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Typhoid fever

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Typhoid fever

  1. 1. Dr Sharad Chaurasia
  2. 2. INTRODUCTION Typhoid fever (Greek- Smoke, Fumes, Stupor) Systemic infection with bacterium Salmonella enterica serotype typhi / paratyphi A/B.
  3. 3. EPIDEMIOLOGY Over 21.7 million cases/ annually >2 lacs death Additional >5.4 million cases – Paratyph. Developed countries- <15/ lacs population Developing countries- 100-1000/lacs.
  4. 4.  In an Indian urban slum showed incidence as high as 2/ 1,000 /yr for children under five 5.1/ 1,000/ yr for children under ten majority of cases occurred in children aged 5 to 12 years and 24.8% of cases were in children up to 5 years of age S. Typhi (75.7%) was the predominant serovar followed by S. Paratyphi A (23.8%) maximum number of enteric fever cases occurred during April to June (dry season) followed by July to September (monsoon season
  5. 5. Typhoid fevers are prevalent in many regions in the World
  6. 6. Contd.. Age – Children and young adults (5-25 years). Recent Study from Delhi shows Typhoid fever also common in < 5 years of age. IP – 10-14 days (3-21 days). MOT – Faeco-oral/Urine-oral route. Through out the year esp. July-September ROI – Man (Cases/Carriers)
  7. 7. Organism Salmonella typhi, a Gram-negative bacteria. Similar but often less severe disease is caused by Salmonella serotype paratyphi A. The ratio of disease caused by S. typhi to that caused by S. paratyphi is about 10 to 1. Many genes are shared with E. coli and at least 90% with S. typhimurium, Polysaccharide capsule Vi: present in about 90% of all freshly isolated S. typhi and has a protective effect against the bactericidal action of the serum of infected patients.
  8. 8. Risk Factors Impaired cell-mediated immunity AIDS Corticosteroid use Malignancy Impaired phagocytic function Hemoglobinopathies Chronic granulomatous disease Malaria Histoplasmosis Schistosomiasis
  9. 9. Risk Factors Extremes of age Neonates Elderly Decreased gastric acidity Antacids or suppression of acid secretion Achlorhydria Altered intestinal function Inflammatory bowel disease Prior antibiotic therapy
  10. 10. Pathogenesis
  11. 11. Contd.. Entry in GIT  localization in Gut associated lymphoid tissue  Lymphatic channel  thoracic duct  circulation  primary silent bacteremia  localization in macrophages of RES in spleen, liver, bone marrow (incubation period 8-14 days)  secondary bacteremia
  12. 12. Clinical Features
  13. 13. Acute non-complicated disease Characterized by Prolonged fever, classic stepladder rise uncommon. Disturbances of bowel function Headache, malaise and anorexia. Bronchitic cough Exanthem (rose spots appr 25%) on the chest, abdomen and back.
  14. 14. Complicated disease 10-15% of typhoid patients CNS (3-35%): Encephalopathy, Typhoid meningitis, encephalomyelitis, Guillain-Barré syndrome, cranial or peripheral neuritis and psychotic symptoms, Coma Vigil. GIT: occult blood in 10-20% of patients, and intestinal hemorrhage in upto 1%. Intestinal perforation has also been reported in up to 1% of hospitalized cases. Others: Hepatitis, myocarditis, pneumonia, Empyema, disseminated intravascular, Osteomyelitis
  15. 15. Diagnosis In endemic area, fever without evident cause more than 7 days should be considered Typhoid until proved otherwise. Blood culture – standard diagnostic method . +ve in 40-60% Failure to isolate the organism (i) the limitations of laboratory media (ii) the presence of antibiotics (iii) the volume of the specimen cultured
  16. 16. 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%
  17. 17. 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.  2 Flagellar or H Antigens are strongly immunogenic and induces antibody formation rapidly and in high titers following infection or immunization.
  18. 18. Contd.. (iv) the time of collection, patients with a history of fever for 7 to 10 days being more likely than others to have a positive blood culture. Bone marrow aspirate culture is the gold standard for the diagnosis of typhoid fever +ve 80-95% Inspite on antibiotics. Stool culture +ve in 30% with acute Typhoid fever. Positivity rate increases with duration of illness. Cultures also been made from blood clots, rose spots, intestinal secretion, urine.
  19. 19. 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.  2 Flagellar or H Antigens are strongly immunogenic and induces antibody formation rapidly and in high titers following infection or immunization.
  20. 20. Immune Response in Typhoid
  21. 21. Widal Test Measures antibody against O & H antigens of S.typhi. Sensitivity-60%; specificity-80%.  O antibodies appear on days 6-8 and H antibodies on days 10-12 Negative in up to 30% of culture-proven cases of typhoid fever S. typhi shares O and H antigens with other Salmonella serotypes and has cross-reacting epitopes with other Enterobacteriacae, and this can lead to false-positive results. Such results may also occur in other clinical conditions, e.g. malaria, typhus, bacteraemia caused by other organisms, and cirrhosis
  22. 22. Contd.. This is acceptable so long as the results are interpreted with care in accordance with appropriate local cut-off values for the determination of positivity A 4 fold rise Ab titre in paired sera highly suggestive >1:160 titre against O & H highly suggestive with relevent clinical findings.
  23. 23. New serological test Specific antibodies usually only appear a week after the onset of symptoms and signs. This should kept in mind when a negative serological test result is being interpreted. New serological tests Typhidot (better), high negative predictive value Dipstick test, DNA Probe PCR
  24. 24. CONTD.. Typhidot – Rapid serological test, detects IgM $ IgG antibody – OMP of s.typhi. Becomes +ve within 2-3 days of infection. Sensitivity-90-98% ; specificity-75-90%. Vi agglutinin reaction test- carrier. CBC- WBC low in relation to fever, leucocytosis common young children Thrombocytopenia marker of severe illness/ accompany DIC.
  25. 25. Oral drugs Cotrimoxazole, Ampicillin, Chlorphenicol Earlier used as 1st line drugs, due to resistance became 2nd line drugs. In endemic area >90% typhoid cases treated at home with proper antibiotics & good nursing care. Patients with persistent vomiting, decreased oral intake, severe diarrhea & abd. Distension require parenteral antibiotic preferably in hospital.
  26. 26. Fluoroquinolones Optimal for the treatment of typhoid fever Not approved by drug controller general of India <18 yrs. Age. Relatively inexpensive, well tolerated and more rapidly and reliably effective than the former first-line drugs, viz. chloramphenicol, ampicillin, amoxicillin and trimethoprim-sulfamethoxazole. The majority of isolates are still sensitive.
  27. 27. Contd.. Attain excellent tissue penetration, kill S. typhi in its intracellular stationary stage in monocytes/macrophages and achieve higher active drug levels in the gall bladder than other drugs. Dose- 15-20 mg/kg/day BD -7 days for NASST and 10-14 days for NARST. Rapid therapeutic response, i.e. clearance of fever and symptoms in three to five days, and very low rates of post-treatment carriage.
  28. 28. Chloramphenicol The disadvantages of using chloramphenicol include a relatively high rate of relapse (57%), long treatment courses (14-21 days) and the frequent development of a carrierstate in adults. The recommended dosage is 50 – 75 (100mg for iv/im) mg per kg per day for 14 -21days divided into four doses per day, or for at least five to seven days after defervescence. Oral administration gives slightly greater bioavailability than intramuscular (i.m.) or intravenous (i.v.) administration of the succinate salt.
  29. 29. Cephalosporins Oral drugs:- Cefixime, Cefpodoxime. Parenteral-Ceftriaxone, cefotaxime, cefoperazone. Cefotaxime: 40-80mg per kg per day in two or three doses Ceftriaxone: 50-75 mg/kg/day OD/BD. Most convenient & widely used. Cefoperazone: 50-100 mg per kg per day
  30. 30. Contd.. In uncomplicated typhoid fever- cefixime DOC as emperical therapy. If by 5th day No clinical improvement & culture inconclusive—ADD second line drugs eg. Azithromycin (drugs sensitivity pattern of the area). In complicated typhoid- DOC 3rd gen. cephal. Parenteral eg. Ceftriaxone. In severe life threatening infection – FQs. May be used. Aztreonam/ Imipenam may also be used.
  31. 31. hegazi8@hotmailcom 36 MEDICAL COMPLICATIONS acute bronchitis and frank lobar pneumonia, toxic myocarditis, venous thrombosis, hemolytic anaemia, acute typhoid nephritis, typhoid meningitis and peripheral neuritis
  32. 32. hegazi8@hotmailcom 37 MEDICAL COMPLICATIONS Myocarditis is extremely common, particularly in the very toxic patient. The cardiac muscle is affected, even in convalescence, and this is shown by a rapid deterioration of the cardiovascular system in a relapse, or after the administration of a general anaesthetic. Febrile albuminuria is common, but true acute typhoid nephritis is rare. Peripheral neuritis and ‘tender toes’. Mild hemolytic anaemia is fairly common in the very toxic typhoid patient. A marked degree is rare, and the mortality rate is high.
  33. 33. Dexamethasone for CNS complication Should be immediately be treated with high-dose intravenous dexamethasone in addition to antimicrobials Initial dose of 3 mg/kg by slow i.v. infusion over 30 minutes 1 mg/kg 6 hourly for 2 days/ 8 doses. Mortality can be reduced by some 80-90% in these high-risk patients
  34. 34. hegazi8@hotmailcom 39 Typhoid Pneumonia Acute bronchitis is so common that it should be considered as a manifestation of the disease itself rather than as a complication.  Typhoid lobar pneumonia presents with the typical symptoms and signs of lobar pneumonia except that ‘rusty’ sputum is uncommon, and the white blood cell count is low.  It responds well to chloramphenicol. A patient with typhoid pneumonia,.
  35. 35. GI complication Patients with intestinal haemorrhage need intensive care, monitoring and blood transfusion. Surgical consultation for suspected intestinal perforation is indicated. If perforation is confirmed, surgical repair should not be delayed longer than six hours. Metronidazole and gentamicin or ceftriazone should be administered before and after surgery . Early intervention is crucial, and mortality rates increase as the delay between perforation and surgery lengthens. Mortality rates vary between 10% and 32%.
  36. 36. hegazi8@hotmailcom 41 The major surgical complications of typhoid fever may include: parotitis, intestinal perforation and haemorrhage, acute cholecystlitis,  paralytic ileus,  orchitis, pyelitis, cystitis, retention of urine, empyema, arthritis and osteomyelitis.
  37. 37. Relapse 5-20% of typhoid fever cases that have apparently been treated successfully. A relapse is heralded by the return of fever soon after the completion of antibiotic treatment. The clinical manifestation is frequently milder than the initial illness. Cultures should be obtained and standard treatment should be administered. Carrier- Temporary carrier(excreate bacilli upto 6-8 wks). eg.incubatory, convalescent state.3 Chronic carrier- excrete bacilli > 3 months after infection.
  38. 38. Paratyphoid fever A,B,C Caused by Salmonella paratyphoid A,B,C.respectively. in no way different from typhoid fever in , pathogenesis, pathology,clinical manifestations, diagnosis, treatment and Prophylaxis
  39. 39. Paratyphoid A,B: incubation period 2~15days, in genaral,8~10 days. milder in severity fewer in complications. Better in prognosis, relapse more common in Paratyphoid A. Treatment same as in typhoid fever.
  40. 40. Paratyphoid C: Always sudden onset. Rapid rise of temperature. Presented in different forms-- Septicemia, Gastroenteritis and Enteric fever Complications--arthritis, abscess formation, cholecystitis, pulmonary complications are commonly seen. Intestinal hemorrhage and perforation not as common as in typhoid fever.
  41. 41. PREVENTION Safe drinking water Effective sewage disposal Hygienic food preparation Mass immunisation:-  Classic heat-inactivated whole cell vaccine—51-88% protection Local discomfort & swelling, systemic side effect.
  42. 42. Vaccination Vi polysaccharide, is given in a single dose Protection begins seven days after injection, maximum protection being reached 28 days after injection when the highest antibody concentration is obtained. Protective efficacy was 72% one and half years after vaccination and was still 55% three years after a single dose. In Asian countries where Vi-negative strains have been reported at the low average level of 3%.
  43. 43. Live oral vaccine Ty2la three doses two days apart on an empty stomach. Protection as from 10-14 days after the third dose. > 5 years. Protective efficacy of the enteric-coated capsule formulation seven years after the last dose is still 62% in areas where the disease is endemic; Antibiotics should be avoided for seven days before or after the immunization
  44. 44. Contd.. Vi conjugated vaccine: Induce T cell dependent response Efficacy- >90% Booster response Doses: 3 mths.- 2 yrs.-2doses at 4-8 wks. Interval followed by booster at 2-2.5 yrs age. Route- intramuscular. >2 yrs.- 2 doses at 4-8 wks. Interval.
  45. 45. MDR TYPHOID Clinical failure presence of persistent symptoms or, development of complications . Microbiological failure positive blood / bone marrow culture at the end of treatment. MDR Typhoid definition Epidemiological- strains resistant =>2 antibiotics in vitro. Clinical- => 2 1st line drugs viz. Amp., Chlo., Cx. Incidence - 49-83% of mdr typhoid in indian children. Mediated by plasmid Quinolone resistance is frequently mediated by single point mutations in the quinolone-resistance–determining region of the
  46. 46. MDR Nalidixic acid resistant: MIC of fluoroquinolones for these strains was 10 times that for fully susceptible strains. Incidence - 49-83% of mdr typhoid in indian children. Mediated by plasmid Quinolone resistance is frequently mediated by single point mutations in the quinolone-resistance–determining region of the gyrA gene
  47. 47. Diagnosis High degree of suspicion viz. prolonged fever, protracted course, unusual/ life threatening complication, slow response to treatment. Culture reports Epidemiological reports.
  48. 48. The future of typhoid fever Cheap,Rapid and reliable serological test Fluoroquinolone and cephalosporin resistant case Combination chemotherapy New drugs mass vaccination in endemic area Typhoid vaccination programme for school children or, with advent of new conjugate vi vaccine, as part of EPI, should be considered.
  49. 49. Mary Mallon (September 23, 1869 – November 11, 1938)
  50. 50. Mary Mallon (September 23, 1869 – November 11, 1938) Also known as Typhoid Mary was the first person in the United States to be identified as a healthy carrier of typhoid fever. She seemed a healthy woman when a health inspector knocked on her door in 1907, yet she was the cause of several typhoid outbreaks.
  51. 51. Mary Mallon (September 23, 1869 – November 11, 1938) Since Mary was the first "healthy carrier" of typhoid fever in the United States, she did not understand how someone not sick could spread disease -- so she tried to fight back. She was forcibly quarantined twice by public health authorities and died in quarantine. Over the course of her career as a cook, she infected 47 people, three of whom died from the disease. It was also possible that she was born with the disease, as her mother had typhoid fever during her pregnancy.
  52. 52. Mary Mallon (September 23, 1869 – November 11, 1938) MaryMallon died on November 11, 1938 at the age of 69 due to pneumonia (not typhoid), six years after a stroke had left her paralyzed. However, an autopsy found evidence of live typhoid bacteria in her gallbladder. Her body was cremated with burial in Saint Raymond's Cemetery in the Bronx.
  53. 53. Salmonella serotype Food Cases Year Salmonella newport Mangoes 78 1999 Salmonella muenchen Orange juice 207 1999 Salmonella agona Dry cereal 209 1998 Salmonella newport Sprouts 135 1996 Salmonella poona Cantaloupes >400 1991 Salmonella javiana Tomatoes 174 1990 Salmonella enteritidis Ice cream (egg) ~250,000 1996 Salmonella typhimurium Milk ~200,000 1984
  54. 54. Serogroup Example (serotype)* Characteristic syndrome A S. paratyphi A Enteric fever B S. paratyphi B Enteric fever or gastroenteritis B S. typhimurium Gastroenteritis B S. heidelberg Gastroenteritis, bacteremia C S. paratyphi C Enteric fever C S. choleraesuis Bacteremia C S. newport Gastroenteritis D S. typhi Enteric fever D S. enteritidis Gastroenteritis D S. dublin Bacteremia
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