title: Mathematical Modeling to Assess the Drivers of the Recent Emergence of Typhoid Fever in Blantyre, Malawi.
abstract: BACKGROUND
  Multiyear epidemics of Salmonella enterica serovar Typhi have been reported from countries across eastern and southern Africa in recent years. In Blantyre, Malawi, a dramatic increase in typhoid fever cases has recently occurred, and may be linked to the emergence of the H58 haplotype. Strains belonging to the H58 haplotype often exhibit multidrug resistance and may have a fitness advantage relative to other Salmonella Typhi strains.
  
  
  METHODS
  To explore hypotheses for the increased number of typhoid fever cases in Blantyre, we fit a mathematical model to culture-confirmed cases of Salmonella enterica infections at Queen Elizabeth Central Hospital, Blantyre. We explored 4 hypotheses: (1) an increase in the basic reproductive number (R0) in response to increasing population density; (2) a decrease in the incidence of cross-immunizing infection with Salmonella Enteritidis; (3) an increase in the duration of infectiousness due to failure to respond to first-line antibiotics; and (4) an increase in the transmission rate following the emergence of the H58 haplotype.
  
  
  RESULTS
  Increasing population density or decreasing cross-immunity could not fully explain the observed pattern of typhoid emergence in Blantyre, whereas models allowing for an increase in the duration of infectiousness and/or the transmission rate of typhoid following the emergence of the H58 haplotype provided a good fit to the data.
  
  
  CONCLUSIONS
  Our results suggest that an increase in the transmissibility of typhoid due to the emergence of drug resistance associated with the H58 haplotype may help to explain recent outbreaks of typhoid in Malawi and similar settings in Africa.
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Pitzer
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre Liverpool School of Tropical Medicine, United Kingdom.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Feasey
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre Department of Microbiology.
authors.forename: Chisomo
authors.initials: C
authors.lastname: Msefula
authors.affiliation: Department of Medicine.
authors.forename: Jane
authors.initials: J
authors.lastname: Mallewa
authors.affiliation: Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre.
authors.forename: Neil
authors.initials: N
authors.lastname: Kennedy
authors.affiliation: Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre.
authors.forename: Queen
authors.initials: Q
authors.lastname: Dube
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Denis
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre Institute of Infection and Global Health, University of Liverpool.
authors.forename: Melita A
authors.initials: MA
authors.lastname: Gordon
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre Division of Infection and Immunity, University College London, United Kingdom.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D000349:Africa; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D050936:Basic Reproduction Number; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008295:Malawi / Q000453:epidemiology; D008962:Models, Theoretical; D010802:Phylogeny; D011156:Population Density; D012477:Salmonella enteritidis / Q000235:genetics / Q000276:immunology; D012485:Salmonella typhi / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D014435:Typhoid Fever / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology / Q000635:transmission*
chemical_list: D000900:Anti-Bacterial Agents
keywords: H58 haplotype; Salmonella Typhi; multidrug resistance; transmission dynamics