Preventing Childhood Tuberculosis in Lesotho (PREVENT Study)

Lesotho, a small, landlocked country completely surrounded by South Africa, is among the world's poorest nations with one of the world's most severe epidemics of tuberculosis (TB) and HIV. TB incidence is the world's highest and approximately 76% of TB patients are HIV coinfected. Data from similar settings suggest that TB incidence in children is approximately 50% of adult TB incidence. The Lesotho National TB Program has adopted World Health Organization's (WHO) isoniazid preventive therapy (IPT) recommendations for child contacts; however, as in other countries in the region, implementation of IPT in children is limited, no clear strategies guide child contact tracing and screening, and no clear methods ensure provision of IPT in children. Thus, it is important to evaluate novel methods to prevent TB in child contacts of adult TB cases.

The purpose of the PREVENT Study is to identify an effective and acceptable intervention that addresses programmatic, structural and psychosocial barriers to contact tracing, screening, and IPT for child contacts of TB patients, with the ultimate goal of improving health outcomes among children in Lesotho. The study is a two-arm cluster randomized trial, randomized at the TB clinic level, which includes ten TB clinics in Berea district. Clinics are randomized to deliver the community-based intervention (CBI) or standard of care (SOC), with stratification by facility type. The experimental intervention will be delivered to all child contacts of adult TB patients in TB clinics randomly assigned to CBI. In TB clinics assigned to SOC, usual care procedures for contact tracing and IPT will be delivered.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Other: Standard of care; Behavioral: Community-based intervention

Detailed Description

The study intervention, community-based intervention (CBI), will contain multiple components, including: 1) Facility Providers. Providers will be trained on study interventions; job aids will be provided. Nurses will use a clinical algorithm based on national guidelines for intensive case finding and screening of child contacts for TB to assess patients without TB symptoms for IPT eligibility; to initiate IPT; and to monitor for side effects, TB symptoms, and adherence. If a child contact develops TB symptoms during IPT, national guidelines will be followed. HIV testing will be strongly promoted in child contacts. Use of simple available clinic IPT registers will be promoted. The PI will establish systems to track IPT use at monthly multi-disciplinary team meetings; clinic staff will review IPT monitoring data for prior months, identify challenges, and develop solutions. IPT registers will link IPT outcome data to TB register data for index cases. 2) Patients and Guardians. Nurses will explain to patients and guardians that IPT can prevent TB, promote IPT initiation, assess IPT adherence and side effects, and encourage follow-up with village health workers (VHW). Nurses will emphasize HIV testing for children. The VHW role will encompass social support, system navigation, referrals, and advocacy. VHW will follow up with guardians of children who miss appointments or report nonadherence, using scripted, illustrated flipcharts targeting children and guardians. VHW will emphasize to guardians the importance of IPT, encourage IPT and visit adherence, offer support and empathy, provide referrals, and advocate for patients. 3) Community Outreach. To investigate household contacts, VHW will visit homes of all adult TB cases at facilities assigned to CBI. All HIV-infected children and children under 5, regardless of HIV status, will be referred to health facilities. VHW will administer TB symptom screening in child contacts in the community, accompany them and their guardians to the clinic, and provide education sessions, support groups, and adherence counseling.

Study assessments include: 1) outcome data via medical records; 2) pre- and post-intervention interviews with providers; 3) post-intervention guardian interviews; and 4) program characteristics data. Stakeholders and policy makers will be engaged early in the process to help ensure successful integration of findings in programmatic contexts. A dissemination strategy will be developed in consultation with stakeholders and will help ensure scaling up of the intervention, if found effective.

All clinical care, including implementation of the combination intervention package at sites randomized to CIP, will be performed by Lesotho Ministry of Health clinic staff (nurses and VHW). All study procedures, including participant interviews, medical record abstraction, and program characteristics surveys will be performed by study staff.

• Study Type: Interventional
• Enrollment (Actual): 562
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Lesotho
  • Berea District
    • Berea, Berea District, Lesotho
      • Berea Hospital
    • Berea, Berea District, Lesotho
      • Holy Family Health Center
    • Berea, Berea District, Lesotho
      • Khubetsoana Health Center
    • Berea, Berea District, Lesotho
      • Koali Health Center
    • Berea, Berea District, Lesotho
      • Kolojane Health Center
    • Berea, Berea District, Lesotho
      • Maluti Hospital
    • Berea, Berea District, Lesotho
      • Pilot Health Center
    • Berea, Berea District, Lesotho
      • St Magdalena Health Center
    • Berea, Berea District, Lesotho
      • St. David Health Center
    • Berea, Berea District, Lesotho
      • St. Theresa Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

The randomized trial will include review of medical records of all adult TB cases who start TB treatment during the study period.

Providers inclusion criteria:

1. Nurse or village healthcare worker(VHW) working in a CBI clinic or VHW working in the community and affiliated with CBI clinic
2. Aged 18 or older
3. English- or Sesotho speaking
4. Capable of informed consent

Guardians inclusion criteria:

1. Guardian of a child contact
2. Aged 18 or older
3. English- or Sesotho speaking
4. Capable of informed consent

Two groups of guardians will be enrolled: guardians who brought their children for TB screening, and guardians who did not bring their children for TB screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Community-based intervention (CBI); Nurse training and mentorship in TB prevention using clinical algorithm based on national guidelines.; Health education using a treatment literacy curriculum for parents and guardians.; Community outreach by trained village health workers.	Behavioral: Community-based intervention; Other Names: CBI
Active Comparator: Standard of Care (SOC); At SOC clinics, patients will receive usual care for management of contact tracing, screening, and IPT provision. Childhood TB in Lesotho is managed by nurses in health centers. Per national guidelines, TB patients are asked to bring in child contacts, who are screened using a simple symptom questionnaire. Children who screen negative are assessed for IPT eligibility. Absent contra-indications (eg, active hepatitis, regular alcohol consumption, peripheral neuropathy), nurses counsel children and guardians on IPT benefits, potential side effects, and importance of adherence. Children requiring chest x-rays or gastric lavage and HIV-infected children under age 1 are referred to the hospital. After initiation, patients and guardians return to the clinic monthly for monitoring for side effects, TB symptoms, adherence, and 30-day supply of isoniazid. If adherence problems are noted, the nurse counsels patient and guardian as appropriate.	Other: Standard of care; Other Names: SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yield of child contacts	Number of child contacts per pulmonary TB case screened, based on review of clinic registers	3 years
Percentage of IPT initiation	Percentage of child contacts identified through contact tracing of new adult TB cases during observation period who initiate IPT, based on review of clinic registers	3 years
Percentage of IPT completion	Percentage of child contacts who complete IPT of those who initiate as determined by provider and recorded in clinic charts	Up to 9 months after IPT initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of HIV testing	Percentage of child contacts identified through contact tracing of new adult TB cases during observation period who are tested for HIV, based on review of clinic registers	3 years

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Yael Hirsch-Moverman, PhD, Columbia University

Publications and helpful links

General Publications

• Hirsch-Moverman Y, Howard AA, Frederix K, Lebelo L, Hesseling A, Nachman S, Mantell JE, Lekhela T, Maama LB, El-Sadr WM. The PREVENT study to evaluate the effectiveness and acceptability of a community-based intervention to prevent childhood tuberculosis in Lesotho: study protocol for a cluster randomized controlled trial. Trials. 2017 Nov 21;18(1):552. doi: 10.1186/s13063-017-2184-0.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: January 21, 2016
• First Posted (Estimate): January 26, 2016

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: HIV; adherence; TB; Lesotho; tuberculosis; retention; community-based intervention
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: AAAN7358; K01AI104351 (U.S. NIH Grant/Contract)