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Understanding Non-Typhoidal Salmonella Infections: Key Points and Insights

Learn about the differences between Typhoidal and Non-typhoidal Salmonella infections, the burden of NTS in sub-Saharan Africa, zoonotic aspects, and more. Explore clinical features, risk factors, and cases from VGH Rounds.

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Understanding Non-Typhoidal Salmonella Infections: Key Points and Insights

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  1. Non-Typhoidal Salmonella (NTS) UBC tropical medicine rounds July 27, 2018 Jan Hajek

  2. Non-Typhoidal Salmonella (NTS)Take home points • Differences (and similarities) between Typhoidal and Non-typhoidal Salmonella • Burden of NTS infections in SSA • Schistosomiasis • NTS is a zoonotic disease - lessons for global antimicrobial resistance • Endovascular disease • Discussion of cases from VGH

  3. Cold-blooded animals and the environment* S. Enterica - warm-blooded mammals

  4. S. Typhimurium entering a HEp-2 cell through bacteria-mediated endocytosis. • Membrane ruffles extend from the cell surface, enclosing and internalizing adherent bacteria.

  5. Pathogenesis Salmonella can survive within macrophages

  6. Clinical featuresTyphoidal vs NTS • S. typhi and paratyphi • Enteric fever (S/SE Asia) • People and Peyer’s patches • Non-typhoidal salmonella • Gastroenteritis • Secondary bacteremia • Deep-seated focal infections (like S. aureus) • Primary bacteremia • Typically seen in immunocompromised hosts • Leading case of bacteremia in Africa

  7. NTS • Gastroenteritis • “Food-poisoning” • 12 – 48 hours later • Range from “cholera-like” to “dystentery-like” • Typically self-limited 3-5 days • Frequent asymptomatic shedding in stool for weeks after acute illness • 8% develop bacteremia • 8% of whom develop deep-seated focus of infection * risk for endovascular infection *

  8. Risk factors for invasive NTS infections • Age • HIV • Sickle cell • Atherosclerosis or endovascular grafts • Other: • Diabetes, cancer, liver disease…. • Early TTP

  9. In high-income countries: • NTS cause a self-limiting diarrhoeal illness in healthy individuals • Bacteremia is unusual and mainly happens in individuals with risk factors • In sub-Saharan Africa: • NTS are consistently the most common causes of bacteremia in both adults and children presenting with fever • Adults – HIV • Children - Malaria, HIV, Malnutrition Lancet 2012; 379: 2489–99

  10. 15,000 adults • 2,000 (13%) bacteremia • 43,000 children • 3,500 (8%) bacteremia • 30% NTS • 18% S. pneumonia • 12% other GNs • 9% S. aureus Lancet Infect Dis 2010; 10: 417–32

  11. TB accounted 30% (166/539) of isolates in the studies that used mycobacterial culture techniques. Lancet Infect Dis 2010; 10: 417–32

  12. SepsisBlood culture results: Canada Uganda (HIV positive) Jacob et al. PLOS ONE 2013; 8: e70305.

  13. NTS in SSAFebrile illness, diarrhea usually absent Lancet 2012; 379: 2489–99

  14. Causes of bacterial meningitisLacor hospital (2003  2006) • Examined the impact of the HiB vaccine (2001) • Children 0 – 5 years • 4,000 children who underwent LP for ?meningitis • 400 had cloudy CSF (WBC >100) • 65% had a positive culture What were the most common bacteria found? Annals of Tropical Paediatrics (2008)

  15. Causes of bacterial meningitisLacor hospital (2003  2006)

  16. Causes of bacterial meningitisLacor hospital (2003  2006)

  17. Most common: • Viral – especially influenza • Streptococcus pneumonia • Non-typhoidal salmonella • TB • Mycoplasma (0.7%) • Legionella, Chlamydia (0%) PLoS ONE 7(8): e43656. 2012

  18. 25 children with Salmonella bacteremia and Schistosomiasis • 19 treated for Schisto  no relapse occurred • 6 treated for just Salmonella  all relapsed after 1 month • No relapse occurred after a second course of antibiotics together with treatment for Schistosomaisis….

  19. Association with Schistosomiasis • 70 children, HIV negative, hospitalized with septicemic salmonellosis • 53 had NTS, 17 had Typhi/Paratyphi • 55 controls • Rectal biopsy was positive for Schistosomiasis in: • 90% with NTS • 65% with typhi or paratyphi • 38% of controls • “Treatment with antibiotics induced apyrexia only after administration of antiparasitic therapy in 30 patients.” Clinical Infectious Diseases 1994;18:103

  20. Clinical Infectious Diseases 1994;18:103

  21. Endovascular infection • 25% of patients > 50 years of age with NTS bacteremia have an underlying endovascular infection • The occurrence of bacteremia without associated recent GI symptoms is ominous and should prompt clinicians to consider whether an underlying immunosuppressive illness or anatomical risk factor is present. • Risk factors: • Age > 50 • Male • Atherosclerosis (PAD, CAD) • Time to positivity

  22. Endovascular infection • 67M presented with back and abdominal pain, fever and malaise • PMHx = Colon cancer, CABG with MVR 5 years ago • Blood cultures positive for S. enteridis • Wife and grandaughter had recent diarrheal illness

  23. Endovascular infection Strahm et al. Journal of Medical Case Reports 2012, 6:243

  24. Endovascular • 65M Japanese, 5-day fever and abdominal pain 54y

  25. Salmonella Aortitis • 77M • Born in China, living in NYC • DM2 and HTN • 10 days of abdominal pain, nausea • TB? • Syphilis aortitis? • IgG4 disease • Other? Parekh PJ, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2014-204525

  26. The ceftiofur story… • Omphalitis • Necrotizing infection of the chicken’s umbilical cord • “Mushy chicken disease” • Risk factors include • Delayed healing of the navel • Poor hygienic conditions • Some farmers used routine ceftiofur injections to prevent the infection…

  27. The ceftiofur storyFrom chickens to people… • Ceftiofur-resistance in Salmonella from retail chicken, correlated with rates of resistance in Salmonella from people Black bar = Cef-Res Salmonella in chicken Red line = Cef-Res Salmonella in patients Salmonella heidelberg EID. 2010 Jan; 16(1): 48–54.

  28. The ceftiofur storyWhat happened in Quebec… • Ceftiofur-resistance in people with Salmonella went down after (voluntary) suspension of ceftiofur use in chickens… EID. 2010 Jan; 16(1): 48–54.

  29. UBC studentReturned from field work in Brazil forests

  30. T2 hyperintense tissue appears to originate from the region of the first rib/sternum articulation on the left. • A tortuous sinus tract through the pectoralis muscle with a large component insinuating through the muscle and extending subcutaneously within left medial anterior chest

  31. Another case, lives in Vancouver 54M • Alcohol-related liver disease, malnutrition • March 5 • Dysuria and hematuria • Urine  Salmonella enterica • Ultrasound  normal kindeys • Cipro x 10 days  bit better, but not 100% • Worse again end of March  to VGH…

  32. Salmonella enteritidis bacteremia Salmonella renal abscess

  33. NTS Clinical features of the 2 disease patterns • Enterocolitis (in rich countries) • Self limited  Immunocompetent individuals • Bacteremia  Immunocompromised, risk groups • “Primary” bacteremia (in poor countries in SSA) • SSA  mimics enteric fever • Especially young children and immunosuppressed (HIV) • HIV, SCD, malignancy, chronic renal or liver disease, diabetes • Elderly and newborn patients

  34. Treatment • Febrile gastroenteritis • 0-14 days • Bacteremia • 7-14 days (immunocompetent, no risk factors) • ≥ 6 weeks (immunocompromised, deep seated infection)

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