Robery Heyderman @ MRF's Meningitis & Septicaemia in Children & Adults 2015
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This document discusses epidemics of non-typhoidal Salmonella sepsis and meningitis in Africa. It notes that invasive non-typhoidal Salmonella (iNTS) disease is a major cause of bloodstream infections and death in Africa, with an estimated 681,316 deaths annually. Two novel Salmonella Typhimurium sequence types have caused epidemics in Malawi since the late 1990s. The emergence of these strains has been linked to the spread of antimicrobial resistance and HIV/AIDS. Ongoing surveillance efforts are aimed at understanding reservoirs and transmission modes to help develop public health interventions against iNTS disease in Africa.
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Robery Heyderman @ MRF's Meningitis & Septicaemia in Children & Adults 2015
- 1. Epidemics of Non-typhoidal Salmonella Sepsis and Meningitis in Africa Meningitis & Septicaemia in Children and Adults November 2015 Rob Heyderman Division of Infection & Immunity, UCL
- 2. Epidemic Meningococcal Meningitis >150,000 cases and 16,000 deaths in 1996 Meningitis belt See review: Greenwood Trans Roy Soc Trop Med 1999; 3:341-353
- 3. Clin Infect Dis 2005; 40:17
- 4. 0 100 200 300 400 500 600 700 Jan -Jun 1998 Jul-D ec 1998 Jan -Jun 1999 Jul-D ec 1999 Jan -Jun 2000 Jul-D ec 2000 Jan -Jun 2001 Jul-D ec 2001 Jan -Jun 2002 Jul-D ec 2002 Jan -Jun 2003 Jul-D ec 2003 Jan -Jun 2004 Jul-D ec 2004 no.isolates 0 10 20 30 40 50 60 70 80 90 100 %MDR S. Enteritidis isolates S. Typhimurium isolates % S. Enteritidis MDR % S Typhimurium MDR Epidemics of Invasive NTS serovars in Malawi Gordon et al Clin infect Dis 2008
- 5. Community-acquired BSI in Africa West & Central Africa North Africa East Africa Southern Africa Adapted from Lancet Infect Dis. 2010 Reddy, Shaw & Crump Salmonella in Africa Consensus Meeting Blantyre, Malawi Heyderman & Crump EID and CID 2015
- 6. Malawi Kenya Mozambique Tanzania The Gambia Burden of Invasive NTS Disease Crump EID 2015 (Systematic Review) • Case fatality ratio 20% • Estimated deaths annually 681,316
- 7. Clinical Features of Invasive NTS Disease Feasey Lancet 2012; 379: 2489–99
- 8. • 278 cases; 45% Salmonella Typhimurium • 54% <15 years • Disease of HIV-infected adults and largely HIV- uninfected neonates • Mortality 47% • Death associated with GCS ≤13 (adj OR 18.7; 95% CI 3–119) Clin Infect Dis 2015;61(S4):S272–82
- 9. Non-typhoidal Salmonella (NTS) Challenges to Established Dogma • Clinical illness due to NTS is most commonly self-limited gastroenteritis • Animals are the reservoir • Transmission from animal contaminated unprocessed & processed foods • All NTS strains are equal
- 10. Kingsley, Msefula et al Genome Res. 2009 The Molecular Basis of Epidemic Salmonella Typhimurium Novel sequence type (ST313) Virulence & Antibiotic Resistance Plasmid (pSLT-BT) = transferable pSLT-BT Typhi
- 11. Intercontinental spread of Salmonella Typhimurium path variants Lineage I: ~52yrs ago HIV emergence Lineage II: ~35yrs ago Chloramphenicol resistance Okoro et al Nature Genetics 2012
- 12. Molecular Basis of Epidemic Salmonella Enteritidis Feasey submitted
- 13. Reduction in BSI and in-patient case fatality in adults with roll-out of ART 1997/8 [Peters et al 2004] 2009/10 [Feasey et al unpublished] n % n % z- test (p- value) All-cause mortality 502/2789 18.0 269/2184 12.3 <0.001 Blood culture-confirmed BSI 171/433 39.5 32/229 14.0 <0.001 Nontyphoidal Salmonellae 54/164 32.9 9/84 10.8 <0.001 S. pneumoniae 49/136 36.0 4/56 8.9 <0.001 Blood-culture negative/contaminated 331/2356 14.0 237/1955 12.1 0.066 2014] [Gordon et al 2001]
- 14. Falling Childhood NTS in Malawi Smoothed Structural Equation Model iNTS Malaria Feasey Neg Trop Dis 2015 Cases/month Cases/year
- 15. • 2009 - Ceftriaxone resistant NTS emerged • 2010 - 6.2% (2/32 isolates) • 2012 - 57% (13/23 isolates) Clin Infect Dis 2015;61(S4):S310–6
- 16. Salmonella BSI in Blantyre (Nov 2010-Oct 2014)Cases/month %ofS.TyphiwhichareMDR Month Feasey Neg Trop Dis 2015; Feasey CID 2015; Pfitzer CID 2015
- 17. Global dissemination of S. Typhi H58 Fiji Emerged ~30 years ago ~ 1,800 isolates 63 countries 6 continents Wong Nature Genetics 2015
- 18. Conclusions • iNTS disease is an important cause of death in Africa • Three epidemics of Salmonella bloodstream infection in Malawi since 1999 • Epidemics of MDR iNTS disease = novel clades • Reservoirs of disease and modes of transmission are unknown • Concerted efforts are required if Public Health interventions including vaccines are to be developed and implemented
- 19. Acknowledgments Gordon Dougan Robert Kingsley Chinyere Okoro Vanesa Wong Nick Thomson Julian Parkhill Cal MacLennan Co-authors of CID Supplement Chisomo Msefula Nick Feasey Melita Gordon Mavuto Mukaka Tonney Nyirenda Mike Moore Brigitte Denis Theresa Allain Joep van Oosterhout Angela Houston Dan Komrower Thandie Mwalukomo Malcolm Molyneux Elizabeth Molyneux Terrie Taylor Stephen Gordon Chris Parry David Lalloo Brian Faragher Lysin Tent Hani Andreas John Remco Peters