Examining Tuberculosis from a Syndemic Perspective

March 24, 2023 | Amelia Poulin-Obregon

March 24 is World Tuberculosis (TB) Day, marking Dr. Robert Koch’s discovery of the bacteria responsible for causing the disease in 1882. At that time, TB caused nearly one in seven deaths in the United States and Europe. Fast forward to present day when significant progress has been made in TB prevention, detection, and treatment. However, there is still a way to go towards achieving TB elimination.

In 2021, TB was the second most deadly infectious disease globally, surpassed only by COVID-19. TB incidence in the United States rebounded in 2021, reversing a trend of steady decreases in the five years prior. Additionally, the number of TB-related deaths in 2020, the most recent year data is available, is at its highest since 2006. While the exact reason for the increased incidence is not clear, it may be due, in part, to the pandemic making people less likely to seek healthcare and a reduced capacity of public health infrastructure, leading to delayed diagnoses.

Efforts to reduce TB are complicated by synergistic disease interactions and societal circumstances that may exacerbate the burden of disease—what is often called a syndemic. While many public health funding mechanisms provide resources and grant objectives by disease area, it’s important to keep in mind that the factors that may put someone at increased risk for TB infection or disease may also make them more susceptible to an array of other health issues. A holistic approach may be more efficient in equitably improving health outcomes among all intersecting disease areas.

Interactions Between TB and Other Disease Areas

COVID-19

The COVID-19 pandemic presented substantial challenges towards controlling the spread of TB, in part, because the crisis forced state health agencies to reallocate resources away from core activities to focus on preventing COVID-19 infection and severe disease. CDC estimates that COVID-19 had an impact on staffing for nearly three in four TB programs; more than 50% of TB programs also reported that COVID-19 impacted diagnosis and treatment of persons with TB.

Further, CDC estimates 41% of adults delayed or avoided medical care due to factors such as stay-at-home orders and closure of healthcare centers, resulting in missed opportunities for TB testing and diagnosis.

From a biological perspective, research has shown that a TB/COVID-19 co-infection may cause more severe disease for both, as well as the possibility of reactivated latent TB after COVID-19 infection. Other implications from co-infection include the potential for missed or misdiagnosis of TB due to similarities in symptoms of COVID-19, and the potential for drug-drug interactions, such as antivirals and corticosteroids with rifampicin.

HIV

Globally, people living with HIV (PLWH) are 18 times more likely to develop TB disease, and TB is a common opportunistic infection of HIV. Because of this strong association, CDC recommends HIV screening for all TB patients, including for those even suspected of having TB. This association can be explained by immunologic interactions in which TB may increase potential for HIV infection, replication, and immune evasion. Further, PLWH often experience testing challenges, including false negative TB test results. These immunologic interactions make it critical to address TB prevention, detection, and treatment in efforts to end the HIV epidemic.

Additionally, immunosuppression caused by HIV has been cited as the most important reason for high TB incidence among people who inject drugs (PWID) and, among PLWH, PWID are at greater risk for TB as compared to other risk groups. An equitable approach to improve TB outcomes should include focused efforts to reach people living with HIV who inject drugs.

Mental Illness

Depression, schizophrenia, and other mental illnesses are associated with increased TB incidence, which is due to a variety of factors. For example, when compared to the general population, people living with mental illness have reduced medication adherence prolonging the infectious period, seek healthcare less often, and have greater distrust of healthcare systems, leading to delayed diagnoses. An integrated approach to mental health and TB is a promising practice, as an improved mental health status has been shown to lead to greater TB treatment compliance.

Substance Use Disorder

Substance use is influenced by a variety of socioeconomic factors, which any effective public health intervention must address. People who use drugs (PWUD) are widely reported to be at greater risk for TB infection and disease; they have also been shown to be more contagious, remain contagious longer, and be more likely to be involved in a localized cluster of cases.

PWUD have also been shown to avoid seeking care because of stigma, or the possibility that they may be hospitalized and experience narcotic withdrawal. Specifically, PWID are shown to experience greater challenges completing medical evaluations, adhering to TB treatment, and presenting for treatment after developing symptoms. These factors may increase transmission rates and lead to severe disease.

Research has shown that, while education and counseling are generally ineffective for compliance in targeted testing, monetary incentives have resulted in improved compliance. Directly observed therapy for PWUD is cost-effective even when incentives are offered.

Contextualizing Social Determinants of Health as TB Risk Factors

Native Hawaiians and Other Pacific Islanders

The rate of TB among Native Hawaiians and other Pacific Islanders is 40 times that of non-Hispanic whites. People who are U.S.-born Native Hawaiian and other Pacific Islander have the highest incidence of TB. A major factor in this disparity is the social and economic conditions that this group faces. Native Hawaiians and other Pacific Islanders have lower educational attainment and health insurance coverage as compared to non-Hispanic whites. Further, Native Hawaiians are more likely to live below the poverty level, experience unemployment, and experience imprisonment.

Despite these challenges, health departments have made great strides in TB control. For example, the Hawaii Department of Health (HDOH) implements risk assessment and screening for school children, college students, food handlers, immigrants, annual screening for healthcare workers, and people living in state-licensed long term care facilities. HDOH has also updated measures to the Hawaii Administrative Rules to reflect best practices, including using a TB Risk Assessment Screening Questionnaire, a new State TB Clearance Form, and blood tests to identify TB infection.

People Experiencing Homelessness

People experiencing homelessness are at increased risk of TB infection because they are more likely to experience substance use, HIV infection, and poor infection prevention and control measures in often crowded shelter environments. Further, people experiencing homelessness often do not have adequate access to medical care, making TB diagnosis difficult. People experiencing homelessness were found to have a tenfold increase in TB incidence when compared to the general population, as well as be less likely to complete treatment and more likely to be a part of a cluster. Focused testing of people experiencing homelessness has been shown to be effective in diagnosing latent TB, and in connecting these people to care and treatment.

Conclusion

These are just a few examples of the syndemics that can affect TB outcomes. Considering recent trends, the disproportionate impact of TB on certain populations, and interactions with other disease areas—it is clear that public health must take a holistic approach to addressing TB. Approaching TB from a syndemic perspective allows health agencies to better address root causes, implement efforts further upstream, and increase the chances that a person will obtain the services they need to be the healthiest they can be. Further, not only may a syndemic perspective be beneficial, but it may also be necessary to address immunologic interactions between disease areas, and end syndemic epidemics.

Health agencies can partner with community-based organizations, associations and other trusted messengers to reach people at most risk for TB. Health agencies can also work to educate providers on risk factors for latent TB, the latest treatment regimens, and other topics to improve TB outcomes. Overall, while syndemic diseases can be quite complex, implementing evidence-based interventions holistically provides critical movement towards ending these epidemics.