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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01766830
Recruitment Status : Completed
First Posted : January 11, 2013
Last Update Posted : October 27, 2016
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
Information provided by (Responsible Party):
Francois CHAPPUIS, 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.

Condition or disease Intervention/treatment Phase
Visceral Leishmaniasis Human African Trypanosomiasis Enteric Fever Melioidosis Brucellosis Leptospirosis Relapsing Fever Rickettsial Diseases HIV Tuberculosis Malaria Amoebic Liver Abscess Device: rk28 ICT Device: IT LEISH (rK39) Device: Immunochromatographic HAT test Device: HAT Serostrip Device: Card Agglutination Trypanosoma Test (CATT)-10 Device: Typhidot M Device: S. typhi IgM/IgG Device: Test-it Typhoid IgM Device: Test-it Leptospirosis IgM Device: Leptospira IgG/IgM Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1927 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: 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
Study Start Date : January 2013
Actual Primary Completion Date : October 2014
Actual Study Completion Date : July 2016

Arm Intervention/treatment
Experimental: Phase 3 Diagnostic
A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Device: rk28 ICT
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)

Device: IT LEISH (rK39)
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.

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

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

Device: Card Agglutination Trypanosoma Test (CATT)-10
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.

Device: Typhidot M
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

Device: S. typhi IgM/IgG
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)

Device: Test-it Typhoid IgM
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.

Device: Test-it Leptospirosis IgM
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

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

Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

Secondary Outcome Measures :
  1. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01766830

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Sihanouk Hospital Center of HOPE
Phnom Penh, Cambodia
Congo, The Democratic Republic of the
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
Sponsors and Collaborators
University Hospital, Geneva
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
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Study Director: François Chappuis, MD, PhD University Hospital, Geneva
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Francois CHAPPUIS, Professor, University Hospital, Geneva Identifier: NCT01766830    
Other Study ID Numbers: WP2-01-FEV
260260 ( Other Grant/Funding Number: European Commission )
First Posted: January 11, 2013    Key Record Dates
Last Update Posted: October 27, 2016
Last Verified: October 2016
Additional relevant MeSH terms:
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Liver Abscess
Typhoid Fever
Rickettsia Infections
Relapsing Fever
Liver Abscess, Amebic
Leishmaniasis, Visceral
Trypanosomiasis, African
Protozoan Infections
Parasitic Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Body Temperature Changes
Signs and Symptoms
Euglenozoa Infections
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Gram-Negative Bacterial Infections