DOI: 10.5061/dryad.rjdfn2z9m
title: Differentiating causes of febrile illness in Burkina Faso: data from an accuracy study comparing gold standard culture techniques with a haemocytometry based algorithm (IMS), procalcitonin (PCT) and C-reactive protein (CRP)

description: Different causes of acute febrile illness due to different infectious
 diseases (e.g. bacterial, viral malaria) may present with a similar
 clinical presentation. We performed a clinical diagnostic study to assess
 the diagnostic accuracy of a new tool - the Infection Manager System (IMS)
 - an algorithm which uses haemocytometric data to predict the cause of
 infection (e.g. bacterial, viral, malaria). The current dataset is a
 subset of data obtained during this study which was performed in a rural
 setting in Burkina Faso. The study was registered at ClinicalTrials.org
 under Identifier NCT02669823. All data used for the manuscript entitled
 "Infection Manager System (IMS) as a new hemocytometry-based
 bacteremia detection tool: a diagnostic accuracy study in a
 malaria-endemic area of Burkina Faso" are included in the current
 subset of data. To test the IMS we collected clinical and demographic data
 from approximately 900 patients aged between 3 months and 100 years
 presenting with an acute febrile illness. Upon inclusion, 2-5 ml EDTA
 anticoagulated blood was sampled for haemocytometry, malaria diagnostics
 (thick- and thin blood films and RDTs) and blood culture. A nasopharyngeal
 swab and aliquots of residual blood and plasma were stored at -80° for
 retrospective analyses. 1. A viral panel on nasopharyngeal swabs 2.
 PCR's for malaria, Salmonella, S. aureus, H. influenzae, S.
 pneumoniae on whole blood or plasma samples and 3. C-reactive protein
 (CRP) and procalcitonin (PCT) levels on plasma samples. Additional
 diagnostics such as chest X-ray, echography, urinalysis, and culture of
 urine, stool, pus, or cerebrospinal fluid were performed on clinical
 indication. In this cohort we attempted to provide a microbiologically
 proven diagnosis for all patients admitted with febrile illness using gold
 standard methods (e.g. blood culture, malaria microscopy and PCR). We then
 assessed the accuracy of the novel IMS to differentiate causes of
 infection against these conventional diagnostic methods. We furthermore
 assessed the accuracy of both CRP and PCT in differentiating causes of
 infection and compared them to the performance of the IMS. We found that
 the IMS had a higher diagnostic accuracy to detect bacteremia than PCT at
 a cut of value of 0.5 µg/L, and was comparable in sensitivity, but
 superior in specificity to CRP at a cut of value of 20 mg/L. Subanalysis
 among patients below the age of five showed that they had a slightly lower
 accuracy of IMS, PCT and CRP. Combining the IMS and CRP did not
 significantly improve accuracy due to the high level of overlap between
 CRP and the IMS. The high negative predictive value of IMS –also in
 non-bacteremic bacterial infections – suggests that the IMS holds promise
 to rationalize antimicrobial prescription in healthcare facilities where
 hematology analyzers are available. The relatively low specificity and PPV
 demonstrate that it is not (yet) suitable as a diagnostic for bacteremia.
description: Data were collected on standardized case report forms (CRFs) and entered
 into a secure database (RedCap, Vanderbilt University, Nashville, USA)
 after conformity check by a medical doctor. Entered data were checked
 against the CRFs by a data manager. Approximately ten percent of patient
 study files were checked by an independent monitor. Results from PCRs and
 ELISAs were entered into an excel database and merged with the principal
 database upon completion of inclusion. Laboratory analyses were performed
 and interpreted by experienced laboratory technicians who were blinded to
 clinical data. Raw data from the haematology analyser was electronically
 transferred to SYSMEX company once every two weeks for storage. SYSMEX had
 no access to the clinical data, researchers were blinded to the
 haematology analyser results until all clinical data were locked into a
 STATA database. Quality control and quality assurance were done in
 accordance with Good Clinical and Laboratory Practice (GCLP) guidelines.
description: NA: Not available Variable Explenation Labels    
   Age_category Age category 1: &lt;5 years 2: 5 years or
 older     sexe Sexe 0: male 1: female  
   pretreatment_malaria Antimalaria medication past 2 weeks 0: no
 1: currently taking 2: currently finished 3: do not know
 pretreatment_antibiotics Antibiotics taken past 2 weeks 0: no 1: currently
 taking 2: currently finished 3: do not know onset_fever Days since onset
 fever         vomiting_anamnestic
 Vomiting 0: no 1: yes     abd_pain abdominal pains 0: no
 1: yes     diarrhoea diarrhoea 0: no 1: yes  
   diarrhoea_frequency number of stools per day 0: &lt;3x per
 day 1: 3 or more per day     diarrhoea_duration_days
 Number of days since onset diarrea      
   runny_nose runny nose 0: no 1: yes    
 earpain earpain 0: no 1: yes     throat_ache throat ache
 0: no 1: yes     cough cough 0: no 1: yes  
   productive_cough productive cough 0: no 1: yes  
   dyspnoa dyspnoea 0: no 1: yes     dysuria
 dysuria 0: no 1: yes     other_miction_problem other
 mictions issues         myalgia
 myalgia 0: no 1: yes     arthralgia arthralgia 0: no 1:
 yes     skin_condition_unspecified rash or other skin
 conditions 0: no 1: yes     iritability iritability 0:
 no 1: yes     convulsions convulsions 0: no 1: yes
     lethargy lethargy 0: no 1: yes    
 pulse_enrollment heartrate at inclusion beats per minute  
     bldpres_enrollment_sys systolic bloodpressure at
 inclusion mmHg       bldpres_enroll_dia
 diastolic bloodpressure at inclusion mmHg      
 temp_enrollment temperature at inclusion celcius    
   rsp_rate_enrollment respiratory rate at inclusion breaths per
 minute       haz06 height for age Z-score
         waz06 weight for age Z-score
         whz06 weight for height
 Z-score         bmiz06 BMI Z-score
         bmi BMI calculated  
       pulmonary_wheezing wheezing at
 auscultation 0: no 1: yes     pulmonary_rhonchi rhonchi
 at auscultation 0: no 1: yes     normal_pulmones normal
 chest auscultation 0: no 1: yes    
 chest_indrawing_enrollment chest indrawing at inclusion 0: no 1: yes
     nasal_flaring_enrollment nasal flaring at inclusion
 0: no 1: yes     abd_auscultation normal abdominal
 auscultation sound 0: no 1: yes     abd_pain_palpation
 pain at abdominal palpation 0: no 1: yes    
 hepatomegaly hepatomegaly 0: no 1: yes     splenomegaly
 splenomegaly 0: no 1: yes     neck_stiffness_enrollment
 neck stiffness  0: no 1: yes     emv_e glasgow
 coma scale; eye         emv_m glasgow
 coma scale; movement         emv_v
 glasgow coma scale; verbal         emv
 total &lt;5 years: max 5 5 or older: max 15    
 Antibiotics_at_admission Antibiotics given at hospitalisation 0: no 1: yes
     Antimalarials_at_admission antimalaria given at
 hospitalisation 0: no 1: yes     Days_of_hospitalisation
 Total days in hospital days       Cured Mode of
 exit out of the hospital 1: cured 2: referred to larger hospital 3: left
 against medical advise 4: died diagnosis_discharge_1 Clinical diagnosis at
 discharge        
 diagnosis_discharge_2 Clinical diagnosis at discharge (second diagnosis)
         malaria_RDT_hrp rapid
 diagnostic test on HRP 0: negative 1: positive    
 malaria_RDT_pldh rapid diagnostic test on pLDH 0: negative 1: positive
     malaria_thick_smear malaria microscopy (&gt;1
 parasite) 0: negative 1: positive    
 malaria_parasite_density microscopy parasite density parasites/ml
       gametocytes gametocytes in microscopy 0:
 negative 1: positive     species_m___1 malaria parasite
 species 0: negative 1: falciparum 2: falciparum+malariae  
 culture_wbclt Conclusion of bloodculture 1 0: negative 1: positive
     pathogen_bloodculture 1 Name pathogen culture 1
         culture_wbclt_2 Conclusion of
 bloodculture 2        
 pathogen_bloodculture_2 Name pathogen culture 2    
     bloodcultures_conclusion Total conclusion both
 cultures Name pathogen       CSF_rdt Rapid
 diagnostic test on cerebrospinal fluid      
   CSF_conc conclusion of culture/RDT cerebrospinal fluid
         stool_cult Stool sample
 culture and microscopy        
 stool_conc Conclusion of the stool culture and microscopy  
       urine_cult Urine microscopy, sediment and
 culture         urine_conc Conclusion
 of urine diagnostics         pus_cult
 Pus culture         pus_conc
 conclusion of the pus culture        
 other_bacterial_pathogens pathogens isolated through other cultures than
 blood culture         ct_malaria_PCR
 malaria PCR Ct-value        
 logstqmalaria log stq malaria PCR      
   ParasitesmL_PCR Conclusion malaria PCR in parasites per ml
         Parasites_uL_PCR Conclusion
 malaria PCR in parasites per ul      
   PCR_Aureus_Cq Cq value of s. aureus PCR on blood  
       PCR_AureusTm Tm value of s. aureus PCR on
 blood         PCR_Haemophilus_Cq Cq
 value of haemophilus PCR on blood      
   PCR_Haemophils_Tm Tm value of haemophilus PCR on blood
         PCR_Pneumoniae_Cq Cq value of
 s pneumoniae PCR on blood        
 PCR_Salmonella_Ct Ct value of Salmonella PCR on blood  
       PCRbacteria_conclusion Summary of
 positive bacterial PCR's on blood      
   Nasopharyngeal swab PCR done on nasopharyngeal swab 0: negative
 1: positive     Nasopharyngeal_Virus Which virus
 isolated in nasopharyngeal swab      
   Nasopharyngeal_Bacteria Which bacteria isolated in
 nasopharyngeal swab         CRP_mgdl
 CRP value in mg/dl analyzed by Eliza      
   PCT_ugL procalcitonin value in ug/L analyzed by Eliza
         Hepatitisserology Serology on
 hepatitits         Ultrasound
 Ultrasound results         Xray X-ray
 results         Other_diagnostic_tests
 Conclusion of not previsouly mentioned additional tests  
       Diagnosis Diagnosis group as reported in
 the diagnostic scheme        
 Diagnosis_2 Potential second diagnosis      
   Diagnosis_3 Potential third diagnosis    
     Coinfection Which type of co-infection  
       WBC white bloodcell count cells/L
       RBC red bloodcell count cells/L
       HGB hemoglobin count g/dl  
     PLT platelet count cells/L    
   NEUT_A neutrophils (absolute number) cells/L  
     LYMP_A lymphocytes (absolute number) cells/L
       MONO_A monocytes (absolute number)
 cells/L       EOSI_A eosinophils 
 (absolute number) cells/L       BASO_A
 basophils  (absolute number) cells/L    
   NEUT_P neutrophils (percentage of leukocytes) %  
     LYMP_P lymphocytes (percentage of leukocytes) %
       MONO_P monocytes (percentage of
 leukocytes) %       EOSI_P eosinophils
 (percentage of leukocytes) %       BASO_P
 basophils (percentage of leukocytes) %      
 NRBC_A Nucleated red blood cells (absolute number) cells/L  
     NRBC_P Nucleated red blood cells (percentage of red
 bloodcells) %       IG_A immature granulocytes
 (absolute number) cells/L       IG_P immature
 granulocytes (percentage of granulocytes) %    
   RET_A reticulocytes (absolute number) cells/L  
     RET_P reticulocytes (percentage of red blood cells)
 %       ASLYMP_A Antibody-synthesizing
 lymphocytes (absolute number) cells/L      
 ASLYMP_P Antibody-synthesizing lymphocytes (percentage) %  
     RELYMP_A reactive lymphocytes (absolute number)
 cells/L       RELYMP_P reactive lymphocytes
 (percentage) %       NEUTRI neutrophil
 reactivity index  cells/L       NEUTGI
 neutrophil granularity index %       Bactscore
 IMS bacterial score         Virscore
 IMS viral score         Malscore IMS
 malaria score        
 IMS_final_full_classification Classification of the IMS