Gonorrhea and Chlamydia

Question 1

Bacteriology of N. gonorrhoeae

Answer 1

• gram (-) diplococci
• human-restricted
• diplococci
• oxidase positive
• won’t grow on blood agar, use chocolate agar or Thayer- Martin as appropriate
• cleared from bloodstream by immune complement: complement deficiencies are predisposing for complications
• NOT encapsulated
• hundreds of serotypes
• very sensitive to dehydration, cold
• plasmid-borne Ab resistance more common than in meningococcus, cephalosporin resistance emerging right now
• gram negative LOS

Question 2

Transmission of N. gonorrhoaea

Answer 2

• transmitted sexually or at birth
• Pili, IgA protease, and Opa virulence factors for attachment to mucosal surfaces and intracellular penetration
• bacterium IS replication-competent, so intracellular penetration is probably for immune evasion
• local immune reaction to endotoxin LOS causes irritation, discharge, containment
• porin A and B confer serum resistence in strains that are more likely to disseminate (Disseminated Gonococcal infection)
• male: usually symptomatic: anterior urethritis
• female: often asymptomatic: cervicitis, Type IV pili confer “twitching motility -> progression to PID, genital tract infections most common, anorectal and pharyngeal also occur
• neonate: purulent conjunctivitis

Question 3

Pathogenesis of Gonorrhaea

Answer 3

• transmitted sexually or at birth
• antibodies, complement, neutrophils restrict infection to local site
• bacteremia can occur in certain strains, predispositions
• extremely contagious sexually (single exposure transmission)
• symptoms develop quickly (no latency)
• infection in children is a reportable marker for sexual abuse
• 700k new infections
• most common in African Americans, rural Southeast, inner cities, young unmarried, low education (socioecomic factors)
• infection rates crashed in 1970s but have been creeping upward more recently

Question 4

Diagnosis of Gonorrhea - Exam

Answer 4

• male- urethritis, dysuria, purulent discharge
• female- purulent vaginal discharge, PID- pain, bleeding, perihepatitis, thick Fallopian tubes or abscess on sonogram
• both: coinfection of pharynx, rectum, eye may occur
• disseminated infection- lack of urogenital symptoms, arthritis/dermatitis, septic arthritis, rarely meningitis, endocarditis
• neonate- bilateral conjunctivitis, if untreated, permanent blindness

Question 5

Diagnosis of Gonorrhea- Lab

Answer 5

• Male- first, test urine and exudate for PMNs and intracellular diplococci, if needed obtain urethral swab for gram stain, culture on Thayer Martin agar, Required if case has legal implications
• Female- obtain endocervical smear, culture on Thayer-Martin
• Disseminated gonococcal infection- gram stain, culture samples from all affected areas, blood, joint fluid may be cultured on nonselective chocolate agar

Question 6

Treatment of Gonorrhea

Answer 6

• begin antibiotics before labs come back
• ceftriaxone, alternate cefixime, cephalosporin
• add axithromycin or doxycycline for coinfection with Chlamydia
• aspirate septic joints
• admit if pregnant, PID, DGI, endocarditis, meningitis, purulent joint infection
• if living in an area with known Ab resistance problems, test cure 1 week after treatment. Otherwise, follow up in 3 months

Question 7

Prevention of Gonorrhea

Answer 7

• Neonate- erythromycin ointment on eyes at birth
• STD: condoms, treat all sexual contacts
• report cases to local health authorities
• expedited partner treatment may be warranted

Question 8

Bacteriology of C. trachomatis

Answer 8

• unique life cycle: dense, rugged elementary bodies attach to cell, endocytosed, survive, unpack into reticulate bodies
• then larger delicate, RBs replicate, metabolize, pack into EBs, escape host cell
• only EBs are infectious, only RBs divide

Question 9

Pathogenesis of Genital Chlamydia trachomatis

Answer 9

• symptoms determined by serovar
• serovars A, B, Bb, C: blinding trachoma: leading cause of preventable blindness, spread by secretions, fomites, endemic to Africa, southern Asia
• Serovars L1-L3: lymphogranuloma venereum- small ulcer proceeds to painfully swollen lymph nodes near genitals, sexually transmitted, endemic to south and central america
• Serovars D-K: genital “chlamydia”- the most common STD in the US, often asymptomatic, may spread sexually or infect newborns at birth

Question 10

Diagnosis of Chlamydia

Answer 10

• blinding tachoma- eyelashes turned inward, travel to endemic area
• LG: buboes, history of sex while traveling
• Genital Chlamydia- history of nonbarrier contraceptives, multiple sexual partners, age <19, socioeconomically disadvantaged

Question 11

Exam for Chlamydia

Answer 11

• female: easily induced endocervical bleeding, mucopurulent endocervical discharge, bleeding, dysuria, abdominal pain, progression to pelvic inflammatory disease
• male: urethral discharge, dysuria, scrotal pain, perineal fullness
• both: Risk of Reiter Syndrome= Reactive Arthritis
• infant: occular trachoma/ pneumonia

Question 12

Labs for Chlamydia

Answer 12

• infant ocular trachoma: stain eye swab with Giema or IF for chlamydial inclusions
• culture- C. trachomatis grows well in many common cell lines, culture required if case has legal implications
• molecular methods like fluorescent hybridization, ELISA, PCR- easier and cheaper than culture, more likely to give a false positive- you detect the chlamydial rRNA
• serology not useful because past infection is too common

Question 13

Treatment for Chlamydia

Answer 13

• antibiotics are indicated, must be able to penetrate infected cell membranes- doxycycline or azithromycin
• peds, pregnanty, allergix- erythromycin and amoxicillin, test the cure
• reinfection is very common
• treat all sexual partners
• condoms
• counsel about risk of Reactive Arthritis sequel

Question 14

Differences between N. gonorrhoeae and N. meningitidis

Answer 14

• not encapsulated
• hundreds of serotypes
• even more sensitive to dehydration, cold
• plasmid-borne antibiotic resistance more common (new and improved with cephalosporin resistance

Question 15

N. gonorrhoeae Virulence factors

Answer 15

• IgA protease clears IgA from mucosal surfaces to facilitate colonization
• Pili attach to columnar and transitional epithelium of mucosal surfaces, antiphagocytic
• Opa- opacity-associated proteins enhance cell adherence and entry
• Porin A and B channels in outer membrane confer serum resistance, enhance cell entry
• LOS: less immunogenic than LPS, but does not induce local inflammatory response (the Drip, the Clap)

Question 16

PID

Answer 16

• follows from mixing bacteria from refluxed menstrual blood or attachment to sperm- can be some twitching motility by pili
• spread of cervical infection to Fallopian tubes creates pain, risks of infertility and ectopic pregnancy
• lower abdominal pain
• vaginal discharge
• dysuria
• tenderness
• intermenstrual bleeding
• Fitz-Hugh-Curtis syndrome: bacteria (either gonorrhea or chlamydia) jump from fallopian tube to liver capsule -> acute perihepatitis
• conogram may show thick Fallopian tubes or abscess

Question 17

Gonorrhea Dissemination

Answer 17

• certain strains more likely to disseminate
• virulence factor is serum resistance including protein Porin A in cell wall (anti-complement)
• more common in women
• asymptomatic infection, menses, pregnancy, and complement C6-C9 deficiency also predispose
• often lack urogenital symptoms
• arthritis/dermatitis syndrome with joint pain and skin pustules
• asymmetric tenosynovitis with pain in wrists and ankles
• moderate fever
• progression to septic asymmetric arthritis (knee common)

Question 18

Gonorrhea Co-infection

Answer 18

• pharynx, rectum, eye
• both men and women
• all appear as irritated/destroyed tissue with discharge

Question 19

Other complications of N gonorrhoeae

Answer 19

• gonococcal meningitis: admit, spinal tap
• endocarditis: echocardiogram, cardio consult- more common in men, aortic valve most common site, subacute onset of fever, chills, sweats, malaise, chest pain, cough

Question 20

Neonate and Gonorrhea

Answer 20

• bilateral conjunctivitis
• generally infected at birth, can happen postpartum or in utero
• eye pain, redness, discharge
• infection may also be pharyngeal, respiratory, rectal or disseminated
• untreated, permanent blindness follows quickly

Question 21

Male testing

Answer 21

• try first: urine and exudate testing
• obtain and centrifuge first- morning void, swab exudate
• gram stain: PMNs indicate urethritis, Gram -, intracellular diplococci indicate gonorrhea
• nucleic acid amplification
• if negative obtain urethral swab
• gram stain is the same, culture on Thayer-Martin: chocolate agar with drugs to inhibit normal flora
• colonies tested for gram-, oxidase+, diplococci
• required if case has legal implications (rape, child abuse)
• most sensitive and specific method

Question 22

Female diagnosis of gonorrhea

Answer 22

• obtain endocervical smear (urethral sample if hysterectomy); wipe off exudate first
• culture on Thayer-Martin

Question 23

Lab for Disseminate Gonorrhea Infection

Answer 23

• swab, gram stain and culture mucosal surfaces and fluid draws
• samples from normally-sterile sites (blood, joint fluid) may be cultured on nonselective chocolate agar
• immunofluorescence may give better results than gram stain on pustule samples
• differentiating N. meningitidis from N gonnorrhoe: only meningococci ferment maltose. Alternatively, immunofluorescence

Question 24

Elementary bodies

Answer 24

• small (0.3-04. um)
• infectious
• rigid outer membrane
• rugged
• bind to receptors on epithelium of lung or mucus membrane and initiate infection

Question 25

Reticulate bodies

Answer 25

• non-infectious intracellular form
• metabolically active
• replicating
• synthesizes its own DNA, RNA and proteins ,but requires ATP from host
• fragile gram(-) membrane
• inclusions accumulate 100-500 progeny before release

Question 26

Immune response to chlamydia

Answer 26

• inflammatory cascade causes some of the symptoms (swelling, discharge) but usually fails to either clear the infection or prevent reinfection
• no useful immune memory (reinfection common)

Question 27

Blinding Trachoma

Answer 27

• infectious eye disease, leading cause of preventable blindness
• 84 million people suffer, 8 million visually impaired
• spread by secretions- direct and fomites
• untreated eyelids turn inward, causing the eyelashes to scratch the cornea
• WHO aims to eradicate by 2020

Question 28

Lymphogranuloma Venereum

Answer 28

• endemic in South and Central America, rare in US (obtain history of sex while traveling)
• a small, painless ulcer proceeds to swollen, painful lymph nodes (buboes)
• symptoms are caused by bacterial replication in the mononuclear phagocytes of the local lymph nodes
• labwork and treatment are the same as for other genital chlamydia
• aspiration of buboes and fistulas may speed healing

Question 29

Genital Chlamydia

Answer 29

• 4 million infections per year
• prevalence rates > 10 in sexually active adolescent females
• often asymptomatic- particularly in male reservoirs
• most commonly local mucosal inflammation and discharge: urethritis or urethritis/vaginitis/cervicitis
• infection increases risk of acquiring HIV
• pregnant women infected with chlamydia can pass the infection to their infants during delivery
• leading cause of PID and infertility in women

Question 30

Risk factors

Answer 30

• nonbarrier contraceptive use
• multiple sexual partners
• single marital status
• age <19
• socioeconomic disempowerment

Question 31

Reiter Syndrome

Answer 31

• reactive arthritis secondary to an immune-mediated response; chlamydia is one of several infections known to trigger it
• defined as conjunctivitis +urethritis +arthritis
• 80% of affected patients are human leucocyte antigen-B27 (HLA-B27)- positive
• treated with NSAIDs may take 2 years to resolve