Vector-Borne DiseasesNCT04034264
Febrile Disease Landscape in Cambodia Via Metagenomic Pathogen Sequencing
An observational study of Vector-Borne Diseases and Emerging Pathogens, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in Cambodia.
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. Read more about this study
- Who is it for?
- Ages 2 months and olderHealthy volunteers can take part
- Conditions the study is for
- Vector-Borne Diseases, Emerging Pathogens
- How many people
- 6,500 participants
- Where
- 6 sitesCambodia
- Study dates
- 23 Jul 2019to 1 Jul 2027
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated ICF.
- Stated willingness to comply with all study procedures.
- Male or female, aged at least 2 months
- Meets one of the following case definitions:
- Febrile patient: has documented fever equal to or greater than 38 degrees celsius in previous 24 hours.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Cambodia6 sites, 6 recruiting
- Recruiting
Kampong Speu Referral Hospital
Chbar Mon
Christina Yek, M.D., (202) 359-2641, christina.yek@nih.gov
- Recruiting
Kantha Bopha Hospital
Phnom Penh
Christina Yek, M.D., (202) 359-2641, christina.yek@nih.gov
- Recruiting
Khmer-Soviet Friendship Hospital
Phnom Penh
Christina Yek, M.D., (202) 359-2641, christina.yek@nih.gov
- Recruiting
National Pediatric Hospital
Phnom Penh
Christina Yek, M.D., (202) 359-2641, christina.yek@nih.gov
- Recruiting
Preah Kossomak Hospital
Phnom Penh
Christina Yek, M.D., (202) 359-2641, christina.yek@nih.gov
- Recruiting
Takeo District Referral Hospital
Takeo
Christina Yek, M.D., (202) 359-2641, christina.yek@nih.gov
About this study
Official title: Characterization of Febrile Disease Landscape in Cambodia Via Metagenomic Pathogen Sequencing
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.
Read more
Objective:
To find pathogens in people who have a fever using metagenomic pathogen sequencing platforms.
Eligibility:
People aged at least 2 months 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.
Read the detailed 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.
- Conditions
- Vector-Borne Diseases, Emerging Pathogens
- Keywords
- Next-Generation Sequencing, Vector-Borne Diseases, Southeast Asia, Agnostic Tools, Febrile Surveillance, Natural History
- Medical subject headings
- Vector Borne Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: Enrollment (between Day 0-2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2019
- Study start23 Jul 2019
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Vector-Borne DiseasesStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 6,500 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christina C Yek, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04034264
- Sponsor's protocol ID
- 999919109
- Other IDs
- 19-I-N109
- Status last verified
- 22 Jul 2026
- First submitted
- 25 Jul 2019
- Last updated
- 16 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21152061Gu 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.
PubMed 30355154Tabor 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.
PubMed 30279400