3. EPIDEMIOLOGY
Over 21.7 million cases/ annually
>2 lacs death
Additional >5.4 million cases – Paratyph.
Developed countries- <15/ lacs population
Developing countries- 100-1000/lacs.
4. In an Indian urban slum showed incidence as high as
2/ 1,000 /yr for children under five
5.1/ 1,000/ yr for children under ten
majority of cases occurred in children aged 5 to 12
years and 24.8% of cases were in children up to 5
years of age
S. Typhi (75.7%) was the predominant serovar
followed by S. Paratyphi A (23.8%)
maximum number of enteric fever cases occurred
during April to June (dry season) followed by July to
September (monsoon season
6. Contd..
Age – Children and young adults (5-25 years).
Recent Study from Delhi shows Typhoid fever also
common in < 5 years of age.
IP – 10-14 days (3-21 days).
MOT – Faeco-oral/Urine-oral route.
Through out the year esp. July-September
ROI – Man (Cases/Carriers)
7.
8. Organism
Salmonella typhi, a Gram-negative bacteria.
Similar but often less severe disease is caused by
Salmonella serotype paratyphi A.
The ratio of disease caused by S. typhi to that
caused by S. paratyphi is about 10 to 1.
Many genes are shared with E. coli and at least
90% with S. typhimurium,
Polysaccharide capsule Vi: present in about 90%
of all freshly isolated S. typhi and has a protective
effect against the bactericidal action of the serum
of infected patients.
9. Risk Factors
Impaired cell-mediated immunity
AIDS
Corticosteroid use
Malignancy
Impaired phagocytic function
Hemoglobinopathies
Chronic granulomatous disease
Malaria
Histoplasmosis
Schistosomiasis
10. Risk Factors
Extremes of age
Neonates
Elderly
Decreased gastric acidity
Antacids or suppression of acid secretion
Achlorhydria
Altered intestinal function
Inflammatory bowel disease
Prior antibiotic therapy
12. Contd..
Entry in GIT localization in Gut associated
lymphoid tissue Lymphatic channel thoracic
duct circulation primary silent bacteremia
localization in macrophages of RES in spleen, liver,
bone marrow (incubation period 8-14 days)
secondary bacteremia
14. Acute non-complicated disease
Characterized by
Prolonged fever, classic stepladder rise
uncommon.
Disturbances of bowel function Headache,
malaise and anorexia.
Bronchitic cough
Exanthem (rose spots appr 25%) on
the chest, abdomen and back.
15.
16. Complicated disease
10-15% of typhoid patients
CNS (3-35%): Encephalopathy, Typhoid meningitis,
encephalomyelitis, Guillain-Barré syndrome, cranial
or peripheral neuritis and psychotic symptoms, Coma
Vigil.
GIT: occult blood in 10-20% of patients, and intestinal
hemorrhage in upto 1%. Intestinal perforation has also
been reported in up to 1% of hospitalized cases.
Others: Hepatitis, myocarditis, pneumonia,
Empyema, disseminated intravascular, Osteomyelitis
17. Diagnosis
In endemic area, fever without evident cause more
than 7 days should be considered Typhoid until
proved otherwise.
Blood culture – standard diagnostic method . +ve in
40-60%
Failure to isolate the organism
(i) the limitations of laboratory media
(ii) the presence of antibiotics
(iii) the volume of the specimen cultured
18. Blood Cultures in Typhoid Fevers
Bacteremia occurs
early in the disease
Blood Cultures are
positive in
1st
week in 90%
2nd
week in 75%
3rd
week in 60%
4th
week and later in 25%
19. Antigenic structure of Salmonella
Two sets of antigens
Detection by serotyping
1 Somatic or 0 Antigens contain long chain
polysaccharides ( LPS ) comprises of heat stable
polysaccharide commonly.
2 Flagellar or H Antigens are strongly immunogenic and
induces antibody formation rapidly and in high titers
following infection or immunization.
20. Contd..
(iv) the time of collection, patients with a history of
fever for 7 to 10 days being more likely than others to
have a positive blood culture.
Bone marrow aspirate culture is the gold standard
for the diagnosis of typhoid fever
+ve 80-95%
Inspite on antibiotics.
Stool culture +ve in 30% with acute Typhoid
fever. Positivity rate increases with duration of
illness.
Cultures also been made from blood clots, rose
spots, intestinal secretion, urine.
21. Antigenic structure of Salmonella
Two sets of antigens
Detection by serotyping
1 Somatic or 0 Antigens contain long chain
polysaccharides ( LPS ) comprises of heat stable
polysaccharide commonly.
2 Flagellar or H Antigens are strongly immunogenic and
induces antibody formation rapidly and in high titers
following infection or immunization.
23. Widal Test
Measures antibody against O & H antigens of S.typhi.
Sensitivity-60%; specificity-80%.
O antibodies appear on days 6-8 and H antibodies on
days 10-12
Negative in up to 30% of culture-proven cases of typhoid
fever
S. typhi shares O and H antigens with other Salmonella
serotypes and has cross-reacting epitopes with other
Enterobacteriacae, and this can lead to false-positive
results. Such results may also occur in other clinical
conditions, e.g. malaria, typhus, bacteraemia caused by
other organisms, and cirrhosis
24. Contd..
This is acceptable so long as the results are
interpreted with care in accordance with appropriate
local cut-off values for the determination of positivity
A 4 fold rise Ab titre in paired sera highly suggestive
>1:160 titre against O & H highly suggestive with
relevent clinical findings.
25. New serological test
Specific antibodies usually only appear a week after
the onset of symptoms and signs. This should kept in
mind when a negative serological test result is being
interpreted.
New serological tests
Typhidot (better), high negative predictive value
Dipstick test,
DNA Probe
PCR
26. CONTD..
Typhidot –
Rapid serological test, detects IgM $ IgG antibody –
OMP of s.typhi.
Becomes +ve within 2-3 days of infection.
Sensitivity-90-98% ; specificity-75-90%.
Vi agglutinin reaction test- carrier.
CBC- WBC low in relation to fever, leucocytosis
common young children
Thrombocytopenia marker of severe illness/
accompany DIC.
27.
28.
29.
30. Oral drugs
Cotrimoxazole, Ampicillin, Chlorphenicol
Earlier used as 1st
line drugs, due to resistance
became 2nd line drugs.
In endemic area >90% typhoid cases treated at
home with proper antibiotics & good nursing care.
Patients with persistent vomiting, decreased oral
intake, severe diarrhea & abd. Distension require
parenteral antibiotic preferably in hospital.
31. Fluoroquinolones
Optimal for the treatment of typhoid fever
Not approved by drug controller general of India <18 yrs.
Age.
Relatively inexpensive, well tolerated and more rapidly
and reliably effective than the former first-line drugs, viz.
chloramphenicol, ampicillin, amoxicillin and
trimethoprim-sulfamethoxazole.
The majority of isolates are still sensitive.
32. Contd..
Attain excellent tissue penetration, kill S. typhi in
its intracellular stationary stage in
monocytes/macrophages and achieve higher
active drug levels in the gall bladder than other
drugs.
Dose- 15-20 mg/kg/day BD -7 days for NASST and
10-14 days for NARST.
Rapid therapeutic response, i.e. clearance of fever
and symptoms in three to five days, and very low
rates of post-treatment carriage.
33. Chloramphenicol
The disadvantages of using chloramphenicol include
a relatively high rate of relapse (57%), long treatment
courses (14-21 days) and the frequent development of
a carrierstate in adults.
The recommended dosage is 50 – 75 (100mg for iv/im)
mg per kg per day for 14 -21days divided into four
doses per day, or for at least five to seven days after
defervescence.
Oral administration gives slightly greater
bioavailability than intramuscular (i.m.) or
intravenous (i.v.) administration of the succinate salt.
34. Cephalosporins
Oral drugs:- Cefixime, Cefpodoxime.
Parenteral-Ceftriaxone, cefotaxime, cefoperazone.
Cefotaxime: 40-80mg per kg per day in two or three
doses
Ceftriaxone: 50-75 mg/kg/day OD/BD.
Most convenient & widely used.
Cefoperazone: 50-100 mg per kg per day
35. Contd..
In uncomplicated typhoid fever- cefixime DOC as
emperical therapy.
If by 5th
day No clinical improvement & culture
inconclusive—ADD second line drugs eg.
Azithromycin (drugs sensitivity pattern of the
area).
In complicated typhoid- DOC 3rd
gen. cephal.
Parenteral eg. Ceftriaxone.
In severe life threatening infection – FQs. May be
used. Aztreonam/ Imipenam may also be used.
36. hegazi8@hotmailcom 36
MEDICAL COMPLICATIONS
acute bronchitis and frank lobar pneumonia,
toxic myocarditis,
venous thrombosis,
hemolytic anaemia,
acute typhoid nephritis,
typhoid meningitis and
peripheral neuritis
37. hegazi8@hotmailcom 37
MEDICAL COMPLICATIONS
Myocarditis is extremely common, particularly in the
very toxic patient. The cardiac muscle is affected, even
in convalescence, and this is shown by a rapid
deterioration of the cardiovascular system in a relapse,
or after the administration of a general anaesthetic.
Febrile albuminuria is common, but true acute typhoid
nephritis is rare.
Peripheral neuritis and ‘tender toes’.
Mild hemolytic anaemia is fairly common in the very
toxic typhoid patient. A marked degree is rare, and the
mortality rate is high.
38. Dexamethasone for CNS
complication
Should be immediately be treated with high-dose
intravenous dexamethasone in addition to
antimicrobials
Initial dose of 3 mg/kg by slow i.v. infusion over 30
minutes
1 mg/kg 6 hourly for 2 days/ 8 doses.
Mortality can be reduced by some 80-90% in these
high-risk patients
39. hegazi8@hotmailcom 39
Typhoid Pneumonia
Acute bronchitis is so common that it should be
considered as a manifestation of the disease itself
rather than as a complication.
Typhoid lobar pneumonia presents with the
typical symptoms and signs of lobar pneumonia
except that ‘rusty’ sputum is uncommon, and the
white blood cell count is low.
It responds well to chloramphenicol. A patient
with typhoid pneumonia,.
40. GI complication
Patients with intestinal haemorrhage need intensive care,
monitoring and blood transfusion.
Surgical consultation for suspected intestinal perforation
is indicated. If perforation is confirmed, surgical repair
should not be delayed longer than six hours.
Metronidazole and gentamicin or ceftriazone should be
administered before and after surgery .
Early intervention is crucial, and mortality rates increase
as the delay between perforation and surgery lengthens.
Mortality rates vary between 10% and 32%.
41. hegazi8@hotmailcom 41
The major surgical complications of
typhoid fever may include:
parotitis,
intestinal perforation and haemorrhage,
acute cholecystlitis,
paralytic ileus,
orchitis,
pyelitis, cystitis, retention of urine,
empyema,
arthritis and osteomyelitis.
42.
43. Relapse
5-20% of typhoid fever cases that have apparently
been treated successfully.
A relapse is heralded by the return of fever soon
after the completion of antibiotic treatment. The
clinical manifestation is frequently milder than
the initial illness. Cultures should be obtained and
standard treatment should be administered.
Carrier- Temporary carrier(excreate bacilli upto
6-8 wks). eg.incubatory, convalescent state.3
Chronic carrier- excrete bacilli > 3 months after
infection.
44. Paratyphoid fever A,B,C
Caused by Salmonella paratyphoid
A,B,C.respectively.
in no way different from typhoid fever in ,
pathogenesis, pathology,clinical
manifestations,
diagnosis, treatment and
Prophylaxis
45. 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.
46. 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.
48. Vaccination
Vi polysaccharide, is given in a single dose
Protection begins seven days after injection,
maximum protection being reached 28 days after
injection when the highest antibody
concentration is obtained.
Protective efficacy was 72% one and half years
after vaccination and was still 55% three years
after a single dose.
In Asian countries where Vi-negative strains have
been reported at the low average level of 3%.
49. Live oral vaccine Ty2la
three doses two days apart on an empty stomach.
Protection as from 10-14 days after the third dose.
> 5 years.
Protective efficacy of the enteric-coated capsule
formulation seven years after the last dose is still
62% in areas where the disease is endemic;
Antibiotics should be avoided for seven days
before or after the immunization
50. Contd..
Vi conjugated vaccine:
Induce T cell dependent response
Efficacy- >90%
Booster response
Doses: 3 mths.- 2 yrs.-2doses at 4-8 wks. Interval
followed by booster at 2-2.5 yrs age. Route-
intramuscular.
>2 yrs.- 2 doses at 4-8 wks. Interval.
51. MDR TYPHOID
Clinical failure
presence of persistent symptoms or, development of complications
.
Microbiological failure
positive blood / bone marrow culture at the end of treatment.
MDR Typhoid definition
Epidemiological- strains resistant =>2 antibiotics in vitro.
Clinical- => 2 1st
line drugs viz. Amp., Chlo., Cx.
Incidence - 49-83% of mdr typhoid in indian children.
Mediated by plasmid
Quinolone resistance is frequently mediated by single point
mutations in the quinolone-resistance–determining region of the
52. MDR
Nalidixic acid resistant: MIC of fluoroquinolones for these strains
was 10 times that for fully susceptible strains.
Incidence - 49-83% of mdr typhoid in indian children.
Mediated by plasmid
Quinolone resistance is frequently mediated by single point
mutations in the quinolone-resistance–determining region of the
gyrA gene
53. Diagnosis
High degree of suspicion viz. prolonged fever,
protracted course, unusual/ life threatening
complication, slow response to treatment.
Culture reports
Epidemiological reports.
54. The future of typhoid fever
Cheap,Rapid and reliable serological test
Fluoroquinolone and cephalosporin resistant case
Combination chemotherapy
New drugs
mass vaccination in endemic area
Typhoid vaccination programme for school
children or, with advent of new conjugate vi
vaccine, as part of EPI, should be considered.
56. Mary Mallon
(September 23, 1869 – November 11, 1938)
Also known as Typhoid Mary
was the first person in the United States to be identified as
a healthy carrier of typhoid fever.
She seemed a healthy woman when a health inspector
knocked on her door in 1907, yet she was the cause of
several typhoid outbreaks.
57. Mary Mallon
(September 23, 1869 – November 11, 1938)
Since Mary was the first "healthy carrier" of typhoid fever in the
United States, she did not understand how someone not sick
could spread disease -- so she tried to fight back.
She was forcibly quarantined twice by public health authorities
and died in quarantine.
Over the course of her career as a cook, she infected 47 people,
three of whom died from the disease.
It was also possible that she was born with the disease, as her
mother had typhoid fever during her pregnancy.
58. Mary Mallon
(September 23, 1869 – November 11, 1938)
MaryMallon died on November 11, 1938 at the age of
69
due to pneumonia (not typhoid), six years after a
stroke had left her paralyzed.
However, an autopsy found evidence of live typhoid
bacteria in her gallbladder.
Her body was cremated with burial in Saint Raymond's
Cemetery in the Bronx.
60. Serogroup Example (serotype)* Characteristic syndrome
A S. paratyphi A Enteric fever
B S. paratyphi B Enteric fever or gastroenteritis
B S. typhimurium Gastroenteritis
B S. heidelberg Gastroenteritis, bacteremia
C S. paratyphi C Enteric fever
C S. choleraesuis Bacteremia
C S. newport Gastroenteritis
D S. typhi Enteric fever
D S. enteritidis Gastroenteritis
D S. dublin Bacteremia
