demam tifoid

DEMAM TIFOIDDEMAM TIFOID

dr Shahrul Rahman, Sp.PD

Departemen Ilmu Penyakit DalamFakultas Kedokteran

Universitas Muhammadiyah Sumatera Utara

PendahuluanPendahuluan

SinonimSinonim Enteric feverEnteric fever Typhus & parathypus abdominalisTyphus & parathypus abdominalis

EtiologiEtiologi

Salmonella typhiiSalmonella typhii Salmonella paratyphi Salmonella paratyphi

A, B dan CA, B dan C

Koloni salmonella pada agar McConkey.

Microbiology :

Most commonly caused by Salmonella typhiSalmonella paratyphi A, B, CThe other serotypes : S.choleraesuis

S.enteretidis S.arizonae

Salmonellosis : Enteric fever Gastroenteritis

Sepsis

OrganismOrganism

Salmonella typhiSalmonella typhi, a Gram-negative bacteria., a Gram-negative bacteria. Similar but often less severe disease is Similar but often less severe disease is

caused by caused by Salmonella Salmonella serotype serotype paratyphi paratyphi A.A. Many genes are shared with Many genes are shared with E. coli E. coli and at and at

least 90% with least 90% with SS. . typhimuriumtyphimurium,, Polysaccharide capsule Vi: present in about Polysaccharide capsule Vi: present in about

90% of all freshly isolated 90% of all freshly isolated S. typhi S. typhi and has a and has a protective effect against the bactericidal protective effect against the bactericidal action of the serum of infected patients.action of the serum of infected patients.

The ratio of disease caused by The ratio of disease caused by S. typhi S. typhi to to that caused by that caused by S. paratyphi S. paratyphi is about 10 to is about 10 to

Facultative anaerobic/aerobic

Gram (-) bacteria

Rods shape

Family Enterobacteriaceae

Motile

Somatic

Flagelar

Vi

antigen

SALMONELLA

Epidemiologi (1)Epidemiologi (1)

Penderita Penderita 3 % carier 3 % carier Endemis di Indonesia Endemis di Indonesia sporadis sporadis Di Indonesia jarang menjadi epidemiDi Indonesia jarang menjadi epidemi Penyakit menular Penyakit menular dpt mewabah dpt mewabah Dlm 1 rumah kasus jarang > 1Dlm 1 rumah kasus jarang > 1 Wajib dilaporkanWajib dilaporkan Sumber penularan sulit ditentukanSumber penularan sulit ditentukan


Sumber penularanSumber penularan Air minum / makananAir minum / makanan Tangan :Tangan :

– Tinja sendiriTinja sendiri– UrineUrine– DahakDahak– muntahmuntah


Daya tahan hidupDaya tahan hidup Air, es, debu, tinja kering, pakaian Air, es, debu, tinja kering, pakaian

weeks weeks Kulit Kulit 1 minggu 1 minggu Berkembang dlm susu Berkembang dlm susu susu susu

rusakrusak


Distribusi :Distribusi : WorldwideWorldwide Pengaruh iklim tidak adaPengaruh iklim tidak ada > banyak di negara berkembang > banyak di negara berkembang

di daerah tropisdi daerah tropis Pria = wanitaPria = wanita 12 - 30 th 12 - 30 th 70-80 % 70-80 % Ringan pada anak & glamurRingan pada anak & glamur

Epidemiology :

Worldwide, except in industrialized regions such us the United State, Canada, western Europe, Australia, and Japan

In the developing world, it affects about 12.5 million persons each year

Over the past 10 years, travelers from the United States to Asia, Africa, and Latin America have been especially at risk

Typhoid fever can be prevented and can usually be treated with antibiotics

Multi-drug resistant strains have appeared in several areas of word

Typhoid epidemiologyTyphoid epidemiology

Infectious Dose : 100,000 organism – ingestion

variable with gastric acidity

and size inoculum

Mode of Transmission :

1. Person-to-person

2. By contaminated food or water

3. By food contaminated by hand of carriers

4. Food contaminated by materials

5. Flies can infect food mechanical vector

Chronic carrierPatient

Healthysubject

StoolVomitUrine

Typhoid fever

IndirectInfection> 90 %

Direct Infection< 10 %

InfectedWaterFood

Route of Transmission of Typhoid Fever

Incubation Period : 1 – 3 weeks

depends on :

size of infecting dose

age

gastric acidity

immunologic status

PatogenesiPatogenesiss

S. Typhi

Mulut Usus

Reseptor vili

Membiak dalam fagosit mononuklear jaringan limfoid

Darah (bakteremia I)

Membiak dlm RES

Darah (bakteremia II)

Limpa,usus,v. fellea & organ lain

Ves. Fellea carrierUsus

Granulomatosa

Villi, cripte kelenjar, lam.

propria, kl. limfe

Multiplikasi dalam fagosit

mononuklear

Pathogenesis :

Ingestion of S.typhi

Infection carried in theLymphoid follicle

Draining mesentericLymph node

Entering thoracic ductsPassed through the heart

Primary bacteremia

Liver, GB, Spleen,BMMultiply within MNPC

Secondary bacteremia

Enter the small intestine

Excreted in stool and Urine

Inflammation, necrosis,Ulceration Payer’s patches

MULTIPLICATION

End incubation period

PATOFISIOLOGIPATOFISIOLOGI

Hubungan Salmonella typhii & Hubungan Salmonella typhii & MakrofagMakrofag

Salmonella

Lewat CR1 & CR3

Fagosom

Lisosom

Fusi fagosom-lisosom

Substansi bakterisidal

Kuman mati

Patologi Patologi Ileum distal

Radang : hiperplasi plaks peyeri

Nodul tifoid

Sumbatan pemb. darah

hipoksia

Nekrose

ulkus

Penyembuhan tanpa bekas

Minggu I

Minggu II

Minggu III

Minggu IV

Perdarahan, perforasi

Pathology :

Payer’s patches :

Hyperplasia during the first week Necrosis in second week Ulceration during third week Healing takes place without scarring during forth week The ulcer are oval shaped, in the long axis of lower ileum Separation of the sloughs hemorrhage and perforation

Dugaan patogenesisDugaan patogenesisSalmonella typhii

endotoksin

makrofag

Monokins

TNF, Fc’ antagonis glucokortiroid, fc’

aktivasi limfosit, IF-1

Metabolit, arakidonat, Ox

radikal

Nekrose sel, gangguan

vaskuler, depresi ss. tulang, demam, abnormalitas lain

Gambaran klinis (1)Gambaran klinis (1) Masa tunas Masa tunas : 10 – 14 hr: 10 – 14 hr Bervariasi Bervariasi : ringan - berat: ringan - berat Mulai = inf. Akut lainMulai = inf. Akut lain

– Minggu IMinggu I DemamDemam MialgiaMialgia SefalgiaSefalgia Anoreksia Anoreksia mual mual muntah muntah Obstipasi/diareObstipasi/diare Abdominal discomfortAbdominal discomfort BatukBatuk epistaksisepistaksis

Gambaran klinis (2)Gambaran klinis (2)

– Minggu IIMinggu II Gejala > jelasGejala > jelas demamdemam Bradikardi relatifBradikardi relatif Lidah tifoid (tengah kotor, tepi hiperemis, Lidah tifoid (tengah kotor, tepi hiperemis,

tremor)tremor) HepatomegaliHepatomegali SplenomegaliSplenomegali MeteorismusMeteorismus Gangguan mental : apati, somnolen, stupor, Gangguan mental : apati, somnolen, stupor,

delirium, koma, psikosisdelirium, koma, psikosis Roseola Roseola jarang jarang

Clinical Manifestations (1):

Febril illness 5 to 21 days

Abdominal pain

chills

constitutional symptoms

in developed country : travelers or visitors from

endemic area

Gambaran klasik demam tifoid

Clinical Manifestations (2):

Anorexia

Nausea

Vomiting

Diarrhea Pea soup stool

Enteric fever syndrome

Fever Chills

Headache Malaise Abdominal pain

Anorexia Weight loss weakness

Rose spots DIC Hepatomegaly

Splenomegaly Bacteremia hypotension

Typhoid fever ( enteric fever )

Classic presentations :

First week of illness : “stepwise” fever &

bacteriemia

Second week : abdominal pain and rash

Third week : hepatosplenomegaly, intestinal

bleeding and perforation, secondary bacteriemia

and peritonitis

Laboratorium(1)Laboratorium(1)

Lekosit : lekopeni Lekosit : lekopeni normal normal lekositosis lekositosis Biakan darah :Biakan darah :

– Positif : diagnosis pasti– Negatif : mungkin +/-– Tergantung dari

Tehnik– Jumlah kuman 10/cc drh perlu diambil 5-10 cc– R/ sebelumnya– Langsung ditanam kirim– Diambil waktu demam

Saat pemeriksaan– Terbaik minggu pertama selanjutnya

Vaksinasi biakan negatif R/ antibiotik biakan negatif


Reaksi widalReaksi widal– Reaksi aglutinasi Ag-Ab– Mencari aglutinin dalam serum

Aglutinin O tubuh kuman : 6 bl (+) Aglutinin H flagella kuman : 1-2 th (+) Aglutinin Vi simpai kuman


Fc’ yg mempengaruhi Rx. widalFc’ yg mempengaruhi Rx. widal– Penderita

Gizi buruk Saat pemeriksaan : minimal mg II peak

mg V R/ antibiotik Penyakit penyerta : agammaglobulinemia,

lekemia, Ca advance R/ immunosupresi / kortikosteroid Vaksinasi kotipa/tipa Inf. Klinis/subklinis salmo. Sebelumnya Rx anamnestis :


Fc’ yg mempengaruhi Rx. widalFc’ yg mempengaruhi Rx. widal– Tehnis

Rx. Silang dg species lain Konsentrasi suspensi antigen Jenis strain salmonella

Widal TestWidal Test

O antibodies appear on days 6-8 and H antibodies on O antibodies appear on days 6-8 and H antibodies on days 10-12days 10-12

Negative in up to 30% of culture-proven cases of Negative in up to 30% of culture-proven cases of typhoid fevertyphoid fever

S. typhi shares O and H antigens with other Salmonella S. typhi shares O and H antigens with other Salmonella serotypes and has cross-reacting epitopes with other serotypes and has cross-reacting epitopes with other Enterobacteriacae, and this can lead to false-positive Enterobacteriacae, and this can lead to false-positive results. Such results may also occur in other clinical results. Such results may also occur in other clinical conditions, e.g. malaria, typhus, bacteraemia caused conditions, e.g. malaria, typhus, bacteraemia caused by other organisms, and cirrhosisby other organisms, and cirrhosis

This is acceptable so long as the results are interpreted This is acceptable so long as the results are interpreted with care in accordance with appropriate local cut-off with care in accordance with appropriate local cut-off values for the determination of positivity. values for the determination of positivity.

Anemia

Leucopenia or leucocytosis

Thrombocytopenia

Abnormal liver function

1.Isolation of Organism :

- Blood cultures : positive in 40 – 80 % patients

during the first 7 – 10 days

- Culturing stool

- urine

- rose spots

- duodenal contents via string capsule : positive in 30 – 40 % patients

- bile

- faeces

2. Detection of antigen in body fluid :

- Coagglutination

- Latex agglutination

- ELISA

- CIEP

Urine test Typhidot

3. Detection of antibodies :

- Widal tube test - Widal slide test - IHA - CIEP - RIA - ELISA

1.Clinical Signs and Symptoms

2.Laboratory findings

3.Isolation of the organism

4.Detection of microbial antigen

5.Titration of antibody against causative agent

PenatalaksananPenatalaksanan

PerawatanPerawatan DietDiet MedikamentosaMedikamentosa Cairan & elektrolitCairan & elektrolit

Penatalaksanan Penatalaksanan perawatanperawatan Suspek d. tifoidSuspek d. tifoid

– Tirah baring absolut : dulu Isolasi Observasi Pengobatan Kesadaran posisi dubah-ubah Bab & bak diperhatikan

– Mobilisasi bertahap (RSCM) Hari ke 2 apireksi duduk waktu makan Hari ke 7 apireksi mulai berdiri Hari ke 10 apireksi jalan Hari ke 13-15 apireksi pulang

Penatalaksanan Penatalaksanan perawatanperawatan Suspek d. tifoidSuspek d. tifoid

– Mobilisasi bertahap (RSWS-makassar)

Hari ke 3 apireksi duduk Hari ke 7 apireksi jalan Hari ke 10 apireksi pulang

Penatalaksanan Penatalaksanan perawatanperawatan Pola perawatan konvensional : mulai Pola perawatan konvensional : mulai

dengan bubur saringdengan bubur saring Lama perawatan 21 hari apireksiaLama perawatan 21 hari apireksia

MRS APIREKSIA

?? 77 33 33 33 55

BaringBaring Duduk Duduk JalanJalan

Bubur Bubur saringsaring Bubur biasaBubur biasa NasiNasi

Hari perawatan

Mobilisasi

Diet

Penatalaksanan Penatalaksanan perawatanperawatan Pola perawatan singkat : mulai Pola perawatan singkat : mulai

dengan nasidengan nasi Lama perawatan : 10 hari apireksiaLama perawatan : 10 hari apireksia

MRS APIREKSIA

?? 33 44 33

BaringBaring DudukDuduk JalanJalan

NasiNasi

Hari perawatan

Mobilisasi

Diet

Penatalaksanan Penatalaksanan perawatanperawatan Pola perawatan sangat singkat : mulai Pola perawatan sangat singkat : mulai

dengan nasidengan nasi Lama perawatan : 7 hari apireksiaLama perawatan : 7 hari apireksia

MRS APIREKSIA

?? 33 44

BaringBaring Duduk/JalanDuduk/Jalan

NasiNasi

Hari perawatan

Mobilisasi

Diet

Penatalaksanan dietPenatalaksanan diet

diet konvensional bubur saringdiet konvensional bubur saring– Maksud bubur saring :Maksud bubur saring :

Memudahkan pencernaan/absorbsiMemudahkan pencernaan/absorbsi beban kerja ususbeban kerja usus– Makan kurang merangsang : Makan kurang merangsang : perdarahan & perdarahan &

perforasiperforasi– Netralisasi asam lambungNetralisasi asam lambung

– Syarat bubur saringSyarat bubur saring Mudah dicerna, porsi kecil, seringkaliMudah dicerna, porsi kecil, seringkali Protein cukupProtein cukup Tidak merangsangTidak merangsang Memenuhi kebutuhan normalMemenuhi kebutuhan normal

Penatalaksanan dietPenatalaksanan diet

– Makanan padatMakanan padat Melancarkan defekasi Melancarkan defekasi bulk forming bulk forming Supaya BB cepat naikSupaya BB cepat naik Sudah jadi bubur di ileum terminalisSudah jadi bubur di ileum terminalis Meningkatkan selera makanMeningkatkan selera makan Disiapkan : mudah,murah,singkatDisiapkan : mudah,murah,singkat Jumlah kalori segera terpenuhiJumlah kalori segera terpenuhi Lebih menyenangkan penderitaLebih menyenangkan penderita Lamanya perawatan lebih singkatLamanya perawatan lebih singkat

Pengobatan Pengobatan

Kloramfenikol Kloramfenikol DOC DOC– Mortalitas Mortalitas < 12 % < 12 % 1 % 1 %– MurahMurah– Kekurangan :Kekurangan :

RelapsRelaps PengidapPengidap ResistensiResistensi Mual, muntahMual, muntah GlositisGlositis EnterokolitisEnterokolitis LekopeniLekopeni Anemi aplastikAnemi aplastik TrombositopeniTrombositopeni AgranulositosisAgranulositosis

– Dosis : Dosis : 50 -60 mg/kg.BB tiap 4-6 jam50 -60 mg/kg.BB tiap 4-6 jam 4 x 500 mg/hr 4 x 500 mg/hr spi 10 hari apireksia spi 10 hari apireksia


Rata-rata pulang 14 hr bebas Rata-rata pulang 14 hr bebas panaspanas– 4 x 250 mg spi 3 hr apireksia4 x 250 mg spi 3 hr apireksia– Istirahat 7 hariIstirahat 7 hari– 4 x 250 mg selama 5 hr4 x 250 mg selama 5 hr– Rata-rata pulang 15 hr apireksiaRata-rata pulang 15 hr apireksia– 4 x 400 mg spi 7 hr apireksia4 x 400 mg spi 7 hr apireksia– 3 x 500 mg spi 7 hr apireksia3 x 500 mg spi 7 hr apireksia– Rata-rata pulang 10 hr apireksiaRata-rata pulang 10 hr apireksia


Tiamfenikol identik kloramfenikolTiamfenikol identik kloramfenikol– Dosis :Dosis :

4 x 500 mg spi 5 hr apireksia4 x 500 mg spi 5 hr apireksia

– Konsentrasi > dlm darahKonsentrasi > dlm darah– > lama dlm badan/empedu> lama dlm badan/empedu– Toksisitas Toksisitas – Kompl. Hematologis Kompl. Hematologis


Ampisilina dan AmoksisilinaAmpisilina dan Amoksisilina– Dosis :Dosis :

2 x 1500 mg 2 x 1500 mg = kloramfenikol= kloramfenikol 3 – 4 x 1000 mg selama 14 hr3 – 4 x 1000 mg selama 14 hr 4 x 1000 mg selama 14 hr4 x 1000 mg selama 14 hr 2 x 1000 mg selama 21 hr2 x 1000 mg selama 21 hr

– Rata-rata perawatan 14 hrRata-rata perawatan 14 hr


KotrimoksazoleKotrimoksazole– Dosis :Dosis :

2 x 2 tablet spi 7 hr apireksia2 x 2 tablet spi 7 hr apireksia

CeftriaksonCeftriakson– Generasi ke-3 sefalosporinGenerasi ke-3 sefalosporin– Dosis :Dosis :

4 gr /hr selama 2-3 hr4 gr /hr selama 2-3 hr

PefloxacinPefloxacin– QuinolonQuinolon– Dosis :Dosis :

400 mg/hr selama 5 – 7 hr400 mg/hr selama 5 – 7 hr


Obat-obat lainObat-obat lain– Ciprofloxacin 500 mg (single dose)Ciprofloxacin 500 mg (single dose)– Ofloxacin Ofloxacin 400 mg 400 mg – NorfloxacinNorfloxacin 400 mg 400 mg

KortikosteroidKortikosteroid– Kontroversi Kontroversi toksis toksis– Membran sel & lisosom Membran sel & lisosom hambat hambat

enzym hidrolaseenzym hidrolase– Dosis :Dosis :

Dexamethasone : 3 mg/kg.BB Dexamethasone : 3 mg/kg.BB 1 1 mg/kg.BB. 6 jam slm 2 hrmg/kg.BB. 6 jam slm 2 hr

Pengobatan khusus Pengobatan khusus

Wanita hamilWanita hamil– Trimester I : kloramfenikolTrimester I : kloramfenikol– Trimester III : tiamfenikolTrimester III : tiamfenikol– Amoksisilin selalu amanAmoksisilin selalu aman– Kloram pd trimester III tdk boleh Kloram pd trimester III tdk boleh

diberi karena :diberi karena : Partus prematurPartus prematur Kematian fetus intrauterinKematian fetus intrauterin Grey syndrome pd neonatusGrey syndrome pd neonatus

Pengobatan khusus Pengobatan khusus Carierr/symptomless excretorCarierr/symptomless excretor

– Tanpa keluhanTanpa keluhan– symptomless excretor : salmonella (+) dl symptomless excretor : salmonella (+) dl

feses/urine < 3 blfeses/urine < 3 bl– Carier > 3 blCarier > 3 bl– Prev. Prev. > 3 % > 3 %– Usia menengahUsia menengah– Wanita > priaWanita > pria– U/ diagnos : kultur 3-6 xU/ diagnos : kultur 3-6 x– R/ :R/ :

Ampisilin/amoksisilin Ampisilin/amoksisilin : 4 x 1 gr/6 jam: 4 x 1 gr/6 jam 4 mg 4 mg

Kotrimoksazole Kotrimoksazole : 2 x 2 tab(480): 2 x 2 tab(480) 4 mg 4 mg Ciprofloxacin Ciprofloxacin : 2 x 750 mg : 2 x 750 mg 4 mg 4 mg Kombinasi dengan kolesistektomiKombinasi dengan kolesistektomi

Treatment of Treatment of uncomplicated typhoiduncomplicated typhoid

Oral drugsOral drugs

Ofloxacin: 15-20 mg / kg for 7-14 Ofloxacin: 15-20 mg / kg for 7-14 daysdays

Azithromycin:8-10 mg/kg for 7 Azithromycin:8-10 mg/kg for 7 daysdays

Cefixime: 20 mg /day for 7-14 Cefixime: 20 mg /day for 7-14 daysdays

Chloramphenicol: 50-75 mg Chloramphenicol: 50-75 mg /kg/day for 14-21 days/kg/day for 14-21 days

FluoroquinolonesFluoroquinolones

Optimal for the treatment of typhoid feverOptimal for the treatment of typhoid fever Relatively inexpensive, well tolerated and more Relatively inexpensive, well tolerated and more

rapidly and reliably effective than the former first-rapidly and reliably effective than the former first-line drugs, viz. chloramphenicol, ampicillin, line drugs, viz. chloramphenicol, ampicillin, amoxicillin and trimethoprim-sulfamethoxazole.amoxicillin and trimethoprim-sulfamethoxazole.

The majority of isolates are still sensitive.The majority of isolates are still sensitive. Attain excellent tissue penetration, kill S. typhi in its Attain excellent tissue penetration, kill S. typhi in its

intracellular stationary stage in intracellular stationary stage in monocytes/macrophages and achieve higher active monocytes/macrophages and achieve higher active drug levels in the gall bladder than other drugs. drug levels in the gall bladder than other drugs.

Rapid therapeutic response, i.e. clearance of fever Rapid therapeutic response, i.e. clearance of fever and symptoms in three to five days, and very low and symptoms in three to five days, and very low rates of post-treatment carriage.rates of post-treatment carriage.

ChloramphenicolChloramphenicol

The disadvantages of using chloramphenicol include The disadvantages of using chloramphenicol include a relatively high rate of relapse (57%), long a relatively high rate of relapse (57%), long treatment courses (14 days) and the frequent treatment courses (14 days) and the frequent development of a carrierstate in adults. development of a carrierstate in adults.

The recommended dosage is 50 - 75 mg per kg per The recommended dosage is 50 - 75 mg per kg per day for 14 days divided into four doses per day, or day for 14 days divided into four doses per day, or for at least five to seven days after defervescence.for at least five to seven days after defervescence.

Oral administration gives slightly greater Oral administration gives slightly greater bioavailability than intramuscular (i.m.) or bioavailability than intramuscular (i.m.) or intravenous (i.v.) administration of the succinate salt.intravenous (i.v.) administration of the succinate salt.

CephalosporinsCephalosporins

Ceftriaxone: 50-75 mg per kg per Ceftriaxone: 50-75 mg per kg per day one or two dosesday one or two doses

Cefotaxime: 40-80 mg per kg per Cefotaxime: 40-80 mg per kg per day in two or three dosesday in two or three doses

Cefoperazone: 50-100 mg per kg Cefoperazone: 50-100 mg per kg per day per day

Multi drugs Resistance Salmonella typhi (MDRST)

Resistance to :

• Chloramphenicol

• Amoxycillin

• Cotrimoxazole

RelapseRelapse

5-20% of typhoid fever cases that have 5-20% of typhoid fever cases that have apparently been treated successfully. apparently been treated successfully.

A relapse is heralded by the return of A relapse is heralded by the return of fever soon after the completion of fever soon after the completion of antibiotic treatment. The clinical antibiotic treatment. The clinical manifestation is frequently milder than manifestation is frequently milder than the initial illness. Cultures should be the initial illness. Cultures should be obtained and standard treatment should obtained and standard treatment should be administered. be administered.

Pencegahan Pencegahan

Usaha terhadap lingkungan hidupUsaha terhadap lingkungan hidup– Penyediaan air minum yg sehatPenyediaan air minum yg sehat– Sistim pembuangan kotoran yg Sistim pembuangan kotoran yg

higieneshigienes– Pemberantasan lalatPemberantasan lalat– Pengawasan thd rumah makan & Pengawasan thd rumah makan &

penjual makananpenjual makanan Usaha terhadap manusiaUsaha terhadap manusia

– ImunisasiImunisasi– Menemukan & mengawasi carierrMenemukan & mengawasi carierr– Pendidikan kesehatan pd masyarakatPendidikan kesehatan pd masyarakat

Typhoid Vaccines :

1.Parenteral killed whole cell vaccines

* Heat and phenol killed

* Acetone killed and dried

2. Live attenuated Ty21a vaccine (TYPHORAL@ )

3. Polysaccharide subunit vaccine (TYPHIM V@)

VaccinationVaccination

Vi polysaccharide, is given in a single dose Vi polysaccharide, is given in a single dose Protection begins seven days after injection, Protection begins seven days after injection, maximum protection being reached 28 days after maximum protection being reached 28 days after

injection when the highest antibody concentration is injection when the highest antibody concentration is obtained. obtained.

Protective efficacy was 72% one and half years Protective efficacy was 72% one and half years after vaccination and was still 55% three years after after vaccination and was still 55% three years after a single dose. a single dose.

In Asian countries where Vi-negative strains have In Asian countries where Vi-negative strains have been reported at the low average level of 3%. been reported at the low average level of 3%.

live oral vaccine Ty2lalive oral vaccine Ty2la

three doses two days apart on an empty stomach.three doses two days apart on an empty stomach. Protection as from 10-14 days after the third dose. Protection as from 10-14 days after the third dose. > 5 years. > 5 years. Protective efficacy of the enteric-coated capsule Protective efficacy of the enteric-coated capsule

formulation seven years after the last dose is stillformulation seven years after the last dose is still 62% in areas where the disease is endemic; 62% in areas where the disease is endemic; Antibiotics should be avoided for seven days before Antibiotics should be avoided for seven days before

or after the immunizationor after the immunization

Komplikasi Komplikasi

IntestinalIntestinal– Perdarahan ususPerdarahan usus– PerforasiPerforasi– Ileus paralitikIleus paralitik

EkstraintestinalEkstraintestinal– KardiovaskulerKardiovaskuler– DarahDarah– ParuParu– Hepar & vesika felleaHepar & vesika fellea– GinjalGinjal– Tulang Tulang – neuropsikiatrikneuropsikiatrik

Komplikasi : Komplikasi : multisystem organmultisystem organ

* Neuropsikiatri* Neuropsikiatri

* Perdarahan* Perdarahan

* Perforasi* Perforasi

* Miokarditis, Pankreatitis, * Miokarditis, Pankreatitis, * Hepatitis * Hepatitis

* Syok septik* Syok septik

Sindrom klinis berupa gangguan kesadaran, Sindrom klinis berupa gangguan kesadaran, dengan atau tanpa gangguan neurologis, dan dengan atau tanpa gangguan neurologis, dan dalam pem. Cairan otak masih dalam batas dalam pem. Cairan otak masih dalam batas normal normal Tifoid Toksik Tifoid Toksik

KOMPLIKASIKOMPLIKASI

1. INTESTINAL1. INTESTINAL Perdarahan ususPerdarahan usus Perforasi ususPerforasi usus Ileus paralitikIleus paralitik

2. EKSTRAINTESTINAL2. EKSTRAINTESTINAL KardiovaskularKardiovaskular HematologiHematologi ParuParu Hepar, saluran empedu, pankreasHepar, saluran empedu, pankreas GinjalGinjal Tulang, sendi, ototTulang, sendi, otot Neuropsikiatri >>>Neuropsikiatri >>>

Komplikasi Komplikasi KardiovaskularKardiovaskular

o Miokarditis 1-5%, paling sering pada Miokarditis 1-5%, paling sering pada anak-anakanak-anak

o Klinis: takikardia, protodiastolic gallop, Klinis: takikardia, protodiastolic gallop, desah sistolik apikal, edema periferdesah sistolik apikal, edema perifer

o EKG: perubahan segmen ST dan gel. T, EKG: perubahan segmen ST dan gel. T, QT memanjang dan low QRS voltageQT memanjang dan low QRS voltage

o Bisa menimbukan abses miokarditis, Bisa menimbukan abses miokarditis, jika ruptur jika ruptur tamponade jantung tamponade jantung

Trombi muralTrombi mural Emboli sistemik dan pulmonalEmboli sistemik dan pulmonal AneurismaAneurisma PerikarditisPerikarditis Kolaps vaskular perifer>>Kolaps vaskular perifer>> Trombosis vena dan arteri.Trombosis vena dan arteri.

Komplikasi DarahKomplikasi Darah

Anemia >>. Khosla Anemia >>. Khosla 80% kasus, morfologi 80% kasus, morfologi normositik normokrom, 2 pasien mikrositer normositik normokrom, 2 pasien mikrositer hipokrom, anemia hemolitik 1 pasien.hipokrom, anemia hemolitik 1 pasien.

Hongkong; GHongkong; G66PD Def. atau PD Def. atau hemoglobinopathihemoglobinopathi

Lekopenia dan limfositosis relatif jarangLekopenia dan limfositosis relatif jarang LekositosisLekositosis Trombositopenia (Jakarta 61,5%)Trombositopenia (Jakarta 61,5%)

Perdarahan akutPerdarahan akut Hemolytic uremic syndrome (HUS)Hemolytic uremic syndrome (HUS) Koagulasi intravaskular diseminataKoagulasi intravaskular diseminata

Komplikasi ParuKomplikasi Paru

Stadium awal ; bronkitis Stadium awal ; bronkitis typhoid lobar pneumonia typhoid lobar pneumonia (pneumo-typhoid) (pneumo-typhoid)

jarang (minggu II/III)jarang (minggu II/III)

1-3%1-3%

Efusi pleuraEfusi pleura PneumothraxPneumothrax empiemaempiema Abses paru <<<Abses paru <<<

Komplikasi hepar, kandung Komplikasi hepar, kandung empedu dan pankreasempedu dan pankreas

Tifoid hepatitis Tifoid hepatitis asimptomatisasimptomatis HepatomegaliHepatomegali Kriteria tifoid hepatitis menurut Khosla :Kriteria tifoid hepatitis menurut Khosla :

1. 1. HepatomegaliHepatomegali

2. Ikterus2. Ikterus

3. Kelainan lab (Bilirubin > 30,6umol/l, SGOT/SGPT 3. Kelainan lab (Bilirubin > 30,6umol/l, SGOT/SGPT meningkat, indeks waktu protrombin menurun)meningkat, indeks waktu protrombin menurun)

4. Kelainan histopatologi 4. Kelainan histopatologi

::3 atau lebih gejala :3 atau lebih gejala : Hepatitis tifosaHepatitis tifosa

Pohan dkk (Jakarta): 4,8% kasus, Pohan dkk (Jakarta): 4,8% kasus, Suling dkk (Manado) 6,2%Suling dkk (Manado) 6,2%

Nelwan RHH; Pankreatitis tifosa Nelwan RHH; Pankreatitis tifosa Kolesistitis akutKolesistitis akut Kolesistitis kronikKolesistitis kronik

Komplikasi RenalKomplikasi Renal

Fungsional atau patologisFungsional atau patologis Akibat gangguan glomerulus Akibat gangguan glomerulus

sementara atau GGA karena sementara atau GGA karena hemolisishemolisis

Khosla Khosla typhoid-nephritis 0,7%, typhoid-nephritis 0,7%, proteinuria 61,34%, pyuria 22%proteinuria 61,34%, pyuria 22%

Pohan dkk Pohan dkk 75,2% proteinuria, 75,2% proteinuria, lekosituria 5,7%lekosituria 5,7%

Retensi urinRetensi urin glomerulonefritisglomerulonefritis PielonefritisPielonefritis SistitisSistitis OrkhitisOrkhitis Basiluria asimptomatis Basiluria asimptomatis stadium dini stadium dini Imune complex-mediated Imune complex-mediated

glomerulonephritisglomerulonephritis “thypoid- “thypoid-nephritis / nephrotyphoidnephritis / nephrotyphoid

Komplikasi Komplikasi neuropsikiatrineuropsikiatri Paling seringPaling sering Insiden berbeda-beda tiap negaraInsiden berbeda-beda tiap negara Khosla ; 36,7%Khosla ; 36,7% Indonesia dan Vietnam 10-40%Indonesia dan Vietnam 10-40%

Tabel 1. Komplikasi neuropsikiatri pada demam tipoid (224 kasus).24

No Manifestasi Jumlah kasus

1 Delirium i) Tanpa konvulsi ii) Dengan konvulsi

140 80 60

2 Semicoma/coma 84 3 Parkinsonian rigidity/Transient Parkinsonism 84 4 Acute Brain Syndrome 24 5 Generelasid Myoclonus 12 6 Meningismus 28 7 Skizoprenia katatonia 6 8 Maniak akut 4 9 Pseudo Bulbar Palsy 2 10 Polyneuropathy 2 11 Hypomania 2 12 Encephalomyelitis 1

Komplikasi lainnyaKomplikasi lainnya : : depresidepresi tulituli transverse myelitistransverse myelitis gangguan ekstrapyramidalgangguan ekstrapyramidal pseudo tumor cerebripseudo tumor cerebri

Komplikasi tulang, Komplikasi tulang, sendi dan ototsendi dan otot

Typhoid osteomyelitisTyphoid osteomyelitis Typhoid spine (diagnosa banding Typhoid spine (diagnosa banding

tbc)tbc) Typhoid arthritisTyphoid arthritis Insiden 2%Insiden 2% PeriostitisPeriostitis Ruptur ototRuptur otot

Komplikasi lain-lainKomplikasi lain-lain

HiperkalsemiaHiperkalsemia ulserasi dekubitusulserasi dekubitus ParotitisParotitis AlopesiaAlopesia FurunkulosisFurunkulosis Spontaneus spleen ruptureSpontaneus spleen rupture AbortusAbortus

DEMAM TIFOID BERATDEMAM TIFOID BERAT

=> => Sindroma klinis berupa gangguan Sindroma klinis berupa gangguan atau penurunan kesadaran akut atau penurunan kesadaran akut (kesadaran berkabut, apatis, delirium, (kesadaran berkabut, apatis, delirium, sopor dan koma) dengan atau tanpa sopor dan koma) dengan atau tanpa disertai kelainan neurologis lainnya.disertai kelainan neurologis lainnya.

= = Demam Tifoid Toksik, Demam Demam Tifoid Toksik, Demam Tifoid ensefalopati, Demam Tifoid Tifoid ensefalopati, Demam Tifoid dengan toksemiadengan toksemia

Patofisiologi belum jelasPatofisiologi belum jelas Hornick dan Greisman; endotoksin Hornick dan Greisman; endotoksin

toksemtoksemiaia

inflamasi inflamasi makrofag makrofag monokin, monokin, asam arakhidonat, radikal bebas asam arakhidonat, radikal bebas Demam Tifoid BeratDemam Tifoid Berat

PENGOBATANPENGOBATAN

ANTIBIOTIKAANTIBIOTIKA PERAWATAN YANG BAIKPERAWATAN YANG BAIK NUTRISINUTRISI CAIRAN DAN ELEKTROLITCAIRAN DAN ELEKTROLIT PENCEGAHAN KOMPLIKASIPENCEGAHAN KOMPLIKASI KORTIKOSTEROID ?KORTIKOSTEROID ?

ANTIBIOTIKAANTIBIOTIKA Kloramfenikol (500 mg / 6 jam selama 14 Kloramfenikol (500 mg / 6 jam selama 14

hari) dapat menurunkan angka kematian hari) dapat menurunkan angka kematian dari 10-15% menjadi 1-4% dari 10-15% menjadi 1-4% resisten, resisten, tidak efektif terhadap karier, aplastik tidak efektif terhadap karier, aplastik anemianemi

Amoxysillin 1 gr/8 jam selama 14 hariAmoxysillin 1 gr/8 jam selama 14 hari AmpicillinAmpicillin CotrimoxazoleCotrimoxazole TiamfenikolTiamfenikol

Fluorokuinolon Fluorokuinolon paling efektif, paling efektif, waktu singkat, pilihan pertama, waktu singkat, pilihan pertama, angka stool carriage lebih rendahangka stool carriage lebih rendah

AzithromycineAzithromycine Sefalosporin generasi ketigaSefalosporin generasi ketiga

Penanganan Demam Tifoid BeratPenanganan Demam Tifoid Berat Makanan (tinggi kalori dan rendah Makanan (tinggi kalori dan rendah

serat) melalui IV atau sondeserat) melalui IV atau sonde Mencegah dan mengawasi Mencegah dan mengawasi

perforasi, perdarahan dan syokperforasi, perdarahan dan syok Keseimbangan cairan dan elektrolitKeseimbangan cairan dan elektrolit

Pada keadaan adanya komplikasi Pada keadaan adanya komplikasi (renal, kardiovaskular, Pernafasan, (renal, kardiovaskular, Pernafasan, neuropsikiatri, tulang, hematologi) neuropsikiatri, tulang, hematologi) => Prosedur medik yang berlaku=> Prosedur medik yang berlaku

Tabel 3. Terapi Demam Tipoid Berat

Sensitifitas Obat parenteral lini pertama Obat parenteral lini kedua

Antibiotika Dosis

harian

(mg/kg)

Lama

(hari)

Antibiotika Dosis

harian

(mg/kg)

Lama

(hari)

Sensitif Fluorokuinolon

(cth, ofloxacin)*

15 10-14 Kloramfenikol

Amoksisillin

Trimethoprim-

Sulphamethoxazole

100

100

8

40

14-21

10-14

10-14

Multidrug-

resistant

Fluorokunolon 15 10-14 Ceftriakson atau

cefotaksim

60

80

10-14

Quinolone-

resistant**

Cefriakson atau

cefotaksim

60

80

10-14 Fluorokuinolon 20 10-14

Treatment of severe Treatment of severe typhoidtyphoid

KortikosteroidKortikosteroid KontroversialKontroversial Hoffman dkk; deksametason menurunkan Hoffman dkk; deksametason menurunkan

angka kematian 55,6% menjadi 10%angka kematian 55,6% menjadi 10% Gaol LM (Medan); pemberian Gaol LM (Medan); pemberian

deksametason dosis tinggi dan rendah deksametason dosis tinggi dan rendah tidak ada perbedaan bermakna tidak ada perbedaan bermakna

Widodo (Jakarta); Deksametason 3 X 5 mg Widodo (Jakarta); Deksametason 3 X 5 mg hasil klinis sama dengan dosis tinggihasil klinis sama dengan dosis tinggi

Hook ; tidak setuju pemberian Hook ; tidak setuju pemberian kortikosteroid (banyak efek samping)kortikosteroid (banyak efek samping)

Dexamethasone for Dexamethasone for CNS complicationCNS complication Should be immediately be treated Should be immediately be treated

with high-dose intravenous with high-dose intravenous dexamethasone in addition to dexamethasone in addition to antimicrobials antimicrobials

Initial dose of 3 mg/kg by slow i.v. Initial dose of 3 mg/kg by slow i.v. infusion over 30 minutesinfusion over 30 minutes

1 mg/kg 6 hourly for 2 days1 mg/kg 6 hourly for 2 days Mortality can be reduced by some 80-Mortality can be reduced by some 80-

90% in these high-risk patients90% in these high-risk patients

Prognosis Prognosis

UmurUmur Kekebalan penderitaKekebalan penderita Juml. & virulensi salmonellaJuml. & virulensi salmonella Cepat & tepatnya terapiCepat & tepatnya terapi Keadaan umumKeadaan umum

Differensial diagnosaDifferensial diagnosa

InfluenzaInfluenza Disentri basilerDisentri basiler Peny. Dgn demam yang lamaPeny. Dgn demam yang lama MalariaMalaria tuberkulosistuberkulosis

demam tifoid

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