The role of bacteriological monitoring using culture and drug susceptibility tests (CDST) on treatment outcomes among MDR/RR-TB patients on treatment: a cohort analysis of patients enrolled on treatment 2010-2015 in Zimbabwe.

INTRODUCTION: an estimated 25% of the world population is infected with Mycobacterium tuberculosis. In 2017, new tuberculosis cases were estimated at 10 million, while 1.6 million tuberculosis related deaths were recorded, 25% residing in Africa. Treatment outcomes of multi drug resistant Tuberculosis patients in Zimbabwe has been well documented but the role of bacteriological monitoring on treatment outcomes has not been systematically evaluated. The objective of the study was to determine the role of bacteriological monitoring using culture and drug susceptibility tests on treatment outcomes among patients with multi drug resistant tuberculosis. METHODS: a retrospective, secondary data analysis was conducted using routinely collected data of patients with multi drug resistant TB in Zimbabwe. Frequencies were used to summarize categorical variables and a generalized linear model with a log-link function and a Poisson distribution was used to assess factors associated with unfavourable outcomes. The level of significance was set at P-Value<0.05. RESULTS: about the study collected data from 473 records of patients with an average age of 36.35 years. Forty-nine percent (49%) were male and 51% were female. Results showed that when a patient has baseline culture result missing, has no culture conversion result, regardless of having a follow up culture and drug susceptibility test result, the risk of developing unfavourable outcomes increase by 3.9 times compared to a patient who has received all the three (3) bacteriological monitoring tests. CONCLUSION: results highlights the need for consistent bacteriological monitoring of patients to avert unfavourable treatment outcomes.

Predictors of mortality and treatment success of multi-drug resistant and Rifampicin resistant tuberculosis in Zimbabwe: a retrospective cohort analysis of patients initiated on treatment during 2010 to 2015.

INTRODUCTION: Zimbabwe is one of the 30 countries globally with a high burden of multidrug-resistant TB or rifampicin-resistant TB. The World Health Organization recommended that patients diagnosed with multidrug-resistant TB be treated with 20-24 month standardized second-line drugs since 2010. However, factors associated with mortality and treatment success have not been systematically evaluated in Zimbabwe. The Objective of the study was to assess factors associated with Mortality and treatment success among multidrug-resistant-TB patients registered and treated under the National Tuberculosis programme in Zimbabwe. METHODS: the study was conducted using secondary data routinely collected from the National tuberculosis (TB) programme. Categorical variables were summarised using frequencies and a generalized linear model with a log-link function and a Poisson distribution was used to assess factors associated with mortality and treatment success. The level of significance was set at P-Value < 0.05. RESULTS: patient antiretroviral therapy (ART) status was a significant associated factor of treatment success or failure (RRR = 3.92, p < 0.001). Patients who were not on ART had a high risk of death by 3.92 times compared to patients who were on ART. In the age groups 45 - 54 years (relative risk ratios (RRR) = 1.41, p = 0.048), the risk of death was increased by 1.41 times compared to other age groups. Patients aged 55 years and above (RRR = 1.55, p = 0.017), had a risk of dying increased by 1.55 times compared to other age groups. Diagnosis time duration of 8 - 30 days (RRR = 0.62, p = 0.022) was found to be protective, a shorter diagnosis time duration between 8 to 30 days reduced the risk of TB deaths by 0.62 times compared to longer periods. Missed TB doses of > 10% (RRR = 2.03, p < 0.001) increased the risk of MDR/RR-TB deaths by 2.03 times compared to missing TB doses of ≤ 10%. CONCLUSION: not being on ART when HIV positive was a major significant predictor of mortality. Improving ART uptake among those ART-naïve and strategies aimed at improving treatment adherence are important in improving treatment success rates.

Catastrophic costs among tuberculosis-affected households in Zimbabwe: A national health facility-based survey.

OBJECTIVES: To determine the incidence and major drivers of catastrophic costs among TB-affected households in Zimbabwe. METHODS: We conducted a nationally representative health facility-based survey with random cluster sampling among consecutively enrolled drug-susceptible (DS-TB) and drug-resistant TB (DR-TB) patients. Costs incurred and income lost due to TB illness were captured using an interviewer-administered standardised questionnaire. We used multivariable logistic regression to determine the risk factors for experiencing catastrophic costs. RESULTS: A total of 841 patients were enrolled and were weighted to 900 during data analysis. There were 500 (56%) males and 46 (6%) DR-TB patients. Thirty-five (72%) DR-TB patients were HIV co-infected. Overall, 80% (95% CI: 77-82) of TB patients and their households experienced catastrophic costs. The major cost driver pre-TB diagnosis was direct medical costs. Nutritional supplements were the major cost driver post-TB diagnosis, with a median cost of US$360 (IQR: 240-600). Post-TB median diagnosis costs were three times higher among DR-TB (US$1,659 [653-2,787]) than drug DS-TB-affected households (US$537 [204-1,134]). Income loss was five times higher among DR-TB than DS-TB patients. In multivariable analysis, household wealth was the only covariate that remained significantly associated with catastrophic costs: The poorest households had 16 times the odds of incurring catastrophic costs versus the wealthiest households (adjusted odds ratio [aOR: 15.7 95% CI: 7.5-33.1]). CONCLUSION: The majority of TB-affected households, especially those affected by DR-TB, experienced catastrophic costs. Since the major cost drivers fall outside the healthcare system, multi-sectoral approaches to TB control and linking TB patients to social protection may reduce catastrophic costs.

Treatment outcomes of multi drug resistant and rifampicin resistant Tuberculosis in Zimbabwe: A cohort analysis of patients initiated on treatment during 2010 to 2015.

BACKGROUND: Zimbabwe is one of the thirty countries globally with a high burden of multidrug-resistant tuberculosis (TB) or rifampicin-resistant TB (MDR/RR-TB). Since 2010, patients diagnosed with MDR/RR-TB are being treated with 20-24 months of standardized second-line drugs (SLDs). The profile, management and factors associated with unfavourable treatment outcomes of MDR/RR TB have not been systematically evaluated in Zimbabwe. OBJECTIVE: To assess treatment outcomes and factors associated with unfavourable outcomes among MDR/RR-TB patients registered and treated under the National Tuberculosis Programme in all the district hospitals and urban healthcare facilities in Zimbabwe between January 2010 and December 2015. METHODS: A cohort study using routinely collected programme data. The 'death', 'loss to follow-up' (LTFU), 'failure' and 'not evaluated' were considered as "unfavourable outcome". A generalized linear model with a log-link and binomial distribution or a Poisson distribution with robust error variances were used to assess factors associated with "unfavourable outcome". The unadjusted and adjusted relative risks were calculated as a measure of association. A 𝑝value< 0.05 was considered statistically significant. RESULTS: Of the 473 patients in the study, the median age was 34 years [interquartile range, 29-42] and 230 (49%) were males. There were 352 (74%) patients co-infected with HIV, of whom 321 (91%) were on antiretroviral therapy (ART). Severe adverse events (SAEs) were recorded in 118 (25%) patients; mostly hearing impairments (70%) and psychosis (11%). Overall, 184 (39%) patients had 'unfavourable' treatment outcomes [125 (26%) were deaths, 39 (8%) were lost to follow-up, 4 (<1%) were failures and 16 (3%) not evaluated]. Being co-infected with HIV but not on ART [adjusted relative risk (aRR) = 2.60; 95% CI: 1.33-5.09] was independently associated with unfavourable treatment outcomes. CONCLUSION: The high unfavourable treatment outcomes among MDR/RR-TB patients on standardized SLDs were coupled with a high occurrence of SAEs in this predominantly HIV co-infected cohort. Switching to individualized all oral shorter treatment regimens should be considered to limit SAEs and improve treatment outcomes. Improving the ART uptake and timeliness of ART initiation can reduce unfavourable outcomes.

Prevalence of drug-resistant tuberculosis in Zimbabwe: A health facility-based cross-sectional survey.

OBJECTIVE: To determine the prevalence of resistance to rifampicin alone; rifampicin and isoniazid, and second-line anti-TB drugs among sputum smear-positive tuberculosis patients in Zimbabwe. DESIGN: A health facility-based cross-sectional survey. RESULTS: In total, 1114 (87.6%) new and 158 (12.4%) retreatment TB patients were enrolled. MTB was confirmed by Xpert MTB/RIF among 1184 (93%) smear-positive sputum samples. There were 64 samples with Xpert MTB/RIF-determined rifampicin resistance. However, two were rifampicin susceptible on phenotypic drug susceptibility testing. The prevalence of RR-TB was [4.0% (95% CI, 2.9, 5.4%), n=42/1043) and 14.2% (95% CI, 8.9, 21.1%; n=20/141) among new and retreatment patients, respectively. The prevalence of MDR-TB was 2.0% (95% CI, 1.3, 3.1%) and 6.4% (95% CI, 2.4, 10.3%) among new and retreatment TB patients, respectively. Risk factors for RR-TB included prior TB treatment, self-reported HIV infection, travel outside Zimbabwe for ≥one month (univariate), and age <15 years. Having at least a secondary education was protective against RR-TB. CONCLUSION: The prevalence of MDR-TB in Zimbabwe has remained stable since the 1994 subnational survey. However, the prevalence of rifampicin mono-resistance was double that of MDR-TB.

Access to second-line drug susceptibility testing results among patients with Rifampicin resistant tuberculosis after introduction of the Hain® Line Probe Assay in Southern provinces, Zimbabwe.

OBJECTIVES: To determine the proportion of rifampicin-resistant tuberculosis (RR-TB) patients who accessed second-line drug susceptibility testing (SL-DST) results following introduction of the Hain technology in southern provinces, Zimbabwe. DESIGN: Cohort study using secondary data. RESULTS: Xpert MTB/RIF results were used to identify 133 RR-TB patients for this study. Their mean age (SD) was 37.9 (11.1) years, 83 (62%) were males and 106 (80%) were HIV-infected. There were 6 (5%) participants who had pre-treatment attrition. Of the 133 pulmonary TB (PTB) patients, 117 (80%) had additional sputum specimens collected; 96 (72%) specimens reached the National TB Reference Laboratory (NTBRL); 95 (71%) were processed; 68 (51%) had SL-DST results. Only 53 (40%) SL-DST results reached the peripheral facilities. Median time from specimen reception at the NTBRL to SL-DSTs was 40 days, interquartile range (IQR: 28-67). Median time from presumptive diagnosis of RR-TB by health care worker to SL-DST results was 50days (IQR: 39-80), and increased to 79days (IQR: 39-101) in facilities >250km from the NTBRL. The proportion with any fluoroquinolone resistance was 9 (13.2%). CONCLUSION: Although RR-TB patients with PTB were initiated timely on treatment, access to SL-DSTs by facilities needs improvement. Health inequities exist as remote areas are less likely to get SL-DST results in time.

Tuberculosis treatment delays and associated factors within the Zimbabwe national tuberculosis programme.

BACKGROUND: Delayed presentation of pulmonary TB (PTB) patients for treatment from onset of symptoms remains a threat to controlling individual disease progression and TB transmission in the community. Currently, there is insufficient information about treatment delays in Zimbabwe, and we therefore determined the extent of patient and health systems delays and their associated factors in patients with microbiologically confirmed PTB. METHODS: A structured questionnaire was administered at 47 randomly selected health facilities in Zimbabwe by trained health workers to all patients aged ≥18 years with microbiologically confirmed PTB who were started on TB treatment and entered in the health facility TB registers between 01 January and 31 March 2013. Multivariate logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for associations between patient/health system characteristics and patient delay >30 days or health system delay >4 days. RESULTS: Of the 383 recruited patients, 211(55%) were male with an overall median age of 34 years (IQR, 28-43). There was a median of 28 days (IQR, 21-63) for patient delays and 2 days (IQR, 1-5) for health system delays with 184 (48%) and 118 (31%) TB patients experiencing health system delays >30 days and health system delays >4 days respectively. Starting TB treatment at rural primary healthcare vs district/mission facilities [aOR 2.70, 95% CI 1.27-5.75, p = 0.01] and taking self-medication [aOR 2.33, 95% CI 1.23-4.43, p = 0.01] were associated with encountering patient delays. Associated with health system delays were accessing treatment from lower level facilities [aOR 2.67, 95% CI 1.18-6.07, p = 0.019], having a Gene Xpert TB diagnosis [aOR 0.21, 95% CI 0.07-0.66, p = 0.008] and >4 health facility visits prior to TB diagnosis [(aOR) 3.34, 95% CI 1.11-10.03, p = 0.045]. CONCLUSION: Patient delays were longer and more prevalent, suggesting the need for strategies aimed at promoting timely seeking of appropriate medical consultation among presumptive TB patients. Health system delays were uncommon, suggesting a fairly efficient response to microbiologically confirmed PTB cases. Identified risk factors should be explored further and specific strategies aimed at addressing these factors should be identified in order to lessen patient and health system delays.