Multidrug-resistant Tuberculosis Cases Research Articles

Localization of Mycobacterium tuberculosis topoisomerase I C-terminal sequence motif required for inhibition by endogenous toxin MazF4.

Only about half the multi-drug resistant tuberculosis (MDR-TB) cases are successfully cured. Thus, there is an urgent need of new TB treatment against a novel target. Mycobacterium tuberculosis (Mtb) topoisomerase I (TopA) is the only type IA topoisomerase in this organism and has been validated as an essential target for TB drug discovery. Toxin-antitoxin (TA) systems participate as gene regulators within bacteria. The TA systems contribute to the long-term dormancy of Mtb within the host-cell environment. Mtb's toxin MazF4 (Rv1495) that is part of the MazEF4 TA system has been shown to have dual activities as endoribonuclease and topoisomerase I inhibitor. We have developed a complementary assay using an Escherichia coli strain with temperature-sensitive topA mutation to provide new insights into the MazF4 action. The assay showed that E. coli is not sensitive to the endoribonuclease activity of Mtb MazF4 but became vulnerable to MazF4 growth inhibition when recombinant Mtb TopA relaxation activity is required for growth. Results from the complementation by Mtb TopA mutants with C-terminal deletions showed that the lysine-rich C-terminal tail is required for interaction with MazF4. Site-directed mutagenesis is utilized to identify two lysine residues within a conserved motif in this C-terminal tail that are critical for MazF4 inhibition. We performed molecular dynamics simulations to predict the Mtb TopA-MazF4 complex. Our simulation results show that the complex is stabilized by hydrogen bonds and electrostatic interactions established by residues in the TopA C-terminal tail including the two conserved lysines. The mechanism of Mtb TopA inhibition by MazF4 could be useful for the discovery of novel inhibitors against a new antibacterial target in pathogenic mycobacteria for treatment of both TB and diseases caused by the non-tuberculosis mycobacteria (NTM).

Recent Discoveries of Nitrogen-Containing Heterocyclic Compounds as InhA Inhibitors against Mycobacterium tuberculosis: An Overview.

It is a formidable challenge to treat tuberculosis as there are increasing cases of multidrugresistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) cases. Moreover, the emergence of totally drug-resistant tuberculosis (TDR-TB) makes it vital and imperative to develop a new generation of anti-tubercular drugs to have control over resistance. The nitrogencontaining heterocyclic class of compounds is being studied extensively to ascertain their anti-TB potentials. Nitrogen-containing compounds have a broad range of targets; wherein, InhA is the most important one. Hence, the primary focus of this review is to summarize the recent developments in the discovery of nitrogen-containing heterocyclic compounds as InhA inhibitors to combat tuberculosis.

Determinants of Multidrug-Resistant Pulmonary Tuberculosis in Indonesia: A Spatial Analysis Perspective

Tuberculosis is caused by Mycobacterium Tuberculosis (MT). MT usually attacks the lungs and causes pulmonary-tuberculosis. Tuberculosis cases in Indonesia keep increasing over the years. The presence of Multidrug-Resistant Tuberculosis (MDR-TB) has been one of the main obstacles in eradicating tuberculosis because it couldn’t be cured using standard drugs. In fact, the success rate of MDR-TB treatment in 2019 at the global level was only 57 percent. Research on MDR-TB can be related to the spatial aspect because this disease can be transmitted quickly. This study aims to obtain an overview and model the number of Indonesia’s pulmonary MDR-TB cases in 2019 using the Geographically Weighted Negative Binomial Regression (GWNBR) method. The independent variables used in the model are population density, percentage of poor population, health center ratio per 100 thousand population, the ratio of health workers per 10 thousand population, percentage of smokers, percentage of the region with PHBS policies, and percentage of BCG immunization coverage. The finding reveals that the model forms 12 regional groups based on significant variables where GWNBR gives better results compared to NBR. The significant spatial correlation implies that the collaboration among regional governments plays an important role in reducing the number of pulmonary MDR-TB.

Evaluation of Rpoβ Gene and Its Various Mutants in Multidrug-Resistant Tuberculosis Cases by GeneXpert Method.

India is one of the countries in the world which contribute to the global burden of multidrug-resistant tuberculosis (MDR-TB). GeneXpert is a method recommended by the World Health Organization (WHO) that uses five overlapping probes (Probe A to E) to detect mutation in the beta subunit of ribonucleic acid (RNA) polymerase gene (Rpoβ)responsible for rifampicin resistance in Mycobacterium tuberculosis (MTB). All the pulmonary and extrapulmonary samples received in tuberculosis (TB) laboratory for testing of MTBfrom January 2018 to December 2020 were analyzed for bacillary load and rifampicin resistance was identified by analyzing the number of missing probes. During the study period, a total of 10,021 samples were tested for MDR-TB. Out of those samples, 2674 samples were positive for MTB of which 2321 were pulmonary samples and 353 were extra-pulmonary samples. Rifampicin resistance was detected in 385 pulmonary samples and 63 extrapulmonary samples. These samples were further differentiated according to the bacillary load. The highest number of mutations was observed in Probe E followed by Probe B, Probe A, and Probe D, and the lowest was observed in Probe C. Also, mutations were associated when all probes were present or a few combinations of probes were missing. GeneXpert assay is a rapid molecular method that detected MTB and rifampicin resistance with a two-hour turnaround. It uses molecular beacons to detect mutation in the Rpoβ gene. This study can be useful in analyzing the prevalence and epidemiology of MTB in a particular demographic area and also the addition of a few more probes can enhance the identification of the mutation in other codons and therefore better therapeutic interventions can be developed accordingly.

IMPLEMENTATION NATIONAL GUIDELINES FOR TUBERCULOSIS CONTROL IN SURABAYA PUBLIC HEALTH CENTERS

Background: Tuberculosis is still endemic in Indonesia with 316 cases per 100,000 population in 2018 and Indonesia has the 3rd highest TB case in the world [1]. The leading causes of the burden of TB in Indonesia include the implementation of the TB program is not by the standards, cross-sector involvement is not optimal, the increase of Multi-Drug Resistant TB cases, and other factors. Suspected case findings and diagnosis are basic things in TB control programs that must be implemented optimally. Purpose: Knowing the implementation of TB control programs in public health centers that focus on screening and diagnosis based on the National Guidelines for TB Control 2014. Methods: This type of research is observational descriptive. Data was collected using a combined closed and open questionnaire and medical record data for public health centers patients from January to December 2019. Informants were selected by purposive sampling. Results: The results showed that 4 public health centers reached the target for finding suspected pulmonary TB cases, but only 2 reached the target proportion of finding new pulmonary TB cases. Inconsistencies in program implementation and obstacles were also found in the field. Conclusion: The success of finding suspected pulmonary TB that is not accompanied by a diagnosis occurs in public health centers that do not implement programs according to national guidelines and some obstacles arise in the field. Evaluation and innovation of TB control programs need to be carried out continuously to achieve the target.

Evaluation of the resistance of Mycobacterium tuberculosis to rifampicin at the regional hospital center of Maradi, Niger Republic.

According to the World Health Organization (WHO) data, 600,000 cases of rifampicin-resistant tuberculosis (TB) have been reported worldwide, including 490,000 cases of multidrug-resistant TB. Thus, through the present study, we proposed to evaluate the resistance of Mycobacterium tuberculosis to rifampicin in the regional hospital of Maradi. Our study involved 887 sputum samples that were GeneXpert tested from January 2016 to December 2020. These data were collected from the laboratory records of the Maradi Regional Hospital and analyzed with SPSS and Excel 2013 software. In total, more than half of the patients were male, i.e., a sex ratio of 3.03. The average age was 41 years. The rate of detection of M. tuberculosis by GeneXpert was 42% and the frequency of resistance to rifampicin was 20%. However, treatment failure and relapse were associated with this monoresistance in 53.95% and 30.26% of cases, respectively. The present study shows a fairly high prevalence of rifampicin resistance in the Maradi region, corresponding to twice the WHO threshold. The vast majority of these cases presented either a therapeutic failure or a relapse. Urgent and effective actions must be taken to significantly reduce the rates of treatment failure and relapse to decrease the rate of monoresistance and thus avoid the emergence of multidrug-resistant strains.

Fluoroquinolone Derivatives in the Treatment of Mycobacterium tuberculosis Infection.

Tuberculosis (TB) is currently one of the leading causes of death due to infective agents, and the growing rate of multidrug-resistant tuberculosis (MDR TB) cases poses an emergent public health threat. Fluoroquinolones are commonly used in the treatment of both MDR TB and drug-sensitive tuberculosis patients who are intolerant to first-line antitubercular agents. Unfortunately, these drugs have mild side effects, relevant to the prolonged treatment regimens and diminished bioavailability due to binding of metal ions. Moreover, the resistance to fluoroquinolones is also on the rise, a characteristic of extensively drug-resistant TB (XDR TB). Here, we developed esters as prodrugs of the fluoroquinolones levofloxacin and ciprofloxacin, with long-chain fatty alcohols. Both the alcohols and the quinolone have previously shown antimycobacterial activity and the aim was to develop esters with improved lipophilicity and capable of delivering the free acid inside mycobacterial cells. The carboxylic acid group of fluoroquinolones is essential to the mode of action but is also responsible for many of its side effects and metal-chelating properties. The synthesis, stability in biological media, and antibacterial activity were evaluated, the latter not only against Mycobacterium tuberculosis but also against other clinically relevant bacterial species, since the parent compounds display a broad spectrum of activity. The biological results show a reduction in the antitubercular activity of the synthesized derivatives, probably due to deficient activation of the ester prodrug. Despite this, it was found that the derivatives exhibit bioactivity against other fluoroquinolone-resistant bacteria, indicating a different mode of action and suggesting that it may be worthwhile to research further modifications to the carboxylic acid group. This might lead to new compounds that are efficient against resistant strains. This idea that the compounds may act by a different mechanism of action was further supported by a brief computer investigation that demonstrated the potential lack of selectivity of the esters to the fluoroquinolone target.

Development and Application of a Multidrug-Resistant Tuberculosis Case Management System - Yunnan Province, China, 2017-2020.

IntroductionTreatment and case management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge in tuberculosis (TB) control and prevention. This pilot study aims to apply and test a new electronic information system in order to help bolster case management of MDR-TB.MethodsThe MDR-TB Case Management System (CMS) was developed and piloted in the Yunnan Tuberculosis Clinical Center (TCC) in 2017. Next, 5 sites in Yunnan were randomly selected and sampled as pilots in 2018. The real-time regular follow-up rate (RFUR) was calculated for pilot sites. Loss to follow-up (LTFU) rates of MDR-TB treatment cohorts between pilot and non-pilot sites were compared by a chi-square test. LTFU for MDR-TB treatment cohorts was then assessed by univariate and multivariate binary logistic regression.ResultsThe average regular follow-up rate was 90.7% in TCC and 73.7% in five other pilot sites of Yunnan Province respectively. The average LTFU rate for pilot sites (9.0%) was lower than non-pilot sites (20.6%, P<0.01). The risk of LTFU during MDR-TB treatment reduced 61.7% in CMS pilot cases (adjusted odds ratio: 0.38, 95% confidence interval: 0.23–0.60) compared with non-pilot cases.ConclusionsAs a significant supplement to the Tuberculosis Information Management System, the CMS strengthened the collection, analysis, and utilization of strategic information for MDR-TB cases. The system improved case management by embedding it as a tool of the Comprehensive Supportive Care service model.

The second national anti-tuberculosis drug resistance survey in Tanzania, 2017-2018.

To determine the levels and patterns of resistance to first- and second-line anti-tuberculosis (TB) drugs among new and previously treated sputum smear positive pulmonary TB (PTB) patients. We conducted a nationally representative cross-sectional facility-based survey in June 2017-July 2018 involving 45 clusters selected based on probability proportional to size. The survey aimed to determine the prevalence of anti-TB drug resistance and associated risk factors among smear positive PTB patients in Tanzania. Sputum samples were examined using smear microscopy, Xpert MTB/RIF, culture and drug susceptibility testing (DST). Logistic regression was used to account for missing data and sampling design effects on the estimates and their standard errors. We enrolled 1557 TB patients, including 1408 (90.4%) newly diagnosed and 149 (9.6%) previously treated patients. The prevalence of multidrug-resistant TB (MDR-TB) was 0.85% [95% confidence interval (CI): 0.4-1.3] among new cases and 4.6% (95% CI: 1.1-8.2) among previously treated cases. The prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) was 1.7% among new TB patients and 6.5% among those previously treated. Drug resistance to all first-line drugs was similar (0.1%) in new and previously treated patients. None of the isolates displayed poly-resistance or extensively drug-resistant TB (XDR-TB). The only risk factor for MDR-TB was history of previous TB treatment (odds ratio=5.7, 95% CI: 1.9-17.2). The burden of MDR-TB in the country was relatively low with no evidence of XDR-TB. Given the overall small number of MDR-TB cases in this survey, it will be beneficial focusing efforts on intensified case detection including universal DST.

Role of HIV Infection in Multi-Drug Resistant Tuberculosis in Parts of Benue State, Nigeria

The pathogenesis of Tuberculosis shows that M. tuberculosis target and persist within phagocytes including T-lymphocytes in blood circulation. As a result, the possibility of cellular interaction between M. tuberculosis and HIV, especially for patients that are co-infected with HIV and TB, and subsequent exchange of genetic material via transduction needs to be investigated. Three hundred and eighty sputum samples mostly from suspected rifampicin-resistance patients were collected from Nigerian Airforce (NAF) Hospital Makurdi, and Federal Medical Centre (FMC) Makurdi. In vitro culture of sputum samples, Drugs Susceptibility Testing (DST) of M. tuberculosis isolates, and transduction protocol were carried out at the National Tuberculosis and Leprosy Training Centre (NTBLTC) Zaria, Nigeria. Statistical analysis was carried out using Student’s t-test. Minitab version 14.0 statistical software was used for data analysis. P-values &lt; 0.05 were considered significant. Twenty-six (9.7%) cases of Multi-drug resistant tuberculosis (MDR-TB) were detected (retreated cases 7.1%; treatment naive 2.6%). Twenty-one (80.8%) were males and 5(19.2%) were females. There was statistical difference in MDR-TB between male and female in Benue State (P&lt;0.05). The mean age group 35-45 years had the highest cases of MDR-TB accounting for 35% of MDR-TB. Human-immunodeficiency virus and Tuberculosis co-infected patients (category I) had the highest MDR-TB incidence of 10(38.5%). There was no significant difference between category-1 and category-III [patient with only TB disease (P&gt;0.05)]. However, there were elevated cases of MDR-TB in category-III patients from 7(26.9%) to 10(38.5%) following transduction protocol. Multi-drugs resistant tuberculosis is prevalent in Benue State, affecting the most economically active youths within the age group of 35-45 years, as a result the need to direct more attention on molecular basis for M. tuberculosis drugs resistance is therefore advocated, in order to win the war against multi-drug resistant tuberculosis.

Case-control study of vitamin D status and adult multidrug-resistant pulmonary TB.

BACKGROUND: India has the highest prevalence of multidrug-resistant TB (MDR-TB) globally. Vitamin D deficiency is potentially an important risk factor for MDR-TB.METHODS: We conducted a case-control study of 90 newly diagnosed adult MDR-TB cases, 180 household controls and 82 non-household controls in Mumbai, India. Serum 25-hydroxyvitamin D (25(OH)D), anthropometry, clinical status and history, dietary data and sociodemographic data were collected from each participant. Interferon-gamma release assay (IGRA) was also performed in controls to assess latent TB. Multivariable regression was performed to estimate associations between 25(OH)D vs. case status and IGRA positivity.RESULTS: Mean participant age was 33.8 ± 12.0 years; 72.8% had 25(OH)D <20 ng/ml. Mean 25(OH)D was significantly (P < 0.05) lower in cases (12.5 ± 7.9) than both household (17.5 ± 11.2) and non-household controls (16.4 ± 9.1). In multivariable models, 25(OH)D concentration was inversely associated with MDR-TB case status among cases and household controls (OR 0.95 per 1 ng/ml, 95% CI 0.92-0.99; P = 0.015), and among cases and non-household controls (OR 0.94 per 1 ng/ml, 95% CI 0.89-1.00; P = 0.033); 53.6% of controls were IGRA-positive. 25(OH)D status was not associated with IGRA positivity.CONCLUSION: Vitamin D status was independently associated with MDR-TB case status. Research should evaluate the effectiveness of vitamin D supplementation in prevention and adjunctive treatment of MDR-TB.

Impact of COVID-19 restrictive measures on income and health service utilization of tuberculosis patients in India

BackgroundThe nationwide lockdown (March 25 to June 8, 2020) to curb the spread of coronavirus infection had significant health and economic impacts on the Indian economy. There is limited empirical evidence on how COVID-19 restrictive measures may impact the economic welfare of specific groups of patients, e.g., tuberculosis patients. We provide the first such evidence for India.MethodsA total of 291 tuberculosis patients from the general population and from a high-risk group, patients from tea garden areas, were interviewed at different time points to understand household income loss during the complete lockdown, three and eight months after the complete lockdown was lifted. Income loss was estimated by comparing net monthly household income during and after lockdown with prelockdown income. Tuberculosis service utilization patterns before and during the lockdown period also were examined. Household income loss, travel and other expenses related to tuberculosis drug pickup were presented in 2020 US dollars (1 US$ = INR 74.132).Results26% of households with tuberculosis patients in tea garden areas and 51% of households in the general population had zero monthly income during the complete lockdown months (April–May 2020). Overall income loss slowly recovered during July–August compared to April–May 2020. Approximately 7% of patients in the general population and 4% in tea garden areas discontinued their tuberculosis medicines because of the complete lockdown.ConclusionDiscontinuation of medicine will have an additional burden on the tuberculosis elimination program in terms of additional cases, including multidrug resistant tuberculosis cases. Income loss for households and poor restoration of income after the lockdown will likely have an impact on the nutrition of tuberculosis patients and families. Tuberculosis patients working in the informal sector were the worst affected group during the nationwide lockdown. This emphasizes that a policy priority must continue to protect those working in informal sectors from the economic consequences of such restrictive measures, including paid sick leave, additional food support, and direct benefit transfers. Alongside ensuring widespread access to COVID-19 vaccines, these policy actions remain pivotal in ensuring the well-being of those who are unfortunate enough to be living with tuberculosis.

Development of Inhalable ATRA-Loaded PLGA Nanoparticles as Host-Directed Immunotherapy against Tuberculosis.

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than Mtb directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent Mycobacterium tuberculosis (Mtb) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 μm as measured by cascade impaction, and a volumetric median diameter of 4.09 μm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB.

Adherence to Recommendations for Βacillus Calmette-Guérin Vaccination of High-risk Neonates in Greece.

In 2016 a Βacillus Calmette-Guérin vaccination policy targeting high-risk neonates for tuberculosis before discharge from maternity hospital was adopted in Greece. Vaccination rates were 38.2% in 2019 and 24.7% in 2020. Vaccination coverage varied by risk group (higher for neonates in close contact with an active noncompliant or multidrug-resistant tuberculosis case and lower for Roma and immigrant neonates).

Factors responsible for default among patients under the revised national tuberculosis control programme

Tuberculosis (TB) is an infectious disease caused by bacillus Mycobacterium tuberculosis. It infects the lungs and causes pulmonary tuberculosis. But it can affect any organ in the human body. Defaulting from treatment has been one of the major obstacles to treatment management and an important challenge for tuberculosis control programmes. Defaulting from therapy is the main reason for its prevalence in our society, leading to relapse and multi-drug resistance TB cases. This study has been done to determine the causes of default among patients undergoing treatment under the Revised National Tuberculosis Control Programme (RNTCP) and their rectification.

Multi Drug Resistance: A Continuous Challenge by a Century Old Mycobacterium Tuberculosis

Background: Tuberculosis is a mycobacterial infection caused by mycobacterium tuberculous bacillus. Anti-tuberculous drugs are drugs used to treat tuberculosis which include first line anti-tuberculosis drugs used to treat tuberculosis initially when the infection is non-resistant these include Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol. Second line anti-tuberculosis drugs which are used to treat resistant tuberculosis or when first line drugs are contraindicated these include Ethionamide, Capreomycin, ciprofloxacin etc. Multidrug-resistant tuberculosis is tuberculosis not responding to 2 first line anti-tuberculosis drugs.&#x0D; Methods: This study was aimed at determining the frequency of MDR pattern in multidrug-resistant tuberculosis cases. The design was cross sectional and the study was conducted at Tuberculosis and chest diseases Center Mirpur Khas in 2017 over two years.&#x0D; Results: Total 458 MDR patients were evaluated 252(55%) females and 206(45%) were males. Isoniazid and Rifampicin were resistant in 97 (21.17%) cases while Isoniazid, Ethambutol and Rifampicin were found to be resistant in 40(8.73%) cases. The resistance for Isoniazid, Pyrazinamide and Rifampicin was observed in 50(10.92%) cases whereas 60(13.10%) patients were resistant to Isoniazid, Rifampicin and Streptomycin. Isoniazid, Ethambutol, Rifampicin and Streptomycin were resistant in 75(16.38%) cases. Isoniazid, Pyrazinamide, Rifampicin and Streptomycin resistance was seen in 40(8.73%) patients and 96(20.96%) of the cases shoed resistance to Isoniazid, Ethambutol, Pyrazinamide and Rifampicin.&#x0D; Conclusion: Multidrug-resistant tuberculosis is highly prevalent in the region.

Novel 2-Nitroimidazole and Imidazooxazole Derivatives and their Activity against Trypanosoma cruzi and Mycobacterium tuberculosis.

Tuberculosis (TB) is one of the top ten causes of death worldwide, while Chagas disease (CD) is the parasitic disease that kills the largest number of people in the Americas. TB is the leading cause of death for patients with AIDS; it kills 1.5 million people and causes 10 million new cases every year. The lack of newly developed chemotherapeutic agents and insufficient access to health care services for a diagnosis increase the incidence of multidrug-resistant TB (MDRTB) cases. Although CD was identified in 1909, the chronic stages of the disease still lack adequate treatment. The purpose of this work was to design and synthesize two new series of 2-nitroimidazole 5a-e and imidazooxazoles 6a-e with 1H-1,2,3-triazolil nucleus and evaluate their activities against Tc and Mycobacterium tuberculosis (Mtb). Two series of five compounds were synthesized in a 3 or 4-step route in moderated yields, and their structures were confirmed by NMR spectral data analyses. The in vitro antitrypanosomal evaluation of products was carried out in an intracellular model using L929 cell line infected with trypomastigotes and amastigote forms of Tc of β-galactosidase-transfected Tulahuen strain. Their antimycobacterial activity was evaluated against Mtb strain H37Rv. In general, 2-nitroimidazolic derivatives proved to be more potent in regard to antitrypanocidal and antimycobacterial activity. The non-cytotoxic 2-nitroimidazole derivative 5b was the most promising with a half maximum inhibitory concentration of 3.2 μM against Tc and a minimum inhibitory concentration of 65.3 μM against Mtb. Our study reinforced the importance of 2-nitroimidazole and 1H-1,2,3-triazole nuclei in antimicrobial activity. In addition, derivative 5b proved to be the most promising, presenting important activity against Tc and Mtb and could be used as a starting point for the development of new agents against these diseases.

Multidrug Resistant Tuberculosis: Trends and Control

Multidrug resistant tuberculosis (MDR-TB) has been an area of growing concern and is posing a threat to the control of tuberculosis (TB). The exact magnitude of problem of resistance to anti-tuberculosis drugs worldwide was not known till the 1994-97 global project on anti-tuberculosis drug resistance surveillance initiated by the World Health Organization (WHO) and International Union Against Tuberculosis and Lung Diseases (IUATLD). The Global Tuberculosis Report 2014 estimated that an 3.5% of newly diagnosed and 20.5% of previously treated.TB cases had MDR-TB. It has been estimated that 480,000 cases emerged and 210,000 deaths occurred due to MDR-TB globally in 2013. In India, estimates showed that the prevalence of MDR-TB among new and previously treated patients was 2.2% and 15%, respectively. It is estimated that 99,000 cases of MDR-TB emerge every year of which 62,000 were among notified cases of TB in 2013. The MDR-TB is a human-made problem and results largely from poorly managed cases of TB. Adequate, timely diagnosis and optimal treatment of MDR-TB will help curb the epidemic. Efforts must be focused on the effective use of anti-tuberculosis drugs in every new patient, so as to prevent the emergence of MDR-TB.

Optimal control strategy for the effectiveness of TB treatment taking into account the influence of HIV/AIDS and diabetes

The aim of this paper is to present an optimal control problem to reduce the MDR-TB (multidrug-resistant tuberculosis) and XDR-TB (extensively drug-resistant TB) cases, using controls in these compartments and controlling reinfection/reactivation of the bacteria. The model used studies the efficacy of the tuberculosis treatment taking into account the influence of HIV/AIDS and diabetes, and we prove the global stability of the disease-free equilibrium point based on the behavior of the basic reproduction number. Various control strategies are proposed with the combinations of controls. We show the existence of optimal control using Pontryagin’s maximum principle. We solve the optimality system numerically with an algorithm based on forward/backward Runge-Kutta method of the fourth-order. The numerical results indicate that the implementation of the strategy that activates all controls and of type I (starting with the highest controls) is the most cost-effective of the strategies studied. This strategy reduces significantly the number of MDR-TB and XDR-TB cases in all sub-populations, which is an important factor in combating tuberculosis and its resistant strains.

Time trend prediction and spatial–temporal analysis of multidrug-resistant tuberculosis in Guizhou Province, China, during 2014–2020

BackgroundGuizhou is located in the southwest of China with high multidrug-resistant tuberculosis (MDR-TB) epidemic. To fight this disease, Guizhou provincial authorities have made efforts to establish MDR-TB service system and perform the strategies for active case finding since 2014. The expanded case finding starting from 2019 and COVID-19 pandemic may affect the cases distribution. Thus, this study aims to analyze MDR-TB epidemic status from 2014 to 2020 for the first time in Guizhou in order to guide control strategies.MethodsData of notified MDR-TB cases were extracted from the National TB Surveillance System correspond to population information for each county of Guizhou from 2014 to 2020. The percentage change was calculated to quantify the change of cases from 2014 to 2020. Time trend and seasonality of case series were analyzed by a seasonal autoregressive integrated moving average (SARIMA) model. Spatial–temporal distribution at county-level was explored by spatial autocorrelation analysis and spatial–temporal scan statistic.ResultsGuizhou has 9 prefectures and 88 counties. In this study, 1,666 notified MDR-TB cases were included from 2014–2020. The number of cases increased yearly. Between 2014 and 2019, the percentage increase ranged from 6.7 to 21.0%. From 2019 to 2020, the percentage increase was 62.1%. The seasonal trend illustrated that most cases were observed during the autumn with the trough in February. Only in 2020, a peak admission was observed in June. This may be caused by COVID-19 pandemic restrictions being lifted until May 2020. The spatial–temporal heterogeneity revealed that over the years, most MDR-TB cases stably aggregated over four prefectures in the northwest, covering Bijie, Guiyang, Liupanshui and Zunyi. Three prefectures (Anshun, Tongren and Qiandongnan) only exhibited case clusters in 2020.ConclusionThis study identified the upward trend with seasonality and spatial−temporal clusters of MDR-TB cases in Guizhou from 2014 to 2020. The fast rising of cases and different distribution from the past in 2020 were affected by the expanded case finding from 2019 and COVID-19. The results suggest that control efforts should target at high-risk periods and areas by prioritizing resources allocation to increase cases detection capacity and better access to treatment.