With No Annual HCW Screening, Treatment of Latent TB Imperative
‘What is the point of identifying latent TB if you don’t treat it?’
By Gary Evans, Medical Writer
As employee health professionals are aware, the CDC dropped its labor-intensive recommendation for annual routine screening of healthcare workers for tuberculosis (TB) in 2019.1
“[TB] case rates in healthcare personnel in the U.S. had fallen to the point that routine annual screening, which was consuming massive amounts of effort and personnel expense for medical center occupational health programs and practices, was really no longer justified,” said Amy Behrman, MD, occupational medicine director at the University of Pennsylvania.
However, there are multiple TB issues to contend with for occupational health departments. These include post-hire pre-placement testing, treating latent TB that could activate later in life, identifying and following up on worker exposures, and the threat of multidrug-resistant strains. Not to mention the COVID-19 pandemic, which is likely the cause of an increase in reported TB cases in the United States and globally.
“During 2022, 8,300 TB cases were reported in the United States, compared with 7,874 during 2021,” the CDC reported.2 In 2021, 10.6 million people worldwide developed active TB — an increase of 4.5% from 2020 — and 1.6 million died, according to the World Health Organization (WHO).3
“We have had six or seven significant TB exposures after active tuberculosis admissions within the last 12 months,” Behrman said at a recent webinar presented by the Association of Occupational Health Professionals in Healthcare (AOHP). “I think we’re going to see this aftermath of COVID-19 and its disruption of countries’ healthcare systems and TB surveillance. We’re not going to see it in gigantic numbers, but I suspect this will remain an active issue. Post-exposure screening remains a no-brainer, but it does seem like it will be a priority for all of us going forward. I have a feeling [the U.S. will see] the rise in active TB cases that is clearly occurring globally.”
Behrman generally defined a healthcare worker TB exposure as wearing neither an N95 respirator nor a powered air purifying respirator while caring for a patient with active TB. This would almost certainly qualify as an exposure, but there is no hard and fast rule in this area because many variables come into play.
For example, there are patient and environmental issues. Patients are a higher risk of transmission if they return high concentrations of acid-fast bacillus on sputum smear and fail to cover their cough or do not wear masks. Environmental issues include inadequate ventilation that results in insufficient dilution or removal of infectious droplets. The CDC recommends known or suspected TB patients be placed in an isolation room under negative air pressure. Healthcare workers should wear respirators in these rooms, but to the extent they do not, or if there is a breach or an undiagnosed case, the risk of transmission is directly proportional to time and intensity of exposure, the CDC noted.4
With exposure definitions dependent on multiple variables, a good rule of thumb is a duration of 15 minutes in which the worker was within six feet of a patient with active TB and neither were wearing a mask, Wendy Thanassi, MD, director of workforce health and wellness at Stanford Medicine, said at the AOHP webinar.
In the absence of routine annual screening of healthcare personnel, it is important to establish a low threshold for defining an exposure and performing post-exposure testing, Behrman added.
Consumption
Much of the world’s TB burden is in Asia and Africa. The United States and other counties that can afford to identify cases and deliver treatment record considerably lower rates of TB. In those countries that cannot take these actions, a preventable, curable disease is like the “consumption” that has taken so many lives over time.
“It was called ‘consumption’ because it’s so metabolically demanding that it leaves people just as skeletons,” Thanassi said. “Exposure is airborne, so it’s largely people in less developed countries who live in a crowded situation together and in close contact with each other all the time. Of these people who develop active TB, about 1.5 million will die every year. About 80% of active TB is from the reactivation of latent TB. [About] 10% of people who are in the United States who do get active TB will die of the disease.”
TB has been a scourge to humans for millennia, Thanassi emphasized, primarily striking the impoverished and dispossessed who eke out an existence on the social margins in crowded conditions.
“We made a huge thing about so many people getting COVID in the last few years, but a third of the people on the planet have had tuberculosis for the last 3,000 years, at least,” Thanassi said. “It’s very hard to prevent, it’s very hard to detect, and it’s very hard to treat once it becomes active. The treatment is a four-drug therapy, which is rifampin, isoniazid, pyrazinamide, and ethambutol — for many, many months. If you have multidrug-resistant TB, that treatment is 18 months — and it carries with it a very high mortality rate.”
TB became treatable in the 1940s and 1950s with streptomycin and the development of isoniazid. If not detected and treated, latent TB can lie dormant in the body for decades, awaiting some compromise of host immunity to emerge as an active infection. In this sense, it may be the ultimate opportunistic infection — a bad seed with immeasurable patience.
“Tuberculosis as a bacillus is covered in this waxy coat that makes it very hard to detect. Because it grows so slowly, it’s very hard to prevent even after exposure,” Thanassi explained. “Of the people who have latent TB, who are the ones at highest risk of [converting] to active disease? People with immune-compromised situations, like organ transplant, HIV, diabetes. [To clarify], people are not at increased risk for getting TB if they have diabetes. They are at increased risk of progressing from latent to active disease if they have diabetes.”
TB in the Foreign Born
In 2022, 73% of TB cases in the United States were foreign born, according to the CDC. Thus, most people who test positive for latent TB on post-hire pre-placement examination in healthcare facilities will be foreign born. The importance of treating latent TB was emphasized in the 2019 TB guidance and follow-up implementation document from the CDC.
“What is the point of identifying latent TB and the risk of reactivation if you don’t do something to prevent active TB and conversion?” Behrman asked. “We know that latent TB treatment is effective in preventing progression in later life to active TB. In our roles treating healthcare personnel, we have some responsibility if not to provide treatment, then to provide effective referral for treatment for latent TB.”
Latent TB is not contagious. The primary goal is to prevent emergence of active disease, and clinicians can contain this risk by eradicating latent TB with short-course drug regimens.
“The preferred regimens are shorter — three to four months, as opposed to six to nine months,” Behrman said. “It’s been found that these short-course regimens are not only more likely to be completed, because human beings are more likely to complete short courses than long courses of treatment — they are equally, if not more, effective than the long-course, single-drug treatments. They are safer — less hepatotoxic.”
That said, treatment of latent TB in public health settings and primary care is suboptimal. “In many settings, including mine, primary care physicians are wary and uncomfortable with treatment,” Behrman said.
Public health departments remain overwhelmed with the aftermath of COVID-19 and emerging infections, Behrman added. In addition, it is not uncommon for healthcare workers to refuse therapy for latent TB offered by their facility. The recommendation from Thanassi and Behrman is to follow up on these healthcare workers annually with a “symptom check” that also could include encouraging treatment for latent TB.
In treating healthcare workers for latent TB, it is important to look for any possible drug interactions, including antiretrovirals, blood thinners, and oral contraceptives.
Vaccine and Drug Resistance
Many healthcare workers from countries with higher TB prevalence have been administered the Bacillus Calmette-Guérin (BCG) TB vaccine, which is not routinely used in the United States. Those vaccinated with BCG may experience a cross reaction and present a false positive with a traditional TB skin test, which creates a raised wheal on the forearm after an intradermal injection of tuberculin protein. Blood tests like interferon-gamma release assays (IGRAs) eliminate this problem and yield a true reading.
“IGRAs do not interact with a BCG vaccine,” Thanassi said. “That is, if somebody was born in a different country where they did get BCG vaccine as a child — once, twice, three, five times in their lifetime — it still is not going to cross react with that IGRA. The skin test is not reliable in the BCG population. More than 50% of the time, those [false] positives will actually be negative on repeat testing.”
Multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB) is impervious to rifampicin and isoniazid, two of the most important drugs for treatment of infections. Globally, there were an estimated 450,000 cases of MDR/RR-TB in 2021, up 3.1% from 437,000 in 2020, the WHO reported. An estimated 191,000 of those with MDR/RR-TB in 2021 died, resulting in a morality rate of 42%.3
It is rare, but the CDC has identified cases over the years of a true superbug: Extensively drug-resistant TB (XDR-TB), which is generally defined as resistant to isoniazid, rifampin, a fluoroquinolone, and a second-line injectable that may include amikacin, capreomycin, and kanamycin. So-called pre-XDR (i.e., resistance to any fluoroquinolone for which testing was performed) was detected in 20% of the MDR/RR-TB globally in 2021, according to the WHO. The mortality rate of different drug-resistant strains of TB is highly influenced by co-infection with HIV. In one study, 80% of patients under antiretroviral treatment for HIV died within two years of acquiring XDR-TB.5
Drug-resistant TB can be acquired directly or develop in people who do not take their medications as prescribed. There is a consensus suggesting the COVID-19 pandemic led to an increase in TB, and if TB remains simmering globally, the broad emergence of a multidrug-resistant strain remains a threat, said Peter Sands, executive director of the nonprofit Global Fund to Fight AIDS, Tuberculosis, and Malaria.
“Neglecting TB isn’t just unjust, it’s also unwise,” Sands noted in an opinion piece. “Drug-resistant TB is, like COVID-19, an airborne respiratory infection. [It] is not quite as contagious as COVID-19, but it’s much more deadly. While the case fatality rate of COVID-19 was in the low single digits, and fell sharply once vaccines were introduced, for drug-resistant TB, the case fatality rate is nearer 50%. But as we have learned with COVID-19, we cannot assume that pathogens will stay the same. A more transmissible drug-resistant TB would be a truly frightening prospect.”6
REFERENCES
- Sosa LE, Njie GJ, Lobato MN, et al. Tuberculosis screening, testing, and treatment of U.S. health care personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019. MMWR Morb Mortal Wkly Rep 2019;68: 439-443.
- Schildknecht KR, Pratt RH, Feng PI, et al. Tuberculosis — United States, 2022. MMWR Morb Mortal Wkly Rep 2023;72:297-303.
- World Health Organization. Tuberculosis deaths and disease increase during the COVID-19 pandemic. Oct. 27, 2022.
- Thanassi W, Behrman AJ, Reves R, et al. Tuberculosis screening, testing, and treatment of US health care personnel: ACOEM and NTCA Joint Task Force on Implementation of the 2019 MMWR Recommendations. J Occup Environ Med 2020;62:e355-e369.
- Gandhi NR, Andrews JR, Brust JCM, et al. Risk factors for mortality among MDR- and XDR-TB patients in a high HIV-prevalence setting. Int J Tuberc Lung Dis 2012;16:90-97.
- Sands P. Tuberculosis: The unseen pandemic. The Global Fund. March 20, 2023.
The CDC dropped its labor-intensive recommendation for annual routine screening of healthcare workers for tuberculosis (TB) in 2019. However, there are multiple TB issues with which occupational health departments must contend. These include post-hire pre-placement testing, treating latent TB that could activate later in life, identifying and following up on worker exposures, and the threat of multidrug-resistant strains.
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