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Chlamydia & chlamydophila


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Chlamydia & chlamydophila

  1. 1. A Presentation by M. Isaac Umapathy, Dept. of Microbiology & Parasitology, Faculty of Medicine, International Medical & Technological University, Dar-Es-Salaam, Tanzania . CHLAMYDIA & CHLAMYDOPHILA
  2. 2. Introduction <ul><li>Chlamydiae are group of tiny bacteria about 0.25 µm in diameter and have the smallest genome known among medically important bacteria (roughly a quarter the size of Escherichia coli ). </li></ul><ul><li>Chlamydia are obligate intracellular bacteria depending on the host cell for energy in the form of adenosine triphosphate (ATP) nicotinamide adenine dinucleotide (NAD + ) that preferentially infect squamocolumnar epithelial cells. </li></ul><ul><li>The chlamydiae can be viewed as gram-negative bacteria that lack mechanisms for the production of metabolic energy and cannot synthesize ATP. </li></ul><ul><li>This defect restricts them to an intracellular existence, where the host cell furnishes energy-rich intermediates. </li></ul><ul><li>All chlamydiae exhibit similar morphologic features, share a common group antigen, and multiply in the cytoplasm of their host cells by a distinctive developmental cycle. </li></ul>
  3. 3. Introduction <ul><li>The chlamydiae were once considered viruses because they are small enough to pass through 0.45 µm filters and are obligate intracellular parasites; however, the organisms have the following properties of bacteria: </li></ul><ul><ul><li>Possess inner and outer membranes similar to those of gram negative bacteria. </li></ul></ul><ul><ul><li>Contain both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). </li></ul></ul><ul><ul><li>Possess prokayotic ribosomes. </li></ul></ul><ul><ul><li>Synthesize their own proteins, nucleic acids, and lipids. </li></ul></ul><ul><ul><li>Suceptible to numerous antibacterial antibiotics. </li></ul></ul><ul><li>Unlike other bacteria, the chlamydiaceae have a unique developmental cycle, forming metabolically inactive infectiuos forms (elementary bodies [EBs]) and metabolically active, noninfectious forms (reticulate bodies [RBs]). </li></ul>
  4. 4. Introduction <ul><li>Chlamydiae that infect humans are divided into three species on the basis of antigenic composition, intracellular inclusions, sulfonamide susceptibility, and disease production. </li></ul><ul><ul><li>Chlamydia trachomatis. </li></ul></ul><ul><ul><li>Chlamydophila pneumoniae. </li></ul></ul><ul><ul><li>Chlamydophila psittaci. </li></ul></ul><ul><li>C trachomatis can be differentiated into 16 serovars (serologically variant strains) based on monoclonal antibody–based typing assays. </li></ul><ul><li>Serovars A, B, Ba, and C are associated with trachoma (a serious eye disease that can lead to blindness), serovars D-K are associated with genital tract infections like nongonococcal urethritis (GNU), vaginitis and cervicitis and L1-L3 are associated with lymphogranuloma venereum (LGV). </li></ul><ul><li>Other species have been placed into the two genera, but they are uncommon human pathogens and infect animals. </li></ul><ul><li>Chlamydophila pneumoniae causes atypical pneumonia . </li></ul><ul><li>Chlamydophila psittaci causes psittacosis. </li></ul><ul><li>Chlamydia pecorum, infects a variety of animals but is not known to infect humans. </li></ul>
  5. 5. Introduction <ul><li>Chlamydoplila abortus infects domestic animals (mainly pregnant sheep and goats) and is occasionally transmitted to pregnant farm workers. </li></ul><ul><li>Ch. caviae causes oculogenital infection in guinea pigs. </li></ul>
  6. 6. History <ul><li>Chlamydia-like disease affecting the eyes of people was first described in ancient Chinese and Egyptian manuscripts. </li></ul><ul><li>A modern description of Chlamydia-like organisms was provided by Halberstaedter and von Prowazek in 1907. </li></ul><ul><li>Chlamydial isolates cultured in the yolk sacs of embryonating eggs were obtained from a human pneumonitis outbreak in the late 1920s and early 1930s, and by the mid-20th Century isolates had been obtained from dozens of vertebrate species. </li></ul><ul><li>The term Chlamydia (a cloak) appeared in the literature in 1945, although other names continued to be used, including Bedsonia, Miyagawanella, ornithosis-, TRIC-, and PLT-agents. </li></ul>
  7. 7. Taxonomy <ul><li>Domain: Bacteria. </li></ul><ul><li>Phylum: Chlamydiae / Verrucomicrobia group. </li></ul><ul><li>Class: Chlamydiae. </li></ul><ul><li>Order: Chlamydiales. </li></ul><ul><li>Family: Chlamydiaceae. </li></ul><ul><li>Genus: Chlamydia. </li></ul><ul><li>: Chlamydophila. </li></ul><ul><li>Species: </li></ul><ul><ul><ul><ul><li>Chlamydia trachomatis. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Chlamydia muridarum. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Chlamydophila pneumoniae.. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Chlamydophila psittaci. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Chlamydophila abortus. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Chlamydophila caviae. </li></ul></ul></ul></ul>
  8. 8. Nomenclature <ul><li>In 1966, Chlamydiae were recognized as bacteria and the genus Chlamydia was validated. </li></ul><ul><li>The Order Chlamydiales was created by Storz and Page in 1971. </li></ul><ul><li>Between 1989 and 1999, new families, genera, and species were recognized. </li></ul><ul><li>The phylum Chlamydiae was established in Bergey's Manual of Systematic Bacteriology. </li></ul><ul><li>By 2006, genetic data for over 350 chlamydial lineages had been reported, four chlamydial families recognized (Chlamydiaceae, Parachlamydiaceae, Simkaniaceae, and Waddliaceae), and another family proposed (Rhabdochlamydiaceae). </li></ul>
  9. 9. Taxonomy <ul><li>The family Chlamydiaceae was formerly classified into four species, belonging to the single genus Chlamydia: </li></ul><ul><ul><li>Chlamydia trachomatis, the cause of human oculogenital infections. </li></ul></ul><ul><ul><li>C. pnueumoniae, the cause of acute respiratory infections. </li></ul></ul><ul><ul><li>C. psittaci, the cause of veterinary and zoonotic infections. </li></ul></ul><ul><ul><li>C. percorum, the cause of veterinary infections. </li></ul></ul><ul><li>In 1999 the taxonomy of the family Chlamydiaceae was revised extensively on the basis of genomic studies. </li></ul><ul><li>Most importantly, the former C. psittaci, (long known to represent a diverse group of organisms) has become the new genus Chlamydophila, which is split into several species. </li></ul><ul><li>C. pnueumoniae, has been reclassified as Chlamydophila pneumoniae. </li></ul>
  10. 10. Taxonomy <ul><li>Chlamydia species: Chlamydia trachomatis is divided into two biovars which reflect fundamental differences in their invasiveness for cell culture, and in their involvement in human disease. </li></ul><ul><ul><li>Those causing trachoma, inclusion conjunctivitis (the so-called TRIC agents and oculogenital infection. </li></ul></ul><ul><ul><li>Those causing a more invasive genital tract infection associated with lymphoid pathology, lymphogranuloma venereum (LGV). </li></ul></ul><ul><ul><li>A former third biovar, which causes pneumonia in mice, has been reclassified as C. muridarum. </li></ul></ul><ul><ul><li>Both the trachoma and the LGV biovars can be divided into serotypes (serovars) on the basis of epitopes carried on their major outer membrane protein (MOMP). </li></ul></ul><ul><ul><li>There are 12 serotypes in the trachoma biovar (with variants within them) which are given the letters A-K (A, B, Ba, C, D, E, F, G, H, I, J & K) and 4 serovars, L1, L2, L2a & L,3, in the LGV biovar. </li></ul></ul><ul><ul><li>There are geographic differences in the distribution of these serovars and it is not uncommon for an individual to be simultaneously infected with more than one. </li></ul></ul>
  11. 11. Taxonomy <ul><ul><li>There is no apparent differences in virulence among them, but single strains of mixed serovars do arise presumably due to recombination events within the gene encoding the major outer membrane proteins. </li></ul></ul><ul><ul><li>This occurs in region of South and East Africa, where there is a high prevalence of genital infections. </li></ul></ul><ul><li>Chlamydophila species: Members of the genus Chlamydophila infect both birds and mammals. </li></ul><ul><ul><li>Ch. psittaci causes respiratory, gut and systemic infections in birds, particularly in psittacine and ornithine birds (budgerigars, parrots) and may lead to severe and sometimes fatal pneumonia in man (psittacosis or ornithosis). </li></ul></ul><ul><ul><li>Ch. pneumoniae, the former TWAR (Taiwan acute respiratory) agent, is a common cause of mild to severe acute respiratory disease in man. </li></ul></ul><ul><ul><li>Ch. abortus causes abortion in sheep, rarely leading to abortion in pregnant women exposed to infected sheep. </li></ul></ul><ul><ul><li>Sheep and goat often carry a related organism Ch. percorum, in their guts. </li></ul></ul><ul><ul><li>Ch. caviae causes oculogenital infection in guinea pigs and is an important experimental model of human infection. </li></ul></ul>
  12. 12. Structure & Chemical Composition <ul><li>In chlamydiae, the outer cell wall resembles the cell wall of gram-negative bacteria. </li></ul><ul><li>It has a relatively high lipid content. </li></ul><ul><li>It is rigid but does not contain a typical bacterial peptidoglycan; however, the chlamydial genome contains the genes needed for peptidoglycan synthesis. </li></ul><ul><li>Penicillin-binding proteins occur in chlamydiae, and chlamydial cell wall formation is inhibited by penicillins and other drugs that inhibit transpeptidation of bacterial peptidoglycan. </li></ul><ul><li>Lysozyme has no effect on chlamydial cell walls. </li></ul><ul><li>N -acetylmuramic acid appears to be absent from chlamydial cell walls. </li></ul><ul><li>Both DNA and RNA are present in elementary and reticulate bodies. </li></ul><ul><li>The reticulate bodies contain about four times as much RNA as DNA, whereas the elementary bodies contain about equal amounts of RNA and DNA. </li></ul><ul><li>In elementary bodies, most DNA is concentrated in the electron-dense central nucleoid. </li></ul><ul><li>Most RNA exists in ribosomes. </li></ul><ul><li>The circular genome of chlamydiae (MW 7 x 10 8 ) is similar to that of bacterial chromosomes. </li></ul>
  13. 13. Structure & Chemical Composition <ul><li>Multiple chlamydial genomes have been sequenced providing insight into the basic biology of the organisms e.g., chlamydiae have a type III secretion system, which may allow them to inject effector proteins into host cells as part of the infectious process. </li></ul>
  14. 14. Morphology <ul><li>Chlamidiae are small, non-motile bacteria. </li></ul><ul><li>Although they stain poorly with Gram’s stain they have the typical LPS of Gram negative bacteria. </li></ul><ul><li>They exhibit a dimorphic growth cycle, in which infection is initiated by environmentally resistant, metabolically inert, infectious structures called elementary bodies, while larger, pleomorphic structures, reticulate bodies, are responsible for intracellular replication. </li></ul><ul><li>Elementary bodies: </li></ul><ul><ul><li>Chlamydial elementary bodies are small, electron dense structures about 300-350 nm in diameter. </li></ul></ul><ul><ul><li>They are generally round, though in some strains of C. pneumoniae they are pear shaped. </li></ul></ul><ul><ul><li>The elementary body is the only one infectious stage of the chlamydial developmental cycle and is the primary target of efforts to prevent chlamydial infection. </li></ul></ul><ul><ul><li>In electron micrographs the most obvious is the electron dense core of DNA, which is tightly compacted onto chamydial histone proteins. </li></ul></ul><ul><ul><li>Short projections of unknown function radiate from the surface of the elementary body. </li></ul></ul>
  15. 15. Morphology <ul><ul><li>The elementary body is thought to be metabolically inert until it attaches to and is ingested by, a susceptible host cell. </li></ul></ul><ul><ul><li>It rigid cell wall contains only small amounts of peptidoglycan and derives its strength mainly from sulpher bridges in the system - and methionine bridge - proteins of the outer membrane. </li></ul></ul>
  16. 16. Morphology <ul><li>Reticulate bodies: </li></ul><ul><ul><li>Typically reticulate bodies have a diameter of around 1µm or more. </li></ul></ul><ul><ul><li>They are non-infectious. </li></ul></ul><ul><ul><li>They are metabolically active, so their cytoplasm is rich in ribosomes, which are required for protein synthesis. </li></ul></ul><ul><ul><li>Their nucleic acid, unlike the elementary body, is diffuse and fibrillar. </li></ul></ul><ul><ul><li>Reticulate bodies, are bounded by an inner cytoplasmic membrane and an external outer envelope covered with projections and rosettes that are similar to, but more numerous than, those seen on elementary bodies. </li></ul></ul><ul><ul><li>Reticulate bodies are often packed around the edge of the intracellular inclusion where they grow, in close apposition to the inclusion membrane. </li></ul></ul><ul><ul><li>The reticulate bodies divide by binary fission in typical bacterial fashion. </li></ul></ul><ul><ul><li>They eventually switch on histone synthesis and differentiate into one or more elementary bodies. </li></ul></ul>
  17. 17. Comparison of Chlamydial Elementary Body & Reticulate Body More Few Projections & rosettes Sensitive Resistant Trypsin digestion Active, replicating stage Relatively inactive Metabolic activity 3:1 (increased ribosomes) 1:1 (condensed DNA core) RNA:DNA ratio Non-infectious Infectious Infectivity to host Fragile, pleomorphic Electron dense core; rigid Morphology 1 µm 0.2 - 0.3 µm Size Reticulate Body Elementary Body Characteristic
  18. 18. Staining Properties <ul><li>Chlamydiae have distinctive staining properties (similar to those of rickettsiae). </li></ul><ul><li>Elementary bodies stain purple with Giemsa stain in contrast to the blue of host cell cytoplasm. </li></ul><ul><li>The larger, noninfective reticulate bodies stain blue with Giemsa stain. </li></ul><ul><li>The Gram reaction of chlamydiae is negative or variable and is not useful in identification of the agents. </li></ul><ul><li>Chlamydial particles and inclusions stain brightly by immunofluorescence, with group-specific, species-specific, or serovar-specific antibodies. </li></ul><ul><li>Fully formed, mature intracellular inclusions of C trachomatis are compact masses near the nucleus which are dark purple when stained with Giemsa stain because of the densely packed mature particles. </li></ul><ul><li>If stained with dilute Lugol's iodine solution, some of the inclusions of C trachomatis (but not Ch pneumoniae or Ch psittaci ) appear brown because of the glycogen matrix that surrounds the particles. </li></ul><ul><li>Inclusions of Ch psittaci are diffuse intracytoplasmic aggregates. </li></ul>
  19. 19. Antigenic Structure <ul><li>Chlamydiae possess shared group (genus)-specific antigens. </li></ul><ul><ul><li>These are heat-stable lipopolysaccharides with 2-keto-3-deoxyoctanoic acid as an immunodominant component. </li></ul></ul><ul><ul><li>Antibody to these genus-specific antigens can be detected by CF and immunofluorescence. </li></ul></ul><ul><li>Species-specific or serovar-specific antigens are mainly outer membrane proteins. </li></ul><ul><ul><li>Specific antigens can best be detected by immunofluorescence, particularly using monoclonal antibodies. </li></ul></ul><ul><ul><li>Specific antigens are shared by only a limited number of chlamydiae, but a given organism may contain several specific antigens. </li></ul></ul><ul><ul><li>There are at least 16 serovars of C trachomatis; these include A, B, Ba, C–K, and L1, L2, L2a, L3. </li></ul></ul><ul><ul><li>Several serovars of C psittaci can be demonstrated by complement fixation (CF) and microimmunofluorescence tests. </li></ul></ul><ul><ul><li>Only one serovar of C pneumoniae has been described. </li></ul></ul>
  20. 20. Growth & Metabolism <ul><li>Chlamydiae require an intracellular habitat, because they are unable to synthesize ATP and depend on the host cell for energy requirements. </li></ul><ul><li>Chlamydiae grow in cultures of a variety of eukaryotic cells lines. </li></ul><ul><ul><li>McCoy cells treated with cycloheximide commonly are used to isolate chlamydiae. </li></ul></ul><ul><ul><li>It may be necessary to treat cells with poly-anionic compounds such as DEAD-dextran to reduce the electrostatic barrier to infection before centrifugation of the chlamydiae or the clinical specimen on to the cells. </li></ul></ul><ul><ul><li>The cells are then incubated in an antimetobolite such as cycloheximide to favour chlamidial competition for host cell amino acid pools. </li></ul></ul><ul><ul><li>The presence of chlamydial inclusions is determined by microscopy in conjunction with a suitable staining method, preferably fluorescence microscopy with labelled monoclonal antibody. </li></ul></ul><ul><ul><li>C pneumoniae grows better in HL or HEp-2 cells. </li></ul></ul><ul><li>All types of chlamydiae proliferate in embryonated eggs, particularly in the yolk sac. </li></ul>
  21. 21. Growth & Metabolism <ul><li>Some chlamydiae have an endogenous metabolism like other bacteria. </li></ul><ul><li>They can liberate CO 2 from glucose, pyruvate, and glutamate; they also contain dehydrogenases. </li></ul><ul><li>Nevertheless, they require energy-rich intermediates from the host cell to carry out their biosynthetic activities. </li></ul><ul><li>The replication of chlamydiae can be inhibited by many antibacterial drugs. </li></ul><ul><li>Cell wall inhibitors such as penicillins and cephalosporins result in the production of morphologically defective forms but are not effective in clinical diseases. </li></ul><ul><li>Inhibitors of protein synthesis (tetracyclines, erythromycins) are effective in most clinical infections. </li></ul><ul><li>C trachomatis strains synthesize folates and are susceptible to inhibition by sulfonamides. </li></ul><ul><li>Aminoglycosides are noninhibitory. </li></ul>
  22. 22. Growth Cycle <ul><li>Chlamydia has a very unique life-cycle, in which in alternates between a non-replicating, infectious elementary body, and a replicating, non-infectious reticulate body. </li></ul><ul><li>The elementary body is the dispersal form of the pathogen, and is analogous to the spore. </li></ul><ul><li>The bacterium induces its own endocytosis upon contact with potential host cells. </li></ul><ul><li>Once inside a cell the elementary body germinates as the result of interaction with glycogen, and converts to its vegetative, reticulate form. </li></ul><ul><li>The reticulate form divides every 2-3 hours, and has an incubation period of about 7-21 days in its host. </li></ul><ul><li>After division, the pathogen reverts back to its elementary form and is released by the cell through exocytosis. </li></ul><ul><li>They are extremely temperature sensitive, and must be refrigerated at 4°C as soon as a sample is obtained. </li></ul>
  23. 23. Figure 47-1 The growth cycle of Chlamydia trachomatis. (Redrawn from Batteiger B, Jones R: Infect Dis Clin North Am 1:55-81, 1987.) Downloaded from: StudentConsult (on 19 November 2007 10:58 AM) © 2005 Elsevier
  24. 24. Host-Parasite Relationship <ul><li>The outstanding biologic feature of infection by chlamydiae is the balance that is often reached between host and parasite, resulting in prolonged persistence of infection. </li></ul><ul><li>Subclinical infection is the rule and overt disease the exception in the natural hosts of these agents. </li></ul><ul><li>Spread from one species to another (eg, birds to humans, as in psittacosis) more frequently leads to disease. </li></ul><ul><li>Antibodies to several antigens of chlamydiae are regularly produced by the infected host. </li></ul><ul><li>These antibodies have little protective effect against reinfection. </li></ul><ul><li>The infectious agent commonly persists in the presence of high antibody titers. </li></ul><ul><li>Treatment with effective antimicrobial drugs (e.g., tetracyclines) for prolonged periods may eliminate the chlamydiae from the infected host. </li></ul><ul><li>Very early, intensive treatment may suppress antibody formation. </li></ul><ul><li>Late treatment with antimicrobial drugs in moderate doses may suppress disease but permit persistence of the infecting agent in tissues. </li></ul>
  25. 25. Host-Parasite Relationship <ul><li>The immunization of humans has been singularly unsuccessful in protecting against reinfection. </li></ul><ul><li>Prior infection or immunization at most tends to result in milder disease upon reinfection, but at times the accompanying hypersensitization aggravates inflammation and scarring (eg, in trachoma). </li></ul>
  26. 26. Clinical Manifestation PID = Pelvic Inflammatory Disease a = Unproven association b = Weak association Ch. Pneumoniae a Ch. Pneumoniae b Atherosclerosis, coronary disease Stroke, multiple sclerosis, sarcoidosis, Alzheimer’s disease Chronic diseases C. trachomatis (D-K) Ch. pneumoniae Simkania negevensis a Ch. abortus Ch. psittaci Neonatal atypical pneumonia Pharyngitis, bronchitis, pneumonia Pneumonia Psittacosis, ornithosis Respiratory tract C. trachomatis (D-K) C. trachomatis (D-K) C. trachomatis (D-K) a Ch. abortus C. trachomatis (L1-L3) Non-specific urethritis, proctatitis, epididymitis Cervicitis, urethritis, endometritis, salpingitis, PID, perihepatitis, peri-appendicitis, infertility with tubal occlusion Abortion, premature birth Sheep related abortion Lymphogranuloma venereum Genital tract Male Female Male and Female C. trachomatis (A,B,Ba,C) C. trachomatis (D-K) C. trachomatis (D-K) Parachlamydiae spp. Trachoma Inclusion conjunctivitis Opthalmia neonatorum Contact lens associated Eye Organism (serovars) Disease Site of infection Human infections caused by Chlamydiae
  27. 27. Pathophysiology <ul><li>The pathophysiologic mechanisms of chlamydiae are poorly understood at best. </li></ul><ul><li>The initial response to infected epithelial cells is a neutrophilic infiltration followed by lymphocytes, macrophages, plasma cells, and eosinophilic invasion. </li></ul><ul><li>The release of cytokines and interferons by the infected epithelial cell initializes this inflammatory cascade. </li></ul><ul><li>Infection with chlamydial organisms invokes a humoral cell response, resulting in secretory immunoglobulin A (IgA) and circulatory immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies and a cellular immune response. </li></ul><ul><li>Recent studies have implicated a 40-kd major outer membrane protein (MOMP) and a 60-kd heat-shock protein (Chsp60) in the immunopathologic response, but further studies are needed to better understand these cell-mediated immune responses. </li></ul><ul><li>Chlamydiae have a unique biphasic life cycle that is adaptable to both intracellular and extracellular environments. </li></ul><ul><li>In the extracellular milieu, the so-called elementary body (EB) is found. EBs are metabolically inactive infectious particles; functionally, they are spore-type structures. </li></ul>
  28. 28. Pathophysiology <ul><li>Once inside a susceptible host cell, the EB prevents phagosome-lysozyme fusion and then undergoes reorganization to form a reticulate body (RB). </li></ul><ul><li>The RB synthesizes its own DNA, RNA, and proteins but requires energy in the form of adenosine triphosphate (ATP) from the host cell. </li></ul><ul><li>After a sufficient amount of RBs have formed, some transform back into EBs, exiting the cell to infect others. </li></ul>
  29. 29. Ocular Infections <ul><li>Trachoma : </li></ul><ul><ul><li>It is caused by several C. trachomatis serovars (A, B, Ba, C) that are spread by eye-seeking flies, fingers and contaminated articles. </li></ul></ul><ul><ul><li>Active trachoma, characterized by the presence of lymphoid follicles on the conjunctiva and intermittent shedding of Chlamydiae, is primarily a disease of children. </li></ul></ul><ul><ul><li>By contrast, blindness occurs mainly in adults. It is caused by conjunctival scarring leading to distortion of the eyelids (entropion) and abration of the cornea by the eye lashes (trichiasis). </li></ul></ul><ul><ul><li>Adults with trachoma rarely shed viable chlamydiae from their eyes, although it is possible to demonstrate the presence of chlamydial antigen or chlamydial nucleic acid. </li></ul></ul><ul><ul><li>Trachoma is generally a clinical diagnosis, which has been simplified by a grading scheme introduced by the World Health organization. </li></ul></ul>
  30. 30. Trachoma Chlamydial infection in the eye causing trachoma. From the Dana Center Trachoma Study.
  31. 31. Pathophysiology <ul><li>Ocular damage is probably largely determined by </li></ul><ul><ul><li>The cell-mediated immune response </li></ul></ul><ul><ul><li>The severity of the original infection in childhood </li></ul></ul><ul><ul><li>The frequency of re-infection </li></ul></ul><ul><ul><li>The prevalence of other agents of bacterial conjunctivitis, such as Moraxella spp., which can exacerbate visual loss </li></ul></ul><ul><ul><li>Host genotypic factors that influence the balance between protective T-helper 1 and T-helper 2 cell mediated immune responses. </li></ul></ul>
  32. 32. Urogenital Infections <ul><li>C trachomatis is a sexually transmitted microorganism responsible for a wide spectrum of diseases that include cervicitis, salpingitis, endometritis, urethritis, epididymitis, conjunctivitis, and neonatal pneumonia. </li></ul><ul><li>In contrast to gonorrhea infection, most men and women who are infected are asymptomatic, and, therefore, diagnosis is delayed until a positive screening result or upon discovering a symptomatic partner. </li></ul><ul><li>Chlamydia has been isolated in approximately 40-60% of males presenting with nongonococcal urethritis. </li></ul><ul><li>Recent epidemiological studies indicate a high prevalence rate of asymptomatic men who act as a reservoir for chlamydial infections. </li></ul><ul><li>A study by Quinn et al (1996) demonstrated that transmission probability in both men and women is estimated at 68%. </li></ul>
  33. 33. Epidemiology <ul><li>Frequency: </li></ul><ul><ul><li>In the US: Chlamydia is the most commonly reported infectious disease in the United States—estimated at 4 million infections annually with prevalence rates of higher than 10% in sexually active adolescent females. </li></ul></ul><ul><ul><li>Internationally: In 1995, the World Health Organization (WHO) estimated 89 million cases of C trachomatis infection worldwide. </li></ul></ul><ul><li>Mortality/Morbidity: Although urogenital carriage of chlamydiae often is asymptomatic, the most common manifestation of disease is local mucosal inflammation associated with a discharge, urethritis in the male, and urethritis/vaginitis/cervicitis in the female. </li></ul><ul><ul><li>Chlamydia is one of the leading causes of pelvic inflammatory disease (PID) and infertility in women. The risk of ectopic pregnancy in women who have had PID is 7-10 times greater than that for women without a history of PID. In 15% of women who have contracted PID, chronic abdominal pain is a long-term manifestation that most likely is related to pelvic adhesions in the ovaries and fallopian tubes. </li></ul></ul><ul><ul><li>Chlamydial infections increase the risk for acquiring HIV infection by increasing genital mucosal inflammation. </li></ul></ul>
  34. 34. Epidemiology <ul><ul><li>Pregnant women infected with chlamydia can pass the infection on to their infants during delivery, which may develop into chlamydial pneumonia or chlamydial conjunctivitis. </li></ul></ul><ul><li>Race: The incidence of chlamydial infection is not related to race per se but rather to the sexual histories of the individuals and, particularly, to the frequency and use (or nonuse) of barrier protection. </li></ul><ul><li>Sex: Although the presence of asymptomatic infection with genitourinary chlamydiae can differ, acquisition is similar for both sexes. </li></ul><ul><li>Age: Age factors in chlamydial genitourinary infection relate to the age of first sexual exposure and the frequency of exposure. </li></ul>
  35. 35. Clinical Manifestation <ul><li>Risk factors </li></ul><ul><ul><li>Nonwhite race </li></ul></ul><ul><ul><li>Multiple sexual partners </li></ul></ul><ul><ul><li>Age younger than 19 years </li></ul></ul><ul><ul><li>Poor socioeconomic conditions </li></ul></ul><ul><ul><li>Single marital status </li></ul></ul><ul><ul><li>Nonbarrier contraceptive use </li></ul></ul><ul><li>Neonatal risk </li></ul><ul><ul><li>Conjunctivitis </li></ul></ul><ul><ul><li>Neonatal pneumonia </li></ul></ul>
  36. 36. Physical Signs & Symptoms <ul><li>Women </li></ul><ul><ul><li>Easily induced endocervical bleeding. </li></ul></ul><ul><ul><li>Mucopurulent endocervical discharge. </li></ul></ul><ul><ul><li>Intermenstrual bleeding. </li></ul></ul><ul><ul><li>Cervical discharge. </li></ul></ul><ul><ul><li>Dysuria. </li></ul></ul><ul><ul><li>Abdominal pain. </li></ul></ul><ul><li>Men </li></ul><ul><ul><li>Urethral discharge. </li></ul></ul><ul><ul><li>Urinary frequency and/or urgency. </li></ul></ul><ul><ul><li>Dysuria. </li></ul></ul><ul><ul><li>Scrotal pain/tenderness. </li></ul></ul><ul><ul><li>Perineal fullness (related to prostatitis). </li></ul></ul>
  37. 37. Figure 47-3 Mucopurulent cervicitis caused by Chlamydia trachomatis. ((From Cohen J, Powderly W: Infectious diseases, ed 2, St Louis, 2004, Mosby. Photo by J. Paavonen.) Downloaded from: StudentConsult (on 19 November 2007 10:58 AM) © 2005 Elsevier
  38. 38. Figure 47-4 Time course of untreated chlamydial urethritis in men. Downloaded from: StudentConsult (on 19 November 2007 10:58 AM) © 2005 Elsevier
  39. 39. Causes <ul><li>Infection with Clamydia species. </li></ul><ul><li>Socio-environmental factors, particularly in trachoma, affecting the number of infecting organisms, which in turn influence the magnitude of the initial inflammatory response and the likelihood of repeated infection. The more severe the inflammatory response the more the more likely there is to be significant fibrosis and damage to tissue. </li></ul><ul><li>Host genotypic factors that regulate the immune response and associated repair mechanisms. </li></ul><ul><li>The potential for self-induced (probably) immune damage to the host arising from chlamydial heat-shock proteins or other chlamydial antigens that are similar to, or mimic, host components. </li></ul><ul><li>The ability of chlamydiae to become sequestered at immunologically privileged or inaccessible sites ( e.g. coronary arteries for Ch. pneumoniae, the joints for reactive arthritis due to C. trachomatis. </li></ul>
  40. 40. Differential Diagnosis <ul><li>Herpes Simplex </li></ul><ul><li>Other Problems to be Considered: </li></ul><ul><li>Gonorrhea. </li></ul><ul><li>Ureaplasma infection. </li></ul><ul><li>Trichomonas infection. </li></ul><ul><li>Foreign body. </li></ul><ul><li>Periurethral abscess. </li></ul><ul><li>Mycoplasma genitalium infection. </li></ul><ul><li>Prostatitis. </li></ul>
  41. 41. Laboratory Diagnosis <ul><li>Because of the possibility of multiple sexually transmitted infections, all patients with any sexually transmitted disease (STD) should be evaluated for chlamydial infection because chlamydial treatment is included in the Centers for Disease Control and Prevention (CDC) STD treatment regimens. </li></ul><ul><li>Cytologic diagnosis </li></ul><ul><ul><li>This is used mainly for the diagnosis of infant inclusion conjunctivitis and in ocular trachoma by the demonstration of intracytoplasmic C trachomatis inclusions in HeLa cells (ie, continuously cultured carcinoma cell line used for tissue cultures). </li></ul></ul><ul><ul><li>Cytologic diagnosis also is used to evaluate endocervical scrapings, but interpretation is difficult and sensitivity and specificity have been low. </li></ul></ul>
  42. 42. Figure 47-5 Chlamydia trachomatis is grown in cell cultures and detected by staining inclusion bodies (arrows) with either iodine or specific fluorescein-labeled antibodies. Downloaded from: StudentConsult (on 19 November 2007 10:58 AM) © 2005 Elsevier
  43. 43. Figure 47-6 Fluorescent-stained elementary bodies in a clinical sample. (From Hart T, Shears P: Color atlas of medical microbiology, London, 2000, Mosby-Wolfe.) Downloaded from: StudentConsult (on 19 November 2007 10:58 AM) © 2005 Elsevier
  44. 44. Laboratory Diagnosis <ul><li>Isolation in cell culture </li></ul><ul><ul><li>C trachomatis grows well in a variety of cell lines (eg, McCoy, HeLa cells) that can be maintained in tissue culture. </li></ul></ul><ul><ul><li>Incubation in tissue culture is 40-72 hours, depending on the cell type and specific biovar. </li></ul></ul><ul><ul><li>Intracytoplasmic inclusions can be detected either by Giemsa stains or by immunofluorescent staining with monoclonal antibodies. </li></ul></ul><ul><ul><li>Because of its high specificity (100%) and sensitivity, cell culture is the only test that should be used to establish the presence or absence of infections in cases with legal implications such as rape or sexual abuse. </li></ul></ul>
  45. 45. Laboratory Diagnosis <ul><li>Antigen detection and nucleic acid hybridization </li></ul><ul><ul><li>By direct fluorescent antibody (DFA) </li></ul></ul><ul><ul><li>By enzyme-linked immunosorbent assay </li></ul></ul><ul><ul><li>Detection of chlamydial ribosomal RNA (rRNA) by hybridization with a DNA probe </li></ul></ul><ul><ul><ul><li>Advantage: This is simpler and less expensive. Most studies report sensitivities greater than 70% and specificities of 97-99% in populations of men and women with a prevalence of infection of 5% or more. Antigen detection may well be the most appropriate diagnostic test for a primary care setting in the United States if a definitive diagnostic test is required. </li></ul></ul></ul><ul><ul><ul><li>Disadvantage: It is less sensitive when compared to tissue culture. In low-prevalence populations (ie, <5% infected), a highly significant proportion of positive test results are false-positive results. Therefore, verification of a positive test result is desirable in certain cases. Such verification can be by culture (eg, a second nonculture test that identifies a different chlamydial antigen or nucleic acid sequence than the first test), a blocking antibody, or competitive probe. </li></ul></ul></ul>
  46. 46. Laboratory Diagnosis <ul><li>Detection of chlamydial genes by DNA amplification tests </li></ul><ul><ul><li>Polymerase chain reaction (PCR) </li></ul></ul><ul><ul><li>Ligase chain reaction (LCR) </li></ul></ul><ul><ul><li>Specific chlamydial rRNA using transcription-mediated amplification </li></ul></ul><ul><ul><li>Both PCR and LCR detect C trachomatis in urine or self-administered vaginal swab specimens with sensitivity comparable to that with urogenital swab specimens. </li></ul></ul>
  47. 47. Laboratory Diagnosis <ul><li>Serology </li></ul><ul><ul><li>Complement fixation test </li></ul></ul><ul><ul><ul><li>All patients with LGV or psittacosis have complement-fixing antibody titers of greater than 1:16. </li></ul></ul></ul><ul><ul><ul><li>Fifteen percent of men with urethritis and 45% of women with endocervical infection have titers 1:16 or greater. </li></ul></ul></ul><ul><ul><li>Microimmunofluorescence test </li></ul></ul><ul><ul><ul><li>This is more sensitive than complement fixation test. </li></ul></ul></ul><ul><ul><ul><li>Results are positive in 99% or more of women with cervicitis and in 80-90% of men with urethritis. </li></ul></ul></ul><ul><li>Antibody classes </li></ul><ul><ul><li>Antichlamydia IgM is uncommon in adults with genital tract infection. </li></ul></ul><ul><ul><li>The prevalence of antichlamydia IgG is high in sexually active adults, even in those who do not have an active infection, and it likely is due to past infection. </li></ul></ul><ul><ul><li>A statistically significant association exists between chlamydia-specific serum IgA and active disease. </li></ul></ul>
  48. 48. Laboratory Diagnosis <ul><ul><li>The sensitivity, specificity, and predictive values are not high enough to make any serology clinically useful in the diagnosis of active disease. Therefore, chlamydial serologies are not recommended for diagnosis of genital tract disease. </li></ul></ul><ul><li>The choice of the most appropriate test depends on the clinical setting, the facilities available, and the relative cost. </li></ul>
  49. 49. Treatment <ul><li>Medical Care: </li></ul><ul><ul><li>Patients should abstain from sexual intercourse for 7 days after single-dose therapy or until the end of a longer regimen. </li></ul></ul><ul><ul><li>Patients also should refrain from sexual intercourse until all of their sex partners have been cured. </li></ul></ul><ul><ul><li>Follow-up culture is not recommended after azithromycin or doxycycline therapy, but it may be considered in pregnancy after erythromycin or amoxicillin therapy. Nonculture tests should be avoided in this circumstance to avoid positive results from nonviable organisms. </li></ul></ul><ul><ul><li>Treatment of genitourinary chlamydial infection clearly is indicated when the infection is diagnosed or suspected. </li></ul></ul><ul><ul><li>Treatment also is indicated for sex partners of the index case if the time of the last sexual encounter was within 60 days of onset, and it should be considered for longer periods for the last sexual partner. </li></ul></ul><ul><ul><li>Treatment of chlamydia is indicated for patients being treated for gonorrhea, as well. </li></ul></ul>
  50. 50. Medication
  51. 51. Medication
  52. 52. Medication
  53. 53. Medication
  54. 54. Medication
  55. 55. Deterrence / Prevention <ul><li>Individuals who are sexually active should be aware of the risk not only of genitourinary chlamydia infection but also of the whole gamut of STDs and that the best way of avoiding infection is to practice safe sex. </li></ul><ul><li>This means using appropriate barrier protection (ie, latex condoms). </li></ul>
  56. 56. Complications <ul><li>Reiter syndrome, a reactive arthritis secondary to an immune-mediated response has been associated (among other things) with a primary chlamydial infection. </li></ul><ul><ul><li>It may present as asymmetric polyarthritis, urethritis, inflammatory eye disease, mouth ulcers, circinate balanitis, and keratoderma blennorrhagica. </li></ul></ul><ul><ul><li>While the etiology of Reiter syndrome may not be completely clear, 2 clear associations are observed. It usually follows an infectious episode, and 80% of affected patients are human leucocyte antigen-B27 (HLA-B27)–positive. </li></ul></ul><ul><ul><li>Deeper pelvic complications in the female. </li></ul></ul><ul><ul><ul><li>PID. </li></ul></ul></ul><ul><ul><ul><li>Potential infertility. </li></ul></ul></ul><ul><ul><ul><li>Spread to the newborn during parturition. </li></ul></ul></ul>
  57. 57. Prognosis <ul><li>Treatment failures with primary therapies are quite rare. </li></ul><ul><li>Relapse may occur with alternative therapies. </li></ul><ul><li>Reinfection is very common and is related to nontreatment of infected sexual partners or acquisition from a new partner. </li></ul>
  58. 58. Patient Education <ul><li>Appropriate counseling of infected individuals must be performed. </li></ul><ul><ul><li>Counsel patients to avoid reinfection from the sexual partner by facilitating treatment of the contact prior to sexual reexposure. </li></ul></ul><ul><ul><li>Counsel patients to use latex condoms to prevent reinfection. </li></ul></ul>
  59. 59. Miscellaneous <ul><li>Medical/Legal Pitfalls: </li></ul><ul><ul><li>Remembering to treat patients for chlamydial genitourinary infection even when gonococcal infection is clearly diagnosed is important. </li></ul></ul><ul><ul><li>Consider testing the cure when treatment with amoxicillin or erythromycin is used instead of the standard doxycycline or azithromycin regimens. </li></ul></ul>
  60. 60. Lymphogranuloma Venereum (LGV) <ul><li>C. trachomatis is an obligate intracellular bacterium. </li></ul><ul><li>Of the 14 known clinical serotypes, only the L1, L2, and L3 serotypes cause LGV. </li></ul><ul><li>These serotypes are more virulent and invasive compared to other chlamydial serotypes. </li></ul><ul><li>Infection occurs after direct contact with the skin or mucous membranes of an infected partner. </li></ul><ul><li>The organism does not penetrate intact skin. </li></ul><ul><li>The organism then travels by lymphatics to regional lymph nodes, where they replicate within macrophages and elicit systemic disease. </li></ul><ul><li>While transmission is predominantly sexual, cases of transmission through laboratory accidents, fomites, and nonsexual contact have been reported. </li></ul>
  61. 61. Lymphogranuloma Venereum (LGV) <ul><li>LGV occurs in 3 stages. </li></ul><ul><ul><ul><li>The first stage, which is often unrecognized, consists of a rapidly healing, painless genital papule or pustule. </li></ul></ul></ul><ul><ul><ul><li>The second stage, consisting of painful inguinal lymphadenopathy, occurs 2-6 weeks after the primary lesion. </li></ul></ul></ul><ul><ul><ul><li>The third stage, which is more common in women, may occur many years after the original infection and is characterized by proctocolitis. </li></ul></ul></ul>
  62. 62. Epidemiology <ul><li>Frequency: </li></ul><ul><ul><li>In the US: Rates of LGV have steadily declined since 1972, with 113 known cases reported in 1997. </li></ul></ul><ul><ul><li>Internationally: LGV is an uncommon disease, although it may account for 2-10% of patients with genital ulcer disease in selected areas of India and Africa. The disease is most commonly found in areas of the Caribbean, Central America, Southeast Asia, and Africa. </li></ul></ul><ul><li>Mortality/Morbidity: </li></ul><ul><ul><li>With appropriate treatment, the disease is easily eradicated. </li></ul></ul><ul><ul><li>Death is a rare complication but could possibly result from a small bowel obstruction or perforation secondary to rectal scarring. </li></ul></ul><ul><ul><li>Morbidity is common, especially during the third stage of the disease, and includes such conditions as proctocolitis, perirectal fissures, abscesses, strictures, and rectal stenosis. </li></ul></ul><ul><ul><li>A chronic inflammatory response may lead to hyperplasia of the intestinal and perirectal lymphatics, causing lymphorrhoids, which are similar to hemorrhoids. </li></ul></ul>
  63. 63. Epidemiology <ul><ul><li>Strictures and fistulous tracts may lead to chronic lymphatic obstruction, resulting in elephantiasis, thickening or fibrosis of the labia, and edema or gross distortion of the penis and scrotum. </li></ul></ul><ul><ul><li>Reports show an association between adenocarcinoma (primarily rectal adenocarcinoma) and chronic untreated LGV. </li></ul></ul><ul><li>Sex: </li></ul><ul><ul><li>LGV is an STD and probably affects both sexes equally, although it is more commonly reported in men. </li></ul></ul><ul><ul><li>This predilection may be because early manifestations of LGV are more apparent in men and are thus diagnosed more readily. </li></ul></ul><ul><ul><li>Men typically present with the acute form of the disease, whereas women often present later, after developing complications from late disease. </li></ul></ul><ul><li>Age: </li></ul><ul><ul><li>LGV may affect any age but has a peak incidence in the sexually active population aged 15-40 years. </li></ul></ul>
  64. 64. Clinical Manifestation <ul><li>The clinical course of LGV consists of the following stages: </li></ul><ul><li>First stage (primary LGV) </li></ul><ul><ul><li>This stage occurs 3-30 days after inoculation. </li></ul></ul><ul><ul><li>Primary LGV begins as a small, painless papule or pustule that may erode to form a small, asymptomatic herpetiform ulcer that usually heals rapidly without scarring. </li></ul></ul><ul><ul><li>The most common sites of infection for men include the coronal sulcus, prepuce, glans, and scrotum. </li></ul></ul><ul><ul><li>Rarely, symptoms of urethritis occur. </li></ul></ul><ul><ul><li>The most common sites of infection in women include the posterior vaginal wall, posterior cervix, fourchette, and vulva. </li></ul></ul><ul><ul><li>The initial lesion, especially in women, often goes unnoticed by the patient. </li></ul></ul>
  65. 65. Clinical Manifestation <ul><li>Second stage (secondary LGV) </li></ul><ul><ul><li>Secondary LGV begins 2-6 weeks after the primary lesion. </li></ul></ul><ul><ul><li>This second stage consists of painful regional lymphadenopathy (usually in the inguinal and/or femoral lymph nodes). </li></ul></ul><ul><ul><li>Painful, swollen lymph nodes coalesce to form buboes, which may rupture in as many as one third of patients. Those that do not rupture harden, then slowly resolve. </li></ul></ul><ul><ul><li>Inguinal lymphadenopathy occurs in only 20-30% of females with LGV; they more typically have involvement of the deep iliac or perirectal nodes and may only present with nonspecific back and/or abdominal pain. </li></ul></ul><ul><ul><li>This stage is when most men present and are diagnosed; most women are not diagnosed in this stage because of their lack of inguinal lymphadenopathy. </li></ul></ul><ul><ul><li>Constitutional symptoms associated with the second stage include fever, chills, myalgias, and malaise. </li></ul></ul>
  66. 66. Clinical Manifestation <ul><ul><li>Systemic spread may lead to the following conditions: </li></ul></ul><ul><ul><ul><li>Arthritis. </li></ul></ul></ul><ul><ul><ul><li>Ocular inflammatory disease. </li></ul></ul></ul><ul><ul><ul><li>Cardiac involvement. </li></ul></ul></ul><ul><ul><ul><li>Pulmonary involvement. </li></ul></ul></ul><ul><ul><ul><li>Aseptic meningitis. </li></ul></ul></ul><ul><ul><ul><li>Hepatitis or perihepatitis. </li></ul></ul></ul>
  67. 67. Clinical Manifestation <ul><li>Third stage (tertiary LGV) </li></ul><ul><ul><li>Tertiary LGV is termed genitoanorectal syndrome. </li></ul></ul><ul><ul><li>This condition is more common in women, secondary to their lack of symptoms during the first two stages. </li></ul></ul><ul><ul><li>Rectal involvement is more common in men who have sex with men and in women who practice anal-receptive intercourse. </li></ul></ul><ul><ul><li>Tertiary LGV is characterized by proctocolitis. </li></ul></ul><ul><ul><li>Symptoms include the following conditions: </li></ul></ul><ul><ul><ul><li>Malaise. </li></ul></ul></ul><ul><ul><ul><li>Weight loss. </li></ul></ul></ul><ul><ul><ul><li>Bloody purulent discharge. </li></ul></ul></ul><ul><ul><ul><li>Fever. </li></ul></ul></ul><ul><ul><ul><li>Rectal pain. </li></ul></ul></ul><ul><ul><ul><li>Tenesmus. </li></ul></ul></ul>
  68. 68. Physical Signs & Symptoms <ul><li>Large fluctuant buboes or any otherwise unexplained perianal deformity in a young female should suggest a diagnosis of LGV. </li></ul><ul><li>First stage (primary LGV) </li></ul><ul><ul><li>The initial lesion is usually a small, unnoticed painless papule, shallow ulcer, or herpetiform lesion in the genital area. </li></ul></ul><ul><ul><li>Initial lesions may be differentiated from the more common herpetic lesions by the lack of pain associated with the lesion. Differentiation from a syphilitic chancre is more problematic and requires serologic testing. </li></ul></ul><ul><li>Second stage (secondary LGV) </li></ul><ul><ul><li>Secondary LGV is characterized by painful lymph nodes (usually unilateral) known as buboes. </li></ul></ul><ul><ul><li>Enlargement of the inguinal nodes above and the femoral nodes below the inguinal ligament leads to the classic groove sign, which is observed in one third of affected men. </li></ul></ul><ul><ul><li>Inguinal lymphadenopathy results from a primary lesion of the anterior vulva, penis, or urethra. </li></ul></ul><ul><ul><li>Perirectal or pelvic lymphadenopathy results from a primary lesion involving the posterior vulva, vagina, or anus. </li></ul></ul><ul><ul><li>Affected nodes often coalesce and form abscesses, which can rupture and form sinus tracts. </li></ul></ul>
  69. 69. Physical Signs & Symptoms <ul><li>Third stage (tertiary LGV) </li></ul><ul><ul><li>Tertiary LGV most often manifests in women. </li></ul></ul><ul><ul><li>Patients initially develop proctocolitis. </li></ul></ul><ul><ul><li>Patients may present with perirectal fistulas, abscesses, strictures, and rectal stenosis. </li></ul></ul><ul><ul><li>Hyperplasia of intestinal and perirectal lymphatics may form lymphorrhoids, which are similar to hemorrhoids. </li></ul></ul><ul><ul><li>Patients may develop strictures and fistulous tracts secondary to repeated tissue scarring and repair. </li></ul></ul><ul><ul><li>Enlargement, thickening, and fibrosis of the labia may occur in women, a condition termed esthiomene. </li></ul></ul><ul><ul><li>Chronic lymphatic obstruction may lead to elephantiasis of the genitals. </li></ul></ul><ul><ul><li>Penile and scrotal edema and distortion have been termed saxophone penis. </li></ul></ul>
  70. 70. Figure 47-2 Patient with lymphogranuloma venereum causing unilateral vulvar lymphedema and inguinal buboes. (From Cohen J, Powderly W: Infectious diseases, ed 2, St Louis, 2004, Mosby.) Downloaded from: StudentConsult (on 19 November 2007 10:58 AM) © 2005 Elsevier
  71. 71. Causes <ul><li>The L1, L2, and L3 serovars of C trachomatis cause LGV. </li></ul><ul><li>Risk factors include residing in or visiting endemic areas, practicing anal-receptive intercourse, eschewing condoms, and working in the commercial sex trade. </li></ul>
  72. 72. Differential Diagnosis <ul><li>Empyema. </li></ul><ul><li>Pleuropulmonary Encephalopathy. </li></ul><ul><li>Dialysis. </li></ul><ul><li>Other Problems to be Considered: </li></ul><ul><li>Granuloma inguinale. </li></ul><ul><li>Cancer. </li></ul><ul><li>Hodgkin disease. </li></ul><ul><li>Inflammatory proctocolitis. </li></ul><ul><li>Mycobacterial infection. </li></ul><ul><li>Fungal infection. </li></ul>
  73. 73. Laboratory Diagnosis <ul><li>Lab Studies: </li></ul><ul><ul><li>Diagnosis is problematic because of the difficulty in culturing the organism and cross-reactivity of the many different serotypes. </li></ul></ul><ul><ul><li>Needle aspiration of an involved bubo is the best method to obtain tissue for culture. </li></ul></ul><ul><ul><li>Culture of C trachomatis, while definitive diagnostically, is technically demanding and expensive and yields an isolate only 30% of the time. </li></ul></ul><ul><ul><li>Because of its systemic nature, the disease produces a strong immunologic response that is readily evident on complement fixation testing. </li></ul></ul><ul><ul><ul><li>Cross-reactivity between various chlamydial infections occurs on complement fixation testing. </li></ul></ul></ul><ul><ul><ul><li>Chlamydial urethritis, cervicitis, or conjunctivitis rarely produces titers greater than 1:16. LGV titers are usually more than 1:1024. </li></ul></ul></ul><ul><ul><ul><li>A complement fixation titer greater than 1:64, when coupled with the appropriate clinical scenario, is considered diagnostic of LGV. </li></ul></ul></ul>
  74. 74. Laboratory Diagnosis <ul><ul><ul><li>Immunofluorescent testing with monoclonal antibodies and polymerase chain reaction (PCR) testing are also reported to be effective; however, these tests are not widely available for commercial use. </li></ul></ul></ul><ul><li>Procedures: Needle aspiration of involved buboes may be performed to ease discomfort or to obtain tissue for culture. </li></ul><ul><li>Histologic Findings: Histologic findings of lymph node biopsies performed in the second and third stages of the disease typically reveal stellate abscesses. </li></ul>
  75. 75. Treatment <ul><li>Medical Care: The complete treatment of patients with LGV includes appropriate antimicrobial coverage and drainage of infected buboes. </li></ul><ul><li>The recommended medical treatment for LGV involves one of the following antibiotic regimens: </li></ul><ul><ul><li>Doxycycline 100 mg PO bid for 21 d </li></ul></ul><ul><ul><li>Erythromycin base 500 mg PO qid for 21 d </li></ul></ul><ul><li>Surgical Care: Needle aspiration or incision and drainage of involved inguinal nodes may be required for pain relief and prevention of ulcer formation. Some of the late complications of the third stage of LGV may require surgical repair. </li></ul><ul><li>Consultations: Surgical consultation for lymphadenopathy is generally not required unless extensive buboes require further exploration. For tertiary disease, appropriate surgical consultation is indicated. </li></ul><ul><li>Activity: No restrictions to physical activities are required; however, patients should abstain from sexual contact until the infection resolves completely. </li></ul>
  76. 76. Medication <ul><li>The goal of therapy is to eradicate the organism. </li></ul><ul><li>Drug Category: Antibiotics -- Totally eradicate the causative organism </li></ul>
  77. 77. Medication
  78. 78. Follow Up <ul><li>Further Outpatient Care: </li></ul><ul><ul><li>For patients who have had incision and drainage of buboes, appropriate outpatient follow-up care may be required to ensure complete healing and to prevent secondary infections. </li></ul></ul>
  79. 79. Deterrence / Prevention <ul><li>Patients, especially those traveling to endemic areas, should be counseled about safe-sex practices, including condom use. Advise the patient to refrain from intercourse with high-risk individuals. </li></ul><ul><li>Inform patients that recovery from infection does not confer immunity against future infection. </li></ul>
  80. 80. Complications <ul><li>Bubo rupture may lead to fistulas and sinus tracts. This complication typically occurs during the first stage (primary LGV) of infection. </li></ul><ul><li>Proctocolitis may lead to fissures, fistulas, abscess, scarring, and strictures. </li></ul>
  81. 81. Prognosis <ul><li>With prompt and appropriate antibiotic therapy, the prognosis is excellent and patients typically make a full recovery. </li></ul><ul><li>Patients must be informed that reinfection and relapses may occur. </li></ul>
  82. 82. Patient Education <ul><li>Inform patients how to avoid high-risk sexual activities by using condoms and avoiding sexual intercourse with high-risk sexual partners. </li></ul>
  83. 83. Miscellaneous <ul><li>Medical/Legal Pitfalls: </li></ul><ul><ul><li>Failure to consider the diagnosis </li></ul></ul><ul><ul><li>Failure to screen for HIV, herpes simplex virus (HSV), and syphilis. </li></ul></ul>
  84. 84. Summary of Chlamydia trachomatis <ul><li>Physiology and Structure </li></ul><ul><ul><li>Small, gram-negative rods with no peptidoglycan layer in cell wall </li></ul></ul><ul><ul><li>Strict intracellular parasite of humans. </li></ul></ul><ul><ul><li>Two distinct forms: infectious elementary bodies and noninfectious reticulate bodies. </li></ul></ul><ul><ul><li>Lipopolysaccharide antigen shared by Chlamydia and Chlamydophila species. </li></ul></ul><ul><ul><li>Major outer membrane proteins are species specific. </li></ul></ul><ul><ul><li>Two biovars associated with human disease: trachoma (with 15 serovars) and lymphogranuloma venereum (LGV; four serovars). </li></ul></ul><ul><ul><li>Infects nonciliated columnar, cuboidal, and transitional epithelial cells. </li></ul></ul><ul><li>Virulence </li></ul><ul><ul><li>Intracellular replication. </li></ul></ul><ul><ul><li>Prevents fusion of phagosome with cellular lysosomes. </li></ul></ul><ul><ul><li>Pathologic effects of trachoma caused by repeated infections. </li></ul></ul>
  85. 85. Summary of Chlamydia trachomatis <ul><li>Epidemiology </li></ul><ul><ul><li>Most common sexually transmitted bacteria in United States. </li></ul></ul><ul><ul><li>Ocular trachoma worldwide (most common in Middle East, North Africa, India), with blindness developing in 7 to 9 million patients. </li></ul></ul><ul><ul><li>LGV highly prevalent in Africa, Asia, and South America. </li></ul></ul><ul><li>Diseases </li></ul><ul><ul><li>Trachoma: Chronic, inflammatory granulomatous process of eye surface, leading to corneal ulceration, scarring, pannus formation, and blindness. </li></ul></ul><ul><ul><li>Adult inclusion conjunctivitis: Acute process with mucopurulent discharge, dermatitis, corneal infiltrates, and corneal vascularization in chronic disease. </li></ul></ul><ul><ul><li>Neonatal conjunctivitis: Acute process characterized by a mucopurulent discharge. </li></ul></ul><ul><ul><li>Infant pneumonia: After a 2- to -3-week incubation period, the infant develops rhinitis, followed by bronchitis with a characteristic dry cough. </li></ul></ul>
  86. 86. Summary of Chlamydia trachomatis <ul><ul><li>Urogenital infections: Acute process involving the genitourinary tract with characteristic mucopurulent discharge; asymptomatic infections common in women. </li></ul></ul><ul><ul><li>Lymphogranuloma venereum: A painless ulcer develops at the site of infection that spontaneously heals, followed by inflammation and swelling of lymph nodes draining the area, then progression to systemic symptoms. </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Culture is highly specific but is relatively insensitive. </li></ul></ul><ul><ul><li>Antigen tests (DFA, ELISA) are relatively insensitive. </li></ul></ul><ul><ul><li>Molecular amplification tests are the most sensitive and specific tests currently available. </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Culture is highly specific but is relatively insensitive </li></ul></ul><ul><ul><li>Antigen tests (DFA, ELISA) are relatively insensitive. </li></ul></ul><ul><ul><li>Molecular amplification tests are the most sensitive and specific tests currently available. </li></ul></ul>
  87. 87. Summary of Chlamydia trachomatis <ul><li>Treatment, Prevention, and Control </li></ul><ul><ul><li>Treat LGV with tetracyclines, macrolides, or sulfisoxazole </li></ul></ul><ul><ul><li>Treat ocular or genital infections with azithromycin or doxycycline </li></ul></ul><ul><ul><li>Treat newborn conjunctivitis or pneumonia with erythromycin </li></ul></ul><ul><ul><li>Safe sex practices and prompt treatment of patient and sexual partners help control infections. </li></ul></ul>
  89. 89. Taxonomy <ul><li>Chlamydophila species: Members of the genus Chlamydophila infect both birds and mammals. </li></ul><ul><ul><li>Ch. Psittaci causes respiratory, gut and systemic infections in birds, particularly in psittacine and ornithine birds (budgerigars, parrots) and may lead to severe and sometimes fatal pneumonia in man (psittacosis or ornithosis). </li></ul></ul><ul><ul><li>Ch. Pneumoniae, the former TWAR (Taiwan acute respiratory) agent, is a common cause of mild to severe acute respiratory disease in man. </li></ul></ul><ul><ul><li>Ch. abortus causes abortion in sheep, rarely leading to abortion in pregnant women exposed to infected sheep. Sheep and goat often carry a related organism Ch. percorum, in their guts. </li></ul></ul><ul><ul><li>Ch. caviae causes oculogenital infection in guinea pigs and is an important experimental model of human infection. </li></ul></ul>
  90. 90. Chlamydophila psittaci <ul><li>Psittacosis is an infection caused by the obligatory intracellular bacterium Chlamydophila psittaci. The term psittacosis is derived from the Greek word for parrot, psittakos, and was first used by Morange in 1892. </li></ul><ul><li>This bacterium can infect parrots, parakeets, canaries, and other avian species (eg, turkeys, pigeons, ducks). Another term for this infection is ornithosis, which describes the infection caused by nonpsittacine birds. </li></ul><ul><li>The largest epidemic occurred in 1930 and affected 750-800 individuals. This epidemic led to the isolation of Ch. psittaci in several laboratories in Europe and the United States. </li></ul><ul><li>Psittacosis is an occupational disease of zoo and pet shop employees, poultry farmers, and ranchers. </li></ul><ul><li>Human-to-human transmission is rare, but possible. These cases may cause more severe disease than avian-acquired psittacosis. </li></ul>
  91. 91. Pathophysiology <ul><li>The primary route for infection is through the respiratory system. </li></ul><ul><li>Infection develops after inhaling organisms from aerosolized dried avian excreta or respiratory secretions from sick birds. </li></ul><ul><li>Ch. psittaci attaches to the respiratory epithelial cells. </li></ul><ul><li>After the initial inoculation, the organism spreads via the blood stream to the reticuloendothelial system. </li></ul><ul><li>Subsequently, secondary bacteremia causes lung infection. </li></ul><ul><li>Humans may acquire disease by handling sick birds. </li></ul><ul><li>Mouth-to-beak resuscitation also is implicated in transmission. </li></ul><ul><li>Transient exposure to infected birds may cause symptomatic infection, even in visitors to pet shops. </li></ul>
  92. 92. Epidemiology <ul><li>Frequency: </li></ul><ul><ul><li>In the US: Reports show up to 200 cases of psittacosis annually. From 1988-97, the US Centers for Disease Control and Prevention (CDC) received 766 reports of psittacosis, which probably is an underestimate of the actual number of cases because psittacosis is difficult to diagnose, is covered by macrolide antimicrobials (which may be employed empirically for therapy of community-acquired pneumonia), and often is not reported. </li></ul></ul><ul><ul><li>Internationally: Psittacosis is found worldwide. The incidence seems to be increasing in developed countries, which is correlated to the import of exotic birds. </li></ul></ul><ul><li>Mortality/Morbidity: The mortality rate prior to the advent of antimicrobial treatment was approximately 15-20%. The mortality rate is less than 1% with appropriate antibiotic therapy. </li></ul><ul><li>Breed: Certain strains of Ch psittaci infect sheep, goats, and cows and may cause chronic infection and abortion. </li></ul>
  93. 93. Epidemiology <ul><li>Race: No race predilection is observed. </li></ul><ul><li>Sex: No sex predilection is observed. </li></ul><ul><li>Age: Psittacosis occurs in all age groups, including children. The infection is more common among individuals in the middle decades of life. </li></ul>
  94. 94. Clinical Manifestation <ul><li>The incubation period generally is 5-14 days. The longest observed incubation time was 54 days. The predominant presentation is respiratory tract infection with constitutional symptoms. Clinical findings are variable. </li></ul><ul><li>Constitutional </li></ul><ul><ul><li>Fever (50-90%). </li></ul></ul><ul><ul><li>Chills. </li></ul></ul><ul><ul><li>Malaise. </li></ul></ul><ul><li>Respiratory </li></ul><ul><ul><li>Cough (50-90%), usually not productive. </li></ul></ul><ul><ul><li>Pleuritic chest pain (rare). </li></ul></ul><ul><ul><li>Dyspnea. </li></ul></ul><ul><ul><li>Sore throat and mild pharyngitis (common). </li></ul></ul><ul><ul><li>Epistaxis (common). </li></ul></ul>
  95. 95. Clinical Manifestation <ul><li>Gastrointestinal </li></ul><ul><ul><li>Nausea and vomiting (uncommon). </li></ul></ul><ul><ul><li>Abdominal pain (uncommon). </li></ul></ul><ul><ul><li>Diarrhea (rare). </li></ul></ul><ul><ul><li>Jaundice (rare). </li></ul></ul><ul><li>Neurological </li></ul><ul><ul><li>Severe headache (common). </li></ul></ul><ul><ul><li>Photophobia (common). </li></ul></ul><ul><ul><li>Agitation and lethargy. </li></ul></ul><ul><li>Dermatological - Includes facial rash (Horder spots). </li></ul>
  96. 96. Figure 47-7 Time course of Chlamydophila psittaci infection. Downloaded from: StudentConsult (on 19 November 2007 10:58 AM) © 2005 Elsevier
  97. 97. Physical Signs & Symptoms <ul><li>Disease may range from mild insidious presentations to severe pneumonia that requires mechanical ventilation. </li></ul><ul><li>Respiratory </li></ul><ul><ul><li>Nonspecific auscultatory findings that often underestimate clinical and radiographic findings may develop. </li></ul></ul><ul><ul><li>Patients may develop fatal pulmonary embolism and pulmonary infarction. </li></ul></ul><ul><ul><li>Pleural effusion is rare. </li></ul></ul><ul><li>Cardiac </li></ul><ul><ul><li>Relative bradycardia is common. </li></ul></ul><ul><ul><li>Physicians may observe pericarditis, culture-negative endocarditis, and myocarditis. </li></ul></ul><ul><li>Gastrointestinal </li></ul><ul><ul><li>Splenomegaly occurs in 10-70% of patients, depending on the study. </li></ul></ul><ul><ul><li>When present, this sign suggests psittacosis in patients with pneumonia. </li></ul></ul>
  98. 98. Physical Signs & Symptoms <ul><li>Neurological </li></ul><ul><ul><li>Patients may develop meningitis, encephalitis, seizures, and Guillain-Barré syndrome, but these are rare. </li></ul></ul><ul><ul><li>Cerebrospinal fluid (CSF) findings usually are normal. </li></ul></ul><ul><li>Dermatological </li></ul><ul><ul><li>Patients may develop Horder spots, which are macular rashes resembling the rose spots observed in typhoid fever but appearing on the face. </li></ul></ul><ul><ul><li>Patients also may develop erythema multiforme and erythema nodosum. </li></ul></ul><ul><li>Hematological </li></ul><ul><ul><li>Patients may develop anemia secondary to hemolysis. </li></ul></ul><ul><ul><li>Disseminated intravascular coagulation may occur in patients with overwhelming infections. </li></ul></ul><ul><li>Renal symptoms include acute glomerulonephritis and tubulointerstitial nephritis. </li></ul><ul><li>Musculoskeletal symptoms include reactive arthritis that usually is polyarticular. </li></ul>
  99. 99. Physical Signs & Symptoms <ul><li>Stages of disease progression </li></ul><ul><ul><li>Flu-like syndromes without radiographic abnormalities. </li></ul></ul><ul><ul><li>Mild-to-moderate pneumonia. </li></ul></ul><ul><ul><li>Severe pneumonia. </li></ul></ul><ul><ul><li>Acute respiratory failure, sepsis, and septic shock. </li></ul></ul>
  100. 100. Causes <ul><li>Psittacosis is an infectious disease caused by the obligatory intracellular bacterium, Ch. psittaci. </li></ul><ul><li>Ch. psittaci is associated with psittacine birds and poultry. </li></ul><ul><li>Psittacosis is an occupational disease of poultry farmers, pet shop workers, and veterinarians. </li></ul><ul><li>Relapses may occur. </li></ul><ul><li>Since the organism is a bacterium, it is unlikely that major protective immunity will develop after a single episode of disease. </li></ul><ul><li>The exact risk of recurrence upon reexposure is unknown. It is reasonable to advise advoidance of infected birds. </li></ul>
  101. 101. Differential Diagnosis <ul><li>Brucellosis. </li></ul><ul><li>Chamydophila pneumonia. </li></ul><ul><li>Infective endocarditis. </li></ul><ul><li>Legionellosis. </li></ul><ul><li>Mycoplasma infections. </li></ul><ul><li>Pneumonia, Bacterial. </li></ul><ul><li>Pneumonia, Fungal. </li></ul><ul><li>Pneumonia, Viral. </li></ul><ul><li>Q Fever. </li></ul><ul><li>Tuberculosis. </li></ul><ul><li>Tularemia. </li></ul><ul><li>Typhoid Fever. </li></ul>
  102. 102. Laboratory Diagnosis <ul><li>White blood cell counts are normal to mildly decreased. </li></ul><ul><li>Liver function tests are usually mildly increased. </li></ul><ul><li>ESR erythrocyte sedimentation rate (ESR) may be elevated. </li></ul><ul><li>Urinalysis may show mild proteinuria with less than 3500 mg per day. </li></ul><ul><li>Culturing of C psittaci is possible, but this practice is avoided because it can be hazardous to laboratory personnel. </li></ul><ul><li>Test acute-phase serum and convalescent-phase serum 2 weeks after onset to confirm a 4-fold or greater rise in the titer. Complement fixation (CF) is not a specific test and may cross-react with other chlamydial species. </li></ul><ul><li>Physicians use microimmunofluorescence (MIF) and polymerase chain reaction (PCR) studies to detect different chlamydia species. PCR may develop into an early and specific detection test. </li></ul><ul><li>Enzyme-linked immunosorbent assay (ELISA) and direct immunofluorescence (DIF) are experimental in this setting, but physicians have used them to help diagnose C psittaci infection. </li></ul><ul><li>Serologic tests are the mainstays of diagnosis; however, because of the delayed appearance of specific antibodies, these tests are not helpful in emergent clinical management. </li></ul>
  103. 103. Laboratory Diagnosis <ul><li>Imaging Studies: </li></ul><ul><ul><li>Chest radiographic findings are abnormal in up to 90% of cases. </li></ul></ul><ul><ul><li>The most common finding is unilateral, lower-lobe dense infiltrate/consolidation. Psittacosis may present in a bilateral, nodular, miliary, or interstitial pattern. </li></ul></ul><ul><ul><li>Rarely, patients may develop pleural effusion. </li></ul></ul><ul><ul><li>Chest radiograph abnormalities resolve within an average of 6 weeks (range 3-20 wk). </li></ul></ul><ul><li>Other Tests: </li></ul><ul><ul><li>Few patients have CSF abnormalities. </li></ul></ul><ul><ul><li>CDC criteria for Ch. psittaci infection include the following: </li></ul></ul><ul><ul><ul><li>Confirmed cases produce a positive culture result for Ch. psittaci from respiratory secretions, a 4-fold increase in antibody titer in 2 serum samples obtained via CF or MIF 2 weeks apart, or immunoglobulin M (IgM) antibodies against Ch. psittaci, as detected by MIF to a reciprocal titer of 16. </li></ul></ul></ul><ul><ul><ul><li>Possible cases show the presence of antibodies against C psittaci with titers of 1:32 by CF or MIF. </li></ul></ul></ul>
  104. 104. Laboratory Diagnosis <ul><li>Histologic Findings: </li></ul><ul><ul><li>Findings may include tracheobronchitis and interstitial pneumonitis with air space involvement and predominant mononuclear cell infiltration. </li></ul></ul><ul><ul><li>Findings also may include macrophages containing cytoplasmic inclusion bodies (ie, Levinthal-Coles-Lillie [LCL] bodies), focal necrosis of hepatocytes along with Kupffer cell hyperplasia in the liver, and hepatic noncaseating granulomata. </li></ul></ul>
  105. 105. Treatment <ul><li>Medical Care: Consider the diagnosis of psittacosis in patients with community-acquired pneumonia who have had exposure to birds. The mainstay of medical care is antibiotic therapy. </li></ul><ul><li>Consultations: </li></ul><ul><ul><li>Notify public health authorities about cases of psittacosis. </li></ul></ul><ul><ul><li>Obtain infectious disease consultation. </li></ul></ul><ul><li>Diet: Patients require no specific diet. </li></ul><ul><li>Activity: Patients do not require activity restrictions. </li></ul>
  106. 106. Medication <ul><li>The goals of pharmacotherapy are to reduce morbidity and to prevent complications. </li></ul><ul><li>Drug Category: </li></ul><ul><ul><li>Antibiotics -- Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the clinical setting. </li></ul></ul><ul><ul><li>Tetracycline and doxycycline are the antibiotics of choice. Treating patients for 2-3 weeks usually prevents relapse. </li></ul></ul><ul><ul><li>Clinical response occurs within 24-72 hours. </li></ul></ul><ul><ul><li>Use erythromycin in children younger than 9 years and in pregnant women. Chloramphenicol is a third alternative antibiotic. </li></ul></ul><ul><ul><li>Doxycycline remains the drug of choice. Macrolide and quinolone failures have been observed. </li></ul></ul>
  107. 107. Medication
  108. 108. Medication
  109. 109. Medication
  110. 110. Follow Up <ul><li>Further Inpatient Care: </li></ul><ul><ul><li>Severe infection requires IV antibiotics and hospital admission. </li></ul></ul><ul><ul><li>Isolation is not indicated during hospital stay. </li></ul></ul><ul><li>Further Outpatient Care: </li></ul><ul><ul><li>Instruct patients to see a physician if symptoms recur (ie, relapse). </li></ul></ul><ul><ul><li>Patients with relapses may need prolonged retreatment (eg, 3-4 wk). </li></ul></ul><ul><li>In/Out Patient Meds: </li></ul><ul><ul><li>Patients may require doxycycline, usually 100 mg IV; alternatively, consider PO administration with the same dose twice a day. </li></ul></ul><ul><ul><li>Chloramphenicol is the third drug of choice, but it rarely is used in the United States. </li></ul></ul><ul><ul><li>Consider changing erythromycin from IV to PO administration (eg, 500 mg qid). </li></ul></ul><ul><ul><li>Chloramphenicol rarely is used in the United States because it may cause agranulocytosis. </li></ul></ul><ul><ul><li>Consider changing quinolones from IV to PO administration. </li></ul></ul>
  111. 111. Follow Up <ul><li>Transfer: </li></ul><ul><ul><li>Transfer patients with acute respiratory failure to an intensive care unit. </li></ul></ul>
  112. 112. Deterrence / Prevention <ul><li>Instruct high-risk individuals to avoid handling newly imported or sick birds. </li></ul>
  113. 113. Complications <ul><li>Acute respiratory failure. </li></ul><ul><li>Pericarditis. </li></ul><ul><li>Myocarditis. </li></ul><ul><li>Culture-negative endocarditis. </li></ul><ul><li>Renal failure (rare, only a few case reports). </li></ul><ul><li>Disseminated intravascular coagulation (rare). </li></ul><ul><li>Arterial embolism (rare, 2 case reports). </li></ul><ul><li>Pancreatitis. </li></ul><ul><li>Reactive arthritis. </li></ul><ul><li>Transverse myelitis. </li></ul><ul><li>Meningitis or encephalitis. </li></ul>
  114. 114. Prognosis <ul><li>Prognosis: </li></ul><ul><ul><li>With appropriate antibiotic therapy, the mortality rate is less than 1%. </li></ul></ul><ul><ul><li>A poor prognosis is associated with hypoxemia and renal failure. </li></ul></ul>
  115. 115. Patient Education <ul><li>Warn pet owners and pet shop and poultry workers to be aware of possible respiratory symptoms and fever. </li></ul>
  116. 116. Miscellaneous <ul><li>Medical/Legal Pitfalls: </li></ul><ul><ul><li>Failure to make the proper diagnosis is a medicolegal pitfall. (Psittacosis may be easily overlooked, but adherence to published guidelines for the management of community-acquired pneumonia covers this pathogen.) </li></ul></ul><ul><ul><li>Failure to realize that the natural history of the disease carries approximately 15% mortality and the concomitant need for appropriate empiric therapy. </li></ul></ul><ul><ul><li>Failure to maintain a high index of suspicion </li></ul></ul><ul><ul><li>Failure to inquire about bird exposure and occupational considerations </li></ul></ul><ul><ul><li>Failure to realize that doxycycline is not recommended for children because it may cause tooth discoloration </li></ul></ul>
  117. 117. Miscellaneous <ul><li>Special Concerns: </li></ul><ul><ul><li>Educate high-risk individuals about the symptoms of psittacosis. These individuals include zoo workers and pet shop owners, among others. Individuals must keep accurate records of all bird transactions. </li></ul></ul><ul><ul><li>Avoid purchasing or selling birds that have ocular or nasal discharge, diarrhea, or low body weight. </li></ul></ul><ul><ul><li>Isolate imported and exotic birds for 30-45 days. Test these birds, or treat them with prophylaxis. </li></ul></ul>
  118. 118. Chlamydophila pneumoniae <ul><li>C. pneumoniae was first isolated from the conjunctiva of a child in Taiwan. </li></ul><ul><li>It was initially considered a psittacosis strain because the morphology of the inclusions produced in cell culture was similar. </li></ul><ul><li>However, it was subsequently shown that the Taiwan isolate (TW-183) was related serologically to a pharyngeal isolate, designated AR-39, and was unrelated to psittacosis strains. </li></ul><ul><li>This new organism was initially called TWAR, then classified as Chlamydia pneumoniae, and, finally, placed in the new genus Chlamydophila. </li></ul><ul><li>Only a single serotype (TWAR) has been identified. Respiratory secretions transmit infection; no animal reservoir has been identified. </li></ul>
  119. 119. Chlamydophila pneumoniae <ul><li>This organism causes pneumonia, phayngitis, bronchitis, otitis, and sinusitis with an incubation period of about 21 days. </li></ul><ul><li>It is suspected to be a significant cause of acute exacerabations of asthama. </li></ul><ul><li>Ch. peumoniae is one of the commonest causes of community acquired pneumonia, seldom identified as the causal agent because laboratory tests for its diagnosis are not widely used. </li></ul><ul><li>The organism is chronic, often insiduous, respiratory pathogen to which there appears to be little immunity. </li></ul><ul><li>Clinical reactivation of existing infection and reinfection and reinfection are probably common, although the two are difficult to distinguish. </li></ul><ul><li>Seroepidemiological studies indicate that some 60 to 80% of people worldwide become infected with Ch. pneumoniae during their life, atan incidence of 1 to 2 % per year. </li></ul>
  120. 120. Chlamydophila pneumoniae
  121. 121. Chlamydophila pneumoniae <ul><li>Ch. pneumoniae is a human pathogen. </li></ul><ul><li>It is an important cause of bronchitis, pneumonia, and sinusitis, infections being transmitted person to person by respiratory secretions. </li></ul><ul><li>Infection is believed to be common (an estimated 200,000 to 300,000 cases of C. pneumoniae pneumonia occur annually), and most common in adults. </li></ul><ul><li>More than 50% of people have serologic evidence of past infections. Most C. pneumoniae infections are asymptomatic or mild, causing a persistent cough and malaise; most patients do not require hospitalization. </li></ul><ul><li>More severe respiratory tract infections typically involve a single lobe of the lungs. </li></ul><ul><li>These infections cannot be differentiated from other atypical pneumonias, such as those caused by Mycoplasma pneumoniae, Legionella pneumophila, and respiratory viruses. </li></ul>
  122. 122. Chlamydophila pneumoniae <ul><li>The role of C. pneumoniae in the pathogenesis of atherosclerosis remains to be defined. </li></ul><ul><li>It is known that C. pneumoniae can infect and grow in smooth muscle cells, endothelial cells of the coronary artery, and macrophages. </li></ul><ul><li>The organism has also been demonstrated in biopsy specimens of atherosclerotic lesions by means of culture, PCR amplification, immunohistologic staining, electron microscopy, and in situ hybridization. </li></ul><ul><li>Thus the association of C. pneumoniae with atherosclerotic lesions is clear. What is not clear is the role of the organism in the development of atherosclerosis. </li></ul><ul><li>The disease is believed to result from an inflammatory response to chronic infection; however, this remains to be proven. </li></ul>
  123. 123. Chlamydophila pneumoniae <ul><li>Diagnosis of C. pneumoniae infections is difficult. </li></ul><ul><li>The organisms do not grow in the cell lines used for the isolation of C. trachomatis, and although C. pneumoniae will grow in the HEp-2 cell line, this cell line is not used in most clinical laboratories. </li></ul><ul><li>Detection of C. pneumoniae by NAATs has been successful, and these tests appear to be the most sensitive diagnostic methods available. </li></ul><ul><li>However, NAATs are not used in most laboratories at this time. CF or MIF tests can be used to make a serologic diagnosis. </li></ul><ul><li>Because the CF test reacts with Chlamydia and Chlamydophila, it is not specific for C. pneumoniae infection. </li></ul><ul><li>The MIF test uses C. pneumoniae EBs as antigen, so it is specific. </li></ul>
  124. 124. Chlamydophila pneumoniae <ul><li>Macrolides (erythromycin, azithromycin, clarithromycin), tetracyclines (tetracycline, doxycycline), or levofloxacin administered for 10 to 14 days has been used to treat infections. </li></ul><ul><li>Control of exposure to C. pneumoniae is likely to be difficult because the bacterium is ubiquitous. </li></ul>
  125. 125. Chlamydophila - Clinical Summaries <ul><li>Chlamydophila pneumoniae </li></ul><ul><ul><li>Respiratory infections: Can range from asymptomatic or mild disease to severe, atypical pneumonia requiring hospitalization. </li></ul></ul><ul><ul><li>Atherosclerosis: C. pneumoniae has been associated with inflammatory plaques in blood vessels; the etiologic role in this disease is controversial. </li></ul></ul><ul><li>Chlamydophila psittaci </li></ul><ul><ul><li>Respiratory infections: Can range from asymptomatic colonization to severe bronchopneumonia with localized infiltration of inflammatory cells, necrosis, and hemorrhage. </li></ul></ul>
  126. 126. Thank You