Oral infections and systemic disease—an emerging problem in medicine

The relationship between oral and general health has been increasingly recognised during the past two decades. Several epidemiological studies have linked poor oral health with cardiovascular disease, poor glycaemic control in diabetics, low birth-weight pre-term babies, and a number of other conditions, including rheumatoid arthritis and osteoporosis. Oral infections are also recognised as a problem for individuals suffering from a range of chronic conditions, including cancer and infection with human immunodeficiency virus, as well as patients with ventilator-associated pneumonia. This review considers the systemic consequences of odontogenic infections and the possible mechanisms by which oral infection and inflammation can contribute to cardiovascular disease, as well as the oral conditions associated with medically compromised patients. A large number of clinical studies have established the clinical efficacy of topical antimicrobial agents, e.g., chlorhexidine and triclosan, in the prevention and control of oral disease, especially gingivitis and dental plaque. The possible risks of antimicrobial resistance are a concern, and the benefits of long-term use of triclosan require further evaluation. Oral infections have become an increasingly common risk-factor for systemic disease, which clinicians should take into account. Clinicians should increase their knowledge of oral diseases, and dentists must strengthen their understanding of general medicine, in order to avoid unnecessary risks for infection that originate in the mouth.     

Episomal and stable expression of the luciferase reporter gene for quantifying Leishmania spp. infections in macrophages and in animal models

We have expressed the reporter firefly luciferase gene (LUC) in Leishmania donovani and Leishmania major either as part of episomal vectors or integrated into the parasite genome under the control of their respective ribosomal promoter regions. An excellent linear correlation between parasite number and luciferase activity was observed with all the transfectants. LUC-expressing recombinant parasites were useful to monitor Leishmania spp. infections in macrophages or in animal models. For prolonged growth in absence of drug selection, such as within animal models, quantitation of parasites is more reliable when the reporter gene LUC is stably integrated in the parasite genome. These recombinant strains should be useful tools to monitor Leishmania growth under a number of conditions.     

Validation of an ELISA for the diagnosis of recent Campylobacter infections in Guillain–Barré and reactive arthritis patients

Weeks or months following Campylobacter infection, a small proportion of infected individuals develop Guillain-Barré syndrome (GBS) or reactive arthritis (ReA). Stool culture for Campylobacter is often negative in these patients, and serology is therefore the method of choice for diagnosing a recent infection with Campylobacter. This study developed a capture ELISA system to detect anti-Campylobacter IgA and IgM antibodies indicative of a recent infection. The sensitivity of the assay was 82.0% in uncomplicated Campylobacter enteritis patients, 96.2% in GBS patients who were culture-positive for Campylobacter, and 93.1% in culture-positive ReA patients, with a specificity of 93.0%. The assay allows identification of Campylobacter infection in patients with post-infectious neurological and rheumatological complications.     

Influence of maternal infections with viral agents or Toxoplasma gondii during pregnancy on fetal IgE production

The importance of maternal infections with Toxoplasma gondii , cytomegalovirus (CMV), Parvovirus B19, respiratory syncytial virus (RSV), and influenza A and B on fetal IgE synthesis was studied in 153 pregnant women. No case of specific IgM activity or viral DNA in cord blood, indicating a congenital infection, was found. From gestational week 15 to delivery, maternal IgG-Ab seroconversion to Parvovirus B19, RSV, influenza A, or influenza B occurred in 47 women. At delivery, serologic signs of past infection with T. gondii were observed in 29 (19%) women, and the corresponding figure for CMV was 117 (77%). The number of women with positive IgG seroconversion during pregnancy or positive IgG-Ab activity toward the studied infectious agents at delivery did not differ significantly among infants with an increased (≥1.3 kU/1; n =51) or with an undetectable (<0.1 kU/l; n =102) cord-blood IgE level. These results show that genetic and other environmental factors probably have a greater influence on fetal IgE synthesis than do maternal infections during pregnancy.     

Diversity of enteric viruses detected in patients with gastroenteritis in a tertiary referral paediatric hospital

The genetic diversity of enteric viruses co-circulating in a cohort of patients with viral gastroenteritis in a large tertiary paediatric hospital in London, UK, was determined. Multiple strains of noroviruses (NV), sapoviruses (SV) and astroviruses (HAsV) were detected in these patients, indicating the likelihood of multiple introductions from different sources, possible sub-clinical infections and simultaneous infection with different viruses in immunocompromised and other patients. Routine screening of immunocompromised patients and infection control procedures are important to prevent nosocomial infection.     

Clinical,immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.     

Correlation between cyclophosphamide-induced viral susceptibility and depletion of Junin virus-induced suppressor populations.

In contrast to lymphocytic choriomeningitis virus, another arenavirus, Junin virus (JV), the etiologic agent of Argentine hemorrhagic fever, when inoculated into suckling mice, induces lethal meningoencephalitis characterized by a delayed-type hypersensitivity (DTH)-like immune response. However, the adult BALB/c mouse is resistant to infection and no DTH reaction can be seen. This different viral sensitivity may be related to the development of an antigen non-specific DTH-suppressor cell pathway at work in the adult mouse. When the resistant mice are treated with cyclophosphamide (Cy) (50 mg/kg each dose) given at days -1,+1,+4 (zero: infection day), animals become susceptible and develop DTH reaction in brain that leads to death. We analyze the influence of the timing of Cy administration on the suppressor system developing after infection. It was found that Cy depletes the previously described JV-induced suppressor populations (Tsv) but a new suppressor cell (Tsv*) is disclosed bearing the Thy 1+ Ly1+2- phenotype which is unable to depress DTH in Cy-treated animals. With only two doses of Cy corresponding to days -1 and +1, the target of Tsv* cells is depleted but the third dose is still required to achieve full depletion of Tsv cells which are able to employ the Cy-resistant antigen-specific suppressor cells as targets. Since the Cy treatment is able to deplete the Tsv population together with the target of Tsv* cells, animals became unable to regulate lethal DTH reaction. Thus, a cellular explanation for an empirically established Cy schedule able to abrogate the adult mouse resistance to JV is proposed.     

Changes in Streptococcus pneumoniae serotypes causing invasive disease with non-universal vaccination coverage of the seven-valent conjugate vaccine

The pneumococcal seven-valent conjugate vaccine (PCV7) has been administered in Portugal since late 2001 through the private sector. To evaluate the impact of PCV7 use, the serotypes and antimicrobial susceptibility of pneumococci causing invasive disease in Portugal during 2003–2005 were determined and compared with available data for the period 1999–2002. Changes in serotype distribution compatible with the introduction of PCV7 were shown for children ≤5 years of age from 2003 onwards and for adults from 2004 onwards. PCV7 use with coverage of 43% of children with four doses in the 2004 birth cohort, although substantially below universal coverage, seems to have contributed to greatly reducing the proportion of invasive infections due to vaccine serotypes  4, 6B, 14 and 23F. Similarly, significant indirect effects on the serotype distribution of pneumococci causing infections in adults were noted, with reductions in the proportion of invasive infections caused by serotypes  4, 5 and 14. These changes were accompanied by an increase in the proportion of two non-vaccine serotypes: 19A isolates in all age groups and 7F isolates in adults. Whereas serotypes  6B, 14 and 19A were associated with multidrug resistance, isolates expressing serotypes  4 and 7F were fully susceptible for the most part. There were no changes in the proportion of resistant isolates within each serotype and, in spite of the changes in serotype prevalence, there was not an overall reduction in the proportion of infections caused by resistant pneumococci.     

A European perspective on intravascular catheter-related infections: report on the microbiology workload, aetiology and antimicrobial susceptibility (ESGNI-005 Study)

The laboratory workload, microbiological techniques and aetiology of catheter-related infections in European hospitals are mostly unknown. The present study (ESGNI-005) comprised a 1-day (22 October 2001), laboratory-based, point-prevalence survey based on a questionnaire completed by microbiology laboratories in European (European Union (EU) and non-EU) hospitals. Also included were questions requesting retrospective information for the year 2000. In total, 151 hospitals from 26 European countries participated, of which 78.1% were teaching institutions. Overall, the estimated population served by these institutions was 121,363,800, and the estimated number of admissions during 2000 was 6,712,050. The total number of catheter tips processed during 2000 was 142,727, or 21/1,000 admissions, of which 23.7% were considered to be positive in the institutions using semiquantitative or quantitative techniques. Overall, EU centres received significantly more catheter tip samples/1,000 admissions and had a significantly higher rate of 'positivity' (p < 0.0001) than non-EU centres. Of the institutions surveyed, 11.4% (7.2% in EU countries and 23.7% in non-EU countries; p 0.04) used only qualitative techniques for catheter tip sample processing. On the day of the study, 167 microorganisms were recovered from significant catheter tip cultures (122 patients), of which Gram-positive bacteria represented 70.7%, Gram-negative bacteria 22.2%, and yeasts 7.2%. The five most common microorganisms were coagulase-negative staphylococci, Staphylococcus aureus, Candida spp., Enterococcus spp. and Pseudomonas spp. Overall, 19% of catheter tip cultures were polymicrobial. In the case of S. aureus, 40% of isolates were resistant to oxacillin, as were 63.4% of coagulase-negative staphylococcus isolates. Of 37 Gram-negative isolates, 35% were resistant to cefotaxime, 31% to ceftazidime, and 27% to ciprofloxacin. Imipenem and cefepime had the lowest reported rates of resistance (11%).