Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.
Humans ; Child ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Tuberculosis, Pulmonary/drug therapy* ; Tuberculosis ; China/epidemiology*

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.
Humans ; Child ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Tuberculosis, Pulmonary/drug therapy* ; Tuberculosis ; China/epidemiology*

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.
Humans ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Latent Tuberculosis/drug therapy* ; HIV Infections/epidemiology* ; Antitubercular Agents/therapeutic use*

OBJECTIVESTo study the etiology, clinical and pathologic characteristics of periductal mastitis with fistula and estimate the effect of anti-mycobacterial agents for periductal mastitis with fistula.

METHODSTotally 27 patients of periductal mastitis with fistula received anti-mycobacteria drugs therapy from December 2008 to September 2011 were analyzed retrospectively. All of the patients were female. The mean age at onset was 28 years (range 15 to 40 years old). The main clinical manifestation of the 27 patients was breast fistula, including 21 patients with single fistula and 6 patients with multiple fistula. Three patients manifested with pure fistula, 14 patients with both fistula and lump, 10 patients with fistula, lump and abscess. The samples including pus or tissues of all patients were underwent bacteria culture and all patients core needle biopsy. All patients were given primary anti-mycobacteria drugs therapy, parts of patients received surgery based on the evaluation of medical treatment.

RESULTSThe common bacteria culture of all patients failed to demonstrate any causative microorganism. Four cases were selected randomly to undergo PCR of mycobacteria, only one case was identified as Massiliense in bacteria culture of mycobacteria. Twenty-seven patients with periductal mastitis with fistula were treated with anti-mycobacterial agents (isoniazid, rifampicin and ethambutol or pyrazinamide of triple oral drugs) for 1 to 3 months, the fistula of all 27 patients were closed well. Sixteen patients were treated with the agents only and cured. Eleven patients received surgical treatment after treated with the medical agents. None of the patients were given mastectomy. All patients had no reccurence until now.

CONCLUSIONSThe periductal mastitis with fistula has a closely relationship with the infection of nontuberculosis mycobacteria. Those patients could be treated with triple anti-mycobacterial agents and could also avoided mastectomy.

Adolescent ; Adult ; Anti-Bacterial Agents ; therapeutic use ; Drug Therapy, Combination ; Ethambutol ; therapeutic use ; Female ; Fistula ; drug therapy ; microbiology ; Humans ; Isoniazid ; therapeutic use ; Mastitis ; drug therapy ; pathology ; Nontuberculous Mycobacteria ; isolation & purification ; Pyrazinamide ; therapeutic use ; Retrospective Studies ; Rifampin ; therapeutic use ; Young Adult

BACKGROUNDChronic intermittent hypoxia is the most important pathophysiologic feature of sleep apnea syndrome. The present study aimed to determine whether chronic intermittent hypoxia, which is associated with sleep apnea syndrome, can cause or increase damage to liver cell ultrastructure induced by isoniazid and rifampicin in mice.

METHODSBased on a 2 × 2 full factorial design consisting of two factors of chronic intermittent hypoxia and isoniazid plus rifampicin, 32 male C57B6J mice were randomized into the control group, the chronic intermittent hypoxia group, the isoniazid plus rifampicin group, and the chronic intermittent hypoxia + isoniazid plus rifampicin group. Twelve weeks after treatment, we examined the ultrastructure of liver cells and quantitatively analyzed mitochondrial morphology in C57B6J mice.

RESULTSChronic intermittent hypoxia did not significantly affect the ultrastructure of liver cells. The main effect of chronic intermittent hypoxia did not lead to an increase of mean profile area or mean perimeter of mitochondria, and a decrease of numerical density on area of mitochondria (all P > 0.05). Isoniazid plus rifampicin significantly affected liver cell ultrastructure. The main effect of isoniazid plus rifampicin resulted in an increase of mean profile area and mean perimeter of mitochondria, and a decrease of numerical density on area of mitochondria (all P < 0.05). Moreover, there was a positive interaction among the chronic intermittent hypoxia and the isoniazid plus rifampicin groups for mean profile area, mean perimeter, and numerical density on area of mitochondria (all P < 0.05).

CONCLUSIONChronic intermittent hypoxia and isoniazid plus rifampicin treatment lead to synergistic liver cell ultrastructural injury.

Animals ; Hypoxia ; drug therapy ; Isoniazid ; therapeutic use ; Liver ; drug effects ; ultrastructure ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Transmission ; Rifampin ; therapeutic use ; Sleep Apnea Syndromes ; complications

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

PURPOSE: The aim of this study was to elucidate the effects of immunocompromising comorbidities on treatment response and adverse reactions in older tuberculosis (TB) patients. MATERIALS AND METHODS: The medical records of 182 patients older than 65 years with proven TB by positive culture of Mycobacterium tuberculosis and with available drug susceptibility tests were reviewed retrospectively. These patients were subsequently assigned to either the comorbidity group (n=78) or non-comorbidity group (n=104) depending on whether they had immunocompromising comorbidities. RESULTS: The mean durations of treatment were 9.9+/-3.3 months in the comorbidity group and 9.3+/-3.2 months in the non-comorbidity group (p=0.21). M. tuberculosis culture results converted to negative in most patients with available follow-up cultures at two months after treatment. The successful treatment rates were 94.9% and 98.9% in the comorbidity and non-comorbidity groups, respectively (p=0.30). The most common side effects of anti-TB treatment were skin rash/pruritus (13% in the comorbidity group vs. 11% in the non-comorbidity group, p=0.79), gastro-intestinal problems (14% vs. 9%, p=0.25) and hepatotoxicity (14% vs. 7%, p=0.09). CONCLUSION: The present study shows that the successful treatment rate for TB is high and that immunocompromising comorbidities have no effect on the response to treatment and adverse effects in older TB patients.
Age Factors ; Aged ; Aged, 80 and over ; Antitubercular Agents/adverse effects/*therapeutic use ; Comorbidity ; Female ; Humans ; *Immunocompromised Host ; Isoniazid/adverse effects/*therapeutic use ; Male ; Retrospective Studies ; Rifampin/adverse effects/*therapeutic use ; Risk Factors ; Treatment Outcome ; Tuberculosis/*drug therapy/epidemiology/immunology

BACKGROUNDGene chip array can differentiate isolated mycobacterial strains using various mycobacterium specific probes simultaneously. Gene chip array can evaluate drug resistance to isoniazid and rifampin of tuberculosis strains by detecting drug resistance related gene mutation. This technique has great potential for clinical application. We performed a retrospective study to investigate the capability of gene chip array in the rapid differentiation of species and detection of drug resistance in mycobacterium, and to evaluate its clinical efficacy.

METHODSWe selected 39 patients (54 clinical mycobacterium isolates), used gene chip array to identify the species of these isolates and detect drug resistance to isoniazid and rifampin in Mycobacterium tuberculosis isolates. Meanwhile, these patients' clinical data were analyzed retrospectively.

RESULTSAmong these 39 patients whose mycobacterium culture were positive, 32 patients' isolates were identified as Mycobacterium tuberculosis, all of them were clinical infection. Seven patients' isolates were identified as non-tuberculosis mycobacterium. Analyzed with their clinical data, only two patients were considered as clinical infection, both of them were diagnosed as hematogenous disseminated Mycobacterium introcellulare infection. The other five patients' isolates were of no clinical significance; their clinical samples were all respiratory specimens. Clinical manifestations of tuberculosis and non-tuberculous mycobacterial infections were similar. Isoniazid resistance was detected in two tuberculosis patients, while rifampin resistance was detected in one tuberculosis patient; there was another patient whose Mycobacterium tuberculosis isolate was resistant to both isoniazid and rifampin (belongs to multidrug resistance tuberculosis). The fact that this patient did not respond to routine anti-tuberculosis chemotherapy also confirmed this result.

CONCLUSIONSGene chip array may be a simple, rapid, and reliable method for the identification of most mycobacterial species and detection of drug resistance in Mycobacterium tuberculosis. It is useful in diagnosis, treatment, and hospital infection control of mycobacterial infections, and it may have a great potential for clinical application.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antitubercular Agents ; therapeutic use ; Female ; Humans ; Isoniazid ; therapeutic use ; Male ; Middle Aged ; Mycobacterium ; classification ; genetics ; pathogenicity ; Mycobacterium tuberculosis ; genetics ; pathogenicity ; Oligonucleotide Array Sequence Analysis ; methods ; Rifampin ; therapeutic use ; Tuberculosis, Multidrug-Resistant ; genetics ; Young Adult

OBJECTIVETo study the prevalence of skin positivity to purified protein derivative (PPD) in human immunodeficiency virus (HIV)-infected patients in Hong Kong.

METHODSConsecutive clients of an HIV clinic were administered the PPD test and 2 units of PPD-RT23 were used. The area of induration was then measured in 48 to 72 h. Results were related to patient characteristics and HIV-related parameters.

RESULTSEight (17.0%) out of 47 clients tested positive to the administration of 2 units of PPD-RT23. If the cutoff were raised to 10 mm according to current practice, only two (4.3%) would test positive.

CONCLUSIONThe prevalence of PPD positivity in HIV-infected patients in Hong Kong is 17%, when a cutoff of 5 mm is used. This figure may form the basis for further studies on the utility of isoniazid preventive therapy in this group of patients.

Adult ; Aged ; BCG Vaccine ; immunology ; Female ; HIV Infections ; complications ; immunology ; Humans ; Isoniazid ; therapeutic use ; Male ; Middle Aged ; Prevalence ; Tuberculin Test ; Tuberculosis ; prevention & control

Objective: To evaluate the diagnostic accuracy of line probe assays for drug- resistant tuberculosis (TB) in China. Methods: Chinese databases (CNKI, Wanfang, SinoMed, VIP Information) and English databases (PubMed, Embase, Cochrane Library) were used to retrieve the literatures regarding the accuracy of line probe assays in the diagnosis of drug-resistant tuberculosis in China between January 1, 2000 and September 1, 2017. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the included studies. Sensitivity and specificity in different studies (using drug sensitivity test or gene sequencing as gold standard) were combined by Meta-analysis using bivariate or univariate model. In addition, subgroup analysis (GenoType MTBDRplus, GenoType MTBDRsl and Reverse dot blot hybridization) and sensitivity analysis were also carried out. Results: A total of 24 literatures involving 82 studies were included in the final analysis. The sensitivity and specificity of line probe assays for rifampicin resistant TB were 0.91(0.88-0.94) and 0.98 (0.97-0.99), respectively. The sensitivity and specificity of line probe assays for isoniazid resistant TB were 0.80 (0.77-0.83) and 0.98 (0.96-0.99), respectively. The sensitivity and specificity of line probe assays for multidrug-resistant TB were 0.81 (0.76-0.85) and 0.99 (0.99-1.00), respectively. The sensitivity and specificity of line probe assays for quinolone resistant TB were 0.92(0.88-0.95) and 0.94 (0.91-0.97), respectively. The sensitivity and specificity of line probe assays for second-line injectable drug resistant TB (including kanamycin, Capreomycin, amikacin) were 0.79(0.58-0.91) and 0.98 (0.90-1.00), respectively. The sensitivity and specificity of line probe assays for extensively drug-resistant TB were 0.46 (0.19-0.75) and 1.00 (0.98-1.00), respectively. Subgroup analysis showed that the overall diagnostic accuracy of GenoType MTBDRplus and GenoType MTBDRsl was higher than that of Reverse dot blot hybridization. According to the results of sensitivity analysis, the results of this study were robust. Conclusion: The diagnostic accuracy of line probe assays for drug-resistant TB is high.
Antitubercular Agents/therapeutic use* ; Biological Assay/methods* ; China ; Humans ; Isoniazid/pharmacology* ; Microbial Sensitivity Tests/methods* ; Mycobacterium tuberculosis/isolation & purification* ; Rifampin/pharmacology* ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant/drug therapy*