Scandinavian journal of infectious diseases. Supplementum最新文献

Witness for the prosecution: There is a growing interest in exploring simpler protease inhibitor (PI)-sparing regimens that could improve patients' quality of life and adherence, provide relief from adverse events and, at the same time, preserve virological and immunological success. Simplified maintenance studies have used switch regimens with equivalent antiretroviral efficacy to PI-containing highly active antiretroviral therapy (HAART), replacing the PI with non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz and nevirapine or with a 3 nucleoside-based maintenance regimen. As simplification strategies apply to patients with undetectable viral load, the conventional methods to measure viral resistance on plasma RNA cannot be applied. The only possibility relies on the determination of mutations within the integrated HIV-DNA in peripheral blood mononuclear cells. A careful anamnestic examination is therefore the only tool the caregiver has to direct his choices. In this respect and in our opinion it would be wise not to simplify treatment with abacavir in those patients who underwent a previous suboptimal therapy with lamivudine or thymidine analogues. Witness for the defence: The antiretroviral therapy that includes PI and 2 nucleoside analogue reverse transcriptase inhibitors (NRTI) was the first HAART in HIV infection: this combination results in a reduction of the risk of progression to AIDS and death, but it shows many problems caused by high tablet volume, dietary restrictions, multiple daily dosing and development of toxicity. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimize toxicity.

Chlamydia pneumoniaeis a fastidious microorganism with a characteristic biphasic lifecycle causing a variety of human respiratory tract infections. There is limited knowledge about the molecular biology of C. pneumoniae, and only a few genes have been sequenced. The structure of the chlamydial surface differs from that of Chlamydia trachomatis. In order to study the surface of C. pneumoniae we generated monoclonal antibodies (MAbs) against C. pneumoniae strain VR-1310 and selected 14 MAbs that reacted with the surface of C. pneumoniae. All MAbs reacted in immunoelectron microscopy with the surface of both whole C. pneumoniae VR-1310 elementary bodies and with purified sarcosyl extracted outer membrane complexes. However, only 2 of the MAbs reacted in immunoblotting with C. pneumoniae proteins and only with antigen that had not been heat treated in SDS-sample buffer. This indicates the dominance of conformational epitopes at the C. pneumoniae surface.

Infection and fever evoke a cytokine-mediated host response resulting in negative nitrogen balance, muscle protein degradation, which includes the skeletal muscles as well as the heart muscle, and deteriorated muscle function. Physical training has an opposite effect. Moderate physical training also stimulates the immune system, whereas exhaustive and longlasting exercise is followed by a temporary immunodeficiency and an increased susceptibility to respiratory tract infections. Exercise in the acute phase of an infection may promote complications including myocarditis. Exercise in myocarditis is associated with increased organism-associated as well as immune mediated tissue damage. An increased sudden death (SUD) rate among young Swedish male orienteers existed in 1979-92, suggesting (a) common underlying cause(s). Myocarditis was one of the most conspicuous histopathological features. Chlamydia pneumoniae, or a similar organism cross reacting in diagnostic tests, is hypothesized to be a factor causing this increased death rate. High frequency of intense exercise sessions, which was a common practice among the deceased, may have been immunosuppressive, promoting the development of severe myocardial disease.

The performance of susceptibility testing depends on high-quality material (disks and media), good laboratory practice (robust methodology and correct handling of material) and antimicrobial breakpoints being set in such a way that they allow for some intralaboratory variation. Thus, breakpoints must not divide homogeneous bacterial populations. Routine susceptibility testing should be checked with both internal and external quality control programs. The internal quality control should be designed to demonstrate the importance of minimizing random errors and to rapidly disclose systematic errors. This can be achieved either through the repeated testing of defined control strains or by systematic comparison of histograms of routine zone diameters with reference histograms supplied by the Swedish Reference Group for Antibiotics (SRGA and SRGA-M). The SRGA-M offers an external quality control program which by its design also functions as an epidemiological surveillance program. The quality control programs are supported by an educational program for laboratory personnel.

Sera from 20 male patients with a diagnosis suggestive of myocarditis, perimyocarditis or pericarditis were found significantly more often to have specific IgA antibodies to Chlamydia pneumoniae than sera from healthy blood donors of the same age and from the same time period. A less pronounced difference in IgG titres was found between patients and blood donors, and IgM antibodies were found only in one patient. A striking variation over time in the prevalence of specific antibodies to C. pneumoniae was seen in consecutive male blood donors over a 5-year observation period. The findings were discussed and it was concluded that C. pneumoniae may be associated with inflammatory heart disease.

The Swedish Reference Group for Antibiotics appointed a subcommittee on methodology (SRGA-M) in 1987 to investigate ways of defining interpretive breakpoints for antimicrobial susceptibility testing. The minimum inhibitory concentration (MIC) breakpoints for susceptibility categories are mainly based on pharmacological properties of the antibiotic, and they are, with few exceptions, valid for all species. However, for several species the MIC breakpoints have failed to distinguish strains with reduced susceptibility from normal susceptible strains. Disk diffusion is the routine method for susceptibility testing in Sweden. Studies of distribution of MICs and zone diameters for clinically important bacterial species have resulted in an emphasis on resistance rather than on susceptibility. The SRGA-M chose to place the zone diameter breakpoints close to the native (often susceptible) population of each species or group of related species. Such species-related zone diameter breakpoints used for susceptibility categories no longer correspond to the pharmacological MIC breakpoints, but divide each species into the fully susceptible (native) population and into those isolates/populations that have acquired a resistance mechanism, resulting in high- or low-grade resistance. By this method the risk of reports of false susceptibility is minimized and early detection of the emergence of antibiotic resistance is ensured.

It is well known that treatment of Chlamydia pneumoniae infections is difficult. High doses and prolonged treatment is often needed to achieve clinical cure despite good in vitro effect of the drugs used. We here discuss different methodological problems in the determination of MIC and MBC values of C. pneumoniae. The length of the preincubation time and the lack of fluctuation of the antibiotic concentrations may affect the outcome of the currently used assay.

Chlamydia pneumoniae infection, in earlier days misdiagnosed as ornithosis, is very common in Norway. The disease develops slowly, a feature that may account for the very large number of subclinical cases, which may be seven fold more common than clinical cases. Subclinical cases produce an antibody response similar to that seen in overt clinical disease. Silent carriage of C. pneumoniae in healthy individuals may be frequent. Therapy based on positive cell culture or polymerase chain reaction (PCR) in the absence of pneumonic symptoms may be questionable. PCR has, however, given the slow development of disease, revealed itself as a handy epidemiological technique useful for the survey of healthy populations.

The role of Chlamydia pneumoniae in atherosclerosis is at present controversial and neglected by researchers studying the pathogenesis of the disease. Numerous seroepidemiological studies have shown an association of C. pneumoniae infection with coronary heart disease and recent studies have indicated the ubiquitous presence of C. pneumoniae in the atherosclerotic lesions. The majority of cardiologists are, as yet, more apt to consider the finding of C. pneumoniae in atherosclerotic lesions as benign particles deposited from the circulation into preformed lesions rather than as a known pathogenic Gram-negative bacterium participating in or initiating an inflammatory process. The latter possibility would result in the oxidation of lipoproteins and the induction of cytokines and proteolytic enzyme production. These phenomena are typical for atherosclerosis. Chlamydia are amenable for treatment with antibiotics, and the therapeutic importance of the verification of bacterial involvement could be significant.