title: Modelling the Contributions of Malaria, HIV, Malnutrition and Rainfall to the Decline in Paediatric Invasive Non-typhoidal Salmonella Disease in Malawi.
abstract: BACKGROUND
  Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous longitudinal data to model the interrelationships between iNTS disease, malaria, HIV and malnutrition.
  
  
  METHODS
  Trends in monthly numbers of childhood iNTS disease presenting at Queen's Hospital, Blantyre, Malawi from 2002 to 2010 were reviewed in the context of longitudinal monthly data describing malaria slide-positivity among paediatric febrile admissions, paediatric HIV prevalence, nutritional rehabilitation unit admissions and monthly rainfall over the same 9 years, using structural equation models (SEM).
  
  
  RESULTS
  Analysis of 3,105 iNTS episodes identified from 49,093 blood cultures, showed an 11.8% annual decline in iNTS (p < 0.001). SEM analysis produced a stable model with good fit, revealing direct and statistically significant seasonal effects of malaria and malnutrition on the prevalence of iNTS disease. When these data were smoothed to eliminate seasonal cyclic changes, these associations remained strong and there were additional significant effects of HIV prevalence.
  
  
  CONCLUSIONS
  These data suggest that the overall decline in iNTS disease observed in Malawi is attributable to multiple public health interventions leading to reductions in malaria, HIV and acute malnutrition. Understanding the impacts of public health programmes on iNTS disease is essential to plan and evaluate interventions.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, 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, Malawi; Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Dean
authors.initials: D
authors.lastname: Everett
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: E Brian
authors.initials: EB
authors.lastname: Faragher
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Roca-Feltrer
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kang'ombe
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Denis
authors.affiliation: Leonard Cheshire Disability & Inclusive Development Centre, University College London, London, United Kingdom; Department of Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Marko
authors.initials: M
authors.lastname: Kerac
authors.affiliation: Department of Pediatrics, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Molyneux
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Molyneux
authors.affiliation: Department of HIV & AIDS, Ministry of Health, Lilongwe, Malawi.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jahn
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
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, Malawi; Division of Infection and Immunity, University College London, London, United Kingdom.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D002648:Child; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology*; D006801:Humans; D008288:Malaria / Q000150:complications / Q000453:epidemiology*; D008295:Malawi / Q000453:epidemiology; D044342:Malnutrition / Q000150:complications / Q000453:epidemiology*; D008954:Models, Biological; D011159:Population Surveillance; D011891:Rain; D012307:Risk Factors; D012475:Salmonella / Q000145:classification; D012480:Salmonella Infections / Q000150:complications / Q000453:epidemiology*; D013997:Time Factors