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KENYATTA UNIVERSITY, NAIROBI, KENYA

SCHOOL OF PURE AND APPLIED SCIENCES


DEPARTMENT OF BIOCHEMISTRY
AND BIOTECHNOLOGY

HUMAN DISEASE AND THERAPEUTIC AGENT


THE RESEARCH TOPIC: GONORRHEA
MAYOWA JOHNSON ABIOYE I81F/23995/2015
NIXON.Reg no
DENNOReg no
CYNTHIA...Reg no

MOLECULAR AND CELL BIOLOGY

SBC:

LECTURER:

OCTOBER, 2016

GONORRHEA
INTRODUCTION
Gonorrhea is the second most commonly reported communicable disease in the United States, accounting for
more than 300,000 cases annually and probably an equal number of cases that are unreported. Gonorrhea is a
major cause of urethritis in men and cervicitis in women The latter can result in pelvic inflammatory disease
(PID), infertility, ectopic pregnancy, and chronic pelvic pain. Invasive infections with Neisseria gonorrhoeae,
including disseminated gonococcal infection, endocarditis, and meningitis, are uncommon but can result in
serious morbidity. It is a sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae. Men
may have burning with urination, discharge from the penis, or testicular pain. Women may have burning with
urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women
include pelvic inflammatory disease and in men include inflammation of the epididymis.
EPIDEMIOLOGY
The epidemiology of gonococcal infections in the United States has undergone major changes in recent years.
Overall rates have declined since the mid1970s, reaching an all-time low of 116.2 cases per 100,000 in 2003.
The highest reported rates of gonococcal infection are seen among adolescents and young adults, minorities,
and persons living in the south-eastern United States. Reported rates of gonococcal infection have also
historically been higher in men than in women, a difference ascribed mainly to the higher rate of
asymptomatic disease in women and the occurrence of infection among MSM. Increased active case finding
in women beginning in the 1970s and the decrease in cases among MSM since the 1980s has resulted in a
nearly equal ratio of cases in men and women nationally (160,106 versus 174,230 in 2003. An analysis of
reported gonorrhea cases in the United States demonstrated that, although gonorrhea rates decreased by more
than 70 percent between 1981 and 1996, rates remained high in specific subpopulations. The rate of infection
also declined among blacks, but less so than in whites. Rates among blacks were 20 times higher in 2003,
respectively, compared with 11 times higher in 1981. In 2003, the reported rates among blacks and whites
were 655.8 and 32.7 cases per 100,000 population.
Risk factors and attack rate for gonorrhea Risk factors and risk markers for gonorrhea include recent
new sexual partner or multiple sexual partners, being unmarried, young age, minority ethnicity, low
educational and socioeconomic levels, substance abuse, and previous gonorrhea. Geographic clustering of
gonorrhea coincides with geographic clustering of many of these risk markers. Combinations of these markers
have been used to identify persons for screening for asymptomatic gonococcal infection.
Molecular epidemiology of gonorrhea Infections with N. gonorrhoeae are caused by a large number of
different strains. Strains are typically characterized by several methods: Serotyping, which is based upon
variations in the major outer membrane protein (protein I, or porin) Auxotyping, which identifies the strain's
growth requirements Antimicrobial susceptibility profiles. These methods have demonstrated remarkable
strain diversity within and among geographic areas, with a small number of

auxotype/serotype classes predominating in most communities. Additional characterization through pulsed


field gel electrophoresis and amplification of the genes for protein I and another outer membrane protein, Opa,
have allowed further discrimination of strains and have been used in outbreak investigations and to identify
sexual partner pairs
Epidemiology of antimicrobial resistance widespread resistance to penicillin and tetracycline in N.
gonorrhoeae led to the abandonment of these drugs as empiric therapies for gonorrhea in the United States in
the 1980s. Almost one fifth of all isolates are resistant to penicillin, tetracycline, or both, although the
prevalence varies geographically Ciprofloxacin resistance increased to 9.8 percent in 2002 compared to 3.1
and 2.1 per cent in 2001 and 2000, respectively. Gender, residence within or outside of London, and recent
sexual contact abroad were not risk factors for having a ciprofloxacin resistant strain in this analysis.
PATHOGENESIS
Infection with N. gonorrhoeae encompasses four specific stages:

Attachment to the mucosal cell surface


Local penetration or invasion
Local proliferation
Local inflammatory response or dissemination

Attachment Initial attachment of gonococci to the surface of columnar epithelial cells is mediated by pili,
which are filamentous outer membrane appendages composed of multiple subunits, the most important of
which is pilin or pile which forms the pilus fiber. Human challenge studies suggest pili are important for
infection and that antipilin antibodies can block binding. Previous studies have suggested Pilnegative variants
are noninfectious. Other outer membrane structures involved in gonococci attachment include: PilC proteins
PilC1 and PilC2 are proteins that copurify with pilin. They play a key role in epithelial cell adherence, but
there is uncertainty about how they interact with pilin, or why they assist with cell attachment. The PilC
protein is located at the tip of the pili Furthermore, binding of PilC competes with pilusmediated but not
Opamediated attachment to human epithelial cells. Opa (opacity related proteins or protein II) is a family of
11 or 12 related proteins that increase colony opacity of N. gonorrhoeae when viewed under a dissecting
microscope. Opa proteins undergo frequent phase and antigenic variation, and only a few Opa types. CD66 is
the epithelial cell receptor for binding Opa ligands. Expression of different members of the CD66 family may
explain preferential binding of gonococci to particular cells, since various Opa variants exhibit different
binding specificities for various CD66 family members.
Local invasion Local invasion initially involves multiple adhesins, as described above, which interact with
a variety of host receptors. As an example, Opa binds to heparan sulfate proteoglycan receptors on host cells.
Following attachment to mucosal cells, gonococci become engulfed in a process known as parasitedirected
endocytosis. This process may involve activation of acidic sphingomyelinase and appears to be enhanced by
Protein I or Por. Porins are trimeric protein structures that form anionselective transmembrane channels. There

are two structurally related forms, Por A and Por B.Purified Por exhibits several functions believed to be
important in cellular invasion:
The ability to insert itself into the host cell membranes
The ability to bind calmodulin
These functions make it possible to induce endocytosis into epithelial cells, blunt polymorphonuclear
leukocyte oxidative burst, and block phagolysosomal fusion. Gonococci are able to undergo intracellular
replication, both within phagocytic vacuoles and within columnar epithelial cells. Gonococci grow in both
aerobic and anaerobic environments. This adaptive response allows it to function as a facilitative intracellular
parasite in endothelial cells and survive and replicate within leukocyte phagolysosomes.
Dissemination Normal human serum can kill circulating gonococci via the activation of complement and
the deposition of terminal complement complex on the cell surface. However, disseminated gonococcal
isolates are typically serum resistant and can induce defective deposition of the terminal complement complex
on the outer membranes. Por A appears to be crucial to the development of serum resistance since
most invasive strains express Por A. In comparison, Por A may be less important for other complications such
as epididymitis in men and pelvic inflammatory disease in women.
Adaptation to evade host immunity In order for Neisseria gonorrhoeae to survive the host immune
response, it has developed complex strategies to avoid host defense mechanisms. Examples of these strategies
include:
Masking of gonococcal antigen (sialylation of LOS) which prevents the binding of bactericidal
antibodies and the activation of complement.
Mimicry (as demonstrated by the similarity of terminal LOS sugars to host glycolipids)
Release of IgA1 proteases.
Blocking antigen by the binding of antibodies to a reduction modifiable protein (Rmp). Rmp is
physically associated with Por on the outer membrane of gonococci and is highly immunogenic for
noncomplementfixing antibodies. Antibodies directed against Rmp bind to the PorRmp complex, and block
the effective deposition of complementfixing antiPor antibodies. (Uptodate 2016).
MODE OF TRANSMISSION
Gonorrhea is caused by the bacterium Neisseria gonorrhoeae. Also, previous infection does not confer
immunity, and a person who has been infected can become infected again by exposure to someone who is
infected, whether or not that person has any infectious signs or symptoms of their own.
Spread
The infection is usually spread from one person to another through vaginal, oral, or anal sex. Men have a 20%
risk of getting the infection from a single act of vaginal intercourse with an infected woman. The risk for men
that have sex with men is higher. Women have a 6080% risk of getting the infection from a single act of

vaginal intercourse with an infected man. A pregnant women can pass on the infection to her unborn infant. A
mother may transmit gonorrhea to her new-born during childbirth When affecting the infant's eyes, it is
referred to as ophthalmia neonatorum. Multiple views of a Neisseria gonorrhoeae bacterium, which causes
gonorrhea. Among children it has been noted to spread through methods other than sex such as through
contaminated objects. These objects have included baths, clothing, and towels. This however is very
uncommon. (Wikipedia 2016a).
CLINICAL SYMPTOMS
In women, the major genitourinary symptoms of gonorrhea include the following:
Vaginal discharge: The most common presenting symptom of gonorrhea, vaginal discharge from
endocervicitis is usually described as thin, purulent, and mildly odorous However, many patients have
minimal or no symptoms from gonococcal cervicitis
Dysuria
Intermenstrual bleeding
Dyspareunia (painful intercourse)
Mild lower abdominal pain
If the infection progresses to pelvic inflammatory disease (PID), symptoms may include the following:
Lower abdominal pain: Most consistent symptom of PID Increased vaginal discharge or mucopurulent
urethral discharge
Dysuria: Usually without urgency or frequency
Cervical motion tenderness
Adnexal tenderness (usually bilateral) or adnexal mass
Intermenstrual bleeding
Fever, chills, nausea, and vomiting (less common)
In males, the major genitourinary symptoms of gonorrhea include the following:
Urethritis: The major manifestation of gonococcal infection in men Initial characteristics include burning
upon urination and a serous discharge a few days later, the discharge usually becomes more profuse, purulent,
and, at times, tinged with blood.
Acute epididymitis: Usually unilateral and often occurs in conjunction with a urethral exudate
Urethral strictures: Have become uncommon in the antibiotic era, but they can present with a decreased and
abnormal urine stream, as well as with the secondary complications of prostatitis and cystitis
Rectal infection: May present with pain, pruritus, discharge, or tenesmus. In males and females, the classic
presentation of disseminated gonococcal infection (DGI) is an arthritisdermatitis syndrome. Joint or tendon
pain is the most common presenting complaint in the early stage of infection. The second stage of DGI is
characterized by septic arthritis. The knee is the most common site of purulent gonococcal arthritis. In

neonates, in whom bilateral conjunctivitis (ophthalmia neonatorum) often follows vaginal delivery from an
untreated mother with a gonococcal infection, symptoms of gonococcal conjunctivitis include the following:
Eye pain
Redness
Purulent discharge
DIAGNOSIS
Culture is the most common diagnostic test for gonorrhea, followed by the deoxyribonucleic acid (DNA)
probe and then the polymerase chain reaction (PCR) assay and ligand chain reaction (LCR). The DNA
probe is an antigen detection test that uses a probe to detect gonorrhea DNA in specimens. Specific culture of
a swab from the site of infection is a criterion standard for diagnosis at all potential sites of gonococcal
infection. Cultures are particularly useful when the clinical diagnosis is unclear, when a failure of treatment
has occurred, when contact tracing is problematic, and when legal questions arise. In patients who may have
DGI, all possible mucosal sites should be cultured (eg, pharynx, cervix, urethra, rectum), as should blood and
synovial fluid (in cases of septic arthritis). Three sets of blood cultures should also be obtained.
MANAGEMENT
For uncomplicated urogenital, anorectal, and pharyngeal gonococcal infection, a drug regimen using
ceftriaxone plus either azithromycin or doxycycline may be used. Antimicrobial drugs used alone or in various
combinations in other gonococcal infections include the following:
Gonococcal arthritis: Ceftriaxone
Gonococcal conjunctivitis: Ceftriaxone
Gonorrhea contributing to PID: Cefoxitin, ceftriaxone, doxycycline, metronidazole.
Gonococcal epididymitis: Ceftriaxone, doxycycline
Disseminated gonococcal infection (DGI): Ceftriaxone, cefotaxime, ceftizoxime
Gonococcal meningitis and endocarditis: Ceftriaxone. (Medscape drug, disease and procedure 2016).
PREVENTION
As with most sexually transmitted diseases, the risk of infection can be reduced significantly by the correct
use of condoms and can be removed almost entirely by limiting sexual activities to a mutually monogamous
relationship with an uninfected person. Those previously infected are encouraged to return for follow up care
to make sure that the infection has been eliminated. In addition to the use of phone contact, the uses of email
and text messaging have been found to improve the retesting for infection. (Wikipedia 2016b)

REFERENCE
Medscape drug, disease and procedure (2016) Gonorrhea: Practice essentials, background, Pathophysiology
available from <http://emedicine.medscape.com/article/218059-overview> (Accessed October 13,
2016)
UPTODATE (2016) Epidemiology, pathogenesis, and clinical manifestations of Neisseria gonorrhoeae
infection available from <http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?
11/43/11953?view=print> (Accessed October 13, 2016)
Wikipedia (2016) Gonorrhea available from < https://en.wikipedia.org/wiki/Gonorrhea> (Accessed October 13,

2016a)
Wikipedia (2016) Gonorrhea available from < https://en.wikipedia.org/wiki/Gonorrhea> (Accessed October 13,

2016b)

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