This retrospective cohort study, 19.1% of referred patients were diagnosed with LTBI during a 51-month period in a routine screening program in a remote Canadian arctic region with a predominantly Inuit population. The cascade of care demonstrated high rates of LTBI treatment initiation (75%) and completion (76%). Older age and receiving a TST during employment screening were associated with non-initiation of treatment while only older age was associated with non-completion of treatment.
Despite the challenges of delivering care in a remote setting, the rate of treatment initiation in the present study was broadly similar to those from large North American studies while the rate of treatment completion was higher. In a 2003 study of over 13,000 LTBI cases across 29 American jurisdictions, 69.9% of all LTBI patients took at least one treatment dose while 63.7% of these patients completed ≥80% of prescribed doses . In a 2010 study involving 32 clinics, 82.9% of LTBI patients offered treatment initiated it and 47.3% of initiators completed 100% of treatment doses within one year . Finally, only 31.3% of patients prescribed LTBI treatment filled prescriptions for all doses in a 2013 analysis of health administrative data in Quebec . The higher rates of treatment completion in Iqaluit may be related to the use of directly observed therapy and a twice weekly regimen which requires fewer total doses than traditional daily therapy.
In our study, non-initiation of treatment among patients for whom treatment was recommended represented the largest source of loss of TST positive patients from the cascade of care. The increased risk of non-initiation among older patients and those identified via employment screening may reflect a less favourable balance of treatment risk and benefit among these groups. The risk of adverse effects, particularly hepatotoxicity, due to isoniazid increases with age [20, 21] which may have led to reluctance among older patients to start treatment. Further, LTBI reactivation risk is highest within the first 2 years following infection . Thus, those with positive testing in screening programs but with unknown or remote TB exposure may anticipate less benefit from treatment than those with a known, recent exposure. Of note, the Canadian TB standards do not include an age-based cut off above which LTBI treatment is not recommended but, instead, recommend weighing the risks and benefits of treatment on an individual basis .
To improve initiation rates, interventions targeting older individuals and those identified via employment screening should be considered. This could include the expanded use of less hepatotoxic regimens such as the 12- week regimen of rifapentine and isoniazid (3HP)  which could be particular beneficial for older patients. Further, providing videos of community elders discussing the nature and benefits of LTBI treatment to older patients may help to assist in establishing understanding and openness to considering such therapies potentially increasing initiation. Finally, providing education regarding the importance of LTBI testing and treatment to employees starting jobs which will require LTBI screening. This may help to shape opinions on these topics early, potentially increasing treatment initiation later when LTBI is diagnosed.
Non-completion of treatment represented the second largest loss of TST positive patients from the cascade of care and was associated with older age. As noted above, adverse effects related to isoniazid are more common among older patients [20, 21] and may have contributed to reduced completion in this group. The use of 3HP has been associated with both increased completion rates and reduced hepatotoxicity compared to isoniazid alone [15, 23]. As such, this alternative regimen may be of particular benefit in this setting with the potential to increase both initiation and completion.
Irregular appointment attendance was the most commonly listed reason for non-completion. The use of shorter treatment regimens has been associated with increased completion . In the present study, the vast of majority of patients (94.3%) used a 9-month regimen. Thus, a change to a shorter regimen, which could include the 3HP regimen mentioned above, may improve appointment attendance by reducing the number of required clinic visits.
Physicians frequently cited discordance between TST and IGRA results as a reason for not offering LTBI treatment. The use of IGRA as a confirmatory test following TST is not endorsed by Canadian or World Health Organization guidelines [13, 24]. However, this strategy is recommended for some low risk patients in American guidelines  and a recent trial found it to be non-inferior to TST alone , suggesting that it may be reasonable in some cases.
A moderate number of patients were lost to follow up before obtaining a TST result and many patients with positive TSTs did not attend physician appointments. Perhaps standardized videos emphasizing TB prevention presented by Inuit community members to Inuit patients could improve attendance.
By including the results of all TSTs performed in Iqaluit over the study period, our study provides a comprehensive overview of LTBI identification and management in the largest community in Canada’s highest TB incidence region. This represents the first comprehensive data published from the Inuit Nunangat. A further strength is that all LTBI treatment in Iqaluit is directly-observed, minimizing misclassification error.
However, the study is limited by the relatively small number of variables on which data were obtained. This is in part related to this study’s retrospective design which meant that only data listed in medical records could be extracted. As a result, the potential impact of important clinical and socioeconomic factors could neither be assessed nor adjusted for. Additionally, post-hoc statistical analysis regarding the listed reasons for treatment non-completion was considered but rejected because numbers in each category were low (n ≤ 16 for all categories), leading to very limited statistical power. This prevented a more detailed analysis of potential causes of non-completion. While power could have been increased by increasing sample size, study dates were limited by the availability of data.
Given these limitations, richer detail may be better obtained in future through qualitative studies exploring patients’ reasons for not initiating or completing treatment. The common themes could then provide targets for future interventions to improve treatment initiation and completion.
A further limitation is that IGRA results were not comprehensively captured. Although it would not have been in keeping with recommended local practices , it is possible that some patients were tested exclusively with IGRA and thus not included in our study.
An additional limitation is that it is possible that some patients underwent LTBI treatment prior to the study but were included following a repeat TST. This could have led to an underestimation of the treatment completion rate. However, we feel that this would not be not common. This is because it is not standard practice in Iqaluit to treat patients unless they have a positive TST (no patient with a negative TST received LTBI therapy during the study period) and nearly all of those with repeat testing initially had negative TSTs (only 6 patients with a positive TST had a repeat test). Since TSTs relatively infrequently revert to negative after treatment , it is unlikely that many of those with repeat TSTs had undergone a previous course of treatment.