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)

NCT01766830 | Completed

• 2 other identifiers: WP2-01-FEV260260
• Study Type: interventional
• Target: 1,927
• Locations: 4 countries
• Sites: 7

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Prevalence of Visceral Leishmaniasis (VL), Human African Trypanosomiasis (HAT) and other Neglected Tropical Diseases (NTDs)

  Number of patients diagnosed with VL, HAT and other NTDs among those presenting with persistent(≥ 1 week) fever in one of the study sites

  18 months

• Identification of clinical and laboratory diagnostic indicators

  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

  18 months

• Identification of reliable Rapid Diagnostic Tests (RDTs)

  Assessment of sensitivity, likelihood ratios and performances (diagnostic accuracy) of the novel study RDTs for VL, HAT, enteric fever and

  18 months

• Predictive values of RDTs

  Predictive values (post-test probabilities) of RDTs, alone and in combination, for the respective target conditions within the multi-disease approach

  18 months

Secondary Outcomes (1)

• Cost-effectiveness of the diagnostic tests

  18 months

Study Arms (1)

Phase 3 Diagnostic

EXPERIMENTAL

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

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

Interventions

rk28 ICT 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)

Phase 3 Diagnostic

IT LEISH (rK39) 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.

Phase 3 Diagnostic

Immunochromatographic HAT test DEVICE

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

Phase 3 Diagnostic

HAT Serostrip DEVICE

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

Phase 3 Diagnostic

Card Agglutination Trypanosoma Test (CATT)-10 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.

Phase 3 Diagnostic

Typhidot M 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

Phase 3 Diagnostic

S. typhi IgM/IgG 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)

Phase 3 Diagnostic

Test-it Typhoid IgM 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.

Phase 3 Diagnostic

Test-it Leptospirosis IgM 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

Phase 3 Diagnostic

Leptospira IgG/IgM DEVICE

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

Phase 3 Diagnostic

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• fever for ≥ 1 week
• ≥ 5 years old (18 years onward in Cambodia)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (7)

Sihanouk Hospital Center of HOPE

Phnom Penh, Cambodia

Location

Reference Hospital Mosango and Kasay Health Centre

Mosango, Bandundu, Democratic Republic of the Congo

Location

Institut National de Recherche Biomédicale

Kinshasa, Democratic Republic of the Congo

Location

Dhankuta District hospital

Dhankutā, Koshi Zone, Nepal

Location

BP Koirala Institute of Health Sciences

Dharān, Nepal

Location

Tabarak Allah Hospital

Tabarak Allah, Al Qaḑārif, Sudan

Location

University of Khartoum

Khartoum, Sudan

Location

Related Publications (2)

• 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.

  PMID: 35491421 DERIVED

• 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.

  PMID: 27812090 DERIVED

Related Links

• NIDIAG Consortium website

MeSH Terms

Conditions

Leishmaniasis, Visceral; Typhoid Fever; Melioidosis; Brucellosis; Leptospirosis; Relapsing Fever; Rickettsia Infections; Tuberculosis; Malaria; Liver Abscess, Amebic

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Burkholderia Infections; Spirochaetales Infections; Borrelia Infections; Tick-Borne Diseases; Rickettsiaceae Infections; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Mosquito-Borne Diseases; Liver Diseases, Parasitic; Amebiasis; Liver Abscess; Abdominal Abscess; Abscess; Suppuration; Liver Diseases; Digestive System Diseases

Study Officials

• François Chappuis, MD, PhD

  University Hospital, Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 11, 2013
• Study Start: January 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: July 1, 2016
• Last Updated: October 27, 2016

Record last verified: 2016-10

Locations

DE (2); NE (2); CA (1); SU (2)