Rapid Diagnostic Tests and Clinical/Laboratory Predictors of Tropical Diseases in Neurological Disorders in DRC

NCT01589289 | Completed Phase 3

• 1 other identifier: WP2-01-NEU
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 1

Brief Summary

The impact of neurological disorders is enormous worldwide, and it is increased in poor settings, due to lack of diagnosis and treatment facilities as well as delayed management. In sub-Saharan Africa, the few observational studies conducted for the past 20 years show that neurological disorders accounted for 7 to 24% of all admissions. Central nervous system (CNS) infections were suspected in one third of all patients admitted with neurological symptoms, with a specific microbial aetiology identified in half of these. Most CNS infections may be considered as "severe and treatable diseases", e.g. human African trypanosomiasis (HAT), cerebral malaria, bacterial meningitis, CNS tuberculosis etc. If left untreated, death or serious sequels occur (mortality rates were as high as 30% in the above mentioned studies), but the outcome may be favourable with timely and appropriate management. In poor settings, such conditions should be targeted in priority in the clinical decision-making process. Unfortunately, most neuro-infections present with non-specific symptoms in their early stages, leading to important diagnostic delays. Moreover, they require advanced diagnostic technology, which is not available in most tropical rural settings: here, you have to rely on clinical judgment and first-line laboratory results, whose confirming or excluding powers are limited or unknown. Several rapid diagnostic tests (RDTs) have been recently developed for conditions like malaria or HIV, but their diagnostic contribution has not been evaluated within a multi-disease approach. Thus, this research aims at improving the early diagnosis of severe and treatable neglected and non-neglected infectious diseases which present with neurological symptoms in the province of Bandundu, Democratic Republic of Congo (DRC), by combining classic clinical predictors with a panel of simple point-of-care rapid diagnostic tests. The evaluation of existing algorithms and elaboration/validation of new guidelines will be described in a subsequent protocol.

Conditions

Neurological Disorders; Cerebral Malaria; Bacterial Meningitis; Central Nervous System Tuberculosis; Neurosyphilis; Cryptococcal Meningitis

Keywords

Diagnostic research; Rapid diagnostic tests; Neurological disorders; Neglected Tropical Diseases; Developing countries

Outcome Measures

Primary Outcomes (4)

• Prevalence of HAT and other NTDs/IDs

  Number of patients diagnosed with HAT and other NTDs/IDs among those presenting with neurological disorders in rural hospitals of Bandundu, DRC (pre-test probability)

  18 months

• Identification of reliable diagnostic tests

  Assessment of the sensitivity, likelihood ratios and performances (diagnostic accuracy) of the novel study RDTs for the respective target conditions, and identification of those that should be included in future diagnostic protocols

  18 months

• Predictive values of RDTs

  Predictive values (post-test probabilities) of novel and existing RDTs, alone and in combination, for the respective target conditions within this multi-disease approach

  18 months

• Identification of clinical and laboratory diagnostic indicators

  Assessment of the specificity of the different clinical and first-line laboratory features for the diagnosis of HAT and other priority NTDs/IDs in the setting, for determining those that should be included in future diagnostic protocols

  18 months

Secondary Outcomes (2)

• Cure rate

  18 months

• Cost-effectiveness of the diagnostic tests

  18 months

Study Arms (1)

Phase 3 RDTs

EXPERIMENTAL

The different interventions will be assessed for estimation of sensitivity, specificity and predictive values in the patients' cohort, for the respective target conditions. \[To be noted that, in addition, also the predictive values of validated RDTs when used alone and in various combinations will be estimated\].

Device: Immunochromatographic HAT tests (DSD); Device: Card Agglutination Trypanosoma Test; Device: TB POC Nucleic Acid Amplification Test (Molbio Diagnostics); Device: TB 3-marker RDT (Tulip diagnostics); Device: Cryptococcal Antigen Lateral Flow Assay (Immy)

Interventions

Immunochromatographic HAT tests (DSD) DEVICE

Immunochromatographic HAT diagnostic tests manufactured by DSD, Korea and FIND

Phase 3 RDTs

Card Agglutination Trypanosoma Test DEVICE

Card Agglutination Trypanosoma Test on whole blood and as dilution

Also known as: CATT

Phase 3 RDTs

TB POC Nucleic Acid Amplification Test (Molbio Diagnostics) DEVICE

TB POC Nucleic Acid Amplification Test: "microPCR handheld device" (Molbio Diagnostics PVT ltd, India)

Also known as: NAAT

Phase 3 RDTs

TB 3-marker RDT (Tulip diagnostics) DEVICE

TB 3-marker RDT: ADA2/IFN-g/LAM (Tulip diagnostics, ltd, India) - pending availability for phase 3 validation

Phase 3 RDTs

Cryptococcal Antigen Lateral Flow Assay (Immy) DEVICE

Cryptococcal Antigen Lateral Flow Assay (Immy, USA)

Also known as: CrAg-LAT

Phase 3 RDTs

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \> 5 years-old AND
• Altered state of consciousness (confusion to coma) OR/AND
• Changes of sleep pattern (daytime slumber, night insomnia)OR/AND
• Cognitive decline OR/AND
• Changes in personality/behaviour (e.g. bouts of mania)OR/AND
• Epileptic seizure(s)OR/AND
• Daily severe/progressive headache OR/AND
• Meningismus (headache, neck stiffness, nausea/vomiting, photophobia)
• Cranial nerve lesions OR/AND
• Sensory-motor deficits or other focal neurological signs (e.g. dysphagia, dysarthria, ataxia, dystonia,...)OR/AND
• Gait disorders (e.g. spastic or ataxic gait)

You may not qualify if:

• Those unwilling or unable to give written informed consent (either directly or via proxy)
• Those unable in the physician's opinion to comply with the study requirements
• Neurological symptom unequivocally related with recent trauma
• Neurological symptom as sequelae of previous well-established neurological events (e.g. stroke,…)
• First seizure below 6 years of age (early onset seizure)

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo: collaborator
• University Hospital, Geneva: collaborator

Study Sites (1)

Reference Hospital Mosango

Mosango, Bandundu, Democratic Republic of the Congo

Location

MeSH Terms

Conditions

Nervous System Diseases; Malaria, Cerebral; Meningitis, Bacterial; Tuberculosis, Central Nervous System; Neurosyphilis; Meningitis, Cryptococcal; Neglected Diseases

Condition Hierarchy (Ancestors)

Central Nervous System Protozoal Infections; Central Nervous System Parasitic Infections; Central Nervous System Infections; Infections; Parasitic Diseases; Malaria; Protozoan Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Central Nervous System Diseases; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis; Neuroinflammatory Diseases; Tuberculosis, Extrapulmonary; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Syphilis; Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Cryptococcosis; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Emmanuel Bottieau, MD

  ITM

  STUDY DIRECTOR

• Marleen Boelaert, MD, PhD

  ITM

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: May 1, 2012
• Study Start: September 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: May 1, 2015
• Last Updated: January 18, 2016

Record last verified: 2016-01

Locations

DE (1)