International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease.

BACKGROUND: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. METHODS: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. RESULTS: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. CONCLUSION: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.

Utility of oropharyngeal real-time PCR for S. pneumoniae and H. influenzae for diagnosis of pneumonia in adults.

A lack of sensitive tests and difficulties obtaining representative samples contribute to the challenge in identifying etiology in pneumonia. Upper respiratory tract swabs can be easily collected and analyzed with real-time PCR (rtPCR). Common pathogens such as S. pneumoniae and H. influenzae can both colonize and infect the respiratory tract, complicating the interpretation of positive results. Oropharyngeal swabs were collected (n = 239) prospectively from adults admitted to hospital with pneumonia. Analysis with rtPCR targeting S. pneumoniae and H. influenzae was performed and results compared with sputum cultures, blood cultures, and urine antigen testing for S. pneumoniae. Different Ct cutoff values were applied to positive tests to discern colonization from infection. Comparing rtPCR with conventional testing for S. pneumoniae in patients with all tests available (n = 57) resulted in: sensitivity 87 %, specificity 79 %, PPV 59 % and NPV 94 %, and for H. influenzae (n = 67): sensitivity 75 %, specificity 80 %, PPV 45 % and NPV 94 %. When patients with prior antimicrobial exposure were excluded sensitivity improved: 92 % for S. pneumoniae and 80 % for H. influenzae. Receiver operating characteristic curve analysis demonstrated for S. pneumoniae: AUC = 0.65 (95 % CI 0.51-0.80) and for H. influenzae: AUC = 0.86 (95 % CI 0.72-1.00). Analysis of oropharyngeal swabs using rtPCR proved both reasonably sensitive and specific for diagnosing pneumonia caused by S. pneumoniae and H. influenzae. This method may be a useful diagnostic adjunct to other methods and of special value in patients unable to provide representative lower airway samples.

Changing epidemiology of group B streptococcal infections among adults in Iceland: 1975-2014.

We studied the bacterial characteristics and incidence of invasive infections caused by group B streptococci (GBS) in adults in Iceland in 1975-2014. A total of 145 isolates were characterized by serotyping, antimicrobial susceptibility, multilocus sequence typing and surface protein gene profiling. Disease incidence increased during the studied period (p <0.001), reaching 2.17 cases/100 000 person-years in 2013-14. Overall, serotype Ia was the most frequently found (23%), but serotypes Ib, II, III and V showed similar prevalence (14%-17%). Although there were notable changes in the proportion of most serotypes during the study period, only the decline of serotype III was statistically supported (p = 0.003) and was reflected in a decrease of clonal complexes CC17 and CC19 that included most serotype III isolates (p <0.04). On the other hand, the increase in frequency of CC1 was caused by two lineages expressing distinct serotypes: ST1/V/alp3 and ST196/IV/eps. Underlying the relative stability of serotype Ia were major changes in the lineages expressing this serotype, with an increase in the relative importance of CC23, including both ST23/Ia/eps and ST24/Ia/bca lineages, and a decrease in CC7. Nine cases of invasive GBS disease were caused by ST7, of possible zoonotic origin. All isolates were susceptible to penicillin. Rates of erythromycin and clindamycin resistance were 8.3% and 9.7%, respectively. An over-representation of resistance solely to clindamycin was associated with the unusual lsaC gene and serotype III ST19/rib lineage (p <0.001).

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012.

Epidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34­4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p<0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections.

Epidemiology of penicillin-non-susceptible pneumococci in Iceland, 1995-2010.

OBJECTIVES: The first penicillin-non-susceptible pneumococci (PNSP) were identified in Iceland in 1988. A rapid increase followed, associated with expansion of a single multiresistant clone, Spain(6B)-2, peaking at 19.8% in 1993. After interventions led to reduced antimicrobial use in children, the prevalence of PNSP decreased until 1995. The aim of this study was to follow the evolution of PNSP from 1995 to 2010, the period preceding the introduction of conjugated pneumococcal vaccines into the vaccination programme. METHODS: The laboratory at the Landspitali University Hospital serves ∼ 85% of the Icelandic population. All pneumococci isolated from 1995 to 2010 (n = 13,937) were stored (-80 °C). Oxacillin-resistant isolates were serotyped and penicillin MICs were determined. Selected strains were genotyped by PFGE and multilocus sequence typing. RESULTS: In 1995, the rate of PNSP was 24.2%, declining to 13.6% in 2001, and then increasing to 38.6% in 2010. Similar changes were observed for resistance to erythromycin and tetracycline. In 1995, 60.7% of PNSP were serotype 6B, mainly the Spain(6B)-2 clone, declining to 5.7% in 2010. PNSP of serotype 19F rapidly increased after 2004 to comprise 85.8% of all serogrouped PNSP in 2010, with most isolates belonging to a single multiresistant PFGE clone identified as sequence type (ST) 271 and ST1968, representing single- and double-locus variants of the international clone Taiwan(19F)-14, respectively. PNSP were most common among young children, from the nasopharynx, middle ear and lower respiratory tract. CONCLUSIONS: The epidemiology of PNSP was dominated by two multiresistant clones. The second expanded rapidly when the first one was disappearing, causing higher antibiotic resistance rates among pneumococci than seen before in Iceland.

Staphylococcus aureus bacteraemia in Iceland, 1995-2008: changing incidence and mortality.

Little is known about temporal changes in the epidemiology of Staphylococcus aureus bacteraemia. The objective of the present study was to analyse changes in the incidence and mortality of adult S. aureus bacteraemia in Iceland. Individuals 18 years or older with a positive blood culture for S. aureus between 1 January 1995 and 31 December 2008 were identified, with the participation of all clinical microbiological laboratories performing blood cultures in Iceland. Infections were categorized as nosocomial, healthcare-associated or community-acquired. National population statistics and dates of death were retrieved from the National Registry. During the study period, 692 individuals from 19 institutions had 721 distinct episodes of S. aureus bacteraemia. The incidence rose from 22.7 to 28.9 per 100,000 per year during the period (p 0.012). Nosocomial infections comprised 46.3% of cases, 14.6% were healthcare-associated, and 39.1% were community-acquired. The proportion of nosocomial infections decreased during the period (p <0.001), whereas an increase was seen in the proportion of community-acquired infections (p <0.001). All-cause 30-day mortality decreased from 25.0% to 8.1% (p 0.001) and 1-year mortality decreased from 37.0% to 27.9% (p 0.061) between the periods 1995-1996 and 2007-2008. Four cases of bacteraemia caused by methicillin-resistant S. aureus were seen (0.6%), none of which was fatal. In conclusion, there was a significant increase in the incidence of S. aureus bacteraemia in Iceland between 1995 and 2008. Concomitantly, there was a significant reduction in mortality, towards one of the lowest reported. Further studies are needed to understand the basis for these changes.

The impact of domestic travel on estimating regional rates of human campylobacteriosis.

Residential locations of cases are often used as proxy measures for the likely place of exposure and this assumption may result in biases affecting both surveillance and epidemiological studies. This study aimed to describe the importance of domestic travel in cases of human campylobacteriosis reported during routine surveillance in Iceland from 2001 to 2005. Various measures of disease frequency were calculated based upon the cases' region of residence, adjusting location of domestic travel cases to their travel region, as well as separate estimations for travellers and non-travellers. Of the 376 cases included in the analysis, 37% had travelled domestically during their incubation period. Five of the eight regions were identified as high-risk when considering domestic travel whereas there were no high-risk regions when considering only region of residence. The change in regional representation of disease occurrence indicates the importance of collecting domestic travel information in ongoing surveillance activities.

Prevalence and genetic relatedness of antimicrobial-resistant Escherichia coli isolated from animals, foods and humans in Iceland.

The prevalence of resistant bacteria in food products in Iceland is unknown, and little is known of the prevalence in production animals. The aim of this study was to investigate the prevalence and genetic relatedness of antimicrobial-resistant Escherichia coli from healthy pigs and broiler chicken, pork, broiler meat, slaughterhouse personnel and outpatients in Iceland. A total of 419 E. coli isolates were tested for antimicrobial susceptibility using a microbroth dilution method (VetMIC), and resistant strains were compared using pulsed-field gel electrophoresis (PFGE). All samples were screened for enrofloxacin-resistant strains with selective agar plates. The resistance rates among E. coli isolates were moderate to high from caecal and meat samples of pigs (54.1% and 28%), broilers (33.6% and 52%) and slaughterhouse personnel (39.1%), whereas isolates from outpatients showed moderate resistance rates (23.1%). Of notice was resistance to quinolones (minimum inhibitory concentrations: nalidixic acid > or = 32, ciprofloxacin > or = 0.12 and enrofloxacin > or = 0.5), particularly among broiler and broiler meat isolates (18.2% and 36%), as there is no known antimicrobial selection pressure in the broiler production in Iceland. The majority (78.6%) of the resistant E. coli isolates was genotypically different, based on PFGE fingerprint analyses and clustering was limited. However, the same resistance pattern and pulsotype were found among isolates from broiler meat and a slaughterhouse worker, indicating spread of antimicrobial-resistant E. coli from animals to humans. Diverse resistance patterns and pulsotypes suggest the presence of a large population of resistant E. coli in production animals in Iceland. This study gives baseline information on the prevalence of antimicrobial-resistant E. coli from production animals, and their food products in Iceland and the moderate to high resistance rates emphasize the need for continuing surveillance. Further studies on the origin of the resistant strains and the genetic relatedness of strains of different origin are needed.

Emergence and spread of vancomycin resistance among enterococci in Europe.

Nowadays, six types of acquired vancomycin resistance in enterococci are known; however, only VanA and to a lesser extent VanB are widely prevalent. Various genes encode acquired vancomycin resistance and these are typically associated with mobile genetic elements which allow resistance to spread clonally and laterally. The major reservoir of acquired vancomycin resistance is Enterococcus faecium; vancomycin-resistant Enterococcus faecalis are still rare. Population analysis of E. faecium has revealed a distinct subpopulation of hospital-acquired strain types, which can be differentiated by molecular typing methods (MLVA, MLST) from human commensal and animal strains. Hospital-acquired E. faecium have additional genomic content (accessory genome) including several factors known or supposed to be virulence-associated. Acquired ampicillin resistance is a major phenotypic marker of hospital-acquired E. faecium in Europe and experience has shown that it often precedes increasing rates of VRE with a delay of several years. Several factors are known to promote VRE colonisation and transmission; however, despite having populations with similar predispositions and preconditions, rates of VRE vary all over Europe.

Risk factors and outcome in ICU-acquired infections.

BACKGROUND: Nosocomial infections are common in intensive care units (ICU). The objectives of this study were to determine risk factors of ICU-acquired infections, and potential mortality attributable to such infections. METHODS: An observational study was performed in a 10-bed multidisciplinary ICU. For a period of 27 months, all patients admitted for >or=48 h were included. Infections were diagnosed according to Centers for Disease Control and Prevention definitions. Airway colonization was explored by molecular typing. Risk factors for infection were determined by multivariable logistic regression. Survival was analyzed with time-varying proportional hazards regression. RESULTS: Of 278 patients, 81 (29%) were infected: urinary tract infections in 39 patients (14%), primary bloodstream infections in 25 (9%), surgical site infections in 22 (8%) and pneumonia in 21 (8%). Of the total of 147 episodes, Gram-negative bacilli were isolated in 90, Gram-positive cocci in 49 and Candida sp. in 25. Risk factors for pneumonia were mechanical ventilation [odds ratio (OR=7.9, CI 1.8-35), lack of enteral nutriment (OR=8.0, CI 1.4-45) and length of time at risk (OR=1.8, CI 1.2-2.8), while gastric acid inhibitors did not affect the risk (OR=0.99, CI 0.32-3.0). Transmission of bacteria from the stomach to the airway was not confirmed. The risk of death was increased as patients were infected with pneumonia [hazard ratio (HR)=3.6; CI: 1.6-8.1], or primary bloodstream infection (HR=2.5; CI: 1.2-5.4), independent of age and disease severity. CONCLUSIONS: Mortality was increased by ICU-acquired pneumonia and primary bloodstream infections. Our findings did not support the gastro-pulmonary hypothesis of ICU-acquired pneumonia. The proposition that blood transfusions increase the risk of ICU-acquired nosocomial infections was not supported.

Onychomycosis in Icelandic children.

BACKGROUND: Onychomycosis is a rare disorder in children. Few studies exist on the incidence or prevalence of onychomycosis in children. OBJECTIVE: To examine the epidemiology of childhood onychomycosis in Iceland during the period 1982-2000. METHODS: Results from all mycological samples taken from children in Iceland from 1982 to 2000 were examined. Information about the requesting physician, unique social security number, date of birth, sex, results of culture and microscopy were registered. Growth of a dermatophyte was taken as an indication of a case of onychomycosis. RESULTS: During the period 1982-2000 a total of 493 samples from 408 Icelandic children, aged 0-17 years, were examined. Dermatophytes were cultured from 148 (30.0%) samples. During the period 1982-85, the mean annual incidence of positive cultures was 1.65 per 100,000, increasing to 21.30 per 100,000 for the years 1996-2000. Trichophyton rubrum was the dominating organism and was found in 102/148 cases positive for the growth of a dermatophyte. The incidence of positive dermatophyte cultures increased with age and was found in eight children aged 0-4, and in 57 children aged 10-14 years. CONCLUSION: Onychomycosis is rare in children, but increases with age. It seems that onychomycosis increased during the study period, but it is not clear if this was due to a true increase in the prevalence of onychomycosis or an increased awareness of onychomycosis, or both.

Nationwide study of recurrent invasive pneumococcal infections in a population with a low prevalence of human immunodeficiency virus infection.

Recurrent invasive infections caused by Streptococcus pneumoniae are rare, and often considered to be indicative of serious underlying illness. However, the prevalence of this problem, and the relevance of specific predisposing conditions, can be hard to assess, since many of the studies are based on specific risk groups. A population-based study of recurrent invasive pneumococcal disease in Iceland during the 30-year period 1975-2004 was performed. Clinical information, including mortality and vaccine use, was analysed retrospectively. Invasive pneumococcal isolates were serotyped and susceptibility testing was performed. During this period, 36 (4.4%) of 819 patients who survived an initial infection experienced recurrence, with a median time between episodes of 9.7 months. Pneumonia with bacteraemia was the most common clinical diagnosis (48% of cases), followed by bacteraemia without a clear focus (21%) and meningitis (13%). Most (94%) of the patients had identifiable predisposing conditions, most commonly, multiple myeloma in adults, and antibody deficiencies in children. Compared with children, adults were more likely to present with pneumonia (65% vs. 18%; p 0.0001). No significant change in the 30-day mortality rate was observed during the three decades of the study. Only 26% of eligible patients received pneumococcal vaccination. Patients with recurrent invasive pneumococcal disease should be investigated thoroughly for underlying diseases. Greater use of pneumococcal vaccines should be encouraged among high-risk patients. More effective preventive and therapeutic measures are needed to improve outcomes.

Streptococcal throat infections and exacerbation of chronic plaque psoriasis: a prospective study.

BACKGROUND: Guttate psoriasis has a well-known association with streptococcal throat infections but the effects of these infections in patients with chronic psoriasis remains to be evaluated in a prospective study. OBJECTIVES: To determine whether streptococcal throat infections are more common in and can cause exacerbation in patients with chronic psoriasis. METHODS: Two hundred and eight patients with chronic plaque psoriasis and 116 unrelated age-matched household controls were followed for 1 year. At recruitment all patients were examined, their disease severity scored and throat swabs taken. Patients and corresponding controls were then re-examined and tested for streptococcal colonization whenever they reported sore throat or exacerbation of their psoriasis during the study period. RESULTS: The psoriasis patients reported sore throat significantly more often than controls (61 of 208 vs. three of 116, P < 0.0001), and beta-haemolytic streptococci of Lancefield groups A, C and G (M protein-positive streptococci) were more often cultured from the patients than the controls (19 of 208 vs. one of 116, P = 0.003). A significant exacerbation of psoriasis (P = 0.004) was observed only if streptococci were isolated and the patients were assessed 4 days or later after the onset of sore throat. No difference was observed between groups A, C or G streptococci in this respect. CONCLUSIONS: This study confirms anecdotal and retrospective reports that streptococcal throat infections can cause exacerbation of chronic plaque psoriasis. It is concluded that psoriasis patients should be encouraged to report sore throat to their physician and that early treatment of streptococcal throat infections might be beneficial in psoriasis. A controlled trial for assessing potential benefits of tonsillectomy in patients with severe psoriasis should also be considered.

Campylobacter spp. in Icelandic poultry operations and human disease.

We describe the observed relationship of campylobacter in poultry operations to human cases in a closed environment. During 1999 in Iceland, domestic cases of campylobacteriosis reached peak levels at 116/100,000 and in 2000 dropped to 33/100,000. Approximately 62% of broiler carcass rinses were contaminated with Campylobacter spp. in 1999. During 2000, only 15% of the broiler flocks tested Campylobacter spp. positive. In 2000, carcasses from flocks which tested positive on the farms at 4 weeks of age were subsequently frozen prior to distribution. We suggest that public education, enhanced on-farm biological security measures, carcass freezing and other unidentified factors, such as variations in weather, contributed to the large reduction in poultry-borne campylobacteriosis. There is no immediate basis for assigning credit to any specific intervention. We continue to seek additional information to understand the decline in campylobacteriosis and to create a risk assessment model for Campylobacter spp. transmission through this well defined system.

Prevalence of resistance to ampicillin, gentamicin and vancomycin in Enterococcus faecalis and Enterococcus faecium isolates from clinical specimens and use of antimicrobials in five Nordic hospitals.

We determined the species distribution and prevalence of ampicillin resistance, high-level gentamicin resistance (HLGR) and vancomycin resistance among clinical enterococcal isolates from five Nordic laboratories (Bergen, Tromsø, Uppsala, Aarhus and Reykjavik). Isolates represented three different groups: (i) all blood culture isolates from 1999; (ii) consecutive in-patient isolates (maximum 40); and (iii) consecutive outpatient isolates (maximum 40) collected during March to May 2000. Antimicrobial use data were collected at the national and hospital level. A high proportion (31.4%) of Enterococcus faecium was detected among blood culture isolates, in contrast to only 4.2% among isolates from outpatients. Ampicillin resistance was not found in Enterococcus faecalis, in contrast to 48.8% in E. faecium isolates. HLGR rates varied considerably between laboratories (1.1-27.6%). Acquired vancomycin resistance was not detected. There were no significant differences in the prevalences of HLGR between in-patient and outpatient isolates at individual hospitals. A cluster of clonally related ampicillin-resistant and HLGR E. faecium isolates was demonstrated in one of the hospitals. The lowest level of hospital antimicrobial use, the lowest proportion of E. faecium and the lowest prevalence of resistance were observed in Reykjavik. The study showed a relatively low level of resistance in enterococci, as compared with most European countries and the USA. However, there were large differences between hospitals with regard to the relative proportion of E. faecium isolates, their susceptibility to ampicillin and gentamicin, as well as the prevalence of HLGR in E. faecalis isolates. This indicates a potential for further improvement of antibiotic policies, and possibly hospital infection control, to maintain the low resistance levels observed in these countries.

Mathematical models as tools for evaluating the effectiveness of interventions: a comment on Levin.

Possible interventions to minimize resistance rates are numerous and can involve reduction and/or change in antimicrobial use, infection control, and vaccinations. As mathematical models are becoming more realistic they can be useful to quantitatively evaluate the relative contribution of individual risk factors and for the planning of future intervention strategies. The fitness cost associated with resistance is an important parameter and small differences can have a profound effect on the results. The mathematical models presented for communities predicted that even with cessation of antibiotic use, the decline in resistance frequency would be slow. This contrasts with successful interventions in Finland and Iceland. Future models have to include important variables such as herd immunity and take into account the heterogeneity of open communities. Provision of susceptible strains from areas with low resistance rates to areas with high resistance rates can have a profound effect on the success of interventions to minimize resistance.

Penicillin pharmacodynamics in four experimental pneumococcal infection models.

Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung). In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h. In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.

Helicobacter pylori antibodies and gastric cancer in Iceland - The decline in IgG antibody level is a risk factor.

H. pylori infection is considered a causal agent of duodenal ulcer and a significant risk factor for gastric cancer. Retrospective cohort studies have demonstrated a significant association between presence of antibody to H. pylori and gastric cancer when using samples obtained years before the diagnosis but not at the time of diagnosis. The present study investigates, in a population-based cohort, whether a decline occurs in H. pylori antibody levels before the diagnosis of stomach cancer. Repeat samples (2 to 5) were available from 23 persons with gastric cancer taken up to 20 years before the diagnosis and 128 control subjects matched for gender, age, time and number of repeat samples. The odds ratio of developing stomach cancer was 1.16 (95% CI 1.05-1.28) for those showing decline in antibody levels of 1 relative antibody activity unit per year versus those with constant or rising levels. We conclude that this decline in antibody levels in cases, and not in controls, supports an active role of H. pylori in the pathogenesis of gastric cancer by causing atrophic gastritis, and provides a better risk assessment for gastric cancer compared to single measurements.

Genetic diversity and clonal patterns among antibiotic-susceptible and -resistant Streptococcus pneumoniae colonizing children: day care centers as autonomous epidemiological units.

Characterization by antibiotype of the 1,096 Streptococcus pneumoniae recovered from 2,111 nasopharyngeal samples of children attending 16 day care centers (DCCs) in Lisbon, Portugal, and molecular typing of 413 drug-resistant pneumococci (DRPn) and 89 fully drug-susceptible pneumococci (DSPn) has allowed several conclusions. (i) There was an increase in the frequency of DRPn colonizing children in DCCs from 40% in 1996 to 45% in 1997 to 50% in 1998. (ii) Drug resistance spread by cross-transmission of DRPn clones. A few (8 out of 57) DRPn clones were repeatedly isolated from a large number of children in several DCCs and during each period of surveillance, suggesting the epidemic nature of these clones, which included lineages representing internationally spread S. pneumoniae clones. (iii) Dissemination of resistance determinants among pneumococci colonizing the nasopharynx occurred. Association of identical pulsed-field gel electrophoresis patterns with diverse antibiotypes among pneumococci colonizing children suggests that the high prevalence of DRPn involves not only cross-transmission of resistant strains but also dispersal of resistance genes through recombinational mechanisms. (iv) DCCs are autonomous epidemiological units. Among the 413 DRPn, 57 different lineages were detected; these lineages were dispersed among the 16 DCCs to produce unique microbiological profiles for each of the DCCs. Higher genetic diversity and less sharing of clonal types were observed among the DSPn.