The Contribution of the Xpert® MTB/RIF Assay to the Surveillance of Drug-Resistant Tuberculosis in the Central African Republic

Introduction: The Central African Republic is one of the 30 high Tuberculosis burden countries in the world, with an incidence of 540 cases per 100,000 population and a mortality of 91 deaths per 100,000 population. Since 2020, following WHO recommendations, the National Reference Laboratory for Tuberculosis has been using the Xpert® MTB/RIF assay as a first-line diagnostic test for the early detection of Drug Resistance Tuberculosis. The goal of this study was to evaluate the contribution of the Xpert® MTB/RIF assay to the surveillance of rifampicin resistance in new and previously treated tuberculosis cases. Materials and Methods: The data relative to the Xpert® MTB/RIF assay carried out on various categories of tuberculosis patients registered at the National Reference Laboratory for Tuberculosis in 2020 were analyzed retrospectively. The categories of tuberculosis patients were new cases, failed treatment cases, relapse cases, lost-to-follow-up cases and multidrug-resistant tuberculosis contact cases. Results: A total of 1404 tuberculosis patients were registered at the NRL-TB in 2020;the mean age was 39.2 years (2 - 90 years) and the male-to-female sex ratio was 1.16:1. Overall, 32.7% (454/1404) proved infected with tuberculosis, of which 22.5% (102/454) cases showed resistance to rifampicin. The primary resistance rate was 9.1% (27/298) and the secondary resistance rate was 46.6% (75/161). Treatment failures and relapsed cases were significantly associated with rifampicin resistance (p 0.005). Conclusion: Large-scale use of Xpert® MTB/RIF, especially in the provinces of the Central African Republic, will help the Ministry of Health to better control Drug Resistance Tuberculosis in the country.

Effectiveness of Health Education Video in Improving Treatment Adherence among Patients with Tuberculosis: An Interventional Study from Bengaluru, India

Background: Non-adherence to tuberculosis (TB) treatment might prolong disease transmission and also increases the risk of drug resistance. Various studies have been carried out to determine the predictors of non-adherence but intervention-based studies to address treatment adherence are scarce. This study intends to estimate the treatment adherence rates following delivery of patient-centered health education videos in the intervention tuberculosis unit (TU) and to compare the treatment adherence with that in the comparison TU. Methods: An interventional study was conducted in two TUs of Bengaluru urban district among all newly diagnosed TB cases on daily regimen treatment over a period of three months from November 2017 to January 2018. A patient centered health education video was developed and shown by the treatment supporters to all eligible participants consenting to participate in the intervention TU. The video was shown once at the beginning of intensive phase treatment and once in the continuation phase of treatment. A total of 100 patients, 21 from intervention TU and 79 from comparison TU formed the study sample. Patient details were obtained from their treatment cards. Data on missed doses per month per patient were also noted. Data were entered into Microsoft excel worksheet and analyzed using statistical package for social sciences. Data are expressed as frequency and percentages. Chi-square test was applied to compare groups. Results: The majority of the study participants were aged between 25 - 44 years. Equal distribution of cases was seen among males and females. Intervention TU had significantly higher number of pulmonary TB cases. Treatment adherence rates were 90.5% and 84.8% at end of intensive phase and 85% and 71.4% at end of continuation phase in the intervention and comparison TU respectively, and this difference was not statistically significant. Conclusion: Use of mobile video-based health education showed better treatment rates and was found to improve TB treatment adherence.

Relationship between Nutritional Support and Tuberculosis Treatment Outcomes in West Bengal, India

Introduction: Poverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome. Methods: This was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death). Results: Of 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51;95% Confidence Intervals: 0.30 - 0.86). Conclusion: Under programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line.

Serum Markers of Systemic Inflammation in Patients with Pulmonary Tuberculosis

Serum markers of systemic inflammation （SAA （serum amyloid protein A）, CRP （C-reactive protein）, cq-AT （ct l-antitripsin）, Hp （haptoglobin） and F （fibrinogen）） have been studied in 317 patients with pulmonary tuberculosis. It was established that sensitivity of SAA as an activity marker was higher than of other acute phase reactants, because its levels were increased in 98.8% patients, whereas the level of CRP exceeded the norm in 80.8%, α1-AT--in 59.3%, Hp----in 43.5% and F--in 63.1% cases. The degree of increase of acute phase reactants directly related to the expressiveness of tuberculosis intoxication, the extent of the process in the lung and the quantity of MTB （M. tuberculosis） in sputum. We concluded that SAA was a useful marker of the process activity in patients with pulmonary tuberculosis and its sensitivity was higher than that of other acute phase reactants.

IFN-<i>γ</i>-, IL-4-, IL-17-, PD-1-Expressing T Cells and B Cells in Peripheral Blood from Tuberculosis Patients

Although the efficacy of tuberculosis (TB) vaccines is tightly linked to cell-mediated immunity, some functions of T and B cells in TB patients remain unclear. To address how Mycobacterium tuberculosis infection inhibits T effector responses, we assessed the proportions of T cell subsets and B cells in peripheral blood from pulmonary TB (PTB) patients, pleural TB (PLTB) patients, and healthy subjects (HS, who showed purified protein derivative (PPD)-positive reactions) with flow cytometry. Compared to HS, PTB and PLTB patients exhibited higher proportions of B cells and Th17 cells, and lower proportions of Th2 cells and ratios of Th1 to Th17 cells and of Th2 to Th17 cells. PTB patients had higher CD4+ T cells and PD-1+ CD4+ T cells than HS. Newly diagnosed PTB patients (nPTB) had higher proportions of B cells than HS;in contrast, PTB patients subjected to effective treatments (oPTB) and HS shared similar proportions of B cells. oPTB patients had higher proportions of CD4+ T cells, Th17 cells, and PD-1+ CD4+ T cells than HS, but this difference did not occur in nPTB patients. These findings suggest that shifting ratios of Th1 to Th17 cells may be beneficial for M. tuberculosis to amplify.

印度结核病流行病学:综述

印度的结核病形势可以用高患病率、高发病率高传染率来描述。自二十世纪50年代以来在印度不同地区进行的疾病监测报告显示:涂阳肺结核患病率为0.6-7.6/1000,培阳肺结核患病率为1.7-9.8/1000,培阳和/或涂阳结核患病率为1.8-12.7/1000。从已进行的有限的研究资料分析,涂阳肺结核的发病率在1.0-1.6/1000之间,培阳肺结核发病率在1.0-2.5/1000之间。根据不同时期在不同地区进行的结核菌素监测估计,结核年感染率(ARTI)为1-2%。在2000-2003年进行的全国范围研究估计,平均ARTI为1.5%。多数在第3级卫生保健中心进行的研究显示在结核病例中人类免疫缺陷病毒(HIV)血清阳性率在增加,不同研究的结果介于0.4%-28.8%之间。新病例中耐多药(MDR)率相对较低,约0.5-5.3%之间。但在复治病例中MDR为8%-67%。

Comparative study on the anti-tuberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiao He extract and JieHeWan

Background:The traditional Chinese medicine NiuBeiXiaoHe(NBXH)extract and Chinese medicine preparation JieHeWan(JHW)exhibit anti-tuberculosis(TB)effects.The anti-TB effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH.Methods:BALB/c mice aged 6-8 weeks were randomly divided into a normal control group,TB model group,JHW treatment group,and NBXH treatment group.After 3 and 13 weeks of treatment,the therapeutic effect in each group was evaluated by comparing lung histopathology,lung and liver colony counts,the number of spots representing effector T cells secreting IFN-γin an enzyme-linked immunospot assay(ELISPOT),and the levels of Th1,Th2,and Th17 cytokines,which were measured by a cytometric bead array(CBA).Mouse RNA samples were subjected to transcriptome sequencing.Results:After 13 weeks of treatment,the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group(P<0.05).Compared with those in the TB model group,the lung colony counts in the JHW and NBXH groups were significantly decreased(P<0.05),and the IL-2 and IL-4 levels in the NBXH group were significantly increased(P<0.05).NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis(M.tuberculosis)infection.According to GO and KEGG analyses,the changes in biological process(BP),cell composition(CC)and molecular function(MF)terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent,but they were mainly related to the immune response and inflammatory response in the mouse TB model.Conclusions:NBXH had therapeutic effects similar to those of JHW in improving lung histopathology,reducing lung colony counts,and regulating the levels of cytokines.NBXH restored significant changes in gene expression and repaired cell damage caused by M.tuberculosis infection by regulating immune-related pathways,which clarified the mechanism of action of NBXH.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Post-exposure prophylaxis(PEP)for leprosy is administered as one single dose of rifampicin(SDR)to the contacts of newly diagnosed leprosy patients.SDR reduces the risk of developing leprosy among contacts by around 60%in the first 2–3 years after receiving SDR.In countries where SDR is currently being implemented under routine programme conditions in defined areas,questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M.tuberculosis strains circulating in these areas.This issue has not been addressed in scientific literature to date.To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis,a meeting was convened with tuberculosis(TB)and leprosy experts.The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of(multi)drug-resistance in M.tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy.They concluded that SDR given to contacts of leprosy patients,in the absence of symptoms of active TB,poses a negligible risk of generating resistance in M.tuberculosis in individuals and at the population level.Thus,the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M.tuberculosis.

Nontuberculous mycobacteria： susceptibility pattern and prevalence rate in Shanghai from 2005 to 2008

Background An increasing incidence of disease caused by nontuberculous mycobacteria （NTM） is being reported. The purpose of this study was to determine the isolation rates of NTM from various clinical specimens, and their antimicrobial susceptibility patterns, over a 4-year period in Shanghai. Methods All NTM isolated between 2005 and 2008 at Shanghai Pulmonary Hospital, a key laboratory of mycobacteria tuberculosis in Shanghai, China, were identified with conventional biochemical tests and 16S rRNA gene sequencing. Antimicrobial susceptibility for all NTM was determined using the BACTEC MGIT 960 system. Results A total of 21 221 specimens were cultured, of which 4868 （22.94%） grew acid fast bacilli （AFB）, and 248 （5.09%） of the AFB were NTM. The prevalence rate of NTM was determined as 4.26%, 4.70%, 4.96% and 6.38% among mycobacteria culture positive samples in years 2005, 2006, 2007 and 2008 respectively. These data indicated that the prevalence rate has continuously increased. Sixteen different species of NTM were identified, the most commonly encountered NTM in Shanghai were M. chelonae （26.7%）, followed by M. fortuitum （15.4%）, M. kansasii （14.2%）, M. avium-intracellulare complex （13.1%） and M. terrae （6.9%）. The rare species identified were M. marinum, M. gastri, M. triviale, M. ulcerans, M. smegmatis, M. phlci, M. 9ordonae, M. szulgai, M. simiae, M. scrofulaceum and M. xenopi. The five most commonly identified NTM species showed high drug resistance to general anti-tuberculosis drugs, particularly, M. chelonae and M. fortuitum appear to be multi-drug resistance. Conclusions The prevalence of NTM in Shanghai showed a tendency to increase over the course of the study. The five most commonly isolated NTM species showed high drug resistance to first line anti-tuberculosis drugs.

Patients direct costs to undergo TB diagnosis

Background:A major impediment to the treatment of TB is a diagnostic process that requires multiple visits.Descriptions of patient costs associated with diagnosis use different protocols and are not comparable.Methods:We aimed to describe the direct costs incurred by adults attending TB diagnostic centres in four countries and factors associated with expenditure for diagnosis.Surveys of 2225 adults attending smear-microscopy centres in Nigeria,Nepal,Ethiopia and Yemen.Adults>18 years with cough>2 weeks were enrolled prospectively.Direct costs were quantified using structured questionnaires.Patients with costs>75^(th) quartile were considered to have high expenditure(cases)and compared with patients with costs<75^(th) quartile to identify factors associated with high expenditure.Results:The most significant expenses were due to clinic fees and transport.Most participants attended the centres with companions.High expenditure was associated with attending with company,residing in rural areas/other towns and illiteracy.Conclusions:The costs incurred by patients are substantial and share common patterns across countries.Removing user fees,transparent charging policies and reimbursing clinic expenses would reduce the poverty-inducing effects of direct diagnostic costs.In locations with limited resources,support could be prioritised for those most at risk of high expenditure;those who are illiterate,attend the service with company and rural residents.

MULTIMODALITY THERAPY INCLUDING SURGICAL RESEC-TION FOR LIMITED SMALL CELL LUNG CANCER

From 1975 through 1990, 199 patients with limited small cell lung cancer (LSCLC) were subjected to multimodality treatment including surgical resection combined with chemotherapy or chemoradiotherapy in our department. The median postoperative survival time of the 199 patients was 39 months, and the 5-year survival rate was 26%, which was decreased with increase of tumor-stage. In comparison of the survival time of patients in Stage Ⅰ and those in Stage Ⅲa, there was a significant difference (P<0.01). There were no significant differences in survival rate of 3 and 5 years between the patients receiving chemotherapy prior to or after surgical resection. The improvement in survival was documented by surgical resection combined with chemotherapy or chemoradiotherapy for LSCLC. The effect of multimodality treatment is correlated with tumor P-TNM staging, the involvement of lymph node, especially that of the mediastinal lymph node, is a negative factor influencing the prognosis. Surgical resection as an initial management, followed by chemotherapy or chemoradiotherapy may be indicated in LSCLC patients of Stage Ⅰ, Stage Ⅱ and some Stage Ⅲa as the cancer can be resected completely.