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Adults infection

*Typhoid fever*
It is an acute systemic infection which is caused by S.typhi or S.paratyphi and
characterized by bacteriemia, intoxication, fever, rashes, affection of lymph nodes, hepatosplenomegaly and formation of ulcer in small intestines.

History:
    The name of the disease is connected with Tyhpus. The symptoms of the disease were first described by Hippocrates 960 BC. Then Low’s called the disease typhoid fever. Bacilli are found by Gavki in the spleen and mesenteric lymph nodes.

Etiology:
    Salmonella belong to enterobacterioce, which have more than 3000 serotype. They are gram negative, flagellated, non-sporing, anaerobic bacilli. Ferment glucose. Based on DNA studying it is divided into: o S. Enterica (S.cholera Swiss). - There are 6 serotypes 1, 2, 3a, 3b, 4 and 6. - S. typhi and S. paratyphi belong to the first group. o S. Bongori. S.typhi is stable in the environment and survives in the ice, feces, eggs, milk for 1-3 months. Heating up to 56 C for 45-60 min destroys the bacteria; they are sensitive to usual disinfectant like Fenol.

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Antigenic structure:    S.typhi has O, H, and Vi (envelope) antigens. It produces endotoxin. Both salmonella can carry U antigen.

Epidemiology:
     Both salmonella are typical intestinal infections, human is the host. Majority of Salmonella are asymptomatic chronic carries. Excretion of pathogens begins in the 7th day of the disease and from the 2nd to 3rd week it is being discharged in urine, saliva, and stool. Acute carries: discharge Salmonella up to 3 months; chronic carries are possible in presence of billiary abnormalities (because Salmonella survives in gallstones). More common in summer, and spring. 1

Adults infection

Way of transmission:
  Fecal oral by ingestion of contaminated water with feces and urine. Direct contact (rare).

Source of infection:
   Contaminated water. Eggs and poultry products. Milk.

Salmonella paratyphi B:
Buffalos can be the host. Rural population is more infected with S.paratyphi B. The main way of transmission is through food (mainly milk).

Geographical distribution:
 High morbidity (100 cases\100000 of population): o South and central Asia. o South-east Asia. Medium morbidity (10-100 cases\100000 of population): o Rest of Asia. o Africa. o Latin America. Low (less than 10 cases\100000 of population): o Australia.

Pathogenesis:
   After penetrating the acidic barrier of the stomach, S.typhi invades the gut and multiplies in the phagocytes of the liver, spleen, lymph nodes and Prey’s patches. Ingestion of 100000 microorganisms can cause salmonellosis (the more is the dose the shorter the oncubation period). Bacteria pass to the ileum were they penetrate the barrier and then asymptomatic bacteriemia take place, S.typhi become ingested by phagocytes but phagocytosis is become limited due to presence of H antigen. Then due to bacteriemia S.typhi invades the gallbladder, and prey’s patches [persistent bacterermia can lead to fever, red spot appearance and general intoxication symptoms]. Then it enters the lumen of the bowel (stool culture will be positive within 2 weeks) or it can pass to the kidney (positive urine culture). o Infiltration of prey’s patches can lead to necrosis (stages): 1. Medullary swelling. 2. Formation of ulcer. 3. Clearing of ulcer. 2

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Adults infection 4. Healing of ulcer without scar. Necrosis persists and affects mesenteric lymph nodes causing central necrosis. Stges of pathogenesis: 1. Ingestion. 2. Regional lymph nodes affection. 3. Bacteriemia (1st week). 4. Disseminated. 5. Allergic. 6. Recovery.

Morphological changes in the intestine:
 After 1 week:    
o Medullar swelling of prey’s patches and proliferation of typhoid cells. After 2 weeks: o Large amount of S.typhi and massive necrosis. After 3 weeks: o Formation of ulcer, perforation and bleeding. After 4 weeks: o Full ablution of ulcer. After 5 weeks: o Healing of ulcer.

Clinical stages of typhoid fever:
I. Incubation period:  Depend on the infection dose and state of immunity.  Usually it last from 7-14 days. i. In parathyphi A: 12-14 days. ii. Paratyphi B: 5-8 days.  20% of patients have transit diarrhea and resolve before the onset of the disease.  Onset of the disease is gradual. Initial stage (1st week): 1. Increase of temperature. 2. Headache. 3. Symptoms of affection of CNS (insomnia, weakness). 1,2,3 are called typhoid triad. 4. Paleness of the skin, and abdominal swelling. 5. Bradycardia, decrease of BP (due to affects of endotoxin) [relative bradycardia, because the temperature increase and the pulse rate decrease]. 6. Padalka symptom: during percussion we can hear a dull sound due to swelling of the lymph nodes [maily found on the iliac fossas]; this symptom may be positive in Yersinosis too with enlarged mediastinal lymph nodes. 3

II.

Adults infection 7. Heaptospleenomeagly (at the end of this stage). 8. Slight diarrhea that turns to constipation. III. Climax of the disease (2-4 weeks): 1. Maximum and stable fever. 2. Intoxication of CNS (dull headache, weakness, intoxication, disturbances of sleep, confusion, delirium [status typhus]). 3. Hepatospleenomegaly. 4. The patient is too weak; he can’t give proper answers or response. 5. Rosy spots (Resola Elevatum): 1. Are septic rashes arising on 8th to 10th day of the disease. 2. These spots are 2-5 mm in diameter pink in color, painless appears on the skin of the abdomen, and chest. 3. Usually there are 3-5 elements, and if you press it turns pale and then become pink again. 4. In severe cases we can see papular rash. 6. Fuliginous tongue [typhoid tongue] (enlarged, furred tongue brown in color, with imprint of teeth on the margins, and bright red tip). 7. Possibilities of bleeding and perforation. Convalescences (on the 5th week): 1. Moderate decrease of temperature. 2. Decrease signs of intoxication. 3. Decrease of headache, better sleeping, and good appetite.

IV.

Fever pattern:
1) Winderlich’s temperature:  Gradual increase of temperature until it reach high figure (39 C) for one week, then it remains stable (stage 2) and then it decrease (convalescence stage). 2) Bodkin’s temperature:  Moderate increase of temperature, then decrease, increase, and finally decrease. 3) Dokovski’s temperature:  High temperature up to 39-40c then it decreases; this pattern last for 18-19 days. 4) Irregular temperature:  No specific pattern, it last for 12-18 days and temperature reaches 38-40c.

Clinical classification of paratyphoid:
1. 2. 3. 4. Typhoid form (A: 50-60%; B: 10-12%). Catarrhal form (A: 20-25%; B: 10-12%). Gastro-intestinal form (B: 60-65%). Mixed. 4

Adults infection

Classification of typhoid fever:
According to the form: a) Typical. b) Atypical: 1. Abortive (short). 2. Sub-clinical. c) Marked: 1. Penumotyphus. 2. Meningotyphus. 3. Encephalotypus. 4. Colonotyphus. According to severity: 1. Mild. 2. Moderate. 3. Severe.

Complications:
1) Abdominal: 1. Intestinal bleeding. 2. Perforation. 3. Hepatitis. 4. Cholecystitis (sub clinical). 2) CVS: 1. Myocarditis. 2. Toxic shock. 3) Respiratory: 1. Bronchitis. 2. Pneumonia. 4) CNS: 1. Encephalopathy. 2. Delirium. 3. Psychic state. 4. Meningitis. 5. Impairment of co-ordination. 5) Blood: 1. Anemia. 2. DIC. 6) Other: 1. Focal abscess. 2. Pharyngitis. 3. Relapse. 5

Adults infection 4. Chronic carrier.

Relapse:
  Typical for typhoid fever (when bacteriemia persist) fever, rashes, affection of CNS. Relapse occurs 10 days after convalescence.

Reasons for relapse:    Signs: 1. 2. 3. 4. Prolong subfebrile temperature. Prolong hepatosplenomegaly. Stable meteorism. Low titer of serum antibiotics. Genetic peculiarities. Immunodeficiency. Improper treatment.

Bleeding:
 It is the most important and severe complication.

Signs (takes place in climax stage): 1. 2. 3. 4. 5. 6. 7. 8. Paleness. Sleepiness. Hiccups. Decrease of temperature. Tachycardia. Decrease of BP. Melena. Pain.

Myocarditis:
  Connected with decrease of BP and no other specific symptoms. ECG: disturbances of rhythm and conductivity.

Toxic shock (climax of the disease):
  Increase of temperature, disturbances of patient’s general condition, and decrease of BP. Tachycardia, dryness of the mouth and dehydration, decrease of BP, anouria, paleness, and acrocyanosis.

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Adults infection

Bronchitis:
 Dry cough and dry rales.

Tonsillitis:
 Hyperemia and hypertrophy.

Prognosis:
 Depends on the geographical area, and the reactivity of the organism.  Mortality rate 10-20%.

Laboratory investigations:
1) General blood test: - Leucopenia from 3rd or 4th day. - Lymphocytosis. - Aneisonophilia. - Thrombocytopenia (climax stage). - Increase of ESR. 2) Urine: - No specific changes. - Slight albuminuria. - Increase of cylinders. 3) Biochemical test: - Level of electrolytes and metabolic disturbances. - DIC. 4) Culture (Specific diagnosis): - Specimen: blood, urine, bile, bone marrow, rosy spots. - Hemo-culture is positive during all feverish period and most positive in the first stage (medium: bile salt agar). Copra-culture and urine culture: are positive from the 2nd week. - Bile (obligatory for diagnosis): duodenal intubation not earlier than 5 weeks [because of threats of proliferation and bleeding]. 5) Serum diagnosis: - Widal test: traditional method, diagnostic titer 1:200. It is not specific due to O antigen it can be positive for other salmonella types. - Indirect hemoagglutination test: is more specific. - Latex agglutination test: for detection of antibodies against Vi antigen. - Immunofluorescent: 100 times more specific than Widal test. - PCR: to detect Vi antigen. Additional methods of examination: 1. X-ray of the lungs. 7

Adults infection 2. X-ray abdomen. 3. ECG. 4. Ultrasound of liver and spleen.

Differential diagnosis between salmonella paratyphi A and B:
Paratyphi A Anthroponosis ill person or carrier Acute onset Longer incubation period (7-14 days) Remittent and sometimes hectic Affection of respiratory system at the begging of the disease: sore throat, cough, dysphonia, dyspepsia, hypermeria of the skin and sclera and signs of pharyngitis for 5 to 7days Rashes are present and are more painful on upper extremities More frequent + Mild Paratyphi B Zooanthropnosis Ill person, liver, poultry products Acute onset Short incubation period (5-8 days) Fever continues for 1-5 days GIT symptoms: nausea, vomiting, chills, sweating, moderate pain. Paleness Absence of rashes or they appears on the 4th or 7th day polymorphic and painful Sever course with sepsis

Source of infection Onset Incubation period Fever Involved system

Rash

Relapse Status typhus Course

Treatment:
       Admission to the hospital even subclinical course. Bed rest for 5-10 days. Diet # 2. Antibiotics up to 10 days of normal temperature. Disintoxication therapy. Vit B and C. Glucocorticoids (in case of shock and collapse).

Antibiotics:
Drug Dose duration Course Levomycintin (chloromfenicol) 50-75mg /kg X4 tab/day 14-21 Uncomplicated Ampicillin 75-100mg/kg X3tab/day 14 Uncomplicated Co-trimaxazol (Biseptol) 8mg/kg X2tab/day 14 Uncomplicated Azithromycin 10mg/kg X1tab/day 7 Uncomplicated Ceftriaxone [drug of choice] 60mg/kg X1tab/day 10-14 complicated Ciprofloxacin [drug of choice in highly 20mg/kg X2tab/day 10-14 Complicated endemic areas] Antibiotics should be prescribed until 2 weeks after temperature normalization to prevent relapse. 8

Adults infection

Prevention:
1. Personal hygiene. 2. Vaccination: a. V capsular polysaccharide. b. Ty 21 A. c. Acetone inactivated parentral vaccine.

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