Multidrug-resistant Tuberculosis Infection Research Articles

IMMUNOLOGICAL CRITERIA OF THE EFFECTIVENESS OF IMMUNOPREVENTIVE OF THE NON-SPECIFIC IMMUNOMODULATOR BIVEL AMONG CONTACTED CHILDREN

The aim of the study - to study the feasibility of using the natural immunomodulator BIVEL (conditionally called BI-V) as a nonspecific immunoprevention of tuberculosis (TB) among contacted children from the focies of chemodrug-resistant tuberculosis infection on the basis of clinical and immunological researches. Research metods. The object of study was 120 contacted from multidrug-resistant tuberculosis infection (FsMDR-TBI) including 75 children and 45 adolescents. The first contact group included 95 children/adolescents who did not receive BI-V and the second one ‒ 25 infected children/adolescents who received BI-V. Immunological studies determining the state of the phagocytic reactivity of immunity (phagocytic number and index, testes redox activity of neutrophils and non-enzymatic cationic lysosomal proteins of granulocytic leukocytes; cellular (CD3+, CD56+, CD3+HLA-DR+, CD4+, CD8+, CD4+/CD8+, CD4+45RA, CD16/56+) and humoral (CD19+, IgA, IgM, IgG, CIC) immunity; interleukins (TNF-α, IL-6, IL-10) and specific immunity (tuberculin diagnostics, Quantiferon test). Statistical analysis of the results obtained based on the software package Excel Results and discussion. On the background of non-specific preventive with the BI-V immunomodulator among contact infected children, normalization of blood phagocytic activity indicators was noted in the form of an increase in phagocytic number, phagocytic index, non-enzymatic cationic lysosomal proteins of granulocytic leukocytes and a decrease in HST test compared to children who had not yet received preventive BI-V. In infected children/adolescents from FsMDR-TBI, while maintaining normal values of CD3+, CD3+CD4+, CD3+CD8+, insignificant functional disorders of the cell response were revealed at the level of immunoregulatory processes due to the dominance of suppressor-cytotoxic reactions were revealed (decrease by 1.3 times IRI CD3+CD4+/CD3+CD8+, p<0.05, relative to donors), balance shift in the regulatory system of pro- and anti-inflammatory cytokines towards pro-inflammatory cytokines (increase by 2.0 times TNF-α/IL-10, p<0.01, relative to normal). The existing deviations in the regulatory system and the cellular response system disappeared after the completion of the autumn-spring BI-V course. Among the children from FsMDR-TBI who took a BI-V preventive course 8% people fell ill with various forms of primary pulmonary TB, among the children who BI-V was not prescribed ‒ 22.1%, p<0.05 during the 4-year observation. The maximum TB level occurred in the first two years of observation in both groups. Conclusions. The results of the appointment of a non-specific immunomodulator BI-V confirmed the feasibility of using this immunomodulator for contacted children and adolescents from FsMDR-TBI.

Particulate matter deposition and its impact on tuberculosis severity: A cross-sectional study in Taipei

The objective of this study was to examine the association between the lung lobe-deposited dose of inhaled fine particulate matter (PM2.5) and chest X-ray abnormalities in different lung lobes of pulmonary tuberculosis (TB), multidrug-resistant tuberculosis (MDR-TB), and non-tuberculosis mycobacteria infections (NTM). A cross-sectional study was conducted between 2014 and 2022, comprising 1073 patients who were recruited from chest department clinic in a tertial refer hospital in Taipei City, Taiwan. Ambient 1-, 7-, and 30-day PM2.5 exposure and the deposition of PM2.5 in different lung lobes were estimated in each subject. The β coefficient for PM2.5 and deposited PM2.5 in lungs with the outcome variables (pulmonary TB, MDR-TB, and NTM infection) was derived through regression analysis and adjusted for age, gender, BMI, smoking status, and family income. We observed that a 1 μg/m3 increase in ambient PM2.5 was associated with an increase of MDR-TB infections of 0.004 times (95%CI: 0.001–0.007). A 1 μg/m3 increase in 1-day and 7-day PM2.5 deposition in left upper lobe and left lower lobe was associated with an increase in chest X-ray abnormalities of 9.19 % and 1.18 % (95%CI: 0.87–17.51 and 95%CI: 0.08–2.28), and 4.52 % and 5.20 % (95%CI: 0.66–8.38 and 95%CI: 0.51–9.89) in left lung of TB patients, respectively. A 1 μg/m3 increase in 30-day PM2.5 deposition in alveolar region was associated with an increase in percent abnormality of 2.50 % (95%CI: 0.65–4.35) in left upper lobe and 3.33 % (95%CI: 0.65–6.01) in right middle lobe, while in total lung was 0.63 % (95%CI: 0.01–1.27) in right upper lobe and 0.37 % (95%CI, 0.06–0.81) in right lung of MDR-TB patients. Inhaled PM2.5 deposition in lungs was associated with an exacerbation of the radiographic severity of pulmonary TB, particularly in pulmonary MDR-TB patients in upper and middle lobes. Particulate air pollution may potentially exacerbate the radiographic severity and treatment resistance in individuals with pulmonary TB.

Characteristics of TB/HIV Co-Infection and Patterns of Multidrug-Resistance Tuberculosis in the Northwest Amhara, Ethiopia.

Multidrug-resistant tuberculosis (MDR-TB) has continued to be a serious public health threat and significantly challenges global TB control and prevention efforts, where the TB/HIV co-infection epidemic makes the situation much worse. The aim of the study was to determine the determinant factors associated with patterns of MDR-TB among pulmonary TB patients in the Northwest Amhara, Ethiopia. A hospital-based cross-sectional study was conducted from May 2022 to February 2023 in the Northwest Amhara, Ethiopia. Data on the participants' socio-demographics and clinical characteristics were obtained using a pre-tested checklist. Phenotypic susceptibility testing to first-line anti-TB drugs was performed on 180 isolates by automated BD BACTEC MGIT 960 system. Logistic regression analysis was performed to determine the association of risk factors with patterns of MDR-TB. A p-value ≤0.05 was considered statistically significant. The overall proportion of TB with HIV co-infected cases was 19.8% (50/252). Culture positivity was confirmed in 203/252 (80.6%) of sputum samples. Among 168 isolates, the DST showed that 119 (70.8%) isolates were pan-susceptible to all first-line drugs and prevalence of any resistance to first-line drugs was 49,168 (29.2%). Among the resistant isolates, 28 (16.7%) were any mono-resistance and 12 (7.1%) were determined to be resistant to MDR-TB. TB with a previous TB treatment (aOR = 6.73, 95% CI: 1.78-25.47, p = 0.005) and HIV co-infected (aOR = 0.252, 95% CI: 0.73-0.875, p = 0.03) were significantly associated with MDR-TB. Higher prevalence of TB and MDR-TB was examined among TB patients in the study area. In the study, history of previous TB treatment was the strongest risk factor MDR-TB infection followed by TB with HIV co-infected cases. Therefore, there is a need of strengthening TB control and prevention programs to reduce the increase of TB incidence, further emergence and transmission of a public health threat of MDR-TB cases.

Contact screening and management in a high-transmission MDR-TB setting in Papua New Guinea: Progress, challenges and future directions

Daru, South Fly District, Papua New Guinea is a high transmission setting for multidrug-resistant tuberculosis (MDR-TB). An emergency response by the Government in 2014 established a high-quality model for treatment and care. Household contact screening and management commenced in 2016 with TB preventive treatment (TPT) for well young child (<5 years) contacts of people with drug-susceptible TB and later expanded to young child contacts of MDR-TB. The model of care is community-based and led by non-specialist health workers, under supervision. An electronic medical record system supports care, reporting and operational research. Community engagement and education has been central, with a concerted focus on peer-led counselling and patient-centred services to improve TPT uptake and completion. Challenges include the application of households as the unit of intervention for detection of active TB and TPT provision. Our implementation experience in Daru has highlighted significant population mixing dynamics with most transmission likely occurring outside the household. We propose a community-wide screening approach with the provision of TPT based on testing to include older children, adolescents, and young adults. As there is the possibility of MDR-TB infection irrespective of the drug susceptibility of the household index case, a novel option is a combination TPT regimen of 6 months of daily isoniazid and levofloxacin (6HLfx). A sensitive aged-related algorithm to detect and exclude active TB is being developed. Ongoing community engagement, quality data systems with operational research to evaluate approaches are critical in high transmission MDR-TB settings.

Attitudes of Healthcare Workers about Prevention and Control of Nosocomial Multidrug-Resistant Tuberculosis Infection in Two Top-Ranked Tuberculosis Specialized Public Hospitals of Ethiopia.

Tuberculosis (TB) exists as a human curse since antiquity. Around 9.5 million cases and 1.5 million deaths were reported due to TB in 2021. Ethiopia is one of the high-burdenmultidrug-resistant (MDR) TB countries. MDR-TB is acquired either by poor adherence to treatment or by primary infection with a drug-resistant strain, which has a high transmission rate from patients to healthcare workers (HCWs). Hospital outbreaks of MDR-TB are common in Africa. Hence, this study aimed to score the attitude of HCWs working in the two nationally top-rankedTB-specialized hospitals in Ethiopia, Saint Peter's and ALERT TB-specialized public hospitals about the infection prevention and control (IPC) of nosocomial MDR-TB. A cross-sectional study was conducted from December 1, 2020, to March 31, 2021. A simple random sampling method was applied to select 384 HCWs. The data collection tool was a self-administered interview structured questionnaire. The data were analyzed using SPSS software. Descriptive statistics were applied to score attitude. Bivariate and multivariable logistic regression models were performed to identify the independent determinants of attitude. The odds ratio was used to test the degree of association between variables at a 95% confidence interval (CI). The level of statistical significance was fixed at p value < 0.05. Among the respondents, 87% of the HCWs held favourable attitudes about the nosocomial MDR-TB-IPC. The favourable attitude score had a significant association with the monthly salary earned between 7001 and 9000 ETB (Ethiopian Birr) (AOR = 3.34, 95% CI: 1.11, 10.05) and the previous training obtained on TB/MDR-TB (AOR = 2.96, 95% CI: 1.32, 6.62). Almost one in seven HCWs has an unfavourable attitude. Prior training received and earning monthly income above 7000 ETB are independent determinants of a favourable attitude score. Refreshment training and a reasonable increment in monthly income should be strengthened in TB-specialized hospitals in Ethiopia.

Characteristics of the course of multidrug-resistant pulmonary tuberculosis in children and adolescents from focuses of chemoresistant tuberculosis infection

Objective — to study the features of multidrug-resistant tuberculosis of the lungs of respiratory organs in children and adolescents from focuses of chemoresistant tuberculosis infection. &#x0D; Materials and methods. To study the features of the course of multidrug-resistant pulmonary tuberculosis (MDR-TB), an analysis of clinical, X-ray, microbiological, and generally accepted laboratory examinations was conducted in 256 patients (102 children and 154 adolescents), who were divided into two groups The main group included 145 patients with MDR-TB: of them, 67 (42.2 %) children and 78 (53.8 %) teenagers from focuses of multidrug-resistant tuberculosis infection (MDR-TBI). The control group consisted of 146 patients with «chemosusceptible» pulmonary tuberculosis (CS-TB), of which 70 (47.9 %) were children and 76 (52.1 %) were adolescents from focuses of chemosusceptible tuberculosis infection (CS-TBI).&#x0D; Results and discussion. In children with multidrug-resistant pulmonary tuberculosis (MDR-TB), along with classic forms of tuberculosis (primary tuberculosis complex — 14.9 % and tuberculosis of the intrathoracic lymph nodes — 14.9 %), miliary tuberculosis (11.9 %), tuberculosis of the lungs and central nervous system (5.9 %), caseous pneumonia (8.9 %) and fibro-cavernous tuberculosis (4.5 %) were diagnosed. In the case of MDR-TB of the lungs, adolescents were statistically significantly more likely to be diagnosed with infiltrative tuberculosis (29.4 %) and disseminated pulmonary tuberculosis (35.9 %). At the same time, destructive changes were observed 1.6 times more often in adolescents with MDR-TB than in children, especially with multiresistant specific process (70.5 % vs. 43.3 %, p &lt; 0.05).In children with MDR-TB, 3.5 times more often than in chemosusceptible tuberculosis, signs of the progression of a specific process due to lymphogenous and hematogenous dissemination in the form of tuberculosis of peripheral, intrathoracic and mesenteric lymph nodes, miliary tuberculosis were observed in adolescents, along with complications of a specific complications of a non-specific nature were observed: respiratory failure and non-specific catarrhal endobronchitis). In both children and adolescents, the intensity of bacterial excretion is greater in the presence of MDR-TB than in CS-TB. In the foci of multiresistant infection, an almost complete coincidence of the nature of MTB resistance in children with the source of infection was established. However, teenagers are most often found to be resistant to the combination of HRSE (66.1 %), HRESZ (13.6 %), unlike adults and children.&#x0D; Conclusions. The majority of contact children and adolescents with MDR-TB was detected when referring to a general practitioner or a pediatrician (62.3 % of children and 70.5 % of adolescents), which became the main reason for underdiagnosis of tuberculosis in children and adolescents in general. Our studies show the importance of a thorough examination of all contact children and adolescents in focuses of tuberculosis infection: anamnesis studies, tuberculin diagnostics (quantiferon test), clinical, radiological and microbiological examination for the timely detection of tuberculosis or infection and the appointment of appropriate chemotherapy or chemoprophylaxis.

Adjunctive Zoledronate + IL-2 administrations enhance anti-tuberculosis Vγ2Vδ2 T-effector populations, and improve treatment outcome of multidrug-resistant tuberculosis1

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) is a refractory disease with high mortality rate due to no or few choices of antibiotics. Adjunctive immunotherapy may help improve treatment outcome of MDR-TB. Our decade-long studies demonstrated that phosphoantigen-specific Vγ2Vδ2 T cells play protective roles in immunity against TB. Here, we hypothesized that enhancing protective Vγ2Vδ2 T-effector cells could improve treatment outcome of MDR-TB. To address this, we employed clinically approved drugs Zoledronate (ZOL) and IL-2 to induce anti-TB Vγ2Vδ2 T-effector cells as adjunctive immunotherapy against MDR-TB infection of macaques. We found that adjunctive ZOL/IL-2 administrations during TB drugs treatment of MDR-TB-infected macaques significantly expanded Vγ2Vδ2 T cells and enhanced/sustained Vγ2Vδ2 T-effector subpopulation producing anti-TB cytokines until week 21. ZOL/IL-2 administrations, while expanding Vγ2Vδ2 T cells, significantly increased/sustained numbers of circulating CD4+ Th1 and CD8+ Th1-like effector populations, with some γδ T- or αβ T-effector populations trafficking to airway at week 3 until week 19 or 21 after MDR-TB infection. Adjunctive ZOL/IL-2 administrations after MDR-TB infection led to lower bacterial burdens in lungs than TB drugs alone, IL-2 alone or saline controls, and resulted in milder MDR-TB pathology/lesions. Thus, adjunctive Zoledronate + IL-2 administrations can enhance anti-TB Vγ2Vδ2 T- and αβ T-effector populations, and improve treatment outcome of MDR-TB.

Peculiarities of the chemo­drug resistance of M. tuberculosis to anti­tuberculous medications among children and adolescents from multidrug­resistant tuberculous focies

Objective — to study the peculiarities of the resistance of M. tuberculosis (MTB) to antimycobacterial drugs (AMBD) among children and adolescents living in multidrug-resistant tuber­culous focies.&#x0D; Materials and methods. 246 children were examined, 145 of them had drug-resistant tuberculosis (TB), 101 children — susceptible form of the specific process, and 102 adult patients who became the source of the disease. Microbiological study in children, adolescents and adults included: detection of MTB in sputum by smear microscopy, seeding on Levenstein—Jensen medium, typing of isolated MTB on BACTEC MGIT 960, determination of drug susceptibility test of MTB strains to AMBD I and II lines, and molecular genetic testing of sputum, including the Gene Xpert MTB/RIF method and the Hain Lifescience linear probe analysis.&#x0D; Results and discussion. Researches show that children under one year of age (29.8 %) and up to 4 years of age (73.1 %) are the most vulnerable to TB in the multidrug-resistant tuberculous focies. Study of the resistance profile of MTB in multidrug-resistant foci was found almost complete coincidence of the profile of the resistance of MTB in children with a source of infection. In particular, children from contact compared with sick adolescents are in 3.5 times more likely to be resistant to the combination of HRS, in 2.7 times — to HR, in 1.8 times — to HRE, in 2.7 times less often — to HRESZ, in 1.6 times — to HRES. In adolescents resistance is most often found to the combination of HRSE (66.1 %), HRESZ (13.6 %), in contrast to the source of TB infection and children. Extensive drug resistance is 2.8 times more common in adolescents than in children (14.1 % vs. 5.0 %, p &gt; 0.01).&#x0D; Conclusions. Researches have shown a high risk of MDR-TB of lungs among children (42.7 %) from multidrug-resistant tuberculous focies. This indicates the need to improve the methods of obtaining respiratory samples to determine the susceptibility/resistance of MTB to AMBD. In the centers of multidrug-resistant tuberculosis infection, more than a third of children (35.8 %) were not vaccinated in the maternity hospital and no chemoprophylaxis was prescribed for contact persons.

Challenges in the screening and treatment of latent multidrug-resistant tuberculosis infection.

Individuals in close contact with multidrug-resistant tuberculosis (MDR-TB) patients are subject to an elevated risk of infection, and may develop latent MDR-TB infection. Numerous studies have described latent tuberculosis infection (LTBI) as a reservoir of new TB disease. The screening and treatment of latent MDR-TB infection are challenging. Hereby, we reviewed the epidemiology, current management and prevention approach of LTBI in MDR-TB close contacts, to provide additional information for future research direction and policy design formulation to reduce the LTBI reservoir.

Optimising tuberculosis care for refugees affected by armed conflicts

Globally, tuberculosis remains a leading cause of death from an infectious disease. 1 WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021https://www.who.int/publications/i/item/9789240037021Date accessed: March 9, 2022 Google Scholar 2022's theme for World TB Day, on March 24, is “Invest to End TB. Save Lives”. Tuberculosis control requires a pragmatic, tailored, multipronged approach to diagnose and treat all people with tuberculosis disease (drug-susceptible, drug-resistant, multidrug-resistant, and extensively drug-resistant tuberculosis) and latent tuberculosis infection, to prevent transmission, and to mitigate the risk of drug resistance. The COVID-19 pandemic has disrupted health services and derailed already overburdened tuberculosis control programmes worldwide, including in eastern Europe, substantially setting back progress 1 WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021https://www.who.int/publications/i/item/9789240037021Date accessed: March 9, 2022 Google Scholar towards achieving the UN Sustainable Development Goal (SDG) and End TB targets. 2 Migliori GB Thong PM Alffenaar JW et al. Gauging the impact of the COVID-19 pandemic on tuberculosis services: a global study. Eur Respir J. 2021; 582101786 Crossref PubMed Scopus (41) Google Scholar The invasion of Ukraine by Russia, and the ongoing armed conflict, is having hugely damaging effects on health services, health infrastructure, and personnel, and further diminishes hope of achieving End TB targets for eastern Europe—now a seemingly insurmountable task. Although incidence rates of tuberculosis in Ukraine have gradually decreased over the past decade, Ukraine features in the WHO list of 20 countries with the highest estimated number of people with incident drug-resistant tuberculosis and it has one of the highest rates of HIV–tuberculosis co-infection and latent multidrug-resistant tuberculosis infection in Europe. 1 WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021https://www.who.int/publications/i/item/9789240037021Date accessed: March 9, 2022 Google Scholar Drug-resistant tuberculosis is difficult to diagnose, expensive to treat, requires long-term treatment, has high mortality, and requires careful follow-up to monitor adverse drug side-effects and ensure a cure.

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis.

Objective Multidrug-resistant tuberculosis (MDR-TB) causes persistent infection and challenges tuberculosis control worldwide. T cell-mediated immunity plays a critical role in controlling Mycobacterium tuberculosis (Mtb) infection, and therefore, enhancing Mtb-specific T cell immune responses represents a promising therapeutic strategy against TB. Cytokine-induced killer (CIK) immunotherapy is based on autologous infusion of in vitro expanded bulk T cells, which include both pathogen-specific and nonspecific T cells from patient peripheral blood mononuclear cells (PBMC) into TB patients. Preclinical mouse studies have shown that the adoptive T cell therapy inhibited Mtb infection. However, the efficacy of CIK immunotherapy in the treatment of MDR-TB infection has not been evaluated in clinical trials. Methods We performed a retrospective study of MDR-TB patients who received CIK immunotherapy in combination with anti-TB chemotherapy and those who had standard chemotherapy. Results Our results showed that CIK immunotherapy in combination with anti-TB chemotherapy treatment increased the conversion rate of sputum smear and Mtb culture, alleviated symptoms, improved lesion absorption, and increased recovery. The kinetics of serology and immunology index monitoring data showed good safety profiles for the CIK treatment. Conclusion Our study has provided strong evidence that CIK immunotherapy in combination with anti-TB chemotherapy is beneficial for MDR-TB patients. A multicenter clinical trial is warranted to evaluate CIK as a new immune therapy for MDR-TB.

The comparative analysis of the drug resistance of mbtin children, adolescents and the sources of infection in the multidrug resistant tuberculosis focies

145 patients (67 children and 78 adolescents) from the multidrug-resistant tuberculosis infection focies took part in the complex microbiological study. The children and adolescents had undergone treatment for the pulmonary multidrugresistant tuberculosis. The study showed that MDR TB was by 1.7 times more often revealed in the adolescents as compared to the children, while the risk of MDR TB was by 3.7 times higher for the children than for the adolescents. The drug resistance profile of the children and the sources of infection almost completely coincided. The resistance to HRSE (66.1%) and HRESZ (13.6%) developed in the adolescents more often than in the children and adults. The study proves the importance of defining the drug resistance profile in the exposed children and adolescents from the multidrugresistant tuberculosis focies.

Telomere length and mitochondrial DNA copy number in multidrug-resistant tuberculosis

Multidrug resistant tuberculosis (MDR-TB) is a severe disease that requires prolonged chemotherapy and is associated with an increased probability of treatment failure and death. MDR-TB is a state of heightened oxidative stress and inflammation, which could be related to the aging-related processes and immunosenescence. We, therefore, tested the hypothesis that MDR-TB is associated with alterations in aging biomarkers in peripheral blood cells. We investigated 51 MDR-TB patients and 57 healthy individuals and carried out an analysis of covariance to assess the possible impact of different variables on biomarker perturbations. The results showed that MDR-TB patients had significantly reduced telomere length (TL) and increased mitochondrial DNA copy number (mtDNA CN) (P < 0.05) in comparison to the controls, and MDR-TB infection was the main influencing factor. Male sex and extrapulmonary TB strongly influenced mtDNA CN increment, and MDR-TB patients with normal weight had longer telomeres than those who were underweight (P < 0.05). In conclusion, the evidence for shorter telomeres and higher mtDNA CN in the peripheral blood cells of MDR-TB patients was obtained indicating the connection between MDR-TB and aging biomarkers. The observed associations highlight a complicated interplay between MDR-TB and immunosenescence, thus further studies are required to achieve full understanding.

Analysis of CD4 and CD8 expression in multidrug-resistant tuberculosis infection with diabetes mellitus: An experimental study in mice

BackgroundTuberculosis (TB) remains a major global health problem, in the top 10 causes of death. As a regulator of the immune response, T-helper (Th) cells activate other lymphocytes from the immune system, such as B cells, to destroy the TB pathogen by releasing CD4 and CD8 Th cells. Diabetes mellitus (DM) is a known cause of developing active pulmonary TB. Few studies have examined the biomolecular expression affecting Mycobacterium tuberculosis (MTB) and multidrug-resistant (MDR) MTB, which are associated with low immunity represented by TB in diabetes and CD4 and CD8 levels. Materials and methodsThis animal study used a post-test control group design. We performed an experimental study using 30 BALB/c mice, each weighing 25 g. It included six experimental animal groups, of which three had a diabetes condition induced using intraperitoneal streptozotocin, and all were infected with MTB or MDR TB. We evaluated the CD4 and CD8 levels in each group and analyzed the differences. ResultsWe found a significant difference in CD4 and CD8 levels in MTB and MDR TB conditions. ConclusionThis study shows that acute infection in experimental mice with MTB and MDR TB with or without diabetes had the highest levels of both CD4 and CD8 cells, which can be a sign of increased cellular immunity in a mice model.

Protocol for a case–control study of vitamin D status, adult multidrug-resistant tuberculosis disease and tuberculosis infection in Mumbai, India

IntroductionVitamin D status may be an important determinant of multidrug-resistant tuberculosis (MDR-TB) infection, progression to disease and treatment outcomes. Novel and potentially cost-effective therapies such as vitamin D supplementation are...

Isoniazid Preventive Therapy in Contacts of Multidrug-Resistant Tuberculosis.

Rationale: The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection.Objectives: To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis.Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index patients with tuberculosis and 14,044 tuberculosis-exposed household contacts who we followed for 1 year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that INH preventive therapy should be provided to contacts aged 19 years old or younger, only half this group received INH preventive therapy.Measurements and Main Results: Among 4,216 contacts under 19 years of age, 2,106 contacts (50%) initiated INH preventive therapy at enrollment. The protective effect of INH was more extreme in contacts exposed to drug-sensitive tuberculosis (adjusted hazard ratio, 0.30; 95% confidence interval, 0.18-0.48) and to multidrug-resistant tuberculosis (adjusted hazard ratio, 0.19; 95% confidence interval, 0.05-0.66) compared with those exposed to mono-INH-resistant tuberculosis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.23-2.80). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received INH preventive therapy compared with 3% (8 of 273) of those who did not.Conclusions: Household contacts who received INH preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. INH may have a role in the management of latent multidrug-resistant tuberculosis infection.

Multidrug-resistant tuberculosis in the United States, 2011-2016: patient characteristics and risk factors.

OBJECTIVE: To determine risk factors for multidrug-resistant tuberculosis (MDR-TB) and describe MDR-TB according to three characteristics: previous TB disease, recent transmission of MDR-TB, and reactivation of latent MDR-TB infection.SETTING and DESIGN: We used 2011-2016 surveillance data from the US National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service and used logistic regression models to estimate risk factors associated with MDR-TB.RESULTS: A total of 615/45 209 (1.4%) cases were confirmed as MDR-TB; 111/615 (18%) reported previous TB disease; 41/615 (6.7%) were attributed to recent MDR-TB transmission; and 449/615 (73%) to reactivation. Only 12/41 (29%) patients with TB attributed to recent transmission were known to be contacts of someone with MDR-TB. For non-US-born patients, the adjusted odds ratios of having MDR-TB were 32.6 (95%CI 14.6-72.6) among those who were known to be contacts of someone with MDR-TB and 6.5 (95%CI 5.1-8.3) among those who had had previous TB disease.CONCLUSION: The majority of MDR-TB cases in the United States were associated with previous TB disease or reactivation of latent MDR-TB infection; only a small proportion of MDR-TB cases were associated with recent transmission.

Clinical course of pregnancy and postpartum in a multidrug-resistant tuberculosis/HIV co-infected patient receiving bedaquiline-containing regimen as antimycobacterial therapy

Background. According to World Health Organization (WHO), experimental studies performed in rats and rabbits have revealed no evidence of harmful side effects of bedaquiline to the fetus. WHO points out that, given the lack of adequate and controlled studies on the effects of bedaquiline on the fetus in pregnant women, and the fact that drug data regarding teratogenicity are limited to nonclinical animal data, this drug may be used when an effective treatment regimen cannot otherwise be provided. However, WHO recommends thorough registering treatment, pregnancy, and postpartum bedaquiline-related outcomes to provide data on appropriate dosing for multidrug-resistant tuberculosis (MDR-TB) treatment during pregnancy and postpartum. However, in the modern literature, there are no data about attributable to bedaquiline adverse events in MDR-TB/HIV co-infected pregnant women and their fetus as well as during the postpartum period.&#x0D; Objective. To update the literature data with the clinical features of pregnancy and postpartum period in a MDR-TB/HIV co-infected patient receiving a bedaquiline-containing regimen as antimycobacterial therapy in the third trimester based on an example from own clinical experience.&#x0D; Methods. We report the clinical case of pregnancy course in the MDR-TB/HIV co-infected woman treated with the bedaquiline-containing regimen as antimycobacterial therapy in the third trimester.&#x0D; Results. In the clinical case presented, the patient demonstrated an initial poor adherence to treatment for both MDR-TB and HIV infection resulting in tuberculous process and HIV rapid progression. Since the patient refused the option of undergoing the therapeutic abortion prior to 22 gestational weeks as the pregnancy was intended, the antimycobacterial therapy regimen was modified by bedaquiline inclusion at 30 weeks’ gestation (the third trimester) for the maternal and neonatal mortality prevention. However, there was no sputum smear conversion on the antimycobacterial therapy regimen including bedaquiline, the patient presented with the signs of endogenous intoxication and nephropathy. Relatedly, neonatal transabdominal ultrasound revealed intrauterine growth retardation, worsening fetoplacental insufficiency (reverse flow) and intrauterine dystrophy. There was abundant placental calcification. Taking into account breech presentation, II degree intrauterine growth retardation, III degree fetoplacental insufficiency (reverse flow), oligohydramnios, fetal distress syndrome and bilateral pyelectasis, the patient was transferred to the Perinatal Centre for planned caesarean section at the 32nd week of gestation. The premature female infant was declared dead some hours later. In the postpartum period, the patient continued the initiated bedaquilinebased antimycobacterial therapy and antiretroviral therapy. However, positive clinical-radiological dynamics and sputum smear conversion have not been achieved.&#x0D; Conclusions. The clinical case presented confirms the literature data that the features of pregnancy and postpartum period in patients with MDR-TB/HIV co-infection are characterized by such complications development as preterm delivery, early neonatal mortality, intrauterine growth retardation, distress syndrome, etc.

Predictors of Multidrug-Resistant Tuberculosis (MDR-TB) in Sudan.

Multidrug-resistant tuberculosis (MDR-TB) is a global public health threat and burden on the health system. This is especially the case in high tuberculosis (TB) prevalence countries, such as Sudan. Consequently, this study aimed to ascertain the predictors of MDR-TB in Sudan to provide future guidance. An unmatched case-control study to assess the predictors of MDR-TB infections among the Sudanese population was conducted from August 2017 to January 2018 at Abu-Anga referral hospital. Patients’ data was gathered from patients’ cards and via interviews. A structured pre-validated questionnaire was used to gather pertinent information, which included sociodemographic characteristics and other relevant clinical data. Univariate and multivariate logistic regression analysis was employed to determine the predictors of MDR-TB infection. 76 of the 183 patients interviewed (41.5%) had MDR-TB cases. The independent predictors for MDR-TB were living in rural areas [adjusted odds ratio (aOR) = 3.1 (95% confidence interval (CI): 1.2–8.2)], treatment failure [aOR = 56.9 (10.2–319.2)], and smoking [(aOR = 4 (1.2–13.2)], whereas other sociodemographic factors did not predict MDR-TB. In conclusion, the study showed that a history of smoking, living in rural areas, and a previous treatment failure were the predictors of MDR-TB in Sudan. The latter factors are most likely due to issues that are related to access and adherence to treatment and lifestyle. The existence of any of these factors among newly diagnosed TB patients should alert clinicians for the screening of MDR-TB. The implementation of directly observed treatment (DOT) and health education are crucial in stopping the spread of MDR-TB in Sudan.

Multidrug-resistant tuberculosis outbreak associated with poor treatment adherence and delayed treatment: Arua District, Uganda, 2013\u20132017

BackgroundIn August 2017, the Uganda Ministry of Health was notified of increased cases of multidrug-resistant tuberculosis (MDR-TB) in Arua District, Uganda during 2017. We investigated to identify the scope of the increase and risk factors for infection, evaluate health facilities’ capacity to manage MDR-TB, and recommend evidence-based control measures.MethodsWe defined an MDR-TB case-patient as a TB patient attending Arua Regional Referral Hospital (ARRH) during 2013–2017 with a sputum sample yielding Mycobacterium tuberculosis resistant to at least rifampicin and isoniazid, confirmed by an approved drug susceptibility test. We reviewed clinical records from ARRH and compared the number of MDR-TB cases during January–August 2017 with the same months in 2013–2016. To identify risk factors specific for MDR-TB among cases with secondary infection, we conducted a case-control study using persons with drug-susceptible TB matched by sub-county of residence as controls. We observed infection prevention and control practices in health facilities and community, and assessed health facilities’ capacity to manage TB.ResultsWe identified 33 patients with MDR-TB, of whom 30 were secondary TB infection cases. The number of cases during January–August 2017 was 10, compared with 3–4 cases in January–August from 2013 to 2016 (p = 0.02). Men were more affected than women (6.5 vs 1.6/100,000, p < 0.01), as were cases ≥18 years old compared to those < 18 years (8.7 vs 0.21/100,000, p < 0.01). In the case-control study, poor adherence to first-line anti-TB treatment (aOR = 9.2, 95% CI: 2.3–37) and initiating treatment > 15 months from symptom onset (aOR = 11, 95% CI: 1.5–87) were associated with MDR-TB. All ten facilities assessed reported stockouts of TB commodities. All 15 ambulatory MDR-TB patients we observed were not wearing masks given to them to minimize community infection. The MDR-TB ward at ARRH capacity was 4 patients but there were 11 patients.ConclusionThe number of cases during January–August in 2017 was significantly higher than during the same months in 2013–2016. Poor adherence to TB drugs and delayed treatment initiation were associated with MDR-TB infection. We recommended strengthening directly-observed treatment strategy, increasing access to treatment services, and increasing the number of beds in the MDR-TB ward at ARRH.