Febrile Disease Landscape in Cambodia Via Metagenomic Pathogen Sequencing

NCT04034264 | Recruiting

• 2 other identifiers: 99991910919-I-N109
• Study Type: observational
• Target: 6,500
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Vector-Borne Diseases; Emerging Pathogens

Keywords

Next-Generation Sequencing; Vector-Borne Diseases; Southeast Asia; Agnostic Tools; Febrile Surveillance; Natural History

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Assessment of reactivity to salivary gland homogenate reactivity of appropriate vector as detected by ELISA or Western blot assays.

  Enrollment (between Day 0-2)

Study Arms (2)

Afebrile close contact

Lived in the same household or worked in the same enclosed workspace daily with a febrile enrollee at the time they got sick with a known highly morbid and/or transmissible pathogen.

Febrile patient

Patients between 2 months and 65 years old who present with fever, or diagnosed with a highly morbid and/or transmissible pathogen by clinically validated tests.

Eligibility Criteria

• Age: 2 Months - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Febrile patients who have documented fever equal to or greater than 38 degrees celsius in previous 24 hours, or those with a highly morbid and/or transmissible pathogen detected using standard clinical tests, who present at a hospital. If there is a highly morbid and/or transmissible pathogen identified from the febrile patient, close contacts will be identified through discussion with the patient.

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

Kampong Speu Referral Hospital

Chbar Mon, Cambodia

RECRUITING

Kantha Bopha Hospital

Phnom Penh, Cambodia

RECRUITING

Khmer-Soviet Friendship Hospital

Phnom Penh, Cambodia

RECRUITING

National Pediatric Hospital

Phnom Penh, Cambodia

RECRUITING

Preah Kossomak Hospital

Phnom Penh, Cambodia

RECRUITING

Takeo District Referral Hospital

Takeo, Cambodia

RECRUITING

Related Publications (3)

• 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.

  PMID: 21152061 BACKGROUND

• 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.

  PMID: 30355154 BACKGROUND

• 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.

  PMID: 30279400 BACKGROUND

MeSH Terms

Conditions

Vector Borne Diseases

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Christina C Yek, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christina C Yek, M.D.

CONTACT

(202) 359-2641; christina.yek@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 26, 2019
• Study Start: July 23, 2019
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-02-23

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)