a guide to screening for and management of hypothalamic-pituitary-adrenal axis suppression
(Health & Medical Publishing Group, 2019) Zollner, E. W.
ENGLISH ABSTRACT: A recently published approach to paediatric asthma management neither recommended screening for nor suggested any management of hypothalamic-pituitary-adrenal axis suppression in asthmatic children treated with corticosteroids. The existing literature on this topic was therefore reviewed and the quality of the evidence assessed. Recommendations for diagnosis, screening and management are made utilising the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

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