Xiaohong Gui

Transmission of MDR and XDR Tuberculosis in Shanghai, China

Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are global health problems. We sought to determine the characteristics, prevalence, and relative frequency of transmission of MDR and XDR TB in Shanghai, one of the largest cities in Asia. Methods TB is diagnosed in district TB hospitals in Shanghai, China. Drug susceptibility testing for first-line drugs was performed for all culture positive TB cases, and tests for second-line drugs were performed for MDR cases. VNTR-7 and VNTR-16 were used to genotype the strains, and prior treatment history and treatment outcomes were determined for each patient. Results There were 4,379 culture positive TB cases diagnosed with drug susceptibility test results available during March 2004 through November 2007. 247 (5.6%) were infected with a MDR strain of M. tuberculosis and 11 (6.3%) of the 175 MDR patients whose isolate was tested for susceptibility to second-line drugs, were XDR. More than half of the patients with MDR and XDR were newly diagnosed and had no prior history of TB treatment. Nearly 57% of the patients with MDR were successfully treated. Discussion Transmission of MDR and XDR strains is a serious problem in Shanghai. While a history of prior anti-TB treatment indicates which individuals may have acquired MDR or XDR TB, it does not accurately predict which TB patients have disease caused by transmission of MDR and XDR strains. Therefore, universal drug susceptibility testing is recommended for new and retreatment TB cases.

Transmission of Drug-Resistant Tuberculosis among Treated Patients in Shanghai, China

We sought to determine whether patients who had therapy failure with increasingly drug-resistant strains of tuberculosis had primary or acquired drug resistance, by genotyping the initial and subsequent drug-resistant clinical isolates of Mycobacterium tuberculosis collected from patients by the Shanghai Centers for Disease Control and Prevention over the course of a 5-year period. The vast majority of patients (27/32) had primary drug resistance, indicating transmission of a drug-resistant strain of M. tuberculosis. Only 16% (5/32) had acquired drug resistance because of a poor treatment regimen or nonadherence to an adequate regimen. Our findings highlight the urgency of increasing efforts to interrupt the transmission of drug-resistant tuberculosis in communities and facilities in Shanghai, China.

Recurrent Tuberculosis and Exogenous Reinfection, Shanghai, China

Of 52 patients with recurrent tuberculosis in Shanghai, Peoples Republic of China, 32 (61.5%) had isolates in which genotype patterns of Mycobacterium tuberculosis differed between first and second episodes. This result indicates that exogenous reinfection is common in an area with a high incidence of tuberculosis.

Selection of Mutations To Detect Multidrug-Resistant Mycobacterium tuberculosis Strains in Shanghai, China

ABSTRACT Novel tools are urgently needed for the rapid, reliable detection of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. To develop such tools, we need information about the frequency and distribution of the mycobacterial mutations and genotypes that are associated with phenotypic drug resistance. In a population-based study, we sequenced specific genes of M. tuberculosis that were associated with resistance to rifampin and isoniazid in 242 phenotypically MDR isolates and 50 phenotypically pan-susceptible isolates from tuberculosis (TB) cases in Shanghai, China. We estimated the sensitivity and specificity of the mutations, using the results of conventional, culture-based phenotypic drug susceptibility testing as the standard. We detected mutations within the 81-bp core region of rpoB in 96.3% of phenotypically MDR isolates. Mutations in two structural genes (katG and inhA) and two regulatory regions (the promoter of mabA-inhA and the intergenic region of oxyR-ahpC) were found in 89.3% of the MDR isolates. In total, 88.0% (213/242 strains) of the phenotypic MDR strains were confirmed by mutations in the sequenced regions. Mutations in embB306 were also considered a marker for MDR and significantly increased the sensitivity of the approach. Based on our findings, an approach that prospectively screens for mutations in 11 sites of the M. tuberculosis genome (rpoB531, rpoB526, rpoB516, rpoB533, and rpoB513, katG315, inhA-15, ahpC-10, ahpC-6, and ahpC-12, and embB306) could detect 86.8% of MDR strains in Shanghai. This study lays the foundation for the development of a rapid, reliable molecular genetic test to detect MDR strains of M. tuberculosis in China.

Prevalence of Fluoroquinolone Resistance among Tuberculosis Patients in Shanghai, China

ABSTRACT We determined the prevalence of fluoroquinolone resistance among the isolates of Mycobacterium tuberculosis from 605 pulmonary tuberculosis patients in Shanghai, China. Mutations in gyrA were found in 81.5% of phenotypically fluoroquinolone-resistant isolates and were used as a molecular marker of fluoroquinolone resistance. gyrA mutations were detected in 1.9% of strains pan-susceptible to first-line drugs and 25.1% of multidrug-resistant strains. Fluoroquinolone resistance was independently associated with resistance to at least one first-line drug and prior tuberculosis treatment.

Deaths among tuberculosis cases in Shanghai, China: who is at risk?

BackgroundInformation about the risk factors associated with death caused by tuberculosis (TB) or death with TB would allow improvements in the clinical care of TB patients and save lives. The present study sought to identify characteristics associated with increased risk of death during anti-TB treatment in Shanghai, a city in China with one of the countrys highest TB mortality rates.MethodsWe evaluated deaths among culture positive pulmonary TB cases that were diagnosed in Shanghai during 2000–2004 and initiated anti-TB therapy. Demographic, clinical, mycobacteriological information and treatment outcomes were routinely collected through a mandatory reporting system.ResultsThere were 7,999 culture positive pulmonary cases reported during the study period. The overall case fatality rate was 5.5% (440 cases), and approximately half (50.5%) of the deaths were attributed to causes other than TB. Eighty-six percent of the deaths were among TB cases age ≥ 60 years. The significant independent risk factors for mortality during anti-TB treatment were advancing age, male sex, sputum smear positivity, and the presence of a comorbidity.ConclusionMore vigorous clinical management and prevention strategies by both the TB control program and other public health programs are essential to improve TB treatment outcomes. Earlier suspicion, diagnosis and treatment of TB, especially among persons older than 60 years of age and those with a comorbid condition, could reduce deaths among TB patients.

Transmission of Mycobacterium tuberculosis in China: A Population-Based Molecular Epidemiologic Study

BACKGROUND Understanding the transmission of Mycobacterium tuberculosis is essential for the development of efficient tuberculosis control strategies. China has the second-largest tuberculosis burden in the world. Recent transmission and infection with M. tuberculosis, particularly drug-resistant strains, may account for many new tuberculosis cases. METHODS We performed a population-based molecular epidemiologic study of pulmonary tuberculosis in China during 1 July 2009 to 30 June 2012. We defined clusters as cases with identical variable number tandem repeat genotype patterns and identified the risk factors associated with clustering, by logistic regression. Relative transmission rates were estimated by the sputum smear status and drug susceptibility status of tuberculosis patients. RESULTS Among 2274 culture-positive tuberculosis patients with genotyped isolates, there were 705 (31.0%) tuberculosis patients in 287 clusters. Multidrug-resistant (MDR) tuberculosis (adjusted odds ratio [aOR], 1.86; 95% confidence interval [CI], 1.25-2.63) and infection with a Beijing family strain (aOR, 1.56; 95% CI, 1.23-2.96) were associated with clustering. Eighty-four of 280 (30.0%) clusters had a putative source case that was sputum smear negative, and 30.6% of their secondary cases were attributed to transmission by sputum smear-negative patients. The relative transmission rate for sputum smear negative compared with sputum smear-positive patients was 0.89 (95% CI, .68-1.10), and was 1.51 (95% CI, 1.00-2.24) for MDR tuberculosis vs drug-susceptible tuberculosis. CONCLUSIONS Recent transmission of M. tuberculosis, including MDR strains, contributes substantially to tuberculosis disease in China. Sputum smear-negative cases were responsible for at least 30% of the secondary cases. Interventions to reduce the transmission of M. tuberculosis should be implemented in China.

Mixed infections of Mycobacterium tuberculosis in tuberculosis patients in Shanghai, China

We applied a 7 loci Variable-Number-Tandem-Repeats (VNTR-7) analysis method to identify mixed infections of Mycobacterium tuberculosis and to estimate the rate of mixed infections among pulmonary tuberculosis patients in Shanghai, China. We validated the VNTR-7 method and used it to genotype an isolate from each of the 249 from pulmonary tuberculosis patients reported from the Songjiang and Chongming districts in Shanghai during 2006. We identified 14 patients with mixed infections, and the estimated rate of mixed infections was 5.6% (14/249) (95% CI 3.1%-9.2%). Mixed infections were observed more frequently among tuberculosis patients undergoing retreatment (15.6%) than among new cases (4.1%) (p<0.05), and among tuberculosis patients whose disease was caused by non-Beijing genotype strains (12.5%) versus Beijing genotype strains (3.5%) (p<0.05). The VNTR-7 method is a highly sensitive, practical tool with relatively high discriminatory power, making it useful for studying mixed infections.

Discriminatory potential of a novel set of Variable Number of Tandem Repeats for genotyping Mycobacterium marinum.

Mycobacterium marinum is a free-living bacterium that infects fish and amphibians, but is also an opportunistic pathogen in humans. Although in previous studies, the bacterium has shown a small number of Variable Number of Tandem Repeat (VNTR) polymorphic loci, the discriminatory power of the known VNTR loci is unlikely to be sufficient to distinguish such a globally ubiquitous waterborne microorganism, which has a presumably high genetic variance. The object of this study was to test M. marinum isolates from east China for strain diversity using previously described loci as well as novel VNTR loci, and to identify more discriminating VNTR loci that could enrich the genotyping tools for M. marinum. We found that 7 of the 12 tested VNTR loci, of which 5 were known loci and 2 loci were newly identified, showed good discriminatory power for the 14 M. marinum clinical isolates (Hunter-Gaston Index [HGI] value=0.990). The pathogenicity of isolates representing different VNTR clusters was also studied in a zebrafish (Danio rerio) infection model; in this model, 6 isolates representing 4 VNTR clusters induced chronic infections, whereas the American strain ATCC BAA-535 caused acute and lethal infections.