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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Rapid Diagnostic Tests in Association With Clinical and Laboratory Predictors for the Diagnosis of Neglected Tropical Diseases in Patients With Neurological Disorders in Rural Hospitals of Bandundu,De

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 clini

Detailed Summary:

The impact of neurological disorders is enormous in terms of mortality, morbidity, physical disability and psychological distress, and it is increased in low-resource settings by lack of diagnosis and of treatment facilities as well as delayed management. The frequency of neurological disorders and the pattern of causative conditions are little documented in low-resource primary care settings.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. Where it has been investigated, up to one third of neurological admissions was related to HIV infection in some settings. Neuro-infections were also the leading aetiologies of common neurological symptoms (such as headache) in African HIV-positive patients, and autopsy studies have demonstrated that CNS infections accounted for 20% of the causes of death in HIV-positive individuals in sub-Saharan Africa.

Most CNS infections may be considered as "severe and treatable diseases", e.g. human African trypanosomiasis (HAT), cerebral malaria, bacterial meningitis, CNS tuberculosis, neurosyphilis, cryptococcal meningitis or toxoplasma encephalitis etc. If left untreated, death or serious sequels usually occur; mortality rates of neurological admissions were as high as 30% in the above mentioned studies. However, outcome may be favourable with timely and appropriate management.

In resource-constrained settings more than elsewhere, such "severe and treatable" conditions should be targeted in priority in the clinical decision-making process. Unfortunately, most neuro-infections present
Sponsor: Institute of Tropical Medicine, Belgium

Current Primary Outcome:

• Prevalence of HAT and other NTDs/IDs [ Time Frame: 18 months ]
  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)
• Identification of reliable diagnostic tests [ Time Frame: 18 months ]
  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
• Predictive values of RDTs [ Time Frame: 18 months ]
  Predictive values (post-test probabilities) of novel and existing RDTs, alone and in combination, for the respective target conditions within this multi-disease approach
• Identification of clinical and laboratory diagnostic indicators [ Time Frame: 18 months ]
  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

Original Primary Outcome:

• Prevalence of HAT and other priority NTDs/IDs [ Time Frame: 18 months ]
  Prevalence of HAT and other priority NTDs/IDs in patients presenting with neurological disorders in rural hospitals of Bandundu, DRC (pre-test probability)
• Sensitivity [ Time Frame: 18 months ]
  Sensitivity of clinical and first-line laboratory features for the diagnosis of HAT and other priority NTDs/IDs in the setting
• Diagnostic accuracy [ Time Frame: 18 months ]
  Performances (diagnostic accuracy) of the novel study RDTs for the respective target conditions
• Predictive values of RDTs [ Time Frame: 18 months ]
  Predictive values (post-test probabilities) of novel and existing RDTs, alone and in combination, for the respective target conditions within this multi-disease approach
• Specificity [ Time Frame: 18 months ]
  Specificity of clinical and first-line laboratory features for the diagnosis of HAT and other priority NTDs/IDs in the setting
• Likelihood ratios [ Time Frame: 18 months ]
  Crude and adjusted likelihood ratios (LR) of clinical and first-line laboratory features for the diagnosis of HAT and other priority NTDs/IDs in the setting

Current Secondary Outcome:

• Cure rate [ Time Frame: 18 months ]
  Number of patients who positively respond to specific/empirical therapies, as assessed as final patient outcomes (cure, referral, sequelae, death)
• Cost-effectiveness of the diagnostic tests [ Time Frame: 18 months ]
  Unit costs of diagnostic tests for the diagnosis of HAT and other priority NTDs/IDs in the setting

Original Secondary Outcome:

• Response to therapies [ Time Frame: 18 months ]
  Response to specific/empirical therapies and in-hospital/final patient outcomes (cure, referral, sequellae, death)
• Costs [ Time Frame: 18 months ]
  Unit costs of diagnostic tests for the diagnosis of HAT and other priority NTDs/IDs in the setting

Information By: Institute of Tropical Medicine, Belgium

Dates:
Date Received: April 26, 2012
Date Started: September 2012
Date Completion:
Last Updated: January 15, 2016
Last Verified: January 2016