https://orcid.org/0009-0002-5001-1309
Figures
Abstract
Background
Migrants from high to low tuberculosis (TB) incidence countries may benefit from screening for latent TB infection (LTBI), but the optimal approaches and effectiveness are not well described.
Methods
Our primary objective was to synthesise evidence for cost-effectiveness, and barriers and facilitators to successful implementation, of LTBI screening programmes for migrants entering high income, low TB burden countries. Evidence was synthesised using rapid review methodologies.
Results
41 studies (including 2 reviews) were included, covering the European region and national programmes. Main settings of LTBI screening were primary care, new arrivals clinics, and schools. The most frequently cited facilitator was structural cohesiveness (integration of health care services, collaboration with community partnerships, and co-ordination of care with social workers or accommodation staff). The most frequently cited barrier was lack of understanding and misconceptions of service users. Economic evaluations consistently demonstrated long term cost-savings for LTBI programmes. Screening migrants from countries of origin of the highest TB burden is more cost-effective but less likely to identify all TB and ultimately eliminate TB compared to screening at a lower TB burden threshold.
Citation: Taylor AE, McDonald E, Henderson H, MacPherson P (2025) The impact of latent tuberculosis screening programmes for migrant populations in high income, low burden countries. PLoS One 20(11): e0335904. https://doi.org/10.1371/journal.pone.0335904
Editor: Lisa Kawatsu, Nagoya City University: Nagoya Shiritsu Daigaku, JAPAN
Received: March 27, 2025; Accepted: October 19, 2025; Published: November 13, 2025
Copyright: © 2025 Taylor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: PM is funded by Wellcome (304666/Z/23/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Tuberculosis (TB) remains a major global public health problem, despite being preventable and treatable. The World Health Organization (WHO) set out it’s End TB Strategy in 2014 to reduce TB incidence by 90%, TB deaths by 95%, and to eliminate catastrophic costs for TB-affected households by 2035 [1]. The TB pre-elimination phase is defined by the WHO as <10/1,000,000 new TB cases per year [2]. In 2023, 60 countries, predominantly in The Americas and European WHO regions, reported TB incidence of <10/100,000, and are thereby well placed to achieve TB elimination [3]. In 2023, there were 1.25 million deaths due to TB, likely returning to the leading cause of death due to an infectious agent worldwide, following the COVID-19 pandemic. There were 10.8 million people notified with TB in 2023, 12% of whom were children and young adolescents [3].
In 2014, 23% of people were estimated to have been exposed to Mycobacterium tuberculosis (MTB) and would have “MTB immunoreactivity” if tested with tuberculin skin tests or interferon gamma release assays [4]. Recent insights into the dynamic nature of transition between TB states emphasises that most TB disease is due to recent infection, with 2% of the global population recently infected with MTB and at greatest risk of disease, and 87% residing in the South-East Asia, Western-Pacific and Africa WHO regions [4–7]. Therefore, people from high TB incidence countries (and especially young children, and people with other risk factors) with immunological evidence of recent MTB infection (hereafter called LTBI), are likely to benefit from LTBI screening and provision of TB preventive therapy (TPT) [8].
International guidance from the WHO and the European Centre for Disease Prevention and Control (ECDC) recommend consideration of systemic screening for certain at-risk groups for LTBI, including people who have migrated from countries with a high TB burden [9,10]. These guidance have been variably implemented in countries with a low incidence of TB. For example, in Scotland, Wales and England, where numbers of people diagnosed with TB increased by 40.8%, 18.7% and 11.0% from 2022 to 2023 respectively, there is national clinical guidance in place recommending the screening of migrants for LTBI from countries with an incidence of >150/100,000 people [11–14]. Whilst an LTBI screening programme has been in place for new entrants to England and Wales since 2015/16, there is no such programme in place in Scotland, where the largest increase across the three nations has been seen [15]. In Scotland, 67.5% of diagnoses were in people born outside of the UK and the most commonly reported risk factor for a TB diagnosis was being a refugee or asylum seeker, with a shift over the last decade from alcohol misuse use as the most frequent risk factor [13].
Implementation of LTBI screening programmes targeted towards migrant populations from high TB incidence countries are an important component of a comprehensive public health approach to achieving TB elimination. LTBI screening programmes for migrant populations require multisectoral interventions, including systematic identification of new migrants from high TB burden countries who may be at risk of TB; screening for LTBI, and supporting TPT initiation and care; and addressing the social determinants of TB. Targeting of screening resources towards this group could also help to address the widening disparities in TB incidence.
The optimal programmatic approaches and cost-effectiveness of LTBI screening programmes have not been well described. Synthesis of existing evidence could support low TB incidence countries such as Scotland to implement effective programmes and accelerate towards elimination of TB. We therefore conducted a rapid literature review to understand how countries with a low TB burden, high income and high net migration are currently approaching screening for LTBI in migrant populations. We synthesised data on implementation approaches, barriers and facilitators to successful programmes, epidemiological impacts, and economic outcomes.
Methods
Rapid review methodologies were used to synthesise available evidence for LTBI screening programmes, in order to facilitate the provision of timely insights to inform policy. Rapid reviews are a relatively novel methodology, used to synthesise evidence in a systematic, resource efficient manner [16]. A search strategy was developed and agreed upon by the research team prior to literature search. Articles were screened at title, abstract and full text stage by a single reviewer (AT), with a second review by PM where requested. A predefined data extraction table was designed and populated in Microsoft Excel, using the key areas of study characteristics, epidemiology, economic evaluations and barriers and facilitators. AT quality assessed individual studies using the appropriate CASP checklist according to the study design [17]. Medline, ProQuest Public Health, Scopus, bibliographic databases were searched by a public health librarian. A grey literature search was conducted, including the Social Policy and Practice database and Government websites of the countries as limited by the above conditions (full list of grey literature sources can be seen in S1 Appendix). References were imported into the reference manager SciWheel for de-duplication and processing.
Inclusion criteria for country of programme were (1) high income countries as defined by the World Bank Group for the 2023/24 fiscal year [18], (2) low TB burden countries (<10/100,000 population) as defined by the World Health Organization 2023 TB burden estimates [19], (3) High net in-migration in 2021 (>10,000 migrants/year) as per the World Bank Group [20] and (4) publication during or after 2000, with evaluation of quantitative and/or qualitative data, collected in part or whole, during or after 2000. Eligible studies evaluated a national or large co-ordinated screening programme, derived from or informing national screening programme guidance, policy or recommendations either in part or whole aimed at migrant populations. Exclusion criteria included smaller ad-hoc studies, studies that were not specific to migrant populations or latent TB, pre-migration screening studies and exclusively port-of-arrival studies. Pre-entry screening programmes were excluded. No limitations were placed on language. The search strategy can be seen in S1 Appendix.
From included studies, we extracted and summarised using narrative synthesis data from three key thematic areas. (1) Logistics, including: data collection period, location, settings, supporting institutions and organisations, community engagement. (2) Implementation of LTBI screening programme: screening target population/s, screening tools, clinical services available, implementation approaches. (3) Evaluation of LTBI screening programme and measures used to assess outcome per report (e.g., identification of LTBI or active TB, treatment initiation and completion, economic evaluations, acceptability).
Ethical committee review or informed consent were not required for this study as data were collected exclusively from published sources.
Results
21 countries met the inclusion criteria; Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Japan, The Netherlands, New Zealand, Norway, Spain, Sweden, Switzerland, United Kingdom of Great Britain and Northern Ireland and the United States of America. Overall, we identified 2118 studies. After deduplication, 1782 unique studies were identified, 194 studies underwent full text screening, and 41 studies met inclusion criteria.
Article characteristics
Characteristics of the 41 included studies are summarised in Table 1. Of the 41 studies, 12 reported data from England; eight from Italy; five from Canada; four from Norway; two each from Australia, Germany and Sweden; and one from Switzerland. There were two European Centre for Disease Prevention and Control (ECDC) review studies that summarised data from the Netherlands, Czechia, Portugal and Spain. Of the 41 studies, 24 highlighted barriers or success factors, 31 investigated epidemiological data, and 11 completed an economic evaluation of the LTBI programme. Eight studies evaluated programmes in a primary care setting (seven of these from England), seven did not specify a setting, six were from reception centres, five in new arrival or specialist migrant clinics, four were schools, three were interview-based studies, three based in TB/infectious disease centres, two in public health services and one each from a nurse-led clinic, homeless migrant clinic and one comparison study of different community settings. Twelve included studies were published in 2019, six in 2018, four in 2020 and 2022, three in 2021, two each in 2010 and 2017, and one each in 2005, 2006, 2009, 2011, 2013, 2014, 2016 and 2023.
Epidemiological analyses
Table 2 gives summary of the larger studies by the countries to meet the inclusion criteria, with all identified studies available in S2 Table.
Primary care-based programmes
Eight studies discussed primary care-based programmes, with seven of these being English studies. England implemented an national LTBI screening programme in 2015/16 which was initially predominantly based in primary care and has since transitioned to being predominantly based in secondary care TB services [38]. Between 2015–22 there was a decreasing positivity rate from 22% to 16% of IGRAs. Of the 45% of people for whom treatment completion data was available, 75% completed treatment [38]. In England, primary care ‘Flag 4’ registrations were used to identify people potentially eligible for LTBI screening. Flag 4 identifies those who have registered with a previous address outside the UK or who have spent more than 3 months outside of the UK. A 2014 study found that 48% of Flag 4 registrations were people from countries of TB burden >150/100,000 and that people from high incidence TB burden countries took 619 days to register with a GP, compared to a median of 181 days [31]. A 2018 study found a large variation (0–88%) in screening uptake between GP surgeries and that 103 people out of 719 with positive IGRAs did not attend for follow up after receiving their positive test result [28].
Reception centres
Six studies published findings from TB screening services based in reception centres. A German study, focusing on asylum-seeking children in reception centres, diagnosed 58/968 (6.0%) children with LTBI and 8/968 (0.8%) with TB disease [41]. Seven of the eight children with TB disease were asymptomatic at the time of diagnosis. This study also found that travel via the Balkan migration route appeared to be a risk factor for TB diagnosis [41]. In Norway, all asylum seekers were identified as eligible for latent TB screening, which was performed via the national reception centre [50,63]. Two Norwegian studies found low levels of specialist review and treatment following positive TSTs, with organisational factors and reluctance of clinicians to treat those without a permanent visa cited as potential explanations [50,63]. Three Italian reception centre screening studies were published, where TB screening services are required for all asymptomatic individuals from high-endemic countries (TB incidence >100/100,000) staying at reception centres for at least six months [45,48,49,62]. Marrone et al. reported country of origin to be a strong predictor of LTBI diagnosis, particularly sub-Saharan Africa [48].
New arrival and specialist migrant clinics
Two Canadian studies described TB screening services delivered in new arrivals clinics [23,26]. Pépin et al. describe the findings of a TB screening programme for refugees, roughly half of whom were from Afghanistan [23]. Of the 3544 refugees seen at the clinic, 441 were diagnosed with LTBI (12.4%) and 374/441 (84.8%) completed treatment. There was a 69.3% compliance with the screening and treatment cascade for all refugees settled in the region, including those who did not present to the clinic. Potential reasons for relatively high compliance rates compared with other TB screening programmes included embedding of the programme in an integrated, family based health care setting, close collaboration with community services and easy access to translators [23]. Three Italian studies described TB screening in specialist migrant clinics [46,47,68]. Of 2,486 asylum seekers screened for TB at the Migrant’s Service in Verona, 28.8% were diagnosed with LTBI [47]. Of the screening population, 91.1% were male and 81.6% were African. The 30.3% of people who started treatment but did not complete it, stopped due to medical conditions or transfer to another centre. The study found similar levels of adherence to screening (83.2–94.3% between asylum seekers of different nationalities, but highly variable treatment completion rates, with 42.3% and 49.1% of migrants from Bangladesh and Pakistan respectively completing treatment, compared to 82.8% and 84.9% of migrants from Ghana and Gambia respectively completing treatment [47]. Bonvicini et al. who enrolled 368 irregular immigrants (those without a valid resident permit and entitlement to a general practitioner) for TB screening in Northern Italy, commented that had they excluded irregular immigrants from countries of a low TB incidence, they would have excluded nearly half of the study population and missed 80% of TB diagnoses [46].
Schools
Four studies conducted TB screening programmes in schools, one in Australia screening children from ‘high risk’ countries of origin, two in Canada screening newly arrived and immigrated school children and a study in Switzerland where children born abroad or moved within the last 12 months from selected countries were screening in a routine school health appointment [21,24,25,30]. In Australia, 846/4736 school children tested using TST had positive results and two were diagnosed with active TB [21]. Brassard et al. reported on a TB screening programme in Montreal where children were tested and the programme cascaded to include families and households of those children diagnosed with LTBI [24]. This study found TST positivity in 542/2524 (21.5%) of children tested and in 211/555 (38.0%) of associates tested, demonstrating the effectiveness of a cascading programme [24]. TST positivity was similar in the second Canadian study, at 777/3401 (22.8) tested school children [25]. In the Swiss study, TB screening was integrated into routine school heath appointments for migrant children from Afghanistan, the African continent, Portugal, Greece, Albania, Western Balkan, Turkey, South and Central America, Russian Commonwealth, and all Asian/Pacific countries, except Australia and New Zealand and 21/1120 (1.9%) of tested children had positive TSTs [30]. Of the 21 children, 14/21 (66.7%) were from the African continent [30].
TB or infectious disease centres
Three studies reported findings from TB screening programmes conducted in dedicated TB or infectious disease centres [36,40,43]. Pareek et al. (2011) evaluated 1229 screened foreign born new entrants to the UK, aged ≤35 years referred to three regional centres in the UK and found a 20% IGRA positivity rate and that 92% of LTBI was detected at screening at an incidence level of ≥150/100,000 including India [40]. Williams et al. described a screening programme for unaccompanied asylum-seeking children newly entered to the UK and seen in two paediatric infectious diseases clinics, who were also screened for other infectious diseases [36]. Most attendees were male (88%). TB tests were positive in 55/238 (23.1%) and 3/238 (1.3%) were diagnosed with active TB. There was a high rate of co-infections found, at 10/201 (5.0%) diagnosed with hepatitis B and 27/164 (16.5) positive tests for schistosomiasis [36]. Russo et al. reported on an Italian programme screening asylum seeker and undocumented migrants in the Brescia area of Italy using either TST only or two step TST followed by a confirmatory IGRA [43]. In total, 170/595 (28.6%) of migrants were diagnosed with LTBI, with the study finding improved screening completion in the IGRA only sub-group but comparable levels of treatment initiation between IGRA only and the two step screening [43].
Other settings
In the Netherlands, TB screening for migrants has been conducted by Public Health Services [55–57]. Spruijt et al. conducted a study across five centres for immigrants not applying for asylum from non-EU countries with a TB incidence of >50/100,000 population intending to stay for more than six months [55]. Of 566 people who received tests, 101 (17.8%) were diagnosed with LTBI and three (0.5%) with active TB. Treatment initiation levels were variable between the five centres (29–86%), impacted by the practices of clinicians, where the highest proportion was achieved by the centre which tested only those they would intend to provide treatment to. Potential reasons for low treatment initiation were identified as clinician concerns, including the public health benefit of treating people who may return to high incidence countries or move on from The Netherlands [55]. In Milan, Italy, a screening programme was provided for all foreign-born individuals registering for accommodation services with no restrictions placed according to TB incidence in country of origin [44]. Of 11,585 people who applied for accommodation and were screened for TB in Milan between 2009 and 2017, 9,486 (81.2%) were migrants. 2666/9486 (28.1%) had positive TSTs and received a confirmatory test using IGRA, 1339 (50.2%) of which were positive. The study presented the top ten countries of origins of migrants according to IGRA positivity rates, and three of the countries with the highest rates had TB incidence of ≤100/100,000; Eritrea, Morocco and Romania. The authors suggested that screening based on country of origin incidence is overly restrictive and vulnerable groups or country-specific factors should be considered in screening and treatment guidance [44].
Economic analyses
The findings of all ten studies performing cost analyses are summarised in Table 3. Evaluations ranged from cost and estimated saving calculations to in-depth modelling studies. All studies concluded that latent TB screening for migrants was cost-effective within certain eligibility criteria specific to each study.
Pareek et al. built a decision analysis model based on screening immigrants 35 years and younger in three centres in the UK using IGRA [40]. The study found the most cost-effective screening options were adults aged 16–35 years from a country of origin with a TB burden of >250/100,000 population and >150/100,000 population with incremental cost effectiveness ratios (ICERs) of £17,956 and £20,819 respectively. However, the former cutoff for screening would identify 29% of LTBI in the migrant population whilst the latter would identify 92%, therefore recommending the lower cutoff. The same study found screening in <16 years at a threshold of TB burden <40/100,000 population to be cost effective and made the recommendation to screen all immigrant children regardless of country of origin incidence due to small population numbers and importance of prioritising children for tuberculosis control [40].
Both Haukaas et al. (Norway) and Shedrawy et al. (Sweden) used Markov modelling [51,53]. The Norwegian study compared four screening scenarios for migrants from countries of TB burden ≥40/100,000, < 35 years and planning on staying in Norway > 2 years [51]. The study found that screening migrants using IGRA was cost effective and highlighted that the biggest cost in a TB programme comes from screening and treating TB disease, not LTBI [51]. The 2021 Swedish study calculated ICERs in terms of societal cost per quality-adjusted life year and found that screening aged 13–19 years was most cost effective, whilst screening above 34 years was not, mainly due to treatment ineligibility [53]. An ECDC report evaluated cost effectiveness of LTBI screening for migrants of countries of TB burden >50/100,000 population in four European countries and found that two step TST was most cost effective from a healthcare perspective, whilst performing a single test was most cost effective from a societal perspective [59]. Russo et al., Italy, noted that whilst there was a cheaper initial cost with TST, the single visit required with the IGRA had an operational advantage and people tested using this method were more likely to complete the screening cascade [43].
Studies in Australia and Canada conducted in 2019 and 2006 respectively found school-based screening programmes to be cost effective through facilitating estimated savings over the cost of the programmes [21,24]. The Canadian study by Brassard et al. screened associated adults of children with positive TSTs which facilitated 26.2% of the net cost savings [24].
Barriers and enablers
The most cited success factors were related to structural cohesiveness: strong co-ordination and integration of health care services (including ‘one-stop-shop’ approaches), collaboration with community partnerships, co-ordination of care with social workers or accommodation staff, and cohesive and streamlined services. Other success factors included delivering services in community settings, taking a whole family-and-friends approach to screening, access to interpreters, ensuring appointment convenience and providing information (including through methods such as leaflets or counselling).
The commonly cited barriers to successful programme delivery were lack of understanding of latent TB and misconceptions, service fragmentation and resource capacity. Service barriers included lack of communication between organisations, data-gaps or sub-optimal data sharing between organisations and treatment or screening delays. Divergence of practice through lack of knowledge of frontline staff, lack of clear treatment guidelines following screening and clinician hesitancy to treat were also cited. Other pertinent barriers include low/no/delayed registration with primary care, temporary nature of accommodation. S3 Table details the frequency with which specific facilitators and barriers were mentioned by the included studies.
Discussion
Achieving the WHO end TB strategy target of reducing TB incidence by 95% by 2035 requires countries with a low TB burden to adopt effective approaches for both active and latent TB infection [1]. Our rapid review synthesised evidence on the effectiveness, cost effectiveness and implementation challenges of latent TB screening programmes for migrants in high-income, low burden countries. The evidence consistently shows that such programmes can be implemented effectively and deliver long term health and economic benefits, though persistent barriers to implementing programs in these population groups remain.
Successful LTBI screening programme were characterised by strong integration of healthcare, community and social services. These factors were important in improving screening uptake and continued participation in the treatment cascade. In contrast, service fragmentation, poor communication between organisations and data sharing limitations were commonly cited barriers. With some migrant populations, such as asylum seekers and refugees, being highly transient, it is vital that there are not missed opportunities due to poor collaboration between services. Stigma among migrants and misconceptions around TB also hindered engagement. Designing services that incorporate community partnerships, offer interpretation support and provide multiple entry points for screening (e.g., primary care, reception centres, community clinics), appear central to improving programme reach and adherence, particularly in the most vulnerable migrant populations.
Economic evaluations consistently demonstrated long-term cost savings across diverse settings, including schools, integrated specialist migrant clinics, local and national programmes. Cost-effectiveness varied according to eligibility and design, emphasising the importance of implementing new programmes with context-specific features and a good baseline knowledge of the populations likely to be targeted and the specific challenges faced. While targeting migrants from the highest TB burden counties was the most cost effective strategy, this approach missed a significant proportion of people with latent TB. Several studies showed that expanding eligibility to include lower-burden countries can remain cost effective while enhancing overall impact.
In recent years, increases in TB mortality have been seen in both high and low burden countries, and 2018 United Nations (UN) reduction targets were not achieved [69,70]. England, Wales, Scotland, The United States of America and Canada have all seen rises in TB incidence [12–14,71,72]. Our findings align with international guidance from the UN which emphasise the importance of national TB strategies with multi-sectoral and integrated, community-based approaches [73]. International guidance regarding latent TB screening is variably implemented. Where guidance is in place, actual programme existence and design are even more variable.
Low burden countries must continue to strength domestic efforts while contributing to global TB elimination through collaborative effort, international alignment and outcome sharing.
Incorporation of recent advancements in LTBI screening and management have the potential to enhance screening programme effectiveness. Shorter treatment regimens, such as three months of rifampicin and isoniazid (3HR) improve adherence compared to traditional six or nine month regimens [74,75]. New Mycobacterium tuberculosis antigen-based skin tests (TBST) which appear to provide comparable specificity and sensitivity to IGRA testing, while retaining the operational simplicity of TST, though current evidence is limited [76]. The implementation of TBST in settings currently using TST or TST followed by confirmatory IGRAs has the potential to reduce false positives and increase cost effectiveness [76].
This study makes several key recommendations for low TB burden, high income countries with high net migration. Investment in latent TB screening programmes by high-income countries with a low TB burden should be prioritised as a core component of TB elimination strategies. Programmes should use flexible, multi-setting screening models to minimise missed opportunities.
There should be strong integration between health services and community organisations to mitigate against the intersecting social and structural barriers faced by migrants. Programmes should be tailored to the specific needs of their vulnerable populations to support diagnosis, treatment and integrated care of these population sub-groups. Shorter treatment regimens and emerging diagnostic tools should be incorporated to improve detection efficiency and treatment adherence.
This study is strengthened by the inclusion of quantitative and qualitative evidence from a range of local, national and international studies globally. However, a limitation of this review is the predominance of studies emerging from select countries; twelve publishing data from England, eight from Italy and five from Canada. 21 countries met our eligibility criteria, but data collated is from a total of nine countries, plus two European reviews. Whilst in some cases, the lack of data is due to no screening programme being present, countries including France, Belgium and Spain have guidance in place regarding TB screening for migrants but no data for inclusion in this review was found. A rapid review methodology may have missed some studies which would have been included a systematic review. The evidence evaluated in this study is regarding high-income, low TB burden, high net migration countries. However, circumstances of individual countries will vary, including the demographics and movement pattern of migrants. When developing a TB screening programme, these individual circumstances should be considered. Widely recognised TB incidence thresholds (>150 per 100,000) for prioritising migrant screening programmes were used in this study. With the need for accelerated efforts to achieve TB elimination, the use of reduced incidence thresholds should be considered, such as the > 100 per 100,000 population for cut off for high incidence laid out in the 2023 TB elimination framework proposed by Migliori et al. [77]. Whilst this study is focused on strategies for LTBI detection in low-burden, high income countries, LTBI screening and management is an important component of TB programmes in countries of moderate and high TB incidence.
Latent TB screening programmes for migrants in high-income, low TB burden countries are critical in striving for TB elimination, and reversing the recent increases in TB incidence seen in some nations. Their success depends on cross-sectoral coordination, community integration, and flexible models tailored to vulnerable populations. Building and strengthening these programmes represent an important step in improving the unequitable health outcomes for migrants and striving for TB elimination.
Supporting information
S2 Table. Summary of literature evaluating epidemiology of migrants eligible for or screened in a latent TB screening programmes.
https://doi.org/10.1371/journal.pone.0335904.s002
(DOCX)
S3 Table. Summary of identified barriers and facilitators.
https://doi.org/10.1371/journal.pone.0335904.s003
(DOCX)
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