DR.SMRUTI HAVAL

M.B.B.S.D.N.B.( FAMILY MEDICINE )

ENTERIC FEVER

HISTORY

In 1906, Irish immigrant Mary Mallon worked as a cook in the

Oyster Bay summer home of New York banker Charles Henry

Warren and his family. By the end of the summer, six members of

the household had contracted typhoid fever. The Warrens hired

sanitary engineer, George Soper, to determine the source of the

disease. Soper concluded that Mallon, while immune herself to the

disease, was its carrier. For three years, she was isolated on North

Brother Island, near Rikers Island, earning the nickname

"Typhoid Mary." Instructed not to cook for others upon her release,

she nevertheless changed her name and became a cook at a

maternity hospital in Manhattan. At least 25 staff members

contracted typhoid. "Typhoid Mary" returned to North Brother

Island, where she lived alone for 23 years, until her death in 1938.

She is shown here on the island in an undated photo. She died of a

stroke after 23 years in quarantine.

Mary Mallon

(wearing glasses)

photographed

with

bacteriologist

Emma Sherman

on North Brother

Island in 1931 or

1932, over 15

years after she

had been

quarantined there

permanently.

In 1880s, the typhoid bacillus was first discovered by

Eberth in spleen sections and mesenteric lymph nodes

from a patient who died from typhoid.

Robert Koch confirmed a related finding and succeeded in

cultivating the bacterium in 1881.

Serodiagnosis of typhoid was thus made possible by 1896.

Wright and his team prepared heat killed vaccine from

S.Typhi in 1896

Typhos in Greek means ,smoke and typhus fever got its name

from smoke that was believed to cause it. Typhoid means typhus-

like and thus the name given to this disease.

The term Typhoid was given by Louis 1829 to distinguish it from

typhus fever.

It is a disease of poor environmental sanitation and hence occurs

in parts of the world where water supply is unsafe and sanitation is

substandard.

term enteric fever or typhoid fever is a communicable

disease, found only in man and includes both typhoid

fever caused by S.Typhi and paratyphoid fever caused by

S.Paratyphi A,Band C.It is an acute generalized infection

of the reticuloendothelial system,intestinal lymphoid

tissue, and the gallbladder.

EPIDEMIOLOGY

According to the World Health Organization,

globally some 16 million cases occur annually

resulting in more than 600,000 deaths. More than 62%

of the global cases occur in Asia, of which, 7 million

occur annually in South East Asia. Other countries

with a high incidence include Central and South

America, Africa and Papua New Guinea.

The incidence of this disease in UK is reported to be just

one case per 1,00,000 population.

In 2O10, for example, 26,55,000 cases (incidence : 500

cases/ million) were reported from Africa with 1,30,000

deaths

The mean incidence of typhoid fever in developing

countries is estimated between 150 cases/million

population/year in Latin America to 1000cases/million

population/year in some Asian countries

INDIA

World largest outbreak of typhoid in SANGLI on

December 1975 to February 1976.This disease is

endemic in India

1992 : 3,52,980 cases with 735 deaths

1999 : 3,57,452 cases and 888 deaths

2005 : 2,78,451 cases and 304 deaths

Case fatality rate due to typhoid has been varying

between 1.1% to 2.5 % in last few years.

International Classification of

Disease Codes for Typhoid fever

Disease ICD-9 ICD-10

Typhoid & paratyphoid fevers 002 A01

Typhoid fever 002.0 A01.0

Salmonellae are gram – ve rods, facultative aerobic, Motile with peritrichate flagella, non-spore-forming

1-3μm ×0.5μm in size

Salmonella currently comprise 2000 serotypes

Two groups a) Enteric fever group

b) Food poisoning group

The bacilli are killed at 55ºc in one hour or at 60ºc in 15 minutes.

They are killed within 5 minutes by mercuric chloride or 5% phenol

Boiling or chlorination of water and pasteurization of milk destroy the bacilli

The proportion of typhoid to paratyphoid A is 10:1, Paratyphoid B is rare and paratyphoid C is very rare in India

Mode of transmission : The disease is transmitted byfaeco - oral route or urine – oral routes – eitherdirectly through hands soiled with faeces or urine ofcases or carriers or indirectly by ingestion ofcontaminated water, milk, food, or through flies.Contaminated ice, ice-creams, and milk products are arich source of infection.

Nutritional status :Malnutrition may enhance the susceptibility to

typhoid fever by altering the intestinal flora or other host defences.

Incubation period : Usually 10-14 days but it may be as short as 3 days

or as long as 21 days depending upon the dose of the inoculums.

Reservoir of infection : Man is the only known reservoir of infection -

cases or carriers.

Period of communicability: A case is infectious as long as the bacilli

appear in stool or urine

Age group : Typhoid fever may occur at any age but it is considered to

be a disease mainly of children and young adults. In endemic areas,

the highest attack rate occurs in children aged 8-13 years. In a recent

study from slums of Delhi, it was found that contrary to popular

belief, the disease affects even children aged 1-5 years.

Gender and race : Typhoid fever cases are more commonly seen in males than in females. On the contrary, females have a special predilection to become chronic carriers.

Occupation : Certain categories of persons handling the infective material and live cultures of S. typhi are at increased risk of acquiring infection.

Socio-economic factors : It is a disease of poverty as it is

often associated with inadequate sanitation facilities and

unsafe water supplies. Carriers may be temporary or

chronic.

Temporary (convalescent or incubatory) carriers usually

excrete bacilli up to 6-8 weeks. By the end of one year, 3-4

per cent of cases continue to excrete typhoid bacilli.

Persons who excrete the bacilli for more than a year after a

clinical attack are called chronic carriers.

PATHOGENESIS

DIAGNOSIS

First week: The disease classically presents with step-ladder fashion rise in temperature (40 - 41°C) over 4 to 5 days, accompanied by headache, vague abdominal pain, and constipation.

Second week: Between the 7 th -10 th day of illness, mild hepato-splenomegaly occurs in majority of patients. Relative bradycardia may occur and rose-spots may be seen.

Third week: The patient will appear in the "typhoid state" which is a state of prolonged apathy, toxaemia, delirium, disorientation and/or coma. Diarrhea will then become apparent. If left untreated by this time, there is a high risk (5-10%) of intestinal hemorrhage and perforation.

Rare complications:

1.NEUROPSYCHIATRIC COMPLICATIONS:

Delirium

Encephalopathy syndrome

Convulsions

Neuritis

Psychosis

HEART IN TYPHIOD:

ECG alteration in cases of typhoid are due to structural

damage to myocardium due salmonella typhi infection.

Clinically myocarditis in case of typhoid suspected if patient

has incordinate tachycardia, diminished intensity and soft

quality first heard sound. gallop rhythm ,rapidly developing

cardiac enlargent,condution defect & signs of CCF.

GI COMPLICATION

INTESTINAL PERFORATION

Patients with intestinal hemorrhage need intensive care, monitoring and blood

transfusion. Intervention is not needed unless there is significant blood loss.

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 if a fluoroquinolone is not being used to treat leakage of

intestinal bacteria into the abdominal cavity. Early intervention is crucial, and

mortality rates increase as the delay between perforation and surgery

lengthens. Mortality rates vary between 10% and 32%

TYPHOID HEPATITIS:

Important complication & should be seriously

consider in patient with fever with jaundice.

OSTEOMYLITIS :

OSTEOOMYLITIS IN SICKLE CELL DISEASE:

RENAL STATUS IN TYPHOID:

Typhoid nephritis leads to renal failure.

Renal involvement is functional or pathological

In form of transient glomerular disease or acute

renal failure due to haemolysis

HAEMATOLOGICAL PROFILE:

Leucopenia

Eosinophilia

Haemolytic uremic syndrome

Harmolytic anaemia

DIC

Normocellular bone marrow

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.

Rose spots

INVESTIGATIONS

Typhoid should be considered in any patient with

prolonged unexplained fever in endemic areas and in

those with a history of recent travel to endemic area.

Prolonged fever, rose spots, relative bradycardia and

leucopenia make typhoid strongly suggestive.

Widal test measures titres of serum agglutinins against

somatic (O) and flagellar (H) antigens which usually

begin to appear during the 2nd week. In the absence

of recent immunization, a high titre of antibody to O

antigen > 1:640 is suggestive but not specific.

Polymerase chain reaction (PCR) can be performed on

peripheral mononuclear cells. The test is more sensitive

than blood culture alone (92% compared with 50-70%)

but requires significant technical expertise

Blood cultures are positive in 70-80% of cases during

the 1st week.

Stool and urine cultures are usually positive (45-75%)

during the 2nd-3rd week.

Bone marrow aspirate cultures give the best

confirmation (85-95%)

The tracing of carriers in cities by sewer – swab

technique

RAPID TESTS FOR DIAGNOSING

TYPHOID

Typhi dot test that detects presence of Ig M and Ig G in one hour (sensitivity>95%, Specificity 75%)

Typhi dot-M, that detects Ig M only (sensitivity 90% and specificity 93%)

Typhi dot rapid (sensitivity 85% and Specificity 99%) is a rapid 15 minute immuno chromatographic test to detect Ig M.

Ig M dipstick test

IDEAL TUBEX: ONLY FOR SALMONELLA TYPHI

Wilson and Blair bismuth sulphite medium jet black colony with a

metallic sheen

Salmonella enterica.

Differential Diagnosis

Other disease or conditions that need to be eliminated

Other infectious diseases Other problems

•Brucellosis

•Infectious mononucleosis

•Leptospirosis

•Malaria

•Miliary tuberculosis

•Rickettsioses

•Tularemia

•Viral hepatitis

•Lymphoma

MANAGEMENT OF TYPHOID FEVER:

General: Supportive care includes

Maintenance of adequate hydration.

Antipyretics.

Appropriate nutrition.

Specific: Antimicrobial therapy is the mainstay treatment. Selection of antibiotic should be based on its efficacy, availability and cost.

Chloramphenicol , Ampicillin ,Amoxicillin , Trimethoprim &Sulphamethoxazole ,Fluroquinolones

In case of quinolone resistance – Azithromycin, 3rd generation cephalosporins (ceftriaxone)

ANTIBIOTICS THERAPY

IN ADULTS

INDICATION AGENT DOSAGE(ROUTE) DURATION

DAYS

EMPERICAL

TREATMENT

CEFTRIAXONE 1-2 G/D(IV) 7-14

AZITHROMYCIN 1 G/D (PO) 5

FULLY SUCEPTIBLE

CIPROFLOXACIN

(FIRST LINE)

500 MG BID (PO)

OR 400 MG q 12 h (IV)

14

AMOXICILLIN(SECOND

LINE)

1 G TID (PO) OR 2 GM q 6

H (IV)

14

CHLORAMPHENICOL 25 MG /KG TID (PO OR IV) 14-21

TRIMETHOPRIM-

SULFAMETHOXAZOLE

160 /800 MG BID (PO) 7-14

MULTIDRUG RESISTANT

CIPROFLOXACIN 500 MG BID (PO)

OR 400 MG q 12 h (IV)

5-7

CEFTRIAXONE 2-3 G/D (IV) 7-14

AZITHROMYCIN 1 GM/D (PO)c 5

NALIDIXIC ACID

RESISTANT

CEFTRIAXONE 2-3 G/D (IV) 7-14

AZITHROMYCIN 1 GM/D (PO) 5

HIGH DOSE

CIPROFLOXACIN

750 MG BID (PO) OR 400

MG q8h (IV)

10-14

Antibiotic Therapy for Non

typhoidal Salmonella

Infection in Adults

INDICATION AGENT DOSAGE(ROUTE) DURATION

DAYS

PREEMTIVE TRETMENTa

CIPROFLOXACINb 500 MG BID (PO) 2-3

BACTEREMIA

CEFTRIXONE 2 G/D (IV) 7-14

CIPROFLOXACIN 400 MG q 12 h (IV) THEN 500 MG BID (PO)

ENDOCARDITIS OR ARTHIRITIS

CEFTRIXONE 2 G/D (IV) 42

CIPROFLOXACIN 400 MG q 8 h (IV) THEN 750 MG BID (PO)

AMPICILLIN 2 GMq 4 h(IV)

MENINGITIS

CEFTRIAXONE 2G q 12 h (IV) 14-21

AMPICILLIN 2G q 4 h (IV)

OTHER LOCALISED INFECTIONS

CEFTRIAXONE 2 G/D (IV) 14-28

CIPROFLOXACIN 400 MG q 12 h (IV) OR 500 MG BID (PO)

AMPICILLIN 2 G q 6 h (IV)

SEVERE GASTROENTERITIS

CIPROFLOXACIN 400 MG q 12 h (IV) OR 500 MG BID (PO) 3-7

TRIMETHOPRIM-

SULFAMETHOXAZOLE

160/800 mg bid (po)

AMOXICILLIN 1 g tid (PO)

CEFTRIAXONE 2G q 6 h (IV)

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

Mortality can be reduced by some 80-90% in these high-

risk patients

SPECIFIC PROTECTION

THREE TYPES OF VACCINES

1. Injectable Typhoid vaccine

(TYPHIM –Vi, TYPHIVAX)

2. The live oral vaccine (TYPHORAL)

3. TAB vaccine

Indications for Vaccination1. Persons with intimate exposure to a

documented S. typhi carrier

2.Microbiology laboratory technologists who

work frequently with S. typhi

3.Immigrants

4. Military personnel

5.Travelers going to endemic areas who will be

staying for a prolonged period of time,

Typhoral1. This is a live-attenuated-bacteria vaccine manufactured

from the Ty21a strain of S. typhi.

2. The efficacy rate of the oral typhoid vaccine ranges

from 50-80%

3. Not recommended for use in children younger than 6

years of age.

4. The course consists of one capsule orally, taken an hour

before food with a glass of water or milk (1stday,3rd day

&5th day)

5. No antibiotic should be taken during this period

6. Immunity starts 2-3 weeks after administration and lasts

for 3 years

7. A booster dose after 3 years

SIDE EFFECTS.

Injectable Typhim -Vi

The most common adverse reactions are injection site

pain, erythema, and induration, which almost always

resolve within 48 hours of vaccination. Occasional fever,

flu-like episodes, headache, tremor, abdominal pains,

vomiting, diarrhea, and cervical pains have been

reported.

Typhoral

Nausea, abdominal pain and cramps, vomiting, fever,

headache, and rash or urticaria may occur in some

instances but are rare.

Injectable Typhim -Vi

1. This single-dose injectable typhoid vaccine, from the

bacterial capsule of S. typhi strain of Ty21a.

2. This vaccine is recommended for use in children

over 2 years of age.

3. Subcutaneous or intramuscular injection

4. Efficacy : 64% -72%

CONTROL OF TYPHOID FEVER

MEASURES DIRECTED TO RESERVOIR

a) Case detection and treatment

b) Isolation

c)Disinfection of stools and urine

d)Detection & treatment of carriers

MEASURES AT ROUTES OF TRANSMISSION

a) Water sanitation

b) Food sanitation

c) Excreta disposal

d) Fly control

MEASURES FOR SUSCEPTIBLES

a) immunoprophylaxis

b)health education

Keep the premises and kitchen utensils clean.

Dispose rubbish properly.

Keep hands clean and fingernails trimmed.

Wash hands properly with soap and water before eating or handling food, and after toilet or changing diapers.

Drinking water should be from the mains and preferably boiled.

Purchase fresh food from reliable sources. Do not patronize illegal hawkers.

Avoid high-risk food like shellfish, raw food or semi-cooked food.

Wear clean washable aprons and caps during food preparation.

Clean and wash food thoroughly.

Scrub and rinse shellfish in clean water. Immerse them in clean water for sometime to allow self-purification.

Remove the viscera if appropriate

HEALTH PROMOTION

Store perishable food in refrigerator, well covered.

Handle and store raw and cooked food especially seafood separately (upper compartment of the refrigerator for cooked food and lower compartment for raw food) to avoid cross contamination.

Clean and defrost refrigerator regularly and keep the temperature at or below 4ºc

Cook food thoroughly.

Do not handle cooked food with bare hands; wear gloves if necessary.

Consume food as soon as it is done.

If necessary, refrigerate cooked leftover food and consume as soon as possible. Reheat thoroughly before consumption. Discard any addled food items.

Exclude typhoid carrier from handling food and from providing care to children.

THE FUTURE OF TYPHOID

Cheap, Rapid and reliable serological test

Fluoroquinolone and cephalosporin resistant case

Combination chemotherapy

New drugs

THANK YOU