Transmission Of Multidrug-resistant Tuberculosis Research Articles

Transmission of multidrug-resistant tuberculosis in Shimen community in Shanghai, China: a molecular epidemiology study

BackgroundMultidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015.MethodsWe used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation.ResultsThe ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0–20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases.ConclusionsThe integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission.

Community transmission of multidrug-resistant tuberculosis is associated with activity space overlap in Lima, Peru

BackgroundTransmission of multidrug-resistant tuberculosis (MDRTB) requires spatial proximity between infectious cases and susceptible persons. We assess activity space overlap among MDRTB cases and community controls to identify potential areas of transmission.MethodsWe enrolled 35 MDRTB cases and 64 TB-free community controls in Lima, Peru. Cases were whole genome sequenced and strain clustering was used as a proxy for transmission. GPS data were gathered from participants over seven days. Kernel density estimation methods were used to construct activity spaces from GPS locations and the utilization distribution overlap index (UDOI) was used to quantify activity space overlap.ResultsActivity spaces of controls (median = 35.6 km2, IQR = 25.1–54) were larger than cases (median = 21.3 km2, IQR = 17.9–48.6) (P = 0.02). Activity space overlap was greatest among genetically clustered cases (mean UDOI = 0.63, sd = 0.67) and lowest between cases and controls (mean UDOI = 0.13, sd = 0.28). UDOI was positively associated with genetic similarity of MDRTB strains between case pairs (P < 0.001). The odds of two cases being genetically clustered increased by 22% per 0.10 increase in UDOI (OR = 1.22, CI = 1.09–1.36, P < 0.001).ConclusionsActivity space overlap is associated with MDRTB clustering. MDRTB transmission may be occurring in small, overlapping activity spaces in community settings. GPS studies may be useful in identifying new areas of MDRTB transmission.

82125 Multiple epidemics of multidrug-resistant tuberculosis revealed by spatial disease mapping and whole-genome sequencing analysis in urban China

ABSTRACT IMPACT: Our study will integrate state-of-the-art methods in pathogen genomics, epidemiology, and geospatial analysis to identify both host- and pathogen-factors driving the MDR-TB transmission and the study outcome can inform the design of targeted interventions OBJECTIVES/GOALS: The emergence of multidrug-resistant tuberculosis (MDR-TB) poses serious challenges for the global eradication of tuberculosis. Recent research has shown that transmission is now the dominant driver of MDR-TB. However, our limited understanding of where and among whom MDR-TB is transmitted hampers efforts to control person-to-person spread. METHODS/STUDY POPULATION: We used several analytic approaches to characterize the dynamics of MDR-TB transmission in Shanghai, China. We identified all culture-confirmed MDR cases between 2009-2016 in the city and 1) estimated individual-level risk factors for MDR disease; 2) mapped the TB cases by their home addresses and used a Bayesian spatial disease mapping method to identify regions with an elevated risk of MDR-TB; and 3) we sequenced all MDR isolates to understand whether transmission explained variance in risk that was not attributable to the distribution of individual or location-specific risk variates. RESULTS/ANTICIPATED RESULTS: There were 1034 MDR-TB cases among 16,315 culture-confirmed TB cases during the study period. Bayesian disease mapping identified spatial heterogeneity of MDR-TB and determined four hotspots with an elevated risk of MDR-TB, none of which were fully explained by individual or regional-covariates (Figure 1). Sequencing revealed that more than 40% of the MDR-TB strains were in genomic clusters, indicating recent MDR-TB transmission. Most importantly, MDR-TB cases in three of the four large clades (&gt;8 isolates) were spatially concentrated in three strain-specific hotspots (Figure 2). DISCUSSION/SIGNIFICANCE OF FINDINGS: With the combination of traditional epidemiological tools, geographical, and genomic methods, this study revealed multiple loci of transmission of specific MDR-TB clades within a single city. Identification of where and among whom MDR-TB is transmitted can inform the design of targeted interventions.

Trends in primary multidrug-resistant tuberculosis in the State of Rio de Janeiro: a retrospective study conducted during 2000-2019.

INTRODUCTION: We analyzed the trends in primary multidrug-resistant tuberculosis (MDR-TB).METHODS: We performed a time series analysis of primary MDR-TB cases reported in the State of Rio de Janeiro (RJ) during 2000-2019. The annual percent change and the average annual percentage change (AAPC) were computed using joinpoint regression analysis. RESULTS: The percentage of cases increased from 7.69% in 2000 to 38.42% in 2018. We observed an upward trend during this period (AAPC = 9.4; 95% confidence interval 1.4-18.0, p < 0.001). CONCLUSIONS: The trend indicates the increasing occurrence of MDR-TB transmission sources in RJ during 2000-2019.

Primary and acquired multidrug-resistant tuberculosis: Predictive factors for unfavorable treatment outcomes in Rio de Janeiro, 2000-2016.

ABSTRACTObjectiveTo identify clinical and demographic factors associated with unfavorable treatment outcomes in patients with primary and acquired multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State.MethodsRetrospective cohort study using data on 2 269 MDR-TB cases in 2000–2016. Factors associated with unsuccessful, loss to follow-up, and death outcomes in patients with primary and acquired resistance were investigated with bivariate and multivariate regression.ResultsPrimary resistance was 14.7% among MDR-TB cases. The unfavorable outcomes proportion was 30.3% in the primary resistance group and 46.7% in the acquired resistance group. There were significant differences in demographic and clinical characteristics between the two groups. Proportionally, the group with primary resistance had more cases among women (46.4% vs. 33.5% in the acquired resistance group), Caucasians (47.3% and 34%), and those with ≥8 years of schooling (37.7% and 27.4%). Extensively drug-resistant TB patients had 12.2-fold higher odds of unsuccessful outcome than MDR-TB patients, and comorbidities had 2-fold higher odds in the primary resistance group. Extensively drug-resistant TB had 5.43-fold higher odds in the acquired MDR-TB group. Bilateral disease and <8 years of schooling were associated with unsuccessful outcome in both groups. Being an inmate had 8-fold higher odds of loss to follow-up in the primary resistance group. Culture conversion by the sixth month was a protective factor for all outcomes.ConclusionsPrimary resistance cases of MDR-TB constitute a different transmission reservoir, which is related to other chronic diseases associated with higher acquisition of TB. The poor results observed in Rio de Janeiro State can contribute to increasing the transmission of primary MDR-TB, thus favoring drug resistance.

Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.

Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

Multidrug-resistant tuberculosis transmission among middle school students in Zhejiang Province, China

BackgroundDespite significant advancements in the treatment and diagnosis of tuberculosis (TB) over the past decade, drug-resistant TB remains an increasing threat to public health. TB outbreaks are most commonly reported in schools considering the delay in TB diagnosis, sustained contact, and overcrowding observed in schools. This report describes multidrug-resistant TB (MDR-TB) transmission in a school in Zhejiang Province. We aimed to raise awareness regarding MDR-TB transmission among students.Case presentationThe index patient was a 16-year-old girl in the second year of junior middle school in Zhejiang Province, China, who had been experiencing persistent cough and expectoration for 37 days since 1 March 2014. She tested positive for smear pulmonary and extrapulmonary TB on 8 April 2014 and was subsequently diagnosed with MDR-TB on 1 May 2014. However, the patient was resistant to isoniazid, rifampicin, ethambutol, and streptomycin. Thus, she was suspended from school for anti-TB treatment. All 54 students who were in close contact with the index patient in the same class were screened, and 5 tested positive on the tuberculin skin test. Their exposure time to the index patient was approximately 37 days. Three classmates were subsequently diagnosed with MDR-TB, with similar resistance profiles nearly two years later. Their average discovery delay was 55 days. These three classmates were also suspended from school for anti-TB treatment. During the treatment period, four students visited the local TB-designated hospital for further consultation every month and were followed up once a month by the local community health service center until they were completely cured.ConclusionsDiscovery delay for an index patient played a primary role in MDR-TB transmission inside the school. To immediately detect TB, morning examinations in schools should be performed. TB trackers and case managers should work closely with public health workers and physicians in cases of TB outbreaks or transmissions involving students. Moreover, individuals who are in close contact with MDR-TB patients should undergo careful clinical follow-up for at least two years. Implementing a joint examination strategy to ensure early detection, diagnosis, and treatment of MDR-TB transmission is recommended.

Multidrug-resistant tuberculosis in the United States, 2011-2016: patient characteristics and risk factors.

OBJECTIVE: To determine risk factors for multidrug-resistant tuberculosis (MDR-TB) and describe MDR-TB according to three characteristics: previous TB disease, recent transmission of MDR-TB, and reactivation of latent MDR-TB infection.SETTING and DESIGN: We used 2011-2016 surveillance data from the US National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service and used logistic regression models to estimate risk factors associated with MDR-TB.RESULTS: A total of 615/45 209 (1.4%) cases were confirmed as MDR-TB; 111/615 (18%) reported previous TB disease; 41/615 (6.7%) were attributed to recent MDR-TB transmission; and 449/615 (73%) to reactivation. Only 12/41 (29%) patients with TB attributed to recent transmission were known to be contacts of someone with MDR-TB. For non-US-born patients, the adjusted odds ratios of having MDR-TB were 32.6 (95%CI 14.6-72.6) among those who were known to be contacts of someone with MDR-TB and 6.5 (95%CI 5.1-8.3) among those who had had previous TB disease.CONCLUSION: The majority of MDR-TB cases in the United States were associated with previous TB disease or reactivation of latent MDR-TB infection; only a small proportion of MDR-TB cases were associated with recent transmission.

The relevance of household contacts tracing among child contacts of patients with multidrug-resistant tuberculosis

BACKGROUND. The World Health Organization (WHO) reports an unknown contact history of pediatric tuberculosis (TB), especially in children younger than 5 years old. Tracing pediatric household contacts of patients with multidrug-resistant TB (MDR-TB) is considered to be a highly effective intervention for detection of new cases of chemoresistant TB in children and timely prevention of its transmission. OBJECTIVE. To study the nature of TB process manifestations and concordance of mycobacterium tuberculosis (MBT) drug resistance profiles in household child contacts of patients with MDR-TB. MATERIALS AND METHODS. The nature of TB process manifestations and concordance of MBT drug resistance profiles in 12 household child contacts of patients with MDR-TB in 6 households (6 adult MDR-TB index patients, IP) were studied. Adults and children were examined and treated in the Pulmonary Tuberculosis Department No 3 and in the Pediatric Department of the Clinical Base of the Department of Phthisiology and Pulmonology of Zaporizhzhia State Medical University at the Municipal Institution “Zaporizhzhia Regional Tuberculosis Clinical Dispensary”. RESULTS AND DISCUSSION. The tracing of children who were household contacts of the MDR-TB IP revealed the following features. The incidence of child TB was 2 times higher than that of contact adults (44 % vs. 20 %). Moreover, the incidence among children younger than 2 years of age was almost 3 times higher than in children across other age groups (54.5 % vs. 18.2 % in children younger than 5 years of age and 18.2 % in children aged 5 years and older). The children were non-BCG vaccinated in 63.6 % of cases. There was an alarmingly high rate of non-BCG vaccinated children, namely 83.3 % among individuals younger than 2 years of age and all of those younger than 5 years of age (100 %). The children mostly presented small clinical forms of non-destructive TB: intrathoracic lymph node TB (36.4 %), MBT complex (36.4 %) and focal TB (18.2 %). Most of the children (63.6 %) who developed TB were detected within the first year of IP with MDR-TB follow-up, and it is worthy of note that in the majority of cases (4 households; 66.6 %). With respect to the concordance of MBT drug resistance profiles between the children and MDR-TB IP in the households, diagnosis in children was microbiologically confirmed in only 3 cases (3 households) demonstrating the complete concordance of profiles in each one. At the same time, the complete concordance of MBT drug resistance profiles between adult household contacts and the MDR-TB IP was also recorded in 3 cases. As is evident, across the household contacts group aged between 0 and 18 years who were exposed to the MDR-TB IP, the most susceptible to develop TB were non-BCG vaccinated children younger than 2 years. More worryingly is that among 3 microbiologically conformed individuals of this age group, 2 children younger than 2 years were found to have their own drug resistant MTB isolates. CONCLUSIONS. Tracing household child contacts of MDR-TB IP is particularly effective for timely detection of active TB within the first year of MDR-TB IP follow-up. Non-BCG vaccinated children younger than 2 years of age are at the highest risk for MDR-TB followed by non-BCG vaccinated children younger than 5 years of age. The early detection and timely antimycobacterial therapy initiation based on drug susceptibility test results of a MDR-TB IP is a guarantee not only for an effective treatment but also for a reduction in the MDR-TB transmission to other persons.

Trends of Two Epidemic Multidrug-Resistant Strains of Mycobacterium tuberculosis in Argentina Disclosed by Tailored Molecular Strategy.

Two Mycobacterium tuberculosis strains-M (sublineage 4.1) and Ra (sublineage 4.3)-have long prevailed in Argentina among patients with multidrug-resistant tuberculosis (MDR-TB). Recently, budget constraints have hampered the surveillance of MDR-TB transmission. Based on whole-genome sequence analysis, we used M- and Ra-specific single nucleotide polymorphisms to tailor two multiplex allele-specific polymerase chain reactions (PCRs), which we applied to 252 stored isolates (95% of all newly diagnosed MDR-TB cases countrywide, 2015-2017). Compared with the latest data available (2007-2009), the M strain has receded (80/324 to 20/252, P < 0.0001), particularly among cross-border migrants (12/58 to 0/53, P = 0.0003) and HIV-infected people (30/97 to 7/74, P = 0.0007), but it still accounts for 4/12 new cases of extensively drug-resistant TB. Differently, the Ra strain remained stable in frequency (39/324 to 33/252) and contributed marginally to the extensive drug-resistance load (1/12). Our novel strategy disclosed recent trends of the two major MDR-TB strains, providing meaningful data to allocate control interventions more efficiently.

Projecting the impact of variable MDR-TB transmission efficiency on long-term epidemic trends in South Africa and Vietnam

Whether multidrug-resistant tuberculosis (MDR-TB) is less transmissible than drug-susceptible (DS-)TB on a population level is uncertain. Even in the absence of a genetic fitness cost, the transmission potential of individuals with MDR-TB may vary by infectiousness, frequency of contact, or duration of disease. We used a compartmental model to project the progression of MDR-TB epidemics in South Africa and Vietnam under alternative assumptions about the relative transmission efficiency of MDR-TB. Specifically, we considered three scenarios: consistently lower transmission efficiency for MDR-TB than for DS-TB; equal transmission efficiency; and an initial deficit in the transmission efficiency of MDR-TB that closes over time. We calibrated these scenarios with data from drug resistance surveys and projected epidemic trends to 2040. The incidence of MDR-TB was projected to expand in most scenarios, but the degree of expansion depended greatly on the future transmission efficiency of MDR-TB. For example, by 2040, we projected absolute MDR-TB incidence to account for 5% (IQR: 4–9%) of incident TB in South Africa and 14% (IQR: 9–26%) in Vietnam assuming consistently lower MDR-TB transmission efficiency, versus 15% (IQR: 8–27%)and 41% (IQR: 23–62%), respectively, assuming shrinking transmission efficiency deficits. Given future uncertainty, specific responses to halt MDR-TB transmission should be prioritized.

Prevalence and Factors Associated with Multidrug-Resistant Tuberculosis (MDR-TB) among Presumptive MDR-TB Patients in Tigray Region, Northern Ethiopia.

Background Tuberculosis (TB) is one of the major public health problems. There are alarming reports of increasing multidrug-resistant tuberculosis (MTR-TB) from various parts of the globe, including Ethiopia. This study was designed to determine the prevalence and factors associated with MDR-TB among presumptive MDR-TB cases in Tigray Regional State, Ethiopia. Methods A cross-sectional study was conducted in Tigray Regional State from 2015 to 2016. Two hundred sputum samples were collected, transported, processed using 2% N-acetyl-L-cysteine-sodium hydroxide, and cultured in LJ medium. Besides, the microscopic examination was performed after ZN staining. Moreover, drug susceptibility test was done using molecular line probe assay. Descriptive statistics and binary and multivariable logistic regression were done. A statistical test was regarded as significant when the P value was <0.05. Results The prevalence of MDR-TB was found to be 18.5%. About one-fourth (26.5%) of the study participants had sputum smear positive for acid-fast bacilli (AFB). TB culture was positive in 37% of the samples, and rifampicin mono-resistant cases accounted for 3.5% of the presumptive MDR-TB cases. Three (1.5%) were new MDR-TB cases, while the rest had been treated previously for TB. Most (63.5%) of the MDR-TB cases were from 15 to 44 years of age. Age was associated with MDR-TB with a crude odds ratio of 1.06 (CI: 1.02–1.10) and adjusted odds ratio of 1.06 (CI: 1.00–1.11). Conclusions The prevalence of MDR-TB was found to be high. Preventive measures should be taken to prevent the transmission of MDR-TB in the community.

Citywide Transmission of Multidrug-resistant Tuberculosis Under China's Rapid Urbanization: A Retrospective Population-based Genomic Spatial Epidemiological Study.

Population movement could extend multidrug-resistant tuberculosis (MDR-TB) transmission and complicate its global prevalence. We sought to identify the high-risk populations and geographic sites of MDR-TB transmission in Shenzhen, the most common destination for internal migrants in China. We performed a population-based, retrospective study in patients diagnosed with MDR-TB in Shenzhen during 2013-2017. By defining genomic clusters with a threshold of 12-single-nucleotide polymorphism distance based on whole-genome sequencing of their clinical strains, the clustering rate was calculated to evaluate the level of recent transmission. Risk factors were identified by multivariable logistic regression. To further delineate the epidemiological links, we invited the genomic-clustered patients to an in-depth social network investigation. In total, 105 (25.2%) of the 417 enrolled patients with MDR-TB were grouped into 40 genome clusters, suggesting recent transmission of MDR strains. The adjusted risk for student to have a clustered strain was 4.05 (95% confidence interval, 1.06-17.0) times greater than other patients. The majority (70%, 28/40) of the genomic clusters involved patients who lived in different districts, with residences separated by an average of 8.76 kilometers. Other than household members, confirmed epidemiological links were also identified among classmates and workplace colleagues. These findings demonstrate that local transmission of MDR-TB is a serious problem in Shenzhen. While most transmission occurred between people who lived distant from each other, there was clear evidence that transmission occurred in schools and workplaces, which should be included as targeted sites for active case finding.The average residential distance between genomic-clustered cases was more than 8 kilometers, while schools and workplaces, identified as sites of transmission in this study, deserve increased vigilance for targeted case finding of multidrug-resistant tuberculosis.

Family cluster of multi-drug resistant tuberculosis in Kingdom of Saudi Arabia

We describe the clinical and genetic characteristics of multi-drug resistant tuberculosis (MDR-TB) in a family cluster in the western region of Kingdom of Saudi Arabia diagnosed between 2012 and 2016. All cases had risk factors for tuberculosis acquisition and they were not household contacts of the index case. Genetic analysis detected both MDR-TB and pre-extensively drug-resistant tuberculosis (pre-XDR TB) strains in the index case and confirmed tuberculosis transmission between two cases. Lack of early diagnosis of MDR-TB by molecular testing and lack of extended contact tracing contributed to the transmission of MDR-TB among this family cluster over four years.

A nationwide study of multidrug-resistant tuberculosis in Portugal 2014\u20132017 using epidemiological and molecular clustering analyses

BackgroundIncreasing multidrug-resistant tuberculosis (MDR-TB) incidence is a major threat against TB eradication worldwide. We aim to conduct a detailed MDR-TB study in Portugal, an European country with endemic TB, combining genetic analysis and epidemiological data, in order to assess the efficiency of public health containment of MRD-TB in the country.MethodsWe used published MIRU-VNTR data, that we reanalysed using a phylogenetic analysis to better describe MDR-TB cases transmission occurring in Portugal from 2014 to 2017, further enriched with epidemiological data of these cases.ResultsWe show an MDR-TB transmission scenario, where MDR strains likely arose and are transmitted within local chains. 63% of strains were clustered, suggesting high primary transmission (estimated as 50% using MIRU-VNTR data and 15% considering epidemiological links). These values are higher than those observed across Europe and even for sensitive strains in Portugal using similar methodologies. MDR-TB cases are associated with individuals born in Portugal and evolutionary analysis suggests a local evolution of strains. Consistently the sublineage LAM, the most common in sensitive strains in Europe, is the more frequent in Portugal in contrast with the remaining European MDR-TB picture where immigrant-associated Beijing strains are more common.ConclusionsDespite efforts to track and contain MDR-TB strains in Portugal, their transmission patterns are still as uncontrolled as that of sensitive strains, stressing the need to reinforce surveillance and containment strategies.

Cross-District Transmission of Multidrug-Resistant Tuberculosis in Shenzhen, a Newly Developed Metropolis of China with Massive Young Migrant Workers

Background: Population movement could extend multidrug-resistant tuberculosis (MDR-TB) transmission and complicate its global prevalence. We sought to identify the high-risk populations and geographic sites of MDR-TB transmission in Shenzhen, the most common destination for internal migrants in China. Methods: We performed a population-based, retrospective study of patients who were diagnosed with MDR-TB in Shenzhen during 2013-2017. By defining genomic clusters with a threshold of 12 SNP distance based on whole-genome sequencing their clinical strains, the clustering rate was calculated to evaluate the level of recent transmission. Risk factors for MDR-TB transmission were identified by multivariable logistic regression. To further delineate the epidemiological links, we invited the genomic-clustered patients to an in-depth social network investigation. Results: In total, 105 (25·2%) of the 417 enrolled MDR-TB patients were grouped into 40 genome clusters, suggesting recent transmission of MDR strains. The adjusted risk for students to have a clustered strain was 4·05 (95% confidential intervals [CI], 1·06-17·0) times greater than other patients. The majority (70%, 28/40) of the genomic clusters involved patients who lived in different districts, with residences separated by an average of 8·76 kilometers. Other than household members, confirmed epidemiological links were also identified among classmates and workplace colleagues. Interpretation: These findings demonstrate that local transmission of MDR-TB is a serious problem in Shenzhen city. While most transmission occurred between people who lived distant from each other, there was clear evidence that transmission occurred in schools and workplaces, which should be included as targeted sites for active case finding. Funding: Sanming Project of Shenzhen (SZSM201611030); and National Science and Technology Major Project of China (2017ZX10201302 & 2018ZX10715012-005) Declaration of Interest: We declare that we have no conflicts of interest. Ethical Approval: The study protocol was approved by the Ethical Review Board of Shenzhen CCDC (No. 20180310).

Prevalence of rifampicin resistant Mycobacterium tuberculosis among presumptive tuberculosis patients in selected governmental hospitals in Addis Ababa, Ethiopia

BackgroundRapid detection of rifampicin resistance is essential for early management and prevention of transmission of multidrug-resistant tuberculosis (MDR-TB). We studied the prevalence of rifampicin resistance of Mycobacterium tuberculosis (MTB) among presumptive TB patients in Addis Ababa, Ethiopia.MethodsA retrospective cross sectional study was conducted in three referral hospitals and the regional laboratory in Addis Ababa city from March 2015 to October 2017. Data was collected by data-extraction sheet from registration books. It was analyzed using SPSS version 20. Statistically significant association was taken with P < 0.05.ResultsA total of 12,414 (11,672 adults and 742 paediatrics) TB presumptive patients were included in the study. The overall prevalence of TB was 15.11% (1876/12414) in all age groups and 13.6%(101/742) among paediatric population. Rifampicin resistant TB was 9.9% (186/1876) in all TB confirmed cases and 7.9% (8/101) in paediatric TB patients. The prevalence of rifampicin resistant TB among new and previously treated was 7.6 and 27.4%, respectively. Sex (being female) and previous TB treatment were significantly associated with rifampicin resistant TB.ConclusionsRifampicin-resistant TB is prevalent both among adult and paediatric TB patients. The strong association of rifampicin resistance with previous treatment in this study suggests the need to improve and monitor the treatment to limit the emergence of drug resistant TB.

Molecular characterisation of multidrug-resistant Mycobacterium tuberculosis isolates from a high-burden tuberculosis state in Brazil.

Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

Transmission of multidrug-resistant tuberculosis in Shanghai: roles of residential status.

Shanghai is a mega city where 39% of the population comprises internal migrants. To examine the different roles played by migrants and permanent residents in the transmission of multidrug-resistant tuberculosis (MDR-TB). We conducted a population-based cohort study to assess MDR-TB transmission in Shanghai between 1 January 2009 and 31 December 2012 using genotyping and geospatial analyses. A total of 367 MDR-TB cases formed the study cohort. Significant differences between MDR-TB cases who were internal migrants and those who were permanent residents were found with regard to age, sex, region, genetic characteristics and treatment outcomes. Permanent residents had a higher transmission rate than internal migrants (OR 3.36, 95%CI 1.86-6.09). Permanent residents and genotypic clustering cases had similar clusters in central downtown and some parts of suburban areas. Most of the clusters of internal migrants were found in rural areas bordering suburban areas. Clusters of genotypic non-clustering cases showed patterns that closely matched those of internal migrants, suggesting acquired drug resistance in migrants. In Shanghai, permanent residents were significantly associated with recent transmission of MDR-TB in central downtown areas. Clustered cases of internal migrants in rural areas were most likely to have contracted MDR-TB through acquired resistance.

775. An Epidemiological Analysis of Patients With Multidrug-Resistant Tuberculosis Among Tibetan Refugees in India

BackgroundGlobally, refugee populations face an increased risk for tuberculosis (TB) due to malnutrition, overcrowding, and poor living conditions. Compared with the general Indian population, Tibetan refugees in India display a higher incidence rate of both TB and multidrug-resistant TB (MDR-TB). The high incidence of MDR-TB in younger population is a serious public health concern.MethodsWe retrospectively reviewed the medical records of patients with MDR-TB treated from January 2010 to December 2013 in Tibetan Delek Hospital, which is the center of TB control among Tibetan refugees. Patients were classified into either new cases (supposed infection by exposure to MDR-TB) or previously treated MDR-TB cases (suspected acquirement of MDR-TB through anti-TB treatment or by MDR-TB exposure after treatment). We compared patients’ age, sex, birthplace, residence type, occupation, contact history, and treatment outcome.ResultsOf 749 patients with TB, we enrolled 134 patients with MDR-TB [median age, 26 (interquartile range: 22–35) years; males, 55%]. The Tibetan ethnicity comprised 96% of the study population, whereas Indians (trans-Himalayan) comprised 4%. The birthplace was Tibet for 22% patients, India for 75%, and Nepal for 2%. New MDR-TB cases were 28% and previously treated MDR-TB cases were 72%. Failure was observed in 42% patients and cured and completed in 54% patients, during their previous TB treatment. The median age was significantly lower in new cases than in previously treated MDR-TB cases (24 vs. 28.5 years; P < 0.01). Tibet was the birthplace of 34% new cases and 18% in previously treated cases (P = 0.04). The residence was of the congregated type in 58% of new cases and 30% in previously treated MDR-TB cases (P = 0.01). The occupation was “student” and “unemployed” in 58% and 8% in new cases and 33% and 24% in previously treated cases, respectively (P = 0.03). Contact history with TB type and treatment outcome were not considerably different, although the rates of cured and completed were high in both new (82%) and previously treated (84%) MDR-TB cases.ConclusionThis study shows that new MDR-TB correlates with younger age, birth in Tibet, congregated residence, and student occupation. Targeting the above-listed characteristics could be effective in further reducing the MDR-TB transmission among Tibetan refugees in India.Disclosures All authors: No reported disclosures.