31 research outputs found
Bordetella species in children with cystic fibrosis: What do we know? The role in acute exacerbations and chronic course
AbstractDespite vaccination, pertussis is still endemic in the Netherlands. A literature search was performed to verify what is known about the role of Bordetella species in children with cystic fibrosis, with regard to the incidence of Bordetella infections, the involvement in pulmonary exacerbations and the influence on chronic course.Little is known about the frequency of Bordetella infections and the involvement of Bordetella species both in relation to the chronic course of cystic fibrosis and to pulmonary exacerbations. Since it is difficult to detect Bordetella species in cultures and few sputum cultures investigated have been obtained during an exacerbation, it is likely that the frequency of Bordetella species in CF patients is underestimated. Identification of Bordetella species in these patients may have serious consequences for the treatment of exacerbations in CF.Future research investigating the role of Bordetella species in cystic fibrosis should use specific techniques to detect Bordetella in cultures
Treatment with highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children is associated with a sustained effect on growth
INTRODUCTION: Growth failure is a common feature of children with human
immunodeficiency virus type 1 (HIV-1) infection. Children who are treated
with mono or dual nucleoside analogue reverse transcriptase inhibitor
(NRTI) therapy show a temporary increase in weight gain and linear growth
rate. In adults, protease-inhibitor-containing antiretroviral therapy is
associated with a sustained weight gain and increased body mass index
(BMI). Experience with protease inhibitors and growth in children is still
limited. The data mainly deal with short-term effects on growth.
OBJECTIVE: To evaluate the effect of highly active antiretroviral therapy
(HAART) on growth in children with HIV-1 infection. DESIGN AND METHODS: We
analyzed selected growth parameters, clinical data, and laboratory results
as part of a prospective, open, uncontrolled, multicenter study to
evaluate the clinical, immunologic, and virologic response to HAART
consisting of indinavir, zidovudine, and lamivudine in children with HIV-1
infection. Height and weight were measured at 0, 12, 24, 36, 48, 60, 72,
84, and 96 weeks after initiation of HAART. Information about the
children's growth before enrollment in the study was retrieved from the
hospital medical records and/or the school doctor or health center. BMI
was calculated. z Scores were used to express the standard deviation (SD)
in SD units from the Dutch reference curves for age and gender. Viral
loads and CD4+ T-cell counts were examined prospectively and related to
these growth parameters. z Scores were also calculated for CD4+ T-cell
counts to correct for age-related differences. A z score of 0 represents
the P50, which is exactly the age/sex-appropriate median. A height z score
of -1 indicates that a child's height is 1 SD below the age- and
gender-specific median height for the normal population. Virologic
responders were defined as those who either reached an undetectable viral
load (1.5 log reduction in viral load compared
with baseline at week 12 after the initiation of HAART, which was
maintained during the follow-up period. RESULTS. PATIENTS: Twenty-four
patients were included (age: 0.4-16.3 years at baseline), with a median
HIV-1 RNA load of 105 925 copies/mL (5.03 log), a median CD4+ T-cell count
of 0.586 x 10(9)/L (median z score: -2.28 SD), a median height z score of
-1.22, a median weight z score of -0.74, and a median baseline BMI z score
of -0.32. Eleven patients were naive to antiretroviral therapy, and 13
patients had received previous treatment with NRTI monotherapy. Twenty
children used indinavir and 4 children used nelfinavir as part of HAART.
VIROLOGIC AND IMMUNOLOGIC RESPONSES TO HAART: Seventeen children were
virologic responders, and 7 children were virologic nonresponders. In
patients naive to NRTIs, median baseline viral loads were significantly
higher than in pretreated patients. However, at weeks 48 and 96, there was
no significant difference between the viral loads of both groups. At
baseline, there was no significant difference in CD4+a T-cell z scores
between virologic responders and nonresponders or between naive and
pretreated patients. During 96 weeks of HAART, the increase of CD4+ T-cell
z score was significantly higher in responders than in nonresponders. The
increase in CD4+ T-cell z score was not significantly different for naive
and pretreated patients. HEIGHT, WEIGHT, AND BMI z SCORE CHANGES: We found
that
Identification of regulatory variants associated with genetic susceptibility to meningococcal disease
Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes
Plasma lipid profiles discriminate bacterial from viral infection in febrile children
Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics
Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.
Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes
Plasma lipid profiles discriminate bacterial from viral infection in febrile children
Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar
Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study
BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC