1. TYPHOID FEVER AND PARATYPHOID FEVER
Guoli Lin
Department of Infectious Diseases
The Third Affiliated Hospital of SYSU

2. Typhoid and Paratyphoid
Definition
Etiology
Pathogenesis
Epidemiology
Clinical manifestations
The laboratory and other examinations
Complications
Diagnosis and differential diagnosis
Prognosis
Treatment
Preventions
Paratyphoid Fever

3. 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

4. Etiology Serotype: D group of Salmonella Gram-negative rod non-spore
flagella
Culture characteristics

5. Antigens: located in the cell capsule
H (flagellar antigen).
O (Somatic or cell wall antigen).
Vi (polysaccharide virulence)
“widel test”

6. A schematic diagram of a single Salmonella typhi cell showing the locations of the H (flagellar), 0 (somatic), and Vi (K envelope) antigens.

7. 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

8. Epidemiology continues to be a global health problem
areas with a high incidence include Asia, Africa and Latin America
affects about people with more than deaths a year. 80% in Asia .
sporadic occur usually, sometimes have epidemic outbreaks.

10. 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

12. Transmission fecal-oral route close contact with patients or carriers
contaminated water and food
flies and cockroaches.

14. 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.

15. Susceptibility and immunity
All seasons, usually in summer and autumn.
Most cases in school-age children and young adults.
both sexes equally susceptible.

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

17. 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).

18. Pathogenesis
 enter spleen, liver and bone marrow (reticulo-endothelial system) further proliferation occurs
 A lot of bacteria enter blood again.
(second bacteremia).
 Recovery

19. LN Proliferate,swell necrosis defervescence stage
S.Typhi.
liver、spleen、gall、
BM ,ect
early stage&acme stage
(1-3W）
2nd bacteremia
S.Typhi eliminated
convalvescence stage
(4-5w)
Bac. In gall
Bac. In feces
stomach
(mononuclear phagocytes )
Lower ileum
peyer's patches &
mesenteric lymph nodes
1st bacteremia
(Incubation stage)
10-14d
LN Proliferate,swell necrosis defervescence stage
（3-4w）
thoracic duct
Enterorrhagia,intestinal perforation

20. proliferation of RES (reticuloendothelial system )
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 Peyer’s patches of the small intestine

21. 回肠：
集合淋巴结(PEYER’SPATCHES)增生

22. 伤寒小结(TYPHOID NODULE)

23. 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.

24. 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

25. Incubation period: 3～60 days(7～14). The initial period (early stage)
Clinical manifestations
Incubation period: 3～60 days(7～14).
The initial period (early stage)
First week.
Insidious onset.
Fever up to 39~400C in 5~7 days
chills、ailment、tired、sore throat、cough ,abdominal discomfort and constipation et al.

26. The fastigium satge
second and third weeks.
Sustained high fever、partly remittent fever or irregular fever. Last 10～14 days.
Gastro-intestinal symptoms: anorexia、abdominal distension or pain、diarrhea or constipation
Neuropsychiatric manifestations: confusion、blunt respond even delirium and coma or meningism

27. Circulation system:
relative bradycardia or dicrotic pulse.
splenomegaly、hepatomegaly
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.

29. fatal complications: intestinal hemorrhage intestinal perforation
severe toxemia

30. defervescence stage convalescence stage
fever and most symptoms resolve by the forth 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

31. 图 典型伤寒自然病程示意图

32. 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

33. Persistent infection:
diseases continue than 5 weeks
Ambulatory infection:
mild symptoms,early intestinal bleeding or perforation.

34. Fulminate infection:
rapid onset, severe toxemia and septicemia.
High fever,chill,circulation failure, shock, delirium, coma, myocarditis, bleeding and other complications, DIC et all.

35. Special manifestations In children
Often atypical
sudden onset with high fever.
Respiratory symptoms and diarrhea, dominant.
Convulsion common in below 3.
relative bradycardia rare.
Splenomegaly, roseola and leucopenia less common.

36. In the aged temperature not high, weakness common.
More complications.high mortality.

37. Recrudescence clinical manifestations reappear
less severe than initial episode
It’s 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.

38. relapse
serum positive of S.typhi after 1～3 weeks of temperature down to normal.
Symptom and signs reappear
the bacilli have not been completely removed
Some cases relapse more than once

39. Leukocytopenia(specially eosinophilic leukocytopenia).
Laboratory findings
Routine examinations:
white blood cell count is normal or decreased.
Leukocytopenia(specially eosinophilic leukocytopenia).
recovery with improvement of diseases
decreased in relapse

40. 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 recrudesce
attention to the use of antibiotics

41. 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

42. Serological tests(Vidal 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.

43. "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.

44. Some cross reaction between group “D” and “A”.
False positive in some infectious diseases.
Some positive in blood culture ,but negative in vidal test.
'Vi" often useful for carrier (1:40)
molecular biological tests: DNA probe or polymerase chain reaction (PCR)

45. 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、and signs of shock followed by dark or fresh blood in the stool.

46. Intestinal perforation:
The more serious .Incidence,1-4%
Commonly appear during weeks.
Take place at the lower end of ileum.
Before perforation,abdominal pain or
diarrhea,intestinal bleeding .
When perforation, abdominal pain, sweating, drop in temperature, and increase in pulse rate, then, rebound tenderness when press abdomen,
abdomen muscle entasia, reduce or disappear in the sonant extent of liver, leukocytosis .
Temperature rise .peritonitis appear.
celiac free air under x-ray.

47. 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

48. Other complications:
toxic encephalopathy.
Hemolytic uremic syndrome.
acute cholecystitis、
meningitis、
nephritis et al.

49. 图 典型伤寒自然病程示意图

50. Diagnosis
Epidemiology data
Typical symptoms and signs
Laboratory findings.

51. Differential diagnosis Viral infections:
such as upper respiratory tract infection.
abrupt onset with fever, headache, leucopenia, sore throat, cough, coryza.
no rose spots, no enlargement of liver & spleen. The course of illness no more than 2 wks.
differential diagnosis depends on typical manifestations and blood culture.

52. Malaria
history of exposure to malaria. Paroxysms(often periodic) of sequential chill,high fever and sweating. Headache, anorexia, splenomegaly, anemia, leukopenia Characteristic parasites in erythrocytes,identified in thick or thin blood smears.

53. Leptospirosis Endemic area,contacted with urine of mice.
Abrupt fever,chills,severe headache,and myalgias, especially of the calf muscles.
Leptospires can be isolated from blood,cerebrospinal fluid.
Special agglutination titers develop after 7 days and may persist at high levels for many years.

54. Epidemic Louse-Borne typhus
prodromal of malaise and headache followed by abrupt chills and fever.
headaches,prostration,persisting high fever.
Maculopapular rash appears on the forth to seventh days on the trunk and in the axillas, spreading to the rest of the body but sparing the face,palms,and soles.
Laboratory confirmation by proteins OX19 agglutination and specific serologic tests.

55. Tuberculosis
continuous high or low fever,fatigue,weight loss,night sweats.
Mild cough
pulmonary infiltration on chest radiograph
positive tuberculin skin test reaction(most cases)
acid-fast bacilli on smear of sputum
sputum culture positive for mycobacterium tuberculosis.

56. Septicemia of Gram-negative bacilli
abrupt onset,high fever,symptom of toxemia.
Chill,sweats.
Shock.
Positive of gram-negative bacilli from blood culture.

57. Prognosis:
Case fatality 0.5～1%.
but high in old ages、infant、and serious complications
Have immunity for ever after diseases
About 3% of patients become fecal carriers .

58. good nursing care and supportive treatment
General treatment
isolation and rest
good nursing care and supportive treatment
close observation T,P,R,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

59. 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.

60. Etiologic and special treatment
1.Quinolones:
first choice
it’s highly against S.typhi
penetrate well into macrophages,and achieve high concentrations in the bowel and bile lumens
Norfloxacin (0.1～0.2 tid～qid/10～14 days).
Ofloxacin (0.2 tid 10～14days).
ciprofloxacin (0.25 tid)
caution: not in children and pregnant

61. 2.Chloramphenicol:
For cases without multiresistant S.typhi.
Children in dose of 50～60mg/kg/per day.
adult 1.5～2g/day. tid.
Unable to take oral medication, the same dosage given introvenously
after defervescence reduced to a half. complete a 10～14 day course.
But ,drug resistance, a high relapse rate,bone marrow toxicity.

62. 4.Treatment of complication.
3.Cephalosporines:
Only third generation effective
Cefoperazone and Ceftazidime.
2～4g/day .10~14 days.
4.Treatment of complication.
Intestinal bleeding:
bed rest, stop diet,close observation T,P,R,BP.
intravenous saline and blood transfusion,and attention to acid-base balances.
sometimes,operative.

63. Perforation:
early diagnosis.
stop diet.
decrease down the stomach pressure.
intravenous injection to maintain electrolyte and acid-base balances.
use of antibiotics.
sometimes operative.

64. bed rest, cardiac muscle protection drugs, dexamethasone, digoxin.
Toxic myocarditis:
bed rest, cardiac muscle protection drugs,
dexamethasone, digoxin.
5.Chronic carrier:
Ofloxacin 0.2 bid or ciprofloxacin 0.5 bid, 4～6 weeks.
Ampicillin 3～6g/day tid plus probenecid 1～1.5g/day. 4～6 weeks.
TMP+SMZ 2 tabs. Bid. 1～3 months.
Cholecystitis may require cholecystectomy.

65. Prophylaxis 1.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

66. 2. Cut of course of transmission
key way
avoid drinking untreated water and food.
3.Vaccination
side-effect more, less use

67. 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

68. 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.

69. 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.

70.
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