Asko Järvinen

The common cold

Summary Despite great advances in medicine, the common cold continues to be a great burden on society in terms of human suffering and economic losses. Of the several viruses that cause the disease, the role of rhinoviruses is most prominent. About a quarter of all colds are still without proven cause, and the recent discovery of human metapneumovirus suggests that other viruses could remain undiscovered. Research into the inflammatory mechanisms of the common cold has elucidated the complexity of the virus-host relation. Increasing evidence is also available for the central role of viruses in predisposing to complications. New antivirals for the treatment of colds are being developed, but optimum use of these agents would require rapid detection of the specific virus causing the infection. Although vaccines against many respiratory viruses could also become available, the ultimate prevention of the common cold seems to remain a distant aim.

Lactobacillus Bacteremia during a Rapid Increase in Probiotic Use of Lactobacillus rhamnosus GG in Finland

Lactobacilli supposedly have low pathogenicity; they are seldom detected in blood culture. Lactobacillus rhamnosus GG, which originates indigenously in the human intestine, became available for use as a probiotic in 1990 in Finland. We evaluated the possible effects of the increased probiotic use of L. rhamnosus GG on the occurrence of bacteremia due to lactobacilli. Lactobacilli were isolated in 0.02% of all blood cultures and 0.2% of all blood cultures with positive results in Helsinki University Central Hospital and in Finland as a whole, and no trends were seen that suggested an increase in Lactobacillus bacteremia. The average incidence was 0.3 cases/100,000 inhabitants/year in 1995-2000 in Finland. Identification to the species level was done for 66 cases of Lactobacillus bacteremia, and 48 isolates were confirmed to be Lactobacillus strains. Twenty-six of these strains were L. rhamnosus, and 11 isolates were identical to L. rhamnosus GG. The results indicate that increased probiotic use of L. rhamnosus GG has not led to an increase in Lactobacillus bacteremia.

Towards tuberculosis elimination: an action framework for low-incidence countries

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions. Action framework for countries with low tuberculosis incidence: a coherent approach for eliminating tuberculosis http://ow.ly/H03ZZ

Lactobacillus Bacteremia, Clinical Significance, and Patient Outcome, with Special Focus on Probiotic L. Rhamnosus GG

Lactobacillus bacteremia is a rare entity, and its clinical significance is poorly defined. We have reviewed the risk factors and outcome for 89 case patients with Lactobacillus bacteremia. Species characterization was done in 53% of the cases, revealing 25 L. rhamnosus strains and 22 other Lactobacillus species. In 11 cases, the strain was identical with the probiotic L. rhamnosus GG. In 82% of the cases, the patients had severe or fatal comorbidities. Predisposing factors to bacteremia were immunosuppression, prior prolonged hospitalization, and prior surgical interventions. No significant differences were observed in these predisposing factors or clinical features between patients with cases associated with the various Lactobacillus species, other than higher C-reactive protein values in patients with L. rhamnosus bacteremia. Mortality was 26% at 1 month and was 48% at 1 year. In multivariate analysis, severe underlying diseases were a significant predictor for mortality (odds ratio [OR], 15.8), whereas treatment with antimicrobials effective in vitro was associated with lower mortality (OR, 0.22). We conclude that lactobacilli in blood cultures are of clinical significance and that their susceptibility should guide decisions about antimicrobial treatment.

Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy

Objective: To determine liver fat content in patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. Background: Lipodystrophy in several animal models is associated with fat accumulation in insulin-sensitive tissues, such as the liver. This causes hyperinsulinaemia, dyslipidaemia and other features of insulin resistance. Design: A cross-sectional study. Subjects and methods: Three age- and weight-matched groups were compared: 25 HIV-positive men with HAART-associated lipodystrophy (HAART+LD+), nine HIV-positive men receiving HAART, but without lipodystrophy (HAART+LD−), and 35 HIV-negative healthy men (HIV−). Liver fat content was measured using proton spectroscopy. Intra-abdominal and subcutaneous fat were determined using magnetic resonance imaging. Results: Liver fat content was significantly higher in the HAART+LD+ (8 ± 10%) than the HIV− (5 ± 7%; P < 0.05) or the HAART+LD− (3 ± 5%; P < 0.01) group. Liver fat content correlated with serum fasting insulin in the HAART+LD+ (r = 0.47; P < 0.05) and HIV− groups (r = 0.65; P < 0.001), but not with the amount of intra-abdominal fat. Within the HAART+LD+ group, serum insulin did not correlate with the amount of intra-abdominal fat. The HAART+LD+ group had a lower serum leptin concentration when compared to the two other groups. Features of insulin resistance, including hepatic fat accumulation, were not found in HAART+LD− group. Conclusions: The severity of the insulin resistance syndrome in patients with HAART-associated lipodystrophy is related to the extent of fat accumulation in the liver rather than in the intra-abdominal region. Fat accumulation in the liver may therefore play a causative role in the development of insulin resistance in these patients.

Infections of the central nervous system of suspected viral origin: a collaborative study from Finland.

We studied 3231 patients with acute central nervous system (CNS) symptoms of suspected viral origin to elucidate the current etiologic spectrum. In 46% of the cases, a viral finding was observed. Varicella-zoster virus (VZV) was the main agent associated with encephalitis, as well as meningitis and myelitis. VZV comprised 29% of all confirmed or probable etiologic agents. Herpes simplex virus (HSV) and enteroviruses accounted 11% each, and influenza A virus 7%. VZV seems to have achieved a major role in viral infections of CNS. In encephalitis in our population, VZV is clearly more commonly associated with these neurological diseases than HSV. The increase in VZV findings may in part be a pseudophenomenon due to improved diagnostic methods, however, a true increase may have occurred and the pathogenetic mechanisms behind this should be elucidated.

Lactobacillus bacteremia, species identification, and antimicrobial susceptibility of 85 blood isolates.

BACKGROUND Data regarding antimicrobial susceptibility of clinical Lactobacillus isolates are scarce, and appropriate interpretation criteria for susceptibility tests are not available. METHODS We examined 85 cases of Lactobacillus bacteremia, of which 47 cases have been included in our previous studies. Overall, 14 antimicrobial agents were evaluated by the E-test method, and these results were compared with disk diffusion test findings. The clinical outcomes of the patients and their antimicrobial treatments were registered. RESULTS The antimicrobial susceptibility of Lactobacillus strains was species dependent. The considerable number of Lactobacillus rhamnosus (n=46), Lactobacillus fermentum (n=12), and Lactobacillus casei (n=12) strains available for testing made it possible to compare the susceptibilities within 1 species, as well. Of the 46 L. rhamnosus isolates, 22 were identified as L. rhamnosus GG type by pulsed-field gel electrophoresis. All Lactobacillus isolates demonstrated low minimum inhibitory concentrations (MICs) of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin. MICs of vancomycin were high (>256 microg/mL) for all other species except Lactobacillus gasseri and Lactobacillus jensenii. Disk diffusion and E-test results were concordant. The MICs of cephalosporins varied; cefuroxime demonstrated a higher level of activity than did ceftriaxone. Benzylpenicillin and ampicillin MICs had variable ranges between different species. Combination therapy was given to 83% of the patients, but, in 54% of them, therapy included only 1 microbiologically active agent, according to results of the susceptibility tests. Mortality at 1 week was 12% among patients who presumably were receiving adequate treatment and 27% among patients who were receiving inadequate treatment (P=.131, by E-test). CONCLUSION Most clinical Lactobacillus blood isolates demonstrated low MICs of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin, but they had variable susceptibility to penicillin and cephalosporins.

Genome Diversification in Staphylococcus aureus: Molecular Evolution of a Highly Variable Chromosomal Region Encoding the Staphylococcal Exotoxin-Like Family of Proteins

ABSTRACT Recent genomic studies have revealed extensive variation in natural populations of many pathogenic bacteria. However, the evolutionary processes which contribute to much of this variation remain unclear. A previous whole-genome DNA microarray study identified variation at a large chromosomal region (RD13) of Staphylococcus aureus which encodes a family of proteins with homology to staphylococcal and streptococcal superantigens, designated staphylococcal exotoxin-like (SET) proteins. In the present study, RD13 was found in all 63 S. aureus isolates of divergent clonal, geographic, and disease origins but contained a high level of variation in gene content in different strains. A central variable region which contained from 6 to 10 different set genes, depending on the strain, was identified, and DNA sequence analysis suggests that horizontal gene transfer and recombination have contributed to the diversification of RD13. Phylogenetic analysis based on the RD13 DNA sequence of 18 strains suggested that loss of various set genes has occurred independently several times, in separate lineages of pathogenic S. aureus, providing a model to explain the molecular variation of RD13 in extant strains. In spite of multiple episodes of set deletion, analysis of the ratio of silent substitutions in set genes to amino acid replacements in their products suggests that purifying selection (selective constraint) is acting to maintain SET function. Further, concurrent transcription in vitro of six of the seven set genes in strain COL was detected, indicating that the expression of set genes has been maintained in contemporary strains, and Western immunoblot analysis indicated that multiple SET proteins are expressed during the course of human infections. Overall, we have shown that the chromosomal region RD13 has diversified extensively through episodes of gene deletion and recombination. The coexpression of many set genes and the production of multiple SET proteins during human infection suggests an important role in host-pathogen interactions.

The Efficacy and Safety of Probiotic Lactobacillus rhamnosus GG on Prolonged, Noninfectious Diarrhea in HIV Patients on Antiretroviral Therapy: A Randomized, Placebo-Controlled, Crossover Study

Abstract Purpose: The aim of this placebo-controlled, crossover study was to evaluate the efficacy and safety of probiotic Lactobacillus rhamnosus GG (LGG) in ameliorating gastrointestinal symptoms in HIV-infected patients on antiretroviral therapy. Method: Infectious causes for diarrhea (bacteria, ova, parasites, and viruses including cryptosporidium, microsporidia, and cyclospora) were excluded with fecal samples before the study. HIV-infected patients with diarrhea for more than 1 month received in randomized order probiotic LGG preparation (containing viable LGG 1-5 × 1010 cfu/dose) and placebo twice a day for 2 weeks. Gastrointestinal symptoms were assessed daily and included the daily number of bowel movements, classification of stool consistency (watery, semi-watery, loose, firm, or foaming), and Visual Analog Scale (VAS) of gastrointestinal symptoms (flatulence, stomach pain, bloating disorders, general well-being). Results: Seventeen HIV-infected patients completed the study. There were no significant differences between the treatment groups in the frequency or the consistency of diarrhea. In the VAS assessments of gastrointestinal symptoms, no difference between LGG and placebo could be detected. No adverse events were reported. The number of HIV RNA copies in the blood and CD4 cell counts remained stable during the study. Conclusion: Probiotic LGG preparation was well-tolerated in HIV infected patients. No significant differences in noninfectious diarrhea or gastrointestinal symptoms compared to placebo could be observed in this crossover study.

Trends and outcome of nosocomial and community-acquired bloodstream infections due to Staphylococcus aureus in Finland, 1995–2001

In Finland, Staphylococcus aureus bloodstream infections are caused predominantly (>99%) by methicillin-sensitive strains. In this study, laboratory-based surveillance data on Staphylococcus aureus bloodstream infections occurring in Finland from 1995 to 2001 were analyzed. Preceding hospitalizations for all persons with Staphylococcus aureus bloodstream infections were obtained from the national hospital discharge registry, and data on outcome was obtained from the national population registry. An infection was defined as nosocomial when a positive blood culture was obtained more than 2 days after hospital admission or within 2 days of admission if there was a preceding hospital discharge within 7 days. A total of 5,045 cases were identified. The annual incidence of Staphylococcus aureus bloodstream infection rose by 55%, from 11 per 100,000 population in 1995 to 17 in 2001. The increase was detected in all adult age groups, though it was most distinct in patients >74 years of age. Nosocomial infections accounted for 51% of cases, a proportion that remained unchanged. The 28-day death-to-case ratio ranged from 1% in the age group 1–14 years to 33% in patients >74 years of age. The 28-day death-to-case ratios for nosocomial and community-acquired infections were 22% and 13%, respectively, and did not change over time. The increase in incidence among elderly persons resulted in an increase in the annual rate of mortality associated with Staphylococcus aureus bloodstream infections, from 2.6 to 4.2 deaths per 100,000 population per year. Staphylococcus aureus bloodstream infections are increasing in Finland, a country with a very low prevalence of methicillin resistance. While the increase may be due in part to increased reporting, it also reflects a growing population at risk, affected by such factors as high age and/or severe comorbidity.