Journal of Infection - Articles in Press

Comparison of same day versus delayed enumeration of TB-specific T cell responses - Corrected Proof

2010-03-08

Summary: Background/objective: Flexibility in sample processing may improve test utility of the quantitative antigen-specific T cell assay (T-SPOT®.TB). We investigated whether delayed sample processing with and without the use of T-Cell Xtend, a proprietary reagent, impacted upon test accuracy.Methods: Blood samples obtained from 363 sequentially recruited tuberculosis suspects or treated patients were processed immediately (day 0) and at different times after receipt of the sample [∼24-h (day 1) or ∼32-h (day 2)] with and without adding T-Cell Xtend.Results: T-Cell-Xtend-independent median ELISPOT counts (spot forming cells per million peripheral blood mononuclear cells) were significantly higher at day 1 versus day 0 (114 vs. 100; n=66; p=0.03); inter-time-point agreement between the results was 95.45% and the conversion/reversion rate was 4.55%. By contrast, counts on day 0 without T-Cell Xtend versus day 1 with T-Cell Xtend were similar (56 vs. 56; n=215), inter-time-point agreement between the results was 97.17%, and the conversion/reversion rate was 2.83%. Counts performed at day 2 with T-Cell Xtend were not significantly different from day 0. These findings were independent of HIV status.Conclusion: There was high agreement between results when samples were processed immediately and after a 24-h delay. However, although the use of T-Cell Xtend appeared to reduce the number of conversions/reversions this reduction was not statistically significant. Larger studies are required to clarify these findings.

Parvovirus B19 infection associated with Hashimoto's thyroiditis in adults - Corrected Proof

2010-03-08

Summary: Objective: Parvovirus B19 is a common human pathogen, which has been linked to autoimmune diseases recently. The aim of the study is to evaluate whether B19 is involved in adult Hashimoto's thyroiditis (HT).Methods: Eighty-six thyroid tissues from the adult patients with a spectrum of thyroid disorders were examined for B19 DNA and capsid protein by nested PCR, in-situ hybridization and immunohistochemistry. The presence of viral DNA in HT epithelium was studied by laser-capture microdissection and sequencing of PCR products. The expressions of nuclear factor-κB (NF-κB) and interleukin-6 were investigated by immunohistochemistry.Results: B19 DNA was significantly present in HT tissues by both PCR (29/32, 90.6%) and in-situ hybridization (23/32, 71.9%, all p < 0.01) compared with normal thyroid tissue (7/16, 43.8%; 2/16, 12.5%). Laser-capture microdissection further confirmed this difference. B19 capsid protein in HT group was significantly higher than that in all the control groups (p < 0.01), and the expression of NF-κB and interleukin-6 in HT tissues was up-regulated. NF-κB was well co-localized with B19 protein in thyroid epithelia by double-labeling immunofluorescence and confocal microscopy.Conclusions: The presence of B19 nuclear acid and viral protein was significantly common in HT tissues and it suggested a possible role of B19 in adult HT.

Invasive fusariosis in patients with hematologic malignancies at a cancer center: 1998–2009 - Corrected Proof

Marcela Campo, Russell E. Lewis, Dimitrios P. Kontoyiannis — 2010-03-04

Summary: Background: Fusarium species cause severe infections in patients with hematologic malignancies. Few data are available concerning the outcome of fusariosis in the era of the expanding antifungal armamentarium.Methods: We retrospectively identified patients with hematologic malignancy and positive cultures for Fusarium species at the MDACC (1998–2009). The diagnosis of proven or probable fusariosis was made according to modified EORTC/MSG criteria.Results: Forty-four cases (75% proven) were identified over study period. Most (71%) patients had uncontrolled hematological malignancy and 21 patients (47%) received hematopoietic stem cell transplantation (85% allogeneic). Most patients (82%) were neutropenic at diagnosis (75% < 100/mm3). Patients had overlapping clinical syndromes: sinus 27%, pulmonary 75%, skin 68%, fungemia 36% and disseminated infection 70%. Bacterial (54%), fungal (36%) and viral (27%) co-infections were common. Most patients (84%) received combination therapy (typically a lipid formulation of amphotericin B and a triazole) with a mean duration of 28 days. Mortality at 12 weeks was 66%; 50% of deaths were attributable to Fusarium. Factors associated with increased likelihood of death at 12 weeks, included albumin <3.5 mg/dL, fungemia, and ICU admission; neutrophil recovery and fusariosis limited to skin were associated with improved survival (P < 0.05). Fungemia with Fusarium spp (OR 15.9; 1.1–231; P = 0.042) was the only risk factor independently associated with 12-week mortality with only 1/17 (6%) of patients still alive at 12 weeks.Conclusions: Fusariosis, although uncommon, continues to have poor prognosis in neutropenic leukemic patients who present with fungemia.

Empiric albendazole therapy and new onset seizures – A cautionary note - Corrected Proof

Patrick Lillie, Hugh McGann — 2010-03-04

Large scale community use of albendazole in “de-worming” campaigns is a well recognised public health measure in areas with high levels of helminth infections. Empirical use of albendazole has also been included in the recent BIS guidelines on eosinophilia. We present a case were inadvertent albendazole administration revealed occult neurocysticercosis.

Mycobacterium vaccae vaccine to prevent tuberculosis in high risk people: A meta-analysis - Corrected Proof

Xiao-yan Yang, Qun-fei Chen, Xiao-hua Cui, Yu Yu, You-ping Li — 2010-03-04

Summary: Objective: To evaluate the effectiveness and safety of Mycobacterium vaccae (MV) in prevention of tuberculosis (TB) among high risk people.Methods: Database of MEDLINE, EMBASE, BIOSIS, SCI, Cochrane Central Register of Controlled Trials, CBM, CNKI and VIP were searched till July 2009. Randomized controlled trials (RCTs) or non-randomized controlled clinical trials (CCTs) investigating MV as interventions in people at high risk of TB were identified for critical appraisal. Two reviewers independently performed data extraction and quality assessment. Effectiveness of MV was summarized in different group of risk people through RevMan 5.0 by The Cochrane Collaboration.Results: Thirteen studies were included. Risk difference (RD) of protection index (PI), its 95% confidence interval (95%CI) and the P value were as following: MV vs. Isoniazid (INH): 0.02 (−0.01, 0.05) (P=0.12); MV vs. (INH plus RFT): 0.00 (−0.00, 0.00) (P=1.00); MV vs. Blank: 0.04 (0.00, 0.08) (P=0.03) for soldiers with PPD strong positive; 0.00 (−0.00, 0.00) (P=0.05) for students with PPD strong positive; 0.20 (0.05, 0.36) (P=0.01) for aged people of clinical cured pulmonary TB, and 0.08 (0.01, 0.14) (P=0.03) for type 2 diabetes mellitus. In HIV-infected people, The Risk Ratio (RR) of MV vs. CV (control vaccine) of positive stimulation index (SI) (≥3) in lymphocyte proliferation assays (LPA) to Mycobacterium vaccae sonicate (MVS) was 2.39 with 95% CI (1.56, 3.66), P<0.0001. Immunization had no adverse effects on CD4 cell count or HIV viral load. The most frequent adverse effects of MV were induration and sore arm.Conclusions: Available evidence shows that MV is effective in preventing TB in PPD strong positive/type 2 diabetes mellitus/aged people of clinical cured pulmonary TB, and is safe, well-tolerated and effective in inducing biologically relevant immune response against TB in HIV-infected patients. High-quality trials aimed at different groups of high risk people are encouraged.

Re: Rapid influenza diagnostic test during the outbreak of the novel influenza A/H1N1 2009 in Thailand: An experience with better test performance in resource limited setting - Corrected Proof

Subhash C. Arya, Nirmala Agarwal — 2010-03-04

We comment on parallel studies at the Faculty of Medicine, Ramathibodi Hospital in Bangkok, Thailand on nasopharyngeal specimens by reverse transcriptase polymerase chain reaction (RT-PCR) and QuickVue influenza A+B test. Existing rapid tests for influenza A (H1N1) virus diagnosis including the QuickVue influenza A+B test would be the only choice in health care centers without laboratory facilities for molecular and virus investigations. Consequently, RT-PCR verification of any negative rapid test would never be possible. Rapid test sensitivity has been very low with a negative test being a poor predictor of absence of infection.

A novel screening method for influenza patients using a newly developed non-contact screening system - Corrected Proof

2010-03-02

Summary: Objectives: In places of mass gathering, rapid infection screening prior to definite diagnosis is vital during the epidemic season of a novel influenza. In order to assess the possibility of clinical application of a newly developed non-contact infection screening system, we conducted screening for influenza patients.Materials and methods: The system is operated by a screening program via a linear discriminant analysis using non-contact derived variables, i.e., palmar pulse derived from a laser Doppler blood-flow meter, respiration rate determined by a 10-GHz microwave radar, and average facial temperature measured by thermography. The system was tested on 57 seasonal influenza (2008–2009) patients (35.7 °C ≤ body temperature ≤ 38.3 °C, 19–40 years) and 35 normal control subjects (35.5 °C ≤ body temperature ≤ 36.9 °C, 21–35 years) at the Japan Self-defense Forces Central Hospital.Results: A significant linear discriminant function (p 10%). The system had a positive predictive value (PPV) of 93%, which is higher than the PPV value (PPV ≤ 65.4%) reported in the recent summary of studies using only thermography performed mainly in hospitals.Conclusions: The proposed system appears promising for application in accurate screening for influenza patients at places of mass gathering.

Fecal carriage of CTXM type extended-spectrum beta-lactamase-producing organisms by children and their household contacts - Corrected Proof

Wai-U Lo, Pak-Leung Ho, Kin-Hung Chow, Eileen L. Lai, Fanny Yeung, Susan S. Chiu — 2010-03-02

Summary: Objectives: To investigate the epidemiology of fecal carriage of CTX-M type extended-spectrum beta-lactamases (ESBL)-producing organisms among children and their household contacts.Methods: Fecal carriage with CTX-M-producing organisms was studied in 53 children and 172 household members. Molecular methods were used to characterize the isolates.Results: The children were mostly healthy and hospitalized for relatively mild febrile illnesses. Overall, the prevalence of fecal carriage of CTX-M-producing bacteria was 43.5% (admission children, 37.7%; household children, 20.7% and household adults, 50.3%). Household colonization index (defined by number of household carriers/total number of members) was significantly higher among families with at least one individual having a history of prolonged (>3 months) out-of-town residence in the previous year (mean±standard deviation; yes group, 0.67±0.36 vs. no group, 0.39±0.28, P=0.009) and was inversely correlated with the living space per person (R-square=0.139, P=0.006). Among 29 households with at least two carriers of CTX-M-producing enterobacteria, six clusters of clonally related strains were shared by 15 individuals from seven households; with both intra- and inter-household transmission.Conclusion: CTX-M beta-lactamases may spread extensively amongst family members in the home.

Activity of tigecycline against Streptococcus pneumoniae, an important causative pathogen of community-acquired pneumonia (CAP) - Corrected Proof

Stephen P. Hawser — 2010-03-02

Tigecycline is approved in the United States and in Europe for the treatment of complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) and was recently approved in the United States for the treatment of community-acquired pneumonia (CAP). Infections due to Streptococcus pneumoniae continue to evolve worldwide and are a major cause of morbidity and mortality. Resistance in S. pneumoniae not only to penicillin but also to cephalosporins, macrolides, trimethoprim/sulfamethoxazole, fluoroquinolones, and tetracycline is well documented. New guidelines for the management of in-patient and out-patient community-acquired pneumonia have recently been published. This study describes the activity of tigecycline against S. pneumoniae, an important etiologic agent that was recently added by the United States Food and Drug Administration (FDA) to the Tygacil® monograph for the treatment of CAP.

2009 H1N1 influenza infection in cancer patients and hematopoietic stem cell transplant recipients - Corrected Proof

2010-02-25

Summary: Objectives: Although usually mild, 2009 H1N1 Influenza has caused up to 6000 deaths in the US. To determine outcome in patients with cancer and/or hematopoietic stem cell transplant (HSCT), we reviewed our recent experience at Memorial Sloan-Kettering Cancer Center (MSKCC).Methods: During the initial NYC outbreak (May 19–June 30, 2009), all respiratory samples at MSKCC were tested for 2009 H1N1 influenza by DFA, culture, and RT-PCR. Medical records were reviewed for all cases.Results: During the 6-week period, 45(11%) of 394 tested patients were diagnosed with 2009 H1N1 Influenza. These included 29(17%) of 167 patients with hematologic conditions compared to 16(7%) of 226 with solid tumors (P < 0.01). 21(22%) of 96 tested HSCT recipients were positive. Cough (93%) and fever (91%) were common. Of 29 patients who were radiographically assessed, 8(27%) had lower airway disease. 17(37%) were hospitalized. None required mechanical ventilation. No deaths were attributed to influenza. All treated patients tolerated antiviral medication.Conclusions: 2009 H1N1 Influenza caused mild symptoms in most patients with cancer and/or HSCT. None died or required mechanical ventilation. Immunosuppression from cancer or its treatment including HSCT may not be a substantial risk for poor outcome, however further studies are needed to validate our results.The consequences of 2009 H1N1 influenza infection among cancer patients and stem cell recipients are unknown. We describe 45 patients with cancer and/or hematologic conditions with 2009 H1N1 influenza, including 21 stem cell transplant recipients. None of the infections resulted in death or severe morbidity.

Effect of GM-CSF in combination with hepatitis B vaccine on revacination of healthy adult non-responders - Corrected Proof

2010-02-25

Summary: Objective: To assess the immune effects and safety of using GM-CSF with the yeast-recombinant hepatitis B virus (HBV) vaccine for the re-vaccination of healthy adults who did not respond to a previous vaccination.Methods: Study participants included 1784 healthy adults and 100 individuals diagnosed as non-responders. These healthy non-responders were randomly assigned to one of the three treatment groups: Group A (34 individuals) was given 150 μg of granulocyte–macrophage colony stimulating factor (GM-CSF) the first day, then 20 μg of the vaccine; Group B (33 individuals) was given 40 μg of the vaccine only; and, group C (33 individuals) was injected with 20 μg of vaccine each time. All participants were injected three times, at time of study enrollment and one and six months later. Anti-HB surface antigen (HBs) antibody titers were tested before treatment and at one (T1), two (T2) and eight (T8) months post-first injection.Results: At T1, the rate of anti-HBs antibody+ in groups A, B and C was 26.47%, 48.48% and 18.18%, respectively (p = .027). At T8, the seropositive rate of group A (64.71%) and group B (75.76%) was significantly higher than in group C (39.39%) (p = .011); the geometric mean of the antibody titer for groups A and B was higher than for group C (p = .0173). All three treatments were safe and well-tolerated.Conclusions: Augmentation of the vaccine dose and co-administration of GM-CSF and the standard vaccine dose are effective for HBV vaccine non-responders. In fact, changing the vaccine dose had a better seropositive response than injecting the vaccine in combination with GM-CSF.

Hepatitis B immunization coverage and risk behaviour among Danish travellers: Are immunization strategies based on single journey itineraries rational? - Corrected Proof

Gerard Sonder, Anneke van den Hoek — 2010-02-18

In their article Schierup Nielsen and colleagues argue that, because in Denmark travellers pay for their own vaccinations, cost-benefit considerations should be made by the traveller. This implies that hepatitis B vaccination is probably not cost-effective for all travellers, with which we strongly agree.

Fosfomycin: An oral agent for urinary infection caused by extended spectrum beta-lactamase producing organisms - Corrected Proof

E.J. Hutley, M.A. Chand, G. Hounsome, M.C. Kelsey — 2010-02-18

We read with interest the recent paper by Falagas et al., which discussed the importance of treating simple lower urinary tract infections in the community. The increasing prevalence of extended-spectrum beta-lactamase (ESBL) producing organisms, particularly in community settings, poses a problem in this context. No oral antimicrobial in standard UK use has retained reliable activity against these organisms, although nitrofurantoin is useful in the case of certain epidemic strains. Nitrofurantoin, however, has limitations as an empirical treatment because of the intrinsic resistance of Proteus spp; it is also restricted for use in pregnancy and in those with impaired renal function. Treatment of simple urinary tract infection with ESBL-producing organisms may therefore force the use of inappropriately broad spectrum carbapenems, requiring arrangements for parenteral therapy.

Rapid MRSA test in exposed persons: Costs and savings in hospitals - Corrected Proof

2010-02-18

Summary: Objective: To study a rapid Xpert polymerase chain reaction (PCR) method in detecting methicillin-resistant Staphylococcus aureus (MRSA) in patients and healthcare workers (HCW) exposed to MRSA, and to estimate savings associated to isolation or work restriction.Methods: A test set of four double (one for the growth and one for the rapid test) pre-wet swabs from the nose, throat, hands/wrists and perineum was studied by a growth method and by the Xpert MRSA test.Results: The total correspondence between the growth and the rapid test was 92.8%. The overall sensitivity, specificity, positive and negative predictive values were for the Xpert MRSA test: 87%, 99.6%, 68.5% and 99.9%, and for the growth test: 76%, 100%, 100%, and 99.8%, assuming a prevalence of MRSA of 0.01%. Among the MRSA positive persons, the Xpert and growth tests detected MRSA in 44.6% and 40% of nose samples, respectively, 38.2% and 45.5% throat samples, 30.8% and 11.5% hands/wrists samples, 44% and 38% perineum samples, and in 81.8% and 77.3% wound samples, respectively. By combining four anatomical sites, the detection rate increased to 87.5% by both methods. The cost for each Xpert and growth test was €50 and €6.25, respectively. The rapid test would save at least €925 per exposed HCW and €550 per patient that were MRSA negative.Conclusion: The MRSA Xpert test is easy to perform, has a high negative predictive value, and may be used to control healthcare workers and patients exposed to MRSA. Sampling from multiple anatomical locations is recommended. Still, more then 10% of MRSA positive cases may not be found.

Bacteremia complicating gram-negative urinary tract infections: A population-based study - Corrected Proof

Majdi N. Al-Hasan, Jeanette E. Eckel-Passow, Larry M. Baddour — 2010-02-12

Summary: Background: Urinary tract infection (UTI) is common and bacteremia complicating this infection is frequently seen. There has been limited data published that characterize bacteremic UTI in a population-based setting over an extended period. We therefore examined the incidence rate, microbiology, outcome, and in vitro antimicrobial resistance trends of bacteremic UTI due to gram-negative bacilli in Olmsted County, Minnesota, from 1/1/1998 to 12/31/2007.Methods: We used Kaplan–Meier method to estimate mortality rates, Cox proportional hazard regression to determine risk factors for mortality, and logistic regression to examine temporal changes in antimicrobial resistance rates.Results: We identified 542 episodes of bacteremic gram-negative UTI among Olmsted County residents during the study period. The median age of patients was 71 years and 65.1% were females. The age-adjusted incidence rate per 100,000 person-years was 55.3 (95% confidence interval [CI]: 49.5–61.2) in females and 44.6 (95% CI: 38.1–51.1) in males. Escherichia coli was the most common pathogen (74.9%). The 28-day and 1-year all-cause mortality rates were 4.9% (95% CI: 3.0–6.8) and 15.6% (95% CI: 12.4–18.8), respectively. Older age was associated with higher mortality; community-acquired infection acquisition and E. coli UTI were both independently associated with lower mortality. During the study period, resistance rates increased linearly from 10% to 24% for trimethoprim-sulfamethoxazole and from 1% to 8% for ciprofloxacin.Conclusions: To our knowledge, this is the first population-based study of bacteremic gram-negative UTI. The linear trend of increasing antimicrobial resistance among gram-negative isolates should be considered when empiric therapy is selected.

Response to Letter to the Editor by Gerard Sonder and Anneke van den Hoek - Corrected Proof

Ulla S. Nielsen, Eskild Petersen, Carsten S. Larsen — 2010-02-01

In their Letter to the Editor, G. Sonder and A. van den Hoek (GS and AH) raise several discussions of interest. Firstly, we agree that high incidences of risk behaviour do not automatically translate into high risks of hepatitis B infection, because the risk of acquiring hepatitis B per risk situation is low, as demonstrated in the low incidence of disease in travellers despite very frequent risky behaviour.

Pseudomonas aeruginosa bacteremia secondary to fingerstick glucose monitoring - Corrected Proof

Shin-Pung P. Jen, Roopali Sharma, Jayashree Ravishankar — 2010-01-15

Summary: Routine fingersticks for blood glucose monitoring are essential for the management of diabetic patients. However, the development of infections following fingersticks is a potential complication of blood glucose monitoring that has been reported in the literature. We describe a case of Pseudomonas aeruginosa bacteremia introduced during a routine fingerstick for blood glucose monitoring in a febrile neutropenic patient.

First detection of the Anaplasma phagocytophilum groEL-A genotype in man - Corrected Proof

2010-01-11

Summary: Objective: Human Granulocytic Anaplasmosis (HGA) is an emerging disease caused by the gram-negative bacterium Anaplasma phagocytophilum which is transmitted by ticks of the genus Ixodes ricinus. For molecular detection of the pathogen by PCR, a conserved portion of the groEL gene within the groESL operon is frequently used as a target. A single G/A polymorphism in this region allows to discriminate between two genotypes, groEL-G and groEL-A.Methods: Total DNA from peripheral blood samples of two HGA patients was analysed by RealTime PCR, employing a protocol designed for genotyping groEL-G- and groEL-A variants of A. phagocytophilum.Results: We confirmed two clinical cases of HGA by PCR; in one patient, and for the first time in a human host, the groEL-A variant was detected, in the other case the pathogen was recognised as the groEL-G variant, up to now representing the only genotype reported in man.Conclusions: It is documented that HGA infections can be caused by two A. phagocytophilum groEL genotypes. At present, the preference of the A. phagocytophilum groEL-G genotype in humans remains unclear, as we describe the first patient with HGA caused by the groEL-A variant. For a conclusive interpretation, more data from HGA patients will be required.

WITHDRAWN: JC Virus in the Irish Population: Significant Increase of Genotype 2 in Immunocompromised Individuals - Corrected Proof

K. Schaffer, N. Sheehy, S. Coughlan, C. Bergin, W.W. Hall — 2009-01-23