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)

Not Applicable

Completed

• Conditions: Visceral Leishmaniasis; Leptospirosis; Malaria; Amoebic Liver Abscess; Human African Trypanosomiasis; Brucellosis; Relapsing Fever; Rickettsial Diseases; Melioidosis; HIV
• Interventions: 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

• Registration Number: NCT01766830
• Lead Sponsor: 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.

Study Timeline

• Study Start: 2013-01
• Study First Submitted: 2013-01-09
• Study First Submitted QC: 2013-01-10
• Study First Posted: 2013-01-11
• Primary Completion: 2014-10
• Study Completion: 2016-07
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-26
• Last Update Posted: 2016-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1927

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase 3 Diagnostic	Test-it Typhoid IgM	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	HAT Serostrip	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	IT LEISH (rK39)	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	Typhidot M	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	rk28 ICT	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	Immunochromatographic HAT test	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	Card Agglutination Trypanosoma Test (CATT)-10	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	Leptospira IgG/IgM	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	S. typhi IgM/IgG	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition
Phase 3 Diagnostic	Test-it Leptospirosis IgM	A total of 10 RDTs will be assessed in the patients cohort for the respective target condition

Primary Outcome Measures

Name	Time	Method
Prevalence of Visceral Leishmaniasis (VL), Human African Trypanosomiasis (HAT) and other Neglected Tropical Diseases (NTDs)	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
Identification of reliable Rapid Diagnostic Tests (RDTs)	18 months	Assessment of sensitivity, likelihood ratios and performances (diagnostic accuracy) of the novel study RDTs for VL, HAT, enteric fever and
Predictive values of RDTs	18 months	Predictive values (post-test probabilities) of RDTs, alone and in combination, for the respective target conditions within the multi-disease approach
Identification of clinical and laboratory diagnostic indicators	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

Secondary Outcome Measures

Name	Time	Method
Cost-effectiveness of the diagnostic tests	18 months	Unit costs of diagnostic tests for the diagnosis of HAT and other priority NTDs/IDs in the setting

Trial Locations

Locations (7)

University of Khartoum; 🇸🇩 Khartoum, Sudan

BP Koirala Institute of Health Sciences; 🇳🇵 Dharan, Nepal

Tabarak Allah Hospital; 🇸🇩 Tabarak Allah, Gedaref, Sudan

Dhankuta District hospital; 🇳🇵 Dhankuta, Koshi Zone, Nepal

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