Febrile Illness
Conditions
Brief summary
This is a bi-centric prospective observational cohort study of adults and children presenting to the emergency room or outpatient department with community febrile illness (with or without signs of focalization) in 2 clinical sites (hospitals) in the DRC. The study will describe the epidemiology, clinical aspects, severity, management and outcome of febrile illnesses using data collected during routine diagnostic and therapeutic procedures. Each patient will be followed for 21 days. The follow-up will include * Daily visits for hospitalized patients, * Telephone calls (or study center visit or home visit) on days 7, 14 and 21 for outpatients and discharged patients. The study has been amended (EC UZA approval in June 2021) to perform a set of laboratory analyses in the partners institutions and at the ITM. We aim as a new primary objective at describing the profile of different biomarkers (C-reactive protein and white blood cell count with differentiation) in participants enrolled with febrile illness, and as secondary objectives to correlate them with outcome (assessed at day 21) and with several etiological diagnoses, especially malaria (as assessed by rapid diagnostic test and blood smear). The purpose is to investigate the potential diagnostic and prognostic value of these biomarkers which are increasingly available at the point-of-care.
Interventions
OTHERObservational study
No intervention (observational study in human participants)
Sponsors
Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
Institute of Tropical Medicine, Belgium
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Months to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ongoing and objectified fever at presentation, or documented at home or other health center within 24 hours prior to presentation, defined by: * Axillary or tympanic temperature \> 37.5°C OR * Oral or rectal temperature \> 38°C 2. Possibility of contact between the patient (or designated relative) and the study team on days 7, 14 and 21 3. Informed consent signed by the patient (adults) or a legally acceptable representative (children or patients whose condition does not allow them to sign informed consent), with the consent of children as young as 12 years of age, whenever possible.
Exclusion criteria
1. Children less than two months old 2. Hospitalization \> 48 h in the last 14 days (to exclude nosocomial fevers)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Survival With Symptom Resolution | Day 21 | Proportion of survival with symptom resolution assessed at day 21, of febrile illnesses |
| CRP Values | Day 0 | CRP values at day 0 (inclusion) |
| White Blood Cell Count | day 0 | white blood cell count with differentiation at day 0 (inclusion) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Initial Hospitalization | Day 21 | Proportion of participants with initial hospitalization (assessed at Day 21) |
| Proportion of Participants With Secondary Hospitalization | Day 21 | Proportion of participants with secondary hospitalization assessed at day 21 |
| Length of Hospital Stay (Initial and/or Secondary Hospitalization) | Day 21 | Length of hospital stay (initial and/or secondary hospitalization) assessed at day 21 |
| Number of Secondary Visits | Day 21 | Number of secondary visits (assessed at Day 21). |
| Proportion of Survival With Symptom Resolution | Day 7 | Proportion of survival with symptom resolution assessed at day 7, of febrile illnesses |
| Severity of Illness | Day 0 | Severity of illness on day 0 as assessed by the ASAPS/IGSA (Simplified ambulatory severity index) score in adult febrile illnesses. IGSA is a clinical severity score designed to estimate the prognosis of patients in emergency settings. It is based on six clinical parameters: age, heart rate (pulse), systolic blood pressure, respiratory rate, body temperature, and Glasgow Coma Scale score. Each parameter is assigned a score from 0 to 4 based on the severity of the observed abnormality. The total score is the sum of the individual scores for each parameter, with a theoretical maximum of 24 points. The ASAPS/IGSA score can be calculated with a calculator via the website of société Française de Médecine d'urgence. A value between 0 and 24 is expected, it's life-threatening if ≥ 8. The lower the total score, the more favorable the prognosis. |
| Frequency of Malaria | Day 21 | Frequency of malaria as detected by rapid test (HRP II antigen) at day 21 in febrile illnesses |
| Parasitemia of Malaria | Day 21 | Parasitemia as detected by thick smear at day 21 in febrile illnesses |
| Patient Outcomes | Day 21 | Association of CRP values and white blood cell counts with patient outcomes |
| Proportion of Survival Without Symptom Resolution | Day 7 | Proportion of survival without symptom resolution assessed at day 7, of febrile illnesses |
| Proportion of Death | Day 7 | Proportion of death assessed at day 7, of febrile illnesses |
Countries
Democratic Republic of the Congo
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants all adults and children presenting to emergency departments or outpatient clinic with community-acquired febrile illness (HGKinshasa children, HGRKimpese adults, HGR Kimpese children) | 997 |
| Total | 997 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 13 |
| Overall Study | Lost to Follow-up | 48 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 5 years |
| Antibiotic no | 873 Participants |
| Antibiotic yes | 124 Participants |
| Antimalarial no | 843 Participants |
| Antimalarial yes | 154 Participants |
| Brachial Perimeter | 15 cm |
| Breathing rate | 28 breaths per minute |
| Diastolic blood pressure | 70 mm Hg |
| Education Child going to school | 468 Participants |
| Education Missing | 413 Participants |
| Education None | 2 Participants |
| Education primary | 1 Participants |
| Education secondary | 58 Participants |
| Education superior | 50 Participants |
| Education unknown | 5 Participants |
| Fever duration | 3 days |
| Heart rate | 108 BPM |
| Height | 118 cm |
| Previous consultation both | 7 Participants |
| Previous consultation formal system | 72 Participants |
| Previous consultation informal system | 11 Participants |
| Previous consultation neither | 907 Participants |
| Previous treatment no | 113 Participants |
| Previous treatment unknown | 9 Participants |
| Previous treatment yes | 875 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 997 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 467 Participants |
| Sex: Female, Male Male | 530 Participants |
| SpO2 | 98 % |
| Syst. Blood pressure | 108 mm Hg |
| Temperature | 37.8 degrees celcius |
| Weight | 19 kg |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 997 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
CRP Values
CRP values at day 0 (inclusion)
Time frame: Day 0
| Arm | Measure | Value (MEAN) |
|---|---|---|
| All Participants | CRP Values | 20 mg/L |
Primary
Proportion of Survival With Symptom Resolution
Proportion of survival with symptom resolution assessed at day 21, of febrile illnesses
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Survival With Symptom Resolution | 96.9 percentage of participants |
Primary
White Blood Cell Count
white blood cell count with differentiation at day 0 (inclusion)
Time frame: day 0
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | White Blood Cell Count | 7 10^9 cells/L |
Secondary
Frequency of Malaria
Frequency of malaria type Plasmodium malariae as detected by thick smear at day 21
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Frequency of Malaria | 1.1 percentage of participants |
Secondary
Frequency of Malaria
Frequency of malaria as detected by rapid test (HRP II antigen) at day 21 in febrile illnesses
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Frequency of Malaria | 31.6 percentage of participants |
Secondary
Frequency of Malaria
Frequency of malaria as detected by rapid test (pLDH antigen) at day 21 in febrile illnesses
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Frequency of Malaria | 22.3 percentage of participants |
Secondary
Frequency of Malaria
Frequency of malaria as detected by thick smear positivity at day 21 in febrile illnesses
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Frequency of Malaria | 25.3 percentage of participants |
Secondary
Frequency of Malaria
Frequency of malaria type Plasmodium falciparum as detected by thick smear at day 21
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Frequency of Malaria | 24.3 percentage of participants |
Secondary
Length of Hospital Stay (Initial and/or Secondary Hospitalization)
Length of hospital stay (initial and/or secondary hospitalization) assessed at day 21
Time frame: Day 21
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Length of Hospital Stay (Initial and/or Secondary Hospitalization) | 5 days |
Secondary
Number of Secondary Visits
Number of secondary visits (assessed at Day 21).
Time frame: Day 21
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Number of Secondary Visits | 4 visits |
Secondary
Parasitemia of Malaria
Parasitemia as detected by thick smear at day 21 in febrile illnesses
Time frame: Day 21
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Parasitemia of Malaria | 8350 trophozoïtes/microliter |
Secondary
Patient Outcomes
Association of CRP values and white blood cell counts with patient outcomes
Time frame: Day 21
Population: overal number of pts analyzed = number resolved + number non resolved
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Participants | Patient Outcomes | CRP clinical outcome Resolution | 19 mg/L |
| All Participants | Patient Outcomes | CRP clinical outcome Non-resolution | 71 mg/L |
p-value: 0.107Fisher Exact
Secondary
Proportion of Death
Proportion of death assessed at day 7, of febrile illnesses
Time frame: Day 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Death | 0.9 percentage of participants |
Secondary
Proportion of Death
Proportion of death assessed at day 21, in febrile illnesses
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Death | 1.3 percentage of participants |
Secondary
Proportion of Death
Proportion of death assessed at day 14, in febrile ilnesses
Time frame: Day 14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Death | 1.1 percentage of participants |
Secondary
Proportion of Participants With Initial Hospitalization
Proportion of participants with initial hospitalization (assessed at Day 21)
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Participants With Initial Hospitalization | 13.3 percentage of participants |
Secondary
Proportion of Participants With Secondary Hospitalization
Proportion of participants with secondary hospitalization assessed at day 21
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Participants With Secondary Hospitalization | 1.1 percentage of participants |
Secondary
Proportion of Survival Without Symptom Resolution
Proportion of survival without symptom resolution assessed at day 14, in febrile illnesses
Time frame: Day 14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Survival Without Symptom Resolution | 3.2 percentage of participants |
Secondary
Proportion of Survival Without Symptom Resolution
Proportion of survival without symptom resolution assessed at day 21, in febrile illnesses
Time frame: Day 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Survival Without Symptom Resolution | 1.8 percentage of participants |
Secondary
Proportion of Survival Without Symptom Resolution
Proportion of survival without symptom resolution assessed at day 7, of febrile illnesses
Time frame: Day 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Survival Without Symptom Resolution | 5.2 percentage of participants |
Secondary
Proportion of Survival With Symptom Resolution
Proportion of survival with symptom resolution assessed at day 14, in febrile illnesses
Time frame: Day 14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Survival With Symptom Resolution | 95.7 percentage of participants |
Secondary
Proportion of Survival With Symptom Resolution
Proportion of survival with symptom resolution assessed at day 7, of febrile illnesses
Time frame: Day 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Proportion of Survival With Symptom Resolution | 93.9 percentage of participants |
Secondary
Severity of Illness
Severity of illness on day 21 as assessed by the ASAPS/IGSA (Simplified ambulatory severity index) score in adult febrile illnesses. IGSA is a clinical severity score designed to estimate the prognosis of patients in emergency settings. It is based on six clinical parameters: age, heart rate (pulse), systolic blood pressure, respiratory rate, body temperature, and Glasgow Coma Scale score. Each parameter is assigned a score from 0 to 4 based on the severity of the observed abnormality. The total score is the sum of the individual scores for each parameter, with a theoretical maximum of 24 points. The ASAPS/IGSA score can be calculated with a calculator via the website of société Française de Médecine d'urgence. A value between 0 and 24 is expected, it's life-threatening if ≥ 8. The lower the total score, the more favorable the prognosis.
Time frame: Day 21
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Severity of Illness | 1 score on a scale |
Secondary
Severity of Illness
Severity of illness on day 21 as assessed by the qSOFA (Quick Sepsis Related Organ Failure Assessment)score in adult febrile illnesses. qSOFA is a clinical tool to identify patients with suspected infection who are at greater risk for poor outcomes, such as in-hospital mortality or prolonged intensive care unit (ICU) stays. It is particularly useful in non-ICU settings like emergency departments. The qSOFA score evaluates 3 clinical criteria, assigning 1 point for each (it's the sum of 3 criteria): * Respiratory Rate: ≥22 breaths per minute. * Systolic Blood Pressure: ≤100 mmHg. * Altered Mental Status: Glasgow Coma Scale (GCS) score \<15. Each criterion is scored as follows: 1 point for meeting the threshold of each criterion. The total qSOFA score ranges from 0-3 points. Interpretation of Scores: 0 point: Low risk for poor outcomes 1. point: Moderate risk; consider monitoring and reassessment 2. or 3 points: High risk; prompt evaluation and intervention recommended
Time frame: Day 21
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Severity of Illness | 1 score on a scale |
Secondary
Severity of Illness
Severity of illness on day 7 as assessed by the ASAPS/IGSA score (Simplified ambulatory severity index score) in adult febrile illnesses. IGSA is a clinical severity score designed to estimate the prognosis of patients in emergency settings. It is based on six clinical parameters: age, heart rate (pulse), systolic blood pressure, respiratory rate, body temperature, and Glasgow Coma Scale score. Each parameter is assigned a score from 0 to 4 based on the severity of the observed abnormality. The total score is the sum of the individual scores for each parameter, with a theoretical maximum of 24 points. The ASAPS/IGSA score can be calculated with a calculator via the website of société Française de Médecine d'urgence. A value between 0 and 24 is expected, it's life-threatening if ≥ 8. The lower the total score, the more favorable the prognosis.
Time frame: day 7
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Severity of Illness | 0 score on a scale |
Secondary
Severity of Illness
Severity of illness on day 0 as assessed by the ASAPS/IGSA (Simplified ambulatory severity index) score in adult febrile illnesses. IGSA is a clinical severity score designed to estimate the prognosis of patients in emergency settings. It is based on six clinical parameters: age, heart rate (pulse), systolic blood pressure, respiratory rate, body temperature, and Glasgow Coma Scale score. Each parameter is assigned a score from 0 to 4 based on the severity of the observed abnormality. The total score is the sum of the individual scores for each parameter, with a theoretical maximum of 24 points. The ASAPS/IGSA score can be calculated with a calculator via the website of société Française de Médecine d'urgence. A value between 0 and 24 is expected, it's life-threatening if ≥ 8. The lower the total score, the more favorable the prognosis.
Time frame: Day 0
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Severity of Illness | 2 score on a scale |
Secondary
Severity of Illness
Severity of illness on day 0 as assessed by the qSOFA (Quick Sepsis Related Organ Failure Assessment) score in adult febrile illnesses. qSOFA is a clinical tool to identify patients with suspected infection who are at greater risk for poor outcomes, such as in-hospital mortality or prolonged intensive care unit (ICU) stays. It is particularly useful in non-ICU settings like emergency departments. The qSOFA score evaluates 3 clinical criteria, assigning 1 point for each (it's the sum of 3 criteria): * Respiratory Rate: ≥22 breaths per minute. * Systolic Blood Pressure: ≤100 mmHg. * Altered Mental Status: Glasgow Coma Scale (GCS) score \<15. Each criterion is scored as follows: 1 point for meeting the threshold of each criterion. The total qSOFA score ranges from 0-3 points. Interpretation of Scores: 0 point: Low risk for poor outcomes 1. point: Moderate risk; consider monitoring and reassessment 2. or 3 points: High risk; prompt evaluation and intervention recommended
Time frame: Day 0
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Severity of Illness | 1 score on a scale |
Secondary
Severity of Illness
Severity of illness on day 14 as assessed by the ASAPS/IGSA (Simplified ambulatory severity index) score in adult febrile illnesses. IGSA is a clinical severity score designed to estimate the prognosis of patients in emergency settings. It is based on six clinical parameters: age, heart rate (pulse), systolic blood pressure, respiratory rate, body temperature, and Glasgow Coma Scale score. Each parameter is assigned a score from 0 to 4 based on the severity of the observed abnormality. The total score is the sum of the individual scores for each parameter, with a theoretical maximum of 24 points. The ASAPS/IGSA score can be calculated with a calculator via the website of société Française de Médecine d'urgence. A value between 0 and 24 is expected, it's life-threatening if ≥ 8. The lower the total score, the more favorable the prognosis.
Time frame: Day 14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Severity of Illness | 1.5 score on a scale |
Secondary
Severity of Illness
Severity of illness on day 7 as assessed by the qSOFA (Quick Sepsis Related Organ Failure Assessment) score in adult febrile illnesses. qSOFA is a clinical tool to identify patients with suspected infection who are at greater risk for poor outcomes, such as in-hospital mortality or prolonged intensive care unit (ICU) stays. It is particularly useful in non-ICU settings like emergency departments. The qSOFA score evaluates 3 clinical criteria, assigning 1 point for each (it's the sum of 3 criteria): * Respiratory Rate: ≥22 breaths per minute. * Systolic Blood Pressure: ≤100 mmHg. * Altered Mental Status: Glasgow Coma Scale (GCS) score \<15. Each criterion is scored as follows: 1 point for meeting the threshold of each criterion. The total qSOFA score ranges from 0-3 points. Interpretation of Scores: 0 point: Low risk for poor outcomes 1. point: Moderate risk; consider monitoring and reassessment 2. or 3 points: High risk; prompt evaluation and intervention recommended
Time frame: Day 7
| Arm | Measure | Value (MEAN) |
|---|---|---|
| All Participants | Severity of Illness | 1 score on a scale |
Secondary
Severity of Illness
Severity of illness on day 14 as assessed by the qSOFA (Quick Sepsis Related Organ Failure Assessment) score in adult febrile illnesses. qSOFA is a clinical tool to identify patients with suspected infection who are at greater risk for poor outcomes, such as in-hospital mortality or prolonged intensive care unit (ICU) stays. It is particularly useful in non-ICU settings like emergency departments. The qSOFA score evaluates 3 clinical criteria, assigning 1 point for each (it's the sum of 3 criteria): * Respiratory Rate: ≥22 breaths per minute. * Systolic Blood Pressure: ≤100 mmHg. * Altered Mental Status: Glasgow Coma Scale (GCS) score \<15. Each criterion is scored as follows: 1 point for meeting the threshold of each criterion. The total qSOFA score ranges from 0-3 points. Interpretation of Scores: 0 point: Low risk for poor outcomes 1. point: Moderate risk; consider monitoring and reassessment 2. or 3 points: High risk; prompt evaluation and intervention recommended
Time frame: Day 14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Severity of Illness | 1 score on a scale |