Dear Editor,
TB may disproportionately affect persons who use drugs (PWUD),1–3 but the TB incidence rate among PWUD has not been estimated in the United States (U.S). California has the highest TB case burden and the highest frequency of current drug use: in 2019, 23.5% of incident TB cases in the U.S. occurred in California (5.3/100,000), and the state has an estimated 4.7 million PWUD.4,5 A better understanding of the intersection between drug use and TB will promote equity-informed interventions that account for social aspects of TB risk.6 In the study presented here, we estimate the incidence of TB disease among PWUD in California, describe the characteristics of TB patients who use drugs, and evaluate drug use as a risk factor for adverse treatment outcomes.
We analyzed surveillance data of incident TB disease reported to the California Department of Public Health (CDPH; Richmond, CA, USA) TB registry in persons ≥12 years of age from 2015–2019. The denominator population of PWUD (who reported drug use in the past year) was derived from the National Survey of Drug Use and Mental Health (NSDUH) of noninstitutionalized civilians who were aged ≥12 years and resided in fixed-address households. We accessed prevalence estimates derived from the NSDUH through the Restricted Online Data Access System.7 NSDUH prevalence estimates are based on 2 years of pooled sample data and, because each year had two estimates (e.g., for 2018 data for 2017–2018 and 2018–2019), we used the average for the annual denominator value. We considered persons with TB who use drugs (PWUD-TB) as patients who reported any injecting or noninjecting drug use in the year preceding TB diagnosis. We used the NSDUH past-year variable ‘Any illicit drug use’ as the PWUD population denominator. We determined whether cases were attributable to recent transmission using a plausible source-case algorithm that associates genetic isolates with likely TB source cases.8 We defined TB treatment noncompletion as premature treatment cessation due to loss to follow-up, refusal, or nonadherence. We defined treatment extension as the completion of an appropriate regimen in more than 12 months, excluding patients with multidrug-resistant TB. We calculated the annual incidence of TB disease among PWUD aged ≥12 years from 2015 to 2019 by dividing the annual frequency of PWUD-TB by the corresponding NSDUH prevalence estimate of past-year drug use for California, stratified by place of birth. We used the χ2 test for comparison of categorical variables and the Wilcoxon rank-sum test for continuous variables (α = 0.05). Finally, we constructed multivariable log-binomial models to determine the independent association of drug use with treatment extension and treatment noncompletion (α = 0.05). This activity was determined to meet the requirements of public health surveillance by the Centers for Disease Control and Prevention (CDC) as defined in 45 CFR 46.102(l)(2), and thus did not require institutional board review. CDPH also determined this work to be non-research. Informed consent was not required.
From 2015 to 2019, drug use was identified in 6.1% (618/10,218) of TB disease patients aged ≥12 years, of whom 497 (80.6%) reported noninjection drug use only, 39 (6.3%) reported injection drug use only, and 81 (13.1%) reported both. The annual TB incidence rate among persons who are noninstitutionalized and not experiencing homelessness is shown in the Table. For the California U.S.-born population, the average annual TB incidence among PWUD was 0.6/100,000 persons, which was lower than the rate of 1.4/100,000 for non-PWUD (rate ratio [RR] 0.4, 95% CI 0.4–0.5). For the California non-US–born population, the average annual incidence among PWUD was 3.4/100,000 persons and 16.3/100,000 among non-PWUD (RR 0.2, 95% CI 0.2–0.2). In sensitivity analysis, where institutionalized and homeless persons with TB were included in the numerator, incidence among both U.S.-born and non-U.S.-born PWUD remained non-elevated in comparison to non-PWUD. U.S.-born TB patients reported drug use (355/1,593, 22.3%) more frequently than non-U.S.-born patients (261/8,352, 3.5%; P ≤0.001). Compared with non-PWUD-TB with pulmonary TB, PWUD-TB with pulmonary TB more often had smear-positive sputum (340/570, 59.7% vs. 3,853/7,584, 50.8%) and computed tomography (CT) imaging or chest radiography with cavities (207/566, 36.6% vs. 1,868/7,561, 24.7%) (both P ≤ 0.001). Drug use was reported in 12.9% (190/1,473) of cases attributed to recent transmission, and recent transmission was significantly more common among PWUD-TB than among non-PWUD-TB (190/618, 30.7% vs. 1,283/9,340, 13.7%; P ≤ 0.001). Drug use was a positive predictor of treatment noncompletion (adjusted prevalence ratio [aPR] 2.8, 95% CI 1.7–4.7) and treatment extension (aPR 1.3, 95% CI 1.01–1.73) among persons with drug-susceptible TB, following adjustment for age, sex, race or ethnicity, origin of birth, site of disease, HIV status, homelessness, incarceration status at diagnosis, and excess alcohol use.
Table.
Estimated annual TB disease incidence among PWUD aged ≥12 years vs. non-PWUD, stratified by origin of birth, excluding institutionalized and homeless TB patients, California, USA, 2015–2019
| Origin | Year | PWUD-TB n |
PWUD population† n |
Incidence/100,000 PWUD % (95% CI) |
Incidence/100,000 non-PWUD % (95% CI)‡ |
RR (95% CI) |
|---|---|---|---|---|---|---|
| U.S.-born | ||||||
| 2015 | 32 | 5,910,000 | 0.5 (0.4–0.7) | 1.4 (1.3–1.6) | 0.4 (0.3–0.5) | |
| 2016 | 33 | 5,999,500 | 0.6 (0.4–0.7) | 1.4 (1.2–1.6) | 0.4 (0.3–0.6) | |
| 2017 | 46 | 6,197,500 | 0.7 (0.5–1.0) | 1.2 (1.0–1.3) | 0.6 (0.5–0.9) | |
| 2018 | 39 | 6,464,500 | 0.6 (0.4–0.8) | 1.3 (1.1–1.5) | 0.5 (0.3–0.6) | |
| 2019 | 31 | 6,623,000 | 0.5 (0.3–0.6) | 1.5 (1.3–1.6) | 0.3 (0.2–0.5) | |
| Non-U.S.-born | ||||||
| 2015 | 22 | 931,000 | 2.4 (1.4–3.4) | 16.7 (15.9–17.5) | 0.1 (0.1–0.2) | |
| 2016 | 32 | 926,500 | 3.5 (2.3–4.7) | 16.2 (15.4–17.0) | 0.2 (0.2–0.3) | |
| 2017 | 33 | 926,500 | 3.6 (2.3–4.8) | 16.4 (15.6–17.2) | 0.2 (0.1–0.3) | |
| 2018 | 34 | 1,001,000 | 3.4 (2.3–4.5) | 16.4 (15.6–17.2) | 0.2 (0.1–0.3) | |
| 2019 | 43 | 1,071,000 | 4.0 (2.8–5.2) | 16.1 (15.3–16.9) | 0.2 (0.2–0.3) | |
*Due to rounding, percentages may not sum to 100%.
†All population estimates from the annual National Survey on Drug Use and Mental Health (see Methods).
‡Annual count of non-PWUD-TB and population estimates used to calculate incidence among non-PWUD are not shown.
PWUD = persons who use drugs; CI = confidence interval; RR = rate ratio.
This investigation has several limitations. Drug use among persons with TB was collected through self-report and consultation of medical records and thus may be underreported. The NSDUH prevalence estimate of past-year drug use could not be stratified by drug type, age group, sex and other covariates, and heterogeneous drug use definitions in the literature (e.g., excluding marijuana, lifetime use, injecting use only) limited direct comparison of our results. Finally, our retrospective descriptive analysis cannot definitively assess drug use as an independent risk factor for TB disease.
In California, the incidence of TB disease was not elevated among PWUD compared to non-PWUD in the general population. This contrasts with prior reports of elevated risk of TB in distinct (primarily urban, injecting and HIV-positive) drug-using cohorts.9–12 Recreational marijuana use, which has not demonstrated a consistent relationship with TB,13 was included in our data sources and may have contributed to our alternative finding. There are several possible interpretations for our study. For example, the population-level rates of TB among PWUD may not necessarily reflect the risk historically found in more selective subpopulations, or our estimates may have been confounded by age or other unmeasured covariates. Further cohort studies are needed to explore potential high-risk subpopulations of PWUD that may benefit from targeted prevention. Despite the non-elevated incidence, TB patients who reported any drug use in the 12 months prior to TB diagnosis were more likely to have extended and incomplete treatment. Augmented TB program support for PWUD, potentially including enhanced case management and intensive contact investigations,14,15 may improve treatment completion and interrupt local chains of transmission. Further work is needed to delineate drug use patterns among persons with TB and produce population-level estimates of drug use by type across demographics.
Acknowledgments
The authors thank all members of the California Department of Public Health, Tuberculosis Control Branch, Richmond, CA, USA, who supported us in completing this manuscript. The findings and conclusions are those of the authors and do not necessarily represent the views or opinions of the U.S. Centers for Disease Control and Prevention, the Agency for Toxic Substances and Disease Registry, the California Department of Public Health, or the California Health and Human Services Agency.
Footnotes
Conflicts of interest: none declared.
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