Temporal association of acute hepatitis A and Plasmodium falciparum malaria in children

Background

In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV) infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists.

Materials and Methods

We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period.

Discussion

Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81–3.1) infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14–0.50) infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively), largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation.

Conclusion

The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.     

PCR improves diagnostic yield from lung aspiration in Malawian children with radiologically confirmed pneumonia

Background

Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid.

Methods

A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid.

Results

Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection.

Conclusions

In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa.     

Viral and atypical bacterial detection in acute respiratory infection in children under five years

Background

Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil.

Methods

Clinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA.

Findings

407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia.

Interpretation

This study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively.     

Identifying low pH active and lactate-utilizing taxa within oral microbiome communities from healthy children using stable isotope probing techniques

Background

Many human microbial infectious diseases including dental caries are polymicrobial in nature. How these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral bacteria have been characterized in vitro, their physiology within the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these species remain uncultivated to date with little known besides their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated species will remain enigmatic despite their apparent disease correlation. To start addressing these knowledge gaps, we applied a combination of Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for in vitro temporal monitoring of metabolites and identification of metabolically active and inactive bacterial species.

Methodology/Principal Findings

Supragingival plaque samples from caries-free children incubated with ¹³C-substrates under imposed healthy (buffered, pH 7) and diseased states (pH 5.5 and pH 4.5) produced lactate as the dominant organic acid from glucose metabolism. Rapid lactate utilization upon glucose depletion was observed under pH 7 conditions. SIP analyses revealed a number of genera containing cultured and uncultivated taxa with metabolic capabilities at pH 5.5. The diversity of active species decreased significantly at pH 4.5 and was dominated by Lactobacillus and Propionibacterium species, both of which have been previously found within carious lesions from children.

Conclusions/Significance

Our approach allowed for identification of species that metabolize carbohydrates under different pH conditions and supports the importance of Lactobacilli and Propionibacterium in the development of childhood caries. Identification of species within healthy subjects that are active at low pH can lead to a better understanding of oral caries onset and generate appropriate targets for preventative measures in the early stages.     

Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapy

Background

Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children.

Methodology/Principal Findings

Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2–16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥10⁴ colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination.

Conclusions/Significance

Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.     

Screening for acute childhood malnutrition during the National Nutrition Week in mali increases treatment referrals

Objective

To evaluate a pilot intervention designed to integrate mid-upper arm circumference (MUAC) screening for acute malnutrition into the semi-annual Child Nutrition Week (Semaine d''Intensification des Activités de Nutrition, or “SIAN”) activities carried out in June 2008.

Design

A cross-sectional survey was conducted in Kolokani and Nara, two health districts in the Koulikoro region of Mali, 4–5 months after the SIAN, using a population-proportionate, multi-stage random sample of: 1) health centers, and 2) households in communities linked to each of the selected health centers. Caregivers of 1543 children who were 6–59 months of age at the time of the SIAN, 17 community-based volunteers and 45 health center staff members were interviewed.

Results

A total of 1278 children 6–59 months (83% of those studied) reportedly participated in SIAN. Of the participating children, 1258 received vitamin A (98% of SIAN participants; 82% of all eligible children), 945 received anti-helminth tablets (84% of participants; 71% of eligibles), and 669 were screened for acute malnutrition (52% of participants; 43% of eligibles). 186 of the children screened (27%) were reportedly identified as acutely malnourished. SIAN screening covered a significantly greater proportion of children than were examined in both community-based (22% of children) and health center-based screening activities (5% of children) combined during the 4-5 months after the SIAN (P<0.0001). In general, community volunteers and health personnel positively evaluated their experience adding MUAC screening to SIAN.

Conclusion

Integrating MUAC screening for acute malnutrition in SIAN permits the assessment of a large number of children for acute malnutrition, and should be continued.     

Impact of temperature and atmospheric pressure on the incidence of major acute cardiovascular events

Background

The impact of meteorological conditions on the occurrence of various cardiovascular events has been reported internationally. Data about the Dutch situation are limited.

Objectives

We sought to find out a correlation between weather conditions and the incidence of major acute cardiovascular events such as type A acute aortic dissection (AAD), acute myocardial infarction (AMI) and acutely presented abdominal aortic aneurysms (AAAA).

Methods

Between January 1998 and February 2010, patients who were admitted to our hospital (Catharina Hospital, Eindhoven, the Netherlands) because of AAD (n = 212), AMI (n = 11389) or AAAA (n = 1594) were registered. These data were correlated with the meteorological data provided by the Royal Dutch Meteorological Institute (KNMI) over the same period.

Results

During the study period, a total number of 11,412 patients were admitted with AMI, 212 patients with AAD and 1593 patients with AAAA. A significant correlation was found between the daily temperature and the number of hospital admissions for AAD. The lower the daily temperature, the higher the incidence of AAD (p = 0.002). Lower temperature was also a predictor of a higher incidence of AMI (p = 0.02). No significant correlation was found between daily temperature and onset of AAAA.

Conclusions

Cold weather is correlated with a higher incidence of AAD and AMI.     

Time distribution of the onset of chest pain in subjects with acute ST-elevation myocardial infarction: an eight-year, single-center study in China

Objective

The objective of this study was to explore the time distribution patterns of the onset of chest pain in subjects with acute ST-elevation myocardial infarction in a Chinese population.

Methods

A total of 1467 patients with acute ST-elevation myocardial infarction were enrolled from 2003 to 2010. The hourly, daily, monthly, seasonal and day-of-week fluctuations in the prevalence of acute ST-elevation myocardial infarction were analyzed.

Results

A peak was found between the morning hours of 07:31 and 08:30. A second peak was observed between 14:31 and 15:30, and a third peak was found between 23:31 and 00:30 (p<0.001). The monthly maximum was recorded in November and the minimum was in April (p<0.001). The number of daily cases was greatest in autumn and lowest in the spring (p = 0.001). Day-of-the-week variations of ST-elevation acute myocardial infarction were not found, except in patients more than 75-years-old.

Conclusions

Periodic variations in the frequency of ST-elevation acute myocardial infarction in Chinese patients showed significant differences with regard to diurnal, monthly and seasonal patterns. The exact mechanisms underlying these circadian variations require further study.     

Iron deficiency and acute seizures: results from children living in rural Kenya and a meta-analysis

Background

There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area.

Methods

We recruited 133 children, aged 3–156 months, who presented to a district hospital on the Kenyan coast with acute seizures and frequency-matched these to children of similar ages but without seizures. We defined iron deficiency according to the presence of malarial infection and evidence of inflammation. In patients with malaria, we defined iron deficiency as plasma ferritin<30µg/ml if plasma C-reactive protein (CRP) was<50mg/ml or ferritin<273µg/ml if CRP≥50mg/ml, and in those without malaria, as ferritin<12µg/ml if CRP<10mg/ml or ferritin<30µg/ml if CRP≥10mg/ml. In addition, we performed a meta-analysis of case-control studies published in English between January 1966 and December 2009 and available through PUBMED that have examined the relationship between iron deficiency and febrile seizures in children.

Results

In our Kenyan case control study, cases and controls were similar, except more cases reported past seizures. Malaria was associated with two-thirds of all seizures. Eighty one (30.5%) children had iron deficiency. Iron deficiency was neither associated with an increased risk of acute seizures (45/133[33.8%] cases were iron deficient compared to 36/133[27.1%] controls, p = 0.230) nor status epilepticus and it did not affect seizure semiology. Similar results were obtained when children with malaria, known to cause acute symptomatic seizures in addition to febrile seizures were excluded. However, in a meta-analysis that combined all eight case-control studies that have examined the association between iron deficiency and acute/febrile seizures to-date, iron deficiency, described in 310/1,018(30.5%) cases and in 230/1,049(21.9%) controls, was associated with a significantly increased risk of seizures, weighted OR 1.79(95%CI 1.03–3.09).

Conclusions

Iron deficiency is not associated with an increased risk of all acute seizures in children but of febrile seizures. Further studies should examine mechanisms involved and the implications for public health.     

Campylobacter jejuni induces acute enterocolitis in gnotobiotic IL-10-/- mice via Toll-like-receptor-2 and -4 signaling

Background

Campylobacter jejuni is a leading cause of foodborne bacterial enterocolitis worldwide. Investigation of immunopathology is hampered by a lack of suitable vertebrate models. We have recently shown that gnotobiotic mice as well as conventional IL-10^−/− animals are susceptible to C. jejuni infection and develop intestinal immune responses. However, clinical symptoms of C. jejuni infection were rather subtle and did not reflect acute bloody diarrhea seen in human campylobacteriosis.

Methodology/Principal Findings

In order to overcome these limitations we generated gnotobiotic IL-10^−/− mice by quintuple antibiotic treatment starting right after weaning. The early treatment was essential to prevent these animals from chronic colitis. Following oral infection C. jejuni colonized the gastrointestinal tract at high levels and induced acute enterocolitis within 7 days as indicated by bloody diarrhea and pronounced histopathological changes of the colonic mucosa. Immunopathology was further characterized by increased numbers of apoptotic cells, regulatory T-cells, T- and B-lymphocytes as well as elevated TNF-α, IFN-γ, and MCP-1 concentrations in the inflamed colon. The induction of enterocolitis was specific for C. jejuni given that control animals infected with a commensal E. coli strain did not display any signs of disease. Most strikingly, intestinal immunopathology was ameliorated in mice lacking Toll-like-receptors-2 or -4 indicating that C. jejuni lipoproteins and lipooligosaccharide are essential for induction and progression of immunopathology.

Conclusion/Significance

Gnotobiotic IL-10^−/− mice develop acute enterocolitis following C. jejuni infection mimicking severe episodes of human campylobacteriosis and are thus well suited to further dissect mechanisms underlying Campylobacter infections in vivo.     

IL-12 RB1 genetic variants contribute to human susceptibility to severe acute respiratory syndrome infection among Chinese

Background

Cytokines play important roles in antiviral action. We examined whether polymorphisms of interleukin (IL)-12 receptor B1 (IL-12RB1) affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS).

Methods

A case-control study was carried out in Chinese SARS patients and healthy controls. The genotypes of 4SNPs on IL-12 RB1 gene, +705A/G,+1158T/C, +1196G/C and +1664 C/T, were determined by PCR-RFLP. Haplotypes were estimated from the genotype data using the expectation-maximisation algorithm.

Results

Comparison between patients and close contacts showed that individuals with the +1664 C/T (CT and TT) genotype had a 2.09-fold (95% confidence interval [CI], 1.90–7.16) and 2.34-fold (95% CI, 1.79–13.37) increased risk of developing SARS, respectively. For any of the other three polymorphisms, however, no significant difference can be detected in allele or genotype frequencies between patients and controls. Additionally, estimation of the frequencies of multiple-locus haplotypes revealed potential risk haplotypes (GCCT) for SARS infection.

Conclusions

Our data indicate that genetic variants of IL12RB1confer genetic susceptibility to SARS infection, but not necessary associated with the progression of the disease in Chinese population.     

Association of alpha B-crystallin genotypes with oral cancer susceptibility, survival, and recurrence in Taiwan

Background

Alpha B-crystallin (CRYAB) is a protein that functions as “molecular chaperone” in preserving intracellular architecture and cell membrane. Also, CRYAB is highly antiapoptotic. Abnormal CRYAB expression is a prognostic biomarker for oral cancer, while its genomic variations and the association with carcinogenesis have never been studied.

Methodology/Finding

Therefore, we hypothesized that CRYAB single nucleotide polymorphisms may be associated with oral cancer risk. In this hospital-based study, the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2 (rs2070894) polymorphisms with oral cancer in a Taiwan population was investigated. In total, 496 oral cancer patients and 992 age- and gender-matched healthy controls were genotyped and analyzed. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the oral cancer and control groups. The CRYAB C-802G G allele conferred an increased risk of oral cancer (P = 1.49×10⁻⁵). Patients carrying CG/GG at CRYAB C-802G were of lower 5-year survival and higher recurrence rate than those of CC (P<0.05).

Conclusion/Significance

Our results provide the first evidence that the G allele of CRYAB C-802G is correlated with oral cancer risk and this polymorphism may be a useful marker for oral cancer recurrence and survival prediction for clinical reference.     

Gene expression associated with white syndromes in a reef building coral,Acropora hyacinthus

Background

Corals are capable of launching diverse immune defenses at the site of direct contact with pathogens, but the molecular mechanisms of this activity and the colony-wide effects of such stressors remain poorly understood. Here we compared gene expression profiles in eight healthy Acropora hyacinthus colonies against eight colonies exhibiting tissue loss commonly associated with white syndromes, all collected from a natural reef environment near Palau. Two types of tissues were sampled from diseased corals: visibly affected and apparently healthy.

Results

Tag-based RNA-Seq followed by weighted gene co-expression network analysis identified groups of co-regulated differentially expressed genes between all health states (disease lesion, apparently healthy tissues of diseased colonies, and fully healthy). Differences between healthy and diseased tissues indicate activation of several innate immunity and tissue repair pathways accompanied by reduced calcification and the switch towards metabolic reliance on stored lipids. Unaffected parts of diseased colonies, although displaying a trend towards these changes, were not significantly different from fully healthy samples. Still, network analysis identified a group of genes, suggestive of altered immunity state, that were specifically up-regulated in unaffected parts of diseased colonies.

Conclusions

Similarity of fully healthy samples to apparently healthy parts of diseased colonies indicates that systemic effects of white syndromes on A. hyacinthus are weak, which implies that the coral colony is largely able to sustain its physiological performance despite disease. The genes specifically up-regulated in unaffected parts of diseased colonies, instead of being the consequence of disease, might be related to the originally higher susceptibility of these colonies to naturally occurring white syndromes.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1540-2) contains supplementary material, which is available to authorized users.     

A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers

Background and Rationale

Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear whether the same acute effects occur in humans.

Methodology/Principal Findings

A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8) and female (7) subjects [18–30 years old, BMI 18.5–25]. Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC) by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203) and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170), whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166) and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184), respectively after olanzapine. Other measures were unchanged.

Conclusions/Significance

Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00741026","term_id":"NCT00741026"}}NCT00741026     

Cytokine profiles, CTL response and T cell frequencies in the peripheral blood of acute patients and individuals recovered from hepatitis E infection

Background

Hepatitis E is a major public health problem in the developing countries. Pathogenesis of hepatitis E virus (HEV) infection is poorly understood.

Methods

This case-control study included 124 Hepatitis E patients (46 acute and 78 recovered), 9 with prior exposure to HEV and 71 anti-HEV negative healthy controls. HEV induced CTL response by Elispot, cytokines/chemokines quantitation by Milliplex assay and peripheral CD4+ & CD8+ T cell frequencies by flow cytometry were assessed.

Results

Among the patient categories, HEV specific IFN-γ responses as recorded by Elispot were comparable. Comparisons of cytokines/chemokines revealed significantly high levels of IL-1α and sIL-2Rα during acute phase. Circulating peripheral CD4/CD8+ T-cell subsets in acute and recovered individuals were comparable compared to controls, while among patient categories CD8+T cell subset was significantly higher in recovered individuals.

Conclusions

Our findings suggest that IL-1α and sIL-2Rα play a role in the pathogenesis of acute Hepatitis E infection. Lack of robust HEV ORF2-specific CTL response in the peripheral blood of HEV infected patients during the acute and recovered phases of the disease may be associated with involvement of innate immune cells/localization of the immune events at the site of infection.     

Hepcidin is an antibacterial, stress-inducible peptide of the biliary system

Background/Aims

Hepcidin (gene name HAMP), an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections.

Methods

Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and –blotting, while prohepcidin levels in human bile were determined by ELISA.

Results

Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC) patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03). In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively). In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p<0.05).

Conclusion

Hepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections.     

Studies on the antibacterial effects of statins--in vitro and in vivo

Background

Statin treatment has been associated with a beneficial outcome on respiratory tract infections. In addition, previous in vitro and in vivo experiments have indicated favorable effects of statins in bacterial infections.

Aim

The aim of the present study was to elucidate possible antibacterial effects of statins against primary pathogens of the respiratory tract.

Methods

MIC-values for simvastatin, fluvastatin and pravastatin against S. pneumoniae, M. catarrhalis and H. influenzae were determined by traditional antibacterial assays. A BioScreen instrument was used to monitor effects of statins on bacterial growth and to assess possible synergistic effects with penicillin. Bacterial growth in whole blood and serum from healthy volunteers before and after a single dose of simvastatin, fluvastatin and penicillin (positive control) was determined using a blood culture system (BactAlert).

Findings

The MIC-value for simvastatin against S pneumoniae and M catarrhalis was 15 µg/mL (36 mmol/L). Fluvastatin and Pravastatin showed no antibacterial effect in concentrations up to 100 µg/mL (230 µmol/L). Statins did not affect growth or viability of H influenzae. Single doses of statins given to healthy volunteers did not affect growth of pneumococci, whereas penicillin efficiently killed all bacteria.

Conclusions

Simvastatin at high concentrations 15 µg/mL (36 µmol/L) rapidly kills S pneumoniae and M catarrhalis. However, these concentrations by far exceed the concentrations detected in human blood during simvastatin therapy (1–15 nmol/L) and single doses of statins given to healthy volunteers did not improve antibacterial effects of whole blood. Thus, a direct bactericidal effect of statins in vivo is probably not the mechanism behind the observed beneficial effect of statins against various infections.     

Microarray Analysis of Microbiota of Gingival Lesions in Noma Patients

Noma (cancrum oris) is a gangrenous disease of unknown etiology affecting the maxillo-facial region of young children in extremely limited resource countries. In an attempt to better understand the microbiological events occurring during this disease, we used phylogenetic and low-density microarrays targeting the 16S rRNA gene to characterize the gingival flora of acute noma and acute necrotizing gingivitis (ANG) lesions, and compared them to healthy control subjects of the same geographical and social background. Our observations raise doubts about Fusobacterium necrophorum, a previously suspected causative agent of noma, as this species was not associated with noma lesions. Various oral pathogens were more abundant in noma lesions, notably Atopobium spp., Prevotella intermedia, Peptostreptococcus spp., Streptococcus pyogenes and Streptococcus anginosus. On the other hand, pathogens associated with periodontal diseases such as Aggregatibacter actinomycetemcomitans, Capnocytophaga spp., Porphyromonas spp. and Fusobacteriales were more abundant in healthy controls. Importantly, the overall loss of bacterial diversity observed in noma samples as well as its homology to that of ANG microbiota supports the hypothesis that ANG might be the immediate step preceding noma.     

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis

Background

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS).

Objectives

To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS.

Methods

Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed.

Results

Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral.

Conclusions

Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.