St.

Scholastica’s Academy – Tabunok

Talisay City, Cebu

CASE STUDY
ON

GONORRHEA
SUBMITTED TO: MS. ALFA JANE MILA, RN
SUBMITTED BY: GROUP 2
Contents
INTRODUCTION ............................................................................................................................................ 3
ANATOMY AND PHYSIOLOGY ....................................................................................................................... 5
Pathophysiology ............................................................................................................................................. 9
Infection of the lower genital tract, the most common clinical presentation, primarily manifests as male urethritis
and female endocervicitis. ............................................................................................................................ 9
Disseminated gonococcal infection....................................................................................................... 9
INFECTION OF THE LOWER FEMALE GENITAL TRACT ......................................................... 10
Medical Management of Gonorrhea ................................................................................................................ 15
Drug Study ................................................................................................................................................... 17

TABLE OF CONTENTS

Introduction

Anatomy and Physiology

Pathophysiology

Medical Management

Laboratory Results

Drug Study

Care Plan
 INTRODUCTION
Gonorrhea is a sexually transmitted disease caused by Neisseria gonorrhoeae, a gram-negative,
intracellular diplococcus. It most commonly involves the cervix, urethra, rectum and pharynx.
Complications include pelvic inflammatory disease, ectopic pregnancy, infertility, and bartholinitis in
women; prostatitis, epididymitis and proctitis in men. Gonorrhea may also invade the bloodstream leading
to disseminated gonococcal infection, which is characterized by arthritis and skin lesions. If gonorrhea is
transmitted to the newborn, it may result in corneal perforation and blindness. Gonorrheal genital infection
is the second most reported STI in the United States and prevalence is highest in persons less than 25
years of age. All clients found to have gonorrhea should be tested for other STIs (chlamydia, syphilis, HIV).

Gonorrhea can be transmitted through sexual contact and sharing of sex toys. Transmission
occurs when secretions from infected mucous membranes or semen of a person with a urethral infection
come into contact with the mucous membranes of another person. Condomless penetrative vaginal sex
and anal sex are the highest-risk behaviours for the transmission of gonorrhea. Gonorrhea can be
transmitted when a person who has the infection in their mouth or throat performs oral sex to another
person or when a person performs oral sex on a person who has a genital infection. Oral-anal contact
(rimming) can transmit gonorrhea as well. Shared sex toys can also transmit gonorrhea. It is theoretically
possible to transmit gonorrhea through a hand job or fingering if infected fluids are present. Gonorrhea can
be passed during childbirth if the newborn has come into contact with infected vaginal discharge or fluid.

Gonorrhea is the second most common notifiable STI in Canada. A notifiable disease must be reported to
public health authorities when an infection is confirmed by a clinic, doctor or laboratory. All people who are
sexually active, including people who experience sexual violence, may be at risk for gonorrhea. The
majority of reported cases of gonorrhea occur in people under the age of 30. Some individuals are at
increased risk of gonorrhea infection: • people who have had sexual contact with a person with a confirmed
or suspected case of gonorrhea • people who have had condomless sex with a resident of an area with
high gonorrhea burden and/or high risk of antibiotic resistance • people with a history of STI infections •
people living with HIV • people who have had condomless sex with multiple partners. There are higher
rates of gonorrhea among gay men and other men who have sex with men (MSM), sex workers and their
sexual partners, Aboriginal people, sexually active youth under 25, street involved youth, and other
homeless populations.

`Untreated gonorrhea infection of the cervix can spread to the uterus and fallopian tubes and
cause pelvic inflammatory disease (PID). This can result in chronic abdominal pain, infertility and an
increased risk of ectopic pregnancy (a potentially serious complication of pregnancy where the embryo
implants outside the uterus). Untreated gonorrhea in the urethra can result in inflammation of the
epididymis (called epididymitis). The epididymis is a tube in the testicle that stores and carries sperm.
Epididymitis can result in infertility; however, this is a relatively rare occurrence. Gonorrhea can be passed
to a newborn during birth. Severe complications from an infection acquired during birth can include
blindness, arthritis, meningitis (inflammation of the protective membrane that surrounds the brain and
spinal cord) and sepsis (infection of the bloodstream). An untreated eye infection (conjunctivitis) caused by
gonorrhea can cause scarring of the cornea. If left untreated, gonorrhea infection can enter the
bloodstream and spread through the body (disseminated gonorrhea). This can lead to arthritis, skin lesions
and tenosynovitis, which is an inflammation of the sheath surrounding the tendons (the tissues that
connect muscle to bone). In rare cases, disseminated gonorrhea may lead to meningitis as well as
inflammation of the heart or liver.

Testing and diagnosis (screening), to screen for gonorrhea, samples are taken from the sites of
suspected infection and tested for the presence of bacteria. Suspected infection in the urinary and genital
tracts may involve providing a urine sample or having a swab of the vagina, cervix or urethra taken. If there
is a discharge from the urethra or vagina, a swab may be taken of the discharge. If someone has had oral
or anal sex, a swab of the throat or rectum may be taken. There are two primary methods of testing
collected samples for gonorrhea: NAATs (nucleic acid amplification tests) and cell cultures. NAATs are
more sensitive than cultures and result in more diagnoses. NAATs can be used to test urine samples and
swabs of the vagina, cervix or urethra. NAATs can be used to detect infection less than 48 hours after a
possible exposure to gonorrhea. NAATs should be used to screen individuals who have no symptoms. In
Canada there are currently no NAATs licensed to detect rectal and throat samples. However, NAATs can
be used to detect gonorrhea in the rectum or throat if the testing laboratory also confirms (validates) a
positive NAAT result by using a second test, which may be a cell culture or another NAAT. Cell culture can
be used to test samples taken from the urethra, vagina, cervix, rectum and throat. Cultures may not detect
an infection if they are obtained less than 48 hours after an exposure. The Public Health Agency of
Canada (PHAC) recommends the use of cultures to determine if the infection is resistant to antibiotics. The
use of cultures is also recommended to test symptomatic gay men and other MSM, in cases of sexual
assault, and to evaluate pelvic inflammatory disease (PID). In addition to NAAT and cell culture testing, a
swab may be taken if there is a discharge from the urethra or vagina to confirm the presence of gonorrhea
bacteria using a microscope. At the time of testing for gonorrhea, additional specimens should also be
obtained from the same sites for chlamydia testing because there are high rates of this infection in people
who have gonorrhea. PHAC also recommends HIV counselling and testing, serological testing for
syphilis,immunization for hepatitis B (if not already immune) and immunization for hepatitis A (if not already
immune) for high-risk individuals (such as MSM and people who use injection).
 ANATOMY AND PHYSIOLOGY

Neisseria gonorrhoeae (the gonococcus) is a Gram-negative diplococcus, an obligate human pathogen,

and the etiologic agent of the sexually transmitted disease, gonorrhea. The gonococcus infects a diverse
array of mucosal surfaces, some of which include the urethra, the endocervix, the pharynx, conjunctiva and
the rectum. In 2013, the Centers for Disease Control and Prevention (CDC) reported that there were
333,004 new cases of gonorrhea in the United States, with an incidence of 106.1 cases per 100,000
population. Worldwide, 106.1 million people are infected by N. gonorrhoeae annually. In most cases, the
disease is a noncomplicated mucosal infection. However, in a few patients, generally with women, more
serious sequelae can occur and include salpingitis (acute inflammation of the fallopian tubes), pelvic
inflammatory disease (PID; an infection in the upper part of the female reproductive system), or, in rare
cases, as a bacteremic infection. If left untreated, these more serious complications can result in sterility,
ectopic pregnancy, septic arthritis, and occasionally death. Approximately 3% of women presenting with a
urogenital infection develop the most severe forms of the disease 5. However, the occurrence of PID has
significantly decreased over time 6,7,8, with an estimated 40,000 cases of infertility in women annually 9.
Dissemination rarely occurs, but when the bacteria do cross the endothelium, they can spread to other
locations in the body. Currently, a more worrying trend has emerged, in that, there now appears to be an
increased risk for HIV infection in patients that are also infected with N. gonorrhoeae 10.

Gonorrhea the disease was initially described approximately 3,500 years ago, but it was not until 1879 that
Albert Neisser determined the etiologic agent of the disease 11. The Neisseriae are usually regarded as
microaerophilic organisms. However, under the appropriate conditions, they are capable of anaerobic
growth 12. In vitro cultivation of this fastidious organism has always been problematic and it was not until
the development of an improved Thayer-Martin medium that early epidemiological studies could be
undertaken. Subsequently, other commercial growth mediums have since been developed which has
allowed for a greater understanding of the disease process.

VIRULENCE FACTORS OF N. GONORRHOEAE

Like many Gram-negative bacterial pathogens, N. gonorrhoeae possesses a wide range of virulence
determinants, which include the elaboration of pili, Opa protein expression, lipooligosaccharide expression
(LOS), Por protein expression and IgA1 protease production that facilitates adaptation within the host.

Type IV pili (Tfp)

Considerable attention was paid to pili stemming from the observations of Kellogg and coworkers that
virulent (T1, T2 organisms) and avirulent (T3, T4 organisms) strains could be differentiated on the basis of
colony morphology isolated gonococci possessed thin hair-like appendages (pili) which were
predominantly composed of protein initially called pilin but subsequently renamed PilE. The elaboration of
pili is a critical requirement for infection as this structure plays a primary role in attaching to human
mucosal epithelial cells, fallopian tube mucosa, vaginal epithelial cells as well as to human
polymorphonuclear leukocytes (PMN’s; neutrophils) . Due to their prominent surface location, pili were
initially thought to be an ideal vaccine candidate as pilus-specific antibodies were observed in genital
secretions. However, two prominent vaccine trials failed, with evidence indicating that pilus protein(s)
underwent antigenic variation.

Gonococcal pili are categorized as Type IV pili, as the PilE polypeptide is initially synthesized with
a short (7 amino acid) N-terminal leader peptide, which is then endo-proteolytically cleaved. The mature
PilE polypeptide is then assembled at the inner membrane into an emerging pilus organelle with the PilE
polypeptides being stacked in an α-helical array. The PilE polypeptide consists of three functional domains
based on sequence characteristics. The N-terminal domain is highly conserved and is strongly
hydrophobic, with this region of the protein comprising the core of the pilus structure. The central part of
the PilE monomer is partially conserved and structurally aligned as a β-pleated sheet. As the C-terminal
domain is hydrophilic, this segment of the protein is exposed to the external environment and undergoes
antigenic variation which allows the bacteria to avoid recognition by the human host’s immune cells
(reviewed).

Assembly of the pilus structure is complicated and involves other proteins besides PilE (e.g., the
pilus tip-located adhesion, PilC) as well as other minor pilus components PilD, PilF, PilG, PilT, PilP and
PilQ. During pilus biogenesis, and prior to assembly, the leader peptide is removed from PilE by the PilD
peptidase. The N-terminal domain then facilitates translocation across the cytoplasmic membrane allowing
PilE subunits to be polymerized at the inner membrane. As the pilus structure is assembled, it is extruded
to the exterior of the outer membrane using the PilQ pore forming complex. PilC is a minor protein located
at the tip of pilus as well as being present at its base. The pilC gene exists as 2 homologous, but non-
identical copies, pilC1 and pilC2 in most gonococcal strains, with only the pilC2 gene being expressed in
piliated N. gonorrhoeae MS11 strains. pilC expression is also subject to RecA-independent phase variation
(on/off switching) due to frequent frameshift mutations occurring within homo-guanine tracts located within
its signal peptide region. PilC participates in pilus biogenesis as well as in host cell adherence,
as pilC mutants prevent the formation of pili by negatively affecting their assembly process, which leads to
the bacteria being unable to adhere to human epithelial cells.

In addition to promoting attachment to host cells, type IV pili are also involved in bacterial twitching motility,
biofilm formation, and DNA transformation. N. gonorrhoeae is naturally competent for transformation in that
it can take up exogenously produced Neisseria-specific DNA containing a 10-bp uptake sequence
(GCCGTCTGAA; DUS). pilE mutations resulting in loss of pilus expression lead to transformation
incompetence. The binding and uptake of exogenous DNAs by N. gonorrhoeae requires type-IV-pili-
structurally-related components, including ComP protein. Despite sharing sequence similarity to PilE in the
N-terminal domain, ComP was shown to be dispensable to Tfp biogenesis. Instead the bacteria were
unable to take up extraneous DNA; subsequent overexpression of ComP increased sequence-specific
DNA binding, suggesting that ComP functions in the DNA binding step of transformation. Recently, ComP
has been shown to preferentially bind to DUS-containing DNAs via an electropositive stripe on its
surface with uptake of the DNA being facilitated by de-polymerization of the pilus structure through PilT
hydrolytic activity. The coordinated physical retraction and elongation of pili can lead to "twitching", a form
of motility that propels the cell along a surface. Retraction is facilitated by PilT activity (an ATPase),
whereas PilF protein promotes pilus elongation at the inner membrane.

Por protein

The outer membrane porin protein, Por, is the most abundant protein in the gonococcus accounting for
approximately 60% of the total protein content 1. The molecular size of Por varies between strains, yet,
within individual strains, it exists as only a single protein species 41. Por has been used as the basis for
serological classification of gonococci 41 with nine distinct serovars being identified 42. Overall, there are
two distinct structural classes (PorA and PorB) 42, with the PorA subgroup tending to be associated with
the more complicated aspects of the disease, whereas the PorB subgroup is more likely to be involved with
uncomplicated mucosal infections 43.

Porins allow the transport of ions and nutrients across the outer membrane and can also contribute to the
survival of the bacteria in host cells 44. Moreover, gonococcal Por protein has been shown to translocate
from the outer membrane into artificial black lipid membranes 45 as well as into epithelial cell membranes,
following attachment of the bacteria 46. Por can also transfer into mitochondria of infected cells which
leads to the formation of porin channels in the mitochondrial inner membrane, causing increased
permeability 47. This causes the release of cytochrome c and other proteins, leading to apoptosis of
infected cells 48. However, Por-induced apoptosis remains controversial. In direct contrast to events with
the gonococcus, Neisseria meningitidis Por, which also interacts with mitochondria, apparently protects
cells from undergoing apoptosis 49. Interestingly, mitochondrial porins and Neisseria PorB share similar
properties, with both protein species being capable of binding nucleotides and exhibiting voltage-
dependent gating 50. Por protein also modulates phagosome maturation by changing the phagosomal
protein composition through the increase of early endocytic markers and the decrease of late endocytic
markers, which ultimately delays phagosome maturation 51.

Opacity-associated protein (Opa)

Opa proteins are integral outer membrane proteins and cause colonies to appear opaque due to inter-
gonococcal aggregation when viewed by phase-contrast microscopy 52,53,54. Opa proteins belong to a
multigene family with a single gonococcal cell possessing up to 12 opa genes that are constitutively
transcribed 55,56. Each gene contains conserved, semivariable and 2 hypervariable regions, with the
hypervariable segments of the proteins being located on the outside of the outer membrane 55. Opa
protein expression can undergo phase variation due to changing the numbers of pentameric repeat units (-
CTCTT-) that are located within the leader peptide encoding region, which results in on/off switching of
expression 57. A single cell is capable of expressing either none to several different Opa proteins 57,58.

Unlike pili, Opa expression is not required for the initial attachment of gonococci to the host. However, as
an infection proceeds, Opa expression varies 58, and Opa-expressing bacteria can be observed in
epithelial cells and neutrophils upon re-isolation from infected human volunteers 59,60. The invasive
capacity of N. gonorrhoeae is determined by the differential expression of Opa 61. Individual Opa proteins
bind to a variety of receptors on human cells through their exposed hypervariable regions. The binding
specificity for human receptors falls into two groups: OpaHS which recognize heparin sulfate
proteoglycans 62,63; and, OpaCEA which recognize the carcinoembryonic antigen cell adhesion molecule
(CEACAM) family that is comprised of the various CD66 molecules 64,65,66,67. CEACAMs are the major
receptors of Opa proteins and are expressed on many different cell types including epithelial, neutrophil,
lymphocyte and endothelial cells 68.

Lipooligosaccharide (LOS)

As with all Gram-negative bacteria, gonococci possess lipopolysaccharide in the outer membrane.
Gonococcal LPS is composed of lipid A and core polysaccharide yet lacks the repeating O-antigens 1.
Accordingly, gonococcal LPS has been designated as lipooligosaccharide (LOS). Due to its surface
exposure, gonococcal LOS is a primary immune target along with the major outer membrane protein
Por 69,70,71. Gonococcal LOS is also toxic to fallopian tube mucosa causing the sloughing off of the
ciliatory cells 72. The LOS oligosaccharide composition is highly variable both in length and in
carbohydrate content. Consequently, heterogeneous LOS molecules can be produced by a single cell.
However, distinct forms of LOS may be a prerequisite for infection in men 73. The most common
carbohydrates associated with isolated LOS molecules are lacto-N-neotetraose (Galβ(1-4)GlcNAcβ(1-
3)Galβ(1-4)Glc) and digalactoside Galα(1-4)Gal and switching from one form to another occurs at high
frequency 74through phase variation of glycosyl transferases 75,76. The variable oligosaccharide portions
of LOS can also mimic host glycosphingolipids, thus promoting bacterial entry 74. In addition, gonococcal
LOS can also be sialylated which renders the bacteria resistant to serum killing 77,78,79,80.
Consequently, gonococcal LOS contributes to gonococcal pathogenicity by facilitating bacterial
translocation across the mucosal barrier as well as by providing resistance against normal human
serum 81,82.

IgA protease

Immunoglobin A (IgA) protease is another virulence factor in N. gonorrhoeae 83. Upon release from the
cell, the protein undergoes several endo-proteolytic cleavages, leading to maturation of the IgA
protease 84. During an infection, the mature protease specifically targets and cleaves IgA1 within the
proline-rich hinge region of the IgA1 heavy chain. The human IgA2 subclass is not cleaved by gonococcal
IgA protease since it lacks a susceptible duplicated octameric amino acid sequence 85. Neisseria IgA
protease also cleaves LAMP1 (a major lysosome associated membrane protein), which leads to lysosome
modification and subsequent bacterial survival 86. Furthermore, iga mutants are defective in transcytosis
of bacteria across an epithelial monolayer 87.
 Pathophysiology

The pathophysiology of N gonorrhoea and the relative virulence of different subtypes depend on the
antigenic characteristics of the respective surface proteins. Certain subtypes are able to evade serum
immune responses and are more likely to lead to disseminated (systemic) infection.
Well-characterized plasmids commonly carry antibiotic-resistance genes, most notably penicillinase.
Plasmid and nonplasmid genes are transmitted freely between different subtypes. The ensuing exchange
of surface protein genes results in high host susceptibility to reinfection. The exchange of antibiotic
resistance genes has led to extremely high levels of resistance to beta-lactam antibiotics. Fluoroquinolone
resistance has also been documented on multiple continents and in widespread populations within the
United States.

Infection of the lower genital tract, the most common clinical presentation, primarily manifests as male
urethritis and female endocervicitis.

Infection of the pharynx, rectum, and female urethra occur frequently but are more likely to be
asymptomatic or minimally symptomatic. Retrograde spread of the organisms occurs in as many as 20% of
women with cervicitis, often resulting in pelvic inflammatory disease (PID), with
salpingitis, endometritis, and/or tubo-ovarian abscess.
Retrograde spread can lead to frank abdominal peritonitis and to a perihepatitis known as Fitz-Hugh-
Curtis syndrome.
Long-term sequelae of PID, such as tubal factor infertility, ectopic pregnancy, and chronic pain, may occur
in up to 25% of affected patients.
Epididymitis or epididymo-orchitis may occur in men after gonococcal urethritis. Lower genital
infection is a risk factor for the presence of other sexually transmitted diseases (STDs), including human
immunodeficiency virus (HIV).
Conjunctivitis can occur in adults, as well as children, following direct inoculation of organisms (usually as
a result of hand-eye inoculation in adults) and can lead to blindness.

Disseminated gonococcal infection

Disseminated gonococcal infection (DGI) occurs following approximately 1% of genital infections.

Patients with DGI may present with symptoms of rash, fever, arthralgias, migratory polyarthritis, septic
arthritis, tendonitis, tenosynovitis, endocarditis, or meningitis.
N gonorrhoeae organisms spread from a primary site, such as the endocervix, the urethra, the pharynx, or
the rectum, and disseminate to the blood to infect other end organs. Usually, multiple sites, such as the
skin and the joints, are infected. Neisserial organisms disseminate to the blood due to a variety of
predisposing factors, such as host physiologic changes, virulence factors of the organism itself, and
failures of the host's immune defenses. [7]
For example, changes in the vaginal pH that occur during menses and pregnancy and the puerperium
period make the vaginal environment more suitable for the growth of the organism and provide increased
access to the bloodstream. (Three fourths of the cases of DGI occur in women; susceptibility is increased if
the primary mucosal infection occurs during menstruation or pregnancy.)
Defects in the host's immune defenses are also involved in the pathophysiology, with certain patients more
likely to develop bacteremia. Specifically, patients with deficiency in terminal complement components are
less able to combat infection, as complement plays an important role in the killing of neisserial organisms.
As many as 13% of patients with DGI have a complement deficiency.
A study of 22 patients with DGI revealed that total serum complement activity was greater than 25% below
the normal mean. Other causes of immunocompromise (eg, HIV, SLE) also predispose to dissemination of
infection.
In addition, certain strains of gonorrhea causing asymptomatic genital infections are seen in association
with DGI.
 GONOCOCCAL INFECTION OF THE MALE URETHRA

N. gonorrhoeae infection of men most commonly occurs as an acute urethritis,

which develops from the concomitant inflammatory response directed at infecting
gonococci (197). However, a small percentage of men will develop
asymptomatic gonococcal urethritis (95, 109, 229). One hallmark of symptomatic
gonococcal disease in men is the presence of a purulent discharge, which is
associated with PMN influx and shedding of urethral epithelial cells. Human
volunteer studies indicate that there is an incubation period from the time of
infection to the onset of clinical symptoms of disease (209). During this time
gonococci are quiescent and cannot be cultured from the urethra for up to 40 h
after the initiation of infection, after which a purulent exudative process begins.
These data suggest that gonococci enter a protective environment early in
disease where they survive and replicate. We would propose that, in men, the
urethral epithelial cell is this sanctuary. In vitro infection assays and microscopic
analyses of patient exudates indicate that gonococci are released from epithelial
cells and that infected epithelial cells are subsequently shed from the mucosal
surface to the urethral lumen. Experimental infection of men also demonstrates
that the chemokine interleukin-8 (IL-8) and the cytokines IL-6 and tumor necrosis
factor alpha (TNF-α) are prevalent within the urethral lumen with progressive
gonococcal disease (197). Recent evidence reveals that LOS elicits TNF-α, IL-
1β, IL-6, and IL-8 secretion from primary urethral epithelial cells (99). Release of
cytokines and chemokines from the urethral epithelium may, therefore,
potentially initiate the inflammatory response associated with gonococcal
urethritis by triggering PMN influx (Fig. 1). PMN influx in conjunction with
cytokine release from the urethral epithelium subsequently might potentiate the
clinical symptoms associated with disease. Unless it is intercepted by effective
antimicrobial therapy, this process is cyclic during the course of infection, with
extension into the upper male genital tract. The human acquired immune
response is ineffective in slowing disease progression or preventing reinfection.
This is exemplified in the diaries of Boswell, which attest to his numerous
separate instances of gonococcal infection, which persisted for months without
therapy (182).

INFECTION OF THE LOWER FEMALE GENITAL TRACT

The majority of gonococci transmitted from men to their partners have sialylated
LOS. However, the presence or the absence of sialic acid on LOS does not
influence the interaction of the gonococcus with primary cervical epithelial cells
(63). It is interesting to speculate that within the lower female genital tract
sialylated gonococci may become modified to enhance disease transmission to
men. That is, neuraminidases produced by the vaginal microflora can potentially
remove sialic acid from sialylated gonococci. Cervical epithelia also produce
neuraminidase; however, the specificity of this enzyme to cleave endogenous or
exogenous substrates exhibits cyclic variability (187). The level of sialic acid
found within the microenvironment of the cervix also exhibits cyclic variation
(187).
In contrast to the inflammatory response generated predominately with
gonococcal infection of the male urethra, 50 to 80% of women with lower genital
tract N. gonorrhoeae infection are asymptomatic (58, 59, 109, 229), and 70 to
90% of women with disseminated infection lack signs of genital tract involvement
(58, 95, 109). Analysis of cervical secretions obtained from normal (i.e.,
uninfected) women and from women infected with the gonococcus also reveal
that an antibody response is not generated with uncomplicated infection (105).
These clinical findings are consistent with the ability of the gonococcus to evade
and subvert host immune function. Further support for this idea is found in the
work of Hedges et al., who found that women with gonococcal cervicitis did not
exhibit elevated local levels of IL-1, IL-6, and IL-8 (105). We have obtained
similar results with multiplex reverse transcription-PCR analysis of RNA collected
from infected and uninfected primary cervical cells and with enzyme-linked
immunosorbent assay analysis of supernatants collected from primary human
ecto- and endocervical infection studies performed with N. gonorrhoeae (our
unpublished data). In contrast, Fichorova et al. have reported increased IL-1, IL-
6, and IL-8 expression in similar studies performed with immortalized vaginal and
cervical epithelia (72), which we have demonstrated to have lost CR3 expression
(64). The release of inflammatory cytokines by the cervical epithelium in
response to N. gonorrhoeae infection therefore remains under question.
Within the lower female genital tract, the cervical epithelia provide a source of
alternative pathway complement activity, albeit at a level comparable to only
approximately 10% of that observed for human serum (191, 247). Within minutes
of infection of primary cervical epithelial cells, complement protein C3b is
deposited on the lipid A portion of gonococcal LOS (63) and is rapidly inactivated
to iC3b (64) (Fig. 1). These data are supported by the predominance of iC3b (in
comparison to C3b) on the surface of clinically isolated gonococci
(114, 157, 254). The affinity of complement factor H (fH) for sialylated LOS (196)
and for porin of a PI.A isotype (195) may augment C3b inactivation. However, in
primary cervical cell culture, C3b inactivation occurs in a kinetically similar
manner on gonococci of either a PI.A or a PI.B isotype and on sialylated
gonococci or on gonococci that are not sialylated (65). fH activity is increased
with decreasing polysaccharide chain length (136). Thus, C3b inactivation could
be augmented by the presence of an LOS within the gonococcal outer
membrane, as opposed to the LPS prevalent among gram-negative bacteria.
The resemblance of gonococcal LOS to human paraglobosides and
glycosphingolipids, some of which serve as precursors for cervical mucus
synthesis and which, consequently, may not be recognized as a complement-
activating surface within the microenvironment of the cervix (146, 147, 148, 170),
may also augment C3b inactivation. In addition to the factor I (fI) cofactor activity
of fH, CD46 can function as a cofactor for fI. However, infection studies
performed with primary cervical epithelial cell cultures suggest that CD46 is not
required for C3b inactivation on gonococci at the level of the uterine cervix (65).
Analysis of clinical biopsies obtained from women with culture-documented
gonococcal cervicitis and infection studies performed with primary human
cervical epithelial cells indicate that CR3 serves as the primary receptor for N.
gonorrhoeae adherence to and invasion of the ectocervix and endocervix
(Fig. 1 and 3) (64). Binding of gonococcal pilus to the I domain of CR3 (65)
probably allows the gonococcus to overcome the electrostatic repulsion between
its own cell surface and that of the cervical cell and may juxtapose the
gonococcus at the cervical cell surface, where complement concentrations would
be expected to allow efficient opsonization for the subsequent intimate
adherence of iC3b and gonococcal porin to the I-domain. Binding of the
gonococcus to CR3 requires the cooperative action of iC3b bound to the
gonococcal surface in conjunction with gonococcal porin and pilus (65). Opa
proteins do not appear to be required for adherence to or invasion of primary
cervical epithelial cells (65, 240). Engagement of CR3 on primary cervical
epithelial cells results in vinculin- and ezrin-enriched focal complex formation
before membrane ruffle formation (67). A signal transduction cascade that is
dependent upon the activation of wortmannin-sensitive kinases (i.e.,
phosphatidylinositol 3-kinase or mitogen-activated protein kinases) (67) and Rho
GTPases (64) initiates ruffling (Fig. 4). Gonococci are then internalized within
macropinosomes (67).

Upon infection of primary cervical epithelial cells, gonococci release a

phospholipase D homolog that gains access to the cervical intracellular
environment nonspecifically through macropinocytosis of gonococci (66).
Gonococcal phospholipase D (NgPLD) appears to promote infection of primary
cervical epithelial cells in several ways. Recent data indicate that this secreted
gonococcal protein augments signaling events that trigger CR3 mobilization to
the surface of primary cervical cells (66). This would ensure gonococcal receptor
availability and, consequently, efficient targeting to and association with the
cervical cell surface. NgPLD also modulates cervical cell signal transduction
events leading to membrane ruffling. Mutant gonococci that lack functional
NgPLD activity do not elicit membrane ruffling, and they are impaired in their
ability to associate with and to invade primary human cervical cells (66). The
specific mechanism(s) (e.g., alternate trafficking and/or inactivation of reactive
oxygen species or other antimicrobial agents) by which NgPLD confers
protection to the gonococcus within the intracellular cervical microenvironment
remains to be determined.
As with invasion of male urethral epithelial cells, the intracellular fate of
gonococci within the cervical epithelium is unclear. Ligand binding to the I-
domain of CR3 does not invoke a proinflammatory response in professional
phagocytic cells (16, 36, 174, 265, 266, 267, 268). Consequently, although this is
speculative, the ability of gonococci to subvert cervical cell signal transduction
cascades and the complement system in such a manner to allow a cooperative
mechanism of CR3-mediated adherence to and invasion of the cervical
epithelium may also enhance its survival within the lower female genital tract.
Gonococcal invasion in the absence of a respiratory burst would be expected to
increase the number of gonococci that survive intracellularly, while inactivation of
the complement system would enhance gonococcal survival extracellularly.
Consequently, subversion of host cell signal transduction and the complement
system by the gonococcus within the lower female genital tract may potentially
allow this bacterium to attain a carrier-like state. Ascending infection of the
uterus and fallopian tubes may occur as a consequence of hormonal changes
that alter the mucosal epithelia, molecules available for gonococcal use, and/or
virulence factors expressed by the gonococcus (for a review, see reference 26).
In this regard, it of interest that menses is associated with an increased risk to
women for PID and for disseminated infection (242). C3 production by the
cervical epithelium exhibits cyclic variability, and the highest levels of C3 are
detected during menses (101, 183). Additionally, a correlation can be made
between the presence or the absence of Opa and the site of gonococcal
isolation (i.e., infection). Transparent, or Opa−, gonococci are predominate within
the fallopian tubes and in the cervix at the time of menses (172). Conversely,
Opa+ gonococci are found predominately within the male urethra and within the
cervix at the time of ovulation (172). The ability of gonococci to use heme,
hemoglobin, and haptoglobin-hemoglobin is also postulated to be responsible for
the increased risk observed for women to develop PID and disseminated
disease during menses (31, 241). Analyses of gonococci clinically isolated from
women support this idea in that there may be a correlation between the
expression of the hemoglobin receptor by gonococci and the onset of the
menses cycle (4). Similar results are obtained in the female mouse model of
genital tract infection in that the presence of hemoglobin selects for gonococci
expressing the hemoglobin receptor (117).

INFECTION OF THE UPPER FEMALE GENITAL TRACT

Approximately 45%percent of women with gonococcal cervicitis will develop an

ascending infection (26, 134), the prerequisite to PID. Ascent to the upper
female genital tract might be facilitated through the ability of gonococci to exhibit
twitching motility, in conjunction with hormonal changes which influence the
expression of complement and molecules serving as gonococcal receptors
within the female genital tract. Microscopic analysis of tissue biopsies indicates
that the expression of CR3 progressively decreases in an ascending manner
from the ectocervix to the fallopian tubes . Conversely, expression of the lutropin
receptor (LHr) increases in an ascending manner from the endometrium to the
fallopian tubes, and expression is up regulated at the time of menses. It is
speculated that the LHr serves as a receptor for gonococcal invasion of
endometrial and fallopian tube epithelia. The interaction of the gonococcus with
the LHr increases the invasive character of the gonococcus for Hec1B
adenocarcinoma endometrial cells and, therefore, is said to occur in a contact-
inducible manner. Human chorionic gonadotropin (hCG), a natural ligand for LHr,
can competitively inhibit the association of gonococci with FTOC and Hec1B
cells, presumably by interfering with an LHr-gonococcus interaction. These data
suggest that gonococci possess a surface molecule that mimics hCG. Recently,
Spence et al. reported that this hCG-like molecule is the ribosomal protein L12.
The LHr is also present on the human uterus, placenta, decidua, and fetal
membranes. Although this is speculative, a gonococcus-LHr interaction
occurring on decidua and placental membranes could potentially result in severe
complications of disease and may, in part, contribute to the increased risk of
spontaneous abortion associated with N. gonorrhoeae infection.
Gonococcal adherence to fallopian tube epithelia occurs selectively on
nonciliated, however, it is the ciliated cells of the fallopian tube epithelia that are
subsequently shed (234). If left untreated, complete loss of ciliary action can
occur. Cytotoxicity of ciliated cells is attributed to gonococcal peptidoglycan
(160) and LOS either directly or indirectly through the induction of increased
local production of the inflammatory cytokine TNF-α (153). It is presumed that
the loss of the ciliated cells within the fallopian tube provides the gonococcus
access to subepithelial tissues. Access to subepithelial tissue is also speculated
to be obtained with invasion of nonciliated cells, after which gonococci are
transcytosed to the basal lateral surface of these cells and released (156). In
Hec1B cells, the gonococcal protein L12 mediates transcytosis to the basal
lateral surface (231); however, this has yet to be demonstrated in FTOC.
Sialylation of intracellular gonococci (before their exocytosis) might potentially
prime these organisms for disseminated infection by the increased serum
resistance observed with sialylation. It is also postulated that while gonococci
appear to initiate upper genital tract infections, gonococcal colonization is short-
lived with increasing anoxic environmental conditions associated with
inflammation and the introduction of secondary, invasive, microorganisms
(47, 52, 167, 168). It is additionally suggested that with extended infections,
gonococci may actually reside within the uterine cul-de-sac of the peritoneal
cavity

History
When, dctrs, victim, ngano ang name kadt,
How does the infection occurs In both male and female
Symptoms causes.
 Medical Management of Gonorrhea

What is the treatment for gonorrhea?

Though gonorrhea is a sexually transmitted disease it can be still be cured with the right
treatment. Centers for Disease Control and Prevention (CDC) recommends two intake two drugs in
order to treat gonorrhea – a single dose of 250mg of intramuscular ceftriaxone and 1g of oral
azithromycin.

Ceftriaxone injection or cephalosporin antibiotics is used to treat certain infections caused by

bacteria found in diseases like gonorrhea. Ceftriaxone injection comes as a powder to be mixed with
liquid, or as a premixed product, to be injected intravenously (into a vein) over a period of 30 or 60
minutes. It is sometimes given as a single dose and sometimes given once or twice a day for 4-14 days,
depending on the type of infection being treated because if too much will be intake on the patient will
be put on high risk of feeling some serious side effects. In taking this medication the patient should
begin to feel better during the first few days of your treatment with ceftriaxone injection. If the
symptoms do not improve or get worse there will be a need to call the patient’s doctor.

Azithromycin is given in conjunction with ceftriaxone as coinfection with chlamydia is common.

Azithromycin is used to treat a wide variety of bacterial infections. It is a macrolide-type antibiotic. It
works by stopping the growth of bacteria. Take this medication by mouth as directed by your doctor,
usually once daily with or without food. You may take this medication with food if stomach upset
occurs. The dosage is based on patient’s medical condition and response to treatment. Taking Antacids
containing aluminum or magnesium is discourage because it may decrease the absorption of
azithromycin if taken at the same time. If you take an antacid that contains aluminum or magnesium,
wait at least 2 hours before or after taking azithromycin. Azithromycin monotherapy given as a single
oral dose of 2 g has demonstrated effectiveness against uncomplicated urogenital gonorrhea; however,
it is not recommended because Neisseria gonorrhoeae Neisseria gonorrhoeae - a bacterial pathogen
responsible for gonorrhea and various sequelae that tend to occur when asymptomatic infection
ascends within the genital tract or disseminates to distal tissues because it has the ability to easily
develop resistance to macrolides and because this regimen has the potential for increased
gastrointestinal side effects.

Alternate therapy

Gentamicin 240mg IMI as a single dose into a large muscle, ideally gluteal. (Due to large
volume, give as two injections at separate sites) with Azithromycin 2 gm orally (B1) PLUS
metoclopramide 10mg as a single dose. Patients receiving systemic aminoglycosides, such as
gentamicin, should be closely monitored for nephrotoxicity. Aminoglycosides are associated with major
toxic effects on the renal tubules. The risks of severe nephrotoxic adverse reactions are increased in
patients with pre-existing renal disease, renal impairment, renal failure, or in those with normal renal
function who receive high doses or prolonged therapy. Nephrotoxicity can manifest as decreased
creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific
gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine). When
monitoring gentamicin serum concentrations during the use of conventional dose regimens, the
manufacturer states that prolonged peak concentrations above 12 mcg/mL should be avoided and
trough concentrations above 2 mcg/mL should be avoided.
In pregnancy

Chlamydia screening is recommended for all women at the onset of prenatal care, and again in
the third trimester for women who are younger than 25 years or at increased risk. Azithromycin has
been shown to be safe in pregnant women and is recommended as the treatment of choice for
chlamydia during pregnancy. Screening for gonorrhea is recommended in early pregnancy for those
who are at risk or who live in a high-prevalence area, and again in the third trimester for patients who
continue to be at risk. The recommended treatment for gonorrhea is ceftriaxone 125 mg
intramuscularly or cefixime 400 mg orally. Hepatitis B surface antigen and serology for syphilis should
be checked at the first prenatal visit. Benzathine penicillin G remains the treatment for syphilis.
Screening for genital herpes simplex virus infection is by history and examination for lesions, with
diagnosis of new cases by culture or polymerase chain reaction assay from active lesions. Routine
serology is not recommended for screening. The oral antivirals acyclovir and valacyclovir can be used in
pregnancy. Suppressive therapy from 36 weeks' gestation reduces viral shedding at the time of delivery
in patients at risk of active lesions. Screening for trichomoniasis or bacterial vaginosis is not
recommended for asymptomatic women because current evidence indicates that treatment does not
improve pregnancy outcomes.

Epidemiologic treatment

Epidemiologic treatment refers to treatment with standard regimens, after laboratory tests
have been taken, but before confirmatory results are available, on the basis that the benefits of treating
outweigh the benefits of not treating The following patients should receive epidemiologic treatment
those who are contacts of a person with proven gonorrhea, those from whom an endocervical,
urethral, rectal or conjunctival smear shows intracellular Gram negative diplococcic. Current gonococcal
treatment regimens include azithromycin 1gm orally which provides epidemiological treatment for
uncomplicated chlamydial infections.

It is important to take all the medication prescribed to cure gonorrhea. Medication for
gonorrhea should not be shared with anyone. Although medication will stop the infection, it will not
repair any permanent damage done by the disease. Antimicrobial resistance in gonorrhea is of
increasing concern, and successful treatment of gonorrhea is becoming more difficult. If a person’s
symptoms continue for more than a few days after receiving treatment, he or she should return to a
health care provider to be reevaluated.
 Drug Study

NAME DOSAGE INDICATION CONTRAINDICATION

Adult: 1–2g IM or IV
once daily or in 2 equally
divided doses; max
4g/day. Gonorrhea:
250mg IM once.
Surgery: a single dose of
1g IV 0.5–2hrs pre-op.
Susceptible bacterial
Children: 0–75mg/kg infections of the lower Hyperbilirubinemic or
per day in equally respiratory tract, skin and premature neonates.
divided doses every skin structure, bone and Concomitant calcium-
generic name: antibiotic
12hrs; max 2g/day. Skin joint, acute otitis media, containing IV solutions
ceftriaxone
and skin structures: may UTIs, septicemia, pelvic or products in
brand name: Rocephin
give once daily or in 2 inflammatory disease neonates. Ceftriaxone
equally divided doses (PID), intraabdominal solutions containing
every 12hrs; max infections, meningitis, lidocaine for IV
2g/day. Meningitis: uncomplicated gonorrhea. administration.
100mg/kg (max 4g) for 1 Surgical prophylaxis.
dose, then 100mg/kg per
day (max 4g/day) once
daily or in 2 equally
divided doses every
12hrs for 7–14 days.
Otitis media: 50mg/kg
(max 1g) IM once.
Mild-to-moderate
susceptible infections
Adult: Infection of
including acute bacterial
pharynx, cervix, urethra,
exacerbations of COPD,
or rectum: Ceftriaxone
acute bacterial sinusitis,
250 mg IM once plus
acute otitis media, Ketolide allergy.
azithromycin 1 g PO
generic name: community-acquired History of cholestatic
once (preferred) or
azithromycin pneumonia, jaundice/hepatic
alternatively doxycycline
brand name: Zithromax, pharyngitis/tonsillitis, dysfunction
100 mg PO q12hr for 7
Zmax uncomplicated skin and associated with prior
days.
skin structure, urethritis, use.
cervicitis, chancroid in
Children: Children and
men. Treatment and
adolescents ≥45 kg: 1 g
prophylaxis of
PO as single dose.
Mycobacterium avium
complex (MAC) infection.
generic name:
doxycycline
brand name: Monodox,
Vibramycin
 Care Plan For A Patient With Gonorrhea
Clinical
Days/Week to visit
Patient How we can Treat? Recommendatio Preferred Test
a doctor
n
In order to prevent
complications during
pregnancy, it is Intramuscular
recommended that ceftriaxone
you get screened for (Rocephin) and
gonorrhea while oral cefixime
Nucleic Acid
pregnant at your first (Suprax) are
Pregnant Woman Amplification Test
prenatal visit. The similar in
(NAAT)
traditional treatment effectiveness for
for uncomplicated gonorrhea
gonorrhea s a dose of during
ceftriaxone, which is pregnancy.
also safe for pregnant
mothers and infants.
The CDC
recommends that all
sex partners of
infected patients
from the preceding
60 days be evaluated, Anyone who is
tested, and treated a single dose of sexually active
for infection. It also 250mg of should get tested
recommends that intramuscular for STDs every
Man Urine Sample
infected patients be ceftriaxone AND year, or more often
instructed to abstain 1g of oral if recommended by
from sexual azithromycin. their health care
intercourse until after provider.
they and their sex
partners have
completed treatment
and no longer have
symptoms.
Any woman who is
sexually active can
get the infection.
Diagnosis is
important for your
health practitioner to
offer you the right
Anyone who is
medication
a single dose of sexually active
(antibiotics).
250mg of should get tested
Partners of women
intramuscular a swab of the for STDs every
Woman who have had the
ceftriaxone AND vagina or cervix year, or more often
infection must get
1g of oral if recommended by
the right treatment
azithromycin. their health care
for gonorrhea since
provider.
their sex partners
may be infected as
well. Proper
medication and
treatment of the
partners also
prevents reinfection
 in the women.
Women who suffer
from PID need more
aggressive
medication that is
effective to eradicate
the bacteria
responsible for
causing gonorrhea.
Women with severe
complications caused
due to the infection
often require
hospitalization and
intravenous
administration of
antibiotics.
A number of
laboratory tests
can be performed
to diagnose
gonorrhea. Your
pediatrician may
can be treated with
take a sample of
antibiotics such as a a single dose of
the discharge from
single high oral dose intramuscular
the cervix or the
of medicines called ceftriaxone.
penis and have it
cephalosporins or
tested in the
fluoroquinolones or a
laboratory. Urine
Children single injection of
tests can also be
ceftriaxone. If a
conducted. If a
young child is Single-dose
newborn has
infected, she may cefixime is
discharge from the
also be treated with recommended
eye, it is tested by
an injection of for children
microscopic
ceftriaxone.
examination and
culture. The sexual
partners of the
infected person
should also be
tested for STIs.
Immediately
after birth,
infants are
routinely given
tetracycline or
Infants erythromycin
ointment in their
eyes to protect
them from
gonorrheal
infection.