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Salmonella Essential learning for Medical Students Dr.T.V.Rao MD Dr.T.V.Rao MD 1

Salmonella Essential learning for Medical Students

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Page 1: Salmonella Essential learning for Medical Students

SalmonellaEssential learning for Medical Students

Dr.T.V.Rao MD

Dr.T.V.Rao MD 1

Page 2: Salmonella Essential learning for Medical Students

Salmonella• Causes Infections in Humans and

vertebrates,• Enteric Fever ( Typhoid fever )• Gastroenteritis• Septicemias,• Carrier state a concern

Dr.T.V.Rao MD 2

Page 3: Salmonella Essential learning for Medical Students

Salmonella • A Very complex group• Contains more > 2,500 spp• Typed on the basis of Serotyping, and species

typing• Divided into two groups 1 Enteric fever group 2 Food poisoning group – 3 Septicemias

Dr.T.V.Rao MD 3

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Key points

• There are more than 2500 different antigenic types of Salmonella; those pathogenic to man are serotypes of S. enterica.

• Most serotypes of S. enterica cause food-borne gastroenteritis and have animal reservoirs.

• S. enterica serotypes Typhi and Paratyphi cause typhoid fever.

Dr.T.V.Rao MD 4

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Enteric FeverTyphoid Fever

• Caused by Salmonella typhi, and other Groups called as Paratyphoid A, B, C

• Salmonella typhi - Causes Typhoid• Salmonella Paratyphi A,B,C Causes Paratyphoid

fevers.• Food Poison group• Spread from Animals – Humans • Causes Gastroenteritis – Septicemias,

Localized InfectionDr.T.V.Rao MD 5

Page 6: Salmonella Essential learning for Medical Students

Salmonella typhi• The bacterium Salmonella typhi is

present only in human beings and is transmitted through contaminated food or water. People with this infection carry the bacterium in their intestines and bloodstream, and those who have recovered from the disease could still have the bacterium in their system; they are known as ‘carriers’ of the disease. Both ill people and carriers shed Salmonella typhi in their stool

Dr.T.V.Rao MD 6

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Food handlers spread the infection

• Both ill people and carriers shed Salmonella typhi in their stool

• Infection is usually spread when food or water is handled by a person who is shedding the bacterium or if sewage water leaks into drinking water or food that is then consumed..

Dr.T.V.Rao MD 7

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Typhoid fevers are prevalent in many regions in the World

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Typhoid Mary Most Dangerous Woman in America

Dr.T.V.Rao MD 9

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Typhoid Mary

• A famous example is “Typhoid” Mary Mallon, who was a food handler responsible for infecting at least 78 people, killing 5. These highly infectious carriers pose a great risk to public health.

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Typhoid Mary• "Typhoid Mary," real name Mary Mallon,

worked as a cook in New York City in the early 1900s. Public health pioneer Sara Josephine Baker, MD, PhD tracked her down after discovering that she was the common link among many people who had become ill from typhoid fever She was traced to typhoid outbreaks a second time so she was put in prison again where she lived until she died.

Page 12: Salmonella Essential learning for Medical Students

French physician Pierre Charles Alexandre Louis first proposed the name “typhoid fever”

William Wood Gerhard who was the first to differentiate clearly between typhus fever and typhoid in 1837.

 

Page 13: Salmonella Essential learning for Medical Students

Carl Joseph Eberth who discovered the typhoid bacillus in 1880.

Georges Widal who described the  ‘Widal agglutination reaction’ of the blood in 1896.

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Morphology of Salmonella

• Gram negative bacilli

• 1-3 / 0.5 microns,

• Motile by peritrichous flagella

Dr.T.V.Rao MD 14

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S.typhi with Flagella

Dr.T.V.Rao MD 15

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Bacteriology –Typhoid fever

• The Genus Salmonella belong to Enterobacteriaceae

• Facultative anaerobe• Gram negative bacilli• Distinguished from

other bacteria by Biochemical and antigen structure

Dr.T.V.Rao MD 16

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Different types of Salmonella

I - entericaII - salamaeIIIa -arizonaeIIIb -diarizonaeIV - houtenaeV - bongoriVI - indica

Page 18: Salmonella Essential learning for Medical Students

Cultural Characters • Aerobic / Facultatively anaerobic• Grows on simple media – Nutrient agar,• Temp 15 – 41ºc / 37º c• Colonies appear as large 2 -3 mm, circular, low

convex,• On MacConkey medium appear Colorless ( NLF )Selective Medium - Wilson Blair Bismuth sulphide

medium. Produce Jet black colonies H2 S produced by Salmonella typhi

Dr.T.V.Rao MD 18

Page 19: Salmonella Essential learning for Medical Students

Enrichment MediumLiquid Medium

• Selenite F medium• Tetrathionate broth • Above medium are used for

isolation of Salmonella from contaminated specimens

• Particularly stool specimens..Dr.T.V.Rao MD 19

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Identifying Enteric Organisms

• Isolates which are Non lactose fermenting • Motile, Indole negative• Urease negative• Ferment Glucose,Mannitol,Maltose• Do not ferment Lactose, Sucrose• Typhoid bacilli are anaerogenic• Some of the Paratyphoid form acid and gas• Further identification done by slide

agglutination testsDr.T.V.Rao MD 20

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Biochemical Characters • Glucose ,Mannitol ,Maltose produce A/G• Salmonella typhi do not produce gas• Lactose/Salicin/sucrose not fermented.• Indole –• Methyl Red +• V P -• Citrate +• Urea –• H2S – produced by Salmonella typhi• Paratyphi A do not produce H2S

Dr.T.V.Rao MD 21

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Resistance of Salmonella

• 55º c – 1 hour• 60º c – 15 MT• Boiling ,Chlorination,

Pasteurization Destroy the Bacilli.

Dr.T.V.Rao MD 22

Page 23: Salmonella Essential learning for Medical Students

SalmonellaAntigenic Structure

• H – Flagellar antigens• O – Somatic antigen,• Vi – Surface antigen in some species only• H antigens also called flagellar antigens, heat

labile protein,• Boiling destroys antigenicity• When mixed with Antiserum produces agglutination

and fluffy clumps are produced• H antigens are strongly immunogenic Induces

antibodies rapidly,

Dr.T.V.Rao MD 23

Page 24: Salmonella Essential learning for Medical Students

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.

Dr.T.V.Rao MD 24

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Flagellar Antigens • Flagellar or H Antigens are strongly

immunogenic and induces antibody formation rapidly and in high titers following infection or immunization. The flagellar antigen is of a dual nature, occurring in one of the two phases.

Dr.T.V.Rao MD 25

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Antigens – Salmonella ( cont )

Dr.T.V.Rao MD 26

• O Antigens • Forms integral part of Cell wall,• Like Endotoxin• 0 Antigens unaffected by boiling.• When mixed with antiserum produce chalky

clumps are formed, take more time reaction, at high temp 50º – 55º c

• O antigens are less immunogenic. than H antigens

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Antigen (Vi) – Salmonella ( contd )• Vi antigens • Many strains in S.typhi covers the O antigens-

prevents agglutination.• Resembles like K antigens • Destroyed after boiling at 60º c / 1 hour.• Vi a polysaccharide • Acts as virulence factor, protects the bacilli against

Phagocytosis and activity of Complement• Poorly immunogenic• Low titer of antibodies are produced, Not diagnostic

Dr.T.V.Rao MD 27

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Classification of Salmonella

• Classified on the basis of Kauffmann-White Scheme

• Structure of 0 and H antigens are taken into consideration,

• More than 2000 species characterized.

Dr.T.V.Rao MD 28

Page 29: Salmonella Essential learning for Medical Students

Kauffmann – White scheme• Serotype 0 antigens H antigens Phase 1 21.Typhi 9,12,(Vi) d 1,22 Paratyphi A 1,2.12 a -3 Paratyphi B 1,4,5,12 b 1,24 Typhimuruim 1,4,5,12 I 1,75 Enteritidis 1,9,12 g m 1,2

Dr.T.V.Rao MD 29

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Antigenic Variation in Salmonella

• May be phenotypic / Genotypic• H to O = loss of Flagella May be phase variation from I to II V to W variation S to R variation

Dr.T.V.Rao MD 30

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Pathogenicity • Salmonella are definite parasites to

humans.• Eg S.typhi.• S.paratyphi A, B ,C• Other groups Salmonella • The important clinical syndromes 1. Enteric fever, Septicemias,

gastroenteritis.Dr.T.V.Rao MD 31

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Enteric Fever: S. typhi• Ileocecal penetration• intraluminal multiplication• mononuclear response (macrophages)• Salmonella remains alive• 2nd week - lymphoid hyperplasia (mesenteric

lymph nodes)• back to bowel

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Enteric FeverTyphoid

• Typhoid – caused by S.typhi• Paratyphoid Caused by

Paratyphi A,B,C• Typhoid --- Like Typhus• Infective dose ID50 / 107,

Dr.T.V.Rao MD 33

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Fever• All the events coincides with Fever and other

signs of clinical illness• From Gall bladder further invasion occurs in

intestines• Involvement of peyr’s patches, gut lymphoid

tissue• Lead to inflammatory reaction, and infiltration

with monocular cells• Leads to Necrosis, Sloughing and formation of

chacterstic typhoid ulcers

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Typhoid fever

Page 36: Salmonella Essential learning for Medical Students

Rashes in Typhoid• May present with rash,

rose spots 2 -4 mm in diameter raised discrete irregular blanching pink maculae's found in front of chest

• Appear in crops of upto a dozen at a time

• Fade after 3 – 4 days

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Dr.T.V.Rao MD 37

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Events in a Typical typhoid Fever

Dr.T.V.Rao MD 38

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Pathology and Pathogenesis

• Bacilli enter through ingestion,• Bacilli attach to Microvilli,ileal mucosa,

penetrate to Lamina propria and sub mucosa • Phagocytosis by Polymorphs and

Macrophages• Enters the mesenteric lymph nodes • Enter the thoracic duct – Blood stream

Dr.T.V.Rao MD 39

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Infective Dose

• For human infections, the number of bacteria that must be swallowed in order to cause infection is uncertain and varies with the serotype. In most of these the median infective dose for most serotypes, including Typhi, has varied from 106 to 109 viable organisms.

Dr.T.V.Rao MD 40

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Pathology and Pathogenesis

• Bacteremia Spread to Liver, Gall bladder, Spleen, Bone marrow, Lymph nodes, Lungs, Multiply in kidneys

Once again spill into Blood streamCauses clinical illness.

Dr.T.V.Rao MD 41

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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 reenter the bloodstream

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Pathology and Pathogenesis• Multiply abundantly in Gall bladder,• Bile rich source of Bacteria • Spill into Intestine, infects payers patches,

Lymph follicles • Inflammation – Undergo necrosis, Slough off• Typhoid ulcers• Typhoid ulcers can cause perforation and

hemorrhage • Duration of Illness 3 – 4 weeks• Incubation 7 -14, ( 3-56 days )

Dr.T.V.Rao MD 43

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What is Enteric Fever Typhoid Fever

• Enteric fever is caused by strains of S. Typhi or S. Paratyphi A, B or C; although S. Paratyphi B, which gene sequence analysis suggests is a variant of S. Java, is more likely to cause non-typhoidal diarrhoea.

Dr.T.V.Rao MD 44

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S.typhi more serious• The clinical features tend to be more

severe with S. Typhi (typhoid fever). After penetration of the ileal mucosa the organisms pass via the lymphatic's to the mesenteric lymph nodes, whence after a period of multiplication they invade the bloodstream via the thoracic duct.

Dr.T.V.Rao MD 45

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Symptoms• No symptoms - if only a mild exposure; some people become "carriers" of

typhoid. • Poor appetite, • Headaches, • Generalized aches and pains, • Fever, Lethargy, Lethargy, • Lethargy, • Diarrhea,• Have a sustained fever as high as 103 to 104 degrees Fahrenheit (39 to 40

degrees Celsius),• Chest congestion develops in many patients, and abdominal pain and

discomfort are common,• Constipation, mild vomiting, slow heartbeat.

Page 48: Salmonella Essential learning for Medical Students

Progress in Enteric Fever• The liver, gall bladder, spleen, kidney and bone

marrow become infected during this primary bacteraemic phase in the first 7-10 days of the incubation period. After multiplication in these organs, bacilli pass into the blood, causing a second and heavier bacteraemia, the onset of which approximately coincides with that of fever and other signs of clinical illness.

Dr.T.V.Rao MD 48

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Progress in Enteric Fever

• From the gall bladder, a further invasion of the intestine results. Peyer's patches and other gut lymphoid tissues become involved in an inflammatory reaction, and infiltration with mononuclear cells, followed by necrosis, sloughing and the formation of characteristic typhoid ulcers occurs.

Dr.T.V.Rao MD 49

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Immunity in Typhoid

• Typhoid bacilli are Intracellular pathogens

• Cell mediated immunity is crucial

Dr.T.V.Rao MD 50

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Early symptoms of Typhoid Fever

• The incubation period is usually 1-2 weeks, and the duration of the illness is about 3-4 weeks. Symptoms include:

• Poor appetite• Headaches• Generalized aches and pains• Fever as high as 104 degrees Farenheit• Lethargy• Diarrhea

Dr.T.V.Rao MD 51

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Diarrhea Nausea Vomiting Stomach pain Headache Fever Onset 12-72 hours after

infection

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Clinical manifestation• Head ache, malise,anorexia ,coated tongue • Abdominal discomfort,• Constipation / Diarrhea • Step ladder type fever,• Relative bradycardia,• A soft palpable spleen• Hepatomegaly• Rose spots appear

Dr.T.V.Rao MD 53

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Events in a Typical typhoid Fever

Dr.T.V.Rao MD 54

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Complications of Enteric fever

• Intestinal perforation,• Hemorrhage,• Circulatory collapse.• Bronchitis Bronchopneumonia,• Meningitis,• Cholecystitis,• Arthritis,Periostitis / Nephritis,• Osteomyletis,

Dr.T.V.Rao MD 55

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Relapses in Typhoid Fever

• Apparent recovery can be followed by relapse in 5-10% of untreated cases. Relapse is usually shorter and of milder character than the initial illness, but can be severe and may be fatal. Severe intestinal haemorrhage and intestinal perforation are serious complications that can occur at any stage of the illness.

Dr.T.V.Rao MD 56

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Other complications• Causes relapses in

particular to patients treated with chloramphenicol.

• S.paratyphi produce septicemias.

Dr.T.V.Rao MD 57

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Typhoid carriers • Salmonella enterica causes

approximately 16 million cases of typhoid fever worldwide, killing around 500,000 per year. One in thirty of the survivors, however, become carriers. In carriers the bacteria remain hidden inside cells and the gall bladder, causing new infections as they are shed from an apparently healthy host.

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Carriers may be 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.

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Carrier Stage in Typhoid Fever• Most people infected with salmonella

continue to excrete the organism in their stools for days or weeks after complete clinical recovery, but eventual clearance of the bacteria from the body is usual. A few patients continue to excrete the salmonellae for prolonged periods. The term chronic carrier is reserved for those who excrete salmonellae for a year or more.

Dr.T.V.Rao MD 60

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Carrier Stage in Typhoid Fever• Chronic carriage can follow symptomatic

illness or may be the only manifestation of infection. It can occur with any serotype, but is a particularly important feature of enteric fever: up to 5% of convalescents from typhoid and a smaller number of those who have recovered from paratyphoid fever become chronic carriers, many for a lifetime.

Dr.T.V.Rao MD 61

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Carrier Stage in Typhoid Fever• The bacilli are most commonly present in

the gall bladder, less often in the urinary tract, and are shed in faeces and sometimes in urine. The long duration of the carrier state enables the enteric fever bacilli to survive in the community in non-epidemic times and to persist in small and relatively isolated communities.

Dr.T.V.Rao MD 62

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Epidemiology• Developed countries - Controlled.• Water supply/ Sanitation /Economically

poor.• S.typhi and S.paratyphi are prevalent in India• Previously Typhi are more common

Paratyphoid A on raise.• Age 5 – 20 years, Sanitation

Dr.T.V.Rao MD 63

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Epidemiology• Sanitation has great role• Source an active patient or a Carrier shed the

Bacilli.• Who are carriers. Convalescent carrier 3 weeks to 3 months Temporary carrier 3 months to 1 year Chronic carrier > 1 year,Women attain more carrier stage

Dr.T.V.Rao MD 64

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Epidemiology (Contd)• Bacilli persist in the Gall bladder and kidney• Food handlers spread the infection• Cooks great role• S.typhi and S.paratyphi in humans• S.para B in Animals,• Typhoid spread through Water, Milk, FoodHIV patients potentially susceptible for Typhoid disease.

Dr.T.V.Rao MD 65

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Dr.T.V.Rao MD 66

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Bacteriological Diagnosis of Typhoid Fever

• Selective media, such as Deoxycholate-citrate agar or xylose-lysine Deoxycholate agar, are used for the isolation of salmonella bacteria from faeces. Fluid enrichment media, such as Tetrathionate or selenite broth, are also useful to detect small numbers of salmonellae in faeces, foods or environmental samples.

Dr.T.V.Rao MD 67

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Bacteriological Diagnosis of Typhoid Fever

• Suspicious colonies from the culture plates are tested directly for the presence of Salmonella somatic (O) antigens by slide agglutination and subcultured to peptone water for the determination of flagellar (H) antigen structure and further biochemical analysis.

Dr.T.V.Rao MD 68

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Bacteriological Diagnosis of Typhoid Fever

• A presumptive diagnosis of salmonellosis can often be made within 24 h of the receipt of a specimen, although confirmation may take another day, and formal identification of the serotype takes several more days. A negative report must await the result of enrichment cultures - at least 48 h.

Dr.T.V.Rao MD 69

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How we Diagnose Typhoid Fever• Diagnosis is made by any blood, bone marrow or

stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar ). In epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of Widal test and cultures of the blood and stool.

Dr.T.V.Rao MD 70

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Laboratory Diagnosis ofTyphoid Fever

• 1 Isolation of Bacilli. A Gold standard • 2 Diagnosis for presence of Antibodies,• Positive Blood culture – A gold standard• Isolation from Feces and Urine ?• Detection of Antibodies Inconclusive.• Newer methods Detection of antigen in Blood and Urine

Dr.T.V.Rao MD 71

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Blood Culture1 st week Positive in 90 %2 nd week Positive in 75 %3 rd week Positive in 60 %> 3 weeks positive in 25 %Draw 5 – 10 cc of Blood by venipuncture. ADD to 50 -100 ml of Bile broth.Incubate at 37 c /Subculture in MacConkey At regular intervals

Dr.T.V.Rao MD 72

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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%

Dr.T.V.Rao MD 73

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Castaneda’s method ofBlood Culture

• Double medium used Solid/Liquid medium in the same Bottle.

• Bottle contains Bile broth/agar slant,• For subculture the bottle is merely tilted.• A subculture into MacConkey at regular

intervals,• Reduces the chances of contamination• Increases the chances of isolation.

Dr.T.V.Rao MD 74

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Salmonella on Mac Conkey's agar

Dr.T.V.Rao MD 75

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Salmonella on XLD agar

Dr.T.V.Rao MD 76

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Clot culture• Clot cultures are more

productive in yielding better results in isolation.

• A blood after clotting, the clot is lysed with Streptokinase ,but expensive to perform in developing countries.

Dr.T.V.Rao MD 77

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Bactec and Radiometric based methods are in recent use

• Bactek methods in isolation of Salmonella is a rapid and sensitive method in early diagnosis of Enteric fever.

• Many Microbiology Diagnostic Laboratories are upgrading to Bactek methods

Dr.T.V.Rao MD 78

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Biochemical Characters

• Non Lactose fermenter,• Motile• Indole – MR + VP - Citrate +• Ferment Glu/Mal/Man• Do not ferment Lactose/Sucrose

Dr.T.V.Rao MD 79

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Slide agglutination tests• In slide agglutination

tests a known serum and unknown culture isolate is mixed, clumping occurs within few minutes

• Commercial sera are available for detection of A, B,C1,C2,D, and E.

Dr.T.V.Rao MD 80

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Culturing other Specimens

• Feces Enrichment in Tetrathionate broth and Selenite broth

• Culturing in MacConkey/DCA/Wilson Blair medium – Large black colonies.

• Urine Culture – positive in 25 % • Other samples Bone Marrow,Bile,CSF/Sputum

Dr.T.V.Rao MD 81

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Serology• WIDAL Test – Tube agglutination test.• Detects O and H antibodies• Diagnosis of Typhoid and Paratyphoid• Testing for H agglutinins in Dryers tubes, a

narrow tube floccules at the bottom• Testing for O agglutinins in Felix tubes, Chalky • Incubated at 37º c overnight

Dr.T.V.Rao MD 82

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Widal Test• In 1896 Widal A professor of

pathology and internal medicine at the University of Paris (1911–29), he developed a procedure for diagnosing typhoid fever based on the fact that antibodies in the blood of an infected individual cause the bacteria to bind together into clumps (the Widal reaction).

Dr.T.V.Rao MD 83

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Widal test• S.typhi O and H tubes• Paratyphi A/B H agglutinins only• Common antigens O in all Factor sharing

12• Significance • I st week negative.• Titers raise in 2nd week Raise of titers

diagnosticDr.T.V.Rao MD 84

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Diagnosis of Enteric FeverWidal test

• Serum agglutinins raise abruptly during the 2nd or 3rd week

• The Widal test detects antibodies against O and H antigens

• Two serum specimens obtained at intervals of 7 – 10 days to read the raise of antibodies.

• Serial dilutions on unknown sera are tested against the antigens for respective Salmonella

• False positives and False negative limits the utility of the test

• The interpretative criteria when single serum specimens are tested vary

• Cross reactions limits the specificity

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Widal Test• Single test not diagnostic.• Paired samples tests• Diagnostic. O > 1 in 80 H > 1in 160H agglutinins appear firstFalse positives in Unapparent infection, Immunization Previously infected

Dr.T.V.Rao MD 86

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Widal test• Anamnestic response previous

infection and responding to unrelated infection

• Other Diagnostic tests CIE and ELISADetection of Circulating antigensCo agglutination test.

Dr.T.V.Rao MD 87

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Limitation of Widal Test• The Widal test is time

consuming and often times when diagnosis is reached it is too late to start an antibiotic regimen.

• In spite of several limitation many Physicians depend on Widal Test

Dr.T.V.Rao MD 88

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False Positive and Negative Reactions with WIDAL Test

• The Widal test should be interpreted in the light of baseline titers in a healthy local population. This is especially important when there is a high local prevalence of non-typhoid salmonellosis. The Widal test may be falsely positive in patients who have had previous vaccination or infection with S typhi.

Dr.T.V.Rao MD 89

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False Positive and Negative Reactions with WIDAL Test

• Widal titers have also been reported in association with the dysgammaglobulinaemia of chronic active hepatitis and other autoimmune diseases.64 '8 '9 False negative results may be associated with early treatment, with "hidden organisms" in bone and joints, and with relapses of typhoid fever. Occasionally the infecting strains are poorly immunogenic.

Dr.T.V.Rao MD 90

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Diagnosis of Carriers and Environments

• Fecal carriers by isolation from specimens. or Bile aspirated.

• Sewer swabs• Bacteriophage

typing

Dr.T.V.Rao MD 91

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Prophylaxis • TAB vaccine S.typhi 1,000 millions S Paratyphi A,B 750 millions. Injected subcutaneously 0.5 ml at 4 – 6 weeks.Live Oral Vaccine TyphoralMutant S.typhi strain Ty 2 1a Lacking enzyme UDP

galctose 4 epimerase 10 to9Viable bacilliGiven orally 1 – 3 – 5 days

Dr.T.V.Rao MD 92

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Key points• Antibiotics have no place in the

management of salmonella gastroenteritis unless invasive complications are suspected.

• Clean water, sanitation and hygienic handling of foodstuffs are the keys to prevention.

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Prevention• Vi Polysaccharide vaccine

– Administered subcutaneously or intramuscular– Confers protection seven days after injection– Approximately 50% efficacy after three years

• Ty 21 vaccine – Live attenuated strain of S. typhi– Administered orally in capsule form– Also available in liquid form which can be taken by

children as young as two years of age

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Vaccines • An Inject able vaccine Typhium Vi• Contains purified Vi polysaccharide

antigen from S.typhi strain Ty2• A single dose, subcutaneous route • Given to children > 5 years• Immunity lasts for 2- 3 years.• Follow a booster

Dr.T.V.Rao MD 95

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Treatment

• Chloramphenicol 1948 /1970 resistance.• Other Important drugs Ampicillin Amoxicillin, Furazolidine Cotromoxazole Chloramphenical resistance /Mexico Kerala

Dr.T.V.Rao MD 96

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Antimicrobial Therapy in Typhoid• With prompt antibiotic therapy, more than

99% of the people with typhoid fever are cured, although convalescence may last several months. The antibiotic chloramphenicol Some Trade Names CHLOROMYCETINis used worldwide, but increasing resistance to it has prompted the use of other antibiotics BACTRIMSEPTRANor ciprofloxacin

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Other Drugs• Fluroquinolones Ciprofloxacillin,

Pefloxacillin Ofloxacillin

Ceftazidime Ceftriaxone / Cefotoxaime

Dr.T.V.Rao MD 98

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Coalition against Typhoid• Since May 2011, the

Coalition against Typhoid (CaT) has featured monthly articles in the WHO’s Global Immunization Newsletters (GIN). The articles, written by CaT members from around the world, highlight important work being done to accelerate adoption of typhoid vaccines.

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Salmonella • WHO: 1,400,000 instances of salmonellosis in

USA• Salmonella costs per year US $3,000,000,000• 2,300 serotypes (S. enterica Typhimurium,

etc)– wide host range (humans, cattle, horses,

rodents, cats, dogs, birds, reptiles)• Multi-drug resistant S.e.Typhimurium DT104

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Salmonella • Most common diseases caused by Salmonella:• gastroenteritis (self-limiting, 2-5 days)• enteric/typhoid fever (incubation 1-10/7-14

days, lasts 2-3 wks)• septicemia (incubation12-36 hrs, may lead to

chronic infection)• symptoms and disease manifestation differ in

hosts

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Food Poisoning• The laboratory diagnosis of bacterial

food poisoning depends on isolation of the causal organism from samples of faeces or suspected foodstuffs. The more common food-poisoning serotypes, such as Enteritidis or Typhimuruim, may be characterized more fully by phage typing and antibiotic resistance typing (see above).

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Salmonellosis• > 2000 known

serotypes• 200 serotypes are

detected each year in the United States

• Two most common (in most countries)– Salmonella Typhimurium

– Salmonella Enteritidis

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Identification of pathogens

• Strains can be differentiated further by plasmid and pulsed-field gel electrophoresis typing so that the isolates from patients may be matched with those from the infected food and from a suspected animal source.

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Salmonella Gastroenteritis• Zoonotic disease• S.enteritidis• S.typhimurium• S.halder• S. agana• S.indiana• Contaminated poultry, Meat Milk, Milk products.• Enters the shells of the Intact eggs – Chicken feed,

and Fecal droppings.

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Nontyphoidal Salmonella

• General Incubation: 6 hrs-10 days; Duration: 2-7 days• Infective Dose = usually millions to billions of cells• Transmission occurs via contaminated food and water• Reservoir:

a) multiple animal reservoirsb) mainly from poultry and eggs (80% cases from eggs)c) fresh produce and exotic pets are also a source of contamination (> 90% of reptile stool contain salmonella bacterium); small turtles ban.

• General Symptoms: diarrhea with fever, abdominal cramps, nausea and sometimes vomiting

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Mechanism of Pathogenicity Gastroenteritis

• ingestion• absorbed to brush border of epithelial cells of

small intestine and colon • migrate to lamina propria, Ileocecal• multiply in lymphoid follicles• Reticuloendothelial hyperplasia and

hypertrophy

Page 108: Salmonella Essential learning for Medical Students

Nontyphoidal Salmonella: Gastroenteritis

• Incubation: 8-48 hrs ; Duration: 3-7 days for diarrhea & 72 hrs. for fever

• Inoculum: large• Limited to GI tract• Symptoms include: diarrhea, nausea, abdominal cramps

and fevers of 100.5-102.2ºF. Also accompanied by loose, bloody stool; Pseudo appendicitis (rare)

• Stool culture will remain positive for 4-5 weeks• < 1% will become carriers

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Nontyphoidal Salmonella:Bacteremia and Endovascular Infections

• 5% develop septicemia; 5-10% of septicemia patients develop localized infections

• Endocarditis: Salmonella often infect vascular sites; preexisting heart valve disease risk factor

• Arteritis: Elderly patients with a history of back/chest + prolonged fever or abdominal pain proceeding gastroenteritis are particularly at risk. - Both are rare, but can cause complications that may lead to death

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Salmonella Gastroenteritis

• Can occur as cross infection• 24 hours• Manifest with Diarrhea, omitting• Abdominal pain mucous and blood in

stools• Last for 2 – 4 days• Some times may lead to septicemias

Dr.T.V.Rao MD 110

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Diagnosis and Treatment

• Isolation by culturing

• Rarely need antibiotics.

• More frequent in Developed nations.

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Salmonella septicemias• S.cholera suis• Deep abscess,

Endocarditis• Isolation from

Blood and Pus.• Chloramphenicol

highly effective

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Don’t eat raw or undercooked food

Cross-contamination of foods should be avoided

Do not prepare food or pour water if you are infected with the bacteria

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Wash hands, kitchen surfaces, and utensils with soap and water after they have come in contact with raw meat or poultry

Wash hands after contact with animal

feces

Avoid direct/indirect contact between reptiles and infants

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Simple hand hygiene and washing can reduce several cases of Typhoid

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• Program created by Dr.T.V.Rao MD for benefit of Medical and Paramedical Students in the

Developing World • Email

[email protected]

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