Multidrug-resistant patients receiving treatment in Niger who are infected with M. tuberculosis Cameroon family convert faster in smear and culture than those with M. tuberculosis Ghana family.

In this study, we analyzed the M. tuberculosis complex (MTBc) population structure among multidrug-resistant TB (MDR-TB) patients in Niger and tested whether the Cameroon family displayed a slower response to MDR-TB treatment. We genotyped baseline clinical isolates that had been collected from pulmonary MDR-TB patients recruited consecutively between 2008 and 2016 in Niger. Spoligotyping was used to analyze the genetic diversity of mycobacterial lineages, and Kaplan Meier's analysis to compare treatment outcomes. A total of 222 MTBc isolates were genotyped; 204 (91,9%) were identified as the Euro-American L4 lineage, with the Ghana family (106, 47,4%) and the Cameroon family (63, 28,4%) being predominant. Patients infected by Cameroon family isolates 61(96,8%) showed faster conversion (log-rank p < 0.01) than those infected with Ghana family isolates (91,5%), and were more likely to experience favorable outcome (adjusted odds ratio [aOR] 4.4; 95%CI 1.1-17.9]; p = 0.015). We found no association between MTBc families and second-line drug resistance profiles (p > 0.05). Our findings show that MDR-TB in Niger is caused by major spoligotypes of the Euro-American L4; with more rapid smear and culture conversion in patients infected with the Cameroon family. These first insights may alert clinicians that slow conversion may be associated with the type of infecting strain.

Impact of ethnic disparities on the treatment outcomes of HIV-negative drug-resistant tuberculosis patients in Kuala Lumpur, Malaysia: A call for a culturally-sensitive community intervention approach.

OBJECTIVE: Little is known about the treatment outcomes of HIV-negative drug-resistant tuberculosis (TB) patients in Malaysia. With respect to this issue, this study aimed to determine factors associated with unsuccessful treatment outcomes among drug-resistant TB patients at the Institute of Respiratory Medicine, Kuala Lumpur, Malaysia. METHODS: This retrospective cohort study involved laboratory-confirmed drug-resistant TB patients from January 2009 to June 2013. Multiple logistic regression was used to model the outcome, which was subsequently defined according to the recent definition by the WHO. Data were analysed using IBM SPSS Statistics for Windows version 22.0. RESULTS: Among the 403 patients who were analysed, 66.7% of them were found to have achieved successful outcomes (cured or completed treatment) while the remaining 33.3% had unsuccessful treatment outcomes (defaulted, treatment failure or died). Multivariable analysis showed that the type of resistance [polyresistant (aOR = 3.00, 95% CI 1.14-7.91), multidrug resistant (MDR) (aOR = 5.37, 95% CI 2.65-10.88)], ethnicity [Malay (aOR = 2.86, 95% CI 1.44-5.71), Indian (aOR = 3.04, 95% CI 1.20-7.70)], and treatment non-compliance (aOR = 26.93, 95% CI 14.47-50.10) were the independent risk factors for unsuccessful treatment outcomes among this group of patients. Notably, the odds of unsuccessful treatment outcome was also amplified among Malay MDR-TB patients in this study (aOR = 13.44, 95% CI 1.99-90.58). CONCLUSION: In order to achieve better treatment outcomes for TB, effective behavioural intervention and thorough investigation on ethnic disparities in TB treatment are needed to promote good compliance.

Genotypic diversity of Mycobacterium tuberculosis isolates from North-Central Indian population.

BACKGROUND: Different strains of Mycobacterium tuberculosis (MTB) are known to have different epidemiological and clinical characteristics. Some of them are widely distributed and associated with drug resistance, whereas others are locally predominated. Molecular epidemiological investigations have always been beneficial in identifying new strains and studying their transmission dynamics. Sahariya a primitive tribe of North Madhya Pradesh, India, has already been reported to have high prevalence of tuberculosis (TB) than their non-tribal neighbours. However, the information about MTB genotypes prevalent in Sahariya tribe and their non-tribal neighbours is not available. METHODS: A total of 214 clinical isolates representing Sahariya tribe and non-tribes were analyzed by spoligotyping and MIRU-VNTR typing. RESULTS: The EAI3_IND/SIT11 genotype was observed as major genotype in Sahariya tribe followed by CAS1_Delhi/SIT26 genotype. A 3.04 fold higher risk of getting TB with EAI3_IND/SIT11 genotype was observed in Sahariya as compared to the non-tribal population. The EAI_IND/SIT11 genotype also found to have more number of MDR-TB cases in Sahariya as well as true and possible transmission links. In Sahariya tribe, 3 clusters (6 isolates) reflected true transmission links, whereas 8 clusters consisted of 26 isolates revealed possible transmission links within the same geographical location or nearby houses. CONCLUSION: The present study highlighted the predominance of EAI3_IND/SIT11 genotype in Sahariya tribe followed by CAS1_Delhi/SIT26 genotype. Combined approach of MIRU-VNTR typing and spoligotyping was observed more favourable in discrimination of MTB genotypes. Further, longitudinal studies using whole genome sequencing can provide more insights into genetic diversity, drug resistance and transmission dynamics of these prevalent genotypes.

Characterization of pncA mutations in multi-drug and pyrazinamide resistant Mycobacterium tuberculosis isolates cultured from Queensland migrants and Papua New Guinea residents.

Outbreak of drug resistant tuberculosis in the Western province, Papua New Guinea is a concern to Queensland, Australia due to migration. We performed pncA mutation analysis and genotyping of multi-drug/pyrazinamide (MDR/PZA) resistant isolates from 18 Queensland (Qld) migrants and 81 Papua New Guinea (PNG) residents, to compare with phenotypic evidence of PZA resistance and to evaluate the genotypes obtained from the two countries. Seven different mutations were seen from Qld isolates of which 2 have not been described previously. A cluster of mutations were found between amino acids L35 and S65. Amongst the PNG isolates, 10 mutations were identified, of which 6 were unique and have not been described previously. Majority of the mutations formed 2 clusters, between amino acids Q10 to A20 and W68 to W119. Mutations identified at nucleotide (nt) position 202 and 307 were found to be the most common types, occurring in 25% and 51% of the PNG isolates respectively. The majority of the mutations were seen in MDR/PZA resistant isolates. These mutations could be utilized for direct screening of PZA resistance from PNG patient samples. Genotypic analysis of the isolates showed strong clustering amongst the PNG isolates as opposed to Qld isolates. A diversity of mutations and genotypes were seen amongst the Qld migrant isolates. Majority of PNG isolates had one genotype with two distinct pncA mutation patterns (T202C and T307G) which highlight on-going transmission. pncA mutation analysis provided a satisfactory alternative to PZA culture DST with high positive predictive value and an improved result turnaround time.

Multidrug-resistant tuberculosis in Queensland, Australia: an ongoing cross-border challenge.

SETTINGp: Multidrug-resistant tuberculosis (MDR-TB) is a growing concern worldwide. In Australia, although the incidence of MDR-TB remains low, Queensland is at an increased risk due to its proximity to Papua New Guinea (PNG). OBJECTIVE: To examine the epidemiology, clinical features and outcomes of MDR-TB in Queensland, with a comparison between cross-border PNG and non-cross-border patients. DESIGN: Retrospective case series of all MDR-TB patients in Queensland between 1 January 2000 and 31 December 2014. RESULTS: Ninety-six patients were diagnosed with MDR-TB in Queensland between 2000 and 2014. The majority were cross-border PNG nationals diagnosed within the Torres Straight Protected Zone (n = 73, 76%). Cross-border patients were younger (27.4 vs. 36.3 years, P = 0.02), had spent less time in Australia before diagnosis (<1 vs. 19 months, P < 0.01), had higher rates of smear positivity (67.1% vs. 40%, P = 0.04) and were less likely to have received a second-line injectable agent (45.8% vs. 71.4%, P = 0.05). Cross-border patients had significantly lower rates of treatment success than non-cross-border patients (47.9% vs. 85.7%; P < 0.01). CONCLUSION: MDR-TB cases in Queensland are largely a result of cross-border PNG nationals, with poorer outcomes seen in this cohort. Continued strengthening of the region's TB programmes, with a focus on cross-border patients, is required.

Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug-resistant and rifampicin-resistant tuberculosis in Han Chinese from Hubei Province.

We determined the high-resolution allele and haplotype frequencies at the human leucocyte antigen (HLA)A, B and DRB1 loci in the Han population of Hubei province, the TB endemic area of Central China, with pulmonary tuberculosis (PTB), and established the relationship between HLA-A, B and DRB1 alleles as well as haplotypes and susceptibility to multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). Blood samples were drawn from 174 patients with MDR/RR-TB and 838 patients with drug-susceptible PTB in ethnic Han population from Hubei province (central China). Four-digit allele genotyping of HLA- A, B and DRB1 loci was performed using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR- SSOP). The allele and haplotype frequencies of HLA-A, B and DRB1 were determined and compared between patients with MDR/RR-TB and patients with drug-susceptible PTB. Statistical analysis of the generated data indicated no departure from expectation of Hardy-Weinberg equilibrium (HWE) at all loci of the control group. Multivariate analysis identified allele DRB1*08:01 (p < .0001; OR = 174.5, 95% CI 15.3-1987.2) as independent predictor of MDR/RR-TB, except for old age (p < .0001; OR = 10. 9, 95% CI 7.6-15.8), previous treatment history (p < .0001; OR = 11.0, 95% CI 7.2-16.7) and poor compliance to treatment (p < .0001; OR = 12.9, 95% CI 8.4-20.0). While in the subgroup of new TB cases, DRB1*08:01 (p < .0001; OR = 80.3, 95% CI 7.0-917.1) and older age (p < .0001; OR = 3.9, 95% CI 2.4-6.4) were independent susceptibility factors for primary MDR/RR-TB. Our results suggest that a combination of clinical and host genetic information about tuberculosis patients may contribute to prediction and early detection of MDR/RR-TB.

[Multidrug-resistant tuberculosis (MDR-TB) in a black African carceral area: Experience of Mali]. / Tuberculose multi-résistante (TB-MR) en milieu carcéral noir africain : expérience du Mali.

INTRODUCTION: Prison constitutes a risk factor for the emergence of multi-drug resistance of tuberculosis (MDR-TB). The aim of this work was to study MDR-TB in a black African carceral center. MATERIAL AND METHODS: Prospective study from January to December 2016 at the central house of arrest for men, Bamako. The study population was composed of tuberculous detainee. The suspicion of MDR-TB was done in any tuberculosis case remained positive in the second month of first-line treatment or in contact with an MDR-TB case. RESULT: Among 1622 detainee, 21 cases of pulmonary tuberculosis were notified (1.29%), with an annual incidence of 13 cases/1000 detainee, they were 16 cases of SP-PTB (microscopy smear positive tuberculosis) and five cases of microscopy smear negative tuberculosis. The mean age was 28±7 years, extremes of 18 and 46 years. A negative association was found between the notion of smoking and occupation in the occurrence of tuberculosis (OR=0.036, [95% CI: 0.03-0.04], P=0.03. Among the 21 tuberculosis cases notified, one confirmed case of MDR-TB was detected (4.7%). In the first semester of 2016 cohort, we notified a cure rate of 87.5% (7/8 SP-PTB cases), and the confirmed MDR-TB case on treatment (21-month regimen), evolution enameled of pulmonary and hearing sequelae at seven months treatment. CONCLUSION: It was the first case of MDR-TB detected in a prison in Mali. Late diagnosis, evolution is enameled of sequelae and side effects.

Prescription practice of anti-tuberculosis drugs in Yunnan, China: A clinical audit.

OBJECTIVES: China has a high burden of drug-resistant tuberculosis (TB). As irrational use and inadequate dosing of anti-TB drugs may contribute to the epidemic of drug-resistant TB, we assessed the drug types and dosages prescribed in the treatment of TB cases in a representative sample of health care facilities in Yunnan. METHODS: We applied multistage cluster sampling using probability proportion to size to select 28 counties in Yunnan. Consecutive pulmonary TB patients were enrolled from either the TB centers of Yunnan Center of Disease Control or designated TB hospitals. Outcomes of interest included the regimen used in the treatment of new and retreatment TB patients; and the proportion of patients treated with adequate dosing of anti-TB drugs. Furthermore, we assess whether there has been reduction in the use of fluoroquinolone and second line injectables in Tuberculosis Clinical Centre (TCC) after the training activity in late 2012. RESULTS: Of 2390 TB patients enrolled, 582 (24.4%) were prescribed second line anti-TB drugs (18.0% in new cases and 60.9% in retreatment cases); 363(15.2%) prescribed a fluoroquinolone. General hospitals (adjusted odds ratio (adjOR) 1.97, 95% confidence interval (CI) 1.47-2.66), retreatment TB cases (adjOR 4.75, 95% CI 3.59-6.27), smear positive cases (adjOR 1.69, 95% CI 1.22-2.33), and extrapulmonary TB (adjOR 2.59, 95% CI 1.66-4.03) were significantly associated with the use of fluoroquinolones. The proportion of patients treated with fluoroquinolones decreased from 41.4% before 2013 to 13.5% after 2013 (adjOR 0.19, 95% CI 0.12-0.28) in TCC. The proportion of patients with correct, under and over dosages of isoniazid was 88.2%, 1.5%, and 10.4%, respectively; of rifampicin was 50.2%, 46.8%, and 2.9%; of pyrazinamide was 67.6%, 31.7% and 0.7%; and of ethambutol was 41.4%, 57.5%, and 1.0%. CONCLUSIONS: The prescribing practice of anti-TB drugs was not standardized, findings with significant programmatic implication.

Delayed and Unreported Drug-Susceptibility Testing Results in the US National Tuberculosis Surveillance System, 1993-2014.

OBJECTIVES: Drug-susceptibility testing (DST) of Mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the spread of drug-resistant tuberculosis. DST is recommended for all culture-confirmed cases of tuberculosis. We examined trends in delayed and unreported DST results in the Centers for Disease Control and Prevention's National Tuberculosis Surveillance System. METHODS: We analyzed culture-confirmed tuberculosis cases reported to the National Tuberculosis Surveillance System during 1993-2014 for annual trends in initial DST reporting for first-line antituberculosis drugs and trends in on-time, delayed, and unreported results. We defined on-time reporting as DST results received during the same calendar year in which the patient's case was reported or ≤4 months after the calendar year ended and delayed reporting as DST results received after the calendar year. We compared cases with on-time, delayed, and unreported DST results by patient and tuberculosis program characteristics. RESULTS: The proportion of cases with reported results for all first-line antituberculosis drugs increased during 1993-2011. Reporting of pyrazinamide results was lower than reporting of other drugs. However, during 2000-2012, of 134 787 tuberculosis cases reported to the National Tuberculosis Surveillance System, reporting was on time for 125 855 (93.4%) cases, delayed for 5332 (4.0%) cases, and unreported for 3600 (2.7%) cases. CONCLUSIONS: Despite increases in the proportion of cases with on-time DST results, delayed and unreported results persisted. Carefully assessing causes for delayed and unreported DST results should lead to more timely reporting of drug-resistant tuberculosis.

Frequency and outcomes of new patients with pulmonary tuberculosis in Hatay province after Syrian civil war.

OBJECTIVE: It is known that tuberculosis is frequently seen among refugees. Hatay province is one of the cities that substantially expose to migration of refugees after Syrian civil war. In this study, it was aimed to compare frequency of new pulmonary tuberculosis (PTB) cases and treatment success/cure rates between Turkish and Syrian patients. FINDINGS: The study included 211 patients with PTB (178 Turkish and 33 Syrian patients) registered to Hatay Tuberculosis Outpatient Clinic between 2010 and 2013. On the basis of years, number of PTB patients registered was 53 (Turkish/Syrian: 52/1) in 2010, 44 (44/0) in 2011, 41 (39/2) in 2012, and 73 (43/30) in 2013. There were no significant differences between Turkish and Syrian patients regarding age groups, gender, marital status, contact history, smear result, and drug sensitivity assays when treatment success was considered (p>0.05). Directly observed therapy (DOT) rate was higher in patients who achieved successful treatment (97.6% vs. 2.4%; p<0.001). Number of patients successfully treated was smaller among Syrian patients (63.6% vs. 88.8%; p<0.001). Leaving the treatment and/or transfer rates were higher among Syrian patients (30.3% vs. 3.9%; p<0.001). During the study period, drug-resistant tuberculosis was detected in one Syrian and 3 Turkish patients. CONCLUSIONS: Although PTB frequency has increased in Hatay province within prior 4 years, treatment success among local population is still within limits established by World Health Organization (WHO). However, the treatment goal could not be achieved when considered together with refugees. To improve treatment success in refugees, implementation of a new national tuberculosis is needed control program in this population.

Paediatric tuberculosis in Queensland, Australia: overrepresentation of cross-border and Indigenous children.

SETTING: Queensland, Australia. BACKGROUND: Understanding paediatric tuberculosis (TB) is important, as children with TB typically reflect recent community transmission. Children pose unique diagnostic challenges and are at risk of developing severe disseminated infection. OBJECTIVE: To describe the epidemiology, presentation and outcomes of children with TB disease in Queensland. DESIGN: This is a retrospective case series of children diagnosed with TB aged 0-16 years notified in 2005-2014. Data collected in the Queensland Notifiable Conditions System were extracted and analysed. RESULTS: Of 127 children diagnosed with TB, 16 were Australian-born (including 12 Indigenous Queenslanders), 41 were overseas-born permanent and temporary residents and 70 were cross-border Papua New Guinea (PNG) children; 88 children had pulmonary disease (with/without other sites) and 39 had extra-pulmonary disease only, with lymph node TB the predominant extra-pulmonary site; 70.1% of children had laboratory confirmation; and 14 cross-border children had multidrug-resistant TB. Treatment outcomes among children residing in Australia were good (100% among Australian-born and 97.2% among permanent and temporary residents), but they were less favourable among PNG children diagnosed in the Torres Strait Protected Zone (76.6%). CONCLUSION: Queensland has unique challenges in TB control, with a high proportion of cross-border diagnoses and over-representation of Indigenous children. Vigilance is needed given the wide spectrum of clinical presentation, particularly in high-risk communities.

Population Pharmacokinetics of Bedaquiline and Metabolite M2 in Patients With Drug-Resistant Tuberculosis: The Effect of Time-Varying Weight and Albumin.

Albumin concentration and body weight are altered in patients with multidrug-resistant tuberculosis (MDR-TB) and change during the long treatment period, potentially affecting drug disposition. We here describe the pharmacokinetics (PKs) of the novel anti-TB drug bedaquiline and its metabolite M2 in 335 patients with MDR-TB receiving 24 weeks of bedaquiline on top of a longer individualized background regimen. Semiphysiological models were developed to characterize the changes in weight and albumin over time. Bedaquiline and M2 disposition were well described by three and one-compartment models, respectively. Weight and albumin were correlated, typically increasing after the start of treatment, and significantly affected bedaquiline and M2 plasma disposition. Additionally, age and race were significant covariates, whereas concomitant human immunodeficiency virus (HIV) infection, sex, or having extensively drug-resistant TB was not. This is the first population model simultaneously characterizing bedaquiline and M2 PKs in its intended use population. The developed model will be used for efficacy and safety exposure-response analyses.

Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population.

INTRODUCTION: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. MATERIAL AND METHODS: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. RESULTS: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. CONCLUSIONS: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines' production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

Tuberculosis and immigration in an area of southwest Madrid.

OBJECTIVE: To describe differences between Spanish and immigrant tuberculosis (TB) cases. DESIGN: Retrospective descriptive study of Spanish and immigrant TB patients diagnosed in a Madrid hospital from 2004 to 2013. RESULTS: A total of 322 patients were analysed, 183 Spanish-born and 139 immigrants (sub-Saharan Africa 32.4%, Morocco 28.8%, Latin America 20.1% and Eastern Europe 17.3%). Immigrants were younger and had a higher rate of human immunodeficiency virus (HIV) infection (P < 0.05). Spanish TB patients were often smokers and immunosuppressed (not HIV) (P < 0.001). No differences in symptoms and site of disease were detected. A higher proportion with isoniazid (INH) resistance was observed among immigrants (14.6% vs. 3.8%, P < 0.05), regardless of country of origin. Being an immigrant was an independent risk factor for INH resistance (OR 4.8, 95%CI 1.3-17.9). CONCLUSION: There is currently no consensus on whether or not it would be appropriate to treat Spanish and immigrant patients with different regimens. Being an immigrant is a clear risk factor for INH resistance. According to our results, it is necessary to evaluate the impact of changing treatment protocols in Madrid, Spain. It is also important to introduce specific strategies for the management of TB among immigrants.

Previous treatment, sputum-smear nonconversion, and suburban living: The risk factors of multidrug-resistant tuberculosis among Malaysians.

The number of multidrug-resistant tuberculosis patients is increasing each year in many countries all around the globe. Malaysia has no exception in facing this burdensome health problem. We aimed to investigate the factors that contribute to the occurrence of multidrug-resistant tuberculosis among Malaysian tuberculosis patients. An unmatched case-control study was conducted among tuberculosis patients who received antituberculosis treatments from April 2013 until April 2014. Cases are those diagnosed as pulmonary tuberculosis patients clinically, radiologically, and/or bacteriologically, and who were confirmed to be resistant to both isoniazid and rifampicin through drug-sensitivity testing. On the other hand, pulmonary tuberculosis patients who were sensitive to all first-line antituberculosis drugs and were treated during the same time period served as controls. A total of 150 tuberculosis patients were studied, of which the susceptible cases were 120. Factors found to be significantly associated with the occurrence of multidrug-resistant tuberculosis are being Indian or Chinese (odds ratio 3.17, 95% confidence interval 1.04-9.68; and odds ratio 6.23, 95% confidence interval 2.24-17.35, respectively), unmarried (odds ratio 2.58, 95% confidence interval 1.09-6.09), living in suburban areas (odds ratio 2.58, 95% confidence interval 1.08-6.19), are noncompliant (odds ratio 4.50, 95% confidence interval 1.71-11.82), were treated previously (odds ratio 8.91, 95% confidence interval 3.66-21.67), and showed positive sputum smears at the 2nd (odds ratio 7.00, 95% confidence interval 2.46-19.89) and 6th months of treatment (odds ratio 17.96, 95% confidence interval 3.51-91.99). Living in suburban areas, positive sputum smears in the 2nd month of treatment, and was treated previously are factors that independently contribute to the occurrence of multidrug-resistant tuberculosis. Those with positive smears in the second month of treatment, have a history of previous treatment, and live in suburban areas are found to have a higher probability of becoming multidrug resistant. The results presented here may facilitate improvements in the screening and detection process of drug-resistant patients in Malaysia in the future.

Mutations in gyrA and gyrB among Fluoroquinolone- and Multidrug-Resistant Mycobacterium tuberculosis Isolates.

In order to correlate the mutations inside the entiregyrAandgyrBgenes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistantMycobacterium tuberculosis(MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, ≤2 µg/ml) and low-level (MIC, 4 to 8 µg/ml) and high-level (MIC, ≥16 µg/ml) OFX-resistant isolates and MFX-susceptible (MIC, ≤0.5 µg/ml) and low-level (MIC, 1 to 2 µg/ml) and high-level (MIC, ≥4 µg/ml) MFX-resistant isolates. Resistance-associated mutations inside thegyrAgene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively;P< 0.001) and a higher prevalence of thegyrBG512R mutation (0.0%, 2.5%, and 16.7%, respectively;P= 0.006). Similarly, compared with MFX-susceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively;P< 0.001) as well as a higher prevalence of thegyrBG512R mutation (0.0%, 0.0%, and 12.9%, respectively;P= 0.011). D94G and D94N mutations ingyrAand the G512R mutation ingyrBwere correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations atgyrAcodons 88 to 94 and thegyrBG512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains.

Mexican American Men's Experience of Living With Tuberculosis on the U.S.-Mexico Border.

The Texas-Mexico border incidence rate of tuberculosis (TB) is 10 times the rate of TB in the United States. Additionally, this area is plagued by antibiotic-resistant TB at a rate that is 70% higher among those living along the border than among nonborder residents. Both the high rate of TB and the emergence of drug-resistant TB increases the importance of controlling TB along the U.S.-Mexico border. Men have higher rates of TB than women, which can be attributed to biological differences and increased environmental exposure. The purpose of this article is to describe the experience of TB for Mexican American men living on the Texas-Mexico border. This a qualitative descriptive study, using participants from a larger study. A purposeful sample was recruited through two south Texas TB clinics. Interviews were audio recorded, transcribed, and translated into English. Data analysis consisted of line-by-line coding, labeling, organizing, and discovering common codes to describe participants' experience of TB and TB treatment. The participants include 13 Mexican American men. Ages ranged from 22 to 76 years. Only one participant was employed during treatment. Years of education ranged from no school to an associate's degree. Five themes were discovered: misinformation, delayed diagnosis, stigma, depression, and loss of community. Participants without social support were further isolated and felt a greater burden of treatment. Two participants contemplated suicide and two others told their families to leave them because they were a burden and infectious. The burden of treatment on the patient is great, especially for Hispanic men.

Immigrants and tuberculosis in Hong Kong.

OBJECTIVE: To examine the impact of immigrant populations on the epidemiology of tuberculosis in Hong Kong. DESIGN: Longitudinal cohort study. SETTING: Hong Kong. PARTICIPANTS: Socio-demographic and disease characteristics of all tuberculosis notifications in 2006 were captured from the statutory tuberculosis registry and central tuberculosis reference laboratory. Using 2006 By-census population data, indirect sex- and age-standardised incidence ratios by place of birth were calculated. Treatment outcome at 12 months was ascertained from government tuberculosis programme record forms, and tuberculosis relapse was tracked through the notification registry and death registry up to 30 June 2013. RESULTS: Moderately higher sex- and age-standardised incidence ratios were observed among various immigrant groups: 1.06 (Mainland China), 2.02 (India, Pakistan, Bangladesh), 1.59 (Philippines, Thailand, Indonesia, Nepal), and 3.11 (Vietnam). Recent Mainland migrants had a lower sex- and age-standardised incidence ratio (0.51 vs 1.09) than those who immigrated 7 years ago or earlier. Age younger than 65 years, birth in the Mainland or the above Asian countries, and previous treatment were independently associated with resistance to isoniazid and/or rifampicin. Older age, birth in the above Asian countries, non-permanent residents, previous history of treatment, and resistance to isoniazid and/or rifampicin were independently associated with poor treatment outcome (other than cure/treatment completion) at 1 year. Birth outside Hong Kong was an independent predictor of relapse following successful completion of treatment (adjusted hazard ratio=1.76; 95% confidence interval, 1.07-2.89; P=0.025). CONCLUSION: Immigrants carry with them a higher tuberculosis incidence and/or drug resistance rate from their place of origin. The higher drug resistance rate, poorer treatment outcome, and excess relapse risk raise concern over secondary transmission of drug-resistant tuberculosis within the local community.