Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive （ss＋ and/or c＋） two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination.

Research Progress of Radical Treatment of Helicobacter Pylori Based on Drug Sensitivity Test as First-Line Treatment

Helicobacter pylori (HP) infection is a global problem that affects about half of the world’s population and requires sufficient attention in clinical and scientific work. Due to differences in economic and medical conditions among countries around the world, there is currently no unified treatment plan for anti-HP. In China, empirical quadruple therapy is mainly used. With the abuse of antibiotics, many patients face the problem of secondary eradication after failure, and the resistance rate of HP is gradually increasing. After eradication failure, drug sensitivity cultivation is carried out to choose sensitive antibiotics for treatment. A new strategy is currently needed to address how to improve the eradication rate of HP during the first eradication. This article aims to discuss the first-line treatment plans and research progress for eradicating HP based on drug sensitivity testing before eradication. Compared with traditional empirical therapies, treatment based on drug sensitivity results can effectively improve the eradication rate of HP, and reduce drug resistance rates, and adverse reactions, among other benefits. .

Use of Cost Effective Semi-Automated (Mannual/Micro) MGIT System over BACTEC 960 to Perform First Line Anti-Tuberculosis Drugs Sensitivity Testing

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.

Synergistic Effects of 18β-glycyrrhetinic Acid Combined with Antituberculosis Drugs against Mycobacterium tuberculosis

The in vitro antibacterial activities of 18β-glycyrrhetinic acid alone or combined with first-line antituberculosis drugs including isoniazid（INH）,rifampicin（RFP） and streptomycin（SM） against Mycobacterium tuberculosis were detected using MABA method.The minimum inhibitory concentrations（MICs） of18β-glycyrrhetinic acid against M.tuberculosis H37Rv（ATCC 27294） and M.bovis（ATCC 19210） were 50 and 100 μg/m L,respectively.The MICs of two clinical drug-susceptible isolates and six drug-resistant isolates were 25-50 and 100-200 μg/m L,respectively.As 18β-glycyrrhetinic acid combined with INH,RFP and SM,they exhibited synergistic effects against six drug-resistant isolates,and MICs decreased significantly：MIC of INH decreased by 2-32 folds（FICIs 0.125-0.375）;MIC of RFP decreased by 4-8 folds（FICIs 0.240-0.490）;MIC of SM decreased by 4-16 folds（FICIs 0.165-0.460）.Traditional medicine monomer had low cytotoxicity on normal cell BHK-21 and could restraint SMMC fission.The results showed that 18β-glycyrrhetinic acid combined with anti-TB drugs（INH,RFP and SM） had good antibacterial activity against M.tuberculosis.These findings indicated that 18β-glycyrrhetinic acid might serve as the potential therapeutic compound for future development of anti-TB drugs.

Experience on the first national anti-TB drug resistance survey(DRS)in Timor-Leste

Background:A national drug resistance survey(DRS)was implemented for the first time in Timor-Leste(TL)in 2019.The primary objective of the survey was to assess the prevalence of drug resistance among new and previously treated pulmonary TB patients in the country.Methods:This nation-wide cross-sectional survey was conducted in 2019 targeting all new and previously treated sputum smear-positive pulmonary TB patients.Sputum samples were submitted to the National TB Reference Laboratory for confirmation of TB and to determine resistance to rifampicin by Xpert MTB/RIF.Culture was performed on solid media,and culture isolates of confirmed TB cases were shipped to the WHO Supranational TB Reference Laboratory in Chennai,India for whole genome sequencing(WGS).Survey summary statistics,data cross-tabulations and analysis of potential risk factors of rifampicin-resistant TB(RR-TB)were conducted using R statistical software(version 3.5.2).Results:A total of 953 sputum-smear positive patients were enrolled,of which 917 were confirmed as positive for TB by either Xpert MTB/RIF or culture.An electronic web-based system was used for entry and storage of the data.Rifampicin resistance was detected among 0.6%(95%CI 0.2-1.3)of new cases and 2.7%(95%CI 0.5-8.2)of previously treated cases.WGS was conducted for validation purposes on 65 randomly selected isolates(29%of RR-TB(2/7)and 7%of RS-TB(63/910)by Xpert MTB/RIF or pDST).The original test results agreed with the WGS validation results for 62/64 isolates(97%).Conclusion:The prevalence of RR-TB in Timor-Leste is relatively low compared to the estimated proportions of RR-TB in the WHO South-East Asia Region(2.5%[95%CI 1.9-3.3]among new cases and 14%[95%CI 7.7-21]among previously treated cases).The rapid sputum collection and transportation mechanism implemented in the survey demonstrates its feasibility in low resource settings and should be replicated for routinely transporting TB specimens from microscopy labs to GeneXpert sites.Establishment of in-country capacity for rapid molecular diagnostics for both first-and second-line DST is an immediate need for achieving universal drug susceptibility testing(DST)to guide appropriate patient management.

Prevalence and Risk Factors Associated with Adverse Drug Reactions among Previously Treated Tuberculosis Patients in China

We assessed the incidence of adverse drug reactions （ADRs） with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen （2HREZS/6HRE） as recommended by the national guidelines.

Interim Outcomes and Adverse Events among Drug-Resistant Tuberculosis Patients Treated with Bedaquiline in the Philippines

Objectives: This study aimed to assess the interim outcomes for drug-resistant tuberculosis (DR-TB) patients treated with bedaquiline regimen under the operational research conditions compared to DR-TB patients treated without bedaquiline in their regimen, and to describe the adverse events that occurred among patients treated with bedaquiline in the Philippines. Design: Patients who were treated with a bedaquiline-containing regimen from June 2016 to May 2017 were included in this study as the intervention group, while patients who were treated without bedaquiline regimen from January 2013 to May 2016 were included as the comparison group. The interim treatment outcomes were compared using Chi-square test. The analysis of time to culture conversion within 6 months of treatment was conducted. A Cox proportional hazard model was constructed to identify the variables associated with a favorable interim treatment outcome. The R program was used for statistical analysis. Results: On the 6th month of treatment, the culture conversion for patients treated with a bedaquiline-containing regimen was significantly higher than with the comparison group [63/75 (84.0%) vs 84/117 (71.8%), p = 0.012)]. Nearly 15% of the patients treated with bedaquiline were lost to follow-up. Frequent adverse events included vomiting, dizziness, nausea, joint pain, and abdominal pain. Conclusion: The patients who were treated with bedaquiline-containing regimen have better interim treatment outcomes than those treated without bedaquiline, but the proportion of patients who were lost to follow-up remains substantial.

Drug resistance mutation profiles of the drug-nave and first-line regimen-treated HIV-1-infected population of Suzhou, China

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance(TDR) and acquired drug resistance mutation(ADR) profiles, we collected blood specimens from 127 drug-naive and 117 first-line drugtreated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified po/fragments from 100 drug-naive and 20 drug-treated samples. We then determined the drugresistant mutations to protease(PR) and reverse-transcriptase(RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted(drug-naive group) and acquired(treated group) resistance mutations, respectively. Six transmitted drugresistant mutations were found, including two mutations(L33F and L76V) in the protease region and four(K70N/E and V179D/E) in the RT region. Only L76 V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

Evaluation of directly observed treatment short courses at a secondary health institution in Ibadan,Oyo State,Southwestern Nigeria

Objective:To evaluate the success rate of tuberculosis intervention programme at a specialist hospital in(?)badan,Nigeria through a retrospective study as well as carry out physicochemical evaluation of anti-tuberculous agents as a way of eliminating drug-related failure.Methods:The retrospective study involved the use of quarterly tuberculosis central register at the Government Chest Hospital,(?)badan between 1st quarter(2003)to 4th quarter(2009).Relevant data were extracted from these register with the aid of data collection forms.The basic physicochemical analyses of the drugs given to the patients were also carried out using the International Pharmacopoeia methods.Results:All the drugs examined for their physicochemical properties passed the International Pharmacopeia recommended tests.A total number of 1 260 patients enrolled at the hospital were assessed through case notes.This comprises of 59.4%males of which69.23%new cases were also males.There was a significant(P<0.05)patient enrollment across the quarters for the seven years.An overall 80.24%cure rate over the 7-period was obtained which is less than the WHO target of 85%.Cure rates were better in females than males.Failure treatment outcomes such as positive(1.51%),deaths(8.73%),defaulted(3.33%)and transferred out(5.95%)were recorded though not statistically significant(P>0.05).Failure rates in all categories were higher in males than females(P>0.05).Conclusions:More enlightenment and counseling is still required to meet up with the target for TB control.

Cost-effectiveness of Osimertinib in activating epidermal growth factor receptor gene(EGFR)-mutations in first-line for advanced non-small cell lung cancer

The introduction of first-or second-generation epidermal growth factor receptor gene(EGFR)tyrosine kinase inhibitors(TKIs)in chemonaive patients with advanced non-small cell lung cancer(NSCLC)has radically changed the treatment in this molecular subgroup,with an improvement in progression-free survival(PFS)compared to standard chemotherapy[1].

The production and sales of antituberculosis drugs in China

Background:Tuberculosis(TB)is a major infectious disease globally.Adequate and proper use of anti-TB drugs is essential for TB control.This study aims to study China’s production capacity and sales situation of anti-TB drugs,and to further discuss the potential for China to contribute to global TB control.Methods:The production data of anti-TB drugs in China from 2011 to 2013 and the sales data from 2010 to 2014 were extracted from Ministry of Industry and Information Technology database of China and IMS Health database,respectively.The number of drugs was standardized to the molecular level of the key components before calculating.All data were described and analyzed by Microsoft Excel.Results:First-line drugs were the majority in both sales(89.5%)and production(92.3%)of anti-TB drugs in China.The production of rifampicin held the majority share in active pharmaceutical ingredients(APIs)and finished products,whilst ethambutol and pyrazinamide were the top two sales in finished products.Fixed-dose combinations only held small percentages in total production and sales weight,though a slight increase was observed.The production and sales of streptomycin showed a tendency of decrease after 2012.The trends and proportion of different anti-TB drugs were similar in production and sales,however,the production weight was much larger than that of sales,especially for rifampicin and isoniazid.Conclusions:First-line drugs were the predominant medicine produced and used in China.While the low production and sales of the second-line TB drugs and FDCs rose concerns for the treatment of multiple drug resistant TB.The redundant production amount,as well as the prompt influence of national policy on drug production and sales,indicated the potential for China to better contribute to global TB control.

Tuberculosis of the Spine (L5, S1) Secondary to Scrofuloderma with Viral Warts in a 15-Year-Old Male

We report this case of a 15-year-old male who presented to the children outpatient clinic (CHOP) of Abia State University Teaching Hospital (ABSUTH), Aba on the 5th of November 2015. He had tuberculosis (TB) of the skin (scrofuloderma) which was not diagnosed and had received treatment other than anti-TB medication. He now presented 9 years after with multiple body discharging sinuses, cicatricial skin lesions, tuberculosis of the spine (L5, S1) with contracture of the Achilles Tendon and genital warts. Subsequent treatment with full anti-TB drugs led to resolution of his illness. A higher index of suspicion is required for early diagnosis of extrapulmonary TB. Prompt and adequate treatment with anti-TB medication ensures cure in such cases. Appropriate control program is also known to improve the outcome and reduce sequelae.