There’s nothing new under the sun

1. There’s nothing new under the sun T Liong Intensive Care Unit United Christian Hospital July 2010

2. History • M/39 • History of splenectomy after trauma in China in 2006 • Vaccination history after splenectomy was unknown • Admission x fever, chills for few daysgeneralised weaknessvomiting/diarrhoea for 1 daycough with occasional BSSseen GP, told to have tonsillitis, given Fleming (amoxil/clavulanic acid) and antacidnoticed bluish discoloration of bil LL

3. P/E BP 92/54 P 150 sinus tachycardia temp 37°C SpO2 97% RAGCS 15/15CVS/chest/abd NADneuro: no neck stiffness no focal neuro signskin:

9. What is this sign called? • Purpura Fulminans • Refer to widespread severe purpura • Characterized by palpable purpuric lesions, spreading ecchymosis, haemorrhagic blisters and distal extremities gangrene • Syndrome of intravascular thrombosis and haemorrhagic infarction of skin • Usually occurs in children, but has been noted in adults

10. Diagnosis? • Meningococcaemia • Septicaemia with DIC • others

11. Investigations • WBC 41.2 Hb 16.0 plt 34 INR 1.9 • Ur 22.4 Cr 474 Na 136 K 5.6 BE -12 • LFT: hepatitis pattern AST 1465 ALT 583 • CRP 318

12. NPA influenza A/B Ag, RT-PCR H1N1 –ve • CSU WCC scanty, culture –ve • Sputum WCC scanty, culture –ve • Blood culture –ve • CXR clear

13. Microbiologist was consulted for alternative method of diagnosis • 16S rRNA gene sequencing • Blood x PCR for 16S rRNA for Strept suis was positive • Streptococcus suis septicaemia was confirmed • Patient works as a butcher

14. 16S rRNA Gene Sequencing for Pathogens Identification in Microbiology Laboratory

15. Conventional methods for microbial identification:depends on morphology, growth, enzymatic activity, metabolism

16. Molecular techniques for microbial identification Stable target Objective No specific growth requirements Easier to standardise

17. 16S rRNA gene Ubiquitous, present in almost all microorgansims Stable and highly conserved molecule Large enough (1,500 bp) to provide distinguishing measurements Extensively studied and represented in databases • Conversed regions - targeted by primers • Hypervariable regions - generate sequence data

18. Identification criteria depends on degree of sequence similarity

19. 16S rRNA gene sequencing process • Bacterial colonies DNA extraction PCR for 16S rRNA gene Purify PCR product Sequence PCR product Purify sequencing product Sequence detection Data assembly and analysis

20. Limitations • Expensive, labor-intensive, require special equipment and expertise • Ambiguous data in databases • sequence errors, incomplete sequences, insufficient strain characterization, limited data • Lack of stringent interpretation criteria for identification • Usually requires a pure culture • Application for direct clinical samples • Yield is often low • Presence of inhibitors, contamination

21. Streptococcus Suis Infection

22. Strept suis infection • Zoonotic microbes most adapted to pigs • In swine, it can be asymptomatic or cause a spectrum of disease • Spread by direct contact or aerosol over short distance • Occasionally cause infection in humans, mainly related to occupational exposure through skin cuts or abrasions while handling infected pig carcass

23. Clinical features • Meningitis, sepsis, less commonly, endocarditis, arthritis, bronchopneumonia • Characteristic complication of Strep suis infection is deafness • Likely permanent, bilateral > unilateral • Notifiable disease in Hong Kong • In year 2009, 6 cases have been notified

24. Toxic Shock Syndrome • CDC Definition:

25. Usually caused by S aureus or Strept. Pyogenes (a member of group A strept) • Sporadic cases of non-group A Streptoccocal TSS 1) Toxic Shock—like Syndrome Caused by Non—Group A β-Hemolytic Streptococci. Arch Intern Med. 1997;157(16):1891-1894 2) An overwhelming post-splenectomy infection with toxic shock syndrome by group B Streptococcus. Japanese Journal of Clinical Hematology 51(4):253-7, 2010 Apr. 3) Acute peritonitis and salpingitis associated with streptococcal toxic shock syndrome caused by Lancefield group G alpha-haemolytic Streptococcus dysgalactiae subsp. equisimilis. Journal of Medical Microbiology. 55(Pt 7):953-6, 2006 Jul 4) An Australian Case of Streptococcus suis Toxic Shock Syndrome associated with occupational exposure to animal carcasses. MJA 2008; 188: 538-9

26. Zichuan >200 patients infected 38 were killed Many had TSS

28. Go back to our patient…

29. Progress • Put on Rocephin since admission • Vigorous fluid resuscitation • Blood test results normalised • Echo: no evidence of SBE • CT thorax: NAD

30. After the patient was stabilized… • Does he need vaccination? • Does he need antibiotic prophylaxis?

31. What kind of vaccination should be given? A) None, because there is a possibility that he has been vaccinated before B) Pneumovax 23 C) Meningococcal vaccine D) H influenzae type b vaccine E) Influenza vaccine F) All of the above G) Any combination

32. Spleen • Immunologic function:- filter the blood of pathogenic bacteria and fungi- synthesizing IgM for opsonizing encapsulated pathogens • Asplenia  risk of overwhelming and life threatening infection

33. In 1969, Diamond introduced a term “overwhelming post-splenectomy infection” (OPSI) – a syndrome of fulminant bacteriaemia or septicaemia that will progress from good health to death within a short time period, < 24 hours. • Risk of infection after splenectomy is infrequent but definite, regardless of age and indication of splenectomy • Early post-op period and younger patients are most susceptible • Age <16, incidence of OPSI and mortality were 4.4% and 2.2% while those in adults were 0.9% and 0.8% respectively

34. Microorganisms responsible for OPSI: • pneumococci (50%) • meningococci (12%) • E Coli (11%) • H Influenzae (8%) • S aureus (8%) • Streptococcus (7%) Singer. Postsplenectomy sepsis. Perspect Pediatr Pathol 1973; 1:285-311 Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 2001; 7:657-660 Williams DN, Kaur B. Postsplenectomy care. Strategies to decrease the risk of infection. Postgrad Med 1996; 100:195-198

35. Pneumococcal vaccine • 2 types of vaccines:- pneumovax 23 – contains capsular polysaccharides from 23 common serotypes of S pneumoniae, cover ~90% of serotypes commonly encountered - 7-valent conjugate pneumococcal vaccine (PCV7) is more immunogenic but protects against smaller no. of serotypes • CDC/British Committee for Standards in Haematology Clinical Haematology Task Force recommended Pneumovax 23 in asplenic adults

36. Meningococcal vaccine • CDC recommends quadrivalent meningococcal vaccine – serotypes A, C, Y and W-135 (MCV4 preferred in aged ≤ 55 years v.s MPSV4 preferred in aged ≥56 years) • British Committee for Standards in Haematology Clinical Haematology Task Force recommended vaccine to protect against serotype C • Type B was the most common serotype in HK, followed by W-135 and serotype C • No commercially available vaccine protects against serotype B

37. H influenzae type B vaccine (Hib) • Efficacy and usefulness of H influenzae type B vaccine is less clear • Most adults already had immunity for H influenzae • Some children had vaccinated in early childhood • Both authorities still recommended that Hib vaccine should be considered

38. Influenza vaccine • No data specify on risk of severe or complicated influenza infections among asplenic patients • Influenza is a risk factor for secondary bacterial infection that may cause severe sepsis in asplenic patients • Both recommended annual influenza vaccine

39. When should the vaccine be given? • Patients who undergo elective splenectomy:- pneumovax 23, meningococcal vaccine, Hib vaccine should be given at least 2 weeks before surgery • If not possible, immunizations can be given after D14 of surgery Shatz et al. Immune responses of splenectomized trauma patients to the 23-valent pneumoccocal polysaccharide vaccine at 1 vs 7 vs 14 days after splenectomy. J Trauma 1998; 44:760

40. When should patients be revaccinated? ※insufficient data concerning safety of pneumovax when administered 3 or more times ‡no data to guide recommendations on revaccination for persons who previously vaccinated with MCV4

41. Antibiotic Prophylaxis • Yes ? No ? • Controversial in adult population:- All studies demonstrated the efficacy of daily antibiotic prophylaxis were from paediatric group 1 ) Jugenburg et al. The morbidity and mortality of paediatric splenectomy: does prophylaxis make a difference? J Paediatr Surg 1999; 34:1064 2) Gaston et al. Prophylaxis with oral penicillinin Children with sickle cell anaemia. A randomized trial. NEJM 1986; 314:1593 - incidence and mortality of OPSI in adult is much lower than paediatric population (4.4% and 2.2 % respectively v.s. 0.9% and 0.8% respectively) - compliance is a problem - drug resistance S. pneumoniae is emerging

42. Individual case reports reported failure of daily antibiotic prophylaxis 1) Evan DI. Fatal post-splenectomy sepsis despite prophylaxis with penicillin and pneumococcal vaccine [Letter] Lancet 1984; 1:1124 2) Brivet et al. Fatal post-splenectomy pneumoccoal sepsis despite pneumoccal vaccine and penicillin prophylaxis [Letter] Lancet 1984; 2: 356-7

43. Antibiotic Prophylaxis • CDC only recommended antibiotic prophylaxis in children with asplenia, duration of such prophylaxis is not clear • American Academy of Paediatrics suggested antibiotic prophylaxis for up to 5 years old • French expert committee recommended 2 years antibiotic prophylaxis post splenectomy • British Committee for Standards in Haematology Clinical Haematology Task Force recommended lifelong antibiotic prophylaxis though no data to support or refute this strategy

44. Conclusion • Strept suis can cause a spectrum of disease, not only meningitis with deafness • TSS not only caused by S aureus or Group A Strep • Introduced a new method for diagnosis • Brief discussion on management of patients after splenectomy

45. End of Presentation