Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. LTBI Screening
2.3. Variables of Interest
2.4. Statistical Analysis
2.5. Ethics
3. Results
3.1. Adverse Events
3.2. Treatment Adherence
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Group A: Perform systematic screening |
|
Group B: Consider systematic screening based on local epidemiology and available resources |
|
Group C: Do not perform systematic screening |
|
Grade | Severity Grade | Definition |
---|---|---|
1 | Mild | Mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated |
2 | Moderate | Moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated |
3 | Severe | Severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated |
4 | Potentially life-threatening | Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death |
Parameter | Grade 1 Mild | Grade 2 Moderate | Grade 3 Severe | Grade 4 Potentially Life Threatening |
---|---|---|---|---|
AST or SGOT | 1.25–<2.5 × ULN | 2.5–<5 × ULN | 5.0–<10 × ULN | ≥10 × ULN |
ALT or SGPT | 1.25–<2.5 × ULN | 2.5–<5 × ULN | 5.0–<10 × ULN | ≥10 × ULN |
Gamma-glutamyl transpeptidase or GGT | 1.25–<2.5 × ULN | 2.5–<5 × ULN | 5.0–<10 × ULN | ≥10 × ULN |
Alkaline Phosphatase | 1.25–<2.5 × ULN | 2.5–<5 × ULN | 5.0–<10 × ULN | ≥10 × ULN |
Amylase | 1.1–1.5 × ULN | 1.6–<3.0 × ULN | 3.0–<5.0 ULN | ≥5.0 × ULN |
Blood urea nitrogen (BUN) | 1.25-2.5 × ULN | 2.6–5 × ULN | 5.1–10 × ULN | >10 ULN |
Creatinine | 1.1–1.5 × ULN | 1.6–3 × ULN | 3.1–6 × ULN | >6 × ULN |
Hemoglobin (female) | 9.5–10.4 g/dL | 8.5–9.4 g/dL | 6.5–<8.5 g/dL | <6.5 g/dL |
Hemoglobin (male) | 10–10.9 g/dL | 9.0–<10 g/dL | 7.0–<9 g/dL | <7 g/dL |
WBC | 2000–2499/mm3 | 1500–1999/mm3 | 1000–1499/mm3 | <1000/mm3 |
Absolute Neutrophil Count | 800–1000/mm3 | 600–799/mm3 | 400–599/mm3 | <400/mm3 |
Absolute Lymphocyte Count | 600–650/mm3 | 500–<600/mm3 | 350–<500/mm3 | <350/mm3 |
Platelets | 100–<125 × 1000/mm3 | 50–<100 × 1000/mm3 | 25–50 × 1000 mm3 | <25 × 1000/mm3 |
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Recently Arrived Migrants N = 81 | Immunosuppressed Persons N = 84 | Household Contacts N = 96 | p Value | |
---|---|---|---|---|
Sex, male | 57 (70.4) | 38 (45.2) | 50 (52.6) | 0.004 |
Median age (years), IQR | 27.0 (22.7–32.8) | 62.4 (49.6–72.4) | 44.9 (32.3–55.0) | <0.001 |
Country of birth | ||||
Spain | 0 | 63 (79.7) | 39 (40.6) | <0.001 |
Comorbidities | 6 (7.4) | 84 (100) | 30 (31.3) | 0.001 |
High blood pressure | 0 | 25 (29.8) | 11 (11.5) | <0.001 |
DM | 0 | 12 (14.3) | 6 (6.3) | <0.001 |
Dyslipidemia | 1 (1.2) | 20 (23.8) | 10 (10.4) | <0.001 |
Neoplasia | 0 | 45 (53.6) | 4 (4.2) | <0.001 |
Autoimmune disease | 0 | 41 (48.8) | 6 (6.3) | <0.001 |
Other | 6 (7.4) | 37 (44.0) | 24 (25.0) | <0.001 |
Concomitant treatment * | 1 (1.2) | 76 (90.5) | 23 (24.0) | <0.001 |
Treatment regimen for LTBI | ||||
3RIF/INH | 80 (98.8) | 10 (11.9) | 67 (69.8) | <0.001 |
6INH | 1 (1.2) | 74 (88.1) | 18 (18.8) | |
4RIF | 11 (11.5) |
Recently Arrived Migrants | Immunosuppressed Persons | Household Contacts | p-Value | |
---|---|---|---|---|
N = 81 | N = 84 | N = 96 | ||
Any AEs | 20 (24.7%) | 49 (58.3%) | 39 (40.6%) | <0.001 |
Gastrointestinal disorders | 7 (8.6%) | 22 (26.2%) | 13 (13.5%) | 0.006 |
Dermatological disorders | 2 (2.5%) | 2 (2.4%) | 2 (2.1%) | 0.984 |
Neurological disorders | 0 | 2 (2.4%) | 2 (2.1%) | 0.396 |
Other | 1 (1.2) | 1 (1.2) | 3 (3.1) | 0.554 |
Hepatic toxicity | 10 (14.3) | 29 (36.7) | 25 (27.8) | 0.008 |
I | 8 | 19 | 15 | |
II | 2 | 5 | 5 | |
III | 0 | 2 | 4 | |
IV | 0 | 3 | 1 | |
Neutropenia | 2 (2.5) | 5 (6.0) | 1 (1.0) | 0.256 |
I | 2 | 1 | 1 | |
II | 0 | 2 | 0 | |
III | 0 | 2 | 0 | |
Severe AE | 1 (1.2) | 7 (8.4) | 11 (11.5) | 0.03 |
Treatment change | 2 (2.5) | 2 (2.5) | 8 (8.3) | 0.089 |
Treatment discontinuation | 1 (1.2) | 5 (6.0) | 1 (1.0) | 0.079 |
All Participants | ||||||
---|---|---|---|---|---|---|
Bivariate | Multivariate | |||||
No AEs N = 153 | AEs N = 108 | OR (95%CI) | p value | OR (95%CI) | p value | |
Sex, Female | 58 (38.2) | 57(58.8) | 1.81 (1.10–2.99) | 0.020 | 1.67 (0.94–2.82) | 0.082 |
Age, mean (SD) | 42.7 (18.8) | 48.4 (18.0) | 1.02 (1.00–1.03) | 0.016 | 0.99 (0.97–1.02) | 0.580 |
LTBI regimen | ||||||
3RIF/INH ** | 104 (68%) | 53 (49.1) | 1 (REF) | 1 (REF) | ||
6INH | 44 (28.8) | 49 (45.4) | 2.18 (1.29–3.69) | 0.003 | 0.79 (0.33–1.88) | 0.594 |
4RIF | 5 (3.3) | 6 (5.6) | 2.35 (0.69–8.07) | 0.173 | 1.41 (0.38–5.27) | 0.611 |
Reason for LTBI treatment | ||||||
Recently arrived migrants * | 35 (22.9) | 20 (18.5) | 1 (REF) | 1 (REF) | ||
Immunosuppressed | 57 (37.3) | 49 (45.4) | 4.27 (2.19–8.31) | <0.001 | 7.36 (2.04–26.58) | 0.002 |
Contact | 9 (6.1) | 39 (36.1) | 2.09 (1.09–3.99) | 0.026 | 2.38 (1.08–5.30) | 0.031 |
Baseline abnormal hepatic profile | 14 (13.6) | 2.43 (1.01–5.85) | 0.048 | 2.28 (0.89–5.82) | 0.084 | |
Concomitant medication | 48 (31.4) | 52 (48.1) | 2.03 (1.22–3.34 | 0.006 | 1.30 (0.52–3.21) | 0.573 |
Excluding Persons LTFU | ||||||
---|---|---|---|---|---|---|
Bivariate | Multivariate | |||||
No AEs N = 137 | AEs N = 99 | OR (95%CI) | p value | OR (95%CI) | p value | |
Sex, female | 53 (39.0) | 52 (52.5) | 1.73 (1.03–2.92) | 40 | 1.58 (0.89–2.82) | 119 |
Age, mean (SD) | 44.4 (18.9) | 47.9 (17.7) | 1.01 (0.99–1.03) | 123 | 0.99 (0.96–1.01) | 241 |
LTBI regimen | ||||||
3RIF/INH ** | 43 (31.4) | 46 (46.5) | 1 (REF) | 1 (REF) | ||
6INH | 89 (65.0) | 47 (47.0) | 2.03 (1.17–3.50) | 11 | 0.77 (0.31–1.89) | 564 |
4RIF | 5 (3.6) | 6 (6.1) | 2.27 (0.66–7.84) | 194 | 1.56 (0.41–5.93) | 513 |
Reason for LTBI treatment | ||||||
Recently arrived migrants * | 47 (34.3) | 17 (17.2) | 1 (REF) | 1 (REF) | ||
Immunosuppressed | 34 (24.8) | 47 (47.5) | 3.82 (1.88–7.76) | <0.001 | 8.25 (2.15–31.67) | 2 |
Contact | 56 (40.9) | 35 (35.4) | 1.73 (0.86–3.47) | 124 | 2.19 (0.95–5.06) | 67 |
Baseline abnormal hepatic profile | 8 (6.0) | 14 (14.7) | 2.73 (1.10–6.81) | 31 | 2.53 (0.96–6.65) | 60 |
Concomitant medication | 47 (34.3) | 49 (49.0) | 1.88 (1.11–3.18) | 20 | 1.19 (0.46–3.03) | 718 |
Treatment Completed N = 229 | LTFU N = 25 | p Value | |
---|---|---|---|
Sex, female | 102 (44.7) | 10 (40.0) | 0.651 |
Age, mean (SD) | 45.8 (18.4) | 36.8 (18.6) | 0.021 |
Reason for LTBI treatment | |||
Recently arrived migrants | 76 (33.2) | 3 (12.0) | <0.001 |
Immunosuppressed | 90 (39.3) | 5 (20.0) | |
Contact | 63 (27.5) | 17 (68.0) | |
LTBI regimen | |||
6INH | 84 (36.7) | 4 (16.0) | 0.041 |
3RIF/INH | 134 (58.5) | 21 (84.0) | |
4RIF | 11 (4.8) | 0 | |
AE | 92 (40.2) | 9 (36.0) | 0.686 |
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Puyana Ortiz, J.D.; Garcés Rodríguez, A.C.; Aznar, M.L.; Espinosa Pereiro, J.; Sánchez-Montalvá, A.; Martínez-Campreciós, J.; Saborit, N.; Rodrigo-Pendás, J.Á.; García Salgado, G.; Broto Cortes, C.; et al. Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain. Trop. Med. Infect. Dis. 2023, 8, 373. https://doi.org/10.3390/tropicalmed8070373
Puyana Ortiz JD, Garcés Rodríguez AC, Aznar ML, Espinosa Pereiro J, Sánchez-Montalvá A, Martínez-Campreciós J, Saborit N, Rodrigo-Pendás JÁ, García Salgado G, Broto Cortes C, et al. Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain. Tropical Medicine and Infectious Disease. 2023; 8(7):373. https://doi.org/10.3390/tropicalmed8070373
Chicago/Turabian StylePuyana Ortiz, Juan David, Andrea Carolina Garcés Rodríguez, María Luisa Aznar, Juan Espinosa Pereiro, Adrián Sánchez-Montalvá, Joan Martínez-Campreciós, Nuria Saborit, José Ángel Rodrigo-Pendás, Guadalupe García Salgado, Claudia Broto Cortes, and et al. 2023. "Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain" Tropical Medicine and Infectious Disease 8, no. 7: 373. https://doi.org/10.3390/tropicalmed8070373
APA StylePuyana Ortiz, J. D., Garcés Rodríguez, A. C., Aznar, M. L., Espinosa Pereiro, J., Sánchez-Montalvá, A., Martínez-Campreciós, J., Saborit, N., Rodrigo-Pendás, J. Á., García Salgado, G., Broto Cortes, C., Delcor, N. S., Oliveira, I., Treviño Maruri, B., Ciruelo, D. P., Salvador, F., Bosch-Nicolau, P., Torrecilla-Martínez, I., Zules-Oña, R., Tórtola Fernández, M. T., & Molina, I. (2023). Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain. Tropical Medicine and Infectious Disease, 8(7), 373. https://doi.org/10.3390/tropicalmed8070373