Salmonellosis, Scrub typhus every things .pptx

Epidemiology

Caused by Salmonella species (Gram-negative, facultative intracellular bacilli, family Enterobacteriaceae).

Two broad clinical entities:

1. Typhoidal Salmonellosis (Enteric fever): S. Typhi and S. Paratyphi (A, B, C).


2. Nontyphoidal Salmonellosis (NTS): S. enteritidis, S. typhimurium, etc.



Transmission: fecal–oral route via contaminated food/water (especially poultry, eggs, dairy).

Risk groups: young children, elderly, immunocompromised (e.g., HIV, sickle cell disease).

Global burden: Major cause of foodborne gastroenteritis and enteric fever in endemic regions (South Asia, Africa).

1. Salmonellosis , Scrub typhus Dr Kushal Raj Joshi, Lecturer Department of Internal Medicine

2. Salmonella Gram-negative, non-spore-forming, facultative anaerobic bacilli 2–3 μ m long by 0.4–0.6 μ m wide Enterobacteriaceae Typhoidal Salmonella (e.g. S. Typhi , S. Paratyphi ): Cause enteric (typhoid) fever , human-restricted Nontyphoidal Salmonella (NTS) : Cause gastroenteritis, localized infections, bacteremia ; infect a wide range of animals and humans

3. >2,500 serotypes Main antigens used : O antigen : Somatic (LPS component) H antigen : Flagellar Vi antigen : Found only in S. Typhi and S. Paratyphi C

4. Groups A, B, C1, C2, D, and E (Based On O antigen) Cause ~99% of human and warm-blooded animal infections Ferment glucose with acid production Reduce nitrates Oxidase negative Motility : Most are motile via peritrichous flagella H₂S production : All except S. Typhi Lactose fermentation : Rare (~1%)

5. Pathogenesis Ingestion of contaminated food or water. Infectious dose: Ranges from 200 to 10⁶ CFU , affecting incubation period and disease severity. Risk factors increasing susceptibility: Low stomach acid (infants, acid suppression therapy, achlorhydria ) Compromised intestinal integrity (IBD, chemotherapy, prior GI surgery, antibiotic use)

6. S. Typhi and S. Paratyphi : Penetrate the gut mucosal barrier via M cells in Peyer’s patches . Use a type III secretion system to: Alter host actin cytoskeleton for uptake Trigger membrane ruffling and bacterium-mediated endocytosis .

7. Phagocytosis by macrophages follows epithelial penetration. Survival mechanisms include: PhoP / PhoQ regulatory system : Modifies outer bacterial membrane to resist host defenses. A second type III secretion system : Delivers proteins into macrophage cytoplasm to remodel the Salmonella-containing vacuole , promoting replication.

8. Disseminate via macrophages through lymphatics to reticuloendothelial system (liver, spleen, lymph nodes, bone marrow). Initial incubation phase is asymptomatic. Clinical symptoms and signs (fever, abdominal pain) result from: Cytokine release in response to growing bacterial load. Development of hepatosplenomegaly likely from cell mediated immune response to S.typhi colonization

9. Late manifestations: Enlargement and Necrosis of Peyer’s patches due to: Bacterial toxins which cause inflammation and cell death by recruiting additional mononuclear cells and lymphocytes Some S. Typhi strains produce toxins contributing to systemic symptoms and neuropsychiatric signs.

10. Nontyphoidal Salmonella (NTS) Causes gastroenteritis , not systemic disease in most cases. Massive neutrophil infiltration (both small and large bowel). Driven by IL-8 secretion Neutrophil degranulation → inflammatory diarrhea due to mucosal damage

11. Enteric (Typhoid) Fever A systemic illness caused by Salmonella enterica serotypes Typhi and Paratyphi (A, B, C) Epidemiology: Reservoir: Only humans (unlike other Salmonella serotypes). Transmission: Fecal-oral route via contaminated food/water; rare sexual and occupational transmission.

12. Global Burden (2017): Cases: ~14.3 million. Deaths: ~136,000. High Incidence Areas: South Central and Southeast Asia (>100/100,000). Risk Factors: Poor sanitation, raw produce, street food, flooding, contact with cases, reduced gastric acidity.

13. Paratyphoid Fever: Less common (1 case per 4 typhoid cases). S. Paratyphi A rising in prevalence, especially in India (possibly due to S. Typhi vaccination).

14. Clinical Features Incubation 5 to 21 days after ingestion. Longer with lower inoculum or in immunocompromised hosts. Classic Stages (in untreated patients) Week 1 Stepwise fever , chills (rigors rare), bacteremia . Relative bradycardia

15. Week 2 Abdominal pain , rose spots (salmon-colored macules on trunk/abdomen). Week 3 Hepatosplenomegaly Intestinal bleeding/perforation ( ileocecal Peyer’s patches necrosis). Secondary bacteremia , peritonitis, septic shock. Possible typhoid encephalopathy (delirium, confusion). Without complications, symptoms resolve over weeks.

16. Gastrointestinal Manifestations Diarrhea : more common in children and HIV patients. Constipation : ~30%, more in adults. Intestinal perforation (TIP) : Usually in week 3, ileum. Higher in Africa (7.6%) vs Asia (0.7%). High mortality: Africa ~20%, Asia ~1%.

17. Neurological Manifestations Common : Headache (44–94%), disturbed sleep Rare but severe : Encephalopathy, psychosis, myelitis , Parkinsonism. Encephalopathy mortality: up to 55% without dexamethasone . CSF: usually normal or mild pleocytosis .

18. Other Extraintestinal Features Respiratory : Cough (20–45%) Musculoskeletal : Myalgia , arthralgia (~20%) Rare : Hepatobiliary , cardiovascular, GU, CNS focal infections.

19. HIV Patients No consistent increase in severity(in contrast to NTS), but risk of: Atypical colitis. Worse outcomes in perforation with low CD4. Chronic Carriers Defined: Excretion >12 months post-infection. Prevalence : 1–6%, more in women & with biliary disease. Infectious risk High Vi antibody titers may suggest carrier state. Risk factor for gallbladder cancer .

20. Diagnosis Culture and Susceptibility Testing (Gold Standard) Blood Culture Positive in 50–70% of patients. Requires several days of incubation. Best early in illness.

21. Stool Culture Positive in 30–40% of cases. Often negative by the time systemic symptoms appear. Other Culture Sources Urine, rose spots, duodenal contents (via string capsule) can also be cultured. Bone Marrow Culture Most sensitive test (>90% sensitivity). Can remain positive even after ≥5 days of antibiotics . Reserved for complicated or resistant cases .

22. Anemia . Leukopenia (adults) or leukocytosis (children). LFTs : Frequently abnormal, sometimes mimics hepatitis. CRP : Often elevated.

23. PCR-based tests Limited sensitivity due to low bacterial load during bacteremia . Not widely used as primary diagnostic tools.

24. Serologic Testing (Limited Use) Widal Test Detects anti-O and anti-H antibodies . Low specificity in endemic regions (due to previous exposure). Requires paired samples for 4-fold rise in titers. Usefulness is geographically variable .

25. Rapid Antibody Tests Tubex ( IgM to LPS): Sensitivity 78%, specificity 87%. Typhidot ( IgM / IgG to outer membrane protein): Sensitivity 84%, specificity 79%. Not accurate enough to replace blood culture . ELISA Anti-Vi ELISA may help identify carriers , but not useful for acute illness . High background levels in endemic areas reduce accuracy. Emerging Tests IgA against Hemolysin E shows promise , currently under development.

26. Treatment I s increasingly complicated by antimicrobial resistance , particularly in Salmonella Typhi and S. Paratyphi . Fluoroquinolone Resistance : South Asia :80% of S. Typhi isolates are fluoroquinolone non-susceptible. A RCT in Nepal had to be terminated due to high treatment failure in the gatifloxacin arm.

27. Ceftriaxone Resistance Caused by ESBL-producing strains (e.g., via plasmids). Increasing reports from India and linked travel to Iraq . These isolates often remain sensitive to: Azithromycin Chloramphenicol Carbapenems

28. Azithromycin Resistance First report of azithromycin resistance (MIC 64 µg/ mL ) came from a traveler from Pakistan . So far, no co-resistance between ceftriaxone and azithromycin observed.

29. Multidrug Resistance (MDR) Defined as resistance to: Ampicillin Trimethoprim-sulfamethoxazole Chloramphenicol Prevalent in Asia, Africa, and the Middle East , though declining in some areas like India . India (2009–2013): 18% MDR S. Typhi India (2017–2020): 2% MDR S. Typhi

30. Extensively Drug-Resistant (XDR) Typhoid Resistance to five key antibiotics ( ampicillin , TMP-SMX, chloramphenicol , fluoroquinolones , and third-gen cephalosporins ). First major outbreak : Pakistan (2016–2018), >5000 cases. International spread to the UK, US . These strains are still susceptible to : Azithromycin Carbapenems

31. Monotherapy is usually sufficient. Choice depends on: Disease severity Local resistance patterns Drug availability Feasibility of oral vs. parenteral therapy

32. EMPIRIC THERAPY Severe or Complicated Disease ( eg , systemic toxicity, depressed consciousness, prolonged fever, organ system dysfunction, or other feature that prompts hospitalization ) Ceftriaxone (or cefotaxime ) 2-4 gm/day for 10-14 days

33. Uncomplicated Disease Azithromycin ( 1 g orally once then 500 mg orally daily OR 1 g orally once daily for 5-7 days) Guided therapy based on Culture and sensitivity Adjunctive Corticosteroids for Severe Cases Severe systemic illness (shock, coma, delirium) Dexamethasone 3 mg/kg IV, then 1 mg/kg every 6 hr × 48 hr Reduced mortality without added complications

34. Ileal Perforation Surgical emergency Segmental resection of perforated ileum Broad-spectrum to cover peritonitis and polymicrobial flora Mortality remains high (14–34%) even with intervention

35. FOLLOW-UP & RELAPSE Clinical improvement usually occurs within 3–5 days of treatment. Defervescence may take 4–6 days – delayed fever does not necessarily mean treatment failure.

36. Relapse : Occurs in 2–3 weeks after resolution of fever. More common with bacteriostatic agents (e.g., chloramphenicol : 10–25% relapse). Newer antibiotics: 1–6% relapse . Treatment : Re-treatment guided by susceptibility testing ; prolonged 3rd-gen cephalosporin is often reasonable.

37. POST-ACUTE SHEDDING & CHRONIC CARRIAGE Post-acute Shedding (≤3 months after infection) food handlers, healthcare workers, childcare workers, and children in daycare Seen in up to 10% of untreated and ~5% of treated children . Start ≥1 week after antibiotic completion and ≥1 month after onset of symptoms 3 stool samples , ≥24h apart. Continue until 3 consecutive negative results.

38. Chronic Carriage (>12 months shedding) Seen in 1–6% post S. Typhi infection. Risk Factors : Age >50 Female sex Gallbladder disease/stones Urinary: kidney stones, schistosomiasis

39. Screening : At least 3 stool samples, ≥24h apart; serology not recommended . Management : Fluoroquinolone -susceptible : Ciprofloxacin or Levofloxacin for 4 weeks . Fluoroquinolone -resistant : Based on susceptibility (e.g., high-dose amoxicillin ×6 weeks, or TMP-SMX ×3 months). If medical therapy fails : Consider cholecystectomy (70–80% success rate).

40. PREVENTION Food & Water Safety Safe water, proper sanitation, hygiene, and food safety education. Vaccination

41. In Endemic Areas (per WHO) : Typhoid Conjugate Vaccines (TCV) preferred. Recommend vaccination for children ≥6 months , with catch-up to 15 years . Nepal: 15months, IM(left outer thigh) E.g., Typbar -TCV , Typhibev , PedaTyph , etc.

42. In Non-Endemic Areas For travelers , lab workers , and contacts of carriers . Live oral vaccine (Ty21a) or Vi polysaccharide IM Revaccination every 2–5 years depending on formulation and risk.

43. Vaccine Efficacy : Typbar -TCV : ~78–85% efficacy (up to 4 years). Highly effective against XDR S. Typhi (~97%). Vi Polysaccharide : 55–69% over 1–3 years. Ty21a Oral : 45–59% over 1–3 years.

44. Durability : Typbar -TCV shows waning protection in young children after 3–5 years. Booster may be needed at school entry age in endemic regions. Investigational Vaccines Bivalent vaccines targeting both S. Typhi and S. Paratyphi A are in development.

45. Scrub typhus a mite-borne infectious disease caused by  Orientia tsutsugamushi Obligate intracellular, gram-negative coccobacillus Cannot grow in cell-free media Infects endothelial cells, monocytes , macrophages, dendritic cells Three main antigenic strains: Karp, Gilliam, Kato – Infection with one strain does not confer immunity to others

46. Estimated 1 million cases/year in Southeast Asia Farmers and people with outdoor exposure most affected Highest incidence in ages 40–60 Summer and Autumn

47. Vector & Reservoir : Larval trombiculid mites ( Leptotrombidium spp.), also called chiggers Maintain infection via transovarial transmission

48. Clinical Manifestations Ranges from asymptomatic infection to multiorgan failure, shock, and death . Severity varies with age , comorbidities , delayed treatment , and geographic factors Asymptomatic seroconversion : Common; only ~15% of seroconverted individuals develop symptoms.

49. Acute Febrile Illness Onset : 6–21 days post-infected mite bite. Initial symptoms : Headache, anorexia, malaise; or sudden fever with chills. Core symptoms : Fever (prolonged, median 14.4 days if untreated) Severe headache Diffuse myalgia

50. Rash Occurs in ~50% of patients. Type : Nonpruritic macular or maculopapular . Distribution : Starts on abdomen → spreads to extremities and face. Rare : Petechiae .

51. Eschar Painless papule → necrosis → black crust (classic eschar ). Variable prevalence: 18% to >78% depending on geography and clinical inspection. Often missed if not examining hidden areas (e.g., skin folds, genitalia).

52. Lymphadenopathy Localized → generalized lymphadenopathy May include splenomegaly , portal triaditis GI : Nausea, vomiting, diarrhea (~25% of patients) Endoscopy: Ulcers, erosions, bleeding lesions in many symptomatic patients Severity may correlate with skin lesions

53. Cardiovascular Relative bradycardia : HR increase <10 bpm per 1°C fever Myocarditis , rarely pericarditis or pericardial effusion Central Nervous System Meningitis , encephalitis , seizures , stroke Altered sensorium common in older adults Tinnitus/hearing loss can be a diagnostic clue Renal Acute kidney injury (AKI) , sometimes requiring dialysis (13% in severe cases)

54. Risk Factors for Severe Disease Older age (≥65 years): ~2x higher complication rate Delayed therapy (>6 days) Complications more common in older adults: AKI, mental confusion, dyspnea

55. Laboratory Findings Thrombocytopenia Elevated: Liver enzymes Bilirubin Creatinine White blood cell count: Often normal , but leukopenia or leukocytosis may occur

56. Diagnosis Suspected/clinical case: Acute undifferentiated febrile illness (UFI) of ≥5 days without eschar <5 days with eschar Probable case: A suspected clinical case with an IgM titer > 1:32 and/or a four-fold increase of titers between two sera confirm a recent infection.

57. Confirmed case: Rickettsial DNA is detected in eschar samples or whole blood by PCR OR Rising antibody titers on acute and convalescent sera detected by Indirect Immune Fluorescence Assay (IFA) or Indirect Immunoperoxidase Assay (IPA)

58. Treatment Doxycycline : 100mg BD for 5-10days Azithromycin : 500 mg OD for 5-7 days