Enteric fever�Salmonella infections by Dr.T.V.Rao MD

Enteric fever�Salmonella infections by Dr.T.V.Rao MD

1. Enteric fever Salmonella infections Dr.T.V.Rao MD Dr.T.V.Rao MD 1

2. Typhoid Fever a Important Communicable disease affects many in the world Dr.T.V.Rao MD 2

3. Salmonella Causes Infections in Humans and vertebrates, Enteric Fever ( Typhoid fever ) Gastroenteritis Septicemias, Carrier state a concern Dr.T.V.Rao MD 3

4. 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 4

5. 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 5

6. Enteric Fever Typhoid 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 Infection Dr.T.V.Rao MD 6

7. 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 stoo l Dr.T.V.Rao MD 7

8. 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 8

9. Typhoid fevers are prevalent in many regions in the World

10. Typhoid Mary Most Dangerous Woman in America Dr.T.V.Rao MD 10

11. 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.

12. 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.

13. 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.  

14. Carl Joseph Eberth who discovered the typhoid bacillus in 1880. Georges Widal who described the   ‘ Widal agglutination reaction ’ of the blood in 1896.

15. Morphology of Salmonella Gram negative bacilli 1-3 / 0.5 microns, Motile by peritrichous flagella Dr.T.V.Rao MD 15

16. S.typhi with Flagella Dr.T.V.Rao MD 16

17. 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 17

18. Different types of Salmonella I - enterica II - salamae IIIa - arizonae IIIb - diarizonae IV - houtenae V - bongori VI - indica

19. Cultural Characters Aerobic / Facultatively anaerobic Grows on simple media – Nutrient agar, Temp 15 – 41 ºc / 37 º 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 H 2 S produced by Salmonella typhi Dr.T.V.Rao MD 19

20. Enrichment Medium Liquid 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 20

21. 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 tests Dr.T.V.Rao MD 21

22. Biochemical Charac ters Glucose ,Mannitol ,Maltose produce A/G Salmonella typhi do not produce gas Lactose/Salicin/sucrose not fermented. Indole – Methyl Red + V P - Citrate + Urea – H 2 S – produced by Salmonella typhi Paratyphi A do not produce H 2 S Dr.T.V.Rao MD 22

23. Resistance of Salmonella 55 º c – 1 hour 60 º c – 15 MT Boiling ,Chlorination, Pasteurization Destroy the Bacilli. Dr.T.V.Rao MD 23

24. Salmonella Antigenic 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 24

25. 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 25

26. 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 26

27. Antigens – Salmonella ( cont ) Dr.T.V.Rao MD 27 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 50 º – 55 º c O antigens are less immunogenic. than H antigens

28. 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 60 º 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 28

29. 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 29

30. Kauffmann – White scheme Serotype 0 antigens H antigens Phase 1 2 1.Typhi 9, 12 ,(Vi) d 1,2 2 Paratyphi A 1,2. 12 a - 3 Paratyphi B 1,4,5, 12 b 1,2 4 Typhimuruim 1,4,5, 12 I 1,7 5 Enteritidis 1,9, 12 g m 1,2 Dr.T.V.Rao MD 30

31. 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 31

32. 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 32

33. Enteric Fever: S. typhi Ileocecal penetration intraluminal multiplication mononuclear response (macrophages) Salmonella remains alive 2nd week - lymphoid hyperplasia (mesenteric lymph nodes) back to bowel

34. Enteric Fever Typhoid Typhoid – caused by S.typhi Paratyphoid Caused by Paratyphi A,B,C Typhoid --- Like Typhus Infective dose ID 50 / 10 7 , Dr.T.V.Rao MD 34

35. 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

36. Typhoid fever

37. 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

38. Dr.T.V.Rao MD 38

39. Events in a Typical typhoid Fever Dr.T.V.Rao MD 39

40. 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 40

41. 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 41

42. Pathology and Pathogenesis Bacteremia Spread to Liver, Gall bladder, Spleen, Bone marrow, Lymph nodes, Lungs, Multiply in kidneys Once again spill into Blood stream Causes clinical illness. Dr.T.V.Rao MD 42

43. 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

44. 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 44

45. 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 45

46. 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 46

47. Manifest with Rose spots High fever Diarrhea Typhoid Meningitis Aches and pains Chest congestion

48. 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.

49. 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 49

50. 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 50

51. Immunity in Typhoid Typhoid bacilli are Intracellular pathogens Cell mediated immunity is crucial Dr.T.V.Rao MD 51

52. 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 52

53. 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

54. Events in a Typical typhoid Fever Dr.T.V.Rao MD 54

55. Complications of Enteric fever Intestinal perforation, Hemorrhage, Circulatory collapse. Bronchitis Bronchopneumonia, Meningitis, Cholecystitis, Arthritis,Periostitis / Nephritis, Osteomyletis, Dr.T.V.Rao MD 55

56. 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

57. Other complications Causes relapses in particular to patients treated with chloramphenicol. S.paratyphi produce septicemias. Dr.T.V.Rao MD 57

58. 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.

59. 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.

60. 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

61. 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

62. 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

63. 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

64. 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

65. 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, Food HIV patients potentially susceptible for Typhoid disease. Dr.T.V.Rao MD 65

66. 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 66

67. 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 67

68. 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 68

69. 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 69

70. Laboratory Diagnosis of Typhoid 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 70

71. Blood Culture 1 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 71

72. Blood Cultures in Typhoid Fevers Bacteremia occurs early in the disease Blood Cultures are positive in 1 st week in 90% 2 nd week in 75% 3 rd week in 60% 4 th week and later in 25% Dr.T.V.Rao MD 72

73. Castaneda’s method of Blood 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 73

74. Salmonella on Mac Conkey's agar Dr.T.V.Rao MD 74

75. Salmonella on XLD agar Dr.T.V.Rao MD 75

76. 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 76

77. 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 77

78. Biochemical Characters Non Lactose fermenter, Motile Indole – MR + VP - Citrate + Ferment Glu/Mal/Man Do not ferment Lactose/Sucrose Dr.T.V.Rao MD 78

79. 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,C 1, C 2, D, and E. Dr.T.V.Rao MD 79

80. 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 80

81. 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 37 º c overnight Dr.T.V.Rao MD 81

82. 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 82

83. 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 diagnostic Dr.T.V.Rao MD 83

84. Diagnosis of Enteric Fever Widal test Serum agglutinins raise abruptly during the 2 nd or 3 rd 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

85. Widal Test Single test not diagnostic. Paired samples tests Diagnostic. O > 1 in 80 H > 1in 160 H agglutinins appear first False positives in Unapparent infection, Immunization Previously infected Dr.T.V.Rao MD 85

86. Widal test Anamnestic response previous infection and responding to unrelated infection Other Diagnostic tests CIE and ELISA Detection of Circulating antigens Co agglutination test. Dr.T.V.Rao MD 86

87. 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 87

88. 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 88

89. 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 89

90. Other Serological tests Indirect hemagglutination, indirect fluorescent Vi antibody, and indirect enzyme-linked immunosorbent assay (ELISA) for immunoglobulin M (IgM) and IgG antibodies to S typhi polysaccharide, as well as monoclonal antibodies against S typhi flagellin, are promising, but the success rates of these assays vary greatly in the literature Source of Information [Typhoid Fever Workup Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD Drugs & Diseases > Infectious Diseases Medscape) Dr.T.V.Rao MD 90

91. Polymerase chain reaction Polymerase chain reaction (PCR) has been used for the diagnosis of typhoid fever with varying success. Nested PCR, which involves two rounds of PCR using two primers with different sequences within the H1-d flagellin gene of S typhi, offers the best sensitivity and specificity. Combining assays of blood and urine, this technique has achieved a sensitivity of 82.7% and reported specificity of 100%. However, no type of PCR is widely available for the clinical diagnosis of typhoid fever. Source of Information [Typhoid Fever Workup Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD Drugs & Diseases > Infectious Diseases Medscape) Dr.T.V.Rao MD 91

92. Diagnosis of Carriers and Environments Fecal carriers by isolation from specimens. or Bile aspirated. Sewer swabs Bacteriophage typing Dr.T.V.Rao MD 92

93. 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 Typhoral Mutant S.typhi strain Ty 2 1a Lacking enzyme UDP galctose 4 epimerase 10 to9 Viable bacilli Given orally 1 – 3 – 5 days Dr.T.V.Rao MD 93

94. 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. Dr.T.V.Rao MD 94

95. 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

96. 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 96

97. Treatment Chloramphenicol 1948 /1970 resistance. Other Important drugs Ampicillin Amoxicillin, Furazolidine Cotromoxazole Chloramphenical resistance /Mexico Kerala Dr.T.V.Rao MD 97

98. 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 CHLOROMYCETIN is used worldwide, but increasing resistance to it has prompted the use of other antibiotics BACTRIM SEPTRAN or ciprofloxaci n

99. Other Drugs Fluroquinolones Ciprofloxacillin, Pefloxacillin Ofloxacillin Ceftazidime Ceftriaxone / Cefotoxaime Dr.T.V.Rao MD 99

100. 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. Dr.T.V.Rao MD 100

101. 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

102. Diarrhea Nausea Vomiting Stomach pain Headache Fever Onset 12-72 hours after infection Symptoms of Salmonellosis

103. Common clinical manifestations of 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 ) septicaemia (incubation12-36 hrs, may lead to chronic infection) symptoms and disease manifestation differ in hosts 103

104. 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). Dr.T.V.Rao MD 104

105. Salmonellosis > 2000 known serotypes  200 serotypes are detected each year in the United States Two most common (in most countries) Salmonella Typhimurium Salmonella Enteritidis

106. 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. Dr.T.V.Rao MD 106

107. 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. Dr.T.V.Rao MD 107

108. 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 reservoirs b) 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 Dr.T.V.Rao MD 108

109. 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

110. 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 Dr.T.V.Rao MD 110

111. 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 Dr.T.V.Rao MD 111

112. 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 112

113. Diagnosis and Treatment Isolation by culturing Rarely need antibiotics. More frequent in Developed nations. Dr.T.V.Rao MD 113

114. Dr.T.V.Rao MD 114

115. Salmonella septicemias S.cholera suis Deep abscess, Endocarditis Isolation from Blood and Pus. Chloramphenicol highly effective Dr.T.V.Rao MD 115

116. 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 How to Prevent Salmonellosis

117. 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 How to Prevent Salmonellosis

118. Simple hand hygiene and washing can reduce several cases of Typhoid

119. Visit for most updated Information For the most up-to-date information, visit the Centers for Disease Control and Prevention Travelers' Health Typhoid resource (www.cdc.gov/travel) Dr.T.V.Rao MD 119

120. Program Created by Dr.T.V.Rao MD for benefit of Medical and Paramedical Professionals in the developing world Email [email protected] Dr.T.V.Rao MD 120