CLINICAL CASE

A 19-year-old woman presents to the physicians office for

the evaluation of a swollen knee. She states that for the past
12 week she has had some achiness in several of her joints
and a low-grade fever, but it seemed to localize to her left
knee approximately 3 days ago.
It has been red, hot, and swollen. She has had no injury to
the area and has never had anything like this before. Her past
medical history is significant for having been treated for
Chlamydia at the age of 17. She takes oral contraceptive pills
regularly. She is sexually active, has been with her most
recent boyfriend for about a month, and has had 5 partners in
her lifetime.
On examination, her vital signs are normal, but you notice
that she walks with a limp. Her general examination is
normal, and her skin is without rash. Her left knee is
erythematous and warm to the touch. There is a visible
effusion. Movement is limited because of pain and stiffness
from the swelling. She refuses a pelvic examination because
she doesnt see what that has to do with her sore knee.
However, she does allow you to perform a joint aspiration.
What are the most likely Gram stain findings of the
aspirated joint fluid?
What cell surface factors facilitate attachment and
penetration of this organism into the host cell?

ANSWERS TO CASE 16: Neisseria

Summary: A 19-year-old woman presents with septic
arthritis. She has had an infection previously with
Chlamydia.
Likely findings on Gram stain of the joint
fluid aspirate: Multiple polymorphonuclear leukocytes
with intracellular gram-negative diplococci. 
Cell surface factors facilitating attachment
and penetration into the host cell: Pili, which attach
to epithelial cells, and Opa protein, which promotes
firm attachment and cell penetration. 

CLINICAL CORRELATION Humans are the only known

reservoir of Neisseria species. Neisseria gonorrhoeae is
transferred from person to person by sexual contact.
Approximately half of infected women have an
asymptomatic carrier state. This is much less common in
men. Neisseria gonorrhoeae causes urethritis in men and
cervicitis in women.
Complications of genital infections include pelvic
inflammatory dis- ease. The organism can also infect the
rectum and oropharynx. Newborns passing through an
infected birth canal may develop conjunctivitis by direct
contact, a disease called ophthalmia neonatorum.
Disseminated disease, including bac- teremia with resultant
joint and/or skin infections is more common in patients with
complement deficiencies. Septic arthritis as a complication

of disseminated disease may present in two forms, either as a

systemic disease with fever, chills, and polyarticular
syndrome, or as a monoarticular suppurative infection of a
single joint without skin lesions or systemic symptoms.
Most cases of disseminated gonococcal disease occur in
persons with an asymptomatic genital infection. Neisseria
meningitidis is carried as normal upper respiratory flora in
approximately 10 percent of the population. The
polysaccharide capsule allows the organism to avoid
phagocytosis and under unknown circumstances enter the
blood and in some cases the central nervous system. The
subsequent inflammatory response induced by the organism
causes shock and dissemi- nated intravascular coagulation.
This is evidenced by skin lesions, which can mimic those
seen in disseminated gonococcal infection. Bacteremia with
or without meningitis usually occurs in teenage children. If
untreated, the disease has a high mortality rate. 
APPROACH
PATIENT

TO

SUSPECTED

GONORRHOEAE

Objectives
1. Know the structure and characteristics of Neisseria
species. 
2. Know the factors associated with the development on
Neisseria infections and diseases.

Definitions
Disseminated intravascular coagulation (DIC): A
complication of septic shock usually caused by endotoxin
produced by the affecting organism.
Ophthalmia neonatorum: Conjunctivitis in the first month
of life usually as a result of N. gonorrhoeae or Chlamydia
trachomatis.
DISCUSSION
Characteristics of Neisseria Species
Neisseria species are aerobic, nonmotile, nonsporeforming, gram-negative cocci. They usually are arranged in
pairs (diplococci) with adjacent sides flat- tened, resembling
kidney beans. Neisseria are fastidious organisms that
require a complex medium and an atmosphere supplemented
with carbon dioxide for optimal growth. Neisseria
gonorrhoeae has specific cell surface components related to
its adherence, cellular penetration, toxicity, and evasion of
host defenses. Cellular adherence is conferred by the
presence of pili, which attach to host epithelial cells and also
provide resistance to killing by host neu- trophils.
The outer membrane also contains the Opa proteins
(opacity proteins), which promote tight attachment and
migration of the bacteria into the host. Then Por proteins
(porin), which form channels (pores) in the outer membrane,
prevent phagolysosome fusion, allowing intracellular
survival. Rmp proteins (reduction-modifiable proteins)

stimulate antibodies, which inhibit host bactericidal

antibodies, protecting the other surface antigens from host
attack.
Plasmid acquisition and transfer appear to play significant
roles in the development of antibiotic resistance by N.
gonorrhoeae. Multiple plasmids, which confer b-lactamase,
have been identified. A conjugative plasmid that causes
high-level tetracycline resistance has also been identified.
These plas- mids are becoming more common, resulting in
more antibiotic-resistant gonococcal disease. LOS
(lipooligosaccharide), also present in the cell wall, produces
the inflammatory response responsible for most of the
symptoms associated with gonococcal disease by its release
of tumor necrosis factor-.
Neisseria meningitidis appear the same as N. gonorrhoeae
on Gram stain. They also produce a polysaccharide capsule
that prevents phagocytosis. Neisseria meningitidis is divided
into 13 serogroups, the most common of which are A,C,Y,
W135, and B.
Diagnosis
Septic arthritis must be differentiated from other
noninfectious forms of arthritis such as rheumatoid arthritis
and gout. Definitive diagnosis is made by analysis of cells
and Gram stain from an aspirate of the joint. Gram stain
would reveal intracellular gram-negative diplococci. A
presumptive diagnosis of gonorrhea can be made from a

smear from a male urethra; otherwise, culture is required for

diagnosis.
Neisseria species are fastidious organisms in that they
require carbon dix- ide atmosphere, and N. gonorrhoeae
also require chocolate agar. Neisseria gonorrhoeae also
may require at least 48 hours for production of small grey
colonies. Selective media such as Thayer Martin or
Martin Lewis is usually needed to isolate N. gonorrhoeae
from nonsterile sites such as the cervix or urethra. Neisseria
gonorrhoeae are quite sensitive to drying, so plates must be
placed in a warm environment quickly to maintain viability.
If a delay in tran- sit to the laboratory is expected to be
longer than several hours, a transport media such as Jembec
is required. Rapid identification can be made from gramnegative diplococci, growing on selective media that are
oxidase positive. Isolates are specifically identified by acid
production from select sugars. Neisseria gonorrhoeae
ferments glucose only, and N. meningitidis ferments both
glucose and maltose. Because of the fastidious nature of N.
gonorrhoeae, genital infections are identified using DNA
probes, which detect both N. gonorrhoeae and C.
trachomatis, which commonly occur together and dont
require live organisms for detection.
Treatment and Prevention
Penicillin is the treatment of choice for meningococcemia.
Approximately 30 percent of N. gonorrhoeae produce blactamase and are therefore resist- ant to penicillin.
Treatment with ceftriaxone or a quinolones is usually

recommended, although increase in resistance to

quinolones has been demonstrated in some geographic
locations. Prevention of meningococcal disease is by
vaccination. A recent CDC recommendation advises
vaccinat- ing all adolescents for meningococcus at the age of
1112 years. Other susceptible persons, such as military
personnel, college students who will be living in dormitories
and asplenic patients, should be vaccinated as well.
Prophylaxis of close contacts is also recommended to
prevent spread of the disease. Prevention of N. gonorrhoeae
includes practicing safe sex and use of a condom, as well as
screening sexually active persons. Screening of pregnant
women for congenitally transmitted infections with
appropriate treatment would prevent infection of the neonate
with N. gonorrhoeae, as well as other congenitally
transmitted infections.