Possible Lifestyle Changes for Chlamydia

Essential Guide to Cure Chlamydia

Is Chlamydia easily curable? The Answer is a big Yes! Chlamydia is one of the sexually transmitted diseases with proven treatment methods. In fact, there are two main treatment options available both of which have guaranteed results: Conventional medicine and natural medicine. These treatment options And lots of other previously unknown facts about Chlamydia have been explained at great length in this eBook. The Essential guide to Cure Chlamydia unveils the mystery of Chlamydia and methodically presents all the important bits of information that you should know about Chlamydia. The Banish Chlamydia Book tackles the sensitive subject of Chlamydia from the perspective of a professional and presents you with a goldmine of information and facts in a way that has never been done before.

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Chlamydial Life Cycle And Persistence

Chlamydia Persistence Cycle

Chlamydiae exhibit a unique obligate intracellular life cycle that is essential for understanding their virulence in both acute and chronic disease. These bacteria have a biphasic life cycle that alternates between a metabolically inert, infectious elementary body (EB) and a noninfectious, metabolically active reticulate body (RB) (see ref. 12 for review). The molecular events of chlamy-dial growth and differentiation have yet to be defined, but their intracellular life cycle has been sufficiently described to document several important fundamental processes essential for chlamydial survival. An EB begins an infection by attaching to a susceptible host cell. This primary interaction likely involves the chlamydial major outer membrane protein (MOMP), although roles have been postulated for glycosaminoglycans and other putative adhesins.(13) After attachment, the EB is internalized into a vesicle that avoids the endosomal pathway and subsequent lysosome fusion.(14) Sphingolipid...

Cook Pj Honeyborne D Chlamydia Pneumoniae. Int J Syst Bacteriol 39 88-90 1989

Grayston IT, Kuo C-C, Campbell LA, Wang S-P. Chlamydia pneumoniae sp. Nov. for Chlamydia sp strain TWAR. Int J Syst Bacteriol 1989 39 88-90. 4. Grayston IT, Campbell LA, Kuo C-C, et al. A new respiratory tract pathogen Chlamydia pneumoniae strain TWAR. J Infect Dis 1990 161 618-625. 5. Beatty WL, Morrison RP, Byrne GI. Persistent chlamydiae from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 1994 58(4) 686-699. 6. Saikku P, Mattila K, Nieminen MS, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1998 2(8618) 983-986. 7. Saikku P, Leinonen M, Tenkanen L, et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki heart study. Ann Intern Med 1992 116 273-278. 9. Dowell SF, Peeling RW, Boman J, et al. Standardizing Chlamydia pneumoniae assays recommendations from the Centers for Disease Control and Prevention (USA) and...

Genetic Susceptibility to Chlamydia trachomatis Determines the Outcome of the Disease Data from a Mouse Model

These results suggest that a different immune response can be correlated with different outcome of the disease. In particular we have focused attention on the time course of two of the well-studied antigens, such as MOMP and OMP2. As reported in Figure 13.5 a the histogram associated with the immunoreactivity time course of MOMP in the two different strains of mice showed different immune responses. Indeed in BALB c the immunostaining of MOMP revealed a rapid increase in expression reaching a high intensity, whereas in C3H the increase was slower and reached an intensity of immunostaining lower than in BALB c. Instead, OMP2 was immunostained only in the C3H mice as shown in the histogram of Figure 13.5 b. From these last results it is clear that different antibodies may be associated with protective or pathological immune responses. For example, a very fast and high response to MOMP is associated with healing, as BALB c mice do not develop chronic salpingitis. On the other hand,...

Chlamydia Antigen Detection By Immunostaining

Demonstration of bacterial DNA by PCR is considered only indirect evidence because the PCR is based on the amplified results. Therefore, many technical pitfalls can affect the final results and false-positive or -negative results are easily introduced, as discussed above. In this regard, direct demonstration of C. pneumoniae by immunostaining with specific antibody is considered more specific in some studies. However, the chance to capture chlamydia antigen by staining should be low because the level of bacteria in blood is predicted to be minimal. Two studies by Bodetti & Timms(5) and ourselves(19) have been conducted to detect C. pneumoniae antigen in blood specimens by immunos-taining with genus- and species-specific FITC-conjugated monoclonal antibodies. Both studies demonstrated the presence of chlamydia antigen by staining in blood samples obtained from healthy subjects. As shown in Fig. 3, even though they were few in number, the usually small chlamydia inclusion bodies in...

Chlamydia trachomatis Immunoproteome

The genus Chlamydia is composed of a group of obligate intracellular gram-negative bacteria, and two main species, C. trachomatis and C. pneumoniae, are associated with human pathologies. Chlamydia trachomatis causes prevalent infections of the mucosal tissue of the eyes and the urogenital tract, and is a major cause of sexually transmitted disease worldwide. Infections are insidious and, though often asymptomatic, can have serious consequences, particularly for women. Left untreated, genital chlamydial infections are chronic, and repeated infections are common. There is a close reciprocal interaction between antibody and antigen. If one wants to monitor an antibody, a purified antigen is needed, and vice versa. Ideally if we want to dissect an antibody response we need to have all proteins expressed by the infecting pathogen, the whole proteome. The genome of C. trachomatis contains 1042 kb, corresponding to 897 predicted proteins (http www.ebi.ac.uk cgi-bin genomes.cgi genomes...

Conclusion Chlamydia pneumoniae Chronic Nonspecific Lung Disease Cnsld And The Dutch Hypothesis

It is now well established that acute Cpn infection can cause acute bronchitis and pneumonia(149,150) and additional evidence presented herein suggests that lower respiratory tract illnesses caused by acute Cpn infection can develop into asthma and chronic bronchitis.(8,151) Chronic Cpn infection has also been associated with a wide variety of chronic upper-airway illnesses(152,l53) as well as with the spectrum of acute and chronic lower-airway conditions including acute bronchitis,(154) asthma and COPD.(81) Taken together, these data suggest a role for Cpn in the entire spectrum of respiratory illnesses embracing the natural history of CNSLD.(19,20,155) Just as early identification and treatment of genital chlamydial infection of women is required to prevent the occurrence of pelvic inflammatory disease and tubal infertility, and timely treatment of eye infection in children is required to prevent blinding trachoma, early identification and treatment of Cpn infection in chronic...

Chlamydia Genomes

Sequencing of Chlamydia genomes has provided new means to analyze the molecular and structural biology of Chlamydia. There are now published five complete genome sequences for C. trachomatis D,(18) C. trachomatis MoPn,(19) and C.pneumoniae CWL029,(20) J138,(21) and AR39.(19) Chlamydia is, the microbe with most sequenced genomes. This has greatly expanded the information concerning the biology of these obligate intracellular pathogens. In addition to provide information on all potential protein products, the genome sequences unexpectedly identified several classes of putative proteins relevant for understanding the structure ofchlamydiae. Chlamydia genomes are small and show striking similarity (1.230.230 nucleotides in C. pneumoniae CWL029, and 1.042.519 in C. trachomatis D). In C. trachomatis, 214 of the C. pneumoniae CWL029 protein-coding sequences are not found, most with no homology to known sequences. The C. pneumoniae genome has the capacity to encode 1052 proteins, of which...

Chlamydia Pneumoniae

Chlamydial Life Cycle

C. pneumoniae was isolated in 1986 (3). It was found to be responsible for a variety of respiratory illnesses including 10 of cases of community-acquired pneumonia. Like the more familiar Chlamydia trachomatis, C. pneumoniae is an obligate intracellular pathogen with a unique life cycle (Fig. 1) (4). Generally, C. pneumoniae enters the body through a respiratory route and exists outside of cells in a spore form called the elementary body. Once inside the host cell it makes use ofthe cell's own metabolic machinery and develops into a metabolically active but noninfectious form called the reticulate body. In this form, the bacterium has the ability to divide and differentiate into new elementary bodies, which can then invade other host cells.

Insights Basic Biology

Understanding the basic biology of the bacteria is a critical first step to developing better treatment strategies. Miyashita et al. have provided an ultrastructural assessment of the C. pneumoniae EB and RB, with particular focus on the surface projections that have been documented in other Chlamydia. In spite of the oft-seen pear-shaped EBs of C. pneumoniae, the authors show that at the electron microscopic level the basic morphology remains the same between all isolates examined. The surface projections span the chlamydial membranes to effectively connect the bacterial cytoplasm with its surrounding environment. RBs also appear to associate with the inclusion membrane in such a way as to allow direct connection with the host cytoplasm. These observations are intriguing and lead to speculation about possible roles for type III secretion and parasite-mediated host cell disruption. Type III secretion is a common Christiansen et al. have reviewed the cell and molecular biology of this...

Insights Respiratory Infections

The association between C. pneumoniae and asthma has gained much credence in recent years. D. Hahn has outlined a role for this organism as an inducer of asthma. Although there is some disagreement in the medical profession vis a vis diagnosing asthma versus chronic bronchitis or emphysema, the clinical manifestations such as wheezing, coughing, and shortness of breath are endpoints that can be useful in determining lung dysfunction. An intriguing theory is that chlamydial infection leads to the establishment of nonatopic asthma in some individuals (see ref. 11 for review). Perhaps the most convincing data in support of this is the amelioration of symptoms in patients treated with antibiotics effective against Chlamydia. Clinical studies have demonstrated a more rapid decline in lung function in patients with C. pneumoniae seroreac-tivity. Because of the increasing numbers of reactive airway diseases in recent decades, the possibility of reversing this trend with antibiotics is an...

Insights Cardiovascular Disease

Chronic infections with C. pneumoniae and the sequelae with which it has been associated could arguably place this bacterium among the most important pathogens in the developed world. The most significant disease state connected to the organism is atherosclerosis and cardiovascular disease.(23) Ngeh and Gupta provide an overview of this association citing the large body of epidemiological studies. This field is highly controversial due in large part to the lack of standardized methods between laboratories for example, there is a variety of home brew methods currently used for DNA extraction and for serological testing. Also, antibiotic treatment studies that have shown inconclusive data may need further refinement to better identify those patients who would have the greatest benefit. Chlamydia pneumoniae as an agent of myocarditis is discussed by Gnarpe and Gnarpe. In spite of the association of this bacterium with atherosclerosis, there have been relatively few documented cases of...

Surface Projections And Related Structures

Scanning electron micrographs of EBs of Chlamydia pneumoniae KKpn-15 (a) and AR-39 (b). Both micrographs show hexagonally arrayed projections in a limited area of the surface. Bars indicate 300 nm. FIGURE 9. Scanning electron micrographs of EBs of Chlamydia pneumoniae KKpn-15 (a) and AR-39 (b). Both micrographs show hexagonally arrayed projections in a limited area of the surface. Bars indicate 300 nm. FIGURE 10. Freeze-replica images of in situ chlamydial bodies and inclusion members of the Chlamydia pneumoniae KKpn-15 strain at 60 h after infection. Chlamydial bodies are cleaved into convex or concave faces. Many B structures are seen (arrowheads). Bars indicate 1 nm. FIGURE 10. Freeze-replica images of in situ chlamydial bodies and inclusion members of the Chlamydia pneumoniae KKpn-15 strain at 60 h after infection. Chlamydial bodies are cleaved into convex or concave faces. Many B structures are seen (arrowheads). Bars indicate 1 nm. FIGURE 11. Freeze-replica images of...

Components Responsible For The Structural Appearance

Because of the lack of tools for genetic manipulation of chlamydiae it is important to be able to study subtractions of the microorganism. The sarcosyl-insoluble chlamydial outer membrane complex (COMC)(11) can be used to identify components responsible for the structural appearance, and electron microscopy of purified COMC shows that the shape of EB is maintained (Fig. 1). SDS-PAGE and immunoblotting have shown that C. pneumoniae COMC contains

Type Iii Secretion System

Surface projections are seen on all Chlamydia species. The projections extend through holes in the outer membrane and protrude from the surface of the chlamydiae. They have a physical resemblance to the Type III secretion apparatus found in other bacteria. The genome sequence identified a complete set of genes with homology to the type III secretion system both in C. trachomatis and in C. pneumoniae.(18,20) The genes were first identified in C. psittaci,(33) and Bavoil and Hsia(34) speculated that the projections represent a type III secretion system (Fig. 2). Analysis of the C. pneumoniae EB proteome demonstrated that members of the Type III secretion system were present.(24) A hypothetical structure of the chlamydial Type III secretion apparatus was presented by Rockey etal.,(35) who suggested YcsC to be anchored in the chlamydial outer membrane (Fig. 2). In agreement with this model Vandahl et al.(28) identified YscC in C. pneumoniae COMC proteome, but not YscL, YscN, and LcrE, the...

Infection In Immunocompromised Subjects

Recent papers have analyzed the potential role of C. pneumoniae as a respiratory pathogen in both pediatric and adult immunocompromised patients. Cosentini et al. report the rate of seroconversion to C. pneumoniae of 26 HIV-infected children and 14 seroreverter children (HIV-negative children born to HIV-positive mothers) over a 3-year study period.(17) The study showed a high incidence of C. pneumoniae infection in HIV-1-infected children. The incidence of C. pneumoniae infection appears to correlate with the degree of immunosuppression and with the viral burden. Because in most cases the infection was asymptomatic, and in symptomatic cases the outcome was often favorable irrespective of the treatment used, it is still unclear whether C. pneumoniae may cause severe forms of infection in this population. This high rate of infection was not confirmed by a different study on adult HIV-positive patients with pneumonia. (18) In this retrospective study, involving 103 episodes of pneumonia...

Pcrmethodological Aspects

The classical DNA extraction protocol is based on purification with organic solvents like phenol chloroform, followed by precipitation with ethanol. Such protocol is labor intensive and takes time, providing more chance for contamination during the extraction. In this regard, a new protocol for purification of DNA using solid-phase carriers has been developed. This protocol is based on the nature of nucleic acids, which can bind to silica or glass particles in the presence of chaotropic agents such as NaI or NaC104. There are several different types of such DNA extraction kit commercially available. Daugharty et al.(10) examined the efficacy of chlamydial DNA isolation from buffy coats spiked with C. pneumoniae elementary bodies (EB) using six different commercial DNA extraction kits. It was concluded in the report that QIAamp Blood Kit (QIAGEN, Valencia, CA) was the most sensitive among the kits tested, including the ELU-QUIK DNA Purification Kit (Schleicher & Schuell, Keene, NH),...

Innate Immune Mechanisms

A preliminary pulmonary infection occurs in the alveoli, where the invading Chlamydia undergoes phagocytosis by dendritic cells(11) or alveolar macrophages.(12'13) Alveolar macrophages are important in regulating both antimicrobial immunity and nonspecific inflammation in the lungs. Prompt destruction of intracellular microbes is dependent on the macrophage activation and associated microbicidal processes by reactive oxygen and nitrogen intermediates. Many intracellular pathogens have, however, evolved specific strategies to resist the antimicrobial activities. Chlamydia can modify the metabolic pathways within eukaryotic cells by inhibiting the phagolysosomal fusion and replicating in a special nonacidic chlamydial inclusion.(14-17) The inhibition involves modification of vacuolar membrane by microbe-specific proteins that are expressed early in the infectious process.(1617) Thus, C. pneumoniae can survive and be metabolically active and can even multiply within phagocytes.(18-21)...

C pneumoniaeSpecific Antibodies

Detection of C. pneumoniae-specific antibodies in human sera was the key to discovery of a new Chlamydia species in the 1980s(91) first associated with pneumonitis 92'93' Since the identification of C. pneumoniae and the development of a microimmunofluorescence (MIF) test for the antibody analysis,(94'95) several seroepidemiological studies have been conducted to enlarge the epidemiological and immunological knowledge on C. pneumoniae infections. The MIF assay recognizes conformational epitopes on intact chlamydial EBs and is generally considered species-specific and the gold standard for C. pneumoniae serology.(96) Enhanced production of antibodies against genus-specific LPS, especially at an acute stage of Chlamydia infection, may, however, interfere with this specificity. Moreover, some of the surface exposure epitopes may be conservative (such as Hsp60 antigen), and primary induction of such response by other Chlamydia species or even other bacteria may add to the interference. A...

Cardiovascular Disease

Likely aggravate the atherosclerotic condition. Chlamydia pneumoniae may play a role in this process. When this organism infects vascular cells, signal transduction pathway activation occurs that results in changes that are characteristically atherogenic. Because signal transduction involves complex pathways with redundant interactions between them, there is great potential for activation to be achieved via limited mechanisms. For example, a single ligand may bind a receptor, which results in the downstream activation of a single mediator that in turn can elicit pleiotropic effects. Consequently, a handful of chlamydial components may elicit activation even in the absence of the organism itself. These soluble mediators may be released by persistent or actively growing organisms in a low percentage of host cells thus failure to detect the organism by culture or PCR may not always eliminate a chlamydial aspect to this disease. Vascular smooth muscle cells (VSMC) are critical components...

C pneumoniae Vaccine Development

Obstacles in achieving a C. pneumoniae vaccine. Chlamydial infections often recur or remain persistent, indicating absence of sterilizing immunity. However, studies in an experimental model of infection with the related organism C. trachomatis indicate a short-lived immunity after natural infection. The resistance to genital chlamydial diseases augments with age (and hence exposure), and vaccination with inactivated organisms produce a short-lived protection against ocular challenge. The immune response against chlamydia can mediate pathogenesis, as exemplified by the sensitization to a more severe disease in individuals vaccinated against C. trachomatis. It is speculated that this may be due to the presence of proinflammatory molecules such as LPS or cross-reactive antigens with host molecules. Protective or adverse effects may not only depend on specific antigen (s) but also on innate immune mechanisms that are mobilized by the infection. Diverse innate immune mechanisms are known...

Ignatius W Fong 1 Introduction

Chlamydia pneumoniae has been associated with cardiovascular disease and stroke in humans by numerous cross-sectional and case-control studies,(1'2) but prospective, longitudinal studies have produced mixed results and most have not confirmed this association 3'4-1 However, pathological studies have established the association of C. pneumoniae antigen or DNA with atherosclerosis from surgical and autopsy vascular specimens, with odds ratio of around 20.(4'5) Although in vitro and cell culture studies have supported biological plausible mechanisms for C. pneumoniae to induce or accelerate atherosclerosis 4-1 they lack the complexity of a real disease, thus limiting the scope of testing the hypothesis of causality. C.pneumoniae has also been demonstrated to produce a mild subclinical respiratory infection in nonhuman primates.(24) Two Cynomolgus monkeys were inoculated in the nose, nasopharynx, and conjunctiva and C. pneumoniae could be isolated from these sites and rectum up to 5 weeks...

Structure Of The Outer Membrane

Chlamydia Pneumoniae

EBs of all chlamydial species are stable against mechanical agitation, such yses of chlamydial organisms,(21) whereas genome sequencing on C. trachomatis FIGURE 6. Negatively stained (a) and shadowcast images (c) of EB outer membranes isolated from purified EBs of the Chlamydia pneumoniae KK.pn-15 strain. (b) Higher magnification obtained from the micrograph shown in (a). The hexagonal structure seen throughout the outer membrane (a) is seen only on the inner face (c). Bars indicate 200 nm. FIGURE 6. Negatively stained (a) and shadowcast images (c) of EB outer membranes isolated from purified EBs of the Chlamydia pneumoniae KK.pn-15 strain. (b) Higher magnification obtained from the micrograph shown in (a). The hexagonal structure seen throughout the outer membrane (a) is seen only on the inner face (c). Bars indicate 200 nm. FIGURE 7. Image processing of the hexagonal structures in the outer membrane of Chlamydia pneumoniae KKpn-15 EB. (a) Diffraction spots obtained by Fourier...

Animal Models Of Myocarditis

Possible role of Chlamydia in the etiology of atherosclerosis(31-33). a-myosin heavy chain. When the Chlamydia 60-kDa outer-membrane-derived peptides were injected into mice, an autoimmune myocarditis developed with perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart. T and B cells were also induced to react to the homologous endogenous heart-muscle-specific peptide. The authors also demonstrated that Chlamydia DNA functioned as an adjuvant to trigger the autoimmune, peptide-induced inflammatory heart disease. They conclude that bacteria of the genus Chlamydia could mediate inflammatory heart disease through antigen mimicry.

HAkAn G Gnarpe and Judya Gnarpe 1 Introduction

The clinical diagnosis of myocarditis or perimyocarditis can be made with reasonable certainty by electrocardiography and by measuring serum markers for myocyte damage, but the etiology is often difficult to establish. On rare occasions, a diagnosis is made from the histopathological analysis of endomyocardial biopsies. A minority of cases of myocarditis or perimyocarditis may develop into dilated cardiomyopathy, and the patient may then present with cardiac insufficiency. Viral agents, like the Coxsackie Bi_5, viruses are well-documented causes of myocarditis. There have been several published reports of Chlamydia psittaci as a cause of myocarditis, perimyocarditis, and endocarditis.(1,2) These reports were published long before it was found that the complement fixation test (CF) measured antibodies to the lipopolysaccharide antigen, which is shared by all three Chlamydiae clinically important for human infection C. psittaci, Chlamydia trachomatis, and Chlamydia pneumoniae. Several...

Joseph Ngeh and Sandeep Gupta l Introduction

Atherosclerosis is now acknowledged as an inflammatory disease.(1-7) The major clinical manifestations of atherosclerotic disease include coronary heart disease (CHD), ischemic stroke, abdominal aortic aneurysm (AAA), and peripheral arterial disease (PAD). These in turn are among the leading causes of death and disability in the world. However, only about 50 of the occurrences of these conditions can be attributed to classical vascular risk factors such as hypertension, smoking, diabetes mellitus, and dyslipidemia.(3,4,7) Novel risk factors such as infection have emerged as potentially important, linking inflammation and the pathogenesis of atherosclerosis. (1-7) Specifically, Chlamydia pneumoniae (C. pneumoniae) is the microorganism most implicated in this infectious hypothesis of atherosclerosis, and will be the focus of discussion.

Kazunobu Ouchi 1 Introduction

The growing data have been indicating that Chlamydia pneumoniae is a common and important respiratory pathogen in children as well as in adults all over the world.(1) This organism causes both upper and lower respiratory tract infections, often mild and self-limiting. C. pneumoniae, like Mycoplasma pneumoniae, has been recognized as a main cause of atypical pneumonia in children.(1) C. pneumoniae causes not only an acute infection but also a chronic infection in children and may trigger exacerbations in their reactive airway disease.(2) However, there are a number of unsolved issues in the diagnosis and treatment for C. pneumoniae infections because of its persistence in nature.

Persistent Infection And Aberrant Forms

Chlamydia Pneumoniae Diagnosis

C. pneumoniae is regarded as a common cause of respiratory tract infections and it can cause prolonged or chronic infections which may be due to persistence for months or years.(14,30) These persistent infections have been implicated in the development of a number of chronic diseases including atherosclerosis, asthma, and obstructive pulmonary diseases (see other chapter) . These persistent chlamydial infections can be established in vitro using several methods involving cytokines,(31-34) antibiotics,(35,36) and deprivation of certain nutrients.(37) Despite differences in treatment, chlamydiae respond to form inclusions containing atypical RBs, which occasionally have been shown to be pleomorphic forms, termed aberrant bodies (ABs). The ABs are generally larger in diameter than typical RBs, and display a sparse densinometric appearance (Fig. 12). No evidence of redifferentiation into EBs has been documented. However, when the growth inhibitory factors are removed, the ABs can be...

Do We Need An Antic pneumoniae Vaccine

Whether there are sufficient benefits tojustify children's vaccination seems at present unlikely, since chlamydial respiratory tract infection in children is generally mild. However, transmission of infection to siblings or parents, and the consequences of infection in asthmatic pediatric patients may here be significant parameters to consider.(4) The prevention of arteriosclerosis by blocking C. pneumoniae infection is unlikely to provide a justification for a vaccine for children, until a truly causal role of C. pneumoniae in the development of atherosclerosis has been shown to exist. If C. pneumoniae is proven to be a cause of atherosclerosis, a therapeutic and effective vaccine would be of immense value. In fact, the development and use of an effective C. pneumoniae vaccine might provide the best experiment to investigate the role of C. pneumoniae in cardiovascular disease.

Animal Model For Sporadic Alzheimers Disease

Chlamydia Pneumonia

Olfactory bulbs from mice infected with C. pneumoniae. BALB c mice were infected intranasally with C. pneumoniae and sacrificed at 3 months postinoculation. Profiles of C. pneumoniae (A, B, arrows) were observed in cells in the olfactory bulbs. (A) A typical inclusion containing chlamydial bodies. Bars 0.4 Hin. FIGURE 3. Olfactory bulbs from mice infected with C. pneumoniae. BALB c mice were infected intranasally with C. pneumoniae and sacrificed at 3 months postinoculation. Profiles of C. pneumoniae (A, B, arrows) were observed in cells in the olfactory bulbs. (A) A typical inclusion containing chlamydial bodies. Bars 0.4 Hin.

Treatment Of C pneumoniae Respiratory Infections

Similarly, File et al.(38) reported a clinical cure rate of 98 among patients with serologic evidence of C. pneumoniae infection who were treated with levofloxacin compared with 93 of those treated with ceftriaxone and or cefuroxime axitiil, plus erythromycin or doxycycline, which was added to the treatment regimen at the investigator's discretion. In the latter group, the response rate did not differ between those patients who had erythromycin or doxycycline added to their treatment regimen and those who were treated with a cephalosporin alone. There was also no difference in the response rate among those patients who had definite serologic evidence of infection, i.e. a 4-fold rise in MIF IgG or IgM, compared with those who had probable infection, i.e. a single IgG> 512 orIgM> 32. The success of the cephalosporin regimens results raise some questions about the specificity of the serologic criteria as these antibiotics have no or poor activity against Chlamydia...

Mechanism Of CpneumoniaeMediated Accentuation Of Autoimmune Disease

One mechanism by which infections can potentially induce autoimmune disease is through molecular mimicry. Following immunization with chlamydial peptides that show homology with MBP, rats developed severe EAE.(52) Our study did not show evidence of molecular mimicry between C. pneumoniae and neural antigens in SJL mice. Animals showed worsening of EAE induced by three different classes of encephalitogenic antigens MBP, MOG, and MSCH suggesting that molecular mimicry is an unlikely explanation for the worsening of the disease. C. pneumoniae in some respects is a compelling candidate as an infectious cause for MS. One of the hallmarks of chlamydial infection is tissue persistence and development of chronic infection. Periodic exacerbations and remissions clinically characterize trachoma, with progressive inflammation to corneal scarring. Meningoencephalitis and other neurological complications have been described for patients infectedwith C. pneumoniae.(58,59)

The Role Of Macrophages In C pneumoniae Immunity

According to the traditional concept of antigen processing and presentation, the APC present antigens to CD4+ and CD8+ T cells in the context of major histocompatibility complex (MHC) class II and class I molecule, respectively 35' In general, MHC class II molecule binds and presents antigens that are processed in the endocytic pathway whereas class I molecule binds peptides that are processed in the cellular cytoplasm derived from endogenous antigens. Chlamydia grows in the endocytic vesicular pathway and generally avoids a fusion with MHC class II-containing endolysosome,(14) but chlamydial peptides processed by professional APC are more likely to be presented by MHC class II molecule to CD4+ cells.(34,36) Description of genes in the chlamydial genome that encode proteins for type III secretion system(37,38) and demonstration of C. pneumoniae proteins secreted into the host cells' cytoplasm(39,40) suggest that some chlamydial peptides are available for MHC class I presentation. This...

For Clinical Coronary Artery Disease

In a small study from London(15) 60 stable post-myocardial infarction male patients who were seropositive to Chlamydia pneumoniae were randomized to receive azithromycin (500 mg day for 3 days n 28 or 500 mg day for 6 days n 12 ) or placebo and followed for 18 months, looking for the endpoints

Morphology

Chlamydiae, obligate intracellular parasites require host cell biosynthetic machinery for several metabolic functions. All chlamydiae multiply through a common, unique developmental cycle in which there are two morphologically and functionally distinct forms one is the infectious elementary body (EB) and the other is the reproductive reticulate body (RB). Morphologically, EBs have a high density and are small in size (0.3 to 0.35 im in diameter), whereas RBs consist of homogeneous internal material and are large in size (0.5 to 2.0 nm in diameter). RBs are metabolically active and reproductive, but noninfectious. In contrast, EBs are infectious but metabolically inactive, suggesting their adaptation to an extracellular environment. This unique developmental cycle occurs in a membrane-bound cytoplasmic vacuole, termed inclusion. In this chapter, we discuss the morphology of Chlamydia pneumoniae as revealed by transmission and scanning electron microscopy.

Secreted Proteins

IncA has a characteristic secondary structure with a long bilobed hydropho-bic region present in amino acids 65-116.(36) This motif was found in 46 potential members of inclusion membrane proteins in the C. trachomatis genome.(37) Searching the C. pneumoniae genome revealed an even higher number of hypothetical Inc proteins.(35) Several of these had homology to genes found in C. trachomatis but over half of the genes in each species had no homology to the genes in the other species. The potential for chlamydiae to export such a high number of Incs to the inclusion membrane generates the possibility that the inclusion membrane can serve functions as inclusion development, avoidance of lysosomal fusion, nutrient acquisition, signaling associated with EB-RB-EB reorganization and vesicle trafficking. How the Incs are secreted and transported to the inclusion membrane and whether this is done by the Type III secretion system remains to be determined. Subtil et al.(38) used a heterologous...

Vesicle Trafficking

Vesicle transport has only been studied for C. trachomatis. When C. trachomatis L2 attaches to susceptible host cells a host cell protein of 70 kDa is phosphorylated(41) and the phosphorylation can be followed in the inclusion membrane during inclusion development. After uptake the phagosome migrates to the perinuclear space transported along microtubules where the Chlamydia-containing vesicles are positioned at the centre of the microtubular network, indicating a microtubule-dependent mode of chlamydial redistribution. Dynein, a microtubule-dependent motor protein known to be involved in directed vesicle transport along microtubules, was found to colocate with perinuclear aggregates of C. trachomatis.(42) Chlamydiae-containing vesicles do not fuse with lysosomes, but fuse with sphingomyelin-containing exocytic vesicles from the Golgi apparatus.(43,44) Analysis of sphingomyelin incorporation showed that no incorporation occurred the first 2 h after infection, but from 4 h after...

Joseph B Muhlestein

Animal Studies of Chlamydia pneumoniae, Atherosclerosis and 13. Chlamydia pneumoniae and 187 14. Chlamydiapneumoniae as a Candidate Pathogen in CHARLES W. STRATTON and SUBRAMANIAM SRIRAM 15. Chlamydia pneumoniae in the Pathogenesis of Alzheimer's Disease 211 16. Chlamydia pneumoniae and Inflammatory Arthritis 227 3. Chlamydia trachomatis, Persistence, and Reactive 4. Chlamydia pneumoniae and 5. Chlamydia pneumoniae and 17. Role of Chlamydia pneumoniae as an Inducer of Asthma 239 DAVID L. HAHN 2. Chlamydia pneumoniae as a Promoter of Asthma Severity 242 2.1. Chlamydiapneumoniae-Asthma Serologic Associations 242 2.2. Results of Antibiotic Treatment Directed against Chlamydial Infection in Asthma 243 3. Chlamydia pneumoniae as an Asthma 248 4. Summary Chlamydia pneumoniae as an Asthma Inducer 249 5. Chlamydia pneumoniae and Lung 251 5.3. Summary Chlamydia pneumoniae and Lung Remodeling 253 6. Conclusion Chlamydia pneumoniae, Chronic Nonspecific Lung Disease 2. Respiratory Disease...

Conclusion

C. pneumoniae has excited considerable attention during the last decade, not only as a respiratory pathogen but because of its association with a number of acute and chronic diseases, including atherosclerosis. The true linkage and causality of C. pneumoniae infection in the development of chronic manifestations remain puzzling. Efficient activation of type 1 T cell responses and secretion of mediates immune defense and provides improved recovery from reinfection. However, the factors that expose some individuals to impaired clearance of Chlamydia or drive immune responses to pathogenic ones are not known. The role of host genetic background, HLA molecules and cytokine gene polymorphism, environmental and epidemiological factors, mixed infections, and species or dose of the infecting agent probably all interact in a final balance of the immune defense mechanisms. A better understanding of the immunoreg-ulatory processes during chlamydial infections in humans is necessary to furnish a...

Antigens

Like other intracellular pathogens, chlamydial biological complexity underscores the likely need of multiple target antigens in a vaccine. Use of whole inactivated chlamydial agents appears to be because of the presence of im-munopathogenic components, plus the fact that early trials indicated that trachoma was exacerbated following episodes of C. trachomatis infection. On the other hand, a live attenuated strain of C. psittaci is used in veterinary medicine as a safe way to prevent abortion in ewes, suggesting that there might be hope for an attenuated vaccine. A live vaccine replicates like the target pathogen and promotes processing and presentation of antigens most similar to a natural infection. Furthermore, while replicating, a live vaccine presumably expresses all or most of its important target immunogens. This may be important for chlamy-diae, which exist in (at least) two developmental forms. Live attenuated vaccines could also stimulate mucosal immune responses and are...

Adjuvants

The innate immune responses will to a large extent determine the quality of the adaptive immune system and thereby the result of infection. The direct importance of the innate immune responses is further illustrated by the life threatening conditions observed in humans and experimental animals showing genetic defects in this system. For recognition of pathogens, plants, insects, and vertebrates have relied upon a system of receptors that share a characteristic cytoplasmic domain termed TIR (toll interleukin-1 receptor domain). Toll-like receptors (TLR) discriminate self' from pathogen-derived ligands also termed pathogen-associated molecular patterns (PAMPs).(9) Different TLRs can discriminate between different PAMPs. Thus, the innate immune system may have evolved to express different TLR (or combinations thereof) within distinct subsets of immunocompetent cells, such as phagocytes and dendritic cells. These receptors generate both shared and unique intracellular signals, which is...

Morphology Of Eb

Chlamydia Pneumoniae Ar39 Infection

The morphology of EBs has been proposed as one of the criteria for distinguishing C. pneumoniae from other chlamydial species.(11' 12) The EBs of the C. pneumoniae TW-183 and AR (TWAR) strains have a wide periplasmic space limited by a wavy outer membrane, creating pear-shaped profiles in thin sections (Fig. 4a,b). In contrast, the EBs of the KKpn strains, which were isolated in Kawasaki Medical School Hospital and number from 1 to 18, were found to be round in shape with a narrow periplasmic space (Fig. 4c) .(9 1315) This morphological difference between the TWAR and KKpn strains was also distinct when purified EBs of both strains were air-dried and then shadowcast (Fig. 5). KKpn EBs have a round fried egg appearance that is indistinguishable from the EBs' of other chlamydiae, such as C. trachomatis, C. psittaci, and C. pecorum, but TWAR EBs have a pear-shaped morphology with a wide, flat outer membrane, perhaps the result of air-drying (Fig. 5) .(16) Moreover, Carter et al.(17)...

Possible Mechanisms

C. pneumoniae has, like other species of Chlamydiae, a tendency to cause chronic or persistent infection. C. trachomatis has been shown inhibiting apop-tosis in Chlamydia-infected cells by inhibition of activation downstream of cas-pase 3 and cleavage of poly (ADP-ribose) polymerase as well as preventing release of mitochondrial cytochrome c.(41) It was recently shown that C.pneumoniae has a similar effect.(42) This inhibition of apoptosis is in part due to induction of IL-10.(43) Rajalingam et al. have also reported that epithelial cells infected with C. pneumoniae are resistant to apoptosis.(44) Macrophages infected with C. pneumoniae in the presence of LDL undergo foam cell degeneration(50) and the component causing this was found to be chlamydial lipopolysaccharide.(51) It has recently been shown that C. pneumoniae and chlamydial Hsp60 can induce cellular oxidation of LDL to a highly atherogenic form.(52) Chlamydial Hsp60 seems to be an important stimulus for inflammatory...

Treatment

Well-controlled studies.(1) In several open, uncontrolled studies investigating patients with C. pneumoniae infection, clinical response did not differ between those patients who had treatment regimen active against C. pneumoniae and those who were treated with antibiotics that have no or poor activity against Chlamydia in vitro. Lack of standardization in diagnosis or of well-controlled studies may be the main reason for this basic confusion. Overall, the use ofmacrolide antibiotics led to 80-100 clinical and around 80 microbiological eradication from the nasopharynx in several recent open, uncontrolled studies.(14,30,31) Treatment with erythromycin for 14 days, clarithromycin for 10 days, or azithromycin for 5 days showed similar clinical and bacteriological responses in these studies. Persistent infection of C. pneumoniae after completion of macrolide treatment was not due to development of resistance to the antibiotics because the minimal inhibitory concentrations and the minimal...

Endocarditis Cases

When serum was tested with complement fixation test to Chlamydia group antigen, the titer was 1 1280. When the sera were investigated using MIF over a period of 121 days, the C. pneumoniae-specific IgG antibody titer had decreased from 1 256 to 1 128, and the specific C. pneumoniae IgM antibody titer had declined from 1 128 at 60 days to 0 at 121 days. The sera had no specific antibodies to C. trachomatis or to nine different strains of C. psittaci. Etienne and coworkers reported a series of 10 cases of Chlamydial endo-cardit is collected between 1983 and 1990 in 1992.(28) The cases were all men with a mean age of 42 (26-59). None had a history of bird contacts. They had all been symptomatic for at least 2 months with weight loss, anorexia, and fever (8 10). Hemodynamic failure was found in seven patients and neurological signs in four. Repeated blood cultures were negative in all. Complement fixation tests for Chlamydia spp. were positive in 6 of 10 cases...

David L Hahn

Chlamydia pneumoniae (Cpn) could have three distinguishable causal effects as an asthma inducer. First, an acute infection (or reactivation of a latent infection) could cause an acute worsening of preexisting asthma. Indeed, it is generally accepted that acute Cpn infection can cause some acute asthma exacerbations(1,2) but most evidence suggests that other organisms mainly respiratory viruses, and, to a lesser extent, Mycoplasma pneumoniae (Mpn(3)) are associated with the majority of asthma exacerbations in both children(4) and adults.(5) Second, because of its propensity to produce persistent infection, Cpn chronic lung infection could cause worsening of established asthma over time. Again, Cpn has been associated with asthma severity(6) and a possible promoting role for Cpn in asthma is a focus of active investigation.(7) Third, an acute primary or secondary Cpn infection, in a previously asymptomatic nonasthmatic individual, could cause acute wheezing that develops into chronic...

Summary

Chlamydia Pneumoniae

Diagrammatic representation of the morphology of the round (a) and pear-shaped (b) EBs of Chlamydia pneumoniae. FIGURE 13. Diagrammatic representation of the morphology of the round (a) and pear-shaped (b) EBs of Chlamydia pneumoniae. In isolated C. psittaci inclusions, the RBs close to the inclusion membrane are closely connected to the inside surface of the inclusion membrane by means of the projections, which appeared to pierce the inclusion membrane.(42) Interestingly, the arrangement of these projections in a hexagonal pattern was also observed on inclusion surfaces exposed by the freeze-replica technique, suggesting strongly that the C. pneumoniae RBs also connect directly with the host cytoplasm through these projections. This evidence evokes a subject of deep interest in the function of the projections, in special reference to the host-parasite relationship during chlamydial multiplication.

Conclusions

It has been widely believed that the blood of healthy individuals should be germ-free. However, as discussed in this chapter at least a significant fraction of the healthy population carries C. pneumoniae in their blood without any clinical symptoms. Because the detection of bacterial antigen, including DNA, in blood may not prove the viability of the bacteria, validation of viability of the organisms determined by PCR is essential for study of Chlamydia infection in certain inflammatory diseases, including atherosclerosis. In addition, the level of C. pneumoniae in blood is also important in determining whether this bacterium is involved in certain diseases because healthy subjects also carry this pathogen in their blood. Thus, there are still many questions which are currently being investigated by several study groups, including ours.

Pmp Structure

The C. pneumoniae pmp gene family is a heterogeneous group of genes with low identity but common characteristics. The majority of the genes have the capacity to encode proteins with sizes 90-100 kDa, and they resemble members of the autotransporter family.(27) Analysis of the C-terminal part of the proteins showed that full length proteins ended with an amphipatic beta-sheet and a terminal phenylalanine residue. In addition, the program AMPHI(29) predicted the C-terminal part of the proteins to form a transmembranic beta-barrel,(27) supposed to be used for translocation of the N-terminal part of the protein to the chlamydial surface (Fig. 2). This is in agreement with the finding that it is the N-terminal part of the Chlamydia psittaci Pomp molecules that are surface exposed.(30) Another characteristic is the presence of repeats of the amino acid motif GGAI and FXXN in the N-terminal part of the proteins. Use of common prediction programs did not reveal any characteristic patterns for...

THE Pmp Gene Family

All Chlamydia species harbor a family of distantly related pomp pmp genes. The genes encode polymorphic membrane proteins whose function is unknown. Genome sequencing(20) revealed the presence of 21 such genes in C. pneumoniae CWL029 (most of the genes are located in two genomic clusters whereas the remaining genes are found as a pair and a single gene at different genomic localizations). Sixteen of the 21 genes were full length genes whereas one was truncated and 4 had small insertions or deletions that caused a premature stop. Most of the genes had a leader sequence with a cleavage site for signal peptidase I, but two of the genes, Pmp 10 and Pmp 11 differed from the others by having a cleavage site for signal peptidase II, indicating that these proteins probably were lipid modified.(3) The first identification of expressed C. pneumoniae Pmp proteins was by Knudsen etal.,(3) who identifiedpmp1, 2, 10 and 11 in an expression library with antibodies raised to denatured C. pneumoniae...

Insertion Sequence and Transposons

ISs are found on the chromosomes of many different sequenced bacterial and archaeal genomes (71). No IS element was identified in a few sequenced genomes, notably, Aeropyrumpernix K1, Aquifex aeolicus VF5, Bacillus subtillis 168, Buchnera sp. strain APS, Chlamydia muridarum, Chlamydia trachomatis D UW-3 CX, C. trachomatis

Epidemiology and Pathogenesis

Risk determinants for HPV infection that have been identified in various cross-sectional and prospective cohort studies include the number of sexual partners (lifetime and recent), age at first intercourse, smoking, oral contraceptive (OC) use, other sexually transmitted infections (STIs) (e.g., chlamydia and herpes simplex vi

CRP as a Marker of Widespread Inflammation

Complex interplay between inflammatory response and progression ofatherosclerosis. Inflammatory response is indeed observed in patients with ACSs. The stimuli for inflammation, however, are poorly understood. Several stimuli may be involved, including oxidized low-density lipoprotein (ox-LDL) and other sources of endothelial injury. Localized or systemic infections, in particular from Helicobacter pylori (HP), Chlamydia pneumoniae (CP), and cytomegalovirus (CMV), have been suggested as promoters of enhanced inflammatory response, but their role is controversial. The inflammatory reaction is responsible for the secondary effects of cytokine production liver synthesis of acute-phase reactants. CRP, SAA, and fibrinogen are the most widely studied acute-phase proteins. CRP itself is responsible for amplification ofthe inflammatory response by a direct effect on endothelium, platelets, coagulation, and eventually thrombosis, and the development of acute atherothrombosis further...

Pathological Evidence

In 1992, Shor et al. (26) described electron microscopic examination of preexisting coronary atherosclerotic plaque taken at autopsy from seven patients. Particles within cells were consistent in morphology with C. pneumoniae, and the same samples, when subjected to an immunocytochemical test specific for that organism, were confirmed to be C. pneumoniae in five of the seven specimens tested. Our laboratory confirmed this ini-tial finding in a group of 90 patients with symptomatic atherosclerosis who underwent directional coronary atherectomy with subsequent percutaneous removal of atherosclerotic plaque (27). By direct immunofluorescence testing, it was found that 79 of the atherectomy specimens had evidence ofthe presence of Chlamydia species. By comparison, no such evidence was found in control subjects or a group of cardiac transplant patients who developed CAD through chronic transplant rejection rather than through typical atherogenesis.

Atherosclerotic Cardiovascular Disease

Cachexia, by virtue of MICS, may predispose CKD patients to atherosclerotic cardiovascular disease 24, 49, 51 . Dialysis patients with coronary heart disease often have hypoalbuminaemia and elevated levels of acute-phase reactants 24 . Moreover, progression of carotid atherosclerosis during dialysis may be related to IL-6 levels 137 . It should be noted that the cascade of inflammatory factors leading to an acute-phase reaction is counter-regulated by various anti-inflammatory cytokines, such as IL-10. Recently, Girndt et al., in a study of 300 haemodialysis patients 138 , showed that the -1082A allele, which is associated with low production of IL-10, is associated with an increased risk of cardiovascular events. Inflammatory processes may promote proliferation and infiltration of inflammatory cells into the tunica intima of small arteries, including the coronary arteries these processes lead to atherosclerosis and stenosis of blood vessels and consequent coronary and other vascular...

DNA Microarray Analysis of Host Pathogen Interaction

Understanding the molecular basis of the host response to bacterial infections is critical for understanding disease mechanisms involved, and in preventing disease and tissue damage resulting from the host response. The global transcription effects on host cells by various bacterial pathogens including Listeria monocytogenes, Salmonella typhimurium, Pseudomonas aeruginosa, Bordetellapertussis,Mycobacterium tuberculosis, H. pylori, and Chlamydia trachomatis have been analyzed by using microarray technology (29,30). Rosenberger et al. (31) identified novel macrophage genes whose level of expression are altered in S. typhimurium infection or when treated with lipo-polysaccharide. Similarly, Cohen et al. (32) identified 74 upregulated RNAs and 23 downregulated host RNAs in L. monocytogenes-infected human promyelocytic THP1 cells. Infection of human bronchial epithelial cells by B. pertussis results in an increase in transcriptional levels of 33 genes and decrease in transcriptional levels...

FK506 Binding Proteins FKBPs

Tetratricopeptide Repeat

Seria meningitidis, Chlamydia trachomatis, Coxiella burnetii, Trypanosoma cruzi, Aeromonas hydrophila, and Salmonella typhimurium. Monoclonal antibodies raised against the active site of L. pneumophila Mip (LpFKBP25) significantly inhibit the early establishment and initiation of an intracellular infection of the bacteria in Acanthamoeba castellanii, the natural host, and in the human U937 macrophages 111 .

Approach To Suspected Pneumonia

Typical community-acquired pneumonia, as opposed to nosocomial or hospital-acquired pneumonia, is most commonly caused by S. pneumoniae, MoraxeUa catarrhalis, or Haemophilus influenzae. Viruses, such as influenza and adenovirus, can also cause pneumonia. Atypical pneumonia, which is characterized by a more insidious onset, a dry cough, muscle aches, headaches, and sore throat, typically is caused by M. pneumoniae. However, other organisms, such as Legionella (typically associated with preceding gastrointestinal symptoms) and Chlamydia pneumoniae, should be considered. In a patient with specific risk factors. Chlamydia psittaci (bird exposure), coc-cidiomycosis (travel to the American southwest), or histoplasmosis (endemic to the Mississippi Valley) may be the cause. In a patient with AIDS or immunosuppression. Pneumocystis carinii should be added to the differential diagnosis. Tuberculosis is a possibility in patients with a history suggestive of exposure or predisposition (e.g those...

Clinical Use of Tetracycline Antibiotics and Currently Used Drugs

Cious against aerobic and anaerobic Grampositive and Gram-negative bacteria. They are generally orally administered and have found extensive use in the treatment of infectious diseases and continue to be widely used, but are now being supplanted by other agents such as the quinolones. Nonetheless, the tetracyclines remain first-line drugs in the treatment of infections caused by pathogens of the family Rickettsiae (causative agents of Rocky Mountain spotted fever, typhus, Q fever, ehrlichiosis), Chlamydia pneumoniae, Mycoplasma pneumoniae, Chlamydia trachomatis, Borrelia burgdorferi (Lyme disease), members of the genus Brucella that cause brucellosis, Calymmatobacterium granulomatis (granuloma inguinale), Vibrio cholera (cholera), and

DNA Microarray Analysis of Bacterial Pathogens

Chlamydia trachomatis is an obligate intracellular pathogen of humans. Isolates are differentiated into biovars based on their in vitro infection properties and type of disease caused. They are grouped into 15 serovars based on antigenic variation of the major outer membrane protein, OmpA. Serovars A to C are the etiological agents of trachoma serovars D to K and L1 to L3 cause cervicitis and urethritis or lymphogranuloma venereum , respectively (14). The genomes ofthree Chlamydia species, C. trachomatis, C. pneumoniae, and C. psittaci have been sequenced (15-17). Comparative analysis of these genomes (1.04-1.3 Mb) showed a high degree of conservation in terms of gene content and gene order with the exception of one polymorphic region named the plasticity zone (PZ), which showed a significant amount of variation among the different The DNA sequences obtained from all the serovars were aligned with the mouse-adapted C. muridarum cytotoxin (TC0438) gene. Analysis of the sequence showed...

Joseph B Muhlestein MD

Introduction Chlamydia pneumoniae Helicobacter pylori Mycoplasma pneumoniae Cytomegalovirus Other Herpesviruses Human Immunodeficiency Virus Influenza Virus Chronic infection has been found to be significantly associated with the development of atherosclerosis and the clinical complications of unstable angina, myocardial infarction, and stroke. A variety of infectious agents have been proposed to be involved in atherothrombosis, and, indeed, the number of implicated agents continues to increase each year. These include specific bacterial and viral agents, as well as a variety of agents associated with periodontal disease. However, failure to confirm initial reports of serological associations also has been common. The infectious agents with the most evidence to support an etiological role in atherosclerosis include Chlamydia pneumoniae and cytomegalovirus. In addition, evidence is mounting for a variety of other potential agents including other herpes viruses, influenza, other...

The Team Approach

Antibiotics are used to treat infectious illnesses by stopping the growth of pathogenic bacteria or by killing the bacteria outright. The drug action is often aimed at ribosomal translation or protein synthesis in the dividing bacteria. Inhibition of cell wall assembly is a common mechanism of antibiotics. Aminoglycosides such as gen-tamicin, tobramicin, streptomycin, and kanamycin are very effective in treating systemic infections from gram-negative bacteria such as Pseudomonas, Proteus, Escherichia coli, Klebsiella, Enterobacter, and Serratia as well as staphylococci. These aminoglycosides exhibit broad-spectrum bacterial action against aerobic gramnegative organisms by binding to their 30S ribosomes, which inhibits protein synthesis. Aminoglycosides are effective against bacteria that are resistant to less toxic drugs such as methicillin. Aminoglycosides can also be used in conjunction with other antibiotics for the treatment of Listeria and gram-positive coccal infections.3...

Interactions between Bacteria and the Centrosome

The most enigmatic feature of CI is the fact that crosses between infected males and infected females, and also those between uninfected males and infected females, are all viable. Early models suggested that Wolbachia somehow disrupts chromatin condensation or the correct formation of the mitotic spindle, and such arguments were favored by findings which showed that Wolbachia, like Chlamydia and Orientia, cluster around the centrosome in infected embryos.

Sports Preparticipation Examination

29.3 A 17-year-old male reports that he has been sexually active with 2 female partners in the past year. He has used condoms sometimes, but not always. He is asymptomatic for anything and has a normal physical examination. Which of the following tests would be recommended to screen him for gonorrhea and Chlamydial B. Serum antibodies to Neisseria gonorrhoeae and Chlamydia trachomatis 29.3 C. Urine for leukocyte esterase is recommended as screening for presumptive gonorrhea or Chlamydia in sexually active males. A urethral swab is more appropriate for diagnostic testing in a male who has a urethral discharge.

Approach To Suspected Endocarditis

Culture-negative endocarditis, an uncommon situation in which routine cultures fail to grow, is most likely a result of prior antibiotic treatment, fungal infection (fungi other than Candida species often require special culture media), or fastidious organisms. These organism can include Ahiotrophia spp, Bartonella spp, Coxiella burnetii. Legionella spp. Chlamydia, and the HACEK organisms (Haemophilus aphrophilus paraphrophilus, Actinobacillus

Bacterial Manipulation of the Microtubule Network

Following phagocytosis or endocytosis, bacteria face the impending threat of being passed into the lysosome for enzymatic destruction. Some, including the actin-tail forming bacteria Shigella and Listeria, escape the endosome entirely, while others have evolved a means of manipulating both the endocytic pathway and the microtubule network to such an extent that their passage to the lysosome is blocked 105 . One of the most ingenious members of this group is Chlamydia, the bacterial genus which is both responsible for a sexually-transmitted disease that constitutes the most common reportable infection in the United States, and is also the world's leading cause of infectious blindness. Chlamydia exist in two morphogenetic forms the infectious elementary bodies (EBs) which are compact and resistant to environmental stresses, and the intracellular reticulate bodies (RBs), which are metabolically active, and replication competent. EBs are phagocytosed, and become surrounded by endosomal...

Clinical Approach

PID, or salpingitis, usually involves Chlamydia, gonorrhea, and other vaginal organisms, such as anaerobic bacteria. The mechanism usually is ascending infection. A common presentation is a young, nulliparous female complaining of lower abdominal or pelvic pain and vaginal discharge. The patient may also have fever and nausea and vomiting if the upper abdomen is involved. The cervix is inflamed therefore, the patient often complains of dyspareunia. The diagnosis of acute salpingitis is made clinically by abdominal tenderness, cervical motion tenderness, and adnexal tenderness (Table 21-1). Confirmatory tests may include a positive gonorrhea or Chlamydia culture or an ultrasound suggesting a TOA. Other diseases that must be considered are acute appendicitis, especially if the patient has right-sided abdominal pain and ovarian torsion, which usually presents as colicky pain and is associated with an ovarian cyst on ultrasound. Renal disorders, such as pyelonephritis or nephrolithiasis,...

Approach To Urinary Tract Infections Definitions

UTI's may involve the kidneys (pyelonephritis), bladder (cystitis), and urethra (urethritis). One in live women will acquire a UTI sometime in her life. The shorter urethra and its proximity to the rectum are the most commonly stated reasons for the increased incidence in women. Pregnancy further predisposes women to UTI's because of incomplete emptying of the bladder, ureteral obstruction, and immune suppression. Pathogenic bacteria include E. coli (isolated 80 of the time), followed by Enterobacter, Klebsiella, Pseudo-monas, Proteus, group B streptococcus. Staphylococcus saprophytics, and Chlamydia. A patient with urethritis has complaints similar to those of cystitis (i.e., urgency, frequency, and dysuria). Sometimes, on palpation of the urethra, purulent drainage expressed. The most commonly isolated organisms are Chlamydia. Gonococcus, and Trichomonas. Urethritis should be suspected in a woman with typical symptoms of UTI yet with sterile culture and no response to standard...

Case

A 16-year-old female presents to your office with the complaint of greenish vaginal discharge for the past 2 months and the recent onset of lower abdominal pain. She reports that her last period was about 2.5 months ago. She is sexually active with two partners and has never used a condom or any other contraception with either. On physical examination she is not febrile with normal blood pressure and pulse. She has greenish discharge from the cervix with friability and cervicitis. There is no cervical motion tenderness. Her urine pregnancy test is positive. A cervical sample is positive for Chlamydia and negative for gonorrhea. Her rapid plasma reagin (RPR) is nonreactive and an HIV test is negative. The patient is treated with appropriate antibiotics and counseled concerning safer sex practices. You also inform the patient regarding her risk for HIV conversion, even though today's test was negative. The patient asks if you are going to tell her mother that she is pregnant and has...

Pneumonias

'Atypical' cases of pneumonia may be caused by Mycoplasma pneumoniae which may be epidemic, or more rarely Chlamydia pneumoniae or psittaci (psitta-cosis ornithosis) Legionella pneumophilia or Coxiella burnetii (Q fever) and a tetracycline or erythromycin clarithromycin should be given by mouth. Treatment of ornithosis should continue for 10 days after the fever has settled and in mycoplasma pneumonia and Q fever a total of 3 weeks treatment may be needed to prevent relapse.

Gonorrhoea

Chlamydia trachomatis is frequently present with Neisseria gonorrhoeae tetracycline by mouth for 7 days or a single oral dose of azithromycin lg will treat the chlamydial urethritis. The vast majority of cases of urethritis with pus in which gonococci cannot be identified are due to sexually-transmitted organisms, usually Chlamydia trachomatis and sometimes Ureaplasma urealyticum. Tetracycline or azithromycin by mouth is effective. Several pathogens are involved including Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma hominis and there may be superinfection with bowel and other urogenital tract bacteria. A combination of antimicrobials is usually required, e.g. metronidazole plus doxycycline by mouth.

Eye infections

In the developed world, the genital (D-K) serotypes of the organism are responsible and the reservoir and transmission is maintained by sexual contact. Endemic trachoma in developing countries is usually caused by serotypes A, B and C. In either case, oral tetracycline is effective. Pregnant or lactating women may receive systemic erythromycin. Neonatal ophthalmia should be treated with systemic erythromycin and topical tetracycline.

Serological Evidence

In 1998, Pekka Saikku and his associates of the University of Helsinki made the first suggestion of an association between C. pneumoniae and coronary artery disease (CAD) (6). They had described an epidemic of mild pneumonia caused by what was then considered to be an unusual strain of Chlamydia psittaci. Following up on earlier reports linking myocarditis and arterial emboli with chlamydial infection, they measured titers of antibody to C. pneumoniae. They discovered that men experiencing acute myocardial infarction (AMI) or with significant CAD were more likely to be seropositive for C. pneumoniae than age- and sex-matched control subjects (Fig. 2). Fig. 2. Graph showing results of MIF (microimmunofluorescence test for antibodies specifically targeted against C. pneumoniae) and LPS (enzyme-linked immunoassay for antibodies against the chlamydial group antigen) assays in patients experiencing AMI in patients with known CAD, and in control subjects (6). Fig. 2. Graph showing results...

Pathogenesis

The cellular immune reaction is mediated by T lymphocytes. Simplistically, activated CD4+ T lymphocytes possessing antigen-specific receptors cross the blood-brain barrier and react with myelin and or oligoden-droglia antigen. Cytokines released by T lymphocytes activate macrophages expressing MHC class II antigen. These macrophages present the myelin antigens to the T cells and, in time, remove the products of myelin disintegration. MBP, proteolipid protein, and myelin oligodendrocyte glycoprotein are major target antigens. The humoral immune reaction is mediated by activated B lymphocytes that secrete myelin-specific antibodies. Several pathogens have been postulated to trigger the immune reaction measles virus, Epstein-Barr virus, human herpes virus 6, retroviruses, canine distemper virus, and Chlamydia pneumoniae. None has yet been confirmed.

Transmission

Screening for other sexually transmitted diseases (syphilis, hepatitis B and C, gonorrhea, chlamydia) should be performed initially and repeated, if needed, because of any ongoing risks identified. Hepatitis B and A vaccination should be offered to those who lack immunity. A purified protein derivative (PPD) test should be done, and if initially negative, repeated annually. Women should have regular Papanicolaou (Pap) smears to evaluate for cervical dysplasia or cancer.

Other bacteria

Another type of ultramicroscopic bacteria is the chlamydiae. Like the rick-ettsiae, the chlamydiae can be seen only with the electron microscope. In humans, chlamydiae cause several diseases, including an eye infection called trachoma and a sexually transmitted disease called chlamydia.

6 Cm Ovarian Cyst

Adnexal Solid Mass

Pelvic inflammatory disease (PID) is most often a result of sexually transmitted infection of the fallopian tubes (salpingitis) or of the tubes and ovaries (salpingo-oophoritis). It is caused by Neisseria gonorrhoeae, Chlamydia trachomatis, and other organisms. Acute disease is associated with very tender, bilateral adnexal masses, although pain and muscle spasm usually make it impossible to delineate them. Movement of the cervix produces pain. If not treated, a tuboovarian abscess or infertility may ensue.