Tropical Infectious Diseases Clinical Trial
Official title:
Optimizing Sysmex Technology as an Innovative Tool to Differentiate Between Malaria (PALUdism) and BACterial Infections in a Malaria Endemic Region
Severe malaria and bacterial Blood Stream Infections (bBSI) are impossible to differentiate clinically. This poses a particular threat in low resource areas, where bBSI is often not diagnosed due to the unavailability of rapid diagnostic means. Even if used appropriately, the sensitivity of blood culture to diagnose bBSI is estimated to be around 50%. To counter the high mortality rate associated with bBSI, antibiotics are often prescribed without microbiological confirmation. Sysmex Company has developed technology that enables the rapid diagnosis of malaria using a venous blood sample. In addition algorithms based on hematological parameters can be used to monitor disease severity and progression, as well as guide further diagnostic testing based on differences seen in these parameters between various types of disease. The algorithms have been developed and tested in adult populations from different industrialized countries and in one Asian population. However no data are available neither from pediatric patients, nor from the sub-Saharan setting where the epidemiology of infectious diseases is very different from the tested settings. The objective of the study is to: 1) Assess the sensitivity and specificity of the Sysmex hematology analyzer based on the new technology to diagnose malaria in subjects older than 3 months, who present with an acute severe febrile illness in a malaria endemic area in sub-Saharan Africa 2) Test and optimize the value of Sysmex analyzers in disease diagnosis and monitoring in children older than 5 years and adults, who present with an acute severe febrile illness in a malaria endemic region in sub-Saharan Africa, to differentiate between severe malaria and bBSI, or a combination of these infections. 3) Explore the value of Sysmex analyzers in disease diagnosis and monitoring in children between 3 months and 5 years of age, who present with an acute severe febrile illness in a malaria endemic region in sub-Saharan Africa.
Analytical plan
Sysmex will be blinded to:
- All clinical data except age and gender of the participant
- All laboratory and imaging data that is not obtained by the XN-analyzers.
The clinical study team will be blinded to:
- Data from the XN-analyzers, excepting the currently validated data that is used for routine
patient care (e.g. total blood count, white blood differentiation)
Two researchers from Sysmex and two researchers from the study team will use the data
available to them (i.e. the data to which they are not blinded) to categorize each patient
according to the following categories (independently from each other) using the predefined
case definitions as mentioned above.
1. Confirmed malaria parasitemia
2. Confirmed bacterial infection
3. Confirmed viral infection
4. Suspected malaria
5. Suspected bacterial infection
6. Suspected viral infection
7. Mixed infection (specified which combination)
8. No infection
Analysis for primary outcome measures
1. Diagnostic sensitivity and specificity of blue laser compared to microscopy/PCR
2. ROC curve to assess best cut-off for the blue laser based on clinical samples
3. Linear regression analysis to compare quantification of parasitemia by blue laser to
microscopy/PCR
4. Compare performance of the blue laser to performance of RDT (in comparison to
microscopy/PCR)
5. Diagnostic sensitivity and specificity of infection manager to detect bBSI in
participants of 5 years and older.
6. Diagnostic sensitivity and specificity of the infection manager to detect bBSI combined
with malaria in participants of 5 years and older.
Case definitions:
Malaria parasitemia is defined as the presence of one or more parasites in malaria microscopy
or a malaria qPCR 18S result over 50 p/ml
Bacterial bloodstream infection is defined as growth of a clinically significant bacterial
organism from blood culture within 5 days of incubation or a (16s) PCR result positive for a
clinically significant organism
Lower respiratory tract infection: a clinical suspicion including cough and/or shortness of
breath, supported by results from chest exam and chest X-ray.
Abscess: in case of superficial abscesses clinical presentation must be confirmed by pus upon
drainage. In case of deep abscesses the clinical presentation must be confirmed by
echography.
Meningitis: A clinical suspicion with decreased conscience and neck stiffness, confirmed by
culture or agglutination performed on cerebrospinal fluid.
Pelvic inflammatory infection: Typical clinical presentation with vaginal discharge
Protrude skin infections: clinical presentation combined with a grown pathogen in skin
culture or presence of pus.
Bacterial gastro-enteritis: Patients with diarrhoea and a grown pathogen from stool culture.
Urinary tract infections: Patients clinical signs of a urinary tract infection and a grown
pathogen from urine culture.
Obvious causes of fever include superficial skin infection, superficial abscesses, otitis,
pharyngitis and tonsillitis.
Viral infections will be diagnosed based on clinical suspicion and confirmed using PCR or
serology.
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