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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)

Citation

Post, Annelies; Kaboré, Berenger; van der Ven, André; de Mast, Quirijn (2021), 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), Dryad, Dataset, https://doi.org/10.5061/dryad.rjdfn2z9m

Abstract

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.

Methods

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.

Usage Notes

NA: Not available

Variable Explenation Labels      
Age_category Age category 1: <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: <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 <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 (>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        

Funding

SYSMEX coproration, Award: Unrestricted research grant

SYSMEX coproration, Award: Unrestricted research grant