The burden of drug resistance tuberculosis in Ghana; results of the First National Survey.

Resistance to Tuberculosis drugs has become a major threat to the control of tuberculosis (TB) globally. We conducted the first nation-wide drug resistance survey to investigate the level and pattern of resistance to first-line TB drugs among newly and previously treated sputum smear-positive TB cases. We also evaluated associations between potential risk factors and TB drug resistance. Using the World Health Organization (WHO) guidelines on conducting national TB surveys, we selected study participants from 33 health facilities from across the country, grouped into 29 clusters, and included them into the survey. Between April 2016 and June 2017, a total of 927 patients (859 new and 68 previously treated) were enrolled in the survey. Mycobacterium tuberculosis complex (MTBC) isolates were successfully cultured from 598 (65.5%) patient samples and underwent DST, 550 from newly diagnosed and 48 from previously treated patients. The proportion of patients who showed resistance to any of the TB drugs tested was 25.2% (95% CI; 21.8-28.9). The most frequent resistance was to Streptomycin (STR) (12.3%), followed by Isoniazid (INH) (10.4%), with Rifampicin (RIF), showing the least resistance of 2.4%. Resistance to Isoniazid and Rifampicin (multi-drug resistance) was found in 19 (3.2%; 95% CI: 1.9-4.9) isolates. Prevalence of multidrug resistance was 7 (1.3%; 95% CI: 0.5-2.6) among newly diagnosed and 12 (25.0%; 95% CI: 13.6-39.6) among previously treated patients. At both univariate and multivariate analysis, MDR-TB was positively associated with previous history of TB treatment (OR = 5.09, 95% CI: 1.75-14.75, p = 0.003); (OR = 5.41, 95% CI: 1.69-17.30, p = 0.004). The higher levels of MDR-TB and overall resistance to any TB drug among previously treated patients raises concerns about adherence to treatment. This calls for strengthening existing TB programme measures to ensure a system for adequately testing and monitoring TB drug resistance

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007-2010

OBJECTIVE: To present a global update of drug-resistant tuberculosis (TB) and explore trends in 1994-2010. METHODS: Data on drug resistance among new and previously treated TB patients, as reported by countries to the World Health Organization, were analysed. Such data are collected through surveys of a representative sample of TB patients or surveillance systems based on routine drug susceptibility testing. Associations between multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection and sex were explored through logistic regression. FINDINGS: In 2007-2010, 80 countries and 8 territories reported surveillance data. MDR-TB among new and previously treated cases was highest in the Russian Federation (Murmansk oblast, 28.9%) and the Republic of Moldova (65.1%), respectively. In three former Soviet Union countries and South Africa, more than 10% of the cases of MDR-TB were extensively drug-resistant. Globally, in 1994 to 2010 multidrug resistance was observed in 3.4% (95% confidence interval, CI: 1.9-5.0) of all new TB cases and in 19.8% (95% CI: 14.4-25.1) of previously treated TB cases. No overall associations between MDR-TB and HIV infection (odds ratio, OR: 1.4; 95% CI: 0.7-3.0) or sex (OR: 1.1; 95% CI: 0.8-1.4) were found. Between 1994 and 2010, MDR-TB rates in the general population increased in Botswana, Peru, the Republic of Korea and declined in Estonia, Latvia and the United States of America. CONCLUSION: The highest global rates of MDR-TB ever reported were documented in 2009 and 2010. Trends in MDR-TB are still unclear in most settings. Better surveillance or survey data are required, especially from Africa and India

Analysis of laboratory testing results collected in an enhanced chlamydia surveillance system in Australia, 2008-2010

Background: Chlamydial infection is the most common notifiable disease in Australia, Europe and the US. Australian notifications of chlamydia rose four-fold from 20,274 cases in 2002 to 80,846 cases in 2011; the majority of cases were among young people aged less than 29 years. Along with test positivity rates, an understanding of the number of tests performed and the demographics of individuals being tested are key epidemiological indicators. The ACCESS Laboratory Network was established in 2008 to address this issue.Methods: The ACCESS Laboratory Network collected chlamydia testing data from 15 laboratories around Australia over a three-year period using data extraction software. All chlamydia testing data from participating laboratories were extracted from the laboratory information system; patient identifiers converted to a unique, non-reversible code and de-identified data sent to a single database. Analysis of data by anatomical site included all specimens, but in age and sex specific analysis, only one testing episode was counted.Results: From 2008 to 2010 a total of 628,295 chlamydia tests were referred to the 15 laboratories. Of the 592,626 individual episodes presenting for testing, 70% were from female and 30% from male patients. In female patients, chlamydia positivity rate was 6.4% overall; the highest rate in 14 year olds (14.3%). In male patients, the chlamydia positivity rate was 9.4% overall; the highest in 19 year olds (16.5%). The most common sample type was urine (57%). In 3.2% of testing episodes, multiple anatomical sites were sampled. Urethral swabs gave the highest positivity rate for all anatomical sites in both female (7.7%) and male patients (14%), followed by urine (7.6% and 9.4%, respectively) and eye (6.3% and 7.9%, respectively).Conclusions: The ACCESS Laboratory Network data are unique in both number and scope and are representative of chlamydia testing in both general practice and high-risk clinics. The findings from these data highlight much lower levels of testing in young people aged 20 years or less; in particular female patients aged less than 16 years, despite being the group with the highest positivity rate. Strategies are needed to increase the uptake of testing in this high-risk group. © 2014 Dimech et al.; licensee BioMed Central Ltd

Multidrug Resistance Among New Tuberculosis Cases Detecting Local Variation Through Lot Quality-assurance Sampling

Background: Current methodology for multidrug-resistant tuberculosis (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. Methods: We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored 3 classification systems-two-way static, three-way static, and three-way truncated sequential sampling-at 2 sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. Results: The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. Conclusions: Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desire

Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007–2010

Objective To present a global update of drug-resistant tuberculosis (TB) and explore trends in 1994-2010. Methods Data on drug resistance among new and previously treated TB patients, as reported by countries to the World Health Organization, were analysed. Such data are collected through surveys of a representative sample of TB patients or surveillance systems based on routine drug susceptibility testing. Associations between multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection and sex were explored through logistic regression. Findings In 2007-2010, 80 countries and 8 territories reported surveillance data. MDR-TB among new and previously treated cases was highest in the Russian Federation (Murmansk oblast, 28.9%) and the Republic of Moldova (65.1%), respectively. In three former Soviet Union countries and South Africa, more than 10% of the cases of MDR-TB were extensively drug-resistant. Globally, in 1994 to 2010 multidrug resistance was observed in 3.4% (95% confidence interval, Cl: 1.9-5.0) of all new TB case's and in 19.8% (95% Cl: 14.4-25.1) of previously treated TB cases. No overall associations between MDR-TB and HIV infection (odds ratio, OR: 1.4; 95% Cl: 0.7-3.0) or sex (OR: 1.1; 95% Cl: 0.8-1.4) were found. Between 1994 and 2010, MDR-TB rates in the general population increased in Botswana, Peru, the Republic of Korea and declined in Estonia, Latvia and the United States of America. Conclusion The highest global rates of MDR-TB ever reported were documented in 2009 and 2010. Trends in MDR-TB are still unclear in most settings. Better surveillance or survey data are required, especially from Africa and India