Childhood tuberculosis deskguide and monitoring: An intervention to improve case management in Pakistan

Background: Childhood tuberculosis (TB) has been a neglected area in national TB control programme (NTCP) in high burden countries. The NTP Pakistan adapted the global approaches by developing and piloting its policy guideline on childhood TB in ten districts of the country. We developed an intervention package including a deskguide and a monitoring tool and tested with the ongoing childhood TB care in a district. The objective of our study was to measure effectiveness of intervention package with deskguide and monitoring tool by comparing TB case finding and treatment outcomes among districts in 2008, and performance assessment in intervention district. Method: An intervention study with cohort design within a routine TB control programme comparing case findings and treatment outcomes before and after the intervention, and in districts with and without intervention. We enrolled all children below 15 years registered at all nine public sector hospitals in three districts of Pakistan. The data was collected from hospital TB records. Results: In eight months during 2007 there were 164 childhood TB cases notified, and after intervention in 2008 a total of 194 cases were notified. In intervention district case finding doubled (110% increase) and correct treatment practice significantly increased in eight months. Successful outcomes were significantly higher in intervention district (37,100%) compared to control district A (18, 18%, p < 0.05) and control district B (41, 72%, p < 0.05). Conclusion: Childhood TB deskguide and structured monitoring was associated with improved case management and it augmented NTP policy. More development and implementation in all health services of the district are indicated.publishedVersio

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk

Funder: Funding details are provided in the Supplementary MaterialAbstractPolygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28–1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08–1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30–1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.</jats:p

Childhood tuberculosis in South Africa : what is the present status?

EditorialThe original publication is available at http://www.samj.org.zaIn a recently published article it was estimated that the incidence of childhood tuberculosis (TB) in the Western Cape was 407 new cases per 100 000 childhood population per year.1 This incidence was approximately half that in the adult population. Children younger than 13 years of age contributed 13.7% of the total TB burden.1 Further, 10% of the children with TB had severe disease including miliary TB, TB meningitis and spinal TB.Publishers' Versio

Clinical features and lung function in HIV-infected children with chronic lung disease

CITATION: Weber, H. C., et al. 2015. Clinical features and lung function in HIV-infected children with chronic lung disease. South African Journal of Child Health , 9(3):72-75, doi:10.7196/SAJCH.7940.The original publication is available at http://www.sajch.org.zaBackground. Although chronic lung disease (CLD) is commonly seen in children with advanced HIV disease, it is poorly studied. Objectives. To report on the clinical manifestations and lung function tests in children with advanced HIV disease at a tertiary care centre, and determine clinical predictors of poor lung function. Methods. We undertook a cross-sectional study of children with advanced HIV disease in whom CLD was suspected. We undertook clinical evaluation and lung function tests, accompanied by a retrospective chart review. Results. In 56 children identified, the median age was 5 (interquartile range (IQR) 2 - 8) years with equal gender ratio. The majority (93%) had been previously treated for tuberculosis and/or pneumonia (71%). The most common CLD identified was lymphocytic interstitial pneumonitis (54%). The median nadir CD4 percentage was 13% (IQR 8.5 - 16%) and the median highest reported viral load was log5.8 (IQR log5.0 - log6.5). The median duration of antiretroviral therapy was 9.8 (IQR 1.1 - 19.5) months. Lung function tests were performed in 27 (48%) children. The median forced expiratory volume in 1 second (FEV1) was 60% (IQR 45.3 - 86.3%) predicted. Previous hospitalisation, respiratory rate, digital clubbing, chest hyperinflation and hyperpigmented skin lesions were associated with a decreased FEV1 in a univariate relationship. In a multiple linear regression analysis, hyperinflation, increased respiratory rate and hyperpigmented skin lesions were associated with poor lung function (percentage FEV1). Conclusion. We identified useful clinical signs predictive of poor lung function in HIV-infected children with CLD, especially in resource-limited settings.http://www.sajch.org.za/index.php/SAJCH/article/view/781Publisher's versio

Computerised tomography findings in lymphobronchial tuberculosis: A comparison between infants and older children

No abstract available

Antenatal tobacco smoke exposure: impact on infant birth outcomes and lower respiratory tract infection in a South African birth cohort

Background The impact of antenatal tobacco smoke exposure, on child health outcomes has not been well studied in African children. This study investigated the prevalence of antenatal tobacco smoke exposure and the associations with infant birth outcomes and lower respiratory tract infection (LRTI) in the Drakenstein Child Health Study (DCHS), a South African birth cohort. Methods Consenting pregnant women were enrolled antenatally and mother-infant pairs followed from birth through the first year of life. Self-reported questionnaires assessed maternal and household smoking and maternal urine cotinine collected antenatally and at birth was measured. Birth outcomes including weight-for-age (WfA) z scores, low birth weight (LBW) and small for gestational age (SGA) were recorded. LRTI defined using WHO criteria was documented by trained study staff during the first year of life. Linear (WfA z-score), logistic (LBW, SGA) and Poisson (LRTI) regressions were used to investigate associations with tobacco smoke exposure. Results 1137 women were enrolled with 1143 live births. Urine cotinine measures classified 352/1093 (32%) as active and 479/1093 (44%) as passive smokers. Median birth weight was 3,085 (IQR2,710 - 3,420) kg; 524 episodes of LRTI occurred. Infants of active smokers had a 0.32 (95%CI 0.10 - 0.53) lower WfA z score and almost doubled risk of being SGA [OR 1 .71 (95%CI 1.11 - 2.64)]. Maternal smoking was associated with an increased risk of LRTI [IR 1.56 (95%CI1.25 - 1.93)]. Variable WfA Z-score (regression co-efficients) WfA Z-score (regression co-efficients) Low birth weight (OR) Low birth weight (OR) Small for Gestational age (OR) Small for Gestational age (OR) LRTI (IRR) LRTI (IRR) Antepartum smoking Crude Adjusted Crude Adjusted Crude Adjusted Crude Adjusted Active -0.44 (-0.62 - 0.26) -0.32 (-0.53 - -0.10) 1.91 (1.21 - 3.05) 1.40 (0.80 -2.47) 1.83 (1.28 - 2.63) 1.71 (1.11 - 2.64) 1.40 (1.16 - 1.69) 1.56 (1.25 - 1.93) Passive -0.01 (-0.18 - 0.16) 0.05 (-0.13 - 0.23) 1.13 (0.71 - 1.80) 1.05 (0.63 - 1.75) 0.80 (0.55 - 1.16) 0.79 (0.53 - 1.17) 1.09 (0.91 - 1.32) 1.11 (0.91 - 1.35) [Tobacco smoke exposure, birth outcomes and LRTI] Conclusions There was a high prevalence of antenatal maternal smoking and tobacco smoke exposure which significantly impacted on infant birth outcomes and LRTI incidence in infants. Urgent and effective interventions to reduce antenatal tobacco smoke exposure are required to improve child health. Funding: Bill &amp; Melinda Gates Foundation (OPP1017641), Discovery Foundation, South African Thoracic Society AstraZeneca Respiratory Fellowship, CIDRI Clinical Fellowship, Medical Research Council, South Africa, National Research Foundation, South Afric