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1 . number 16 Done by Nebal AlGallab Corrected by Doctor Hamed Alzoubi

2 The last page includes definitions for the asterisked words * Main Lecture s Points 1) Spirochetes o Trepanoma o Borrelia o Liptospiral 2) Chlamydia o Trachomatis o Psittaci o Pneumonia Spirochetes Spirochetes are tiny gram negative organisms that look like corkscrews, they are devided into 3 genera : 1) Trepanoma T.pallidum T.pertenue T.endemicum T.carateum other non pathogenic spp T.Pallidum (Syphillis) Treponema pallidum is the infectious agent responsible for the sexually transmitted disease syphilis*. Belongs to spirochetes which are thin walled, flexible spiral rods.

Motile by flagella: At both sides wrap around the bacterial cell body In contrast to other motile bacteria, these flagella do not protrude into the surrounding medium but are enclosed within the

3 Motile by flagella: At both sides wrap around the bacterial cell body In contrast to other motile bacteria, these flagella do not protrude into the surrounding medium but are enclosed within the bacterial outer membrane. Has not been grown on bacteriologic media. Electron micrograph of T.Pallidum, the flagella (arrowheads) are inserted at the tip and follow the helical contour of the bacterial cell enclosed within the outer membrane. Transmission: Sexually (mainly) Contact with skin lesions Congenital (mother to baby) Blood donation during primary and secondary stages Incubation period: 210 weeks (usually 3 weeks). Pathogenesis: Human pathogen (only human) No toxins Multiplication at primary site of infection leading to a painless ulcer called Chancre* Infectious dose* less than 10 organisms Widespread via blood to many tissues

4 If untreated, patients with syphilis will progress through 3 clinical stages, with a latent period between stages 2 and 3. Stages of Syphilis: Early (primary and secondary), latent, and tertiary stages Overall and the early diseases: 1/3 will heal without treatment 1/3 will go to latent 1/3 into tertiary Primary Syphilis The primary lesion of syphilis is a painless chancre on genitalia, cervix or anogenital area Usually single Disappear spontaneously in 36 weeks (it s actually erupt at the site of inoculation 36 weeks after the initial contact) Infectious Inguinal LNE (caused swelling to lymph nodes) Exudates used for diagnosis. Secondary syphilis Untreated patients enter the bacteremic stage, or secondary syphilis: 212 weeks after chancre disappeared Non specific symptoms (e.g fever, malaise, lethargy*, headache, lymph node enlargement) Maculopapular* and pustular rash mainly on trunk and extremities Heals spontaneously There might be Multiplication and production of lesion in lymph nodes, liver, joints, muscles, skin and mucous membranes

Latent syphilis No lesion but serological evidence exists (serologic test remain positive) Early and late latent ( Early latent phase may reactivate and manifest as a secondary lesion i.

granulomatous lesions (Gummas) o Cardiovascular: aneurysm* of ascending aorta, aortitis o Neurosyphilis: e.

5 Latent syphilis No lesion but serological evidence exists (serologic test remain positive) Early and late latent ( Early latent phase may reactivate and manifest as a secondary lesion i.e infectious) Tertiary Develops over 330 years Slow inflammatory damage to organ tissue, small blood vessels, and nerve cells It can be grouped into 3 general categories: o Skin and bone granulomatous lesions (Gummas) o Cardiovascular: aneurysm* of ascending aorta, aortitis o Neurosyphilis: e.g Meningoencephalitis and paralysis Congenital syphilis Occurs in the fetus of an infected pregnant woman (Blood placenta fetus) Fetuses that acquire the infection have a high mortality rate, intrauterine death, abortion, low birth weight Facial abnormalities e.g saddle shape nose Diagnosis

1 Detection of the organism in the exudates and lesions using dark field E.M or phase contrast, Immunofluorescent antibodies Low sensitivity. 2 Serology* I.

6 1 Detection of the organism in the exudates and lesions using dark field E.M or phase contrast, Immunofluorescent antibodies Low sensitivity. 2 Serology* I. Nonspecific antibodies (12 weeks after the primary chancre appears) Extra note to understand the technique, you can ignore it Infection with syphilis results in cellular damage and the release into the serum of a number of lipids, including cardiolipin, the body produces antibodies against these antigens, we therefore quantitatively measure the titer of the antibodies that bind to these lipids. If a patient's serum has these antibodies, we suspect that he/she has syphilis. The two most common tests employing this technique and detecting anticardiolipin antibodies are: a) Rapid Plasma Reagin (RPR) test b) Venereal Disease Research Laboratory (VDRL) II. Specific antibodies These tests should be used to confirm that a positive result with a nonspecific test is truly due to syphilis. a) Fluorescent Treponema antibodies absorption (FTAAbs): patient's serum is first absorbed with nonpathogenic treponemes to remove crossreacting antibodies before reaction with T. pallidum antigens. b) Treponema Pallidum Haemagglutinin Antibodies (TPHA) Sensitivity of serological test in syphilis Treatment

7 Penicillin G If allergic, Doxycycline or erythromycin is a good alternative In neurosyphilis use penicillin and Doxycycline together. Prevention No vaccine Early diagnosis and treatment of case and contact is important Sexually transmitted: Test for syphilis if any sexually transmitted disease (STD) exists. 2) Borrelia Burgdorferi Borrelia are larger than the Treponema, and therefore can be viewed under a light microscope Cause Lyme disease, which is the most commonly reported tickborne illness in the USA The animals reservoir for Borrelia burgdorferi includes Wild animals, Rodents, Birds..Incub Systemic diseases include Arthritis, CNS, Cardic Abnormalities Painless skin lesion (Single/Multiple) Recurrent Recurrent fever, can be fatal 3) Liptospira Liptospiral diseases Zoonosis Mildsevere fatal systemic Weils s disease High fever vasculitis Bleeding Jaundice* Diagnosis Serological Tests, Special culture

8 Chlamydia Small obligate intracellular parasites It s classified as gram negative because it stains red with Gram stain technique and has an inner and outer membrane. Unlike other gramnegative bacteria, it does not have a peptidoglycan layer. Energy parasites, using a cell membrane transport system that steals an ATP from the host cell and spits out an ADP (can t make ATP by itself) The Chlamydia life cycle is complex as the bacteria exist in 2 forms: I. Elementary body (EB) o Infectious form bind to columnar epithelial cells (macrophages) o Nonreplicating, nonmetabolically active form o Resistant to harsh conditions o The outer membrane has extensive disulfide bond crosslinkages that confer stability for extracellular existence II. Reticulate bodies (RB) o Noninfectious form o Replicating, metabolically active form o The outer membrane has fewer disulphide bond crosslinkage (fragile membrane) so it s an intracellular form Developmental cycle of chlamydia 1) The infectious particle, elementary body (EB) attaches to and enters (via Endocytosis/Phagocytosis) host cells (Epithelial/Macrophage). 2) Once within an endosome, the EB inhibits phagosomelysosome fusion and is not destroyed, It transforms into Reticulate body (RB) by breakdown of disulphide bond. 3) Once enough RBs have formed, some transform back into EB. 4) The life cycle is completed when the host cell liberates the elementary body (EB), which can now infect more cells.

9 Family: Chlamydiaceae Genus 1: Chlamydia (C.trachomatis) Genus 2: Chlamydophilia (C.psittaci, C.pneumoniae) There are 3 species of Chlamydia: Chlamydia trachomatis Causes many infections, include: Inclusion conjunctivitis* Infant pneumonia (during baby's passage through an infected birth canal). Ocular lymphogranuloma venerium Urogenital infections Lymphogranuloma venerium (STD) Trachoma o a type of chronic conjunctivitis that is currently the leading cause of preventable blindness in the world o It is a disease of poverty, prevalent in overcrowd parts of the world (Endemic in Africa, Middle East, India, SE Asia United States American Indians)

vessel formation) Flow of tears impeded (Secondary infections) o Diagnosis Send the sample to Histo Cytology staining with Iodine not sensitive Antigen detection (ELISA or IF) (Group

10 o Infection of children o Transmission: droplets, hands, contaminated clothing, flies, contaminated birth canal. o Clinical syndrome Trachoma Chronic or repeated infection (Follicle formation on conjunctiva Scarring of the conjunctiva) Eyelids turn in and abrade cornea (Ulceration Scarring Blood vessel formation) Flow of tears impeded (Secondary infections) o Diagnosis Send the sample to Histo Cytology staining with Iodine not sensitive Antigen detection (ELISA or IF) (Group specific LPS Strain specific outer membrane proteins) Serology (Can t distinguish between current or past infection Detection of high titer IgM antibodies can be helpful) Nucleic acid probes (Several kits available May eventually replace culture) Iodinestained inclusion bodies

11 o Treatment and prevention Vaccines are of little value Tetracycline, erythromycin and sulphonamides Treatment of patients and their sexual partners Safe sexual practices Treatment coupled with improved sanitation Chlamydia (Chlamydophilia) psittaci infects a lot of species of birds Cause Psittacosis*, Ornithosis (Parrot fever) Pathogenesis Inhalation of organisms in bird droppings (Person to person transmission is rare) Hematogenous* spread to spleen and liver (Local necrosis of tissue) Hematogenous spread to lungs and other organs Lymphocytic inflammatory response (Edema, infiltration of macrophages, necrosis and occasionally haemorrhage Mucus plugs* may develop in alveoli) Cyanosis and anoxia* Diagnosis Fourfold rise in titer Treatment Tetracycline or erythromycin Quarantine* of imported birds Control of bird infection Antibiotic supplementation of food Chlamydia (Chlamydophilia) pneumonia

12 Atypical pneumonia, because the pneumonia is very different from a typical bacterial pneumonia caused by Streptococcus pneumonia. Person to person spread Respiratory droplets Diagnosis: Serology Treatment: Tetracycline or erythromycin Definitions Aneurysm: an excessive localized enlargement of an artery caused by a weakening of the artery wall. Anoxia: an absence of oxygen. Chancre: a painless ulcer, particularly one developing on the genitals as a result of venereal disease. Hematogenous: originating in or carried by the blood. Inclusion conjunctivitis: an infectious disease especially of newborn infants characterized by acute conjunctivitis and the presence of large inclusion bodies and caused by a chlamydia (C. trachomatis). Infectious dose (ID): is the amount of pathogen required to cause an infection in the host. Jaundice: a medical condition with yellowing of the skin or whites of the eyes, arising from excess of the pigment bilirubin and typically caused by obstruction of the bile duct, by liver disease, or by excessive breakdown of red blood cells.

13 Maculopapular rash: is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. Mucus plug: An accumulation of mucus and thick fluid that blocks the opening of the cervix (the opening from the uterus to the vagina) during pregnancy, it serves to protect the uterus and the fetus by preventing bacteria from entering the uterus. Psittacosis: a contagious disease of birds, caused by chlamydiae and transmissible (especially from parrots) to human beings as a form of pneumonia. Quarantine: a state, period, or place of isolation in which people or animals that have arrived from elsewhere or been exposed to infectious or contagious disease are placed. Serology: the scientific study or diagnostic examination of blood serum, especially with regard to the response of the immune system to pathogens or introduced substances. Lethargy: lack of energy and enthusiasm. Syphilis: a chronic bacterial disease that is contracted chiefly by infection during sexual intercourse, but also congenitally by infection of a developing fetus. Prayer is the best Medicine God is the best Doctor

د. حامد الزعبي. Spirochaetes

د. حامد الزعبي. Spirochaetes د. حامد الزعبي Spirochaetes Treponema (T. pallidum) (T. pertenue) (T.endemicum) (T. carateum) orher non pathogenic spp T. pallidum Syphilis: Belongs to spirochetes which are thin walled, flexible spiral