Effect of the Xpert MTB/RIF on the detection of pulmonary tuberculosis cases and rifampicin resistance in Shanghai, China.

BACKGROUND: Xpert MTB/RIF (Xpert) is an automated molecular test recommended by World Health Organization (WHO) for diagnosis of tuberculosis (TB). This study evaluated the effect of Xpert implementation on the detection of pulmonary TB (PTB) and rifampicin-resistant TB (RR-TB) cases in Shanghai, China. METHODS: Xpert was routinely implemented in 2018 for all presumptive PTB patients. All PTB patients above 15 years-old identified within the Provincial TB Control Program during the first half of each of 2017 and 2018, were enrolled to compare the difference in proportions of bacteriological confirmation, patients with drug susceptibility test (DST) results for rifampicin (ie, DST coverage) and RR-TB detection before and after Xpert's implementation. RESULTS: A total of 6047 PTB patients were included in the analysis with 1691 tested by Xpert in 2018. Percentages of bacteriological confirmation, DST coverage and RR-TB detection in 2017 and 2018 were 50% vs. 59%, 36% vs. 49% and 2% vs. 3%, respectively (all p-values < 0.05). Among 1103 PTB patients who completed sputum smear, culture and Xpert testing in 2018, Xpert detected an additional 121 (11%) PTB patients who were negative by smear and culture, but missed 248 (23%) smear and/or culture positive patients. Besides, it accounted for an increase of 9% in DST coverage and 1% in RR-TB detection. The median time from first visit to a TB hospital to RR-TB detection was 62 days (interquartile range -IQR 48-84.2) in 2017 vs. 9 days (IQR 2-45.7) in 2018 (p-value < 0.001). In the multivariate model, using Xpert was associated with decreased time to RR-TB detection (adjusted hazard ratio = 4.62, 95% confidence interval: 3.18-6.71). CONCLUSIONS: Integrating Xpert with smear, culture and culture-based DST in a routine setting significantly increased bacteriological confirmation, DST coverage and RR-TB detection with a dramatic reduction in the time to RR-TB diagnosis in Shanghai, China. Our findings can be useful for other regions that attempt to integrate Xpert into routine PTB and RR-TB case-finding cascade. Further study should focus on the identification and elimination of operational level challenges to fully utilize the benefit of rapid diagnosis by Xpert.

Establishment and development of national community-based collaborative innovation demonstration areas to achieve the control target of hepatitis B in China.

BACKGROUND: The major infectious diseases of hepatitis B has constituted an acute public health challenge in China. An effective and affordable HBV control model is urgently needed. A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control. METHODS: Based on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening. Moreover, HBV field research strategy was popularized in CCI-HBV areas. After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage. And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations. In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents' epidemiological data. In addition, a special quality control team was set up for CCI project. RESULTS: After two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people. The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing. CONCLUSIONS: CCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention. We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect. The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China. To provide policymakers with a feasible model, our results are directly applicable. TRIAL REGISTRATION: The project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled "The prevention and control of AIDS, viral hepatitis and other major infectious diseases", Grant Nos. 2009ZX10004901, 2011ZX10004901, 2013ZX10004904, 2014ZX10004007 and 2014ZX10004008.

Time to Multidrug-Resistant Tuberculosis Treatment Initiation in Association with Treatment Outcomes in Shanghai, China.

In high tuberculosis (TB)-burden countries such as China, the diagnosis of multidrug-resistant tuberculosis (MDR-TB) using conventional drug susceptibility testing (DST) takes months, making treatment delay inevitable. Poor outcomes of MDR-TB might be associated with delayed, even inappropriate, treatment. The purposes of this study were to investigate the time to MDR-TB treatment initiation and to assess the association between early treatment and treatment outcomes. Between April 2011 and December 2014, this population-based retrospective cohort study collected the demographic and clinical characteristics and the drug susceptibility profiles of all registered MDR-TB patients in Shanghai, China. The dates of TB and MDR-TB diagnoses, DST performance, and treatment initiation were extracted to calculate the times to treatment. In total, 284 of 346 MDR-TB patients were eligible for analysis, and 68.3% (194/284) had favored outcomes. The median time to treatment initiation from TB diagnosis was 172 days among those with favored outcomes and 190 days among those with poor outcomes. Treatments initiated within 60 days after performing DST (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.22 to 5.36) and empirical treatments (OR, 2.09; 95% CI, 1.01 to 4.32) were positively associated with favored outcomes. Substantial delays to MDR-TB treatment were observed when conventional DST was used. Early treatment predicted favored outcomes. Rapid diagnostic methods should be scaled up and improvements should be made in patient management and information linkage to reduce treatment delay.

Streptococcus pneumoniae and Haemophilus influenzae type b carriage in Chinese children aged 12-18 months in Shanghai, China: a cross-sectional study.

BACKGROUND: The bacteria Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) are leading causes of childhood pneumonia and meningitis and are major contributors to worldwide mortality in children younger than 5 years of age. Asymptomatic nasopharyngeal carriage of pneumococcus and Hib was determined for healthy children in Shanghai in 2009. METHODS: Children from 5 immunization clinics were enrolled in this study. Specimens from the nasopharynx were collected and cultured in Columbia and chocolate agar to identify pneumococcal and Hib carriage. Pneumococcal specimens were serotyped with the Neufeld test, and antibiotic resistance for pneumococcal and Hib specimens used the E-test method. Significance of risk factors for carriage was assessed through chi-square tests. RESULTS: Among 614 children, 16.6% had pneumococcal carriage and 8.0% Hib carriage. The predominant serotype of pneumococcus that was isolated was 19 F (52.9%); serotype coverage was 68.6% for both 7-valent pneumococcal conjugate vaccine (PCV) and PCV-10, and 82.3% for PCV-13. Household residency and father's education were both significantly related to pneumococcal and Hib carriage. The majority of S. pneumoniae isolates were sensitive to most antimicrobials but there were high levels of resistance to azithromycin (51.0 %) and erythromycin (51.0%). Haemophilus influenzae isolates were sensitive to almost all antimicrobials tested although 12.2% of isolates were resistant to ampicillin. CONCLUSIONS: The pneumococcal and Hib vaccines require payment, and the children with the highest burden of disease may not be receiving these vaccines. Moreover, the presence of high antibiotic susceptibility towards pneumococcus, and to a lesser extent towards Hib, underscores the need for preventive protection against these diseases. Public funding of pneumococcal and Hib vaccines would be one mechanism to increase uptake of these vaccines.

Tuberculosis-associated mortality in Shanghai, China: a longitudinal study.

OBJECTIVE: To determine excess mortality in a cohort of people with tuberculosis in Shanghai. METHODS: Participants were local residents in 4 (of 19) districts in Shanghai, registered in one of four tuberculosis clinics between January 1, 2004 and December 31, 2008. Baseline data were collected at the most recent diagnosis of tuberculosis and mortality was assessed between March and May of 2014. We calculated standardized mortality ratios (SMR) and case-fatality rates for all participants and for subgroups. Univariate and multivariate Cox regression models were used to quantify associations between co-morbidities and mortality from all causes and from tuberculosis. FINDINGS: We registered 4569 subjects in the cohort. Overall, the cohort had an SMR for deaths from all causes of 5.2 (95% confidence interval, CI: 4.8-5.6). Males had a higher SMR than females (6.1 versus 3.0). After adjustment for age and sex, hazard ratios (HR) for deaths from all causes were significantly greater in previously treated people (HR: 1.26; 95% CI: 1.08-1.49) and sputum smear-test positive people (HR: 1.55; 95% CI: 1.35-1.78). The risk of death from tuberculosis was also significantly greater for previously treated people (HR: 1.88; 95% CI: 1.24-2.86) and smear positive people (HR: 3.16; 95% CI: 2.06-4.87). CONCLUSION: People with tuberculosis in Shanghai have an increased risk of mortality. Earlier diagnosis and more vigilant follow-up may help to reduce mortality in this group.

Efforts to reduce the disparity between permanent residents and temporary migrants: Stop TB experiences in Shanghai, China.

OBJECTIVE: Eight of 17 districts of Shanghai have offered transportation and living allowances subsidies to patients with tuberculosis (TB) among the migrant population. The study aimed to assess the impact of the subsidising initiative on the treatment success rate (TSR) and identify the social determinants of treatment outcomes. METHODS: The participants included 7072 residents and 5703 migrants who were registered in the TB Information Management System with smear-positive pulmonary TB from January 2006 to December 2010. The Cochran-Armitage test was employed to test the trends of TSR and logistic regressions to identify the factors associated with treatment outcome. RESULTS: Without subsidies, migrant TB cases had lower odds of successful treatment [OR = 0.20 (95% CI 0.18-0.23)] than resident cases. Subsidisation was associated with a 65% increased odds ratio of success [1.65 (1.40-1.95)] among migrant cases. The TSR has stabilised at 87% for both permanent residents and temporary migrants since 2009. Living in districts with a population density ≥20,000/km(2) was associated with a low odds ratio [0.42 (0.26-0.68)] among resident cases, whereas among migrant cases those living in districts out of central downtown had a higher odds ratio of treatment success [peripheral downtown: 1.73 (1.36-2.20), suburban: 1.69 (1.16-2.46)]. The TB cases in districts with 2.0-2.9 TB specialists/100 cases had a higher odds ratio [2.99 (1.91-4.69)] of successful treatment than cases from districts with fewer specialists. CONCLUSIONS: Besides free medical services, transport and living allowance subsidies to migrant patients with TB improved the treatment outcome significantly.

Epidemiology of norovirus infections among diarrhea outpatients in a diarrhea surveillance system in Shanghai, China: a cross-sectional study.

BACKGROUND: Norovirus is an important cause of gastroenteritis both in children and adults. In China, few studies have been conducted on adult populations. This study aimed to determine the contribution of norovirus to gastroenteritis, characterize the features of norovirus infections, compare them with other pathogens, and test the effectiveness of the surveillance system. METHODS: A citywide surveillance network on diarrhea patients was established. Samples were collected with intervals from both children and adults among diarrhea outpatients in hospitals and tested for viruses using rRT-PCR and for bacteria in CDCs. Patient information was acquired through interviews and recorded into a dedicated online system. The Pearson χ2 test, multivariate logistic regression models and discriminant models were fitted into its comparisons with the non-norovirus group and other pathogens. RESULTS: Norovirus was detected in 22.91% of sampled diarrhea patients. The seasonal distribution of norovirus infections was different from non-norovirus patients (p<0.001), with a half-year peak. Higher proportions of males (p=0.001, OR=1.303, 95% CI=1.110-1.529), local citizens (p<0.001) and officials/clerks (p=0.001, OR=1.348, 95% CI=1.124-1.618) were affected with norovirus when compared with non-norovirus patients. Diarrhea patients affected with norovirus featured nausea (p<0.001, OR=1.418, 95% CI=1.176-1.709) and vomiting (p<0.001, OR=1.969, 95% CI=1.618-2.398), while fewer manifested fever (p=0.046, OR=0.758, 95% CI=0.577-0.996) and abdominal pain (p=0.018, OR=0.815, 95% CI=0.689-0.965). Children were more vulnerable to rotavirus (p=0.008, OR=1.637, 95% CI=1.136-2.358) and bacteria (p=0.027, OR=1.511, 95% CI=1.053-2.169) than norovirus. There was a seasonal difference between the GI and GII genotypes (p<0.001). Officials or clerks were more easily affected with GI than GII (p=0.006, OR=1.888, 95% CI=1.205-2.958). CONCLUSIONS: This study was based on a citywide hospital-sentinel surveillance system with multiple enteric pathogens included. Norovirus was recognized as the most prevalent enteric pathogen in Shanghai. The seasonal peak was from October to April. Males had a higher prevalence than females. Local citizens and officials/clerks were more vulnerable to norovirus than other pathogens. Compared with rotavirus and bacteria, children were less frequently affected by norovirus. Nausea and vomiting were typical of norovirus, whereas fever and abdominal pain were uncommon symptoms of this pathogen. GI and GII infections were centered in different seasons. Officials and clerks were more easily affected by GI than GII.

Risk factors for influenza A(H7N9) disease--China, 2013.

BACKGROUND: The majority of human cases of novel avian influenza A(H7N9), which emerged in China in spring 2013, include reported exposure to poultry. However, specific host and exposure risk factors for disease are unknown, yet critical to design prevention measures. METHODS: In April-June 2013, we conducted a case-control study in 8 Chinese provinces. Patients with laboratory-confirmed A(H7N9) (n = 89) were matched by age, sex, and neighborhood to controls (n = 339). Subjects completed a questionnaire on medical history and potential exposures, including poultry markets and other poultry exposure. We used conditional logistic regression to calculate matched and adjusted odds ratios (ORs) for the association of A(H7N9) virus infection with potential risk factors. RESULTS: Fifty-five percent of patients compared with 31% of controls reported any contact with poultry (matched OR [mOR], 7.8; 95% confidence interval [CI], 3.3-18.8). Sixty-seven percent of patients compared with 35% of controls visited a live poultry market (mOR, 5.4; CI, 3.0-9.7). Visiting live poultry markets increased risk of infection even after adjusting for poultry contact and other confounders (adjusted OR, 3.4; CI, 1.8-6.7). Backyard poultry were not associated with increased risk; 14% of cases did not report any poultry exposure or market visit. Obesity (mOR, 4.7; CI, 1.8-12.4), chronic obstructive pulmonary disease (mOR, 2.7; CI, 1.1-6.9), and immunosuppressive medications (mOR, 9.0; CI, 1.7-47.2) were associated with A(H7N9) disease. CONCLUSION: Exposures to poultry in markets were associated with A(H7N9) virus infection, even without poultry contact. China should consider permanently closing live poultry markets or aggressively pursuing control measures to prevent spread of this emerging pathogen.

Novel avian influenza A(H7N9) virus in tree sparrow, Shanghai, China, 2013.

In spring 2013, influenza A(H7N9) virus was isolated from an apparently healthy tree sparrow in Chongming Dongping National Forest Park, Shanghai City, China. The entire gene constellation of the virus is similar to that of isolates from humans, highlighting the need to monitor influenza A(H7N9) viruses in different species.

Genetic epidemiology and plasmid-mediated transmission of mcr-1 by Escherichia coli ST155 from wastewater of long-term care facilities.

Long-term care facilities (LTCFs) for older people play an important and unique role in multidrug-resistant organism transmission. Herein, we investigated the genetic characteristics of mobile colistin resistance gene (mcr-1)-carrying Escherichia coli strains isolated from wastewater of LTCFs in Shanghai. Antimicrobial susceptibility test was carried out by agar dilution methods. Whole-genome sequencing and plasmid sequencing were conducted, and resistance genes and sequence types of colistin in E. coli isolates were analyzed. Core genome multilocus sequence typing (cgMLST) analysis was performed by the Ridom SeqSphere+ software. Phylogenetic tree through the maximum likelihood method was constructed by MEGA X. Out of 306 isolates, only 1 E. coli named ECSJ33 was found, and the plasmid pECSJ33 from ECSJ33 harbored the mcr-1 gene that was located with 59,080 bp belonging to IncI2 type. The plasmid pECSJ33 was capable of conjugation with an efficiency of 2.9 × 10-2. Bioinformatic analysis indicated pECSJ33 shared backbone with the previously reported mcr-1-harboring pHNGDF93 isolated from fish source. Moreover, the cgMLST analysis revealed that ECSJ33 belongs to different lineages from those reported from previous E. coli strains but shared high similarity to NCTC11129 in cluster 11. The phylogenetic tree revealed MCR-1 of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Our study firstly reports detection of genome sequence of a multidrug-resistant mcr-1-harboring E. coli ST155 from wastewater of LTCF source in China. The data may prove that the plasmid pECSJ33 belongs to food origin and help to understand the antimicrobial resistance mechanisms and genomic features of colistin resistance under One Health approach.IMPORTANCEOne Escherichia coli named ECSJ33 was found from wastewater of a long-term care facility (LTCF) and the plasmid pECSJ33 from ECSJ33 harbored the mobile colistin resistance gene (mcr-1) that was located with 59,080 bp belonging to IncI2 type, which was capable of conjugation with an efficiency of 2.9 × 10-2. This paper firstly reports an mcr-1-carrying E. coli strain ST155 isolated from LTCF in China. Comparative genomics analysis indicated pECSJ33 shared backbone with the previously reported mcr-1-harboring pHNGDF93 isolated from fish source. The phylogenetic tree revealed MCR-1 protein of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Therefore, the pECSJ33 could be considered as food-origin transmission mcr-1-harboring plasmid.

Establishment and application of recombinase polymerase amplification combined with a lateral flow dipstick for the detection of mcr-1 in uncultured clinical samples.

OBJECTIVES: The rapid dissemination of the mcr-1 gene via plasmid-mediated transfer has raised concerns regarding the efficacy of colistin as a last-resort treatment for multidrug-resistant Gram-negative bacterial infections. Current mcr-1 gene detection methods mainly focus on cultured bacteria, which is a complex and time-consuming process requiring skilled personnel, making it unsuitable for field analysis. METHODS: A rapid detection technique combining recombinase polymerase amplification with a lateral flow dipstick targeting uncultured clinical samples was developed. RESULTS: This new method targeting the mcr-1 gene region (23 232-23 642 bp, no. KP347127.1) achieved a low detection limit of 10 copies/µL. The whole process was carried out with high specificity and was completed within 20 min. The evaluation assay was conducted using 45 human faecal samples; 16 strains yielded a 98% accuracy, closely matching antimicrobial susceptibility outcomes. CONCLUSIONS: The novel method integrates nucleic acid extraction, isothermal amplification, and a test assay, suggesting the potential for timely colistin resistance surveillance in frontline disease control and healthcare settings, supporting future prevention and clinical standardization efforts.

Multidrug-resistant atypical variants of Shigella flexneri in China.

We identified 3 atypical Shigella flexneri varieties in China, including 92 strains with multidrug resistance, distinct pulse types, and a novel sequence type. Atypical varieties were prevalent mainly in developed regions, and 1 variant has become the dominant Shigella spp. serotype in China. Improved surveillance will help guide the prevention and control of shigellosis.

A reported death case of a novel bunyavirus in Shanghai, China.

This paper describes the first case of infection with a recently described novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), in Shanghai, China. The case is originally from Chizhou City, Anhui province within an endemic area for SFTSV. We describe the etiology, epidemiological characteristics, clinical diagnosis and treatment of this fatal case. This case is unique because major cause of death was renal failure, whereas other reported cases have been due to hemorrhage. The investigation and response to this case provides meaningful insight for the early and rapid diagnosis, treatment, prevention and control of severe fever with thrombocytopenia syndrome virus in non-endemic regions in China and globally.

The development of a combined mathematical model to forecast the incidence of hepatitis E in Shanghai, China.

BACKGROUND: Sporadic hepatitis E has become an important public health concern in China. Accurate forecasting of the incidence of hepatitis E is needed to better plan future medical needs. Few mathematical models can be used because hepatitis E morbidity data has both linear and nonlinear patterns. We developed a combined mathematical model using an autoregressive integrated moving average model (ARIMA) and a back propagation neural network (BPNN) to forecast the incidence of hepatitis E. METHODS: The morbidity data of hepatitis E in Shanghai from 2000 to 2012 were retrieved from the China Information System for Disease Control and Prevention. The ARIMA-BPNN combined model was trained with 144 months of morbidity data from January 2000 to December 2011, validated with 12 months of data January 2012 to December 2012, and then employed to forecast hepatitis E incidence January 2013 to December 2013 in Shanghai. Residual analysis, Root Mean Square Error (RMSE), normalized Bayesian Information Criterion (BIC), and stationary R square methods were used to compare the goodness-of-fit among ARIMA models. The Bayesian regularization back-propagation algorithm was used to train the network. The mean error rate (MER) was used to assess the validity of the combined model. RESULTS: A total of 7,489 hepatitis E cases was reported in Shanghai from 2000 to 2012. Goodness-of-fit (stationary R2=0.531, BIC= -4.768, Ljung-Box Q statistics=15.59, P=0.482) and parameter estimates were used to determine the best-fitting model as ARIMA (0,1,1)×(0,1,1)12. Predicted morbidity values in 2012 from best-fitting ARIMA model and actual morbidity data from 2000 to 2011 were used to further construct the combined model. The MER of the ARIMA model and the ARIMA-BPNN combined model were 0.250 and 0.176, respectively. The forecasted incidence of hepatitis E in 2013 was 0.095 to 0.372 per 100,000 population. There was a seasonal variation with a peak during January-March and a nadir during August-October. CONCLUSIONS: Time series analysis suggested a seasonal pattern of hepatitis E morbidity in Shanghai, China. An ARIMA-BPNN combined model was used to fit the linear and nonlinear patterns of time series data, and accurately forecast hepatitis E infections.

[Study and application of transmission tracking analysis technique during incubation period of respiratory infectious diseases].

OBJECTIVE: To develop a new transmission tracking analysis technique during incubation period of respiratory infectious diseases, and to discuss its practical value in the field survey of infectious diseases. METHODS: The classical epidemiological theory was integrated with geographic information system. The transmission tracking analysis technique was established based on the modeling platform ArcGIS Engine Developer Kit 9.3, using the techniques of address matching, shortest path analysis and buffer analysis, and programming by Visual C++. Eight serious sever acute respiratory syndrome (SARS) cases in Shanghai in year 2003 were then chose as prototype to set up the test cases A-H. The electronic map and population density data were separately collected from Institute of Surveying and Mapping in Shanghai and Shanghai statistical yearbook 2003, to calculate and explore the parameters as length of transmission path, area of buffer zone and key departments by single and multi case analysis module. RESULTS: The single case transmission tracking analysis showed that the length of transmission track of case A was 129.89 km during April 25th to 29th in 2003, including 12 tracing point and 108 intimate contacts, and the total area of buffer zone was 7.11 km(2) including 81 important institutes, naming 72 schools, 6 kindergartens and 3 gerocomiums. The multi-case transmission tracking analysis showed that the 8 cases shared 5 tracks without any temporal communication. However, there was a spatial communication whose length was 1.42 km and area was 0.60 km(2). There were no important institutes found in this communication area. CONCLUSION: Transmission tracking technique is practicable and efficient to trace the source of infection, analyze the transmission tracks, establish the isolation buffer area and explore the important geographic positions in epidemiological investigation.

Stability and genetic insights of the co-existence of blaCTX-M-65, blaOXA-1, and mcr-1.1 harboring conjugative IncI2 plasmid isolated from a clinical extensively-drug resistant Escherichia coli ST744 in Shanghai.

Background: Co-existence of colistin, ß-lactam and carbapenem in multidrug-resistant Enterobacteriaceae isolates poses a serious threat to public health. In this study, we investigated and characterized the co-occurrence of blaCTX-M-65, blaOXA-1, and mcr-1.1 strain isolated from a clinical extensively-drug-resistant Escherichia coli ST744 in Shanghai. Methods: Antimicrobial susceptibility test was carried out by agar dilution methods. Whole genome sequencing was conducted, and resistance genes, and sequence types of colistin in E. coli isolates were analyzed. Plasmid stability and amino acid mutations were assessed in E. coli isolates. Results: A colistin resistant E. coli ST744, named ECPX221, was identified out of 145 fecal samples collected. The strain carries a 60,168 IncI2 plasmid with the mcr-1.1 gene. The strain also has blaCTX-M-65, blaOXA-1, dfrA14, qnrS1, cmlA5, arr2, ampC, aph(4)-Ia, sul1, and aadA5 resistance genes. The plasmid pECPX221 was capable of conjugation with an efficiency of 2.6 × 10-2. Notably, 45% of the transconjugants were determined as mcr-1.1-harboring in the colistin-free environment after 60 generation of passage. No mutations occurred in pmrB, mgrB, and phoPQ gene in the mcr-1.1-harboring transconjugants. Bioinformatic analysis indicated pECPX221 shared highly similar backbone with the previously reported mcr-1.1-harboring pAH62-1, pMFDS1339.1, pSCZE4, and p2018-10-2CC. Furthermore, sequencing and phylogenetic analyses revealed a similarity between other MCR-1-homolog proteins, indicating that ECPX221 was colistin resistant. Conclusion: The stable transferable mcr-1.1-harboring plasmid found in the E. coli ST744 strain indicated the high risk to disseminate the extensively-drug-resistance phenotype among Enterobacteriaceae.

Effect of mobile health reminders on tuberculosis treatment outcomes in Shanghai, China: A prospective cohort study.

Background: Poor adherence increases the risk of unfavorable outcomes for tuberculosis (TB) patients. Mobile health (mHealth) reminders become promising approaches to support TB patients' treatment. But their effects on TB treatment outcomes remain controversial. In this prospective cohort study, we evaluated the effect of the reminder application (app) and the smart pillbox on TB treatment outcomes compared with the standard care in Shanghai, China. Methods: We recruited new pulmonary TB (PTB) patients diagnosed between April and November 2019 who were aged 18 or above, treated with the first-line regimen (2HREZ/4HR), and registered at Songjiang CDC (Shanghai). All eligible patients were invited to choose the standard care, the reminder app, or the smart pillbox to support their treatment. Cox proportional hazard model was fitted to assess the effect of mHealth reminders on treatment success. Results: 260 of 324 eligible patients enrolled with 88 using standard care, 82 the reminder app, and 90 the smart pillbox, followed for a total of 77,430 days. 175 (67.3%) participants were male. The median age was 32 (interquartile range [IQR] 25 to 50) years. A total of 44,785 doses were scheduled for 172 patients in the mHealth reminder groups during the study period. 44,604 (99.6%) doses were taken with 39,280 (87.7%) monitored by the mHealth reminders. A significant time-dependent downward linear trend was observed in the monthly proportion of dose intake (p < 0.001). 247 (95%) patients were successfully treated. The median treatment duration of successfully treated patients in the standard care group was 360 (IQR 283-369) days, significantly longer than those in the reminder app group (296, IQR 204-365, days) and the smart pillbox group (280, IQR 198-365, days) (both p < 0.01). Using the reminder app and the smart pillbox was associated with 1.58 times and 1.63 times increase in the possibility of treatment success compared with the standard care, respectively (both p < 0.01). Conclusion: The reminder app and the smart pillbox interventions were acceptable and improved the treatment outcomes compared with the standard care under the programmatic setting in Shanghai, China. More high-level evidence is expected to confirm the effect of mHealth reminders on TB treatment outcomes.

Genotypic and spatial analysis of transmission dynamics of tuberculosis in Shanghai, China: a 10-year prospective population-based surveillance study.

Background: With improved tuberculosis (TB) control programs, the incidence of TB in China declined dramatically over the past few decades, but recently the rate of decrease has slowed, especially in large cities such as Shanghai. To help formulate strategies to further reduce TB incidence, we performed a 10-year study in Songjiang, a district of Shanghai, to delineate the characteristics, transmission patterns, and dynamic changes of the local TB burden. Methods: We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in Songjiang during 2011-2020. Genomic clusters were defined with a threshold distance of 12-single-nucleotide-polymorphisms based on whole-genome sequencing, and risk factors for clustering were identified by logistic regression. Transmission inference was performed using phybreak. The distances between the residences of patients were compared to the genomic distances of their isolates. Spatial patient hotspots were defined with kernel density estimation. Findings: Of 2212 enrolled patients, 74.7% (1652/2212) were internal migrants. The clustering rate (25.2%, 558/2212) and spatial concentrations of clustered and unclustered patients were unchanged over the study period. Migrants had significantly higher TB rates but less clustering than residents. Clustering was highest in male migrants, younger patients and both residents and migrants employed in physical labor. Only 22.1% of transmission events occurred between residents and migrants, with residents more likely to transmit to migrants. The clustering risk decreased rapidly with increasing distances between patient residences, but more than half of clustered patient pairs lived ≥5 km apart. Epidemiologic links were identified for only 15.6% of clustered patients, mostly in close contacts. Interpretation: Although some of the TB in Songjiang's migrant population is caused by strains brought by infected migrants, local, recent transmission is an important driver of the TB burden. These results suggest that further reductions in TB incidence require novel strategies to detect TB early and interrupt urban transmission. Funding: Shanghai Municipal Science and Technology Major Project (ZD2021CY001), National Natural Science Foundation of China (82272376), National Research Council of Science and Technology Major Project of China (2017ZX10201302-006).

Relationship of close contact settings with transmission and infection during the SARS-CoV-2 Omicron BA.2 epidemic in Shanghai.

INTRODUCTION: We analysed case-contact clusters during the Omicron BA.2 epidemic in Shanghai to assess the risk of infection of contacts in different settings and to evaluate the effect of demographic factors on the association of infectivity and susceptibility to the Omicron variant. METHODS: Data on the settings and frequency of contact, demographic characteristics and comorbidities of index cases, contacts and secondary cases were analysed. Independent effect of multiple variables on the risk for transmission and infection was evaluated using generalised estimating equations. RESULTS: From 1 March to 1 June 2022, we identified 450 770 close contacts of 90 885 index cases. The risk for infection was greater for contacts in farmers' markets (fixed locations where farmers gather to sell products, adjusted OR (aOR): 3.62; 95% CI 2.87 to 4.55) and households (aOR: 2.68; 95% CI 2.15 to 3.35). Children (0-4 years) and elderly adults (60 years and above) had higher risk for infection and transmission. During the course of the epidemic, the risk for infection and transmission in different age groups initially increased, and then decreased on about 21 April (17th day of citywide home quarantine). Compared with medical workers (reference, aOR: 1.00), unemployed contacts (aOR: 1.77; 95% CI 1.53 to 2.04) and preschoolers (aOR: 1.61; 95% CI 1.26 to 2.05) had the highest risk for infection; delivery workers (aOR: 1.90, 95% CI 1.51 to 2.40) and public service workers (aOR: 1.85; 95% CI 1.64 to 2.10) had the highest risk for transmission. Contacts who had comorbidities (aOR: 1.10; 95% CI 1.09 to 1.12) had a higher risk for infection, particularly those with lung diseases or immune deficiency. CONCLUSION: Farmers' markets and households were the main setting for transmission of Omicron. Children, the elderly, delivery workers and public service workers had the highest risk for transmission and infection. These findings should be considered when implementing targeted interventions.

Analysis of circulating respiratory syncytial virus A strains in Shanghai, China identified a new and increasingly prevalent lineage within the dominant ON1 genotype.

Respiratory syncytial virus A (RSV-A) is one of the commonest pathogens causing acute respiratory tract infections in infants and children globally. The currently dominant circulating genotype of RSV-A, ON1, was first detected in Shanghai, China in 2011, but little data are available regarding its subsequent circulation and clinical impact here. In this work, we analyzed RSV-A infection in a cohort of patients hospitalized for acute respiratory infections in Shanghai Children's Hospital, and RSV-A was detected in ~10% of these cases. RSV-A G gene sequencing revealed that all successfully sequenced strains belonged to ON1 genotype, but in phylogenetic analysis, the majority of these sequences formed a clade separate from the four previously established lineages within ON1. The new lineage, denoted ON1-5, was supported by phylogenetic analyses using additional G gene sequences from RSV-A strains isolated in Shanghai and elsewhere. ON1-5 first appeared in 2015 in China and the Netherlands, and has since spread to multiple continents and gained dominance in Asia. In our cohort, ON1-5 was not associated with markedly different clinical presentations compared to other ON1 lineages. ON1-5 strains are characterized by four amino acid variations in the two mucin-like regions of G protein, and one variation (N178G) within the highly conserved CCD domain that is involved in receptor binding. These data highlight the continuous evolution of RSV-A, and suggest the possibility of the virus acquiring variations in domains traditionally considered to be conserved for fitness gain.