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 lepraeMengandug 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.

LeprosyLeprosyCara infeksinya belum diketahui, tapi mungkin melalui respiratory dropletsKebanyakan orang resisten terhadap infeksi dan tidak sampai berkembang active diseaseKontak yang lama dan intim dengan pasien lepromatous via :Nasal secretionSkin lesionsInhalationTransmisi

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 eyebrowsthick or lumpy earlobesloss of feeling (burns or scars)painless ulcers on the feetdrop feetdeformities 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)

Ada dua bentuk utama : 1. Tuberculoid leprosy (TT) 2. Lepromatous leprosy (LL)Bentuk lain: Borderline leprosy Low TT BT BB BL LL High prognosis jejek Manifestasi Klinis

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.

Acid fast, auramine-rhodamine stains Skin lesions or nasal scraping Anaesthetic checks Granulomatous formationLepromin skin test : not for Lepromatous leprosyDiagnosis

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

Treatment

HERPESVIRIDAE

Human Herpes Viruses

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 capsidGenom : linear, DNA untai gandaProtein: > 35 jenis protein pada virionEnvelope: glikoprotein, reseptor FcReplikasi: nucleus bertunas dari membran nuclear.

Ciri khas infeksi virus herpes:1.Menyebabkan infeksi laten2. Menetap secara indefenitif pada penderita3. Sering reaktif pada immunosuppressed host

Infeksi virus herpes pada manusia1. Virus herpes simpleks tipe 1hanya pada manusia, tidak memiliki vektor/reservoir hewanInfeksi laten: Sacral gangliaUsia terinfeksi: anak balitaTransmisi/ penularan: kontak langsung, salivaGejala 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 mudaTransmisi: sexual

Gejala klinis:

Inf primer: Inf neonatalInf primer/ recurent: herpes kulit di bawah pinggang, pd tangan, siku, herpetic withlow, genital herpes, herpes meningitis.

3. Virus Varicella-ZosterVaricella (chickenpox)=cacar airSangat menular, terutama pada anakMasa inkubasi : : 10-21 hr, transmisi: sal nafas, conjuctivaKlinis: 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 ganglionInflamasi& nyeri hebat pd ganglia unilateral pada badan, kepala & leher.

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

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

Human Herpes Virus 8Disebut juga KSHV (Kaposis Sarcoma asscociated Herpes Virus), sexually transmitted.Virus dijumpai pada 90% penderita Sarcoma Kaposi (tumor vascular) pada penderita AIDS.

POXVIRIDAELargest & most complex of virusesThree pox viruses of medical important: Smallpox virus, vaccinia virus, and molluscum contagiosum.

POXVIRIDAEStructure & 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 virus1967 : WHO worldwide campaign to eradicate smallpox1980 : 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 tractAfter 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 :Incubation period of variola (smallpox) = 12 daysFever & malaise : 1-5 daysExanthems 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: 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 groupb. 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 PapovavirusesVirion: IcosahedralComposition: DNA (10%), protein (90)%Genome: ds DNA, circular, MW 3-5 millionEnvelope: noneReplication: nucleusOutstanding characteristic:- Stimulate cell DNA synthesis- Polyomaviruses are significant causes of human disease- Viral oncoprotein interact with cellular tumor supressor proteins

Important properties of PapovavirusesOncogenic potential tumor in natural hostResult of natural infection: Benign tumor (wart)Target tissue: Surface epitheliaMost significant human illness: Skin warts, laryngeal papillomas, cervical carcinomaImportant animal isolates: Papillomaviruses from cows and rabbits

PapillomavirusCause: 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 HPVClinical LesionsSuspected oncogenic potential1Plantar wartsBenign2Common wartsBenign3, 10, 28Flat warts, epidermo-dysplacia verruciformisRarely malignant5,8Epidermodysplasia verruciformis in patients with CMI deficiency30% progress to malignancy7Hands warts of meat & animal handlersbenign

6, 11Anogenital condylomas; laryngeal papillomas : dysplasia and intra - epithelial neoplasmas, grades I & IILow9, 12, 14 15, 17 19 25 36, 40Epidermodysplasia verruciformisSome progress to Ca (e.g. HPV 12,17, 2013, 32Oral local eipthelial hyperplasiaPossible progression to Ca

16, 18, 31, 33,35, 39High grade dysplasia and carcinomas of genital mucosa,laryngeal and esophageal carcinomas;Bowen diseaseHigh correlation with genital and oral carcinoma26, 27, 29Cutaneous warts?30, 40Laryngeal CaMaligna37KeratoacanthomaBenign41, 42Genital wartsBenign

Leprosy (Hansen's Disease)M. lepraecausative agentchronic disease disfigurementrarely seen in the U.S. common in third worldmillions of cases infects the skin low temperature

tuberculoid few organisms active cell-mediated immunity

lepromatous immunosuppression few organisms Leprosy

in vitro unculturable

in vivo growth low temperature armadillo mouse footpadProduction of M. leprae antigens and pathogenesis studies

lepromin skin testing

acid-fast stains skin biopsies

clinical picture Leprosy

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