Patient- and provider-level risk factors associated with default from tuberculosis treatment, South Africa, 2002: a case-control study

<p>Abstract</p> <p>Background</p> <p>Persons who default from tuberculosis treatment are at risk for clinical deterioration and complications including worsening drug resistance and death. Our objective was to identify risk factors associated with tuberculosis (TB) treatment default in South Africa.</p> <p>Methods</p> <p>We conducted a national retrospective case control study to identify factors associated with treatment default using program data from 2002 and a standardized patient questionnaire. We defined default as interrupting TB treatment for two or more consecutive months during treatment. Cases were a sample of registered TB patients receiving treatment under DOTS that defaulted from treatment. Controls were those who began therapy and were cured, completed or failed treatment. Two respective multivariable models were constructed, stratified by history of TB treatment (new and re-treatment patients), to identify independent risk factors associated with default.</p> <p>Results</p> <p>The sample included 3165 TB patients from 8 provinces; 1164 were traceable and interviewed (232 cases and 932 controls). Significant risk factors associated with default among both groups included poor health care worker attitude (new: AOR 2.1, 95% CI 1.1-4.4; re-treatment: AOR 12, 95% CI 2.2-66.0) and changing residence during TB treatment (new: AOR 2.0, 95% CI 1.1-3.7; re-treatment: AOR 3.4, 95% CI 1.1-9.9). Among new patients, cases were more likely than controls to report having no formal education (AOR 2.3, 95% CI 1.2-4.2), feeling ashamed to have TB (AOR 2.0, 95% CI 1.3-3.0), not receiving adequate counseling about their treatment (AOR 1.9, 95% CI 1.2-2.8), drinking any alcohol during TB treatment (AOR 1.9, 95% CI 1.2-3.0), and seeing a traditional healer during TB treatment (AOR 1.9, 95% CI 1.1-3.4). Among re-treatment patients, risk factors included stopping TB treatment because they felt better (AOR 21, 95% CI 5.2-84), having a previous history of TB treatment default (AOR 6.4, 95% CI 2.9-14), and feeling that food provisions might have helped them finish treatment (AOR 5.0, 95% CI 1.3-19).</p> <p>Conclusions</p> <p>Risk factors for default differ between new and re-treatment TB patients in South Africa. Addressing default in both populations with targeted interventions is critical to overall program success.</p

Impact of community tracer teams on treatment outcomes among tuberculosis patients in South Africa

BACKGROUND: Tuberculosis (TB) indicators in South Africa currently remain well below global targets. In 2008, the National Tuberculosis Program (NTP) implemented a community mobilization program in all nine provinces to trace TB patients that had missed a treatment or clinic visit. Implementation sites were selected by TB program managers and teams liaised with health facilities to identify patients for tracing activities. The objective of this analysis was to assess the impact of the TB Tracer Project on treatment outcomes among TB patients. METHODS: The study population included all smear positive TB patients registered in the Electronic TB Registry from Quarter 1 2007-Quarter 1 2009 in South Africa. Subdistricts were used as the unit of analysis, with each designated as either tracer (standard TB program plus tracer project) or non-tracer (standard TB program only). Mixed linear regression models were utilized to calculate the percent quarterly change in treatment outcomes and to compare changes in treatment outcomes from Quarter 1 2007 to Quarter 1 2009 between tracer and non-tracer subdistricts. RESULTS: For all provinces combined, the percent quarterly change decreased significantly for default treatment outcomes among tracer subdistricts (−0.031%; p < 0.001) and increased significantly for successful treatment outcomes among tracer subdistricts (0.003%; p = 0.03). A significant decrease in the proportion of patient default was observed for all provinces combined over the time period comparing tracer and non-tracer subdistricts (p = 0.02). Examination in stratified models revealed the results were not consistent across all provinces; significant differences were observed between tracer and non-tracer subdistricts over time in five of nine provinces for treatment default. CONCLUSIONS: Community mobilization of teams to trace TB patients that missed a clinic appointment or treatment dose may be an effective strategy to mitigate default rates and improve treatment outcomes. Additional information is necessary to identify best practices and elucidate discrepancies across provinces; these findings will help guide the NTP in optimizing the adoption of tracing activities for TB control

Molecular analysis of genetic mutations among cross-resistant second-line injectable drugs reveals a new resistant mutation in Mycobacterium tuberculosis

Mutations causing mono and cross-resistance among amikacin, kanamycin and capreomycin of second-line injectable drugs (SLIDs) namely are not well understood.We investigated 124 isolates of Mycobacterium tuberculosis for mutations within rrs, eis, tlyA and efflux pump (Rv1258c and Rv0194) genes involved in resistance towards SLIDs. The distribution of mutations across these genes were significantly different in strains with mono-resistance or cross-resistance. A new mutation G878A was found in rrs gene, among strains with capreomycin mono-resistant, or in strains with cross-resistance of capreomycin, kanamycin and amikacin. This mutation was associated with the Euro-American X3 lineage (P b 0.0001). Mutations in the two efflux genes Rv1258c and Rv0194 were confined to strains with only capreomycin/amikacin/kanamycin cross-resistance. Wefurther investigated the minimuminhibitory concentration of capreomycin on isolateswith newG878Amutation ranging from 8 μg/mL to 64 μg/mL. Inclusion of G878A on new molecular assays could increase the sensitivity of capreomycin resistance detection.Lesibana Malinga received PhD funding from National Research foundation (Innovation Fund) and University of Pretoria.http://www.elsevier.com/locate/diagmicrobiohb2016Internal Medicin

Tuberculosis among health care workers in KwaZulu-Natal, South Africa: a retrospective cohort analysis

Background Tuberculosis (TB) is an occupational hazard for health care workers (HCWs) who are at greater risk of developing TB than the general population. The objective of this study was to compare the difference in TB incidence among HCWs with versus without a history of working in TB wards, to estimate the incidence of TB among HCWs, and to identify risk factors for TB disease in HCWs. Methods A retrospective cohort study (January 2006 to December 2010) was conducted in three district hospitals in KwaZulu-Natal, South Africa. Data were abstracted via chart review from occupational health medical records. Bivariate and multivariate analyses were performed using a Poisson multilevel mixed model. Results Of 1,313 (92%) medical charts reviewed with data on location of work documented, 112 (9%) cases of TB were identified. Among HCWs with TB 14 (13%) had multidrug-resistant TB. Thirty-six (32%) were cured, 33 (29%) completed treatment, and 13 (12%) died. An increased incidence of TB was reported for HCWs with a history of working in TB wards (incidence rate ratio [IRR] 2.03, 95% CI 1.11-3.71), pediatric wards (IRR 1.82 95% CI 1.07-3.10), outpatient departments (IRR 2.08 95% CI 1.23-3.52), and stores/workshop (IRR 2.38 95% CI 1.06-5.34) compared with those without such a history. HCWs living with HIV had a greater incidence of TB (IRR 3.2, 95% CI 1.54-6.66) than HIV-negative HCWs. TB incidence among HCWs was approximately two-fold greater than that of the general population over the study period. Conclusions HCWs working in a TB ward had an increased incidence of TB. However, a greater incidence of TB was also found in HCWs working in other wards including pediatric wards, outpatient departments and stores. We also identified a greater incidence of TB among HCWs than the general population. These findings further support the need for improved infection control measures not only in TB or drug-resistant TB wards or areas perceived to be at high-risk but also throughout hospitals to protect HCWs. Additionally, it is recommended for occupational health services to routinely screen HCWs for TB and provide HCWs with access to care for TB and HIV

Draft Genome Sequences of Two Extensively Drug-Resistant Strains of Mycobacterium tuberculosis Belonging to the Euro-American S Lineage

We report the whole-genome sequencing of two extensively drug-resistant tuberculosis strains belonging to the Euro-American S lineage. The RSA 114 strain showed single-nucleotide polymorphisms predicted to have drug efflux activity

Prevalence of drug-resistant tuberculosis and imputed burden in South Africa : a national and sub-national cross-sectional survey

BACKGROUND : Globally, per-capita, South Africa reports a disproportionately high number of cases of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We sought to estimate the prevalence of resistance to tuberculosis drugs in newly diagnosed and retreated patients with tuberculosis provincially and nationally, and compared these with the 2001–02 estimates. METHODS : A cross-sectional survey was done between June 15, 2012–June 14, 2014, using population proportionate randomised cluster sampling in the nine provinces in South Africa. 343 clusters were included, ranging between 31 and 48 per province. A patient was eligible for inclusion in the survey if he or she presented as a presumptive case during the intake period at a drug resistance survey enrolling facility. Consenting participants (≥18 years old) completed a questionnaire and had a sputum sample tested for resistance to first-line and second-line drugs. Analysis was by logistic regression with robust SEs, inverse probability weighted against routine data, and estimates were derived using a random effects model. FINDINGS : 101 422 participants were tested in 2012–14. Nationally, the prevalence of MDR tuberculosis was 2·1% (95% CI 1·5–2·7) among new tuberculosis cases and 4·6% (3·2–6·0) among retreatment cases. The provincial point prevalence of MDR tuberculosis ranged between 1·6% (95% CI 0·9–2·9) and 5·1% (3·7–7·0). Overall, the prevalence of rifampicin-resistant tuberculosis (4·6%, 95% CI 3·5–5·7) was higher than the prevalence of MDR tuberculosis (2·8%, 2·0–3·6; p=0·01). Comparing the current survey with the previous (2001–02) survey, the overall MDR tuberculosis prevalence was 2·8% versus 2·9% and prevalance of rifampicin-resistant tuberculosis was 3·4% versus 1·8%, respectively. The prevalence of isoniazid mono-resistant tuberculosis was above 5% in all provinces. The prevalence of ethionamide and pyrazinamide resistance among MDR tuberculosis cases was 44·7% (95% CI 25·9–63·6) and 59·1% (49·0–69·1), respectively. The prevalence of XDR tuberculosis was 4·9% (95% CI 1·0–8·8). Nationally, the estimated numbers of cases of rifampicin-resistant tuberculosis, MDR tuberculosis, and isoniazid mono-resistant tuberculosis for 2014 were 13 551, 8249, and 17 970, respectively. INTERPRETATION : The overall prevalence of MDR tuberculosis in South Africa in 2012–14 was similar to that in 2001–02; however, prevalence of rifampicin-resistant tuberculosis almost doubled among new cases. Furthermore, the high prevalence of isoniazid mono-resistant tuberculosis, not routinely screened for, and resistance to second-line drugs has implications for empirical management.President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention under the terms of 1U19GH000571.http://www.thelancet.com/infection2019-07-01hj2018Medical Microbiolog

Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients

Loss to follow-up (LFU) of 2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU. We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan–Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU. Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3–11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36–50 years (HR 1.3, 95% CI 1.0–1.6; p=0.04) compared with age 0–25 years, being HIV positive (HR 1.8, 95% CI 1.2–2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6–1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4–0.6; p<0.01) compared with no serious adverse event. Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months

Prevalence of bacteriologically confirmed pulmonary tuberculosis in South Africa, 2017-19 : a multistage, cluster-based, cross-sectional survey

DATA SHARING : Individual, deidentified participant data, including data dictionaries, may be shared. Templates of the informed consent forms may be shared upon request. The data will be available following publication, with no end date, and will be shared with anyone who wishes to access them with a clear data sharing agreement, for any purpose of analyses. For data access, please contact the corresponding author and the tuberculosis programme at the National Department of Health in South Africa.BACKGROUND : Tuberculosis remains an important clinical and public health issue in South Africa, which has one of the highest tuberculosis burdens in the world. We aimed to estimate the burden of bacteriologically confirmed pulmonary tuberculosis among people aged 15 years or older in South Africa. METHODS : This multistage, cluster-based, cross-sectional survey included eligible residents (age ≥15 years, who had slept in a house for ≥10 nights in the preceding 2 weeks) in 110 clusters nationally (cluster size of 500 people; selected by probability proportional-to-population size sampling). Participants completed face-to-face symptom questionnaires (for cough, weight loss, fever, and night sweats) and manually read digital chest X-ray screening. Screening was recorded as positive if participants had at least one symptom or an abnormal chest X-ray suggestive of tuberculosis, or a combination thereof. Sputum samples from participants who were screen-positive were tested by the Xpert MTB/RIF Ultra assay (first sample) and Mycobacteria Growth Indicator Tube culture (second sample), with optional HIV testing. Participants with a positive Mycobacterium tuberculosis complex culture were considered positive for bacteriologically confirmed pulmonary tuberculosis; when culture was not positive, participants with a positive Xpert MTB/RIF Ultra result with an abnormal chest X-ray suggestive of active tuberculosis and without current or previous tuberculosis were considered positive for bacteriologically confirmed pulmonary tuberculosis. FINDINGS : Between Aug 15, 2017, and July 28, 2019, 68 771 people were enumerated from 110 clusters, with 53 250 eligible to participate in the survey, of whom 35 191 (66·1%) participated. 9066 (25·8%) of 35 191 participants were screen-positive and 234 (0·7%) were identified as having bacteriologically confirmed pulmonary tuberculosis. Overall, the estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 852 cases (95% CI 679–1026) per 100 000 population; the prevalence was highest in people aged 35–44 years (1107 cases [95% CI 703–1511] per 100 000 population) and those aged 65 years or older (1104 cases [680–1528] per 100 000 population). The estimated prevalence was approximately 1·6 times higher in men than in women (1094 cases [95% CI 835–1352] per 100 000 population vs 675 cases [494–855] per 100 000 population). 135 (57·7%) of 234 participants with tuberculosis screened positive by chest X-ray only, 16 (6·8%) by symptoms only, and 82 (35·9%) by both. 55 (28·8%) of 191 participants with tuberculosis with known HIV status were HIV-positive. INTERPRETATION : Pulmonary tuberculosis prevalence in this survey was high, especially in men. Despite the ongoing burden of HIV, many participants with tuberculosis in this survey did not have HIV. As more than half of the participants with tuberculosis had an abnormal chest X-ray without symptoms, prioritising chest X-ray screening could substantially increase case finding.Global Fund, Bill & Melinda Gates Foundation, USAID.http://www.thelancet.com/infectionhj2023Medical Microbiolog

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB