The absence of HIV seropositivity contrasts with a high prevalence of markers of sexually transmitted infections among registered female sex workers in Toliary,Madagascar

In a cross-sectional study in 1998 we assessed human immunodeficiency virus (HIV) and syphilis infections and their risk factors among the 316 registered female sex workers (FSWs) of Toliary, south-west Madagascar. No case of HIV infection was detected, but 18.4% of registered FSWs had syphilis. Only half of these women regularly used condoms. In a multiple logistic regression analysis, risk factors for syphilis infection were multiple clients per week and, paradoxically, regular use of condoms. The variables associated with irregular use of condoms were younger ages of registered FSWs, multiple clients per week and Malagasy clients. The high prevalence of syphilis infection associated with irregular use of condoms might facilitate a very fast spread of HIV infection among these FSWs. Promotion of condom use and surveillance of sexually transmitted infections and HIV infection incidence are needed in the south of Madagascar.     

Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells.

Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line.     

Endocrine involvement in pediatric-onset Langerhans' cell histiocytosis: a population-based study

OBJECTIVE: To document the frequency and outcome of endocrine involvement in pediatric-onset Langerhans' cell histiocytosis (LCH), and the association with other types of organ involvement. STUDY DESIGN: This retrospective nationwide multicenter study involved 589 patients with pediatric-onset LCH, 148 of whom had endocrine dysfunction. Median follow-up was 11.6 years. RESULTS: Pituitary dysfunction was present in 145 patients, and 141 had diabetes insipidus (DI). The estimated 10-year risks of pituitary involvement were 24.2% +/- 1.8%. GH deficiency occurred in 61 patients. Median age at onset was 2.8 years for LCH, 3.9 years for DI, and 7.7 years for GH deficiency. The risk of cranial involvement; ear, nose, and throat involvement; pneumothorax; and cholangitis was significantly higher in patients with endocrinopathy. The chronology of episodes did not support a causal link between pituitary involvement and involvement of other organs. Systemic treatment of LCH did not prevent pituitary involvement. The most severe complication was a neurodegenerative syndrome, which affected 4.3% and 10.8% of patients, respectively, 5 and 15 years after initial diagnosis, and appeared to be linked to pituitary involvement. CONCLUSION: Patients who develop endocrine LCH disorders are at a high risk of neurodegenerative LCH and require long-term follow-up.     

Mapping vaccine hesitancy—Country-specific characteristics of a global phenomenon

The term vaccine hesitancy refers to delay in acceptance or refusal of vaccines despite the availability of vaccination services. Different factors influence vaccine hesitancy and these are context-specific, varying across time and place and with different vaccines. Factors such as complacency, convenience and confidence are involved. Acceptance of vaccines may be decreasing and several explanations for this trend have been proposed. The WHO Strategic Advisory Group of Experts (SAGE) on Immunization has recognized the global importance of vaccine hesitancy and recommended an interview study with immunization managers (IMs) to better understand the range of vaccine hesitancy determinants that are encountered in different settings. Interviews with IMs in 13 selected countries were conducted between September and December 2013 and various factors that discourage vaccine acceptance were identified. Vaccine hesitancy was not defined consistently by the IMs and most interpreted the term as meaning vaccine refusal. Although vaccine hesitancy existed in all 13 countries, some IMs considered its impact on immunization programmes to be a minor problem. The causes of vaccine hesitancy varied in the different countries and were context-specific, indicating a need to strengthen the capacity of national programmes to identify the locally relevant causal factors and to develop adapted strategies to address them.     

Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features, learning difficulties, and macrocephaly with frequent pre- and postnatal overgrowth with advanced bone age. Here, we report on our experience in the molecular diagnostic of Sotos syndrome on 116 patients. Using direct sequencing and a quantitative multiplex PCR of short fluorescent fragments (QMPSF)-based assay allowing accurate detection of both total and partial NSD1 deletions, we identified NSD1 abnormalities in 104 patients corresponding to 102 Sotos families (90%). NSD1 point mutations were detected in 80% of the index cases, large deletions removing the NSD1 gene entirely in 14%, and intragenic NSD1 rearrangements in 6%. Among the 69 detected distinct point mutations, 48 were novel. The QMPSF assay detected an exonic duplication and a mosaic partial deletion. QMPSF mapping of the 15 large deletions revealed the heterogeneity of the deletions, which vary in size from 1 to 4.5 Mb. Clinical features of NSD1-positive Sotos patients revealed that the phenotype in patients with nontruncating mutations was less severe that in patients with truncating mutations. This study confirms the heterogeneity of NSD1 alterations in Sotos syndrome and therefore the need to complete sequencing analysis by screening for partial deletions and duplications to ensure an accurate molecular diagnosis of this syndrome.     

Impact of a Pneumococcal Conjugate Vaccination Program on Carriage among Children in Norway

In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes.Streptococcus pneumoniae is a leading cause of otitis media, sinusitis, pneumonia, and meningitis worldwide (35). S. pneumoniae colonizes the nasopharynx and is considered a part of the normal flora in early childhood (1). Following the implementation of childhood vaccination with the seven-valent conjugated pneumococcal vaccine (PCV7), reports from several locations have described declines in carriage of the seven serotypes included in the vaccine, i.e., serotypes 4, 6B, 9V, 14, 18C, 19F and 23F (4, 6, 13, 19, 24). Due to reduced transmission of PCV7 serotypes, the incidence of invasive pneumococcal disease (IPD) declines also among the unvaccinated, which is an indirect effect of conjugate pneumococcal vaccination. However, the effect of PCV7 may in part be eroded over time as non-PCV7 serotypes emerge as a more frequent cause of IPD (11). In the United States, non-antimicrobial-susceptible clones seem to have an advantage among the emerging and expanding non-PCV7 serotypes, both in asymptomatic colonization and IPD (10, 20). This is primarily demonstrated by increasing incidence rates of drug-resistant clones of serotype 19A (23).PCV7 was introduced into the Norwegian childhood vaccination program in a dose schedule of two doses and one boost (2 + 1 dose schedule) in July 2006 and has been offered free of charge to all children born in 2006 and since. A high level of effectiveness of the vaccination program among children was demonstrated quickly after vaccine introduction, and the effect included a decline in IPD caused by erythromycin-resistant S. pneumoniae (34).As part of the Norwegian surveillance of PCV7 introduction, a cross-sectional study of nasopharyngeal carriage of Streptococcus pneumoniae among children attending day care centers (DCC) was performed in the early autumn of 2006. Data from this study, with exception of data regarding 38 vaccinated participants, have been reported previously (33). To assess the impact of the 2 + 1 dose schedule PCV7 vaccination program on carriage of S. pneumoniae, a follow-up was performed in 2008. Serotyping, antimicrobial susceptibility testing, and genotyping of the isolates from 2008 were performed, and the results were compared to those from analyses of the previous collection. Shifts in clonal compositions of the pneumococcal populations were analyzed and are reported here.Limited outpatient use of antimicrobial agents is recommended in Norway, and the levels of nonsusceptibility to antimicrobials among S. pneumoniae isolates from both local infections and IPD are low (25). Hence, emphasis has been put on post-PCV7 changes in nonsusceptibility to antimicrobials and nonsusceptible clones in a setting with limited antimicrobial use and resistance.     

Brominated Flame Retardants in Fish of Lake Geneva (Switzerland)

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) were determined in fish (Salmo trutta forma lacustris) from Lake Geneva. Brominated flame retardants were detected in all nine samples with an average concentration for the sum of BDE-28, BDE-47, BDE-49, BDE-66, BDE-99, BDE-100, BDE-119, BDE-153, BDE-154 and BDE-209 of 207 ng per g lipid weight (ng g lw⁻¹). The congener patterns were dominated by BDE-47. The average concentration of HBCD was 168 ng g lw⁻¹.