Transmission Of Drug-resistant Strains Research Articles

Trends of Drug-Resistant Tuberculosis in an Urban and a Rural Area in China: A 10-Year Population-Based Molecular Epidemiological Study.

Drug resistance is the critical determinant for appropriate tuberculosis (TB) treatment regimens and an important indicator of the local TB burden. We aimed to investigate and compare trends in TB drug resistance in the urban Songjiang District of Shanghai from 2011 to 2020, and the rural Wusheng County of Sichuan Province from 2009 to 2020, to assess the effectiveness of local TB control and treatment programs. Whole-genome sequencing data of Mycobacterium tuberculosis were used to predict drug-resistance profiles and identify genomic clusters. Clustered, retreated cases of drug-resistant TB with identical resistance mutations, as well as all new resistant cases, were defined as transmitted resistance. The Cochran-Armitage trend test was used to identify trends in the proportions. Differences between groups were tested using the Wilcoxon rank sum or chi-square tests. The annual proportions of rifampicin-resistant (RR), isoniazid-resistant (INH-R) and multidrug-resistant (MDR) TB cases did not change significantly in Songjiang. In Wusheng, however, the percentage of total TB cases that were RR decreased from 13.2% in 2009 to 3.7% in 2020, the INH-R cases decreased from 16.5% to 7.3%, and the MDR cases decreased from 10.7% to 3.7%. In retreated cases, the percentage of drug resistance decreased in both Songjiang and Wusheng, suggesting improved treatment programs. Transmitted resistance accounted for more than two thirds of drug-resistant cases over the entire study periods, and in recent years this proportion has increased significantly in Songjiang. In both urban Songjiang and rural Wusheng, drug-resistant TB is mostly the result of transmission of drug resistant strains and the percentage of transmitted resistance will likely increase with on-going improvements in the TB treatment programs. Reducing the prevalence of drug resistance depends principally upon decreasing transmission through the prompt diagnosis and effective treatment of drug-resistant TB cases.

Prevalence of Primary Drug Resistance Among Newly Diagnosed HIV-1-Infected Individuals in Hunan Province, China.

At present, research on the prevalence of primary drug resistance (PDR) in Hunan Province is limited. Therefore, we explored the current status of HIV-1 PDR in Hunan to provide a basis for antiretroviral therapy (ART) and a theoretical foundation for prevention and control of the HIV/AIDS epidemic. Three hundred seventy newly diagnosed HIV-1-infected individuals who had not received ART in Hunan province, China, were enrolled in the study. Plasma samples were collected, RNA was extracted, two rounds of gene amplification were carried out with the in-house method, and subtype analysis and drug resistance analysis were carried out with relevant software. We found that the most prevalent subtypes of HIV-1 in Hunan Province are CRF_01AE (126/359, 35.1%) and CRF07_BC (85/359, 23.7%). The PDR rate among newly diagnosed HIV/AIDS patients was 10.0% (36/359). Among them, the drug resistance rates of protease inhibitors, nucleotide reverse transcriptase inhibitors, non-nucleotide reverse transcriptase inhibitors, and integrase inhibitors were 0.3% (1/359), 3.3% (12/359), 8.36% (30/359), and 0.6% (2/359), respectively. The distribution of HIV-1 subtypes in Hunan Province is diverse and complex, and the PDR rate has exceeded the low-level warning line set by the World Health Organization (<5%). Therefore, we should conduct pretreatment drug resistance assays to determine the optimal primary ART so that patients can obtain better antiretroviral treatment outcomes and transmission of drug-resistant strains in the population can be blocked.

Epidemic Characteristics of HIV Drug Resistance in Hefei, Anhui Province.

To study the characteristics of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hefei, a cross-sectional survey was used to collect 816 samples from newly reported HIV infections from 2017 to 2020 and 127 samples from HIV infections with virological failure from 2018 to 2019 in Hefei. HIV drug resistance levels and drug resistance mutations were interpreted using the Stanford Drug Resistance Database. Molecular networks were constructed by HIV-TRACE. Among the newly reported infections in Hefei, the prevalence of PDR was 6.4% (52/816). The drug resistance mutations were mainly V179E/D/T (12.4%), K103N (1.3%), and V106I/M (1.3%). In addition, it was found that the CRF55_01B subtype had a higher drug resistance rate than other subtypes (p < 0.05). Molecular network analysis found that K103N and V179E may be transmitted in the cluster of the CRF55_01B subtype. The prevalence of ADR among HIV infections with virological failure was 38.6% (49/127), and the drug resistance mutations were mainly M184V (24.4%), K103N/S (15.7%), Y181C (11.0%), G190S/A/E (10.2%), and V106M/I (10.2%). The molecular network was constructed by combining HIV infections with virological failure and newly reported infections; M184V and Y181C may be transmitted between them. The chi-square trend test results indicated that the higher the viral load level, the greater the number of newly reported infections linked to the infections with virological failure in the molecular network. In conclusion, interventions should focus on infections of the CRF55_01B subtype to reduce the transmission of drug-resistant strains. However, improving the treatment effect of HIV infections is beneficial for reducing the second-generation transmission of HIV.

Multi Drug Resistant Tuberculosis Detection by Phenotypic Method inTreatment Naïve Pulmonary Tuberculosis Patients

Background and Aims The emergence of multi drug-resistant tuberculosis MDR-TB in treatment naiumlve Pulmonary Tuberculosis PTB is an epidemiological indicator indicating transmission of drug-resistant strains in the community. This study aimed to assess the patterns of drug resistance to any first-line anti-TB drugs and MDR-TB in culture-positive TB isolates obtained from treatment naiumlve PTB in a tertiary care hospital.Methods A total of 240 culture-positive TB isolates obtained from newly diagnosed pulmonary TB patients during the study period September 2018- June 2021 were enrolled in this study. All culture-positive isolates were subjected to phenotypic drug susceptibility testing DST by the conventional 1 proportion method against all the five first-line anti-tubercular antibiotics.Results Of the 240 isolates 127 52.9 were susceptible to all the first-line anti-tubercular drugs. Mono resistance to Rifampicin Isoniazid Streptomycin and Pyrazinamide was observed in 11 4.6 8 3.3 15 6.3 and 14 5.8 of the isolates respectively. Resistance to Ethambutol was not exhibited by any of the isolates. The proportion of MDR-TB in the study was 12.5.Conclusions The study has identified a high rate of MDR-TB in the study area indicating the need to strengthen and expand the National level TB eradication programmes for early identification and proper treatment to interrupt the chain of transmission of MDR-TB in the community

Distribution patterns of drug resistance Mycobacterium tuberculosis among HIV negative and positive tuberculosis patients in Western Kenya

IntroductionGlobally anti-tuberculosis drug resistance is one of the major challenges affecting control and prevention of tuberculosis. Kenya is ranked among 30 high burden TB countries globally. However, there is scanty information on second line antituberculosis drug resistance among tuberculosis patients. Therefore, this study aimed at determining Mycobacterium tuberculosis drug resistant strain distribution pattern in 10 counties of Western Kenya among HIV positive and negative patients.MethodA cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling one high volume health facility from each sub-county. Consenting study subjects with at least two smear positive sputum at the time of enrolment were randomly selected. The collected sputum was decontaminated with N-acetyl-l-cysteine-sodium hydroxide (NALC-NaOH) and then stained with Ziehl Neelsen Stain before visualizing the presence of bacilli under microscope at ×100 magnification with oil immersion. Further, the identified bacilli were cultured and susceptibility test carried out using known first and second line antimycobacterial tuberculosis. HIV testing was carried out using Determine® HIV-1/2 rapid test (Abbot Diagnostics, Maidenhead, United Kingdom). Those who had smear converted were dropped from the study. Finally, drug susceptibility pattern across the 10 counties of Western Kenya was evaluated.ResultsOur study showed that Mycobacterium tuberculosis drug resistance among HIV negative and positive cases in Western Kenya was prevalent in all the 10 counties surveyed. Based on the drug susceptibility tests, 53.2% and 42.7% of the study samples were resistant to at least one antituberculosis drug among HIV negative and HIV positive patients respectively. The data analysis revealed that among the HIV-positive and HIV-negative patients, resistance to INH was predominant (28.5%, and 23.6%, respectively), followed by RIF (16.4% and 14.6% respectively). Second-line drug resistant strains identified among HIV negative patients included Ethionamide (0.3%), Gatifloxacin (0.3%), Amikacin (0.3%) and Capreomycin (0.3%). There was no second line drug monoresistance among HIV positive TB patients. Multi/poly drug resistance were noted among HIV-negative patients in, INH + AMK (0.7%), INH + PZA (1%), INH + GFX (0.7%, INH + ETO (0.7%, STY + ETO (1%), ETH + ETO (1.0%), INH + KAN (0.7%) and INH + CAP (0.7%) strains/cases at 95% confidence interval. Among HIV positive patients INH + GFX (1.1%), INH + ETO (0.4%) and INH + KAN (0.4%) strains of M. tuberculosis were identified with a confidence interval of 95%. Geographical distribution patterns analysis of M. tuberculosis drug polyresistant strains across the 10 counties were recorded. Among HIV TB patients, resistant strains were identified in Nyamira (INH + GFX, INH + KAN), Bungoma ((ETO + STY), Busia (ETH + ETO and STY + ETO) Homabay (RIF + AMK. ETO + ETH and ETO + STY), Kisumu (ETH + ETO and PZA + ETO) and in Kakamega, Kisii and Vihiga (INH + KAN and RIF + AMK). There was no M. tuberculosis polyresistant strain identified in Migori and Siaya counties. Among HIV positive TB patients, M. tuberculosis resistant strains were identified in three counties, Nyamira (INH + KAN) Homabay (INH + GFX and INH + AMK) and Kakamega (INH + GFX). There was no polyresistant M. tuberculosis strain identified in Migori, Bungoma, Kisii, Vihiga, Busia, Siaya and Kisumu Counties.DiscussionThe distribution patterns of M. tuberculosis drug resistance among HIV negative and positive TB patients could be as a result of reported high prevalence of HIV in Western Kenya counties especially the area under study. Tuberculosis is one of the opportunistic diseases that have been shown to be the major cause of AIDS among HIV infected patients. Resent reports by National AIDS Control Council shows that Kisumu, Siaya, Homabay, Migori, Busia have the overall leading in HIV prevalence in Kenya. The low prevalence of drug resistant strains among HIV tuberculosis patients could be as a result of drug adherence attitude adopted by HIV patients, availability of continuous counselling and close follow up and notification by healthcare workers and community health volunteers.ConclusionDrug resistant M. tuberculosis strains prevalence is still high among HIV negative and positive patients in Western Kenya with the most affected being HIV negative TB patients. It is therefore probable that the existing control measures are not adequate to control transmission of drug resistant strains. Further, miss diagnosis or delayed diagnosis of TB patients could be contributing to the emergence of M. tuberculosis drug polyresistant strains.RecommendationBased on the result of this study, regular TB drug resistance surveillance should be conducted to ensure targeted interventions aimed at controlling increased transmission of the tuberculosis drug resistant strains among HIV/AIDS and HIV negative patients. There is also need for improved drug resistant infection control measures, timely and rapid diagnosis and enhanced and active screening strategies of tuberculosis among suspected TB patients need to be put in place. Further, studies using a larger patient cohort and from counties across the country would shed much needed insights on the true national prevalence of different variants of M. tuberculosis drug resistance.

PATTERNS OF SUSCEPTIBILITY TESTING OF ANTITUBERCULOSIS DRUGS AMONG PATIENTS ATTENDING TUBERCLOSIS CLINIC IN KAKAMEGA TEACHING AND REFERALL HOPITAL KENYA

Drug Resistance Tuberculosis (DR TB) is a form of tuberculosis infection that is resistance to treatment with Rifampicin and Isoniazid with or without resistance to one or more other drugs used in the first line treatment of tuberculosis (Mitchison, 2012). Kenya is ranked 13th among the 22 high TB burden countries worldwide (WHO, 2013). MDR TB is a global health security risk and carries grave consequences for those affected (WHO, 2014). Its development is associated with high mortality rates and low levels of productivity among workers due to the high cost of care which imposes a heavy economic burden on the nation (Eduardo, 2011). DR TB therefore poses a major challenge to tuberculosis care and control (Ellen &amp; McNerney, 2008). Limited literature talks about the exact prevalence of resistance to anti-tuberculosis drugs in populations with high rates of tuberculosis (WHO, 2015). In addition, only a few isolated cases of multiple drug resistant tuberculosis have been reported in Kenya (Ogaroet.al., 2012). This study aimed at determining the burden of pattern of Drug Restance TB via determination of the prevalence of TB and the gene resistance patterns to the two most commonly used anti- TB drugs Rifampicin and Isoniazid. A cross-sectional study was conducted among new and re-treatment cases of tuberculosis referral patients in Kakamega county teaching and referral hospital between June and August 2018. A total of 138 patients were enrolled for the study and the health facility TB register questionnaire was used to obtain data on demographic factors of the patients. Data generated was analyzed using the statistical package for social sciences (SPSS) version 22.0 to find case summaries. Descriptive statistical tests were performed on the data including means, modes, percentages, standard deviations and percentiles. Data was then presented in pie-charts, bar graphs and tables. Out of the 138 cases seventy (50.7%) were male and sixty-eight (49.3%) female. All the study cases were new. Twenty-eight (20.3%) of the isolates became positive for MTB. Of these, eight (5.7%) isolates showed resistance to either of the two first line drugs tested while twenty (14.5%) were fully susceptible. None of the isolates tested became positive for Drug resistant tuberculosis. Notably most of the resistant cases were found to be among HIV positive patients (4.3%) with (1.4%) of the cases being from HIV negative patients. This study revealed high levels of drug resistance among new cases of untreated patients. This implies ongoing transmission of drug resistant strains in the community.

Natural Products with Inhibitory Activity against Human Immunodeficiency Virus Type 1.

Infections caused by human immunodeficiency virus (HIV) are considered one of the main public health problems worldwide. Antiretroviral therapy (ART) is the current modality of treatment for HIV-1 infection. It comprises the combined use of several drugs and can decrease the viral load and increase the CD4+ T cell count in patients with HIV-1 infection, thereby proving to be an effective modality. This therapy significantly decreases the rate of morbidity and mortality owing to acquired immunodeficiency syndrome (AIDS) and prolongs and improves the quality of life of infected patients. However, nonadherence to ART may increase viral resistance to antiretroviral drugs and transmission of drug-resistant strains of HIV. Therefore, it is necessary to continue research for compounds with anti-HIV-1 activity, exhibiting a potential for the development of an alternative or complementary therapy to ART with low cost and fewer side effects. Natural products and their derivatives represent an excellent option owing to their therapeutic potential against HIV. Currently, the derivatives of natural products available as anti-HIV-1 agents include zidovudine, an arabinonucleoside derivative of the Caribbean marine sponge (Tectitethya crypta), which inhibits the reverse transcriptase of the virus. This was the first antiviral agent approved for treatment of HIV infection. Additionally, bevirimat (isolated from Syzygium claviflorum) and calanolide A (isolated from Calophyllum sp.) are inhibitors of viral maturation and reverse transcription process, respectively. In the present review, we aimed to describe the wide repertoire of natural compounds exhibiting anti-HIV-1 activity that can be considered for designing new therapeutic strategies to curb the HIV pandemic.

Factors associated with culture conversion among adults treated for pulmonary extensively drug-resistant tuberculosis during 2018-2019 in the Russian Federation: an observational cohort study.

Treatment outcomes for Multidrug/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) remain poor across the globe and in the Russian Federation. Treatment of XDR-TB is challenging for programmes and patients often resulting in low success rates and onward transmission of drug-resistant strains. Analysis of factors affecting culture conversion rate among XDR-TB patients may serve as a basis for optimization of treatment regimens. We conducted a retrospective cohort study using health records from 54 patients with pulmonary XDR-TB treated at a tertiary level facility in the Russian Federation. The study population included adult patients with culture-positive pulmonary XDR-TB who started treatment between 1 January 2018-30 June 2019. Culture conversion was defined as two consecutive negative cultures, collected at least 30 days apart. The date of sputum culture conversion was taken from the first of two consecutive negative sputum cultures fulfilling these criteria. We measured time to culture conversion using cumulative incidence functions accounting for competing risks and applied binary cause-specific Cox regressions to assess associated factors. Sputum culture conversion was recorded for 43 (79.6%) patients. Median time to culture conversion adjusted for competing risk of loss to follow up was 4 months [95% confidence interval (CI): 2-5]. The number of patients who had culture converted by treatment months 2, 4, and 6 were 12 (22%), 29 (54%) and 38 (70%) respectively. In unadjusted analysis, positive baseline sputum smear microscopy [hazard ratio (HR): 0.34, 95% CI: 0.18-0.66; p=0.001), hepatitis C (HR: 0.35, 95% CI: 0.14-0.89; p=0.023], and human immunodeficiency virus (HR: 0.30 95%, CI: 0.09-0.97; p=0.045), and receipt of fewer than 4 effective drugs in the treatment regimen (HR: 0.13, 95% CI: 0.03-0.60; p=0.009) were associated with delayed culture conversion. When compared to their combined use, patients receiving regimens with bedaquiline only (HR: 0.12, 95% CI: 0.03-0.49; p=0.003) orlinezolid only(HR: 0.21, 95% CI: 0.06-0.69; p=0.010) were less likely to achieve timely culture conversion. Factors delaying sputum culture conversion should be considered in the management of patients with XDR-TB and considered by clinicians for regimen design and treatment strategies. Our study outlines the importance of simultaneous inclusion of bedaquiline and linezolid in treatment regimens for patients with XDR-TB to reduce time to sputum conversion and increase treatment success.

Primary drug resistance among Mycobacterium tuberculosis isolates from treatment naïve and new pulmonary tuberculosis patients in relation to their socio-economic status

BACKGROUND: Multidrug-resistant Tuberculosis (TB) has become an area of growing concern throughout the World, despite the global efforts in eliminating TB. Detection of primary drug resistance in treatment naïve patients, either due to spontaneous mutation or due to transmission of drug-resistant strains is an important indicator of the presence of drug-resistant strains in the community.OBJECTIVES: The objective is to estimate the prevalence of primary drug resistance in treatment naïve pulmonary TB patients and to identify the socio-economic class of the resistant population.MATERIALS AND METHODS: A total of 272 treatment naïve presumptive TB patients were enrolled in the study from September 2018 to December 2020. The samples were subjected to GeneXpert, for detecting the presence of Mycobacterium TB (MTB) along with Rifampicin (RIF) resistance detection. Phenotypic drug susceptibility testing (DST) was performed on all positive mycobacterial cultures using the 1% proportion method against first-line anti-tuberculous drugs. Socioeconomic status of the patients was also assessed based on updated Kuppuswamy Socioeconomic scale (2018).RESULTS: Of the 272 samples subjected to GeneXpert MTB/RIF assay, MTB was detected in 193 (71%) samples and RIF resistance (rpoB gene) was detected in 25 (9%) samples. Phenotypic DST detected multidrug-resistant (MDR) in 22 (8%) samples. Majority of the MDR patients (55%) were belonging to the upper lower (IV) class of Kuppuswamy socio-economic scale.CONCLUSION: High prevalence of MDR-TB among treatment naïve pulmonary TB patients was noted in patients belonging to Class IV of Kuppuswamy socio-economic scale.

Impact of GeneXpert MTB/RIF\xae on treatment initiation and outcomes of RIF-resistant and RIF-susceptible TB patients in Vladimir TB dispensary, Russia

BackgroundThe main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology.MethodsAll adult patients suspected of having TB during February–December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups.ResultsOf 402 patients screened for TB during February–December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06).Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26).ConclusionWe observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB.

Mutation and Transmission Profiles of Second-Line Drug Resistance in Clinical Isolates of Drug-Resistant Mycobacterium tuberculosis From Hebei Province, China.

The emergence of drug-resistant tuberculosis (TB) is involved in ineffective treatment of TB, especially multidrug resistant/extensively resistant TB (MDR/XDR-TB), leading to acquired resistance and transmission of drug-resistant strains. Second-line drugs (SLD), including both fluoroquinolones and injectable drugs, were commonly proved to be the effective drugs for treatment of drug-resistant TB. The purpose of this study was to investigate the prevalence of SLD-resistant strains and its specific mutations in drug-resistant Mycobacterium tuberculosis clinical isolates, and to acknowledge the transmission pattern of SLD resistance strains in Hebei. The genes gyrA, gyrB, rrs, eis promoter and tlyA of 257 drug-resistant clinical isolates were sequenced to identify mutations that could be responsible for resistance against fluoroquinolones and second-line injectable drugs. Each isolate was genotyped by Spoligotyping and 15-loci MIRU-VNTR. Our results indicated that 48.2% isolates were resistant to at least one of five SLD. Of them, 37.7% isolates were resistant to fluoroquinolones and 24.5% isolates were resistant to second-line injectable drugs. Mutations in genes gyrA, gyrB, rrs, eis promoter and tlyA were detected in 73 (75.3%), 7 (7.2%), 24 (38.1%), 5 (7.9%), and 3 (4.8%) isolates, respectively. The most prevalent mutations were the D94G (23.7%) in gyrA gene and the A1401G (33.3%) in rrs gene. A combination of gyrA, rrs and eis promoter can act as a valuable predicator for predicting XDR phenotype. These results highlight the development of rapid diagnosis are the effective manners for the control of SLD-TB or XDR-TB.

Prevalence of Rifampicin Resistance Tuberculosis in Newly Diagnosed and Previously Treated Pulmonary Tuberculosis Patients Attending the Department of Pulmonary Medicine , Muzaffarnagar Medical College, Muzaffarnagar

Background: Multidrug-resistant tuberculosis (MDR-TB) prevalence is increasing throughout the world. Although, most important risk factor for development of MDR-TB is inadequate and irregular previous treatment for tuberculosis, but newly treated patients are also at risk due to either spontaneous mutations or transmission of drug-resistant strains. The conventional tuberculosis drug susceptibility tests are sensitive and specific but they are not rapid. Newer molecular methods help in rapid diagnosis. GeneXpert MTB/RIF is a rapid method to detect MTB and rifampicin resistance. Rifampicin resistance is an initial indicator of multidrug resistance. We have tried to ascertain the prevalence of Rifampicin resistance in newly diagnosed and previously treated pulmonary tuberculosis patients. Methods: This study was a prospective cross sectional study that involved all newly diagnosed and previously treated pulmonary tuberculosis patients attending the Department of Pulmonary Medicine, Muzaffarnagar Medical College, Muzaffarnagar from January 2018 to Dec 2018. In the District Hospital, Muzaffarnagar,the sputum specimens were sent for GeneXpert MTB/RIF .On the basis of the result, the patients were labelled as Rifampicin resistance. Results: A total no of 118 sputum samples were sent to District Hospital,Muzaffarnagar for GeneXpert MTB/RIF . Among these 118 patients, 102 patients were newly diagnosed pulmonary tuberculosis and 16 patients were previously treated pulmonary tuberculosis . Prevalence of Rifampicin resistance TB was found to be 0.98 % among newly diagnosed pulmonary tuberculosis, and 25 % among previously treated pulmonary tuberculosis patients. Conclusion: In conclusion, our results showed that the prevalence of Rifampicin resistance TB was high in previously treated pulmonary tuberculosis patient in comparison to newly diagnosed pulmonary tuberculosis patient. Proper administration of first line drugs for susceptible cases is most efficient method in preventing drug resistance.

Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012-2016.

To investigate transmission of drug-resistant strains of Mycobacterium tuberculosis in Tunisia, we performed whole-genome sequencing on 46 multidrug-resistant strains isolated during 2012–2016. Core-genome multilocus sequence typing grouped 30 strains (65.2%) into 3 clusters, indicating extensive recent transmission and Haarlem clone predominance. Whole-genome sequencing might help public health services undertake appropriate control actions.

Management of multidrug-resistant tuberculosis in the 21st century.

The spread of drug-resistant tuberculosis (TB) continues to be a global health crisis with increasing cases of multidrug-resistant TB (MDR-TB) being diagnosed worldwide. The identification and clinical management of MDR-TB is associated with additional problems related to resistance, diagnosis and treatment as compared to drug-susceptible TB. Treatment of MDR-TB usually involves therapy with long regimens of second-line drugs up to 24 months resulting in higher risks of serious adverse effects, lack of compliance and heightened economic burden on the patients. Issues such as increasing transmission of drug-resistant strains, poor diagnostic coverage and lengthy, toxic treatments need to be overcome by innovative approaches such as quick diagnostic tools and shorter drug regimens as already recommended by the World Health Organization (WHO) in its 2018 Global Tuberculosis Report. This review highlights the challenges being faced by clinicians worldwide in the diagnosis and treatment of MDR-TB.

Optimising the accuracy of HIV drug resistance assays

About 22 million people globally received antiretroviral therapy (ART) in 2017. 1 UNAIDSMiles to go. Closing gaps, breaking barriers, righting injustices. Joint United Nations Programme on HIV/AIDS, Geneva2018 Google Scholar In patients on ART, viral suppression is crucial for both the individual patient's clinical benefit and the community's HIV prevention benefit. A key reason for failure to achieve viral suppression is resistance to one or more drugs in the patient's antiretroviral regimen. Maintenance of a strict daily pill regimen can be challenging for patients; suboptimal adherence fosters drug resistance and the transmission of drug-resistant strains of HIV to others. Furthermore, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTls) is widespread, emanating from previous use of nevirapine as a single drug regimen for prevention of mother-to child transmission. 2 Gupta RK Gregson J Parkin N et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect Dis. 2018; 18: 346-355 Summary Full Text Full Text PDF PubMed Scopus (228) Google Scholar Clinically relevant thresholds for ultrasensitive HIV drug resistance testing: a multi-country nested case-control studyUltrasensitive resistance testing for pretreatment drug resistance improved identification of people at risk of virological failure; however, this came with a reduction in our ability to identify people with viral suppression, especially at very low thresholds. Further modelling is needed to estimate the optimal trade-off for the 5% and 20% thresholds, balancing improved case finding against unnecessary regimen switching. Full-Text PDF

Factors associated with the drug-resistant tuberculosis incidence rate in Brazil.

The selection and transmission of drug-resistant strains of tuberculosis (TB) hamper disease control. To identify health conditions, demographic and socio-economic factors, as well as individual factors associated with the incidence of drug-resistant TB (DR-TB), in Brazil at the municipal level. This was an ecological study covering Brazilian municipalities that had reported DR-TB cases in 2014. Associations were evaluated in a multilevel analysis using negative binomial regression. In the multilevel model, males (incidence rate ratio [IRR] 2.6, 95% confidence interval [CI] 2.3-2.93) and Black persons (IRR 1.82, 95%CI 1.61-2.05) had a higher risk of DR-TB. Compared with those aged 60 years, persons aged 15-59 years (IRR 1.72, 95%CI 1.40-2.11) also had a higher risk. The following contextual factors were associated with the incidence rate (IR) of DR-TB: proportion of previously treated patients (IRR 1.27, 95%CI 1.1-1.5), acquired immune-deficiency syndrome IR (IRR 1.13, 95%CI 1.02-1.25), Municipal Human Development Index (IRR 0.72, 95%CI 0.64-0.81) and the Gini coefficient (IRR 0.86, 95%CI 0.78-0.95). We have identified individual and contextual factors associated with the incidence of DR-TB. Our results may help improve integrated public health interventions aimed at controlling DR-TB in Brazil.

HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan.

The use of antiretroviral therapy has reduced rates of mortality and morbidity in patients with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS). However, transmission of drug-resistant strains poses a challenge to control the spread of HIV-1. Primary resistance to integrase strand-transfer inhibitors (INSTIs) is rare despite their increased use. The prevalence of transmitted drug resistance (TDR) to INSTIs was 0.9% in northern Taiwan. This study was to analyse the prevalence and risk factors of TDR to INSTIs in southern Taiwan. In this study, we enrolled antiretroviral treatment-naïve HIV-1-infected subjects who underwent voluntary counselling and testing from 2013 to 2016 in southern Taiwan. Genotypic drug resistance, coreceptor tropism (CRT) and INSTI resistance were determined. Logistic regression was used to analyse the risk factors for INSTI polymorphic substitution. Sequences were obtained from 184 consecutive individuals, of whom 96.7% were men who have sex with men and 3.3% were heterosexual. Of the patients, 10% (19/183) had hepatitis B and 33.3% (61/183) had syphilis infection. Subtype B HIV-1 strains were found in 96.1% of the patients. Fifteen patients (8.4%, 15/178) harboured nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors or protease inhibitors resistance. CCR-5 coreceptors were used by 71.4% (130/184) of the patients. None of the patients had INSTI resistance-associated mutations, however 16 patients had INSTI polymorphic substitutions, and they were associated with a higher HIV viral load (p = 0.03, OR 2.4, CI 1.1–5.3) and syphilis infection (p = 0.03, OR 3.7, CI 1.1–12.0). In conclusion, no signature INSTI resistance-associated mutations were detected in our cohort. Continued monitoring of TDR to INSTI is needed due to the increased use of INSTIs.

Acquired Resistance to Antituberculosis Drugs in England, Wales, and Northern Ireland, 2000-2015.

Among tuberculosis (TB) patients, acquired resistance to anti-TB drugs represents a failure in the treatment pathway. To improve diagnosis and care for patients with drug-resistant TB, we examined the epidemiology and risk factors associated with acquired drug resistance during 2000–2015 among TB patients in England, Wales, and Northern Ireland. We found acquired resistance in 0.2% (158/67,710) of patients with culture-confirmed TB. Using multivariate logistic regression, we identified the following factors associated with acquired drug resistance: having pulmonary disease; initial resistance to isoniazid, rifampin, or both; a previous TB episode; and being born in China or South Africa. Treatment outcomes were worse for patients with than without acquired resistance. Although acquired resistance is rare in the study area, certain patient groups are at higher risk. Identifying these patients and ensuring that adequate resources are available for treatment may prevent acquisition of resistance, thereby limiting transmission of drug-resistant strains of mycobacteria.

Genotypic drug resistance using whole-genome sequencing of Mycobacterium tuberculosis clinical isolates from North-western Tanzania

BackgroundDrug resistant Tuberculosis (TB) is considered a global public health threat. Whole-genome sequencing (WGS) is a new technology for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles and genotypes for epidemiologic surveillance. Therefore, we used WGS to determine genotypic drug resistance profiles and genetic diversity of drug resistant Mycobacterium tuberculosis isolates from Mwanza, North-western Tanzania. MethodsA cross-sectional study was conducted at the Bugando Medical Center (BMC) from September 2014 to June 2015. Consecutively, smear-positive newly diagnosed TB patients aged ≥18 years were enrolled. Sputum samples were cultured on Löwenstein-Jensen (LJ) slants. Mycobacterial genomic DNA was extracted for WGS to determine drug resistant mutations for first and second line drugs as well as the spoligotypes. ResultsA total of 78 newly diagnosed patients with pulmonary TB with a median age of 37 [IQR: 30–46] years were enrolled. Of these, 57.8% (45/74) were males and 34.6% (27/78) were HIV positive. Mycobacterium tuberculosis genomic DNA for WGS was obtained from isolates in 74 (94.9%) patients. Of the 74 isolates, six (8.1%) isolates harbored mutations for resistance to at least one drug. The resistance to the drugs was isoniazid 3/74 (4.1%), rifampicin mono-resistant 2/74 (2.7%), ethambutol 2/74 (2.7%) and streptomycin 1/74 (1.4%). None was isoniazid mono-resistant. Of the 74 only one (1.4%) patient had MDR-TB. The resistance to ethionamide, the second line drug, was detected in one patient (1.4%). None was resistant to pyrazinamide, fluoroquinolones, kanamycin, amikacin, or capreomycin. The mutations detected were mabA-inhA promoter region C(-15)T and katG Ser513Thr for isoniazid; rpoB His526Leu and rpoB Ser531Leu for rifampicin; embB Met306Val and embB Met306Ile for ethambutol; rpsL Lys43Arg for streptomycin; and mabA-inhA promoter region C(-15)T for ethionamide. The spoligotypes of the drug resistant Mycobacterium tuberculosis were distinct to all six isolates and belonged to T1, T2, T3-ETH, CAS1-DELHI, EAI5 and LAM11-ZWE lineages. ConclusionThe genetic drug resistance profile of Mycobacterium tuberculosis isolates from North-western Tanzania comprises of the common previously reported mutations. The prevalence of resistance to first and second line drugs including MDR-TB is low. Six drug resistant strains exhibited different spoligotypes, suggesting limited transmission of drug resistant strains in the region.

Comparative Prevalence of Plasmodium falciparum Resistance-Associated Genetic Polymorphisms in Parasites Infecting Humans and Mosquitoes in Uganda.

Controlling malaria in high transmission areas, such as much of sub-Saharan Africa, will require concerted efforts to slow the spread of drug resistance and to impede malaria transmission. Understanding the fitness costs associated with the development of drug resistance, particularly within the context of transmission, can help guide policy decisions to accomplish these goals, as fitness constraints might lead to decreased transmission of drug-resistant strains. To determine if Plasmodium falciparum resistance-mediating polymorphisms impact on development at different parasite stages, we compared the genotypes of parasites infecting humans and mosquitoes from households in Uganda. Genotypes at 14 polymorphic loci in genes encoding putative transporters (pfcrt and pfmdr1) and folate pathway enzymes (pfdhfr and pfdhps) were characterized using ligase detection reaction-fluorescent microsphere assays. In paired analysis using the Wilcoxon signed-rank test, prevalences of mutations at 12 loci did not differ significantly between parasites infecting humans and mosquitoes. However, compared with parasites infecting humans, those infecting mosquitoes were enriched for the pfmdr1 86Y mutant allele (P = 0.0001) and those infecting Anopheles gambiae s.s. were enriched for the pfmdr1 86Y (P = 0.0001) and pfcrt 76T (P = 0.0412) mutant alleles. Our results suggest modest directional selection resulting from varied fitness costs during the P. falciparum life cycle. Better appreciation of the fitness implications of drug resistance mediating mutations can inform optimal malaria treatment and prevention strategies.