Epidemiology and Genomics of Invasive Nontyphoidal Salmonella Infections in Kenya.

BACKGROUND In Kenya, invasive nontyphoidal Salmonella (iNTS) disease causes severe bacteremic illness among adults with human immunodeficiency virus (HIV) and especially among children <5 years of age coinfected with HIV or malaria, or who are compromised by sickle cell disease or severe malnutrition. The incidence of iNTS disease in children ranges from 166 to 568 cases per 100,000 persons per year. METHODS We review the epidemiology of iNTS disease and genomics of strains causing invasive illness in Kenya. We analyzed a total of 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools from pediatric admissions in 2005-2013. Testing for antimicrobial susceptibility to commonly used drugs and whole-genome sequencing were performed to assess prevalence and genetic relatedness of multidrug-resistant iNTS strains, respectively. RESULTS A majority (88/114 [77%]) of Salmonella Typhimurium and 30% (24/79) of Salmonella Enteritidis isolates tested were found to be multidrug resistant, whereas a dominant Salmonella Typhimurium pathotype, ST313, was primarily associated with invasive disease and febrile illness. Analysis of the ST313 isolates has identified genome degradation, compared with the ST19 genotype that typically causes diarrhea in humans, especially in industrialized countries, adapting a more host-restricted lifestyle typical of Salmonella Typhi infections. CONCLUSIONS From 2012, we have observed an emergence of ceftriaxone-resistant strains also showing reduced susceptibility to fluoroquinolones. As most cases present with nonspecific febrile illness with no laboratory-confirmed etiology, empiric treatment of iNTS disease is a major challenge in Kenya. Multidrug resistance, including to ceftriaxone, will pose further difficulty in management of iNTS disease in endemic areas.

[1]  J. Cheesbrough,et al.  Salmonella bacteraemia among young children at a rural hospital in western Zaire. , 1993, Annals of tropical paediatrics.

[2]  D. Mabey,et al.  Neglected tropical diseases. , 2010, British medical bulletin.

[3]  P. McDermott,et al.  Antimicrobial resistance among gram-negative foodborne bacterial pathogens associated with foods of animal origin. , 2004, Foodborne pathogens and disease.

[4]  P. Bahwere,et al.  Community-acquired bacteremia among hospitalized children in rural central Africa. , 2001, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[5]  R. Breiman,et al.  Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006–2009 , 2012, PloS one.

[6]  B. Lowe,et al.  Prognostic indicators of early and late death in children admitted to district hospital in Kenya: cohort study , 2003, BMJ : British Medical Journal.

[7]  Georgios S. Vernikos,et al.  Comparative genome analysis of Salmonella Enteritidis PT4 and Salmonella Gallinarum 287/91 provides insights into evolutionary and host adaptation pathways. , 2008, Genome research.

[8]  Julian Parkhill,et al.  Evolution of MRSA During Hospital Transmission and Intercontinental Spread , 2010, Science.

[9]  D. Conway,et al.  A Decline in the Incidence of Invasive Non-Typhoidal Salmonella Infection in the Gambia Temporally Associated with a Decline in Malaria Infection , 2010, PLoS ONE.

[10]  S. Kariuki,et al.  Increasing prevalence of multidrug-resistant non-typhoidal salmonellae, Kenya, 1994-2003. , 2005, International journal of antimicrobial agents.

[11]  J. Crump,et al.  Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis. , 2010, The Lancet. Infectious diseases.

[12]  K. Maitland,et al.  Assessment of severe malnutrition among hospitalized children in rural Kenya: comparison of weight for height and mid upper arm circumference. , 2005, JAMA.

[13]  S. Kariuki,et al.  Characterisation of community acquired non-typhoidal Salmonella from bacteraemia and diarrhoeal infections in children admitted to hospital in Nairobi, Kenya , 2006, BMC Microbiology.

[14]  M. Quail,et al.  High-Resolution Single Nucleotide Polymorphism Analysis Distinguishes Recrudescence and Reinfection in Recurrent Invasive Nontyphoidal Salmonella Typhimurium Disease , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  John J Boland,et al.  Growth Promoting Antibiotics in Food Animal Production: An Economic Analysis , 2007, Public health reports.

[16]  J. Crump,et al.  Global Burden of Invasive Nontyphoidal Salmonella Disease, 2010 , 2015, Emerging infectious diseases.

[17]  K. Marsh,et al.  Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case–control study , 2009, The Lancet.

[18]  M. Molyneux,et al.  Epidemics of invasive Salmonella enterica serovar enteritidis and S. enterica Serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  T. Hald,et al.  Attributing foodborne salmonellosis in humans to animal reservoirs in the European Union using a multi-country stochastic model , 2014, Epidemiology and Infection.

[20]  Sheng Chen,et al.  Emergence of Clinical Salmonella enterica Serovar Typhimurium Isolates with Concurrent Resistance to Ciprofloxacin, Ceftriaxone, and Azithromycin , 2014, Antimicrobial Agents and Chemotherapy.

[21]  S. Kariuki,et al.  Antimicrobial resistance and management of invasive Salmonella disease. , 2015, Vaccine.

[22]  P. Griffin,et al.  Outbreaks of Salmonella infections attributed to beef – United States, 1973–2011 , 2014, Epidemiology and Infection.

[23]  J. Meng,et al.  Characterization of extended-spectrum beta-lactamases-producing Salmonella strains isolated from retail foods in Shaanxi and Henan Province, China. , 2014, Food microbiology.

[24]  G. Dougan,et al.  Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. , 2009, Genome research.

[25]  K. Maitland,et al.  HIV infection, malnutrition, and invasive bacterial infection among children with severe malaria. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  Q. Bassat,et al.  Community-Acquired Bacteremia Among Children Admitted to a Rural Hospital in Mozambique , 2009, The Pediatric infectious disease journal.

[27]  Gemma C. Langridge,et al.  Ceftriaxone-Resistant Salmonella enterica Serotype Typhimurium Sequence Type 313 from Kenyan Patients Is Associated with the blaCTX-M-15 Gene on a Novel IncHI2 Plasmid , 2015, Antimicrobial Agents and Chemotherapy.

[28]  N. Mirza,et al.  Problems of Salmonella infections in a hospital in Kenya. , 1981, East African Medical Journal.

[29]  B. Lowe,et al.  Salmonella Bacteremia in Kenyan Children , 2006, The Pediatric infectious disease journal.

[30]  J. Morvan,et al.  Bacteremia in adults admitted to the Department of Medicine of Bangui Community Hospital (Central African Republic). , 2003, Acta tropica.

[31]  K. Maitland,et al.  Bacteremia among children admitted to a rural hospital in Kenya. , 2005, The New England journal of medicine.

[32]  Alexandros Stamatakis,et al.  RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models , 2006, Bioinform..

[33]  J. Crump,et al.  Antimicrobial Resistance among Invasive Nontyphoidal Salmonella enterica Isolates in the United States: National Antimicrobial Resistance Monitoring System, 1996 to 2007 , 2011, Antimicrobial Agents and Chemotherapy.

[34]  K. Laupland,et al.  Salmonella enterica bacteraemia: a multi-national population-based cohort study , 2010, BMC infectious diseases.

[35]  E. Barzilay,et al.  Increase in resistance to ceftriaxone and nonsusceptibility to ciprofloxacin and decrease in multidrug resistance among Salmonella strains, United States, 1996-2009. , 2013, Foodborne pathogens and disease.

[36]  S. Kariuki,et al.  Invasive multidrug-resistant non-typhoidal Salmonella infections in Africa: zoonotic or anthroponotic transmission? , 2006, Journal of medical microbiology.

[37]  W. Dolmans,et al.  Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia , 2001, Tropical medicine & international health : TM & IH.

[38]  R. Breiman,et al.  Mortality Trends Observed in Population-Based Surveillance of an Urban Slum Settlement, Kibera, Kenya, 2007–2010 , 2014, PloS one.

[39]  S. Kariuki,et al.  Trends in bloodstream infections among human immunodeficiency virus-infected adults admitted to a hospital in Nairobi, Kenya, during the last decade. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  G. Dougan,et al.  Antibacterial resistance in sub‐Saharan Africa: an underestimated emergency , 2014, Annals of the New York Academy of Sciences.

[41]  J. Wain,et al.  Intra-continental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa , 2012, Nature Genetics.

[42]  M. Molyneux,et al.  Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. , 2007, The Journal of infectious diseases.

[43]  D. Warrell,et al.  Life-threatening bacteraemia in HIV-1 seropositive adults admitted to hospital in Nairobi, Kenya , 1990, The Lancet.

[44]  L. Majtánová,et al.  Increasing trend of resistance to nalidixic acid and emerging ceftriaxone and ciprofloxacin resistance in Salmonella enterica serovar Typhimurium in Slovakia, 2005 to 2009. , 2010, Diagnostic microbiology and infectious disease.