UNIVERSITY OF SANTO TOMAS

FACULTY OF PHARMACY
DEPARTMENT OF PHARMACY

GONORRHOEA
Submitted by:
30 Miguel, Karen D.
31 Moron, Rey Sebastian S.
33 Pazon, Andrew D.

Submitted to:
Maam Rebecca G. David, M.S.Phar
PHARCARE 2
Public Health

November 15, 2016

GONORRHOEA
BRIEF HISTORY
The earliest written description of gonorrhea dates from 1400 BC in the Book of
Leviticus. Leviticus 15:2 refers to men with urethral discharges along the lines, When
any man has a discharge from his body, his discharge is unclean. Further, earliest
records of this disease are found during the reign of Louis IX in 1256 in France. Several
troops of military men back then have paid several visits in what they call brothels, or
places where people engage in a sexual activity with a prostitute. In 1879, a German
physician named Albert Neisser discovered the strain of bacteria responsible for
gonorrhea, which is, Neisseria gonorrhoeae. [1]
1. DEFINITION

Merriam-Webster
a contagious inflammation of the genital mucous membrane caused by the gonococcus
called also clap. [2]
Medicine Net
a bacterial infection that is transmitted by sexual contact. Gonorrhea is one of the oldest
known sexually transmitted diseases (STDs), and it is caused by the Neisseria
gonorrhoeae bacteria. [3]
The Free Dictionary
a sexually transmitted disease caused by gonococcal bacteria that affects the mucous
membrane chiefly of the genital and urinary tracts and is characterized by an acute
purulent discharge and painful or difficult urination, though women often have no
symptoms. [4]
Gonorrhea is a contagious disease that is contracted most often by a person
through direct sexual contact with an infected person. It ranks second among the most
common sexual diseases in the world, falling behind Chlamydia which tops the list. It is
transmitted by the bacteria Neisseria gonorrhoeae which attacks the mucous membrane
and can infect several parts of the body such as the penis, vagina, cervix, anus, urethra,
and even the throat, mostly characterized by an acute purulent discharge and painful or
difficult urination, though women often have no symptoms.
ETYMOLOGY [5]
gonos = gonads
rhoia = flow
literally means flow from the gonads

2. SYNONYMS

gonorrhoea [6]

gonococcus/gonococci [6]

gonococcal infection [6]

the Clap [6]

the Drip [6]

the Dose [6]

ETIOLOGIC AGENT
Neisseria gonorrhoeae
SCIENTIFIC CLASSIFICATION [7]
Kingdo
m:

Bacteria

Phylum: Proteobacteria
Class:

Betaproteobacter
ia

Order:

Neisseriales

Family:

Neisseriaceae

Genus:

Neisseria

Species: N. gonorrhoeae

3. MORPHOLOGICAL DESCRIPTION
CHARACTERISTICS [8]
gram negative

obligate aerobes, specifically microaerophilic and capnophilic

fastidious 3 to 5% of CO2

optimum temperature: 32 to 38OC of incubation temperature

generally non-motile

non-spore formers

non-capsulated

PHYSICAL APPEARANCE [8]

shape: coccus, sometimes describe as coffee bean-like or kidney-like

appearance: appears in pairs

colonial appearance: varies depending on the degree of piliation of the

organisms

if piliated, small, glistening, raised colonies

if non-piliated, larger, nonglistening, flatter colonies

LOCALIZED SITES [8]

Neisseria gonorrhoeae thrives in the mucous membranes. It attacks the mucous
membrane and can infect several parts of the body such as the penis, vagina, cervix,
anus, urethra, and even the throat. It specifically attaches to the columnar, cuboidal or
transitional epithelium.
VIRULENCE FACTORS [9]
Although Neisseria gonorrhoeae has been recognized as the cause of gonorrhea
for nearly a century, little is known of the specific components of gonococci that enable
them to interact with human tissues and to evade the host's antibacterial defenses. The
following are the virulence factors of the bacteria.

pili (fimbriae)
o responsible for tight binding of the bacteria to nonciliated mucosal cells
(the tight binding prevents the gonococci from being washed away by
vaginal discharge or urine)
o anti-phagocytic (inhibits phagocytosis by neutrophils)
o antigenic variation
o twitching motility

endotoxin lipooligosaccharide (LOS)

o responsible for cell damage

o triggers inflammatory response by activation of complement, attraction

and feeding by phagocytes, and lysing of the phagocytes
o binds sialic acid to form a microcapsule which provides resistance

Outer cell membrane proteins

Protein I Por (Porin)

o forms pores for nutrients to pass into the cell and wastes to exit
o interferes with degranulation of neutrophils and phagolysosome fusion,
thus protecting the bacteria from the hosts inflammatory response. It also
facilitates invasion into epithelial cells and resistance to complementmediated serum killing.

Protein II Opa (Opacity)

o mediates the tight binding and penetration of the bacteria into the
epithelial cell
o binds to LOS of an adjacent bacterium, which allows for the construction
of a microcolony which may be functionally analogous to a biofilm

IgA protease
o hydrolyzes IgA which is the hosts main defense against the bacteria

PATHOGENESIS [9]
The following are the steps involved in the pathogenesis of Neisseria
gonorrhoeae.
1. Adherence to the Host Cell
-

Neisseria gonorrhoeae adheres to the mucosal cells.

virulence factors involved:

pili

protein 2 - OPA

2. Invasion through the Epithelium

-

Neisseria gonorrhoeae enters the epithelium from the mucosal surface to the
subepithelial spaces.

virulence factors involved:

protein 1 - PORIN

protein 2 - OPA

3. Colonization and Growth

-

Neisseria gonorrhoeae gets nutrients from the pores and forms microcolonies.

virulence factor involved:

protein 1 - PORIN

protein 2 - OPA

4. Tissue Damage
-

Progressive mucosal cell damage is accompanied by a vigorous neutrophil

response, release of TNF.

virulence factors involved:

protein 1 - OPA

lipooligosaccharide toxin

ANTIGENIC VARIATION [9]

Antigenic variation is a mechanism by which the bacteria, Neisseria
gonorrhoeae, alters its surface proteins in order to evade a host immune response. The
following proteins exhibit antigenic variation:

pili

protein 2 OPA

BIOCHEMICAL PROPERTIES [9]

ferments glucose

oxidase-positive

catalase-positive

4. CLINICAL HORIZON
SIGNS AND SYMPTOMS [10]
Many men with gonorrhea are asymptomatic. When present, signs and
symptoms of urethral infection in men include dysuria or a white, yellow, or green
urethral discharge that usually appears one to fourteen days after infection. In cases
where urethral infection is complicated by epididymitis, men with gonorrhea may
also complain of testicular or scrotal pain.
Most women with gonorrhea are asymptomatic. Even when a woman has
symptoms, they are often so mild and nonspecific that they are mistaken for a bladder
or vaginal infection. The initial symptoms and signs in women include dysuria, increased
vaginal discharge, or vaginal bleeding between periods. Women with gonorrhea are at
risk of developing serious complications from the infection, regardless of the presence
or severity of symptoms.

COMPLICATIONS IN WOMEN

Pelvic Inflammatory Disease

[11]

Pelvic inflammatory disease (PID) is a clinical syndrome that results from the
ascension of microorganisms from the cervix and vagina to the upper genital tract. It
can lead to infertility and permanent damage of a womans reproductive organs.

Ectopic Pregnancy [11]

An ectopic pregnancy is a pregnancy that occurs outside the uterus lining,

meaning the fertilized egg attaches somewhere other than the uterus. An ectopic
pregnancy never results in a live birth and can be a serious medical complication for a

woman. Sometimes an ectopic pregnancy is referred to as a tubal pregnancy because

most often (but not always), a tubal pregnancy develops in one of the fallopian tubes.

Fitz-Hugh-Curtis Syndrome [11]

Fitz-Hugh-Curtis syndrome is a rare disorder that occurs almost exclusively in

women. It is characterized by inflammation of the membrane lining the stomach
(peritoneum) and the tissues surrounding the liver (perihepatitis). Common symptoms
include severe pain in the upper right area (quadrant) of the abdomen, fever, chills,
headaches, and a general feeling of poor health (malaise). Fitz-Hugh-Curtis syndrome
is a complication of pelvic inflammatory disease (PID), a general term for infection of the
upper genital tract in women. Infection is most often caused by Neisseria gonorrhoeae
and Chlamydia trachomatis.

SYMPTOMS IN BOTH MEN AND WOMEN

Rectal Infection [10]

Rectal infections may result from perineal contamination with infected cervical
secretions. Symptoms of rectal infection in both men and women may include
discharge, anal itching, soreness, bleeding, or painful bowel movements. Rectal
infection also may be asymptomatic.

Pharyngeal Infection [10]

Pharyngeal infection may be the sole site of infection if oral-genital contact is the only
exposure. Most often asymptomatic, but symptoms, if present, may include pharyngitis,
tonsillitis, snd fever.

Conjunctivitis [12]
Adult Gonococcal Conjunctivitis is a type of bacterial conjunctivitis that is caused
by the bacteria Neisseria gonorrhoeae, which is responsible for sexually transmitted
diseases (STDs) in adults. The highly acute and dangerous eye disorder is also termed
as Gonorrheal Conjunctivitis. Symptoms include redness and tearing, eye irritation with

purulent conjunctival exudate, eye pain and eyelid inflammation (with gritty feeling of
sand-like particles inside the eye), and blurred vision.

Disseminated Gonococcal Infection (DGI) [13]

Over time, the bacteria that causes gonorrhea can spread to the bloodstream
and other parts of the body. This can lead to a serious medical condition known as
disseminated gonococcal infection (DGI). DGI can develop within two weeks of being
infected with gonorrhea. Once in the bloodstream, gonorrhea can affect various tissues
and cause permanent damage.
Symptoms that commonly occur with DGI include:
fever or chills

feeling ill or generally unwell (malaise)

pain in the joints

swelling of the joints

pain in the tendons of the wrists or heels

a skin rash with pink or red spots that become filled with pus

5. INCUBATION PERIOD
The incubation period for gonorrhea is usually 2-7 days after exposure to an
infected partner. But sometimes symptoms may not develop for up to 30 days.
Gonorrhea may not cause symptoms until the infection has spread to other areas of the
body. [14]
6. PERIOD OF COMMUNICABILITY
Gonorrhea is communicable from the time the infection is acquired until the patient is
adequately treated. Communicability is for as long as the person harbors the organism.
It may extend for months in untreated individuals. Asymptomatic infected persons are
generally considered to be equally infectious as symptomatic individuals. All sexual
contacts within 60 days of the onset of symptoms or diagnosis of gonorrhea should be
evaluated and treated. Effective treatment ends communicability within hours. [15]
7. LABORATORY DIAGNOSIS
The genus Neisseria contains a number of species which are normal flora and
pathogens of humans and animals. Rapid tests have been developed to identify and

distinguish N. gonorrhoeae, from the commensal Neisseria and related species which
are normal flora. commensal Neisseria species may be incorrectly identified as N.
gonorrhoeae. Such incorrect identifications may result in serious social and medicolegal
consequences for patients and their families.
IDENTIFICATION OF N. GONORRHOEAE FROM RELATED SPECIES
ACID DETECTION TEST
Principle
Patterns of acid production from the carbohydrates - glucose, maltose, lactose,
sucrose, (and fructose) - are used to identify Neisseria and related species. In contrast
to most bacteria which produce acid by a fermentative pathway, Neisseria spp. produce
acid by an oxidative pathway. This is an important distinction because more acid is
produced by fermentation than by oxidation.
Medium & Reagents

Selective (Modified Thayer-Martin; MTM) medium or a nonselective (chocolate or

equivalent) medium.
QuadFERM+: Commercial acid detection test (for glucose, maltose, sucrose, and
lactose) that includes a DNase and beta-lactamase test.

Results

Positive reaction is recorded when the color in the test medium is more
orange/yellow than the color in the control medium.

Negative reaction is recorded when the color in the test medium is the same, or
a darker red, than the color in the control medium.

Acid only from glucose

Acid from Glucose and Maltose

ENZYME SUBSTRATE TEST

Principle
The production of three enzymes - a glycosidase (beta-galactosidase) and two
aminopeptidases (gamma-glutamylaminopeptidase and hydroxyprolylaminopeptidase) has been used to differentiate between Neisseria and related species isolated on
selective medium for N. gonorrhoeae.
Medium/Reagents

Pureculture, on chocolate (or equivalent) medium of gram-negative, oxidasepositive diplococci that have been isolated on a selective medium (Modified
Thayer-Martin or equivalent medium) for N. gonorrhoeae.

Gonochek-II: Commercial enzyme substrate test

Results
Postive reaction: cell suspension turns pink-red; the organism produces
hydroxyprolylaminopeptidase and may be identified presumptively as N.
gonorrhoeae.

Negative Reaction: If the cell suspension remains unchanged in color or turns a

pale yellow, the organism is M. catarrhalis.

NITRATE REDUCTION TEST

Principle
Bacterial species may be differentiated on the basis of their ability to reduce
nitrate to nitrite or nitrogenous gases. Among the Neisseriaceae of human origin, strains
of Neisseria
mucosa, Moraxella
catarrhalis,
and Kingella
denitrificans reduce
nitrate. The nitrate reduction test permits differentiation between these species which
are nitrate positive and N. gonorrhoeae(nitrate-negative).
Medium & Reagents

Chocolate agar
Nitrate broth (Heart infusion broth containing 0.2% potassium nitrate)

Results
Postive Reaction: An organism may be reported as nitrate-positive if a red color
develops in the medium after Nitrate reagents A and B are added to the medium,
Negative reaction: The absence of a red color after the addition of both
reagents does not automatically mean that the organism is unable to reduce
nitrate. Addition of Zinc Powder.

POLYSACCHARIDE FROM SUCROSE TEST

Principle

Some bacterial species produce a starch-like polysaccharide from sucrose which

stains dark blue-purple to black with iodine. Among the Neisseria spp., N.
perflava biovar
perflava, N.
mucosa, N.
sicca, N.
flavescens,
and N.
polysaccharea produce polysaccharide from sucrose.
Reagents & Equipment

Medium: Polysaccharide medium (Tryptic soy agar containing 1% sucrose)

Reagent: Lugol's iodine solution (Gram's iodine solution diluted 1:4)

Results

"Polysaccharide-positive" if the growth of an isolate turns dark brown, purple,

or black after the addition of Gram's iodine solution.

"Polysaccharide-negative" if the color of the growth does not change color

other than the color contributed by the iodine reagent.

DNASE TEST
Principle
The deoxyribonuclease (DNase) test detects the degradation of DNA by bacterial
species that produce DNase.

Medium/Reagents

DNase tests may be performed on plate media which incorporate indicators.

However, most media for DNase tests do not support the growth of
fastidious Neisseria species.

QuadFERM+: Commercial, an acid detection test, includes a DNase test.

Results
Positive reaction is recorded when the color in the test medium is more
orange/yellow
Negative reaction is recorded when the color in the test medium is the same, or
a darker red.
DNase-negative

DNase-positive

IDENTIFICATION OF N. GONORRHOEAE
N. gonorrhea can be identified using several diagnostic laboratories. The
sensitivity and specificity of these techniques vary widely.
NUCLEIC ACID AMPLIFICATION TESTING (NAAT)
It is recommended as the optimal method for the diagnosis of infections caused
by N. gonorrhea in men and women with and without symptoms. Compared with
culture, commercially available NAAT offers rapid results (within hours) and
enhanced sensitivity. It also enables the detection of N. gonorrhea from clinical
samples without the requirement of bacterial viability. Additional advantage is that
NAAT retains accuracy with patient-collected specimens (vaginal swab in women
and urine in men). The main drawback to NAAT methodology is that it does not
determine antimicrobial susceptibility, which is paramount if antibiotic resistant
infection is suspected. [16]

GRAM STAIN (MICROSCOPY)

The main role of microscopy is in the diagnosis in a symptomatic man. Due to its
high specificity, a Gram stain of a male urethral specimen that demonstrates
polymorph nuclear leukocytes with intracellular gram-negative diplococci can be
considered diagnostic for infection with N. gonorrhoeae in men.
The sensitivity of the microscopy is highest in symptomatic men (urethral Gram
stain) specific, and cost effective. A urethral Gram stain has low sensitivity in women
compared with men due to the possible presence of other nonpathogenic Gramnegative diplococci in cervical secretions; thus, other diagnostic methods are
generally preferred in women. [16]
CULTURE
The main advantage of culture is to assess antibiotic susceptibilities, which is of
particular importance when antibiotic resistant infection is suspected. Resistance of
the gonococcus to several classes of antibiotics and the emergence of gonococcal
resistance to the currently recommended classes of antibiotics (cephalosporins and
macrolides) has highlighted the importance of maintaining culture capacity.
Culture of N. gonorrhoeae requires the use of Thayer-Martin agar, enriched with
blood or hemoglobin, glucose, amino acids and antibiotics (colistin, vancomycin,
nystatin, etc.), to suppress the growth of commensal neisseriae, and Gram-positive
and Gram-negative bacteria and fungi. The major disadvantage to culture is that
results are not usually available until 48 hours, and the sensitivity of culture declines
in asymptomatic infection. [16]
NUCLEIC ACID HYBRIDIZATION (NUCLEIC ACID PROBE) TESTS
Genetic probe methods require invasive testing using a direct swab from the
endocervix or urethra. The main advantage of these tests is their low cost; however,
because their sensitivity is considerably lower than NAAT and because NAAT have
become more cost-competitive, these tests are not used as frequently. One
advantage of the probe assays is that sample storage and transport are less critical
than culture. Culture generally requires that the sample be sent to the laboratory
within 24 hours, while sample stability for DNA probe assays is up to seven days at
room temperature. [16]
ANTIGEN DETECTION
An enzyme immunoassay (EIA) was developed to detect gonococcal antigens
from cervical swab or urine specimens but is not widely used because its positive
predictive value is only acceptable in populations with a high prevalence of infection.

These tests lack sensitivity and specificity when used for cervical, pharyngeal and
rectal samples. [16]
8. TREATMENT
GONORRHEA TREATMENT FOR ADULTS
Adults with gonorrhea are treated with antibiotics. Due to emerging strains of
drug-resistant Neisseria gonorrhea, the Centers for Disease Control and Prevention
recommends that uncomplicated gonorrhea be treated only with the antibiotic
ceftriaxone given as an injection in combination with either azithromycin or
doxycycline two antibiotics that are taken orally.
Some research indicates that oral gemifloxacin or injectable gentamicin,
combined with oral azithromycin, is highly successful in treating gonorrhea. This
treatment may be helpful in treating people who are allergic to cephalosporin
antibiotics, such as ceftriaxone. [17]
GONORRHEA TREATMENT FOR BABIES
Babies born to mothers with gonorrhea receive a medication in their eyes soon
after birth to prevent infection. If an eye infection develops, babies can be treated
with antibiotics. [17]
9. PROGNOSIS
Gonorrhea is a treatable sexually transmitted disease but if left untreated, it can
cause serious health problems such as infertility, meningitis and septicaemia. A
gonorrhea infection that has not spread can almost always be cured with antibiotics.
Gonorrhea that has spread is a more serious infection. Most of the time, it gets
better with treatment.
GONORRHEA COMPLICATIONS IN WOMEN
Pelvic inflammatory disease (PID) is the commonest complication of untreated
Gonorrhea in women. This is a serious infection of the female reproductive tract as it
can lead to scarring of the fallopian tubes. Scarring of the fallopian tubes can cause
infertility. [18]
Complications of Gonorrhea in pregnant woman: Untreated Gonorrhea in pregnancy
increases the risk of:

Miscarriage.
Preterm delivery.

GONORRHEA COMPLICATIONS IN MEN

Untreated gonorrhea can cause epididymitis (this is a painful condition of the
testicles). It can cause infertility if not treated appropriately. If the prostate is affected,
it can lead to scarring of the urethra, making urination difficult. [18]
OTHER COMPLICATIONS ASSOCIATED WITH GONORRHEA
Rarely the infection can enter the bloodstream and cause infection of the joints,
heart valves, or brain. Infection with gonorrhea similar to other sexually transmitted
diseases increases your risk of getting HIV infection (HIV or human
immunodeficiency virus causes AIDS). [18]
10. PREVENTION
Steps to reduce your risk of gonorrhea:

Abstaining from sex is the surest way to prevent gonorrhea. But if you choose
to have sex, use a condom during any type of sexual contact.
You and your partner must be tested for sexually transmitted infections. Find
out whether both of you have sexually transmitted infections, including
gonorrhea.
Don't have sex with someone who has any unusual symptoms.
Consider regular gonorrhea screening if you have an increased risk. You may
be at increased risk of gonorrhea if you have had gonorrhea or other sexually
transmitted infections in the past. [19]

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1.