Typhoid Fever


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Typhoid Fever

  1. 1. Typhoid Fever Prof. Nooruddin Jaffer Professor of Medicine Hamdard Medical College Karachi Pakistan
  2. 2. Introduction <ul><li>Typhoid fever is a severe multisystemic illness characterized by the classic prolonged fever, sustained bacteremia, and bacterial invasion and multiplication within the mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer patches. </li></ul>
  3. 3. Introduction <ul><li>Occurs only in humans </li></ul><ul><li>Potentially fatal if untreated. </li></ul><ul><li>Typhoid fever is most prevalent in underdeveloped countries </li></ul>
  4. 4. Epidemiology <ul><li>Typhoid and paratyphoid fever infections are encountered worldwide but are primarily found in those countries of the developing world where sanitary conditions are poor. </li></ul><ul><li>Indian subcontinent, Southeast and Far East Asia, the Middle East, Africa, Central America, and South America. </li></ul>
  5. 5. Epidemiology <ul><li>In endemic areas, children aged 1-5 years are at the highest risk because of waning passively acquired maternal antibody and a lack of acquired immunity. </li></ul>
  6. 6. Etiologic Agent <ul><li>Causative agent is Salmonella typhi , a gram-negative bacteria, member of genus Salmonella and familyEnterobacteriaceae </li></ul><ul><li>Salmonellae are grouped based on the somatic O and further divided into serotypes based on flagellar H a gram-negative and surface Vi (virulence) antigens. </li></ul>
  7. 7. Transmission <ul><li>Contaminated food and beverages handled by persons shedding S typhi from stool (or less commonly urine) </li></ul><ul><li>Water from sewage contaminated with S typhi . </li></ul>
  8. 8. Transmission <ul><li>Increased susceptibility is related to </li></ul><ul><ul><li>Increased bacterial load: Ingestion of 10 5 organisms led to clinical disease in 25%, ingestion of 10 7 in 50%, and 10 9 organisms in 95%. </li></ul></ul><ul><ul><li>A gastric pH of > than 1.5 </li></ul></ul><ul><ul><li>Patients on antacids </li></ul></ul><ul><ul><li>Gastrectomy </li></ul></ul><ul><ul><li>Achlorhydria due to aging </li></ul></ul>
  9. 9. Pathogenesis <ul><li>The hallmark of typhoid fever is the invasion of and multiplication within the mononuclear phagocytic cells in the liver, spleen, lymph nodes, and Peyer patches of the ileum. </li></ul>
  10. 10. Pathogenesis <ul><li>From the Peyer patches S typhi is internalized and transported to the underlying lymphoid tissues. </li></ul><ul><li>Then the organisms travel to the mesenteric lymph nodes, multiply, and then enter the blood stream via the thoracic duct (transient primary bacteremia) to seed other tissues . </li></ul>
  11. 11. Pathogenesis <ul><li>Then the organisms may invade any organ but most commonly are found in reticuloendothelial tissues of the liver, spleen, bone marrow, gallbladder, and Peyer patches in the terminal ileum. </li></ul>
  12. 12. Pathogenesis <ul><li>The Peyer patches become hyperplastic with infiltration of chronically inflamed cells, which may lead to necrosis of the superficial layer and ulcer formation, with potential hemorrhage from blood vessel erosion or peritonitis from transmural perforation </li></ul>
  13. 13. Symptoms <ul><li>The incubation period averages 10-20 (range 3-56) days. </li></ul><ul><li>Patients remain asymptomatic during the incubation period </li></ul><ul><li>As bacteremia develops, patient notices the onset of fever, which typically increases in a step-wise fashion over 2-3 days. </li></ul>
  14. 14. Symptoms <ul><li>Constipation and mild nonproductive cough are common . </li></ul><ul><li>Abdominal pain and diarrhea </li></ul><ul><li>Delirium </li></ul><ul><li>Anorexia, weakness, malaise. </li></ul>
  15. 15. Signs <ul><li>Relative bradycardia </li></ul><ul><li>Pink papules (rose spots)(2-4mm) that fade with pressure develop on the upper abdomen and lower chest between the 7 th and 12 th days caused by bacterial embolization </li></ul>
  16. 16. Signs <ul><li>During the second week of illness, the patient has a toxic appearance and seems apathetic with sustained pyrexia. </li></ul><ul><li>The abdomen is distended slightly, and splenomegaly is common </li></ul>
  17. 17. Signs <ul><li>In the third week, patient’s toxicity increases and weight loss is common. A delirious state (typhoid state) emerges. </li></ul><ul><li>Abdominal distension develops, and liquid, foul, green-yellow diarrhea occurs </li></ul><ul><li>thready pulse and tachypnea, </li></ul><ul><li>Death occur at this stage from toxemia, myocarditis, intestinal hemorrhage, or perforation. </li></ul>
  18. 18. Signs <ul><li>In the fourth week, the fever, mental state, and abdominal distension slowly improve but intestinal complications may still occur. </li></ul><ul><li>Convalescence is prolonged, and most relapses occur at this stage </li></ul>
  19. 19. Complications <ul><li>Intestinal </li></ul><ul><ul><li>Intestinal hemorrhage </li></ul></ul><ul><ul><li>perforation </li></ul></ul>
  20. 20. Complications <ul><li>Hepatobiliary </li></ul><ul><ul><li>Mild elevation of transaminases </li></ul></ul><ul><ul><li>Jaundice </li></ul></ul><ul><ul><li>Hepatitis with hepatomegaly </li></ul></ul><ul><ul><li>Pancreatitis </li></ul></ul><ul><li>Acute renal failure </li></ul>
  21. 21. Complication <ul><li>Cardiac </li></ul><ul><ul><li>Nonspecific electrocardiographic changes </li></ul></ul><ul><ul><li>Toxic myocarditis </li></ul></ul><ul><ul><li>Pericarditis </li></ul></ul>
  22. 22. Complication <ul><li>Neuropsychiatric </li></ul><ul><ul><li>A toxic confusional state, characterized by disorientation, delirium, and restlessness </li></ul></ul><ul><ul><li>Facial twitching or convulsions </li></ul></ul><ul><ul><li>Encephalomyelitis </li></ul></ul><ul><ul><li>Multiple brain abscesses </li></ul></ul>
  23. 23. Complications <ul><li>Hematologic </li></ul><ul><ul><li>DIC </li></ul></ul><ul><ul><li>Hemolytic-uremic syndrome </li></ul></ul><ul><ul><li>Hemolysis </li></ul></ul>
  24. 24. Investigations <ul><li>Anemia, Elevated ESR, Thrombocytopenia, and relative Lymphopenia. </li></ul><ul><li>Elevated PT and APTT, </li></ul><ul><li>Liver transaminase values are usually elevated to twice the reference range, as is serum bilirubin. </li></ul><ul><li>Mild hyponatremia and hypokalemia are common. </li></ul>
  25. 25. Investigation <ul><li>Clinical diagnosis is suggested by assays that identify Salmonella antibodies, antigens, or DNA and is then confirmed by isolation of the organism. </li></ul>
  26. 26. Investigation <ul><li>Definitive diagnosis of typhoid fever requires isolation of the organism from blood or bone marrow. </li></ul><ul><li>The most sensitive method of isolating S typhi is obtaining a bone marrow aspirate (BMA) culture (90% sensitive). </li></ul>
  27. 27. Investigation <ul><li>S typhi can be isolated from BMA even if patients have been taking antibiotics for several days </li></ul><ul><li>This test may be indicated in patients whose initial blood culture results are negative, presumably because of prior antibiotic therapy. </li></ul>
  28. 28. Investigation <ul><li>If BMA cannot be performed, blood, intestinal secretions, and stool culture findings are usually positive in approximately 85-90% of patients with typhoid fever during the first week, declining to 20-30% later in the course of the disease. </li></ul>
  29. 29. Investigation <ul><li>S typhi has been isolated from the cerebrospinal fluid, peritoneal fluid, mesenteric lymph nodes, resected intestine, pharynx, tonsils, abscess, bone, and urine, among others. </li></ul>
  30. 30. Investigation <ul><ul><li>The Widal test is the traditional serologic test. The test measures agglutinating antibodies against flagellar (H) and somatic (O) antigens of S typhi . </li></ul></ul>
  31. 31. Investigation <ul><ul><li>Studies have shown that sensitivity, specificity of this test vary among laboratories, rendering test's value to the clinician questionable. This variation is caused by differences in patient population, antigens, and techniques. </li></ul></ul><ul><ul><li>The Widal reaction is indicative of typhoid fever in only 40-60% of patients at the time of admission. </li></ul></ul>
  32. 32. Investigation <ul><li>Indirect hemagglutination, indirect fluorescent Vi antibody, and indirect enzyme-linked immunosorbent assay for immunoglobulin M (IgM) and immunoglobulin G antibodies to S typhi polysaccharide are available. </li></ul>
  33. 33. Investigation <ul><li>Although not commercially available, DNA probes have been developed for identifying S typhi from bacterial culture isolates and directly from blood. </li></ul>
  34. 34. Treatment <ul><li>Antibiotic therapy is essential and should begin empirically if the clinical evidence is strong. </li></ul><ul><li>Antimicrobials shorten the course, reduce the rate of complications if begun early, and reduce the case-fatality rate. </li></ul>
  35. 35. Treatment <ul><li>Because of the efficacy and low relapse and carrier rates associated the fluoroquinolones and the third-generation cephalosporins are the antibiotics of choice to treat MDR typhoid fever. </li></ul><ul><li>Because of its low cost, chloramphenicol is still used in other areas where local strains are sensitive. </li></ul>
  36. 36. Treatment <ul><li>The cost and need for IV administration are significant disadvantages of third-generation cephalosporins </li></ul><ul><li>Furazolidone and azithromycin are also used to treat typhoid in children </li></ul>
  37. 37. Treatment of carriers <ul><ul><li>Prolonged courses of amoxicillin or co-trimoxazole </li></ul></ul><ul><ul><li>Ciprofloxacin (750 mg bid) and norfloxacin (400 mg bid) have been much more effective, </li></ul></ul><ul><ul><li>In nonendemic countries, patients should be kept under bacteriological surveillance after clinical recovery until 6 consecutive negative results are obtained on fecal and urine cultures. </li></ul></ul>
  38. 38. Treatment <ul><li>Surgical intervention is favored for management of intestinal perforation. </li></ul><ul><li>Early diagnosis is key to lower mortality. </li></ul><ul><li>Cholecystectomy can be performed for eradicating the carrier state. </li></ul>
  39. 39. Prevention <ul><li>In endemic countries, the most cost-effective strategy for reducing the incidence of typhoid fever is the institution of public health measures to ensure safe drinking water and sanitary disposal of excreta . </li></ul>
  40. 40. Prevention <ul><li>Health care workers should pay strict attention to adequate hand washing and safe disposal of feces and urine. </li></ul>
  41. 41. Prevention <ul><li>Immunization with typhoid vaccines at regular intervals also considerably reduces the incidence of infections. </li></ul><ul><li>Vaccination is indicated for travelers to areas associated with a risk of exposure , persons with intimate exposure (eg, household) to a documented S typhi carrier, and microbiology laboratory personnel. </li></ul>
  42. 42. Vaccines <ul><li>Vi capsular polysaccharide vaccine </li></ul><ul><li>Ty21is an oral vaccine containing live attenuated S typhi Ty21a strains in an enteric-coated capsule </li></ul><ul><li>Parenteral heat-phenol–inactivated vaccine </li></ul>
  43. 43. Vaccines <ul><li>Vi capsular polysaccharide vaccine composed of purified Vi antigen, the capsular polysaccharide elaborated by S typhi isolated from blood cultures. </li></ul>
  44. 44. Vaccines <ul><li>Ty21is an oral vaccine containing live attenuated S typhi Ty21a strains in an enteric-coated capsule </li></ul>
  45. 45. Vaccines <ul><li>Acetone-inactivated parenteral vaccine </li></ul><ul><li>Parenteral heat-phenol–inactivated vaccine </li></ul>
  46. 46. Patient Education <ul><li>Typhoid vaccination is recommended at least 1 week prior to travel to highly disease-endemic areas </li></ul><ul><li>Because the protection offered by vaccination is at best partial, close attention to personal, food, and water hygiene should be maintained . </li></ul>
  47. 47. Thank You