Bms166 Slide Tetanusbacterial Toxins

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Tetanus = Bacterial Toxins

Kiking Ritarwan Localized or generalized muscle stiffness Superimposed paroxysmal tonic spasm (tetanospasmin) Tetanospasmin blocks inhibitory interneurons Autonomic instability Normal mental status

Tetanus is a toxic infection caused by the anaerobe Clostridium tetani. Spores exist in the soil and faeces, portal of entry resulting in human disease include traumatic and surgical wound, injection side (parenteral drug abusers), skin ulcers, burn and injected umbilical cords. Producing exotoxins (tetanospasmin and tetanolysin). Tetanospasmin is a very potent neurotoxin p probably is solely responsible for the disease. y y p Tetanolysin has no recognised pathogenic activity.

Tetanus germs are found everywhere, usually in soil, d t and manure. il dust, d Enter a wound produce a poison spreads throughout the body body. The first signs : Headache and spasms of the j p jaw muscles. Irritable Muscle spasms : neck, arms, legs, stomach. Convulsions broken bones.

Etiologi g

Clostridium tetani

Ada 2 bentuk : 1. Vegetatif : basil gram positif, obligat anaerob ukuran :0,5-1,7 m x 2,1-18,1 m motil, motil flagel 2. Spora : bentuk squash racket tahan terhadap panas, resisten terhadap berbagai desinfektan, dapat hidup bertahun desinfektan Spora tumbuh saat bersentuhan dengan luka (potensial redox ) Eksotoksin : Tetanospasmin (Tetanus toksin) Tetanolysin

Clostridium tetani : bentuk spora dan vegetatif


An aerobic gram positive bacillus Noncapsulated Sporm forming Found in soil, house dust, animal Intestine and human feces

Epidemiologi Negara terbelakang, iklim tropis, lembab >>> Seluruh usia neonatus, usia muda >>> WHO, 1995 eradikasi : 800.000-1 juta/thn kematian tetanus neonatal Afrika, Asia Tenggara endemik Insidens 18 per 100.000 populasi/ tahun 100 000 Cvjetanovic : Afrika : 28/100.000 Asia : 15/100.000 Eropa : < 0,1/100.000 Amerika Utara : < 0,1/100.000

Patofisiologi
C.tetani masuk ketubuh melalui LUKA dalam kondisi anaerob spora berkembang toksin diproduksi(TETANOSPASMIN)
Retrograde intraneuronal transport/ axon terminal Motor neuron p perifer/ med spinalis/ batang otak p g memblokade pelepasan inhibitory p p y neurotransmitter glycine and GABA di terminal presinaptik

akibatnya eksitasi firing rate motor neuron meningkat tanpa ada inhibisi sehingga otot lebih meningkat tonus dan spasmenya

Jk blokade di MNJ maka toxin menginhibisi pelepasan Ach presinaptik bisa menjadi PARALISIS

Tahapan tetanospasmin : berikatan, internalisasi dan aktifitas

Focus of infection
Infected laceratioof puncture wound Infected chronic wound and abscesses Exposure via i t E i intravenous d drug abuse b Neonates No identifiable cause Possible causes: otitis media Burns media, Burns, Intranasal foreign bodies, corneal abrasion, abrasion dental or surgical procedures procedures.

Gambaran Klinis
Masa inkubasi : jumlah toksin dan status imunisasi MI biasanya 8 hari (3 21 hari) semakin jauh tempat trauma dari SSP MI >> Periode of onset : 1- 7 hari MI dan periode of onset << keparahan >> Klasifikasi tipe klinis (4) : Generalized tetanus (Tetanus umum) Localized tetanus (Tetanus lokal) Cephalic tetanus (Tetanus sefalik) Tetanus neonatorum

Tetanus Umum Paling umum : 80% dari kasus Paling karakteristik : Lock j / t i L k jaw/ trismus Dapat disertai : kaku kuduk, disfagia, rigiditas abdomen, temperatur ( 0C) p (2-4 ) Kasus berat risus sardonicus, opisthotonos Karakteristik : spasme akut, paroksismal, nyeri, kejang rangsang Problem spasme obstruksi jalan nafas apneu Masa inkubasi : 7-21 hari (tergantung jarak luka dengan CNS). Pemulihan 4 minggu

Tetanus Lokal Bentuk paling ringan Simptom awal : kaku, spt diikat, nyeri otot kaku diikat disekitar luka, twitching & spasme singkat Sering luka di tangan atau lengan Manufer diagnostik
Recruitment spasm

mendahului onset Tetanus umum Angka kematian 1% Prognosa : Baik

Tetanus Sefalik

Bentuk yang tidak lazim Terjadi dgn Otitis media atau trauma kepala Disfungsi saraf kranial N.VII >>> Berkembang tetanus umum atau tetap lokal Masa Inkubasi : 1 atau 2 hari Otot yang terkena paralisa Sering fatal prognosis buruk

Tetanus Neonatorum
= tetanus umum akibat infeksi pada neonatus p Di negara miskin dari seluruh kematian neonatus MI : 3 10 hari sesudah lahir Disease of the seventh day Terjadi karena imunitas maternal Tanah, kotoran hewan tali pusat tehnik aseptik yang kurang Tanda-tanda : lemah, tidak mampu menghisap spasme, rigiditas opisthotonos Angka kematian : > 70%

Tingkat keparahan
Table 1. Klasifikasi keparahan tetanus : Kriteria Patel-Joag Patel Joag Kriteria 1 : Lockjaw, isolaterd spasm ,dysphasia, stiffness of muscle back Kriteria 2 : Spasme, tanpa mempertimbangkan frekuensi atau keparahan Kriteria 3 : Masa inkubasi tujuh hari (waktu diantara trauma dan tanda pertama) Kriteria 4 : Periode of onset 48 ja ( a tu antara tanda pe ta a( oc ja ) da te a e ode o o set 8 jam (waktu a ta a ta da pertama(lockjaw) dan kejang pertama) Kriteria 5 : Peningkatan temperature : rectal 1000F, atau aksiler 990F Grading : g Grade 1 : Kasus ringan : terdapat satu criteria, biasanya kriteria 1 atau 2 (tidak ada kematian) Grade 2 : Kasus sedang : terdapat 2 kriteria, biasanya kriteria 1 dan 2. Biasanya masa inkubasi lebih dari 7 hari dan onset lebih dari 48 jam ( j (kematian 10%) ) Grade 3 : Kasus berat : terdapat 3 kriteria, biasanya masa inkubasi kurang dari 7 hari atau onset kurang dari 48 jam (kematian 32%) Grade 4 : Kasus sangat berat : terdapat 4 kriteria (kematian 60%) Grade 5 : Calculated mortality : kelima criteria, termasuk puerperal dan tetanus y , p p neonatorum (kematian 84%)

DIAGNOSA
Hanya secara klinis Tes untuk konfirmasi (-)
Studi bakteriologi 1/3 pasien Penyebab nerve palsy lain

Tetanus lokal mengenai > 1saraf cranial

TEST SPATULA

Diagnosa Banding g g
1. 1 2. 3. 4. 5. 6. 7. 7 8. Keracunan striknin Reaksi Distonia Meningitis Penyakit temporomandibuler joint, proses inflamasi gigi, mulut, tonsil dan faring Rabies Tetani Stiff-man syndrome Stiff d Psychogenic disorders

Tabel 2. Diagnosa banding tetanus Simptom Trismus Kaku kuduk Disfagia Spasme Neonatal tetanus Diagnosa banding Alveolar/dental patologi Temporo-mandibular disease Muscle spasm Meningitis e gts Acute pharyngeal disease Keracunan striknin Lesi intrakranial Drug-induced dystonic reactions Sepsis Meningitis Konvulsi

PENATALAKSAAN
Rawat di ICU Ruang rawat yang tenang stimulasi <<< Prinsip manejemen : eradikasi kuman netralisit toksin diluar SSP minimalisir efek toksin di SSP Portal of entry eksisi luka gangren (+) amputasi debridement spasme terkontrol

Imunoterapi
pengobatan untuk menetralisir Tetanospasmin imunisasi aktif

Human Tetanus Immunoglobulin (HTIG) 3.000 5.000 3 000 5 000 IU/ i m i.m. Equine Antitetanus serum (ATS) uji hipersensitifitas, desensitisasi j p harga lebih murah Sebaiknya 20.000 U diberikan IM sedgkan 10.000 U diberikan IV sesudah 48 jam pemberian pertama Intravenous Immune globulin (IVIG) pemberian antitoksin sebelum debridement

Kontrol Jalan nafas dan Ventilasi


spasme tetanik obstruksi jalan nafas Endotracheal tube (ETT) T k Trakeostomi t i moderate & severe d t mengurangi bentuk vegetatif Sensitif Metronidazole, PNC, Sefalosporin, Imipenem, makrolid Imipenem makrolid, tetrasiklin PNC central GABA antagonist => sdh ditinggalkan Dosis : 100.000-200.000 IU/kg/hari M t id Metronidazole l antibiotik pilihan tibi tik ilih Dosis : 500 mg/ 8 jam/IV + dgn clindamisin, erithromisin, tetrasiklin, vancomysin

Antibiotika

Kontrol Rigiditas & Spasme

Benzodiazepine : agonis GABA dosis d i ~ 500 mg/ h i / hari tetanus neonatorum 15-40mg/kg/hr Diazepam,Lorazepam, Midazolam Diazepam 0,1 mg/kg IV/ 4 j g g jam ( (dewasa 500 mg/ hr dan neonatus 15-40 mg/ hr), atau midazolam 0,1 mg/ kgBB IV/ IM/ 4 jam, atau midazolam 2 10 mg/ jam IV j t id l 2/j IV, atau propanolol infuse 1-10 mg / jam.

Blokade NMJ
Obat GABAergik gagal blok NMJ Vecuronium (0,1 mg/kg IV 6-8mg/jam) ( , g g gj ) Pancuronium : takikardi, hipertensi, CO mengaburkan efek otonom Terapi disfungsi otonom sympathetic overactivity (SOA) th ti ti it Labetolol esmolol clonidine morfin sulfat Labetolol, esmolol, clonidine, Magnesium sulfat

Nutrisi
aktifitas otot & otonom kebutuhan nutrisi >> ganggguan gastric emptying time nutrisi vena sentral

Komplikasi
komplikasi penyakit & komplikasi terapi komplikasi pernafasan komplikasi kardiovaskuler dan otonom p komplikasi sistemik lain

Tabel 3. Komplikasi tetanus Sistim Komplikasi Jalan nafas Aspirasi * Laryngospasm/obstruction* Sedative associated obstruction* Respirasi Apnu* Hipoksia* Gagal nafas tipe I* ( g p (atelektasis, aspirasi,pneumonia) p p ) Gagal nafas tipe II* (spasme laring, prolonged truncal spasm, sedasi berlebihan) ARDS* Komplikasi ventilasi bantuan yang lama (mis.pneumonia) Komplikasi trakeostomi (mis.stenosis trakea)

Kardiovaskuler Takikardi* Hipertensi* Iskemia* Hipotensi* Bradikardi* Takiaritmia, bradiaritmia Takiaritmia bradiaritmia* Asistole* Gagal jantung*

Tabel 3. (lanjutan) Ginjal High output renal failure* Oliguric renal failure* U a y stasis and ect o Urinary stas s a d infection Gastric stasis Ileus Diare Pendarahan* Berat b d B t badan menurun* * Tromboemboli* Sepsis dan multiple organ failure* Fraktur vertebra selama spasme Avulsi tendon selama spasme

Gastrointestinal

Lain-lain L i l i

Pencegahan Imunisasi Aktif Profilaksis Tetanus Toksoid imunitas 5 thn Imunisasi ibu hamil mencegah tetanus neonatorum I Imunitas ditransfer secara pasif : ibu it dit f if ib fetus f t Imunisasi paska trauma Rekomendasi profilaksis : - kondisi luka - riwayat imunisasi y Antitoksin : HTIG 250 unit ATS 1500 unit

TABLE 12.1 Immunization against tetanus ---------------------------------------------------------------------------------------------------------------------------------------Subject/vaccine and dose Age/interval ---------------------------------------------------------------------------------------------------------------------------------------Children (age less than 7 years)* 1-DPT 6-8 weeks of age 2-DPT 4-8 weeks after previous dose 3-DPT 4-8 weeks after previous dose 4-DPT 1 year after previous dose Booster DPT 4-6 years of age Booster Td every 10 years after previous dose Adults and children older than 7 years not previously immunized* 1 Td 1-Td first encounter 2-Td 4-8 weeks after previous dose 3-Td 6 months1 year after previous dose Booster-Td every 10 years after previous dose Pregnant women* Previously i P i l immunized : i d Booster TT during first 6 months of pregnancy (optimal) Or as late as 6 weeks before delivery Previously unimmunized : 1-TT first encounter during p g g pregnancy y 2-TT 4 weeks after previous dose ---------------------------------------------------------------------------------------------------------------------------------------* American Academy of Pediatrics (Peter et al. 1994); * World Health Organization, Expanded Programme on Immunization (Whitman et al. 1992) Abbreviations ; DPT, diphtheria and tetanus toxoids and pertussis vaccine adsorbed : Td, tetanus and DPT Td reduced-dose diphtheria toxoids adsorbed; TT, tetanus toxoid.

TABLE 12.2. Guidelines for tetanus prophylaxis in wound management


______________________________________________________________________ Vaccination status Clean, minor wounds Tetanus-prone wounds* Td+ TIG Td+ TIG++ ______________________________________________________________________ Unknown or <3 doses 3 doses Last booster < 5 years Last b L t booster 5 10 years t 5-10 Last booster > 10 years Yes No N No Yes No No No N No Yes No Yes Y Yes No No No N Yes

Recommendations of the Advisory Committee on Immunization Practices-United States (CDC, 1992). (CDC 1992) * Wounds contaminated with dirt, faeces, soil, saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns and frostbite. Wounds presenting after delay or requiring debridementdue to the p y q g presence of necrotic tissue. * Td : tetanus and reduced-dose diphthetia toxoids adsorbed; for children less than 7 years, DPT (diphtheria and tetanus toxoids and pertussis vaccine adsorbed) is preffered. ++ 250 500 units human tetanus immune globulin; given intramuscularly in another area 250-500 it h t t i l b li i i t l l i th than the Td.

Prognostic Score for Tetanus of Gallais et al


Parameter incubation Finding g < 7 days >= 7 days extension < 2 days >= 2 days portal of entry l f intramuscular injections i l i j i umbilical uterine surgical burn compound fracture all other portals or unknown paroxysms >= 4 per hour p present but < 4 per hour p rectal temperature > 38.4 C <= 38 C pulse in beats per minute adults > 120 neonate > 150 adults <= 120 neonate <= 150 Score 1 0 1 0 2 1 0 1 0 1 0 1 0

Score 0 1 2 3 4 5 6 7

Mortality Rate 0% 4.22% 13.63% 30.43% 57.14% 70.73% 70 73% 94.73% 100%

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