Determinants of mortality among patients with drug-resistant tuberculosis in northern Nigeria.
ABSTRACT: BACKGROUND:Drug-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. METHODS:Demographic 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. RESULTS:Mean 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. CONCLUSION:Both 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.
Project description:BACKGROUND:There were an estimated 580,000 new cases of multidrug/rifampicin resistant TB (DR-TB) in 2015, and only 20% were initiated on treatment. This study explored health system and patient factors associated with initiation and timeliness of treatment among DR-TB patients in Nigeria, ranked 4th globally for estimated TB cases in 2015. METHODS:A retrospective cohort study using 2015 diagnosis and treatment data from the Nigerian TB program electronic records examined "treatment ever received" (yes/no) and "treatment within 30 days" (yes/no). We compared health system and patient characteristics using binomial logistic regression, while controlling for confounders. RESULTS:Of 996 patients diagnosed nationwide in 2015 (aged 0-87 years, median 34), 47.8% were never treated. Of those treated (n = 520), 51.2% were treated within the 30 days prescribed in the National treatment guideline. Healthcare facility locations were significantly associated with ever receiving treatment and timely treatment. Predictors of timely treatment at the national level also included level of care and patient treatment history. The South-West zone, where DR-TB programs started, showed overall better access to DR-TB healthcare. CONCLUSIONS:Healthcare facility geographic locations were significantly associated with treatment initiation and timeliness. Significant regional differences in access to DR-TB care in Nigeria persist, reflecting uneven contexts for national DR-TB treatment rollout.
Project description:A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting.LFT, defined as interruption of treatment for ?2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013.Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment.LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.
Project description:Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR antiretroviral therapy (ART) clinics in the southwest and north central regions in Nigeria. Smear-positive sputum samples were submitted for GenoType MTBDRplus testing (n = 415); mutations were confirmed through sequencing. Our results show high rates of DR-TB in Nigerian HIV-infected individuals (7.0% for rifampin [RIF] and 9.3% for RIF or isoniazid [INH]). Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted.
Project description:Since in low incidence TB countries population migration and complex treatment of drug-resistant tuberculosis (DR-TB) patients are major issues, we aimed to analyse patient risk factors associated with the incidence of poor outcome of TB treatment among DR-TB patients in the Netherlands. This retrospective cohort study included adult patients with confirmed DR-TB treated from 2005 to 2015. We obtained data from a nationwide exhaustive registry of tuberculosis patients in the Netherlands. Predictors for unsuccessful TB treatment (defaulted and failed treatment) and TB-associated mortality were analysed using multivariate logistic regression. Among 10,303 registered TB patients, 545 patients with DR-TB were analysed. Six types of DR-TB were identified from the included patients, i.e. isoniazid mono- or poly-resistance (68%); rifampicin mono- or poly-resistance (3.1%); pyrazinamide mono-resistance (8.3%); ethambutol mono-resistance (0.1%); multidrug-resistance (18.9%); and extensively drug-resistance (0.7%). The majority of patients were foreign-born (86%) and newly diagnosed TB (89%) patients. The cumulative incidence of unsuccessful treatment and mortality were 5 and 1%, respectively. Among all DR-TB cases, patients with Multi Drug-Resistant Tuberculosis (MDR-TB) (OR 4.43; 95%CI 1.70-11.60) were more likely to have unsuccessful treatment, while miliary and central nervous system TB (OR 15.60; 95%CI 2.18-111.52) may also be predictors for TB mortality. Additionally, patients with substance abuse and homelessness tend to have unsuccessful treatment. In recent years, we identified a low incidence of DR-TB as well as the poor outcome of DR-TB treatment. The majority of cases were primary drug-resistant and foreign-born. To further improve treatment outcome, special attention should be given to the high-risk DR-TB patients.
Project description:BACKGROUND:Nigeria had the most AIDS-related deaths worldwide in 2014 (170,000), and 46% were associated with tuberculosis (TB). Although treatment of people living with HIV (PLHIV) with antiretroviral therapy (ART) reduces TB-associated morbidity and mortality, incident TB can occur while on ART. We estimated incidence and characterized factors associated with TB after ART initiation in Nigeria. METHODS:We analyzed retrospective cohort data from a nationally representative sample of adult patients on ART. Data were abstracted from 3,496 patient records, and analyses were weighted and controlled for a complex survey design. We performed domain analyses on patients without documented TB disease and used a Cox proportional hazard model to assess factors associated with TB incidence after ART. RESULTS:At ART initiation, 3,350 patients (95.8%) were not receiving TB treatment. TB incidence after ART initiation was 0.57 per 100 person-years, and significantly higher for patients with CD4<50/?L (adjusted hazard ratio [AHR]: 4.2, 95% confidence interval [CI]: 1.4-12.7) compared with CD4?200/?L. Patients with suspected but untreated TB at ART initiation and those with a history of prior TB were more likely to develop incident TB (AHR: 12.2, 95% CI: 4.5-33.5 and AHR: 17.6, 95% CI: 3.5-87.9, respectively). CONCLUSION:Incidence of TB among PLHIV after ART initiation was low, and predicted by advanced HIV, prior TB, and suspected but untreated TB. Study results suggest a need for improved TB screening and diagnosis, particularly among high-risk PLHIV initiating ART, and reinforce the benefit of early ART and other TB prevention efforts.
Project description:Background. Despite the dramatic scale-up of antiretroviral therapy in low- and middle-income countries, tuberculosis (TB) is still the main cause of death among HIV-infected patients in resource-limited settings. Previous studies in patients with TB meningitis suggest that the use of higher doses of common anti-TB drugs could reduce mortality. Methods. Using clinical data from an HIV cohort study in India, we compared the mortality among HIV-infected patients diagnosed with TB according to the regimen received during the first two weeks of treatment: standard anti-tuberculosis therapy (ATT) (N = 847), intensified ATT (N = 322), and intensified ATT with streptomycin (N = 446). The intensified ATT comprised double dose of rifampicin and substitution of ethambutol with levofloxacin. Multivariate analysis was performed using Cox proportional hazard models and inverse probability of treatment weighting (IPTW) based on propensity scores. Patients with TB meningitis were excluded. Results. The use of intensified ATT alone did not improve survival. However, when streptomycin was added, the use intensified ATT was associated with reduced mortality in Cox models (adjusted hazard ratio 0.72, 95% CI [0.57-0.91]) and after IPTW (hazard ratio 0.77, 95% CI [0.67-0.96]). Other factors associated with improved survival were high serum albumin concentration, high CD4 lymphocyte cell-counts, and high glomerular filtration rates. Factors associated with increased mortality were high urea concentrations, being on antiretroviral therapy at the time of ATT initiation and high BUN/creatinine ratio. In an effect modification analysis, the survival benefits of the intensified ATT with streptomycin disappeared in patients with severe hypoalbuminemia. Conclusion. The results of this study are in accordance with a previous study from our cohort involving patients with TB meningitis, and suggest that an intensified 2-week ATT with streptomycin could reduce mortality in HIV infected patients with TB. As this is an observational study, we should be cautious about our conclusions, but given the high mortality of HIV-related TB, our findings deserve further research.
Project description:INTRODUCTION:Tuberculosis (TB) mortality estimates derived only from cohorts of patients initiated on TB treatment do not consider outcomes of patients with pretreatment loss to follow-up (LFU). We aimed to assess the effect of pretreatment LFU on TB-associated mortality in the six months following TB diagnosis at public health facilities in Uganda. METHODS:At ten public health facilities, we retrospectively reviewed treatment data for all patients with a positive Xpert®MTB/RIF test result from January to June 2018. Pretreatment LFU was defined as not initiating TB treatment within two weeks of a positive test. We traced patients with pretreatment LFU to ascertain their vital status. We performed Kaplan Meier survival analysis to compare the cumulative incidence of mortality, six months after diagnosis among patients who did and did not experience pretreatment LFU. We also determined the health facility level estimates of TB associated mortality before and after incorporating deaths prior to treatment initiation among patients who experienced pretreatment LFU. RESULTS:Of 510 patients with positive test, 100 (19.6%) experienced pretreatment LFU. Of these, we ascertained the vital status of 49 patients. In the six months following TB diagnosis, mortality was higher among patients who experienced pretreatment LFU 48.1/1000py vs 22.9/1000py. Hazard ratio [HR] 3.18, 95% confidence interval [CI] (1.61-6.30). After incorporating deaths prior to treatment initation among patients who experienced pretreatment LFU, health facility level estimates of TB associated mortality increased from 8.4% (95% CI 6.1%-11.6%) to 10.2% (95% CI 7.7%-13.4%). CONCLUSION:Patients with confirmed TB who experience pretreatment LFU have high mortality within the first six months. Efforts should be made to prioritise linkage to treatment for this group of patients. Deaths that occur prior to treatment initation should be included when reporting TB mortality in order to more accurately reflect the health impact of TB.
Project description:<h4>Objectives</h4>Provision of drug-resistant tuberculosis (DR-TB) treatment is scarce in resource-limited settings. We assessed the feasibility of ambulatory DR-TB care for treatment expansion in rural Eswatini.<h4>Methods</h4>Retrospective patient-level data were used to evaluate ambulatory DR-TB treatment provision in rural Shiselweni (Eswatini), from 2008 to 2016. DR-TB care was either clinic-based led by nurses or community-based at the patient's home with involvement of community treatment supporters for provision of treatment to patients with difficulties in accessing facilities. We describe programmatic outcomes and used multivariate flexible parametric survival models to assess time to adverse outcomes. Both care models were costed in supplementary analyses.<h4>Results</h4>Of 698 patients initiated on DR-TB treatment, 57% were women and 84% were HIV-positive. Treatment initiations increased from 27 in 2008 to 127 in 2011 and decreased thereafter to 51 in 2016. Proportionally, community-based care increased from 19% in 2009 to 77% in 2016. Treatment success was higher for community-based care (79%) than clinic-based care (68%, P = 0.002). After adjustment for covariate factors among adults (n = 552), the risk of adverse outcomes (death, loss to follow-up, treatment failure) in community-based care was reduced by 41% (adjusted hazard ratio 0.59, 95% CI: 0.39-0.91). Findings were supported by sensitivity analyses. The care provider's per-patient costs for community-based (USD13 345) and clinic-based (USD12 990) care were similar.<h4>Conclusions</h4>Ambulatory treatment outcomes were good, and community-based care achieved better treatment outcomes than clinic-based care at comparable costs. Contextualised DR-TB care programmes are feasible and can support treatment expansion in rural settings.
Project description:BACKGROUND:In 2011, South Africa improved its ability to test for rifampicin-resistant TB (RR-TB) by introducing GeneXpert MTB/RIF. At the same time, the South African National TB program adopted a policy decentralized, outpatient treatment for drug resistant (DR-) TB. We aim to analyze the impact of these changes on linkage to care and DR-TB treatment outcomes. METHODS:We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 (early cohort) and 07/2013-06/2014 (late cohort) with records of patients initiating DR-TB treatment at one of the city's four public sector treatment sites. We determine the proportion of persons diagnosed with RR-TB who initiated DR-TB treatment and report time to treatment initiation (TTI) before and after the implementation of Xpert MTB/RIF roll-out in Johannesburg, South Africa. We conducted a sub-analysis among those who initiated DR-TB treatment at the decentralized outpatient DR-TB centers to determine if delays in treatment initiation have a subsequent impact on treatment outcomes. RESULTS:Five hundred ninety four patients were enrolled in the early cohort versus 713 in the late cohort. 53.8 and 36.8% of patients were diagnosed with multi-drug resistant TB in the early and late cohorts, respectively. The proportion of RR-TB confirmed cases diagnosed by Xpert MTB/RIF increased from 43.4 to 60.5% between the early and late cohorts, respectively. The proportion who initiated treatment increased from 43.1% (n?=?256) to 60.3% (n?=?430) in the late cohort. Pre-treatment mortality during the early and the late cohort reduced significantly from 17.5 to 5.8% while lost to follow-up remained high. Although TTI reduced by a median of 19?days, from 33?days (IQR 12-52) in the early cohort to 14?days (IQR 7-31) in the late cohort, this did not translate to improved treatment outcomes and we found no difference in terms of treatment success or on-treatment mortality for those that initiated without delay vs. those that deferred initiation. CONCLUSION:Pre-treatment mortality reduced significantly during late Xpert MTB/RIF coverage but there was no significant difference after treatment was initiated. Despite improvements there is still a significant diagnosis and treatment gap for patients diagnosed with RR-TB and improving treatment outcomes remains critical.
Project description:<h4>Background</h4>Adverse events (AEs) are common during treatment of drug-resistant tuberculosis (DR-TB). Little is known about the health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of AEs on HRQoL.<h4>Methods</h4>We conducted a cross-sectional study among adult patients with laboratory-confirmed rifampicin resistant tuberculosis (TB) on DR-TB treatment at a public-sector outpatient DR-TB clinic in Johannesburg, South Africa between 02/2015-01/2018. Data on HRQoL using the Medical Outcomes Short Form-36 (SF-36) questionnaire and self-reported AEs were collected by trained interviewers through face-to-face interviews. We report averages for the eight major domains and mental (MCS) and physical health (PCS) component summary scores, stratified by whether AEs were reported in the last four weeks. For comparative purposes, we enrolled two other patient groups and included data on a separate group of healthy adults.<h4>Results</h4>We enrolled 149 DR-TB patients (median age 36?years IQR 29-43, 55% male, 77.9% HIV-positive, 81% on ART, 61.8% on a standard long-course regimen and 44.3% on DR-TB treatment for less than 6?months). 58/149 (38.9%) patients reported a total of 122 AEs in the preceding 4?weeks, of these the most common were joint pain (n?=?22), peripheral neuropathy (n?=?16), hearing loss (n?=?15), nausea and vomiting (n?=?12) and dizziness or vertigo (n?=?11). SF-36 domains and summary scores (MCS and PCS) were lower in those who reported an AE compared to those who did not, and both were lower than healthy adults. Compared to those who did not report an AE, patients who reported AEs were more likely to have a low MCS (aRR 2.24 95% CI 1.53-3.27) and PCS (aRR 1.52 95% CI 1.07-2.18) summary score. HRQoL was lower among those on DR-TB treatment for 6?months or less.<h4>Conclusion</h4>Results show that DR-TB had a substantial impact on patients' quality of life, but that AEs during the early months on treatment may be responsible for reducing HRQoL even further. Our findings highlight the negative effects of injectable agents on HRQoL. Patients require an integrative patient-centered approach to deal with DR-TB and HIV and the potential overlapping toxicities which may be worsened by concurrent treatment.