Clinical trial NCT01766830: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Visceral Leishmaniasis
Human African Trypanosomiasis
Enteric Fever
Melioidosis
Brucellosis
Leptospirosis
Relapsing Fever
Rickettsial Diseases
HIV
Tuberculosis
Malaria
Amoebic Liver Abscess
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine, Belgium
name: B.P. Koirala Institute of Health Sciences
name: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
name: University of Khartoum
name: Sihanouk Hospital Center of HOPE
First posted: 2013-01-11
Enrollment: 1927
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility 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

Primary outcomes:
measure: Prevalence of Visceral Leishmaniasis (VL), Human African Trypanosomiasis (HAT) and other Neglected Tropical Diseases (NTDs)
timeFrame: 18 months
measure: Identification of clinical and laboratory diagnostic indicators
timeFrame: 18 months
measure: Identification of reliable Rapid Diagnostic Tests (RDTs)
timeFrame: 18 months
measure: Predictive values of RDTs
timeFrame: 18 months
Secondary outcomes:
measure: Cost-effectiveness of the diagnostic tests
timeFrame: 18 months
Other outcomes:
Locations:
city: Phnom Penh
country: Cambodia
facility: Sihanouk Hospital Center of HOPE
city: Mosango
country: Congo, The Democratic Republic of the
facility: Reference Hospital Mosango and Kasay Health Centre
state: Bandundu
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Institut National de Recherche Biomédicale
city: Dhankuta
country: Nepal
facility: Dhankuta District hospital
state: Koshi Zone
city: Dharan
country: Nepal
facility: BP Koirala Institute of Health Sciences
city: Tabarak Allah
country: Sudan
facility: Tabarak Allah Hospital
state: Gedaref
city: Khartoum
country: Sudan
facility: University of Khartoum
Study officials:
affiliation: University Hospital, Geneva
name: François Chappuis, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.