Lecture 12 Microbiology 2021 PDF

Lecture 12 Microbiology: Spirochetes, Rickettsiae, Chlamydia  Content Microbiology: Spirochetes, Rickettsiae, Chlamydia Overview: biological characteristics, infection and immunity, pathogenesis and diagnosis, treatment and prevention of the microbial infection...

Lecture 12 Microbiology: Spirochetes, Rickettsiae, Chlamydia  Content Microbiology: Spirochetes, Rickettsiae, Chlamydia Overview: biological characteristics, infection and immunity, pathogenesis and diagnosis, treatment and prevention of the microbial infection 1. Spirochetes Leptospira & Leptospiriosis Treponema pallidum & Syphilis Borrelia burgdorferi & Lyme disease 2. Rickettsiae & the diseases 3. Chlamydia Chlamydia trachoma, genital infection and inclusion conjunctivitis Chlamydia pneumoniae & respiratory infections Chlamydia psittaci & psittacosis  Spirochetes Gram-negative human pathogens Free living saprophites, or commensals of animals, not primary pathogens – Treponema – Leptospira – Borrelia  T. pallidum has an outer sheath or glycosaminoglycan coating. Inside the sheath is the outer membrane, which contains peptidoglycan and maintains the structural integrity of the organisms. Typical Spirochetes Spirochete from Greek for “coiled hair”  Spirochetes Spirochetes -are elongated motile, flexible bacteria twisted spirally along the long axis. Contain – endoflegalla which are polar flagella wound along the helic alprotoplasmic cylinder and situated between the outer membrane and cell wall Spiral structure is wound around endoflagella Motility includes rotation an flexion Many are thin and take stain poorly Spirochetes are Gram negative, but are poorly stained and difficult to see under the light microscope. Dark field microscopy, immunofluorescenece, or special staining techniques should be applied. Endoflagella Endoflagella (axial filaments) are the flagella-like organelles in the periplasmic space encased by the outer membrane. The endoflagella begin at each end of the organism and wind around it, extending to and overlapping at the midpoint. Inside the endoflagella is the inner membrane (cytoplasmic membrane) that provides osmotic stability and covers the protoplasmic cylinder. A series of cytoplasmic tubules (body fibrils) are inside the cell near the inner membrane. Treponemes reproduce by transverse fission.  Genus Treponema Thin, regular, coiled cells May be aerobic or anaerobic Live in the oral cavity, intestinal tract, and perigenital regions of humans and animals Many are part of nasopharyngeal flora Pathogens are strict parasites with complex growth requirements Require live cells for cultivation  Treponema Pallidum: The Spirochete of Syphilis Humans are the natural host Extremely fastidious and sensitive; Cannot survive long outside of the host Sexually transmitted and transplacental  Live cells show characteristic rotating motility and sudden 90-degree angle flexion Treponema pallidum is extremely susceptible to any deviations of from physiology conditions. It rapidly dies on drying and is readily killed by a wide range of detergents and disinfectants  Visualization The spirals are so thin that they are not readily seen unless immunofluorescent stain or dark-field illumination is used. They do not stain well with aniline dyes, but they can be seen in tissues when stained by a silver impregnation method.  Culture Pathogenic T. pallidum has never been cultured continuously on artificial media, in fertile eggs, or in tissue culture. Genome The T. pallidum genome is a circular chromosome of approximately 1,138,000 base pairs, which is small for bacteria. Most pathogenic bacteria have transposable elements, but T. pallidum does not, which suggests that the genome is highly conserved and may explain its continued susceptibility to penicillin.  Spirochetal diseases The oral cavity harbors a number of nonpathogenic species of Treponema and Borrelia as part of the flora Over growth of Spirochetae causes trench mouth (Vincent infection). The pathogenesis of this infection is correlated with immunocompromise, sever malnutrition and neglect of basic hygiene The term “trench mouth” refers to occurrence of these infections in troops under the appalling conditions that existed in the trenches during the World War I  Treponema pallidum Treponema pallidum – a causative agent of syphilis Disease first recongnized in the 16th century as the “great pox” rapidly spread in Europe Some argue that it was brought back from New World by the sailors with Christopher Columbus.  Syphilis The current name, syphilis, which was not used until the end of the 18th century, comes from the poem "Syphilissive morbus Gallicus" ("Syphilis or the French Disease") written by the Italian physician Girolamo Fracastoro and published in 1530. The poem, which includes medical and philosophic explanations of the nature of the new disease, is derived from Ovid's poem about Syphilus. In Fracastoro' s work, Syphilus is a shepherd who incurs the wrath of the Sun god and is punished with morbus gallicus, "the French Disease."  Pathogenesis and Host Response Treponema palludum is an exclusively human pathogen. Spirochete binds to epithelium (mucous membrane or abraded skin), multiplies, and penetrates into capillaries Rapidly within minutes the infection moves into circulation and multiplies, within hours it is already established in the distant tissues Untreated syphilis marked by 3 clinical stages: – Primary, secondary, tertiary Infection is acquired from direct sexual contact with a person who has an active primary or secondary syphilis lesion or through trans-placental route. Tertiary syphilis is not infectious Spirochete appears in lesions and blood during first 2 stages – communicable  Forms of syphilis Primary syphilis – appearance of hard chancre at site of inoculation Appears on 10-90 days after infection; Without the pain. The inflammation is characterized by a predominance of lymphocytes and plasma cells. Chancre heals spontaneously. Primary syphilis lesion, chancre Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person. Approximately 3 to 90 days after the initial exposure (average 21 days) a skin lesion, called a chancre, appears at the point of contact. This is classically a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders between 0.3 and 3.0 cm in size. The lesion, however, may take on almost any form. In the classic form, it evolves from a macule to a papule and finally to an erosion or ulcer. Lesions may be painful or tender, and they may occur outside of the genitals (2–7%). The most common location in women is the cervix (44%), the penis in heterosexual men (99%), and anally and rectally relatively commonly in men who have sex with men (34%). Lymph node enlargement frequently (80%) occurs around the area of infection, occurring seven to 10 days after chancre formation. The lesion may persist for three to six weeks without treatment, heals spontaneously. Secondary syphilis Secondary syphilis – fever, headache, sore throat, red or brown rash on skin, palms, and soles; rash disappears spontaneously/. Secondary lesions appear 2-10 weeks after the primary lesion and consist of a red maculopapular rash anywhere on the body, including the hands and feet, and moist, pale papules (condylomas) in the anogenital region, axillae, and mouth. The patient may also have syphilitic meningitis, chorioretinitis, hepatitis, nephritis (Immune complex type), or periostitis. The secondary lesions also subside spontaneously. Both primary and secondary lesions are rich in spirochetes and are highly infectious.  Symptom of secondary syphilis Condylomata lata Syphilitic infection may remain subclinical, and the patient may pass through the primary or secondary stage (or both) without symptoms or signs yet develop tertiary lesions. Fever, malaise and other manifestations of systemic disease are typical. Skin lesions are distributed on the trunk and extremities, often including palms, soles and face and can mimic a variety of infections and noninfectious skin eruptions. About 1/3 of patients develop painless mucosal warty erosions called condylomata lata. These lesions usually develop in warm, moist sites such as genitals and perineum. Lymphadenipathy and maculopapular rash are generalized. Spirochetes are abundant. Lesions resolve, but disease continues in 1/3 of patients  In about 30% of cases, early syphilitic infection progresses spontaneously to complete cure without treatment. In another 30%, the untreated infection remains latent (principally evident by positive serologic test results). In the remainder, the disease progresses to the “tertiary stage” characterized by the development of granulomatous lesions (gummas) in the skin, bones, and liver; degenerative changes in the central nervous system (meningovascular syphilis, paresis, tabes); or cardiovascular lesions (aortitis, aortic aneurysm, aortic valve insufficiency). In all tertiary lesions, treponemes are very rare, and the exaggerated tissue response must be attributed to hypersensitivity to the organisms. However, treponemes can occasionally be found in the eye or central nervous system in late syphilis Syphilitic eye diseases  Symptoms of tertiary syphilis Tertiary syphilis – about 30% of infections enter in tertiary stage; can last for 20 years or longer; numerous pathologic complications occur in susceptible tissues and organs – Neural, cardiovascular symptoms, gummas develop Congenital syphilis – nasal discharge, skin eruptions, bone deformation, nervous system abnormalities Gumma  Tertiary syphilis 1/3 of untreated patients develop tertiary syphilis. The manifestation develops between 5 - 20 years and depends on the sites involved, the most important of which are nervous and cardiovascular systems Neurosyphilis The most common entity is chronic meningitis with fever, headache, focal neurologic findings, and increased cells and protein in the cerebrospinal fluid (CSF). Cortical degeneration of the brain causes mental changes ranging from decreased memory to hallucinations. Chronic meningitis leads to degenerative changes and psychosis. Demelietion caused peripherial neuropathies, dorsal root gangliia produces syndrom called tabes dorsalis Tabes dorsalis  Neurosyphilis Cranial neuropathy (neurosensory loss) Dementia Loss of reflexes Personality changes Pupillary abnormalities Sezuries Strokes Friedrich Nietzsche, Vladimir Lenin, Al Capone Syphilitic eye diseases The most advanced central nervous system (CNS) (Retinitis, uveitis) findings include combination of neurologic deficits and behavioral disturbances called paresis, hich is also menominic (personality, affect, reflexes, eyes, sensorium, intellect, speech) for the myriads of changes seen.  Cardiovascular syphilis Cardiovascular syphilis is due to arthritis involving the vacsa vasorum of the aorta and aneurysm. The expanding aneurysm can produce AORT pressure necrosis of adjuscent A structures or even rapture. A localized granulomatous reaction of T. pallidum infection is called gumma may be found in skin, bones, joints and other organs. Gummas are desturctive, localized granulomas. Figure 1 This PA chest radiograph displays hyperexpanded left and right lungs (LL, RL), dilated ascending aorta (A), large left ventricle (LV), metal buckshot (small arrows), notching of the posterior inferior right fourth rib, posterior inferior left fifth and sixth ribs (single long arrows), and cephalization in the lungs and the heart below the left hemidiaphragm (LD). C= clavicle; CP= coracoid process; FR= first rib; P= left pulmonary artery; RD= right hemidiaphragm. - See more at: http://www.hcplive.com/journals/family-practice-recertification/2014/july-2014/a-man-with-syphilis-heart-failure-and  Manifestations of syphilis Syphilis is usually acquired by the direct contact of mucous membranes during sexual intercourse. The disease begins with a lesion in the point of entry usually a genital ulcer. After healing of the ulcer the organism spreads systematically and the disease returns weeks later as a generalized maculopappular rash called secondary syphilis. The disease then enters a second eclipse phase called latency. The latent infection may be cleared by the immune system or re-appear as the tertiary syphilis years to decades later. Tertiary syphilis is characterized by focal lesion whose locate determines the injury. Isolated foci in bone or liver may be unnoticed, but infection of cardiovascular or nervous systems can be devastating. Progressive dementia or a ruptured aortic aneurysm are two of many fatal outcomes of untreated syphilis.  Congenital syphilis Syphilis is transmitted from the mother to the baby trough the placenta. The more recent the infection, especially during the pregnancy, the more damaging to the baby. COMPLICATIONS: Miscarriage Enlarged liver and spleen Still birth Hydrocephalus Meningitis Mental Retardation Convulsions Sever Skin Rashes Blindness Deafness Deformities of face, nose, teeth, jaw, leg bones  Serology The spirochetes cause the development of a distinct antibody-like substance, reagin, which gives positive complement fixation (CF) and flocculation test results with aqueous suspensions of cardiolipin extracted from normal mammalian tissues. Both reagin and antitreponemal antibody can be used for the serologic diagnosis of syphilis.  Immune response Slow multiplication rate combined with the low antigen content in the outer membrane results in the minimal triggers of immune response. Prolonged delayed type hypersensitivity response (DTH) is typical to the persisting infection. Immunity develops slowly and incompletely The immune mechanisms involve both humoral and cell-mediated response. Antibodies to treponemal Outer Membrane Proteins (OMP) are associated with re-infection resistance Activated macrophages play a major role in clearance of T. pallidum from early syphilis lesions. The relapsing course of primary and secondary syphilis may reflect the shifts in the balance between developing cellular immunity and suppression of T-lymphocytes  Diagnosis Stages of syphilis mimic other diseases Consider symptoms, history, microscopic, and serological testing – Rapid plasma reaction (RPR), Veneral disease research laboratory (VDRL), FTA-ABS Microsciopy: Direct detection is spirochetes (dark field microscopy, silver staining, etc.) Serology: nonspecific and specific tests Nontreponemal tests measure antibodies against cardiolipin (a lipid complex initially extracted from beef heart). Anti-cardiolipin antibody is called reagin. Antibody peaks in secondary syphilis. Nonspecific reactions are linked to autoimmune diseases. Treponemal tests detect antibodies specific to T. pallidum, such as indirect immunofluorescent procedure called the treponemal antibody (FTA-ABS), which uses spirochetes fixed to slides. Immunohemagglutination test for T. pallidium (MHA-TP) uses antigens attached to the surface of erythrocytes, which then agglutinate in the presence of antibody. Treponemal test are more specific, they are used for confirmation of positive RPR and VDRL tests. These tests are not useful for screening of after therapy as they remain positive for life, except for the immunocompromized. Usually two step process is required: initial screening with nonspecific tests followed by the specific tests.  Treatment Penicillin in concentrations of 0.003 U/mL has definite treponemicidal activity, and penicillin is the treatment of choice. Syphilis of less than 1 year duration is treated by a single injection of benzathine penicillin G 2.4 million units intramuscularly. In older or latent syphilis, benzathine penicillin G intramuscularly is given three times at weekly intervals. In neurosyphilis, the same therapy is acceptable, but larger amounts of intravenous penicillin are sometimes recommended. Other antibiotics (eg, tetracyclines or erythromycin) can occasionally be substituted.  Nonsyphilitic Treponematoses Resemble syphilis; rarely transmitted sexually or congenitally; cutaneous and bone diseases endemic to specific regions Bejel – T. pallidum subspecies endemicum; deforming childhood infection of the mouth, nasal cavity, body, and hands Yaws – T. pallidum subspecies pertenue; invasion of skin cut, causing a primary ulcer that seeds a second crop of lesions Pinta – T. carateum; superficial skin lesion that depigments and scars the skin Bejel Yaws Pinta  Treatment and prevention Penicillin G at all stages of syphilis Hypersensitive to penicillin may be treated with doxycycline Save sex practices (condoms)  Leptospira and Leptospirosis Tight, regular individual coils with a bend or hook at one or both ends L. biflexa – harmless, free-living saprobe L. interrogans – causes leptospirosis, a zoonosis – Bacteria shed in urine; infection occurs by contact with contaminated urine; targets kidneys, liver, brain, eyes – Sudden high fever, chills, headache, muscle aches, conjunctivitis, and vomiting – Long-term infections may affect kidneys and liver – 50-60 cases a year in U.S. Leptospira  Borrelia: Arthropod-Borne Spirochetes Large, 3-10 coils irregularly spaced Borrelioses transmitted by arthropod vector B. hermsii – relapsing fever B. burgdorferi – Lyme disease Borrelia miyamotoi - Lyme-like disease Gram-negative spiochetes Microaerophilic  Staining The organisms are highly flexible and move both by rotation and by twisting. Borreliae stain readily with bacteriologic dyes as well as with blood stains such as Giemsa stain or Wright stain. Culture The organism can be cultured in fluid media containing blood, serum, or tissue, but it rapidly loses its pathogenicity for animals when transferred repeatedly in vitro.  Antigenic Structure Antibodies develop in high titer after infection with borreliae. The antigenic structure of the organisms changes in the course of a single infection. The antibodies produced initially act as a selective factor that permits the survival only of antigenically distinct variants. The relapsing course of the disease appears to be caused by the multiplication of such antigenic variants, against which the host must then develop new antibodies. Ultimate recovery (after 3–10 relapses) is associated with the presence of antibodies against several antigenic variants.  B. Hermsii – Relapsing Fever Mammalian reservoirs – squirrels, chipmunks, wild rodents Tick-borne The incubation period is 3–10 days. Sudden onset with high fever, shaking, chills, headache, and fatigue. The fever persists for 3–5 days and then declines, leaving the patient weak but not ill. The afebrile period lasts 4–10 days and is followed by a second attack of chills, fever, intense headache, and malaise, nausea, vomiting, muscle aches, abdominal pain; extensive damage to liver, spleen, heart, kidneys, and cranial nerves Parasite changes and immune system tries to control it – Recurrent relapses There are 3–10 such recurrences, generally of diminishing severity Tetracycline  Forms of Relapsing Fever Forms of Relapsing Fever are linked to the mode of transmission and the Borrelia species involved. Louse borne (epidemic) form – body lice Relapsing fever (endemic) form – tick borne  B.Burgdorferi – Lyme Disease Carried by white-footed mouse, transmitted by Ixodes ticks Complex 2-year cycle involving mice and deer (vertebrates other than deer may be infected by both adult and nymph staged of tick, but human Lyme disease is primarily acquired from nymphs in spring, mostly at night). Deer are essential for mating and survival of the tick, and thus the disease do not occur in areas in which deer are not abundant. Nonfatal, slowly progressive syndrome that mimics neuromuscular and rheumatoid conditions 50-70% get bull’s eye rash Fever, headache, stiff neck, and dizziness If untreated can progress to cardiac and neurological symptoms, polyarthritis Tetracycline, amoxicillin Vaccine for dogs, human vaccine discontinued Insect repellant containing DEET Cycle of Lyme disease  Views of Lyme disease skin rash Bull’s eye pattern Erythema migrans  Manifestation Spreading lesion from bite site is most characteristic finding Erythrema migrans and febrile aches mark acute disease Nerve palsies and cardic findings appear later Fluctuating arthritis may become chronic  B. miyamotoi Infection with the recently emerging pathogen B. miyamotoi typically presents as a febrile illness, with high fever (≥40°C), fatigue, headache, myalgia, arthralgia, and nausea. In some patients, leukopenia, thrombocytopenia, and elevated transaminases have also been reported. In contrast to Lyme disease, the typical skin lesions (erythema migrans) are absent with B. miyamotoi infection. Symptoms of infection usually resolve within 1 week of starting antibiotic therapy. In severely immunocompromised patients, meningoencephalitis has been described as a complication of B. miyamotoi infection. Infection with B. miyamotoi should be considered in patients with an acute febrile illness following the exposure to Ixodes ticks in areas where Lyme disease is also present.  Diagnosis Culture is not practical Serologic tests are not definitive The current recommendation is to first perform a screening test (enzyme immunoassay) followed by immunosorbent (Western blot) , which detects specific antigens of the organism  Treatment Treatment in the early phase is an easy mission by amoxicillin or doxycycline, amoxacillin, cefuoxime orally for few weeks. The recommended regimen in late stages include parenteral ceftriaxone, analgesics to control the severe pain, and anti-inflammatory drugs, usually required for months. Azithromycin and clarithromycin are alternatives Ceftriaxone or intravenous Penicillin G is recommended for patients with neurologic involvement of cardiovascular findings such as atrioventicular heart block. Continued treatment 30-60 days is required.  Prevention Most exposures are in May through July, when the nymphal stage of the ticks is most active; however, the larval stage (August and September) and adult stage (spring and fall) also feed on humans and can transmit B. burgdorferi Clothing covering hands and knees Removal of the tick by its head with tweezers Prophylactic doxycycline may be used after a tick bite, but only in a highly endemic regions Vaccine no longer available because of its low demand  Family Rickettsiaceae Contains about 23 species of pathogens, mainly in the genus Rickettsia Cause diseases called rickettsioses All are intracellular parasites requiring live cells for cultivation Spend part of their life cycle in arthropod vectors Rickettsioses are important emerging diseases  Rickettsia Obligate intracellular parasites Gram-negative cell wall Among the smallest bacteria Nonmotile, pleomorphic rods or coccobacilli Ticks, fleas, and lice are involved in their life cycle Bacteria enter endothelial cells and cause necrosis of the vascular lining – vasculitis, Vasculitis vascular leakage, and thrombosis  Specific Rickettsioses Epidemic typhus – R. prowazekii carried by lice; starts with a high fever, chills, headache, rash; Brill-Zinsser is a chronic, recurrent form Endemic typhus – R. typhi, harbored by mice and rats; occurs sporadically in areas of high flea infestation; milder symptoms Rocky Mountain spotted fever – R. rickettsii zoonosis carried by dog and wood ticks; most cases in Southeast and on eastern seaboard; distinct spotted rash; may damage heart and CNS Scrub typhus - caused by Orientia tsutsugamushi (from Japanese tsutsuga "illness" and mushi "insect") Ehrlichia genus contains 2 species of rickettsias; tick-borne bacteria cause human monocytic and granulocytic ehrlichiosis Rocky Mountain Spotted Fever  Epidemiology Most rickettsiae have animal reservoirs and are spread by tick, fleas, mites, or lice, which are prominent components of their life cycles. The classical example of rickettsial disease is epidemic typhus, but the most important ricketsiosis year to year is Rocky Mountain spotted fever (RMSF). Both types of rickettsial disease are characterized by fever, rash and myalgias/myositis. In RMSF the rash appears first on the palms and soles, wrists and ankles and it migrates centripetally. In endemic typhus , the rash begins on the trunk and spreads to the extrimities, travelling in the opposite directions. Both disease may be fatal as the result of fatal vascular collapse. Most cases in children Rash in RMSF  Manifestation of RMSF The incubation period between the tick bite and the onset of illness is usually 6 to 7 days, but may be from 2 days to 2 weeks. Symptoms: fever, headaches, rash, toxicity, mental confusion, and myalgia Complications: thrombocytopenia, encephalitis, vascular collapse, renal and heart failure  Diagnosis and treatment Most often specific therapy must be started solely on the basis of clinical signs, symptoms and epidemiologic considerations Antibiotic therapy is highly effective if given during the fist week of illness. Antibiotic of choice – doxycycline Sulfonamides may worsen the disease process and are contraindicated. Before specific therapy became available, the mortality rate associated with RMSF was 25%. Treatment has reduced this figure to 5%- 7%. Death results primarily in patients in whom diagnosis and therapy are delayed into the 2nd week of illness. Prevention: Frequent deticking. Avoidance, and protective clothing is important in prevention. Rickettsia pox – a benign rickettsia Cause – Ricketsia akari Transmitted by rodent mite Distinguishing feature – eschar at the site of the bite and vascular rash The rash does not occur in palms and soles House mouse and semidomestic rodents are primary reservoirs The humans become infected the mite seeks an alternative host Therapy - Doxycycline Endemic Louse-Borne Typhus Fever Cause – R. prowazekii Transmitted by body louse Appears in the misery times (war, famine) creating the conditions favorable for human body lice (crowding, infrequent bathing). This is the only rickettsial disease that can occur as epidemic, especially among homeless population Infection involved feeding and defecation of the louse Fever, headache and rash appears in 1-2 weeks after the bite. The rash appears first on trunk and then spreads centrifugally to the extremities In untreated disease a fatality rate is high and increases with the age from 10% to 60% Diagnosis – serology tests Therapy – doxycycline, should start immediately on clinical suspicion Louse control is primary prevention  Endemic (murine) Typhus Cause – R. typhi Transmitted to humans by the rat flea Urban rodents are the reservoir Resembles typhus, but less severe Because R. prowazekii and R. typhi share the antigens, the two illnesses may not be separated by serology tests In untreated patients the illness lasts 12 to 14 days Mortality and complications are rare Therapy - doxycycline  Related to the Rickettsioses Coxiella burnetti Bartonella sp.  Coxiella Burnetti Causes Q fever Intracellular parasite Produces an unusual resistant spore Harbored by a wide assortment of vertebrates and arthropods Infectious material includes urine, feces, milk, and airborne particles Usually inhaled causing pneumonitis, fever, hepatitis Tetracycline treatment Tumor like vascular lesion Vaccine available filled with bacteria  C. burnetii is a small obligate organism that has a membrane similar to Gram-negative bacteria. However, it does not stain with the Gram-stain but does stain with Gimenez. C. burnetii is resistant to drying. This organism may survive pasteurization at 60°C for 30 minutes and can survive for months in dried feces or milk. This may be because of the formation of endospore-like structures by C. burnetii. Coxiellae grow only in cytoplasmic vacuoles.  Antigens When grown in cell culture, C. burnetii exhibits various phases. These phases are associated with differences in virulence. Phase I is the virulent form that is found in humans with Q fever and in infected vertebrate animals. It is the infectious form of the organism and the lipopolysaccharide expressed during this phase appears to be a key virulence factor. Phase II forms are not infectious and occur only by serial passage in cell cultures. Patients with clinical illness mount antibodies to both phase I and phase II antigens.  Epidemiology C. burnetii is found in ticks, which transmit the agent to sheep, goats, and cattle, but transmission by ticks to humans is uncommon. Workers in slaughterhouses and in plants that process wool and cattle hides have contracted the disease as a result of handling infected animal tissues. C. burnetii is transmitted by the respiratory pathway rather than through the skin.  Q Fever – clinical findings This disease is recognized around the world and occurs mainly in persons associated with goats, sheep, dairy cattle, or parturient cats. Infections may be acute or chronic. Acute disease resembles influenza, nonbacterial (atypical) pneumonia, and hepatitis. There is a rise in the titer of specific antibodies to C. burnetii, phase II. Transmission results from inhalation of dust contaminated with the organism from placenta, dried feces, urine, or milk or from aerosols in slaughterhouses. Chronic Q fever is infection that lasts more than 6 months. Infective endocarditis is the most common form of disease in this phase. Blood cultures for bacteria are negative, and there is a high titer of antibodies to C. burnetii, phase I. Virtually all patients have preexisting valve abnormalities or have some form of immune compromise  Laboratory findings C. burnetii can be cultivated in cell cultures, but this should only be done in experienced biosafety level 3 laboratories. Serology is the diagnostic method of choice, and indirect immunofluorescence is considered the best method. PCR has been useful in diagnosing culture-negative endocarditis caused by C. burnetii.  Treatment Treatment Doxycycline is the drug of choice for the treatment of acute Q fever. The newer macrolides have also been shown to be effective in the treatment of acute pneumonia. Chronic Q fever requires prolonged treatment for 18 months or longer with a combination of doxycycline and hydroxychloroquine.  Prevention The presently recommended conditions of “high-temperature, short-time” pasteurization at 71.5°C for 15 seconds are adequate to destroy viable Coxiella species. For C. burnetii, an investigational vaccine made from infected egg yolk sacs is available. This vaccine has been used for laboratory workers who handle live C. burnetii but currently is only commercially available in Australia  Bartonella Species Small gram-negative, fastidious, cultured on blood agar Cause: – Trench fever (Bartonella quintana), spread by lice – Cat-scratch disease (Bartonella henselae), a lymphatic infection associated with a clawing injury by cats – Bacillary angiomatosus in AIDS patients Tetracycline, erythromycin, and rifampin  Cat-scratch disease Lymph node enlargement Treatment: Azythromicin, erythromycin  The Chlamydiaceae Obligate intracellular parasites, require matabolites from host cells Small, gram-negative cell wall , including an outer membrane, contains lipopolysaccharade and proteins Lacks peptidoglycan layer The outer membrane includes a major outer membrane protein (MOMP) which is immunogenic 3 out of 9 species cause diseases in humans: Chlamydia trachomatis (cause genital infection and conjuctivities) and, Chlamydia psittaci, and Chlamydia pneumoniae (cause respiratory infections) Alternate between 2 stages: – Elementary body – small metabolically inactive, extracellular, infectious form released by the infected host – Reticulate body – noninfectious, actively dividing form, grows within host cell vacuoles Two major forms of the organism: Elementary body (EB) and intracellular replicative form (RB). EB is a metabolically inetr form Stages of intracellular development of Chlamydia Attachments to the plasma membrane of the susceptible target cell Induction of its own endocytosis EB converts to RB The organism inhibits lysosomal fusion and forms its own membrane bound vesicle called the inclusion After RB increase in number, the process reverses and the RB’s reorganize and condense to yield multiple Ebs. EBs are then released by exocytosis Cell apoptosis is regulated by a chlamydia ptotease like activity factor (CPAF). In the growth phase apoptosis is inhibited, but at the release stage cell death proceeds. Clamydia trachomatis  Chlamydia Trachomatis Human reservoir 2 strains Trachoma – attacks the mucous membranes of the eyes, genitourinary tract, and lungs – Ocular trachoma – severe infection, deforms eyelid and cornea, may cause blindness – Inclusion conjunctivitis – occurs as baby passes through birth canal; prevented by prophylaxis – Sex Transmitted Disease (STD) – second most prevalent STD; urethritis, cervicitis, salpingitis (pelvic inflammatory disease - PID), infertility, scarring Lymphogranuloma venereum – disfiguring disease of the external genitalia and pelvic lymphatics  The pathology of primary ocular chlamydial infection C trachomatis, is the most important human pathogen and a major cause of genital infection, called nongonococcal uretritis (NGU), mucopurulent cervicities (serotypes D-K), colorectal and genital infection called lymphoganuloma venerium (LGV) (serotypes L1 and L3) and inclusion conjuctivities (serotypes A, B, Ba, C).  Transmission Chlamydia can be transmitted during vaginal, anal, or oral sex. Chlamydia can also be passed from an infected mother to her baby during vaginal childbirth (with subsequent neonatal eye infection or pneumonia). Approximately 75% women who have Chlamydia have no symptoms. About 25% women with Chlamydia could mention all typical symptoms - if Chlamydia symptoms do occur, they usually appear within 1 to 3 weeks after infection exposure and/or transmission. Chlamydia symptoms include: abnormal vaginal discharge (mucus or pus), smelling yellowish discharge from the cervix, frequent urges to urinate (much more than usual), burning sensation or pain during urination, abdominal and/or low back pain, nausea, fever (often low-grade fever), Pain during intercourse, vaginal bleeding between periods, vaginal bleeding after sex, eye infections (conjunctivitis).  Epidemiology C trachomatis is the most common cause of chronic follicular conjunctivitis (ie, follicular conjunctivitis lasting for >16-28 d). The organism also causes 3 clinical syndromes, which include the following: trachoma, adult inclusion conjunctivitis, and neonatal conjunctivitis. The adult disease is transmitted sexually or from hand-to-eye contact. Gonorrhea is the most common co-infection with adult inclusion conjunctivitis. Rarely, the adult disease is transmitted from eye-to-eye contact (eg, sharing mascara). Formities, fingers and flies involved in transmission of trachoma  Manifestation – eye and pulmonary infections C. trachomatis serovars A-C is usually seen in less developed countries and often leads to blindness. Inclusion conjuctivities (IC), an acute infection commonly caused by serovars D and K is usually not associated with chronically or permanent discharge. IC continues for 5-12 days after birth. Untreated it may persist for 3 to 12 months. It occurs in newborns and adults worldwide. Trachoma- chronic inflammation of the eyelids and increased vascularization of the corneal conjuctiva are followed by severe corneal scarring and conjunctival deformities. Visual loss often occurs 15-20 years after the initial infection. C. trachomtis may cause pneumonia syndrome (5-10%). The illness usually develops in infants between 6 weeks and 6 months of age and had a gradual onset. The child usually is afebrile, but develops difficulty in feeding, a characteristic staccato (pertussis like ) cough, and shortness of breath. The disease is rarely fatal, but may be associated with decreased pulmonary function later in life. Limphogranuloma venereum Occurres principally in South America, Africa, Southeast Asia, India and Carribbean counties. The clinical course is characterized by a transient genital lesion (small painless ulcer or papula) that is followed by multilocular superlative involvement of the inguinal lymph nodes. The skin over the node may be thinned and multiple draining fistulas develop. Systemic symptoms: fever. Headache, arthralgia, and myalgia.  Diagnosis of chlamydial infection Epithelial cells from conjuctiva, urethra and cervics are required Culture is carried out. Results require 3-7 days Immunology methods: Direct fluorecsent antibody method (DFA) Immunoassay method Nucleic acid amplification (NAA) tests – the newest method  Treatment Tetracyclines Macrolides Some fluoroquinolones First line therapy – azithromycin (a single oral dose for non LGV). Doxycycline is a fist line drug for LGV Erythromycin and fluoroquinolones are alternatives  Prevention Detection of infection in the sexually active individuals and appropriate treatment, including infected women with erythromycin late in pregnancy.  Chlamydophila – A New Genus Contains members that used to be members of genus Chlamydia Chlamydophila pneumoniae – causes an atypical pneumonia that is serious in asthma patients C. psittaci – airborne infection, causes ornithosis, a zoonosis transmitted to humans from bird vectors; highly communicable among all birds; pneumonia or flulike infection with fever, lung congestion – human psittacosis Psittacosis – occupational disease Human –to –human transmission is rare  Clinical disease and treatment The incubation period for psittacosis is 5 to 15 days Psittacosis – an acute infection of lower respiratory tract Acute onset with fever, headache, malaise, muscle ache, dry hacking cough, bilateral pneumonia Systemic complications: myocarditis, endocarditis, hepatitis, the liver and spleen are often enlarged. Treatment: doxycycline (preferred), tetracycline, azithromycion, or erythromycin are effective if given early in the course of illness.  Chlamydophila pneumoniae (Walking pneumonia) Spread from person–to-person Outbreaks of community acquired pneumonia caused by C. pneumoniae have been reported, as well as apparent nosocomial spread. Risk group – elderly Manifestation – pharyngitis, lower respiratory tract diseases, or both. Pharyngitis or laryngitis may occur 1 to 3 weeks prior before bronchitis or pneumoniae, and cough may persist for weeks Diagnosis: serological test (immunofluorescence), culture or NAA method. Treatment: macrolides (erythromycin, clorithromycin, azithromycin), doxycyline, and floroquinolones.  Reading Chapter 24. Spirochetes: Treponema, Borrelia, and Leptospira Chapter 26. Rickettsia and Related Genera