Our Strategy

The PEARL study is a before and after evaluation of a population-wide systematic screening intervention, combined with a comprehensive treatment and prevention program for both TB and leprosy. The implementation study is a quasiexperimental interrupted time series design.

The study intervention comprises population-wide systematic screening and treatment of TB disease, TB infection and leprosy, together with the provision of leprosy prophylaxis to those not requiring treatment. In practice this equates to universal leprosy prophylaxis, given that TB and leprosy treatment, as well as TPT with rifamycin-based regimens, provides adequate leprosy prophylaxis. The study intervention is delivered over a period of 3 years.

The study population comprises all residents of South Tarawa. All adults, adolescents and children aged three and above are included. Children aged less than three years are included if they have documented household contact with someone who had TB (in the past 1 year), or leprosy (at any time since they were born). Household contact is defined as being between two people who have regular meals prepared in the same kitchen. Members of the study population are only excluded if they prefer not to participate.

Study inclusion and exclusion criteria:

Inclusion

• Everyone aged ≥3 years

• Children aged <3yrs who have had household contact with someone with TB in the past 12 months, or with someone with leprosy since birth

Exclusion

• Refuse participation

All households are enumerated based on location and demographic data collected during the 2020 census (Kiribati National Statistics Office 2021, unpublished). Study staff visit each residence, collect GPS coordinates, ascertain eligibility in a brief household survey conducted with the household head, and invite eligible participants for screening. During the first clinic visit, study personnel obtain written informed consent from adult participants (≥18 years of age), or parents/legal guardians in those aged <18 years, with verbal assent from children aged 10-18 years. Identifying information is collected at registration, including a photograph and a biometric identifier to aid future re-identification (facial coordinate scan ‘health selfie’, Simprints Technology Limited, Cambridge, UK). Study nurses complete a short TB symptom questionnaire and a brief physical examination for signs and symptoms suggestive of TB disease (visible lymph node mass or gibbus) or leprosy (suggestive skin lesions or altered shape of face, nose, ears, hands or feet).

A tuberculin skin test (TST) is placed using the Mantoux method and sputum collection is attempted in all participants aged ≥10 years; age-appropriate diagnostic specimens may be collected in children <10 years who have symptoms suggestive of TB, but it is not part of the screening procedure. Sputum specimens are tested using Xpert® MTB/RIF Ultra, recently endorsed by WHO as a sensitive front-line diagnostic test26. A digital chest X-ray (CXR) is performed on everyone aged ≥10 years, and children aged <10 years with symptoms suggestive of TB. CXR interpretation is conducted with computer-aided detection (CAD) software certified for use in TB screening (CAD4TB v6, Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands). The use of CAD software for TB screening is recommended by recent WHO guidelines, and good experiences with implementation have been reported in a variety of settings27 28. Screening CXRs for participants aged <15 years will also be interpreted by study medical staff, with the age threshold for CAD interpretation to be re-evaluated as evidence and experience accumulates during the intervention period.

At a second clinic visit two days later, the TST is read and considered positive if induration is ≥10mm, or ≥5mm if the participant has had household contact with a person with infectious TB in the past 12 months. The CXRs of all participants with a CAD score of ≥50 (and a random selection of those with scores <50), M. tuberculosis detected on Xpert® MTB/RIF Ultra or symptoms suggestive of TB will be reviewed by a study doctor. The CAD threshold score will be adjusted if necessary to optimise screening performance in the study population. Patients with bacteriologically confirmed or clinically diagnosed TB disease or leprosy will be referred to the Kiribati NTP or NLP for treatment, with close coordination between study and program clinicians.

Participants who are eligible, have no contraindications and accept TPT, are offered a choice of short-course rifamycin-based regimens according to clinical characteristics, patient preference and availability. Currently used regimens are: 12 weekly doses of isoniazid and rifapentine (3HP), four months of daily rifampicin (4R), or 3 months of daily isoniazid and rifampicin (3RH, preferred for young children due to availability of child-friendly water-dispersible formulations). Dosing is chosen according to recommendations from the WHO and the Kiribati NTP. In participants with a documented history of household contact with someone diagnosed with DR-TB, TPT using six months of daily levofloxacin is considered under expert guidance. New evidence and normative guidance supporting the use of shorter TPT regimens may be released during the study. Consistent with the implementation approach, additional regimens may be offered to participants in collaboration with the Kiribati NTP and with updated ethical approval.