Rapid Diagnostic Tests and Clinical/Laboratory Predictors of Tropical Diseases in Neurological Disorders in DRC
Rapid Diagnostic Tests and Clinical/Laboratory Predictors of Tropical Diseases in Neurological Disorders in DRC
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.
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 with non-specific symptoms in their early stages, leading to
 important diagnostic delays. Moreover, neurological diagnoses frequently require advanced
 technology, but this is far beyond reach of most tropical rural settings, where you have to
 rely on clinical judgment and first-line laboratory results. However, the confirming or
 excluding powers of most clinical and laboratory features are limited or have never been
 adequately quantified, in particular in settings lacking reference diagnostic methods.
 Several rapid diagnostic tests (RDTs) have been developed in the last decade for conditions
 like malaria or HIV infection, but their diagnostic contribution has never been evaluated
 within a multi-disease approach. Most CNS infections with worldwide distribution affect
 disproportionally the (sub)-tropical regions, while others are restricted to the tropics.
 Also, many infections with potential neuropathogenicity belong to the group of 17 Neglected
 Tropical Diseases (NTDs) on which attention has been recently brought. As said above, most of
 them may be considered as "severe and treatable"; however, in most tropical settings,
 epidemiology of NTDs and other infectious diseases (IDs) is largely unknown, seriously
 impairing the case finding and clinical decision-making.

 The aim of this research therefore is to improve the early diagnosis of severe and treatable
 neglected and non-neglected infectious diseases which may present with neurological symptoms
 in the province of Bandundu, Democratic Republic of Congo (DRC). This will be achieved
 through the elaboration and validation of new diagnostic guidelines based on epidemiological
 evidence, combining classic clinical predictors with a panel of simple point-of-care rapid
 diagnostic tests, and designed with a "panoramic" (not-to-miss) approach.

 In particular, the investigators hope to determine the pre-test probability of HAT and other
 priority neglected tropical diseases/infectious diseases in patients presenting with
 neurological disorders; to assess the predictive weight of clinical and first-line laboratory
 features in the diagnosis of HAT and other priority NTDs/IDs; to assess the sensitivity,
 specificity and predictive values of novel point-of-care RDTs for the diagnosis of HAT and
 other priority NTDs/IDs in patients with neurological disorders; and to assess the diagnostic
 performances of combinations of novel and existing RDTs for diagnosing HAT and other priority
 NTDs/IDs in patients with neurological disorders. Enrolled patients will be managed according
 the current standard of care in Bandundu, DRC and with the treatments locally available
 through health facilities/programs.

 The objectives and methodology of this second step of our research (evaluation of existing
 algorithms and elaboration/validation of new guidelines) will be described in a subsequent
 protocol. Another similar study (described in another protocol) will be conducted in parallel
 to explore the aetiologies of prolonged fever in the same setting.
Inclusion Criteria:

 -  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)

 Exclusion Criteria:

 -  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)