Nontuberculous Mycobacterial Infections: Negligent and Emerging Pathogens

Nontuberculous mycobacteria (NTM) are a heterogeneous group of microorganisms other than Mycobacterium tuberculosis (M. tuberculosis) complex and Mycobacterium leprae. NTM infections have increased globally and are now considered an emerging infection as they are often encountered in developed countries. NTMs require extended treatment adding considerably to the economic burden. The increasing number of patients with immunocompromised disorders, increasing usage of immunosuppressive agents, general awareness of the NTM diseases due to the advancement in molecular diagnostic techniques and aging of the population increase the prevalence rate of NTM infections. However, several barriers such as the requirement of better diagnostic techniques, settled treatment guidelines, clinician awareness and knowledge of pathogenesis are limiting and NTM infections are often not treated promptly. Etiology and epidemiology of NTM infections [Mmycobacterium avium complex (slowly growing mycobacteria, SGM) and rapidly growing mycobacteria (RGM)] are discussed in this chapter. Clinical features, diagnosis and currently available treatment guidelines for these infections in skin, eye and lung are summarized. Suggestions for future research directions are suggested particularly for the better understanding of host-pathogen crosstalk and new therapeutic strategies

Hybrid Derivative of Cathelicidin and Human Beta Defensin-2 Against Gram-Positive Bacteria: A Novel Approach for the Treatment of Bacterial Keratitis

Bacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3. Minimal inhibitory concentrations (MICs) and time-kill kinetics assay were performed to determine the concentration- and time-dependent antimicrobial activity and cytotoxicity was evaluated against human corneal epithelial cells and erythrocytes. In vivo safety and efficacy of the most promising peptide was examined in the corneal wound healing and Staphylococcus aureus (ATCC SA29213) keratitis murine models, respectively. A second-generation HyHDP (CaD23), based on rational hybridization of the middle residues of LL-37 and C-terminal of HBD-2, was developed and was shown to demonstrate good efficacy against methicillin-sensitive and methicillin-resistant S. aureus [MIC = 12.5–25.0 μg/ml (5.2–10.4 μM)] and S. epidermidis [MIC = 12.5 μg/ml (5.2 μM)], and moderate efficacy against P. aeruginosa [MIC = 25-50 μg/ml (10.4–20.8 μM)]. CaD23 (at 25 μg/ml or 2× MIC) killed all the bacteria within 30 min, which was 8 times faster than amikacin (25 μg/ml or 20× MIC). After 10 consecutive passages, S. aureus (ATCC SA29213) did not develop any antimicrobial resistance (AMR) against CaD23 whereas it developed significant AMR (i.e. a 32-fold increase in MIC) against amikacin, a commonly used treatment for BK. Pre-clinical murine studies showed that CaD23 (0.5 mg/ml) achieved a median reduction of S. aureus bioburden by 94% (or 1.2 log10 CFU/ml) while not impeding corneal epithelial wound healing. In conclusion, rational hybridization of human-derived HDPs has led to generation of a potentially efficacious and safe topical antimicrobial agent for treating Gram-positive BK, with no/minimal risk of developing AMR

Microbial exposure during early human development primes fetal immune cells

Human fetal immune system begins to develop early during gestation, however factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in-utero and their contribution towards activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S-rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta and lungs, in 2nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph-node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualised discrete localisation of bacteria-like structures and eubacterial-RNA within 14th week fetal gut lumen. These findings indicate selective presence of live-microbes in fetal organs during 2nd trimester of gestation and have broader implications towards establishment of immune competency and priming before birt

Role of biofilm formation, its triggered immune responses and potential new treatments for bacterial eye infections

Bacterial keratitis is the most important leading cause of corneal opacification and blindness around the world. Mycobacterial keratitis is very hard to eradicate while Pseudomonas keratitis is very common and prone to drug resistance problems. In this study, we investigated the Pseudomonas keratitis as a biofilm mode of infection that induces cyclic-di-GMP signaling and forms phagocyte-tolerant microcolonies on mouse cornea. The increased c-di-GMP content in P. aeruginosa was responsible for decreased levels in cytokine production. C-di-GMP reducing agent (Sodium Nitroprusside) was shown to enhance the efficacy of Colisitin treatment in Pseudomonas keratitis. Mycobacteria readily formed biofilms on mouse cornea comprising of large amounts of extracellular DNA. A strong synergism between Amikacin and Fluoroquinolones against Mycobacterium fortuitum has been observed. DNase addition further enhanced the efficacy of anti-mycobacterial drugs by breaking the mycobacterial biofilm matrix. New treatment strategy (combination of Amikacin, Fluoroquinolones and DNase) showed the best efficacy for converting mycobacterial infections.​Doctor of Philosophy (SBS

Effect of disinfectant solutions on pseudomonas aeruginosa

70 p.Pseudomonas aeruginosa is one of the most common pathogens that can cause opportunistic infection in immunocompromised patients. It is one of the most common pathogens that can cause respiratory problems in infected patients, cystic fibrosis and other hospital acquired infections. Cancer patients and burn patients can suffer more serious signs and symptoms than other individuals. It is also the leading cause of nosocomial infections and hospital acquired pneumonia in intensive care unit (ICU). It can be spread by health care workers, staff, cleaners and medical equipments. Moreover, it becomes the major problem in health care because of its characteristics of developing resistance to antibiotics and forming biofilms. This report is to carry out the minimal inhibitory concentration of common floor cleaners against Pseudomonas aeruginosa (PAOl) and determine the resistance of PAOl with floor cleaners. In this study, four common floor cleaners were chosen for minimal inhibitory concentration and five floor cleaners were chosen to test the formation of resistance of PAOl. The time killing methods were analyzed. Phenol coefficient test was carried out as standard to compare with other floor cleaners. In this study, resistance was formed in two floor cleaners beyond 1 MIC and resistance was formed in 1 MIC in the other three solutions. Therefore, Pseudomonas aeruginosa (PAOl) can form resistance easily with the floor cleaners.Master of Science (Biomedical Engineering

Relationship between organizational justice and citizenship behavior: The mediating effect of organizational commitment.

Today, changes in organizational environments call for voluntary behavior from members of an organization. Employees react and elicit different behaviors depending on different external and internal stimuli. Employees exhibit two types of behaviors: in-role and extra-role behavior, which is also known as the organizational citizenship behaviors (OCB). OCB can be classified into two_ citizenship behaviors towards individuals and citizenship behaviors towards the organization. This study tries to find the relationship between organizational justice (OJ) and citizenship behaviors (OCB) of both of OCBI and OCBO among employees, using affective commitment as a mediator, a proxy to social identification. A total of 96 employees from seven hotels in Yangon and Mandalay were collected as sample. With the permission of their supervisors, each employee received a structured questionnaire, with five-point Likert scales for each question. Multiple regression analysis was used to explore the relationship between OJ, OCBs and commitment, using SPSS 22. Baron and Kenny approach was used to determine the mediation role of commitment and it was found that OJ has positive significant relationship both on commitment and OCB. Commitment was found to have a partial mediating effect on OJ and OCB relationship

Relationship between Organizational Justice and Citizenship behavior: The Mediating Effect of Organizational Commitment

Today, changes in organizational environments call for voluntary behavior from members of an organization. Employees react and elicit different behaviors depending on different external and internal stimuli. Employees exhibit two types of behaviors: in-role and extra-role behavior, which is also known as the organizational citizenship behaviors (OCB). OCB can be classified into two_ citizenship behaviors towards individuals and citizenship behaviors towards the organization. This study tries to find the relationship between organizational justice (OJ) and citizenship behaviors (OCB) of both of OCBI and OCBO among employees, using affective commitment as a mediator, a proxy to social identification. A total of96 employees from seven hotels in Yangon and Mandalay were collected as sample. With the permission of their supervisors, each employee received a structured questionnaire, with five-point Likert scales for each question. Multiple regression analysis was used to explore the relationship between OJ, OCBs and commitment, using SPSS 22. Baron and Kenny approach was used to determine the mediation role of commitment and it was found that OJ has positive significant relationship both on commitment and OCB. Commitment was found to have a partial mediating effect on OJ and OCB relationship

Auxiliary midwives in hard to reach rural areas of Myanmar: filling MCH gaps

Abstract Background Auxiliary Midwives (AMWs) are community health volunteers supporting the work of midwives, especially maternal and child health services in hard to-reach areas in Myanmar. This paper assessed the contributions of AMW to maternal and child health services, factors influencing their productivity and their willingness to serve the community. Method The study applied quantitative cross-sectional survey using census method. Total of 1,185 AMWs belonging to three batches: trained prior to 2000, between 2000 and 2011, and in 2012, from 21 townships of 17 states and regions in Myanmar participated in the study. Multiple logit regression was used to examine the impact of age, marital status, education, domicile, recruitment pattern and ‘batch of training’, on AMW’s confidence level in providing care, and their intention to serve the community more than 5 years. Results All AMWs were able to provide essential maternal and child health services including antenatal care, normal delivery and post-natal care. They could identify and refer high-risk pregnancies to larger health facilities for proper management. On average, 9 deliveries, 11 antenatal and 9 postnatal cases were performed by an AMW during the six months prior to this study. AMWs had a comparative advantage for longer service in hard-to-reach villages where they lived, spoke the same dialect as the locals, understood the socio-cultural dimensions, and were well accepted by the community. Despite these contributions, 90 % of the respondents expressed receiving no adequate supervision, refresher training, replenishment of the AMW kits and transportation cost. AMWs in the elder age group are significantly more confident in taking care of the patients than those in the younger groups. Over 90 % of the respondents intended to stay more than five years in the community. The confidence in catering services appeared to have significant association with a longer period of stay in AMW jobs as evidenced by the odds ratio of 3.5, compared to those reporting unconfident. Conclusions Comprehensive support system and national policy are needed to sustain and strengthen the contributions of AMWs, in sharing the workload of midwives, particularly in hard-to-reach areas of Myanmar