Cryptococcal Meningitis Clinical Trial
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,Democratic Republic of Congo
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.
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Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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