1. Introduction

Asbestos, in all its forms, is universally recognized as a carcinogen to humans, causing a spectrum of diseases that includes mesothelioma, lung cancer, laryngeal cancer, ovarian cancer, asbestosis, and non-neoplastic pleural lesions [1]. By December 2022, asbestos had been banned in 69 countries [2], including six Latin American countries, Colombia being one of the countries that recently approved a complete asbestos ban in 2019 [3]. However, despite these bans, asbestos remains legally used in many low- and middle-income countries, which frequently grapple with inadequate health and environmental institutions to effectively address this persistent hazard.

The asbestos industry started operations in Colombia in 1942 when an asbestos-cement facility was established in Sibaté, a city located 25 Km from the capital, Bogotá [4]. Subsequently, additional asbestos cement facilities emerged in Cali and Barranquilla (1944), along with two in Manizales in 1967 and 1982 [4]. Additionally, an asbestos friction products plant commenced operations in Bogotá in 1960, while a chrysotile asbestos mine began operations in 1980 in the municipality of Campamento (Antioquia) [4]. Unfortunately, the available information concerning these facilities remains quite limited, and the current and cumulative number of workers involved in these operations is unknown.

In response to concerns raised by local inhabitants, the Sibaté study was initiated in early 2015. Over time, an international consortium of researchers from Colombia, Italy, and France has contributed to a series of publications that have unveiled several critical findings: 1) [5, 6, 7] the first mesothelioma cluster that has been reported in Colombia; 2) landfilled zones with the presence in specific locations of an underground layer of friable asbestos (see Table 1); 3) mesothelioma patients diagnosed at a very young age, suggesting exposure during childhood or adolescence; and 4) the occurrence of non-occupational exposures in the city, since only one out of 13 certain mesothelioma cases studied in detail worked in the asbestos-cement facility.

When reviewing studies that report a relatively high incidence rate or mortality from mesothelioma in various regions or countries worldwide, common characteristics emerge. Firstly, the majority of these studies documenting an excess number of cases are conducted in high-income countries. Secondly, most of these studies rely on a combination of global, national, and regional vital statistics and health information systems, often incorporating cancer, and, in some cases, mesothelioma registries. In our analysis, we identified studies reporting a relatively high incidence rate or mortality from mesothelioma using cancer registries in Italy (i.e., National Bureau of Statistics – ISS [8]; National Mortality Database – ISS [9], Italian National Institute for Statistics [10, 11], case control study of Casale Monferrato [12], cohort study of Casale Monferrato) [13], Belgium (i.e., WHO Mortality Database (WMD)) [14], The Netherlands (i.e., Dutch Cancer Register) [15], United Kingdom (i.e., Thames Cancer Registry) [16], Germany (i.e., German Federal Statistical Office and WMD) [17], Spain (i.e., National Statistics Institute [18], Spanish Employment Ministry) [19], Denmark (i.e., Danish Cancer Registry) [20], Brazil (i.e., DATASUS Database) [21], United States (i.e., Libby-based Center for Asbestos Related Diseases [22], Public Health Service Hospital in Santa Fe, New Mexico [23], Connecticut Tumor Registry [24], California Cancer Registry [25], New Jersey State Cancer Registry) [26], China (i.e., Da-yao county hospital records [27] and Yuyao People’s Hospital Patients) [28], Peru (i.e., Mortality data from Peru Ministry of Health – MINSA) [29], South Korea (i.e. Korea Central Cancer Registry) [30], and France (Cancer Registry of New Caledonia) [31, 32]. There are also studies about the incidence of mesothelioma in multiple European countries [33], using the WHO/International Agency for Research on Cancer (IARC) Database.

Moreover, several studies employ mesothelioma registries to determine the frequency and distribution of mesothelioma cases in specific countries and regions. Examples include Italy [34, 35, 36, 37, 38, 39, 40, 41], the United Kingdom (i.e., British Mesothelioma Register) [42], and Australia (i.e., Western Australia Mesothelioma Registry) [43, 44, 45, 46, 47]. It is crucial to acknowledge the limited number of mesothelioma registries worldwide. A literature review identified mesothelioma registries in Italy, France, the United Kingdom, Australia, and South Korea [48]. A study reported additional mesothelioma registries in Belgium, Germany, Japan, South Africa, and Turkey [49]. Another article reported mesothelioma registries in different Latin American countries (i.e., Argentina, Brazil, Colombia, Costa Rica, Panamá, México, Peru, Nicaragua, and Venezuela), pooled in a database called MeSO-CLICaP Platform [50]. The MeSO-CLICap database represents a one-time initiative by the Latin American Consortium for Lung Cancer Research (CLICAP), led by a team of dedicated oncology researchers. This database was established to retrospectively document and report on cases of mesothelioma identified within their clinical practice [51]. However, this database is not publicly available [51].

Similar to the protocols applied in the Sibaté study, some studies conducted in Turkey identified mesothelioma cases directly in the field by interviewing the patients or their families, and assessed potential asbestos exposure [52, 53, 54].

This paper outlines the methods employed during the Sibaté study, which aimed to investigate a substantial number of asbestos related diseases (ARD) cases reported by the inhabitants of the municipality, in the absence of reliable health databases usable for assessing the occurrence of any ARD or a mesothelioma registry. The aim of this paper is to provide a practical guide to investigators engaged in bringing to light previously undetected, if not undetectable, localized excesses of ARD whose discovery might open the way to environmental cleanup, health protection, and increased awareness of asbestos burden of diseases in the affected communities.

2. Materials and Methods

The information available in the Colombian official morbidity and mortality database (SISPRO) was not reliable, since it did not identify the ARD cases that local inhabitants were denouncing [5]. Consequently, a different approach was used to investigate the public health situation in Sibaté. Based on this experience, we describe a protocol that can be followed to determine if there is an excess number of ARD in a region where an asbestos-processing facility or a mine currently operates or operated in the past, or where there is a suspicious of an unusual occurrence of ARD without knowledge of any sources of asbestos exposure.

The proposed protocol includes the following steps, and is shown in Figure 1:

1. Understand and fulfill the ethical requirements: Begin by comprehending and adhering to the ethical requirements for conducting research involving human subjects. Determine which are the ethical guidelines, requirements, and laws that apply to your study at both international and local levels. You may need approval from an ethics committee, responsible for reviewing and approving your research protocols and tools, including interviews, focus groups, and informed consent forms. In fact, such approval is often a requirement of scientific journals for publication. This step should precede all other project activities. If your institution lacks an Institutional Review Board (IRB) or equivalent (e.g., an ethics committee) to approve your project, you may need to seek approval from another committee for your study. Several international ethical guidelines can be consulted for this step, including the Belmont Report [55] and the Guiding Principles for Ethical Research of the U.S. National Institutes of Health [56].
2. Review existing sources of information: Examine existing sources of information that could be utilized to identify cases of Asbestos-Related Diseases (ARD), such as cancer registries, death certificates, and health databases, among others. Ensure the obtained information is valid and reliable. Does the morbidity and mortality data align with what you are observing in the field? Do the numbers make sense? Ensure compliance with ethical requirements identified in Step 1, as assessing some of these sources may necessitate prior ethical approval.
3. Identify the cases in the field: When existing sources of information are insufficient for identifying cases, you must directly locate cases within the study area. If feasible, engage in participative communication to coordinate this stage with local authorities. Additionally, try to identify community leaders who can assist in this phase. Identifying cases entails an intensive field search, often conducted through face-to-face structured interviews with members of the target population. Several considerations for this stage include:
   1. Ethical Approval for Research Tools: Note that the research tools you employ, both qualitative and quantitative, may require ethical approval.
   2. Informed Consent: Prior to participating in the study, volunteers must have read, comprehend, and signed informed consent forms.
   3. Design of Interview Questions: Carefully design the questions for the interviews, possibly involving key social actors with a direct interest in the topic. Test the proposed interview model with focus groups as part of the research tool development process, especially considering the potential limited literacy on asbestos risk and ARD among participants. Testing the structured interview and assembling focus groups also necessitates ethical approval and informed consent. While designing interview questions, verify that you gather all the necessary information for the study’s reliability. Provide study participants with contact information through which they can reach the research team if they have questions or wish to provide additional information. Furthermore, inquire whether study participants would be available for future contact by the research team, either for clarification of their responses or for subsequent study phases. For epidemiological estimates required later in the investigation of ARD, the minimum information needed from each patient includes: i – Gender, ii – Age, iii – Current residence, iv – Previous residences, v – Age at the time of disease diagnosis, vi – Diagnostic center, vii – Years of residence at the study location, viii – Identity of the person answering the structured interview (patient or family member), ix – Occupational history, x – Age of death (if applicable), xi – History of potential asbestos exposure events. Additionally, demographic information from other participants that have not been diagnosed with an ARD should also be collected.
   4. Monitor Non-Respondents: Keep a record of the number of non-respondents of the structured interview so that you can calculate the response percentage.
   5. Establish Eligibility Criteria: Define the criteria for eligibility for inclusion in the structured interview and, if necessary, for obtaining a representative sample of eligible persons.
   6. Geographical Information: It is crucial to collect the location information of respondents in the structured interview. If possible, supplement their place of residence with geographical coordinates.
   7. Identify Asbestos Exposure Sources: Ideally during the structured interview, you should attempt to identify potential sources of asbestos exposure for the cases. This includes both occupational and residential history, hobbies and activities that may involve interactions with asbestos, and presence of asbestos containing materials in current and previous residences or in other facilities where the patient spent time.
4. Validate ARD cases: Validate ARD cases identified through structured interviews. When an individual (or a family member) reports an ARD diagnosis, it requires validation. Validation is crucial because there can be confusion in the naming of diseases. For example, in the Sibaté study, we discovered that many people use the term “asbestosis” for diseases associated with asbestos exposure, but the original diagnosis might be mesothelioma or lung cancer. Furthermore, mesothelioma is a rare and challenging disease to diagnose. Therefore, validating self-reported ARD diagnosis reduces study uncertainty. To validate ARD cases, a copy of the medical record, including histopathology report for cancers, is needed. Even if the medical record confirms the reported ARD, it is not sufficient for proper validation. The medical record should be reviewed by an ad hoc panel of physicians following reliable guidelines.
5. Determine Excess ARD cases: Determine if the number of ARD cases exceeds expectations. For validated cases, estimate the age-adjusted incidence rate of the disease(s) of interest [57, 58]. If previous research has not been conducted, we recommend focusing on mesothelioma before studying other ARDs, since mesothelioma is specifically associated with asbestos and is considered a sentinel disease of asbestos exposure [59]. To assess whether there is an excess number of cases, we recommend estimating the age-adjusted incidence rate, since it allows for a straightforward comparison with rates observed in other regions and countries worldwide. For ARD information, a valuable source is the IARC report Cancer Incidence in Five Continents, which is periodically updated. The latest report (i.e., XI) to date was released on March 2021 [60].
6. Determine Asbestos Exposure Sources: Determine potential sources of asbestos exposure in the population. The information collected from the structured interview could assist in this process. This is a critical step because sources leading to asbestos exposure may still be active and may require urgent interventions, including risk communication and management plans. Since the highest asbestos exposures tend to occur in occupational settings, it is important to determine the gender distribution of the workforce at the asbestos-processing facility in the study area. Analyze whether the incidence rates by gender provide additional insights into the situation. If the workforce is predominantly male and you observe high incidence rates in females, you may have important exposure sources outside the asbestos-processing facility, including para-occupational exposures. To standardize exposure classification, the categories proposed in the Italian Mesothelioma National Register [61] are a useful guideline.
7. Communicating Findings: Communicate the study findings with health and environmental authorities and the general public [62, 63, 64]. If during the study you discover situations that might represent an imminent risk to the community, promptly inform local authorities so they can design a risk management strategy. When communicating findings to the public, consider several aspects: 1 – do not to generate panic, 2 – respect individuals and protect the anonymity of patients and their families, 3 – if the media are involved, provide scientific information in plain language to ensure the delivery of accurate messages. Writing a media statement can be very helpful. It is good practice to wait for peer validation of results before disseminating study findings to the public. This reduces the risk of disseminating incorrect or misleading results that could misinform and harm the public. The World Health Organization offers free online courses on risk communication on emergency situations [65].

3. Results

The protocol described above was applied in the Sibaté study in the following way:

4. Discussion

The operation of asbestos-processing facilities or asbestos mines poses an imminent health risk for the workers involved in these activities, their relatives, and for the residents who live in the vicinity [4, 69, 70, 71, 72]. Therefore, it is imperative to establish robust and reliable surveillance systems for both ARD and environmental asbestos contamination. Such systems facilitate early ARD diagnosis and the control and remediation of active asbestos sources. Unfortunately, asbestos is still predominantly used in low- and middle-income countries, which may lack the institutional capacity and technical knowledge to effectively manage the associated risks. Consequently, it is of paramount importance for governments to implement environmental monitoring strategies to identify potential sources or circumstances of asbestos exposure, along with epidemiological surveillance of populations at risk due to their residence location, para-occupational exposure, and/or occupation. The Italian Mesothelioma National Registry is an example of a successful model for surveillance.

In the absence of robust surveillance strategies or reliable health information systems, this article presents a methodology for studying the potential health impacts of asbestos-processing facilities on individuals residing in the facilities’ influence areas. However, this strategy is resource and time-intensive and may not be suitable for large populations. Therefore, the proposed protocol should be considered a non-definitive approach to understanding and addressing health risks in regions where such facilities operate.

An additional approach for validating self-reported ARD cases, currently in progress within the Sibaté study, though not included in this protocol, involves re-analyzing tissue samples preserved in paraffin blocks used for the initial medical diagnosis of ARD cases. Collecting tissue samples can be complex and may not always be feasible, and it also requires ethical approval. When attempted within the framework of the Sibaté study, it was revealed that each medical center had its own protocols and requirements for providing the tissue samples. Additionally, such analysis requires the involvement of a pathologist and incurs additional laboratory costs.

One of the primary limitations of the proposed strategy is the constraint on the number of individuals that can be followed and characterized, considering the potentially vast number of people at risk. A study conducted by members of our research group quantified this challenge in Colombia [4]. For instance, in Sibaté alone, based on the 2018 census, the population living near the asbestos-cement facility ranged from 12 individuals within a 500-meter radius to 932,838 individuals within a 10,000-meter radius [4]. Among those within the 10,000-meter radius, 304,842 people were aged 19 or younger [4]. Nationwide, in Colombia, where six asbestos-processing facilities and an asbestos mine used asbestos until the asbestos ban took effect on January 1st 2021, the 2018 census indicated 13,285 individuals lived within a 500-meter radius of these facilities and the mine, expanding to 6,724,677 individuals living within a 10,000-meter radius [4]. Given these figures, it is important to emphasize that the methodology proposed in this article does not replace the need for surveillance programs and reliable health databases. Such programs should be defined ad hoc in each country or area contemplating the priorities and the balance between costs and benefits, considering the economic costs, technical feasibility, the estimated time needed for their implementation, and the expected benefits in mitigating the health risk over time, among others.

The relatively low number of certain mesothelioma cases identified in Sibaté to date warrants further discussion. Colombia lacks comprehensive information on the history of the asbestos industry, leading to a lack of data on the number and characteristics of workers employed in the asbestos-cement facility in Sibaté. Additionally, active participation from the workers’ union has not been achieved, further limiting the ability to identify workers who may have developed ARD.

While the Sibaté study has primarily focused on mesothelioma thus far, it is essential to recognize the significance of all ARD, each of which has substantial and adverse societal impacts. In the future, the Sibaté study aims to encompass a broader spectrum of ARD.

Despite the concerning findings of the Sibaté study, as of September 2023, neither risk communication nor risk management plans have been implemented for Sibaté.

5. Conclusions

Implementing the protocol described in this article requires collaboration among experts from various disciplines, including epidemiologists, exposure assessors, physicians, engineers, geographers, social scientists (such as anthropologists, sociologists, psychosocial and communication experts), and public health experts, among others. The specific disciplines needed for the study may vary depending on the local health, environmental, social, and economic conditions of the area where the study is conducted. Expertise in asbestos-related issues is also indispensable. In the case of Sibaté, international collaboration and the willingness of experts from Italy and France to contribute to understanding the problem were pivotal to the study’s success. Such collaborations are highly recommended when addressing the complexity of public health problems arising from asbestos use.