Neisseriae

February 8, 2008
CASE 3
R.R., 40 YEAR OLD MALE, WITH A
CHIEF COMPLAINT OF FEVER OF
1 DAY DURATION
HISTORY OF THE PRESENT
ILLNBESS(HPI) SHOWED THAT
THE FEVER WAS HIGH GRADE,
WITH BODY MALAISE AND CHILLS.
HE NOTED RASHES WHICH WERE
INITIALLY PINPOINT AND RED
THEN INCREASING IN SIZE, BUT
NON-PRURITIC. MOST OF THE
RASHES STARTED ON HIS BACK.
THERE IS A HISTORY OF TRAVEL
TO AN ARMY CAMP 3 DAYS AGO.
ON PHYSICAL EXAMINATION
BP 80/60mmHg
PR 90/MIN
T: 101 F
(+) NUCHAL RIGIDITY
MULTIPLE CONFLUENT
PURPURIC LESIONS ON HIS
BACK AND LEGS
CBC SHOWED LOW PLATELETS,
ELEVATED WBC
LUMBAR TAP SHOWED GRAM (-)
NEGATIVE DIPLOCOCCI IN THE
CSF
IMPRESSION:?
Neisseriaceae

fourteen genera including Neisseria,

Chromobacterium, Kingella, and
Aquaspirillum.
two important human pathogens, N.
gonorrhoeae and N. meningitidis.
Neisseria gonorrhoeae

Gram-negative coccus
0.6 to 1.0 µm in diameter
seen in pairs with adjacent flattened
sides(diplococci)
found intracellularly in
polymorphonuclear leukocytes
has fimbriae, which play a major role
in adherence, extend several
micrometers from the cell surface.
gonococci produces acid from
glucose only
N.gonorrhoea
susceptible to temperature changes,
drying, uv light
Media: hemoglobin, NAD, yeast
extract and other supplements are
needed for isolation and growth of the
organism
grown at 35-36 degrees in an
atmosphere of 3-10% added CO2.
Virulence factors

Pil E
major fimbrial protein
initial binding to epithelial cells
P.II (Opa)
outer membrane protein
contributes to invasion
Virulence factors
P.I (Por)outer membrane porin
may prevent phagolysosome
formation in neutrophils
reduce oxidative burst
LOS
outer membrane lipooligosaccharide
elicits inflammatory response
triggers release of TNF
Virulence factors

P.III (Rmp)
outer membrane protein
elicits formation of ineffective
antibodies that block that block
bactericidal antibodies against P.I
and LOS
PATHOGENESIS OF THE
INFECTION
Sexual contact

bacteria adhere to non-ciliated

columnar epithelial cells thru the aid
of fimbriae(PilE and opa)

they are surrounded by the microvilli,

drawn to the surface of the mucosal
cell
PATHOGENESIS
bacteria enter the epithelial
cells:parasite-directed endocytosis

the membrane of the mucosal cell

retracts

membrane-bound vacuole that

contains the bacteria( 1 bacteria per
cell)
PATHOGENESIS

vacuole is transported to the base of

the cell

bacteria are released by exocytosis

into the subepithelial
tissue(neisseriae are not destroyed
within the endocytic vacuole)
PATHOGENESIS
the P.II from one bacterium will bind to
LOS of an adjacent bacterium

Microcolony;biofilm

macrophages start to phagocytose the

bacteria
( protein P.I inhibit the ability of phagocytes
to kill ingested bacteria)
PATHOGENESIS
bacterial lipooligosaccharide LOS and
peptidoglycan are released by
autolysis of cells.

activate the host alternative

complement pathway

LOS stimulates TNF;causes cell

damage
PATHOGENESIS

phagocytes die and release the

ingested bacteria

activation of complement pathway

Formation of purulent discharge

<>
Stimulates local IgA; IgG
serum sensitive strains
uncomplicated genital infections
killed by normal human serum
mediated by IgM and IgG which recognize
sites on the LOS
Serum resistant strains
disseminated infections
not killed by most normal human serum
IgA blocks the IgG-mediated bactericidal
activity of the serum
EXPOSURE may not lead to
disease
due to variations in the size or
virulence of the inoculum
natural resistance
specific immunity
50% infective dose (ID50) of about
1,000 bacteria
NONSPECIFIC IMMUNITY AND
NATURAL RESISTANCE
changes in the genital pH and
hormones may increase resistance
Urine contains bactericidal and
bacteriostatic components
urine pH, osmolarity, and the
concentration of urea
some males do not develop a
gonorrhea infection when exposed.
NATURAL ANTIBODIES AND
CROSS-REACTIVE ANTIGENS
uninfected individuals have serum
antibodies that react with gonococcal
antigens
result from colonization or infection by
Gram-negative bacteria
cross-reactive antigens
"natural antibodies"
LIPOOLIGOSACCHARIDE (LOS)

profound effect on the virulence and

pathogenesis
several antigenic types of LOS
LOS produces mucosal damage in
fallopian tube organ cultures
brings about the release of enzymes, such
as proteases and phospholipases
indirect role in mediating tissue damage
associated with a serum-resistant
phenotypes of N. gonorrhoeae
PATHOGENIC TO HUMANS ONLY

The bacteria binds only human

transferrin and lactoferrin
specific
exclusively human pathogens.
TRANSMISSION
almost exclusively by sexual contact
Any sexually active person can be infected
with gonorrhea.
sexually active teenagers
young adults
African Americans
multiple sex partners
males
minority and inner-city populations.
TRANSMISSION

contracted from a sex partner who is

either asymptomatic;minimal
symptoms
efficiency of transmission after one
exposure is about 35 percent from an
infected woman to an uninfected man
50 to 60 percent from an infected
man to an uninfected woman
TRANSMISSION
90 percent of men with urethral
gonorrhea will develop symptoms
within 5 day
fewer than 50 percent of women with
genital gonorrhea will do so
asymptomatic infections are at higher
risk of developing pelvic inflammatory
disease and disseminated
gonococcal infection
GONORRHEA

Anterior urethritis
mucous membranes of the urethra
copious discharge of pus
more apparent in the male
generally limited to superficial
mucosal surfaces lined with columnar
epithelium
GONORRHEA

most frequently involved

urethra
cervix
rectum
pharynx
conjunctiva.
GONORRHEA
young girls:vulvovaginitis
squamous epithelium, which lines the
adult vagina, is not susceptible to
infection
prepubescent vaginal epithelium has
not been keratinized
Mucosal infections are usually
characterized by a purulent
discharge.
GONORRHEA IN MALES

Most common symptom is a discharge

scanty, clear or cloudy fluid
copious and purulent
Dysuria
redness, swelling, heat, and pain in
urethral tissues
intense burning and pain upon urination
asymptomatic: important reservoir for
transmission; increased risk for developing
complications
“the drip”
EPIDIDIMYTIS
FEMALES
endocervical infection in
uncomplicated cases
vaginal discharge
dysuria
50% :asymptomatic.
COMPLICATIONS

MALE
prostatitis
orchitis
FEMALES
salpingitis, with or without ovarian
involvement (ovaritis)
pelvic inflammatory disease (PID).
FALLOPIAN TUBE ABSCESS
INFERTILITY DUE TO PID
OTHER SITES OF INFECTION
Rectal infections (proctitis) in women
one-third of women with cervical
infection
autoinoculation with cervical discharge
rarely symptomatic
Rectal infections in homosexual men
anal intercourse
often symptomatic
treat partners
PROCTITIS
OTHER SITES OF INFECTION

Ocular infections
corneal scarring
perforation
ophthalmia neonatorum
silver nitrate or an antibiotic to the
newborns
OPHTHALMIA NEONATORUM
GONORRHEAL CONJUNCTIVITIS
TREATMENT

third-generation cephalosporin or a
fluoroquinolone
antibiotic for Chlamydia trachomatis:
doxycycline
Sex partners should be referred and
treated
resistant strains: ceftriaxone,
cefixime, ciprofloxacin, or oflaxacin
UNCOMPLICATED GONORRHEA

Ceftriaxone 125 mg IM in a single

dose
OR
Cefixime 400 mg orally in a single
dose or 400 mg by suspension
(200 mg/5ml)
PLUS
TREATMENT FOR CHLAMYDIA
NEISSERIA MENINGITIDIS

identical to Neisseria gonorrhoeae

antiphagocytic polysaccharide capsule:
important virulence factor.
grouped based on capsular
polysaccharides
12 serogroups
associated with disease in humans are A,
B, C, Y, and W135.
NEISSERIA MENINGITIDIS
peptone-blood base medium in a
moist chamber containing 5-10%
CO2
susceptible to temperatures above or
below 37 degrees
rapid autolysis after death, both in
vitro and in vivo
accounts for the dissemination of
lipopolysaccharide or endotoxin
during septicemia
NEISSERIA MENINGITIDIS

colonize the posterior nasopharynx of

humans
humans are the only known host
CARRIERS

Individuals who are colonized the bacteria

transmit disease to nonimmune individuals
individuals in close contact with a case of
meningococcal meningitis become carriers
20 % contact group become carriers
80 % at the height of an epidemic.
CARRIERS
inhabits the human nasopharynx
without causing detectable disease
carrier state may last for a few days
to months
reservoir for meningococcal infection
stimulates host immunity
5 TO 30% of normal individuals are
carriers at any given time, yet few
develop meningococcal disease
EPIDEMICS/OUTBREAKS

3 or more cases in a 3-month period

primary attack rate of at least 10

cases per 100,000 population
OUTBREAKS
Serogroups A, B, and C account for
most cases worldwide
Serogroups A and C
Asia and Africa
serogroups B and C
Europe
North America
South America.
DOCUMENTED CASES
African meningitis belt

serogroup A meningococcal disease

has been endemic for over a century.

Ethiopia in eastern Africa to Senegal

in West Africa
HOST DEFENSES AGAINST
MENINGOCOCCUS
systemic infections occur only in
individuals who lack serum bacterial
antibodies
capsular or noncapsular (cell wall)
antigens of the invading strain

patients deficient in the late-acting

complement components.
HOST DEFENSES
antibodies are produced in response to
colonization
N. meningitidis
N. lactamica
nonpathogenic Neisseria species
normal inhabitants of the upper
respiratory tract
antibodies to cross-reacting antigens on
Escherichia coli.
HOST DEFENSES

high attack rates in infants from 6 to 9

months old
maternal antibodies are decreasing
complement deficiencies (C5, C6, C7,
or C8) may develop
meningococcemia despite protective
antibody
HOST DEFENSES

More prone to the infection

chronic irritation of the mucosa:
dust or low humidity
damage to the mucosa :
concurrent upper respiratory
infection.
PATHOGENESIS

Meningococci are spread via

respiratory droplets
transmission requires aspiration of
infective particles
attach to the nonciliated columnar
epithelial cells of the nasopharynx
usiing fimbriae
PATHOGENESIS

Invasion of the mucosal cells

bloodstream and CNS invasion
bacteria undergoes autolysis during
growth and released parts of their cell
walls in a soluble form
major virulence factors:
lipooligosaccharide,LOS
polysaccharide capsule.
PATHOGENESIS

Endotoxin
Cytokines
free radicals
damage the vascular endothelium
producing platelet deposition
vasculitis.
SIGNS AND SYMPTOMS

INFANTS
onset: abrupt or insidious
rare signs of meningeal irritation
Irritability and refusal to take food
vomiting; dehydration
fever is typically absent in children less
than 2 months old
hypothermia is more common
s/s in infants

latter stages
apnea
seizures
disturbances in motor tone
coma
OLDER CHILDREN/ADULTS

onset: abrupt or insidious

fever and altered mental status:
the most consistent findings
headache is an early complaint;
very severe
OLDER CHILDREN/ADULTS

nausea, vomiting, and

photophobia
convulsions or coma
signs of meningeal irritation such
as spinal rigidity, hamstring
spasms and exaggerated reflexes
MILD FORM

The mildest form of disease:

transient bacteremic illness
fever and malaise
resolve spontaneously in 1 to 2
days.
RASH
Petechiae
purpura
DAY 1 TO 3: 30 to 60% of patients with
meningococcal disease, with or without
meningitis
more prominent in areas of the skin
subjected to pressure
axillary folds
the belt line
back.
RASH

Confluence of lesions results in

hemorrhagic patches, often with
central necrosis.

Impaired protein C anticoagulation

pathway: purpura fulminans
RASH OF MENINGOCOCCEMIA
PURPURA
PURPURA FULMINANS
Fulminant meningococcemia
5 to 15% of patients
high mortality rate
ABRUPT ONSET
sudden high fever
chills
myalgias
weakness
nausea
vomiting
headache.
Fulminant meningococcemia

Apprehension, restlessness, and

delirium occur within the next few
hours
Widespread purpuric and ecchymotic
skin lesions appear suddenly
(+) or no signs of meningitis
Fulminant meningococcemia

Pulmonary insufficiency
death within 24 hours of being
hospitalized despite appropriate
antibiotic therapy and intensive care.
BILATERAL ADRENAL HEMORRHAGE:
WATERHOUSE-FREIDRICHSEN
SYNDROME
LAB EXAMS

Definitive diagnosis: culture of

meningococci from blood, spinal fluid,
joint fluid, or, occasionally, from skin
lesions.
LAB EXAMS

Normal to elevated WBC

Low platelet count
CSF pressures are elevated, with
elevated protein levels and low
glucose levels.
Findings on CSF Gram stain are
positive in about 50% of patients
LAB EXAMS

Detection of meningococcal capsular

polysaccharide in CSF: rapid
diagnosis.
Polymerase chain reaction (PCR) ;
90% sensitivity
CXR: pneumonia; ARDS
2D-ECHO: pericarditis.
Lumbar puncture
TREATMENT

Penicillin is the drug of choice to treat

meningococcemia and
meningococcal meningitis
Rapid absorption thru inflammed
meninges
TREATMENT

Amputation
Pericardiocentesis may be required if
pericarditis is complicated by
tamponade.
TREATMENT OF CONTACTS

500- to 800-fold greater attack rate

among household contacts than
among the general population.
Chemoprophylaxis
Rifampin is the chemoprophylactic
agent of choice.
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