Paul L. Andersen

FAILURE TO DEMONSTRATE CHLAMYDIA PNEUMONIAE IN SYMPTOMATIC ABDOMINAL AORTIC ANEURYSMS BY A NESTED POLYMERASE CHAIN REACTION (PCR)

OBJECTIVE To investigate whether Chlamydia pneumoniae is present in symptomatic abdominal aortic aneurysms (AAA). METHOD AND MATERIALS After optimisation of DNA extraction procedures an inhibitor-controlled nested polymerase chain reaction (PCR) amplifying fragments of the gene encoding the C. pneumoniae specific major outer membrane protein was performed on 124 wall-specimens from 20 patients with symptomatic AAA. RESULTS None of the specimens contained C. pneumoniae-specific DNA. Minor inhibition of the PCR was noticed especially in media specimens. CONCLUSION Using a sensitive and specific nested PCR, we were not able to detect C. pneumoniae in symptomatic AAA. The failure to detect C. pneumoniae in symptomatic AAA, combined with previously reported positive findings in atherosclerotic lesions, supports the hypothesis that AAA and atherosclerosis might be two different disease entities.

Pathogenesis of lower respiratory tract infections due to Chlamydia,Mycoplasma,Legionella and viruses

Acute infection of the lower respiratory tract comprises bronchitis, bronchiolitis, and pneumonia. From a clinical point of view it may be difficult to distinguish these disease entities and one infection may progress into another. The most common pathogens causing these infections are the primary respiratory viruses (respiratory syncytial virus (RSV), influenza virus, adenoviruses, parainfluenza virus, and rhinovirus1 2), Mycoplasma pneumoniae ,3 and Chlamydia species.4-6 Legionella may cause pneumonia and non-pneumonic upper respiratory tract infection and approximately 85% of c ases are caused by L pneumophila . Long lasting sequelae such as bronchiectasis, lung fibrosis, and decreased lung function are seen after lower respiratory tract infections7-10 and it has been debated whether respiratory tract infection can cause chronic bronchial asthma.6 11-13 Acute bronchitis is an inflammatory condition of the bronchi often caused by infectious agents, although in many cases no aetiology can be established.14 15 It shares many pathological and clinical features with bronchiolitis, and the same agents may induce both conditions. Most cases of acute bronchitis of known aetiology are due to respiratory viruses such as influenza virus, adenovirus, RSV, rhinovirus, and coronavirus,1 2 16 and a few are caused by M pneumoniae , Bordetella pertussis and C pneumoniae .4 5 15 17 Legionella infections limited to the bronchial tree are not described. ### ADHERENCE OF PATHOGENS The pathogenesis has not been studied for all agents, but the transmission of disease is thought to occur through droplet spread from an infected person. After inhalation the infectious agent may adhere to different receptors such as acid containing glycoproteins or the adhesion molecule ICAM-1 on respiratory epithelial cells.18 19 The infectious chlamydial particle is the elementary body that attaches itself to and enters a susceptible cell where it changes to the larger metabolically active reticulate body.20 …

Chlamydia pneumoniae in Children with Otitis Media

In this study the polymerase chain reaction was used to test for the presence of Chlamydia pneumoniae DNA in 118 middle-ear aspirates from 20 children with acute otitis media (AOM) and 53 children with otitis media with effusion (OME). C. pneumoniae was detected in 8 samples obtained from 5 children with OME and, together with Streptococcus pneumoniae, in a sample from 1 child with AOM. The mean age of these five children (6.6 +/- 1.4 years) was significantly higher than that of the 48 children with OME in whom C. pneumoniae could not be detected (4.3 +/- 1.9 years). The presence of C. pneumoniae in 9.4% of the examined children with OME suggests that C. pneumoniae might be a significant supplementary factor in the etiology of this common childrens disease.

Pneumocystis carinii-induced activation of the respiratory burst in human monocytes and macrophages

Human monocytes and monocyte‐derived macrophages were studied for their ability to phagocytose Pneumocystis carinii and produce superoxide (O−2) during the process. One × 106 freshly isolated monocytes. incubated with 0.1 – 3.75 × 106P. carinii cysts, increased O−2 production in a dose‐related way. Antibodies were essential for the process since opsonized, but not unopsonized, pneumocysts induced O−2 production significantly above the response obtained by lung tissue from rats (10.7 and 4.9 versus 30 fmol/cell per 90 min). The difference between pneumocysts opsonized in untreated versus complement‐depleted serum was not significant (10.7 versus 12.6 fmol/cell per 90 min). Monocyte‐derived macrophages also activated the respiratory burst when stimulated with pneumocysts, and this effect could be significantly increased, from 4.2 to 8.8 fmol/cell per 90 min, when cells were primed with interferon‐gamma (IEN‐γ). Cells primed with IL‐3 also increased O2 production, though to a lesser extent. In contrast, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) had only a small effect on the respiratory burst in cells stimulated with P. carinii. Priming with IEN‐γ increased the rate of phagocytosis in macrophages. After incubation for 90 min or more, however, the percentage of cells with phagocytic vacuoles was only slightly higher in IFN‐γ‐primed cells. When examined by electron microscopy (EM), most vacuoles contained partially or totally degraded pneumocysts. In conclusion, we have demonstrated the ability of monocytes and monocyte‐derived macrophages to ingest and degrade pneumocysts. activating the respiratory burst during the process.

Low Levels of IgG Antibodies Against Pneumocystis carinii Among HIV-infected Patients

IgG antibodies against Pneumocystis carinii (P. carinii) were detected by an ELISA method using urea-extracted material from human and rat P. carinii as the antigen. Carbohydrate formed a major part of the antigen responsible for reactivity in the ELISA assay, since periodate treatment reduced the reactivity of most sera tested. Cross-reactivity between human and rat P. carinii was detected. However, human serum recognized antigens specific for human P. carinii. With the ELISA method IgG antibody levels were compared between blood donors (n = 40), asymptomatic HIV-antibody positive patients (n = 30) and AIDS patients with (n=22) and without previous P. carinii pneumonia (PCP) (n=21). HIV-infected patients had significantly lower antibody reactivity against the microorganism compared with blood donors. Among HIV-antibody positive patients the highest antibody reactivity was seen in PCP patients. The antibody response to PCP was impaired, since an equal number of patients had an increase and a decrease in antibody reactivity. In conclusion, carbohydrate formed an important part of the P. carinii immunogenic antigen. Cross-reactivity between rat and human P. carinii was demonstrated, but reactivity was somewhat lower using antigen from rats. The antibody level was lower in HIV-infected patients and the ability to mount an antibody response to the infection was impaired, suggesting that the poor antibody response may contribute to the liability of HIV-infected patients to have PCP.

Incidence and Relative Risk for Hepatitis A, Hepatitis B and Tuberculosis and Occurrence of Malaria among Merchant Seamen

The purpose of the study was to assess the incidence and relative risk of hepatitis A and B and tuberculosis among Danish merchant seamen. We also assessed the occurrence of malaria. The study was based on record linkage of a research database containing data on 24,132 Danish male seamen and the Registry for Notifiable Infectious Diseases in Denmark, supplemented by data from other sources. The standardized incidence ratio (SIR) for hepatitis A for male seamen was 1.77 (0.91-3.10) as compared with the incidence in the general population. The incidence was 0.9 notified cases/10,000 years. The SIR for hepatitis B for male seamen was 3.02 (1.79-4.78), the main risk factors being intravenous drug use and casual sex abroad. Tuberculosis was not more common among seamen than in non-seamen. The results have implications for vaccination strategies in this occupational group. Malaria occurred frequently in the seamen, especially among those involved in West African trade. Irregular use of malaria prophylaxis and probably chloroquine resistance were of importance in some cases. To detect further cases of hepatitis A and B and malaria, other sources were reviewed. Only a few extra cases were identified. The registry of notifiable infectious diseases was thus found to be rather complete.

Acute oral candidiasis during febrile episodes in immunocompromised patients with haematologic malignancies.

To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long-lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum.

Antibodies against Hepatitis Viruses in Merchant Seamen

Seamen constitute a special group of international travellers who may run an increased risk of contracting hepatitis, because of visits to foreign ports and the particular environment on board ship. The purpose of the survey was to assess the prevalence of serological markers for hepatitis A, B and C virus infection among seamen and to identify present and previous risk factors for infection. 515 seamen were studied. The prevalence of antibodies against hepatitis A was 0.3% in subjects below 40 years of age, increasing with age above 40 years, and highest among those who had sailed in international trade. The prevalence of antibodies against hepatitis B was 2.7% in subjects below 40 years of age, increasing to 35.7% in the group above 60 years of age. Hepatitis C antibodies occurred in 1.2%. Vaccination of sailors against hepatitis A should follow the same recommendations as to other travellers. The prevalence of hepatitis B was higher than in reference groups of non-seamen but, because hepatitis B is only one of many blood-borne diseases, prevention should be directed towards changes in behaviour rather than vaccination, except for special groups. Young seamen in international trade were found to be most at risk of contracting sexually transmitted diseases.

A Review of Macrolide Treatment of Atherosclerosis and Abdominal Aortic Aneurysms

Seroepidemiological studies have shown an association between Chlamydia pneumoniae and atherosclerosis, the risk of acute myocardial infarction and abdominal aortic aneurysms (AAA). Several studies have detected C. pneumoniae in atherosclerotic lesions from coronary and carotid arteries, in AAA, and in sclerotic aortic valves. However, culturing of C. pneumoniae is difficult and has seldomly succeeded from atherosclerotic lesions. Thus, the pathogenicity is unknown, and the significance of detecting the organism is unresolved. Nevertheless, in a large observational study comparing the risk of cardiovascular events among recipients of macrolide versus pencillins, macrolide treatment reduced the risk of such events after relevant adjustment. Furthermore, in two out of three minor randomized clinical trials were patients with ischaemic heart disease were randomized into antibiotic treated and placebo groups, a significant reduction in serious end-points were noticed in patients receiving macrolide. Similarly, two other minor randomized trials showed that macrolide treatment inhibited growth of small AAA. Macrolide therapy thus seems potential to improve the outcome of severe ischaemic heart disease, and growth of AAA. If true, it not known whether this is transient because of macrolides non-specific anti-inflammatory effect or latent infection, or permanent because of eradicating C. pneumoniae organisms. In order to clarify this, large and long term randomized trials are needed, as well as diagnostic methods that can differentiate between individuals who are or are not infected with C. pneumoniae. The latter are needed in order to clarify the impact of the presence of C. pneumoniae and to avoid overconsumption of antimicrobials, which can result in serious ecological problems.