Febrile Disease Landscape in Cambodia Via Metagenomic Pathogen Sequencing

NCT ID: NCT04034264

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

6500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-07-23

Study Completion Date

2026-07-01

Brief Summary

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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....

Detailed Description

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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.

Conditions

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Vector-Borne Diseases Emerging Pathogens

Keywords

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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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.
* 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.
Minimum Eligible Age

2 Months

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christina C Yek, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

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Kampong Speu Referral Hospital

Chbar Mon, , Cambodia

Site Status RECRUITING

Kantha Bopha Hospital

Phnom Penh, , Cambodia

Site Status RECRUITING

Khmer-Soviet Friendship Hospital

Phnom Penh, , Cambodia

Site Status RECRUITING

National Pediatric Hospital

Phnom Penh, , Cambodia

Site Status RECRUITING

Preah Kossomak Hospital

Phnom Penh, , Cambodia

Site Status RECRUITING

Takeo District Referral Hospital

Takeo, , Cambodia

Site Status RECRUITING

Countries

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Cambodia

Central Contacts

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Christina C Yek, M.D.

Role: CONTACT

Phone: (202) 359-2641

Email: [email protected]

Facility Contacts

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Christina Yek, M.D.

Role: primary

Christina Yek, M.D.

Role: primary

Christina Yek, M.D.

Role: primary

Christina Yek, M.D.

Role: primary

Christina Yek, M.D.

Role: primary

Christina Yek, M.D.

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 21152061 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30355154 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30279400 (View on PubMed)

Other Identifiers

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19-I-N109

Identifier Type: -

Identifier Source: secondary_id

999919109

Identifier Type: -

Identifier Source: org_study_id