title: Evaluation of case definitions to detect respiratory syncytial virus infection in hospitalized children below 5 years in Rural Western Kenya, 2009-2013.
abstract: In order to better understand respiratory syncytial virus (RSV) epidemiology and burden in tropical Africa, optimal case definitions for detection of RSV cases need to be identified.
  
  
  
  We used data collected between September 2009 - August 2013 from children aged <5 years hospitalized with acute respiratory Illness at Siaya County Referral Hospital. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of individual signs, symptoms and standard respiratory disease case definitions (severe acute respiratory illness [SARI]; hospitalized influenza-like illness [hILI]; integrated management of childhood illness [IMCI] pneumonia) to detect laboratory-confirmed RSV infection. We also evaluated an alternative case definition of cough or difficulty breathing plus hypoxia, in-drawing, or wheeze.
  
  
  
  Among 4714 children hospitalized with ARI, 3810 (81 %) were tested for RSV; and 470 (12 %) were positive. Among individual signs and symptoms, cough alone had the highest sensitivity to detect laboratory-confirmed RSV [96 %, 95 % CI (95-98)]. Hypoxia, wheezing, stridor, nasal flaring and chest wall in-drawing had sensitivities ranging from 8 to 31 %, but had specificities >75 %. Of the standard respiratory case definitions, SARI had the highest sensitivity [83 %, 95 % CI (79-86)] whereas IMCI severe pneumonia had the highest specificity [91 %, 95 % CI (90-92)]. The alternative case definition (cough or difficulty breathing plus hypoxia, in-drawing, or wheeze) had a sensitivity of [55 %, 95 % CI (50-59)] and a specificity of [60 %, 95 % CI (59-62)]. The PPV for all case definitions and individual signs/symptoms ranged from 11 to 20 % while the negative predictive values were >87 %. When we stratified by age <1 year and 1- < 5 years, difficulty breathing, severe pneumonia and the alternative case definition were more sensitive in children aged <1 year [70 % vs. 54 %, p < 0.01], [19 % vs. 11 %, p = 0.01] and [66 % vs. 43 %, p < 0.01] respectively, while non-severe pneumonia was more sensitive [14 % vs. 26 %, p < 0.01] among children aged 1- < 5 years.
  
  
  
  The sensitivity and specificity of different commonly used case definitions for detecting laboratory-confirmed RSV cases varied widely, while the positive predictive value was consistently low. Optimal choice of case definition will depend upon study context and research objectives.
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. oteebryan@gmail.com.
authors.forename: Bryan O
authors.initials: BO
authors.lastname: Nyawanda
authors.affiliation: Division of Global Health Protection, Centers for Disease Control and Prevention, Nairobi, Kenya.|Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Mott
authors.affiliation: Division of Global Health Protection, Centers for Disease Control and Prevention, Nairobi, Kenya.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Njuguna
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Lilian
authors.initials: L
authors.lastname: Mayieka
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Sammy
authors.initials: S
authors.lastname: Khagayi
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Reuben
authors.initials: R
authors.lastname: Onkoba
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Caroline
authors.initials: C
authors.lastname: Makokha
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Otieno
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Godfrey M
authors.initials: GM
authors.lastname: Bigogo
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Katz
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Feikin
authors.affiliation: Division of Global Health Protection, Centers for Disease Control and Prevention, Nairobi, Kenya.|Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Verani
mesh_terms: D002648:Child; D002673:Child, Hospitalized; D002675:Child, Preschool; D019937:Diagnostic Techniques and Procedures; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya / Q000453:epidemiology; D008297:Male; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D012424:Rural Population; D012680:Sensitivity and Specificity
keywords: Case definitions; Respiratory syncytial virus; Sensitivity and specificity