TYPHOID FEVER

Dr.Rahul.K.RDept. of Swasthavritta

Amrita School of Ayurveda

Typhoid Fever• Fever cased due to a systemic infection caused by Salmonella typhi.• Found only in man.• Characterized by continues fever for 3 to 4 weeks.• Relative Bradycardia

• Sphygmothermic dissociation or Faget sign. {Liebermeister's rule ( In normal fever)}

• Lymphoid tissue involved with constitutional symptoms.• Also called Enteric fever• Disease occur sporadically, epidemically or endemically.

Problem statement• Occurs in all part of the world with sub standard water supply and sanitation.• Uncommon in developed countries.• Developing areas of Asia, Africa Latin America the disease became a public

problem.• In 1940 introduction of antibiotics reduce mortality and morbidity rate

drastically.• 2004 WHO estimates the typhoid fever burden @ 21million cases / year of

which 2,16,000 – 6,00,000 death/year.• In 1950 antibiotic resistant organism became a growing problem

Problem statement (WORLD)• 1989 drug resistance was reported in many countries. • >50% strains in Asia may already be resistant to most of antibiotics.• MDR strains become resistant to all 3 first line antibiotics.

• Chloramphenicol• Ampicillin• cortimoxazole

• Compared with sensitive strain a 10 fold higher rate of post treatment symptomatic bacterial carriers are reported with MDR S.typhi infection.

• Without effective treatment the fever kills 10% of the infected.• Huge socio-economic impact because typhoid survivors take several

months to recover.

High endemicity (>100 cases per lac per year) Medium endemicity (10 cases per lac per year) Low endemicity (<10 cases per lac per year)

India• World largest outbreak of typhoid in SANGLI (Maharashtra State) on

December 1975 to February 1976. This disease is endemic in India• 1992 :3,52,980 cases with 735 deaths• 1993 :3,57,452 cases and 888 deaths• 1994 :2,78,451 cases and 304 deaths• 2011 :1.06million cases & 346 deaths• Prevalence- 88 cases/lac population• Death rate due to typhoid is 0.029/lac population.• In south-East Asia 50% or more of the strains of bacteria has MDR

IN KERALA 2014

Total typhoid cases is 1956

District Wise Surveillance Data

2014

Highest no: of cases were reported in Palakkad(433)Alappuzha and Kasaragod with zero cases

IN KERALA 2015

Total cases till June2015 -861

District Wise Surveillance Data

2015

Highest no of cases in Palakkad-316Least in Kasaragod with 0 cases

Epidemiological determinantsAGENT FACTOR

• S.typhi is the major cause of enteric fever.• S.para A & S.para B are relatively infrequent.• S. typhi is a gram-negative, facultative aerobic, non spore forming bacteria

that is motile due to its peritrichous flagella• S.typhi has three antigens

1. Antigen O2. Antigen H3. Antigen Vi

• At least 80 phage types.• Phage typing- useful epidemiological tool in tracing source of epidemics.• Bacterium survives intracellularly in tissues of various organs.

Epidemiological determinantsAGENT FACTOR

• They are readily killed by • Drying • Pasteurization• Common disinfectants

• Factors influencing the onset of disease in man are infecting dose and virulence of the organism

Epidemiological determinantsRESERVOIR OF INFECTION

• Man is the only known reservoir of infection ie case & carriers• Case

• May be mild/ missed /severe.• Is infectious as long as bacilli appear in stool or urine.

• Carrier • may be temporary (incubatory / convalescent) or chronic.• Convalescent carriers excrete bacilli for 6 to 8 weeks then the amount diminishes

rapidly.• 3months - <4% carrier state.• 1 year - < 3% carrier state.• After 1 year, carriers are called chronic carriers (2to5% cases)• They excrete bacilli for up to 50 years, continues or intermittently.• Famous ‘Typhoid Mary’ is a case of chronic carrier.

CONT..• Faecal carriers are frequent than urinary carriers.• Chronic urinary carriers are associated with urinary track abnormalities.

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.

• Mary Mallon was a cook in Oyster Bay, New York in early 1900s.

• Gave rise to more than 1300 cases in her life time.

• She died of pneumonia after 26 years in quarantine.

Epidemiological determinantsSOURCES OF INFECTION

• Two types of sources• Primary source• Secondary source

• Primary sources of infection are faeces and urine of case / carriers.

• Secondary sources are contaminated• Water• Food• Fingers • flies

Host factorsAGE• Highest incidence occurs in 5-19 years of age.• After the age of 20 the incidence fall probably due to acquisition of

immunity from clinical or subclinical cases.SEX• Cases more in Males than Female• Carrier rate is more in females.

Host factorsIMMUNITY• All ages are susceptible to infections• antibody may be stimulated by infection or immunization.• Antibody against (O) antigen is higher in patient with the disease • Antibody against (H) antigen is higher in immunized person. • S. typhi is intracellular organism so cell mediated immunity plays a

major role in combating the infection.• Typhoid fever not always confer solid immunity, second attack may

occur when challenged with large oral dose.• Factors contributing to resistance are gastric acidity & intestinal local

immunity.

Environmental & social factors• Fever observed all through the year• Peak incidence is reported during July-September

(rainy season & increase in fly population)• Outside the human boy bacilli found in water, ice, food , milk & soil.• Bacilli do not multiply in water, perishes with in 48hrs to 7 days.• Survive in ice and ice-creams for upto 1 month.• survive in soil irrigated with sewage for upto 70days, 35days in dry

summer.

Cont…• Bacilli Multiply & survive in food, grows rapidly in milk with

out altering the taste.• Vegetables grown in sewage farms and washed in

contaminated water are +ve health hazard.• Contaminated drinking water• Open air defecation & urination• Low standard of food & personal hygiene ignorance.• Typhoid fever therefore be regarded as a index of general

sanitation in any country.

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

bacilli ingested.

MODE OF TRANSMISSION

Faeces and urine

from cases or carriers

water

soil

flies

fingers

Foods raw or cooked

Mouth of well

persons

• The disease is transmitted by “faecal-oral route” or “urine–oral routes” either directly through hands soiled with faeces or urine of cases or carriers or indirectly by ingestion of contaminated water, milk, food, or through flies.

• Contaminated ice, ice-creams, and milk products are a rich source of infection.

CLINICAL FEATURES• First week: malaise, headache, cough & sore throat in prodromal stage.

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 or ‘pea soup Diarrhoea’.

• Second week: Between the 7th -10th day of illness the fever reach a plateau, patient looks toxic, exhausted and often prostrated.

• Mild hepatosplenomegaly occurs in majority of patients.• Relative bradycardia may occur and rose-spots may be seen.

• Principally on trunk• Pink papule 2-3mm diameter, • Fades on pressure, disappear in 3-4days.

Cont.• Third week: The patient will appear in the "typhoid state" which is a

state of prolonged apathy, toxaemia, delirium, disorientation and/or coma.

• Diarrhoea will then become apparent. If left untreated by this time, there is a high risk (5-10%) of intestinal haemorrhage and perforation (sudden drop in temperature & sign of shock)

• Serious complications in 10% cases if disease persist longer than 2weeks• Rare complications:

• Hepatitis, Pneumonia, Thrombophlebitis, Myocarditis, Cholecystitis, • Nephritis, Osteomyelitis, and Psychosis.• 2-5% patients may become Gall-bladder carriers

Case fatality rate• Fatality rate ranges from 1% TO 4%• Fatality rate in children aged less than 4 years- 4%• Fatality rate in children aged greater than 4 years – 0.4%• Untreated cases fatality rate may rise to 10-20%

Ingestion of contaminated food or water Salmonella bacteria

Invade small intestine and enter the bloodstream

Carried by white blood cells in the liver, spleen, and bone marrow

Multiply and re enter the bloodstream

Bacteria invade the gallbladder, biliary system, and the lymphatic tissue of the bowel and multiply in high numbers

Then pass into the intestinal tract and can be identified for diagnosis in cultures from the stool tested in the laboratory

Laboratory diagnose of typhoidMICROBIOLOGICAL PROCEDURE• Isolation of S.typhi bacteria from blood, bone marrow and stool• Blood culture is a chief support of diagnosis.SEROLOGICAL PROCEDURE• Widal test is a tube agglutination test employed in the

serological diagnosis of enteric fever. • The test is named after Georges Fernand Isidore Widal, a

French physician and bacteriologist.• Slide Widal test is more popular among diagnostic laboratories.

SEROLOGICAL PROCEDURE• Flexi-Widal test measures agglutinating antibodies against O & H antigen.

• O antibody appears in 6-8days• H antibody appears in 10-12days after onset of disease.• Test performed in acute serum.• Moderate sensitivity & specificity. • -ve for 30% known cases (may be due to prior antibiotic treatment)• O & H antigen are also present in other salmonella serotypes.• Has cross reacting epitopes with other enterobacteriea leads to false +ve results.

• Malaria, typhus etc

Laboratory diagnose of typhoidNEW DIAGNOSTIC TEST• IDL Tubex test.

• Detect IgM09 antibody from patient.• Result with in 10 minutes.• Inhibition Magnetic Binding Immunoassay.

• Typhidot • Detection of IgM & IgG antibodies• Typhidot test gave a sensitivity of 100 % and

specificity of 80 % .• Typhidot M – modified form

• Detects IgM (against LPS of S. typhi)

CONTROL & PREVENTION• Control and elimination of typhoid fever is with in the scope of modern

public health• May developed countries typhoid become exotic.• There are three line of defence against the disease.

1. Control of reservoir.2. Control of sanitation.3. Immunization.

• Weakest link of transmission is sanitation which is amenable to control.

Control of reservoir • Usual method of control of reservoir are

• Identification• Isolation• Treatment• Disinfection

Control of reservoir• CASES

i. Early diagnosis:• Early symptoms are nonspecific.• Culture of blood & stool are important investigations in diagnosis.

ii. notification:• Done where such notification is mandatory.

iii. Isolation:• Better to transfer the case to hospital for treatment and prevent spread.• Should be isolated till 3 bacteriologically –ve stools/urine reports are obtained on 3

separate days.iv. Treatment:

• Fluoroquinolone is the drug of choice.• Patient seriously ill and toxic may be given an injection of Hydrocortisone 100mg daily

for 3-4days

Cont..

Treatment of typhoid fever

Susceptibility Antibiotic Daily dose

mg/kg

Days Antibiotic Daily dosemg/kg

Days

Fully sensitive FluoroquinoloneCiprofloxacin/

ofloxacin

15 5-7 ChloramphenicolAmoxicillinTMP-SMX

50-7575-100

8-40

14-211414

Multidrugresistance

FluoroquinoloneOr Cefixime

1515-20

5-77-14

AzithromycinCefixime

8-1015-20

77-14

Quinoloneresistance

AzithromycinOr Ceftriaxone

8-1075

710-14

Cefixime 20 7-14

OPTIMAL THERAPY ALTERNATIVE EFFECTIVE DRUGS

Control of reservoir• CASES

v. Disinfection• The source of infection (urine & stools) should be received in closed container and

disinfected with 5% Cresol for at least 2hours.• Soiled cloths and linen should be soaked in 2% chlorine & steam sterilized.• Doctors & Nurses should disinfect their hands

vi. Follow up• Examination of stool & urine should be done for S.typhi 3-4months after discharge &

again after 12months to prevent carrier state.

• Early diagnosis and treatment reduce mortality rate to 1% compared to 30% in untreated cases.

Control of reservoir• CARRIER

Carriers are the ultimate source of typhoid fever.Carrier identification & treatment is most radical way of control typhoid.

i. Identification:• Identified by culture and serological examination.• Duodenal drainage establish the presence of salmonella in biliary tract in carriers.• The Vi antibodies are present in 80% of chronic carrier.

ii. Treatment:• Intense course of Ampicillin/amoxicillin 4-6gm/day + Probenecid (2gm/day) for 6weeks. (70% success

rate)• Cholecystectomy with concomitant ampicillin therapy as the most successful approach of treatment.• Urinary carriers are easy to treat, nephrectomy is done when kidney is damaged.

Cont..

Control of reservoiriii. Surveillance

• Carrier should be kept under surveillance.• Should be prevented from handling food, milk or water.

iv. Health education• Health education regarding washing of hands with soap, after defecation & urination and

before preparing food.

• Management of carrier continue to be a unsolved problem, this is the basic problem in elimination of typhoid fever.

Control of Sanitation• Protection and purification of drinking water supplies.• Improvement of basic sanitation.• Promotion of food hygiene.

• Proper sanitation along with health education result in steady reduction of typhoid morbidity.

Interrupts transmission ofTyphoid fever

Immunization • Its a complimentary approach to prevent typhoid.• It doesn’t get a 100% protection, but lowers incidents & complications

of infection.• Given to any age above 2 years.• Its recommended to:

1. Who living in endemic area.2. Household contact.3. Groups at high risk (school children, Hospital staff)4. Travellers proceeding to endemic area.5. Those attending melas and yatras.

Anti-Typhoid Vaccines• Killed whole cell parenteral vaccine (1896-1960).

• Gives effective protection • Produce strong side effects.

• Two safe and effective vaccines are now available • Defined subunit antigen• Whole cell live attenuated bacteria

Anti-Typhoid VaccinesVi polysaccharide vaccine• First licensed in US in 1994.• Contains purified Vi capsular polysaccharide from Ty2 S.typhi.• Elicit T-cell independent IgG response• Administered subcutaneously/intramuscularly.• Single human dose 25µg of antigen.• Vaccine is stable for 6months at 37°C.• Recommended storage temp 2-8°C.• It doesn’t elicit immune response in children less than 2 years.

• Vaccine is licensed for individuals aged ≥2years.• 1 dose is required • Confers protection 7 days after injection• Revaccination recommended every 3 years.• Can be administered along with other vaccines relevant for

international travellers.Safety • No serious adverse events.

Anti-Typhoid VaccinesTy21a Vaccine• Oral vaccine with live attenuated Ty2 strain of S.typhi (mutated multiple

genes)• Lyophilized vaccine are available as enteric coated capsules.• Protection is influenced by no: of doses and there spacing.• Storage 2-8°C, stable for 14days @ 25°C.Schedule• Licensed for use in individuals aged ≥5 years• 3 dose regimen is recommended.• Administered every other day on 1,3&5th day.• Immunity is achieved after 7days after last dose.• Revaccination recommended every 3 years in endemic areas & travellers

Safety and precautions• Proguanil & antibiotic drugs should be stopped 3 days before until 3

days after giving Ty21a.• Ty21a is well tolerated and has low adverse reaction• Not recommended in

• congenital or acquired immune deficiency• Immunosuppressive & antimitotic drugs• Acute febrile illness and acute intestinal infections.

Thank you