Determinants of mortality among patients with drug-resistant tuberculosis in northern Nigeria

Abstract

BackgroundDrug-Resistant tuberculosis (DR-TB) is estimated to cause about 10% of all TB related deaths. There is dearth of data on determinants of DR-TB mortality in Nigeria. Death among DR-TB treated cohorts in Nigeria from 2010 to 2013 was 30%, 29%, 15% and 13% respectively. Our objective was to identify factors affecting survival among DR-TB patients in northern Nigeria.MethodsDemographic and clinical data of all DR-TB patients enrolled in Kano, Katsina and Bauchi states of Nigeria between 1st February 2015 and 30th November 2016 was used. Survival analysis was done using Kaplan-Meier and multiple regression with Cox proportional hazard modeling.ResultsMean time to death during treatment is 19.2 weeks and 3.9 weeks among those awaiting treatment. Death was recorded among 38 of the 147 DR-TB patients assessed. HIV co-infection significantly increased probability of mortality, with an adjusted hazard ratio (aHR) of 2.35, 95% CI: 1.05–5.29, p = 0.038. Treatment delay showed significant negative association with survival (p = 0.000), not starting treatment significantly reduced probability of survival with an aHR of 7.98, 95% CI: 2.83–22.51, p = 0.000. Adjusted hazard ratios for patients started on treatment more than eight weeks after detection or within two to four weeks after detection, was beneficial though not statistically significant with respective p-values of 0.056 and 0.092. The model of care (facility vs. community-based) did not significantly influence survival.ConclusionBoth HIV co-infected DR-TB patients and DR-TB patients that fail to start treatment immediately after diagnosis are at significant risk of mortality. Our study showed no significant difference in mortality based on models of care. The study highlights the need to address programmatic and operational issues pertaining to treatment delays and strengthening DR-TB/HIV co-management as key strategies to reduce mortality.

Poor treatment outcome and its predictors among drug-resistant tuberculosis patients in Ethiopia: A systematic review and meta-analysis

“…Relatively lower mortality rates were reported from Kenya (Kiprotich et al, 2014), Sudan (Ali et al, 2019), Egypt (Gadallah et al, 2016), Brazil (Gayoso et al, 2018), USA (Kurbatova et al, 2012), Lativa (Leimane et al, 2005), Tanzania (Mollel and Chilongola, 2017), and China (Zhang et al, 2018). However, higher mortality reported from Pakistan (Kanwal et al, 2017), Nigeria (Bajehson et al, 2019), Eastern Europe (Balabanova et al, 2016), South Africa (Chingonzoh et al, 2018;Farley et al, 2011;Schnippel et al, 2015), Lesotho (Dheda et al, 2012), South Korea (Jeon et al, 2011), Bulgaria (Milanov et al, 2015) and Peru (Mitnick et al, 2013). The pooled incidence density rate of mortality in this study was 9.28/1000 PMs.…”

“…Even though treatments of MDR-TB save the lives of millions globally, a significant proportion of patients are still dying or have a poor treatment outcome. It was reported elsewhere that the majority of deaths and poor treatment outcomes occur during the first months of the MDR-TB treatment course (Bajehson et al, 2019;Balabanova et al, 2016;Chingonzoh et al, 2018;Farley et al, 2011;Kanwal et al, 2017;Schnippel et al, 2015;Dheda et al, 2012;Jeon et al, 2011); individual studies conducted in Ethiopia also supported this (Ketema et al, 2019;Alene et al, 2017;Getachew et al, 2013;Girum et al, 2017;Shimbre et al, 2020;Gebre et al, 2020;Fantaw et al, 2018). However, there is no comprehensive report on the time to poor treatment outcome and its predictors among patients treated for MDR-TB in Ethiopia.…”

“…The poor treatment outcome is the share of different risk factors. Among the risk factors are being HIV positive, the weight of the patient, age of the patient, presence of other comorbidities or co-infections, smoking, alcohol, patient condition, delay to start treatment, resistance to more than two anti-TB drugs and involvement of TB outside the lungs are reported (Chung-Delgado et al, 2015;Ketema et al, 2019;Bajehson et al, 2019;Balabanova et al, 2016;Chingonzoh et al, 2018;Khan et al, 2015;Farley et al, 2011;Li et al, 2016;Makhmudova et al, 2019;Kurbatova et al, 2012;Bei et al, 2018;Alene et al, 2017;Limenih and Workie, 2019;Woldeyohannes et al, 2019).…”

Unfavorable outcomes to second-line tuberculosis therapy among HIV-infected versus HIV-uninfected patients in sub-Saharan Africa: A systematic review and meta-analysis

“…Similarly, the risk of death during treatment with second-line anti-tuberculosis drugs was significantly increased by 50% (1.50 times higher) among HIV-infected patients compared with those HIV-uninfected ones. Consistently, variable but positive relationships indicated between mortality during course of the second-line anti-tuberculosis regimen and presence of HIV-infection with 1.46 (in a study with 3,802 participants) [ 68 ]; 1.7 (for ART initiated) and 2.3 (for no ART) (in a study with 3,566 participants) [ 69 ]; 2.35 (in a study with 147 participants) [ 70 ]; 4.2 (in a study with 1,768 participants) [ 71 ]; 5.6 (in a study with 2,097 participants) [ 72 ]; 5.6 (in a study with 1,209 participants) [ 73 ]; and 29.9 (in a study with 50 participants) [ 74 ] times higher risks or odds of death in the HIV-infected patients than in those HIV-uninfected counterparts. Again, reports for the rates of mortality during the second-line TB therapy among HIV-infected versus HIV-uninfected patients showed 14% versus 6% in a study with 206 participants [ 75 ], 20% versus 9% in a study with 671 participants [ 76 ], and 72% versus 20% in a study with 173 participants [ 77 ]; all of them aligned with our study finding.…”

Treatment delay in childhood pleural tuberculosis and associated factors

“…For example, in a meta-analysis, treatment delay was identified as a predictor of poor treatment outcome (death and failure) [ 13 ]. A study conducted by Bajehson et al found a significant negative association between treatment delay and survival [ 14 ]. One possible explanation for this is that delay is significantly associated with clinical severity at presentation [ 15 ].…”