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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Hospital, Geneva
Sponsor:
Collaborators:
Institute of Tropical Medicine, Belgium
B.P. Koirala Institute of Health Sciences
Institut National de Recherche Biomédicale, Kinshasa, DRC
University of Khartoum
Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia
Information provided by (Responsible Party):
Francois CHAPPUIS, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01766830
First received: January 9, 2013
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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 Intervention
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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Prevalence of Visceral Leishmaniasis (VL), Human African Trypanosomiasis (HAT) and other Neglected Tropical Diseases (NTDs) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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 clinical and laboratory diagnostic indicators [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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

  • Identification of reliable Rapid Diagnostic Tests (RDTs) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Predictive values (post-test probabilities) of RDTs, alone and in combination, for the respective target conditions within the multi-disease approach


Secondary Outcome Measures:
  • Cost-effectiveness of the diagnostic tests [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Unit costs of diagnostic tests for the diagnosis of HAT and other priority NTDs/IDs in the setting


Estimated Enrollment: 2170
Study Start Date: January 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01766830

Contacts
Contact: François Chappuis, MD, PhD +41 22 372 96 20 françois.chappuis@hcuge.ch
Contact: Ninon Horié, MSc +41 79 553 32 53 nhor@hcuge.ch

Locations
Cambodia
Sihanouk Hospital Center of HOPE Recruiting
Phnom Penh, Cambodia
Contact: Kruy Lim, MD    +855 11 623 808    kruylim@sihosp.org   
Contact: Thong Phe, MD       thongphe@sihosp.org   
Principal Investigator: Kruy Lim, MD         
Sub-Investigator: Thong Phe, MD         
Congo, The Democratic Republic of the
Reference Hospital Mosango Recruiting
Mosango, Bandundu, Congo, The Democratic Republic of the
Contact: Deby Mukendi, MD       debymukendi@yahoo.fr   
Sub-Investigator: Deby Mukendi, MD         
Institut National de Recherche Biomédicale Active, not recruiting
Kinshasa, Congo, The Democratic Republic of the
Nepal
Dhankuta District hospital Recruiting
Dhankuta, Koshi Zone, Nepal
BP Koirala Institute of Health Sciences Recruiting
Dharan, Nepal
Contact: Suman Rijal, MD, PhD    +977 25 531254    sumanrijal2@yahoo.com   
Principal Investigator: Suman Rijal, MD, PhD         
Sub-Investigator: Basudha Khanal, PhD         
Sub-Investigator: Narayan Bhattarai, MSc         
Sub-Investigator: Nisha Bhatta, MD         
Sudan
Tabarak Allah Hospital Recruiting
Tabarak Allah, Gedaref, Sudan
Sub-Investigator: Husam Elshikh, MD         
Sub-Investigator: Ahmed Mohamed, MD         
University of Khartoum Active, not recruiting
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, DRC
University of Khartoum
Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia
Investigators
Study Director: François Chappuis, MD, PhD University Hospital, Geneva
  More Information

Additional Information:
No publications provided

Responsible Party: Francois CHAPPUIS, Professor, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01766830     History of Changes
Other Study ID Numbers: WP2-01-FEV, 260260
Study First Received: January 9, 2013
Last Updated: May 13, 2014
Health Authority: Belgium: Ethics Committee
Nepal: Health Research Council
Sudan: Ministry of Health
Congo, Democratic Republic of the: Ministry of Health
Cambodia: Ministry of Health

Additional relevant MeSH terms:
Amebiasis
Abscess
Brucellosis
Fever
Leishmaniasis
Leishmaniasis, Visceral
Leptospirosis
Weil Disease
Liver Abscess
Liver Abscess, Amebic
Malaria
Melioidosis
Relapsing Fever
Rickettsia Infections
Trypanosomiasis
Trypanosomiasis, African
Tuberculosis
Typhoid Fever
Suppuration
Infection
Inflammation
Pathologic Processes
Gram-Negative Bacterial Infections
Bacterial Infections
Body Temperature Changes
Signs and Symptoms
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic

ClinicalTrials.gov processed this record on July 29, 2014