TYPHOID FEVER

DEFINITIONS
Typhoid fever is an acute infectious disease caused by gram-negative bacteria Salmonella typhi. During an infection, the germs multiply in phagocytic cells mononuclear and continuously released into the bloodstream.

Etiology
The cause of typhoid fever is S. typhi, the gram-negative bacteria that don’t have capsule, have flagella that it's almost always on the move by using flagella peritrichous. There are several other species paratyphi A, B, and C which is the cause of paratyphoid fever. Having a somatic antigen (O) of the oligosaccharide, flagellar antigen (H) consisting of protein and envelope antigen (K) consisting of polysaccharides.

Pathogenesis
1. S. typhi: transmission occurs via oral (food or water contaminated with S. typhi)
a. Passing through the "barrier" of gastric acid resulting in the decrease of acidity of gastric acid-alkaline food.
b. Passing through the "barrier" small intestine, (decrease in intestinal peristalsis) and disruption of production or function of intestinal mucosal IgA
c. Stick and into the small intestine epithelial cells, basolateral move in the direction, out of the small intestine epithelial cells, into the lamina propria.
d. Phagocyted by macrophage cells, but was able to continue to live in it, carried on in mesenteric lymph nodes, and then through the ductus thoracicus into the general blood circulation / circulation, resulting bacteremia I which showed no clinical symptoms (asymptomatic)
2. In addition to the epithelial cells lining the small intestine, S. typhi can enter through the cell-M which is above the "Plaque de Peyer" small intestine, phagocyted by macrophage cells, carried to the mesenteric lymph nodes, and then go into the general blood circulation.
3. Bacteremia occurs 24-72 hours after infection.
4. Most S. typhi in macrophages out of circulation into the tissues and organs nonlimfoid breed therein.
5. S. typhi that is in the macrophages can survive and multiply inside macrophages fagosom. Tues finally experienced lysis, S. typhi out into the general blood circulation, occurs bacteremia II is accompanied by clinical symptoms (symptomatic) fever, headache, muscle joints etc.. Clinical symptoms are caused by the influence of endotoxin on the hypothalamus, as well as the influence of proinflammatory cytokines produced by macrophages infected with S. typhi.

CLINICAL SYMPTOMS
The period of typhoid fever shoots last between 10-14 days. Clinical symptoms that arise are very varied from mild to severe, from asymptomatic until the disease is typically accompanied by a picture of complications up to death.
1. In the first week of clinical symptoms of the disease is found in the complaints and symptoms similar to acute infectious diseases in general are fever, headache, dizziness, muscle pain, anorexia, nausea, vomiting, or diarrhea obstipation, bad feeling in lower stomach, cough and epistaxis.
2. On physical examination found only body temperature to rise. The nature of the fever is rising slowly, especially in the afternoon until the evening. In the second week of the symptoms become more obvious in the form of fever, relative bradycardia (increase in body temperature is not followed by increase in pulse rate 8 times per minute), a webbed tongue (gross in the middle, edge and red tip and tremor), hepatomegaly, splenomegaly, and meteorismus
 .3. Somnolen of central nervous disorders, stupor, delirium or psychosis and even coma. Roseolae rarely found in people in Indonesia.


DIAGNOSTIC STEPS
1. Anamnesis
2. Clinical Alerts
3. Laboratory
a. Leukopenia, anesonofilia
b. Bile culture (): blood at week I (in the second week may be negative); feces week II week III urine.
c. Widal reaction (): titer> 1 / 200. Usually positive for the week II
d. Identification of Antigen: Elisa, PCR, IgM S. Typhi


LABORATORY EXAMINATION
a. Blood
It often happens leukopenia, leukocytes can also be normal or leukocytosis. AST / ALT levels are often elevated but will return after recovery. Germs cultured highest at I-week illness, a definitive diagnosis of typhoid fever. Week I: 80-90%, week II: 20-25%, week III: 10-15%.
b. Urine
Urine culture was highest at week II / II, a definitive diagnosis or illness (carrier).
c. Feces
Found a lot of erythrocytes in the stool. Germs cultured in the week II / II, a definitive diagnosis or carrier post typhi.
d. Serology
Is often done Widal test. Widal test done to detect antibodies to the germ S. Typhi with an antibody called aglutinin. Used as aglutinin is aglutinin O and H. The higher the titer the more likely it is infected. Currently there is no common opinion on a significant aglutinin diagnostic titer for typhoid fever.
e. Bone Marrow
Creating a culture of bone marrow. Highly sensitive (95%), not affected by administration of antibiotics and disease phase.


DIFFERENTIAL DIAGNOSIS
1. Viral hepatitis
2. Malaria
3. Cytomegalovirus
4. Leptospirosis
5. Influenza
6. Bronchitis
7. Bronchopneumonia
8. Gastroenteritis
9. TBC
10. UTI



MANAGEMENT
a. Bed rest
b. Diets low in fiber, high calorie and protein
c. Antimicrobial, which is often used is as follows:
1.    Chloramphenicol, a dose of 4 x 500 mg per day given up to 7 days free of heat.
2.    Tiamfenikol, the same dose of chloramphenicol
3.    Cotrimoxazole, 2 x 2 tablet (1 tablet contains 400 mg sulfamethoxazole and trimethoprim 80 mg) was given for 2 weeks.
4.    Ampicillin or amoxicillin, the dose of 50-150 mg / KgBW for 2 weeks
5.    Third-generation cephalosporin, for example ceftriaxonewith 3-4 grams daily dose for 3-5 days
6.    Fluoroquinolone class:
-    Norfloxacin dose of 2 x 400 mg / day for 14 days
-    Ciprofloxacin dose of 2 x 500 mg / day for 6 days
-    Ofloxacin dose of 2 x 400 mg / day for 7 days
-    Pefloxacin dose of 400 mg / day for 7 days
-    Fleroxacindose of 400 mg / day for 7 days
-    In pregnant women that can be used are ampicillin, amoxicillin and ceftriaxone

PREVENTION
Cleanliness
-    • Personal: with hand washing.
-    • The disposal of feces and urine.
-    • Provision of clean water.
-    Immunization
• Children over 2 years.
-    • Contact with patients.
-    • Events outside the Ordinary.
-    • Travelling to endemic areas.
-    • Tyvium - Typherix ® i.m ® 3 years.
-    • Vivotif ® Oral.


COMPLICATIONS
a. Intestinal
1. Intestinal bleeding
In the intestine of infected Peyeri plaque (particularly the terminal ileum) can form ulcers / wound oval-shaped and extends to the axis of the intestine. If the wound penetrates the gut lumen and the blood vessels so there is bleeding.
2. Intestinal Perforation
Occurs in approximately 3% of patients treated. Usually arise in the third week but can also occur in the first week. In addition to common symptoms of typhoid is common, the patient complained of typhoid fever with perforation of severe abdominal pain especially in the lower right quadrant which then spread throughout the abdomen and is accompanied by signs of ileus. Weaken bowel sounds in 50% of deaf patients and sometimes the liver is not found because of abdominal free air. Other signs of perforation are rapid pulse, blood pressure down and may even shock. Leukocytosis with a shift to the left to bolster the perforation

b. EXTRA intestinal Complications Hematological
Complications hematological form of thrombocytopenia, hipofibrino-genemia, increased prothrombin time, increased partial thromboplastin time, increased fibrin degration product until disseminate intravascular coagulation (KID) can be found in most patients with typhoid fever. Trombositoponia have often found, this may occur because of decreased production of platelets in bone marrow during the process of infection or increased destruction of platelets in the reticuloendothelial system. Drugs also play a role.

1. Typhoid hepatitis
Mild to moderate swelling of the liver are found in 50% of cases with typhoid fever and more prevalent due to S typhi than S. Paratyphi. To distinguish whether hepatitis due to typhoid, viral, malaria or Amoeba then need to be considered physical, laboratory parameters, and if necessary histopathological liver. In typhoid fever increased transaminase enzymes are not relevant to the increase in serum bilirubin (to differentiate it by because of viral hepatitis.) Typhoid hepatitis can occur in patients with malnutrition and poor immune system. Although very rare, complications can occur hepatoencephalopathy
2. Myocarditis
Myocarditis occurs in 1-5% patients with typhoid fever while electrocardiographic abnormalities may occur in 10-15% sufferer. Patients with myocarditis are usually without symptoms of cardiovascular or chest pains, arrhythmia and congestive heart failure, or cardiogenic shock. While pericarditis is very rare. Persistent electrocardiographic changes accompanied by arrhythmias have a poor prognosis. The disorder is caused by damage of myocard by the germ S. tyhphi and myocarditis frequently as a cause of death. Usually seen in severely ill patients, a state of acute and fulminant.
3. Neuropsychiatric / Typhoid Toxic
Delerium neuropsychiatric manifestations can be either with or without seizures, a semi-coma, Parkinsonism Parkinson rigidytyltransient acute brain syndrome, generalized mioclonus, meningismus, cyitotoxic schizophrenia, acute mania, hipomania, encephalomyelitis, meningitis, peripheral polineuritis, Guillain-Barre syndrome and psychosis.