Print-Reproductive System Infections

Microbiota & reproductive system
8/19/2017 1
infections
Reproductive
Microbiota of RS
system infections
Non-sexually Sexually
transmitted transmitted
disease disease

8/19/2017 2
infections
1. Microbiota of reproductive system
Permanent colonization
Urethra & vagina
Influenced by estrogen hormone action

On vaginal epithelial cell
Estrogen enhance glycogen deposition
Glycogen converted to lactic acid
By lactobacilli acidic pH
Inhibits potential pathogen growth

8/19/2017 3
infections
Cont
New born girl
Lactobacillus at birth
Colonize up to 6 weeks
Then maternal estrogen lost other colonizer
Staphylococci, streptococci & Enterobacteriaceae
Estrogen produced at puberty
Lactobacilli dominates
Others
G +ve Staphylococci, Streptococci, Enterococci
G -ve Enterobacteriaceae, ..

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infections
Cont
Consist d/t microbes

Dominant
Lactobacilli, streptococci & CNS (coagulase-negative staphylococci)
Rarely cause disease
Transit colonizer fecal organisms
E.g. Enterococcus, Enterobacteriaceae
Can cause UTI
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infections
2. Reproductive system infections
Reproductive system
Entry to d/t infectious disease
Transmission
Sexually or non-sexually transmitted

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infections
2.1. Non-sexually transmitted disease
Non-sexually transmitted disease
Bacteria Fungi
Bacterial Vulvovaginal
vaginosis candidiasis

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infections
A. Bacterial vaginosis
Bacterial vaginosis
Common in childbearing years
No inflammatory changes vaginosis than vaginitis
Pregnant women with disease
7 fold premature birth/complication risk
Symptoms
50% asymptomatic
Thin, grayish-white, vaginal discharge
Slightly bubbly & appears homogeneous
Characteristic pungent fishy odor

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infections
Cont
No clear etiological agent
Constant finding
Decrease vaginal lactobacilli
Conditions responsible may cause
Suppressing lactobacilli or
Promoting other microbiota
Commonly identified bacteria
Gardnerella vaginalis aerotolerant gram +ve
Streptococci strictly anaerobic

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infections
Cont
Pure cultures of these species
Not consistently produce bacterial vaginosis
The discharge from people
Produce the disease

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infections
Cont
Key change in disease

Decrease in normal vaginal acidity
Marked normal vaginal flora change
sloughed epithelial cell with bacterial mass
From vaginal wall
No inflammation
Unless co-infected

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infections
Cont
No clear agent
Epidemiology not well understood
Common in
Sexually active women
Sexually abused children
Risk factors
Sexual promiscuity
A new sex partner
Using an intrauterine device (IUD)
No evidence of sexual transmission

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infections
Cont
Usually clinical
Amsel criteria having 3 out of 4
Increased white homogeneous vaginal discharge;
Vaginal discharge pH >4.5
Liberation of a distinct fishy odor
Microscopic demonstration
Clue cells (vaginal epithelial cells
-Bacteria coated
No proven preventive measure

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infections
B. Vulvovaginal candidiasis
Vulvovaginal candidiasis
2nd common vaginal symptom cause
Disruption of normal microbiota
Involve vagina & external genitalia
Symptoms
Itching & burning
Scanty & whitish vaginal discharge
Involved area
Usually red & swollen

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infections
Cont
Candida albicans 30% normal flora
Vaginal colonization by C. albicans

Normal
Keep in cheek by vaginal lactobacilli
Compete for nutrients
Balance disturbed
E.g. Bread spectrum antibiotics
Uncontrolled diabetes mellitus glucose in urine
Oral contraceptives
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infections
Cont
Candida albicans
Multiply
Initiate inflammatory response

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infections
Cont
Not sexually transmitted
Minimizing bread spectrum antibiotics

Treating underlying condition DM

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infections
2.2. Sexually transmitted disease
STD
Protozoal
Bacterial Viral
STD
Chlamydial
Chancroi Trichomo
Gonorrhea genital system Syphilis
d niasis
infection
Genital herpes Papilloma

HIV
simplex virus STD

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infections
2.2.1. Bacterial STD
Most bacterial STD agent
Poor environment survival
Require intimate physical contact

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infections
A. Gonorrhea
STD d/t manifestations
Genital Gonorrhea
Rectal gonorrhea
Rectal intercourse
Pharyngeal gonorrhea
Oral-genital intercourse
Pelvic inflammatory disease (PID) 10-20% of women
Disseminated gonococcal infection

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infections
Cont
2-5 days incubation

Can be asymptomatic male & female
Men
Characterized by urethritis
Pain during urination
Purulent urethral discharge
Women Milder & limited medical attention
Painful urination
Purulent Vaginal discharge
Become gonorrhea carriers 50%

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infections
Cont
Neisseria gonorrhoeae
Gram ve diplococci, LOS, plli
Cultivated on chocolate agar fastidious
Only infect humans
Sensitive for d/t environmental factors

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infections
1. Attachment pilli + protein N. gonorrhoeae
Non-ciliated epithelial cell
Non-capsulated
Form micro colony

4. Cytoplasm multiplication
3. Endocytosis
Nucleus
5. Sub mucosal escape
6. Usually controlled
By phagocytosis
No capsule
7. Local infection
8. Rarely dissemination
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infections
Cont...
Infection acquired
Sexual transmission
Rates in adolescents
Very high
Major reservoir for continued spread
Asymptomatic patient
Screening studies
50% women infected are asymptomatic

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infections
Cont
Microscopy Gram stain

Gram-negative diplococci
Culture
Chocolate agar & other media
DNA amplification technique
Sensitive but expensive

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infections
Cont.
Safe sexual intercourse

Using condoms,
Vaginal foams,.. inhibit bacterial growth

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infections
B. Chlamydial genital system infection
Chlamydial infections
Has similarity with gonorrhea
Has urethritis, fallopian tube damage
Female
Ascend & cause PID & sterility
Male
Infect epididymis & sterility

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infections
Cont
Mostly asymptomatic
After 7-14 days incubation
Men
Urethral discharge thin, gray white
Painful testes sometimes
Women
Increased vaginal discharge
Painful urination
Abnormal vaginal bleeding
Upper or lower abdominal pain

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infections
Cont
By Chlamydia trachomatis
Small was considered virus
Obligate intracellular
Lack cell wall
Has IM, OM, LPS, major outer membrane protein (MOMP)
> 15 serological variant (serovars) A, B,C, D,
Based on outer membrane & nucleotide
A, B, C trachoma
D-K STD

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infections
Cont
Complex life cycle

Two form life cycle
Extracellular elementary body (EBs)
Intracellular reticulate body (RBs)
Osmotically fragile
Lack extensive protein cross linking
Protected intracellular
Metabolically active

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infections
Cont
Elementary body
Adapted for extracellular survival
Much like a spore
Infective form transmitted
Attachment
Epithelial cell induce endocytosis
Transformation EB to RB
Enlarged in endocytic vacuole
Resist phagosome-lysosome fusion
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infections
Cont
RB multiplication
Reproduce by binary fission
Many elementary bodies
In intracellular membrane-bound
Membrane then ruptures
Transformation
RBs to EBs
Releasing EBs
Infect new cell or
Transmit to other person

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infections
Cont
Inflammation
Infected cell release cytokine
Inflammation initiated
Tissue damage
Mainly by cell mediated immunity
Direct cell distraction in replication
Site involved
Men Urethra, tubules,
Women
Urethra
Cervix bleed easily
E.g. During sexual intercourse
Uterus pain & bleeding
Fallopian tubes sterility
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infections
Cont
14% sexually active women high school & college

Asymptomatic carriers
Non-sexually transmitted infection exist
E.g. newborn from canal
Pneumonia, conjunctivitis

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infections
Cont
Antigen detection
From clinical specimen using antibody
Cell culture
PCR

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infections
C. Syphilis
3 weeks incubation
Has different manifestation
Syphilis clinical course
4 phases

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infections
Cont
Characterized by 1 local skin lesion

At site of infection
Site depending on sexual type
External genitalia/cervix but
Anal or oral area
Usually painless
The fully developed ulcer Painless & hard chancre
With firm base & raised margins
Ulcer Heal/ disseminate
Lymph & bd
Goes unnoticed female & homosexual men
Lesion in vagina/anus
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infections
Cont
Disseminated syphilis
1-3 months later
Prominent skin lesion all body part
Also lymph node enlargement, fever,
The lesion/rash
Infectious like primary chancre
Lesions resolve spontaneously
2/3 patients illness enters latent state
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infections
Cont
No clinical manifestations
Sero positive for many yrs
Few case progress

After long latent period
Devastating destruction
Any organ/tissue Gumma on skin
E.g. Arthritis, blindness,
Granulomatous lesion (gummas) bones, skin, ..

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infections
Cont
Treponema pallidum
Highly sensitive to d/t agent
Drying, disinfectants
Require direct contact
No toxin & enzyme produced
Less studied limited vitro growth

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infections
Cont
Attach
Mucous membranes/skin
Multiplication
Mostly localized area
Spread
Using lymph & blood
Many of bacterial manifestation
Inflammatory response to bacteria
Bacteria can resist
Immune killing
Unknown mechanism spread
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infections
Cont
Only parasite of humans

Transmission
Sexual intercourse
Kissing secondary stage

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infections
Cont
Microscopy using special microscope
Exudates sample dark field/fluorescent
Serological test
The non treponemal test
Measure Ab against cardiolipin
-Released during tissue damage
-Prepared Agn Derived from beef heart
VDRL (Venereal Disease Research Laboratory)
RPR test (rapid plasma reagin)
are positive during first 4-6 weeks of infection and may
revert negative during tertiary phase or after successful
treatment.
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infections
Cont
Treponemal test use T. pallidum as Agn
Fluorescent labled treponemal antibody absorbation
(FTA-ABS)
Microhemagglutination test for T. pallidum
(MHA-TP)
Remain positive (persistent positive).
Nucleic acid based test PCR
Detect from genital lesion, CSF, bd (also infant )

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infections
Cont
No protective vaccine
Safe sexual practice
Proper treatment both sexual partners

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infections
D. Chancroid
Chancroid
Bacteria STD
Has genital sore
Symptoms
Figure: Swollen groin lymph nodes
Single/multiple genital sore
Called soft chancres painful
Enlarged groin lymph node swelling
Commonly diagnosed in men
Most female asymptomatic

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infections
Cont
Haemophilus ducreyi
Gram ve rode

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infections
Cont
Little known
Small pimple appear at inoculation site
Few days later ulcerates
Bacteria access lymph node
Inflammation enlarged
Pus filled node expose to surface
Release their content
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infections
Cont
Common in tropical countries
Clinical
Looking lesions
Gram stain
Culture
Abstinence, monogamous, condom

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infections
2.2.2. Viral STD
Viral STD
Are common, incurable
Can be sever & long lasting

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infections
A. Genital herpes simplex
Genital Herpes Simplex
Among top 3/4 STD
Symptoms
2-20 days after exposure
Genital itching, burning, sever pain
Red blister/sore (in 3 days)
Break & ulcerate
Slowly dry & heal without scar
Common recurrence
75% patients recur in a year
Severity & frequency (number) decrease with year

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infections
Cont
Herpes simplex virus 2 (HSV2)

Enveloped sensitive to acid, detergent, drying
Linear DS DNA

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infections
Cont
Envelop fuse with CM

DNA access nucleus
Lesion begun
Infecting multiple epithelial cells
Lysis after replication fluid filled blister
Full of infectious virion
Blister rupture painful ulcer
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infections
Cont
Latency nerve cells
Minimal gene expression
Activation infect nerve innervating cells
Genital herpes
Create high risk for new born
If mother has primary infected near delivery
~1/3 of baby get infection
Cause disability/death
If recurrent infection low risk to baby
Mother antibody prevent mother
-Able to cross placenta
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infections
Cont
No animal reservoirs
Sensitive to d/t agent
Transmission sexual
Fomite rare transmission

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infections
Cont
Microscopy
Direct sample analysis CPE
Antigen detection
Virus isolation
Cotton swab/fluid aspiration
Gene detection
PCR
Avoid sexual intercourse during lesion


8/19/2017 56
infections
B. Papilloma virus STD:
Genital wart & cervical cancer
Sexually transmitted human papillomaviruses
Common STD agent
Symptoms
Warts develop
Penis head/shaft
Vagina vaginal openings
Around anus
Warts rarely bleed
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infections
Cont
Human papillomaviruses
Non-enveloped, Icosahedral (spherical)
DS circular DNA, 55nm
D/t outcome infected cells
Lytic infection
Latent infection
Transformation
Fig: Human papillomaviruses: electron microscope
HPV
>100 types based on DNA sequence homology
~30 transmitted by sexual contact
~15 can cause cancer
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infections
Cont
Infect epithelial cell

Latent infection
Can stay life long or
Eliminated by immunity after few years
Wart mainly by HPV1-4 mechanism
Not clearly known
Genome found in infected cell as extra chromosome
Develop after 3 month infection
Can obstruct urethra/birth canal
New born infection
Obstruct respiratory tract (1 in 100, 000 birth)

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infections
Cont
Cervical cancer
Viral genome integrate host chromosome
Code proteins excessive cell growth
Mainly caused by
HPV16 & HPV18
Cervical cancer agents also cause
Penis & anal cancer

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infections
Cont
Transmission
Sexual intercourse
Single exposure 60% transfer

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infections
Cont
Fig: Abnormal Paps mear
Pap (papanicolaou) smear using microscope

Taking cervix & vaginal scraping epithelial cells
Clear area (Vacuolated) & nuclei doubling
PCR
From cervical swab & tissue specimens
Diagnosis & HPV typing
Cell culture
Difficult to cultivate

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infections
Cont

Routine & regular Pap smear
Every 12 month
Prevent/promote early treatment
Vaccination
D/t vaccines with d/t HPV combination
E.g. divalent (HPV16 & 18) girls starting 11 yrs
Boys prevent penile & anogenital warts
Vaccinated women not protect all HPV strain
Not replace Pap smear

8/19/2017 63
infections
C. Acquired Immunodeficiency
Syndrome (AIDS)
AIDS
Most important STD
The end stage of HIV infection
Symptoms
Acute phase
6 days-6 weeks of getting virus
Fever, headache, muscle aches,
Enlarged lymph node
Milder & resolve spontaneously
Individuals may not have symptoms at all

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infections
Cont
Latent phase
Asymptomatic 5-10 yrs
Generalized lymphadenopathy (swelling)
Advanced phase
CD4 depletion & viral load
Immunodeficiency lead AIDS devt
Human immunodeficiency virus (HIV)

HIV1 & HIV2
SS +ve sense, enveloped, RNA virus

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infections
Cont
HIV
Mainly attack CD4 cells
Reverse transcription
RNA-DNA DNA-DNA enter nucleus
Integrate transcribed
Marked immune cell depilation
Destroyed by virus & CD8 cells
Susceptible to infections & cancer
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infections
8/19/2017 67
infections
Cont
HIV1 (1981 USA) & HIV2 (1984 West Africa)
Transmission
Sexual, contaminated bd, mother-to-fetus
Molecular after 6-10 days

Virus isolation
Serology
Current HIV test: KHB STAT-PAK Uni-glod
Education
Male circumcision
Bd, bd product & organ screening
Infection control
8/19/2017 68
infections

Print-Reproductive System Infections

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Microbiota & reproductive system

Microbiota & reproductive system

Influenced by estrogen hormone action

Microbiota & reproductive system

Microbiota & reproductive system

Consist d/t microbes

Microbiota & reproductive system

Non-sexually transmitted disease

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

Key change in disease

Microbiota & reproductive system

Microbiota & reproductive system

No proven preventive measure

Microbiota & reproductive system

Microbiota & reproductive system

Candida albicans 30% normal flora

Vaginal colonization by C. albicans

Microbiota & reproductive system

Not sexually transmitted

Minimizing bread spectrum antibiotics

Microbiota & reproductive system

Genital herpes Papilloma

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

2-5 days incubation

Microbiota & reproductive system

Microbiota & reproductive system

Form micro colony

Microbiota & reproductive system

Microscopy Gram stain

Microbiota & reproductive system

Safe sexual intercourse

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

Complex life cycle

Microbiota & reproductive system

Microbiota & reproductive system

14% sexually active women high school & college

Microbiota & reproductive system

Safe sexual intercourse

Microbiota & reproductive system

Microbiota & reproductive system

Characterized by 1 local skin lesion

Few case progress

Microbiota & reproductive system

Microbiota & reproductive system

Only parasite of humans

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

Microbiota & reproductive system

Common in tropical countries

Abstinence, monogamous, condom

Microbiota & reproductive system

Microbiota & reproductive system

Herpes simplex virus 2 (HSV2)

Microbiota & reproductive system