OpenUCT :: Browsing by Author "Zar, Heather"

Browsing by Author "Zar, Heather"

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Open Access
Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules
(BioMed Central Ltd, 2009) le Roux, Stanzi; Cotton, Mark; Golub, Jonathan; le Roux, David; Workman, Lesley; Zar, Heather
BACKGROUND:Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa. Isoniazid prophylaxis can reduce tuberculosis incidence in this population. However, for the treatment to be effective, adherence to the medication must be optimized. We investigated adherence to isoniazid prophylaxis administered daily, compared to three times a week, and predictors of adherence amongst HIV-infected children. METHODS: We investigated adherence to study medication in a two centre, randomized trial comparing daily to three times a week dosing of isoniazid. The study was conducted at two tertiary paediatric care centres in Cape Town, South Africa. Over a 5 year period, we followed 324 HIV-infected children aged [greater than or equal to] 8 weeks. Adherence information based on pill counts was available for 276 children. Percentage adherence was calculated by counting the number of pills returned. Adherence [greater than or equal to] 90% was considered to be optimal. Analysis was done using summary and repeated measures, comparing adherence to the two dosing schedules. Mean percentage adherence (per child during follow-up time) was used to compare the mean of each group as well as the proportion of children achieving an adherence of [greater than or equal to] 90% in each group. For repeated measures, percentage adherence (per child per visit) was dichotomized at 90%. A logistic regression model with generalized estimating equations, to account for within-individual correlation, was used to evaluate the impact of the dosing schedule. Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants. RESULTS: The overall adherence to isoniazid was excellent, with a mean adherence of 94.7% (95% confidence interval [CI] 93.5-95.9); similar mean adherence was achieved by the group taking daily medication (93.8%; 95% CI 92.1-95.6) and by the three times a week group (95.5%; 95% CI 93.8-97.2). Two-hundred and seventeen (78.6%) children achieved a mean adherence of [greater than or equal to] 90%. Adherence was similar for daily and three times a week dosing schedules in univariate (odds ratio [OR] 0.88; 95% CI 0.66-1.17; P = 0.38) and multivariate (adjusted OR 0.85; 95% CI 0.64-1.11; P = 0.23) models. Children from overcrowded homes were less adherent (adjusted OR 0.71; 95% CI 0.54-0.95; P = 0.02). Age at study visit was predictive of adherence, with better adherence achieved in children older than 4 years (adjusted OR 1.96; 95% CI 1.16-3.32; P = 0.01). CONCLUSION: Adherence to isoniazid was excellent regardless of the dosing schedule used. Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing, without compromising adherence or efficacy.TRIAL REGISTRATION:Clinical Trials NCT00330304
Open Access
Ambulatory and hospitalized childhood pneumonia: a longitudinal study in a peri-urban low-income community with high vaccination coverage in Sub-Saharan Africa
(2022) le Roux, David; Zar, Heather; Nicol, Mark
Background Child pneumonia is a substantial cause of childhood mortality and morbidity; it is the largest single cause of under-5 mortality outside the neonatal period. Incidence of child pneumonia, and pneumonia mortality, have decreased substantially due to improved socio-economic attainment, improved HIV programs, coverage of new conjugate vaccines against Streptococcus pneumoniae (PCV) and Haemophilus influenzae type B (Hib), access to early antibiotic therapy, and changing prevalence of pneumonia risk factors. Measurement of community-based pneumonia incidence is difficult; risk factors for pneumonia incidence and factors associated with pneumonia mortality are poorly described in low- and middle-income countries. Careful measurement of pneumonia incidence, and prospective analysis of risk factors is necessary to appreciate the evolving complexities of pneumonia causality and mortality. The aim of this work was to describe the incidence and severity of pneumonia in a birth cohort of children in the first 2 years life; and identify risk factors for pneumonia and for severe outcomes. Methods A prospective birth cohort, the Drakenstein Child Health Study, enrolled mother-infant pairs in two communities outside Cape Town, South Africa. Pregnant women were recruited and followed through pregnancy, labour and delivery, and the first 2 years of the child's life. Comprehensive data collection of risk factors was done through the first 2 years of life. A community pneumonia surveillance system was established; active case finding was used for birth cohort participants over 4 respiratory seasons. Children were examined at scheduled visits and at the time of pneumonia events. Pneumonia or severe pneumonia was diagnosed according to revised World Health Organisation (WHO) guidelines. Chest x-rays were classified according to WHO guidelines. Predictors of ambulatory and hospitalized pneumonia were explored with Poisson regression using generalized estimating equations clustered on mother-infant pairs. Factors associated with death or admission to intensive care unit were analysed with prevalence ratios from modified Poisson regression with robust variance estimation. Findings From March 2012 to March 2015, 1137 pregnant women were enrolled, delivering 1143 live-born infants. Household environmental tobacco smoke exposure was common: 82% of children were exposed in the first 6 months of life. Maternal HIV infection was common: 249 (22%) of 1143 children were HIV-exposed, but only 2 children became HIV-infected. Coverage of primary series of hexavalent vaccine, PCV and Hib was excellent (92%). During the study period (2012 to 2017), there were 795 pneumonia episodes (621 (78%) ambulatory, 274 (22%) hospitalised) in the first 2 years of life. Pneumonia incidence was higher in the first year of life (0.51 episodes per child year (e/cy)) and decreased to 0.25 e/cy in the second year. Active case finding in the birth cohort was more accurate than passive surveillance performed at the community clinics; pneumonia incidence measured by passive surveillance was significantly lower (incidence rate ratio 0.72, 95% CI 0.58 – 0.89) compared to active surveillance. Pneumonia mortality was low: 1.7% of hospitalised cases, and 0.35% of all clinical cases. There was marked variability in pneumonia incidence from year to year during the study. Many risk factors for pneumonia did not have fixed effects, but had different impacts at different ages, and variable effect on ambulatory and hospitalised pneumonia. In multivariable regression, adjusted incidence rate ratios were calculated for 5 risk factors (age< 6 months, male sex, low birth weight (<2500g), maternal smoking, delayed vaccines), which were associated with consistent effects on ambulatory and hospitalised pneumonia. Risk factors for serious outcomes of pneumonia (death or admission to intensive care unit) were identified: age under 2 months, low birth weight and hypoxia. Conclusion In this birth cohort, with low socio-economic status but high vaccination coverage, we demonstrated higher-than expected incidence of pneumonia, but very low mortality, with specific risk factors identified. Active surveillance was important for accurate detection of pneumonia. Children born at low birth weight are at increased risk for pneumonia and for serious outcomes. Pulse oximetry to detect hypoxia, and access to oxygen for children with hypoxic pneumonia, should be included in guidelines. These data will have global applicability for estimation of child pneumonia incidence in regions where direct measurement is impossible. These data can be applied to epidemiology and disease-modelling for child health; they will contribute to long-term morbidity follow-up studies; and they will contribute to understanding the constantly-evolving epidemiology of child pneumonia.
Open Access
Chronic morbidities in perinatally HIV-acquired adolescents on antiretroviral therapy
(2022) Mahtab, Sana; Zar, Heather; Myer, Landon
of children perinatally infected with HIV, with an increasing number surviving into adolescence, accompanied by the development of chronic comorbidities. However, there is limited knowledge on the spectrum of comorbidities, determinants, and risk factors among youth living with perinatally acquired HIV (YLPHIV) especially in sub-Saharan Africa, with most data from high-income countries. There is a critical need for data on health and chronic comorbidities among YLPHIV from countries with a high HIV prevalence. Aim: To investigate the spectrum and determinants of HIV-associated comorbidities among YLPHIV on ART in Cape Town, South Africa. Specific objectives were to investigate cardiovascular, musculoskeletal, mental health and metabolic outcomes in YLPHIV compared to HIV-uninfected adolescents. Method: In a prospective study YLPHIV on ART were enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) from seven health-care sites in Cape Town, South Africa, between July 2013 – April 2015. Eligibility criteria were adolescents, 9-14 years old, with perinatally acquired HIV, been on ART for at least six months, and who were aware of their HIV status. A control group of HIVuninfected adolescents' frequency-matched by age and sex was also enrolled. The cohort was longitudinally followed for development or progression of comorbidities with clinical and laboratory measurements. Comorbidities assessed included: (1) cardiovascular health: echocardiography was used to investigate cardiac structure and endothelial peripheral arterial tonometry technique (EndoPAT) was used for endothelial function. The pathobiological determinants of atherosclerosis in youth (PDAY) risk score was used to assess long-term cardiovascular risk for atherosclerotic disease at the coronary artery (CA) and abdominal aorta (AA). A PDAY score ≥1 was regarded as elevated; (2) bone health: quantitative ultrasound was used to evaluate calcaneal stiffness index (SI); (3) mental health: the Child Behavior Checklist (CBCL) and BECK youth inventories were utilised. The association of mental health with metabolic abnormalities was investigated. Statistical analyses included descriptive data and regression modelling analysis, using the software, Stata® 14.2 to 16 (Stata Corp LP. College Station, Texas, USA). Results: Overall, 515 YLPHIV and 110 HIV-uninfected participants with median age 12.0 years (IQR 11.9, 10.7) and 11.8 years (IQR 11.7, 10.0) were enrolled; YLPHIV with median duration of ART of 7.6 years (IQR: 4.6–9.2), also had a median CD4 cell count of 713 cells/mm3 (IQR: 561.0–957.5), and 387 (75%) had a viral load (VL) of 500 cell/mm3 (RR 1.04, p=0.76), VL (RR 1.01, p=0.78) or current ART class (protease inhibitor-based vs non-nucleoside inhibitor-based, RR 0.90, p=0.186) were not associated with ED after adjustment. At 48 months of follow-up, among YLPHIV, 8% (n=17) had sustained viraemia, and 54% (n=118) had transient viraemia through this period. The median duration on ART was 12 years (IQR 8-14); 57% (n=124) were on a non-nucleoside reverse transcriptase inhibitor-based ART, while the rest received protease inhibitor-based ART. Few YLPHIV met the criteria for hypertension (2%, n=4) or hyperglycaemia (0.5%, n=1). None of the HIV-uninfected youth had hypertension or hyperglycaemia. Fewer YLPHIV smoked compared to the uninfected youth (15.6% vs 11.5%, p=0.50. Elevated PDAY scores for CA (30.3% [n=66] vs 31.3% [n=10], p=0.74) and AA (18.4% [n=40] vs 21.9% [n=7], p=0.20), respectively among YLPHIV and HIV-uninfected adolescents differed slightly but did not reach statistical significance. Among YLPHIV, sustained viraemia [adjusted odds ratio (aOR)=18.4, p50 copies/ml (OR=2.06, p=0.023) were associated with an increased risk of low SI, while the use of efavirenz (OR=0.41, p=0.009) was associated with a decreased risk of low SI. YLPHIV had more impairment in mental health in several domains: functional competence (40% vs 25%, p=0.02), self-concept (23% vs 9%, p=0.03), higher depression (6% vs 2%, p< 0.01), anger (6% vs 2%, p=0.04), and disruptive behaviour (4% vs 0%, p p<0.01). Among YLPHIV, higher levels of anger were associated with increased total cholesterol and low-density lipoprotein (LDL) levels (ß=0.010, p=0.041 and ß=0.012, p=0.048, respectively), higher disruptive behaviour with increased LDL levels (ß=0.010, p=0.043), and severer CBCL-internalizing problems with low albumin levels (ß=-0.067, p=0.052) after adjusting for age, sex, and BMI z-score. Conclusion: YLPHIV are at higher risk of having subclinical cardiac structural abnormality and ED compared to uninfected adolescents. Both groups had a substantial proportion with high PDAY scores reflecting increased aggregate atherosclerotic risk. Bone health was worse among YLPHIV. HIV-related factors such as ART initiation at an older age, advanced clinical disease, and specific ARTs were significant risk factors for these conditions. Mental health impairment was common and associated with increased lipid concentration in YLPHIV. These data highlight a high prevalence of chronic comorbidities in YLPHIV, specific risk factors associated with these and provide information for strengthened strategies to prevent or monitor HIV-associated illnesses.
Open Access
Clinical indicators of Pneumocystis jiroveci pneumonia (PCP) in South African children infected with human immunodeficiency virus
(2005) Fatti, Geoffrey Libero; Swingler, George H; Zar, Heather
Pneumocystis pneumonia (PCP) is an important cause of morbidity and mortality amongst HIV-infected children in Africa. Definitive diagnostic resources for PCP in Africa are limited due to their expense and technical difficulty, however recognising and treating children at risk is essential. As management decisions for children with pneumonia are made primarily on a clinical basis in many African regions, it is important to attempt to define a valid clinical diagnostic technique for PCP that could be used by clinicians to determine the use of correct empirical antibiotic therapy. The objectives of this study were to identify clinical features (associated with PCP in HIV-infected children hospitalised with pneumonia, to determine the combination of features that best predicts PCP in these children, and to calculate the diagnostic accuracy of these features. This study was a re-analysis of a database of a prospective study. Consecutive children below ten years of age, with a primary diagnosis of pneumonia or severe pneumonia, and who were known to be HIV-infected or were suspected of having HIV infection, were included prospectively over a 12 month period. Clinical data and diagnostic testing for PCP were obtained on admission. Bi and multivariate analysis of associations of the clinical variables with PCP were performed using logistic regression, to identify the combination of variables that best predicted PCP. The diagnostic accuracy of the best predicted features were calculated.
Open Access
Congenital lung mass in anasymptomatic patient
(2006) Zar, Heather; McIvor, Bruce; Furlan, Gisella; Jedeikin, Leon; Pitcher, Richard
A routine 20-week antenatal ultrasound scan showed a congenital lesion of the left fetal lung, measuring approximately 25 mm x 25 mm x 30 mm. The mass showed no sonographic change through the remainder of an uneventful pregnancy. The baby was delivered by elective caesarean section at 38 weeks' gestation, with a birth weight of 2 900 g, and had no postnatal complications. A chest radiograph performed in the early neonatal period was normal, but a contrasted single-slice helical computed tomography (CT) chest scan at age 6 weeks demonstrated the small, oval, solid mass in the left lower lobe, with no associated mediastinal shift (Fig. 1). The vascular supply of the lesion could not be identified on this scan.
Open Access
Dietary and environmental factors associated with symptoms or diagnosis of asthma in Cape Town school children : findings from the International Study of Asthma and Allergies in Childhood (ISAAC) phase three study
(2007) Mahlati, Unati; Zar, Heather; Ehrlich, Rodney
The prevalence of current wheeze and asthma in school children in Cape Town has been reported to be increasing. The multi centre International Study of Asthma and Allergies in Childhood Phase 3 (ISAAC 3) offered an opportunity to investigate the relationship between environmental or dietary risk factors and asthma symptoms or diagnosis.
Open Access
Early determinants of lung function in African infants
(2016) Gray, Diane Margaret; Zar, Heather; Hall, Graham L
Childhood respiratory disease remains a major contributor of morbidity and mortality globally and both paediatric and adult chronic respiratory illness is increasing in prevalence worldwide. This burden of respiratory disease is heaviest in low-middle income countries (LMIC), areas that have a high prevalence of known risk factors for respiratory disease, such us overcrowding, poverty and environmental air pollution. Much chronic respiratory illness has its origin in early life; further low lung function in infancy is associated with later respiratory illness. However, there is limited data on lung function in African infants despite a high prevalence of respiratory disease. Understanding the determinants of infant lung function will improve our understanding of prevention and management of respiratory disease. This thesis aimed to describe lung function in South African infants from six weeks to one year and to investigate the impact of prenatal and early environmental exposures on lung function in infancy. Infants enrolled in the Drakenstein Child Health Study, a multidisciplinary birth cohort study investigating the aetiology and outcome of early life lower respiratory tract infections (LRTI), were included. Seven hundred and forty one infants were enrolled from June 2012 to February 2015. Infants had lung function measured at six (4-10) weeks of age and one year (11-14 months). Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, exhaled nitric oxide, sulphur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal exposures was collected using questionnaires and urine cotinine. Household benzene was measured antenatally. The chapters of the thesis are presented as published manuscripts that describe the establishment of infant lung function for the first time in South Africa and the development of normative lung function in the first year of life. The final chapters investigate the impact of early life exposures, most notably LRTI, on lung function at six weeks and one year. The thesis concludes that infant lung function testing is feasible in a community setting in 11 a LMIC like South Africa. Size, gender and ethnicity are important determinants of lung function. Lung function of South African infants is not well predicted by European reference equations, highlighting the importance of using population specific reference data when interpreting lung function tests. The study identifies several factors including maternal smoking, maternal alcohol and household benzene exposure during pregnancy, associated with altered early lung function. In addition tracking of lung function in the first year of life is described in this cohort of African infants living in a high respiratory disease burden setting. The study identifies risk factors for impaired lung function at one year independent of low baseline lung function: LRTI, household smoke exposure and infant nutrition, factors amenable to public health intervention. Given the fact that infant lung function tracks into later life and plays a role in chronic respiratory disease, preventing respiratory illness in young children, reducing exposure to environmental tobacco and maximising nutrition are key priorities in the strengthening of child respiratory health. Long-term study of lung function and respiratory disease in these infants is a priority in order to develop new strategies to strengthen child health.
Open Access
The efficacy of prophylactic antibiotics in the management of pneumonitis following kerosene (paraffin) ingestion in children
(2013) Balme, Kate Helene; Zar, Heather; Mann, Michael
Includes abstract. Includes bibliographical references.
Open Access
Environmental risk factors for asthma in 13-14 year old African children
(2018) Ayuk, Adaeze Chikaodinaka; Erhlich, Rodney; Myer, Landon; Ramjith, Jordache; Zar, Heather
BACKGROUND: Asthma prevalence in African children is high and increasing, with more severe disease than that in high income countries. Specific factors driving the rising prevalence or disease severity are poorly understood. The aim of this study was to investigate environmental factors associated with asthma and severity in African children using data obtained from International Study of Asthma and Allergies in Childhood, (ISAAC) III. METHODS: A population based cross-sectional study of children aged 13-14 years from 10 African centres who participated in ISAAC III from randomly selected schools. The prevalence of asthma or severe asthma was calculated for each centre. Self-reported environmental exposures included engaging in physical exercise, television watching, biomass and ETS exposure, consumption of paracetamol, large family sizes and having pets in the home. Univariable and multivariable analyses were done adjusting for centre variations. Odds ratio and respective 95% confidence intervals (CI) were calculated. RESULTS: Amongst 28490 adolescents from 232 schools in 10 African centres (4 middle income and 6 low income), the prevalence of asthma was 12.8% (CI 12.4-13.2), while prevalence of severe disease was 8.7% (CI 8.4-8.0). Factors most strongly associated with asthma were maternal smoking (OR= 1.41; 95% CI: 1.23 - 1.64), exposure to open fire heating (OR=1.28; 95% CI: 1.08 - 1.51) and electric heating (OR=1.13; 95% CI: 1.01 - 1.28), engaging in strenuous exercise (OR= 1.29; 95% CI: 1.11 - 1.50 and monthly use of paracetamol (OR 1.23; 95% CI 1.13 - 1.33, while having an elder sibling was protective for asthma (OR=0.87; 95% CI 0.77 – 0.98). Factors strongly associated with severe asthma were maternal smoking (OR=1.61; 95% CI: 1.38 - 1.89), having a cat pet at home (OR=1.14; 95% CI: 1.04 - 1.25), engaging in≥3 weekly physical exercise (OR=1.42; 95% CI: 1.23 - 1.64) and monthly consumption of paracetamol (OR=1.20; 95% CI: 1.07 - 1.34). CONCLUSION: There was a high prevalence of severe asthma in African children. Several environmental exposures were associated with asthma or with severe disease. Strategies to reduce harmful environmental exposures must be strengthened to reduce the burden of childhood asthma in Africa.
Open Access
Epidemiology of pertussis in children hospitalised with respiratory tract infection
(2021) Muloiwa, Rudzani; Zar, Heather; Hussey, Gregory
The availability of an effective vaccine against Bordetella pertussis substantially reduced the morbidity and mortality from pertussis, however, in the last decade there appears to have been a substantial increase in pertussis cases as reported mainly in high income countries. Although it is believed that the greatest burden of pertussis, including deaths, is in low- and middle-income countries (LMICs), there seem to be little data available to back this up. This thesis set out to find data that will give some insight into the burden of pertussis in a low- and middle-income setting in infants and children with severe lower respiratory tract infection (LRTI). Given the paucity of data in LMICs, the thesis started by systematically searching for existing data that will give some indication of the possible extent of the pertussis problem in these countries. Secondly, a prospective study was conducted at a children's hospital. As hospital admission is a marker of severe disease, these children were targeted as the appropriate population in which to meaningfully conduct a primary study on the burden of pertussis. In addition to quantifying the burden by describing the prevalence of confirmed pertussis in this group of children, the study set out to look for potential factors that may be associated with increased risk of pertussis. LRTI are now commonly known to be associated with identification of multiple organisms in respiratory samples, this study aimed to also look at organisms that are detected with Bordetella pertussis; and investigate whether this association was in any way associated with severe disease or negative outcomes. Finally, this study hoped to identify clinical features that could be used to develop a more reliable clinical case definition of pertussis. Chapter 1 gives a background that justifies the undertaking of this study. In chapter 2 a systematic review quantifies, using the best available data, the burden of pertussis in LMICs. Chapter 3 clarifies the methods briefly described in the rest of the manuscript. The burden of pertussis due to the two organisms known to cause the disease, Bordetella pertussis and Bordetella parapertussis, is described in some detail. In both this chapter and the earlier mentioned systematic review (chapter 2), the burden of pertussis is stratified by subgroups to identify potential risk factors. The issue of risk is formally and specifically taken up in the chapter that follows (chapter 5) where potential risk factors are analysed, and the independent impact for some of these factors is established. The last two results chapters (chapters 6 and 7) deal respectively with the conundrum of finding other respiratory organism in the same specimen with Bordetella pertussis and failure to find useful clinical criteria that can help with improved diagnosis of pertussis. While there is no established pattern noted between pertussis and most organisms, a few give signals of being independently associated with Bordetella pertussis even if the clinical relevance is not clear at the moment. In the final chapter of the thesis (chapter 8) I conclude the thesis by making an argument that although there are still knowledge gaps, the thesis gives a clear indication that pertussis remains a serious problem in LMICs especially for some groups that show increased risk of the disease or its severe consequences.
Open Access
Evaluation of diagnostic advances in musculoskeletal tuberculosis; the automated xpert MTB/RIF assay
(2016) Held, Michael; Zar, Heather; Dunn, Robert
The aim of this thesis was to investigate the diagnostic accuracy of Xpert for musculoskeletal TB and for rifampicin resistance against a gold standard of culture or histology. Site of disease, HIV status, and age of patients, and accuracy in spinal compared to extraspinal TB were investigated as secondary objectives. The overarching hypothesis was that Xpert is more accurate and would provide results faster than the gold standard for musculoskeletal TB, and that it would have a higher yield in HIV infected patients, adult patients, and patients with spinal disease.
Open Access
Evaluation of diagnostic advances in Musculoskeletal Tuberculosis; the automated xpert MTB/RIF assay
(2019) Held, Michael; Dunn, R; Zar, Heather
Background Xpert MTB/RIF (Xpert) is a rapid, automated, onsite nucleic acid amplification test for tuberculosis (TB). It is effective for the diagnosis of pulmonary TB but there is limited evidence for its usefulness in extrapulmonary TB, particularly musculoskeletal TB. Aims and hypothesis The aim of this thesis was to investigate the diagnostic accuracy of Xpert for musculoskeletal TB and for rifampicin resistance against a gold standard of culture or histology. Site of disease, HIV status, and age of patients, and accuracy in spinal compared to extraspinal TB were investigated as secondary objectives. The overarching hypothesis was that Xpert is more accurate and would provide results faster than the gold standard for musculoskeletal TB, and that it would have a higher yield in HIV infected patients, adult patients, and patients with spinal disease. Methods Prospective studies of patients with suspected musculoskeletal TB, at the tertiary care hospitals Groote Schuur and Red Cross Children’s Hospital in Cape Town, South Africa, were undertaken from June 2013 to March 2015. The diagnostic accuracy of Xpert was compared to culture or histopathology. Findings 206 biopsies of 201 patients older than 13 years of age (23% HIV positive) were analysed. The sensitivity and specificity of Xpert was 92.3% and 99.1% respectively. Xpert detected 8 cases more than culture (p = 0.069) and positive results were available 17 days earlier (<0.001). The sensitivity of Xpert in HIV positive patients was 96.9% (31/32) versus 89.6% (43/48) in HIV negative patients (p=0.225). The sensitivity of Xpert for spinal biopsies was 93.8% (95% CI 86.0-97.9) with specificity of 97.6% (95% CI 87.4 – 99.9), compared to extraspinal biopsies with a sensitivity of 81.8% (95% CI 48.2 – 99.7, p=0.164) and specificity of 100% (95% CI 95.1 – 100%, p=0.186). 109 osteoarticular samples of children 12 years of age or younger, with a median age of 5.6 years (IQR 2.2 – 8.7) were analysed. Xpert provided a sensitivity of 73.9% (95% CI 51.6-89.8) with a specificity of 100% (95% CI 95.7 - 100) and was available at a mean of 0.8 days (0.46- 1.4) compared to 21 days (19 – 30) for culture (p< 0.001). All rifampicin resistant cases were correctly diagnosed. A trend towards higher sensitivity in spinal tissue as well as HIV infected patients was observed. This study also provides evidence that Xpert has a lower sensitivity in children than in adults, yet, still detects more cases of paediatric musculoskeletal TB and is faster than culture. Histology was a useful test for the diagnosis of musculoskeletal TB, especially in children, and should be used alongside Xpert to provide the highest yield possible to detect TB. Conclusion: These first large studies on the accuracy of Xpert for musculoskeletal TB provide evidence for the usefulness of Xpert in the diagnosis of spinal TB, extraspinal TB, in HIV positive patients, and in childhood musculoskeletal TB. Based on these results, Xpert should be recommended as the initial test for diagnosis as it is more sensitive and faster than the gold standard of liquid culture.
Open Access
Evaluation of the Diagnostic Performance of Lung Ultrasound Compared to Chest X-rays for Diagnosis of Pneumonia in Children
(2019) Stadler, Jacob A M; Zar, Heather; Andronikou, Savvas
Pneumonia remains a global health priority in children. It is the leading cause of death in children outside the neonatal period, over 90% of which occur in low-resource settings, and a major cause of morbidity, accounting for over 100 million episodes globally each year. Early, correct diagnosis is a modifiable factor which can potentially improve pneumonia outcomes. Current guidelines recommend the use of clinical signs and symptoms alone to make a diagnosis of pneumonia in low risk, ambulatory cases with clinically mild disease. However, clinical diagnosis lacks specificity and may lead to antibiotic overuse and drive antibiotic resistance. Addition of chest X-ray (CXR) to diagnostic algorithms improves specificity, but CXR use is limited by radiation exposure and relatively high costs, limiting access in low-resource settings. Current guidelines therefore reserve CXR for moderate to severe disease and hospitalised cases, even in well-resourced settings. Lung ultrasound (LUS) is a promising imaging modality which uses no radiation, is less costly than CXR and can improve the time to results when used as a point-of-care tool by clinicians outside the radiology department. These characteristics make LUS, at least theoretically, a potential option either as add-on screening test aimed at decreasing unnecessary antibiotic prescription or as a lower risk, lower cost definitive diagnostic test capable of replacing CXR, or both. The objective of this study was to understand the role of LUS as a diagnostic test for pneumonia in children by performing a structured literature review and metaanalysis summarizing the current evidence comparing diagnostic performance of LUS and CXR, and by reporting previously unpublished data from the Drakenstein Child Health Study comparing diagnostic performance of LUS and CXR for pneumonia in children in a resource-constrained, African setting.
Open Access
High incidence of antimicrobial resistant organisms including extended spectrum beta-lactamase producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus in nasopharyngeal and blood isolates of HIV-infected children from Cape Town, South Africa
(BioMed Central Ltd, 2008) Cotton, Mark; Wasserman, Elizabeth; Smit, Juanita; Whitelaw, Andrew; Zar, Heather
BACKGROUND:There is little information on nasopharyngeal (NP) flora or bacteremia in HIV-infected children. Our aim was to describe the organisms and antimicrobial resistance patterns in children enrolled in a prospective study comparing daily and three times weekly trimethoprim-sulfamethoxazole (TMP-SMX) and isoniazid (INH) or placebo prophylaxis. METHODS: NP swabs were taken at baseline from HIV-infected children enrolled in the study. Standard microbiological techniques were used. Children were grouped according to previous or current exposure to TMP-SMX and whether enrolled to the study during a period of hospitalization. Blood culture results were also recorded within 12 months of baseline. RESULTS: Two hundred and three children, median age 1.8 (Interquartile [IQ]: 0.7-4) years had NP swabs submitted for culture. One hundred and eighty-four (90.7%) had either stage B or C HIV disease. One hundred and forty-one (69.8%) were receiving TMP-SMX and 19 (9.4%) were on antiretroviral therapy. The majority, 168 (82%) had a history of hospitalization and 91 (44.8%) were enrolled during a period of hospitalization. Thirty-two subjects (16.2%) died within 12 months of study entry.One hundred and eighty-one potential pathogens were found in 167 children. The most commonly isolated organisms were Streptococcus pneumoniae (48: 22.2%), Gram-negative respiratory organisms (Haemophilus influenzae and Moraxella catarrhalis) (47: 21.8%), Staphylococcus aureus (44: 20.4%), Enterobacteriaceae 32 (14.8%) and Pseudomonas 5 (2.3%).Resistance to TMP-SMX occurred in > 80% of pathogens except for M. catarrhalis (2: 18.2% of tested organisms). TMP-SMX resistance tended to be higher in those receiving it at baseline (p = 0.065). Carriage of Methicillin resistant S. aureus (MRSA) was significantly associated with being on TMP-SMX at baseline (p = 0.002). Minimal inhibitory concentrations (MIC) to penicillin were determined for 18 S. pneumoniae isolates: 7 (38.9%) were fully sensitive (MIC [less than or equal to] 0.06 mug/ml), 9 (50%) had intermediate resistance (MIC 0.12 - 1 mug/ml) and 2 (11.1%) had high level resistance (MIC [greater than or equal to]2 mug/ml). Fifty percent of Enterobacteriaceae produced extended spectrum beta-lactamases (ESBL) (resistant to third generation cephalosporins) and 56% were resistant to gentamicin. Seventy-seven percent of S. aureus were MRSA. Carriage of resistant organisms was not associated with hospitalization.On multivariate logistic regression, risk factors for colonization with Enterobacteriaceae were age [less than or equal to] one year (Odds ratio 4.4; 95% Confidence Interval 1.9-10.9; p = 0.0008) and CDC stage C disease (Odds ratio 3.6; 95% Confidence Interval 1.5-8.6; p = 0.005)Nineteen (9.4%) subjects had 23 episodes of bacteremia. Enterobacteriaceae were most commonly isolated (13 of 25 isolates), of which 6 (46%) produced ESBL and were resistant to gentamicin. CONCLUSION: HIV-infected children are colonized with potential pathogens, most of which are resistant to commonly used antibiotics. TMP-SMX resistance is extremely common. Antibiotic resistance is widespread in colonizing organisms and those causing invasive disease. Antibiotic recommendations should take cognizance of resistance patterns. Antibiotics appropriate for ESBL-producing Enterobacteriaceae and MRSA should be used for severely ill HIV-infected children in our region. Further study of antibiotic resistance patterns in HIV-infected children from other areas is needed.
Open Access
Human rhinovirus infection in young African children with acute wheezing
(BioMed Central Ltd, 2011) Smuts, Heidi; Workman, Lesley; Zar, Heather
BACKGROUND:Infections caused by human rhinoviruses (HRVs) are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. METHODS: Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. RESULTS: HRV was detected in 128 (58.2%) of children, most (72%) of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35%) were hospitalized for treatment and 3 (2%) were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52%) followed by HRV-A (37%) and HRV-B (11%). Infection with other respiratory viruses occurred in 20/128 (16%) of HRV-positive children and in 26/92 (28%) of HRV-negative samples. CONCLUSION: HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.
Open Access
Improved detection of Pneumocystis jirovecii in upper and lower respiratory tract specimens from children with suspected pneumocystis pneumonia using real-time PCR: a prospective study
(BioMed Central Ltd, 2011) Samuel, Catherine M; Whitelaw, Andrew; Corcoran, Craig; Morrow, Brenda; Hsiao, Nei-Yuan; Zampoli, Marco; Zar, Heather
BACKGROUND: Pneumocystis pneumonia (PCP) is a major cause of hospitalization and mortality in HIV-infected African children. Microbiologic diagnosis relies predominantly on silver or immunofluorescent staining of a lower respiratory tract (LRT) specimens which are difficult to obtain in children. Diagnosis on upper respiratory tract (URT) specimens using PCR has been reported useful in adults, but data in children are limited. The main objectives of the study was (1) to compare the diagnostic yield of PCR with immunofluorescence (IF) and (2) to investigate the usefulness of upper compared to lower respiratory tract samples for diagnosing PCP in children. METHODS: Children hospitalised at an academic hospital with suspected PCP were prospectively enrolled. An upper respiratory sample (nasopharyngeal aspirate, NPA) and a lower respiratory sample (induced sputum, IS or bronchoalveolar lavage, BAL) were submitted for real-time PCR and direct IF for the detection of Pneumocystis jirovecii. A control group of children with viral lower respiratory tract infections were investigated with PCR for PCP. RESULTS: 202 children (median age 3.3 [inter-quartile range, IQR 2.2 - 4.6] months) were enrolled. The overall detection rate by PCR was higher than by IF [180/349 (52%) vs. 26/349 (7%) respectively; p < 0.0001]. PCR detected more infections compared to IF in lower respiratory tract samples [93/166 (56%) vs. 22/166 (13%); p < 0.0001] and in NPAs [87/183 (48%) vs. 4/183 (2%); p < 0.0001]. Detection rates by PCR on upper (87/183; 48%) compared with lower respiratory tract samples (93/166; 56%) were similar (OR, 0.71; 95% CI, 0.46 - 1.11). Only 2/30 (6.6%) controls were PCR positive. CONCLUSION: Real-time PCR is more sensitive than IF for the detection of P. jirovecii in children with PCP. NPA samples may be used for diagnostic purposes when PCR is utilised. Wider implementation of PCR on NPA samples is warranted for diagnosing PCP in children.
Open Access
Incidence of bacteraemia in HIV-infected children in Africa, and the impact of highly active antiretroviral therapy
(2010) Le Roux, David Martin; Zar, Heather
From November 2002 to December 2006, a placebo-controlled, randomized trial investigated the incidence of tuberculosis and the overall mortality in a cohort of HIV-infected children in Cape Town, South Africa. They were randomized to receive either Isoniazid Preventive Therapy (IPT) or placebo. In addition, they were randomized to receive trimethoprim/sulfamethoxaxole prophylaxis on either a daily or a three-times-per-week schedule. The aim: To describe the incidence of bacteraemia, and the spectrum of organisms cultured. To determine if there was a difference in the incidence of bacteraemia between children using Isoniazid Preventive Therapy (IPT) versus placebo; and to determine if there was a difference in the incidence of bacteraemias between the groups using daily versus thrice-weekly trimethoprim/sulphamethoxazole prophylaxis.
Open Access
Isoniazid preventive therapy in HIV infected children on antiretroviral therapy living in a high tuberculosis prevalence area a randomized controlled trial
(2012) Gray, Diane Margaret; Zar, Heather
Tuberculosis (TB) and HIV are dual epidemics and a public health crisis in Southern Africa. An estimated 2.5 million children are living with HIV, of which 2.3 million live in Sub-Saharan Africa, with an estimated 230 000 child deaths from AIDS. In 2010 there were an estimated 8 million incident cases of tuberculosis (TB) globally, 1.2 million amongst people living with HIV. Over 1 million TB related deaths occurred, a third of which occurred amongst people living with HIV.[4] The African region accounts for 26% of the global TB burden and 82% of the TB cases among people living with HIV. TB and HIV are a deleterious combination. TB is a common cause of acute and chronic respiratory disease and a leading cause of death amongst HIV infected children in TB endemic areas.
Open Access
Longitudinal changes in clinical symptoms and signs in children with confirmed, unconfirmed, and unlikely pulmonary tuberculosis
(2021) Copelyn, Julie; Eley, Brian; Zar, Heather
Background: The paucibacillary nature of paediatric pulmonary tuberculosis (PTB) makes microbiological diagnosis difficult and limits the usefulness of microbiology for assessing treatment efficacy. Clinical response to treatment has thus been used by clinicians to monitor disease activity, as well as by researchers in clinical case definitions of intrathoracic TB to differentiate those with unconfirmed PTB from those with other lower respiratory tract infections (LRTIs). There is, however, limited data on the expected pattern and timing of resolution of symptoms and signs, and whether this does indeed differ between those with PTB and those without. Objectives: To longitudinally investigate clinical response to TB treatment in children treated for PTB, to compare this to the clinical course of children with other LRTIs, and to identify factors associated with persistence of symptoms and signs. Methods: This study is a secondary analysis of data collected prospectively in a TB diagnostic study from 1 February 2009 to 31 December 2018. We enrolled children ≤15 years with features suggestive of PTB. Study participants were categorized into 3 groups according to NIH consensus definitions; confirmed PTB, unconfirmed PTB and unlikely PTB. Children were followed at 1 and 3 months after enrolment. Those with confirmed or unconfirmed TB were also followed at 6 months. At enrolment and follow-up symptoms of PTB were recorded using a standardized questionnaire and physical examination was done including anthropometry and respiratory parameters. Data were analysed using STATA version 16.1. The effect of potential predictors of persistence of symptoms and signs was explored with univariable and multivariable logistic regression modelling. Results: Two thousand and nineteen children were included in this analysis, 427 (21%) with confirmed PTB, 810 (40%) with unconfirmed PTB, and 782 (39%) with unlikely PTB. Symptoms resolved rapidly in the vast majority of participants. At 1 month, 9.2% (129/1402) of all participants who had a cough and 11.1% (111/999) of those with loss of appetite at baseline reported no improvement in these symptoms. At 3 months this declined to 2.0% (24/1222) and 2.6% (23/886) respectively, with no differences between the groups. Clinical signs persisted in a greater proportion of participants. At 3 months, tachypnoea persisted in 56.7% (410/723) of participants. Abnormal auscultatory findings (including wheeze, crackles, reduced breath sounds or abnormal breath sounds) similarly persisted in almost a third of participants, with greater proportion in the confirmed group (37.1%) than unconfirmed (23.0%) and unlikely (26.2%) groups (p=0.002). Children living with HIV and those with abnormal baseline chest radiographs had greater odds of persistence of signs or symptoms (including cough, loss of appetite, abnormal auscultatory findings, or no weight improvement if underweight at baseline). No features of clinical response differentiated those with PTB from those without. Conclusion: Symptoms resolved rapidly in the majority of children investigated for PTB whilst clinical signs took longer to resolve. The timing and pattern of resolution of symptoms and signs cannot differentiate those with PTB from those without – and is thus not a suitable parameter for confirming disease classification in paediatric TB research.
Open Access
Lung function in healthy South African adult females
(2015) Smith, Emilee; Myer, Landon; Zar, Heather
Background: Accurate and appropriate spirometry reference values allow for early detection of respiratory illness and perform an important role in monitoring lung health. There is, in general, a scarcity of data from Africa, and the Global Lung Initiative (GLI) has published global reference equations but models did not include data from African studies. The aim of this study was to investigate lung function in a group of healthy South African females and the applicability of the GLI reference equations. Methodology: Maternal lung function testing was undertaken at 6 to 10 weeks post-partum as part of a birth cohort study, the Drakenstein Child Health Study. Pre- and post-bronchodilator spirometry was performed according to a standardised protocol and correlated with clinical information. Bronchodilator response was assessed by repeating spirometry 15 minutes after administration of inhaled 400mcg salbutamol. Results: A total of 462 women were included, mean age 17 years (range 18- 42 years). The GLI reference equations fitted the observed lung function results well for the group of mothers who did not self-report smoking or asthma. There were 64 (14%) mothers with an abnormal Forced Expiratory Volume in 1 Second (FEV 1) result, 60 (13%) mothers with an abnormal Forced Vital Capacity (FVC), and 35 (8%) mothers with an abnormal FEV 1 /FVC ratio. There were 22 (5%) mothers who had reversible FEV 1; the rate of undiagnosed reversibility was 4% of the cohort. High body mass index was associated with a higher risk for poor FVC and FEV 1 /FVC lung function, OR 1.40 (CI: 1.01, 1.65) and OR 1.25 (CI 1.10, 1.95) respectively. Mothers with a higher socio-economic status had better FEV 1 with the adjusted SES OR 0.65 (CI 0.36, 1.08). Conclusions: There was a high prevalence of abnormal lung function in this cohort of South African adult females and a number of cases of undiagnosed reversibility. Spirometry testing is important to diagnose lung disease in South African communities. The GLI's reference equations were appropriate and applicable for a cohort of South African adult women.