EFRIDA WARGANEGARA

II. OBSTETRIC AND

PERINATAL INFECTIONS
Sexually Transmitted Diseases (STD) / Venerial Diseases (VD)
: are infections that are often, if not always, passed from
person to person contact.

A wide variety of infectious microorganism can be spread by
sexual contact, these range from microscopic viruses (HIV) to
visible insect (pubic louse)

STD usually result from having vagina, oral and anal sex with
an infected partner, but occasionally they may be transmitted
by kissing or close body contact

Agents of some STD may be transmitted through food and
water or blood transfusion, contaminated medical instruments,
or needles use by injecting drug users


SEXUALLY TRANSMITTED
(VENEREAL) DISEASES
Traditionally, five disease have been clasification
as STD (Earliest): Syphilis, Gonorrhea,
Chancroid, Lymphogranuloma Venereum (LGV)
and Granuloma Inguinale.

However, many others diseases are sexual
transmitted, including : Genital Herpes, Hepatitis,
Moluscum Contagiosum, Pubic Lice, Scabies,
and HIV infection, which cause AIDS
CLASSIFICATION OF STD
STD are sometimes grouped by symptoms and sign
they cause.

Syphilis, Genital Herpes and Chancroid -> all cause
Ulcers (sores) on the skin or membranes lining the
vagina or mouth.

Both Gonorrhea & Chlamydial infections cause :
- In Men : Urethritis (inflamation & discharge of
the urethra)
- In Women : Cervicitis (inflamation & discharge
of the urethra), and Pelvic infections
- In Newborn : Eye infectons
CLASSIFICATION OF STD
Type of Infections Infectious Agents
Inflamatory (Exudative Infections)
Urethritis, Cervicitis




Vaginitis

Neisseria gonorrhoeae (Gonorrhoeae)
Chlamydia trachomatis (NGU or
Cervicitis)
Mycoplasma hominis, Mycoplasma
genitalium
Trichomonas vaginalis (trichomoniasis)
Candida albicans (Candidiasis)
Gardnerella/Mobiluncus spp (bacterial
vaginosis)
Genital Ulcers (Nonexudative Infections)
Syphilis
Herpes
Chancroid
Lymphogranuloma Venereum
Genital Warts (Condylomata acuminata)

Treponema pallidum
HSV-2 >> HSV-1
Haemophilus ducreyi
Chlamydia trachomatis
Human papillomavirus (HPV)
Sexually Transmitted Systemic Infections
AIDS
Pelvic Inflamatory Disease (PID)

HIV-1, HIV-2
Polymicrobic : N.go, C.trach. anaerob
Cancer (Neoplasia)
Cervical carcinoma
Kaposi Sarcoma

HPV
Human Herpes Virus type 8
OBacterial
Neisseria gonorrhoeae
Chlamydia trachomatis
Treponema pallidum
Haemophilus ducryei
(chancroid)
Lymphogranuloma
Mycoplasma
Ureaplasma
Calymmatobacterium
granulomatis
Gardnerella vaginalis

OViruses
Herpes simplex II
Hepatitis B , C
HIV
Papillomavirus
OYeasts and fungi
Candida albicans
Candida glabrata
Candida tropicalis

OParasites
Trichomonas
vaginalis
Entamoeba
histolytica
Giardia lamblia
Sarcoptes scabiei
Phitirius pubis


1. Neisseria gonorrhoeae
2. Chlamydia trachomatis
3. Treponema pallidum
4. Hemophilus ducreyi
5. Ureaplasma urealyticum
6. Human Imunodefeciency Virus (HIV)
7. Human Papilloma Virus (HPV)
8. Candida albicans
General characteristics :
N. go : L.S. Neisser, who first isolated it in 1879
Small Gram-negatif diplococcus
A kidney bean morphologic appearance
often called gonococcus
Very fragile organisme, rapidly killed by most
antiseptic and desinfectans
All species are aerobic or facultative anaerob
Pathogens grow better in 5-10% carbonoxidase
Produce enzyme cytochrome oxidase Oxidase
test -positive
1. Neisseria gonorrhoeae
Paracitize the membrane mucosa of human
(cervix, urethtra, rectum, oropharynx dan
nasoharynx)

Most transmission therefore is during sexual
intercourse, except :
- vulvovaginitis in prepubertal girls and
- conjuctivitis in newborn
- Keratitis (when transmitted to the eye by
fingertip, towel, or other object ->
conjuctivitis -> infecrie corneal)

Cause symptomatic and asymptomatic
infections (ora and nasopharynx)


1). NEISSERIA GONORRHOEAE
Gonococcus invade host cells by process similar to
phagocytosis
Clinical sign : due to migration of WBC and activation
of complement at the site infection
Gonococcus are known to persist in the infected
host, probably due to their phagocytosis by epithelial
cells protect them from the phagocytic activities of
WBC

Produces IgAase that degrades IgA; this antibody
probably plays a key early role in mucosal infections.
(IgAase is also found in Haemophilus and
streptococcal organisms).

Possesses a plasmid that codes for penicillinase
production.

Possesses pili, which are protein surface
fibrils that mediate attachment to the
mucosal epithelium.

Pili undergo phase variation (on/off switch
of pili production). Nonpiliation greatly
reduces virulence.

Pili also exhibit antigenic variation and have
the capacity to produce millions of variants,
which is partly responsible for the lack of
protection against subsequent infection.

Pathogenicity
Possesses outer membrane proteins that
form porins (PI and PIII) and that determine
clumping (PII) or opacity. PII- strains are
isolated from disseminated forms. Pili and PII
play major roles in adherence

Possesses endotoxin activity that damages
mucosal cells. Unlike most LPSs, N.
gonorrhoeae lacks lengthy O-antigenic side
chains and is termed lipo-oligosacharide
(LOS)

Pathogenicity
Results in mucous membrane infections, primarily in the
anterior urogenital tract.

epidemic, the highest incidence in the most sexually
active groups (age 15-25 years).

is absent in 20% to 80% of infected women and 10% of
infected men; these asymptomatic carriers may
transmit the bacteria to consorts, causing
symptomatic gonorrhea.

Is compared with other sexually transmitted
diseases

repeated infection may cause scarring with
subsequent sterility in either gender and may
predispose women to ectopic pregnancy.

Clinical Manifestation
Reflects various types of infections including:

1. Urethritis in men is characterized by thick, yellow, purulent
exudate containing bacteria and numerous neutrophils;
frequent, usually in 2-5 days, painful /difficult
urination/dysuria; and possibly an erythematous meatus.
Complications : epididymitis and prostatitis in males.

2. Endocervicitis or urethritis in women is characterized
by a purulent vaginal discharge, frequent, painful
urination, and abdominal pain. Approximately 50% of
cases go undiagnosed. Complications : arthritis, pelvic
inflammatory disease, and sterility.

3. Rectal infections (prevalent in homosexual males),
characterized by painful defecation, discharge,
constipation, and proctitis.



Clinical Manifestation

4. Pharyngitis : characterized by purulent exudate, the
mild form mimics viral sore throat, whereas the severe
form mimics streptococcal sore throat.

5. Disseminated infection (bloodstream invasion) :
infection in which organisms initially localize in the
skin, causing dermatitis (a single maculo-papular,
erythematous lesion), spread to the joints, causing
overt, painful arthritis of the hands, wrists, elbows,
and ankles.

7. Infant eye infection (ophthalmia neonatorum), which is
contracted during passage through the birth canal,
characterized by severe, bilateral purulent
conjunctivitis, may rapidly lead to blindness.

Gambar Go.
1. Identification

a. Gram-negative, intracellular and extracellular diplococci.
Numerous neutrophils appear in purulent exudate in
men. Because of endocervical localization, a charac-
teristic Gram stain of organisms is less likely in females

b. Culture should be immediately placed on warm Thayer-
Martin chocolate agar in a candle jar.
c. Oxidase test is positive.
d. Organisms utilize glucose but not maltose.

e. Newer techniques involve immunofluorescence, enzyme-
linked immunosorbent assay (ELISA) on gene probes on
a clinical swab.
The gonococcus requires : enriched medium with increased CO2
tension for growth.

Cultured on modified Thayer Martin (MTM) Chocolate agar. MTM
Chocolate agar is selective for pathogenic Neisseria contains
enrichment factors to promote the growth of gonococci,
antibiotics to inhibit normal body flora : vancomycin to inhibit
gram-positive bacteria; colistin to inhibit gram-negative
bacteria; trimethoprim to suppress Proteus; and nystatin to
inhibit yeast.

The "chocolate" color : hemoglobin enrichment added to the
medium, incubated under increased CO2 tension such as that
provided by a candle jar. (Transgrow Medium is a convenient
flask containing MTM Chocolate agar and CO2.)

N. go forms small, grayish-white to colorless, mucoid colonies in
48 hours at 35 37o C


2. Clinical Specimens

In women, both genital and rectal cultures should
be obtained.

If a speculum or anoscope is used, lubricant
should not be used because it kills many
organisms and reduces the chance for a successful
culture.

The organisms are labile, and specimens should be
plated immediately.

If disseminated gonorrhea is present, blood and
synovial fluid should be cultured; culture of skin
lesions is rarely successful.


1. Treatment
a. Ceftriaxone should be given, followed by a tetracycline to treat
possible chlamydial infection.
b. In approximately 50% of cases, pelvic inflammatory disease is
severe enough to warrant hospitalization.
c. Pelvic inflammatory disease predisposes the patient to repeated
episodes caused by other bacteria and to ectopic pregnancy.

2. Prevention
a. The patient's sexual partners should be treated and condom use
should be encouraged.
b. Asymptomatic patients should be identified by culture & treated.
c. To prevent neonatal gonococcal conjunctivitis, topical silver
nitrate or tetracycline should be used; the antibiotic is preferred
because it also kills Chlamydia trachomatis, if present.
The organism is an obligate intracellular parasite that
exclusively infects humans (it cannot synthesize its own
ATP or grow on artificial medium), it was once thought
to be a virus, size 0,2 t-1.0 um, have no peptidoglycan
layer in the cell wall (different from Rickettsiae)

Because of Chlamydia's unique developmental cycle, it
was taxonomically classified in a separate order.

Chlamydia has a genome size of approximately 500-1000
kilobases and contains both RNA and DNA. The
organism is also extremely temperature sensitive and
must be refrigerated at 4
0
C as soon as a sample is
obtained.



They have unusual developmental cycle in which
two forms of m.o. exist :
a. Elemnentary bodies extracelluler and infectious
form
b. Reticulate bodies intracellueler and
noninfectious form

Chlamydia trachomatis infection is one of the most
common sexually transmitted infections world wide

Occurring in men and women under the age of 25.

This is most likely an underestimate, since half of
people with chlamydia likely have gonorrhea too.


Chlamydia trachomatis



- Serovars L
1
-L
3

- Serovars D-K
Lymphogranuloma
Venereum (LGV)
1. Urethritis
2. Cervicitis
3. Pelvic Inflamatory Disease (PID)
4. Inclusion conjuctivitis -Newborn
5. Neonatal Pneumonia
6. Assocoation with cervical cancer
Chlamydia psittacci pneumonia (human psittacosis,
avian chlamydiosis)
Chlamydia pneumoniae - pneumonia
A. Elementary bodies (EB) - EB are the small (0.3
- 0.4 m) infectious form of the chlamydia.
They possess a rigid outer membrane that is
extensively cross-linked by disulfide bonds.
Because of their rigid outer membrane the
elementary bodies are resistant to harsh
environmental conditions encountered when
the chlamydia are outside of their eukaryotic
host cells.
The elementary bodies bind to receptors on
host cells and initiate infection. Most chlamydia
infect columnar epithelial cells but some can
also infect macrophages.

B. Reticulate bodies (RB) - RB are the non-
infectious intracellular from of the chlamydia.

They are the metabolically active replicating
form of the chlamydia.
They possess a fragile membrane lacking the
extensive disulfide bonds characteristic of the
EB.

Once inside the endosome, the glycogen produced causes
the elementary body to "germinate" into the vegetative
form, the reticulate body.

This form divides by binary fission at approximately 2-3
hours per generation. It has an incubation period of 7-21
days in the host.

It contains no cell wall and (when stained with iodine) is
detected as an inclusion in the cell. After division, the
reticulate body transforms back to the elementary form
and is released by the cell by exocytosis.

One phagolysosome usually produces 100 1000
elementary bodies.

Diagnosis of C. trachomatis infection is based on
clinical sign and symptoms, that are difficult to
differentiate with N. gonorrhoeae infection and
other aetiologic.

Laboratory examination is very useful to confirm
the definitive organisms. C. trachomatis infection

Collection of specimens

Chlamydia is an intracellular pathogen. Obtain swab
specimens containing epithelial cells of cervix, rectum
or urethra.

+Urethra : Patient should not urinate within 1 hour prior
to specimen collection. The swab should be inserted 2
cm into the urethra. Use firm pressure to scrape cells
from the mucosal surface. If possible repeat with
second swab.


+Cervix : Remove mucous/pus with a swab, discard,
and use firm and rotating pressure to obtain specimen
with another swab. May be combined with a urethral
swab into same transport medium. This combination of
cervical and urethral method is highly recommended.

+Rectum : Sample anal crypts with a swab. Avoid
contamination with fecal material.


1. Subtypes D-K

cause a sexually transmitted disease that may involve an
associated inclusion conjunctivitis.

are a prominent cause of nongonococcal urethritis (NGU)
in men and urethritis, cervicitis, salpingitis, & pelvic
inflammatory disease in women.

produce a relatively high incidence of asymptomatic or
relatively inapparent infections.

can produce a self limiting inclusion co~junctivitis in
neonates delivered through an infected birth canal.

may cause neonatal pneumonia
2. Subtype Ll, L2, L3

causes a sexually transmitted disease called lympho-
granuloma venereum (LGV), which is characterized by a
suppurative inguinal adenitis.

Characterized by acute inguinal lymphadenitis & genital
ulceration, it is also called :
Durand-Nicolas-Faver disease
Tropical or climate bubo
Poradenitis
Lymphopathia venereum
Lymphogranuloma inguinale

may cause lymphadenitis to progress to lymphatic
obstruction and rectal strictures if the disease is untreated.

Chlamydia
trachomatis
Urethritis
P.I.D.
Chronic
Arthritis
Infertility
Neonatal
Conjunctivitis
Acute Arthritis
Hepatitis
Detection of the bacterium can be accomplished
using both non-culture and culture tests :

1. Cytology - Examination of stained cell scrapings
for the presence of inclusion bodies has been
used for diagnosis using Giemsa and iodine
staining, but this method is not as sensitive as
other methods.

2. Leukocyte esterase tests:
detects enzymes produced by leukocytes
containing the bacteria in urine

3. Culture - Culture is the most specific method for
diagnosis of C. trachomatis infections.

4. Antigen detection - Direct immunofluorescence
and ELISA kits that detect the group specific LPS
or strain-specific outer membrane proteins are
available for diagnosis


5. Serology - Serological tests for diagnosis are of
limited value in adults, since the tests do not
distinguish between current and past infections.
Detection of high titer IgM antibodies is indicative
of a recent infection. Detection of IgM antibodies
in neonatal infection is useful.


6. Nucleic acid probes - Three new tests based on
nucleic acid probes are available, uses DNA
complementary to specific ribosomal RNA
sequences. These tests are sensitive and specific
and may replace culture as the method of choice.



1. Treatment is with doxycycline or erythromycin.

2. Prevention is by diagnosing mothers of infected
neonates and urging standard control measures
(e.g., use of condoms) to help prevent sexual
transmission.


General characteristics

is a corkscrew-shaped, motile organism with unusual
morphologic appearance of the outer envelope, three
axial filaments, a cytoplasmic membrane-cell wall
complex with endotoxin, and a protoplasmic cylinder.


causes chronic, painless infections that may last 30
to 40 years if untreated.

decreases in number as host defenses are
stimulated, causing disappearance of symptoms;
subsequently, organisms multiply and symptoms
reappear.

1. Subspecies pallidum causes SYPHILIS, which is
sexually transmitted, epidemic worldwide, and may
affect any tissue.

2. Subspecies pertenue causes yaws (seen in hot tropical
climates, not in the United States). Yaws involves bone
and soft tissues.

3. Subspecies carateum causes pinta (seen in Central
and South America). Pinta involves the skin only.

4. All three subspecies are morphologically and
antigenically identical; differentiation is based solely on
clinical manifestations.

Pathogenicity
Immunosuppressive treponemal components are
responsible for the chronic nature of syphilis and
for subsequent emergence of different stages.

Clinical disease SYPHILIS

1. Vascular involvement leads to endarteritis and
periarteritis, resulting in inhibited blood
supply and necrosis.
2. Lymphocyte and plasma cell inf'iltration occurs
at sites of infection.


The pathogenesis of syphilis varies considerably. It may involve
many tissues of the body and is generally divided into three
stages :

1. Primary Syphilis single lesion appears on the cervix and penis.
Primary lesion may be also on cutaneus or mucous membrane
surface : scroutum, labia, rectum .
At the initial site of infection, a papule with erythema, induration
with a firm base (a hard chancre), but painless, and develops
into an ulcerated sore
the time required for the appearance of chanre 10 90 days,
average 3 weeks. If untreated it may disappear spontaneusly
within 4 12 weeks. Enlarged lymph node near the initial lesion
and then reaching blood stream and infecting other tissues
Material from the lesion is highly infectious



Clinical disease SYPHILIS
2. Secondary Syphilis - Symptom of secondary syphilis may appears
6 weeks several months after infection. Disseminated infection
with lesions in almost all tissues; macular mucocutaneous rash
on the trunk or limbs; there are may be papular rash on trunk and
limbs, palam and hands, may recur if untreated.
Patient in the primary and secondary stage are highly infectious
The spirochete can be demonstrated in any cutaneus or mucous
membrane lesions by dark-field microscopy
Serological examination during this stage reveals high antibody
titers that remain relatively high for up to two years after
infection, after that often negative
However, some treponemes remain viable after the
disappearance of the secondary symptoms and give rise to a
quiescent period called Latent Syphilis

Clinical disease SYPHILIS
3. Latent Syphilis This stage is subdivided into early and latent
periode.
Early laten syphilis : is a lateny infection of two years or less, the
patient may have relaps which secondary symptom reappear and
render the patient potentially infectious; and the Late latent
syphilis : noninfectious stage, is a latent infection of more than 2
years.

4. Tertiary or Late Syphilis Gummaa are the most typical tertiary lesion
on yhe part of the host; the most destructive involve the CV and CNS
(neurosyphilis, aortitis and CNS problems may be fatal)

In utero infection has severe manifestations, including abortion, stillbirth,
birth defects, or latent infection (most common) with the snuffles
(rhinitis) followed by a rash and desquamation.


Clinical disease SYPHILIS
Syphilis
HIV
Transmission.
Chronic
Arthritis
Hepatitis
Congenital
Transmission
Chancres
Lymph-
adenopathy
Cardiovascular
Gumma
Neurosyphilis
Meningitis
Tabes dorsalis
General paresis
Clinical specimens
a. Lesion exudate should be obtained from a pustule
or an ulcer for darkfield microscopy.
b. The organism cannot be grown in vitro.

Identification
Syphilis is identified partly on the basis of clinical
manifestations.
Darkfield microscopy of lesion exudate may
demonstrate cork-screw-shaped spirochetes (the
organisms are too thin to identify by Gram stain).
Serology. Two antibodies are produced in response to T.
pallidum infection:

(1) Nontreponemal (reaginic) antibodies (these
are not IgE)

- are nonspecific (positive in many related or chronic
diseases) but economical as a screening test.
- are identified by other screens: Venereal Disease
Research Laboratory (VDRL) test, rapid plasma reagin
(RPR) card test, or automated reagin test (ART).
- titers are decreased in tertiary syphilis (even if untreated).
If treated, a positive reagin test after 1 year suggests
persistent infection, reinfection, or a false-positive result.
(2) Specific treponemal antibodies

- are more specific, but tests are costly and are
used only to confirm a positive reagin test.
- are screened for by fluorescent treponemal
antibody absorption (FTA-abs) test, T. pallidum
hemagglutination (TPHA) test, and the rarely
used T. pallidum immobilization (TPI) test.
- titers remain positive in most people even with
proper treatment.
- biologic false-positive results may confuse the
diagnosis (positive serology in the absence of
treponemal disease).

1. Treatment
a. Long-acting penicillin should be given.
b. Jarisch-Herxheimer reaction immediately after
antibiotic therapy for secondary syphilis
involves intensification of manifestations for
12 hours; this indicates that penicillin is
effective.
c. With treatment, reagin-based serologic tests
become negative 6 months after primary
syphilis and 12 months after secondary
syphilis; beyond the secondary stage, the
patient may remain seropositive for years.

2. Prevention
a. Use of a condom minimizes transmission.
b. All sexual contacts should be treated
prophylactically with penicillin.
c. In pregnant patients, serologic syphilis tests
should be performed during the first and third
trimesters.

1. Mycoplasma hominis
2. Mycoplasma genitalium
3. Ureaplasma urealyticum : is a prokaryote
that lacks a cell wall and can be cultured
in the lab. However, this organism is often
seen in normal individuals and culturing
the organism has questionable value in
diagnosing NGU.

U. urealyticum and M. hominis colinize the
Genitourinary tract of sexually active men and women
Both organism are opportunisyic pathogens and can
be transmitted by sexual contact
Colonization occurs initialy during birth as infeant
passes through the birth canal, increases after
pubertas and increased sexual activity
U. urealyticum : has been implicated as one of
the causes of NGU
In women : appears to be an opportunistic
pathogen during pregnancy cause of
chorioamnionitis leads to premature labor and
delivery
Stillbirths and perinatals death have been
associated with infection
Congenital and neonatal pneumonia, septcemia,
and meningitis have been associated with
infection of chorioamnion by U.ueralyticum
Therapy NGU : Tetracyclin, if allergy may be take
erythromycin, sexual partner also threated
G. vaginalis is a rod shaped
gram negative (variable)
facultative anaerob bacteria
Increase in vagina with
decrease in Lactobacilly and
increase in anaerobes;
difficult to cultivate.
More commonly causes
nonspesific vaginitis
(bacterial vaginosis) but can
on occasion cause NGU in
males.

Three of the four criteria should be positive
Thin homogenous discharge
pH of discharge >4.5.
Clue cells in saline wet mount or Gram
stain of vaginal discharge
Mixture of vaginal discharge and 10%
KOH liberates an "amine-like" or "fishy"
odor.

Products like douches or deodorant sprays that
mask vaginal odor should not be used to treat BV.
Although they may temporarily eliminate odor,
they will not cure the condition.
It is important to tell your patient not to douche or
use a feminine hygiene spray for a few days
before their appointment. These products may
actually hide important clues that can help in
diagnosing BV, and may make the condition
worse.
Antibiotic therapy: metronidazole or clindamycin
for 7 days.

Chancroid or soft chancre
disease is an acute sexually
transmitted disease
characterized by genital
ulceration and suppuration
Ducrey's bacillus) is a Gram(-
) rod which grows in
chains.

The organism enters the body through
skin abrasions.
It induces a papule or vesicle which
ulcerates.
There is a dense inflammatory exudate
with PMNs but not mononuclear cells.
Incubation period of 1-14 days after
exposure before you get the
development of the characteristic lesion,
the soft chancre.


Chancre development begins as a small
inflammatory papule.
The lesion is a true ulcer.
In contrast to the syphilis chancre, the chancroid
is extremely painful.
Accompanying chancroid development is an
acute, painful inflammatory inguinal
lymphadenopathy in > 50% of cases.



The chancroid lacks
induration and is
referred to as a soft
chancre.



Initially the lesion is
typically solitary but
by autoinoculation
multiple lesions
develop.
Granuloma inguinale (also called lupoid
ulceration granuloma of the pudenda and
granuloma contagiosa) is a chronic, indolent,
ulcerative, granulomatous disease of the skin
and lymphatics.

Gram -rod with characteristic bipolar staining so
they have a safety pin-like appearance in
stained tissue preparation : Donovan bodies

+Genital lesions are present in 90% of infected
patients and in 80% of these there is no other
area of involvement.
+Initially the lesions are papules that tend to
ulcerate slowly.
+The ulcerated lesions are irregular in shape
with a rolled border on a beefy red,
cobblestone base
+Patients develop subcutaneous granulomas in
the inguinal regions; they do not involve the
lymph nodes usually, so we call them pseudo-
buboes.

The organism gains entry by direct inoculation
through skin abrasions or mucous
membranes.
One or more indurated papules form which
progress to characteristic ulceration.
The most important sign is the presence of
mononuclear cells with intra cytoplasmic
vacuoles packed with the bacteria or Donovan
bodies as they are called.

In order of preference :

Trimethoprim-sulfamethoxazole one double-strength tablet
orally twice a day for a minimum of 3 weeks, OR
Doxycycline 100 mg orally twice a day for a minimum of 3
weeks.
Alternative therapy
Ciprofloxacin 750 mg orally twice a day for a minimum of 3
weeks, OR
Erythromycin base 500 mg orally four times a day for a
minimum of 3 weeks.
Follow-up weekly
Check sex partners
The HIV has become an important challenge
to the medical community since the
manifestation of infection by the virus were
first duscovered in 1979.

Infection by HIV leads ti progressive
deterioration of the immune system

This deterioration leads t0 the final stage of
HIV diseases called AIDS

To date AIDS is an incurable condition and no
vaccine is available
Preferentially binds to the CD4 receptor found on
helper T cells & monocytes; the destruction of
these cells ultimately disables the immune system
& makes the infected individual vulnerable to
opportunistic infections
Transmitted through sexual contact, IV drug use,
vertically (mother to child)
Display antigenic variation
Has a long latency period (average 10 years)
Can currently be managed with antiviral drugs but
is otherwise nearly 100% fatal
HIV nononcogenic retrovirus
Retroviridae - Lentivirinae
Robert Gallo et al (1978) : isolated retrovirus
from the lymphocytes of leukemia patient
HTLV-I
A second virus : HTLV-II was isolated in Seattle
USA from the cells of patient with a rare
hairy cell leukemia
The illness of AIDS was first described in male
homosexuals in 1981, and the virus was
isolated by the end of 1983
Essex et al (1983) : 25 30 % AIDS
Ag-Ab membrane HTLV-I
The first isolation of retrovirus from AIDS case
was made by Luc Montagnier & Barr-Sinoussi at
the Pasteur Institute Paris (1983) LAV
The virus isolated from haemofilia patient
with lymphadenopathy
It was quickly confirmed by Robert Gallo (1984)
HTLV-III
Levy (1984) : isolated AIDS-related retrovirus
ARV
Luc Montagnier (1986) isolated a fourth human
retrovirus from AIDS in West Africa
HIV-2
Subfamily Disease caused Natural hosts
Oncovirinae
HTLV-I


HTLV-II
Spumavirinae

Lentivirinae
HIV-1
HIV-2

SIV

Adult T-cell leukemia,
lymphoma, tropical
spastic paraparesis
Hairy cell leukemia
Inapparent
persistent infection

Immunodeficiency
Immunodeficiency

Immunodeficiency

Human


Human
Primates & other
animals

Human
Human & primates
Monkey
The human AIDS virus are not homogenous, most
are variants of HIV-1
A second virus HIV-2 seems prevalent only in West
Africa, much less virulent
Only about 40% of the sequences of HIV-1 and HIV-
2 are identical
Based on env gene sequences
9 subtypes of HIV-1 A I
5 subtypes of HIV-2 A E
These subtypes are referred as clades. Within
subtype there is extensive variability


Virion : spherical, 80 100 nm, cylindric
core
Genome : SS-RNA, linear, positive sense,
9 10 kb
Proteins : envelope glycoprotein, reverse
transcriptase enzyme contained inside
virions, protease required for production of
infectious virus
Envelope : present
Replication : reverse transcriptase makes DNA
copy from from genomic RNA; provirus DNA
is template for viral RNA
Maturation : particles bud from plasma
membrane
OThe virus contains the three genes required for
a replication
gag : encodes the core protein (group-specific antigens
pol : encodes the reverse transcriptase enzyme
(polymease)
env : encodes the glycoproteins that form projections on the
envelope of the particle
OUp to six additional genes regulate viral
expression & important in disease pathogenesis
in vivo. Although these auxiliary genes show a
little sequence homology among lentivirus, their
functions are conserved
O Additional genes :
tat or tax : transactivating regulatory gene encodes a
nonstructural proteins that alters the transcription or
translational efficiency of other viral gene
rev : regulator of expression of virion
O gp 120 : responsible for virus attachment to
the CD4 molecule and coreceptors & carries
the major antigenic determinants that elicit
neutralizing Abs
O gp 41 : contain transmembrane domain that
anchors the glycoprotein in the viral
envelope and a fusion domain that facilitate
viral penetration into target cells
HIV completely inactivated by treatment for 10 minutes
at room temperature with :
10 % household bleach
50 % ethanol
35 % isopropanol
0,5 % Lysol
0,5 % paraformaldehyde
0,3 % hydrogen peroxide
Also inactivated by extremes pH : pH 1.0 & 13.0
When HIV present in clotted or unclotted blood in
needle or syringe, exposure to undiluted bleach at
least 30 seconds for inactivation
HIV inactivated by heating at 56
0
C for 10 minutes
IN VIVO
T lymphocyte, CD4+
Monocyte/
macrophage
Epithelial Langerhans
cells
Dendritic cells
Endothelial cells of
the brain
Microglia, astroglia,
oligodendroglia
Cells of retina, cervix
and colon
IN VITRO
T lymphocyte, CD4+
Monocyte/
macrophage
Microglia
Precursor CD 34+
cells
Monocytic & T-cell
lines
Glioma & neuro-
blastoma cell lines
Tumor cell lines
MODE OF TRANSMISSION
+ Parenteral (IV, drug use)
+ Mucosal (sexual contact)
+ Vertical (mother to child)

Free HIV HIV in CD4+ T cells

regional lymph nodes

Cellular IR Humoral IR
Limphopenia
CD4+ cells
Free virus & p24 in blood
Number of infected CD4

Virus rapid replication
with control of IR

2 4 weeks

Total lymphocyte CD8
Antibody + : 2 3 weeks months

Stages :
Primary infection
Dissemination of virus to lymphoid organs
Clinical latency
Elevated HIV expression
Clinical disease
Death
The duration between primary infection &
progression to clinical disease 10 years
Death usually 3 years after onset of clinical
syndrome
Following primary infection,
viral replication occurs &
viremia detectable for about 8
12 weeks
Virus is widely disseminated
throughout the body & the
lymphoid organs become
seeded
The period of clinical latency may last for as
long as 10 years. During this period, there is a
high level of ongoing viral replication,
estimated that 10 billion HIV particles are
produced & destroyed each day.

The half life of virus in plasma is about 6
hours, and the virus life cycle (from the time
of infection of cells to the production of new
progeny that infect the next cell) averages 2.6
days
AIDS is characterized by a pronounced
suppression of the immune system & the
development of unusual neoplasms (especially
Kaposis sarcoma) or a wide variety of severe
opportunistic infections

Plasma viral load :
the amount of HIV in the blood (viral load) is of
significant prognostic value. Plasma HIV RNA
levels can be determined using a variety of
commercially available assays.

1. Category A :
Asymptomatic
Persistent generalized adenopathy
Symptomatic, acute (primary) HIV
infection

2. Category B :
Some conditions are diagnosed

3. Category C :
Any of some conditions are diagnosed

AIDS is diagnosed if the patient meets criteria
for category A3, B3, C1, C2, or C3

CD4+ T-cells
Clinical
AB
category
C

500/l

200 499/l

<200/l


A1B1

A2B2

A3B3

C1

C2

C3
PROTOZOA
Toxoplasma gondii
Isospora belli
Cryptosporidium sp.

FUNGI
Candida albicans
Cryptococcus
neoformans
Coccidioides immitis
Histoplasma
capsulatum
Pneumocystis carinii

BACTERIA
Mycobacterium avium- intracellulare
Mycobacterium tuberculosis
Listeria monocytogenes
Nocardia asteroides
Salmonella sp.
Streptococcus sp.

VIRUS
Cytomegalovirus
Herpes simplex virus
Varicella-zoster virus
Adenovirus
JC human papovavirus
Hepatitis B virus

Evidence of HIV infection :
1. Virus isolation
Cultured from lymphocyte in peripheral blood or
other specimens, but time consuming
2. Serologic determination of antiviral Abs
ELISA, antibody repeated
Confirmation : immunofluorescence &
radioimmunoprecipitation,
Western blot : at least 2 bands of p24, gp41 or
gp120/gp 160 should be present
3. Measurement of viral nucleic acid or Ag
RT-PCR
Examination of immunity status
- CD4, CD8
- Hematology

Examination of opportunistic infection /
malignancy
1. Positive HIV infection :
- patient sera up to 15 months of age, HIV +, even mother has no HIV
- patient sera < 15 months of age, HIV +, mother HIV +, lymphocyte
count
- p24 Ag +
- HIV culture +, Ag +, RT-ase enzyme +, probe +
- Positive test with specific tests

2. Negative HIV :
screening & confirmation tests

3. Inconclusive :
- Screening test for HIV +, confirmation, Ag, & culture are negative
- Baby < 15 month of age HIV -, mother HIV +

ONNRTI (NON-NUCLEOSIDE ANALOG REVERSE
TRANSCRIPTASE INHIBITOR
* Nevirapine
* Delavirdine mesylate

ONRTI (NUCLEOSIDE ANALOG REVERSE
TRANSCRIPATSE INHIBITOR)
* Didanosine (ddI) * Lamivudine (3TC)
* Zalzitabine (ddC) * Stavudine (d4T)
* Zidovudine (AZT : Azydothymidine

OPROTEASE INHIBITOR
* Indinavir * Ritonavir
* Nelfinavir mesylate * Saquinavir

sel
sel
sel
sel
Hub. sebab-akibat antara interaksi inf. virus dan timbulnya tumor, khususnya yang
bersifat ganas -----> sulit dibuktikan
Hewan percobaan sebagai model, banyak kelemahan, o.k. virus bersifat tropisme.
Artinya : Vir. menyerang manusia belum tentu
menyerang hewan dan sebaliknya.
Virus penyebab Tumor umumnya adalah Virus Laten.

Postulat Koch tak berlaku untuk Virus tumorigenik
sebagai alternatif dikenal

Postulat Evans
1. Ada korelasi antara insidensi penyakit dengan kontak dalam suatu kaitan
waktu yang jelas.
2. Ada korelasi antara penyakit dan kekebalan terhadap virus yang diduga
sebagai penyebab.
3. Virus atau genomnya dapat dipertunjukkan pada sel tumor.
4. Virus yang diduga sebagai penyebab, mampu mentrans formasi sel
normal secara in-vitro.
5. Ada korelasi antara vaksinasi dan insidensi penyakit.

Bukti :
1. Adenovirus
Beberapa tipe bila disuntikan pada hewan ttt ------>
- Sarkoma
- Limfo sarkoma
2. Tumor manusia = Tumor hewan yang jelas disebab-
kan oleh virus.
Ada persamaan : - Klinik
- Patologik
- Epidemiologik
3. Virus Tumor hewan = Virus manusia
Ada persamaan : - Biokimiawi
- Biofisika
- Antigenik
4. Veruca Vulgaris Papova virus
Moluscum contagiosum Pox virus

1. Papovaviridae
Papova : Papilloma, Polyoma dan Simian Vacuolating

Suatu virus telanjang dengan genom DNA untai ganda banyak di alam,
menyerang manusia dan hewan.

Virus Papilloma Virus Polyoma
nukleokapsid 55 nm 45 nm
genom >, pada salah satu pada kedua rantai DNA
rantai DNA
hospes seluler : epitel per- mll saluran napas/cerna
mukaan, menimbulkan --> masuk aliran darah
kelainan pd port dentry --> ke organ-organ dalam :
hati, ginjal, otak.



HPV : Human Papilloma Virus
> 60 tipe virus
Masing-masing tipe mempunyai cara predileksi tersendiri
Bereplikasi dalam inti sel hospes.
Bagaimana terjadinya belum jelas oleh karena Virus Papilloma sulit dibiak dalam
media buatan
Menyerang sel epitel gepeng kulit dan mukosa.
Tipe Virus yang menyerang kulit dan mukosa berbeda.
Kelainan bersifat lokal, ditandai oleh perubahan morfologi & hiperplasia akibat
percepatan proliferasia dan terhambatnya degeneralisasi sel.
Sifat kelainan :
U tetap jinak
U displastik --> ditandai mitosis tidak terkontrol &
perubahan kromosom.
U Ca, ditandai oleh invasi sel kejaringan sekitar atau
metastase jauh ke organ lain.
Bagaimana proses karsinogenesis oleh Virus Papilloma
-----> belum jelas
Tergantung : jenis, besar, lokasi kelainan.

Ekstirpasi / Insisi lesi
Kauterisasi atau Cryosurgery
Lesi jinak : hindari radiasi, oleh karena diduga merangsang
rekombinasi genetik antara fragmen gen virus dan gen sel
sehingga terjadi konversi lesi dari jinak menjadi ganas.
Khemoterapi
Podophyllin untuk condiloma acuminata
Interferon

Nitrogen cair : untuk Veruka pada kulit
Dulu : Virus oncorna (RNA oncogenic)

Sekarang diklasifikasikan sebagai virus Retro oleh karena
mengandung suatu polimerase DNA yang diatur RNA (reverse
transkiptase)
Genom RNA untai tunggal
Terdiri dari beberapa bagian yang mengatur sintesis protein
struktural maupun non struktural yi :
gen gag : mengatur sintesa protein struktural yi
untuk protein kapsid dan pelapis asam
nukleat.
gen pol : untuk enzim reverse transkriptase
gen env : untuk protein selubung

Dibagi atas 3 sub famili :

1. On cornavirinae
4 Grup A
4 Grup B --> Mammary Tumor Virus (Mencit)
4 Grup C --> HTLV I, II, III
(Human Tlyphotropic Virus)
4 Grup D --> Mason Pfizer Virus (Kera)
2. Lentivirinae
HIV I dan II
(Human Immunodeficiency Virus)
3. Spumavirinae
Human foamy Virus
Dari sub famili Oncornavirinae yang dapat menginfeksi manusia adalah
group C yaitu HTLV
Penyebab AIDS : Acquired Imuno Deficiency Syndrome
Gejala :
* Disfungsi seluler yang berat
* Infeksi oportunistik berat :
- Kandida esopagitis
- Herpes mukokutan kronik
- Toksoplasmosis
- Sitomegalovirus
- Kriptosporodiosis
* Gangguan neurologik
* Keganasan : Sarkoma Kapossi
Patogenesis : Sangat kompleks
Target inisial HIV adalah molekul CD4 t.u. CD4 pada sel T helper
Monosit
Makrofag
Virus dapat menyerang sel jaringan yang mempunyai CD4 seperti : - eritrosit
- epitel ginjal
- sel astrosit pada otak
- sel glia

SYSTEMIC MYCOSIS : Opportunistic

Disease Agents

Candidiasis Candida albicans; Candida sp.

Cryptococcosis Cryptococcus neoformans

Aspergillosis Aspergillus fumigatus;
Aspergillus sp.

Zygomycosis Mucor, Rhizopus, Absidia
Pathogenic Opportunistic

Agent dimorphic fungus non-dimorphic fungus

Port dentre lung (per inhalation ) lung & others

Disease usually chronic usually acute

Patients could be healthy patients usually ill
patient
CANDIDIASIS = Candidosis

acute / chronic fungal infections, involving, the mouth,
vagina, skin nails, bronchi / lung, alimentary tract,
urinary tract, blood steam and less commonly, the heart or
meningen

are caused by Candida albicans or other species

are predisposed by : extremes of age, wasting, &
nutritional disease, excessive moisture, pregnancy,
diabetes, long-term antibiotics, & steroid use, indwelling
catheter, immunosupressed & AIDS

are generally treated with imidazoles, polyenes or both
Candida albicans :

is part of the normal flora of the skin, mucous
membranes & GI tract along with other Candida
sp.

normal colonization must be distinguised from
infection

form elongated budding forms called
pseudohyphae, which are often seen in clinical
material along with true hyphae, blastoconidia &
yaest cells
Clinical features : oral thrush

is a yeast infectoins of the oral mucocutaneus
membranes

manifest as white curd-like patches in the oral
cavity

occurs in premature infants; older infants being
treated with antibiotics, immunosuppressed
patients, long-term antibiotics & AIDS patients
Clinical features : Vulvovaginitis

is a yeast infection of the vagina; manifest with a
thick yellow-white discharge, a burning sensation,
curd-like patches on the vaginal mucosa &
inflamation of perineum

is predisposed by diabetes, antibiotic therapy,
oral contraceptive use & pregnancy

may be trasmitted to sexual partner as balanitis
Clinical features : Cutaneus candidiasis

involves the nails ( onychomycosis; paronychis ), skin
folds ( intertriginosa ) or groin ( such as diaper rash )
may be eczematoid or vesicular / pustular; is predisposed
by moist condition

Clinical feature : alimetary tract disease :

is usually an extension of oral thrush & may include
esophagitis & ultimately the entire gastrintestinal tract

is found in patients with AIDS or other
immunosuppressive disorder, particularly those patients
on long-term antibiotics therapy
Clinical feature :
Chronic mucocutaneus candidiasis

is a chronic, often disfiguring, infections of the epithelial
surfaces of the body

is diagnosed microscipically & by the lack of cell
mediated immunity

Clinical feature :
Bronchopulmonary infections

occurs in patient with chronic lung disease; its usually
manifested by persistent cough
Clinical feature :
Candidemia / blood borne infections

occurs most commonly in patients with indwelling
catheter; these infections are manifested by fever,
macronodular skin lesion & endopthalmitis

Clinical feature : Endocarditis

occurs in patient who have manipulated or damaged
valves, or in IV drug abusers

Clinical feature : Cerebrospinal infections

may occur in compromised patients
Laboratory diagnosis :

direct microscopic examination : wet mount of the skin /
nail scraping or exudate, demonstration of the presence of
pseudohyphae / hyphae, & yeast in the tissue

culture : of the specimens on to SDA at room temperature,
Candida will grows as yaest-like colony

C. albicans be identified by :
* germ tube test -- yeast germination in serum at 37
0
C
* culture on corn-meal-agar -- reveals chlamydospres
* culture on Eosin-methylen-blue-agar : reveals spider
colony
* fermentation test of : glucose, lactose, maltose,
sacharose
serologic : high levels of Candida precipitins or antigens