The MycobacteriaThe Mycobacteria(Acid Fast Bacilli)(Acid Fast Bacilli)

Obligate pathogens

• Mycobacterium. tuberculosis - TB • Mycobacterium bovis - bovine TB • Mycobacterium. leprae - Hansen's disease (leprosy)

Emerging DiseasesEmerging Diseases

• Hansen’s Disease(1873) – Leprosy• caused by Mycobacterium leprae• large amounts of mycolic acids on the cell

surface• multiplies very slowly• mostly infects skin, nerves and mucous

membranes• never cultivated in laboratory media or cell

culture, but has been cultivated in mouse foot pads

Emerging DiseasesEmerging Diseases

• Leprosy• route of infection is not known, but probably via

respiratory droplets• most people are resistant and do not develop active

disease

Long and close contract with lepromateous patients

Nasal secretion

Skin lesions

Inhalation

Transmissions:Transmissions:

Emerging DiseasesEmerging Diseases

• Leprosy – the disease process

• patients develop discolored patches on skin that do not itch or hurt

• ringworm-like patches, may have raised edges

• patients experience loss of feeling within the patch of discolored skin

LeprosyLeprosy

Emerging DiseasesEmerging Diseases

• Leprosy – other symptoms• 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

Classical facial appearance of advanced leprosy

• Leprosy – diagnosis

• in more advanced disease patient experiences numbness or tingling in hands and feet

• enlarged nerves appear in arms and neck

• leprosy bacilli can be found in skin lesions

• painless ulcers become infected

• infected ulcers become necrotic

• lack of pain allows infection to become deep and attack bone

Two main forms:

1. Tuberculoid leprosy (TT)

2. Lepromatous leprosy (LL)

Others forms: Borderline leprosy

Low TT BT BB BL LL High

Poor prognosis

Diseases ProductionDiseases Production

Emerging DiseasesEmerging Diseases

• Tuberculoid Leprosy (TT)• usually in persons with relatively high

resistance

• no bacilli in skin smear

• person cannot pass leprosy on to others

• skin patches are few, are variable in appearance, but often have raised margins and flat centers

Emerging DiseasesEmerging Diseases

• Tuberculoid Leprosy (TT)

• usually only involves loss of feeling in skin patches

• when hands or feet involved it often happens early and causes loss of feeling or strength in only one hand or foot

• usually responds quickly to treatment

Emerging DiseasesEmerging Diseases

• Borderline Leprosy

• few to many bacilli in skin smears

• 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

Emerging DiseasesEmerging Diseases

• Borderline Leprosy

• Depending on where it falls along the line between the two extremes, borderline leprosy is divided into:

»borderline tuberculoid (BT)

»borderline (BB)

»borderline lepromatous (BL)

Emerging DiseasesEmerging Diseases

• Lepromatous Leprosy (LL)

• in persons with very low resistance

• large numbers of leprosy bacilli in skin patches

• patients are infectious until treated

• numerous skin patches, often with raised lumps or thickened areas

Emerging DiseasesEmerging Diseases

• Lepromatous Leprosy (LL)

• facial skin becomes thick, lumpy, reddish, especially over the eyebrows, cheeks, nose, and ears.

• bridge of the nose may gradually sink in

• nerve damage and paralysis appear late if not treated

Emerging DiseasesEmerging Diseases

• Lepromatous Leprosy (LL)

• loss of feeling and strength affects both hands and both feet equally

• response to treatment is often slow

• treatment must be continued for at least 2 years

• Acid fast, auramine-rhodamine stains

• Skin lesions or nasal scraping

• Anaestheic checks

• Granulomatous formation

Lepromin skin test : not for Lepromatous leprosy

DiagnosisDiagnosis

Tuberculoid leprosy:

Dapsone combined with rifampin

Lepromatous leprosy: Dapsone, rifampin and clofazimine

Borderline leprosy: with ENL

(erythema nodusum leprosum)Thalidomine

TreatmentTreatment

HERPESVIRIDAEHERPESVIRIDAE

Human Herpes VirusesHuman Herpes Viruses

1. Herpes simpleks virus type 1.

2. Herpes simpleks virus type 2.

3. Variocella zoster virus.

4. Cytomegalovirus

5. Epstein Barr virus

6. Human Herpes Virus 6.

7. Human Herpes Virus 7.

8. Kaposi’s Sarcoma Herpesvirus (KSHV).

Sifat-sifat Virus Herpes 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 manusiaInfeksi 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. 2. Virus herpes simpleks tipe 2Virus 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 hwerpes, herpes meningitis.

3. Virus Varicella-Zoster3. Virus Varicella-ZosterA. Varicella (chickenpox)=cacar air

• Sangat menular, terutama pada anak

• m.i : 10-21 hr, transmisi: sal nafas, conjuctiva

• GK: 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:

• Infeksi akut pada syaraf & dorsal root ganglion

• Inflamasi& nyeri hebat pd ganglia unilateral pada badan, kepala & leher.

Human herpes virus 6Human herpes virus 6• T- lymphtropic HHV 6: 1986.

• GK: 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 (Kaposi’s Sarcoma asscociated Herpes

Virus), sxually transmitted.

• Virus dijumpai pada 90% penderita Sarcoma Kaposi (tumor vascular) pd penderita AIDS.

POXVIRIDAEPOXVIRIDAE• Largest & most complex of viruses

• Three pox viruses of medical important:

Smallpox virus, vaccinia virus, and molluscum contagiosum.

POXVIRIDAEPOXVIRIDAE

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 & VARIOLAVACCINIA & VARIOLA(Poxvirus infection in humans)(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: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: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 reticulo-

endothelial cells throughout the body

3. secondary phase of multiplication in those cells

4. secondary, more intense viremia

5. clinical disease

Clinical findings :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 1st sign of lesion)

and leaving pink that faded slowly

Laboratory diagnosis: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: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)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.

PapovaviridaePapovaviridae

Important properties of PapovavirusesImportant 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 human disease

- Viral oncoprotein interact with cellular tumor supressor proteins

Important properties of PapovavirusesImportant 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

PapillomavirusPapillomavirus• Cause: skin warts, plantar warts, flat warts,

genital condylonmas, 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

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