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)
Data files
Feb 15, 2021 version files 700.13 KB
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IMS_DRYAD-2.xlsx
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 |