Effect of Community Active Case Finding Strategies for Detection of Tuberculosis in Cambodia

NCT04094350 | Completed

• 1 other identifier: NIHA-2018-005
• Study Type: interventional
• Target: 2,004
• Locations: 1 country
• Sites: 3

Brief Summary

Tuberculosis (TB) is a highly stigmatized disease, and approximately one-third of the Cambodian population living with TB are undetected. Therefore, it is vital to find these missing cases and promptly link them to care to reduce disease progression and interrupt further transmission. The integration of community-based, peer-driven intervention in TB active case finding (ACF) is relatively novel. In partnership with KHANA, the National Center for Tuberculosis and Leprosy Control (CENAT), and the Cambodia Anti-Tuberculosis Association (CATA), we will conduct a pragmatic cluster randomized controlled trial comparing 1) the ACF with the seed-and-recruit model; 2) ACF targeting household and neighborhood contacts; 3) ACF targeting the older population using mobile screening units; and 4) passive case finding (PCF) approach. The primary outcome will be the case notification rate in the intervention and control districts during the study period. We will also determine additionality, comparing the yield in each arm with its respective historical baseline and the cumulative yield over the implementation period. The secondary outcomes include the number needed to screen to detect one TB case, cost-effectiveness (direct and indirect costs per TB case notified), and the treatment outcome of all people with TB in this study. The project will be carried out over two years in eight operational districts (province name in parenthesis) - Koh Soutin (Kampong Cham), Stong (Kampong Thom), Kanchreach (Prey Veng), Choeung Prey (Kampong Cham), Dambae (Thbong Khmum), Boribo (Kampong Chhnang), Ponhea Leu (Kandal), and Phnom Srouch (Kampong Speu) - in Cambodia. The selection was also based on the number of health centers to increase comparability and generalizability of study findings. This study will randomize currently underserved operational districts (without active intervention at least in the past six months from the implementation date) to receive the interventions (ACF) and PCF as the control. The results from this proposal will enable a nationwide scale-up of an effective intervention that is contextualized and complies with the principles set by the national TB program to find undiagnosed cases and control TB in Cambodia. Also, this project will complement existing ACF programs in Cambodia by expanding ACF to other operational districts that are currently not served by the Global Fund, its implementing partners, and other organizations. Findings from this trial could also potentially inform active case finding strategies in other countries with a high TB burden.

Conditions

Tuberculosis

Keywords

Tuberculosis; Community health services; Cambodia; Contact tracing; Mass screening; Referral and consultation; Peer group

Outcome Measures

Primary Outcomes (3)

• Number of TB cases notified per 10000 population

  Number of TB cases notified per 10000 population by each operational district included in this study per year

  During the intervention period (1 year)

• Additional number of TB cases

  Additional number of TB cases reported compared to historical baseline (same period in the preceding 1 year)

  During the intervention period (1 year)

• Number of TB cases diagnosed per 1000 population screened

  Number of TB cases diagnosed per 1000 population screened during one year of the intervention period

  During the intervention period (1 year)

Secondary Outcomes (3)

• Number of people with TB who have completed TB treatment and successfully treated

  Six months after TB treatment initiated

• Number of people needed to screen to detect one case

  During the intervention period (1 year)

• Cost-effectiveness

  During the intervention period (1 year)

Study Arms (4)

ACF with a seed-and-recruit model

EXPERIMENTAL

Active case finding with a seed-and-recruit model to be implemented by KHANA. Target group: key populations for TB (people living with HIV, TB contacts, people with diabetes, people who use/inject drugs) and presumptive TB cases

Other: ACF targeting household and neighborhood contacts; Other: ACF targeting the older population using mobile screening units; Other: Passive case finding

ACF targeting household and neighborhood contacts

EXPERIMENTAL

Active case finding targeting household and neighborhood contacts to be implemented by CENAT. Target group: household contacts, immediate neighbors of people diagnosed with TB in the last 2 years, and other presumptive TB cases

Other: ACF with a seed-and-recruit model

ACF targeting the older population

EXPERIMENTAL

Active case finding targeting the older population (people aged 55 and older) using mobile screening units to be implemented by CATA. Target group: elderly above age of 55 and other presumptive TB cases

Other: ACF with a seed-and-recruit model

Passive case finding

NO INTERVENTION

Passive case finding strategy is a default setup in the national health system. PCF relies on the self-presentation of presumptive TB cases to the health centers to be diagnosed with TB.

Interventions

ACF with a seed-and-recruit model OTHER

The intervention will take place for 12 months. In the intervention clusters, potential seeds - TB survivors, people living with HIV, and household contacts of people with TB - will be approached by the research team. Seeds will be trained and act as recruiters in the community to refer presumptive TB cases to the attached health centers. The research team will work with staff at the health centers to facilitate screening and enrollment of recruits who are diagnosed with TB to care. New people with TB who have the potential to be a recruiter will be invited and trained to recruit their peers in the community who may have TB for TB screening. Seeds will be trained to identify people who may have TB and equipped with health promotion skills to impart knowledge and practices about TB. We will follow-up all people with TB referred by seeds for six months from the treatment initiation.

ACF targeting household and neighborhood contacts; ACF targeting the older population

ACF targeting household and neighborhood contacts OTHER

In this arm, community health volunteers will recruit household contacts of people with TB and TB survivors diagnosed during the preceding two years. Immediate neighbors (10 nearest households) of the index cases (people with TB) who are symptomatic will also be invited by the community health volunteers to the screening session. Next nearest households within the same village will be approached if the number of presumptive TB cases in the 10 nearest households is low. The one-off screening session will be held at the nearest health center on specific days. Presumptive TB cases will be screened for symptoms on-site, and chest x-ray (CXR) will be taken. Sputum samples from presumptive TB cases with abnormal (CXR) will be collected for GeneXpert testing. Test results will be communicated to the newly diagnosed people with TB, and they will be referred to the health centers for treatment and follow-up.

ACF with a seed-and-recruit model

ACF targeting the older population using mobile screening units OTHER

The outreach team will conduct training and sensitization of the target population of the activities. The schedule of a one-off screening session will be made known to the communities in the districts before the screening day. Each person who visits the screening session will be screened. Demographic information and presence of TB symptoms will be collected at registration by a trained staff. A chest x-ray will then be performed on-site for all persons exhibiting TB symptoms and all elderly aged 55 and above regardless of symptoms. When CXR findings are abnormal, sputum samples will be collected for GeneXpert testing on-site as well. Test results will be communicated to the participants on the spot or via phone calls, and people with TB will be referred for treatment and follow-up at the health center where screening is conducted or a center of their choice. Should the health center of their choice do not fall within the selected sites, follow-up will be conducted via phone calls.

ACF with a seed-and-recruit model

Passive case finding OTHER

Passive case finding (PCF) strategy is a default setup in the national health system. PCF relies on the self-presentation of presumptive TB cases to the health centers to be diagnosed with TB.

ACF with a seed-and-recruit model

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presumptive TB cases will be referred to the health centers for TB screening and diagnosis in the intervention arms and self-presented to the health centers in the control arm. We will include the aggregated number of cases diagnosed and notified from all arms regardless of age. In this project, an individual is defined as a presumptive TB case if he/she exhibits any of the following symptoms19:
• Pulmonary TB (PTB): A cough more than two weeks and at least one general symptom
• Extra-pulmonary TB (EPTB): Presence of symptoms, depending on the location of TB, (e.g., cervical lymph node, swollen backbone, swollen articulation, etc.) and at least one general symptom
• General symptoms: Fever, night sweat for more than two weeks or unintentional weight loss (\>5% reduction in usual body weight over the last 6 to 12 months)20
• People newly diagnosed with TB age 18 and above\* from the selected health centers. We will only include all people with TB aged 18 years or over with TB (all-forms) for the baseline and follow-up survey.

You may not qualify if:

• We will exclude those who refused to participate.

Sponsors & Collaborators

• National University of Singapore: lead
• KHANA Center for Population Health Research: collaborator

Study Sites (3)

KHANA Center for Population Health Research

Phnom Penh, 2361, Cambodia

Location

Cambodia Anti-Tuberculosis Association

Phnom Penh, 2589-384, Cambodia

Location

National Center for Tuberculosis and Leprosy Control

Phnom Penh, 2589, Cambodia

Location

Related Publications (13)

• Kranzer K, Afnan-Holmes H, Tomlin K, Golub JE, Shapiro AE, Schaap A, Corbett EL, Lonnroth K, Glynn JR. The benefits to communities and individuals of screening for active tuberculosis disease: a systematic review. Int J Tuberc Lung Dis. 2013 Apr;17(4):432-46. doi: 10.5588/ijtld.12.0743.

  PMID: 23485377 BACKGROUND

• Pascom AR, Szwarcwald CL, Barbosa Junior A. Sampling studies to estimate the HIV prevalence rate in female commercial sex workers. Braz J Infect Dis. 2010 Jul-Aug;14(4):385-97.

  PMID: 20963326 BACKGROUND

• Simoni JM, Nelson KM, Franks JC, Yard SS, Lehavot K. Are peer interventions for HIV efficacious? A systematic review. AIDS Behav. 2011 Nov;15(8):1589-95. doi: 10.1007/s10461-011-9963-5.

  PMID: 21598034 BACKGROUND

• Marton KI, Sox HC Jr, Krupp JR. Involuntary weight loss: diagnostic and prognostic significance. Ann Intern Med. 1981 Nov;95(5):568-74. doi: 10.7326/0003-4819-95-5-568.

  PMID: 7294545 BACKGROUND

• GBD Tuberculosis Collaborators. The global burden of tuberculosis: results from the Global Burden of Disease Study 2015. Lancet Infect Dis. 2018 Mar;18(3):261-284. doi: 10.1016/S1473-3099(17)30703-X. Epub 2017 Dec 7.

  PMID: 29223583 RESULT

• Mhimbira FA, Cuevas LE, Dacombe R, Mkopi A, Sinclair D. Interventions to increase tuberculosis case detection at primary healthcare or community-level services. Cochrane Database Syst Rev. 2017 Nov 28;11(11):CD011432. doi: 10.1002/14651858.CD011432.pub2.

  PMID: 29182800 RESULT

• Eang MT, Satha P, Yadav RP, Morishita F, Nishikiori N, van-Maaren P, Weezenbeek CL. Early detection of tuberculosis through community-based active case finding in Cambodia. BMC Public Health. 2012 Jun 21;12:469. doi: 10.1186/1471-2458-12-469.

  PMID: 22720878 RESULT

• Morishita F, Eang MT, Nishikiori N, Yadav RP. Increased Case Notification through Active Case Finding of Tuberculosis among Household and Neighbourhood Contacts in Cambodia. PLoS One. 2016 Mar 1;11(3):e0150405. doi: 10.1371/journal.pone.0150405. eCollection 2016.

  PMID: 26930415 RESULT

• Murray EJ, Bond VA, Marais BJ, Godfrey-Faussett P, Ayles HM, Beyers N. High levels of vulnerability and anticipated stigma reduce the impetus for tuberculosis diagnosis in Cape Town, South Africa. Health Policy Plan. 2013 Jul;28(4):410-8. doi: 10.1093/heapol/czs072. Epub 2012 Sep 2.

  PMID: 22945548 RESULT

• Yaesoubi R, Cohen T. Identifying dynamic tuberculosis case-finding policies for HIV/TB coepidemics. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9457-62. doi: 10.1073/pnas.1218770110. Epub 2013 May 20.

  PMID: 23690585 RESULT

• Koura KG, Trebucq A, Schwoebel V. Do active case-finding projects increase the number of tuberculosis cases notified at national level? Int J Tuberc Lung Dis. 2017 Jan 1;21(1):73-78. doi: 10.5588/ijtld.16.0653.

  PMID: 28157468 RESULT

• Yi S, Ngin C, Tuot S, Chhoun P, Chhim S, Pal K, Mun P, Mburu G. HIV prevalence, risky behaviors, and discrimination experiences among transgender women in Cambodia: descriptive findings from a national integrated biological and behavioral survey. BMC Int Health Hum Rights. 2017 May 23;17(1):14. doi: 10.1186/s12914-017-0122-6.

  PMID: 28535758 RESULT

• Teo AKJ, Prem K, Evdokimov K, Ork C, Eng S, Tuot S, Chry M, Mao TE, Hsu LY, Yi S. Effect of community active case-finding strategies for detection of tuberculosis in Cambodia: study protocol for a pragmatic cluster randomized controlled trial. Trials. 2020 Feb 24;21(1):220. doi: 10.1186/s13063-020-4138-1.

  PMID: 32093778 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

A1CF protein, human

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Siyan Yi, PhD

  National University of Singapore

  PRINCIPAL INVESTIGATOR

• Alvin Teo, MPH

  National University of Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Project coordinators and residents in the selected operational districts will not be masked to the intervention. However, all case finding activities will be done without reference to the intervention group. The data analysts will be masked to intervention allocation and will only analyse de-identified data.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: A 12-moth pragmatic cluster randomized controlled trial will be conducted to evaluate different TB case-finding strategies. Eights operational districts consisting a total of 70 health centers will be randomized into one of the four groups (2 operational district per group): 1) Active case finding (ACF) with the seed-and-recruit model by KHANA, 2) ACF targeting household and neighborhood contacts by the National Center for Tuberculosis and Leprosy Control (CENAT), 3) ACF targeting the older population using mobile screening units by Cambodia Anti-Tuberculosis Association (CATA) and 4) Passive case finding (PCF).

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: September 18, 2019
• Study Start: December 16, 2019
• Primary Completion: November 30, 2021
• Study Completion: January 31, 2022
• Last Updated: November 29, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)