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Background: Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, but also a common colonizer of the upper respiratory tract. The emergence and spread of antibiotic resistant pneumococcal strains has threatened effective therapy. The long-term effects of measures aiming to limit pneumococcal spread are poorly understood. Computational modeling makes it possible to conduct virtual experiments that are impractical to perform in real life and thereby allows a more full understanding of pneumococcal epidemiology and control efforts. Methods: We have developed a contact network model to evaluate the efficacy of interventions aiming to control pneumococcal transmission. Demographic data from Sweden during the mid-2000s were employed. Analyses of the model's parameters were conducted to elucidate key determinants of pneumococcal spread. Also, scenario simulations were performed to assess candidate control measures. Results: The model made good predictions of previous findings where a correlation has been found between age and pneumococcal carriage. Of the parameters tested, group size in day-care centers was shown to be the most important factor for pneumococcal transmission. Consistent results were generated from the scenario simulations. Conclusions: We recommend, based on the model predictions, that strategies to control pneumococcal disease and organism transmission should include reducing the group size in day-care centers.

Background: Hepatitis C virus (HCV) infection is a major global public health problem in both developed and developing countries. The prevalence and genetic diversity of HCV in pregnant women in Gabon, central Africa, is not known. We therefore evaluated the prevalence and the circulating genotypes of HCV in a large population cohort of pregnant women. Methods: Blood samples (947) were collected from pregnant women in the five main cities of the country. The prevalence was evaluated by two ELISA tests, and the circulating genotypes were characterized by sequencing and phylogenetic analysis. Results: Twenty pregnant women (2.1%) were infected with HCV. The seroprevalence differed significantly by region (p = 0.004) and increased significantly with age (p = 0.05), being 1.3% at 14-20 years, 1.1% at 21-25 years, 1.9% at 26-30 years, 4.1% at 31-35 years and 6.0% at > 35 years. Sequencing in the 5'-UTR and NS5B regions showed that the circulating strains belonged to genotypes 4 (4e and 4c). Conclusion: We found that the HCV seroprevalence in pregnant women in Gabon is almost as high as that in other African countries and increases with age. Furthermore, only genotype 4 (4e and 4c) was found. More extensive studies aiming to evaluate the prevalence and heterogeneity of HCV genotypes circulating in the general population of the country are needed.

Objectives To follow a population of preschool children with and without parent reported wheeze over a period of 6-11 years to determine prognosis and its important predictive factors.

Design Longitudinal series of five postal surveys based on the international study of asthma and allergies in childhood questionnaire carried out between 1993 and 2004.

Setting Two general practice populations, south Manchester.

Participants 628 children aged less than 5 years at recruitment and those with at least six years’ follow-up data.

Main outcome measures Parent completed questionnaire data for respiratory symptoms and associated features.

Results Of 628 children included in the study, 201 (32%) had parent reported wheeze at the first observation (baseline), of whom 27% also reported the symptom on the second occasion (persistent asthma). The only important baseline predictors of persistent asthma were exercise induced wheeze (odds ratio 3.94, 95% confidence interval 1.72 to 9.00) and a history of atopic disorders (4.44, 1.94 to 10.13). The presence of both predictors indicated a likelihood of 53.2% of developing asthma; if only one feature was present this decreased to 17.2%, whereas if neither was present the likelihood was 10.9%. Family history of asthma was not predictive of persistent asthma among children with preschool wheeze.

Conclusion Using two simple predictive factors (baseline parent reported exercise induced wheeze and a history of atopic disorders), it is possible to estimate the likelihood of future asthma in children presenting with preschool wheeze. The absence of baseline exercise induced wheeze and a history of atopic disorders reduces the likelihood of subsequent asthma by a factor of five.

Objective To assess the association between genitourinary infections in the month before conception to the end of the first trimesterand gastroschisis.

Design Case-control study with self reported infections from a computer assisted telephone interview.

Setting National birth defects prevention study, a multisite, population based study including 10 surveillance systems for birth defects in the United States.

Participants Mothers of 505 offspring with gastroschisis and 4924 healthy liveborn infants as controls.

Main outcome measure Adjusted odds ratios for gastroschisis with 95% confidence intervals.

Results About 16% (n=81) of case mothers and 9% (n=425) of control mothers reported a genitourinary infection in the relevant time period; 4% (n=21) and 2% (n=98) reported a sexually transmitted infection and 13% (n=67) and 7% (n=338) reported a urinary tract infection, respectively. Case mothers aged <25 years reported higher rates of urinary tract infection alone and in combination with a sexually transmitted infection compared with control mothers. In women who reported both types of infection, there was a greater risk of gastroschisis in offspring (adjusted odds ratio 4.0, 95% confidence interval 1.4 to 11.6).

Conclusion There is a significant association between self reported urinary tract infection plus sexually transmitted infection just before conception and in early pregnancy and gastroschisis.

Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality.

Design Randomised placebo controlled trial.

Setting Bandim Health Project’s demographic surveillance system in Guinea-Bissau, covering approximately 90 000 inhabitants.

Participants 4345 infants due to receive BCG.

Intervention Infants were randomised to 50 000 IU vitamin A or placebo and followed until age 12 months.

Main outcome measure Mortality rate ratios.

Results 174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration.

Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival.

Trial registration Clinical trials NCT00168597.

Objectives To estimate the prevalence of body piercing, other than of earlobes, in the general adult population in England, and to describe the distribution of body piercing by age group, sex, social class, anatomical site, and who performed the piercings. To estimate the proportion of piercings that resulted in complications and the proportion of piercings that resulted in professional help being sought after the piercing.

Design Cross sectional household survey.

Setting All regions of England 2005.

Participants 10 503 adults aged 16 and over identified with a two stage selection process: random selection of geographical areas and filling predefined quotas of individuals. Results weighted to reflect the national demographic profile of adults aged 16 and over.

Main outcome measures Estimates of the prevalence of body piercing overall and by age group, sex, and anatomical site. Estimates, in those aged 16-24, of the proportion of piercings associated with complications and the seeking of professional help.

Results The prevalence of body piercing was 1049/10 503 (10%, 95% confidence interval 9.4% to 10.6%). Body piercing was more common in women than in men and in younger age groups. Nearly half the women aged 16-24 reported having had a piercing (305/659, 46.2%, 42.0% to 50.5%). Of the 754 piercings in those aged 16-24, complications were reported with 233 (31.0%, 26.8% to 35.5%); professional help was sought with 115 (15.2%, 11.8% to 19.5%); and hospital admission was required with seven (0.9%, 0.3% to 3.2%).

Conclusions Body piercing is common in adults in England, particularly in young women. Problems are common and the assistance of health services is often required. Though serious complications requiring admission to hospital seem uncommon, the popularity of the practice might place a substantial burden on health services.

Background: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children Methods: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. Results: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. Conclusions: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia.

Background: This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant Enterococcus species. Methods: A descriptive study was performed by reviewing the blood cultures from febrile neutropenic patients in two study periods i.e., 1999-00 and 2001-06. Blood cultures were performed using BACTEC 9240 automated system. Isolates were identified and sensitivities were done using standard microbiological procedures. Results: Seven twenty six febrile neutropenic patients were admitted during the study period. A total of 5840 blood cultures were received, off these 1048 (18%) were culture positive. Amongst these, 557 (53%) grew Gram positive bacteria, 442 (42%) grew Gram negative bacteria, 43 (4%) fungi and 6 (1%) anaerobes. Sixty out of 1048 (5.7 %) positive blood cultures were polymicrobial. In the Gram negative bacteria, Enterobacteriaceae was the predominant group; E. coli was the most frequently isolated organism in both study periods. Amongst non- Enterobacteriaceae group, Pseudomonas aeruginosa was the commonest organism isolated during first study period followed by Acinetobacter spp. However, during the second period Acinetobacter species was the most frequent pathogen. Amongst the Enterobacteriaceae group statistically significant resistance appeared in the second study period against ceftriaxone, quinolone and piperacillin/tazobactam, no resistance observed in this group for imipenem/ meropenem. The susceptibility pattern of Acinetobacter species shifted from sensitive to highly resistant one with significant p values against ceftriaxone, quinolone, piperacillin/tazobactam and imipenem/ meropenem. Amongst Gram positive bacteria, MRSA isolation rate remained static, vancomycin resistant Enterococcus species emerged in second half of study while no Staphylococcus species resistant to vancomycin was noted. Conclusion: This rising trend of highly resistant organisms stresses the increasing importance of continuous surveillance system and stewardship of antibiotics as strategies in the overall management of patients with febrile neutropenia.

Background: The nosocomial infections surveillance system must be strongly effective especially in highly critic areas, such as Intensive Care Units (ICU). These areas are frequently an epidemiological epicentre for transmission of multi-resistant pathogens, like Acinetobacter baumannii. As an epidemic outbreak occurs it is very important to confirm or exclude the genetic relationship among the isolates in a short time. There are several molecular typing systems used with this aim. The Repetitive sequence-based PCR (REP-PCR) has been recognized as an effective method and it was recently adapted to an automated format known as the DiversiLab system. Methods: In the present study we have evaluated the combination of a newly introduced software package for the control of hospital infection (VIGI@ct) with the DiversiLab system. In order to evaluate the reliability of the DiversiLab its results were also compared with those obtained using f-AFLP. Results: The combination of VIGI@ct and DiversiLab enabled an earlier identification of an A.baumannii epidemic cluster, through the confirmation of the genetic relationship among the isolates. This cluster regards 56 multi-drug-resistant A. baumannii isolates from several specimens collected from 13 different patients admitted to the ICU in a ten month period. The A. baumannii isolates were clonally related being their similarity included between 97 and 100%. The results of the DiversiLab were confirmed by f-AFLP analysis. Conclusion: The early identification of the outbreak has led to the prompt application of operative procedures and precautions to avoid the spread of pathogen. To date, 6 months after the last A. baumannii isolate, no other related case has been identified.

Background: : Hepatitis A virus (HAV) is an enteric, viral, infectious disease endemic in many developing countries such as Madagascar. Infection is often subclinical or asymptomatic in children; however, symptomatic acute infections become more common with increasing age. In some developing countries, improvements in living conditions have led to changes in the epidemiological pattern of HAV infection. There are very few reports on the prevalence of HAV in Madagascar. This study was to determine the seroprevalence of hepatitis A virus antibodies in relation to age in the city of Antananarivo, Madagascar. MethodS: Serum samples collected in 2004 during a cross-sectional survey of individuals aged between two and 24 years from Antananarivo were tested for anti-HAV antibody using a commercial enzyme immunoassay kit. Subjects were investigated using a standardized social and medical history questionnaire. Results: : 926 subjects were enrolled including 406 males and 520 females. There were 251 children under 10 years old and 675 subjects between 10 and 24 years old. Of the 926 serum samples tested, 854 (92.2%) were positive for anti-HAV antibodies. The number of seropositive samples was similar for males and females. The overall seroprevalence was 83.7% (210/251) for children under 10 years old and 95.5% (644/675) for subjects aged between 10 and 24 years (p < 0.001). CONCLUSION: Despite improvements in sanitary conditions and hygiene over the last few years, the prevalence of HAV in Antananarivo is high. Only children under five years old remain susceptible to HAV infection. Immunization against HAV is not needed at the present time in the Madagascan population, but should be recommended for travellers.

Background: How HIV-1 enter into the eyes remains obscure. We postulated that HIV-1 Tat protein can alter the expression of specific tight-junction proteins and disturb the blood retinal barrier, and contributes to HIV trafficking into the eyes. This study is to determine the effects of HIV-1 Tat proteins on the barrier function and tight-junction protein expression of retinal pigment epithelial cell (RPE). Methods: A human RPE cell line (D407) cultured on microporous filter-supports was used. After treating with HIV-1 Tat protein, transepithelial electrical resistance (TER) of confluent RPE cells was measured by epithelial voltmeter. The permeability of the RPE cells to sodium fluorescein was measured. The expressions of the occludin and claudins were determined by real-time polymerase chain reaction, immunofluorescence, and Western blot analysis. Activation of ERK1/2 was detected by Western blot analysis with specific antiphospho protein antibodies. NF-κB DNA binding activity was determined by transcription factor assay. Specific pharmacologic inhibitors directed against the MAPKs were used to analyze the signaling involved in barrier destruction of RPE cells exposed to HIV-1 Tat. Results: Treating cultured human retinal pigment epithelial cells with 100 nM Tat for 24 hours increased the permeability and decreased the TER of the epithelial monolayer. HIV-1 Tat also disrupted and downregulated the tight-junction proteins claudin-1, claudin-3, and claudin-4 in these cells, whereas claudin-2 was upregulated, and the expression of occludin was unaffected. HIV-1 Tat protein also induced activation of ERK1/2 and NF-κB. HIV-1 Tat protein induced barrier destruction, changes in expression of TJs, and activation of ERK1/2 and NF-κB were abrogated by inhibitor of ERK1/2 and NF-κB. Conclusion: HIV-1 Tat protein causes increases in the paracellular permeability of RPE cells in vitro concomitant with changes in expression of certain transmembrane proteins associated with the tight junction. The effects of HIV-1 Tat on barrier function of the RPE may be mediated by ERK MAPK and NF-κB activation, which may represent potential targets for novel therapeutic approaches for the retinopathy induced by HIV infection.

Objective To determine the persistence of bactericidal antibody titres following immunisation with serogroup C meningococcal glycoconjugate vaccine at age 6-15 years in order to examine changes in persistence of antibodies with age.

Design Observational study.

Setting Secondary and tertiary educational institutions in the United Kingdom.

Participants Healthy adolescents aged 11-20 years previously immunised between 6 and 15 years of age with one of the three serogroup C meningococcal vaccines.

Intervention Serum obtained by venepuncture.

Main outcome measures Percentage of participants with (rabbit complement) serum bactericidal antibody titres of at least 1:8; geometric mean titres of serogroup C meningococcal serum bactericidal antibody.

Results Five years after immunisation, 84.1% (95% confidence interval 81.6% to 86.3%) of 987 participants had a bactericidal antibody titre of at least 1:8. Geometric mean titres of bactericidal antibody were significantly lower in 11-13 year olds (147, 95% confidence interval 115 to 188) than in 14-16 year olds (300, 237 to 380) and 17-20 year olds (360, 252 to 515) (P<0.0001 for both comparisons). Within these age bands, no significant difference in geometric mean titres of bactericidal antibody between recipients of the different serogroup C meningococcal vaccines was seen. More than 70% of participants had received a vaccine from one manufacturer; in this cohort, geometric mean titres were higher in those immunised at aged 10 years or above than in those immunised before the age of 10.

Conclusions Higher concentrations of bactericidal antibody are seen five years after immunisation with serogroup C meningococcal vaccine at age 10 years or above than in younger age groups, possibly owing to immunological maturation. This provides support for adolescent immunisation programmes to generate sustained protection against serogroup C meningococcal disease not only for the vaccine recipients but also, through the maintenance of herd immunity, for younger children.