Febrile Disease Landscape in Cambodia Via Metagenomic Pathogen Sequencing

Vector-Borne Diseases Clinical Trial

Official title:

Characterization of Febrile Disease Landscape in Cambodia Via Metagenomic Pathogen Sequencing

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04034264
• Other study ID #: 999919109
• Secondary ID: 19-I-N109
• Status: Recruiting
• Start date: July 23, 2019
• Est. completion date: July 1, 2026

Study information

• Verified date: February 12, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Christina C Yek, M.D.
• Phone: (202) 359-2641
• Email: christina.yek[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: Vector-borne diseases are caused by the bite of an infected mosquito, fly, flea, tick, or other blood-feeder. These diseases cause almost 1 million deaths per year. And they are on the rise, particularly in Southeast Asia in particular. Researchers think that these diseases make up about 10 percent of fevers in Cambodia. But many of these illnesses are never diagnosed. Studying these diseases can help find new ways to identify and treat them. Objective: To find pathogens in people who have a fever using metagenomic pathogen sequencing platforms. Eligibility: People aged 2 months to 65 years with a fever of at least 38 degrees Celsius or those diagnosed with infection by a pathogen of concern who visit the referral hospital in Cambodia. Close contacts of people diagnosed with infection by a pathogen of concern may also be enrolled. Design: Participants will be screened with their medical history. Children will be weighed to make sure they are big enough to give blood samples. Participants will share data about their sex, age, and where they live. They will answer more questions about their heath history. They will answer questions about and any places to which they have recently traveled. They will take a questionnaire. They will have a blood test. If they have respiratory symptoms, they will have a nasal swab. Participants may be contacted within 1-2 weeks (early) and/or within 3 months (late) from their enrollment date to provide an optional follow-up blood samples and nasal swabs.

Description:

Vector-borne diseases continue to cause significant global morbidity and mortality, particularly in Southeast Asia. However, given a lack of diagnostics available in resource-poor countries, many vector-borne diseases are never diagnosed and therefore their impact is underappreciated. Cross-sectional retrospective surveys have revealed higher than expected antibody prevalence to a number of diseases including mosquito-borne viruses and ectoparasite-borne rickettsial diseases. Here, we aim to collect specimens from individuals with acute febrile illness or red flag pathogens to better describe the febrile disease landscape of Cambodia using novel genomics technologies (unbiased next-generation sequencing) to investigate possible infectious etiologies of illnesses of unexplained etiology in Cambodian children and adults. If a highly transmissible and/or highly virulent (red flag) pathogen of public health concern is identified, we will take a convalescent sample from the individual and screen his/her close contacts with serological and molecular assays to add an additional layer of understanding of the disease burden. With the current rise of vector-borne diseases around the world, we hope the results of this study contribute to better understanding the epidemiology and burden for vector-borne diseases in this region.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6500
• Est. completion date: July 1, 2026
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Months to 65 Years

Eligibility

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria: Provision of signed and dated informed consent form. Stated willingness to comply with all study procedures. Male or female, aged 2 months to 65 years.

Meets one of the following case definitions:

• Febrile patient: has documented fever equal to or greater than 38 degrees celsius in previous 24 hours.
• Red flag patient: is an individual with disease relating to a red flag pathogen (see list, below), with confirmed standard laboratory testing (e.g., blood culture, polymerase chain reaction [PCR]) for the pathogen in question.
• Afebrile close contact: is an afebrile individual who lived in the same household or worked in the same enclosed workspace on a daily basis with a red flag patient at the time they got sick with a known pathogen.

Red Flag Pathogens:

• Yersinia pestis
• Corynebacterium diphtheriae
• Salmonella typhi
• Salmonella paratyphi
• Streptococcus suis
• Burkholderia cepacia or pseudomallei
• Avian influenza
• Swine influenza
• Betacoronaviruses
• Nipah virus
• Measles virus
• Chikungunya virus
• Zika virus
• SFTS virus (severe fever with thrombocytopenia syndrome) Willing to allow biological samples to be stored for future research and for all de-identified metagenomic sequencing data to be stored in publicly accessible databases. EXCLUSION CRITERIA: Any underlying, chronic, or current medical condition that, in the opinion of the investigator, would interfere with participation in the study (e.g., inability or great difficulty in drawing blood). Any febrile individual who has had surgery in the prior month. Any patient who enrolled and exited this study within 30 days of the initial study blood draw, or afebrile close contact who enrolled and exited within 14 days.

Related Conditions & MeSH terms

• Vector Borne Diseases
• Vector-Borne Diseases

Locations

Country	Name	City	State
Cambodia	Kampong Speu Referral Hospital	Chbar Mon
Cambodia	National Pediatric Hospital	Phnom Penh
Cambodia	Preah Kossomak Hospital	Phnom Penh
Cambodia	Takeo District Referral Hospital	Takeo

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Cambodia, 

References & Publications (3)

Gu W, Miller S, Chiu CY. Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection. Annu Rev Pathol. 2019 Jan 24;14:319-338. doi: 10.1146/annurev-pathmechdis-012418-012751. Epub 2018 Oct 24. — View Citation

Tabor A, Valle MR. Report from the 'One Health' 9th Tick and Tick-Borne Pathogen Conference and the 1st Asia-Pacific Rickettsia Conference, Cairns, Australia, 27th August-1st September 2017. Vet Sci. 2018 Oct 2;5(4):85. doi: 10.3390/vetsci5040085. — View Citation

Vong S, Khieu V, Glass O, Ly S, Duong V, Huy R, Ngan C, Wichmann O, Letson GW, Margolis HS, Buchy P. Dengue incidence in urban and rural Cambodia: results from population-based active fever surveillance, 2006-2008. PLoS Negl Trop Dis. 2010 Nov 30;4(11):e903. doi: 10.1371/journal.pntd.0000903. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of pathogen sequences	This is an attempt to characterize what fraction of unexplained febrile illness is vector-borne in peri-urban Cambodia. Data from this study will be used to guide future studies.	Enrollment (between Day 0-2)
Secondary	Assessment of reactivity to salivary gland homogenate reactivity of appropriate vector as detected by ELISA or Western blot assays.	Characterizing vector salivary protein reactivity profiles (mosquitos, ticks, fleas) in Cambodians with vector-borne disease is the first step to better understanding transmission patterns, responsible vectors, and Cambodian people s risk of exposure to these vectors.	Enrollment (between Day 0-2)