Health Screening Strategies for Artisanal and Small-Scale Miners for Tuberculosis, Human Immunodeficiency Virus and Silicosis: A Case of the USAID-Supported Kunda Nqob'iTB Project in Zimbabwe.

Artisanal and small-scale mining is characterized by excessive exposure to physical, chemical, ergonomic, psychosocial and biological hazards. There is a high burden of tuberculosis (TB), human immunodeficiency virus (HIV) infections and silicosis among artisanal and small-scale miners (ASMs). The aim of this project report is to describe lessons learned from strategies implemented to reach ASMs with screening services for TB, HIV and silicosis in Zimbabwe through the Kunda-Nqob'i TB (KNTB) project supported by the United States Agency for International Development (USAID). The intervention package for screening ASMs for TB, HIV and silicosis included service provision through two occupational health clinics at two provincial hospitals and a mobile workplace-based screening (WBS) facility at the mining sites. From 1 October 2020 to 30 September 2023, 10,668 ASMs were screened, with a high number of cases of silicosis (21%) and TB (7.4%). There was a high burden of HIV (30%) in ASMs attending the occupational health clinics. The two occupational health clinics screened 3453 ASMs, while the mobile WBS activities screened 7215 ASMs during the period. A total of 370 healthcare workers (doctors/clinical officers, nurses, environmental health technicians and district tuberculosis and Leprosy control officers) were trained on TB and the fundamental diagnostic principles of silicosis. The KNTB project has been successful in reaching out to many ASMs operating in remote and hard-to-reach mining areas. The KNTB project has brought to light the positive health-seeking behavior of ASMs operating in remote areas. The project has brought to the fore the effectiveness of multi-stakeholder engagement and collaboration in reaching out to ASMs in remote areas with health screening services. There is a high burden of TB, HIV and silicosis in ASMs. Screening for TB, HIV and silicosis using workplace-based screening and occupational health clinics is an effective strategy and should be rolled out to all areas with high artisanal and small-scale mining activity.

Knowledge, Attitudes, and Practices of Artisanal and Small-Scale Miners regarding Tuberculosis, Human Immunodeficiency Virus, and Silicosis in Zimbabwe.

In Zimbabwe, artisanal and small-scale miners (ASMs) have a high prevalence of tuberculosis (TB), human immunodeficiency virus (HIV), and silicosis. Previous studies on ASMs utilised programme data, and it was not possible to understand reasons for the high prevalence of these comorbidities. We conducted a cross-sectional study to investigate the knowledge, attitudes, and practices of ASMs regarding TB, HIV, and silicosis. We enrolled a convenience sample of 652 ASMs. Their mean (standard deviation) age was 34.2 (10.8) years. There were 602 (92%) men and over 75% had attained secondary education. A total of 504 (80%) of the ASMs knew that TB is a curable disease, and 564 (87%) knew that they were at higher risk of TB than the general population. However, they were less likely to know that HIV increases the risk of TB disease, 340 (52%), with only 226 (35%) who perceived the risk of TB infection to be high among ASMs. Only 564 (59%) were aware that silica dust causes permanent and incurable lung diseases. Six hundred and twenty (97%) showed a positive attitude towards healthcare when they were sick, and 97% were willing to use special respirators to prevent dust inhalation. On practices, only 159 (30%) reported consistent use of either cloth or respirators to prevent dust inhalation. Three hundred and five (49%) ASMs reported consistent use of condoms outside their homes and 323 (50%) reported use of water to suppress dust. Only 480 (75%) of ASMs sought healthcare services when sick. ASMs cited challenges of accessing healthcare services due to lack of money to pay for healthcare (50%), long distances to clinics (17%), and the shortage of medicines at clinics (11%). Effective control of TB, silicosis, and HIV among ASMs requires addressing the identified knowledge gaps and barriers that are faced by ASMs in accessing personal protective equipment and healthcare services. This will require multisector collaboration and the involvement of ASMs in co-designing a package of healthcare services that are tailored for them.

The Triple Burden of Tuberculosis, Human Immunodeficiency Virus and Silicosis among Artisanal and Small-Scale Miners in Zimbabwe.

Artisanal and small-scale mining is characterized by an excessive exposure to silica-containing dust, overcrowding, poor living conditions and limited access to primary health services. This poses a risk to tuberculosis, HIV infection and silicosis. The main purpose of the study is to evaluate the burden of tuberculosis, HIV and silicosis among artisanal and small-scale miners. We conducted a cross sectional study on 3821 artisanal and small-scale miners. We found a high burden of silicosis (19%), tuberculosis (6.8%) and HIV (18%) in a relatively young population, with the mean age of 35.5 years. Men were 1.8 times more likely to be diagnosed with silicosis compared to women, adjusted prevalence ratio [aPR = 1.75 (95% CI: 1.02-2.74)]. Artisanal and small-scale miners who were living with HIV were 1.25 times more likely to be diagnosed with silicosis compared to those who were negative, [aPR = 1.25 (1.00-1.57)]. The risk of silicosis increased with both duration as a miner and severity of exposure to silica dust. The risk of tuberculosis increased with the duration as a miner. Zimbabwe is currently experiencing a high burden of TB, silicosis and HIV among artisanal and small-scale miners. Multi-sectoral and innovative interventions are required to stem this triple epidemic in Zimbabwe.

Retention and performance of peer educators and sustainability of HIV prevention services for adolescents in the Zimbabwe Smart-LyncAges project: an ecological study.

Introduction: in 2016, the partner-funded Smart-LyncAges participatory learning project explored the feasibility of a youth-friendly package including incentivized peer educators (PEs) to enhance adolescent sexual and reproductive health (ASRH) and voluntary medical male circumcision (VMMC) linkages. After 12 months of implementation, funding reduction resulted in reduced direct project monitoring and discontinuation of monetary incentives for PEs. We assessed if reduced funding after one year of implementation affected the performance and retention of PEs and uptake of VMMC and HIV testing in ASRH services by adolescents in Bulawayo City (urban) and Mount (Mt) Darwin District (rural) in Zimbabwe. Methods: our study was an ecological study using routine data collected from March 2016 to February 2017 (intensive support) and March 2017 to February 2018 (reduced support). All the ASRH and VMMC sites in Mt Darwin and Bulawayo were involved. Participants included 58 PEs and all adolescents accessing VMMC and ASRH services. Retention of PEs measured by the submission of monthly reports and uptake of VMMC and HIV testing were the primary outcome measures. Results: the Smart-LyncAges project engaged 58 PEs with 80% aged 20-24 years. Two-thirds were male and 60% were engaged in peer education before the project. Retention of PEs was not negatively affected by funding reduction, with 70% retained up to 11 months after funding reduction. However, their performance, measured by submission of monthly activity reports and the number of adolescents reached with VMMC and HIV messages, declined while uptake of both VMMC and HIV testing was sustained. Conclusion: sustained uptake of services was possibly due to heightened awareness of service availability and demand generation in the first year of implementation. Peer-led interventions are effective for health information dissemination. Monetary incentives determine performance, but are not the only reason for retention.

Tuberculosis and Silicosis Burden in Artisanal and Small-Scale Gold Miners in a Large Occupational Health Outreach Programme in Zimbabwe.

Artisanal and small-scale miners (ASMs) labour under archaic working conditions and are exposed to high levels of silica dust. Exposure to silica dust has been associated with an increased risk of tuberculosis and silicosis. ASMs are highly mobile and operate in remote areas with near absent access to health services. The main purpose of this study was to evaluate the prevalence of tuberculosis, silicosis and silico-tuberculosis among ASMs in Zimbabwe. A cross-sectional study was conducted from 1 October to 31 January 2021 on a convenient sample of 514 self-selected ASMs. We report the results from among those ASMs who attended an outreach medical facility and an occupational health clinic. Data were collected from clinical records using a precoded data proforma. Data variables included demographic (age, sex), clinical details (HIV status, GeneXpert results, outcomes of chest radiographs, history of tuberculosis) and perceived exposure to mine dust. Of the 464 miners screened for silicosis, 52 (11.2%) were diagnosed with silicosis, while 17 (4.0%) of 422 ASMs were diagnosed with tuberculosis (TB). Of the 373 ASMs tested for HIV, 90 (23.5%) were sero-positive. An HIV infection was associated with a diagnosis of silicosis. There is need for a comprehensive occupational health service package, including TB and silicosis surveillance, for ASMs in Zimbabwe. These are preliminary and limited findings, needing confirmation by more comprehensive studies.

Early retention among pregnant women on 'Option B + ' in urban and rural Zimbabwe.

BACKGROUND: In 2013, the World Health Organisation (WHO) recommended Option B+ as a strategy to prevent mother-to-child transmission (PMTCT) of HIV. In option B+ , lifelong antiretroviral therapy (ART) is offered to all HIV positive pregnant and breastfeeding women to reduce MTCT rate to less than or equal to 5%. Its success depends on retaining women on ART during pregnancy, delivery and breast-feeding period. There is limited data on early retention on ART among pregnant women in Zimbabwe. We therefore assessed early retention among women on Option B + from antenatal care (ANC) until 6 months post ANC booking and at delivery in Bulawayo city and Mazowe rural district of Zimbabwe. METHODS: We collected data for pregnant women booking for ANC between January and March 2018, comparing early retention among ART naïve women and those already on ART. The two cohorts were followed up for 6 months post ANC booking, and this was done in two districts. Data were collected from routine tools used at facility level which include ANC, delivery and ART registers. The Kaplan-Meier survival analysis was used to estimate retention probabilities at 1, 3 and 6 months post-delivery and for retention at delivery proportions were used. Poisson regression was used to investigate factors associated with non-retention at 6 months post ANC booking. RESULTS: A total of 388 women were included in the study with median age of 29 years (IQR: 25-34). Two-thirds booked in their second trimester. Retention at 3 and 6 months post ANC booking was 84% (95% CI 80-88) and 73% (95% CI 69-78) respectively. At delivery 81% (95% CI 76-84) were retained in care, 18% lost-to-follow-up and 1% transferred out. In this study we did not find marital status, gestation age, facility location, ART status at ANC booking, to be associated with loss to follow-up. CONCLUSION: In this study, we found low retention at 3, 6 months and delivery, a threat to elimination of Mother-to-child Transmission of HIV in Zimbabwe. Our findings emphasize the need for enhanced interventions to improve early retention such as post-test counselling, patient tracing and visit reminders.

Anti-retroviral therapy after "Treat All" in Harare, Zimbabwe: What are the changes in uptake, time to initiation and retention?

Background: In Zimbabwe, Harare was the first province to implement "Treat All" for people living with human immunodeficiency virus (PLHIV). Since its roll out in July 2016, no study has been conducted to assess the changes in key programme indicators. We compared antiretroviral therapy (ART) uptake, time to ART initiation from diagnosis, and retention before and during "Treat All". Methods: We conducted an ecological study to assess ART uptake among all PLHIV newly diagnosed before and during "Treat All". We conducted a cohort study to assess time to ART initiation and retention in care among all PLHIV newly initiated on ART from all electronic patient management system-supported sites (n=50) before and during "Treat All". Results: ART uptake increased from 65% (n=4619) by the end of quarter one, 2014 to 85% (n=5152) by the end of quarter four, 2018.  A cohort of 2289 PLHIV were newly initiated on ART before (April-June 2015) and 1682 during "Treat all" (April-June 2017). Their age and gender distribution was similar. The proportion of PLHIV in early stages of disease was significantly higher during "Treat all" (73.2% vs. 55.6%, p<0.001). The median time to ART initiation was significantly lower during "Treat All" (31 vs. 88 days, p<0.001). Cummulative retention at three, six and 12 months was consistently lower during "Treat all" and was significant at six months (74.9% vs.78.1% p=0.022). Conclusion: Although there were benefits of early ART initiation during "Treat All", the programme should consider strategies to improve retention.

Declining Trends in Childhood TB Notifications and Profile of Notified Patients in the City of Harare, Zimbabwe, from 2009 to 2018.

Globally, childhood tuberculosis (TB among those aged <15 years) is a neglected component of national TB programmes in high TB burden countries. Zimbabwe, a country in southern Africa, is a high burden country for TB, TB-HIV, and drug-resistant TB. In this study, we assessed trends in annual childhood TB notifications in Harare (the capital of Zimbabwe) from 2009 to 2018 and the demographic, clinical profiles, and treatment outcomes of childhood TB patients notified from 2015-2017 by reviewing the national TB programme records and reports. Overall, there was a decline in the total number of TB patients (all ages) from 5,943 in 2009 to 2,831 in 2018. However, the number of childhood TB patients had declined exponentially 6-fold from 583 patients (117 per 100,000 children) in 2009 to 107 patients (18 per 100,000 children) in 2018. Of the 615 childhood TB patients notified between 2015 and 2017, 556 (89%) patient records were available. There were 53% males, 61% were aged <5 years, 92% were new TB patients, 85% had pulmonary TB, and 89% were treated for-drug sensitive TB, 3% for drug-resistant TB, and 40% were HIV positive (of whom 59% were on ART). Although 58% had successful treatment outcomes, the treatment outcomes of 40% were unknown (not recorded or not evaluated), indicating severe gaps in TB care. The disproportionate decline in childhood TB notifications could be due to the reduction in the TB burden among HIV positive individuals from the scale up of antiretroviral therapy and isoniazid preventive therapy. However, the country is experiencing economic challenges which could also contribute to the disproportionate decline in childhood TB notification and gaps in quality of care. There is an urgent need to understand the reasons for the declining trends and the gaps in care.

Children and adolescents on anti-retroviral therapy in Bulawayo, Zimbabwe: How many are virally suppressed by month six?

Background: Zimbabwe is one of the countries in sub-Saharan Africa disproportionately affected by human immunodeficiency virus. In the "treat all" era, we assessed the gaps in routine viral load (VL) monitoring at six months for children (0-9 years) and adolescents (10-19 years) newly initiated on anti-retroviral therapy (ART) from January 2017 to September 2018 at a large tertiary hospital in Bulawayo. Methods: In this cohort study using secondary data, we considered first VL done within six to nine months of starting therapy as 'undergoing VL test at six months'. We classified repeat VL≥1000 copies/ml despite enhanced adherence counselling as virally unsuppressed. Results: Of 295 patients initiated on ART, 196 (66%) were children and 99 (34%) adolescents. A total 244 (83%) underwent VL test at six months, with 161 (54%) virally suppressed, 52 (18%) unsuppressed and 82 (28%) with unknown status (due to losses in the cascade). Switch to second line was seen in 35% (18/52). When compared to children, adolescents were less likely to undergo a VL test at six months (73% versus 88%, p=0.002) and more likely to have an unknown VL status (40% versus 22%, p=0.001). Conclusion: At six months of ART, viral suppression was low and losses in the cascade high.

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.

Community attitudes on tuberculosis in Botswana: an opportunity for improving the National Tuberculosis Programme outcomes, 2011.

OBJECTIVES: The Botswana tuberculosis HIV Knowledge Attitude and Practice study sought to assess knowledge, attitudes and practices of communities on TB and identify sources of their information on this disease and HIV. Specific objectives of the study were to: (a) collect baseline information on the knowledge, attitudes, and practices about tuberculosis treatment seeking and adherence behaviors in Botswana. (b) Identify barriers which discourage people who may have smear positive tuberculosis from testing and getting treatment (e.g. social stigma) and constraints which prevent them from initiating and completing treatment. RESULTS: Approximately 92% of respondents (n = 2029), reported that having TB was not something embarrassing, while about 97% (n = 2030) were not ashamed of having a family member with TB. Approximately 95% (n = 2030) expressed willingness to accommodate their relatives with TB at their homes or, work with TB patients (n = 2026). About 21% of the respondents however, believed in myths that TB infection is a result of either having sex with women who had miscarried (n = 2028), or food poisoning (n = 2031) while about 17% believed that TB infection is a result of sleeping with a widow or widower (n = 2031).

Evaluation of a Mobile Health Approach to Tuberculosis Contact Tracing in Botswana.

Tuberculosis (TB) contact tracing is typically conducted in resource-limited settings with paper forms, but this approach may be limited by inefficiencies in data collection, storage, and retrieval and poor data quality. In Botswana, we developed, piloted, and evaluated a mobile health (mHealth) approach to TB contact tracing that replaced the paper form-based approach for a period of six months. For both approaches, we compared the time required to complete TB contact tracing and the quality of data collected. For the mHealth approach, we also administered the Computer System Usability Questionnaire to 2 health care workers who used the new approach, and we identified and addressed operational considerations for implementation. Compared to the paper form-based approach, the mHealth approach reduced the median time required to complete TB contact tracing and improved data quality. The mHealth approach also had favorable overall rating, system usefulness, information quality, and interface quality scores on the Computer System Usability Questionnaire. Overall, the mHealth approach to TB contact tracing improved on the paper form-based approach used in Botswana. This new approach may similarly benefit TB contact tracing efforts in other resource-limited settings.

Advanced immune suppression is associated with increased prevalence of mixed-strain Mycobacterium tuberculosis infections among persons at high risk for drug-resistant tuberculosis in Botswana.

We examined factors associated with mixed-strain Mycobacterium tuberculosis infections among patients at high risk for drug-resistant tuberculosis in Botswana. Thirty-seven (10.0%) of 370 patients with tuberculosis had mixed M. tuberculosis infections, based on 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping. In log-binomial regression analysis, age <37 years (adjusted prevalence ratio [PR], 1.92; 95% confidence interval [CI], 1.01-3.57) and prior tuberculosis treatment (adjusted PR, 2.31; 95% CI, 1.09-4.89) were associated with mixed M. tuberculosis infections. Among human immunodeficiency virus-infected patients, prior tuberculosis treatment (adjusted PR, 2.11; 95% CI, 1.04-4.31) and CD4(+) T-cell count of <100 cells/µl (adjusted PR, 10.18; 95% CI, 2.48-41.71) were associated with mixed M. tuberculosis infections. Clinical suspicion of mixed M. tuberculosis infections should be high for patients with advanced immunosuppression and a prior history of tuberculosis treatment.

Successful MDR-TB treatment regimens including amikacin are associated with high rates of hearing loss.

BACKGROUND: Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients. METHODS: Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss. RESULTS: 437 MDR-TB patients were included, 288 (66%) of whom were HIV co-infected. 270 (62%) developed hearing loss, of whom 147 (54%) had audiometry. Of the 313 (72%) patients who completed treatment, 228 (73%) had a good outcome (cure or treatment completion). Good outcome was associated with longer amikacin treatment (adjusted OR [aOR] 1.13, 95% CI 1.06 - 1.21) and higher dosage (aOR 1.90, 95% CI 1.12 - 2.99). Longer amikacin duration (aOR 1.98, 95% CI 1.86 - 2.12) and higher dosage per weight per month (aOR 1.15, 95% CI 1.04 - 1.28) were associated with development of hearing loss. Amikacin treatment duration modified the effect of the dosage on the risk of hearing loss, increasing this risk as the duration increased. CONCLUSIONS: Amikacin was effective for MDR-TB treatment, but was associated with a high incidence of hearing loss especially in our study population. Total treatment duration and average monthly amikacin dose were associated with improved outcomes; however these were also associated with development of hearing loss.

Longer hospital stay is associated with higher rates of tuberculosis-related morbidity and mortality within 12 months after discharge in a referral hospital in Sub-Saharan Africa.

BACKGROUND: Nosocomial transmission of pulmonary tuberculosis (PTB) is a problem in resource-limited settings. However, the degree of TB exposure and the intermediate- and long-term morbidity and mortality of hospital-associated TB is unclear. In this study we determined: 1) the nature, patterns and intensity of TB exposure occurring in the context of current TB cohorting practices in medical centre with a high prevalence of TB and HIV; 2) the one-year TB incidence after discharge; and 3) one-year TB-related mortality after hospital discharge. METHODS: Factors leading to nosocomial TB exposure were collected daily over a 3-month period. Patients were followed for 1-year after discharge. TB incidence and mortality were calculated and logistic regression was used to determine the factors associated with TB incidence and mortality during follow up. RESULTS: 1,094 patients were admitted to the medical wards between May 01 and July 31, 2010. HIV was confirmed in 690/1,094 (63.1%) of them. A total of 215/1,094 (19.7%) patients were diagnosed with PTB and 178/1,094 (16.3%) patients died during the course of their hospitalization; 12/178 (6.7%) patients died from TB-related complications. Of the 896 (83.7%) discharged patients, 41 (4.6%) [corrected] were diagnosed with TB during the year of follow up. Overall, 123/896 (14%) patients died during the follow up period, of whom 26/123 (21%) died from TB. [corrected] One-year TB incidence rate and TB-associated mortality were associated with the number of days that the patient remained hospitalized, the number of days spent in the cohorting bay (regardless of whether the patient was eventually diagnosed with TB or not), and the number and proximity to TB index cases. There was no difference in the performance of each of these 3 measurements of nosocomial TB exposure for the prediction of one-year TB incidence. CONCLUSION: Substantial TB exposure, particularly among HIV-infected patients, occurs in nosocomial settings despite implementation of cohorting measures. Nosocomial TB exposure is strongly associated with one-year TB incidence and TB-related mortality. Further studies are needed to identify strategies to reduce such exposure among susceptible patients.

Mixed Mycobacterium tuberculosis complex infections and false-negative results for rifampin resistance by GeneXpert MTB/RIF are associated with poor clinical outcomes.

The Xpert MTB/RIF (Xpert) assay is becoming a principal screening tool for diagnosing rifampin-resistant Mycobacterium tuberculosis complex (MTBC) infection. However, little is known about the performance of the Xpert assay in infections with both drug-sensitive and drug-resistant strains (mixed MTBC infections). We assessed the performance of the Xpert assay for detecting rifampin resistance using phenotypic drug sensitivity testing (DST) as the reference standard in 370 patients with microbiologically proven pulmonary tuberculosis. Mixed MTBC infections were identified genetically through 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analysis. Logistic regression was used to identify the factors associated with poor (defined as treatment failure, default, and death from any cause) or good (defined as cure or successful treatment completion) clinical outcomes. The analytic sensitivity of the Xpert assay for detecting rifampin resistance was assessed in vitro by testing cultures containing different ratios of drug-sensitive and drug-resistant organisms. Rifampin resistance was detected by the Xpert assay in 52 (14.1%) and by phenotypic DST in 55 (14.9%) patients. Mixed MTBC infections were identified in 37 (10.0%) patients. The Xpert assay was 92.7% (95% confidence interval [CI], 82.4% to 97.9%) sensitive for detecting rifampin resistance and 99.7% (95% CI, 98.3% to 99.9%) specific. When restricted to patients with mixed MTBC infections, Xpert sensitivity was 80.0% (95% CI, 56.3 to 94.3%). False-negative Xpert results (adjusted odds ratio [aOR], 6.6; 95% CI,1.2 to 48.2) and mixed MTBC infections (aOR, 6.5; 95% CI, 2.1 to 20.5) were strongly associated with poor clinical outcome. The Xpert assay failed to detect rifampin resistance in vitro when <90% of the organisms in the sample were rifampin resistant. Our study indicates that the Xpert assay has an increased false-negative rate for detecting rifampin resistance with mixed MTBC infections. In hyperendemic settings where mixed infections are common, the Xpert results might need further confirmation.

Clinical outcomes among persons with pulmonary tuberculosis caused by Mycobacterium tuberculosis isolates with phenotypic heterogeneity in results of drug-susceptibility tests.

BACKGROUND: Patients with multidrug-resistant (MDR) tuberculosis may have phenotypic heterogeneity in results of drug-susceptibility tests (DSTs). However, the impact of this on clinical outcomes among patients treated for MDR tuberculosis is unknown. METHODS: Phenotypic DST heterogeneity was defined as presence of at least 1 Mycobacterium tuberculosis isolate susceptible to rifampicin and isoniazid recovered <3 months after MDR tuberculosis treatment initiation from a patient with previous documented tuberculosis due to M. tuberculosis resistant to at least rifampicin and isoniazid. The primary outcome was defined as good (ie, cure or treatment completion) or poor (ie, treatment failure, treatment default, or death). A secondary outcome was time to culture conversion. Cox proportional hazard models were used to determine the association between phenotypic DST heterogeneity and outcomes. RESULTS: Phenotypic DST heterogeneity was identified in 33 of 475 patients (7%) with MDR tuberculosis. Poor outcome occurred in 126 patients (28%). Overall, patients with MDR tuberculosis who had phenotypic DST heterogeneity were at greater risk of poor outcome than those with MDR tuberculosis but no phenotypic DST heterogeneity (adjusted hazard ratio [aHR], 2.1; 95% confidence interval [CI], 1.2-3.6). Among HIV-infected patients with MDR tuberculosis, the adjusted hazard for a poor outcome for those with phenotypic DST heterogeneity was 2.4 (95% CI, 1.3-4.2) times that for those without phenotypic DST heterogeneity, whereas among HIV-negative patients with MDR tuberculosis, the adjusted hazard for those with phenotypic DST heterogeneity was 1.5 (95% CI, .5-4.3) times that for those without phenotypic DST heterogeneity. HIV-infected patients with MDR tuberculosis with phenotypic DST heterogeneity also had a longer time to culture conversion than with HIV-infected patients with MDR tuberculosis without phenotypic DST heterogeneity (aHR, 2.9; 95% CI, 1.4-6.0). CONCLUSIONS: Phenotypic DST heterogeneity among persons with HIV infection who are being treated for MDR tuberculosis is associated with poor outcomes and longer times to culture conversion.