Τρίτη, 12 Μαρτίου 2019

Mycobacteriology

The unexplained increase of nontuberculous mycobacteriosis
Octavio Miguel Rivero-Lezcano, Carolina González-Cortés, Mehdi Mirsaeidi

International Journal of Mycobacteriology 2019 8(1):1-6

Epidemiological data show a worldwide increase in nontuberculous mycobacteriosis. Although it has been partially attributed to the improvement of microbiological methodologies that has allowed a better recovery and identification of nontuberculous mycobacteria (NTM), it is generally accepted that there is a genuine incidence augmentation. The reasons of the increase are likely multifactorial, depending on the nature of the pathogen, the host, and their interaction. Mycobacteria from the Mycobacterium tuberculosis complex has been regarded as pathogenic and NTM as opportunistic and nontransmissible. Nevertheless, few differences have been found in either their phenotypic or genotypic characteristics. The phenomenon of M. tuberculosis adaptation to the human host may be taking place again in NTM as a consequence of human environmental alterations that facilitate the interaction with the pathogen. The current worsening of the immunological status of increasing numbers of individuals, a result of factors such as malnutrition (obesity and diabetes), population aging or the widespread use of immunosuppressive medication, may be allowing the rapid evolution and person-to-person transmission of NTM. It is likely that mycobacteriosis incidence will keep escalating. New measures should be taken to deal with these diseases, including their reportability and the implementation of strain genotyping that would shed light on the NTM dissemination routes from the environment or human hosts. 


Antimycobacterial strategies to evade antimicrobial resistance in the nontuberculous mycobacteria
Beverley Cherie Millar, John Edmund Moore

International Journal of Mycobacteriology 2019 8(1):7-21

The nontuberculous mycobacteria (NTM) have recently emerged as important bacterial pathogens of both animals and humans. Of particular, concern is the high level of antimicrobial resistance (AMR) displayed by these organisms, which complicates treatment and potential successful outcomes. This review, therefore, wishes to examine novel compounds and approaches to combatting AMR in the NTMs, specifically examining antimycobacterial (NTM) compounds from plants and venoms, as well as examining synergistic and combination effects with other antimicrobials. Novel and modified drugs including new inhaled drugs are examined, as well as the repurposing of existing drugs for antimycobacterial activity. Many of these novel interventions are at various stages of development, from initial concept through to licensed intervention. The challenge remains to translate these interventions from in vitro laboratory models to effective in vivo interactions. When these are realized, then we will have the opportunity of overcoming NTM AMR, to the benefit of medicine, society, and humanity. 


Drug resistance profile of Mycobacterium tuberculosis isolates from patients referred to tuberculosis reference laboratory in Kosovo
Rrezarta Bajrami, Gjyle Mulliqi, Arsim Kurti, Greta Lila, Lul Raka

International Journal of Mycobacteriology 2019 8(1):22-24

Background: Drug-resistant tuberculosis (TB) continues to threaten TB control and remains a major global public health concern. The poor patient adherence in TB treatment is the cornerstone of emerging multidrug-resistant TB (MDR-TB). The aim of this study was to evaluate the resistance of Mycobacterium tuberculosis to the first-line TB drugs among isolates from clinical specimens. Methods: A laboratory-based study was conducted in the Department of Microbiology, within the National Institute of Public Health of Kosovo, from January 2017 to September 2018. Sputum and other clinical specimens were obtained from patients with pulmonary and extrapulmonary TB. The specimens were stained with Ziehl–Neelsen, inoculated on Löwenstein–Jensen media for 6–8 weeks, and tested for sensitivity against the first-line TB drugs (isoniazid [INH], rifampicin [RIF], ethambutol [EMB], and streptomycin [SM]). Results: Of the 316 M. tuberculosis isolates collected, 31.6% showed resistance to first-line TB drugs. Among these resistant isolates, 31% showed resistance to at least one of the first-line TB drugs and 0.3% showed MDR. Resistance to EMB, INH, RIF, and SM was seen in 17%, 8%, 3%, and 72% of isolates, respectively. Polyresistance was seen in 3% of the isolates. Conclusion: Our study confirms that resistance to streptomycin was the most common phenomenon. The resistance pattern identified in this study could assist clinicians in providing appropriate treatment regimen to TB patients and improve their clinical outcome. 


Detection of multidrug resistant Mycobacterium tuberculosis in Tabuk, Saudi Arabia, using Genotype MTBDRplus
Eltayib Hassan Ahmed-Abakur, Tarig Mohammed Saad Alnour

International Journal of Mycobacteriology 2019 8(1):25-28

Background: The global increase in the rates of multidrug-resistant (MDR) tuberculosis (TB) has made the timely identification of resistant Mycobacterium tuberculosis complex strains an important emergence to achieve effective disease management and to prevent their spread in the community. The present study aimed to determine the MDR-TB in Tabuk province, north of the Kingdom of Saudi Arabia. Methods: The GenoType MTBDRplus assay was used to determine the mutations associated with isoniazid (INH) and rifampicin (RIF) resistances. A total number of 61 confirmed M. tuberculosis positive-sputum samples were scanned for the mutation in the rpoB, inhA, and katG genes. Results: The present study revealed that 67.2% of the samples were susceptible, 29.5% were monoresistant, and 3.3% were MDR. Conclusions: The monoresistant showed 26.2% for INH and 3.3% for RIF. The early detection of MDR could guide the starting of appropriate regimen of treatment. 


A retrospective study of the severe and uncommon variants of erythema nodosum leprosum at a tertiary health center in central India
Vaishali H Wankhade, Pritica Debnath, Rajesh Pratap Singh, Gitesh Sawatkar, Dharitri Mukund Bhat

International Journal of Mycobacteriology 2019 8(1):29-34

Background: Erythema nodosum leprosum (ENL) classically presents with tender, coppery, evanescent nodules along with constitutional features and visceral involvement. However, uncommon morphological variants of ENL-like erythema nodosum necroticans, erythema multiforme (EM)-like ENL, Sweet's syndrome (SS)-like ENL, Lucio phenomenon, and reactive perforating type of ENL have also been described in the literature. The primary objective of this study was to describe the clinical features of the severe and uncommon morphological variants of ENL. Methods: This was an observational case series with retrospective review of records of all ENL patients with ulceronecrotic lesions admitted in the Department of Dermato-venereo-leprology of a tertiary health center of central India over a period of 2 years. Results: Eighteen patients were included, all of whom had ulceronecrotic lesions. Four out of them had EM like ENL, two had SS-like presentation, and one of them had annular bullous lesions over old infiltrated plaques of leprosy. Conclusions: Uncommon variants of ENL can be very commonly misdiagnosed in patients, especially in those who have not been previously diagnosed with leprosy. Hence, a high index of suspicion is required in such cases to avoid delay in the diagnosis and resulting morbidity. 


Treatment outcomes and associated factors in tuberculosis patients at Jimma University Medical Center: A 5-year retrospective study
Gemeda Abebe, Zegeye Bonsa, Wakjira Kebede

International Journal of Mycobacteriology 2019 8(1):35-41

Background: Monitoring the outcome of tuberculosis (TB) treatment and investigating factors associated with unsuccessful outcome are essential, as unsuccessful treatment fuels resistance to antibiotics. This study aimed to investigate the treatment outcome and associated factors with an unsuccessful outcome at Jimma University Medical Center (JUMC), Southwest Ethiopia. Methods: A 5-year retrospective analytical study, including all types of TB cases who sought care at JUMC between September 1, 2012, and August 31, 2017, was conducted. Treatment outcomes and TB types were categorized according to the National TB Control guideline. Bivariate analysis was used to analyze the association between treatment outcome and potential variables. Results: Overall data from 1249 patients' records were included in the study. The proportion of male patients was higher (815, 65.3%) than that of females. The mean age (± standard deviation, range) of the cases was 26 (±11. 6, 1–71) years. Of the total, 292 (23.3%) were smear-positive pulmonary TB (PTB), 489 (39.2%) smear-negative PTB, and 468 (37.5%) extra-PTB (EPTB) cases. Available treatment outcomes indicate that 253 (20.2%) were cured, 850 (68.0%) completed therapy, 58 (4.8%) died, 83 (6.6%) defaulted, and 5 (0.4%) failed the therapy. About 76 (5.6%) cases were transferred out and 44 (3.2%) cases were lost to follow-up. In total, 146 (11.7%) patients had an unsuccessful outcome. Unsuccessful treatment outcome was associated with smear-negative PTB (odds ratio [OR] =2.0, 95% confidence intervals [CI] =1.1, 3.7), EPTB (OR = 2.1, 95% CI = 1.2, 3.4), and unknown human immunodeficiency virus (HIV) status (OR = 7.9, 95% CI = 2.5, 25.0). Conclusion: The treatment success rate of overall TB patients is lower than end TB Strategy target of ≥90% success rate. Smear-negative PTB, EPTB cases, and those with unknown HIV status tend to have unsuccessful outcome. 


Common alternative diagnoses among a pediatric hospital-based cohort evaluated for tuberculosis in Karachi, Pakistan: The need for facilitated referral in tuberculosis clinics
Sadia Shakoor, Fatima Mir, Rumina Hasan

International Journal of Mycobacteriology 2019 8(1):42-47

Background: Children evaluated for tuberculosis (TB) are often diagnosed with miscellaneous conditions that mimic TB. Knowledge of differentials informs policy on service provision through liaison with referral centers offering definitive diagnosis and treatment for common alternative disorders. Methods: We reviewed medical records of children who were offered diagnostic testing for TB (culture or Xpert MTB/RIF) at a tertiary care hospital in Karachi, Pakistan to identify common alternative diagnoses among children who are evaluated for TB. Results: From January 2014 to December 2015, of 126 culture or Xpert MTB/RIF negative children presenting with chronic symptoms, 31 were diagnosed and treated for TB based on clinical criteria (5 of 48 children with pulmonary and 26 of 78 with extrapulmonary presentations; 10.4% and 33.3%, respectively). Among remaining 95 patients, common alternative diagnoses to pulmonary TB (n = 43) were bacterial pneumonia or empyema (60.5%, n = 25) and underlying bronchiectasis (20.9%, n = 9). Among 52 extrapulmonary presentations, the most common alternative diagnoses were lymphoproliferative disorders (n = 11, 21.1%), bacterial infections (n = 11, 21.1%), and autoimmune disorders (n = 9, 17.3%). Of note, five children were diagnosed with underlying primary immunodeficiencies (9.6%). Children with alternative disorders were treated for TB in 25 of 95 cases (26.3%). Although 77.8% (n = 98) children were followed up at the facility, 15.9% (n = 20) were lost to follow-up. Conclusions: Pediatric TB mimics many disorders that primary level centers are not equipped to diagnose or manage, leading to suboptimal outcomes. Knowledge of common alternative diagnoses is essential to inform facilitated referral for common mimicking disorders in children. 


Survey of local fauna from endemic areas of Northern Queensland, Australia for the presence of Mycobacterium ulcerans
Avishek Singh, John Hannan William McBride, Brenda Govan, Mark Pearson

International Journal of Mycobacteriology 2019 8(1):48-52

Background: Buruli ulcer (BU), regionally known as the Daintree ulcer or Bairnsdale ulcer is caused by the environmental pathogen Mycobacterium ulcerans (MU). This disease is characterized by extensive and painless necrosis of skin and soft tissue with the formation of large ulcers and has been reported in >33 countries worldwide. This organism is geographically restricted and in Australia, the disease has been reported primarily in coastal Victoria and the Mossman–Daintree areas of northern Queensland. Australia is the only country where nonhuman cases of BU have been confirmed. The common ringtail possums and mountain brushtail possums have been suggested as potential animal reservoirs of MU in coastal Victoria, Australia. The exact mode of transmission of this disease remains unknown. Methods: In this study, we surveyed local fauna from endemic areas of northern Queensland, Australia, for the presence of MU in scat samples. We collected 140 bandicoot, four white-tailed rats, and two possum scat samples from 56 overnight trapping sessions. Samples were examined for the presence of MU DNA by the polymerase chain reaction. Results: Two out of five samples did not contain a sufficient amount of DNA to detect IS2606 and the ketoreductase B (KR) domain of the mycolactone polyketide synthase gene, which is represented by higher cycle threshold (Ct) values for IS2404 shown in table below. Despite of having desired Ct values for IS2404, one IS2404 positive sample possibly contained DNA of closely related M. ulcerans subspecies with lower copy number of IS2606 that do not commonly cause disease in human. All three targets: IS2404, IS2606 and KR were detected from the remaining two scat samples. Conclusion: We confirm the presence of M. ulcerans DNA in the scat samples collected from a Buruli ulcer endemic region of Northern Queensland, Australia. 


Blood cytokine responses to early secreted protein antigen-6/culture filtrate protein-10 tuberculosis antigens 2 months after antituberculosis treatment among patients with drug-susceptible pulmonary tuberculosis
Happiness Cornel Mvungi, Peter Masunga Mbelele, Joram Josephat Buza, Stellah George Mpagama, Elingarami Sauli

International Journal of Mycobacteriology 2019 8(1):53-59

Background: Human tuberculosis is a chronic inflammatory disease caused by mycobacterium tuberculosis. Pulmonary tuberculosis is the result of the failure of host immune system to control mycobacterium tuberculosis. The aim of the study was to asses the changes of the cytokines in active pulmonary tuberculosis patients before and after the use of anti-TB therapy. Methods: Multiple cytokine responses in active tuberculosis (TB) patients were investigated in this study following anti-TB drug therapy after 2 months. Ninety-six participants with pulmonary TB were engaged in the study between May 2018 and October 2018. Samples of blood were taken early before treatment at 0 and 2 months after using anti-TB therapy. The levels of interferon-gamma (IFN)-γ, interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor (TNF)-α in whole blood plasma collected from the QuantiFERON-TB Gold Plus were measured. Results: Compared with baseline levels, TNF-α, IL6 and IL10 were significantly lower following treatment whereas the IFN-γ and IL-4 increased significantly after treatment. The responses of five cytokines varied significantly after treatment (P < 0.0001) where IFN-γ was highest compared to other cytokines with 123.6%, AUC=0.757 and P < 0001, TNF-α AUC: 0.529 and P = 0.743, IL-4 AUC:0.557 and P = 0.514, IL-6 AUC:0.629 and P = 0.047, IL-10 AUC:0.549 and P = 0.581. Conclusion: It is concluded that changes of cytokines that observed during the treatment of TB patients play a very important role in monitoring pulmonary TB and can be suitable biomarkers to assess the effectiveness of anti-TB therapy in patients with TB. 


Tuberculosis transmission in the population of patients from the Krakow Region (Poland) based on the epidemiological and molecular methods
Katarzyna Kruczak, Ewa Augustynowicz-Kopeć, Monika Kozińska, Grażyna Passak-Stańda, Ewa Niżankowska-Mogilnicka, Krzysztof Sładek

International Journal of Mycobacteriology 2019 8(1):60-69

Background: The transmission of tuberculosis may affect the incidence rate of the disease in Poland. Genetic methods are of assistance in tracing the infection transmission, identifying its sources, determining the risk groups, and focusing on the preventive actions. Objectives: The objectives of this study lie in an assessment of tuberculosis transmission by genetic methods with the assistance of the standard epidemiologic interview. Methods: The genome DNA of 275 Mycobacterium tuberculosis (Mtb) strains from tuberculosis patients, inhabitants of the city of Krakow, was subjected to a genetic analysis via the spoligotyping method and the IS6110-Mtb1–Mtb2 polymerase chain reaction (PCR) method. If the DNA profiles were identical in both of the PCRs, they were considered identical and classified within one molecular family. Results: Among 275 strains, 104 genetic patterns (spoligotypes) were identified. Two hundred and three strains were divided into 66 molecular families (clusters) and analyzed with the IS6110- Mtb1–Mtb2 PCR method. Eighteen clusters were separated. In the Mtb1–Mtb2 clusters, 21 patients were in the risk groups (the homeless, prisoners, and nursing home residents). We did not confirm any direct or temporary contacts between the patients constituting the Mtb1–Mtb2 clusters (apart from the risk groups). However, the patients in these clusters often lived in the same parts of Krakow. Conclusions: The standard epidemiologic interview in tuberculosis patients should be combined with genetic methods. Active transmission of tuberculosis occurs largely among the individuals maintaining probably periodic contacts. The patients who are in the risk groups may play an important role in the transmission of tuberculosis. 


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