DRAFT TM

CASE 2 : Thypoid Fever

FK UNPAD 2015 - ANANTARA

BY ALKA
 I. Body Thermoregulation (case 1)
II. Fever (case 1)
III. Anatomy of Small Intestine
Terdiri dari 3 : duodenum, ileum, jejunum diukur dari pyloric
orifice hingga ileocecal junction
A. Duodenum :
- dibagi menjadi 4 bagian
Superior part (1st) : 2 cm di awal intraperitoneal (duodenal cap/
bulb), 3 cm sisanya retroperitoneal.
Post : common bile duct & gastroduodenal a. Sup :
hepatoduodenal lig. Inf : greater omentum
Descending (2nd) : retroperitoneal, terdapat common bile duct dan main pancreatic duct di medial wall di
ampulla of vater (greater papilla) . Diatasnya 2 cm terdapat lesser papilla opening dari accessory pancreatic duct
Horizontal (3rd) : retroperitoneal, sejajar dg L3, di himpit antara SMA (ant) dan IVC (post)
Ascending (4th): intraperitoneal, berbatasan dg jejunum di duodenojejunal junction level L2. Perbatasan ini
membentuk sudut “duodenal flexure” yang disokong oleh ligament of Treitz. Ligament ini menjadi landmark
membedakan perdarahan GI atas dan bawah.
- Suplai artery : supraduodenal a. , ant & post superior pancreaticoduodenal a., ant & post inferior
pancreaticoduodenal a
- Venous drainage : ant & post superior pancreaticoduodenal v., ant & post inf pancreaticoduodenal v.
B. Ileum
C. Jejunum

IV. Histology of Small Intestine (Review)

A. Mucosa
1) Epitel : simple kolumnar yg dapat menghasilkan mukus untuk melindungi dari asam lambung
2) Lamina propria : loose CT, terdapat SM, gastric gland, limfosit, sel plasma, fibroblast, sel mast
3) Muscularis mucosa : outer longitudinal, inner circular,
B. Submucosa : dense irregular CT. Terdapat Meissner (submucosal plexus), terdapat artery & vena
C. Muscularis externa : inner oblique, middle circular, outer longitudinal. Aurbach (myenteric) plexus diantara
middle dan outer SM
D. Serosa
 V. Typhoid Fever CS
A. Definisi

Typhoid fever, also known as enteric fever, is a potentially fatal multisystemic illness caused primarily by Salmonella
enterica, subspecies enterica serovar typhi and, to a lesser extent, related serovars paratyphi A, B, and C.

B. Epidemiologi

The highest rates of infection are in children under 5 years of age, persons aged 20 to 30, and those older than 70. If
one household member becomes infected, the probability that another will become infected approaches 60%.
Nearly one-third of all Salmonella epidemicsoccur in nursing homes, hospitals, mental health facilities, and other
institutions.

C. RF & Etio

 Oral transmission via food or beverages handled by an often asymptomatic individual—a carrier—who
chronically sheds the bacteria through stool or, less commonly, urine
 Hand-to-mouth transmission after using a contaminated toilet and neglecting hand hygiene
 Oral transmission via sewage-contaminated water or shellfish (especially in the developing world)

D. Patgen Patfis

E. Manifestasi

Classically, the course of untreated typhoid fever is divided into four distinct stages, each lasting about a week.
Over the course of these stages, the patient becomes exhausted and emaciated.

 In the first week, the body temperature rises slowly, and fever fluctuations are seen with
relative bradycardia (Faget sign), malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of
cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells
(leukopenia) occurs with eosinopenia and relative lymphocytosis; blood cultures are positive
for Salmonella Typhi or S. paratyphi. The Widal test is usually negative in the first week.[16]
 In the second week, the person is often too tired to get up, with high fever in plateau around 40 °C (104 °F) and
bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium is
frequent, often calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous
 fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi are heard in
lung bases.
 The abdomen is distended and painful in the right lower quadrant, where borborygmi can be heard. Diarrhea
can occur in this stage: six to eight stools in a day, green, comparable to pea soup, with a characteristic smell.
However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender,
and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood
cultures are sometimes still positive at this stage.
 (The major symptom of this fever is that the fever usually rises in the afternoon up to the first and second
week.)
 In the third week of typhoid fever, a number of complications can occur.
 By the end of third week, the fever starts subsiding.

F. Diagnosis

i. Uji widal
- Nilai diagnostik tes Widal adalah melihat adanya kenaikan titer antibodi yang bermakna dalam darah
terhadap antigen O (somatik) dan/atau antigen H (flagellar) Salmonella enterica serotype typhi pada 2 kali
pengambilan spesimen serum dengan interval waktu 10-14 hari. Level tersebut diukur dengan
menggunakan dilusi ganda serum pada tabung tes. Biasanya, antibodi O terlihat pada hari ke 6-8 dan
antibodi H terlihat pada hari ke 10-12 setelah munculnya gejala penyakit demam typhoid. Tes biasanya
dilakukan pada serum akut (serum yang pertama kali diambil saat pertama kali kontak dengan pasien).
- Tes Widal memerlukan dua kali pengambilan spesimen, yaitu pada masa akut dan masa convalesencence
dengan interval waktu 10-14 hari. Diagnosis ditegakkan dengan melihat adanya kenaikan titer lebih atau
sama dengan 4 kali liter masa akut.
- Prinsip : Pasien typhoid akan memiliki antibodi di dalam serumnya yang mana dapat bereaksi dan
beraglutinasi dengan antigen Salmonella enterica serotype typhi pada tes aglutinasi tabung maupun tes
aglutinasi slide.
- Terjadinya aglutinasi menandakan tes Widal positif dan jika reaksi positif diobservasi dalam 20 ul sampel tes,
hal ini mengindikasikan adanya level klinis yang signifikan.
- Tes Widal umumnya menunjukan hasil positif pada hari ke 5 atau lebih setelah terjadinya infeksi bakteri
Salmonella enterica serotype typhi. Oleh karena itu bila infeksi baru berlangsung beberapa hari sering kali
hasil tes Widal menunjukan hasil negatif dan menjadi positif bilamana pemeriksaan diulang beberapa hari
kedepan. Dengan demikian hasil tes Widal negatif terutama pada beberapa hari pertama demam belum
dapat menyingkirkan kemungkinan terjadinya demam typhoid. Tes Widal memiliki sensitifitas dan
spesifisitas yang rendah.

ii. Uji TUBEX

Uji semikuantitatif untukdeteksi antibody anti S. Thypi O9. Hasil positif menunjukkan infeksi Salmonella serogroup
D, dan tidak spesifik S. Thypi.

iii. Uji Typhidot

Deteksi igG dan igM paa protein membran luar S.thypi. Hasil positif diperoleh 2-3 hari setelah infeksi dan spesifik
mengidentifikasi IgG dan IgM S. thypi

iv. IgM dipstick

Deteksi khusus igM spesifik S. Thypi pada spesimen serum atau darah dengan menggunakan strip yg mengandung
antigen LPS S.thypi dan anti IgM sebagai kontrol. Akurasi diperoleh bila pemeriksaan dilakukan 1 minggu setelah
timbul gejala

v. Kultur darah/stool/bone marrow

G. DDx
- Dengue
- Malaria
- Rickettsial diseases
- Tuberculosis (TB)

H. Manajemen

I. Preventif

3 pilar strategis:

1) Mengobati
2) Mengatasi faktor rantai penularan
3) Perlindungan dini

 Perbaikan sanitasi lingkungan

1) Penyediaan air bersih terklorinasi tidak tercemar limbah dan kotoran lainnya.untuk air minum harus
dimasak sampai mendidih + 10 menit
2) Jamban tidak terkontaminasi lalat dan serangga
3) Pengelolaan air limbah, kotoran dan sampah tidak mencemari lingkungan
4) Control dan pengaasan terhadap kebersihan lingkungan
5) Perilaku hidup bersih dan lingkungan bersih

 Peningkatan kebersihan makanan dan minuman Golden rules of WHO

1) Pilih hati-hati makanan yang sudah diproses
2) Panaskan kembali secara benar
3) Hindari kontak makanan mentah dan matang
4) Cuci tangan dengan sabun
5) Bersihkan permukaan dapur
 6) Lindungi makanan dari serangga dan binatang
7) Gunakan air bersih
8) Menggunakan cara cermat dan bersih dalam pengolahan dan penyajian makanan
9) Penggunaan ASI untuk bayi
10) Memasak dan pasteurisasi susu serta produk lainnya
11) Quality control kepada hasil pertanian
12) Pengawasan terhadap restoran dan industry makanan
13) Pendidikan kesehatan masyarakat tentang PHBS

 Pencegahan dengan imunisasi

3 jenis vaksin
1) Oral Ty 21a Vivotif Berna
Daya proteksi 100% tapi di Indonesia hanya tersedia 36-66%. Tersedia dalam kapsul yang diminum selang
sehari dalam 1 minggu, 1 jam sebelum makan. tahun. Lama proteksi 5 tahun.
2) Paraenteral sel utuh typa Biofarma
Mengandung sel utuh bakteri typhi yang dimatikan. Daya proteksi 79-89% untuk K vaccine (acetone) dan
51-66% untuk L vaccine (heat activated Phenol preserved)
3) Polisakarida typhim vi Aventis Pasteur merrieux
Dari polisakarida Vi dari bakteri salmonella. Daya proteksi 60-70% lewat IM dan booster setiap 3 tahun

VI. Microbiology of Salmonella sp.

A. Morfologi
- Salmonella belong to proteobacterial family as Escherichia coli, the family Enterobacteriaceae, trivially known
as "enteric" bacteria.
- Salmonellae are Gram-negative, flagellated, Non spore forming, non capsulated, facultatively anaerobic bacilli
possessing three major antigens: H or flagellar antigen; O or somatic antigen; and Vi antigen (possessed by
only a few serovars. O antigens occur on the surface of the outer membrane and are determined by specific
sugar sequences on the cell surface. Vi antigen is a superficial antigen overlying the O antigen; it is present in a
few serovars, the most important being S typhi.
- The most commonly used media selective for Salmonella are SS agar, bismuth sulfite agar, Hektoen enteric
(HE) medium.
- Urease negative , H2S produced from thiosulfate
- Lactose negative; acid and gas from glucose, mannitol, maltose, and sorbitol

B. Virulensi

As with other Gram-negative bacilli, the cell envelope of salmonellae contains a complex lipopolysaccharide (LPS)
that may function as an endotoxin. LPS consist of three components, an outer O-polysaccharide coat, a middle
portion (the R core), and an inner lipid A coat. Lipopolysaccharide structure is important for several reasons. First,
the nature of the repeating sugar units in the outer O-polysaccharide chains is responsible for O antigen specificity;
it may also help determine the virulence of the organism. Salmonellae lacking the complete sequence of O-sugar
repeat units are called rough because of the rough appearance of the colonies; they are usually avirulent or less
virulent than the smooth strains which possess a full complement of O-sugar repeat units. Second, antibodies
directed against the R core (common enterobacterial antigen) may protect against infection by a wide variety of
Gram-negative bacteria sharing a common core structure or may moderate their lethal effects. Third, the endotoxin
component of the cell wall may play an important role in the pathogenesis of many clinical manifestations of Gram-
negative infections.

C. Transmisi

The infecting dose of S enterica infection varies widely with the serotype(200-106 bacteria), but is generally
considerably higher than Shigella. This makes human-to-human transmission by direct contact unlikely, so these
infections are transmitted by circumstances in which the bacteria increase their numbers by growth in
contaminated foods before ingestion. Achlorhydric individuals or those taking antacids can be infected with smaller
inocula.

D. Manifestasi

Gastroenteritis, enteric fever, Bacteremia & metastatic infection, chronic carrier state
VII. BHP
- Memilih lab exam yang tepat untuk onset tertentu
- Memilih obat dengan menentukan manfaat lebih besar dari efek samping (chlorampenicol efek samping nya
depression of bone marrow  aplastic anemia)
- Memantau vital sign karena minggu ke 2 critical

VIII. PHOP
- Edukasi PHBS
-

IX. CRP