Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study

Background

There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali.

Methods

A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression.

Results

Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively).

Conclusions

In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.     

Prediction of Asthma Exacerbations in Children by Innovative Exhaled Inflammatory Markers: Results of a Longitudinal Study

Background

In asthma management guidelines the primary goal of treatment is asthma control. To date, asthma control, guided by symptoms and lung function, is not optimal in many children and adults. Direct monitoring of airway inflammation in exhaled breath may improve asthma control and reduce the number of exacerbations.

Aim

1) To study the use of fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC), in the prediction of asthma exacerbations in a pediatric population. 2) To study the predictive power of these exhaled inflammatory markers combined with clinical parameters.

Methods

96 asthmatic children were included in this one-year prospective observational study, with clinical visits every 2 months. Between visits, daily symptom scores and lung function were recorded using a home monitor. During clinical visits, asthma control and FeNO were assessed. Furthermore, lung function measurements were performed and EBC was collected. Statistical analysis was performed using a test dataset and validation dataset for 1) conditionally specified models, receiver operating characteristic-curves (ROC-curves); 2) k-nearest neighbors algorithm.

Results

Three conditionally specified predictive models were constructed. Model 1 included inflammatory markers in EBC alone, model 2 included FeNO plus clinical characteristics and the ACQ score, and model 3 included all the predictors used in model 1 and 2. The area under the ROC-curves was estimated as 47%, 54% and 59% for models 1, 2 and 3 respectively. The k-nearest neighbors predictive algorithm, using the information of all the variables in model 3, produced correct predictions for 52% of the exacerbations in the validation dataset.

Conclusion

The predictive power of FeNO and inflammatory markers in EBC for prediction of an asthma exacerbation was low, even when combined with clinical characteristics and symptoms. Qualitative improvement of the chemical analysis of EBC may lead to a better non-invasive prediction of asthma exacerbations.     

Molecular Detection of Streptococcus pneumoniae on Dried Blood Spots from Febrile Nigerian Children Compared to Culture

Background

Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture.

Methods

Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples.

Results

A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4–90.1%) and 62.5% (95% CI 24.5–91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture.

Conclusions

Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens.     

Pathways activated during human asthma exacerbation as revealed by gene expression patterns in blood

Background

Asthma exacerbations remain a major unmet clinical need. The difficulty in obtaining airway tissue and bronchoalveolar lavage samples during exacerbations has greatly hampered study of naturally occurring exacerbations. This study was conducted to determine if mRNA profiling of peripheral blood mononuclear cells (PBMCs) could provide information on the systemic molecular pathways involved during asthma exacerbations.

Methodology/Principal Findings

Over the course of one year, gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared using oligonucleotide arrays. For each of 118 subjects who experienced at least one asthma exacerbation, the gene expression patterns in a sample of peripheral blood mononuclear cells collected during an exacerbation episode were compared to patterns observed in multiple samples from the same subject collected during quiescent asthma. Analysis of covariance identified genes whose levels of expression changed during exacerbations and returned to quiescent levels by two weeks. Heterogeneity among visits in expression profiles was examined using K-means clustering. Three distinct exacerbation-associated gene expression signatures were identified. One signature indicated that, even among patients without symptoms of respiratory infection, genes of innate immunity were activated. Antigen-independent T cell activation mediated by IL15 was also indicated by this signature. A second signature revealed strong evidence of lymphocyte activation through antigen receptors and subsequent downstream events of adaptive immunity. The number of genes identified in the third signature was too few to draw conclusions on the mechanisms driving those exacerbations.

Conclusions/Significance

This study has shown that analysis of PBMCs reveals systemic changes accompanying asthma exacerbation and has laid the foundation for future comparative studies using PBMCs.     

Spectrum of Microbial Diseases and Resistance Patterns at a Private Teaching Hospital in Kenya: Implications for Clinical Practice

Background

Accurate local prevalence of microbial diseases and microbial resistance data are vital for optimal treatment of patients. However, there are few reports of these data from developing countries, especially from sub-Saharan Africa. The status of Aga Khan University Hospital Nairobi as an internationally accredited hospital and a laboratory with an electronic medical record system has made it possible to analyze local prevalence and antimicrobial susceptibility data and compare it with other published data.

Methods

We have analyzed the spectrum of microbial agents and resistance patterns seen at a 300 bed tertiary private teaching hospital in Kenya using microbial identity and susceptibility data captured in hospital and laboratory electronic records between 2010 and 2014.

Results

For blood isolates, we used culture collection within the first three days of hospitalization as a surrogate for community onset, and within that group, Escherichia coli was the most common, followed by Staphylococcus aureus. In contrast, Candida spp. and Klebsiella pneumoniae were the most common hospital onset causes of bloodstream infection. Antimicrobial resistance rates for the most commonly isolated Gram negative organisms was higher than many recent reports from Europe and North America. In contrast, Gram positive resistance rates were quite low, with 94% of S. aureus being susceptible to oxacillin and only rare isolates of vancomycin-resistant enterococci.

Conclusions

The current report demonstrates high rates of antimicrobial resistance in Gram negative organisms, even in outpatients with urinary tract infections. On the other hand, rates of resistance in Gram positive organisms, notably S. aureus, are remarkably low. A better understanding of the reasons for these trends may contribute to ongoing efforts to combat antimicrobial resistance globally.     

The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study

Background

The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society.

Methods

A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics.

Results

A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000).

Conclusions

A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.     

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     

Vitamin D Supplementation for Childhood Asthma: A Systematic Review and Meta-Analysis

Importance

There is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes.

Objectives

The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma.

Data Sources

We searched MEDLINE, Embase, CENTRAL, and CINAHL through July 2014.

Study Selection

We included RCTs that evaluated vitamin D supplementation in children versus active control or placebo for asthma.

Data Extraction and Synthesis

One reviewer extracted data and one reviewer verified data accuracy. We qualitatively summarized the main results of efficacy and safety and meta-analyzed data on comparable outcomes across studies. We used GRADE for strength of evidence.

Main Outcome Measures

Main planned outcomes measures were ED visits and hospitalizations. As secondary outcomes, we examined measures of asthma control, including frequency of asthma exacerbations, asthma symptom scores, measures of lung function, β₂-agonist use and daily steroid use, adverse events and 25-hydroxyvitamin D levels.

Results

Eight RCTs (one parallel, one crossover design) comprising 573 children aged 3 to 18 years were included. One study (moderate-quality, n = 100) reported significantly less ED visits for children treated with vitamin D. No other studies examined the primary outcome (ED visits and hospitalizations). There was a reduced risk of asthma exacerbations in children receiving vitamin D (low-quality; RR 0.41, 95% CI 0.27 to 0.63, 3 studies, n = 378). There was no significant effect for asthma symptom scores and lung function. The serum 25(OH)D level was higher in the vitamin D group at the end of the intervention (low-quality; MD 19.66 nmol/L, 95% CI 5.96 nmol/L to 33.37 nmol/L, 5 studies, n = 167).

Limitations

We identified a high degree of clinical diversity (interventions and outcomes) and methodological heterogeneity (sample size and risk of bias) in included trials.

Conclusions and Relevance

Randomized controlled trials provide some low-quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations. Evidence on the benefits of vitamin D supplementation for other asthma-related outcomes in children is either limited or inconclusive. We recommend that future trials focus on patient-relevant outcomes that are comparable across studies, including standardized definitions of asthma exacerbations.     

Medical Diagnoses Associated with Substance Dependence among Inpatients at a Large Urban Hospital

Background

There are limited data on reasons for hospital admission among patients dependent on substances other than alcohol. We compared primary discharge diagnoses for heroin- or cocaine-dependent patients to non-dependent patients.

Material and Methods

We evaluated a cohort of patients admitted to a general medicine service at a public teaching hospital during July 2005-June 2008. Through bedside interviews, we identified patients who had substance-use disorders. We categorized patients by substance used, route of administration, and dependent or non-dependent use. We grouped diagnostic codes (i.e., ICD-9) using Healthcare Utilization Project categories. We excluded HIV-infected patients.

Results

Of 11,397 patients, 341 (3.0%) were dependent on inhalational heroin, 260 (2.3%) on non-injection cocaine, and 106 (0.9%) on injection heroin. Compared to non-dependent patients, inhalational heroin-dependent patients were over three-fold more likely to have been admitted for respiratory diseases (28% vs. 8%, p<0.01); this association was strongest for asthma exacerbation (OR=7.0; 95% CI, 4.7 to 70.4, p<0.01). Of the 225 admissions for an asthma exacerbation, 44 (19.6%) had co-occurrent heroin-dependence. The most frequent diagnostic category among cocaine-dependent patients was circulatory, which was similar to non-dependent patients (22% vs. 21%, p=0.92).

Discussion

There is a strong association between heroin dependence and hospital admission for an asthma exacerbation. Provision of specialized substance-use treatment for inhalational heroin users will be necessary to reduce the frequency of exacerbations and repeat hospital admissions.     

Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

Background

The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques.

Methods

A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures.

Results

66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007).

Conclusion

Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.     

Impaired macrophage phagocytosis of bacteria in severe asthma

Background

Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria.

Methods

Phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry.

Results

There were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups.

Conclusions

Persistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation.     

Impaired Innate COPD Alveolar Macrophage Responses and Toll-Like Receptor-9 Polymorphisms

Background

Dysfunctional innate responses of alveolar macrophages to nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae contribute to morbidity in chronic obstructive pulmonary disease (COPD). Our earlier studies discovered impaired COPD alveolar macrophage responses to Toll-like receptor (TLR) ligands of nontypeable H. influenzae and provide rationale for further evaluation of TLR signaling. While the role of TLR single nucleotide polymorphisms is increasingly recognized in inflammatory diseases, TLR single nucleotide polymorphisms in COPD have only recently been explored. We hypothesized that specific TLR polymorphisms are associated with dysfunctional innate immune COPD alveolar macrophage responses and investigated polymorphisms of TLR2(Arg753Gln), TLR4(Thr399Ile; Asp299Gly), and TLR9(T1486C; T1237C).

Methods

DNA was purified from cells of 1) healthy nonsmokers (n = 20); 2) COPD ex-smokers (n = 83); 3) COPD active smokers (n = 93). DNA amplifications (polymerase chain reaction) were performed for each SNP. Alveolar macrophages from each group were incubated with nontypeable H. influenzae, M. catarrhalis and S. pneumoniae. Cytokine induction of macrophage supernatants was measured and the association with TLR single nucleotide polymorphism expression was determined.

Results

No significant inter-group differences in frequency of any TLR SNP existed. However both TLR9 single nucleotide polymorphisms were expressed in high frequency. Among COPD ex-smokers, diminished IL-8 responsiveness to nontypeable H. influenzae, M. catarrhalis and S. pneumoniae was strongly associated with carriage of TLR9(T1237C) (p = 0.02; p = 0.008; p = 0.02), but not TLR9(T1486C). Carriage of TLR9(T1237C), but not TLR9(T1486C), correlated with diminished FEV₁%predicted (p = 0.037).

Conclusion

Our results demonstrate a notable association of TLR9(T1237C) expression with dysfunctional innate alveolar macrophage responses to respiratory pathogens and with severity of COPD.     

Emerging,Non-PCV13 Serotypes 11A and 35B of Streptococcus pneumoniae Show High Potential for Biofilm Formation In Vitro

Background

Since the use of pneumococcal conjugate vaccines PCV7 and PCV13 in children became widespread, invasive pneumococcal disease (IPD) has dramatically decreased. Nevertheless, there has been a rise in incidence of Streptococcus pneumoniae non-vaccine serotypes (NVT) colonising the human nasopharynx. Nasopharyngeal colonisation, an essential step in the development of S. pneumoniae-induced IPD, is associated with biofilm formation. Although the capsule is the main pneumococcal virulence factor, the formation of pneumococcal biofilms might, in fact, be limited by the presence of capsular polysaccharide (CPS).

Methodology/Principal Findings

We used clinical isolates of 16 emerging, non-PCV13 serotypes as well as isogenic transformants of the same serotypes. The biofilm formation capacity of isogenic transformants expressing CPSs from NVT was evaluated in vitro to ascertain whether this trait can be used to predict the emergence of NVT. Fourteen out of 16 NVT analysed were not good biofilm formers, presumably because of the presence of CPS. In contrast, serotypes 11A and 35B formed ≥45% of the biofilm produced by the non-encapsulated M11 strain.

Conclusions/Significance

This study suggest that emerging, NVT serotypes 11A and 35B deserve a close surveillance.     

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.     

Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease

Background

Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD.

Methods

In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations.

Results

There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70.

Conclusions

Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.     

Prevalence and Antimicrobial Resistance of Microbes Causing Bloodstream Infections in Unguja,Zanzibar

Background

Bloodstream infections (BSI) are frequent and cause high case-fatality rates. Urgent antibiotic treatment can save patients’ lives, but antibiotic resistance can render antibiotic therapy futile. This study is the first to collect epidemiological data on BSI from Unguja, Zanzibar.

Methods

Clinical data and blood for culturing and susceptibility testing of isolated microbes were obtained from 469 consecutively enrolled neonates, children and adults presenting with signs of systemic infections at Mnazi Mmoja Hospital (MMH), Zanzibar.

Results

Pathogenic bacteria were recovered from the blood of 14% of the patients (66/469). The most frequently isolated microbes were Klebsiella pneumoniae, Escherichia coli, Acinetobacter spp. and Staphylococcus aureus. Infections were community-acquired in 56 patients (85%) and hospital-acquired in 8 (12%) (data missing for 2 patients). BSI caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (E. coli, K. pneumoniae) was found in 5 cases, of which 3 were community-acquired and 2 hospital-acquired. Three of these patients died. Six of 7 Salmonella Typhi isolates were multidrug resistant. Streptococcus pneumoniae was found in one patient only.

Conclusions

This is the first report of ESBL-producing bacteria causing BSI from the Zanzibar archipelago. Our finding of community-acquired BSI caused by ESBL-producing bacteria is alarming, as it implies that these difficult-to-treat bacteria have already spread in the society. In the local setting these infections are virtually impossible to cure. The findings call for increased awareness of rational antibiotic use, infection control and surveillance to counteract the problem of emerging antimicrobial resistance.     

Effect of Saccharomyces boulardii and Mode of Delivery on the Early Development of the Gut Microbial Community in Preterm Infants

Background

Recent advances in culture-independent approaches have enabled insights into the diversity, complexity, and individual variability of gut microbial communities.

Objectives

To examine the effect of oral administration of Saccharomyces (S.) boulardii and mode of delivery on the intestinal microbial community in preterm infants.

Study Design

Stool samples were collected from preterm newborns randomly divided into two groups: a probiotic-receiving group (n = 18) or a placebo group (n = 21). Samples were collected before probiotic intake (day 0), and after 2 and 6 weeks of supplementation. The composition of colonizing bacteria was assessed by 16S ribosomal RNA (rRNA) gene sequencing of fecal samples using the Ion 16S Metagenomics Kit and the Ion Torrent Personal Genome Machine platform.

Results

A total of 11932257 reads were generated, and were clustered into 459, 187, and 176 operational taxonomic units at 0 days, 2 weeks, and 6 weeks, respectively. Of the 17 identified phyla, Firmicutes Actinobacteria, Proteobacteria, and Bacteroidetes were universal. The microbial community differed at day 0 compared with at 2 weeks and 6 weeks. There was a tendency for increased bacterial diversity at 2 weeks and 6 weeks compared with day 0, and infants with a gestational age of 31 weeks or higher presented increased bacterial diversity prior to S. boulardii administration. Firmicutes and Proteobacteria remained stable during the observation period, whereas Actinobacteria and Bacteroidetes increased in abundance, the latter particularly more sharply in vaginally delivered infants.

Conclusion

While the mode of delivery may influence the development of a microbial community, this study had not enough power to detect statistical differences between cohorts supplemented with probiotics, and in a consequence, to speculate on S. boulardii effect on gut microbiome composition in preterm newborns.     

On the Ecology and Conservation of Sericinus montelus (Lepidoptera: Papilionidae) – Its Threats in Xiaolongshan Forests Area (China)

Contents and Methods

Here we present a detailed analysis of the life history, mobility and habitat requirements of the butterfly Sericinus montelus on the basis of extensive field observations, experimental breeding, capture-mark- recapture (CMR) and transect surveys.

Life History

We found that S. montelus has three generations per year and overwinters as pupae on shrub branches in Xiaolongshan. The adults of first generation have a peak of emergence in late April. The second generation emerges at the end of June and the third in early to middle August. Within the study region, larvae of S. montelus are monophagous on Aristolochia contorta. Adults fly slowly and lay eggs in clusters.

Key Factors

Life tables show that natural enemies and human activities such as mowing, weeding and trampling during the egg and larval stages are key factors causing high mortality, killing up to 43% of eggs and 72% of larvae thereby limiting population growth and recovery.

Population Ecology

The populations of S. montelus in Xiaolongshan have a rather patchy distribution. According to CMR data, adults fly a maximum distance of 700m within a lifespan of 6 days. The host plant A. contorta, grows along the low banks of fields, irrigation ditches and paths, and can be highly affected by agricultural activities, like mowing, weeding and herding, which impact larval survival.

Population Maintenance

For S. montelus should mainly focus on reducing agricultural threats to the host plant A. contorta and on increasing habitat connectivity.     

Type 2 Diabetes Mellitus Is Associated with Strongyloides stercoralis Treatment Failure in Australian Aboriginals

Objective

To explore the efficacy of ivermectin in the treatment of serologically diagnosed cases of Strongyloides stercoralis (S. stercoralis) infection in an Aboriginal community and to describe factors that may influence the outcome of treatment.

Methods

Longitudinal study of a group of 92 individuals with serologically diagnosed S. stercoralis treated with ivermectin and followed up over a period of approximately 6 months. Main outcomes were serological titers pre and post treatment, diabetic status, and duration of follow up.

Findings

Treatment success was achieved in 62% to 79% of cases dependent on the methods employed for the diagnosis of infection and assessment of treatment outcome. Type 2 Diabetes Mellitus (T2DM) was found to be significantly associated with treatment failure in this group for two of the three methods employed.

Interpretation

Ivermectin has been confirmed as an effective treatment for S stercoralis infection in this setting. T2DM appears to be an independent risk factor for treatment failure in this population, and plausible mechanisms to explain this observation are presented.     

Inhibiting AKT Phosphorylation Employing Non-Cytotoxic Anthraquinones Ameliorates TH2 Mediated Allergic Airways Disease and Rhinovirus Exacerbation

Background

Severe asthma is associated with T helper (T_H) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.

Objective

To determine the anti-inflammatory potential of anthraquinones in-vivo.

Methods

BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.

Results

Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of T_H2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.

Conclusion

Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT.