OpenUCT :: Browsing by Author "Zar, Heather J"

Browsing by Author "Zar, Heather J"

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Open Access
Admission trends at Red Cross War Memorial Children's Hospital, Cape Town: 2004 to 2013
(2016) Isaacs, Yumnah; Myer, Landon; Zar, Heather J
Background: Hospital database research has the potential to provide useful insights into health systems functioning, population health, clinical conditions and epidemiological trends thereof. This type of research is routinely done in countries that have large national hospital databases where results are usually extrapolated to the national population. South Africa does not have a national hospital database, but individual healthcare institutions, such as the Red Cross War Memorial Children's Hospital (RCCH) in Cape Town, collects routine patient data in a computerised database that if tapped should yield valuable information about child health of the catchment population as well as of the functioning of that health institution. Methods: Selected data from the RCCH database were converted into spreadsheet format and then exported into a statistical programme, Stata. Variables included patient demographic details, ICD-10 diagnostic codes, length of hospital stay and outcomes at discharge. Stata was used to clean and code the data and perform basic descriptive analyses of contained variables. Medians and interquartile ranges described numerical variables. Frequencies, proportions and percentages described categorical variables. Appropriate tests of statistical significance were performed where applicable. Admission and mortality trends were analysed across a decade and common conditions were explored. Findings and Conclusions: Overall admissions to RCCH increased by 9.3% across a decade while the number of new patients decreased by 8.6%, indicating an increase in readmissions. In-patient mortality decreased consistently across a decade despite an increase in admissions, which suggests an improvement in quality of care. The median ages of admissions and deaths increased across the decade, which correlates with less HIV and improved management thereof. Infections remain the commonest causes of in-hospital mortality. Admissions and mortality for diarrhoea and pneumonia displayed a consistent decline across 6 years corresponding with the introduction of new vaccines; however, diarrhoea and lower respiratory tract illness remained the commonest causes of medical admission. Injuries were the commonest reason for surgical admissions. Computerised hospital databases contain useful information for healthcare research.
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Childhood pneumonia - progress and challenges
(Health and Medical Publishing Group, 2006) Zar, Heather J; Madhi, Shabir A
Remarkable progress has been made in the development of antimicrobial therapy, effective vaccines and pneumonia management guidelines in the past 50 years. However, pneumonia is currently the leading cause of death in children younger than 5 years in developing countries, accounting for approximately 20% of childhood deaths. This article reviews changes in the epidemiology, management and prevention of childhood pneumonia in developing countries, specifically in Africa and South Africa, and addresses future challenges. MAIN FINDINGS: The HIV epidemic has sharply increased the incidence, severity of, and mortality due to, childhood pneumonia. Bacterial infection remains a major cause of pneumonia mortality. Additional pathogens such as Pneumocystis jirovecii and Gram-negative bacteria are found in HIV-infected children, associated with a high mortality. Mycobacterium tuberculosis is an important cause of acute pneumonia in both HIV-infected and uninfected children. Use of case management guidelines can substantially reduce neonatal, infant and under-5 mortality and pneumonia-specific mortality. General preventive interventions including micronutrient supplementation with zinc and vitamin A, and immunisations can substantially reduce the burden of childhood pneumonia. Despite a lower efficacy in HIV-infected children, vaccination protects against disease in a significant proportion of children. In South Africa, new advances over the past 50 years have included greater access to primary health care for children, the use of Integrated Management of Childhood Illness guidelines in primary care, development of guidelines for diagnosis and management of childhood pneumonia and adoption of an expanded immunisation programme that includes coverage for Haemophilus influenzae type b. The pneumococcal conjugate vaccine recently licensed in South Africa also has the potential to significantly reduce the burden of childhood pneumonia. Recent roll-out of the national antiretroviral programme can reduce the incidence and severity of HIV-associated pneumonia through the prevention of HIV infection, use of cotrimoxazole prophylaxis and treatment with antiretrovirals. CONCLUSION: Available, effective interventions for prevention and treatment of childhood pneumonia exist; the challenge is to achieve widespread implementation and high coverage rates in developing countries. Greater access to newer vaccines and to antiretroviral therapy and co-trimoxazole prophylaxis in HIV-infected children is necessary to further reduce the burden of childhood pneumonia and the discrepancies in global child lung health.
Open Access
Clinical features and outcome of patients with severe lower respiratory tract infection admitted to a Paediatric Intensive Care Unit in the Western Cape, South Africa
(2016) Hutton, Hayley; Zar, Heather J; Argent, Andrew
Objective: Acute lower respiratory tract infection (ALRTI) remains an important cause of childhood morbidity and mortality in low and middle income countries (LMIC). This study aims to describe the clinical features of children admitted to a Pediatric Intensive Care Unit (PICU) with severe ALRTI and to investigate risk factors, clinical course and in-hospital outcome. Design: Retrospective cohort study Setting: Red Cross War Memorial Children's Hospital, Cape Town, South Africa Patients: 265 children (0-12years) admitted to the PICU during 2012 with a primary diagnosis of ALRTI. Intervention: None. Measurements and main results: 265 patients [median (interquartile range, IQR) age 4 months (2-12months)] were admitted with ALRTI, 157(59.3%) were male. Co-morbid disease was present in 102(38.5%) including cardiac disease in 42(15.9%) or tuberculosis in 7(6.4%) . While only 27(10.2%) were HIV infected, 87(32.8%) children were HIV exposed. The in-hospital mortality was 34(12.8%); 24(9.1%) died in PICU and a further 10 in the medical wards following discharge from PICU. The median duration of ICU and hospital stay was 4.0 days (2.0-8.0) and 12.5 days (7.9-28.0) respectively. Most [192 (72.5%)] children required invasive ventilatory support, while 42 (15.8%) patients required cardiac inotropic support. Risk factors for mortality included severe malnutrition (Odds ratio (OR) 8.25; 95% CI 1.47- 46.21); informal housing without access to piped water and/or electricity (OR11.87; CI 1.89- 20.81); or need for inotropic support (OR 44.35; CI 8.20-239.92). HIV exposure or infection was associated with a significantly longer duration of hospital stay (p=0.002). Conclusion: Severe ALRTI occurs predominantly in young infants and is associated with a high mortality. Several sociodemographic risk factors impact on the risk of severe disease and poorer outcome.
Open Access
Comparison of a real-time multiplex PCR and sequetyping assay for pneumococcal serotyping
(Public Library of Science, 2015) Dube, Felix S; van Mens, Suzan P; Robberts, Lourens; Wolter, Nicole; Nicol, Paul; Mafofo, Joseph; Africa, Samantha; Zar, Heather J; Nicol, Mark P
BACKGROUND: Pneumococcal serotype identification is essential to monitor pneumococcal vaccine effectiveness and serotype replacement. Serotyping by conventional serological methods are costly, labour-intensive, and require significant technical expertise. We compared two different molecular methods to serotype pneumococci isolated from the nasopharynx of South African infants participating in a birth cohort study, the Drakenstein Child Health Study, in an area with high 13-valent pneumococcal conjugate vaccine (PCV13) coverage. METHODS: A real-time multiplex PCR (rmPCR) assay detecting 21 different serotypes/-groups and a sequetyping assay, based on the sequence of the wzh gene within the pneumococcal capsular locus, were compared. Forty pneumococcal control isolates, with serotypes determined by the Quellung reaction, were tested. In addition, 135 pneumococcal isolates obtained from the nasopharynx of healthy children were tested by both serotyping assays and confirmed by Quellung testing. Discordant results were further investigated by whole genome sequencing of four isolates. RESULTS: Of the 40 control isolates tested, 25 had a serotype covered by the rmPCR assay. These were all correctly serotyped/-grouped. Sequetyping PCR failed in 7/40 (18%) isolates. For the remaining isolates, sequetyping assigned the correct serotype/-group to 29/33 (88%) control isolates. Of the 132/135 (98%) nasopharyngeal pneumococcal isolates that could be typed, 69/132 (52%) and 112/132 (85%) were assigned the correct serotype/-group by rmPCR and sequetyping respectively. The serotypes of 63/132 (48%) isolates were not included in the rmPCR panel. All except three isolates (serotype 25A and 38) were theoretically amplified and differentiated into the correct serotype/-group with some strains giving ambigous results (serotype 13/20, 17F/33C, and 11A/D/1818F). Of the pneumococcal serotypes detected in this study, 69/91 (76%) were not included in the current PCV13. The most frequently identified serotypes were 11A, 13, 15B/15C, 16F and 10A. CONCLUSION: The rmPCR assay performed well for the 21 serotypes/-groups included in the assay. However, in our study setting, a large proportion of serotypes were not detected by rmPCR. The sequetyping assay performed well, but did misassign specific serotypes. It may be useful for regions where vaccine serotypes are less common, however confirmatory testing is advisable.
Open Access
Detection of Streptococcus pneumoniae from different types of nasopharyngeal swabs in children
(Public Library of Science, 2013) Dube, Felix S; Kaba, Mamadou; Whittaker, Elizabeth; Zar, Heather J; Nicol, Mark P
BACKGROUND: A better understanding of the epidemiology of nasopharyngeal carriage of Streptococcus pneumoniae is important to assess the impact of vaccination and the pathogenesis of pneumococcal disease. We compared the recovery of S. pneumoniae from nylon flocked, Dacron and rayon swabs. METHODS: The recovery of S. pneumoniae from mocked specimens using flocked, Dacron and rayon swabs were compared by culture. The yield from paired nasopharyngeal (NP) samples obtained from healthy children sampled with flocked and Dacron swabs was also determined using culture and lytA -targeted real-time polymerase chain reaction (qPCR). RESULTS: Using mock specimen, the percentage recovery of S. pneumoniae ATCC 49619 (serotype 19F) strain from the flocked swabs was 100%, while it was 41% from Dacron swabs and 7% from rayon swabs. Similar results were observed for S. pneumoniae serotypes 1 and 5. S. pneumoniae was cultured from 18 of 42 (43%) paired NP samples from the healthy children (median age 8 [interquartile range (IQR) 5-16] months). The median number of colony-forming units (CFU) recovered from flocked swabs was two-fold higher (8.8×10 4 CFU/mL [IQR, 2.0×10 2 - 4.0×10 5 CFU/mL]) than Dacron swabs (3.7×10 4 CFU/mL [IQR, 4.0×10 2 -3.2×10 5 CFU/mL], p = 0.17). Using lytA -targeted qPCR from paired NP samples, the median copy number of S. pneumoniae detected from flocked swabs was significantly higher than from Dacron swabs (3.0×10 5 genome copies/mL [IQR, 1.3×10 2 −1.8×10 6 ] vs. 9.3×10 4 genome copies/mL [IQR, 7.0×10 1 −1.1×10 6 ]; p = 0.005). CONCLUSION: Flocked swabs released more S. pneumoniae compared to both Dacron and rayon swabs from mock specimens. Similarly, higher bacterial loads were detected by qPCR from flocked swabs compared with Dacron swabs from healthy children.
Open Access
Diagnosis of pulmonary tuberculosis in children - what's new?
(2007) Zar, Heather J
The global burden of paediatric tuberculosis (TB) has been underappreciated. Control programmes, focused on adult infectious cases, have largely based case detection and reporting on sputum smear results. However, evidence suggests that in developing countries, where most disease occurs, childhood TB constitutes a large proportion of the TB caseload, contributing approximately 15 - 20% of all cases.
Open Access
Epidemiology of pertussis in children hospitalised with respiratory tract infection
(2021) Muloiwa, Rudzani; Zar, Heather J; Hussey, Gregory D
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 starts 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, as data has been emerging that in the context of immunisation, the clinical presentation of pertussis may no longer be following a classical pattern, this study hoped to identify clinical features that could be used to develop a more reliable clinical case definition of pertussis. 2 Chapter 1 gives a background that justifies the undertaking of this study as well as give a summary of the methods used to answer the question of the thesis. The chapter also gives an indication of the structure that the thesis follows. In chapter 2 a systematic review quantifies the burden of pertussis in LMICs using the best available data. In chapter 3 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 4) where potential risk factors are analysed, and the independent impact for some of these factors is established. The last two results chapters (chapters 5 and 6) 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, specifically in children presenting with acute severe lower respiratory tract infection. 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 7) 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
Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling
(2021-01-11) Ramjith, Jordache; Roes, Kit C; Zar, Heather J; Jonker, Marianne A
Introduction Recurrent episodes of pneumonia are frequently modeled using extensions of the Cox proportional hazards model with the underlying assumption of time-constant relative risks measured by the hazard ratio. We aim to relax this assumption in a study on the effect of factors on the evolution of pneumonia incidence over time based on data from a South African birth cohort study, the Drakenstein child health study. Methods We describe and apply two models: a time-constant and a time-varying relative effects model in a piece-wise exponential additive mixed model’s framework for recurrent events. A more complex model that fits in the same framework is applied to study the continuously measured seasonal effects. Results We find that several risk factors (male sex, preterm birth, low birthweight, lower socioeconomic status, lower maternal education and maternal cigarette smoking) have strong relative effects that are persistent across time. When time-varying effects are allowed in the model, HIV exposure status (HIV exposed & uninfected versus HIV unexposed) shows a strong relative effect for younger children, but this effect weakens as children grow older, with a null effect reached from about 15 months. Weight-for-length at birth shows a time increasing relative effect. We also find that children born in the summer have a much higher risk of pneumonia in the 3-to-8-month age period compared with children born in winter. Conclusion This work highlights the usefulness of flexible modelling tools in recurrent events models. It avoids stringent assumptions and allows estimation and visualization of absolute and relative risks over time of key factors associated with incidence of pneumonia in young children, providing new perspectives on the role of risk factors such HIV exposure.
Open Access
Humoral immune responses to Pneumocystis jirovecii antigens in HIV-infected and uninfected young children with pneumocystis pneumonia
(Public Library of Science, 2013) Djawe, Kpandja; Daly, Kieran R; Levin, Linda; Zar, Heather J; Walzer, Peter D
BACKGROUND: Humoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood. METHODS: Consecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC) were analyzed. RESULTS: 149 children were enrolled of whom 96 (64%) were HIV-infected. PcP occurred in 69 (72%) of HIV-infected and 14 (26%) of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP. CONCLUSIONS: Young HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP.
Open Access
The impact of isoniazid preventative therapy and antiretroviral therapy on tuberculosis (TB) in HIV-infected children in a high TB incidence setting
(2011) Frigati, Lisa Jane; Zar, Heather J
The aim of this study is to investigate the combined effect of IPT [INH preventative therapy] and ART [antiretroviral therapy] on TB incidence in HIV-infected children. A cohort analysis will be performed using data from a prospective, double-blinded placebo controlled trial of INH versus placebo in HIV-infected children in Cape Town, South Africa.
Open Access
Incorrect use of a homemade spacer for treatment of recurrent wheezing in children - a cause for concern
(2005) Zar, Heather J; Motala, Cas; Weinberg, Eugene
Inhaled bronchodilators, particularly β2-agonists, are one of the most effective therapies for rapid reversal of airway narrowing in acute asthma. In children bronchodilators are best given using a metered dose inhaler (MDI) with attached spacer; this is as effective as nebulised therapy, with fewer side-effects. 1,2 However, a spacer must be used with a MDI as children are unable to synchronise inspiration with actuation of the MDI nor can they breath hold at the end of inspiration, particularly when there is lower airways obstruction as occurs during an acute asthma attack.1,2 A modified 500 ml plastic bottle spacer has been found to be as effective as a conventional smallvolume spacer for delivery of bronchodilators in children with acute wheezing.3-5 In contrast, a cup has been shown to be a very poor spacer, with poor efficacy when used for giving bronchodilators in the treatment of acute asthma.3-5
Open Access
Indoor air pollution and environmental tobacco smoke exposure in a South African birth cohort study
(2018) Vanker, Aneesa; Zar, Heather J; Gie, Robert P
middleincome countries (LMIC) and a major reason for health care visits and hospitalisation. Environmental exposures to indoor air pollution (IAP) or tobacco smoke are important risk factors for childhood respiratory disease. Despite increased electrification, many communities in LMIC rely on alternate fuel sources for household cooking or heating. The impact of antenatal or postnatal exposures on early childhood respiratory disease has not been comprehensively studied in LMIC especially in Africa. The aim of this work was to investigate the impact of IAP and environmental tobacco smoke (ETS) exposure on child health and early-life respiratory disease in the Drakenstein Child Health Study (DCHS), a South African birth cohort study. The DCHS investigates the epidemiology and impact of early-life exposures on child health including lung disease. The study is set in a peri-urban poor community in the Western Cape, South Africa. Pregnant women were enrolled from two public primary healthcare clinics, Mbekweni (serving a predominantly black African population) and Newman (predominantly mixed-ancestry population) and 1000 mother-infant pairs longitudinally followed from birth through 1 year of life. The thesis chapters are presented as published manuscripts that describe IAP and ETS exposure in the 2 communities in the DCHS cohort from the antenatal period and the impact of these exposure on child health and lung diseases, LRTI and wheezing illness in the first year of life. To measure exposures comprehensively, two home visits, one in the antenatal period (third trimester) and the second postnatally (between 4 and 6 months of the infant’s life), were conducted to assess the home environment and to measure the most common indoor air pollutants and by-products of combustion. Devices placed in participants’ homes measured exposure to particulate matter (PM10), carbon monoxide (CO), nitrogen dioxide (NO2), sulphur dioxide (SO2) and volatile organic compounds (VOC). Maternal and infant urine cotinine measures were used to validate self-reported tobacco smoking and exposure. Study staff trained in recognition of LRTI or wheeze documented all episodes, which were categorised according to WHO case definition criteria. Exposure to IAP was comprehensively assessed in over 800 homes antenatally and postnatally providing important South African data on IAP and potential sources of exposure. Tobacco smoke exposure was assessed longitdunially by maternal self-report using validated scales and by measurement of urine cotinine in mothers and infants. Tobacco smoke exposure was found to be highly prevalent with a smoking prevalence of >50% in mixedancestry mothers. Alarmingly, 18% of infants were born with urine cotinine levels in keeping with active smoking, while a further 30% had levels indicating passive smoke exposure. Key findings were despite 92% of homes reporting access to electricity, there was still a reliance on cheaper alternate fuels. Tobacco smoking prevalence amongst pregnant women was high (32%), as was household exposure to tobacco smoke (44%). ETS exposure was associated with low birth weight and antenatal IAP or ETS exposure was significantly associated with increased LRTI. ETS exposure was also associated with wheezing illnesses. A novel finding was that antenatal exposure to toluene, a volatile organic compound, was associated with severe LRTI and hospitalisation. The timing of environmental exposures on the subsequent development of LRTI in infancy has not been well described. An important finding was that antenatal exposures were the main risk factors associated with LRTI, with maternal smoking in pregnancy or PM10 exposure most strongly associated with LRTI. Wheezing illness was associated with both antenatal and postnatal maternal smoking and antenatal maternal smoke exposure and postnatal household member smoking. Both IAP and ETS exposure impacted on both maternal and infant nasopharyngeal bacterial carriage which may be a precursor to the development of LRTI. Environmental exposures therefore had a substantial impact on child health and on LRTI and wheezing illness. The effect on LRTI of antenatal compared with postnatal exposure suggests an in utero developmental lung effect. This study highlights antenatal and early life as a critical period for lung development. Urgent and effective smoking cessation programmes targeting women of child bearing age as well as public health interventions to reduce IAP are required. Woman of childbearing age, pregnant women and children in poor communities represent vulnerable populations at risk for long-term health effects of these exposures.
Open Access
Investigating associations between maternal mental health on wheeze through two years of age in a South African birth cohort study
(2017) Macginty, Rae; Lesosky, Maia; Zar, Heather J; Stein, Dan J; Barnett, Whitney
Background: Wheezing is one of the most common respiratory illnesses in children worldwide. Severe wheeze can result in significant morbidity, caregiver burden and increased health care costs. In addition, early childhood wheeze may be associated with reduced lung function, diminished airway responsiveness, increased risk of asthma in late childhood and subsequent respiratory disease including asthma in adulthood. This is particularly true in those experiencing recurrent wheeze episodes, which in the presence of viral respiratory tract infections, are believed to lead to asthma diagnosis. Thus, it is imperative to understand the risk factors for early childhood wheeze to reduce the increasing burden of respiratory illness. Recent research has seen a shift to maternal psychosocial risk factors and the impact these have on child respiratory health outcomes, such as wheeze. Various studies, largely conducted in High Income Countries (HIC), have found associations between antenatal or postnatal psychosocial risk factors, such as depression, psychological distress, and Intimate Partner Violence (IPV), and child wheeze and/or asthma diagnosis in early stages of life. However, these studies predominantly considered those in low-income urban regions that were predisposed to respiratory illnesses, including wheeze and asthma. Utilising the techniques and knowledge gained from previous studies, this research considers the relationship between antenatal or postnatal maternal psychosocial exposures and the onset and recurrence of child wheeze in a South African setting. In the study population used for this research, the reported prevalence of antenatal psychological distress and depression was 23% and 20%, respectively, while 34% of the women were exposed to antenatal IPV. Often those suffering from poor mental health in these contexts are not recognised and therefore remain untreated. In addition, service provision in these settings is also generally poor. The combination of low levels of social and psychiatric support, with unique political and socio-economic risk factors, may result in more persistent and severe forms of psychosocial exposure in Low Middle Income Countries (LMIC). Given the high prevalence of psychosocial risk factors, as well as the high prevalence of child wheeze, South Africa provides an excellent platform to investigate the association between maternal antenatal or postnatal psychosocial exposure and the development and recurrence of child wheeze in an LMIC context. Methods: The data used for this research was provided by the Drakenstein Child Health Study (DCHS), a prospective birth cohort study conducted in the Drakenstein region, a peri-urban region outside of Paarl in the Western Cape of South Africa. Pregnant women over 18 years old, between 20-28 weeks' gestation, living in the region were enrolled in a parent study, in order to investigate the epidemiology and aetiology of respiratory illnesses in children. The parent study considered various risk factors, including psychosocial risk factors such as maternal depression, psychological distress and IPV, which were measured antenatally and postnatally by validated questionnaires. In the context of this research, wheeze was considered to be present if it was identified during any routine study follow-up visit, as well as at an unscheduled lower respiratory tract infection (LRTI) episode visit during the first two years of life. Recurrent wheeze was defined as experiencing two or more episodes of wheeze in a 12-month period. Logistic regression was used to investigate the relationship between antenatal and postnatal psychosocial risk factors and child wheeze. Results: From the results, postnatal psychological distress and IPV were associated with experiencing at least one episode of child wheeze (adjusted OR = 2.10, 95% CI: 1.16-3.79 and 1.60, 95% CI: 1.11-2.29 respectively) and recurrent wheeze (adjusted OR = 2.33, 95% CI: 1.09- 4.95 and 2.22, 95% CI: 1.35-3.63 respectively), within the first two years of life. No associations were found between antenatal psychosocial risk factors and child wheeze. Of clinical covariates explored, maternal smoking and household smoke exposure, birth weight, gestational age, sex and population group were associated with the presence of wheeze. All of these clinical covariates, as well as alcohol consumption were associated with recurrent child wheeze. Conclusion: Maternal postnatal psychological distress and postnatal IPV had the strongest impact on predicting wheeze outcomes. These findings suggest that screening and treatment programs which address maternal postnatal psychosocial risk factors may lessen the burden of childhood wheeze in LMIC settings.
Open Access
Lung function in HIV-infected children and adolescents
(BioMed Central, 2018-06-25) Githinji, Leah N; Gray, Diane M; Zar, Heather J
Background The advent of antiretroviral therapy has led to the improved survival of human immunodeficiency virus (HIV)-infected children to adulthood and to HIV becoming a chronic disease in older children and adolescents. Chronic lung disease is common among HIV-infected adolescents. Lung function measurement may help to delineate the spectrum, pathophysiology and guide therapy for HIV-related chronic lung disease. Aim The aim of this study was to review the available data on the spectrum and determinants of lung function abnormalities and the impact of antiretroviral therapy on lung function in perinatally HIV-infected children and adolescents. Methods Electronic databases “PUBMED”, “African wide” and “CINAHL” via EBSCO Host, using the MeSH terms “Respiratory function” AND “HIV” OR “Acquired Immunodeficiency Syndrome” AND “Children” OR “Adolescents”, were searched for relevant articles on lung function in HIV-infected children and adolescents. The search was limited to English language articles published between January 1984 and September 2017. Results Eighteen articles were identified, which included studies from Africa, the United States of America (USA) and Italy, representing 2051 HIV-infected children and adolescents, 68% on antiretroviral therapy, aged from 50 days to 24 years. Lung function abnormalities showed HIV-infected participants had increased irreversible lower airway expiratory obstruction and reduced functional aerobic impairment on exercise, compared to HIV-uninfected participants. Mosaic attenuation, extent of bronchiectasis, history of previous pulmonary tuberculosis or previous lower respiratory tract infection and cough for more than 1 month were associated with low lung function. Pulmonary function tests in children established on antiretroviral therapy did not show aerobic impairment and had less severe airway obstruction. Conclusion There is increasing evidence that HIV-infected children and adolescents have high prevalence of lung function impairment, predominantly irreversible lower airway obstruction and reduced aerobic function.
Open Access
Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs
(BioMed Central, 2017-07-25) Morin, Alexander M; Gatev, Evan; McEwen, Lisa M; MacIsaac, Julia L; Lin, David T S; Koen, Nastassja; Czamara, Darina; Räikkönen, Katri; Zar, Heather J; Koenen, Karestan; Stein, Dan J; Kobor, Michael S; Jones, Meaghan J
Background: Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array. Results: Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods. Conclusions: Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.
Open Access
Maternal participant experience in a South African birth cohort study enrolling healthy pregnant women and their infants
(BioMed Central, 2016-07-19) Barnett, Whitney; Brittain, Kirsty; Sorsdahl, Katherine; Zar, Heather J; Stein, Dan J
Background: Critical to conducting high quality research is the ability to attract and retain participants, especially for longitudinal studies. Understanding participant experiences and motivators or barriers to participating in clinical research is crucial. There are limited data on healthy participant experiences in longitudinal research, particularly in low- and middle-income countries. This study aims to investigate quantitatively participant experiences in a South African birth cohort study. Methods: Maternal participant experience was evaluated by a self-administered survey in the Drakenstein Child Health Study, a longitudinal birth cohort study investigating the early life determinants of child health. Pregnant mothers, enrolled during the second trimester, were followed through childbirth and the early childhood years. Satisfaction scores were derived from the participant experience survey and quantitatively analyzed; associations between satisfaction scores and sociodemographic variables were then investigated using a linear regression model. Results: Data were included from 585 pregnant mothers (median age 26.6 years), who had participated in the study for a median time of 16 months. Overall participant satisfaction was high (median score 51/60) and associated with increased attendance of study visits. Reasons for participating were a belief that involvement would improve their health, their child’s health or the health of family and friends. Potential reasons for leaving the study were inconvenience, not receiving clinical or study results, and unexpected changes in study visits or procedures. Variables associated with higher overall satisfaction scores were no prior participation in research, higher socioeconomic status, less intensive follow-up schedules and having experienced stressful life events in the past year. Conclusions: Satisfaction scores were high and associated with increased visit attendance. Participants’ perceived benefits of study participation, most notably the potential for an improvement in the health of their child, were a significant motivator to enroll and remain in the study. The consistent theme of perceived health benefits as a motivator to join and remain in the study raises the question of whether participation in research results in actual improvements in health.
Open Access
New imaging approaches for improving diagnosis of childhood tuberculosis
(Health and Medical Publishing Group, 2014) Bélard, Sabine; Andronikou, Savvas; Pillay, Tanyia; Grobusch, Martin P; Zar, Heather J
In South Africa (SA), childhood tuberculosis (TB) still accounts for considerable morbidity and mortality. The incidence of TB disease and risk of progression to severe or disseminated forms are especially high in young children or those with HIV infection. Childhood TB presents most commonly as primary TB, often with non specific signs and symptoms; TB may also present as acute pneumonia. The clinical diagnosis can therefore be challenging. Furthermore, due to difficulty in obtaining good-quality specimens and the paucibacillary nature of childhood TB, microbiological confirmation is only achieved in a minority of children, especially in settings where there is limited capacity for microbiological confirmation.
Open Access
Optimizing 16S rRNA gene profile analysis from low biomass nasopharyngeal and induced sputum specimens
(2020-05-12) Claassen-Weitz, Shantelle; Gardner-Lubbe, Sugnet; Mwaikono, Kilaza S; du Toit, Elloise; Zar, Heather J; Nicol, Mark P
Careful consideration of experimental artefacts is required in order to successfully apply high-throughput 16S ribosomal ribonucleic acid (rRNA) gene sequencing technology. Here we introduce experimental design, quality control and “denoising” approaches for sequencing low biomass specimens. Results We found that bacterial biomass is a key driver of 16S rRNA gene sequencing profiles generated from bacterial mock communities and that the use of different deoxyribonucleic acid (DNA) extraction methods [DSP Virus/Pathogen Mini Kit® (Kit-QS) and ZymoBIOMICS DNA Miniprep Kit (Kit-ZB)] and storage buffers [PrimeStore® Molecular Transport medium (Primestore) and Skim-milk, Tryptone, Glucose and Glycerol (STGG)] further influence these profiles. Kit-QS better represented hard-to-lyse bacteria from bacterial mock communities compared to Kit-ZB. Primestore storage buffer yielded lower levels of background operational taxonomic units (OTUs) from low biomass bacterial mock community controls compared to STGG. In addition to bacterial mock community controls, we used technical repeats (nasopharyngeal and induced sputum processed in duplicate, triplicate or quadruplicate) to further evaluate the effect of specimen biomass and participant age at specimen collection on resultant sequencing profiles. We observed a positive correlation (r = 0.16) between specimen biomass and participant age at specimen collection: low biomass technical repeats (represented by < 500 16S rRNA gene copies/μl) were primarily collected at < 14 days of age. We found that low biomass technical repeats also produced higher alpha diversities (r = − 0.28); 16S rRNA gene profiles similar to no template controls (Primestore); and reduced sequencing reproducibility. Finally, we show that the use of statistical tools for in silico contaminant identification, as implemented through the decontam package in R, provides better representations of indigenous bacteria following decontamination. Conclusions We provide insight into experimental design, quality control steps and “denoising” approaches for 16S rRNA gene high-throughput sequencing of low biomass specimens. We highlight the need for careful assessment of DNA extraction methods and storage buffers; sequence quality and reproducibility; and in silico identification of contaminant profiles in order to avoid spurious results.
Open Access
Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children
(2006) Zar, Heather J; Langdon, Grant; Apolles, Patti; Eley, Brian; Hussey, Gregory; Smith, Peter
Background. Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5 - 10 µg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. Objective. To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIVinfected children. Methods. A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. Results. Median (25th - 75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5 - 1.5) µg/ml, 1.94 (1.4 - 2.2) µg/ml and 7.68 (6.1- 7.8) µg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4 - 8.8) µg/ml and 9.25 (8.2 - 10.3) µg/ml respectively. Conclusion. Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children.
Open Access
Pneumocystis pneumonia in South African children diagnosed by molecular methods
(BioMed Central, 2014-01-10) Morrow, Brenda M; Samuel, Catherine M; Zampoli, Marco; Whitelaw, Andrew; Zar, Heather J
Background: Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR. Methods: A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded. Results: 202 children [median (interquartile range, IQR) age 3.2 (2.1– 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 – 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality. Conclusions: The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.