Rapid Diagnostic Tests and Clinical/Laboratory Predictors of Tropical Diseases In Patients With Persistent Fever in Cambodia, Nepal, Democratic Republic of the Congo and Sudan (NIDIAG-Fever)

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

Sponsors

Lead Sponsor: University Hospital, Geneva

Collaborator: Institute of Tropical Medicine, Belgium
B.P. Koirala Institute of Health Sciences
Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
University of Khartoum
Sihanouk Hospital Center of HOPE

Source University Hospital, Geneva
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.

Overall Status Completed
Start Date January 2013
Completion Date July 2016
Primary Completion Date October 2014
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Prevalence of Visceral Leishmaniasis (VL), Human African Trypanosomiasis (HAT) and other Neglected Tropical Diseases (NTDs) 18 months
Identification of clinical and laboratory diagnostic indicators 18 months
Identification of reliable Rapid Diagnostic Tests (RDTs) 18 months
Predictive values of RDTs 18 months
Secondary Outcome
Measure Time Frame
Cost-effectiveness of the diagnostic tests 18 months
Enrollment 1927
Condition
Intervention

Intervention Type: Device

Intervention Name: rk28 ICT

Description: rk28 ICT is an immunochromatographic assay intended for qualitative detection of IgG antibodies directed towards VL in human serum, plasma or whole blood. It is manufactured by EASE-Medtrend (Shanghai, China)

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: IT LEISH (rK39)

Description: IT LEISH is an immuno-chromatographic test, using the recombinant antigen K39, to detect the presence of antibodies against Leishmania spp. It is manufactured by BioRad laboratories, USA.

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: Immunochromatographic HAT test

Description: This is a lateral flow immunochromatographic test manufactured by Standard Diagnostics (Korea) in collaboration with FIND.

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: HAT Serostrip

Description: The HAT Serostrip is an immunochromatographic assay developed by Coris BioConcept, France, which is designed for remote field use in individual HAT suspects.

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: Card Agglutination Trypanosoma Test (CATT)-10

Description: The Card Agglutination Trypanosoma test (CATT) has been used for many years at large scale for mass screening of mostly asymptomatic individuals (CATT-R250). Unfortunately, its operating characteristics have only been evaluated in the context of patients with persistent fever. Although it is not strictly an RDT, the CATT is rather easily performed in remote settings, in particular since a new and more robust format (CATT-D10) allows to test a lower number of patients in peripheral health facilities. It is manufactured by the Institute of Tropical Medicine of Antwerp, Belgium.

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: Typhidot M

Description: The Typhidot M test is a dot enzyme immunoassay that detects IgM and IgG directed against Salmonella typhi. It is manufactured by Reszon Diagnostics International, Malaysia

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: S. typhi IgM/IgG

Description: The Salmonella typhi IgG/IgM Rapid Test is an immunochromatographic assay for the qualitative differential detection of IgG and IgM antibodies to Salmonella typhi in human serum, plasma or whole blood. It is manufactured by Standard Diagnostics (Korea)

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: Test-it Typhoid IgM

Description: Test-it Typhoid IgM lateral flow assay is a one-step immunochromatographic assay which uses a lipopolysaccharide (LPS) antigen derived from salmonella typhi for the detection of specific IgM antibodies. It is manufactured by Life Assay, South Africa.

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: Test-it Leptospirosis IgM

Description: The Test-it™ Leptospira lateral flow device detects IgM antibodies in humans against Leptospira in whole blood or serum. It is manufactured by Life Assay, South Africa

Arm Group Label: Phase 3 Diagnostic

Intervention Type: Device

Intervention Name: Leptospira IgG/IgM

Description: This test enables the differential detection of IgG and IgM antibodies to Leptospira interrogans. It is manufactured by Standard Diagnostics, Korea

Arm Group Label: Phase 3 Diagnostic

Eligibility

Criteria:

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

Gender: All

Minimum Age: 5 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
François Chappuis, MD, PhD Study Director University Hospital, Geneva
Location
Facility:
Sihanouk Hospital Center of HOPE | Phnom Penh, Cambodia
Reference Hospital Mosango and Kasay Health Centre | Mosango, Bandundu, Congo, The Democratic Republic of the
Institut National de Recherche Biomédicale | Kinshasa, Congo, The Democratic Republic of the
Dhankuta District hospital | Dhankuta, Koshi Zone, Nepal
BP Koirala Institute of Health Sciences | Dharan, Nepal
Tabarak Allah Hospital | Tabarak Allah, Gedaref, Sudan
University of Khartoum | Khartoum, Sudan
Location Countries

Cambodia

Congo, The Democratic Republic of the

Nepal

Sudan

Verification Date

October 2016

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University Hospital, Geneva

Investigator Full Name: Francois CHAPPUIS

Investigator Title: Professor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Phase 3 Diagnostic

Type: Experimental

Description: A total of 10 RDTs will be assessed in the patients cohort for the respective target condition

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Diagnostic

Masking: None (Open Label)

Source: ClinicalTrials.gov