Evaluation of Rapid Diagnostic Tests (RDT) in Association With Clinical and Laboratory Predictors for the Diagnosis of Neglected Tropical Diseases (NTD) in Patients Presenting With Persistent Fever (≥1 Week) in Cambodia, Nepal, Democratic Republic of the Congo and Sudan
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University Hospital, Geneva
- Enrollment
- 1,927
- Locations
- 10
- Primary Endpoint
- Prevalence of Visceral Leishmaniasis (VL), Human African Trypanosomiasis (HAT) and other Neglected Tropical Diseases (NTDs)
Study Overview
Brief Summary
Tropical fevers have been a diagnostic challenge from the antiquity. Nowadays, despite the availability of good diagnostic capacities, undifferentiated febrile illnesses continue to be a thorny problem for travel physicians. In developing countries, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers even more complex. Health care workers must often rely on syndrome-oriented empirical approaches to treatment and might overestimate or underestimate the likelihood of certain diseases. For instance Neglected Tropical Diseases (NTD) contribute substantially to the burden of persistent (more than 1 week) fevers in the Tropics, causing considerable mortality and major disability. These diseases are however rarely diagnosed at primary health care (PHC) level. The difficulty in establishing the cause of febrile illnesses has resulted in omission or delays in treatment, irrational prescriptions with polytherapy, increasing cost and development of drug resistance.
In resource-limited settings, clinical algorithms constitute a valuable aid to health workers, as they facilitate the therapeutic decision in the absence of good laboratory capacities. There is a critical lack of appropriate diagnostic tools to guide treatment of NTDs. While clinical algorithms have been developed for some NTDs, in most cases they remain empirical. Besides, they rarely take into account local prevalence data, do not adequately represent the spectrum of patients and differential diagnosis at the primary care level and often have not been properly validated. The purpose of the study is to develop evidence-based Rapid Diagnostic Test (RDT)-supported diagnostic guidelines for patients with persistent fever (≥ 1 week) in the Democratic Republic of the Congo (DRC), Sudan, Cambodia and Nepal.
Detailed Description
This study is part of a large European Union (EU)-funded research project called NIDIAG that aims at developing integrated, evidence-based syndromic approach to improve management of NTD-related clinical syndromes. NIDIAG targets three non-specific clinical syndromes: the persistent fever, neurological, and intestinal syndrome. The objective of the project is to establish diagnostic guidelines for each of this syndrome, with a particular focus on severe and treatable neglected infectious diseases. The developed guidelines should integrate relevant Point-of-Care (POC)tests.
The persistent fever syndrome targeted by NIDIAG is defined as presence of fever for at least one week. The list of diseases - both NTD and other Infectious Diseases (ID) - that frequently cause persistent (≥1 week) fever in the study countries includes: Visceral Leishmaniasis (VL), Human Africa Trypanosomiasis (HAT), Enteric (typhoid, paratyphoid) fever, Malaria, Brucellosis, Melioidosis, Tuberculosis, Amoebic liver abscess, Relapsing fever, HIV, Rickettsial diseases, and Leptospirosis. The study will try to identify clinical and laboratory predictors of these diseases as well as validate existing RDTs.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 5 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •fever for ≥ 1 week
- •≥ 5 years old (18 years onward in Cambodia)
Exclusion Criteria
- •unwilling or unable to give written informed consent
- •unable in the study physician's opinion to comply with the study requirements
- •existing laboratory confirmed diagnosis
- •need of immediate intensive care due to shock or respiratory distress
Outcomes
Primary Outcomes
Prevalence of Visceral Leishmaniasis (VL), Human African Trypanosomiasis (HAT) and other Neglected Tropical Diseases (NTDs)
Time Frame: 18 months
Number of patients diagnosed with VL, HAT and other NTDs among those presenting with persistent(≥ 1 week) fever in one of the study sites
Identification of reliable Rapid Diagnostic Tests (RDTs)
Time Frame: 18 months
Assessment of sensitivity, likelihood ratios and performances (diagnostic accuracy) of the novel study RDTs for VL, HAT, enteric fever and
Predictive values of RDTs
Time Frame: 18 months
Predictive values (post-test probabilities) of RDTs, alone and in combination, for the respective target conditions within the multi-disease approach
Identification of clinical and laboratory diagnostic indicators
Time Frame: 18 months
Sensitivity, specificity, crude and adjusted likelihoods ratios (LR), and predictive values (post-test probabilities) of clinical and first-line laboratory predictors for the diagnosis of VL, HAT and other NTDs
Secondary Outcomes
- Cost-effectiveness of the diagnostic tests(18 months)
Investigators
Francois CHAPPUIS
Professor
University Hospital, Geneva