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Mycobacteria

(Acid Fast Bacilli)


Obligate pathogens

Mycobacterium tuberculosis - TB
Mycobacterium bovis - bovine TB
Mycobacterium leprae - Hansen's disease,

(leprosy) ,Morbus Hansen

Morbus Hansen ( Leprosy )


Penyebab : Mycobacterium leprae
Mengandug sejumlah besar mycolic acids di
permukaan selnya.
Berkembang biak lambat sekali.
Menginfeksi kulit, saraf,dan selaput lendir.
Belum dapat dibiakkan di Laboratorium
atau cell culture, tapi sudah dapat dibiakkan
di mouse foot pads dan armadillo.

Leprosy

Leprosy

Cara infeksinya belum diketahui, tapi mungkin melalui


respiratory droplets
Kebanyakan orang resisten terhadap infeksi dan tidak
sampai berkembang active disease

Transmisi

Kontak yang lama dan intim dengan pasien


lepromatous via :
Nasal secretion
Skin lesions
Inhalation

Perjalanan Penyakit :
Di kulit pasien timbul discolored patches
yang tidak itch or hurt
Patches seperti pada tinea (ringworm-like
patches), dengan pinggir yang meninggi.
Pasien mengeluh adanya loss of feeling within
the patch of discolored skin

Leprosy

Leprosy gejala-gejala lain:

loss of eyebrows
thick or lumpy earlobes
loss of feeling (burns or scars)
painless ulcers on the feet
drop feet
deformities of hands and/or feet

Facial appearance yang klasik pada advanced leprosy

Mycobacterium leprae

ulcers, resorption of bone


worsened from careless use of hands (nerve damage)

Diagnosis Lepra:
Pada penyakit yang telah lama, pasien mengeluh
adanya numbness or tingling di tangan dan kaki
( hands and feet)
Pembesaran syaraf di lengan dan leher
Mycobacterium leprae dijumpai di lesi kulit.( skin
lesions)
Ulkus yang tidak nyeri (painless ulcers)
terinfeksi ; kemudian ulkus yang terinfeksi ini
akan mengalami nekrosis.
Karena tanpa nyeri, infeksinya akan menyerang
jaingan lebih dalam ( tulang)

Manifestasi Klinis
Ada dua bentuk utama :
1. Tuberculoid leprosy (TT)

2. Lepromatous leprosy (LL)


Bentuk lain: Borderline leprosy
Low

TT

BT

BB

BL

prognosis jejek

LL

High

Tuberculoid Leprosy (TT)


Biasanya pada pasien dengan daya tahan tubuh
yang relatif tinggi.
Pada skin smear tidak dijumpai bakteri.
Pasien tidak menularkan penykit ke orang lain.
Skin patches sedikit, bentuknya variabel , tapi
sering bagian pinggr meninggi dan bagian central
rata ( flat )

Tuberculoid Leprosy (TT)


Biasanya pasien mengeluh adanya loss of
feeling in skin patches
Jika tangan atau kaki terlibat dan
menyebabkan loss of feeling pada salah
satu tangan atau kaki saja.
Respons terhadap pengobatan biasanya
cepat

Borderline Leprosy
Pada skin smears dijumpai sedikit atau
banyak bakteri .
many skin patches, some feeling loss, patches
about the same on both sides of the body
severe nerve damage, loss of feeling and
strength, deformities in both hands and both
feet

Borderline Leprosy
Borderline leprosy dibagi atas
Borderline

tuberculoid (BT)

Borderline (BB)
Borderline lepromatous (BL)

Lepromatous Leprosy (LL)


Pada pasien dengan daya tahan tubuh
rendah
Pada skin patches dijumpai sejumlah besar
Mycobacterium leprae
Pasien adalah infectious sehingga diobati
Skin patches, sering disertai dengan
daerah-daerah menebal atau raised lumps

Lepromatous Leprosy (LL)


Facial skin becomes thick, lumpy, reddish,
terutama diatas alis mata, pipi, hidung dan
telinga.
Bridge of the nose mungkin secara
perlahan-lahan akan mencekung ( sink )
Jika tidak diobati maka akan terjadi
kerusakan saraf dan paralisis

Lepromatous Leprosy (LL)


Loss of feeling and strength affects
both hands and both feet equally
Respons teradap pengobatan seringkali
lambat.
Pengobatan mesti dilanjutkan sampai
paling sedikit 2 tahun lamanaya.

Diagnosis
Acid fast, auramine-rhodamine stains
Skin lesions or nasal scraping
Anaesthetic checks
Granulomatous formation
Lepromin skin test : not for Lepromatous leprosy

Treatment
Tuberculoid leprosy:
Dapsone combined with rifampin
Lepromatous leprosy:
Dapsone, rifampin and clofazimine
Borderline leprosy: with ENL
(erythema nodusum leprosum)
Thalidomine

HERPESVIRIDAE

Human Herpes Viruses


1.
2.
3.
4.
5.
6.
7.
8.

Herpes simpleks virus type 1.


Herpes simpleks virus type 2.
Varicella zoster virus ( VZV)
Cytomegalovirus ( CMV)
Epstein Barr virus ( EBV)
Human Herpes Virus 6.
Human Herpes Virus 7.
Kaposis Sarcoma Herpesvirus (KSHV).

Sifat-sifat Virus Herpes

Virion: spheris, icosahedral capsid


Genom : linear, DNA untai ganda
Protein: > 35 jenis protein pada virion
Envelope: glikoprotein, reseptor Fc
Replikasi: nucleus bertunas dari membran nuclear.
Ciri khas infeksi virus herpes:
1 .Menyebabkan infeksi laten
2 . Menetap secara indefenitif pada penderita
3. Sering reaktif pada immunosuppressed host

Infeksi virus herpes pada manusia


1. Virus herpes simpleks tipe 1
- hanya pada manusia, tidak memiliki vektor/reservoir hewan
- Infeksi laten: Sacral ganglia
- Usia terinfeksi: anak balita
- Transmisi/ penularan: kontak langsung, saliva
- Gejala Klinis:
a. Inf. Primer:gingingostomatitis, pharyngotonsilitis,
keratoconjuctivitis, inf neonatal.
b. Recurent inf: fever, keratitis.
c. Inf primer/ recurrent: Herpes kulit di atas pinggang, pd tangan,
siku, herpatic withlow, eczema herpeticum, genital herpes,
herpes encephalitis, herpes meningitis.

2. Virus herpes simpleks tipe 2

Tidak memiliki vektor/ resevoir hewan.


Usia terinfeksi: dewasa muda
Transmisi: sexual

Gejala klinis:
1. Inf primer: Inf neonatal
2. Inf primer/ recurent: herpes kulit di bawah pinggang, pd
tangan, siku, herpetic withlow, genital herpes, herpes
meningitis.

3. Virus Varicella-Zoster
A. Varicella (chickenpox)=cacar air
Sangat menular, terutama pada anak
Masa inkubasi : : 10-21 hr, transmisi: sal nafas, conjuctiva
Klinis: malaise, demam, diawali rash pada badan kemudian
pada wajah, kaki & tangan, 2-4 hr kemudian muncul makula,
papul;a dan erupsi vesicular pada kulit dan mukosa.
Komplikasi: encephalitis, pneumonia.
B. Zoster ( Herpes Zoster )
Infeksi akut pada syaraf & dorsal root ganglion
Inflamasi& nyeri hebat pd ganglia unilateral pada badan,
kepala & leher.

Human herpes virus 6


T- lymphtropic HHV 6: 1986.
Klinis:: exanthema subitum pd infant (roseola infantum)
demam, skin rash.

Human Herpes Virus 7


T-lyphotropic HHV 7: 1990
Inf pada anak. Dekat dg sifat cytomegalovirus.

Human Herpes Virus 8


Disebut juga KSHV (Kaposis Sarcoma asscociated Herpes Virus),
sexually transmitted.
Virus dijumpai pada 90% penderita Sarcoma Kaposi (tumor
vascular) pada penderita AIDS.

POXVIRIDAE

Largest & most complex of viruses


Three pox viruses of medical important:
Smallpox virus, vaccinia virus, and molluscum
contagiosum.

POXVIRIDAE
Structure & composition:
- Oval or brick shaped, 400nm (length) x 230nm ()
external surface shows ridges, contains core & lateral
bodies
- Composition: DNA (3%),protein (90%), lipid(5%)
- Genome: linear double stranded DNA, MW 85-150x106
rich in adenine & thymine bases, low
guanine-plus-cytosine
- Contain >100 polypeptides many enzimes in core
- Envelope (+)

Structure & composition:


- Very resistant to inactivation
- Parapoxvirus: * 260x160nm, smaller than
orthopoxvirus
* genomes: MW 85X106, have a
higher guanine-plus-cytosine
content (63%)
- Unique among DNA viruses :
the entire multiplication cycle takes place in
cytoplasm of infected cells

VACCINIA & VARIOLA


(Poxvirus infection in humans)

1798 : Jenner introduced vaccination with live


virus
1967 : WHO worldwide campaign to
eradicate smallpox
1980 : smallpox was officially declared
eliminated

Composition of vaccinia & variola viruses:


# Host :
- variola : only humans & monkeys
- vaccinia : broad host range, including
rabbits & mice
# Grow on chorioallantoic membrane of 10-12 days
old chick embryo, but variola produces much
smaller pocks
# Grow in several types of chick & primate cell
lines

Pathogenesis of smallpox:

- Portal of entry : mucous membranes of upper


respiratory tract
- After viral entry :
1. primary multiplication in the lymphoid tissue
draining the site of entry
2. transient viremia and infection of reticuloendothelial cells throughout the body
3. secondary phase of multiplication in those cells
4. secondary, more intense viremia
5. clinical disease

Clinical findings :
Incubation period of variola (smallpox) = 12 days
1. Fever & malaise : 1-5 days
2. Exanthems appear : - papular (1-4 days)
- vesicular (1-4 days)
- pustular (2-6 days)

3. Crusts formed (2-4 weeks after 1

st

and leaving pink that faded slowly

sign of lesion)

Laboratory diagnosis:
a. Isolation & identification :
- skin lesions specimen (choice for viral isolation)
- direct exam (electron microscope) :
rapid identification of viral particles ( 1 hr)
differentiate poxvirus infection from
chickenpox
- viral isolation is carried out by inoculation of
vesicular fluid onto the chorioallantoic
membrane of chick embryos

Laboratory diagnosis:
- in 2-3 days vaccinia pocks are large with
necrotic centers, whereas variola pocks are
much smaller
- cell cultures also be used for viral isolation
(orthopox, parapoxviruses)
- agar gel precipitation detect viral antigen,
identifies orthopoxviruses as a group
b. Serology : HI, Nt, ELISA, RIA or
immunofluorescence tests
- antibodies appear after 1st week infection
- cannot distinguish among orthopoxviruses

Molluscum contagiosum (MCV)

MCV: transmitted by close personal

contact, including sexually.


The disease is quite common in children,
and the lesions can be wide spread in
patients with reduced cellurar immunity.
In immunocompetent patients, the lesions
are self-limited but may last for month.

Clinical

Findings:
Causes small, pink, papular, wartlike
benign tumors of the skin or mucous
membranes. The lesions have a
characteristic cup-shaped crater with a
white core.

Papovaviridae

Important properties of Papovaviruses

Virion: Icosahedral
Composition: DNA (10%), protein (90)%
Genome: ds DNA, circular, MW 3-5 million
Envelope: none
Replication: nucleus
Outstanding characteristic:
- Stimulate cell DNA synthesis
- Polyomaviruses are significant causes of
- Viral oncoprotein interact with cellular

human disease
tumor supressor proteins

Important properties of Papovaviruses

Oncogenic potential tumor in natural host


Result of natural infection: Benign tumor (wart)
Target tissue: Surface epithelia
Most significant human illness: Skin warts,

laryngeal papillomas, cervical carcinoma


Important animal isolates: Papillomaviruses from
cows and rabbits

Papillomavirus

Cause: skin warts, plantar warts, flat warts,

genital condylomas, laryngeal papillomas in


human.
HPV :
- sexually transmitted genital lesions,
- premalignant and malignant disease of
vulva, cervix, penis and anus.
- genital condylomas, dysplasia to
invasive cervical cancer (HPV type 16, 18,
and 11, 31, 33, 35).
- Laryngeal papilloma in children: HPV 6, 11

Asosiasi HPV dengan lesi klinis


Types HPV Clinical Lesions

Suspected
oncogenic potential

Plantar warts

Benign

Common warts

Benign

3, 10, 28

Flat warts, epidermodysplacia verruciformis

Rarely
malignant

5,8

Epidermodysplasia
verruciformis in patients
with CMI deficiency

30%
progress to
malignancy

Hands warts of meat & benign


animal handlers

6, 11

Anogenital condylomas; Low


laryngeal papillomas :
dysplasia and intra epithelial neoplasmas,
grades I & II

9, 12, 14
15, 17
19 25
36, 40

Epidermodysplasia
verruciformis

Some progress to
Ca (e.g. HPV
12,17, 20

13, 32

Oral local eipthelial


hyperplasia

Possible
progression to Ca

16, 18, 31, 33,


35, 39

High grade dysplasia and


carcinomas of genital
mucosa,laryngeal and
esophageal
carcinomas;Bowen
disease

High
correlation
with genital
and oral
carcinoma

26, 27, 29

Cutaneous warts

30, 40

Laryngeal Ca

Maligna

37

Keratoacanthoma Benign

41, 42

Genital warts

Benign

Leprosy (Hansen's Disease)


M. leprae
causative agent

chronic disease

disfigurement
rarely seen in the U.S.
common in third world
millions of cases
infects the skin
low temperature

Leprosy
tuberculoid
few organisms
active cell-mediated immunity
lepromatous
immunosuppression
few organisms

Production of M. leprae antigens and


pathogenesis studies
in vitro
unculturable
in vivo growth
low temperature
armadillo
mouse footpad

Leprosy
lepromin
skin testing
acid-fast stains
skin biopsies
clinical picture

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