Composition of human faecal microbiota in resistance to Campylobacter infection

In mice, specific species composition of gut microbiota enhances susceptibility to Campylobacter jejuni but little is known about the specific composition of the human gut microbiota in providing protection from infections caused by enteropathogens. Healthy adult individuals, who travelled in groups from Sweden to destinations with an estimated high risk for acquisition of Campylobacter infection, were enrolled. Faecal samples, collected before travelling and after returning home, were cultured for bacterial enteropathogens, and analysed for Campylobacter by PCR and for the species composition of the microbiota by 16S amplicon massive parallel sequencing. The microbiota compositions were compared between persons who became infected during their travel and those who did not. A total of 63 participants completed the study; 14 became infected with Campylobacter, two with Salmonella and 47 remained negative for the enteropathogens tested. After exclusion of samples taken after antimicrobial treatment, 49 individuals were included in the final analyses. Intra-individual stability of the microbiota was demonstrated for samples taken before travelling. The original diversity of the faecal microbiota was significantly lower among individuals who later became infected compared with those who remained uninfected. The relative abundances of bacteria belonging to the family Lachnospiraceae, and more specifically its two genera Dorea and Coprococcus, were significantly higher among those who remained uninfected. The travel-related infection did not significantly modify the faecal microbiota composition. Species composition of human gut microbiota is important for colonization resistance to Campylobacter infection. Especially individuals with a lower diversity are more susceptible to Campylobacter infection. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.Peer reviewe

Specific antibodies against vaccine-preventable infections: a mother-infant cohort study

OBJECTIVES: To determine maternal and neonatal specific antibody levels to selected vaccine-preventable infections (pertussis, Haemophilus influenzae type b (Hib), tetanus and pneumococcus). DESIGN: Prospective cohort study. SETTING: A UK secondary care maternity unit (March 2011-January 2012). PARTICIPANTS: Mothers and infants within 72 h of delivery were eligible. Unwell individuals, mothers less than 18 years of age, and infants born at less than 36 weeks gestation, or weighing less than 2500 g, were excluded. HIV-infected mothers were included. 112 mother-infant pairs were recruited. Samples from 111 mothers and 109 infants (108 pairs) were available for analysis. OUTCOME MEASURES: Specific antibody levels were determined using standard commercial ELISAs. Specific antibody to pertussis antigens (PT and FHA) of >50 IU/ml, defined as 'positive' by the test manufacturer, were interpreted as protective. Antitetanus antibody titres >0.1 IU/ml and anti-Hib antibody titres >1 mg/l were regarded as protective. RESULTS: Only 17% (19/111) of women exhibited a protective antibody response against pertussis. 50% (56/111) of women had levels of antibody protective against Hib and 79% (88/111) against tetanus. There was a strong positive correlation between maternal-specific and infant-specific antibodies' responses against pertussis (rs=0.71, p<0.001), Hib (rs=0.80, p<0.001), tetanus (rs=0.90, p<0.001) and pneumococcal capsular polysaccharide (rs=0.85, p<0.001). Only 30% (33/109) and 42% (46/109) of infants showed a protective antibody response to pertussis and Hib, respectively. Placental transfer (infant:mother ratio) of specific IgG to pertussis, Hib, pneumococcus and tetanus was significantly reduced from HIV-infected mothers to their HIV-exposed, uninfected infants (n=12 pairs) compared with HIV-uninfected mothers with HIV-unexposed infants (n=96 pairs) by 58% (<0.001), 61% (<0.001), 28% (p=0.034) and 32% (p=0.035), respectively. CONCLUSIONS: Low baseline antibody levels against pertussis in this cohort suggest the recently implemented UK maternal pertussis immunisation programme has potential to be effective

p16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters

Background: Currently, staging of head neck squamous cell carcinoma (HNSCC) is on the basis of primary tumor extension (cT), lymph node involvement (cN) and distant metastasis (cM). The aim of cancer staging was to improve diagnosis, prognosis and to compare outcome results. A new subgroup of oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV) infection is reported to show an increasing incidence. These HPV-positive OPSCC show distinct molecular differences, specific p16 overexpression and a significantly better prognosis. Therefore, the aim of this study was to evaluate the prognostic influence of p16 expression in OPSCC and compare its relevance with the established prognostic markers cT and cN classification and the clinical stages I-IV. Patients and methods: Immunohistochemistry for p16 was carried out on the basis of a tissue microarray including 102 OPSCC patients with corresponding retrospective clinicopathological and follow-up data. Results: p16 is the strongest independent prognostic marker in OPSCC, surpassing the significance of cT and cN classification as well as the clinical stages I-IV. Prognosis of p16-positive OPSCC of an advanced stage reached or even exceeded prognosis of the next clinically smaller conventionally staged group of tumors. Conclusion: p16 is the most relevant prognostic marker in OPSCC and should be considered for inclusion into the official staging system of HNSC

Persistence of Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia.

BACKGROUND: The widespread use of pneumococcal conjugate vaccine (PCV) has brought about a dramatic decrease in pneumococci of vaccine serotypes (VTs) but nonvaccine serotypes (NVTs) have emerged. METHODS: We conducted a cross-sectional survey (CSS) among infants who received 3 doses of 13-valent PCV (PCV13) and their mothers 5 years (CSS3) after PCV13 introduction. Nasopharyngeal swab samples were collected and cultured for isolation of Streptococcus pneumoniae. Whole-genome sequencing of the nontypeable strains was performed. Data were compared with those from 2 previous surveys conducted before PCV13 introduction (CSS1) and 1 year later (CSS2). RESULTS: Among infants, VT carriage decreased from 33.3% (113/339) in CSS1 to 11.4% (40/351) in CSS3 (P = .001) while NVTs increased from 53.1% (180/339) in CSS1 to 74.4% (261/351) in CSS3 (P < .001). Among mothers, there was a significant decrease in VTs between CSS2 8.4% (29/347) and CSS3 5.6% (19/342) (P = .006). NVTs increased from 16.6% (55/331) in CSS1 to 32.2% (110/342) in CSS3 (P < .001). In CSS3, the most prevalent VTs were 7F in infants and 3 in mothers, and the most prevalent NVTs were serogroup 16 and nontypeables, respectively. Genomic analysis showed that VTs were more likely than NVTs to lose their ability to express the capsule. CONCLUSIONS: Five years after PCV13 introduction, we show both direct (infants) and indirect effects (mothers) of the vaccine, while NVT replacement has occurred in both groups. Ongoing circulation of VTs warrants further study of their relevance in any consideration of a reduced dose schedule

Childhood tuberculosis: progress requires an advocacy strategy now

Childhood tuberculosis (TB) is a preventable and curable infectious disease that remains overlooked by public health authorities, health policy makers and TB control programmes. Childhood TB contributes significantly to the burden of disease and represents the failure to control transmission in the community. Furthermore, the pool of infected children constitutes a reservoir of infection for the future burden of TB. It is time to prioritise childhood TB, advocate for addressing the challenges and grasp the opportunities in its prevention and control. Herein, we propose a scientifically informed advocacy agenda developed at the International Childhood TB meeting held in Stockholm, Sweden, from March 17 to 18, 2011, which calls for a renewed effort to improve the situation for children affected by Mycobacterium tuberculosis exposure, infection or disease. The challenges and needs in childhood TB are universal and apply to all settings and must be addressed more effectively by all stakeholders

A 15-year perspective of the fabry outcome survey

The Fabry Outcome Survey (FOS) is an international long-term observational registry sponsored by Shire for patients diagnosed with Fabry disease who are receiving or are candidates for therapy with agalsidase alfa (agala). Established in 2001, FOS provides long-term data on agala safety/efficacy and collects data on the natural history of Fabry disease, with the aim of improving clinical management. The FOS publications have helped establish prognostic and severity scores, defined the incidence of specific disease variants and implications for clinical management, described clinical manifestations in special populations, confirmed the high prevalence of cardiac morbidity, and demonstrated correlations between ocular changes and Fabry disease severity. These FOS data represent a rich resource with utility not only for description of natural history/therapeutic effects but also for exploratory hypothesis testing and generation of tools for diagnosis/management, with the potential to improve future patient outcomes

Formal asymptotic limit of a diffuse-interface tumor-growth model

We consider a diffuse-interface tumor-growth model which has the form of a phase-field system. We characterize the singular limit of this problem. More precisely, we formally prove that as the coefficient of the reaction term tends to infinity, the solution converges to the solution of a novel free boundary problem. We present numerical simulations which illustrate the convergence of the diffuse-interface model to the identified sharp-interface limit