ARF & RHD Primordial and Primary Prevention Bart Currie Infectious Diseases Department, Royal Darwin Hospital Global and Tropical Health Division, Menzies Northern Territory Medical Program, Flinders & CDU
Group A Streptococcal Diseases Streptococcus pyogenes = Gp A streptococcus = GAS • • Pharyngitis Pyoderma Cellulitis Invasive Diseases • Septicemia • Pneumonia, osteomyelitis, septic arthritis, meningitis • Puerperal sepsis# # • Necrotising fasciitis • Streptococcal toxic shock (like) syndrome - STSS • Post-streptococcal sequelae • Acute rheumatic fever (ARF) • Glomerulonephritis (APSGN)
Throat and skin and ARF and APSGN ARF ? Skin GAS ? ? priming APSGN Throat GAS
Pathogenesis of Acute Rheumatic Fever Organism factor(s) Host factor(s) (“Rheumatogenicity”) (Genetic susceptibility) Abnormal immune response Acute rheumatic fever
Age and Gp A streptococcal sequelae John Mathews drew this many years back…….
Throat and skin and ARF and APSGN ARF ? Skin GAS ? ? priming APSGN Throat GAS
Preventing ARF and RHD Primordial prevention GAS infection Primary prevention -Sore throat Rx -? Vaccine -? Skin sore Rx ARF Secondary prevention -Regular penicillin Often prolonged asymptomatic period of RHD Cardiac surgery Stroke, endocarditis Tertiary prevention -Heart failure medication -Surgery -Anticoagulation Death
Preventing ARF and RHD Primordial prevention GAS infection Primary prevention -Sore throat Rx -? Vaccine -? Skin sore Rx ARF Secondary prevention -Regular penicillin Often prolonged asymptomatic period of RHD Cardiac surgery Stroke, endocarditis Tertiary prevention -Heart failure medication -Surgery -Anticoagulation Death
Prof Graeme Maguire
Primordial prevention of ARF/RHD • • • Housing Education Employment Communications Transport & access to services Mc. Donald E et al. BMC Public Health 2008; 8: 153 Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
GAS Transmission and Crowding Warren Air Force Base, Wyoming USA Bed distance from “colonised” barracks mate correlated with GAS acquisition Ë 0 -5 feet > 60 GAS acquisitions/100, 000 man weeks Ë> 30 feet < 20 GAS acquisitions/100, 000 man weeks Wannamaker LW. 1954
The Big Picture “ Now, I keep saying that I don’t care what colour you are or where you come from, but if you’re living in a small house with large numbers of people, then you’re going to get sick. ” Puggy Hunter, NACCHO Chairman, 2001
Pyoderma and crowding Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
Primordial prevention of ARF/RHD • • • Housing Education Employment Communications Transport & access to services Mc. Donald E et al. BMC Public Health 2008; 8: 153 Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
Primordial prevention of pyoderma • • • Housing Education Employment Communications Transport & access to services Mc. Donald E et al. BMC Public Health 2008; 8: 153 Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
Preventing ARF and RHD Primordial prevention GAS infection Primary prevention -Sore throat Rx -? Vaccine -? Skin sore Rx ARF Secondary prevention -Regular penicillin Often prolonged asymptomatic period of RHD Cardiac surgery Stroke, endocarditis Tertiary prevention -Heart failure medication -Surgery -Anticoagulation Death
Primary Prevention of ARF/RHD • Prophylactic antibiotics for GAS • Treating GAS pharyngitis • Treating GAS pyoderma? • A GAS vaccine
Primary prevention of pyoderma • Hand washing – can it become routine and sustainable? • Swimming pools – positive reports but confounders • Treatment of scabies – directed and mass treatment – Galiwin’ku trial • Community campaigns and healthy skin days – Wadeye and East Arnhem data • BPG in APSGN outbreaks – stop GAS transmission? • Vaccines – for Gp A Strep and scabies; imminent? ? Carapetis J et al. Pediatr Infect Dis J 1997 ; 16: 494 -9 Johnston F et al. Pediatr Infect Dis J 1999; 18: 327 -32 Wong LC et al. Med J Aust 2001; 175: 367 -70 Lehmann D et al. BMJ 2003; 327: 415 -9 Luby S et al. Lancet 2005; 366: 225 -33 La Vincente S et al. Plo. S Neglected Trop Dis 2009; 3: e 444 Andrews R et al, PLo. S Neglected Trop Dis 2009; 3: e 554
www. nt. gov. au/health/cdc
Primary prevention of pyoderma • Hand washing – can it become routine and sustainable? • Swimming pools – positive reports but confounders • Treatment of scabies – directed and mass treatment – Galiwin’ku trial • Community campaigns and healthy skin days – Wadeye and East Arnhem data • BPG in APSGN outbreaks – stop GAS transmission? • Vaccines – for Gp A Strep and scabies; imminent? ? Carapetis J et al. Pediatr Infect Dis J 1997 ; 16: 494 -9 Johnston F et al. Pediatr Infect Dis J 1999; 18: 327 -32 Wong LC et al. Med J Aust 2001; 175: 367 -70 Lehmann D et al. BMJ 2003; 327: 415 -9 Luby S et al. Lancet 2005; 366: 225 -33 La Vincente S et al. Plo. S Neglected Trop Dis 2009; 3: e 444 Andrews R et al, PLo. S Neglected Trop Dis 2009; 3: e 554
Primary prevention of pyoderma • Hand washing – can it become routine and sustainable? • Swimming pools – positive reports but confounders • Treatment of scabies – directed and mass treatment – Galiwin’ku trial • Community campaigns and healthy skin days – Wadeye and East Arnhem data • BPG in APSGN outbreaks – stop GAS transmission? • Vaccines – for Gp A Strep and scabies; imminent? ? Carapetis J et al. Pediatr Infect Dis J 1997 ; 16: 494 -9 Johnston F et al. Pediatr Infect Dis J 1999; 18: 327 -32 Wong LC et al. Med J Aust 2001; 175: 367 -70 Lehmann D et al. BMJ 2003; 327: 415 -9 Luby S et al. Lancet 2005; 366: 225 -33 La Vincente S et al. Plo. S Neglected Trop Dis 2009; 3: e 444 Andrews R et al, PLo. S Neglected Trop Dis 2009; 3: e 554
Scabies
Why is scabies so hard to eradicate? 2 1 3 3 4: population mobility 3
Primordial prevention of scabies • • • Housing Education Employment Communications Transport & access to services Mc. Donald E et al. BMC Public Health 2008; 8: 153 Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
Primordial prevention of pyoderma • • • Housing Education Employment Communications Transport & access to services Mc. Donald E et al. BMC Public Health 2008; 8: 153 Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
Primordial prevention of trachoma • • • Housing Education Employment Communications Transport & access to services Mc. Donald E et al. BMC Public Health 2008; 8: 153 Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
Primordial prevention of ARF/RHD • • • Housing Education Employment Communications Transport & access to services Mc. Donald E et al. BMC Public Health 2008; 8: 153 Mc. Donald M et al. Clin Infect Dis 2006; 43: 683 -9 Bailie R et al. BMC Public Health 2010; 10: 147
What we know we don’t know • Who are the “ 3 -6%” susceptible? – what is the genetic basis of this? • What is the immunopathogenetic process? – we need a diagnostic blood test for ARF • Which Gp A strep emm types – how restricted? – what about GCS and GGS (horiz gene transfer)? • What have skin GAS got to do with it? • How to make primordial prevention a reality? • How to best choose when to Tx “throats” • What is the PK/PD of benzathine penicillin? • How do we optimise secondary prophylaxis? – dosing, intervals, adherence, pain, site, i-fat?
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