Microbiology of Reproductive System

Adugna Negussie (PhD)

Assistant Professor of Clinical Laboratory Science,
Medical Microbiology
Course outline
• Major Bacteria infecting the Reproductive system
• Treponema pallidum: Syphilis
• Neisseria gonorrhoeae: Gonorrhea
• Chlamydia trachomatis: Lymphogranulomavenereum
• Gardnerella vaginalis: Vaginitis
• Haemophilis ducreyi: Chancroid
• Klebsiella granulomatis: Granuloma inguinale (donovanosis)
• Mycoplasma genitalium
• Ureaplasma urealyticum
• Major viruses infecting the Reproductive system
• Human papillomavirus
• Herpes simplex virus: Genital herpes
• Major parasites infecting the Reproductive system
• Trichomonasvaginalis
• Pediculosis pubis
• Major fungi infecting the Reproductive system
• Candida albicans
Learning Objectives
By the end of this section, you will be able to:
• Identify the most common bacterial pathogens that can cause
infections of the reproductive system.

• Compare the major characteristics of specific bacterial diseases

affecting the reproductive system.
• Identify the most common viral, parasitic and fungal pathogens
that can cause infections of the reproductive system.

• Compare the major characteristics of specific etiologic agents of

reproductive system diseases affecting the reproductive system.
 Sexually Transmitted Infections (STI’s)
• Infections that spread primarily through person-to-person
sexual contact.
• May be caused by a bacteria, virus, fungus, or other organism.
• Some are curable, some are not.
• Left untreated, STIs can cause pain, sickness, infertility, birth
defects, and sometimes, death.
• More than one STI at a time and get the same STI more than
once.
• There are at least 25 different sexually transmitted diseases
with a range of different symptoms.
• Affect not only the genital tract, but also
• the skin, mucous membranes, blood, lymphatic and
digestive systems, and many other body areas.
Immunity of STI

• Intact mucosal layer of vagina

• Microbiota at genital
• Discharge with acidic PH
Factors contributing to high rates of STIs
• Multiple sexual partners and unprotected sex--especially
prevalent behavior in adolescence and early adulthood.
• Limited access to health care.
• Practitioners do not ask questions about patients’ sexual
behaviors.
• Some diseases have no obvious symptoms.
• Difficulty talking to partner.
Types of Reproductive System
Infections based on etiology

• Bacterial Infections of the Reproductive System

• Viral Infections of the Reproductive System

• Fungal Infections of the Reproductive System

• Protozoan Infections of Urogenital System

Ulcerative and non-ulcerative genitalia DDX
Bacterial Infections of the Reproductive System
Chlamydia
• Chlamydia is one of the most common sexually transmitted diseases.
• Caused by bacterium Chlamydia trachomatis that infects the urogenital system
• Transmission: primarily penile-vaginal, oral-genital, oral-anal, or genital-anal
contact; can also be spread by fingers from one body site to another.
• Symptoms:
• In majority of cases, none!
• if present:
• Women: Asymptomatic (80%), mild irritation or itching, Cervicitis,
urethritis and salpingitis, burning urination, slight vaginal discharge,
Postpartum fever
• Increased rate
• Premature delivery
• Ectopic pregnancy
• Men: urethral discharge, burning urination
• Symptomatic (75%)
• Urethritis, dysuria and pyuria
• Cause of nongonococcal urethritis (35 - 50%)
• Common cause of postgonococcal urethritis
Chlamydia (cont.)
• Consequences if left untreated:
• Women: pelvic inflammatory disease (PID)
• Bacterial infection spreads from cervix up into uterine lining,
fallopian tubes, and possibly ovaries.
• Symptoms of PID include disrupted menstruation, chronic pelvic
pain, lower back pain, fever, nausea, vomiting, and headache.
• Even after treatment, scar tissue from PID can block fallopian
tubes and cause infertility or ectopic pregnancy (very
dangerous).
• In addition, chlamydial infections may be associated with an
increased risk of cervical cancer.
• Men: epididymitis (infection of the epididymis) or urethritis
(infection of the urethral tube)
• Symptoms of epididymitis: heaviness in testis; small, hard,
painful swelling in testis; inflamed scrotum
• Symptoms of urethritis: penile discharge, burning urination
Chlamydia (cont.)
• Consequences if left untreated, cont.:
• Trachoma:
• a chronic, contagious form of conjunctivitis caused by
chlamydia infection.
• World’s leading cause of preventable blindness.

• Common cause of eye infections in newborns, who can

become infected as they pass through birth canal.
• Consequences for babies born to infected mothers:
• Babies of infected mothers can also develop pneumonia
caused by chlamydia infection
• Chlamydia infection can lead to premature delivery
Chlamydia (cont.)
• Certain serovars of C. trachomatis can cause an infection of the
lymphatic system in the groin known as lymphogranuloma
venereum
• This condition is commonly found in tropical regions and can
also co-occur in conjunction with human immunodeficiency
virus (HIV) infection
• After the microbes invade the lymphatic system, buboes
(large lymph nodes form and can burst), releasing pus through
the skin.
• The male genitals can become greatly enlarged and in women
the rectum may become narrow.
 Diagnosis
● Clinical picture:
Male (discharge, dysuria, scrotal pain, fever)
Female (discharge, postcoital bleed, pelvic
pain)
● Nucleic Acid Amplification Tests (NAATs)
as initial test Lymphogranuloma venereum infection
● Cell culture can cause swollen lymph nodes in the
groin called buboes.
Treatment:
• 7-day treatment of doxycycline, or one
dose of azithromycin or doxycycline.
• Erythromycin, levofloxacin, and ofloxacin
are alternatives.
• All exposed sexual partners should be
treated.

Chlamydia trachomatis inclusion bodies within McCoy cell monolayers.

Inclusion bodies are distinguished by their brown color.
Neisseria gonorrhoeae
• Neisseria gonorrhoeae, often called gonococcus or GC.
• An obligate parasite of the human urogenital tract., which
have fimbriae that allow the cells to attach to epithelial cells.
• Have lipopolysaccharide endotoxin called lipooligosaccharide as part
of the outer membrane structure that enhances its pathogenicity.
 Has no polysaccharide capsule but has multiple serotypes based on
the antigencity of its pilus protein.
 There is a marked antigenic variation in the gonococcal pili as a
result of chromosomal rearrangement.
 More than 100 serotypes are known.
 A known cause of the clap, gonorrhea one of a common sexually
transmitted disease of the reproductive system that is especially
prevalent in individuals between the ages of 15 and 24.
 Virulence factors
1. Pili: mediate initial attachment to non – ciliated human cells and resistance to
phagocytosis (interferes with neutrophil killing).
2. Por protein (Protein I): pores on the surface of bacteria through which nutrients
enter the cell.
 Promotes intracellular survival by preventing phago-lysosome fusion in
neutrophils.
3. Opa (Protein II): Important for firm attachment and invasion of bacteria to host cells.
4. RMP (protein III): protects other surface antigens (por proteins and lipo
oligosaccaride) from bacterial antibodies.
5. Lipooligosaccharide (LOS) : responsible for most of the symptoms / toxicity of
gonorrhea due to endo-toxin effect of LOS.
o Gonococcal LOS triggers an intense inflammatory response.
6. Transferrin and lactoferrin binding proteins
Mediate acquisition of iron for bacterial metabolism.
7. Beta- lactamase
Hydrolyzes beta -lactam ring in penicillin.
Gonorrhea
• Transmission: penile-vaginal, oral-genital, oral-
anal, or genital-anal contact
• In addition to causing urethritis, N.
gonorrhoeae can infect other body tissues such as
the skin, meninges, pharynx, and conjunctiva
• Symptoms:
• Male early symptoms:
• foul-smelling, cloudy penile discharge,
• burning urination
• symptoms may clear up, but does not
necessarily mean bacteria are
gone
• Female early symptoms:
• usually go undetected
• inflamed cervix, mild discharge
• burning urination
Gonorrhea (cont.)
• Consequences if left untreated:
• Men: prostate abscesses, difficult urination, possible sterility
due to scar tissue in epididymis after epididymitis.

• Women: PID (often more severe than w/chlamydia infection),

ectopic pregnancy, severe pelvic pain due to scar-tissue
adhesions across pelvis

• Both sexes: can enter bloodstream and spread throughout

body in ~2% of cases, causing fever, loss of appetite, arthritic
pain, can invade heart, liver, CNS

• Can cause blindness in infants (due to conjunctivitis)

Clinical Manifestations cont’d
Other diseases
• Anorectal Gonorrhea

• Pharyngeal Gonorrhea

• Ocular Gonorrhea in Adults

• Gonococcal Arthritis: Disseminated gonococcal infection (DGI)

• results from gonococcal bacteremia

• Advanced case In women pelvic inflammatory disease(PID)

19
Laboratory
diagnosis
• Specimen: Urethral swab, cervical swab, eye
swab.
Figure . ….. Left: N. gonorrhoeae Gram stain
• Smear: Gram-negative intracellular and/or of pure culture
extra diplococci. Right: N. gonorrhoeae Gram stain of a pustular
exudates
• Culture: Requires an enriched media
• Chocolate agar
• Thayer-Martin agar and/or
• Modified New York City medium
• Grows best in carbon dioxide enriched aerobic
atmosphere with optimal temperature of 35-
370c.
• Serology: Antibodies to gonococcal pili & outer
membrane proteins using RIA and/or ELISA.
• Genetic probes: For detection of nucleic acids.
Treatment
 Drug of choice (CDC) : Ceftriaxone, doxycycline, ciprofloxacin, or oflaxacin.

 Penicillin resistance due to beta- lactamase enzyme producing N. gonorrhoeae

have been identified.
 For ophthalmia neonatorum - 1% silver nitrate , 1% tetracycline or 0.5%
erythromycine eye ointments.
 Often, chlamydia infections accompany gonorrhea infection--dual therapy will
treat both infections

Prevention and control

 Early detection and treatment of cases.

 Using condom

 Health education

 There is no effective vaccine to prevent gonorrhea

Nongonococcal Urethritis
• Any urethral inflammation not caused by gonorrhea
• Main infecting organisms: Chlamydia trachomatis and
Mycoplasma genitalium
• Can also result from other infectious agents, allergic
reactions to vaginal secretions, or irritation from soaps,
contraceptives, or deodorant sprays
• Prevalence: quite common in men; symptoms in women are
usually undetected
• Transmission: mainly through penile-vaginal coitus
• Symptoms:
• Men: penile discharge, burning urination
• Women: frequently, no symptoms; may have mild itching,
burning urination, vaginal discharge of pus
Nongonococcal Urethritis (cont.)

• Consequences if left untreated:

• Men: can spread to prostate, epididymis, or both
• Women: cervial inflammation, PID

• Treatment:
• 7-day treatment of doxycycline, or one dose of
azithromycin
• All exposed sexual partners should be treated
Treponema pallidum
• Treponema pallidum is the gram-negative spirochete.
• T. pallidum has a relatively simple genome and lacks
lipopolysaccharide endotoxin characteristic of gram-
negative bacteria.
• Contain lipoproteins that trigger an immune response in the host,
causing tissue damage that may enhance the pathogen’s ability to
disseminate while evading the host immune system.
• After entering the body, T. pallidum moves rapidly into the
bloodstream and other tissues.
• Cause a disease syphilis
• Syphilis is spread through direct physical (generally sexual) contact:
penile-vaginal, oral-genital, oral-anal, or genital-anal contact.
• If not treated effectively, syphilis progresses through three distinct
stages: primary, secondary, and tertiary.
Virulence factors / Determinants of
Pathogenicity
• Outer membrane proteins are associated with adherence to the
surface of host cells
• Molecular mimicry
• They are poorly immunogenic
• Produce hyaluronidase, which facilitate perivascular infiltration

• Adsorbs host cell fibronectin, that protect against phagocytosis

• Tissue destruction and lesions are primarily result of host’s immune

response (immunopathology)

25
25
 Modes of
transmission Sexual
Untreated cases of syphilis manifests in
several stages
blood
• Stage I (primary syphilis) Transfusion
vertical
• Stage II (secondary syphilis)
• Latent syphilis
• Stage III (tertiary or late syphilis).
Stages of Syphilis
Syphilis
• Symptoms:
• Primary syphilis: Single, painless sore (chancre)
• Women: on inner vaginal walls or cervix, sometimes on labia
• Men: glans of penis, penile shaft, or scrotum
• Can also occur on lips or tongue (infected orally) or in rectum/anus
(infected through anal intercourse).
• Primary syphilis appears as a single lesion on the cervix, penis,
or anus within 10 to 90 days of transmission. Such lesions
contain many T. pallidum cells and are highly infectious.

Glans of penis labia anus

 • Secondary disease 2-10 weeks after primary lesion
• Systemic spread -flu-like symptoms
• Widely disseminated mucocutaneous rash, skin
particularly, often on palms, soles of feet.
• Severity can vary from barely noticeable to severe.
• Does not hurt or itch
•The secondary lesions of the skin and mucus membranes
Secondary are highly contagious
Syphilis • - Highly infectious
• Generalized immunological response
28
Latent Stage Syphilis
• Following secondary disease, host enters latent period
• no symptoms; no longer contagious after 1 year of
latent stage (except pregnant woman to fetus--at all
stages)
• First 4 years = early latent

• Subsequent period = late latent

• About 40% of late latent patients progress to late tertiary

syphilitic disease

29
 Tertiary Syphilis
• It is a slowly progressive, destructive
inflammatory disease that may affect
any organ
• They are caused by the body’s
hyperimmune reaction to remaining
spirochetes
• Cause localized granulomatous dermal
lesions (gummas)
• Few organisms are present
• Granulomas reflect containment
by the immunologic reaction of
the host to chronic infection
• severe symptoms anywhere--such as
heart failure, blindness, paralysis, liver
damage, mental disturbance, death 30
 Tertiary Syphilis cont’d….
• Late neurosyphilis develops in about 1/6 untreated cases,
usually more than 5 years after initial infection leads to
paralysis

• Central nervous system and spinal cord involvement

• Dementia, seizures, wasting, etc.

• Cardiovascular involvement appears 10-40 years after
initial infection
• Lead to aortic damage or aneurisms
• Resulting myocardial insufficiency and death

31
Progression of Untreated Syphilis

Late benign Gummas in skin and soft tissues

Tertiary Stage

32
 Congenital Syphilis
• Congenital syphilis is passed by mother to fetus when untreated primary
or secondary syphilis is present.
• In many cases, infection may lead to miscarriage or stillbirth.
• Children born with congenital syphilis show symptoms of
secondary syphilis and may develop mucus patches that deform the nose.
• In infants, gummas can cause significant tissue damage to organs and
teeth.
• Many other complications may develop, such as osteochondritis, anemia,
blindness, bone deformations, neurosyphilis, and cardiovascular lesions.
• Abortion, neonatal mortality, and late mental or physical problems
• Because congenital syphilis poses such a risk to the fetus, expectant
mothers are screened for syphilis infection during the first trimester of
pregnancy as part of the TORCH panel of prenatal tests.
 Laboratory diagnosis
• Specimen collection
• Tissue exudates, serous fluid, secretions for 1 0, 20, early congenital syphilis
• Blood, CSF, plasma for 20, latent, 30 and late congenital syphilis
• Specimen should be collected with care as the lesions are highly infectious
• Microscopic examination
• Dark field, phase contrast
• T. pallidum is identified by its slender spiral structure and slow movement
• Direct Flourescent Antibody staining
• They are treated with fluorescent tagged anti treponema pallidum antiserum
• Observe under fluorescent microscope
• The test can be made more reliable by using specific monoclonal antibody
• Silver stain
• Diagnosis by microscopy is done in primary and secondary stage and congenital
syphilis with superficial lesion.
• Culture: can not be cultivated

34
 Laboratory diagnosis
Cont’d
Non-specific treponemal tests specific treponemal tests
Serologic test Serologic test
• Screening tests that detect nonspecific • It is a protein Ag present in T.
antibodies which called reagin antibodies pallidum.
(those for lipid antigens produced
during infection ) rather than those produced • Antibody to this antigen appears in
against the spirochete. serum of syphilitic patients.
• VDRL (Venereal Disease Research • FTA-Abs (Fluorescent
Laboratory) treponemal antibody
• RPR (Rapid plasma reagin) absorption test).
• Automated reagin test (ART)
• Toludine Red Unheated Serum Test
• TPHA (T. pallidum
(TRUST) haemagglutination assay).
• Treponemal antigen tests • TPPA (T. pallidum particle
• Cross-react with antigens other than T. agglutination assay).
pallidum ssp. Pallidum • MHA-
• The disadvantage in these tests is the antigen TP( Microhemagglutination
is non- specific and hence gives rise to
biological false positive reaction. assay for antibody test T.
• A reactive VDRL test on CSF, in the absence of pallidum) test
blood contamination of the CSF, is considered • Treponemal antigen-based EIAs
diagnostic neurosyphilis
Progression of Untreated Syphilis

36
Prevention & Treatment of Syphilis
Penicillin G remains drug of choice. Other options include tetracycline
and doxycycline.
• WHO monitors treatment recommendations

• 7-10 days continuously for early stage

• At least 21 days continuously beyond the early stage

• Prevention with barrier methods (e.g., condoms)

• Prophylactic treatment of contacts identified through

epidemiological tracing.
• Treated patients need blood tests at 3-month intervals to make
sure they are free of bacterium.
• To prevent birth defects, death to fetus, it is recommended that
all pregnant women are tested for syphilis at first prenatal visit.
37
 Haemophilus ducreyi
• Short, ovoid, Gram negative bacilli, may show bipolar staining.
• It is a fastidious gram-negative coccobacillus.
• Require factor X but not V factor for growth
Pathogenicity and clinical manifestation
• H. ducreyi causes chancroid, or soft sore.
• It is sexually transmitted and a common cause of genital ulceration.
• The ulcers are painful, shallow and tend to be ragged with marked swelling and
tenderness and it bleed easily.
• Often there is also painful swelling of inguinal lymph nodes, and abscesses (buboes)
may form.
• Chancroid increases the risk of infection with HIV and facilitates transmission of the
virus.
• Lesions of chancroid on the penis, showing a draining bubo (arrow) in the
adjacent groin area. Chancroid is caused by Haemophilus ducreyi (Fig).
• It increases the risk of HIV
 Lab diagnosis
• Specimens
• Specimens should be collected from the base and margins of ulcers following cleansing
with a saline swab (exclude necrotic tissue).

• Specimens for culture must be delivered to the laboratory with the minimum of delay.

• When this is not possible the swab should be placed in Amies transport medium and
delivered the same day to the laboratory or sent in an insulated cool box to reach the
laboratory within 48 h.
Culture
• H. ducreyi is difficult to isolate.
• It is grown best from scrapings of the ulcer base on
• chocolate agar containing 1% IsoVitale X and vancomycin, 3 g/mL, and incubated in 5-
10% CO2 at 33-36 °C for 2-3 days.
• GC agar base with added haemoglobin, vancomycin, and fetal calf serum.
• The organism grows slowly, producing small grey-yellow or brown colonies usually within 2–4
days.
Biochemical tests
• Slowly oxidase positive (colour develops after 15–20 seconds).
• Catalase, urease, and indole negative.
• Ornithine decarboxylase (ODC) negative.
• delta-Aminolevulinic acid (ALA) negative.
 Treatment
• There is no permanent immunity following chancroid infection.

• Recommended treatments for chancroid include antibiotics such

as azithromycin, ciprofloxacin, erythromycin and ceftriaxone.

• Treatment with intramuscular ceftriaxone, oral trimethoprim-

sulfamethoxazole, or oral erythromycin often results in healing
in 2 weeks.
 Mycoplasma and Ureaplasma

• Smallest free-living bacteria (0.1-0.3)um

• No cell wall (resistant to penicillin and
cephalosporins)
• Susceptible to tetracyclines and
erythromycin
• Cell membrane contains sterols (unique
property)
• Strict aerobes
• Small colonies (fried-egg appearance)
 Pathogenic Mycoplasma and
Ureaplasma
• Mycoplasma pneumonia : Respiratory tract
• Mycoplasma hominis : Respiratory tract,
Genitourinary tract
• Mycoplasma genitalium : Genitourinary tract
• Mycoplasma fermentans : Respiratory tract,
Genitourinary tract
• Ureaplasma urealyticum : Respiratory tract,

Asymptomatic carriage common Genitourinary tract

• Three Mycoplasma species, are human urogenital pathogens.

• M.Genitalium & U. urealyticum: nongonococcal urithrits
• M. Hominis : pyelonephritis, pelvic inflammatory disease,
postpartum fever
Mycoplasma & Ureaplasma
Diagnosis
• Culture ( slow)
• Molecular Diagnosis
- PCR
• Serology
- Cold agglutinin (sensitivity 65%, poor specificity)
- ELISA
Treatment
- Erythromycin
- Fluoroquinolones
- Tetracycline
Vaccination :
- No effective vaccine available
Bacterial Vaginitis
and Vaginosis
• Vaginitis is an inflammation of vaginal mucosa that may extend
to the vulva and is commonly associated with a white or yellow
discharge.
• Occasionally vaginitis may be associated with dysuria and
dyspareunia.
• Unusual vaginal symptoms (i.e. unusual discharge or any form of
abnormal vaginal sensation) with or without mucosal
inflammation.
• Often caused by a bacterial infection
• It is also possible to have an imbalance in the normal vaginal
microbiota without inflammation called bacterial vaginosis (BV).
 Bacterial Vaginitis
and Vaginosis
• Bacterial Vaginosis: polymicrobial vaginal infection involving a
reduction in the amount of Lactobacilli bacteria and an
overgrowth of anaerobic bacteria.
• Vaginosis may be asymptomatic or may cause mild symptoms
such as a thin, white-to-yellow, homogeneous vaginal discharge,
burning, odor, and itching.
• The major causative agent is Gardnerella vaginalis, a gram-
variable to gram-negative pleomorphic bacterium.
• Other causative agents include anaerobic species such as
members of the genera Bacteroides and Fusobacterium.
• Additionally, ureaplasma and mycoplasma may be involved.
• The disease is usually self-limiting, although antibiotic treatment
is recommended if symptoms develop.
Gardnerella vaginalis
• Condition first described by Gardner and Dukes in 1955.
• G. vaginalis appears to be more virulent than other vaginal
bacterial species potentially associated with BV.
• Like Lactobacillus spp., G. vaginalis is part of the normal
vaginal microbiota, but when the population
of Lactobacillus spp. decreases and the vaginal pH
increases, G. vaginalis flourishes, causing vaginosis by
attaching to vaginal epithelial cells and forming a thick
protective biofilm.
• G. vaginalis also produces a cytotoxin called vaginolysin that
lyses vaginal epithelial cells and red blood cells.
• Most common infective cause of vaginal discharge in women
of childbearing age.
Factors predispose BV
• Prominent factors that may predispose patients to BV include:

• Recent antibiotic usage

• Decreased estrogen production of the patient

• Wearing an intrauterine device (IUD)

• Douching

• Sexual activity that could lead to transmission ( e.g. having

a new sexual partner or a recent increase in the number of
sexual partners)
Pathogenesis
• Normal vaginal flora in women of reproductive age is predominately
lactobacilli. (Bit unusual)
• At puberty eostrogen levels increase, stimulates glycogen uptake by
vaginal epithelial cells. Glycogen one of main food sources of
lactobacilli.
• Lactobacilli produce both lactic acid and hydrogen peroxide.
• Vaginal epithelial cells also produce lactic acid as a by-product of
glycogenolysis.
• This makes the vaginal pH acidic
• The hydrogen peroxide is also toxic against other bacterial species.
• Lactobacilli are very low virulence bacteria. (Pro-biotic yoghurts
etc), therefore its predominance is thought to have a protective
effect against vaginal/pelvic infections.
• At menopause, eostrogen levels decrease so lactobacilli often
become non-dominant. Makes BV more difficult to diagnose
 Diagnosis of bacterial
•
vaginosis
The first is to use a DNA probe
• The second method is to assay for sialidase activity (sialidase is an enzyme
produced by G. vaginalis and other bacteria associated
with vaginosis ,including Bacteroides spp., Prevotella spp.,
and Mobiluncus spp.).
• The third method is to assess gram-stained vaginal smears for microscopic
morphology and relative numbers and types of bacteria, squamous
epithelial cells, and leukocytes.
• By examining slides prepared from vaginal swabs, it is possible to distinguish
lactobacilli (long, gram-positive rods) from other gram-negative species
responsible for BV.
• A shift in predominance from gram-positive bacilli to gram-negative
coccobacilli can indicate BV.
• Additionally, the slide may contain so-called clue cells, which are epithelial
cells that appear to have a granular or stippled appearance due to bacterial
cells attached to their surface.
• Amsel, Nugent and Hay diagnostic criteria
Microscopy, clue
cell
Presentation of BV
Amsel’s Criteria (introduced 1984)
(3 out of 4 criteria below required to establish the diagnosis )

• Presumptive diagnosis of bacterial vaginosis

• Assessment of clinical symptoms and evaluation of vaginal
fluids using Amsel’s diagnostic criteria which include 3 out of 4
of the following characteristics
1. Vaginal discharge, thin white/grey
2. Fish like odour. (accentuated by addition of Potassium
Hydroxide KOH)
3. Vaginal PH >4.5 (Litmus paper is a bedside test)
4. Presence of clue cells on laboratory examination.

What are the problems with Amsel’s criteria?

Introduced
1991
Hay’s Criteria (2002)
The consequences of Bacterial
Vaginosis
• Causal relationship between BV and endometrial
bacterial colonisation, endometritis, premature
labour, post-partum fever, post-hysterectomy vaginal
cuff cellulitis and post-abortal infection.

• BV is a risk factor for HIV transmission (&other STDs).

May be due to the lack of hydrogen peroxide
producing lactobacilli in the vaginal flora of women
with BV
Bacterial
vaginosis :Treatment
• Metronidazole 400mg orally bd for 7 days.

• Clindamycin 300mg orally bd for 7 days.

• Metronidazole and Clindamycin gels can also be used.

 Trichomoniasis
Trichomonas
• Common in women and men vaginalis

• Primarily spread through sexual contact

• Symptoms (women):
• White or yellow-green discharge, frothy, w/unpleasant odor
• Irritated vaginal and vulval tissues -- can increase a woman’s
susceptibility to HIV infection
• If untreated, can damage cervical cells, may lead to cervical
cancer; in pregnant women, can lead to premature rupture of
amniotic sac and preterm delivery
• Symptoms (men): usually none, may have frequent or painful
urination or slight urethral discharge
• Treatment: metronidazole (Flagyl)
• All sexual partners should be treated
 Granuloma Inguinale
(Donovanosis)
• Granuloma inguinale (donovanosis) is a genital ulcerative disease
caused by the intracellular gram-negative bacterium Klebsiella
granulomatis.

• Granuloma inguinale is one of several causes of genital ulcers.

• Granuloma inguinale is most commonly seen in tropical regions

of the world.

• Extragenital infection can occur with infection extension to the

pelvis, or it can disseminate to intra-abdominal organs, bones, or
the mouth.

• The lesions also can develop secondary bacterial infection and

can coexist with other sexually transmitted pathogens.
 Clinical features
• The disease is characterized as painless, slowly progressive
ulcerative lesions on the genitals or perineum without
regional lymphadenopathy; subcutaneous granulomas
(pseudobuboes) also might occur.

• The lesions are highly vascular (i.e., beefy red appearance)

and can bleed.
 Granuloma Inguinale
(Donovanosis)
• Diagnostic Considerations
• The causative organism of granuloma inguinale is difficult to culture, and
diagnosis requires visualization of dark-staining Donovan bodies on tissue
crush preparation or biopsy.
• Although no FDA-cleared molecular tests for the detection of K.
granulomatis DNA exist, molecular assays might be useful for identifying the
causative agent.
• Treatment
• Azithromycin 1 gm orally once weekly or 500 mg daily for > 3 weeks and
until all lesions have completely healed.
Alternative
• Doxycycline 100 mg orally 2 times/day for at least 3 weeks and until all
lesions have completely healed OR
• Erythromycin base 500 mg orally 4 times/day for >3 weeks and until all
lesions have completely healed OR
• Trimethoprim-sulfamethoxazole one double-strength (160 mg/800 mg)
tablet orally 2 times/day for > 3 weeks and until all lesions have
completely healed
Viral Infections of the
Reproductive System
• Several viruses can cause serious problems for the human
reproductive system.

• Most of these viral infections are incurable, increasing the risk

of persistent sexual transmission.
• Herpes Simplex Virus (HSV)
• Human papillomavirus (HPV)
• Hepatitis B virus
• Hepatitis C virus
• Human immunodeficiency virus (HIV)
 Genital Herpes
• Genital herpes is a common condition caused by the herpes
simplex virus (HSV).
• HSV an enveloped, double-stranded DNA virus that is
classified into two distinct types.
• Herpes simplex virus has several virulence factors, including
infected cell protein (ICP), which helps in replication and
inhibits the maturation of dendritic cells as a mechanism of
avoiding elimination by the immune system.
• Surface glycoproteins on the viral envelope promote the
coating of herpes simplex virus with antibodies and
complement factors, allowing the virus to appear as “self”
and prevent immune system activation and elimination.
Genital Herpes
• There are two herpes simplex virus types: HSV-1 and HSV-2
• HSV-1 is usually oral herpes (cold sores) but can infect genitals; HSV-2
usually causes genital lesions but can also infect the mouth.
• Symptoms include blisters and sores in the genital region that last for
1 or 2 weeks.
• Symptoms can disappear for long periods, but the virus never leaves
the body.
• Transmission:
• Genital herpes: penile-vaginal, oral-genital, oral-anal, or genital-
anal contact
• Oral herpes: through kissing, or oral-genital contact
• Contact with person who is shedding
• Can still transmit herpes even if no lesions are present.
• Vertical transmission (very rare)
• Through the birth canal
 Signs &
symptoms
• It is a lifelong infection with exacerbations and remissions
• Primary Herpes Infection:
• Painful shallow ulcers (Around the mouth (oral herpes type 1) or
on genitalia( genital herpes Type 2))
• In Immunocompromised patients, symptoms are more severe with
increased instances of shedding
• Herpes encephalitis
• Herpes viral meningitis
• Herpes esophagitis Urethritis

Oral herpes Gingivosomatitis

Herpitica Vulvovaginitis
Diagnosis &
complications
• Diagnosis:
• Clinical presentation and history
• PCR
• Tzanck smear w/ Giemsa stain shows multinucleated giant epithelial cells.
• Dacron Swab from base of genital lesion can be tested by:
1. viral culture
2. herpes simplex virus (HSV) antigen detection
3. polymerase chain reaction (PCR) of HSV DNA
4. Serologic testing for antibody for current or past infection if necessary
• Complications:
• Rectal infection may lead to proctitis
• Genital pain, Urethritis, Cervicitis.
• Aseptic meningitis
• Involvement of sacral autonomic plexus leading to urine retention
• Increased risk of acquiring and transmitting HIV.
Presence of HSV in the birth
canal during delivery
Causes:
• neonatal herpes:(a serious and sometimes fatal condition)
Neonatal herpes can cause an overwhelming infection
resulting in central nervous system damage, mental
retardation, or death.

Medication:
• 1st line: oral Acyclovir, valacyclovir, or famcyclovir +
symptomatic treatment for pain
• 2nd line: topical antiviral + symptomatic treatment.
 Human Papillomavirus
• Warts of all types are caused by a variety of strains of human
papillomavirus (HPV).
• Condylomata acuminata, more commonly called genital warts or
venereal warts, are an extremely prevalent STI caused by certain strains
of HPV.
• Condylomata are irregular, soft, pink growths that are found on external
genitalia or the anus.
• HPV is a small, non-enveloped virus with a circular double dsDNA
genome.
• Researchers have identified over 200 different strains (called types) of
HPV, with approximately 40 causing STIs.
• Over 90% warts are caused by HPV types 6 and 11.
• HPV types 16 and 18 are known to cause cancer.
• Oncogenic HPV types can also cause oropharyngeal cancer, anal cancer,
vaginal cancer, vulvar cancer, and penile cancer.
Human Papillomavirus
• HPV infection is often asymptomatic and self-limiting.
• Genital HPV infection often co-occurs with other STIs
like syphilis or gonorrhea
• HPV virulence factors include proteins (E6 and E7) that are
capable of inactivating tumor suppressor proteins, leading
to uncontrolled cell division and th development of cancer.
• In females, warts occur around mostly in the vagina, anus,
and cervix.
• In males, genital warts are less common but might present
on the tip of the penis.
• Mode of transmission: Sexual contact & Direct skin contact
Signs &
Symptoms
• Signs and symptoms:
• Genital warts present as soft,
moist, pink/flesh-colored genitalia
bumps.
• Usually painless.
• Cauliflower-like appearance
of condylomata acuminata
HPV
◦Complications Genital warts
may occur around the anus
• HPV is the main risk factor for
cervical cancer,(And rarely
Vulvar/Vaginal,Rectal cancer)
as such we have to perform a
Pap smear screening test for
early detection of cervical
cancer in females.
 Warts

Condylomata acuminata are

lesions produced by human
Warts Plantar
papillomavirus
Treatment
• Visible genital warts are removed by either cryotherapy
(freezing) or chemical treatment; larger warts may require
minor surgery to remove
• Removal doesn’t necessarily prevent recurrence
• Warts may disappear on their own

• New: prevention via vaccine

• Gardisil: vaccine against 4 strains of HPV that together cause
70% of cervical cancers and 90% of genital warts
• Most health officials believe vaccination before puberty is
best, before teens become sexually active
Human Immunodeficiency
Virus (HIV)
• HIV class: Lentivirus
• Retrovirus: single stranded RNA transcribed to double
stranded DNA by reverse transcriptase
• Integrates into host genome
• High potential for genetic diversity
• Can lie dormant within a cell for many years, especially in
resting (memory) CD4+ T4 lymphocytes
• HIV invades the helper T cells to replicate itself.
 Modes of HIV/AIDS Transmission

Sharing Needles
Unsafe Intercourse

Bodily Fluids

Mother-to-Baby: Before Birth, During Birth

or
Postpartum
The HIV replication cycle

75
 gp120 env protein binds to CD4 molecule

 CD4 found on T-cells , macrophages, and microglial cells

 Binding to CD4 is not sufficient for entry

 V3 loop of gp120 env protein binds to co-receptor

 CCR5 receptor - used by macrophage-tropic HIV variants

 CXCR4 receptor - used by lymphocyte-tropic HIV variants

Risk factors and stages of
HIV infection
• Risk factors:
• STIs (due to open sores)
• Unprotected sex
• Multiple sexual partners
• Uncircumcised males
• Stages of HIV infection
• Acute HIV infection
• Chronic HIV infection
• AIDS
 HIV Evasion Methods

• Makes (1010 ) 10 billion copies/day -> rapid mutation of HIV

antigens

• Integrates into host DNA

• Depletes CD4 lymphocytes

• Down-regulation of MHC-I process

• Impairs Th1 response of CD4 helper T lymphocyte

• Infects cells in regions of the body where antibodies penetrate

poorly, e.g., the central nervous system 79
Natural History of HIV-1
Diagnosis & complications
• Rapid tests
• KHB, Statpac, Unigold..
• ELISA
• Screening
• High sensitivity
• PCR
• Measure the viral load
• DNA PCR
• ANTIGEN (Ag) in plasma/serum (p24)
• Western Blot
• Confirmatory test
Treatment of HIV
Antiviral Therapy
• Triple therapy HAART:
• 2 nucleoside reverse transcriptase inhibitors
• Zidovudine, Nevirapine
• Protease inhibitor
• Saquinavir, Indiniavir
Hepatitis Virus
• Viral hepatitis is a systemic disease primarily involving the liver.
• Hepatitis B, C and D can be transmitted through sexual
contact, but HepB are transmitted more often through sex.
• In the nucleus, the partially double-stranded viral genome is
converted to covalently closed circular double-stranded DNA
(cccDNA).
• HCV is a positive-stranded RNA virus, classified as family
Flaviviridae, genus Hepacivirus.
• HDV is a defective virus that acquires an HBsAg coat for
transmission.
• It is often associated with the most severe forms of hepatitis in
HBsAg-positive patients.
Virus Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Family Picornaviridae Hepadnaviridae Flaviviridae Unclassified Unclassified

Genus Hepatovirus Orthohepadnaviru Hepacivirus Deltavirus Hepevirus

s

Virion 27 nm, icosahedral 42 nm, spherical 60 nm, spherical 35 nm, 30–32 nm,
spherical icosahedral

Envelope No Yes (HBsAg) Yes Yes (HBsAg) No

Genome ssRNA dsDNA ssRNA ssRNA ssRNA
Genome size 7.5 kb 3.2 kb 9.4 kb 1.7 kb 7.6 kb
Stability Heat- and acid- Acid-sensitive Ether-sensitive, acid- Acid-sensitive Heat-stable
stable sensitive

Transmission Fecal-oral Parenteral Parenteral Parenteral Fecal-oral

Prevalence High High Moderate Low, regional Regional
Fulminant Rare Rare Rare Frequent In pregnancy
disease

Chronic disease Never Often Often Often Never

Oncogenic No Yes Yes ? No
Hepatitis B

Courtesy of: the CDC Public Health Image Library

On the left is a photograph of hepatitis B virus particles, taken using an electron

microscope. The patient on the right has a distended abdomen from a chronic
hepatitis B infection.
87
Serological Markers of Acute HBV
Infection
HBV DNA

HBeAg Anti-HBe
Anti-HBs
Anti-
HBc

HBsAg Anti-HBc
IgM

00 22 44 66
Months
Months Years
Years
Adugna, MLT, Microbiologist
 Assay Results

Interpretation
HBsAg Anti-HBs ofAnti-HBc
HBV Serologic
Interpretation Markers in
Positive
PatientsNegative Negative
with Hepatitis .
Early acute HBV infection. Confirmation is required to
exclude nonspecific reactivity.

Positive (±) Positive HBV infection, either acute or chronic. Differentiate

with IgM anti-HBc. Determine level of replicative
activity (infectivity) with HBeAg or HBV DNA.

Negative Positive Positive Indicates previous HBV infection and immunity to

hepatitis B.
Negative Negative Positive Possibilities include: HBV infection in remote past;
"low-level" HBV carrier; "window" between
disappearance of HBsAg and appearance of anti-HBs;
or false-positive or nonspecific reaction. Investigate
with IgM anti-HBc. When present, anti-HBe helps
validate the anti-HBc reactivity.

Negative Negative Negative Never infected with HBV. Possibilities include another
infectious agent, toxic injury to liver, disorder of
immunity, hereditary disease of the liver, or disease
of the biliary tract.

Negative Positive Negative Vaccine-type response.

Fungal Infections of the Reproductive System
• Only one, Candida major fungal pathogen affects the urogenital system.
• Candida is a genus of fungi capable of existing in a yeast form or as a
multicellular fungus, dimorphic.
• Candida spp. are commonly found in the normal, healthy microbiota of the
skin, gastrointestinal tract, respiratory system, and female urogenital tract.
• They can be pathogenic due to their ability to adhere to and invade host
cells, form biofilms, secrete hydrolases (e.g., proteases, phospholipases, and
lipases) that assist in their spread through tissues, and change their
phenotypes to protect themselves from the immune system.
• Typically, only cause disease in the female reproductive tract under
conditions that compromise the host’s defenses.
• While there are at least 20 Candida species of clinical importance, C.
albicans is the species most commonly responsible for fungal vaginitis.
Risk Factors
• Pregnancy
• Diabetes
• Use of broad spectrum antibiotics
• This can alter the normal vaginal micro-biota, allowing candida the
opportunity to flourish and grow.
• Use of corticosteroids
• The immunosuppressive action of corticosteroids can allow
commensal candida the opportunity to thrive excessively.
• Immunosuppression or compromised immune system
• HIV or cancer patients. May be associated with a more advanced and
potentially life-threatening candida infection, or recurrent candidiasis
which is difficult to treat.
• Vaginal douche , bubble bath, shower gel, tight cloths.

• Underlying dermatitis e.g. eczema

Clinical Features
• Pruritus vulva
• Itchiness of the vulva
• Vaginal discharge
• Usually white, curd-like and non-offensive in candida
infections.
• Dysuria (superficial dysuria)
• Erythema and swelling of the vulva
• Satellite lesions
• Red, pustular lesions with superficial white/creamy
pseudomembranous plaques that can be scraped off.
• Curd-like or cheesy discharge in vagina
 Diagnosis of vaginal
candidiasis
• Microscopic evaluation of vaginal secretions.
• Culture but are less useful because Candida is
part of the normal microbiota and will regularly
appear.
• Candida is a dimorphic fungus, so it does not
only exist in a yeast form; cultivation can be
used to identify chlamydospores and
pseudohyphae, which develop from germ
tubes.
• The presence of the germ tube can be used in a
diagnostic test in which cultured yeast cells are
combined with rabbit serum and observed
after a few hours for the presence of germ
tubes.
• Molecular tests are also available if needed
Treatment
• Topical antifungal medications for vaginal candidiasis
include butoconazole, miconazole, clotrimazole, tioconazole
, and nystatin.
• Oral treatment with fluconazole can be used.
• There are often no clear precipitating factors for infection, so
prevention is difficult.
Ectoparasitic infections

• Ectoparasites: parasitic organisms that live on the outer skin

surfaces

• 2 common STIs caused by ectoparasites:

• Pubic lice

• Scabies
Pubic lice
• Pubic lice, also called crabs, are tiny insects that live on your pubic
hair, near your genitals.
• Caused by biting louse called Phthirius pubis.
• Offten associated w/presence of other STIs.
• Transmitted during sexual contact when two people bring their
pubic areas together
• Lice can live away from the body for as long as 1 day--can drop
off onto underclothes, bedsheets, etc, and eggs deposited by
female louse can survive for several days
• Therefore, it is possible to get pubic lice by sleeping in
someone’s bed or wearing someone’s clothes

Female pubic louse

Pubic lice (cont.)
• Symptoms:
• Itching (that’s not relieved by
scratching).
• Can also leave bluish-grayish
marks on the thighs
and pubic
area from bites.
• Self-diagnosis is possible by
locating a louse on a pubic hair.
• Treatment:
• medicinal lotion (1% permethrin
or pyrethrin) applied to all
affected areas + all areas w/body
hair (genitals, armpits, scalp, even
eyebrows);
• wash all clothes and bedding that
were exposed
Scabies
• Caused by: parasitic mite called
Sarcoptes scabiei
• Female mite burrows beneath skin
to lay eggs--hatched egg grows
into adult that on host’s
skin
Scabies mite
• Too small to be seen by naked eye
• Prevalence: not reported to health agencies--
worldwide, estimated at ~300 million cases/yr.
• Transmission:
• by close physical contact, both sexual and
nonsexual.
• Can be transferred on clothing or bedding
(can live away from host for up to 3 days).
• In addition to sexually active people,
school children, nursing home residents,
and indigent people are at risk.
Scabies (cont.)

• Symptoms:
• Small vesicles or pimple-like
bumps, red rash
• Intense itching
• Favorite sites of infestation:
webs and sides of fingers, wrists,
abdomen, genitals, buttocks,
and female breasts
• Treatment:
• medicinal lotion (prescription &
nonprescription available) applied at
bedtime, then washed off after 8 hrs
• wash all clothes and bedding that were
exposed