A programmatic latent tuberculosis infection (LTBI) intervention led to completion rates of 92.7% for LTBI screening and 82.5% for TB preventive therapy (TPT) among elderly patients with poorly controlled diabetes, according to study findings published in Clinical Infectious Diseases.

In this prospective study, investigators recruited 1057 patients with poorly controlled diabetes from April 2018 to June 2020 at a medical center in Taichung, Taiwan, and a regional hospital in Kaohsiung, Taiwan.

A collaborative multidisciplinary team, including endocrinologists and pulmonologists, evaluated each patient to determine the TPT given based on safety and convenience. The 2 TPT regimens were weekly rifapentine plus isoniazid (3HP) for 3 months or daily isoniazid (9H) administered for 9 months. The 3HP regimen was recommended for patients with no contraindications, concomitant liver diseases, or abnormal liver function test results. In addition, a directly observed therapy program was used to monitor all patients.


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The primary outcomes were the QuantiFERON-TB (QFT) positive rate and the TPT regimen completion rate. QFT positivity was defined as a minimum difference of 0.35 IU/mL in the interferon-gamma level between TB antigen and nil tubes. The rate of TPT completion was 12 doses within 16 weeks for the 3HP regimen and 270 doses within 12 months for the 9H regimen.

Among all 1057 patients with poorly controlled diabetes, 980 (92.7%) underwent QFT testing, 261 (26.7%) were QFT positive, and 2 (0.2%) had indeterminate QFT results. Among the 261 QFT-positive patients, 59 refused TPT, and 2 had active TB. The study authors initiated TPT in 200 patients: 138 (69%) on the 3HP regimen and 62 (31%) on the 9H regimen.

The investigators found the following predictors for QFT positivity:

  1. Age per year increment (adjusted odds ratio [aOR], 1.02; 95% CI, 1.00-1.04; P =.026)
  2. Duration of diabetes (aOR, 1.04; 95% CI, 1.02-1.07; P <.001)
  3. Stage 3 or higher chronic kidney disease (aOR, 1.80; 95% CI, 1.23-2.65; P =.003)
  4. Metformin use (aOR, 0.56; 95% CI, 0.39-0.80; P =.001)
  5. Dipeptidyl peptidase-4 inhibitor use (aOR, 1.51; 95% CI, 1.08-2.13; P =.018)

The TPT completion rates were 84.1% for 3HP and 79.0% for 9H (P =.494). The number of patients discontinuing TPT due to adverse drug reactions was 20 of 139 (14.5%) for the 3HP group and 8 of 62 (12.9%) for the 9H group (P =.764).

Multivariate logistic regression analysis indicated that the specific regimen was not a significant predictor for permanent TPT discontinuation among all 200 patients and subgroups (aOR, 0.76; 95% CI, 0.27-2.16; P =.609).

It was noted that metformin use may protect these patients against TB infection via the drug’s ability to enhance the function of phagolysosomes, modulate the innate host response to the bacteria, and reduce chronic inflammation of the infected lung.

“Because the prevalence of LTBI exceeds 25% in elderly patients with [poorly controlled diabetes], programmatic LTBI interventions integrating health professionals, endocrinologists, and pulmonologists can facilitated the successful implementation of LTBI policy to achieve high screen and completion rates, regardless of the regimen,” the study authors concluded.

Reference

Huang H-L, Huang W-C, Lin K-D, et al. Completion rate and safety of programmatic screening and treatment for latent tuberculosis infection in elderly patients with poorly controlled diabetic mellitus: a prospective multicenter study. Clin Infect Dis. Published online March 3, 2021. doi:10.1093/cid/ciab209