The collaborative framework for the management of tuberculosis and type 2 diabetes syndemic in low- and middle-income countries: a rapid review

The coexisting burden of tuberculosis (TB) and diabetes mellitus type 2 (T2D) has become an important global public health concern [1]. According to the World Health Organization (WHO) global TB report 2023, there were 7.5 million people newly diagnosed and 1.30 million deaths resulting from TB [2]. In 2021, there were 537 million cases and 6.7 million deaths due to diabetes (90–95% T2D) were registered [3]. The synergies between TB infection and T2D have been known for years, though most of the research carried out in developed countries because in the past, non-communicable diseases (NCDs) such as T2D have not been considered of public health relevance in developing countries [4]. This is changing rapidly with T2D being already a major and increasing public health threat in low- and middle-income countries (LMIC) [1]. This increasing trend is driven mainly by demographic and epidemiological transitions that also accelerate the nutritional (lifestyle) transitions, leading to increased rates of obesity and T2D [5]. The increasing numbers of T2D in LMIC coincides with still much prevalent TB, in a situation that can be defined as syndemic. The term syndemic refers to synergistic health problems that affect the health of a population within the context of persistent and economic inequalities [4]. It was developed by a medical anthropologist Merrill Singer in the early 1990s to call attention to the synergistic nature of the health and social problems facing the poor and underserved [6]. Syndemic is used when communities experience co-occurring epidemics that additively increase negative health consequences [7].

According to the most recent data from the World Bank low-income countries represent 9% of the world population while 76% of the world population were classified as middle-income countries [8]. Thus, LMIC host 85% of the world’s population and bear a disproportionate burden of about 95% of TB cases and 75% of people living with T2D [9, 10].

A meta-analysis conducted in 2018 on the prevalence of TB in T2D patients in African and Asian countries found a pooled prevalence of 4.72% (95% CI: 3.62–5.83) [11]. A systematic review conducted in 2019 on the co-existence of T2D and TB in LMIC reported a wide range among the studies reviewed from 1.8% to 45% of TB patients also reporting T2D [12].

Based on earlier published summary effect estimates, T2D increases the risk of active TB by 3.11–fold and latent TB by 1.18–fold [12, 13]. Conversely, TB can constitute a risk factor for T2D temporarily causing impaired glucose tolerance and predisposing patients to T2D [14].

Given the relevance of the issue and the absence of international guidelines on the co-management and control of both TB and T2D, the WHO and the International Union Against Tuberculosis and Lung Disease (The Union) launched in 2011 a policy framework to address the growing TB-T2D syndemic, known as the collaborative framework for care and control of TB and T2D (The Union-WHO Framework) [15, 16]. This framework aims to guide national programmes on the prevention and control of T2D and TB on how to establish a coordinated response to both diseases, and clinicians on integrated TB-T2D care. It is also intended to help stimulate operational research. As more scientific evidence is documented from the countries experience, this framework should be further developed into global policy and guidelines for collaborative activities. The Union-WHO Framework recommends three important intervention strategies[17]., namely, 1) establishing mechanisms of collaboration between TB and T2D control programmes, 2) detection and management of TB in patients with T2D, and 3) detection and management of T2D in TB patients.

The rational for The Union-WHO Framework takes in consideration that in all high TB burden countries there is an established national TB control programme. It also takes as example of feasibility, the best practices of the collaboration between TB and HIV/AIDS programmes during the last decades that has helped avoid unnecessary duplication of service delivery structures by installing for example, one-stop consultations and overall improving coordination of activities in resource-scarce health-care services [15, 17].

A previous scoping review [17] of the 10 years of implementation of The Union-WHO Framework, at global level, demonstrated that although gaps still exist in research aimed at providing evidence of improved techniques for detecting TB-T2D comorbidity, bi-directional screening is feasible and can potentially improve the diagnosis and co-management of individuals with TB and T2D [16].

The purpose of this review is to map the available evidence on the implementation of the collaborative framework and bi-directional TB-T2D health services as an initiative for co-management in patients in LMIC. This review will add to the existing knowledge by mapping the evidence in low-resource settings also facing the consequences of demographic and epidemiological transitions and the coexistence of the syndemic burden of both communicable and NCDs.

The initial search through the electronic databases, yielded a total of 1793 articles. Four hundred and twenty-one (421) articles were excluded due to duplication. Articles were screened by title and abstract and 1307 articles were excluded because they were out of topic. Finally, 65 full text articles assessed for eligibility and 41 excluded because they did not meet the inclusion criteria: 29 studies were exclusively on HIV as co-infection and 12 studies were not conducted in LMIC. Figure 1 shows the PRISMA flow chart demonstrating the screening results from each stage.

This rapid review mapped existing literature on the implementation of The Union-WHO Framework, as well as on the bi-directional interventions of TB and T2D, in LMIC, and provided an overview of the extent of implementation from 2011 to 2022. Our review found evidence of these initiatives in 16 countries, most of them from Africa. We identified that all studies that explicitly mentioned adopting The Union-WHO framework [29‐32]are from the sub-Saharan Africa region. This suggests awareness and gradual adoption of the approach proving that with an adequate reorganisation of available resources it is possible to properly implement collaborative TB and T2D activities in resource-limited settings.

Findings pointed that it is valuable, feasible and effective to implement bi-directional co-management, and this is supported by the high prevalence of TB and T2D co-existence observed in these studies, combined with the availability of a well-structured TB programme [5, 29, 33‐39, 41‐43, 45, 49‐51]. This was congruent with the findings of Harries et al., who found that the implementation of The Union-WHO framework has the potential do stimulate and strengthen the scale-up of NCDs care and prevention programmes, which may help in reducing the global syndemic of T2D and TB.[52] This was also reported in other studies [53, 54]. However, two countries with low burden of TB and T2D did not provide evidence to support the bi-directional screening and recommend that screening should be done on a case-by-case basis [40, 48, 50]. Findings also pointed to the gaps and barriers that should be overcome to ensure a functional and effective integration of services for the co-management of TB-T2D comorbidity [37, 44, 49].

A predominant number of studies on screening for T2D among TB patients and vice versa, and co-management of TB-T2D comorbidity revealed that screening is feasible within routine practices in the healthcare system, for example using directly observed therapy (DOT) centres, resulting in earlier identification of cases and opportunities for better management of comorbidity [33, 34, 41]. This is in contrast with the findings of other studies which concluded that screening should be done on a case-by-case basis [40], especially in countries with a low burden of tuberculosis[48]. This suggests that country specific context matters and although the review intended to map evidence from LMIC, these countries do not have static and homogeneous characteristics[55].

The association between TB and T2D was identified as strong with a cross prevalence in the study groups much higher than that reported in the general population[35, 36, 38, 39, 43, 50, 51, 56], providing strong evidence that TB-T2D co-management should be prioritised. However, to ensure an efficient implementation of bi-directional activities some identified barriers should be overcome [37, 49]. This is aligned with the findings of the study by Foo et al., who found similar barriers [57]. Nevertheless, existing enablers are an important starting point [37, 49]. Other studies also demonstrated aligned facilitators, such as, the existing health systems used for TB that could be adapted to T2D management [57, 58]. Although these studies do not clearly mention that the ongoing TB-T2D bi-directional interventions were adopted from the Union-WHO Framework, its implementation is aligned with the framework’s guidelines. This may suggest that country national policy and guidelines for the co-management of TB and T2D are, indeed, based on The Union-WHO Framework whether clearly stated or not.

This review revealed that it is valuable, feasible and effective to implement bi-directional TB and T2D activities (screening and management) according to the Union-WHO Framework recommendations, especially in countries that face TB-T2D syndemic. Additionally, it was apparent that gaps still exist in research aimed at providing evidence of costs to implement collaborative activities. There is need for TB and T2D services integration that should be done through the well-stablished TB programme. This integration of two vertical programmes, could ensure patient-centeredness, continuum of care and ultimately contribute for health systems strengthening.