Publications by authors named "Heather J Zar"

294 Publications

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

Obstet Gynecol 2021 Oct;138(4):633-646

Department for Health Evidence, Radboud Institute for Health Sciences, and the Radboud REshape Innovation Center, Radboud University Medical Center, Nijmegen, the Netherlands; the Environmental Research Group, King's College, London, United Kingdom; the Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden; the Singapore Institute for Clinical Sciences, Singapore; the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; the Department of Child and Adolescent Psychiatry, the Department of Psychology, Education and Child Studies, Erasmus School of Social and Behavioral Sciences, and the Department of Pediatrics, Erasmus University Rotterdam, Rotterdam, the Netherlands; the Department of Pharmacy (Centre IMAGe), Centre Hospitalier Universitaire Sainte-Justine and Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada; the Division of Reproductive and Perinatal Health, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; the Department of Health Science, Medical Faculty, Lund University, Lund, Sweden; the Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; the Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; the Department of Obstetrics & Gynecology, NorthShore University HealthSystem, and the University of Chicago Pritzker School of Medicine, Chicago, Illinois; the School of Public Health and the Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland; the London School of Hygiene and Tropical Medicine, London, United Kingdom; the Elisabeth TweeSteden Hospital (ETZ), Tilburg, the Netherlands; the Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland; the Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom; Wayne State University, Detroit, Michigan; the Department of Public Health Science, Karolinska Institutet, Stockholm, Sweden; the PharmacoEpidemiology & Drug Safety Research Group, School of Pharmacy, University of Oslo, and the Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway; the Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; the University of York, York, United Kingdom; the Faculty of Health, School of Nursing, York University, Toronto, Ontario, Canada; the Department of Psychiatry, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey; the School of Nursing and Midwifery, Aga Khan University, Karachi, Pakistan; the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota; the Department of Psychiatry and Mental Health, University of Cape Town, and the South African Medical Research Council, Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa; the Charles Perrens Hospital and the Bordeaux Population Health Center, INSERM 1219, Bordeaux University, Bordeaux, France; the Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; the "Alexandra" General Hospital of Athens, Athens, Greece; the Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands; the STIS and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; the Department of Medical Psychology, Radboud Institute for Health Sciences, and the Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.

Objective: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores.

Data Sources: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016.

Methods Of Study Selection: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis.

Tabulation, Integration, And Results: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8).

Conclusion: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores.

Systematic Review Registration: PROSPERO, CRD42016035711.
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http://dx.doi.org/10.1097/AOG.0000000000004538DOI Listing
October 2021

Pulmonary cysticercosis in an urban South African child.

Pediatr Pulmonol 2021 Sep 28. Epub 2021 Sep 28.

Dept Paediatrics & Child Health, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.

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http://dx.doi.org/10.1002/ppul.25682DOI Listing
September 2021

Alcohol use is associated with mental health problems and brain structural alterations in adolescents with perinatally acquired HIV infection on ART.

Alcohol 2021 Sep 15. Epub 2021 Sep 15.

Department of Psychiatry and Mental Health, University of Cape Town, South Africa. Electronic address:

Alcohol use, presents unique challenges for HIV-1 treatment in adolescents with perinatally acquired infection. The effects of alcohol on host-virus interaction in the brain and the immune system remains understudied in this population. Adolescents with perinatally acquired HIV infection (PHIV) well established on ART, from the Cape Town Adolescent Antiretroviral Cohort who self-reported alcohol use (PHIV+alcohol) (n=26) were compared to age matched 26 PHIV (PHIV-alcohol) and 26 healthy controls (HC) who reported no use of alcohol. Participants completed clinical investigations including highly-sensitive CRP (hs-CRP), a comprehensive neurocognitive test battery and mental health measures. In addition, we investigated the relationship between alcohol use in PHIV and diffusion tensor imaging (DTI) and structural brain magnetic resonance imaging (MRI) to determine fractional anisotropy (FA), mean diffusivity (MD), grey and white matter volumes and cortical thickness. PHIV (mean age 12,5 years; mean age of ART initiation 3.15 years) reported an occasional weekend drinking pattern of alcohol use. hs-CRP was significantly different between groups, with PHIV+alcohol higher than PHIV-alcohol and HC. General intelligence, attention, working memory, processing speed and executive function were more impaired in the PHIV+alcohol than PHIV alone, with HC having the highest scores. In addition, self-concept was significantly lower in PHIV+alcohol. The Child Behavior Checklist (CBCL) Externalizing behaviour, internalising behaviour and CBCL Total problems were significantly higher in PHIV+alcohol. FA of the superior corona radiata, superior fronto-occipital fasciculus and corpus callosum was significantly lower in PHIV+alcohol compared to PHIV-alcohol and MD of the corona radiata was significantly increased in PHIV+alcohol. The cortical thickness of the lateral orbitofrontal, middle frontal and precentral gyri were significantly lower in PHIV+ alcohol compared to PHIV-alcohol and HC. In conclusion PHIV associated impairments in systemic inflammation, cognitive function, mental health and changes in brain structure may be exacerbated by alcohol use, even if only occasional use. However, the study is cross-sectional, which is not able to distinguish between cause and effect.
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http://dx.doi.org/10.1016/j.alcohol.2021.09.006DOI Listing
September 2021

Antibodies to Seasonal Coronaviruses Rarely Cross-React with SARS-CoV-2: Findings from an African Birth Cohort.

Pediatr Infect Dis J 2021 Sep 17. Epub 2021 Sep 17.

From the Department of Paediatrics and Child Health, and SA-MRC Unit on Child & Adolescent Health, University of Cape Town and Red Cross War Memorial Children's Hospital, Cape Town, South Africa Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Australia Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa Great Ormond Street Institute of Child Health, University College London Great Ormond Street Children's Hospital NHS Foundation Trust, London, United Kingdom.

Antibodies to seasonal human-coronaviruses (sHCoV) may cross-protect against SARS-CoV-2. We investigated antibody responses in biobanked serum obtained before the pandemic from infants with polymerase chain reaction-confirmed sHCoV. Among 141 samples with antibodies to sHCoV, 4 (2.8%) were positive for SARS-CoV-2-S1 and 8 (5.7%) for SARS-CoV-2-S2. Antibodies to sHCoV rarely cross-react with SARS-CoV-2 antigens and are unlikely to account for mild pediatric illness.
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http://dx.doi.org/10.1097/INF.0000000000003325DOI Listing
September 2021

An evaluation of an influenza vaccination campaign targeting pregnant women in 27 clinics in two provinces of South Africa, 2015 - 2018.

BMC Health Serv Res 2021 Sep 9;21(1):941. Epub 2021 Sep 9.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.

Introduction: Despite prioritization, routine antenatal influenza vaccine coverage is < 16% in South Africa. We aimed to describe maternal influenza vaccine coverage in 27 antenatal clinics (ANCs) in Gauteng and Western Cape (WC) Provinces, where in collaboration with the Department of Health (DoH), we augmented the annual influenza vaccination programme among pregnant women.

Methods: From 2015 through 2018, 40,230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression.

Results: We screened 62,979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27,068 in Gauteng and 35,911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49,355/62682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7 p < 0.001). Women aged 25-29 and > 35 years were less likely to be vaccinated than women aged 18-24 years (OR = 0.9 p = 0.053; OR = 0.9 p < 0.001). HIV positive status was not associated with vaccination (OR = 1.0 p = 0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12723), refusal/indecision (25.8%, 3285), and current illness that contraindicated vaccination (19.6%, 2489).

Conclusion: Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.
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http://dx.doi.org/10.1186/s12913-021-06962-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427945PMC
September 2021

Vitamin D concentrations in infancy and the risk of tuberculosis in childhood: A prospective birth cohort in Cape Town, South Africa.

Clin Infect Dis 2021 Aug 26. Epub 2021 Aug 26.

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, and SA-MRC Uniton Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.

Introduction: Low vitamin D may increase the risk of tuberculosis; however, previous observational cohort studies have had variable results. We investigated the relationship between vitamin D levels in infancy and subsequent development of tuberculosis throughout childhood.

Methods: We enrolled pregnant women between 20-28 weeks' gestation attending antenatal care in a peri-urban South African setting in the Drakenstein Child Health Study. Serum 25(OH)D concentrations were measured in newborn infants between 6-10 weeks of age. Children were followed prospectively for tuberculosis infection and disease using annual tuberculin skin testing, radiographic examinations, and microbiological diagnosis with GeneXpert, culture, and smear testing. Univariable and multivariable Cox regression was performed and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.

Results: Children were followed for tuberculosis for a median of 7.2 years (IQR, 6.2-7.9). Among 744 children (< 1% living with HIV, 21% HIV-exposed living without HIV), those who were vitamin D deficient in early infancy were not at increased risk of developing tuberculosis (AHR, 0.8; 95% CI, 0.4-1.6). Infants in the lowest vitamin D concentration tertile were at similar risk of tuberculosis compared to the highest tertile (AHR, 0.7; 95% CI, 0.4-1.4). Vitamin D deficiency was associated with tuberculin conversion ≤2 years of age at a <30nmol/l (AOR, 1.9; 95% CI, 1.2-3.2), but not <50nmol/l (AOR, 1.5; 95% CI, 0.8-2.9), cutoff.

Conclusion: In a setting with hyperendemic tuberculosis, vitamin D levels in infancy did not predict tuberculosis at any point in childhood. However, very low vitamin D levels were associated with tuberculin conversion in young children.
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http://dx.doi.org/10.1093/cid/ciab735DOI Listing
August 2021

Factors associated with serious outcomes of pneumonia among children in a birth cohort in South Africa.

PLoS One 2021 13;16(8):e0255790. Epub 2021 Aug 13.

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and SA-MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.

Background: Child hospitalization for pneumonia remains common, and pneumonia is a major cause of child mortality. Early identification of clinical factors associated with serious outcomes may help target risk-mitigation strategies.

Methods: Pneumonia cases occurring in the Drakenstein Child Health Study, a prospective birth cohort outside Cape Town, South Africa were analysed, and factors associated with serious outcomes of pneumonia were identified. Pregnant women were enrolled antenatally, followed through pregnancy, and mother-child pairs from birth to 2 years. Active surveillance for pneumonia was done. Children hospitalized with pneumonia had chest radiography and blood drawn for inflammatory markers; course, outcome and duration of hospitalization were investigated. Serious outcomes were defined as in-hospital mortality or admission to intensive care unit (ICU). Prolonged hospitalization was also explored as a proxy for severity. Features associated with serious outcomes or prolonged hospitalization were analysed using modified Poisson regression.

Results: Among 1143 live born infants, there were 174 hospitalized pneumonia events in 133 children under 2 years. Three children (1.7%) died, 14 (8%) required ICU admission for respiratory support. In modified Poisson regression, age < 2 months, preterm birth, or hypoxia (oxygen saturation <92%) were significantly associated with serious outcomes. Preterm birth, low birth weight, HIV exposure, stunting, or underweight-for-age (UWFA) were associated with prolonged hospitalization. Chest radiography, elevated C reactive protein, white blood cell and neutrophil counts were not useful to predict death or ICU admission in children hospitalized with pneumonia.

Conclusions: In this cohort, death from pneumonia was rare, but clinical features associated with serious outcomes and prolonged hospitalization were identified. These may help with risk stratification, to identify children who may benefit from enhanced monitoring or earlier escalation to respiratory support.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255790PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363001PMC
August 2021

Cystic fibrosis in South Africa: spectrum of disease and determinants of outcome.

ERJ Open Res 2021 Jul 2;7(3). Epub 2021 Aug 2.

Dept of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.

Introduction: Little is known about cystic fibrosis (CF) in low- to middle-income settings. This study aimed to describe the spectrum and outcomes of CF in South Africa (SA) from the recently established SA CF registry (SACFR).

Methods: Demographic, diagnosis and clinical data were extracted from the SACFR. Cross-sectional univariable and multivariable regression analysis of best forced expiratory volume in 1 s (FEV; age≥6 years) and nutrition (all ages) in 2018 was conducted to investigate factors associated with severe lung disease (SLD; FEV ≤3.0 z-score) and undernutrition.

Results: By December 2018, ancestry of 447 individuals included in the SACFR was Caucasian (315; 70%), mixed (87; 19%) and black African (41; 9%). Median diagnosis age was 7.6 months (IQR 2.7-37.1). Genotype was p.Phe508del homozygous (220; 49%); p.Phe508del heterozygous (144; 32%) and neither p.Phe508del or unknown Cystic Fibrosis Transmembrane Conductance Regulator () variant in 83 (19%); the second most frequent variant was 3120+1G>A, common in black Africans. Median age of patients in 2018 was 14.7 years (IQR 7.4-24.4). SLD was independently associated with chronic methicillin-resistant (MRSA) (adjusted odds ratio( aOR) 16.75; 95% CI 1.74-161.50), undernutrition (aOR 5.20; 95% CI 2.23-12.13) and age (aOR 2.23 per 10 years; 95% CI 1.50-3.31). Undernutrition was associated in univariable analysis with low weight at diagnosis, non-Caucasian ancestry, chronic infection and lower socioeconomic status.

Conclusion: Interventions targeting MRSA infection and nutrition are needed to improve CF outcomes in SA. Most people with CF in SA are eligible for highly effective CFTR modulator therapy.
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http://dx.doi.org/10.1183/23120541.00856-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326682PMC
July 2021

HIV-Related Stigma and Psychological Adjustment Among Perinatally HIV-Infected Youth in Cape Town, South Africa.

AIDS Behav 2021 Jul 27. Epub 2021 Jul 27.

Department of Psychiatry and Mental Health in the Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

The effect of chronic HIV-infection on psychological adjustment, including the impact of HIV-related stigma in perinatally HIV-infected (PHIV+) youth across Africa is largely unknown. This study examined psychological adjustment and HIV-related stigma using the Strengths and Difficulties Questionnaire (SDQ) and a 10-item stigma questionnaire in a cohort of PHIV+ youth in Cape Town, South Africa. The relationships between SDQ scores, elevated viral load, and suboptimal antiretroviral therapy (ART) adherence were also explored. Among 473 PHIV+ youth (aged 9-14 years, on ART > 6 months at enrollment), higher perceived HIV-related stigma was associated with higher scores across all adolescent and caregiver-reported SDQ difficulty subscales. Higher socioeconomic status (SES) was associated with lower scores on adolescent self- and caregiver-reported hyperactivity subscales. Higher adolescent-reported prosocial scores were associated with lower odds of self-reported suboptimal ART adherence, and higher caregiver-reported conduct scores were associated with higher odds of elevated viral load. No associations were observed between perceived HIV-related stigma and treatment outcomes. These findings highlight the potentially detrimental impact of perceived stigma on psychological adjustment in PHIV+ youth. The use of psychosocial metrics and interventions aimed at reducing illness related stigma in PHIV+ youth is also considered.
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http://dx.doi.org/10.1007/s10461-021-03398-3DOI Listing
July 2021

Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020.

Euro Surveill 2021 07;26(29)

School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.29.2001600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299743PMC
July 2021

Investigating pupillometry to detect emotional regulation difficulties in post-traumatic stress disorder.

World J Biol Psychiatry 2021 Jul 19:1-9. Epub 2021 Jul 19.

Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.

Objective: Individuals with posttraumatic stress disorder (PTSD) have been found to exhibit emotional regulation difficulties. However, the specific neural mechanisms that underlie these difficulties remain understudied. This study aimed to use pupillometry as an index function of parasympathetic nervous system activation, to investigate the mechanisms underlying emotional regulation difficulties in individuals with PTSD.

Method: A total of 87 trauma-exposed mothers (34 with PTSD and 53 non-PTSD controls) completed an eye tracking assessment in which pupillary dilation in response to emotionally valenced stimuli was measured. The participants also completed two self-report measures of emotional regulation, namely the Difficulties in Emotional Regulation Scale and the Emotional Regulations Questionnaire. Linear mixed-effect modelling was used to assess potential group differences.

Results: The PTSD group exhibited increased pupillary dilation to positively valenced stimuli compared to the non-PTSD group. However, no significant associations between the self-report measures and pupillary response to emotionally valenced stimuli were found.

Conclusion: Increased pupillary dilation in PTSD may reflect impaired parasympathetic nervous system processes. The lack of association of these measures with self-reported emotion regulation may suggest reporting biases. Larger studies with more generalised populations are required to consolidate these preliminary findings.
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http://dx.doi.org/10.1080/15622975.2021.1935316DOI Listing
July 2021

The association between mental health and metabolic outcomes in youth living with perinatally acquired HIV in the Cape Town Adolescent Antiretroviral Cohort.

AIDS Care 2021 Jul 8:1-8. Epub 2021 Jul 8.

SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.

Youth living with perinatally acquired HIV (YLPHIV) have been found to have a range of mental disorders. Some adult HIV studies have linked mental health to adverse metabolic outcomes due to dysregulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, but this association has not previously been explored in YLPHIV.We investigated the association of mental health measures with metabolic outcomes in YLPHIV and HIV-uninfected youth (HIV-U) and linear regression was used to assess the adjusted associations.Overall, 203 YLPHIV (median age = 10.7years; 52% female; mean duration on ART 8 years, 12% CD4 count <500 cells/µL, 18% viral load >50 copies/mL) and 44 HIV-U (median age = 10.3 years; 55% female) were enrolled. YLPHIV had higher median total cholesterol (4.2 vs 3.9 mmol/L, = 0.049) and triglyceride (0.9 vs 0.7 mmol/L, < 0.001) compared to HIV-U. We found higher percentage of poor functional competence (40% vs 25%, = 0.02) and self-concept (23% vs 9%, = 0.03) and higher depression (6% vs 2%, < 0.01), anger (6% vs 2%, = 0.04) and disruptive behaviour (4% vs 0%, < 0.01) in YLPHIV as compared to HIV-U. Among YLPHIV, higher scores of anger were associated with higher total cholesterol and higher low-density lipoprotein (ß = 0.010, = 0.041 and ß = 0.012, = 0.048 respectively) and disruptive behaviour with higher low-density lipoprotein (ß = 0.010, = 0.043) after adjusting for age, sex and BMIZ.This is the one of first study to investigate the association of mental health with metabolic outcomes among YLPHIV. The association of increased anger and disruptive behaviour with increased lipid concentration is a novel finding. Further longitudinal studies are needed to evaluate the causal relationships between mental health and metabolic outcomes.
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http://dx.doi.org/10.1080/09540121.2021.1950605DOI Listing
July 2021

Maternal psychosocial risk factors and child gestational epigenetic age in a South African birth cohort study.

Transl Psychiatry 2021 07 2;11(1):358. Epub 2021 Jul 2.

Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.

Accelerated epigenetic aging relative to chronological age has been found to be associated with higher risk of mortality in adults. However, little is known about whether and how in utero exposures might shape child gestational epigenetic age (EA) at birth. We aimed to explore associations between maternal psychosocial risk factors and deviation in child gestational EA at birth (i.e., greater or lower EA relative to chronological age) in a South African birth cohort study-the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression; psychological distress; and alcohol/tobacco use. Child gestational EA at birth was calculated using an epigenetic clock previously devised for neonates; and gestational EA deviation was calculated as the residuals of the linear model between EA and chronological gestational age. Bivariate linear regression was then used to explore unadjusted associations between maternal/child risk factors and child gestational EA residuals at birth. Thereafter, a multivariable regression method was used to determine adjusted associations. Data from 271 maternal-child dyads were included in the current analysis. In the multivariable regression model, maternal PTSD was significantly and negatively associated with child gestational EA residuals at birth (β = -1.95; p = 0.018), controlling for study site, sex of the child, head circumference at birth, birthweight, mode of delivery, maternal estimated household income, body mass index (BMI) at enrolment, HIV status, anaemia, psychological distress, and prenatal tobacco or alcohol use. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA deviation are warranted.
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http://dx.doi.org/10.1038/s41398-021-01434-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253754PMC
July 2021

Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank.

BMJ Open 2021 07 2;11(7):e048338. Epub 2021 Jul 2.

Department of Paediatrics, University of Turku, Turku, Finland.

Introduction: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.

Methods And Analysis: Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.

Ethics And Dissemination: Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.

Prospero Registration Numbers: CRD42020132990, CRD42020171624.
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http://dx.doi.org/10.1136/bmjopen-2020-048338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256789PMC
July 2021

Central white matter integrity alterations in 2-3-year-old children following prenatal alcohol exposure.

Drug Alcohol Depend 2021 08 24;225:108826. Epub 2021 Jun 24.

Department of Pediatrics and Child Health, University of Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa.

Background: Prenatal alcohol exposure (PAE) remains a potentially preventable, but pervasive risk factor to neurodevelopment. Yet, evidence is lacking on the impact of alcohol on brain development in toddlers. This study aimed to investigate the impact of PAE on brain white matter integrity in 2-3-year-old children.

Methods: Children (n = 83, 30-37 months old) of the Drakenstein Child Health Study birth cohort, underwent diffusion MRI on a 3 T Siemens scanner during natural sleep. Parameters were extracted in children with PAE (n = 25, 56 % boys) and unexposed controls (n = 58, 62 % boys) using Tract-based Spatial Statistics, and compared by group. The contribution of maternal tobacco smoking to white matter differences was also explored.

Results: Children with PAE had altered fractional anisotropy, radial diffusivity and axial diffusivity in brain stem, limbic and association tracts compared to unexposed controls. Notably lower fractional anisotropy was found in the uncinate fasciculus, and lower mean and radial diffusivity were found in the fornix stria terminalis and corticospinal tract (FDR corrected p < 0.05). There was a significant interaction effect of PAE and prenatal tobacco exposure which lowered mean, radial and axial diffusivity in the corticospinal tract significantly in the PAE group but not controls.

Conclusion: Widespread altered white matter microstructural integrity at 2-3 years of age is consistent with findings in neonates in the same and other cohorts, indicating persistence of effects of PAE through early life. Findings also highlight that prenatal tobacco exposure impacts the association of PAE on white matter alterations, amplifying effects in tracts underlying motor function.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299546PMC
August 2021

Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.

Lancet Glob Health 2021 08 21;9(8):e1077-e1087. Epub 2021 Jun 21.

Vienna Vaccine Safety Initiative, Berlin, Germany; Université Bourgogne-Franche Comté, Besançon, France.

Background: Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age.

Methods: We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570).

Findings: 203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome.

Interpretation: We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(21)00218-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298256PMC
August 2021

The association between bacteria colonizing the upper respiratory tract and lower respiratory tract infection in young children: a systematic review and meta-analysis.

Clin Microbiol Infect 2021 Sep 7;27(9):1262-1270. Epub 2021 Jun 7.

Division of Medical Microbiology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Australia.

Background: Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI).

Objectives: To systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children.

Data Sources: MEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science.

Study Eligibility Criteria: Studies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls.

Participants: Children under 5 years with and without acute LRTI.

Methods: Three reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel-Haenszel fixed- or random-effects models.

Results: Most eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23-2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17-3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04-1.90). High density colonization with S. pneumoniae (>6.9 log copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive.

Conclusions: Detection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.
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http://dx.doi.org/10.1016/j.cmi.2021.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437050PMC
September 2021

Prevalence and Correlates of Vitamin D Deficiency among Young South African Infants: A Birth Cohort Study.

Nutrients 2021 Apr 29;13(5). Epub 2021 Apr 29.

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, and SA-MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town 7700, South Africa.

Early-life vitamin D deficiency is associated with adverse child health outcomes, but the prevalence of vitamin D deficiency and its correlates in infants remains underexplored, particularly in sub-Saharan Africa. We aimed to investigate the prevalence of vitamin D deficiency and its correlates among young infants in South Africa. This study included 744 infants, aged 6-10 weeks from the Drakenstein Child Health Study, a population-based birth cohort. Infants were categorized into distinct categories based on serum 25(OH)D concentration level including deficient (<50 nmol/L), insufficient (50-74 nmol/L), and sufficient (≥75 nmol/L). Using multivariable Tobit and logistic regression models, we examined the correlates of serum 25(OH)D levels. The overall prevalence of vitamin D deficiency was 81% (95% confidence intervals (CI]) 78-83). Multivariable regression analysis showed that serum 25(OH)D concentration was independently associated with study site, socioeconomic status, and sex. Birth in winter and breastfeeding were the strongest predictors of lower serum 25(OH)D concentration levels. Compared to non-breastfed children, children breastfed were at higher risk of vitamin D deficiency (AOR, 1.96; 95% CI, 1.04-3.67) and breastfeeding for more than one month was associated with greater likelihood of vitamin D deficiency (AOR, 5.40; 95% CI, 2.37-12.32) and lower vitamin D concentrations (-16.22 nmol/L; 95% CI, -21.06, -11.39). Vitamin D deficiency in infants is ubiquitous, under-recognised, and strongly associated with season of birth and breastfeeding in this setting. Nutritional interventions with vitamin D supplementation in national health programs in low- and middle-income countries are urgently needed to improve early-life vitamin D status in infants.
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http://dx.doi.org/10.3390/nu13051500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146842PMC
April 2021

The relationship between childhood trauma, socioeconomic status, and maternal depression among pregnant women in a South African birth cohort study.

SSM Popul Health 2021 Jun 17;14:100770. Epub 2021 Mar 17.

Alan J. Flisher Centre for Public Mental Health, Department of Psychiatry and Mental Health, University of Cape Town, 46 Sawkins Road, Rondebosch, Cape Town, 7700, South Africa.

Background: Maternal depression is an important cause of morbidity and mortality. Experiences of childhood trauma contribute to maternal depression, potentially causing adult socio-economic disparities in mental health. We investigate whether adult socioeconomic status (SES) mediates the relationship between childhood trauma and antenatal depression.

Methods: We analyzed data from two sociodemographically distinct peri-urban sites in the Western Cape, South Africa in a birth cohort study, the Drakenstein Child Health Study: Mbekweni (N = 510) and TC Newman (N = 413). Data were collected from pregnant women between 28 and 32 weeks' gestation.

Results: Associations between trauma and depressive symptoms differed by site ( =2163.6, df = 1419, p < 0.01); direct effects of trauma on depression were 0.24 mean increased symptoms in Mbekweni (p < 0.01) and 0.47 in TC Newman (p < 0.01). Trauma was differentially associated with SES (Mbekweni: -0.10, p = 0.07; TC Newman: -0.05, p = 0.37) and SES with depression (Mbekweni: -0.18, p < 0.01; TC Newman: -0.02, p = 0.62) across both sites. Indirect effects of trauma on depression through SES were 0.018 (95% C.I. -0.002-0.039) in Mbekweni and 0.001 (95% C.I. -0.004-0.006) in TC Newman, suggesting mediation was not supported. SES was a stronger indicator of depression risk in relatively poorer Mbekweni.

Conclusion: Neighborhood-level effects and poverty are potentially important modifiers, and points of intervention, for maternal mental health outcomes.
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http://dx.doi.org/10.1016/j.ssmph.2021.100770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025055PMC
June 2021

Asthma in South African adolescents: a time trend and risk factor analysis over two decades.

ERJ Open Res 2021 Apr 6;7(2). Epub 2021 Apr 6.

University of Cape Town, Dept of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, and the SA-MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.

Background: South Africa has undergone major economic and health system changes, impacting the epidemiology of childhood asthma. This study aimed to investigate prevalence time trends of asthma in South African adolescents over two decades and to identify associated risk factors.

Methods: A cross-sectional survey was conducted in 2017, in a randomised sample of 13-14-year-old Cape Town adolescents, using the standardised Global Asthma Network written, video and environmental questionnaires. Using time-trend analysis, the prevalence and severity of asthma were compared with data from the 2002 ISAAC phase III study. Environmental and social risk factors were analysed.

Results: A total of 3979 adolescents were included. The prevalence of lifetime and current asthma were 34.5% and 21.3%, respectively, on the self-report written questionnaire, similar to 2002 results. The prevalence of severe asthma in the previous 12 months increased, measured by wheeze limiting speech (7.8% to 11.8%), four or more attacks of wheezing (5.0% to 5.8%) or woken by wheeze on one or more nights per week (5.0% to 6.9%). The video questionnaire revealed increases in lifetime (16.9% to 22.5%), current (11.2% to 18.7%) and severe asthma (12.1% to 14.8%). Multivariate analysis showed associations between current asthma and smoking, female sex, pet exposure and higher socioeconomic status. Severe asthma was associated with smoking, pet exposure, outdoor pollution exposure and informal housing; 33% of those with severe or current asthma had been diagnosed.

Conclusion: The prevalence of asthma is high, with increasing rates of severe asthma in adolescents. Underdiagnosis is a major concern and reduction in exposure to environmental factors, particularly smoking, and improved socioeconomic development are needed.
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http://dx.doi.org/10.1183/23120541.00576-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021807PMC
April 2021

Asthma in South African adolescents: a time trend and risk factor analysis over two decades.

ERJ Open Res 2021 Apr 6;7(2). Epub 2021 Apr 6.

University of Cape Town, Dept of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, and the SA-MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.

Background: South Africa has undergone major economic and health system changes, impacting the epidemiology of childhood asthma. This study aimed to investigate prevalence time trends of asthma in South African adolescents over two decades and to identify associated risk factors.

Methods: A cross-sectional survey was conducted in 2017, in a randomised sample of 13-14-year-old Cape Town adolescents, using the standardised Global Asthma Network written, video and environmental questionnaires. Using time-trend analysis, the prevalence and severity of asthma were compared with data from the 2002 ISAAC phase III study. Environmental and social risk factors were analysed.

Results: A total of 3979 adolescents were included. The prevalence of lifetime and current asthma were 34.5% and 21.3%, respectively, on the self-report written questionnaire, similar to 2002 results. The prevalence of severe asthma in the previous 12 months increased, measured by wheeze limiting speech (7.8% to 11.8%), four or more attacks of wheezing (5.0% to 5.8%) or woken by wheeze on one or more nights per week (5.0% to 6.9%). The video questionnaire revealed increases in lifetime (16.9% to 22.5%), current (11.2% to 18.7%) and severe asthma (12.1% to 14.8%). Multivariate analysis showed associations between current asthma and smoking, female sex, pet exposure and higher socioeconomic status. Severe asthma was associated with smoking, pet exposure, outdoor pollution exposure and informal housing; 33% of those with severe or current asthma had been diagnosed.

Conclusion: The prevalence of asthma is high, with increasing rates of severe asthma in adolescents. Underdiagnosis is a major concern and reduction in exposure to environmental factors, particularly smoking, and improved socioeconomic development are needed.
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http://dx.doi.org/10.1183/23120541.00576-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021807PMC
April 2021

The interplay between environmental exposures and COVID-19 risks in the health of children.

Environ Health 2021 03 26;20(1):34. Epub 2021 Mar 26.

Superfund Research Program, National Institute of Environmental Health Sciences, 530 Davis Drive, Durham, NC, 27709, USA.

Background: An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution.

Objectives: To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps.

Methods: An international group of researchers interested in children's environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps.

Discussion: Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a "dirty" environment in conveying protection - an example of the "hygiene hypothesis"; and what are the long term health effects of SARS-Cov-2 infection in early life.

Conclusion: A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.
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http://dx.doi.org/10.1186/s12940-021-00716-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996114PMC
March 2021

The child ecosystem and childhood pulmonary tuberculosis: A South African perspective.

Pediatr Pulmonol 2021 07 25;56(7):2212-2222. Epub 2021 Mar 25.

Department of Paediatrics and Child Health, Red Cross Childrens Hospital and SA-MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, Western Cape, South Africa.

Introduction: This study investigates drivers of childhood pulmonary tuberculosis (PTB) using a childhood ecosystem approach in South Africa. An ecosystem approach toward identifying risk factors for PTB may identify targeted interventions.

Methods: Data were collected as part of a prospective cohort study of children presenting at a primary care facility or tertiary hospital with possible TB. Characterization of the childhood ecosystem included proximal, medial, and distal determinants. Proximal determinants included child characteristics that could impact PTB outcomes. Medial determinants included relational factors, such as caregiver health, which might impact interactions with the child. Distal determinants included macro-level determinants of disease, such as socioeconomic status and food insecurity. Children who started on TB treatment were followed for up to 6 months. Multivariate regression models tested independent associations between factors associated with PTB in children.

Results: Of 1202 children enrolled, 242 (20%) of children had confirmed PTB, 756 (63%) were started on TB treatment, and 444 (37%) had respiratory conditions other than TB. In univariate analyses, childhood malnutrition and caregiver smoking were associated with treated or confirmed PTB. In multivariate analyses, proximal factors, such as male gender and hospitalization, as well as low socioeconomic status as a distal factor, were associated with PTB.

Conclusions: Interventions may need to target subgroups of children and families with elevated proximal, medial, and distal risk factors for PTB. Screening for risk factors, such as caregiver's health, may guide targeting. The provision of social protection programs to bolster economic security may be an important intervention for attenuating childhood exposure to risk factors.
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http://dx.doi.org/10.1002/ppul.25369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477372PMC
July 2021

Tuberculosis infection and disease in South African adolescents with perinatally acquired HIV on antiretroviral therapy: a cohort study.

J Int AIDS Soc 2021 03;24(3):e25671

Department of Paediatrics and Child Health, University of Cape Town, Cape, South Africa.

Introduction: There are limited data on Tuberculosis (TB) in adolescents with perinatally acquired HIV (APHIV). We examined the incidence and determinants of TB infection and disease in the Cape Town Adolescent Antiretroviral Cohort (CTAAC).

Methods: Youth between nine and fourteen years on antiretroviral therapy (ART) for more than six months in public sector care, and age-matched HIV-negative adolescents, were enrolled between July 2013 through March 2015 and followed six-monthly. Data were censored on 31 October 2018. Symptom screening, chest radiograph, viral load, CD4 count, QuantiFERON (QFT) and sputum for Xpert MTB/RIF, microscopy, culture and sensitivity were performed annually. TB infection was defined by a QFT of >0.35 IU/mL. TB diagnosis was defined as confirmed (culture or Xpert MTB/RIF positive) or unconfirmed (clinical diagnosis and started on TB treatment). Analyses examined the incidence and determinants of TB infection and disease.

Results: Overall 496 HIV+ and 103 HIV-negative participants (median age at enrolment 12 years (interquartile range, IQR 10.6 to 13.3) were followed for a median of 3.1 years (IQR 3.0 to 3.4); 50% (298/599) were male. APHIV initiated ART at median age 4.4 years (IQR 2.1 to 7.6). At enrolment, 376/496 (76%) had HIV viral load <40 copies/mL, median CD4 count was 713 cells/mm and 179/559 (32%) were QFT+, with no difference by HIV status (APHIV 154/468, 33%; HIV negative 25/91, 27%; p = 0.31). The cumulative QFT+ prevalence was similar (APHIV 225/492, 46%; 95%CI 41% to 50%; HIV negative 44/98, 45%; 95% CI 35% to 55%; p = 0.88). APHIV had a higher incidence of all TB disease than HIV-negative adolescents (2.2/100PY, 95% CI 1.6 to 3.1 vs. 0.3/100PY, 95% CI 0.04 to 2.2; IRR 7.36, 95% CI 1.01 to 53.55). The rate of bacteriologically confirmed TB in APHIV was 1.3/100 PY compared to 0.3/100PY for HIV-negative adolescents, suggesting a fourfold increased risk of developing TB disease in APHIV despite access to ART. In addition, a positive QFT at enrolment was not predictive of TB in this population.

Conclusions: High incidence rates of TB disease occur in APHIV despite similar QFT conversion rates to HIV-negative adolescents. Strategies to prevent TB in this vulnerable group must be strengthened.
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http://dx.doi.org/10.1002/jia2.25671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957181PMC
March 2021

The neurocognitive profile of post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and PTSD with comorbid MDD.

Brain Behav 2021 04 5;11(4):e01950. Epub 2021 Mar 5.

Department of Psychiatry & Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Objective: Neurocognitive dysfunction has been associated with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, although PTSD is often comorbid with MDD, there is little neurocognitive work to date on individuals who suffer from both PTSD and MDD. Here, we compared neurocognitive domains in individuals with PTSD, MDD, and comorbid PTSD and MDD with those of healthy controls.

Methods: Participants comprised of mothers enrolled in the Drakenstein Child Health Study, a study exploring child health determinants in the Drakenstein district, Western Cape. N = 175 mothers (between 18 and 50 years) were recruited and divided into 4 groups: PTSD, MDD, PTSD with MDD, and healthy controls. Participants were assessed using the computerized NIH Toolbox, and paper and pencil neurocognitive tests. Domains assessed included executive function, memory, attention, learning, and processing speed.

Results: Distinct patterns of neurocognitive dysfunction were observed in this sample. PTSD was associated with more intrusion errors and MDD was associated with delayed recall impairment, relative to healthy controls. PTSD with comorbid MDD was associated with processing speed impairments, relative to healthy controls, and monodiagnostic groups. No group differences were observed on measures of attention and executive function.

Conclusion: Distinct patterns of neurocognitive dysfunction were associated with diagnoses of MDD and PTSD. Greater anticipated dysfunction and impairment in comorbid PTSD and MDD was not observed, however. Further work is needed to replicate and extend these findings.
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http://dx.doi.org/10.1002/brb3.1950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035469PMC
April 2021

Improving lung health in low-income and middle-income countries: from challenges to solutions.

Lancet 2021 Mar 22;397(10277):928-940. Epub 2021 Feb 22.

British Thoracic Society Global Health Group, London, UK; Department of Respiratory Sciences, University of Leicester, Leicester, UK.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.
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http://dx.doi.org/10.1016/S0140-6736(21)00458-XDOI Listing
March 2021

Youth perinatal HIV-associated neurocognitive disorders: association with functional impairment.

AIDS Care 2021 Feb 24:1-5. Epub 2021 Feb 24.

Department of Psychiatry and Mental Health, University of Cape Town (UCT), Cape Town, South Africa.

HIV-associated functional impairment may cause cognitive impairment secondary to the viral infection, hence, associations between cognitive impairment and functional impairment in youth living with HIV are important to assess. We sought to determine whether cognitive impairment is associated with functional impairment and if it carries higher risk for also having functional impairment. We collected parent-rated information regarding youth functional impairment on four different measures and administered a cognitive battery to youth to determine cognitive impairment, 203 HIV-infected youth and 44 HIV-uninfected controls. Degree of cognitive impairment correlated strongly with decreased function: CBCL,  = -.17,  = .01; VABS2,  = -.28,  < .001; repeated-grades,  = .26,  < .001. Presence of cognitive impairment was associated with increased risk of functional impairment: 3.47 (CIS); 1.71 (CBCL); 2.17 (VABS2); 2.97 (repeated-grades). Repeated-grades strongly associated with cognitive impairment and functional impairment. We found strong associations between HIV-infected youth functional impairment on CBCL, VABS2 and repeated-grades with degree of cognitive impairment; and that when cognitive impairment was present youth had higher risk of experiencing functional impairment as well. Asking whether youth have repeated a grade at school could be a helpful screening question for assessing potential functional impairment and provide clinicians with an indication as to whether a further in-depth assessment is required.
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http://dx.doi.org/10.1080/09540121.2021.1891191DOI Listing
February 2021

Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures.

J Neurovirol 2021 Feb 7. Epub 2021 Feb 7.

Department of Neurology, David Geffen School of Medicine, at the University of California, Los Angeles, CA, USA.

We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock. However, whether epigenetic age acceleration in PHIV+ impacts brain development at the macro- and microstructural levels of brain anatomy has not been studied. We report on a cross-sectional study of PHIV+ enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 180 PHIV+ aged 9 to 12 years. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration (AgeAccelerationResidual) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent T1 structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). In order to investigate the associations of chronological age, sex, epigenetic age acceleration and treatment variables (CNS penetration effectiveness score (CPE)) of antiretroviral regimen on brain structure in PHIV+, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, cortical surface area and DTI measures of white matter microstructural integrity. The mean DNAm age (16.01 years) of the participants was higher than their mean chronological age (10.77 years). Epigenetic age acceleration contributed more to regional alterations of brain volumes, cortical thickness, cortical surface areas and neuronal microstructure than chronological age, in a range of regions. CPE positively contributed to volume of the brain stem. Understanding the drivers of epigenetic age acceleration could lead to valuable insights into structural brain alterations, and the persistence of neurocognitive disorders in seen in PHIV+ .
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http://dx.doi.org/10.1007/s13365-021-00947-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346577PMC
February 2021
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