Introduction

Tuberculosis preventive treatment is a cornerstone of the pathway to tuberculosis elimination [1]. The 2023 United Nations High-Level Meeting on the fight against tuberculosis committed to providing 45 million courses of tuberculosis preventive treatment until 2027 [2]. This is an ambitious target, as the world has not yet achieved the goal set by the United Nations High-Level Meeting, held in 2018 [3], to provide 30 million courses of tuberculosis preventive treatment. The least progress was among contacts of people with pulmonary tuberculosis, especially those over 5 years of age [4].

Some advancements have been made in tests for tuberculosis infection in the past decade, and shorter and safer tuberculosis preventive treatment regimens are now available [4]. However, several obstacles remain to achieving the United Nations High-Level Meeting goals. These obstacles include the loss of tuberculosis infection contacts at various steps of the cascade of care [5], often due to factors such as client and healthcare worker beliefs [6–8], need for testing, and stockouts of Purified Protein Derivative [9], among others.

The Brazilian National Tuberculosis Program has recommended, among other indications, treating tuberculosis contacts of all ages since 2010. With a few specific exceptions, contacts undergo a tuberculin skin testing (TST) and if positive (≥5 mm), they undergo chest radiography (CXR). interferon-gamma release assays (IGRA) are available for specific populations, such as children (2–10 years old), people living with HIV or using immunosuppressive therapy and transplant candidates. If there are no radiological signs of tuberculosis, tuberculosis preventive treatment is prescribed. Currently, the first-choice regimen is 3HP (12 weekly doses of rifapentine and isoniazid) for those between 10 and 50 years of age, and 3HR (3 months of daily isoniazid and rifampicin) for those under 10. For those over 50 years of age or with underlying liver disease, 4R (4 months of rifampicin) is the recommended regimen. All tests and treatments are free of charge [10,11].

In 2023, Brazil reported 80,012 new cases of tuberculosis, of which 70,273 were pulmonary. According to the country’s demographics, there are 2.7 inhabitants per household on average. This translates to an average of 1.7 household (resident) contacts. We would expect at least 119,464 contacts initiating evaluation for tuberculosis and tuberculosis infection, and with an expected 50%−60% eligibility for tuberculosis preventive treatment, at least 60,000 individuals should start tuberculosis preventive treatment yearly. Instead, in 2023, 20,365 contacts initiated tuberculosis preventive treatment in the country [10–12]. The main losses in the cascade of care still occur during testing for tuberculosis infection: over 50% of the identified contacts do not complete initial evaluation with a tuberculosis infection test [13]. Initial training in the ExpandTPT program resulted in a substantial increase in the identification of contacts, but not in the proportion of contacts tested. This could be due to contacts not presenting for testing or healthcare workers not offering the necessary tests.

Thus, despite the recommendations, tuberculosis preventive treatment prescription remains slow in the country. In close partnership with the Brazilian National Tuberculosis Program, the Brazilian Tuberculosis Research Network (www.redetb.org.br), in collaboration with the McGill International Tuberculosis Centre, conducted the ExpandTPT project [14] to scale up tuberculosis preventive treatment in five high tuberculosis-burden cities. We conducted a baseline needs assessment to scale up tuberculosis infection diagnosis and tuberculosis preventive treatment of public primary care units with the highest monthly numbers of new tuberculosis diagnosed in these cities.

Materials and methods

Results and discussion

Two hundred and eighty-five clinics fulfilled the criteria and were included in the study, of which 168 were Family Health Clinics and 117 were traditional clinics.

Table 1 summarizes the needs assessment findings. Most clinics 221/283 (78%, 95%CI: 73%−82%) did not offer TST on-site; they referred contacts to other clinics. Of the 62 clinic that offered TST, only three offered it daily. Most 52/62 (84%, 95%CI: 74%−93%) offered the test from once to three times weekly. Only one of the 62 clinics offered TST on demand, i.e., without need to schedule. Other findings related to TST were the low number of health care workers qualified to read TST induration in the unit 80/285 (28%, 95%CI: 22%−33%), and the large number of units without a dedicated fridge to store PPD 98/28 (35%, 95%CI: 29%−40%). Tuberculosis blood test IGRA is generally not collected onsite 151/156 (97%, 95%CI: 94%−99%), contacts are referenced to a laboratory where the test is available. The mean distance between the referenced laboratory and clinic is 6.7 km (95%CI: 5%−7%), the mean turnaround time for IGRA results is 11.7 days (95%CI: 9%−13%).

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Table 1. Needs assessment for scaling up tuberculosis preventive treatment in 285 primary care clinics in 5 high burden cities in Brazil (n = number of clinics assessed)^a.

https://doi.org/10.1371/journal.pone.0326428.t001

With regards to tuberculosis exclusion, most clinics 249/285 (87%, 95%CI: 83%91%) do not have radiologic equipment onsite. Clients are referred to other primary or secondary clinics or use private radiologic services (paid by the government).

Our findings in the current study suggest that at least part of this initial loss in household contact assessment can be attributed to health services limitations. Clinics do not offer TST, a simple and cost-effective test that could be available in all primary care clinics [18] or perhaps in an area where TB was very decentralized or had fewer cases, at least be offered closer to home. Another potential solution for units with small number of TB diagnosis would be the procurement of PPD vials with one or at most five doses. The scarcity of personnel considered qualified to perform TST is partially a consequence of the stringent criteria that has been used in the last decades to certify healthcare workers in Brazil: they needed to read at least 100 indurations with an 80% concordance with the trainer [19]. However, based on data from the ExpandTPT project and other evidence, these training recommendations have recently been updated, with the aim of expanding the qualification of professionals throughout the country [20].

There was heterogeneity in the number of clinics offering TST across the cities. In Rio de Janeiro, we found a greater number of professionals and clinics offering the test. This scenario may be explained by the conduct of multiple research projects on latent tuberculosis infection in the city with the intensification of local training, but the test still needs to be expanded.

In addition, the need for a dedicated fridge is a bottleneck in some small clinics in the rural areas. The National Immunization Program recommendation that prohibits the storage of PPD with vaccines is unjustified [19]. Finally, recurrent stockouts of PPD jeopardize training and implementation of more widespread testing in the country [9,21].

Based on these findings, the ExpandTPT project, in partnership with the Brazilian MoH, is offering training on the National Guidelines and increasing the TST network to a wide range of clinics by training more healthcare workers. In our initial assessment of the cascade of care in these cities, exclusion of tuberculosis with chest X-rays was not a substantial barrier: of those with a positive tuberculosis infection test, 80% underwent a chest X-ray, but the expansion of the TST network may have an impact on the availability of chest X-rays for all eligible contacts.

The World Health Organization has recommended offering tuberculosis preventive treatment without testing in countries where tests are not available. However, a recent individual patient metanalysis has shown that tuberculosis preventive treatment is beneficial for those who have a positive test, both in high-income low-tuberculosis burden and low-middle income high-burden countries [22]. Brazil has a structured public health system, and national recommendations guide testing, through the tuberculin skin test or IGRA, to direct preventive tuberculosis treatment to those who present positive results and are at greater risk of illness [10,11].

Our study has limitations. Self-reported data by clinic staff may potentially generate bias. Thus, true data may be still worse. Another limitation is the absence of health system users’ perspective that could influence adherence to testing and tuberculosis preventive treatment uptake.

Conclusions

In conclusion, the primary care network was not ready, at the time of this evaluation, to scale up testing for tuberculosis infection and thus offering tuberculosis preventive treatment. Softening of training, availability of PPD or the newer tuberculosis-specific skin tests approved by the World Health Organization, and a widespread cold chain are necessary to scale up tuberculosis preventive treatment in the country.

Supporting information