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1.
Pediatr Pulmonol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571431

RESUMO

OBJECTIVE: The association of perinatal psychological adversity (ie, stressors and distress) with infant lung function (ILF) and development is not well studied in Africa and elsewhere. We determined the association between maternal perinatal psychological adversity and ILF in African infants. DESIGN: Prospective longitudinal follow up of the Drakenstein Child Health Study birth cohort. PARTICIPANTS: Seven hundred and sixty-two infants aged 6 to 10 weeks and 485 infants who had data for both maternal perinatal psychological adversity and ILF (measured at 6 to 10 weeks and 12 months). METHODS: The main analyses were based on cross-sectional measures of ILF at each assessment (6 to 10 weeks or 12 months), using generalized linear models, and then on the panel-data of both longitudinal ILF assessments, using generalised estimating equations, that allowed specification of the within-group correlation structure. RESULTS: Prenatal intimate partner violence (IPV) exposure was associated with reduced respiratory resistance at 6 to 10 weeks (beta coefficient [ß] = -.131, P = .023); postnatal IPV with reduced ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF /tE ) at 12 months (ß = -.206, P = .016); and prenatal depression with lower respiratory rate at 6 to 10 weeks (ß = -.044, P = .032) and at 12 months (ß = -.053, P = .021). Longitudinal analysis found an association of prenatal IPV with reduced tPTEF /tE (ß = -.052, P < .0001); postnatal IPV with decreased functional residual capacity (FRC; ß = -.086, P < .0001); prenatal posttraumatic stress disorder with increased FRC (ß = .017, P < .0001); prenatal depression with increased FRC (ß = .026, P < .0001) and postnatal depression with increased FRC (ß = .021, P < .0001). CONCLUSION: Screening for psychological adversity and understanding the mechanisms involved may help identify children at risk of altered lung development and inform approaches to treatment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31515160

RESUMO

BACKGROUND: HIV infection is known to cause developmental delay, but the effects of HIV exposure without infection during pregnancy on child development are unclear. We compared the neurodevelopmental outcomes of HIV-exposed uninfected and HIV-unexposed children during their first 2 years of life. METHODS: Pregnant women (>18 years of age) at 20-28 weeks' gestation were enrolled into the Drakenstein Child Health cohort study while attending routine antenatal appointments at one of two peri-urban community-based clinics in Paarl, South Africa. Livebirths born to enrolled women during follow-up were included in the birth cohort. Mothers and infants received antenatal and postnatal HIV testing and antiretroviral therapy per local guidelines. Developmental assessments on the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), were done in a subgroup of infants at 6 months of age, and in the full cohort at 24 months of age, with assessors masked to HIV exposure status. Mean raw scores and the proportions of children categorised as having a delay (scores <-2 SDs from the reference mean) on BSID-III were compared between HIV-exposed uninfected and HIV-unexposed children. FINDINGS: 1225 women were enrolled between March 5, 2012, and March 31, 2015. Of 1143 livebirths, 1065 (93%) children were in follow-up at 6 months and 1000 (87%) at 24 months. Two children were diagnosed with HIV infection between birth and 24-month follow-up and were excluded from the analysis. BSID-III assessments were done in 260 (24%) randomly selected children (61 HIV-exposed uninfected, 199 HIV-unexposed) at 6 months and in 732 (73%) children (168 HIV-exposed uninfected, 564 HIV-unexposed) at 24 months. All HIV-exposed uninfected children were exposed to antiretrovirals (88% to maternal triple antiretroviral therapy). BSID-III outcomes did not significantly differ between HIV-exposed uninfected and HIV-unexposed children at 6 months. At 24 months, HIV-exposed uninfected children scored lower than HIV-unexposed for receptive language (adjusted mean difference -1·03 [95% CI -1·69 to -0·37]) and expressive language (-1·17 [-2·09 to -0·24]), whereas adjusted differences in cognitive (-0·45 [-1·32 to 0·43]), fine motor (0·09 [-0·49 to 0·66]), and gross motor (-0·41 [-1·09 to 0·27]) domain scores between groups were not significant. Correspondingly, the proportions of HIV-exposed uninfected children with developmental delay were higher than those of HIV-unexposed children for receptive language (adjusted odds ratio 1·96 [95% CI 1·09 to 3·52]) and expressive language (2·14 [1·11 to 4·15]). INTERPRETATION: Uninfected children exposed to maternal HIV infection and antiretroviral therapy have increased odds of receptive and expressive language delays at 2 years of age. Further long-term work is needed to understand developmental outcomes of HIV-exposed uninfected children, especially in regions such as sub-Saharan Africa that have a high prevalence of HIV exposure among children. FUNDING: Bill & Melinda Gates Foundation, SA Medical Research Council, Wellcome Trust.

3.
Pediatr Pulmonol ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475477

RESUMO

INTRODUCTION: Chest ultrasound is increasingly used to radiologically diagnose childhood pneumonia, but there are limited data on its use for pulmonary tuberculosis (PTB). AIM: Compare chest ultrasound with a chest X-ray (CXR) findings. METHODS: Children (up to 13 years) with suspected PTB were enrolled. Bedside chest ultrasound findings were compared to CXR. The analysis was stratified by PTB category: confirmed PTB (microbiologically confirmed), unconfirmed PTB (clinical diagnosis with negative microbiological tests), or unlikely PTB (other respiratory diseases with improvement without tuberculosis treatment). RESULTS: One hundred fifty-nine children were enrolled (57% boys, median age 26.6 months [interquartile range 15.1-59.3]). Ultrasound detected abnormalities in 72% (n = 114), CXR in 56% (n = 89), P < .001. Pleural effusion was detected on ultrasound in 15% (n = 24) compared 9% (n = 14) on CXR, P = .004, more in confirmed PTB (33%, n = 12 vs 8%, n = 4 unlikely PTB, P = .013). Ultrasound detected enlarged mediastinal lymph nodes more commonly (22%, n = 25) than CXR (6%, n = 10, P = .001); the size of lymph nodes in the unlikely category (1.0 cm) was smaller than the other two PTB categories (1.4 and 1.5 cm, P = .001). Inter-reader agreement (kappa Cohen) was higher for ultrasound than CXR for several findings (consolidation 0.67 vs 0.47, pleural effusion 0.86 vs 0.56, enlarged lymph nodes 0.56 vs 0.27). CONCLUSION: Ultrasound detected abnormalities more frequently than CXR with the higher inter-reader agreement; ultrasound abnormalities were most common in children with confirmed PTB. Ultrasound is a promising modality for detecting abnormalities in PTB. Further studies should evaluate the diagnostic accuracy of ultrasound against a gold standard.

4.
PLoS Med ; 16(9): e1002920, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31560687

RESUMO

BACKGROUND: Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities. METHODS AND FINDINGS: The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks' gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning 1 domain affected, and 75 (10.2%) had delay in all domains. Bivariate and multivariable analyses revealed several factors that were associated with developmental outcomes. These included protective factors (maternal education, higher birth weight, and socioeconomic status) and risk factors (maternal anaemia in pregnancy, depression or lifetime intimate partner violence, and maternal HIV infection). Boys consistently performed worse than girls (in cognition [ß = -0.74; 95% CI -1.46 to -0.03, p = 0.042], receptive language [ß = -1.10; 95% CI -1.70 to -0.49, p < 0.001], expressive language [ß = -1.65; 95% CI -2.46 to -0.84, p < 0.001], and fine motor [ß = -0.70; 95% CI -1.20 to -0.20, p = 0.006] scales). There was evidence that child sex interacted with risk and protective factors including birth weight, maternal anaemia in pregnancy, and socioeconomic factors. Important limitations of the study include attrition of sample from birth to assessment age and missing data in some exposure areas from those assessed. CONCLUSIONS: This study provides reliable developmental data from a sub-Saharan African setting in a well-characterised sample of mother-child dyads. Our findings highlight not only the important protective effects of maternal education, birth weight, and socioeconomic status for developmental outcomes but also sex differences in developmental outcomes and key risk and protective factors for each group.

5.
Paediatr Respir Rev ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31422032

RESUMO

OBJECTIVES: To review epidemiology, aetiology and management of childhood pneumonia in low-and-middle-income countries. DESIGN: Review of published English literature between 2013 and 2019. RESULTS: Pneumonia remains a major cause of morbidity and mortality. Risk factors include young age, malnutrition, immunosuppression, tobacco smoke or air pollution exposure. Better methods for specimen collection and molecular diagnostics have improved microbiological diagnosis, indicating that pneumonia results from several organisms interacting. Induced sputum increases microbiologic yield for Bordetella pertussis or Mycobacterium tuberculosis, which has been associated with pneumonia in high TB prevalence areas. The proportion of cases due to Streptococcus pneumoniae and Haemophilus influenzae b has declined with new conjugate vaccines; Staphylococcus aureus and H. influenzae non-type b are the commonest bacterial pathogens; viruses are the most common pathogens. Effective interventions comprise antibiotics, oxygen and non-invasive ventilation. New vaccines have reduced severity and incidence of disease, but disparities exist in uptake. CONCLUSION: Morbidity and mortality from childhood pneumonia has decreased but a considerable preventable burden remains. Widespread implementation of available, effective interventions and development of novel strategies are needed.

6.
J Affect Disord ; 259: 279-287, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31454590

RESUMO

BACKGROUND: Perinatal depression affects 21-50% of women in South Africa and poses significant health risks to mothers and children. Trajectories of depressive symptoms change over time and have not been well characterized during the perinatal period in low and middle-income countries. METHODS: Data from women enrolled in a population-based birth cohort study in Paarl, South Africa with at least 3 depression measures from pregnancy through 18 months postpartum (N = 831) were analyzed. Depressive symptoms were measured continuously using the Edinburgh Postnatal Depression Scale (EPDS). Group-based trajectory models were used to estimate trajectories of depressive symptoms during the perinatal period and multinomial multivariable models to identify predictors of trajectory group membership. RESULTS: Five distinct trajectory patterns of depressive symptoms were identified: moderate levels of depressive symptoms during pregnancy but minimal postpartum (3.5%), minimal levels during pregnancy and increasing postpartum (3.7%), unstable levels peaking at 12 months postpartum (6.6%), mild levels with slight decrease postpartum (82.9%), and severe levels during pregnancy and postpartum (3.1%). Membership in the chronic severe symptom group was associated with stressful life events, sexual intimate partner violence and tobacco use. LIMITATIONS: Modeling limitations prevented determining how changes in psychosocial predictors over time may influence depressive symptom trajectories. CONCLUSIONS: Mild to severe depressive symptoms during pregnancy/postpartum were common among this South African cohort. Interventions to treat women with severe chronic depressive symptoms with co-occurring psychosocial issues are urgently needed.

7.
J Int AIDS Soc ; 22(8): e25386, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441211

RESUMO

INTRODUCTION: Adolescents with perinatally acquired HIV (PHIV) are at risk of chronic disease due to long-standing immune suppression, HIV disease and antiretroviral therapy (ART) exposure. However, there are few data on multisystem disease in this population. We investigated the overlapping burden of neurocognitive, cardiovascular, respiratory and/or renal impairment among PHIV positive (PHIV+) adolescents. METHODS: In this cross-sectional analysis, participants aged 9 to 14 years on ART for >6 months were recruited from seven sites across Cape Town from July 2013 through March 2015, together with age-matched HIV-negative (HIV-) adolescents. Impairment at enrolment was assessed across neurocognitive functioning (using the youth-International HIV Dementia Scale); cardiac function (echocardiogram abnormality); respiratory function (abnormal spirometry) and renal function (abnormal glomerular filtration rate). RESULTS AND DISCUSSION: Overall, 384 PHIV+ and 95 HIV- adolescents were included (mean age, 11.9 years; 49% female). Median age of ART initiation was 4.2 years (IQR: 1.7 to 7.6) and median CD4 count was 709 (IQR: 556 to 944) with 302 (79%) of PHIV+ adolescents virologically suppressed. Abacavir and Zidovudine were the most commonly used nucleoside reverse transcriptase inhibitors (NRTIs) with 60% of adolescents on non-nucleoside reverse transcriptase inhibitors (NNRTI) and 38% on a protease inhibitor (PI). Among PHIV+ adolescents, 167 (43.5%) had single system impairment only, 110 (28.6%) had two systems involved, and 39 (10.2%) had three or four systems involved. PHIV+ participants had more 2-system and 3-system impairment than HIV-, 110 (28.6%) versus 17 (17.9%), p = 0.03 and 39 (10.2%) versus 3 (4.3%), p = 0.03. PHIV+ participants who had failed a year of school (73.8% vs. 46.4%, p = 0.00) and with a viral load >1000 copies/mL at enrolment (16.8% vs. 8.1%, p = 0.03) were more likely to have dual or multisystem impairment. Of those with cardiac impairment, 86.7% had an additional system impaired. Similarly, in those with neurocognitive impairment, almost 60% had additional systems impaired and of those with respiratory impairment, 74% had additional systems impaired. CONCLUSIONS: Despite relatively early ART initiation, there is a substantial burden of multisystem chronic impairment among PHIV+ adolescents. This phenomenon needs to be further explored as this population ages and begins to engage in adult lifestyle factors that may compound these impairments.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31381861

RESUMO

RATIONALE: Microbiological confirmation of pulmonary tuberculosis in children is desirable. OBJECTIVES: To investigate the diagnostic accuracy and incremental yield of Xpert-Ultra, a new rapid test, on repeated induced sputum, nasopharyngeal aspirates and combinations of specimens. METHODS: Consecutive South African children hospitalized with suspected pulmonary tuberculosis were enrolled. MEASUREMENTS: Induced sputum and nasopharyngeal aspirates were obtained. Nasopharyngeal aspirates were frozen; induced sputum underwent liquid culture, an aliquot was frozen. Ultra was performed on thawed nasopharyngeal aspirates and induced sputum specimens individually. Children were categorised as confirmed, unconfirmed or unlikely tuberculosis according to NIH consensus case definitions. The diagnostic accuracy of Ultra was compared with liquid culture on induced sputum. MAIN RESULTS: 195 children [median age 23·3 months, 32(16·4%) HIV-infected] had one induced sputum and nasopharyngeal aspirate; 130 had two nasopharyngeal aspirates. There were 40(20·5%) culture confirmed cases. Ultra was positive on nasopharyngeal aspirates in 26(13·3%) and on induced sputum in 31(15·9%). Sensitivity and specificity of Ultra on one nasopharyngeal-aspirate were 46% and 98% respectively, similar by HIV status. Sensitivity and specificity of Ultra on one induced sputum were 74·3% and 96·9% respectively. Combining one nasopharyngeal aspirate and one induced sputum increased sensitivity to 80%. Sensitivity using Ultra on two nasopharyngeal aspirates was 54.2%, increasing to 87.5% with an induced sputum Ultra. CONCLUSIONS: Induced sputum provides a better specimen than repeated nasopharyngeal aspirate for rapid diagnosis using Ultra. However, Ultra testing of combinations of specimens provides a novel strategy that can be adapted to identify most children with confirmed pulmonary tuberculosis.

9.
Sci Rep ; 9(1): 10789, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346252

RESUMO

Microbiological diagnosis of pediatric pulmonary tuberculosis (TB) is challenging due to the difficulty of collecting and testing sputum from children. We investigated whether easily-obtained oral swab samples are useful alternatives or supplements to sputum. Oral swabs and induced sputum (IS) were collected from 201 South African children with suspected pulmonary TB. IS samples were tested by mycobacterial culture and Xpert MTB/RIF. Oral swabs were tested by PCR targeting IS6110. Children were categorized as Confirmed TB (microbiologic confirmation on IS), Unconfirmed TB (clinical diagnosis only), or Unlikely TB (recovery without TB treatment). Relative to Confirmed TB, PCR on two oral swabs per child was 43% sensitive and 93% specific. This sensitivity fell below that of sputum Xpert (64%). Among children with either Confirmed or Unconfirmed TB, PCR on two oral swabs per child was 31% sensitive and 93% specific, which was more sensitive than sputum testing among this group (21%). Although oral swab analysis had low sensitivity in sputum-positive children, it detected TB in a significant proportion of sputum-negative children who were clinically diagnosed with TB. Specificity at 93% was suboptimal but may improve with the use of automated methods. With further development, oral swabs may become useful supplements to sputum as samples for diagnosis of pulmonary TB in children.

10.
Pediatr Pulmonol ; 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31338996

RESUMO

INTRODUCTION: Chronic lung disease is common in perinatally HIV-infected children as they increasingly surviving into adolescence. There are few data on the radiologic spectrum of disease in this population. METHODS: Contrasted high-resolution computed tomography (HRCT) was performed in ambulatory South African adolescents enrolled in a prospective study of perinatally-infected adolescents aged 9 to 14 years established on combined antiretroviral therapy (cART) and followed for 36 months. Consecutive participants with reduced lung function (defined by a forced expiratory volume in 1 second [FEV1] of <80% normal and/or lung diffusion capacity [DLCO] <80% normal] underwent HRCT. History, clinical, and laboratory data were collected. Two radiologists blinded to clinical data and to each other, reported scans using standardized methodology; a third radiologist resolved discrepancies. RESULTS: Amongst 100 participants undergoing HRCT, median age was 13.8 years (12.8-15.1). The median duration on cART was 8.4 years (IQR = 5.7-9.8). Mosaic attenuation was the most common finding (73%). Of these 71 (91%) demonstrated associated air trapping radiologically consistent with bronchiolitis obliterans. Bronchiectasis occurred in 39% with significant correlation between extent of bronchiectasis and mosaic attenuation (r = 0.57, P < .001). Prior hospitaliszation for childhood pneumonia at any time before enrollment was associated with mosaic attenuation (OR = 3.9, 95%CI, [1.2-12.5]); prior pulmonary tuberculosis (TB) was associated with the combination of mosaic attenuation and bronchiectasis (OR = 4.9, 95%CI, [1.6-15.7]). Most participants (86%) with mosaic attenuation had stage III or IV HIV disease at time of HIV diagnosis (OR = 3.6; [0.9-14.9]). Inter observer agreement between the two readers was good for bronchiectasis (K = 0.71) and moderate for mosaic attenuation (K = 0.51). DISCUSSION: Despite well-controlled HIV and long duration of cART, HRCT changes were common in perinatally HIV-infected adolescents. There was a high prevalence of small airways disease with and without associated bronchiectasis. These changes were associated with prior pulmonary TB or prior severe pneumonia. Strategies to prevent and treat early life respiratory infection must be strengthened to reduce the burden of chronic lung disease in HIV-infected adolescents.

11.
Nat Commun ; 10(1): 2548, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186427

RESUMO

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.


Assuntos
Metilação de DNA/genética , DNA/sangue , Interação Gene-Ambiente , Estudos de Coortes , Epigênese Genética , Feminino , Sangue Fetal , Genótipo , Humanos , Recém-Nascido , Masculino , Gravidez , Fatores de Risco
12.
Nutrients ; 11(6)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226873

RESUMO

The human breast milk (HBM) bacteriome is an important, continuous source of microbes to the neonate in early life, playing an important role in shaping the infant's intestinal bacteriome. Study of the composition of the HBM bacteriome is an emerging area of research, with little information available, particularly from low- and middle-income countries. The aim of this study was to characterize the diversity of bacterial communities in HBM samples collected between 6-10 weeks postpartum from lactating South African women and to study potential influencing factors of the bacteriome. Using 16S rRNA gene sequencing of samples from 554 women, we demonstrated that the HBM bacteriome was largely dominated by the phyla Firmicutes (mean relative abundance: 71.1%) and Actinobacteria (mean relative abundance: 16.4%). The most abundant genera identified from the HBM bacteriome were Streptococcus (mean relative abundance: 48.6%), Staphylococcus (mean relative abundance: 17.8%), Rothia (mean relative abundance: 5.8%), and Corynebacterium (mean relative abundance: 4.3%). "Core" bacterial genera including Corynebacterium, Streptococcus, Staphylococcus, Rothia, Veillonella, Gemella, Acinetobacter, Micrococcus and a genus belonging to the Enterobacteriaceae family were present in 80% of samples. HBM samples were classified, according to their bacteriome, into three major clusters, dominated by the genera Staphylococcus (cluster 1), a combination of Staphylococcus and Streptococcus (cluster 2), and Streptococcus (cluster 3). The cluster groups differed significantly for Shannon and chao1 richness indices. Bacterial interactions were studied using co-occurrence networks with positive associations observed between the abundances of Staphylococcus and Corynebacteria (members of the skin microflora) and between Streptococcus, Rothia, Veillonella, and Gemella (members of the oral microflora). HBM from older mothers had a higher Shannon diversity index. The study site was associated with differences in HBM bacteriome composition (permutational multivariate analysis of variance using distance matrices (PERMANOVA), p < 0.05). No other tested socio-demographic or psychosocial factors were associated with HBM bacterial composition.

13.
J Acquir Immune Defic Syndr ; 81(4): e109-e116, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31241543

RESUMO

BACKGROUND: The impact of HIV and antiretrovirals (ART) on long-term mental health in perinatally infected children has not been well studied in sub-Saharan Africa where HIV is most prevalent. SETTING: Cape Town, South Africa. METHODS: We investigated mental health measures, including depression, anxiety, attention-deficit hyperactivity disorder, motivation, disruptive behavior, and functioning in perinatally infected adolescents (PHIV+) stable on ART within the Cape Town Adolescent Antiretroviral Cohort. Two hundred four adolescents living with HIV (median age 10 years; mean CD4 953) and a sample of 44 uninfected adolescents were enrolled. The Beck Youth Inventories, Children's Motivation Scale, Conner's Parent's Rating Scale, and Child Behavior Checklist were administered. Among PHIV+, we explored independent associations between HIV-related stigma, recent life stressors, sociodemographic, clinical, and caregiver-related variables, and mental health measures. RESULTS: PHIV+ had poorer functional competence, self-concept and motivation, higher levels of disruptive behavior, depression and attention-deficit hyperactivity disorder symptoms and clinically significant anger and disruptive behavior. Within the PHIV+ group, the loss of both biological parents was associated with higher levels of disruptive behavior. Within the PHIV+, factors associated with mental health symptoms and poorer functioning were mostly sociodemographic factors, HIV-related stigma, and life stressors. Age of initiation of ART was associated with self-concept, and failing first-line ART with internalizing and externalizing behavior problems. CONCLUSIONS: PHIV+ are likely to face future physical and psychological health consequences related to the functional competence challenges they face if mental health care is not made a priority in the fight against HIV.

14.
J Neurovirol ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165369

RESUMO

Neurotoxicity associated with the antiretroviral efavirenz (EFV) has been documented in HIV-infected adults, but there are no data on the impact of EFV on brain function in adolescents. We investigated potential alterations in fronto-striatal function associated with EFV use in adolescents. A total of 86 adolescents underwent a Stop Signal Anticipation Task (SSAT) during functional MRI (fMRI), 39 HIV+ adolescents receiving EFV, 27 HIV+ adolescents on antiretroviral therapy without EFV (matched on age, gender, education, CD4 cell count and HIV viral load) and 20 HIV- matched controls (matched on age and gender). The task required participants to give timed GO responses with occasional STOP signals at fixed probabilities. Reactive inhibition was modelled as a correct STOP response and proactive inhibition was modelled after response slowing as the STOP probability increases. A priori mask-based regions associated with reactive and proactive inhibition were entered into two respective multivariate ANOVAs. The EFV treatment group showed significantly blunted proactive inhibitory behavioural responses compared to HIV+ adolescents not receiving EFV. There was no difference in reactive inhibition between treatment groups. We also demonstrated a significant effect of EFV treatment on BOLD signal in proactive inhibition regions. There was no difference in regions involved in reactive inhibition. We found no differences between adolescents not receiving EFV and HIV- controls, showing that functional and behavioural differences were unique to the EFV group. Here, we demonstrate for the first time a potential adverse impact of EFV on higher cortical function in young HIV+ adolescents.

15.
Lancet Respir Med ; 7(6): 544-552, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31078497

RESUMO

Tuberculosis is a major cause of death and disability among children globally, yet children have been neglected in global tuberculosis control efforts. Historically, tuberculosis in children has been thought of as a family disease, and because of this, household contact tracing of children after identification of an adult tuberculosis case has been emphasised as the principal public health intervention. However, the population-level effect of household contact tracing is predicated on the assumption that most paediatric tuberculosis infections are acquired within the household. In this Personal View, we focus on accumulating scientific evidence indicating that the majority of Mycobacterium tuberculosis transmission to children in high-burden settings occurs in the community, outside of households in which a person has tuberculosis. We estimate the population-attributable fraction of M tuberculosis transmission to children due to household exposures to be between 10% and 30%. M tuberculosis transmission from the household was low (<30%) even in children younger than age 5 years. We propose that an effective public health response to childhood tuberculosis requires comprehensive, community-based interventions, such as active surveillance in select settings, rather than contact tracing alone. Importantly, the historical paradigm that most paediatric transmission occurs in households should be reconsidered on the basis of the scientific knowledge presented.

16.
Paediatr Respir Rev ; 31: 52-57, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30987798

RESUMO

Pediatric asthma has been increasing in LMICs (Low Middle-Income Countries), leading to an important burden for both children and national health systems. Implementing measures to achieve control are influenced by the degree of organization health systems have, the availability and affordability of essential asthma medications, and the effective implementation of asthma programs and asthma guidelines. In this review authors give an updated view of the current situation of these components of asthma management in LMICs.

17.
Clin Infect Dis ; 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30938406

RESUMO

BACKGROUND: Despite increased access to highly active antiretroviral therapy (HAART), lung disease remains common in HIV-infected adolescents. There is limited information on changes in lung function over time in perinatally HIV-infected adolescents on HAART. OBJECTIVE: To investigate the progression of spirometry findings over 2 years in HIV-infected adolescents on HAART in a prospective cohort, the Cape Town Adolescent Anti-retroviral cohort (CTAAC). METHODS: HIV-infected adolescents aged 9-14 years, with at least 6 months of HAART, and a comparator group of healthy HIV-uninfected, age-matched controls were enrolled in CTAAC. Spirometry and bronchodilator testing was done at baseline, 12 and 24 months. Mixed-effect models were used to compute longitudinal changes in lung function. RESULTS: Five hundred and fifteen HIV-infected adolescents, mean (SD) age, 12 (1.6) years, 50.4% male; and 110 HIV-uninfected adolescents, mean (SD) age 11.8 (1.8), 45.6% male, were tested at baseline, 477 (93%) HIV-infected and 102 (93%) HIV-uninfected at 12 months and 473 (92%) HIV-infected and 97 (88%) uninfected adolescents at 24 months. Only 5.4% of the HIV-infected adolescents had HIV viral load>10000 copies/ml at baseline. FEV1 and FVC were lower in the HIV-infected compared to the uninfected adolescents and tracked with no deterioration or catch up over 2 years. Previous pulmonary tuberculosis (PTB) or lower respiratory tract infection (LRTI) was significantly associated with reduced FEV1 and FVC, p<0.05 for both. CONCLUSION: HIV-infected adolescents had lower lung function over 2 years than HIV-uninfected. This study highlights the need for lung function surveillance and prevention of LRTIs and PTB in HIV-infected adolescents.

19.
BMJ Open ; 9(3): e018277, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867198

RESUMO

OBJECTIVES: Better understanding of psychosocial risk factors for food insecurity (FI) during pregnancy and how they interact is crucial, given long-term health implications for maternal and child health. We investigated the association between maternal childhood trauma as well as intimate partner violence (IPV) and FI among pregnant women in South Africa, in the Drakenstein Child Health Study, and whether maternal depression mediates these relationships. SETTING: Two primary care clinics in Paarl, South Africa. PARTICIPANTS: 992 pregnant women; inclusion criteria were clinic attendance and remaining in area for at least 1 year; women were excluded if a minor. METHODS: We examined psychosocial predictors of FI using multivariate regression. Mediation analyses investigated whether depression mediated the relationship between IPV and FI as well as between childhood trauma and FI, including disaggregation by two study communities. FI was assessed using an adapted US Department of Agriculture food security scale; households were coded as food insecure where 2 of 5 affirmative responses were recorded. RESULTS: Among 992 pregnant women, there were high rates of IPV (7%-27%), depression (24%) and childhood trauma (34%). In multivariate cross-sectional analysis, emotional IPV (adjusted OR [aOR] 1.60; 95% CI 1.04 to 2.46), depression (aOR 1.05; 95% CI 1.01 to 1.08) and childhood trauma (aOR 1.52; 95% CI 1.08 to 2.15) predicted FI. In mediation models, depression partially mediated the relationship between emotional IPV and FI as well as physical IPV and FI; depression partially mediated the relationship between childhood trauma and FI. Differing degrees of mediation were found when applied to communities. CONCLUSIONS: Antenatal maternal depression, IPV and childhood trauma were highly prevalent and associated with FI. Depression, IPV and trauma screening services should be considered within routine antenatal care and may offer an opportunity to identify and intervene. Community-level differences in risk and in mediation analyses indicate that contextual tailoring of interventions may be important.

20.
Clin Infect Dis ; 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925191

RESUMO

BACKGROUND: Childhood lower respiratory tract infections (LRTIs) cause substantial morbidity and under-5 child mortality. The epidemiology of LRTI is changing in low- and middle-income countries with expanding access to conjugate vaccines, yet there are few data on the incidence and risk factors for LRTI in these settings. METHODS: A prospective birth cohort enrolled mother-infant pairs in 2 communities near Cape Town, South Africa. Active surveillance for LRTI was performed for the first 2 years of life over 4 respiratory seasons. Comprehensive data collection of risk factors was done through 2 years of life. World Health Organization definitions were used to classify clinical LRTI and chest radiographs. RESULTS: From March 2012 to February 2017, 1143 children were enrolled and followed until 2 years of age. Thirty-two percent of children were exposed to antenatal maternal smoking; 15% were born at low birth weights. Seven hundred ninety-five LRTI events occurred in 429 children by February 2017; incidence of LRTI was 0.51 and 0.25 episodes per child-year in the first and second years of life, respectively. Human immunodeficiency virus (HIV)-exposed, uninfected infants (vs HIV-unexposed infants) were at increased risk of hospitalized LRTI in the first 6 months of life. In regression models, male sex, low birth weight, and maternal smoking were independent risk factors for both ambulatory and hospitalized LRTI; delayed or incomplete vaccination was associated with hospitalized LRTI. CONCLUSIONS: LRTI incidence was high in the first year of life, with substantial morbidity. Strategies to ameliorate harmful exposures are needed to reduce LRTI burden in vulnerable populations.

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