Syphilis and Gonorrhea:Syphilis:Caused by: Treponema pallidum

Classification: Spirochaetaceae; Spirochaetes; Treponema

Epidemiology:Sexually transmitted diseases are the most common infectious diseases.

In sub-Saharan Africa, syphilis contributes to approximately 20% of perinatal deaths.

In the United States, rates of syphilis as of 2007 were six times greater in men than women.

Untreated Syphilis has a mortality of 58%, with a greater death rate in males.

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Death rate from Syphilis per 100,000 cases in 2004:Red: more than 500 death cases. Dark-yellow: 210-250 death cases.Yellow: 150-200 death cases.

Microscopic characteristics and Cell structure: -Treponema pallidum is a Gram-negative long, slender, flexible, spiral bacterium.-Poorly stained by Gram’s stain.-Visualized by Darkfield microscope or fluorescent microscope.- Highly motile : Rotary Corkscrew-like motility.

-The microbial cell envelope composed of : inner membrane, a thin peptidoglycan cell wall, and an outer membrane. -Endoflagella are located in the periplasmic space. -It is very small in size with a length that ranges from 6 to 20 μm and a width of 0.1 to 0.18 μm.

Microscopy and cell Structure:n

Cultivation of Treponema pallidum and metabolic activity:

-Treponema pallidum has very limited metabolic capacity.

-It is unable to survive without a host for more than a few days.

-This is due to its small genome (single double stranded circular

DNA chromosome).

-Thus its inability to make most of it’s macronutrients ( fatty

acids, nucleotides, enzyme cofactors and most amino

acids).

- Although it contains the enzymes necessary for glycolysis, it lacks

those which are required for the citric acid cycle as well as those

needed for oxidative phosphorylation.

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-Treponema pallidum is a chemoheterotrophic, secretes the enzyme hyaluronidase. -The microbe is also Microaerophilic, requires a very low concentration of oxygen to grow.

-The bacterium does not grow in conventional culture.

-The microbe is extremely fastidious, and fragile; sensitive to disinfectant, heat, and drying.

-Animal inoculation could be used for cultivation of microbe in vivo.

Pathogenesis: Transmission:-Sexual route, Transplacental , Blood transfusion, sharing needles, direct Broken skin contact.

Establishment of infection:- The bacterium enters the body through a break in the skin, or by penetrating mucous membranes of the genitalia.- Production of Hyaluronidase; virulence factor, that destroy the polysaccharide (hyaluronic acid) that holds host cells together in the extracellular matrix. (Hyaluronic acid is an glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues).

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-Colonization of tissue at low oxygen level.-Tissue destruction and lesions (chancres) due to immune response.

-Chancres contain polymorphonuclear leukocytes and macrophage.-Dissemination of spirochetes in the bloodstream; endarteritis and periarteritis.

Clinical Picture of Treponema pallidum:

1-Primary Syphilis:

Approximately 21 days after the initial exposure, a skin lesion

( chancre) appears at the point of contact.

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A chancre is a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders between 0.3 and 3.0 cm in size.

This primary lesion heals spontaneously, but the microbe continues to spread via lymph and blood.

An asymptomatic period (lasting for 24 weeks) followed by secondary stage.

Chancre could present at site of inoculation such as penis, labia, and vagina.

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2-Secondary Syphilis: -The appearance of a red, maculopapular rash on almost any part of the body (palms of the hands and soles of feet).-A macule is a change in surface color, without elevation or depression.-A papule is a circular, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 5 to 10 mm in diameter.

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-Secondary syphilis could be accompanied by: 1- hepatitis.2- meningitis.3- nephritis. 4- chorioretinitis.

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3-Latent stage : After healing of secondary syphilis, the microbe enters a latency period that can last 3 to 10 years. In this period: 1-No primary or secondary symptoms (asymptomatic period). 2- Serologic tests show positive results. 4- Tertiary syphilis: Tertiary syphilis may occur approximately three to 15 years after the initial infection. It is divided into three different forms: A- Gummatous syphilis ( granulomatous lesions of liver, skin, and bones (15%). B- Neurosyphilis (6.5%). C- Cardiovascular syphilis (10%).

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Laboratory diagnosis: Clinical specimens: Exudate (pus), tissue biopsy, and serum specimens.1- Direct: In Microbiology Lab: A- Darkfield Microscopy: Rotary Corkscrew-like motility with 90 ˚ angulation. B- Immunofluorescent microscopy: staining of microbe by anti-Treponema antibodies. In Histology Lab: Brightfield Microscopy: modified Steiner silver stain.

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n 2- Indirect : In Serology Lab:

A-Nontreponemal test (non-specific): for screening. Detection of Anti-Cardiolipin antibodies by VDRL or RPR test.

-Venereal disease research laboratory (VDRL): the flocculation is seen by microscopic examination.

-Rapid plasma reagin (RPR): the flocculation is seen by naked eyes.These tests measure antibodies to lipoidal material released from

damaged host cells .

B- Treponemal test (specific): for confirmation . Detection of anti-treponema antibodies by TPHA or FTA.

-T. pallidum haemagglutination assay (TPHA). -Flurescent treponemal antibody (FTA).

These tests detect antibodies specific for cellular components of the organism.

Gonorrhea: Gonorrhea is a specific type of urethritis that practically always involves mucous membranes of the urethra, resulting in a copious or purulent discharge of pus.

Gonorrhea is referred to as Gonococcus infection; Neisseria gonorrhoeae infection.Gonorrhea is a common sexually transmitted infectious disease.

WHO estimates that 62 million cases of gonorrhea appear each year.Blacks accounted for 69% of all gonorrhea cases in 2010."

Epidemiology: n

Microscopic features:Neisseria gonorrhoeae is a Gram-negative cocci, 0.6 to 1.0 µm in diameter, usually seen in pairs with adjacent flattened sides. The organism is frequently found as intracellular coffee bean-shaped diplococci in polymorphonuclear leukocytes of the gonorrhea pustular exudate.

Cultural characteristics:

Neisseria gonorrhoeae species are fastidious Gram-negative cocci.They grow on chocolate agar incubated with 5-10% carbon dioxide.NAD and Hemoglobin should be present for microbial isolation.Neisseria is usually isolated on Thayer-Martin agar ; an selective media contain antibiotics ( Vancomycin, Colistin, and Nystatin).

Virulence factors and pathogenesis: -Lipopolysaccharide ( LPS) capsular material; anti-phagocytic activity.-Adhesion Pili for attachment of microbe to epithelial cells.-Toxicity of LPS, acts as polyclonal cell activator.-IgA proteases production. Steps of disease establishment :-The attachment of microbe via its pili to the non-ciliated columnar epithelial cells of mucosal surfaces of urethra and cervix.-Invasion, macrophages release TNF.-Neutrophils aggregation, tissue destruction, and chemotaxis.

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Clinical picture N. gonorrhoeae:

-Urethritis in male: dysuria, redness, swelling, burning with

urination, and discharge from the penis.

-The infection could be disseminated to the epididymis

(epididymitis), prostate gland (prostatitis), testicular tissue

(orchitis).

-In female, Cervical involvement could extend through the uterus to

the fallopian tubes resulting in salpingitis, or to the ovaries

resulting in ovaritis. (Pelvic inflammatory disease).

- Vulvovaginitis is associated with Gonorrhea in young girls.

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One of the complication of gonorrhea is systemic dissemination resulting in skin pustules, septic arthritis, meningitis or endocarditis.

ophthalmia neonatorum

(Gonococcal infection of infant’s eyes).

Disseminated Gonococcal infection;

Skin lesions and ulceration.

Laboratory diagnosis:Clinical specimens: Urethral discharge, vaginal discharge.

1-Direct microscopy: Gram’s stain: Gram’s negative diplococci (Intracellular).

2-PCR: detection of microbial genetic material.

3- Culture: on TM media; identification of Neisseria.

4-Antibiotic sensitivity test: Third generation Cephalosporin.