Characteristics of the study population:
During the study period, in all healthcare institutions of the Khabarovsk Krai, 2661 patients were diagnosed with TB, of which 1544 patients were found to have an active pulmonary tuberculosis and 101 patients were excluded from the study due to resistance types other then MDR/RR-TB. 3 patients were excluded due to an incomplete set of variables. In total, 1440 patients were included in this study. Participants had a median age of 41 years, and 73.5% of them were male. MDR/RR was detected in 618 (42.9%, 95% CI 40.3–45.5%) of the study participants. 69.4% of participants resided in cities and 989 (68.7%) of them had no official record of employment. 61.5% were living in separate apartments and 151 (10.5%) patients were homeless in the time of TB diagnosis. There were also 2.01 times more homeless among re-treatment cases than in new TB cases (16,5% vs 8.2%). Alcoholism was reported in 3.5% of all cases and in 62.5% of patients, TB was discovered actively with the annual chest x-ray in primary healthcare facilities (PHF). More than half (55.1%) of all cases showed signs of cavitary disease. Disabilities have been reported in 6% of the entire sample and 8.3% were tested positive for HIV. 78 patients (5.4%) were in detention or had an official history of incarceration in the time of diagnosis. Incarcerated patients had a much higher prevalence of resistance in question (93.6%, 95% CI 85.6–97.8%) compared to the population without a history of imprisonment (40.0%, 95% CI 37.4–42.7%) (p<0.001).
There were 394 re-treatment patients, which comprised 27.4% of the total study sample. The re-treatment patients had greater prevalence of MDR-TB (64.6%, 95% CI 59.8–69.4%) than the new patients (34.8%, 95% CI 31.8–37.7%) (p<0.001) (Table 1).
Factors associated with MDR/RR-TB:
With the 1440 cases entered into the multilevel model, a history of imprisonment and history of previous treatment became the strongest associative factors with MDR/RR-TB. In these cases, risk of having MDR/RR-TB was 16.53 times higher (95% CI 5.37 to 50.88, p<0.001) and 2.82 times higher (95% CI 2.16 to 3.66, p<0.001) respectively.
Other influencing factors included presence of disability (adjusted OR (AOR) is 2.32, 95% CI 1.38 to 3.89, p=0.001), cavitary disease (AOR is 1.76, 95% CI 1.37 to 2.25, p<0.001), positive HIV status (AOR 1.55, 95% CI 1.01 to 2.39, p=0.046), age (AOR for being older than 41 years is 1.36, 95% CI 1.06 to 1.76, p=0.013) and place of residence (AOR for residing in the city is 1.44, 95% CI 1.09 to 1.89, p=0.01) (Table 2).
The multilevel model for the newly diagnosed patients was composed of 1047 cases. Of these, 364 had MDR/RR-TB (34.7%). History of imprisonment again became the strongest associative factor, with 11.9 times higher risk of MDR/RR-TB (95% CI 2.94 to 43.78, p<0.001).
Among all remaining factors, three showed association with presence of MDR/RR-TB. First, patients with underlying cavitary disease were 1.96 times more likely to have MDR/RR-TB (95% CI 1.46 to 2.63, p<0.001). Second, patients who were living in сities were 1.841 times more likely to have MDR/RR-TB (95% CI 1.25 to 2.44, p=0.001). Third, positive HIV status was associated with a 1.67 times increase in terms of the MDR/RR-TB risk (95% CI 1.01 to 2.77, p=0.047) (Table 3).
393 cases were included in multilevel model for re-treatment patients. Here, four variables proved to be significant, with a history of incarceration remaining the strongest associative factor among all. In these cases, such patients were 38.5 times more likely to have MDR/RR-TB (95% CI 3.64 to 407.42, p=0.002). Elsewhere, the presence of disability led to a ratio of 4.43 times more likely to have MDR/RR-TB (95% CI 1.47 to 13.38, p=0.008). Other two significant variables were official records of employment (AOR 4.32, 95% CI 1.74 to 10.71, p=0.002) and being discovered actively by PHF (AOR 1.79, 95% CI 1.05 to 3.05, p=0.03) (Table 3).
Table 2
Multivariable analysis for estimation of prevalence of MDR/RR-TB in the entire sample (n = 1440)
Variable | Prevalence of MDR/RR-TB (%) | AOR (95% CI) | p Multilevel |
Gender Female Male | | 43.1 41.4 | 1.21 (0.93 to 1.57) 1 (reference) | 0.156 |
Age, median years (range) >=41 years <41 years | | 48 37.9 | 1.36 (1.06 to 1.76) 1 (reference) | 0.013 |
Place of residence City Countryside | | 44.2 40.0 | 1.43 (1.09 to 1.89) 1 (reference) | 0.010 |
Social status (whole variable) Working Retired Student Not organized child In military service Not working | | 39.3 29.3 35.7 50 100 46.3 | - 1.08 (0.79 to 1.47) 0.65 (0.43 to 0.98) 0.94 (0.41 to 2.15) 0.75 (0.09 to 6.53) - 1 (reference) | 0.432 0.639 0.042 0.879 0.792 0.999 |
Living conditions (whole variable) Bed in designated facility Room in dormitory Room in separate apartment Separate house Separate apartment Homeless | | 51.3 86.4 46.2 9.1 43.9 39.3 | 0.71 (0.19 to 2.65) 0.98 (0.29 to 3.37) 0.14 (0.02 to 1.17) 1.13 (0.72 to 1.75) 0.80 (0.54 to 1.18) 1 (reference) | 0.125 0.608 0.978 0.069 0.595 0.258 - |
Substances abuse (whole variable) Alcoholism Drug abuse No official records | | 39.2 75 43 | 0.84 (0.45 to 1.56) 2.35 (0.23 to 24.25) 1 (reference) | 0.656 0.569 0.475 - |
Circumstance of TB discovery Discovered actively by healthcare facility Visit with symptoms to healthcare facility | | 45.8 38.1 | 1.24 (0.97 to 1.60) 1(reference) | 0.088 |
Imprisonment history Being in detention or history of detention No official history of detention | | 93.6 40.0 | 16.53 (5.37 to 50.88) 1 (reference) | <0.001 |
Cavitary disease Presence of cavities No cavities | | 47.4 37.5 | 1.76 (1.37 to 2.25) 1 (reference) | <0.001 |
Disabilities No disability Presence of disability | | 41.4 67.4 | 2.32 (1.38 to 3.89) 1 (reference) | 0.001 |
TB localization: Pulmonary TB Non thoracic TB TB of lungs’ lymph system, pleural | | 43.4 0 34.5 | (-) 1.27 (0.55 to 2.94)- 1 (reference) | 0.859 0.581 - 0.999 |
HIV status Positive Negative | | 53.8 41.9 | 1.55 (1.01 to 2.39) 1 (reference) | 0.046 |
Treatment history with I and R: Retreatment No history | | 64.6 34.8 | 2.82 (2.16 to 3.66) 1 (reference) | <0.001 |
HIV – human immunodeficiency virus, TB – tuberculosis, MDR/RR – multidrug resistance/Rifampin resistance, AOR – adjusted odds ratio, |
Table 3
Multivariable analysis for estimation of prevalence of MDR-TB in the new cases (n=1046) and retreatment cases (n=394)
Variable | New cases (n=1046) | Retreatment cases (n=394) |
Prevalence of MDR-TB (%) | AOR (95% CI) | p Multilevel | Prevalence of MDR-TB (%) | AOR (95% CI) | p Multilevel |
Gender Female Male | 36.4 34.1 | 1.25 (0.92 to 1.69) 1 (reference) | 0.157 - | 65.6 61.5 | 1.24 (0.71 to 2.18) 1 (reference) | 0.441 - |
Age, median years (range) >=41 years <41 years | 39.5 30.0 | 1.34 (0.99 to 1.81) 1 (reference) | 0.013 - | 58.1 71.6 | 0.65 (0.38 to 1.09) 1 (reference) | 0.108 - |
Place of residence City Countryside | 37.2 28.9 | 1.841 (1.32 to 2.57) 1 (reference) | 0.010 - | 66.7 63.6 | 1.27 (0.72 to 2.26) 1 (reference) | 0.408 - |
Social status (whole variable) Working Retired Student Not organized child In military service Not working | 30.5 24.8 30.8 50.0 100.0 37.9 | - 0,83 (0.58 to 1.19) 0.66 (0.41 to 1.07) 0.75 (0.31 to 1.86) 0.81 (0.09 to 6.81) - 1 (reference) | 0.604 0.639 0.042 0.879 0.792 0.999 - | - 82.9 45.9 100.0 0.0 0.0 64.2 | - 4,32 (0.58 to 1.19) 0.66 (0.29 to 1.49) - - - 1 (reference) | 0.008 0.002 0.042 0.999 0.999 0.999 - |
Living conditions (whole variable) Bed in designated facility Room in dormitory Room in separate apartment Separate house Separate apartment Homeless | 66.7 22.2 0.0 37.3 33.7 37.2 | 0.73 (0.12 to 4.37) 0.64 (0.12 to 3.43) - 1.379 (0.79 to 2.40) 0.98 (0.60 to 1.61) 1 (reference) | 0.534 0.608 0.978 0.999 0.595 0.28 - | 93.8 100.0 100.0 60.6 59.1 70.3 | 0.43 (0.05 to 3.68) - - 0.78 (0.35 to 1.77) 0.52 (0.26 to 1.05) 1 (reference) | 0.526 0.439 0.999 0.999 0.560 0.070 - |
Substances abuse (whole variable) Alcoholism Drug abuse No official records | 32.4 66.7 34.8 | - 0.97 (0.47 to 1.99) 1.15 (0.09 to 14.14) 1 (reference) | 0.991 0.935 0.914 - | 57.1 100.0 64.8 | - 0.48 (0.13 to 1.73) - 1 (reference) | 0.539 0.266 0.999 - |
Circumstance of TB discovery Discovered actively by healthcare facility Visit with symptoms to healthcare facility | 35.3 34.0 | 1.18 (0.88 to 1.57) 1 (reference) | 0.278 | 69.6 53.0 | 1.79 (1.06 to 3.05) 1 (reference) | 0.030 |
Imprisonment history Being in detention or history of detention No official history of detention | 82.6 33.7 | 11.9 (3.08 to 45.93) 1 (reference) | <0.001 | 98.2 59.2 | 38.55 (3.65 to 407.42) 1 (reference) | 0.002 |
Cavitary disease Presence of cavities No cavities | 40.1 28.6 | 1.95 (1.45 to 2.62) 1 (reference) | <0.001 | 65.2 63.8 | 1.46 (0.87 to 2.44) 1 (reference) | 0.151 |
Disabilities Presence of disability No disability | 48.9 34.1 | 1.66 (0.87 to 3.15) 1 (reference) | 0.119 | 87.8 61.9 | 4.44 (1.47 to 13.38) 1 (reference) | 0.008 |
TB localization: TB of lungs’ lymph system, pleural Non thoracic TB Pulmonary TB | 38.5 0.0 35.0 | (-) 1.69 (0.71 to 4.04)- 1 (reference) | 0.494 0.235 0.999 - | 0.0 0.0 65.3 | -- 1 (reference) | 0.999 0.999 0.999 - |
HIV status Positive Negative | 46.8 33.8 | 1.67 (1.01 to 2.77) 1 (reference) | 0.047 | 67.5 64.3 | 1.48 (0.62 to 3.53) 1 (reference) | 0.378 - |
Previous therapy More than 180 days Less than 180 days | - | - | - | 61.4 69.7 | 0.92 (0.56 to 1.51) 1 (reference) | 0.732 - |
Previous therapy outcome Not effective course Other Transferred Interrupted course Effective course | - | - | - | 79.3 0.0 100.0 52.5 61.4 | - 1.379 (0.79 to 2.40) - - 0.98 (0.60 to 1.611 1 (reference) | 0.061 0.621 0.999 0.999 0.089 - |
HIV – human immunodeficiency virus, TB – tuberculosis, MDR/RR – multidrug resistance/Rifampin resistance, AOR – adjusted odds ratio |
Interpretation of Interviews:
Findings of quantitative data analysis were partially supported by interviews with patients, health managers, and physicians.
All aspects of TB care in Russia are free of charge. The whole system was designed to provide universal, quality and specialized care that is centralized in TB-designated facilities (TBDF), as depicted on the Figure 1. The one exception from the system is penitentiary facilities that operate separately. As was reported by interviewees, poor nutrition and living conditions, overcrowding, treatment regimens neglect by prisons’ medical stuff and prisoners, make these institutions the breeding ground for drug resistance. After releasing from detention, prisoners mostly disappear from epidemiological surveillance and, even if they show up for further treatment, they often fail to adhere to the regimen and follow-up procedures and there is no legal tools for healthcare providers to enforce surveillance on them.
There was a consensus among interviewees, that the main obstacle toward achieving full patient’s compliance, is the length of therapy. Patients become progressively tired as the treatment advances, especially those ones with drug resistance, whose regimens usually last for 24 months or even more. That, combined with insufficient awareness about consequences of intermitted treatment, leads patients to drop out from the treatment, usually as soon as symptoms disappear.
Healthcare providers stated that both outcome and history of previous treatment contribute to the resistance development contrary to our results that mere fact of previous treatment history is increasing risk of resistance presence regardless of its outcome. Same goes for social status and living conditions, which, according to our statistical data, do not influence resistance development, but from a clinical standpoint, socially disadvantaged patients (particularly homeless ones) display a greater tendency to acquire MDR/RR TB. Other substantial problem, that was not supported by data but reported by interviewees, is a greater frequency of alcohol and substances abuse. MDR/RR –TB prevalence in those groups is significantly higher than average.
Significance of disability as a risk factor was a surprise for interviewees; physicians stated that some patients purposely do not comply with treatment in order to worsen their condition and acquire disability status for receiving social security benefits.
City dwellers have better access to healthcare in general and have a far greater capacity to complete annual chest X-rays in particular. Therefore, cities tend to see a far greater number of people diagnosed with TB than in rural areas. Likewise, the increased population density in cities provides more chances to contract MDR / RR - TB. This can explain an emerging trend observed by physicians - namely, the increase in the prevalence of MDR / RR-TB among newly diagnosed patients.