Multidrug-resistant Tuberculosis Surveillance Research Articles

Retrospective analysis of multidrug-resistant tuberculosis case notifications in Australia (1999-2018).

This study describes the epidemiology and treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) cases notified in Australia between 1999 and 2018, and investigates whether current data fields in the national tuberculosis (TB) dataset allow description and measurement of surveillance information pertaining to the diagnosis and clinical management of MDR-TB. In May 2019, de-identified demographic, clinical, laboratory, drug susceptibility, treatment, risk factor and outcome data for all MDR-TB case notifications were extracted from the Australian National Notifiable Disease Surveillance System. The dataset included ten treatment outcome categories, which were aggregated to four categorical outcomes for descriptive and inferential analyses. The majority of cases were overseas-born (91%). Absolute case numbers increased over time; however, the MDR-TB notification rate remained fairly stable during the study period. Treatment success was achieved in nearly two-thirds of cases (62.1%). Whilst timeframes between initial presentation, specimen collection, case notification and treatment commencement were calculated, current data fields in the national dataset precluded measurement and description of other parameters deemed important for MDR-TB surveillance. This study demonstrates that while Australia's MDR-TB burden is low, cases will continue to occur until TB control improves in countries with which Australia shares cultural and migration links. Australia should continue to support national and regional TB control programmes to sustain progress towards national elimination of TB. This study's findings support a review of data fields in the national TB dataset with potential expansion or adjustment to improve national data reporting, including the monitoring of evidence-based recommendations for the prevention and management of MDR-TB.

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012\u20132017) retrospective study

BackgroundIn Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar’s MDR-TB cascade of care.MethodsFor 2012–2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar’s TB and MDR-TB cascade of care.ResultsThe geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients’ sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival.ConclusionsAn expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

Trends in prevalence of multi drug resistant tuberculosis in sub-Saharan Africa: A systematic review and meta-analysis.

BackgroundMultidrug resistant tuberculosis (MDR-TB), is an emerging public health problem in sub-Saharan Africa (SSA). This study aims to determine the trends in prevalence of MDR-TB among new TB cases in sub-Saharan Africa over two decades.MethodsWe searched electronic data bases and accessed all prevalence studies of MDR-TB within SSA between 2007 and 2017. We determined pooled prevalence estimates using random effects models and determined trends using meta-regression.ResultsResults: We identified 915 studies satisfying inclusion criteria. Cumulatively, studies reported on MDR-TB culture of 34,652 persons. The pooled prevalence of MDR-TB in new cases was 2.1% (95% CI; 1.7–2.5%). There was a non-significant decline in prevalence by 0.12% per year.ConclusionWe found a low prevalence estimate of MDR-TB, and a slight temporal decline over the study period. There is a need for continuous MDR-TB surveillance among patients with TB.

A Novel Molecular Strategy for Surveillance of Multidrug Resistant Tuberculosis in High Burden Settings.

BackgroundIn South Africa and other high prevalence countries, transmission is a significant contributor to rising rates of multidrug resistant tuberculosis (MDR-TB). Thus, there is a need to develop an early detection system for transmission clusters suitable for high burden settings. We have evaluated the discriminatory power and clustering concordance of a novel and simple genotyping approach, combining spoligotyping with pncA sequencing (SpoNC), against two well-established methods: IS6110-RFLP and 24-loci MIRU-VNTR.MethodsA total of 216 MDR-TB isolates collected from January to June 2010 from the NHLS Central TB referral laboratory in Braamfontein, Johannesburg, representing a diversity of strains from South Africa, were included. The isolates were submitted for genotyping, pncA sequencing and analysis to the Centre for Tuberculosis in South Africa and the Public Health Research Institute Tuberculosis Center at Rutgers University in the United States. Clustering rates, Hunter-Gaston Discriminatory Indexes (HGI) and Wallace coefficients were compared between the methods.ResultsOverall clustering rates were high by both IS6110-RFLP (52.8%) and MIRU-VNTR (45.8%), indicative of on-going transmission. Both 24-loci MIRU-VNTR and IS6110-RFLP had similar HGI (0.972 and 0.973, respectively), with close numbers of unique profiles (87 vs. 70), clustered isolates (129 vs. 146), and cluster sizes (2 to 26 vs. 2 to 25 isolates). Spoligotyping alone was the least discriminatory (80.1% clustering, HGI 0.903), with 28 unique types. However, the discriminatory power of spoligotyping was improved when combined with pncA sequencing using the SpoNC approach (61.8% clustering, HGI 0.958). A high proportion of MDR-TB isolates had mutations in pncA (68%, n = 145), and pncA mutations were significantly associated with clustering (p = 0.007 and p = 0.0013 by 24-loci MIRU-VNTR and IS6110-RFLP, respectively), suggesting high rates of resistance to pyrazinamide among all MDR-TB cases and particularly among clustered cases.ConclusionWe conclude that SpoNC provides good discrimination for MDR-TB surveillance and early identification of outbreaks in South Africa, with 24-loci MIRU-VNTR applied for pncA wild-type strains as needed.

A study of multidrug-resistant tuberculosis in risk groups in the city of Santos, São Paulo, Brazil.

Monitoring the extent of and trends in multidrug-resistant tuberculosis (MDR-TB) is a priority of the Brazilian National Tuberculosis Control Programme. The current study aimed to estimate the incidence of MDR-TB, describe the profile of TB drug resistance in risk groups and examine whether screening for MDR-TB adhered to the recommended guidelines. A descriptive study that examined diagnosed cases of pulmonary TB was conducted in the city of Santos, Brazil, between 2000-2004. Of the 2,176 pulmonary TB cases studied, 671 (30.8%) met the criteria for drug sensitivity testing and, of these cases, 31.7% (213/671) were tested. Among the tested cases, 9.4% were resistant to one anti-TB drug and 15% were MDR. MDR was observed in 11.6% of 86 new TB cases and 17.3% of 127 previously treated cases. The average annual incidence of MDR-TB was 1.9 per 100,000 inhabitants-years. The extent of known MDR-TB in the city of Santos is high, though likely to be underestimated. Our study therefore indicates an inadequate adherence to the guidelines for MDR-TB screening and suggests the necessity of alternative strategies of MDR-TB surveillance.

Multidrug-resistant tuberculosis today

The World Health Organization (WHO) and its partners have long conducted efforts to improve tuberculosis (TB) case surveillance and programme monitoring and evaluation. WHO’s 2011 report on global TB control1 provided the most reliable information ever generated on the burden of disease and death caused by TB and multidrug-resistant TB (i.e. disease marked by in vitro resistance to at least isoniazid and rifampicin), treatment outcomes, financing mechanisms and new TB diagnostics, drugs and vaccines. The Global Project on Anti-tuberculosis Drug Resistance Surveillance, launched in 1994, has generated reliable drug resistance estimates for 127 countries based on representative studies that followed standard methods and separately looked at resistance among new and retreatment cases.2 The article by Zignol et al. in this issue of the Bulletin3 draws on those estimates to portray the best of current knowledge on anti-TB drug resistance, multidrug-resistant TB (MDR-TB) and extensively-drug-resistant TB (XDR-TB) (i.e. MDR-TB disease marked by additional in vitro resistance to at least one fluoroquinolone and one injectable drug). Zignol et al.’s report confirms that a belt of MDR-TB exists in eastern Europe and central Asia, as suggested by a recent study describing record rates of MDR-TB in Minsk, Belarus,4 where about half of all TB cases harbour MDR-TB strains. The finding that many countries in the same area still lack reliable MDR-TB surveillance systems is therefore highly worrisome. Efforts to understand how MDR-TB is evolving in African countries, India and the Russian Federation are also critically important. XDR-TB has been identified wherever it has been studied. In countries reporting nationally representative data, 10% of MDR-TB cases are extensively drug-resistant. The availability of good data for multiple years from 51 countries has finally made it possible to study trends in anti-TB drug resistance and to objectively examine why MDR-TB is increasing in some parts of the world and decreasing in others. We must now explore the determinants of these trends, learn from model programmes and delve into poorly understood areas and into the factors that influence how fast MDR-TB is declining in different places – slowly in Russian Federation oblasts, moderately fast in Estonia and Latvia, and fast in the United States of America. Furthermore, Zignol et al.’s suggestion that in the Republic of Korea therapeutic practices within the private sector may explain the increase in MDR-TB raises challenging questions. Finally, Zignol et al.’s report shows that MDR-TB surveillance is improving and is a useful source of data for investigating the basic determinants of MDR-TB. Sex did not emerge as an important determinant, and the long-feared association between MDR-TB and human immunodeficiency virus (HIV) infection was not supported by the study findings. However, the unavailability of data on HIV serostatus for many countries – not surprising since only 34% of the world’s confirmed TB cases are tested for HIV1 – dictates caution in interpreting this finding. It also reminds us of how difficult it is to incorporate HIV testing in TB drug resistance surveys and of how far away we are from fully implementing the 12 activities for collaborative control of TB and HIV infection recommended by WHO.5,6 The mismanagement of non-drug-resistant TB cases, which leads to drug resistance, is a continuing problem everywhere, even in high-income European countries with low TB incidence.7 The resulting growing reservoir of difficult-to-treat cases poses a challenge to national TB programmes and health systems all over the world.8 The number of incurable XDR-TB cases is on the rise in several countries, and properly caring for these cases, and especially for those experiencing treatment failure, is difficult and has obvious logistical, ethical and economic implications.8 Zignol et al.’s lucid report paves the way for targeted public health action in MDR-TB prevention and control. Although new molecular technologies, including line probe assays and Xpert® MTB/RIF, can allow the rapid diagnosis of thousands of MDR-TB cases, not all countries will be ready to treat those cases in compliance with appropriate guidelines. This obviously poses some risk of generating new super-resistant strains. On the positive side, at least two new forthcoming drugs – bedaquiline and delamanid – will reinforce our treatment armamentarium. The data presented by Zignol et al. should prompt us to make every effort to ensure their proper use.

La multirésistance (MDR) de Mycobacterium tuberculosis aux antibiotiques en France depuis 1992

Purpose. – Multidrug resistant tuberculosis (MDR-Tb) is a threat to tuberculosis control programmes. Data from MDR-Tb surveillance in France since 1992 are reported. Design. – Annual surveys were performed to collect all culture-positive cases of tuberculosis in France. Information on MDR-Tb cases included age, sex, country of birth, site of Tb, HIV co-infection, date of first diagnosis of Tb and drug susceptibility. Results. – The annual prevalence of MDR-Tb cases was 0.6% on average and remained stable during the study period. A majority of MDR-Tb cases were male (70%), foreign-born (56%), and previously treated (66%). HIV co-infection, present in 21% of patients, was associated with primary MDR-Tb. Among MDR-Tb cases, 16% have been notified at least two different years suggesting they remained sources of MDR infection for long. Conclusion. – The low and stable prevalence rate of MDR-Tb reflects the adequate treatment of new cases of tuberculosis in France. However, because 16% of notified MDR-Tb cases remained culture-positive for years, there is room for improved treatment of these cases.