Neisseria and ChlamydiaKen B. Waites, M.D., F(AAM)

Objectives• To review and discuss

• microbiological characteristics• epidemiology• virulence factors• associated diseases • laboratory detection

Of:

Neisseria meningitidisNeisseria gonorrhoeaeChlamydia trachomatisChlamydophila pneumoniaeChlamydophila psittaci

Neisseria meningitidisNeisseria meningitidis

N. meningitidis

• Oxidase positive• Gram-negative diplococci

• Capnophilic (5 - 7% CO2)

• Non-motile• Grows on chocolate &

sheep blood agar

The Meningococcal Cell Wall

N. meningitidis Pathogenesis

• Polysaccharide capsule

• Lipopolysaccharide (endotoxin)

• IgA protease

Nasopharynx

Blood

CSF(50%)

N. meningitidis Serotypes

• 13 serogroups based on polysaccharide capsule antigens– A, B and C > 90% of cases globally

– A - epidemics in developing countries

– B, C, and Y – sporadic and outbreaks in developed countries

Colony Morphology

Oxidase Positive

N. meningitidisCarbohydrate Metabolism

U.S: • Leading cause of bacterial meningitis in older

children and young adults – Community -sporadic– Institutional- outbreaks

• Afflicts approx. 2,800 persons per yr. in U.S.• 10 – 15% mortality • 11-19% have permanent sequelae• Invasive disease can be fatal within hours

Worldwide:• Only form of meningitis that causes epidemics

N. meningitidis Epidemiology

N. meningitidis Epidemiology

• Humans – only reservoir

• Spread by respiratory droplets or oral secretions

• Nasopharyngeal colonization ~ 10-15%

N. meningitidis Risk Factors

• Household contact of primary case or carrier

• Crowding (boarding schools, military camps)

• Socioeconomic status

• Exposure to tobacco smoke

• Recent viral upper respiratory infection

• Asplenia

• Properdin or terminal complement deficiency

Meningococcal Disease

• Meningitis

• Bacteremia

• Meningococcemia (sepsis)• Purpura fulminans • Waterhouse - Friderichsen Syndrome

• Respiratory tract infection

• Focal infection

• Chronic meningiococcemia

Meningococcal Meningitis Clinical Symptoms

• Headache• Stiff neck• Photophobia• Altered mental status• Fever• Nausea, vomiting• Petechial or purpuric rash• Pneumonia

Petechiae

Purpura

Waterhouse – Friderichsen Syndrome

Neisseria meningitidis

It’s bad – don’t get it!

Meningococcal Meningitis Prognosis

• Associated with fatal outcome: Shock Purpuric rash Low or normal WBC Age ≥ 60 yrs Coma

• 10% of those who recover Permanent neurologic disability Hearing loss Limb loss

Prevention of Meningococcal Disease

• Chemoprophylaxis after exposure

• Vaccination–New conjugate vaccine licensed in

2005

• Recommended for: U.S. military personnelChildren 11-12 yrs Persons at risk during outbreak Travel to high risk area College students AspleniaComplement deficienciesLaboratory workers

Meningococcal Vaccine

Vaccine Limitations

• No protection against Serogroup BPolysialic capsule not immunogenic

• Not useful in children < 2 yrs• 2 vaccines now available in US

– MPSV4 – persons 11-55 yrs– MCV4 – persons 2-10 yrs & > 55 yrs

• New conjugate vaccine MCV4 may– Provide longer immunity– Reduce carriage

Epidemiology of Major STDs in USA

Neisseria gonorrhoeae

Neisseria gonorrhoeae Characteristics

• Kidney-shaped• Nonmotile• Gram-negative

diplococci• Require specialized

medium & incubation conditions for growth

N. Gonorrhoeae Pathogenesis• Venereal or vertical transmission• Pili enhance attachment to cells• Opacity (opa) proteins in outer membrane facilitate cell

invasion• Endotoxin• Peptidoglycan - tissue toxin• Intracellular location• IgA protease• Antigenic variation -no permanent immunity following

infection• Penicillin resistance - plasmid & chromosomal

N. Gonorrhoeae Detection• Gram stain of urethral discharge

in male

– Gram-negative diplococci in PMNs

• Culture

– necessary in females

– very susceptible to cold stress & drying

– oxidase positive

– glucose utilization

– Requires CO2

• Nucleic Acid Amplification Chocolate agar + antibiotics (Thayer-Martin)

N. Gonorrhoeae Diseases• Cervical/urethral gonorrhoea

– 20-30% likelihood of transmission

• Asymptomatic carriage - women• Complications

– arthritis– pelvic inflammatory disease– infertility– proctitis– pharyngitis– ophthalmia neonatorum

male urethritis

Ophthalmia neonatorum

• Neonatal gonococcal or chlamydial ocular infection

• Acquired by passage through infected birth canal

Neisseria gonorrhoeaePrevention

• No effective vaccine

• Use of condoms

• Education

• Silver nitrate or antimicrobial drops in neonate eyes

ChlamydiaChlamydia trachomatistrachomatis

Chlamydia trachomatis Characteristics

• Obligate intracellular pathogens• Lacks peptidoglycan• Unique intracytoplasmic growth

cycle• Depend on host for ATP • Growth within cytoplasmic

inclusion – prevents phagolysosome fusion

• Stain with Giemsa• 15 serovars

Chlamydia Life Cycle

Chlamydia trachomatisPathogenesis

• Ocular Infections: PMNs monocytes macrophages plasma cells lymphoid follicles fibrosis, scarring

• Genital Infections: organism attached to mucosal epithelium induces inflammation & discharge

• Not as pyogenic as N. gonorrhoeae

Chlamydia trachomatisDetection

• Cell culture, stain inclusions with monoclonal antibodies

• Nucleic acid amplification (method of choice)

• Antigen detection - cheaper than nucleic amplification but less sensitive

Ocular Trachoma• 400 million children & adults worldwide

• C. trachomatis serovars A, B, Ba, C

• Most common in developing countries

• Follicular keratoconjunctivitis

Neonatal Infections due to C. trachomatis

• Inoculation at birth from infected mothers– Inclusion keratoconjunctivitis – Pneumonitis

C. trachomatis Genital Disease in Adults

• Cervicitis in women

• Non-gonococcal urethritis in men

• One of the most common STDs

• Complications: infertility, ectopic pregnancy, salpingitis

• Many women asymptomatic

Lymphogranuloma Venereum

• Caused by C. trachomatis serovars L1,L1,L3

• Inguinal lymphatic involvement with obstruction

• Much less common than chlamydial urethritis

Prevention of C. trachomatis Infections

• No effective vaccine

• No protective immunity following infections

• Improve socioeconomic & hygiene conditions

• Education

Chlamydophila psittaci

• Disease of parrots & parakeets sometimes transmitted to humans

• Respiratory infection (pneumonitis)

• Serologic diagnosis• Transmitted in bird

droppings

Chlamydophila pneumoniae

• New species (1980s)• Acute lower respiratory illness,

pharyngitis, sinusitis• Similar to mycoplasma• Frequently asymptomatic• Detected by PCR, cell culture,

serology• Diagnostic testing not widely

available• Relation to other chronic

inflammatory conditions such as atherosclerosis and coronary artery disease?