Journal of Infection

Recurrent bacteraemia: A 10-year regional population-based study of clinical and microbiological risk factors

2010-01-04

Summary: Background: A population-based nested case-control study was conducted in order to characterize patient factors and microbial species associated with recurrent bacteraemia.Methods: All patients with bacteraemia in a Danish region during 1996–2006 were investigated. Recurrence was defined based on pathogen identity, site of infection and time frame, and not restricted to homologous pathogens.Results: We identified 8672 patients with first-time bacteraemia, of whom 1003 (12%) had a recurrence within 1year. The proportion of mono-microbial bacteraemia was similar for first (86%) and recurrent episodes (84%). An unknown focus was common in both episodes (22.7 and 29.1%, respectively). Independent predictors of a recurrence (incidence rate ratio, 95% confidence interval) included health care-associated (2.4; 1.9–3.0) and nosocomial bacteraemia (2.1; 1.8–2.6), poly-microbial Gram-positive bacteraemia (2.7; 1.6–4.6), and fungaemia (2.2; 1.4–3.5), a Charlson co-morbidity index score of 1–2 (1.7; 1.4–2.1), inappropriate empirical antimicrobial chemotherapy (1.3; 1.1–1.5), a gastro-intestinal tract focus (2.3; 1.7–3.0), a liver/biliary tract focus (2.7; 2.0–3.6), an iv-catheter focus (2.0; 1.4–2.8), endocarditis (2.7; 1.6–4.3), and an unknown focus (1.9; 1.5–2.3).Conclusions: This study showed recurrent bacteraemia to be common and the following risk factors were identified: a health care-associated or nosocomial origin, poly-microbial or fungal aetiology, a focus within the abdomen, endocardium, iv-catheter-related or unknown, a Charlson co-morbidity index score of >1 and inappropriate empirical antimicrobial chemotherapy.

Epidemiology of invasive pneumococcal disease in the pre-conjugate vaccine era: England and Wales, 1996–2006

2010-01-04

Summary: Objective: To describe the epidemiology of invasive pneumococcal disease (IPD) in England & Wales in the pre-conjugate vaccine era.Methods: We analysed reports of culture-confirmed IPD submitted to the national surveillance system between July 1996 and June 2006.Results: The incidence of IPD was 10 per 100,000 overall, and increased over time. The typical pattern of IPD by age was observed, with the highest incidence in young children and older adults. There was little change in IPD incidence in the elderly, despite the widespread use of 23-valent pneumococcal polysaccharide vaccines since 2003. The distribution of serotypes changed over time; notably the proportion of cases caused by serotype 14 decreased, and the proportion due to serotype 1 increased. The incidence of meningitis was 0.6 per 100,000 overall, and as a proportion of all IPD cases was most common in children under 1 year of age (30%). Particular serotypes were significantly associated with a presentation of meningitis, after controlling for age and year, and the case:carrier ratio varied markedly by serotype.Conclusions: This paper provides a baseline for evaluating the impact of 7-valent pneumococcal conjugate vaccines, introduced in September 2006. Ongoing high-quality laboratory-based surveillance of IPD in all age groups is essential.

Phenotypic and molecular characterization of invasive serogroup W135 Neisseria meningitidis strains from 1990 to 2005 in Brazil

Ana Paula S. Lemos, Lee H. Harrison, Melina Lenser, Claudio T. Sacchi — 2010-01-27

Summary: Objective: Neisseria meningitidis serogroup W135 has been associated with global outbreaks since the 2000 Hajj. Considering that N. meningitidis serogroup W135 is the third most prevalent serogroup isolated in Brazil in the last 10 years, and the possibility that the Hajj-related N. meningitidis serogroup W135 clone has been causing disease in Brazil, the present study characterized invasive N. meningitidis serogroup W135 isolates recovered in Brazil from 1990 to 2005.Methods: The isolates were characterized by serotyping, PorA and PorB VR typing, FetA and 16S rRNA typing, multilocus sequence typing (MLST) and pulsed field gel electrophoresis (PFGE).Results: Based on MLST, 73% of the isolates were clustered in one major clone of ST-11 complex/ET37 complex. Strains of this clone had the same STs, serotypes and PorA VR types as found in Hajj-related N. meningitidis serogroup W135 clone. One of these strains had the Hajj-2000 outbreak strain genotype, including 16S rRNA gene sequence 31 and 84% relatedness by PFGE.Conclusion: Taken together, these data suggest that the Hajj-related N. meningitidis serogroup W135 clone is present in Brazil but has not yet caused a substantial number of infections. Given the emergence of N. meningitidis serogroup W135 globally and the unpredictability of meningococcal disease epidemiology, continued surveillance for this invasive N. meningitidis serogroup W135 clone is needed for control and prevention strategies.

Early identification of leptospirosis-associated pulmonary hemorrhage syndrome by use of a validated prediction model

2010-01-18

Summary: Objective: To identify prediction factors for the development of leptospirosis-associated pulmonary hemorrhage syndrome (LPHS).Methods: We conducted a prospective cohort study. The study comprised of 203 patients, aged ≥14 years, admitted with complications of the severe form of leptospirosis at the Emílio Ribas Institute of Infectology (Sao Paulo, Brazil) between 1998 and 2004. Laboratory and demographic data were obtained and the severity of illness score and involvement of the lungs and others organs were determined. Logistic regression was performed to identify independent predictors of LPHS. A prospective validation cohort of 97 subjects with severe form of leptospirosis admitted at the same hospital between 2004 and 2006 was used to independently evaluate the predictive value of the model.Results: The overall mortality rate was 7.9%. Multivariate logistic regression revealed that five factors were independently associated with the development of LPHS: serum potassium (mmol/L) (OR = 2.6; 95% CI = 1.1–5.9); serum creatinine (μmol/L) (OR = 1.2; 95% CI = 1.1–1.4); respiratory rate (breaths/min) (OR = 1.1; 95% CI = 1.1–1.2); presenting shock (OR = 69.9; 95% CI = 20.1–236.4), and Glasgow Coma Scale Score (GCS) < 15 (OR = 7.7; 95% CI = 1.3–23.0). We used these findings to calculate the risk of LPHS by the use of a spreadsheet. In the validation cohort, the equation classified correctly 92% of patients (Kappa statistic = 0.80).Conclusions: We developed and validated a multivariate model for predicting LPHS. This tool should prove useful in identifying LPHS patients, allowing earlier management and thereby reducing mortality.

Monocyte HLA-DR expression as predictor of poor outcome in neonates with late onset neonatal sepsis

Ferah Genel, Fusun Atlihan, Elif Ozsu, Erhan Ozbek — 2010-01-07

Summary: Objectives: Down regulation of HLA-DR expression on monocytes has been reported in adult sepsis. The aims of this study were, first to evaluate monocyte HLA-DR expression in late onset neonatal infection and second to investigate the prognostic value of monocyte HLA-DR expression at onset of symptoms for the final outcome.Methods: Peripheral blood samples were taken from neonates, who were classified into three groups: late onset neonatal sepsis group (n=40); non-infective disorders group (n=24) and the control group (n=25). Monocyte expression of HLA-DR was determined by flow cytometry.Results: The percentage of monocytes expressing HLA-DR was lower in neonates with late onset sepsis (p<0.05). Of the 40 septic patients enrolled in the study, 32 survived, while 8 died. The percentage of HLA-DR expressing monocytes was significantly lower in the non-survivor sepsis group (16.6%) compared with that in the survivor sepsis group (45.2%). The optimal cutoff value of HLA-DR for predicting mortality was 30% with 87% sensitivity and 81% specificity. Patients with monocyte HLA-DR expression ≤30% had lower survival rate with a 30-fold higher risk of mortality (Odds ratio 30; 95% CI 3–295).Conclusion: According to our findings, monocyte HLA-DR expression seems to be an early predictive marker for the prognosis in late onset neonatal sepsis.

Clinical, epidemiological and virological features of dengue virus infections in vietnamese patients presenting to primary care facilities with acute undifferentiated fever

2010-02-04

Summary: Objectives: To explore clinical and virological characteristics and describe the epidemiology of dengue in patients who presented with acute undifferentiated fever (AUF) at primary health centers (PHC) in Binh Thuan Province, Vietnam.Methods: A prospective observational study was conducted from 2001 to 2006 to study the aetiology in AUF patients. Demographic and clinical information was obtained, and dengue polymerase chain reaction (RT-PCR) and serology were performed on a random selection of patients.Results: Three hundred fifty-one serologically confirmed dengue patients including 68 primary and 283 secondary infections were included in this study. In 25% (86/351) dengue virus (DENV) was detected by RT-PCR among which 32 DENV-1, 16 DENV-2, 1 DENV-3 and 37 DENV-4 were identified. The predominant dengue serotype varied by year with seasonal fluctuation: DENV-4 in 2001–2002, DENV-1 and DENV-2 from 2003 to 2006. Primary dengue was more common in children. Higher viraemia levels (P=0.010) were found in primary infections compared to secondary infections. DENV-1 infected patients had higher viraemia levels than DENV-2 (P=0.003) and DENV-4 (P<0.001) infected patients. Clinical symptoms were often seen in adults. Few differences in clinical symptoms were found between primary and secondary infection and no significant differences in clinical symptoms between the serotypes were observed.Conclusions: Our data provide insight in the epidemiology, clinical profile and virological features of mild symptomatic dengue patients who presented to PHC with AUF in Vietnam.

Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related anemia

2010-01-14

Summary: Objectives: In a previous retrospective study we have shown that circulating antibodies to endogenous erythropoietin (anti-EPO) are associated with HIV-1-related anemia. The present longitudinal cohort study was conducted to examine the effect of anti-EPO on the risk of developing anemia over time.Methods: The study population consisted of 113 HIV-1 seropositive patients, who were screened for the presence of anti-EPO, with a mean±SD follow up of 105±40 months, for a total of 2190 visits. Anti-EPO were detected with an ELISA assay.Results: Anti-EPO were detected in 41% (46/113) at enrollment and 29% (320/1094) for all visits, and were associated with higher EPO levels for all visits (45.7±60.4 vs. 31.8±31.7IU/ml, p<0.001). After adjusting for other significant confounders, anti-EPO has been associated with increased risk of anemia both at enrollment (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.25–20.49) as well as for all visits ([OR], 2.15; 95% [CI]: 1.29–3.56). During follow up, a decline in prevalence of both anti-EPO and anemia was observed as the percentage of patients receiving HAART was increasing.Conclusions: Anti-EPO are an independent risk factor for anemia in HIV-1-infected patients. HAART seems to reduce both anti-EPO and anemia prevalence.

New insights in diagnosing Schistosoma myelopathy

2009-12-25

Summary: At present non-invasive tests for diagnosing Schistosoma myelopathy are sub-optimal. We present a novel serological method, using paired liquor and serum samples, resulting in the diagnosis of Schistosoma myelopathy in a male patient with proximal muscle weakness. The patient recovered after praziquantel treatment.

In vitro drug susceptibility of Mycobacterium bovis BCG Connaught and Tokyo strains

2010-01-28

Intravesical treatment with the biological response modifier, live attenuated Mycobacterium bovis BCG, has been established as the most effective immunotherapy for superficial bladder cancer. BCG therapy using Connaught, Pasteur, Armand-Frappier, Tokyo, Tice, Glaxo/Evans, Moreau and RIMV causes a significant reduction in the rate of relapse, prolongs the progression-free interval and has become a standard treatment. These BCG strains do not differ in terms of preventing tumor progression, with a complete response rate of 70–75%, and are reported to cause remissions within a 5-year period in 70% of patients. BCG immunoadjuvant therapy is an excellent example of the importance of local immune reactions in cancer immunotherapy. The majority of patients experience minor adverse events, such as hematuria, cystitis, fever, and malaise, mainly due to a bladder inflammatory response usually contributing to an improved response to BCG therapy.

Spectrum of neurological disease in patients with discordant HIV-1 RNA levels in plasma and cerebrospinal fluid

A. Scourfield, L. Waters, M. Nelson — 2010-01-07

Cerebrospinal fluid (CSF) HIV-1 RNA levels are generally accepted to be 1–2 log10 copies/ml lower than in the plasma. There are increasing reports of discordance between CSF and plasma viral load levels as shown in a recent report by Garvey et al. who described a case of detectable HIV-1 RNA in CSF despite full suppression of viral replication in the plasma.

Improving evaluations of T-cell assays for diagnosing active Mycobacterium tuberculosis infection

Andrew Kirby — 2010-01-06

Evaluations of T-cell assays for diagnosing active Mycobacterium tuberculosis (TB) infection were recently published in the Journal of Infection by Liao et al., Kim et al. and Clark et al. (December 2009). These evaluations presented evidence of T-cell assays clinical accuracy, i.e. can the tests detect the presence and absence of active TB infection. Unfortunately, knowledge of T-cell assays clinical accuracy offers only moderate help in deciding if the tests are clinically useful in an individual patient. To better understand clinical usefulness, evaluations should investigate how a patient's management is altered by their use, that is: does the test help you treat the patient quicker, cheaper, or better; does it make no difference or does it lead to harm? At present the debate about T-cell assays for diagnosing active TB infection seems focused on their clinical accuracy. A simple Medline search, based on the term ELISPOT and Tuberculosis, demonstrates this. This search identified seven studies into the clinical accuracy of T-cell assays to diagnose active TB infection. Only one reported clinical usefulness. It included just seven patients with active TB, with the T-cell assays prompting early initiation of anti-tuberculous therapy in three patients. This provides preliminary evidence that despite the limitations of the T-cell assays: their clinical sensitivity being reported as low as 70% by Liao et al., their clinical usefulness is worthy of investigation.

Gram stain/aolc screening for detection of catheter related bloodstream infection

2010-01-25

Conventional methods for diagnosing CRBSI such as quantitative or semiquantitative catheter-tip cultures require removal of the CVC. However, CVCs removed on suspicion of CRBSI prove to be the source of blood stream infection in only 15% of cases. It has been shown that clinically suspected CRBSI can be detected by the differential time to positivity (DTP) method or Gram/acridine-orange leukocyte cytospin (AOLC) test without catheter removal. Whether microorganisms can be detected in blood drawn from CVCs before symptoms of CRBSI become manifest using the Gram/AOLC method has not been investigated. The aim of this prospective pilot study was to investigate whether the Gram stain/AOLC method might be a potentially useful way to anticipate the diagnosis of CRBSI.