title: Effect of diagnostic testing on medicines used by febrile children less than five years in 12 malaria-endemic African countries: a mixed-methods study.
abstract: BACKGROUND
  In 2010, WHO revised guidelines to recommend testing all suspected malaria cases prior to treatment. Yet, evidence to assess programmes is largely derived from limited facility settings in a limited number of countries. National surveys from 12 sub-Saharan African countries were used to examine the effect of diagnostic testing on medicines used by febrile children under five years at the population level, including stratification by malaria risk, transmission season, source of care, symptoms, and age.
  
  
  METHODS
  Data were compiled from 12 Demographic and Health Surveys in 2010-2012 that reported fever prevalence, diagnostic test and medicine use, and socio-economic covariates (n=16,323 febrile under-fives taken to care). Mixed-effects logistic regression models quantified the influence of diagnostic testing on three outcomes (artemisinin combination therapy (ACT), any anti-malarial or any antibiotic use) after adjusting for data clustering and confounding covariates. For each outcome, interactions between diagnostic testing and the following covariates were separately tested: malaria risk, season, source of care, symptoms, and age. A multiple case study design was used to understand varying results across selected countries and sub-national groups, which drew on programme documents, published research and expert consultations. A descriptive typology of plausible explanations for quantitative results was derived from a cross-case synthesis.
  
  
  RESULTS
  Significant variability was found in the effect of diagnostic testing on ACT use across countries (e.g., Uganda OR: 0.84, 95% CI: 0.66-1.06; Mozambique OR: 3.54, 95% CI: 2.33-5.39). Four main themes emerged to explain results: available diagnostics and medicines; quality of care; care-seeking behaviour; and, malaria epidemiology.
  
  
  CONCLUSIONS
  Significant country variation was found in the effect of diagnostic testing on paediatric fever treatment at the population level, and qualitative results suggest the impact of diagnostic scale-up on treatment practices may not be straightforward in routine conditions given contextual factors (e.g., access to care, treatment-seeking behaviour or supply stock-outs). Despite limitations, quantitative results could help identify countries (e.g., Mozambique) or issues (e.g., malaria risk) where facility-based research or programme attention may be warranted. The mixed-methods approach triangulates different evidence to potentially provide a standard framework to assess routine programmes across countries or over time to fill critical evidence gaps.
authors.affiliation: Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, SE-751 85, Uppsala, Sweden. emily.johansson@kbh.uu.se.
authors.forename: Emily White
authors.initials: EW
authors.lastname: Johansson
authors.affiliation: Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, Oxford, UK. peter.gething@zoo.ox.ac.uk.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gething
authors.affiliation: Global Health - Health Systems and Policy, Department of Public Health Sciences, Karolinska Institutet, SE-171 77, Stockholm, Sweden. helena.hildenwall@ki.se.
authors.forename: Helena
authors.initials: H
authors.lastname: Hildenwall
authors.affiliation: Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, Oxford, UK. bonnie.mappin@zoo.ox.ac.uk.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Mappin
authors.affiliation: University of Gothenburg, The Sahlgrenska Academy, Health Metrics, Box 414, SE-405 30, Gothenburg, Sweden. max.petzold@amm.gu.se.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. max.petzold@amm.gu.se.
authors.forename: Max
authors.initials: M
authors.lastname: Petzold
authors.affiliation: Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, SE-751 85, Uppsala, Sweden. stefan.peterson@kbh.uu.se.|Global Health - Health Systems and Policy, Department of Public Health Sciences, Karolinska Institutet, SE-171 77, Stockholm, Sweden. stefan.peterson@kbh.uu.se.|Makerere University School of Public Health, College of Health Sciences, PO Box 7072, Kampala, Uganda. stefan.peterson@kbh.uu.se.
authors.forename: Stefan Swartling
authors.initials: SS
authors.lastname: Peterson
authors.affiliation: Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, SE-751 85, Uppsala, Sweden. katarina.selling@kbh.uu.se.
authors.forename: Katarina Ekholm
authors.initials: KE
authors.lastname: Selling
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine; D004338:Drug Combinations; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008288:Malaria / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D012306:Risk; D012621:Seasons; D012959:Socioeconomic Factors
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C031327:artemisinin