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)

NCT ID: NCT01766830

Last Updated: 2016-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1927 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2016-07-31

Brief Summary

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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

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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.

Conditions

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Visceral Leishmaniasis Human African Trypanosomiasis Enteric Fever Melioidosis Brucellosis Leptospirosis Relapsing Fever Rickettsial Diseases HIV Tuberculosis Malaria Amoebic Liver Abscess

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Phase 3 Diagnostic

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

Group Type EXPERIMENTAL

rk28 ICT

Intervention Type DEVICE

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)

IT LEISH (rK39)

Intervention Type DEVICE

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.

Immunochromatographic HAT test

Intervention Type DEVICE

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

HAT Serostrip

Intervention Type DEVICE

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

Card Agglutination Trypanosoma Test (CATT)-10

Intervention Type DEVICE

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.

Typhidot M

Intervention Type DEVICE

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

S. typhi IgM/IgG

Intervention Type DEVICE

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)

Test-it Typhoid IgM

Intervention Type DEVICE

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.

Test-it Leptospirosis IgM

Intervention Type DEVICE

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

Leptospira IgG/IgM

Intervention Type DEVICE

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

Interventions

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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)

Intervention Type 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.

Intervention Type DEVICE

Immunochromatographic HAT test

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

Intervention Type 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.

Intervention Type 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.

Intervention Type 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

Intervention Type 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)

Intervention Type 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.

Intervention Type 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

Intervention Type 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

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role collaborator

B.P. Koirala Institute of Health Sciences

OTHER

Sponsor Role collaborator

Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo

OTHER

Sponsor Role collaborator

University of Khartoum

OTHER

Sponsor Role collaborator

Sihanouk Hospital Center of HOPE

OTHER

Sponsor Role collaborator

University Hospital, Geneva

OTHER

Sponsor Role lead

Responsible Party

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Francois CHAPPUIS

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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François Chappuis, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Geneva

Locations

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Sihanouk Hospital Center of HOPE

Phnom Penh, , Cambodia

Site Status

Reference Hospital Mosango and Kasay Health Centre

Mosango, Bandundu, Democratic Republic of the Congo

Site Status

Institut National de Recherche Biomédicale

Kinshasa, , Democratic Republic of the Congo

Site Status

Dhankuta District hospital

Dhankutā, Koshi Zone, Nepal

Site Status

BP Koirala Institute of Health Sciences

Dharān, , Nepal

Site Status

Tabarak Allah Hospital

Tabarak Allah, Al Qaḑārif, Sudan

Site Status

University of Khartoum

Khartoum, , Sudan

Site Status

Countries

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Cambodia Democratic Republic of the Congo Nepal Sudan

References

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Bottieau E, Van Duffel L, El Safi S, Koirala KD, Khanal B, Rijal S, Bhattarai NR, Phe T, Lim K, Mukendi D, Kalo JL, Lutumba P, Barbe B, Jacobs J, Van Esbroeck M, Foque N, Tsoumanis A, Parola P, Yansouni CP, Boelaert M, Verdonck K, Chappuis F. Etiological spectrum of persistent fever in the tropics and predictors of ubiquitous infections: a prospective four-country study with pooled analysis. BMC Med. 2022 May 2;20(1):144. doi: 10.1186/s12916-022-02347-8.

Reference Type DERIVED
PMID: 35491421 (View on PubMed)

Alirol E, Horie NS, Barbe B, Lejon V, Verdonck K, Gillet P, Jacobs J, Buscher P, Kanal B, Bhattarai NR, El Safi S, Phe T, Lim K, Leng L, Lutumba P, Mukendi D, Bottieau E, Boelaert M, Rijal S, Chappuis F. Diagnosis of Persistent Fever in the Tropics: Set of Standard Operating Procedures Used in the NIDIAG Febrile Syndrome Study. PLoS Negl Trop Dis. 2016 Nov 3;10(11):e0004749. doi: 10.1371/journal.pntd.0004749. eCollection 2016 Nov.

Reference Type DERIVED
PMID: 27812090 (View on PubMed)

Related Links

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http://www.nidiag.org/

NIDIAG Consortium website

Other Identifiers

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260260

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

WP2-01-FEV

Identifier Type: -

Identifier Source: org_study_id