Outbreaks Of Multidrug-resistant Tuberculosis Research Articles

Outbreak of Multidrug-Resistant Tuberculosis - Kansas, 2021-2022.

An outbreak of multidrug-resistant (MDR) tuberculosis (TB) involved 13 persons in four households in a low-income, under-resourced urban Kansas community during November 2021-November 2022. A majority of the seven adults identified in the Kansas outbreak were born outside the United States in a country that had experienced an MDR TB outbreak with the same genotype during 2007-2009, whereas most of the six children in the Kansas outbreak were U.S.-born. Prompt identification, evaluation, and treatment of persons with MDR TB and their contacts is essential to limiting transmission.

Multidrug-Resistant Tuberculosis Outbreak among Immigrants in Tokyo, Japan, 2019-2021.

In mid-September 2019, a teenage Chinese male student and part-time waiter in Tokyo was diagnosed with multidrug-resistant (MDR) sputum smear-positive pulmonary tuberculosis (TB). This study describes the outbreak investigation of his friends and colleagues at the restaurant. We investigated 6 friends and 15 colleagues; 5 friends and 13 colleagues underwent interferon-γ release assay (IGRA). Of these, 3 friends (60.0%) and 4 colleagues (30.8%) were IGRA-positive. Each of the friends and colleagues was found to have MDR-TB (20% and 7.7%, respectively). Challenges during the investigation were the unavailability of regimens for latent TB infection (LTBI) for contacts with MDR-TB, budgetary constraints concerning implementing computed tomography (CT) scans for the contacts, frequent address changes of foreign-born patients and contacts, investigation during the coronavirus disease pandemic, and variations of alphabetical expression of the names of the patients and contacts, particularly for those from China. It is recommended that the national government officially adopt prophylaxis regimens for LTBI with MDR-TB, address the budgetary constraints regarding CT scans, and deploy liaison officers for coordinating investigations involving many foreign-born patients and contacts scattered in multiple municipalities. The names of foreign-born persons could more accurately be identified using both the alphabet and Chinese characters.

CRISPRi chemical genetics and comparative genomics identify genes mediating drug potency in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection is notoriously difficult to treat. Treatment efficacy is limited by Mtb’s intrinsic drug resistance, as well as its ability to evolve acquired resistance to all antituberculars in clinical use. A deeper understanding of the bacterial pathways that influence drug efficacy could facilitate the development of more effective therapies, identify new mechanisms of acquired resistance, and reveal overlooked therapeutic opportunities. Here we developed a CRISPR interference chemical-genetics platform to titrate the expression of Mtb genes and quantify bacterial fitness in the presence of different drugs. We discovered diverse mechanisms of intrinsic drug resistance, unveiling hundreds of potential targets for synergistic drug combinations. Combining chemical genetics with comparative genomics of Mtb clinical isolates, we further identified several previously unknown mechanisms of acquired drug resistance, one of which is associated with a multidrug-resistant tuberculosis outbreak in South America. Lastly, we found that the intrinsic resistance factor whiB7 was inactivated in an entire Mtb sublineage endemic to Southeast Asia, presenting an opportunity to potentially repurpose the macrolide antibiotic clarithromycin to treat tuberculosis. This chemical-genetic map provides a rich resource to understand drug efficacy in Mtb and guide future tuberculosis drug development and treatment.

First outbreak of multidrug-resistant tuberculosis (MDR-TB) in Denmark involving six Danish-born cases

BackgroundDenmark is a low-incidence country for tuberculosis (TB) and multidrug-resistant (MDR) TB at 5 and 0.05 cases per 100,000 population, respectively. Until 2018, the transmission of MDR-TB was nonexistent except for a few pairwise related family cases. In this study, we describe the first MDR-TB outbreak in Denmark. MethodsOn the basis of genotyping of all Mycobacterium tuberculosis (Mtb) culture-positive cases in Denmark spanning 3 decades, 6 molecular- and epidemiologically linked Danish-born cases were identified as the first cluster of an MDR-TB in Denmark. The primary case was diagnosed posthumously in 2010 followed by 5 epidemiologically linked cases from 2018 to 2019. Results and conclusionThrough a combination of routine Mtb genotyping and clinical epidemiological surveillance data, we identified the first Danish MDR-TB outbreak spanning 10 years and were able to disclose the specific transmission pathways in detail, which helped guide the outbreak investigations. The occurrence of an MDR-TB outbreak in a resource-rich low TB incidence setting such as Denmark highlights the importance of a collaborative control system combining classic contact tracing; timely identification of drug-resistant TB through rapid diagnostics; and a close collaboration between clinicians and classical- and molecular epidemiologists for the benefit of TB control.

A Tuberculosis Outbreak During the COVID-19 Pandemic - Hubei Province, China, 2020.

What is already known about topic? Multidrug-resistant tuberculosis (MDR-TB) has become a growing threat to public health. There were few reports about family-to-school MDR-TB outbreaks in China, especially during the coronavirus disease 2019 (COVID-19) pandemic. What is added by this report? A tuberculosis (TB) outbreak happened in Hubei Province during the COVID-19 pandemic. The transmission chain was probably from a father （MDR-TB case）with retreated TB history to his daughter, who then spread TB to her classmates. What are the implications for public health practice? We should enhance TB control both in schools and households, including strengthening TB/MDR-TB detection, health education, and ventilation. The TB contact screening cannot only be limited to outside school settings and should be conducted in the school when a TB student is absent from school for 2 or 3 months, or even longer especially during the COVID-19 pandemic.

A multidrug-resistant tuberculosis outbreak in a language school: Tokyo, Japan, 2019-2020.

Japan has successfully reduced the burden of tuberculosis (TB) in the past seven decades; however, there are still some issues in eliminating TB. Its presence in immigrants, particularly multidrug-resistant (MDR) TB, is one of them. In mid-September 2019, a teenage Chinese male student in a morning class of a Japanese language school in Tokyo, Japan, was diagnosed with sputum smear-positive pulmonary MDR-TB. The outbreak cases were analyzed in a cohort study. We investigated 138 students and 18 teachers, of whom 81 (51.9%) were male, 115 (73.7%) were aged from 20 to 29 years, and 124 (76.9%) were from China. Four other students in the same classroom and another in a different classroom from the index patient in the morning classes were also diagnosed with MDR-TB disease by the end of November 2020. In addition, 31 cases of latent TB infection (LTBI) were detected among the students and teachers. Students in the same classroom had the highest risk of TB infection (78.9%, 95% confidence interval [CI]: 54.4%-93.9%) with a relative risk of 8.6 (95% CI: 3.9-19.0), followed by students in the other classrooms of the morning classes (25.9%, 95% CI: 15.0%-39.7%) with a relative risk of 2.8 (95% CI: 1.2-6.8), compared with the afternoon class students (9.2%, 95% CI: 3.5-19.0) who had minimal contact with the index patient. National TB programs should adopt prophylaxis regimens for MDR-TB LTBI cases and provide prophylaxis to them, particularly if related to an outbreak. The Japanese government should screen immigrants for TB, particularly those from TB-endemic areas.

The emergency response to multidrug-resistant tuberculosis in Daru, Western Province, Papua New Guinea, 2014-2017.

A response to an outbreak of multidrug-resistant tuberculosis (MDR-TB) on Daru Island, South Fly District (SFD), Western Province, Papua New Guinea (PNG) was implemented by a national emergency response taskforce. To describe programmatic interventions for TB in SFD and evaluate characteristics of TB case notifications, drug resistance and treatment outcomes. This was a retrospective cohort study based on routine programmatic data for all patients enrolled on TB treatment at Daru General Hospital from 2014 to 2017. The response involved high-level political commitment, joint planning, resource mobilisation, community engagement and strengthening TB case detection and treatment. Of 1548 people enrolled on TB treatment, 1208 (78%) had drug-susceptible TB (DS-TB) and 333 (21.5%) had MDR-TB. There was an increase in MDR-TB as a proportion of all TB. Treatment success rates increased over the study period from 55% to 86% for DS-TB, and from 70% to 81% for MDR-TB from 2014 to 2015. The 2014 case notification rate for TB in SFD was 1031/100 000, decreasing to 736/100 000 in 2017. The outbreak was stabilised through the response from the national and provincial governments and international partners. Additional interventions are needed to decrease the TB burden in Daru.

Multidrug-resistant tuberculosis outbreak associated with poor treatment adherence and delayed treatment: Arua District, Uganda, 2013\u20132017

BackgroundIn August 2017, the Uganda Ministry of Health was notified of increased cases of multidrug-resistant tuberculosis (MDR-TB) in Arua District, Uganda during 2017. We investigated to identify the scope of the increase and risk factors for infection, evaluate health facilities’ capacity to manage MDR-TB, and recommend evidence-based control measures.MethodsWe defined an MDR-TB case-patient as a TB patient attending Arua Regional Referral Hospital (ARRH) during 2013–2017 with a sputum sample yielding Mycobacterium tuberculosis resistant to at least rifampicin and isoniazid, confirmed by an approved drug susceptibility test. We reviewed clinical records from ARRH and compared the number of MDR-TB cases during January–August 2017 with the same months in 2013–2016. To identify risk factors specific for MDR-TB among cases with secondary infection, we conducted a case-control study using persons with drug-susceptible TB matched by sub-county of residence as controls. We observed infection prevention and control practices in health facilities and community, and assessed health facilities’ capacity to manage TB.ResultsWe identified 33 patients with MDR-TB, of whom 30 were secondary TB infection cases. The number of cases during January–August 2017 was 10, compared with 3–4 cases in January–August from 2013 to 2016 (p = 0.02). Men were more affected than women (6.5 vs 1.6/100,000, p < 0.01), as were cases ≥18 years old compared to those < 18 years (8.7 vs 0.21/100,000, p < 0.01). In the case-control study, poor adherence to first-line anti-TB treatment (aOR = 9.2, 95% CI: 2.3–37) and initiating treatment > 15 months from symptom onset (aOR = 11, 95% CI: 1.5–87) were associated with MDR-TB. All ten facilities assessed reported stockouts of TB commodities. All 15 ambulatory MDR-TB patients we observed were not wearing masks given to them to minimize community infection. The MDR-TB ward at ARRH capacity was 4 patients but there were 11 patients.ConclusionThe number of cases during January–August in 2017 was significantly higher than during the same months in 2013–2016. Poor adherence to TB drugs and delayed treatment initiation were associated with MDR-TB infection. We recommended strengthening directly-observed treatment strategy, increasing access to treatment services, and increasing the number of beds in the MDR-TB ward at ARRH.

An Outbreak of Multidrug-Resistant Tuberculosis in a Secondary School — Hubei Province, 2019

What is already known about this topic? Multidrug-resistant tuberculosis (MDR-TB) is a type of tuberculosis with resistance to common treatments such as isoniazid and rifampicin. MDR-TB is a major global health challenge and needs to be controlled tightly through prevention measures, early diagnosis, and full treatment and management. What is added by this report? This outbreak was the first MDR-TB related public health emergency in Hubei Province. In total, five MDR-TB cases and nine clinically diagnosed cases were identified within one class in a secondary school. Students and teachers from other classes were monitored, but no other cases were found. What are the implications for public health practice? The implementation of TB prevention and control measures in schools is important to increase knowledge on TB and to raise awareness on protecting personal wellbeing. The Automatic Early Warning Information System alerted the local health department and allowed for a timely response to prevent further disease spread.

Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study

Global roll-out of rapid molecular assays is revolutionising the diagnosis of rifampicin resistance, predictive of multidrug-resistance, in tuberculosis. However, 30% of the multidrug-resistant (MDR) strains in an eSwatini study harboured the Ile491Phe mutation in the rpoB gene, which is associated with poor rifampicin-based treatment outcomes but is missed by commercial molecular assays or scored as susceptible by phenotypic drug-susceptibility testing deployed in South Africa. We evaluated the presence of Ile491Phe among South African tuberculosis isolates reported as isoniazid-monoresistant according to current national testing algorithms. We screened records of 37 644 Mycobacterium tuberculosis positive cultures from four South African provinces, diagnosed at the National Health Laboratory Service-Dr George Mukhari Tertiary Laboratory, to identify isolates with rifampicin sensitivity and isoniazid resistance according to Xpert MTB/RIF, GenoType MTBDRplus, and BACTEC MGIT 960. Of 1823 isolates that met these criteria, 277 were randomly selected and screened for Ile491Phe with multiplex allele-specific PCR and Sanger sequencing of rpoB. Ile491Phe-positive strains (as well as 17 Ile491Phe-bearing isolates from the eSwatini study) were then tested by Deeplex-MycTB deep sequencing and whole-genome sequencing to evaluate their patterns of extensive resistance, transmission, and evolution. Ile491Phe was identified in 37 (15%) of 249 samples with valid multiplex allele-specific PCR and sequencing results, thus reclassifying them as MDR. All 37 isolates were additionally identified as genotypically resistant to all first-line drugs by Deeplex-MycTB. Six of the South African isolates harboured four distinct mutations potentially associated with decreased bedaquiline sensitivity. Consistent with Deeplex-MycTB genotypic profiles, whole-genome sequencing revealed concurrent silent spread in South Africa of a MDR tuberculosis strain lineage extending from the eSwatini outbreak and at least another independently emerged Ile491Phe-bearing lineage. Whole-genome sequencing further suggested acquisition of mechanisms compensating for the Ile491Phe fitness cost, and of additional bedaquiline resistance following the introduction of this drug in South Africa. A substantial number of MDR tuberculosis cases harbouring the Ile491Phe mutation in the rpoB gene in South Africa are missed by current diagnostic strategies, resulting in ineffective first-line treatment, continued amplification of drug resistance, and concurrent silent spread in the community. VLIR-UOS, National Research Foundation (South Africa), and INNOVIRIS.

The use of whole-genome sequencing incluster investigation of a multidrug-resistant tuberculosis outbreak.

We used whole-genome sequencing (WGS) to delineate transmission networks and investigate the benefits of WGS during cluster investigation.We included clustered cases of multidrug-resistant (MDR) tuberculosis (TB)/extensively drug-resistant (XDR) TB linked by mycobacterial interspersed repetitive unit variable tandem repeat (MIRU-VNTR) strain typing or epidemiological information in the national cluster B1006, notified between 2007 and 2013 in the UK. We excluded from further investigation cases whose isolates differed by greater than 12 single nucleotide polymorphisms (SNPs). Data relating to patients' social networks were collected.27 cases were investigated and 22 had WGS, eight of which (36%) were excluded as their isolates differed by more than 12 SNPs to other cases. 18 cases were ruled into the transmission network based on genomic and epidemiological information. Evidence of transmission was inconclusive in seven out of 18 cases (39%) in the transmission network following WGS and epidemiological investigation.This investigation of a drug-resistant TB cluster illustrates the opportunities and limitations of WGS in understanding transmission in a setting with a high proportion of migrant cases. The use of WGS should be combined with classical epidemiological methods. However, not every cluster will be solvable, regardless of the quality of genomic data.

Implications of a school outbreak of multidrug-resistant tuberculosis in Northern China.

In this study, we identified a multidrug-resistant tuberculosis (MDR-TB) outbreak in a high school in northern China. The aim of this work was to describe TB transmission, drug resistance and treatment outcomes for this patient cluster. In January 2017, pulmonary TB was identified in a 17-year-old boy in northern China. Subsequently, a total of 11 TB cases were identified during 6-month follow-up of attendees of the same school. Of five students with latent TB infection (LTBI) receiving isoniazid preventive therapy (IPT), two pulmonary TB cases (40.0%) emerged in March and April, for an active case rate not significantly different from that of the non-IPT group (4/16, 25.0%, P = 0.598). All TB patients were first treated with a standardised first-line treatment regimen administered by the local TB hospital, with 11 of 12 active TB patients exhibiting poor treatment outcomes. Further data demonstrated that all nine patient isolates collected during this outbreak were MDR-TB and shared a common genotypic profile. In conclusion, our data demonstrate that diagnostic delay for the index MDR-TB case of this outbreak played a primary role in transmission of MDR-TB infection within a school setting. Importantly, IPT failed to prevent progression of MDR-TB from LTBI to active TB.

Performance of a highly successful outbreak strain of Mycobacterium tuberculosis in a multifaceted approach to bacterial fitness assessment

Determining bacterial fitness represents a major challenge and no single parameter can accurately predict the ability of a certain pathogen to succeed. The M strain of Mycobacterium tuberculosis managed to spread and establish in the community and caused the largest multidrug-resistant tuberculosis outbreak in Latin America. We have previously shown that the M strain can manipulate the host immune response, but we still have no direct evidence, other than epidemiology, that can account for the enhanced fitness of the M strain. Our objective was to further characterize the performance of the outbreak strain M in different fitness assays. Two main aspects were evaluated: (1) molecular characterization of selected isolates from the M outbreak and related strains and (2) comparative fitness and in vivo performance of representative M strain isolates vs. the non-prosperous M strain variant 410. Our approach confirmed the multifaceted nature of fitness. Altogether, we conclude that the epidemiologically abortive strain 410 was vulnerable to drug-driven pressure, a weak competitor, and a stronger inductor of protective response in vivo. Conversely, the isolate 6548, representative of the M outbreak peak, had a growth disadvantage but performed very well in competition and induced lung damage at advanced stages in spite of reaching relatively low CFU counts. Integration of these observations supports the idea that the M strain managed to find a unique path to success.

A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study

SummaryBackgroundThe risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan.MethodsOn April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control.FindingsBetween Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.InterpretationOur data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto.FundingThe Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG).

Challenges of Tuberculosis in Iran

Background: Despite the implementation of the national control program, tuberculosis is one of the greatest health problems in Iran. The prevalence of different strains in specific ethnic populations suggests that Mycobacterium tuberculosis transmission has been limited and restricted to close contact. Objectives: In the present review, we describe the epidemiology of tuberculosis in Iran. Methods: In this review article, databases including Scopus, PubMed, and Google scholar were used to search for the epidemiology of tuberculosis in Iran. Results: Since 1996, tuberculosis incidence has been decreased as the national tuberculosis control program was established in Iran. However, due to the emergence of drug-resistant strains, recurrence of the disease, and association of tuberculosis with HIV pandemic, tuberculosis is becoming a health problem in Iran like many other parts of the world. Moreover, several other factors such as poverty, homelessness, inadequate access to health services, and lack of infrastructure in public health play an important role in worsening the situation. The distribution of the disease is not similar in all parts of Iran and it is higher in the western and eastern parts than the central areas. Conclusions: Review of the studies revealed that levels of multidrug-resistant tuberculosis among new tuberculosis patients are increasing in Iran and the vaccination system needs to be reformed. Because of the increasing number of patients coming from neighboring countries with multidrug-resistant tuberculosis, this area needs more stewardship and control in order to prevent the outbreak of multidrug-resistant tuberculosis. Finally, by improving the healthcare system, it is trusted that a more noteworthy number of these patients will be cured in Iran.

Impact of Infection Control Measures to Control an Outbreak of Multidrug-Resistant Tuberculosis in a Human Immunodeficiency Virus Ward, Peru.

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000—56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug–susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB–coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective.

Rapid and simple identification of Beijing genotype strain of Mycobacterium tuberculosis using a loop-mediated isothermal amplification assay.

Beijing genotype strains of Mycobacterium tuberculosis are geographically widespread and pose a notorious public health problem, these strains causing outbreaks of multidrug-resistant tuberculosis (TB); some studies have reported an association with drug resistance. Because the prevalence of Beijing strain has a substantial impact on TB control programs, the availability of a rapid and reliable method for detecting these strains is important for epidemiological monitoring of their circulation. The main methods currently used to identify Beijing genotype strains are IS6110 DNA fingerprinting, spoligotyping and PCR to detect specific deletions such as region of difference (RD)207. More recently, multiplex PCR assay using a Beijing-specific single nucleotide polymorphism (SNP) has been developed for detecting Beijing lineage strains. However, these methods are time-consuming and technically demanding. In the present study, a loop-mediated isothermal amplification (LAMP) assay that allows specific identification of Beijing genotype strain was developed. This Beijing genotype strain-identifying LAMP assay was performed 214 clinical isolates and the results compared with those of conventional PCR that targeted RD207 and Rv0679c-targreting multiplex PCR for Beijing lineage identification. LAMP assay showed 100% sensitivity and specificity compared with RD207-PCR. Furthermore, the sensitivity and specificity were 99.3% and 100%, respectively, compared with Rv0679c-multiplex PCR. This LAMP assay could be used routinely in local laboratories to monitor the prevalence of the Beijing genotype strain and thereby used to help control the spread of these potentially highly virulent and drug resistant strains.

MDR-TB Outbreak among HIV-Negative Tunisian Patients followed during 11 Years.

BackgroundMultidrug-resistant tuberculosis (MDR-TB) outbreaks that evolve, from the outset, in a context strictly negative for HIV infection deserve special consideration since they reflect the true intrinsic epidemic potential of the causative strain. To our knowledge, the long-term evolution of such exceptional outbreaks and the treatment outcomes for the involved patients has never been reported hitherto. Here we provide a thorough description, over an 11-year period, of an MDR-TB outbreak that emerged and expanded in an HIV-negative context, Northern Tunisia.Methodology/Principal FindingsFrom October 2001 to June 2011, the MDR-TB outbreak involved 48 HIV-negative individuals that are mainly young (mean age 31.09 yrs; 89.6% male) and noninstitutionalized. Drug susceptibility testing coupled to mutational analysis revealed that initial transmission involved an isolate that was simultaneously resistant to isoniazid, rifampicin, ethambutol, and streptomycin. The causative Haarlem3-ST50 outbreak strain expanded mainly as an 11-banded IS6110 RFLP profile (77.1%), from which a 12-banded subclone evolved. After undergoing a 2-year treatment with second-line drugs, 22 (45.8%) patients were cured and 3 (6.2%) completed treatment, thus yielding an overall treatment success rate of 52.1%. Among the patients that experienced unfavorable treatment outcomes, 10 (20.8%) failed treatment, 3 (6.2%) were lost to follow-up, 5 (10.4%) died, and 5 (10.4%) could not be evaluated. Poor adherence to treatment was found to be the main independent predictor of unfavorable outcomes (HR: 9.15; 95% CI 1.72–48.73; P = 0.014). Intriguingly, the evolved 12-banded subclone proved significantly associated with unfavorable outcomes (HR: 4.90; 95% CI 1.04–23.04, P = 0.044). High rate of fatality and relapse was further demonstrated at the long-term, since 70% of those whose treatment failed have died, and 24% among those deemed successfully treated have relapsed.Conclusions/SignificanceTaken together, the data obtained in this study indicate that MDR-TB clinical isolates could become fit enough to cause large and severe outbreaks in an HIV-negative context. Such MDR-TB outbreaks are characterized by low treatment success rates and could evolve towards increased severity, thus calling for early detection of cases and the necessity to raise the bar of surveillance throughout and beyond the treatment period.

An outbreak of multidrug-resistant tuberculosis among a family

Tuberculosis is a major public health problem and it may be complicated by multidrug-resistant tuberculosis (MDR-TB). Wide transmission among immunocompetent contacts of the index case is possible. If you detect tuberculosis in two contacts of the index case, it is called an outbreak. The aim of our paper is to evaluate the characteristics of a MDR-TB outbreak affecting 7 people in a family treated during 2012–2014 in Istanbul Yedikule Training and Research Hospital for Chest Disease and Thoracic Surgery, Turkey. The cultures, spoligotyping, and DNA fingerprinting revealed the same Mycobacterium tuberculosis species as T1 genotype and ST53 subtype. All patients were negative for human immunodeficiency virus and free of other underlying diseases.

Outbreak of Multidrug-resistant Tuberculosis in Two Secondary Schools

ObjectivesTo describe an outbreak of multidrug-resistant tuberculosis (MDR-TB) in two schools. MethodsThis was a prospective, observational study of an outbreak of MDR-TB in 2 schools located in the towns of Onda and Nules, in the Spanish province of Castellon, from the moment of detection in November 2008 until November 2014, including patient follow-up and contact tracing. ResultsFive cases of MDR-TB were diagnosed. Overall attack rate was 0.9%, and among the contacts traced, 66 had latent tuberculous infection, with an infection rate of 14.4%. Molecular characterization of the 5 M. tuberculosis isolates was performed by restriction fragment length polymorphism (RFLP) analysis of the IS6110 sequence. In all 5 patients, cultures were negative at 4-month follow-up, showing the efficacy of the treatment given. No recurrence has been reported to date. ConclusionsIn the context of globalization and the increased prevalence of MDR-TB, outbreaks such as the one presented here are only to be expected. Contact tracing, strict follow-up of confirmed cases, the availability of fast diagnostic techniques to avoid treatment delay, and chemoprophylaxis, together with the molecular characterization of strains, are still essential.