Dr. B.

Srinivasa Rao MD Department of Internal Medicine Rajiv Gandhi Institute of Medical Sciences Srikakulam

Typhoid and Paratyphoid

Definition
Complications

Etiology

Diagnosis and differential

Pathogenesis Clinical

diagnosis
Prognosis

manifestations
The laboratory and other

Treatment Preventions Paratyphoid Fever

examinations

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Department of Internal Medicine, RIMS, Srikakulam

Definition of Typhoid fever

Acute enteric infectious disease
caused by Salmonella typhi (S.Typhi). prolonged fever, Relative bradycardia, apathetic facial

expressions, roseola, splenomegaly, hepatomegaly, leukopenia.

intestinal perforation, intestinal hemorrhage

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 Antigens: located in the cell capsule

H (flagellar antigen).

O (Somatic or cell wall antigen) Vi (polysaccharide virulence)

Widal test

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Department of Internal Medicine, RIMS, Srikakulam

A schematic diagram of a single Salmonella typhi cell showing the locations of the H (flagellar), 0 (somatic), and Vi (K envelope) antigens.
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 Endotoxin A variety of plasmids Resistance: Live 2-3 weeks in water. 1-2

months in stool.
Die out quickly in summer Resistance to drying and cooling

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Department of Internal Medicine, RIMS, Srikakulam

Source of infection
Cases and chronic carriers
Cases discharge from incubation, more in 2~4

weeks after onset, a few (about 2~5%) last longer

than 3 months

chronic carrier Typhoid Mary

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Transmission

fecal-oral route

close contact with patients or carriers contaminated water and food flies and cockroaches.

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Department of Internal Medicine, RIMS, Srikakulam

Susceptibility and immunity

all people equally susceptible to infection acquired immunity can keep longer, reinfection are rare immunity is not associated with antibody level of H, O

and Vi. No cross immunity between typhoid and paratyphoid.

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Susceptibility and immunity

All seasons, usually in Summer & Rainy seasons Most cases in school-age children and young adults. both sexes equally susceptible.

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Pathogenesis
gastrointestinal tract host-pathogen interactions The amount of bacilli infection (>105baeteria)

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Pathogenesis
ingested orally
Stomach barrier (some Eliminated)
enters the small intestine

Penetrate the mucus layer enter mononuclear phagocytes of ileal Peyer's patches and mesenteric lymph nodes

proliferate in mononuclear phagocytes spread to blood. initial bacteremia (Incubation period).

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Pathogenesis
enter spleen, liver and bone marrow (reticuloendothelial system) further proliferation occurs A lot of bacteria enter blood again. (second bacteremia). Recovery
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S.Typhi.
2nd bacteremia

liverspleengall BM ,ect early stage&acme stage (1-3W

stomach

(monon

Bac. In gall

uclear phagoc ytes )

Lower ileum

Bac. In feces

peyer's patches & mesenteric lymph nodes

LN Proliferate,swell
necrosis defervescence stage

S.Typhi eliminated convalvescence stage (4-5w) 1st bacteremia (Incubation stage) 10-14d
15

thoracic duct

Enterorrhagia,i ntestinal 3/18/2012 perforation

3-4w

Department of Internal Medicine, RIMS, Srikakulam

Pathology
essential lesion:
proliferation of RES (reticuloendothelial system ) specific changes in lymphoid tissues and mesenteric lymph nodes. "typhoid nodules Most characteristic lesion: ulceration of mucous in the region of the Peyers patches of the small intestine

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Peyers Patches

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Typhoid Nodule

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Major findings in lower ileum

Hyperplasia stage(1st week):

swelling lymphoid tissue and proliferation of macrophages. Necrosis stage(2nd week): necrosis of swelling lymph nodes or solitary follicles.
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Major findings in lower ileum

Ulceration stage(3rd week):

shedding of necrosis tissue and formation of ulcer ----intestinal hemorrhage, perforation . Stage of healing (from 4th week): healing of ulcer, no cicatrices and no contraction

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Clinical manifestations
Incubation period: 360 days(714). The initial period (early stage) First week. Insidious onset. Fever up to 39~400C in 5~7 days chillsailmenttiredsore throatcough ,abdominal discomfort and constipation et al.

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The Fastigium Stage

second and third weeks.
Sustained high feverpartly remittent fever or irregular

fever. Last 1014 days.

Gastro-intestinal symptoms: anorexiaabdominal

distension or paindiarrhea or constipation

Neuropsychiatric manifestations: confusionblunt respond

even delirium and coma or meningism

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 Circulation system:

relative bradycardia or dicrotic pulse.

splenomegalyhepatomegaly

toxic hepatitis.
Roseola :30%, maculopapular rash

a faint pale color, slightly raised round or lenticular, fade on pressure

2-4 mm in diameter, less than 10 in number

on the trunk, disappear in 2-3 days.
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Fatal Complications:

Intestinal Hemorrhage
Intestinal Perforation

Severe Toxemia

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Defervescence stage
fever and most symptoms resolve by the fourth week of

infection. Fever come down, gradual improvement in all symptoms and signs, but still danger

Convalescence stage
the fifth week. disappearance of all symptoms, but can

relapse

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Clinical forms:
Mild infection:

very common seen recently symptom and signs mild good general condition temperature is 380C short period of diseases recovery expected in 1~3 weeks seen in early antibiotics users young children mild more easy to misdiagnose Department of Internal Medicine, RIMS,
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 Persistent infection:

diseases continue than 5 weeks

Ambulatory infection:
mild symptoms, early intestinal bleeding or perforation.

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 Fulminant infection:

rapid onset, severe toxemia and septicemia. High fever, chill, circulation failure, shock, delirium, coma, myocarditis, bleeding and other complications,

DIC et all.

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Special manifestations
In children
Often atypical sudden onset with high fever Respiratory symptoms and diarrhea, dominant Convulsion common in < 3 Relative bradycardia rare Splenomegaly, Roseola and leucopenia less common

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In the aged
temperature not high weakness common More complications

high mortality

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Recrudescence
clinical manifestations reappear less severe than initial episode Its temperature recrudesce when temperature start to

step down but abnormal in the period of 2-3 weeks and

persist 5~7 days then back to normal

seen in patients with short therapy of antibiotics

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Relapse
Serum positive of S.typhi after 13 weeks of

temperature down to normal.

Symptom and signs reappear
The bacilli have not been completely removed

Some cases relapse more than once

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Laboratory findings

Routine examinations:
white blood cell count is normal or decreased.
Leukocytopenia(specially eosinophilic leukocytopenia).

recovery with improvement of diseases

decreased in relapse

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Bacteriological examinations:
Blood culture: the most common use
80~90% positive during the first 2 weeks of illness 50% in 3rd week not easy in 4th week re-positive when relapse and recrudescence Attention to the use of antibiotics

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 The bone marrow culture

the most sensitive test specially in patients pretreated with antibiotics.

Urine and stool cultures

increase the diagnostic yield positive less frequently stool culture better in 3~4 weeks
The duodenal string test to culture bile useful

for the diagnosis of carriers.

Rose spots: Not use routinely
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Serological tests(Widal test):

five types of antigens:
somatic antigen(O),flagella(H) antigen, and paratyphoid fever flagella(A,B,C) antigen.

Antibody reaction appear during first week 70% positive in 3~4 weeks and can prolong to several months in some cases, antibodies appear slowly, or remain at a low

level,
some(10~30%) not appear at all.
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 "O" agglutinin antibody titer 1:80 and "H" 1:160 or "O"

4 times higher supports a diagnosis of typhoid fever

"O" rises alone, not "H", early of the disease. Only "H"

positive, but "O" negative, often nonspecifically elevated by immunization or previous infections or anamnestic reaction.
Antibody level maybe lower when have used antibiotics

early.
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 Some cross reaction between group D and A.

False positive in some infectious diseases

Some positive in blood culture ,but negative in Widal

'Vi" often useful for carrier (1:40)

Molecular Biological tests: DNA probe or Polymerase Chain Reaction (PCR)

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Complications
Intestinal hemorrhage
Commonly appear during the second-third week of illness

difference between mild and greater bleeding, often caused by unsuitable food, diarrhea et al
serious bleeding in about 2~8% - a sudden drop in temperature

rise in pulse & signs of shock followed by dark or fresh blood in the stool

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Intestinal perforation:
The more serious complication, incidence,1-4%

Commonly appear during 2-3 weeks

Perforating at the lower end of ileum. Before perforation, look for abdominal pain or diarrhea, intestinal

bleeding When perforation - abdominal pain, sweating, drop in temperature, and increase in pulse rate, rebound tenderness, abdomen muscle rigidity, decrease or disappear in the sonant extent of liver Leukocytosis Temperature rise - peritonitis Celiac free air under x-ray.
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 Toxic hepatitis:
common,1-3 weeks hepatomegaly, ALT elevated get better with improvement of diseases in 2~3

weeks
Toxic myocarditis.

seen in 2-3 weeks, usually severe toxemia.

Bronchitis, bronchopneumonia.

seen in early stage of Internal Medicine, RIMS, Department

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Other complications:
Toxic Encephalopathy.
Hemolytic Uremic Syndrome. Acute Cholecystitis Meningitis Nephritis
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Differential diagnosis
Viral infections Malaria

Leptospirosis
Epidemic Louse Bone Typhus

Tuberculosis
Gram ve Bacilli Septicemia
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Prognosis:
Case fatality 0.51%.
but high in old age, infant & serious complication

Have immunity forever after disease

About 3% of patients become fecal carriers

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TREATMENT
General treatment
isolation and rest good nursing care and supportive treatment close observation Temp, PR, RR, BP, abdominal condition

and stool
suitable diet include easy digested food or half-liquid food

drink more water

intravenous injection to maintain water and acid-base and

electrolyte balance
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Symptomatic treatment for high fever:

physical measures firstly
antipyretic drugs such as aspirin should be

administrated with caution

delirium, coma or shock,2-4mg dexamethasone in

addition to antibiotics reduces mortality

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Etiologic and special treatment

Quinolones:

first choice its highly against S.typhi penetrate well into macrophages, and achieve high

concentrations in the bowel and bile lumens

Norfloxacin (0.10.2 tidqid/1014 days). Ofloxacin (0.2 tid 1014days).

Ciprofloxacin (0.25 tid)

Caution: not in children and pregnant

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 Chloramphenicol:
For cases without multi-resistant S.typhi Children in dose of 5060mg/kg/per day

Adult 1.52g/day. TID

Drug Resistance, High relapse rate, Bone marrow toxicity

Cephalosporins:
Only third generation effective are Cefoperazone and

Ceftazidime 24g/day for 10~14 days

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Treatment of Complication
Intestinal bleeding:
bed rest, stop diet, close observation Temp,PR,RR,BP intravenous saline and blood transfusion

attention to acid-base balances

Sometimes, Operative

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 Perforation:
early diagnosis stop diet & decrease down the stomach pressure intravenous injection to maintain electrolyte and acid-

base balance & Use of Antibiotics

Sometimes Operative.

Toxic myocarditis:
bed rest, cardiac muscle protection drugs, dexamethasone, Digoxin

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Chronic carrier:
Ofloxacin 200mg bid or Ciprofloxacin 500mg bid, 46

weeks
Ampicillin 36g/day tid plus Probenecid 11.5g/day. 46

weeks.
TMP+SMZ

2 tabs. Bid. 13 months.

Cholecystitis may require cholecystectomy.

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Prophylaxis
Control source of infection
Isolation and treatment of patients stool culture one time per 5 days if negative continued two times ,without isolation Control of carriers

Observation of 25 days(15 days in paratyphoid) when close contact

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Cut of course of transmission

key way

avoid drinking untreated water and food.

Vaccination
side-effect more, less use

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Paratyphoid fever A,B,C

Caused by Salmonella paratyphoid A,B,C respectively

in no way different from typhoid fever in epidemiology,

pathogenesis, pathology, clinical manifestations, diagnosis, treatment and prophylaxis

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Paratyphoid A,B:
incubation period 2~15days, in genaral,8~10 days.

milder in severity
fewer in complications. Better in prognosis, relapse more common in Paratyphoid A. Treatment same as in typhoid fever.

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Paratyphoid C:
Always sudden onset.
Rapid rise of temperature. Presented in different forms-- Septicemia, Gastroenteritis and

Enteric fever
Complications--arthritis, abscess formation, cholecystitis,

pulmonary complications are commonly seen.

Intestinal hemorrhage and perforation not as common as in

typhoid fever.
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