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1.  Do children’s upper respiratory tract infections benefit from probiotics? 
BMC Infectious Diseases  2014;14:194.
The microbiota of the gastrointestinal tract have profound influence at multiple levels, even on the development and maintenance of lung immunity and inflammation. Aim of this review is to evaluate the current knowledge about the specific impact on children’s respiratory tract infections from probiotics, live microbes with the power to modify intestinal microbial populations and exert subsequent benefits for the host.
The role of probiotics in gastrointestinal and allergic diseases has been largely assessed, but the number of studies performed so far in the field of respiratory tract infections is small, though some data show that probiotic administration might display clinical advantages. Probiotic strain identity and host genetic differences may account for differential modulation of immune responses by probiotics. Current laboratory and clinical data regarding the possibility of the role of probiotics on preventing the development of respiratory tract infections are contradictory, and are somewhat insufficient to recommend strongly their routine use. Further study of gastrointestinal-respiratory interactions is likely to yield important insights into the pathogenesis of different pulmonary diseases, and improve our knowledge in the prophylactic role of probiotics in children affected by recurrent upper respiratory tract infections.
A better understanding of the effects of different probiotic strains and a deeper insight into their mechanisms of action are needed for the validation of specific strains carrying a potential to modify the frequency and severity of RTIs in infants and children. No data have been collected in pediatric patients with chronic underlying diseases, and yet there are no published data concerning treatment of RTIs with probiotics. The very few studies published so far do not indicate which micro-organism or administration regimen might exert beneficial effects as a prevention tool of RTIs both in healthy children and in those with recurrent RTIs. Further research to establish the role of probiotics in the treatment and prevention of RTIs, including those involving the lower respiratory tract, are required and should also clarify if any susceptible subgroups of respiratory diseases exist, and how these subgroups benefit from supplementation with certain probiotic strains.
PMCID: PMC3984429  PMID: 24720809
Acute otitis media; Children; Prevention; Probiotics; Respiratory tract infection; Upper respiratory tract infections
2.  Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae 
BMC Infectious Diseases  2014;14:176.
KPC-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality; however, their virulence determinants are not well defined.
We investigated the virulence and plasmid transferability among KPC-containing K. pneumoniae isolates.
KPC-2 and -3 were successfully conjugated and retained by a virulent K2 K. pneumoniae recipient isolate. Antimicrobial susceptibility testing showed KPC-2 and -3 donor strains were resistant to more than four classes of antibiotics while the K2 isolate was only initially resistant to ampicillin. After conjugation of KPC-2 and -3, the K2 K. pneumoniae transconjugants became resistant to all beta-lactams. Additionally, the KPC K2 K. pneumoniae transconjugants continued to retain its high serum resistance and murine lethality.
Conjugation and retainment of KPC by virulent K2 K. pneumoniae and the ability of the tranconjugants to maintain its high serum resistance and murine lethality after conjugation was demonstrated in this study. These findings are concerning for the potential of KPC-like genes to disseminate among virulent K. pneumoniae isolates.
PMCID: PMC3976155  PMID: 24678611
Klebsiella pneumoniae; Virulence; Plasmid mediated resistance
3.  Epidemiologic characterization of 30 confirmed cases of human infection with avian influenza A(H7N9) virus in Hangzhou, China 
BMC Infectious Diseases  2014;14:175.
We examined the clinical and epidemiological characteristics of 30 cases of human infection with avian influenza A(H7N9) virus in Hangzhou and investigated their external environments to provide evidence for contact tracing and disease prevention and control.
The cases confirmed from April 1 through May 1, 2013 were studied. Field epidemiologic surveys were conducted to collect the clinical and epidemiologic data. Case-related and environmental specimens were collected for etiologic detection.
Thirty cases of human infection with avian influenza A(H7N9) virus were confirmed in Hangzhou from April 1 through May 1, 2013, including one pregnant woman and three deaths. The median age of the patients was 62 years (range: 38–86 years). Twenty-three of the patients were men (76.67%). The median duration between disease onset and occurrence of respiratory failure and confirmed diagnosis was 5 and 6 days, respectively. Maximum medical observation of 666 close contacts of the patients revealed no irregularity. Of 314 external environmental specimens, the overall positive detection rate of H7N9 nucleic acid was 28.98%. Eight districts of Hangzhou city had positive detections in the external environments, the highest rate being in Yuhang District (78.13%). Statistical analysis of the specimen collection locations indicates a significant difference between the case-linked locations and the non-case locations (χ 2  = 16.563, p < 0.05) in terms of H7N9 viral nucleic acid detection rate. No epidemiologic link has been found among the 30 cases.
Most of the infected were retired individuals aged 60 years or older. Men made the majority. The cases are sporadic at present, with no evidence of human-to-human transmission. Exposures to poultry and live poultry markets may be important sources of infection.
PMCID: PMC3977889  PMID: 24678603
Human avian influenza; H7N9 subtype; Epidemiologic characteristics; External environmental detection
4.  Two cases of cardiac device-related endocarditis due to Streptococcus dysgalactiae subsp. equisimilis (group C or G streptococci) 
BMC Infectious Diseases  2014;14:174.
Cardiac device-related endocarditis is a very rare clinical manifestation of S. dysgalactiae subsp. equisimilis disease. This pathogen is a common cause of cellulitis. We here report two cases of cardiac device-related endocarditis due to Streptococcus dysgalactiae subsp. equisimilis. Blood cultures yielded this pathogen and both patients had recurrent bacteremia. Transthoracic and transesophageal echocardiography revealed lead vegetations. This is a new description of this pathogen to cause cardiac device-related endocarditis.
Case presentation
The first case is a 79-year-old finnish woman who received a dual-chamber pacemaker for intermittent complete heart block in April 2011. She had three episodes of S. dysgalactiae subsp. equisimilis bacteremia. During first episode she had arthritis of glenohumeral joint. Focus was unknown in the second and third bacteremic episodes. During third bacteremic episode transesophageal echocardiography (TEE) revealed lead vegetation. Patient underwent successful complete system removal. She was treated with benzylpenicillin four million IU six times a day for four weeks intravenously. The second case is a 92-year-old finnish man. A dual-chamber pacemaker was implanted on June 2012 due to total heart block. He had recurrent S. dysgalactiae subsp. equisimilis bacteremia with cellulitis. During the second bacteremic episode transthoracic echocardiography (TTE) was performed because of persistent fever. Echocardiography revealed lead vegetation. Abdominal CT revealed also an abscess in the psoas region. This elderly patient was very fragile, and the pacemaker system was not extracted. Therapy was continued with benzylpenicillin four million IU six times a day for six weeks intravenously and thereafter suppressive treatment with amoksisillin 500 mg three times a day was initiated.
Streptococcus dysgalactiae subsp. equisimilis (group C and G streptococci) seldom cause cardiac device endocarditis. Both patients had recurrent bacteremia of S. dysgalactiae subsp. equisimilis and echocardiography revealed cardiac device-related endocarditis. These cases emphasize the importance of considering endocarditis in elderly persons having cardiac devices together with the presence of unexplained bacteremia, fever without focus or persistent fever.
PMCID: PMC3976168  PMID: 24678588
Streptococcus dysgalactiae subsp. equisimilis; Group G streptococci; Cardiac device; Endocarditis; Lead extraction
5.  Higher risk of renal impairment associated with tenofovir use amongst people living with HIV in India: A comparative cohort analysis between Western India and United Kingdom 
BMC Infectious Diseases  2014;14:173.
Data on the renal safety of Tenofovir (TDF) in Low and Middle Income Countries (LMICs) is scarce. We compared development of various forms of renal impairment with use of TDF-containing antiretroviral therapy (ART) between a cohort from the Institute of Infectious Diseases (IID) Pune, Western India and the Royal Free Hospital (RFH) London, UK.
This is a retrospective analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and 24 months post TDF initiation using the Modification of Diet in Renal Disease (MDRD) equation. In people living with Human Immunodeficiency virus (PLHIV) with pre-TDF eGFR > 90 ml/min/1.73 m2 time to development of and factors associated with progression to eGFR < 60 ml/min/1.73 m2 were calculated using standard survival methods.
A total of 574 (59% Caucasian) at the RFH, and 708 (100% Indian ethnicity) PLHIV from IID were included. Baseline median eGFR were similar; RFH 102 (IQR 89, 117), IID 100 (82, 119). At 24 months, mean (SD) decline in eGFR was -7(21) at RFH (p < 0.0001) and -7(40) at IID (p = 0.001). Amongst those with pre-TDF eGFR > 90 ml/min/1.73 m2 PLHIV at IID were more likely to develop an eGFR < 60 ml/min/1.73 m2 (aHR = 7.6 [95% CI 3.4, 17.4] p < 0.0001) and had a faster rate of progression estimated using Kaplan Meier methods. Risk factors included age (per 10 years older: aHR = 2.21 [1.6, 3.0] p < 0.0001) and receiving concomitant ritonavir boosted Protease Inhibitor (PI/r) (aHR = 2.4 [1.2, 4.8] p = 0.01).
There is higher frequency of treatment limiting renal impairment events amongst PLHIV receiving TDF in Western India. As TDF scale up progresses, programs need to develop capacity for monitoring and treatment of renal impairment associated with TDF.
PMCID: PMC3984028  PMID: 24679159
Tenofovir; Nephrotoxicity; India
6.  Antimicrobial susceptibility patterns of Ureaplasma species and Mycoplasma hominis in pregnant women 
BMC Infectious Diseases  2014;14:171.
Genital mycoplasmas colonise up to 80% of sexually mature women and may invade the amniotic cavity during pregnancy and cause complications. Tetracyclines and fluoroquinolones are contraindicated in pregnancy and erythromycin is often used to treat patients. However, increasing resistance to common antimicrobial agents is widely reported. The purpose of this study was to investigate antimicrobial susceptibility patterns of genital mycoplasmas in pregnant women.
Self-collected vaginal swabs were obtained from 96 pregnant women attending an antenatal clinic in Gauteng, South Africa. Specimens were screened with the Mycofast Revolution assay for the presence of Ureaplasma species and Mycoplasma hominis. The antimicrobial susceptibility to levofloxacin, moxifloxacin, erythromycin, clindamycin and tetracycline were determined at various breakpoints. A multiplex polymerase chain reaction assay was used to speciate Ureaplasma positive specimens as either U. parvum or U. urealyticum.
Seventy-six percent (73/96) of specimens contained Ureaplasma spp., while 39.7% (29/73) of Ureaplasma positive specimens were also positive for M. hominis. Susceptibilities of Ureaplasma spp. to levofloxacin and moxifloxacin were 59% (26/44) and 98% (43/44) respectively. Mixed isolates (Ureaplasma species and M. hominis) were highly resistant to erythromycin and tetracycline (both 97% resistance). Resistance of Ureaplasma spp. to erythromycin was 80% (35/44) and tetracycline resistance was detected in 73% (32/44) of Ureaplasma spp. Speciation indicated that U. parvum was the predominant Ureaplasma spp. conferring antimicrobial resistance.
Treatment options for genital mycoplasma infections are becoming limited. More elaborative studies are needed to elucidate the diverse antimicrobial susceptibility patterns found in this study when compared to similar studies. To prevent complications in pregnant women, the foetus and the neonate, routine screening for the presence of genital mycoplasmas is recommended. In addition, it is recommended that antimicrobial susceptibility patterns are determined.
PMCID: PMC3976045  PMID: 24679107
Pregnant women; Ureaplasma spp.; Mycoplasma hominis; Antimicrobial susceptibilities
7.  Increased incidence of invasive bacterial disease in chronic obstructive pulmonary disease compared to the general population-a population based cohort study 
BMC Infectious Diseases  2014;14:163.
Innate defence mechanisms of the airways are impaired in chronic obstructive pulmonary disease (COPD), predisposing patients to lower respiratory tract infections, but less is known about the association with other infections. In this population-based cohort study, we investigated the associations between COPD and invasive bacterial disease by comparing incidence rates of bacteraemia in COPD patients and randomly selected reference individuals from the general population.
In this population based cohort study all patients with COPD, ≥40 years of age, who were discharged from hospitals in southern Sweden between 1990 and 2003 were identified in the Swedish Inpatient Register (n = 15,403). Age and gender matched reference individuals were randomly selected from the general population. Records were cross-referenced to the microbiological databases covering the region, 1990–2010. The hazard ratios (HR) of bloodstream infections and hospitalisations for infections were estimated by Cox proportional hazards regression.
We found that individuals with COPD had a 2.5-fold increased incidence of bacteraemia compared to the reference individuals from the general population adjusted for other co-morbidity and socio-economic status (hazard ratio: 2.5, 95% confidence interval: 2.2-2.7). The increased incidence of bacteraemia was paralleled by an increased incidence of hospitalisation for non-respiratory infections, i.e., skin infections, pyelonephritis, or septic arthritis. Despite higher absolute rates of bloodstream infections among COPD patients than among the general population, the distribution of different pathogens was similar.
In summary this population-based study shows COPD is associated with an increased incidence of invasive bacterial infections compared to the general population, indicating a general frailty of acquiring severe infections in addition to the specific susceptibility to infections of respiratory origin. The underlying contributory factors (e.g. smoking, corticosteroid use, co-morbid diseases or a frailty inherent to COPD itself) need to be disentangled in further studies.
PMCID: PMC3976148  PMID: 24661335
Bacteraemia; Epidemiology; Chronic obstructive pulmonary disease; Infection; Sepsis
8.  Clade homogeneity and Pol gene polymorphisms in chronically HIV-1 infected antiretroviral treatment naive patients after the roll out of ART in Ethiopia 
BMC Infectious Diseases  2014;14:158.
Despite the increasing use of antiretroviral treatment (ART) recent data on frequency and pattern of drug resistance mutations in Ethiopia is not available. Furthermore with increasing mobility of people HIV-1 subtypes other than the predominant subtype C may likely be introduced from the neighbouring countries. This study was aimed to determine the molecular characterization and pre-antiretroviral treatment resistance mutations among HIV-1 chronically infected ART naïve patients after the roll out of ART in Ethiopia.
Viral RNA was determined in 160 baseline plasma samples. The entire PR and the first 335 codons (76%) of the RT regions of the pol gene of the HIV-1 genome (N = 160) were amplified and sequenced using an in-house assay. Genotypic drug resistance was defined as the presence of one or more resistance-related mutations as specified by the consensus mutation of Stanford University HIVDB and the International Antiviral Society (IAS) mutation lists.
A predominance of HIV-1 subtype C (98.7%) was observed. The level of drug resistance is found to be 5.6% and 13.1% according to the Stanford University HIVDB drug resistance interpretation algorithms and the International Antiviral Society mutation lists, respectively. Mutations conferring simultaneous resistance to NRTIs and NNRTIs were not detected and no major PR mutation was found. However, a high rate of polymorphic changes both in PR and RT regions were observed. Moreover, twenty four (15%) monophyletic transmission clusters with bootstrap value of 99% were found.
Strong evidence for consistent HIV-1C clade homogeneity and low influx of other variant into the country was found. The level of drug resistance observed in chronically infected treatment naïve patients which exceeds the WHO estimates suggests the need for incorporation of HIV-1 drug resistance testing prior to ART initiation. The occurrence of monophyletic transmission clusters affecting (24/160) individuals indicates their potential risk related practice. Thus, an intensified public health intervention program and monitoring of HIV drug resistance testing appears indispensible.
PMCID: PMC3976149  PMID: 24655349
Antiretroviral drug resistance; HIV subtype; Protease; Reveres transcriptase
9.  Antibiotic treatment of acute uncomplicated cystitis based on rapid urine test and local epidemiology: lessons from a primary care series 
BMC Infectious Diseases  2014;14:137.
Acute uncomplicated cystitis (AUC) is an ideal target of optimization for antibiotic therapy in primary care. Because surveillance networks on urinary tract infections (UTI) mix complicated and uncomplicated UTI, reliable epidemiological data on AUC lack. Whether the antibiotic choice should be guided by a rapid urine test (RUT) for leukocytes and nitrites has not been extensively studied in daily practice. The aim of this primary care study was to investigate local epidemiology and RUT-daily use to determine the optimal strategy.
General practitioners included 18–65 years women with symptoms of AUC, performed a RUT and sent urines for analysis at a central laboratory. Different treatment strategies were simulated based on RUT and resistance results.
Among 347 enrolled patients, 78% had a positive urine culture. Escherichia coli predominated (71%) with high rates of susceptibility to nitrofurantoin (100%), fosfomycin (99%), ofloxacin (97%), and even pivmecillinam (87%) and trimethoprim-sulfamethoxazole (87%). Modelization showed that the systematic use of RUT would reduce by 10% the number of patients treated. Fosfomycin for patients with positive RUT offered a 90% overall bacterial coverage, compared to 98% for nitrofurantoin. 95% for ofloxacin, 86% for trimethoprim-sulfamethoxazole and 78% for pivmecillinam.
Local epidemiology surveillance data not biased by complicated UTI demonstrates that the worldwide increase in antibiotic resistance has not affected AUC yet. Fosfomycin first line in all patients with positive RUT seems the best treatment strategy for AUC, combining good bacterial coverage with expected low toxicity and limited effect on fecal flora.
Trial registration
The current study was registered at (NCT00958295)
PMCID: PMC3975248  PMID: 24612927
Acute uncomplicated cystitis; Urinary tract infection; Primary care; Rapid urine test; Antibiotic policy
10.  Non-conversion of sputum culture among patients with smear positive pulmonary tuberculosis in Cameroon: a prospective cohort study 
BMC Infectious Diseases  2014;14:138.
We investigated the determinants of sputum culture non-conversion following intensive phase of treatment, and assessed the effects on the outcome among patients treated for a first episode of smear positive tuberculosis (TB).
This was a prospective cohort study spanning October 2009 to May 2012, among patients treated for a first episode of smear positive pulmonary tuberculosis in the Chest service of the Yaounde Jamot Hospital, Cameroon. Logistic regressions models were used to relate baseline characteristics with non-conversion of sputum cultures after the intensive phase of treatment.
A total of 953 patients were admitted to the service during the study period, including 97 (10.2%) who had a positive sputum smear at the end of the intensive phase of anti-tuberculosis treatment. Eighty-six patients with persistent of smear positive sputa at the end of intensive phase of TB treatment were included, among whom 46 (53%) had positive sputum culture for Mycobacterium tuberculosis (C+). The absence of haemoptysis [adjusted odd ratio 4.65 (95% confidence intervals: 1.14-18.95)] and current smoking [7.26 (1.59-33.23)] were the main determinants of sputum culture non-conversion. Of the 46C + patients, 7 (15%) were resistant to at least one anti-tuberculosis drug. Treatment failure rate was 28% among C + patients and 8% among C– patients (p = 0.023). The sensitivity and specificity were 78.6% and 55.4% for culture non-conversion after intensive treatment, in predicting anti-TB treatment failure.
Failure rate is high among patients with positive sputum culture after intensive treatment, even in the absence of multi-drug resistant bacilli. Treatment should be closely monitored in these patients and susceptibility to anti-tuberculosis drugs tested in the presence of persistent positive smears following the intensive phase of treatment.
PMCID: PMC3984706  PMID: 24618155
Mycobacterium tuberculosis; Culture conversion; Outcome; Cameroon
11.  The geographic distribution patterns of HIV-, HCV- and co-infections among drug users in a national methadone maintenance treatment program in Southwest China 
BMC Infectious Diseases  2014;14:134.
HIV-, HCV- and HIV/HCV co-infections among drug users have become a rapidly emerging global public health problem. In order to constrain the dual epidemics of HIV/AIDS and drug use, China has adopted a methadone maintenance treatment program (MMTP) since 2004. Studies of the geographic heterogeneity of HIV and HCV infections at a local scale are sparse, which has critical implications for future MMTP implementation and health policies covering both HIV and HCV prevention among drug users in China. This study aimed to characterize geographic patterns of HIV and HCV prevalence at the township level among drug users in a Yi Autonomous Prefecture, Southwest of China.
Data on demographic and clinical characteristics of all clients in the 11 MMTP clinics of the Yi Autonomous Prefecture from March 2004 to December 2012 were collected. A GIS-based geographic analysis involving geographic autocorrelation analysis and geographic scan statistics were employed to identify the geographic distribution pattern of HIV-, HCV- and co-infections among drug users.
A total of 6690 MMTP clients was analyzed. The prevalence of HIV-, HCV- and co-infections were 25.2%, 30.8%, and 10.9% respectively. There were significant global and local geographic autocorrelations for HIV-, HCV-, and co-infection. The Moran’s I was 0.3015, 0.3449, and 0.3155, respectively (P < 0.0001). Both the geographic autocorrelation analysis and the geographic scan statistical analysis showed that HIV-, HCV-, and co-infections in the prefecture exhibited significant geographic clustering at the township level. The geographic distribution pattern of each infection group was different.
HIV-, HCV-, and co-infections among drug users in the Yi Autonomous Prefecture all exhibited substantial geographic heterogeneity at the township level. The geographic distribution patterns of the three groups were different. These findings imply that it may be necessary to inform or invent site-specific intervention strategies to better devote currently limited resource to combat these two viruses.
PMCID: PMC3975583  PMID: 24612875
HIV; HCV; Co-infection; Geographic distribution; Geographic autocorrelation analysis; Geographic scan statistic
12.  Patient and heath system delays in the diagnosis and treatment of new and retreatment pulmonary tuberculosis cases in Malawi 
BMC Infectious Diseases  2014;14:132.
Tuberculosis (TB) control remains a challenge in Malawi despite the National TB Control Program since 1984. This study aimed at measuring patient and health system delays and identifying factors associated with these delays.
A cross-sectional survey of 588 pulmonary TB patients was conducted in three TB centres in Blantyre, Lilongwe, and Mzuzu, between July and December 2011 using a semi-structured questionnaire. Patient delay was defined as the time interval between the onset of TB symptom(s) (a common symptom being coughing) to the first visit to any health provider. Health system delay was the interval from the first care-seeking visit at any health provider to the initiation of anti-tuberculosis treatment. Participants were invited to participate in the study during intensive phase of treatment. The characteristics associated with patient and health system delays were analyzed.
The median patient delay was 14 days for both new and retreatment TB cases (interquartile range [IQR] 14 – 28 and 7 – 21, respectively). The median health system delay was 59 days (IQR 26 – 108) for new and 40.5 days (IQR 21–90) for retreatment cases. Factors associated with longer patient delay in new cases included primary education (adjusted odds ratio [AOR] 2.2, 95% CI 1.3 – 3.9) and knowledge that more than three weeks of coughing is a sign of TB (AOR 1.9, 1.1 – 3.3). In retreatment cases, distance >10 Km (AOR 3.3, 1.1 – 9.6) and knowledge that more than three weeks of coughing is a sign of TB (AOR 3.7, 1.3 – 10.7; p < 0.05) were significant factors. Making the first visit to a health centre (OR 1.9, 0.9 – 3.8) or a drug store/ traditional healer (OR 5.1, 1.1 – 21.7) in new TB cases were associated with a longer health system delay (p < 0.05) while smear negative (OR 6.4, 1.5 – 28.3), and smear unknown or not done (OR 6.1, 1.3 – 26.9) among retreatment cases were associated with a longer health system delay (p < 0.05).
Effective management and new diagnostic techniques are needed especially among retreatment cases. It is also needed to address geographic barriers to accessing care and increasing TB awareness in the community.
PMCID: PMC3976046  PMID: 24606967
Patient delay; Health system delay; Tuberculosis; Case detection
13.  Comparative evaluation of TK SLC-L, a rapid liquid mycobacterial culture medium, with the MGIT system 
BMC Infectious Diseases  2014;14:130.
The present study was conducted to assess the efficiency of using TK SLC-L (Salubris, Inc.) for the primary isolation of mycobacteria from clinical samples by comparing it to the MGIT detection system (Becton Dickinson Diagnostic Instrument Systems). Although TK SLC, a biphasic medium, has been evaluated previously, this is the first study to evaluate TK SLC-L, a liquid medium.
Clinical specimens from a total of 146 clinically suspected cases of tuberculosis were studied. Each processed sample was evaluated by ZN staining and inoculated into TK SLC-L and MGIT tubes. The TK SLC tubes were incubated in a MYCOLOR TK while the MGIT tubes were incubated in a MGIT system. Growth, indicated by automated systems, was confirmed through production of a smear and microscopic evaluation after ZN staining.
Mycobacterial growth was positive in 35 TK SLC-L and in 34 MGIT samples. Although the growth detection time was approximately 3 to 5 days shorter, on average, with the MGIT system, the contamination rate was significantly lower using TK SLC-L. The total time spent for the repetition of cultures for contaminated samples in MGIT make the total return time for culture results equal to or longer than the time required by TK SLC-L.
The TK Culture System using TK SLC-L is an efficient system and possible alternative to other rapid mycobacterial culture systems.
PMCID: PMC3946173  PMID: 24597726
14.  Focal bone lesions in hiv-positive patient treated with tenofovir 
BMC Infectious Diseases  2014;14:131.
Tenofovir is a widely used antiviral drug for the treatment of HIV and HBV infection. Although its side effects on renal function and bone metabolism are well known, there are no reports on focal bone lesions caused by this drug. Our case suggests this new, unusual but important scenario.
Case presentation
We report on a 46-year-old HIV-positive man treated with an antiretroviral regimen containing tenofovir who suddenly developed localized inflammatory bone lesions. The examinations performed ruled out all the disorders commonly associated with this clinical pattern, and the patient’s conditions improved only after the suspension of tenofovir.
The case study suggests a rare but severe adverse event, which should be taken into account when physicians treat HIV-positive patients with focal inflammatory bone lesions
PMCID: PMC3975803  PMID: 24602357
HIV; Tenofovir; Bone lesions
15.  Is elevated Red cell distribution width a prognostic predictor in adult patients with community acquired Pneumonia? 
BMC Infectious Diseases  2014;14:129.
Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. We recently demonstrated that among young patients (<60 years old) with CAP, elevated red blood cell distribution width (RDW) level on admission was associated with significant higher rates of mortality and severe morbidity. We aimed to investigate the prognostic predictive value of RDW among CAP patients in general population of internal wards.
The cohort included patients of 18 years old or older who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between January 1, 2005 and December 31, 2010. Patients were retrospectively analyzed for risk factors for a primary endpoint of 90-day mortality. Secondary endpoint was defined as complicated hospitalization (defined as at least one of the following: In- hospital mortality, length of stay of at least 10 days or ICU admission). Binary logistic regression analysis was used for the calculation of the odds ratios (OR) and p values in univariate and multivariate analysis to identify association between patient characteristic, 90-day mortality and complicated hospitalization.
The cohort included 3815 patients. In univariate analysis, patients with co-morbid conditions tended to have a complicated course of CAP. In multivariate regression analysis, variables associated with an increased risk of 90-day mortality included age > 70 years, high Charlson comorbidity index (>2), Hb < 10 mg/dl, Na <130 meq/l, blood urea nitrogen (BUN) >30 mg/dl, systolic blood pressure < 90 mmHg and elevated RDW >15%. Variables associated with complicated hospitalization included high Charlson comorbidity index, BUN > 30 mg/dl, hemoglobin < 10 g/dl, heart rate >124 bpm, systolic blood pressure < 90 mmHg and elevated RDW. Mortality rate and complicated hospitalization were significantly higher among patients with increased RDW regardless of the white blood cell count or hemoglobin levels.
Elevated RDW levels on admission are associated with significant higher rates of mortality and severe morbidity in adult patients with CAP. RDW as a prognostic marker was unrelated with hemoglobin levels, WBC count, age or Charlson score.
PMCID: PMC3973886  PMID: 24597687
Community acquired pneumonia; Red blood cell distribution width; Mortality; Complicated hospitalization
16.  Incidence, pathogens and resistance patterns of nosocomial infections at a rural hospital in Gabon 
BMC Infectious Diseases  2014;14:124.
Nosocomial infections pose substantial risk to patients receiving care in hospitals. In Africa, this problem is aggravated by inadequate infection control due to poor hygiene, resource and structural constraints, deficient surveillance data and lack of awareness regarding nosocomial infections. We carried out this study to determine the incidence and spectrum of nosocomial infections, pathogens and antibiotic resistance patterns in a tertiary regional hospital in Lambaréné, Gabon.
This prospective case study was carried out over a period of six months at the Albert Schweitzer Hospital, Lambaréné, Gabon. All patients admitted to the departments of surgery, gynecology/obstetrics and internal medicine were screened daily for signs and symptoms of hospital-acquired infections.
A total of 2925 patients were screened out of which 46 nosocomial infections (1.6%) were diagnosed. These comprised 20 (44%) surgical-site infections, 12 (26%) urinary-tract infections, 9 (20%) bacteraemias and 5 (11%) other infections. High rates of nosocomial infections were found after hysterectomies (12%) and Caesarean sections (6%). Most frequent pathogens were Staphylococcus aureus and Escherichia coli. Eight (40%) of 20 identified E. coli and Klebsiella spp. strains were ESBL-producing organisms.
The cumulative incidence of nosocomial infections in this study was low; however, the high rates of surgical site infections and multi-resistant pathogens necessitate urgent comprehensive interventions of infection control.
PMCID: PMC3943987  PMID: 24592922
Nosocomial infections; Antibiotic resistance; Gabon
17.  Comparative impact of antiretroviral drugs on markers of inflammation and immune activation during the first two years of effective therapy for HIV-1 infection: an observational study 
BMC Infectious Diseases  2014;14:122.
Few studies have compared the impact of different antiretroviral regimens on residual immune activation and inflammation with discordant results. Aim of the study was to investigate the impact of various antiretroviral regimens on markers of immune activation and inflammation during the first two years of effective therapy.
We studied HIV-infected antiretroviral-naïve patients who began cART with either abacavir/lamivudine or tenofovir/emtricitabine, combined with ritonavir-boosted lopinavir (LPV/r), atazanavir (ATV/r) or efavirenz (EFV). All the patients had a virological response within 6 months, which was maintained for 2 years with no change in their ART regimen. C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), monokine induced by interferon-γ (MIG) and interferon-γ-inducible protein-10 (IP-10) were measured in stored plasma obtained at cART initiation and 24 months later. Mean changes from baseline were analyzed on loge-transformed values and multivariable linear regression models were used to study the effect of the treatment components, after adjusting for factors that might have influenced the choice of ART regimen or biomarker levels. Differences were expressed as the mean fold change percentage difference (Δ).
Seventy-eight patients (91% males) with a median age of 43 years met the inclusion criteria. Their median baseline CD4 cell count was 315/mm3 and HIV-1 RNA level 4.6 log10 copies/ml. During the 2-years study period, IL-6, IP-10 and MIG levels fell significantly, while hs-CRP and sCD14 levels remained stable. IP-10 and MIG levels declined significantly less strongly with ATV/r than with EFV (IP-10Δ -57%, p = 0.011; MIGΔ -136%, p = 0.007), while no difference was noted between LPV/r and EFV. The decline in IL-6 did not differ significantly across the different treatment components.
After the first 2 years of successful cART, IL-6, IP-10 and MIG fell markedly while hs-CRP and sCD14 levels remained stable. The only impact of ART regimen was a smaller fall in markers of immune activation with ATV/r than with EFV. Our results suggest that these markers could be worthwhile when evaluating new antiretroviral drugs.
PMCID: PMC3945800  PMID: 24589015
HIV; cART; Immune activation; Inflammation; Markers
18.  An atypical winter outbreak of hand, foot, and mouth disease associated with human enterovirus 71, 2010 
BMC Infectious Diseases  2014;14:123.
To analyze the epidemiological characteristics and pathogenic molecular characteristics of an hand, foot, and mouth disease (HFMD) outbreak caused by enterovirus 71 in Linyi City, Shandong Province, China during November 30 to December 28, 2010.
One hundred and seventy three stool specimens and 40 throat samples were collected from 173 hospitalized cases. Epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak.
Among the 173 cases reported in December 2010, the male–female ratio was 1.88: 1; 23 cases (13.3%) were severe. The majority of patients were children aged < 5 years (95.4%). Some patients developed respiratory symptoms including runny nose (38.2%), cough (20.2%), and sore throat (14.5%). One hundred and thirty eight EV71 positive cases were identified based on real time reverse-transcription PCR detection and 107 isolates were sequenced with the VP1 region. Phylogenetic analysis of full-length VP1 sequences of 107 Linyi EV71 isolates showed that they belonged to the C4a cluster of the C4 subgenotype and were divided into 3 lineages (Lineage I, II and III). The two amino acid substitutions (Gly and Gln for Glu) at position 145 within the VP1 region are more likely to appear in EV71 isolates from severe cases (52.2%) than those recovered from mild cases (8.3%).
This outbreak of HMFD was caused by EV71 in an atypical winter. EV71 strains associated with this outbreak represented three separate chains of transmission. Substitution at amino acid position 145 of the VP1 region of EV71 might be an important virulence marker for severe cases. These findings suggest that continued surveillance for EV71 variants has the potential to greatly impact HFMD prevention and control.
PMCID: PMC3974002  PMID: 24589030
Hand; Foot; and mouth disease; HFMD; Enterovirus 71; Phylogenetic analysis; Subgenotype C4
19.  Impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients 
BMC Infectious Diseases  2014;14:125.
The immunologic environment during HIV/M. tuberculosis co-infection is characterized by cytokine and chemokine irregularities that have been shown to increase immune activation, viral replication, and T cell dysfunction.
We analysed ex vivo plasma samples from 17 HIV negative and 16 HIV pulmonary tuberculosis co infected cases using Luminex assay to see impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients before and after anti Tuberculosis treatment.
The median plasma level of IFN-γ, IL-4, MCP-3, MIP-1β and IP-10 was significantly different (P < 0.05) before and after treatment in HIV negative TB patients but not in HIV positive TB patients. There was no significant difference between HIV positive and HIV negative TB patients (P > 0.05) in the plasma level of any of the cytokines or chemokines before treatment and anti TB treatment did not change the level of any of the measured cytokines in HIV positive tuberculosis patients. The ratio of IFN-γ/IL-10 and IFN-γ/IL-4 showed a significant increase after treatment in HIV negative TB cases but not in HIV positive TB cases which might indicate prolonged impairment of immune response to TB in HIV positive TB patients as compared to HIV negative tuberculosis patients.
HIV positive and HIV negative Tuberculosis patients display similar plasma cytokine and chemokine pattern. However, anti TB treatment significantly improves the Th1 cytokines and level of chemokines but does not restore the immune response in HIV positive individuals.
PMCID: PMC3974017  PMID: 24592945
Pulmonary tuberculosis; HIV; Cytokines and chemokines
20.  Community-onset bloodstream infection with multidrug-resistant organisms: a matched case-control study 
BMC Infectious Diseases  2014;14:126.
Multidrug-resistant (MDR) organisms have been increasingly reported at hospital admission. Recognising the magnitude, trend and predictors for MDR organisms in community-onset bloodstream infections (COBSI) is crucial for guiding empiric antibiotic prescribing.
Positive blood culture isolates recovered from patients presenting to the emergency department during a ten-year period (1st Jan 2002-31st Dec 2011) were assessed. Trend analyses of MDR organisms were performed. Risk factors for COBSI caused by an MDR organism and predictors for 30-day mortality were also determined.
A total of 1721 positive blood culture isolates were identified during the study period with a yearly incidence of 30-43 isolates/10 000 ED presentations. The proportion of MDR Escherichia coli causing COBSI increased from 9%-26% (P < 0.001), whilst methicillin-resistant Staphylococcus aureus remained at high levels (20%-30%). A total of 360 patients were included in a matched case-control (1:1) study, and residents in long-term care facilities (adjusted odds ratio [AOR], 4.9 [95% CI, 2.1-11.6]), home wound care (AOR, 5.5 [95% CI, 1.6-18.7]), underlying immunosuppression (AOR, 3.5 [95% CI, 1.6-7.7]), recent surgery (AOR, 3.5 [95% CI, 1.1-11.6]), and exposure to antibiotics within 3 months (AOR, 5.5 [95% CI, 2.8-10.6]) were independently associated with MDR COBSI. High risk source of COBSI, age and Pitt bacteraemia score were independent predictors for 30-day mortality.
A concerning trend in MDR organisms causing bloodstream infection from the community is occurring. Risk factors for MDR organisms have been identified to assist in empiric antibiotic prescribing for those presenting to hospital with sepsis.
PMCID: PMC3975842  PMID: 24592979
Multidrug-resistant; Empiric antibiotic therapy; Bacteraemia; Enterobacteriaceae; Staphylococcus
21.  Aetiology, antimicrobial therapy and outcome of patients with community acquired severe sepsis: a prospective study in a Norwegian university hospital 
BMC Infectious Diseases  2014;14:121.
Severe sepsis is recognized as an inflammatory response causing organ dysfunction in patients with infection. Antimicrobial therapy is the mainstay of treatment. There is an ongoing demand for local surveillance of sepsis aetiology and monitoring of empirical treatment recommendations. The present study was established to describe the characteristics, quality of handling and outcome of patients with severe sepsis admitted to a Norwegian university hospital.
A one year prospective, observational study of adult community acquired case-defined severe sepsis was undertaken. Demographics, focus of infection, microbiological findings, timing and adequacy of empirical antimicrobial agents were recorded. Clinical diagnostic practice was evaluated. Differences between categorical groups were analysed with Pearson’s chi-squared test. Predictors of in-hospital mortality were identified in a multivariate stepwise backward logistic regression model.
In total 220 patients were identified, yielding an estimated annual incidence of 0.5/1000 inhabitants. The focus of infection was established at admission in 69%. Respiratory tract infection was present in 52%, while genitourinary, soft tissue and abdominal infections each were found in 12-14%. Microbiological aetiology was identified in 61%; most prevalent were Streptococcus pneumoniae, Escherichia coli and Staphylococcus aureus. Independent predictors of in-hospital mortality were malignancy, cardiovascular disease, endocarditis, abdominal infections, undefined microbiological aetiology, delay in administration of empirical antimicrobial agents ≥ 6 hours and use of inadequate antimicrobial agents. In patients ≥ 75 years, antimicrobial therapy was less in compliance with current recommendations and more delayed.
Community acquired severe sepsis is common. Initial clinical aetiology is often revised. Compliance with recommendations for empirical antimicrobial treatment is lowest in elderly patients. Our results emphasizes that quick identification of correct source of infection, proper sampling for microbiological analyses, and fast administration of adequate antimicrobial agents are crucial points in the management of severe sepsis.
PMCID: PMC3975934  PMID: 24588984
Severe sepsis; Epidemiology; Aetiology; Antimicrobial therapy; Compliance; Outcome
22.  Glutathione S-transferase L1 multiplex serology as a measure of cumulative infection with human papillomavirus 
BMC Infectious Diseases  2014;14:120.
Several assays are used to measure type-specific serological responses to human papillomavirus (HPV), including the bead-based glutathione S-transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in epidemiologic research, as a measure of cumulative HPV infection and future immune protection among HPV-unvaccinated women.
We tested enrollment sera from participants in the control arm of the Costa Rica Vaccine Trial (n = 488) for HPV16 and HPV18 using GST-L1, VLP-ELISA, and two assays that measure neutralizing antibodies (cLIA and SEAP-NA). With statistical adjustment for sampling, we compared GST-L1 serostatus to established HPV seropositivity correlates and incident cervical HPV infection using odds ratios. We further compared GST-L1 to VLP-ELISA using pair-wise agreement statistics and by defining alternate assay cutoffs.
Odds of HPV16 GST-L1 seropositivity increased with enrollment age (OR = 1.20 per year, 95%CI 1.03-1.40) and lifetime number of sexual partners (OR = 2.06 per partner, 95%CI 1.49-2.83), with similar results for HPV18. GST-L1 seropositivity did not indicate protection from incident infection over 4 years of follow-up (HPV16 adjusted OR = 1.72, 95%CI 0.95-3.13; HPV18 adjusted OR = 0.38, 95%CI 0.12-1.23). Seroprevalence by GST-L1 (HPV16 and HPV18, respectively) was 5.0% and 5.2%, compared to 19.4% and 23.8% by VLP-ELISA, giving positive agreement of 39.2% and 20.8%. Lowering GST-L1 seropositivity cutoffs improved GST-L1/VLP-ELISA positive agreement to 68.6% (HPV16) and 61.5% (HPV18).
Our data support GST-L1 as a marker of cumulative HPV infection, but not immune protection. At lower seropositivity cutoffs, GST-L1 better approximates VLP-ELISA.
PMCID: PMC3973893  PMID: 24588945
23.  Estimating the under-reporting of norovirus illness in Germany utilizing enhanced awareness of diarrhoea during a large outbreak of Shiga toxin-producing E. coli O104:H4 in 2011 – a time series analysis 
BMC Infectious Diseases  2014;14:116.
Laboratory-confirmed norovirus illness is reportable in Germany since 2001. Reported case numbers are known to be undercounts, and a valid estimate of the actual incidence in Germany does not exist. An increase of reported norovirus illness was observed simultaneously to a large outbreak of Shiga toxin-producing E. coli O104:H4 in Germany in 2011 – likely due to enhanced (but not complete) awareness of diarrhoea at that time. We aimed at estimating age- and sex-specific factors of that excess, which should be interpretable as (minimal) under-reporting factors of norovirus illness in Germany.
We used national reporting data on laboratory-confirmed norovirus illness in Germany from calendar week 31 in 2003 through calendar week 30 in 2012. A negative binomial time series regression model was used to describe the weekly counts in 8∙2 age-sex strata while adjusting for secular trend and seasonality. Overall as well as age- and sex-specific factors for the excess were estimated by including additional terms (either an O104:H4 outbreak period indicator or a triple interaction term between outbreak period, age and sex) in the model.
We estimated the overall under-reporting factor to be 1.76 (95% CI 1.28-2.41) for the first three weeks of the outbreak before the outbreak vehicle was publicly communicated. Highest under-reporting factors were here estimated for 20–29 year-old males (2.88, 95% CI 2.01-4.11) and females (2.67, 95% CI 1.87-3.79). Under-reporting was substantially lower in persons aged <10 years and 70 years or older.
These are the first estimates of (minimal) under-reporting factors for norovirus illness in Germany. They provide a starting point for a more detailed investigation of the relationship between actual incidence and reporting incidence of norovirus illness in Germany.
PMCID: PMC3941256  PMID: 24580831
Norovirus; Gastroenteritis; Epidemiology; Disease notification; Time series analysis; Public health; Population surveillance; Under-reporting
24.  Sero-prevalence and risk factors of hepatitis B virus and human immunodeficiency virus infection among pregnant women in Bahir Dar city, Northwest Ethiopia: a cross sectional study 
BMC Infectious Diseases  2014;14:118.
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are the two most important agents of infectious diseases. Both HBV and HIV share common modes of transmission and have serious effects on both pregnant women and infants. In Bahir Dar city administration, there is a scarcity of information on sero-prevalence of HIV and HBV infection among pregnant women. The main objective of this study was to assess sero-prevalence and risk factors of HIV and HBV infection among pregnant women attending antenatal care in Bahir Dar city, Northwest Ethiopia.
A cross-sectional study was conducted from March 2013 to April 2013. Socio-demographic and explanatory variables were collected using a structured questionnaire by face to face interview. Hepatitis B surface antigen (HBsAg) was detected using an enzyme linked immunosorbent assay (ELISA). HIV infection was also detected using the national HIV test algorithms. The results were analyzed with descriptive statistics and binary logistic regression. The odds ratio and 95% Confidence intervals were calculated.
A total of 318 pregnant women with the mean age of 25.72 (SD. ±5.14) years old were enrolled. Overall, 21/318 (6.6%) and 12 /318 (3.8%) of the pregnant women were positive for HIV and HBsAg, respectively. Of these, HIV/HBV co-infection rate was 4 (19.0%). Previous history of blood transfusion (AOR = 3.7, 95% CI, 9.02-14.84), body tattooing (AOR = 5.7, 95% CI, 1.24-26.50), history of surgery (AOR = 11.1, 95% CI, 2.64-46.88) and unsafe injection (AOR = 5.6, 95% CI, 1.44-22.19) were significantly associated with HBV infection. Previous history of piercing with sharp materials (AOR = 3.0, 95% CI 1.17-7.80) and history of abortion (AOR = 6.6, 95% CI 2.50-17.71) were also statistically significant for HIV infection.
This study indicates that HIV and HBV infections are important public health issues in our region that need to be addressed. All pregnant women need to be screened for both HIV and HBV infections during antenatal care. Furthermore, health education about modes of transmission of HIV and HBV has to be given.
PMCID: PMC3942511  PMID: 24580859
HBV; HIV; Pregnancy; Ethiopia
25.  Therapy duration and long-term outcomes in extra-pulmonary tuberculosis 
BMC Infectious Diseases  2014;14:115.
Tuberculosis is classified as either pulmonary or extra-pulmonary (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis, as “the other” which is not pulmonary.
This is a retrospective cohort study of all patients treated for EPTB in the state of Texas between January 2000 and December 2005, who had no pulmonary disease. Clinical and epidemiological factors were abstracted from electronic records of the Report of Verified Case of Tuberculosis. The long-term outcome, which is death by December 2011, was established using the Social Security Administration Death Master File database. Survival in EPTB patients was compared to those with latent tuberculosis, as well as between different types of EPTB, using Cox proportional hazard models. A hybrid of the machine learning method of classification and regression tree analyses and standard regression models was used to identify high-order interactions and clinical factors predictive of long-term all-cause mortality.
Four hundred and thirty eight patients met study criteria; the median study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1) years. The overall all-cause mortality rate was 0.025 (95% confidence interval [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors of poor long-term outcome were age (hazard ratio [HR] for each year of age-at-diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV-infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis was no different from latent tuberculosis, while meningitis had the poorest long-term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27-0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and 0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and therapy duration for each type of EPTB was a unique “V” shaped curve, with the lowest mortality observed at different therapy durations for each, beyond which mortality increased.
EPTB is comprised of several different diseases with different outcomes and durations of therapy. The “V” shaped relationship between therapy duration and outcome leads to the hypothesis that longer duration of therapy may lead to higher patient mortality.
PMCID: PMC3943436  PMID: 24580808
Extra-pulmonary tuberculosis; Therapy duration; Survival; Peritoneal; Meningitis

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