Tuberculosis patients' reasons for, and suggestions to address non-uptake of HIV testing: a cross-sectional study in the Free State Province, South Africa

<p>Abstract</p> <p>Background</p> <p>South Africa endorses the global policy shift from primarily client-initiated voluntary counselling and testing (VCT) to routine/provider-initiated testing and counselling (PITC). The reason for this policy shift has been to facilitate uptake of HIV testing amongst at-risk populations in high-prevalence settings. Despite ostensible implementation of routine/PITC, uptake amongst tuberculosis (TB) patients in this country remains a challenge. This study presents the reasons that non-tested TB patients offered for their refusal of HIV testing and reflects on all TB patients' suggestions as to how this situation may be alleviated.</p> <p>Methods</p> <p>In February-March 2008, a cross-sectional survey was conducted amongst 600 TB patients across 61 primary health care facilities in four sub-districts in the Free State. Patient selection was done proportionally to the numbers registered at each facility in 2007. Data were subjected to bivariate tests and content analysis of open-ended questions.</p> <p>Results</p> <p>Almost one-third (32.5%) of the respondents reported that they had not undertaken HIV testing, with the most often offered explanation being that they were '<it>undecided</it>' (37.0%). Other self-reported reasons for non-uptake included: fear (e.g. of testing HIV-positive, 19.0%); perception of being at low risk of HIV infection (13.4%); desire first to deal with TB 'on its own' (12.5%); and because HIV testing had not been offered to them (12.0%). Many patients expressed the need for support and motivation not only from health care workers (33.3%), but also from their significant others (56.6%). Patients further expressed a need for (increased) dissemination of TB-HIV information by health care workers (46.1%).</p> <p>Conclusions</p> <p>Patients did not undergo HIV testing for various patient-/individual-related reasons. Non-uptake of HIV testing was also due to health system limitations such as the non-offer of HIV testing. Other measures may be necessary to supplement routine/provider-initiation of HIV testing. From the TB patient's perspective, there is a need for (improved) dissemination of information on the TB-HIV link. Patients also require (repeated) motivation and support to undergo HIV testing, the onus for which rests not only on the public health authority and health care workers, but also on other people in the patients' social support networks.</p

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.</p

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Cerebral white matter in early puberty is associated with luteinizing hormone concentrations

Puberty is a period in which cerebral white matter grows considerably, whereas gray matter decreases. The first endocrinological marker of puberty in both boys and girls is an increased secretion of luteinizing hormone (LH). Here we investigated the phenotypic association between LH, global and focal gray and white matter in 104 healthy nine-year-old monozygotic and dizygotic twins. Volumetric MRI and voxel-based morphometry were applied to measure global gray and white matter and to estimate relative concentrations of regional cerebral gray and white matter, respectively. A possible common genetic origin of this association (genetic correlation) was examined. Results showed that higher LH levels are associated with a larger global white matter proportion and with higher regional white matter density. Areas of increased white matter density included the cingulum, middle temporal gyrus and splenium of the corpus callosum. No association between LH and global gray matter proportion or regional gray matter density was found. Our data indicate that a common genetic factor underlies the association between LH level and regional white matter density. We suggest that the increase of white matter growth during puberty reported earlier might be directly or indirectly mediated by LH production. In addition, genes involved in LH production may be promising candidate genes in neuropsychiatric illnesses with an onset in early adolescence

Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge

Objective: To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of community midwives. Study design: Pre- and postductal oxygen saturations (SpO2) were measured ≥1 hour after birth and on day 2 or 3. Screenings were positive if the SpO2 measurement was 3%. Positive screenings were referred for pediatric assessment. Primary outcomes were sensitivity, specificity, and false-positive rate of pulse oximetry screening for CCHD. Secondary outcome was detection of noncardiac illnesses. Results: The prenatal detection rate of CCHDs was 73%. After we excluded these cases and symptomatic CCHDs presenting immediately after birth, 23 959 newborns were screened. Pulse oximetry screening sensitivity in the remaining cohort was 50.0% (95% CI 23.7-76.3) and specificity was 99.1% (95% CI 99.0-99.2). Pulse oximetry screening was false positive for CCHDs in 221 infants, of whom 61% (134) had noncardiac illnesses, including infections (31) and respiratory pathology (88). Pulse oximetry screening did not detect left-heart obstructive CCHDs. Including cases with prenatally detected CCHDs increased the sensitivity to 70.2% (95% CI 56.0-81.4). Conclusion: Pulse oximetry screening adapted for perinatal care in home births and early postdelivery hospital discharge assisted the diagnosis of CCHDs before signs of cardiovascular collapse. High prenatal detection led to a moderate sensitivity of pulse oximetry screening. The screening also detected noncardiac illnesses in 0.6% of all infants, including infections and respiratory morbidity, which led to early recognition and referral for treatment