Showing papers in "BMC Infectious Diseases in 2013"
TL;DR: Egypt is confronted with an HCV disease burden of historical proportions that distinguishes this nation from others, and policymakers, public health and medical care stakeholders need to introduce and implement further prevention measures targeting the routes of HCV transmission.
Abstract: Egypt has the highest prevalence of hepatitis C virus (HCV) in the world, estimated nationally at 14.7%. Our study’s objective was to delineate the evidence on the epidemiology of HCV infection among the different population groups in Egypt, and to draw analytical inferences about the nature of HCV transmission in this country. We conducted a systematic review of all data on HCV prevalence and incidence in Egypt following PRISMA guidelines. The main sources of data included PubMed and Embase databases. We also used a multivariate regression model to infer the temporal trend of HCV prevalence among the general population and high risk population in Egypt. We identified 150 relevant records, four of which were incidence studies. HCV incidence ranged from 0.8 to 6.8 per 1,000 person-years. Overall, HCV prevalence among pregnant women ranged between 5-15%, among blood donors between 5-25%, and among other general population groups between 0-40%. HCV prevalence among multi-transfused patients ranged between 10-55%, among dialysis patients between 50-90%, and among other high risk populations between 10% and 85%. HCV prevalence varied widely among other clinical populations and populations at intermediate risk. Risk factors appear to be parenteral anti-schistosomal therapy, injections, transfusions, and surgical procedures, among others. Results of our time trend analysis suggest that there is no evidence of a statistically significant decline in HCV prevalence over time in both the general population (p-value: 0.215) and high risk population (p-value: 0.426). Egypt is confronted with an HCV disease burden of historical proportions that distinguishes this nation from others. A massive HCV epidemic at the national level must have occurred with substantial transmission still ongoing today. HCV prevention in Egypt must become a national priority. Policymakers, and public health and medical care stakeholders need to introduce and implement further prevention measures targeting the routes of HCV transmission.
364 citations
TL;DR: In patients with relapsing infections, the majority of serial isolates recovered from these individuals were observed to be strong biofilm producers in vitro, and strains from patients with persistent infections are positive for biofilm formation.
Abstract: Biofilm formation is a major virulence factor contributing to the chronicity of infections. To date few studies have evaluated biofilm formation in infecting isolates of patients including both Gram-positive and Gram-negative multidrug-resistant (MDR) species in the context of numerous types of infectious syndromes. Herein, we investigated the biofilm forming capacity in a large collection of single patient infecting isolates and compared the relationship between biofilm formation to various strain characteristics. The biofilm-forming capacity of 205 randomly sampled clinical isolates from patients, collected from various anatomical sites, admitted for treatment at Brooke Army Medical Center (BAMC) from 2004–2011, including methicillin-resistant/methicillin susceptible Staphylococcus aureus (MRSA/MSSA) (n=23), Acinetobacter baumannii (n=53), Pseudomonas aeruginosa (n=36), Klebsiella pneumoniae (n=54), and Escherichia coli (n=39), were evaluated for biofilm formation using the high-throughput microtiter plate assay and scanning electron microscopy (SEM). Relationships between biofilm formation to clonal type, site of isolate collection, and MDR phenotype were evaluated. Furthermore, in patients with relapsing infections, serial strains were assessed for their ability to form biofilms in vitro. Of the 205 clinical isolates tested, 126 strains (61.4%) were observed to form biofilms in vitro at levels greater than or equal to the Staphylococcus epidermidis, positive biofilm producing strain, with P. aeruginosa and S. aureus having the greatest number of biofilm producing strains. Biofilm formation was significantly associated with specific clonal types, the site of isolate collection, and strains positive for biofilm formation were more frequently observed to be MDR. In patients with relapsing infections, the majority of serial isolates recovered from these individuals were observed to be strong biofilm producers in vitro. This study is the first to evaluate biofilm formation in a large collection of infecting clinical isolates representing diverse types of infections. Our results demonstrate: (1) biofilm formation is a heterogeneous property amongst clinical strains which is associated with certain clonal types, (2) biofilm forming strains are more frequently isolated from non-fluid tissues, in particular bone and soft tissues, (3) MDR pathogens are more often biofilm formers, and (4) strains from patients with persistent infections are positive for biofilm formation.
308 citations
TL;DR: The literature suggests that AGWs are widespread and the prevalence depends on study methodology as suggested by higher rates reported from routine genital examinations versus those from treatment records, but there remains a need for more population-based studies from certain regions including Africa, Latin America and Southern Asia to further elucidate the global epidemiology of this disease.
Abstract: Anogenital warts (AGWs) are a common, highly infectious disease caused by the human papillomavirus (HPV), whose high recurrence rates contribute to direct medical costs, productivity loss and increased psychosocial impact. Because of the lack of a systematic review of the epidemiology of AGWs in the literature, this study reviewed the published medical literature on the incidence and prevalence of AGWs. A comprehensive literature search was performed on the worldwide incidence and prevalence of AGWs between 2001 and 2012 using the PubMed and EMBASE databases. An additional screening of abstracts from relevant sexual health and infectious disease conferences from 2009 to 2011 was also conducted. Only original studies with general adult populations (i.e., at least including ages 20 through 40 years) were included. The overall (females and males combined) reported annual incidence of any AGWs (including new and recurrent) ranged from 160 to 289 per 100,000, with a median of 194.5 per 100,000. New AGW incidence rates among males ranged from 103 to 168 per 100,000, with a median of 137 per 100,000 and among females from 76 to 191 per 100,000, with a median of 120.5 per 100,000 per annum. The reported incidence of recurrent AGWs was as high as 110 per 100,000 among females and 163 per 100,000 among males. Incidence peaked before 24 years of age in females and between 25 and 29 years of age among males. The overall prevalence of AGWs based on retrospective administrative databases or medical chart reviews or prospectively collected physician reports ranged from 0.13% to 0.56%, whereas it ranged from 0.2% to 5.1% based on genital examinations. The literature suggests that AGWs are widespread and the prevalence depends on study methodology as suggested by higher rates reported from routine genital examinations versus those from treatment records. However, there remains a need for more population-based studies from certain regions including Africa, Latin America and Southern Asia to further elucidate the global epidemiology of this disease.
294 citations
TL;DR: Proper screening (which must include serology) is mandatory in high - risk patients, for instance candidates to immunosuppressive medications, currently or previously living in endemic countries.
Abstract: Background
Strongyloidiasis is commonly a clinically unapparent, chronic infection, but immuno suppressed subjects can develop fatal disease. We carried out a review of literature on hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), in order to describe the most challenging aspects of severe strongyloidiasis.
278 citations
TL;DR: Comparison with molecular analysis suggests that the detection threshold of FISH and culture is related to organism abundance and, furthermore, culture tends to select for rapidly growing organisms.
Abstract: Bacteria and fungi are believed to influence mucosal inflammation in chronic rhinosinusitis (CRS). However their presence and relationship to disease is debated. This study used multiple detection methods to compare microbial diversity and microbial abundance in healthy and diseased sinonasal mucosa. The utility of contemporary detection methods is also examined. Sinonasal mucosa was analyzed from 38 CRS and 6 controls. Bacterial and fungal analysis was performed using conventional culture, molecular diagnostics (polymerase chain reaction coupled with electrospray ionization time-of-flight mass spectrometry) and fluorescence in situ hybridization.
Microbes were detected in all samples, including controls, and were often polymicrobial. 33 different bacterial species were detected in CRS, 5 in control patients, with frequent recovery of anaerobes. Staphylococcus aureus and Propionibacterium acnes were the most common organisms in CRS and controls, respectively. Using a model organism, FISH had a sensitivity of 78%, and a specificity of 93%. Many species were detected in both CRS and controls however, microbial abundance was associated with disease manifestation. This study highlights some cornerstones of microbial variations in healthy and diseased paranasal sinuses. Whilst the healthy sinus is clearly not sterile, it appears prevalence and abundance of organisms is critical in determining disease. Evidence from high-sensitivity techniques, limits the role of fungi in CRS to a small group of patients. Comparison with molecular analysis suggests that the detection threshold of FISH and culture is related to organism abundance and, furthermore, culture tends to select for rapidly growing organisms.
233 citations
TL;DR: Bacteria isolated from females were less resistant than those isolated from males and this difference increased with the patient age, but the fluoroquinolones should not be suitable to treat male infections and the trimethoprim-sulfamethoxazole shall not be used in the treatment of UTI at this level.
Abstract: Urinary tract infection (UTI) is one of the most common infectious diseases at the community level. In order to assess the adequacy of the empirical therapy, the prevalence and the resistance pattern of the main bacteria responsible for UTI in the community (in Aveiro, Portugal) was evaluated throughout a ten-year period. In this retrospective study, all urine samples from patients of the District of Aveiro, in ambulatory regime, collected at the Clinical Analysis Laboratory Avelab during the period 2000–2009 were analysed. Samples with more than 105 CFU/mL bacteria were considered positive and, for these samples, the bacteria were identified and the profile of antibiotic susceptibility was characterized. From the 155597 samples analysed, 18797 (12.1%) were positive for bacterial infection. UTI was more frequent in women (78.5%) and its incidence varied with age, affecting more the elderly patients (38.6%). Although E. coli was, as usual, the most common pathogen implicated in UTI, it were observed differences related to the other bacteria more implicated in UTI relatively to previous studies. The bacteria implicated in the UTI varied with the sex of the patient, being P. aeruginosa a more important cause of infection in men than in women. The incidence of the main bacteria changed over the study period (P. aeruginosa, Klebsiella spp and Providencia spp increased and Enterobacter spp decreased). Although E. coli was responsible for more than an half of UTI, its resistance to antibiotics was low when compared with other pathogens implicated in UTI, showing also the lowest percentage of multidrug resistant (MDR) isolates (17%). Bacteria isolated from females were less resistant than those isolated from males and this difference increased with the patient age. The differences in sex and age must be taken into account at the moment of empirical prescription of antimicrobials. From the recommended antimicrobials by the European Association of Urology guidelines, the first line drugs (pivmecillinam and nitrofurantoin) and the alternative antibiotic amoxicillin-clavulanic acid (AMX-CLA) are appropriate to treat community-acquired UTI, but the fluoroquinolones should not be suitable to treat male infections and the trimethoprim-sulfamethoxazole (SXT) shall not be used in the treatment of UTI at this level.
222 citations
TL;DR: There is evidence that HCV screening of PWID and HBsAg screening of pregnant women and migrants is cost-effective and cost-effectiveness analyses may need to take effect of antiviral treatment on preventing HBV and HCV transmission into account.
Abstract: Treatment for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is improving but not benefiting individuals unaware to be infected. To inform screening policies we assessed (1) the hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibody (anti-HCV-Ab) prevalence for 34 European countries; and (2) the cost-effectiveness of screening for chronic HBV and HCV infection. We searched peer-reviewed literature for data on HBsAg and anti-HCV-Ab prevalence and cost-effectiveness of screening of the general population and five subgroups, and used data for people who inject drugs (PWID) and blood donors from two European organizations. Of 1759 and 468 papers found in the prevalence and cost-effectiveness searches respectively, we included 124 and 29 papers after assessing their quality. We used decision rules to calculate weighted prevalence estimates by country. The HBsAg and anti-HCV-Ab prevalence in the general population ranged from 0.1%-5.6% and 0.4%-5.2% respectively, by country. For PWID, men who have sex with men and migrants, the prevalence of HBsAg and anti-HCV-Ab was higher than the prevalence in the general population in all but 3 countries. There is evidence that HCV screening of PWID and HBsAg screening of pregnant women and migrants is cost-effective. The prevalence of chronic HBV and HCV infection varies widely between European countries. Anti-HCV-Ab screening of PWID and HBsAg screening of pregnant women and migrants have European public health priority. Cost-effectiveness analyses may need to take effect of antiviral treatment on preventing HBV and HCV transmission into account.
219 citations
TL;DR: SSTIs represent a significant burden to the health care system and there were strong age group by race/ethnicity interactions, with African Americans aged 18 to <50 years being disproportionately at risk for SSTIs compared to persons in that age group belonging to other race/ Ethnicity groups.
Abstract: Skin and soft tissue infections (SSTIs) are commonly occurring infections with wide-ranging clinical manifestations, from mild to life-threatening. There are few population-based studies of SSTIs in the period after the rapid increase in community-acquired methicillin-resistant Staphyloccus aureus (MRSA). We used electronic databases to describe the incidence, microbiology, and patient characteristics of clinically-diagnosed skin and soft tissue infections (SSTIs) among members of a Northern California integrated health plan. We identified demographic risk factors associated with SSTIs and MRSA infection. During the three-year study period from 2009 to 2011, 376,262 individuals experienced 471,550 SSTI episodes, of which 23% were cultured. Among cultured episodes, 54% were pathogen-positive. Staphylococcus aureus (S. aureus) was isolated in 81% of pathogen-positive specimens, of which nearly half (46%) were MRSA. The rate of clinically-diagnosed SSTIs in this population was 496 per 10,000 person-years. After adjusting for age group, gender, race/ethnicity and diabetes, Asians and Hispanics were at reduced risk of SSTIs compared to whites, while diabetics were at substantially higher risk compared to non-diabetics. There were strong age group by race/ethnicity interactions, with African Americans aged 18 to <50 years being disproportionately at risk for SSTIs compared to persons in that age group belonging to other race/ethnicity groups. Compared to Whites, S. aureus isolates of African-Americans and Hispanics were more likely to be MRSA (Odds Ratio (OR): 1.79, Confidence Interval (CI): 1.67 to 1.92, and, OR: 1.24, CI: 1.18 to 1.31, respectively), while isolates from Asians were less likely to be MRSA (OR: 0.73, CI: 0.68 to 0.78). SSTIs represent a significant burden to the health care system. The majority of culture-positive SSTIs were caused by S. aureus, and almost half of the S. aureus SSTIs were methicillin-resistant. The reasons for African-Americans having a higher likelihood, and Asians a lower likelihood, for their S. aureus isolates to be methicillin-resistant, should be further investigated.
210 citations
TL;DR: It is confirmed that in Europe HZ incidence increases with age, and quite drastically after 50 years of age, while in all of the 21 studies included in the present review, incidence rates were higher among women than men, and this difference increased with age.
Abstract: Herpes zoster (HZ) is caused by reactivation of the varicella-zoster virus (VZV) and mainly affects individuals aged ≥50 years. The forthcoming European launch of a vaccine against HZ (Zostavax®) prompts the need for a better understanding of the epidemiology of HZ in Europe. Therefore the aim of this systematic review was to summarize the available data on HZ incidence in Europe and to describe age-specific incidence. The Medline database of the National Library of Medicine was used to conduct a comprehensive literature search of population-based studies of HZ incidence published between 1960 and 2010 carried out in the 27 member countries of the European Union, Iceland, Norway and Switzerland. The identified articles were reviewed and scored according to a reading grid including various quality criteria, and HZ incidence data were extracted and presented by country. The search identified 21 studies, and revealed a similar annual HZ incidence throughout Europe, varying by country from 2.0 to 4.6/1 000 person-years with no clearly observed geographic trend. Despite the fact that age groups differed from one study to another, age-specific HZ incidence rates seemed to hold steady during the review period, at around 1/1 000 children <10 years, around 2/1 000 adults aged <40 years, and around 1–4/1 000 adults aged 40–50 years. They then increased rapidly after age 50 years to around 7–8/1 000, up to 10/1 000 after 80 years of age. Our review confirms that in Europe HZ incidence increases with age, and quite drastically after 50 years of age. In all of the 21 studies included in the present review, incidence rates were higher among women than men, and this difference increased with age. This review also highlights the need to identify standardized surveillance methods to improve the comparability of data within European Union Member States and to monitor the impact of VZV immunization on the epidemiology of HZ. Available data in Europe have shortcomings which make an accurate assessment of HZ incidence and change over time impossible. However, data are indicative that HZ incidence is comparable, and increases with age in the same proportion across Europe.
189 citations
TL;DR: Results suggest a therapeutic role for vitamin D in the treatment of TB and lead to significant increase in MTBs-induced IFN-g secretion in patients with baseline ‘Deficient’ 25-hydroxyvitamin D serum levels.
Abstract: Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery. Two hundred and fifty nine patients with pulmonary TB were randomized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses. Assessments were performed at 4, 8 and 12 weeks. Early secreted and T cell activated 6 kDa (ESAT6) and Mycobacterium tuberculosis sonicate (MTBs) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks. Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student’s t-test and Chi2 tests. After 12 weeks, the vitamin D supplemented arm demonstrated significantly greater mean weight gain (kg) + 3.75, (3.16 – 4.34) versus + 2.61 (95% CI 1.99 – 3.23) p 0.009 and lesser residual disease by chest radiograph; number of zones involved 1.35 v/s 1.82 p 0.004 (95% CI 0.15, 0.79) and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline ‘Deficient’ 25-hydroxyvitamin D serum levels (p 0.021). Supplementation with high doses of vitamin D accelerated clinical, radiographic improvement in all TB patients and increased host immune activation in patients with baseline ‘Deficient’ serum vitamin D levels. These results suggest a therapeutic role for vitamin D in the treatment of TB. ClinicalTrials.gov; No. NCT01130311; URL: clinicaltrials.gov
188 citations
TL;DR: It is believed that, for listeriosis outbreaks, adapting the exposure window for documenting patients’ food histories in accordance with the clinical form of infection will facilitate the identification of food products as the source of contamination.
Abstract: Listeriosis is a foodborne infection with a low incidence but a high case fatality rate. Unlike common foodborne diseases, the incubation period can be long. The first incubation periods were documented during a large listeriosis outbreak published in 1987 by Linnan and al. in the New England Journal of Medicine (range: 3 days to 70 days). Data on the incubation period of listeriosis are scarce. Our study aim was to estimate precisely the incubation period of listeriosis using available data since 1987. We estimated the incubation period of listeriosis using available published data and data from outbreak investigations carried out by the French National Institute for Public Health Surveillance. We selected cases with an incubation period calculated when a patient had a single exposure to a confirmed food source contaminated by Listeria monocytogenes. We identified 37 cases of invasive listeriosis (10 cases with central nervous system involvement (CNS cases), 15 bacteraemia cases and 12 pregnancy-associated cases) and 9 outbreaks with gastroenteritis. The overall median incubation period of invasive listeriosis was 8 days (range: 1–67 days) and differed significantly by clinical form of the disease (p<0.0001). A longer incubation period was observed for pregnancy-associated cases (median: 27.5 days; range: 17–67 days) than for CNS cases (median: 9 days; range: 1–14 days) and for bacteraemia cases (median: 2 days; range: 1–12 days). For gastroenteritis cases, the median incubation period was 24 hours with variation from 6 to 240 hours. This information has implications for the investigation of food borne listeriosis outbreaks as the incubation period is used to determine the time period for which a food history is collected. We believe that, for listeriosis outbreaks, adapting the exposure window for documenting patients’ food histories in accordance with the clinical form of infection will facilitate the identification of food products as the source of contamination. We therefore propose to take an exposure window of 14 days before the diagnosis for CNS and bacteraemia cases, and of 6 weeks before the diagnosis, for pregnancy-associated cases.
TL;DR: This in-depth analysis of the molecular clock revealed that it is slow and variable over short time scales, which limits its usefulness in transmission studies, but the investigation of tuberculosis transmission will benefit greatly from routine whole genome sequencing.
Abstract: Background: Mycobacterium tuberculosis is characterised by limited genomic diversity, which makes the application of whole genome sequencing particularly attractive for clinical and epidemiological investigation. However, in order to confidently infer transmission events, an accurate knowledge of the rate of change in the genome over relevant timescales is required. Methods: We attempted to estimate a molecular clock by sequencing 199 isolates from epidemiologically linked tuberculosis cases, collected in the Netherlands spanning almost 16 years. Results: Multiple analyses support an average mutation rate of ~0.3 SNPs per genome per year. However, all analyses revealed a very high degree of variation around this mean, making the confirmation of links proposed by epidemiology, and inference of novel links, difficult. Despite this, in some cases, the phylogenetic context of other strains provided evidence supporting the confident exclusion of previously inferred epidemiological links. Conclusions: This in-depth analysis of the molecular clock revealed that it is slow and variable over short time scales, which limits its usefulness in transmission studies. However, the superior resolution of whole genome sequencing can provide the phylogenetic context to allow the confident exclusion of possible transmission events previously inferred via traditional DNA fingerprinting techniques and epidemiological cluster investigation. Despite the slow generation of variation even at the whole genome level we conclude that the investigation of tuberculosis transmission will benefit greatly from routine whole genome sequencing.
TL;DR: Patients who receive intravenous colistin should be closely monitored and Cmin levels might be a new useful tool to predict acute kidney injury (AKI), when using the RIFLE criteria.
Abstract: Data regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels. A prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. One hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT. When using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.
TL;DR: The simultaneous use of more than one strategy, including cocooning strategy plus vaccination of adolescents and adults, seems to be the most reasonable preventive measure for the control of pertussis.
Abstract: Resurgence of pertussis in the post-vaccination era has been reported in Western countries. A shift of cases from school-age children to adolescents, adults and children under 1 year of age has been described in the last decade, and mortality rates in infants are still sustained. We aimed to review and discuss the possible vaccination strategies which can be adopted in order to improve the pertussis control, by searches of Pubmed, and websites of US and European Centers for Disease Control and Prevention, between 1st January 2002, and 1st March 2013. The following vaccination strategies have been retrieved and analysed: the cocooning strategy, the immunization of pregnant women and newborns, vaccination programs for preschool children, adolescents, adults and health-care workers. Cost-effectiveness studies provide some contrasting data, mainly supporting both maternal vaccination and cocooning. Adolescent and/or adult vaccination seems to be cost-effective, however data from observational studies suggest that this vaccination strategy, used alone, leads to a reduced pertussis burden globally, but does not affect the disease incidence in infants. Moreover, substantial logistical and economic difficulties have to be overcome to vaccinate the largest number of individuals. The simultaneous use of more than one strategy, including cocooning strategy plus vaccination of adolescents and adults, seems to be the most reasonable preventive measure. The development of new highly immunogenic and efficacious pertussis vaccines continues to be a primary objective for the control of pertussis.
TL;DR: Advanced immunosuppression at baseline and previous exposures to unsupervised brief cycles of ART significantly impaired treatment outcomes at a time when structured ART was finally introduced in his cohort.
Abstract: The impact of extended use of ART in developing countries has been enormous. A thorough understanding of all factors contributing to the success of antiretroviral therapy is required. The current study aims to investigate the value of cross-sectional drug resistance monitoring using DNA and RNA oligonucleotide ligation assays (OLA) in treatment cohorts in low-resource settings. The study was conducted in the first cohort of children gaining access to structured ART in Peru. Between 2002–5, 46 eligible children started the standard regimen of AZT, 3TC and NFV Patients had a median age of 5.6 years (range: 0.7-14y), a median viral load of 1.7·105 RNA/ml (range: 2.1·103 – 1.2·106), and a median CD4-count of 232 cells/μL (range: 1–1591). Of these, 20 patients were classified as CDC clinical category C and 31/46 as CDC immune category 3. At the time of cross-sectional analysis in 2005, adherence questionnaires were administered. DNA OLAs and RNA OLAs were performed from frozen PBMC and plasma, RNA genotyping from dried blood spots. During the first year of ART, 44% of children experienced virologic failure, with an additional 9% failing by the end of the second year. Virologic failure was significantly associated with the number of resistance mutations detected by DNA-OLA (p < 0.001) during cross-sectional analysis, but also with low immunologic CDC-scores at baseline (p < 0.001). Children who had been exposed to unsupervised short-term antiretrovirals before starting structured ART showed significantly higher numbers of resistance mutations by DNA-OLA (p = 0.01). Detection of M184V (3TC resistance) by RNA-OLA and DNA-OLA demonstrated a sensitivity of 0.93 and 0.86 and specificity of 0.67 and 0.7, respectively, for the identification of virologic failure. The RT mutations N88D and L90M (NFV resistance) detected by DNA-OLA correlated with virologic failure, whereas mutations at RT position 215 (AZT resistance) were not associated with virologic failure. Advanced immunosuppression at baseline and previous exposures to unsupervised brief cycles of ART significantly impaired treatment outcomes at a time when structured ART was finally introduced in his cohort. Brief maternal exposures to with AZT +/− NVP for the prevention of mother-to-child transmission did not affect treatment outcomes in this group of children. DNA-OLA from frozen PBMC provided a highly specific tool to detect archived drug resistance. RNA consensus genotyping from dried blood spots and RNA-OLA from plasma consistently detected drug resistance mutations, but merely in association with virologic failure.
TL;DR: This study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and it is demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.
Abstract: The female genital tract is an important bacterial habitat of the human body, and vaginal microbiota plays a crucial role in vaginal health. The alteration of vaginal microbiota affects millions of women annually, and is associated with numerous adverse health outcomes, including human papillomavirus (HPV) infection. However, previous studies have primarily focused on the association between bacterial vaginosis and HPV infection. Little is known about the composition of vaginal microbial communities involved in HPV acquisition. The present study was performed to investigate whether HPV infection was associated with the diversity and composition of vaginal microbiota. A total of 70 healthy women (32 HPV-negative and 38 HPV-positive) with normal cervical cytology were enrolled in this study. Culture-independent polymerase chain reaction-denaturing gradient gel electrophoresis was used to measure the diversity and composition of vaginal microbiota of all subjects. We found significantly greater biological diversity in the vaginal microbiota of HPV-positive women (p < 0.001). Lactobacillus, including L. gallinarum, L. iners and L. gasseri, was the predominant genus and was detected in all women. No significant difference between HPV-positive and HPV-negative women was found for the frequency of detection of L. gallinarum (p = 0.775) or L. iners (p = 0.717), but L. gasseri was found at a significantly higher frequency in HPV-positive women (p = 0.005). Gardnerella vaginalis was also found at a significantly higher frequency in HPV-positive women (p = 0.031). Dendrograms revealed that vaginal microbiota from the two groups had different profiles. Our study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and we have demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.
TL;DR: In this article, the authors quantified the relationship between meteorological variables and the incidence of hand, foot, and mouth disease (HFMD) among children in Guangzhou, China, and found that a 1°C increase in temperature led to an increase of 1.86% (95% CI: 0.92, 2.81%) in the weekly number of cases in the 0-14 years age group.
Abstract: Over the last decade, major outbreaks of hand, foot, and mouth disease (HFMD) have been reported in Asian countries, resulting in thousands of deaths among children. However, less is known regarding the effect of meteorological variables on the incidence of HFMD in children. This study aims at quantifying the relationship between meteorological variables and the incidence of HFMD among children in Guangzhou, China. The association between weekly HFMD cases in children aged <15 years and meteorological variables in Guangzhou from 2008 to 2011 were analyzed using the generalized additive model (GAM) and time-series method, after controlling for long-term trend and seasonality, holiday effects, influenza period and delayed effects. Temperature and relative humidity with one week lag were significantly associated with HFMD infection among children. We found that a 1°C increase in temperature led to an increase of 1.86% (95% CI: 0.92, 2.81%) in the weekly number of cases in the 0–14 years age group. A one percent increase in relative humidity may lead to an increase of 1.42% (95% CI: 0.97, 1.87%) in the weekly number of cases in the 0–14 years age group. This study provides quantitative evidence that the incidence of HFMD in children was associated with high average temperature and high relative humidity. The one-week delay in the effects of temperature and relative humidity on HFMD is consistent with the enterovirus incubation period and the potential time lag between onset of children’s sickness and parental awareness and response.
TL;DR: The findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.
Abstract: Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case–control approach. The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.
TL;DR: This study is novel in providing evidence for the widespread nature of fungi in the sputum of healthy and asthmatic individuals as well as differences in the pattern of fungi present in asthma patients and controls.
Abstract: Background
There is emerging evidence for the presence of an extensive microbiota in human lungs. It is not known whether variations in the prevalence of species of microbiota in the lungs may have aetiological significance in respiratory conditions such as asthma. The aim of the study was to undertake semi-quantitative analysis of the differences in fungal species in pooled sputum samples from asthma patients and controls.
Methods
Induced sputum samples were collected in a case control study of asthma patients and control subjects drawn from the community in Wandsworth, London. Samples from both groups were pooled and then tested for eukaryotes. DNA was amplified using standard PCR techniques, followed by pyrosequencing and comparison of reads to databases of known sequences to determine in a semi-quantitative way the percentage of DNA from known species in each of the two pooled samples.
Results
A total of 136 fungal species were identified in the induced sputum samples, with 90 species more common in asthma patients and 46 species more common in control subjects. Psathyrella candolleana, Malassezia pachydermatis, Termitomyces clypeatus and Grifola sordulenta showed a higher percentage of reads in the sputum of asthma patients and Eremothecium sinecaudum, Systenostrema alba, Cladosporium cladosporioides and Vanderwaltozyma polyspora showed a higher percentage of reads in the sputum of control subjects. A statistically significant difference in the pattern of fungi that were present in the respective samples was demonstrated using the Phylogenetic (P) test (P < 0.0001).
This study is novel in providing evidence for the widespread nature of fungi in the sputum of healthy and asthmatic individuals. Differences in the pattern of fungi present in asthma patients and controls merit further investigation. Of particular interest was the presence of Malassezia pachydermatis, which is known to be associated with atopic dermatitis.
TL;DR: Transmission models have been used to understand complex systems and to predict the impact of control policies and methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses.
Abstract: Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time. MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings. In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries. The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data. Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models.
TL;DR: The authors' estimates combine published data and provide sufficient quantitative detail to allow for these estimates to be used in a wide range of clinical and modeling applications and can translate into improved prevention and control efforts in settings with transmission or the risk of transmission.
Abstract: Accurate knowledge of incubation period is important to investigate and to control infectious diseases and their transmission, however statements of incubation period in the literature are often uncited, inconsistent, and/or not evidence based. In a systematic review of the literature on five enteric viruses of public health importance, we found 256 articles with incubation period estimates, including 33 with data for pooled analysis. We fit a log-normal distribution to pooled data and found the median incubation period to be 4.5 days (95% CI 3.9-5.2 days) for astrovirus, 1.2 days (95% CI 1.1-1.2 days) for norovirus genogroups I and II, 1.7 days (95% CI 1.5-1.8 days) for sapovirus, and 2.0 days (95% CI 1.4-2.4 days) for rotavirus. Our estimates combine published data and provide sufficient quantitative detail to allow for these estimates to be used in a wide range of clinical and modeling applications. This can translate into improved prevention and control efforts in settings with transmission or the risk of transmission.
TL;DR: Clinical manifestations of penicilliosis marneffei are different between patients with and without HIV infection, and physician’s awareness of this disease in HIV-uninfected patients may prompt the diagnosis and timely treatment, and can lead to a better outcome.
Abstract: Penicilliosis marneffei is increasingly observed in individuals without HIV infection. This study aimed to compare the clinical and laboratory features among HIV infected and uninfected individuals with penicilliosis marneffei. A retrospective cohort study was conducted between January 1, 2007 and December 31, 2011 at Chiang Mai University Hospital. We included individuals who were ≥15 years of age and presented with culture-proven P. marneffei infection. 116 HIV-infected and 34 HIV-uninfected patients were enrolled. Comparing to HIV-infected patients, HIV-uninfected patients were older; less likely to have fever, splenomegaly, and umbilicated skin lesions; more likely to have Sweet’s syndrome and bone and joint infections; had higher white blood cell count, platelet count, and CD4 cell count; had lower alanine transaminase (ALT); and less likely to have positive fungal blood cultures. The mortality rates were 20.7% and 29.4% among HIV infected and uninfected patients, respectively. Clinical manifestations of penicilliosis marneffei are different between patients with and without HIV infection. Physician’s awareness of this disease in HIV-uninfected patients may prompt the diagnosis and timely treatment, and can lead to a better outcome.
TL;DR: A compact representation of contact patterns that can correctly inform computational models designed to discover risk groups and evaluate containment policies is presented, providing a first step towards the definition of synopses of high-resolution dynamic contact networks.
Abstract: The integration of empirical data in computational frameworks designed to model the spread of infectious diseases poses a number of challenges that are becoming more pressing with the increasing availability of high-resolution information on human mobility and contacts. This deluge of data has the potential to revolutionize the computational efforts aimed at simulating scenarios, designing containment strategies, and evaluating outcomes. However, the integration of highly detailed data sources yields models that are less transparent and general in their applicability. Hence, given a specific disease model, it is crucial to assess which representations of the raw data work best to inform the model, striking a balance between simplicity and detail. We consider high-resolution data on the face-to-face interactions of individuals in a pediatric hospital ward, obtained by using wearable proximity sensors. We simulate the spread of a disease in this community by using an SEIR model on top of different mathematical representations of the empirical contact patterns. At the most detailed level, we take into account all contacts between individuals and their exact timing and order. Then, we build a hierarchy of coarse-grained representations of the contact patterns that preserve only partially the temporal and structural information available in the data. We compare the dynamics of the SEIR model across these representations. We show that a contact matrix that only contains average contact durations between role classes fails to reproduce the size of the epidemic obtained using the high-resolution contact data and also fails to identify the most at-risk classes. We introduce a contact matrix of probability distributions that takes into account the heterogeneity of contact durations between (and within) classes of individuals, and we show that, in the case study presented, this representation yields a good approximation of the epidemic spreading properties obtained by using the high-resolution data. Our results mark a first step towards the definition of synopses of high-resolution dynamic contact networks, providing a compact representation of contact patterns that can correctly inform computational models designed to discover risk groups and evaluate containment policies. We show in a typical case of a structured population that this novel kind of representation can preserve in simulation quantitative features of the epidemics that are crucial for their study and management.
TL;DR: Real-time PCR and Gram stain were highly accurate in diagnosing meningitis caused by S. pneumoniae, N. meningitidis, and H. influenzae, and might be useful when antibiotics were previously administered.
Abstract: BACKGROUND: Although cerebrospinal fluid (CSF) culture is the diagnostic reference standard for bacterial meningitis, its sensitivity is limited, particularly when antibiotics were previously administered. CSF Gram staining and real-time PCR are theoretically less affected by antibiotics; however, it is difficult to evaluate these tests with an imperfect reference standard. METHODS AND FINDINGS: CSF from patients with suspected meningitis from Salvador, Brazil were tested with culture, Gram stain, and real-time PCR using S. pneumoniae, N. meningitidis, and H. influenzae specific primers and probes. An antibiotic detection disk bioassay was used to test for the presence of antibiotic activity in CSF. The diagnostic accuracy of tests were evaluated using multiple methods, including direct evaluation of Gram stain and real-time PCR against CSF culture, evaluation of real-time PCR against a composite reference standard, and latent class analysis modeling to evaluate all three tests simultaneously. RESULTS: Among 451 CSF specimens, 80 (17.7%) had culture isolation of one of the three pathogens (40 S. pneumoniae, 36 N. meningitidis, and 4 H. influenzae), and 113 (25.1%) were real-time PCR positive (51 S. pneumoniae, 57 N. meningitidis, and 5 H. influenzae). Compared to culture, real-time PCR sensitivity and specificity were 95.0% and 90.0%, respectively. In a latent class analysis model, the sensitivity and specificity estimates were: culture, 81.3% and 99.7%; Gram stain, 98.2% and 98.7%; and real-time PCR, 95.7% and 94.3%, respectively. Gram stain and real-time PCR sensitivity did not change significantly when there was antibiotic activity in the CSF. CONCLUSION: Real-time PCR and Gram stain were highly accurate in diagnosing meningitis caused by S. pneumoniae, N. meningitidis, and H. influenzae, though there were few cases of H. influenzae. Furthermore, real-time PCR and Gram staining were less affected by antibiotic presence and might be useful when antibiotics were previously administered. Gram staining, which is inexpensive and commonly available, should be encouraged in all clinical settings.
TL;DR: Elevated resistance to desiccation, high biofilm-forming capacity on abiotic surfaces and adherence to A549 cells might have favoured the spread and persistence in the hospital environment of A. baumannii strains assigned to distinct MLST genotypes.
Abstract: Acinetobacter baumannii is responsible for large epidemics in hospitals, where it can persist for long time on abiotic surfaces. This study investigated some virulence-related traits of epidemic A. baumannii strains assigned to distinct MLST genotypes, including those corresponding to the international clones I-III as well as emerging genotypes responsible for recent epidemics. Genotyping of bacteria was performed by PFGE analysis and MLST according to the Pasteur’s scheme. Biofilm formation on polystyrene plates was assessed by crystal violet staining; resistance to desiccation was evaluated on glass cover-slips when kept at room-temperature and 31% relative humidity; adherence to and invasion of A549 human alveolar epithelial cells were determined by the analysis of viable bacteria associated with or internalized by A549 human alveolar epithelial cells; Galleria mellonella killing assays were used to analyze the virulence of A. baumannii in vivo. The ability to form biofilm was significantly higher for A. baumannnii strains assigned to ST2 (international clone II), ST25 and ST78 compared to other STs. All A. baumannii strains survived on dry surfaces for over 16 days, and strains assigned to ST1 (international clone I) and ST78 survived for up to 89 and 96 days, respectively. Adherence to A549 pneumocytes was higher for strains assigned to ST2, ST25 and ST78 than other genotypes; a positive correlation exists between adherence and biofilm formation. Strains assigned to ST78 also showed significantly higher ability to invade A549 cells. No significant differences in the killing of G. mellonella worms were found among strains. Elevated resistance to desiccation, high biofilm-forming capacity on abiotic surfaces and adherence to A549 cells might have favoured the spread and persistence in the hospital environment of A. baumannii strains assigned to the international clones I and II and to the emerging genotypes ST25 and ST78.
TL;DR: The study suggested pathogenic activity of HPIV in gastrointestinal illness may differ by patient age, and no significant differences were seen in clinical presentation between patients solely infected withHPIV and patients co-infected with HPIV and other respiratory pathogens.
Abstract: Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China. Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients’ clinical presentations were recorded for further analysis. Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015), “abnormal pulmonary breathing sound” (p<0.001), “dyspnoea” (p<0.001), “pneumonia” (p=0.01), and “diarrhoea” (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was “Expectoration” (p<0.001). Co-infections were common, with 33.3%–63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens. HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.
TL;DR: Large proportions of children and adults in Beijing have evidence of anti-S IgG against four the HCoVs, and first infections by all four non-SARS H coVs takes place during childhood.
Abstract: Non-severe acute respiratory syndrome (non-SARS)-related human coronaviruses (HCoVs), including HCoV-229E, -HKU1, -NL63, and -OC43, have been detected in respiratory tract samples from children and adults. However, the natural prevalence of antibodies against these viruses in serum among population is unknown. To measure antibodies to the spike (S) protein of the four common non-SARS HCoVs, recombinant S proteins of the four HCoVs were expressed and characterised in 293 T cell. An S-protein-based indirect immunofluorescence assay (IFA) was then developed to detect anti-S IgG and IgM for the four individual HCoVs and applied to serum samples from a general asymptomatic population (218 children and 576 adults) in Beijing. Of 794 blood samples tested, only 29 (3.65%) were negative for anti-S IgG. The seropositivity of the four anti-S IgG antibodies was >70% within the general population. The majority of seroconversions to four-HCoV positivity first occurred in children. Both S-IgG and S-IgM antibodies were detectable among children and increased with age, reaching a plateau at 6 years of age. However, no anti-S IgM was detected in healthy adults. Large proportions of children and adults in Beijing have evidence of anti-S IgG against four the HCoVs, and first infections by all four non-SARS HCoVs takes place during childhood.
TL;DR: Lipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatics dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV Patients.
Abstract: Metabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined. Untargeted metabolomic profiling of plasma was performed for 32 HIV patients with low nadir CD4 counts (<300 cells/ul) on protease inhibitor (PI)-based ART and 20 healthy controls using liquid or gas chromatography and mass spectrometry. Effects of Hepatitis C (HCV) co-infection and relationships between altered lipid metabolites and markers of inflammation, microbial translocation, and hepatic function were examined. Unsupervised hierarchical clustering, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), Random forest, pathway mapping, and metabolite set enrichment analysis (MSEA) were performed using dChip, Metaboanalyst, and MSEA software. A 35-metabolite signature mapping to lipid, amino acid, and nucleotide metabolism distinguished HIV patients with advanced disease on PI-based ART from controls regardless of HCV serostatus (p<0.05, false discovery rate (FDR)<0.1). Many altered lipids, including bile acids, sulfated steroids, polyunsaturated fatty acids, and eicosanoids, were ligands of nuclear receptors that regulate metabolism and inflammation. Distinct clusters of altered lipids correlated with markers of inflammation (interferon-α and interleukin-6), microbial translocation (lipopolysaccharide (LPS) and LPS-binding protein), and hepatic function (bilirubin) (p<0.05). Lipid alterations showed substantial overlap with those reported in non-alcoholic fatty liver disease (NALFD). Increased bile acids were associated with noninvasive markers of hepatic fibrosis (FIB-4, APRI, and YKL-40) and correlated with acylcarnitines, a marker of mitochondrial dysfunction. Lipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatic dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV patients.
TL;DR: The ATLAS scoring system may be useful in stratifying CDI patients so that appropriate therapies can be chosen to maximize cure rates, as well as for categorization of patients in CDI therapeutic studies in order allow comparisons of patient groups.
Abstract: Clostridium difficile infection (CDI) continues to be a frequent and potentially severe infection. There is currently no validated clinical tool for use at the time of CDI diagnosis to categorize patients in order to predict response to therapy. Six clinical and laboratory variables, measured at the time of CDI diagnosis, were combined in order to assess their correlation with treatment response in a large CDI clinical trial database (derivation cohort). The final categorization scheme was chosen in order to maximize the number of categories (discrimination) while maintaining a high correlation with clinical cure assessed two days after the end of therapy. Validation of the derived scoring scheme was done on a second large CDI clinical trial database (validation cohort). A third comparison was done on the two pooled databases (pooled cohort). In the derivation cohort, the best discrimination and correlation with cure was seen with a five-component ATLAS score (age, treatment with systemic antibiotics, leukocyte count, albumin and serum creatinine as a measure of renal function), which divided CDI patients into 11 groups (scores of 0 to 10 inclusive) and was highly correlated with treatment outcome (R2=0.95; P<0.001). This scheme showed excellent prediction of cure in the validation cohort (overall Kappa=95.2%; P<0.0001), as well as in the pooled cohort, regardless of treatment (fidaxomicin or vancomycin). A combination of five simple and commonly available clinical and laboratory variables measured at the time of CDI diagnosis, combined into a scoring system (ATLAS), are able to accurately predict treatment response to CDI therapy. The ATLAS scoring system may be useful in stratifying CDI patients so that appropriate therapies can be chosen to maximize cure rates, as well as for categorization of patients in CDI therapeutic studies in order allow comparisons of patient groups.
TL;DR: The mechanisms associated with decreased K. pneumoniae carbapenem susceptibility were likely due to the presence of cephalosporinases coupled with porin alterations, which resulted from the presenceof the insertion sequences in the outer membrane encoding genes.
Abstract: Healthcare-associated infections caused by Klebsiella pneumoniae isolates are increasing and few effective antibiotics are currently available to treat patients. We observed decreased carbapenem susceptibility among K. pneumoniae isolated from patients at a tertiary private hospital that showed a phenotype compatible with carbapenemase production although this group of enzymes was not detected in any sample. The aim of this study was to describe the epidemiology and clinical outcomes associated with carbapenem-resistant K. pneumoniae and to determine the antimicrobial resistance mechanisms. Risk factors associated with carbapenem-resistant K. pneumoniae infections were investigated by a matched case–control study from January 2006 through August 2008. A cohort study was also performed to evaluate the association between carbapenem resistance and in-hospital mortality. Bacterial identification and antimicrobial susceptibility were determined by Vitek 2 and Etest. Carbapenemase activity was detected using spectrophotometric assays. Production of beta-lactamases and alterations in genes encoding K. pneumoniae outer membrane proteins, OmpK35 and OmpK36, were analyzed by PCR and DNA sequencing, as well as SDS-Page. Genetic relatedness of carbapenem resistant isolates was evaluated by Pulsed Field Gel Electrophoresis. Sixty patients were included (20 cases and 40 controls) in the study. Mortality was higher for patients with carbapenem-resistant K. pneumoniae infections compared with those with carbapenem-susceptible K. pneumoniae (50.0% vs 25.7%). The length of central venous catheter use was independently associated with carbapenem resistance in the multivariable analysis. All strains, except one, carried bla
CTX-M-2, an extended-spectrum betalactamase gene. In addition, a single isolate also possessed bla
GES-1. Genes encoding plasmid-mediated AmpC beta-lactamases or carbapenemases (KPC, metallo-betalactamases or OXA-carbapenemases) were not detected. The K. pneumoniae multidrug-resistant organisms were associated with significant mortality. The mechanisms associated with decreased K. pneumoniae carbapenem susceptibility were likely due to the presence of cephalosporinases coupled with porin alterations, which resulted from the presence of the insertion sequences in the outer membrane encoding genes.