1. Mt. Temple, Canadian Rockies - June 2006

2. NEISSERIA (Gram-negative diplococci)
Neisseria gonorrhoeae (always considered pathogenic, even without symptoms)
Neisseria meningitidis
Neisseria sicca, Neisseria mucosa, Neisseria lactamica

3. PASTEURELLACEAE (small Gram-negative bacilli)
Haemophilus - H. influenzae, H. parainfluenzae
Actinobacillus - A. actinomycetemcomitans
Pasteurella - P. multocida

4. NEISSERIA (Gram-negative diplococci)
N. gonorrhoeae
The most common sexually transmitted disease in the U.S.
N. meningitidis
Colonizes the upper respiratory tract.
Meningitis, septicemia, pneumonia, arthritis, urethritis.
N. sicca, N. mucosa, N. lactamica
Commensals in the oro- and nasopharynx.
Isolated reports of meningitis, osteomyelitis, endocarditis,
respiratory infections, acute otitis media and acute sinusitis.

5. Neisseria
meningitidis
Gram-staining
(Gram-negative
diplococci)

6. Neisseria gonorrhoeae
Small Gram-negative diplococci with pili,
non-motile, cytochrome oxidase positive,
strict oxidative metabolism of glucose.
Virulence Factors:
Pili - mediate attachment to mucosal cell surfaces; antiphagocytic.
Pilin proteins - more than 100 serotypes; marked antigenic variations.
Non-piliated bacteria are avirulent.

7. N. gonorrhoeae - Virulence Factors
Por (Protein I) - forms pores in the surface
Opa (Protein II) - attachment to epithelial cells
Tbp1 and Tbp2 - transferrin-binding proteins (Fe)
Lbp - lactoferrin-binding protein (Fe)
LOS - lipooligosaccharide (endotoxin activity)
IgA protease - hydrolyzes secretory IgA
Penicillinase - b-lactamase (plasmid-encoded)

8. N. gonorrhoeae - Epidemiology
Disease occurs only in human >400,000 cases/year
Transmission: sexual contact
(risk 50% for women, 20% for men)
The major reservoir is an asymptomatic carrier

9. N. gonorrhoeae - Clinical Symptomes
Men: acute urethritis, a purulent urethal discharge and dysuria, rare complications (epididymitis, prostatitis).
Women: the endocervix (but isolation from vagina, urethra and rectum) - a purulent vaginal discharge, intermenstrual bleeding, dysuria, abdominal pain;
in 10-20% - ascending genital infections (salpingitis, tuboovarian abscesses, pelvic inflammatory disease), can result in sterility.

10. N. gonorrhoeae - Clinical Symptomes
Disseminated infections - septicemia, infection of skin and joints
Perihepatitis (Fitz-Hugh-Curtis syndrome)
Anorectal gonorrhea in women and homosexual men
Pharyngitis
Purulent conjuctivitis - newborns infected during delivery (ophthalmia neonatorum)

11. N. gonorrhoeae - Treatment
Penicillin G is NOT recommended (240 x increase in the therapeutic dose since 1945)
Resistance to penicillin :
b-lactamase (penicillinase) (a transmissible plasmid)
The chromosomally mediated resistance also to tetracyclines, erythromycin, and amidoglycosides (changes of the cell surface that prevent antibiotic
binding and penetration)
CDC recommendations - ceftriaxone, cefixim, or fluoroquinolone (initial therapy) combined with tetracycline, doxycycline or azithromycin (Chlamydia)

12. N. gonorrhoeae
Multiple infections in sexually promiscuous individuals (lack of protective immunity)
Variability in the immunodominant portion of
the pilin protein (ineffectiveness of vaccines)
Universal ocular prophylaxis - only in newborns -
within 1 hour after birth
1% silver nitrate solution is the classic method (conjunctival irritation)
1% tetracycline or 0.5% erythromycin eye ointments

13. Factors responsible for meningococcal disease:
Neisseria meningitidis
The colonization of the nasopharynx (pili).
Systemic spread without antibody-mediated phagocytosis (protection by a prominent polysaccharide capsule).
Toxic effects mediated by lipopolisaccharide (LPS) - endotoxin.

14. Scanning electron micrograph:
attachment of N. meningitidis
by pili to the microvilli of
noncilited cells
in the nasopharynx
Scanning

15. N. meningitidis - Epidemiology
Respiratory droplets
Humans are the only natural carriers
(10-30% of population/nasopharynx)
Endemic disease is most common in children younger than 5 years of age
During the first months of life, maternal antibodies are protective
Passive (maternal) immunity wanes and before acquired immunity develops, children are susceptible to infection

16. N. meningitidis - Clinical Syndromes
Meningitis
2,500-3,000 cases per year in the U.S. (abrupt, intense headache, stiff neck, vomiting, coma, meningal signs, fever). Lethal 100% without antibiotics, less than 10%
with antibiotics.
Meningococcemia (septicemia) - with or without meningitis is a life-threatening disease, mortality rate 25%; severe fever, widespread coagulation, cardiovascular collapse.
Waterhouse-Friderichsen syndrome (bilateral destruction of the adrenal glands).
Pneumonia, arthritis, urethritis.

17. Neisseria meningitidis has become
a leading cause of bacterial meningitis
in the U.S. after dramatic reductions
in the incidence of
Streptococcus pneumoniae and
Haemophilus influenzae type b (HIB)
infections have been achieved as
a result of using conjugate vaccines.

18. Skin lesions in patient with meningococcemia

19. N. meningitidis Laboratory Diagnosis
(blood, cerebrospinal fluid [CSF] [Gram-staining])
Treatment
Penicillin G (rare resistance to penicillin), chloramphenicol
broad-spectrum cephalosporins
Carriers: Sulfonamides, Rifampin for sulfonamide-resistant strains.
Outbreaks: Rifampin

20. N. meningitidis - Vaccines
Tetravalent capsular polysaccharide vaccine
(Menomune-A,C,Y,W-135) (Sanofi Pasteur, Inc.)
against four (A, C, Y, and W-135) of the five pathogen serogroups.
Highly effective in adults but not in infants and children less than two years of age; immunity ~3 years.
No vaccines available against serogroup B
N. meningitidis (MenB) disease, is responsible for
32% of meningococcal disease in the U.S. and
45% to >80% in Europe.

21. N. meningitidis - Vaccines
The MenB capsular polysaccharide is identical to a widely distributed human carbohydrate (a self-antigen).
The immunity to N. meningitidis group B must develop naturally after exposure to cross-reacting antigens.
Vaccination with Menomune - to control an outbreak of disease with a serogroup present in the vaccine,
for travelers to hyperendemic areas, or for individuals at increased risk (patients with complement deficiency).

22. In January 2005, a quadrivalent meningococcal
polysaccharide-diphtheria toxoid conjugate vaccine
[MCV4] Menactra (Aventis Sanofi Pasteur, Inc.) was
licensed for use among persons aged years.
CDC recommends routine vaccination of
young adolescents (at aged years)
with MCV4 at the preadolescent health-care visit
(at age years).
By 2008, the goal will be routine vaccination with
MCV4 off all adolescents beginning at age 11.

23. Nepal 1999

24. PASTEURELLACEAE (small Gram-negative bacilli)
Haemophilus
Encapsulated H. influenzae
(meningitis, epiglottitis, otitis, sinusitis)
Non-encapsulated H. influenzae
(primarily pediatric ear and sinus infections)
H. parainfluenzae (dental plaque, periodontal disease)
Actinobacillus - A. actinomycetemcomitans (isolated from the oral cavity, associated with periodontitis and endocarditis)
Pasteurella - P. multocida (animal exposure)

25. Haemophilus
Most species of Haemophilus (from the Greek words for "blood loving") require two components:
Heme (X factor)
NAD (factor V) (heated blood agar "chocolate agar")
LPS present in the cell wall (Gram-negative)

26. Haemophilus Polysaccharide capsule (six antigenic serotypes: a - f)
Before the introduction of vaccines directed against H. influenzae type b antigen (HIB), this serotype was responsible for over 95% of Haemophilus infections.
After the introduction of the vaccines, serotypes a and f, and non-encapsulated H. influenzae emerged
as important pathogens.

27. Haemophilus Pathogenesis and Immunity
H. parainfluenzae and non-encapsulated H. influenzae colonize the upper respiratory tract within the first few months of life - 80% children; 20-50% healthy adults
They can spread locally - otitis media, sinusitis, bronchitis, pneumonia

28. Haemophilus Pathogenesis and Immunity
Encapsulated H. influenzae is rarely isolated from the upper respiratory tract BUT is a common cause of diseases in children (meningitis, epiglottitis, cellulitis).
The major virulence factor in H. influenzae type b is the antiphagocytic polysaccharide capsule (polyribitol phosphate, PRP) (anti-PRP antibodies).
Anti-IgA1-specific proteases - facilitate colonization.

29. Haemophilus - Epidemiology
The majority of facultatively anaerobic Gram-negative bacilli (rods) in the oral cavity belong to the genus Heamophilus.
There is no animal reservoir.
Most of the isolates are non-encapsulated H. influenzae.
H. influenzae type b - rarely isolated in healthy children.
H. parainfluenzae - 10% of the bacterial flora in saliva, associated with dental plaque and periodontal disease.
Non-encapsulated H. influenzae and other Haemophilus species - ear and sinus infections (primarily pediatric), pulmonary disease (the elderly).

30. Clinical Syndromes
Meningitis, epiglottitis, cellulitis, arthritis, conjuctivitis and Brazilian Purpuric Fever.
Otitis, sinusitis, infections of lower respiratory tract, chancroid, other infections (dental abscesses).

31. H. influenzae and Streptococcus pneumoniae
The two most common causes of acute and chronic otitis and sinusitis.

32. H. influenzae - Treatment
Without antimicrobial therapy mortality rate in patients with meningitis and epiglottitis approaches 100%.
Ceftriaxone - the treatment of choice for H. influenzae meningitis or other systemic infections.
From 20 to 30% of H. influenzae type b isolates produce
b-lactamase.
Less severe infections (sinusitis or otitis media) - amoxicilin-clavulanate or trimethoprim sulfamethoxazole.

33. H. influenzae - Vaccine Contains the capsular polysaccharide of
H. influenzae type b conjugated to diphteria toxoid or other carrier protein (HIB).
Depending upon the carrier protein, it is given between 2 and 15 months of age.
More effective than the unconjugated vaccine.
Reduced the incidence of meningitis by ~90% in immunized children.

34. Actinobacillus Small, facultative anaerobic, Gram-negative bacilli
(CO2 for growth on chocolate agar or blood agar media).
Part of the normal oropharyngeal population (approx. 20% of healthy individuals).
A. actinomycetemcomitans - associated with juvenile and adult periodontitis and endocarditis (underlying cardiac disease and spread from the oral cavity following dental procedures or in patients with periodontitis).

35. Pasteurella multocida
The natural reservoir is the respiratory and GI tracts domestic (dogs and cats) and wild animals.
Localized cellulitis and lymphadenitis after
an animal bite or scratch.
Exacerbation of chronic respiratory disease in patients with pulmonary disfunction.
Systemic infection in immunocompromised patients.
Treatment: Penicillin G, tetracyclin, cephalosporins.

36. Once upon the time … I had a dog. His name was Nikodem.