Cy-Tb for Detecting Mycobacterium Tuberculosis Infection in Indonesian Population

Tuberculosis (TB), a preventable and treatable disease, continues to be a significant global health problem. In 2022, it was the second leading cause of death from a single infectious agent, claiming more lives than HIV/AIDS. With over 10 million people contracting TB annually, urgent action is necessary to achieve the UN and WHO's goal of eliminating TB by 2030.

The reported global number of people newly diagnosed with TB was 7.5 million in 2022. This is the highest number since WHO began global TB monitoring in 1995, above the pre-COVID baseline (and previous historical peak) of 7.1 million in 2019, and up from 5.8 million in 2020 and 6.4 million in 2021. The number in 2022 probably includes a sizeable backlog of people who developed TB in previous years, but whose diagnosis and treatment was delayed by COVID-related disruptions that affected access to and provision of health services. India, Indonesia, and Phillipines, which collectively accounted for a large share (more than 60%) of the g lobal reductions in the number of people newly diagnosed with TB in 2020 and 2021, all recovered to above 2019 levels in 2022. According to the Global TB Report published by WHO in 2023, Indonesia is in second place after India with 1,060,000 cases and 134,000 deaths. There are around 15 people who die from TB every hour in Indonesia.

TB screening, also referred to as active TB case finding, aims to facilitate the early detection of TB disease, allowing for timely diagnosis and initiation of appropriate treatment. This approach minimizes delays in care, improves treatment outcomes, reduces long-term health consequences, and alleviates the social and economic burden experienced by patients and their families. In addition, early identification and treatment of individuals with active TB reduce the duration of infectiousness, thereby limiting transmission within households, workplaces, schools, and other community settings. Consequently, TB screening contributes to reducing the incidence of TB infection as well as the overall incidence and prevalence of TB disease.

Passive detection of TB through healthcare facility attendance alone is inadequate to identify all individuals with TB disease. Ongoing case-detection gaps, particularly in vulnerable groups, along with diagnostic delays and continued community transmission, emphasize the need for more active TB case-finding strategies. Systematic screening for TB disease among populations at high risk is a core element of the first pillar of the WHO End TB Strategy, aiming to promote the early identification and diagnosis of all individuals with TB.

This study aims to compare the Cy-Tb test with the IGRA (blood test) to detect TB infection in individuals who are close contacts and household contacts of patients with TB. The study also aims to evaluate the safety of the Cy-Tb test, the costs and benefits of its use, and participants' opinions regarding the Cy-Tb test compared with the IGRA.

This study is conducted by the Department of Child Health, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo General Hospital, Jakarta, and the Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia/Persahabatan General Hospital, Jakarta, with support from PT Bio Farma as the study sponsor.

No informado en este registro.

Diagnostic Test: Cy-Tb test · Diagnostic Test: IGRA test

Participants will undergo a small Cy-Tb injection into the skin of the arm. Participants and their parents/guardians will receive a card to record any local symptoms, such as redness or itching, following the injection.

A small amount of blood will be collected from the participant's arm for IGRA testing.

Plazo: 48-72 hours

The induration should be measured 48-72 hours after the injection. Measure the diameter of the induration transversely to the long axis of the forearm with a caliper. Normally the induration and erythema will decrease after 4 days and disappear within 28 days after the injection. An induration of ≥ 5 mm in Cy-Tb is considered as a positive result, which indicates infection with Mycobacterium tuberculosis. The induration can be seen as a raised area with clearly defined margin at and around the injection site. Although erythema can accompany the induration, only the induration should be measured. The main trial objectives were to compare the positive coincidence rate of Cy-Tb to IGRA test in identifying TB infection.

Plazo: 48-72 hours

The proportion of participants with a positive Cy-Tb test result (induration ≥5 mm) compared with the IGRA test result in identifying Mycobacterium tuberculosis infection. The Cy-Tb induration will be measured transversely to the long axis of the forearm using a caliper. Only induration will be measured, excluding erythema.

Plazo: 28 days

The number and proportion of participants experiencing adverse events following Cy-Tb administration within 28 days after injection. Adverse events will be monitored and recorded throughout the 28-day follow-up period, including the occurrence, severity, duration, and relationship to Cy-Tb administration, where applicable.

Plazo: 28 days

The incremental cost-effectiveness ratio (ICER) will be calculated by comparing the difference in costs between Cy-Tb and IGRA with the difference in their effectiveness in identifying Mycobacterium tuberculosis infection. The ICER represents the additional cost required to achieve one additional unit of effectiveness when using Cy-Tb compared with IGRA.

Plazo: 1 month

The proportion of participants with concordant results between the Cy-Tb test and IGRA test in identifying Mycobacterium tuberculosis infection. Agreement will be assessed by comparing the positive and negative results of both tests. The agreement rate will be calculated as the number of participants with concordant test results divided by the total number of participants tested with both methods, expressed as a percentage.

Plazo: 28 days

The incidence and proportion of participants experiencing adverse events following Cy-Tb administration. Adverse events will be recorded, including their type, frequency, severity, duration, and relationship to Cy-Tb administration, where applicable.

Plazo: 30 minutes

The number and proportion of participants experiencing immediate adverse events within 30 minutes after Cy-Tb intradermal injection. Participants will be monitored for any immediate adverse events, including local or systemic reactions, during the 30-minute observation period.

Plazo: 28 days

The number and proportion of participants experiencing serious adverse events (SAEs) within 28 days after Cy-Tb administration. Serious adverse events will be assessed based on their seriousness, including events resulting in death, life-threatening conditions, hospitalization or prolongation of existing hospitalization, persistent or significant disability, or congenital anomalies. The relationship between the serious adverse events and Cy-Tb administration will also be assessed.

Plazo: 28 days

The acceptability of the Cy-Tb test among tuberculosis (TB) close contacts and household contacts will be assessed based on participants' willingness to undergo the test, completion of the test procedure, and willingness to undergo the test again if needed. Acceptability will be evaluated using participant responses collected during the study.

Cy-Tb for Detecting Mycobacterium Tuberculosis Infection in Indonesian Population