Gonococcal Disease: Sterility and Transmission

• Neisseria meningitidis, often called the meningococcus, causes life-threatening sepsis (meningococcemial and meningitis.
• Neisseria gonorrhoeae, often called the gonococcus, causes the sexually transmitted disease (STD) gonorrhea.

Neisseria meningitidis

• Virulence factors include a polysaccharide capsule, endotoxin LPS (lipopolysaccharide), IgA protease, pili.
• The polysaccharide capsule is antiphagocytic unless specific antibodies coat the bacterium.
• At least 13 serogroups (A, B, C, D, E, H, I, K, L, X, Y, Z, and W-135) are categorized based on antigenic capsular polysaccharides.
• Meningitis is usually caused by serogroups A, B, and C.
• Endotoxin LPS causes blood vessel destruction (hemorrhage), seen on the skin as petechiae.
• The same process of blood vessel hemorrhage can damage the adrenal glands.
• IgA protease cleaves IgA antibodies in half.
• It can extract iron from human transferrin via a non-iron requiring mechanism.
• Pilishas allow attachment to human nasopharyngeal cells and also undergo antigenic variation.
• It can be part of the normal flora of the nasopharynx.
• Asymptomatic nasopharyngeal infection allows development of anti-meningococcal antibodies (natural immunization).
• High-risk groups: Infants aged 6 months - 2 years, army recruits, college freshmen. Infants are susceptible due to waning maternal antibodies and not yet manufacturing their own.
• Maternal protective antibodies cross the placenta during pregnancy, providing protection to the newborn for the first few months of life.

Meningococcal Disease

• Neisseria meningitidis spreads via respiratory secretions.
• Can invade the bloodstream (bacteremia) from the nasopharynx, leading to meningitis and/or deadly sepsis (meningococcemia).
• A petechial rash indicates invasive meningococcal infection, caused by endotoxin release, vascular necrosis, and hemorrhage into the surrounding skin.

Meningococcemia

• Intravascular multiplication results in abrupt onset of spiking fevers, chills, arthralgia, muscle pains, and petechial rash.
• Fulminant meningococcemia (Waterhouse-Friderichsen syndrome) is septic shock with bilateral hemorrhage into the adrenal glands causing adrenal insufficiency.
• Symptoms include abrupt onset of hypotension, tachycardia, rapidly enlarging petechial skin lesions, disseminated intravascular coagulation (DIC), and coma.
• Death can occur rapidly (6-8 hours).

Meningitis

• Most common form of meningococcal disease, primarily affecting infants < 1 year of age.
• Infants usually display nonspecific findings of infection: fever, vomiting, irritability, and/or lethargy.
• A bulging open anterior fontanelle may be a sign of meningitis in neonates, while slightly older infants may display a stiff neck, as well as positive Kernig's and Brudzinski's signs.
• Petechial skin rash may occur.
• Diagnosis: Gram stain and culture from blood, cerebrospinal fluid, or petechial scrapings.
• Grows best on heated blood agar (chocolate agar) or Thayer-Martin VCN media.

Diagnosis and Treatment

• Neisseria grow best on blood agar that has been heated so that the agar turns brown (Called chocolate agar).
• The classic medium for culturing Neisseria is called the Thayer-Martin VCN media.
• The addition of a high concentration of CO2 further promotes the growth of Neisseria.
• V stands for vancomycin, which kills gram-positive organisms.
• C stands for Colistin which kills all gram-negative organisms (except Neisseria).
• N stands for nystatin, which eliminates fungi.
• Differentiation between Neisseria species is based on Neisseria meningitidis' ability to produce acid from maltose metabolism, while Neisseria gonorrhoeae cannot.
• Prompt treatment with penicillin or ceftriaxone is required at the first indication of disseminated meningococcemia.
• Close contacts of an infected patient are treated with rifampin or ciprofloxacin.
• Immunization with purified capsular polysaccharides.
• The Group B polysaccharide vaccine is not available due to it not inducing immunity.

Neisseria gonorrhoeae

• Virulence factors include Pili, Protein I, Opa proteins, LOS(Lipopolysaccharide)
• Complex genes code for pili, undergoing multiple recombinations for hypervariable amino acid sequences to avoid antibody attack and prevent phagocytosis.
• Outer membrane protein porins (PorA and PorB) (formerly called Protein I) appear to promote invasion into epithelial cells.
• Opa proteins promote adherence and invasion into epithelial cells; expression leads to opaque colonies.
• Overall pill, porins and Opa proteins allow the gonococci eo bind to a Fallopian tube non-clilated epithelial cell.
• The gonococcal endotoxin then destroys the cilia on neighboring cells
• The gonococcus is then taken up by endocytosis, transported in the endocytotic vacuole (where it multiplies) and is released under the subepithelial space where it can cause more system infection

Virulence Factors of Neisseria gonorrhoeae

• Adherence via type IV pili and Opa protein.
• Release of LOS (lipooligosaccharide) and OMVS (outer membrane vesicles).
• Peptidoglycan, LOS, and OMVS cause NOD and TLR activation.
• HBP causes acti pendant Influx inflammation cytokine, chemokine and adherence and N. gonorrhoeae strophilis

Gonococcal Disease

• Neisseria gonorrhoeae penetrates mucous membranes of the urethra in men, causing urethritis.
• Most men will complain of painful urination along with a purulent urethral disc both asymptomatic and symptomatic men can pass this infection to another sexual partner.
• Fortunately, this disease is easily cured by a small dose of ceftriaxone.
• Men having sex with men results in rectal gonococcal infection; can cause anal pruritis, tenesmus, and/or rectal bleeding, and purulent discharge.
• Women can also develop gonococcal urethritis and Neisseria gonorrhoeae infects the columnar epithelium of the cervix.
• Urethritis in women is more likely to be asymptomatic with minimal urethral discharge.
• If symptoms develop, the woman may complain of lower abdominal discomfort, pain with sexual intercourse, and a urulent vaginal discharge.
• Both asymptomatic and symptomatic women can transmit this infection.
• A gonococcal infection of the cervix can progress to pelvic inflammatory disease (PID).

Gonococcal Disease in Both Men and Women

• Rarely, Neisseria gonorrhoeae can invade the bloodstream.
• Manifestations include fever, joint pains, and skin lesions, usually erupting on the extremities.
• Pericarditis, endocarditis, and meningitis are rare but serious complications of a disseminated infection.
• Acute onset of fever occurs along with swelling two joints.
• Without prompt antibiotic therapy, progressive destruction of the joint will occur.
• Examination of synovial fluid usually reveals increased white blood cells.
• Gram stain and culture of the synovial fluid confirms the diagnosis.
• Gonococcal arthritis is the the kind of septic arthritis in young, sexually active individuals
• Gonorrhea may also be transmitted anally or orally, wherever there is a transmission of body fluids.

Gonococcal Disease in Infants

• Neisseria gonorrhoeae can be transmitted from a pregnant woman to her child during delivery, resulting in ophthalmia neonatorum.
• This eye infection usually occurs on the first or second day of life and can damage the cornea, causing blindness.
• Because neonatal Chlamydia eye infections are also a threat, erythromycin eye drops are given to all newborns.
• Gonococcal conjunctivitis can also occur in adults.

Pelvic Inflammatory Disease (PID)

• PID is an infection of the uterus (endometritis), fallopian tubes (salpingitis), and/or ovaries (oophoritis).
• Patients can present with fever, lower abdominal pain, abnormal menstrual bleeding, and cervical motion tenderness.
• Cases of PID occur within one week of the onset of menstruation since it allows bacteria to spread from the cervix to the upper genital tract.
• An intrauterine device (IUD) increases the risk of a cervical gonococcal infection progressing to PID.

Complications of PID

• Sterility: Scarring of fallopian tubes most commonly causes it by Occluding lumen and prevents sperm from reaching the ovulated egg.
• Ectopic pregnancy: The risk of a fetus developing at a site other than the uterus is significantly increased with previous fallopian tube inflammation (salpingitis).
• Abscesses may develop in the fallopian tubes, ovaries, or peritoneum.
• Peritonitis: Bacteria may spread from ovaries and fallopian tubes to infect the peritoneal fluid.
• Peri-hepatitis (Fitz-Hugh-Curtis syndrome): Infection of capsule that surrounds the liver by Neisseria Gonorrhoeae

Diagnosis and Treatment

• Diagnosis of Neisseria gonorrhoeae infection is best made by Gram stain and culture on Thayer-Marin VCN medium.
• Therefore, only Neisseria (both Neisseria meningitidis and Neisseria gonorrhosse) are able to grow on this culture medium.
• The addition of a high concentration of CO2 further promotes the growth of Neisseria.

Antibiotic resistance

Examples of mechanisms of antibiotic resistance

• Inactivation of antibiotic drug by enzymes.
• Inhibition of drug uptake.
• Drug inactivating
• There is a plasmid with the tot gene sequence that encodes a protein activation of that protects ribosomes from the effects of tetracycline.
• The mer gene locus encodes an efflux pump that prevents accumulation of antibiotics in cell.
• Chromosomally mediated antibiotic resistance to beta-lactams.
• The pen A locus represents a mutation that alters penicilin binding protein 2 the transpeptidase required to synthesize peptidogtycan to reduce Les affinity for penicilin.
• Multiple mutations in the chromosomal gyrą, and gyrß genes that encode the DNA gyrases confer resistance to ciprofloxacin.

Explore the mechanisms of gonococcal disease leading to sterility in women and modes of transmission from pregnant women to their children. Learn about dermatological manifestations, risk factors, and diagnostic methods. Test your knowledge about Neisseria gonorrhoeae and related complications.