The past, present and future of tuberculosis treatment / 浙江大学学报·医学版

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.

A comparison of binocular and monocular surgery on the effect of eye-covering pretreatment on emergence delirium after general anesthesia in pre-school aged children / 中国实用护理杂志

Objective:To evaluate the effect of eye-covering pretreatment on acute delirium in ophthalmology preschool-age children who underwent binocular and monocular surgery by general anesthesia.Methods:The 300 preschool-age children who underwent general anesthesia of elective ophthalmic surgery in the Second Affiliated Hospital, Zhejiang University School of Medicine, from August 2019 to February 2021 were selected as the research object. They were divided into control group and blindfold group with 150 cases each by random number-table. Children in the control group received regular education on cartoon animation videos before surgery; children in the blindfold group received eye-covering pretreatment on the basis of cartoon animation videos(monocular surgery with monocular cover, binocular surgery with binocular cover). The Modified Yale Preoperative Anxiety Scale (m-YPAS) , the Nursing Delirium Screening Scale(NU-DESC), the incidence rate of delirium and the score of postoperative nursing difficulty were compared between two groups.Results:The 271 cases were completed in this study, including 129 cases(monocular surgery 66 cases, binocular surgery 63 cases) in the blindfold group and 142 cases (monocular surgery 73 cases, binocular surgery 69 cases) in the control group. The preoperative m-YPAS score, the postoperative NU-DESC score, the incidence rate of acute delirium and postoperative nursing care difficulty score of monocular surgery in the blindfold group , monocular surgery was (40.28 ± 15.02) points, 1.00 (0.00, 2.00) points, 27.3%(18/66), 1.00 (1.00, 2.00) points,and binocular surgery was (41.69 ± 16.35) points, 1.00 (0.00, 2.00), 39.7%(25/63), 1.00(1.00, 2.00); in the control group, monocular surgery was (46.28 ± 15.76) points, 2.00 (1.00, 3.00) points, 67.1% (49/73), 2.00 (1.00, 3.00) points, and binocular surgery was (47.77 ± 14.82) points, 3.00 (2.00, 4.00) points, 82.6% (57/69) and 2.00 (1.50, 3.00) points respectively. The difference between the two groups was statistically significant ( t= -2.29, -2.24, Z values were -5.74 - -2.95, χ2= 32.94, 25.78, all P<0.05). The preoperative m-YPAS score, the postoperative NU-DESC score, the incidence rate of acute delirium and postoperative nursing care difficulty score of monocular surgery patients in the blindfold group had no significantly statistical difference with that of binocular surgery patient (all P>0.05) . Conclusions:Monocular/ binocular eye-covering pretreatment can effectively decrease the preoperative m-YPAS score, the postoperative NU-DESC score, incidence rate of acute delirium and the postoperative nursing care difficulty in preschool-age children who underwent general anesthesia both monocular or binocular surgery. There was no difference in the application effect of monocular or binocular surgery.

Effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker on clinical characteristics of coronavirus disease 2019 patients with hypertension / 中华内科杂志

Objective:To analyze the effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) on coronavirus disease 2019 (COVID-19) patients with hypertension, and to provide an evidence for selecting antihypertensive drugs in those patients.Methods:Clinical data were retrospectively analyzed in 58 COVID-19 patients with hypertension admitted to Shanghai Public Health Clinical Center from January 20 to February 22, 2020, including epidemiological history, clinical manifestations, laboratory findings, chest CT and outcome. Patients were divided into ACEI/ARB group and non-ACEI/ARB group.Results:Twenty-six patients were in ACEI/ARB group and the other 32 patients in non-ACEI/ARB group, with median age 64.0 (49.5, 72.0) years and 64.0 (57.0, 68.8) years respectively. The median time to onset was 5(3, 8) days in ACEI/ARB group and 4 (3, 7) days in non-ACEI/ARB group, the proportion of patients with severe or critical illness was 19.2% and 15.6% respectively. The main clinical symptoms in two groups were fever (80.8% vs. 84.4%) and cough (23.1% vs. 31.3%). The following parameters were comparable including lymphocyte counts, C-reactive protein, lactate dehydrogenase, D-dimer, bilateral involvement in chest CT (76.9% vs. 71.9%), worsening of COVID-19 (15.4% vs. 9.4%), favorable outcome (92.3% vs. 96.9%) between ACEI/ARB group and non-ACEI/ARB group respectively (all P>0.05). However, compared with non-ACEI/ARB group, serum creatinine [80.49 (68.72, 95.30) μmol/L vs. 71.29 (50.98, 76.98) μmol/L, P=0.007] was higher significantly in ACEI/ARB group. Conclusions:ACEI/ARB drugs have no significant effects on baseline clinical parameters (serum creatine and myoglobin excluded) , outcome, and prognosis of COVID-19 patients with hypertension. Antihypertensive drugs are not suggested to adjust in those patients, but the potential impairment of renal function as elevation of serum creatinine should be paid attention in patients administrating ACEI/ARB drugs.

Characteristics of Childhood Tuberculosis and Advances in Its Diagnosis and Treatment / 医药导报

Objective To explore the characteristics of childhood tuberculosis and recent advances in the diagnosis and treatment of this disease in order to improve its diagnosis and treatment. Methods Key words“child”“tuberculosis”“diagno-sis” and “treatment” were used to retrieve relevant literatures from Pubmed,Web of Science,CNKI and Wanfang databases.The literatures were reviewed and clinical experience summarized. Results Disseminated tuberculosis and extrapulmonary tubercu-losis were common in children with tuberculosis. It was difficult to collect with samples of diagnostic value for detection. There counterparts were no systematic diagnosis and treatment programs available for children with drug-resistant tuberculosis,and phar-maceutical dosage forms tailored for children were lacking. Conclusion Tuberculosis in children is more complex to diagnose and treat than in adult counterpart.Diagnosis of this disease relies on a variety of diagnostic methods.It's still challenging to control childhood tuberculosis.

Evaluation of the diagnostic value of Xpert Mycobacterium tuberculosis/rifampin assay in extrapulmonary ;tuberculosis / 中华传染病杂志

Objective To detect Mycobacterium tuberculosis (MTB)and its resistance against rifampin (RIF ) by applying Xpert MTB/RIF assay in the clinical samples from patients with extrapulmonary tuberculosis,and to discuss the value of this assay in extrapulmonary tuberculosis. Methods Totally 300 clinical samples from the patients who were highly suspected with extrapulmonary tuberculosis and hospitalized in Department of Tuberculosis Section,Shanghai Public Health Clinical Center of Fudan University from May 2014 to May 2015 were collected.Smear and fluorescence staining microscopy,MGIT 960 BACTEC liquid culture,Xpert MTB/RIF assay were applied to detect MTB in these samples.Meanwhile,all the patients received the peripheral blood T-cell spot of tuberculosis test (T-SPOT.TB).The sensitivity and specificity of Xpert MTB/RIF assay for MTB and its resistance against rifampin (RIF)in extrapulmonary tuberculosis samples were evaluated.The measurement data of two independent samples were analyzed by using t test and enumeration data were analyzed by usingχ2 test.Results Totally 282 out of 300 clinical samples from patients with extrapulmonary tuberculosis were included in this study,and 62.7% were male with average age of (32.1 ±24.6 )years and 37.3%were female with average age of (37.8 ±21 .0)years.When MGIT 960 BACTEC liquid culture results were considered as standard diagnosis,the sensitivity,specificity,positive predictive value and negative predictive value of Xpert MTB/RIF assay were 53.8% (95 %CI :37.4%—69.6%),100.0% (95 %CI :86.3%—100.0%),100.0% (95 %CI :80.8%—100.0%)and 63.3% (95 %CI :48.3%—76.2%), respectively.The sensitivity of Xpert MTB/RIF assay in smear-positive/culture-positive samples was 92.3% (95 %CI :62.1 %— 99.6%),while that in smear-negative/culture-positive samples was only 34.6% (95 %CI :17.9%— 55 .6%).Xpert MTB/RIF assay had advantage for detecting MTB in fine needle aspirates,pus,stool and urine,but not in serous effusion and cerebrospinal fluid.However,the sensitivities of MGIT BACTEC 960 liquid culture,fluorescence smear and T-SPOT.TB were 25 .8%, 21 .8% and 70.2%,respectively,and the specificities were 95 .5 %,90.3% and 51 .6%,respectively. The diagnostic value of Xpert MTB/RIF assay was not significantly different from those of MGIT BACTEC 960 liquid culture and fluorescence smear (χ2 =0.61 and 3.45 ,respectively;both P >0.05 ), while it was significantly different from T-SPOT.TB (χ2 =50.58,P <0.05).The sensitivity of T-SPOT. TB was significantly superior to Xpert MTB/RIF assay,but the specificity was relatively low.The sensitivity and specificity of Xpert MTB/RIF assay in RIF resistance detection were 71 .4% (95 %CI :30.3%—94.9%)and 100.0% (95 %CI :86.7%—100.0%),respectively.Conclusions The sensitivity and specificity of Xpert MTB/RIF assay in detecting MTB in fine needle aspirates,pus,stool and urine are relatively high,but not in serous effusion and cerebrospinal fluid.However,the pros of rapid detection and the ability of detecting RIF resistance are useful for the diagnose of extrapulmonary tuberculosis in clinical settings.

Detection of Mycobacterium in fine-needle aspiration biopsy specimens from children with tuberculous lymphadenitis / 中华微生物学和免疫学杂志

Objective To improve the diagnosis of tuberculosis ( TB) by analyzing Mycobacterium infection in fine-needle aspiration biopsy specimens from children with tuberculous lymphadenitis .Methods Fine-needle aspiration biopsy was performed on 269 children with tuberculous lymphadenitis diagnosed by Shanghai Public Health Clinical Center from January 2011 to September 2013 .The needle aspiration biopsy specimens were processed for acid-fast bacillus (AFB) smear test, mycobacterial culture and Mycobacterium identification ( p-nitrobenzoic acid inhibition test ) .Results Cytological diagnosis of tuberculous lymphade-nitis was made for 269 patients.The positive results by AFB smear test were detected in 63.19% of 269 specimens (n=170) and 40.15%(n=108) specimens were positive in mycobacterial culture .The differ-ence between the two tests were significant (P<0.01).The positive rate of Mycobacterium detected by using BACTEC MGIT 960 automated system and L?wenstein-Jensen culture method were 38 .66% ( n=104 ) and 28.99%(n=78), respectively, showing the significant difference between two tests (P<0.05).AFB smear test in combination with mycobacterial culture could precisely diagnose 70.63% of tuberculous lym-phadenitis in children.Of the 108 clinical isolates, 105 strains (97.2%) were Mycobacterium tuberculosis complex and the rest were non-tuberculous Mycobacterium strains (2.8%).Conclusion The positive rate by AFB smear test was significantly increased in fine needle aspiration biopsy specimens after a series of treatments including sample digestion , centrifugation and precipitation , but the positive rate of mycobacterial culture was reduced .Diagnostic accuracy could be significantly improved by using BACTEC MGIT 960 sys-tem.Mycobacterium tuberculosis complex was the predominant pathogenic bacterium in children with tubercu-lous lymphadenitis .

Clinical comparison of one recovered case and one fatal case of human infection with H7N9 avian influenza in Shanghai Public Health Clinical Center in China

H7N9 avian influenza is the latest subtype of influenza virus to emerge in the world. By April 17, 2013 in Shanghai, a total of 31 confirmed cases were reported, and 11 of these patients died. The epidemiological characteristics and the clinical progress of this new human flu infection are still not clear. Thirteen confirmed patients have now been treated in Shanghai Public Health Clinical Center. Among the first batch of patients, hospitalised at the beginning of April 2013, two who were admitted with the same estimated date of onset of disease had very different outcomes. After active treatment at the Centre, one recovered by April 18, 2013, but one patient entered critical condition and died on April 11, 2013. The clinical and laboratory characteristics in hospital are here analysed and compared to learn more about H7N9 avian influenza. Confirmation that the observed differences are valuable for prognosis and treatment decisions for H7N9 patients awaits authentication by analysis of more patients.

Rapid molecular assay and strain typing methods of extrapulmonary tuberculosis / 中华检验医学杂志

[Abstract] Objective To evaluate the effect of Mycobacterium tuberculosis Direct Assay (MTD) for rapid detecting Mycobacterium tuberculosis rRNA and Multi-locus PCR for M.bovis BCG strain typing in patients with suspected extra-pulmonary tuberculosis.Methods From June 2010 to December 2011,47 children and 75 adult patients with suspected extra-pulmonary tuberculosis in Shanghai public health clinical center were recruited.Also 48 non-tuberculosis patients were taken as a negative control.Clinical specimens from these patients were collected.Acid fast stain,solid culture,liquid culture,and MTD were used to detect all clinical specimens simultaneously.Screen tuberculosis strains of the culture isolates by MPT64 antigen assay and use Multi-locus PCR for the BCG strain genotyping of the isolates without MPT64 antigen.SPSS16.0 was used to analyse the results.Results The sensitivity for acid fast stain,solid culture,liquid culture and MTD test was 10.7％ (13/122),11.5％ (14/122),16.4％ (20/122) and 37.7％ (46/122),respectively.And the specificity of MTD was 100.0％.Six clinical isolates from children were identified as BCG by Multi-locus PCR typing,the same with chemical tests.Conclusions The MTD assay and the MGIT960 liquid culture are effective and reliable method for diagnosing extra-pulmonary tuberculosis.And Multi-locus PCR can be assisted for the early diagnosis of extra-pulmonary tuberculosis patients with suspected BCG infection.

Factors related to in-hospital deaths in patients co-infected with human immunodeficiency virus and tuberculosis / 中华传染病杂志

Objective To evaluate the risk factors associated with in-hospital death in patients co-infected with human immunodeficiency virus and Mycobacterium tuberculosis (HIV-TB). Methods A retrospective case-control study was performed in patients admitted to Shanghai Public Health Clinical Center from November 2004 to May 2009. Fifty-three HIV-TB patients who died during hospitalization were matched with 79 HIV-TB co-infected patients who survived during hospitalization.Clinical, demographic, and radiological characteristics of the two groups were compared by the retrospective case-control study method. Multivariate Logistic stepwise regression analysis was performed to explore the risk factors contributing to death in HIV-TB co-infected patients. Results Among the 459 co-infected patients, 53 (11.5%) cases died during hospitalization and 25 cases died during the first week in hospital. Sixty-four point two percent dead patients (34/53) died from tuberculosis. Several factors were associated with worse prognosis in the death group compared to the survival group, which included body weight≤50 kg (χ2 = 7.50), positive for acid-fast bacilli in sputum smear or culture exam (χ2= 4. 04, 14. 27), drug-resistant/multi-drug resistant Mycobacterium tuberculosis infection (χ2 =9.00,6.39), extra-pulmonary tuberculosis infection (χ2 =6.99), retreated tuberculosis (χ2 = 5. 92), non-standardized anti-tuberculosis treatment (χ2 = 12. 07), extensive pulmonary TB infection (lesions ≥50% of lung fields, χ2 = 20. 21), co-infection with fungi (χ2 =3.46), respiratory failure (χ2 = 4.27), non-pulmonary organ impairment (χ2 = 3.46), HIV infection longer than 5 years (χ2 = 7. 19), non-standardized highly active antiretroviral therary treatment (χ2 =5.16) and CD4+ T lymphocyte count ≤ 200 × 106/L (χ2= 12.99) (all P＜0. 05). Multivariate Logistic regression analysis showed that non-standardized anti-TB treatment, extensive pulmonary TB infection, multi-drug resistant TB infection and CD4+ T lymphocyte count ≤ 200 × 106/L were the major risk factors related to in-hospital mortality. Conclusions Non-standardized anti-TB treatment,extensive pulmonary TB infection, multi-drug resistant TB infection and CD4+ T lymphocyte count ≤200 × 106/L are the major risk factors related to in-hospital mortality in the patients co-infected with TB and HIV.

Enzyme-linked immunospot assay combined with serum latex agglutination test for diagnosis of pulmonary tuberculosis and concomitant pulmonary cryptococcosis / 中国感染与化疗杂志

Objective To evaluate the value of enzyme-linked immunospot assay (TB ELISPOT) combined with serum latex agglutination test (LA) for diagnosis of pulmonary tuberculosis plus pulmonary cryptococcosis.Methods Serum and biopsy specimens of 76 patients, who were suspected of pulmonary tuberculosis and/or pulmonary cryptococcosis based on clinical and imaging features, were collected from March 2006 to September 2008 in Shanghai Public Health Clinical Center. TB ELISPOT assay, LA and histopathological examination were performed in all the patients. Results Histopathological and pathogenic examination confirmed pulmonary cryptococcosis in 15 cases and pulmonary tuberculosis in 22 cases, pulmonary tuberculosis plus pulmonary cryptococcosis in 8 cases. The sensitivity and specificity of TB ELISPOT were 91% and 94.4%. The sensitivity and specificity of LA were both 100%. TB ELISPOT assay and LA test were both positive in the 8 cases of pulmonary tuberculosis plus pulmonary cryptococcosis.Conclusions The value of enzyme-linked immunospot assay combined with serum latex agglutination test is high for diagnosis of pulmonary tuberculosis plus pulmonary cryptococcosis.