Anatomy and taxonomic status of the chasmosaurine ceratopsid Nedoceratops hatcheri from the upper Cretaceous Lance Formation of Wyoming, U.S.A

Background

The validity of Nedoceratops hatcheri, a chasmosaurine ceratopsid dinosaur known from a single skull recovered in the Lance Formation of eastern Wyoming, U.S.A., has been debated for over a century. Some have argued that the taxon is an aberrant Triceratops, and most recently it was proposed that N. hatcheri represents an intermediate ontogenetic stage between “young adult” and “old adult” forms of a single taxon previously split into Triceratops and Torosaurus.

Methodology/Principal Findings

The holotype skull of Nedoceratops hatcheri was reexamined in order to map reconstructed areas and compare the specimen with other ceratopsids. Although squamosal fenestrae are almost certainly not of taxonomic significance, some other features are unique to N. hatcheri. These include a nasal lacking a recognizable horn, nearly vertical postorbital horncores, and relatively small parietal fenestrae. Thus, N. hatcheri is tentatively considered valid, and closely related to Triceratops spp. The holotype of N. hatcheri probably represents an “old adult,” based upon bone surface texture and the shape of the horns and epiossifications on the frill. In this study, Torosaurus is maintained as a genus distinct from Triceratops and Nedoceratops. Synonymy of the three genera as ontogenetic stages of a single taxon would require cranial changes otherwise unknown in ceratopsids, including additions of ossifications to the frill and repeated alternation of bone surface texture between juvenile and adult morphotypes.

Conclusions/Significance

Triceratops, Torosaurus, and likely Nedoceratops, are all distinct taxa, indicating that species richness for chasmosaurine ceratopsids in the Lance Formation just prior to the Cretaceous-Paleocene extinction was roughly equivalent to that earlier in the Cretaceous.     

Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile

Background

Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections.

Methods

PACT utilises the ability of light-activated photosensitisers (PS) to produce reactive oxygen species (ROS) such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29.

Results

Three PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm²) without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT.

Conclusion

This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.     

Martharaptor greenriverensis, a New Theropod Dinosaur from the Lower Cretaceous of Utah

Background

The Yellow Cat Member of the Cedar Mountain Formation (Early Cretaceous, Barremian?) of Utah has yielded a rich dinosaur fauna, including the basal therizinosauroid theropod Falcarius utahensis at its base. Recent excavation uncovered a new possible therizinosauroid taxon from a higher stratigraphic level in the Cedar Mountain Formation than F. utahensis.

Methodology/Principal Findings

Here we describe a fragmentary skeleton of the new theropod and perform a phylogenetic analysis to determine its phylogenetic position. The skeleton includes fragments of vertebrae, a scapula, forelimb and hindlimb bones, and an ischium. It also includes several well-preserved manual unguals. Manual and pedal morphology show that the specimen is distinct from other theropods from the Cedar Mountain Formation and from previously described therizinosauroids. It is here named as the holotype of a new genus and species, Martharaptor greenriverensis. Phylogenetic analysis places M. greenriverensis within Therizinosauroidea as the sister taxon to Alxasaurus + Therizinosauridae, although support for this placement is weak.

Conclusions/Significance

The new specimen adds to the known dinosaurian fauna of the Yellow Cat Member of the Cedar Mountain Formation. If the phylogenetic placement is correct, it also adds to the known diversity of Therizinosauroidea.     

A New Brachylophosaurin Hadrosaur (Dinosauria: Ornithischia) with an Intermediate Nasal Crest from the Campanian Judith River Formation of Northcentral Montana

Background

Brachylophosaurini is a clade of hadrosaurine dinosaurs currently known from the Campanian (Late Cretaceous) of North America. Its members include: Acristavus gagslarsoni, which lacks a nasal crest; Brachylophosaurus canadensis, which possesses a flat paddle-shaped nasal crest projecting posteriorly over the dorsal skull roof; and Maiasaura peeblesorum, which possesses a dorsally-projecting nasofrontal crest. Acristavus, from the lower Two Medicine Formation of Montana (~81–80 Ma), is hypothesized to be the ancestral member of the clade. Brachylophosaurus specimens are from the middle Oldman Formation of Alberta and equivalent beds in the Judith River Formation of Montana; the upper Oldman Formation is dated 77.8 Ma.

Methodology/Principal Findings

A new brachylophosaurin hadrosaur, Probrachylophosaurus bergei (gen. et sp. nov.) is described and phylogenetically analyzed based on the skull and postcranium of a large individual from the Judith River Formation of northcentral Montana (79.8–79.5 Ma); the horizon is equivalent to the lower Oldman Formation of Alberta. Cranial morphology of Probrachylophosaurus, most notably the nasal crest, is intermediate between Acristavus and Brachylophosaurus. In Brachylophosaurus, the nasal crest lengthens and flattens ontogenetically, covering the supratemporal fenestrae in large adults. The smaller nasal crest of Probrachylophosaurus is strongly triangular in cross section and only minimally overhangs the supratemporal fenestrae, similar to an ontogenetically earlier stage of Brachylophosaurus. Sutural fusion and tibial osteohistology reveal that the holotype of Probrachylophosaurus was relatively more mature than a similarly large Brachylophosaurus specimen; thus, Probrachylophosaurus is not simply an immature Brachylophosaurus.

Conclusions/Significance

The small triangular posteriorly oriented nasal crest of Probrachylophosaurus is proposed to represent a transitional nasal morphology between that of a non-crested ancestor such as Acristavus and the large flat posteriorly oriented nasal crest of adult Brachylophosaurus. Because Probrachylophosaurus is stratigraphically and morphologically intermediate between these taxa, Probrachylophosaurus is hypothesized to be an intermediate member of the Acristavus-Brachylophosaurus evolutionary lineage.     

Genetic Diversity of Cryptosporidium in Children in an Urban Informal Settlement of Nairobi,Kenya

Introduction

Globally Cryptosporidium and Giardia species are the most common non-bacterial causes of diarrhoea in children and HIV infected individuals, yet data on their role in paediatric diarrhoea in Kenya remains scant. This study investigated the occurrence of Cryptosporidium species, genotypes and subtypes in children, both hospitalized and living in an informal settlement in Nairobi.

Methods

This was a prospective cross-sectional study in which faecal specimen positive for Cryptosporidium spp. by microscopy from HIV infected and uninfected children aged five years and below presenting with diarrhoea at selected outpatient clinics in Mukuru informal settlements, or admitted to the paediatric ward at the Mbagathi District Hospital were characterized. The analysis was done by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) of the 18srRNA gene for species identification and PCR-sequencing of the 60 kDa glycoprotein (GP60) gene for subtyping.

Results

C. hominis was the most common species of Cryptosporidium identified in125/151(82.8%) of the children. Other species identified were C. parvum 18/151(11.9%), while C. felis and C. meleagridis were identified in 4 and 2 children, respectively. Wide genetic variation was observed within C. hominis, with identification of 5 subtype families; Ia, Ib, Id, Ie and If and 21 subtypes. Only subtype family IIc was identified within C. parvum. There was no association between species and HIV status or patient type.

Conclusion

C. hominis is the most common species associated with diarrhoea in the study population. There was high genetic variability in the C. hominis isolates with 22 different subtypes identified, whereas genetic diversity was low within C. parvum with only one subtype family IIc identified.     

Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression

Introduction

Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice.

Methods

We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA).

Results

Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses.

Conclusion

These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.     

A new troodontid theropod, Talos sampsoni gen. et sp. nov., from the Upper Cretaceous Western Interior Basin of North America

Background

Troodontids are a predominantly small-bodied group of feathered theropod dinosaurs notable for their close evolutionary relationship with Avialae. Despite a diverse Asian representation with remarkable growth in recent years, the North American record of the clade remains poor, with only one controversial species—Troodon formosus—presently known from substantial skeletal remains.

Methodology/Principal Findings

Here we report a gracile new troodontid theropod—Talos sampsoni gen. et sp. nov.—from the Upper Cretaceous Kaiparowits Formation, Utah, USA, representing one of the most complete troodontid skeletons described from North America to date. Histological assessment of the holotype specimen indicates that the adult body size of Talos was notably smaller than that of the contemporary genus Troodon. Phylogenetic analysis recovers Talos as a member of a derived, latest Cretaceous subclade, minimally containing Troodon, Saurornithoides, and Zanabazar. MicroCT scans reveal extreme pathological remodeling on pedal phalanx II-1 of the holotype specimen likely resulting from physical trauma and subsequent infectious processes.

Conclusion/Significance

Talos sampsoni adds to the singularity of the Kaiparowits Formation dinosaur fauna, which is represented by at least 10 previously unrecognized species including the recently named ceratopsids Utahceratops and Kosmoceratops, the hadrosaurine Gryposaurus monumentensis, the tyrannosaurid Teratophoneus, and the oviraptorosaurian Hagryphus. The presence of a distinct troodontid taxon in the Kaiparowits Formation supports the hypothesis that late Campanian dinosaurs of the Western Interior Basin exhibited restricted geographic ranges and suggests that the taxonomic diversity of Late Cretaceous troodontids from North America is currently underestimated. An apparent traumatic injury to the foot of Talos with evidence of subsequent healing sheds new light on the paleobiology of deinonychosaurians by bolstering functional interpretations of prey grappling and/or intraspecific combat for the second pedal digit, and supporting trackway evidence indicating a minimal role in weight bearing.     

Occupational Exposure to Swine,Poultry, and Cattle and Antibody Biomarkers of Campylobacter jejuni Exposure and Autoimmune Peripheral Neuropathy

Introduction

Foodborne Campylobacter jejuni infection has been associated with an increased risk of autoimmune peripheral neuropathy, but risks of occupational exposure to C. jejuni have received less attention. This study compared anti-C. jejuni IgA, IgG, and IgM antibody levels, as well as the likelihood of testing positive for any of five anti-ganglioside autoantibodies, between animal farmers and non-farmers. Anti-C. jejuni antibody levels were also compared between farmers with different animal herd or flock sizes. The relationship between anti-C. jejuni antibody levels and detection of anti-ganglioside autoantibodies was also assessed.

Methods

Serum samples from 129 Agricultural Health Study swine farmers (some of whom also worked with other animals) and 46 non-farmers, all from Iowa, were analyzed for anti-C. jejuni antibodies and anti-ganglioside autoantibodies using ELISA. Information on animal exposures was assessed using questionnaire data. Anti-C. jejuni antibody levels were compared using Mann-Whitney tests and linear regression on log-transformed outcomes. Fisher’s Exact Tests and logistic regression were used to compare likelihood of positivity for anti-ganglioside autoantibodies.

Results

Farmers had significantly higher levels of anti-C. jejuni IgA (p < 0.0001) and IgG (p = 0.02) antibodies compared to non-farmers. There was no consistent pattern of anti-C. jejuni antibody levels based on animal herd or flock size. A higher percentage of farmers (21%) tested positive for anti-ganglioside autoantibodies compared to non-farmers (9%), but this difference was not statistically significant (p = 0.11). There was no significant association between anti-C. jejuni antibody levels and anti-ganglioside autoantibodies.

Conclusions

The findings provide evidence that farmers who work with animals may be at increased risk of exposure to C. jejuni. Future research should include longitudinal studies of exposures and outcomes, as well as studies of interventions to reduce exposure. Policies to reduce occupational exposure to C. jejuni should be considered.     

A subadult specimen of Rubeosaurus ovatus (Dinosauria: Ceratopsidae), with observations on other ceratopsids from the two medicine formation

Background

Centrosaurine ceratopsids are well known from the middle Campanian Upper Two Medicine Formation of Montana. Four taxa have been named: Brachyceratops montanensis, Rubeosaurus ovatus, Einiosaurus procurvicornis, and Achelousaurus horneri. Rubeosaurus has been historically the most enigmatic of these taxa; only two specimens, the holotype caudal parietal bar and a referred incomplete skull, have been assigned to Rubeosaurus.

Methodology/Principal Findings

A revised interpretation of the parietal processes of USNM 14765, the partial skeleton of a subadult centrosaurine formerly referred to Brachyceratops, indicates that it shares a P5 spike with the holotype of Rubeosaurus ovatus and should therefore be referred to that taxon. Brachyceratops is considered a nomen dubium.

Conclusions/Significance

USNM 14765 provides additional anatomical information for Rubeosaurus ovatus. These new data are incorporated into a recent phylogenetic analysis of centrosaurine relationships; Rubeosaurus appears as the sister taxon of a clade composed of Einiosaurus, Achelousaurus, and Pachyrhinosaurus.     

Chlamydia trachomatis Frequency in a Cohort of HPV-Infected Colombian Women

Background

Chlamydia trachomatis (C. trachomatis), an obligate intracellular bacterium, is the commonest infectious bacterial agent of sexual transmission throughout the world. It has been shown that the presence of this bacteria in the cervix represents a risk regarding HPV persistence and, thereafter, in developing cervical cancer (CC). Prevalence rates may vary from 2% to 17% in asymptomatic females, depending on the population being analysed. This study reports the identification of C. trachomatis in a cohort of 219 HPV-infected Colombian females.

Methods

C. trachomatis infection frequency was determined during each of the study’s follow-up visits; it was detected by amplifying the cryptic plasmid sequence by polymerase chain reaction (PCR) using two sets of primers: KL5/KL6 and KL1/KL2.Infection was defined as a positive PCR result using either set of primers at any time during the study. Cox proportional risk models were used for evaluating the association between the appearance of infection and a group of independent variables.

Results

Base line C. trachomatis infection frequency was 28% (n = 61). Most females infected by C. trachomatis were infected by multiple types of HPV (77.42%), greater prevalence occurring in females infected with HPV-16 (19.18%), followed by HPV-58 (17.81%). It was observed that females having had the most sexual partners (HR = 6.44: 1.59–26.05 95%CI) or infection with multiple types of HPV (HR = 2.85: 1.22–6.63 95%CI) had the greatest risk of developing C. trachomatis.

Conclusions

The study provides data regarding the epidemiology of C. trachomatis /HPV coinfection in different population groups of Colombian females and contributes towards understanding the natural history of C. trachomatis infection.     

Simultaneous [18F]FDG-PET/MRI: Correlation of Apparent Diffusion Coefficient (ADC) and Standardized Uptake Value (SUV) in Primary and Recurrent Cervical Cancer

Objectives

Previous non–simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs). The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment.

Methods

We included 31 patients with histologically confirmed primary (n = 14) or recurrent cervical cancer (n = 17) who underwent simultaneous whole-body ¹⁸F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV.

Results

92 lesions were detected. We found a significant inverse correlation between SUV_max and ADC_min (r = -0.532, p = 0.05) in primary tumors as well as in primary metastases (r = -0.362, p = 0.05) and between SUV_mean and ADC_min (r = -0.403, p = 0.03). In recurrent local tumors we found correlations for SUV_max and ADC_min (r = -0.747, p = 0.002) and SUV_mean and ADC_min (r = -0.773, p = 0.001). Associations for recurrent metastases were not significant (p>0.05).

Conclusions

Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions.

Key Point 1

This study investigates the correlation of functional parameters in a simultaneous PET/MRI.

Key Point 2

We found significant inverse correlations between ADC and SUV in cervical carcinoma which could increase knowledge about tumor biology.     

Carvacrol Codrugs: A New Approach in the Antimicrobial Plan

Objective

The increasing prevalence of antibiotic-resistant bacterial infections led to identify alternative strategies for a novel therapeutic approach. In this study, we synthesized ten carvacrol codrugs – obtained linking the carvacrol hydroxyl group to the carboxyl moiety of sulphur-containing amino acids via an ester bond – to develop novel compounds with improved antimicrobial and antibiofilm activities and reduced toxicity respect to carvacrol alone.

Method

All carvacrol codrugs were screened against a representative panel of Gram positive (S. aureus and S. epidermidis), Gram negative (E. coli and P. aeruginosa) bacterial strains and C. albicans, using broth microdilution assays.

Findings

Results showed that carvacrol codrug 4 possesses the most notable enhancement in the anti-bacterial activity displaying MIC and MBC values equal to 2.5 mg/mL for all bacterial strains, except for P. aeruginosa ATCC 9027 (MIC and MBC values equal to 5 mg/mL and 10 mg/mL, respectively). All carvacrol codrugs 1-10 revealed good antifungal activity against C. albicans ATCC 10231. The cytotoxicity assay showed that the novel carvacrol codrugs did not produce human blood hemolysis at their MIC values except for codrugs 8 and 9. In particular, deepened experiments performed on carvacrol codrug 4 showed an interesting antimicrobial effect on the mature biofilm produced by E. coli ATCC 8739, respect to the carvacrol alone. The antimicrobial effects of carvacrol codrug 4 were also analyzed by TEM evidencing morphological modifications in S. aureus, E. coli, and C. albicans.

Conclusion

The current study presents an insight into the use of codrug strategy for developing carvacrol derivatives with antibacterial and antibiofilm potentials, and reduced cytotoxicity.     

First Report of Clostridium difficile NAP1/027 in a Mexican Hospital

Background and Objective

Clostridium difficile NAP1/ribotype 027 is associated with severe disease and high mortality rates. Our aim was to determine the prevalence of NAP1/ribotype 027 among C. difficile isolates in a tertiary care hospital, and review the main clinical data.

Methods

We included 106 stool samples from 106 patients. Samples were tested for A&B toxins and were cultured on CCFA agar. The genes tcdA, tcdB, tcdC, cdtA, and cdtB were amplified using PCR in clinical isolates. The tcdA 3’-end deletion analysis, PCR-ribotyping, and pulsed-field gel electrophoresis (PFGE) were also performed. Stool samples that were positive for culture were tested by the GeneXpert C. difficile assay. Clinical data were collected.

Results

Thirty-six patients tested positive for A&B toxins; and 22 patients had positive culture for C. difficile, 14 of which tested positive for the A&B toxins and all 22 patients tested positive by the GeneXpert C. difficile assay. Risk factors included an average hospital stay of 16.1 days prior to toxin detection, average antibiotic use for 16.2 days, and a median of 3 antibiotics used. The 30-day crude mortality rate was 8.4%. Six of the 22 patients died, and 3 of those deaths were directly attributed to C. difficile infection. The majority of isolates, 90.9% (20/22), carried genes tcdB, tcdA, cdtA, and cdtB; and these strains carried the corresponding downregulator gene tcdC, with an 18-bp deletion. PFGE was performed on 17 isolates, and one main pattern was observed. Analysis of the ribotyping data showed similar results.

Conclusion

The above findings represent the clonal spread of C. difficile in our institution, which mainly includes the NAP1/027 strain. This is the first report of C. difficile ribotype NAP1/027 in Mexico.     

An Economic Analysis of Strategies to Control Clostridium Difficile Transmission and Infection Using an Agent-Based Simulation Model

Background

A number of strategies exist to reduce Clostridium difficile (C. difficile) transmission. We conducted an economic evaluation of “bundling” these strategies together.

Methods

We constructed an agent-based computer simulation of nosocomial C. difficile transmission and infection in a hospital setting. This model included the following components: interactions between patients and health care workers; room contamination via C. difficile shedding; C. difficile hand carriage and removal via hand hygiene; patient acquisition of C. difficile via contact with contaminated rooms or health care workers; and patient antimicrobial use. Six interventions were introduced alone and "bundled" together: (a) aggressive C. difficile testing; (b) empiric isolation and treatment of symptomatic patients; (c) improved adherence to hand hygiene and (d) contact precautions; (e) improved use of soap and water for hand hygiene; and (f) improved environmental cleaning. Our analysis compared these interventions using values representing 3 different scenarios: (1) base-case (BASE) values that reflect typical hospital practice, (2) intervention (INT) values that represent implementation of hospital-wide efforts to reduce C. diff transmission, and (3) optimal (OPT) values representing the highest expected results from strong adherence to the interventions. Cost parameters for each intervention were obtained from published literature. We performed our analyses assuming low, normal, and high C. difficile importation prevalence and transmissibility of C. difficile.

Results

INT levels of the “bundled” intervention were cost-effective at a willingness-to-pay threshold of $100,000/quality-adjusted life-year in all importation prevalence and transmissibility scenarios. OPT levels of intervention were cost-effective for normal and high importation prevalence and transmissibility scenarios. When analyzed separately, hand hygiene compliance, environmental decontamination, and empiric isolation and treatment were the interventions that had the greatest impact on both cost and effectiveness.

Conclusions

A combination of available interventions to prevent CDI is likely to be cost-effective but the cost-effectiveness varies for different levels of intensity of the interventions depending on epidemiological conditions such as C. difficile importation prevalence and transmissibility.     

The Effect of Probiotic Treatment on Patients Infected with the H7N9 Influenza Virus

Background

A novel avian-origin influenza A (H7N9) virus emerged and spread among humans in Eastern China in 2013. Prophylactic treatment with antibiotics and probiotics for secondary infection is as important as antiviral treatment. This study aims to assess the ability of probiotic treatment to restore internal homeostasis under antibiotic pressure and to reduce/ameliorate the risk of secondary infections resulting from infection with the H7N9 virus.

Methods

This is a retrospective study in archival samples. Between April 1 and May 10, 2013, 113 stool, sputum, and blood specimens were collected and analyzed by denaturing gradient gel electrophoresis (DGGE) to determine the composition of the patient microbiomes. Microbial diversity was calculated using Gel-Pro analyzer and Past software. Cluster analysis of DGGE pattern profiles was employed to create a phylogenetic tree for each patient, and multidimensional scaling (MDS) and principal component analysis (PCA) were performed to visualize relationships between individual lanes.

Results

Five patients had secondary infections, including Klebsiella pneumonia, Acinetobacter baumanii and Candida albicans infection. The DGGE profiles of fecal samples obtained at different time points from the same individual were clearly different, particularly for patients with secondary infections. Shannon’s diversity index and evenness index were lower in all infected groups compared to the control group. After B. subtilis and E. faecium or C. butyricum administration, the fecal bacterial profiles of patients who had not been treated with antibiotics displayed a trend of increasing diversity and evenness. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients, but administration of B. subtilis and E. faecium appeared to reduce/ameliorate secondary infection in one patient.

Conclusion

H7N9 infection might decrease intestinal microbial diversity and species richness in humans. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients. B. subtilis and E. faecium may also play a role in reducing/ameliorating secondary infection in these patients.     

Effects of Vaccination with 10-Valent Pneumococcal Non-Typeable Haemophilus influenza Protein D Conjugate Vaccine (PHiD-CV) on the Nasopharyngeal Microbiome of Kenyan Toddlers

Objective

Pneumococcal conjugate vaccines reduce the prevalence of vaccine serotypes carried in the nasopharynx. Because this could alter carriage of other potential pathogens, we assessed the nasopharyngeal microbiome of children who had been vaccinated with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV).

Methods

Profiles of the nasopharyngeal microbiota of 60 children aged 12-59 months, who had been randomized to receive 2 doses of PHiD-CV (n=30) or Hepatitis A vaccine (n=30) 60 days apart, were constructed by 16S rRNA gene pyrosequencing of swab specimens collected before vaccination and 180 days after dose 1.

Results

Prior to vaccination, Moraxella catarrhalis (median of 12.3% of sequences/subject), Streptococcus pneumoniae (4.4%) and Corynebacterium spp. (5.6%) were the most abundant nasopharyngeal bacterial species. Vaccination with PHiD-CV did not significantly alter the species composition, abundance, or prevalence of known pathogens. Distinct microbiomes were identified based on the abundances of Streptococcus, Moraxella, and Haemophilus species. These microbiomes shifted in composition over the study period and were independent of age, sex, school attendance, antibiotic exposure, and vaccination.

Conclusions

Vaccination of children with two doses of PHiD-CV did not significantly alter the nasopharyngeal microbiome. This suggests limited replacement carriage with pathogens other than non-vaccine strains of S. pneumoniae.

Trial Registration

clinicaltrials.gov NCT01028326     

Intramuscular Immunisation with Chlamydial Proteins Induces Chlamydia trachomatis Specific Ocular Antibodies

Background

Ocular infection with Chlamydia trachomatis can cause trachoma, which is the leading cause of blindness due to infection worldwide. Despite the large-scale implementation of trachoma control programmes in the majority of countries where trachoma is endemic, there remains a need for a vaccine. Since C. trachomatis infects the conjunctival epithelium and stimulates an immune response in the associated lymphoid tissue, vaccine regimens that enhance local antibody responses could be advantageous. In experimental infections of non-human primates (NHPs), antibody specificity to C. trachomatis antigens was found to change over the course of ocular infection. The appearance of major outer membrane protein (MOMP) specific antibodies correlated with a reduction in ocular chlamydial burden, while subsequent generation of antibodies specific for PmpD and Pgp3 correlated with C. trachomatis eradication.

Methods

We used a range of heterologous prime-boost vaccinations with DNA, Adenovirus, modified vaccinia Ankara (MVA) and protein vaccines based on the major outer membrane protein (MOMP) as an antigen, and investigated the effect of vaccine route, antigen and regimen on the induction of anti-chlamydial antibodies detectable in the ocular lavage fluid of mice.

Results

Three intramuscular vaccinations with recombinant protein adjuvanted with MF59 induced significantly greater levels of anti-MOMP ocular antibodies than the other regimens tested. Intranasal delivery of vaccines induced less IgG antibody in the eye than intramuscular delivery. The inclusion of the antigens PmpD and Pgp3, singly or in combination, induced ocular antigen-specific IgG antibodies, although the anti-PmpD antibody response was consistently lower and attenuated by combination with other antigens.

Conclusions

If translatable to NHPs and/or humans, this investigation of the murine C. trachomatis specific ocular antibody response following vaccination provides a potential mouse model for the rapid and high throughput evaluation of future trachoma vaccines.