Bacterial Infections and Mycoses Commons^™

Model-Based Dose-Exposure-Response Assessment For Lead And Backup Spectinamide In A Mouse Model Of Tuberculosis, Santosh Janardan Wagh

Theses and Dissertations (ETD)

Despite decades of research, tuberculosis remains the oldest pathogen-based disease that is the leading cause of death from a single infectious agent. Among many anti-tubercular therapies under investigation, the semisynthetic compounds spectinamides are a promising novel class of anti-tuberculosis agents. One such lead candidate, spectinamide 1810, and backup spectinamide 1599 have demonstrated excellent efficacy, safety, and drug-like properties in various in vitro and in vivo assessments. The dose-ranging and dose fractionation studies were designed to characterize the dose-exposure-response relationship for lead and backup spectinamide in a mouse model of Mycobacterium tuberculosis infection. In this current study, we used 26 and …

Role Of Cerebral Vasculature And Effect Of Circulating Exosomes In Propagation Of Systemic Inflammatory Responses Into The Central Nervous System, Mahesh Chandra Kodali

Theses and Dissertations (ETD)

Sepsis-associated encephalopathy (SAE) is an acutely progressing brain dysfunction induced by systemic inflammation. The mechanism of initiation of neuroinflammation during SAE, which ultimately leads to delirium and cognitive dysfunction, remains elusive. The goal of this project was to study the molecular events of SAE to capture its onset and progression into the central nervous system (CNS), and further identify the cellular players involved in mediating acute inflammatory signaling. Gene expression profiling on the cerebral vessels isolated from the brains of the mice treated with peripheral lipopolysaccharide (LPS) revealed that the cerebral vasculature responds within minutes to acute systemic inflammation by …

A Case Of Plesiomonas Bacteremia Without Reported Freshwater Exposure, Abigail E. Mcdonald

HCA Healthcare Journal of Medicine

Introduction: Plesiomonas shigelloides is a member of the Enterobacteriaceae family generally found in freshwater. There is little substantive data about the prevalence or distribution of Plesiomonas within the United States. Plesiomonas are most commonly associated with mild, self-limited watery diarrhea among healthy individuals followed by infective colitis. Bacteremia is the most common extraintestinal manifestation of Plesiomonas. Few cases of Plesiomonas bacteremia can be found in the literature.

Clinical Findings: An elderly female with multiple comorbidities was admitted to our hospital for evaluation of generalized cramping abdominal pain of several days duration. She denied any freshwater or saltwater exposure. The …

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …

Diabetes Mellitus Does Not Predict Discharge In Hospitalized Patients With Acute Pyelonephritis: A Study From Karachi, Pakistan, Syed Furrukh Omair, Fazal Ur Rehman, Imrana Amin, Syed Ahsan Ali, Bakhtawar J. Rind, Bilal Ahmed

Section of Nephrology

Introduction: The incidence of acute pyelonephritis (APN) in the diabetic population is comparatively higher and tends to be more complicated, with serious outcomes. Although complicated pyelonephritis (PN) needs hospital admission and intravenous antibiotics, the magnitude of hospital stay due to comorbidities is limited. This study's aim was to assess the impact of diabetes mellitus on length of hospital stay among patients with PN.
Methods: We did a retrospective data review of 520 randomly selected hospitalized patients of PN from March 2015 to December 2019 from a tertiary care center. Electronic medical records were used for identifying medical conditions through ICD-10 …

Response Of Extensively Drug Resistant Salmonella Typhi To Treatment With Meropenem And Azithromycin, In Pakistan, Sonia Qureshi, Abdullah B. Naveed, Mohammad Tahir Yousafzai, Khalil Ahmad, Sarwat Ansari, Heeramani Lohana, Aiman Mukhtar, Farah Naz Qamar

Department of Paediatrics and Child Health

Introduction: Salmonella Typhi is one of the leading health problems in Pakistan. With the emergence of extensively drug resistant (XDR) Salmonella Typhi, treatment options are limited. Here we report the clinical manifestations and the response to treatment of patients with XDR Typhoid fever. The patients were treated with either Meropenem or Azithromycin or a combination of both.
Methods: We reviewed the records of culture confirmed XDR typhoid who visited Aga Khan University Hospital (AKUH), Karachi and Aga Khan Secondary Care Hospital, Hyderabad from April 2017 to June 2018. Symptoms developed during disease, unplanned treatment extension and complications developed while on …

Evaluating Implementation Of "Management Of Possible Serious Bacterial Infection (Psbi) When Referral Is Not Feasible" In Primary Health Care Facilities In Sindh Province, Pakistan, Maria Asif Bhura, Shabina Ariff, Shamim Ahmad Qazi, Zaitoon Qazi, Imran Ahmed, Yasir Bin Nisar, Zamir Suhag, Abdul Wahab Soomro, Sajid Bashir Soofi

Woman and Child Health

Background: The World Health Organization (WHO) launched a guideline in 2015 for managing Possible Serious Bacterial Infection (PSBI) when referral is not feasible in young infants aged 0-59 days. This guideline was implemented across 303 Basic Health Unit (BHU) Plus primary health care (PHC) facilities in peri-urban and rural settings of Sindh, Pakistan. We evaluated the implementation of PSBI guideline, and the quality of care provided to sick young infants at these facilities.
Methods: Thirty (10%) out of 303 BHU Plus facilities were randomly selected for evaluation. A survey team visited each facility for one day, assessed the health system …

Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette

Theses and Dissertations (ETD)

Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …

Brucellosis In Pakistan: A Neglected Zoonotic Disease, Meesha Iqbal, Zafar Fatmi, Mumtaz Ali Khan

Community Health Sciences

Brucellosis is a zoonotic disease; endemic but neglected in the South Asian countries including Pakistan. It causes economic loss to the livestock sector and leads to systemic infection in humans. Brucellosis was neglected in Pakistan since long. According to the Staged Tool for the Elimination of Brucellosis (STEB), Pakistan carries a grim landscape of the disease with no structured control activities. This article describes the five-year national brucellosis control strategic plan (2018-2023) formulated by the government of Pakistan using the one-health approach for the prevention and control of disease across the country. The plan incorporates components of surveillance, research, diagnostic …

Tuberculosis Of The Flexor Carpi Radialis Muscle - A Case Report, Shah Fahad, Naveed Baloch, Nasir Ud Din

Section of Orthopaedic Surgery

Tuberculosis involving almost any organ of the body is a major problem in developing countries. The most commonly affected site in tuberculosis is the lung. Of the extra pulmonary tuberculosis, musculoskeletal involvement accounts for 1-5% of the cases. Muscular involvement in tuberculosis is a rare manifestation of extra pulmonary tuberculosis. Unusual presentations often go undetected and are associated with a diagnostic and therapeutic delay. This case report presents tuberculosis of the flexor carpi radialis.

Sepsis Knowledge Among Adults Living In Tippecanoe County, Jessica Devine

The Journal of Purdue Undergraduate Research

No abstract provided.

Intensive Animal Farming Conditions Are A Major Threat To Global Health, Cynthia Schuck-Paim

Animal Sentience

Wiebers & Feigin accurately propose that reducing the risks posed by infectious disease outbreaks and other global health challenges will depend critically on transitioning away from intensive animal farming practices. Creating the right incentive structure for this transition to happen is one of the great challenges in the years to come, but a much-needed step to ensure the health and well-being of current and future generations.

Cyclic Peptide [R4w4] In Improving The Ability Of First-Line Antibiotics To Inhibit Mycobacterium Tuberculosis Inside In Vitro Human Granulomas, Joshua Hernandez, David Ashley, Ruoqiong Cao, Rachel Abrahem, Timothy Nguyen, Kimberly To, Aram Yegiazaryan, Ajayi Akinwale David, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Tuberculosis (TB) is currently one of the leading causes of global mortality. Medical non-compliance due to the length of the treatment and antibiotic side effects has led to the emergence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (M. tb) that are difficult to treat. A current therapeutic strategy attempting to circumvent this issue aims to enhance drug delivery to reduce the duration of the antibiotic regimen or dosage of first-line antibiotics. One such agent that may help is cyclic peptide [R₄W₄], as it has been shown to have antibacterial properties (in combination with tetracycline) …

Sepsis Pathophysiology, Samantha Kingsley

Nursing Student Class Projects (Formerly MSN)

Sepsis is one of the most common diagnoses in medical intensive care units (MICUs) worldwide. Sepsis is a medical emergency where prompt intervention is vital to promoting positive patient outcomes. Septic shock develops when sepsis has progressed to the point of persistent hypotension despite appropriate fluid resuscitation. It is important to recognize the early signs of sepsis and intervene to prevent further progression. As the understanding of the pathophysiology has developed further over the years, the treatments and outcomes associated with sepsis have also improved. However, prompt recognition and intervention have always been at the forefront of management and should …

The Inhibitory Effects Of An Antimicrobial Gel On The Staphylococcus Species, Mara Trinkle

Undergraduate Honors Theses

The prevalence of antibiotic resistant bacteria has made the choices for topical treatments for patients who experience burns wounds extremely limited. The Staphylococcus genus is naturally occurring in and on the human body but can become harmful once it enters the bloodstream. A novel antimicrobial gel has been shown by our laboratory to inhibit both the planktonic growth and biofilm formation of Staphylococcus aureus in previous studies. The antimicrobial gel is made of seven natural compounds including antioxidants (vitamin C and E). We wanted to examine the effects of the antimicrobial gel on numerous other Staphylococcal species because it is …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Environmental Surveillance As A Tool For Identifying High-Risk Settings For Typhoid Transmission, Jason R. Andrews, Alexander T. Yu, Senjuti Saha, Jivan Shakya, Kristen Aiemjoy, Lily Horng, Farah Qamar, Denise Garret, Stephen Baker, Samir Saha, Stephen P. Luby

Department of Paediatrics and Child Health

Enteric fever remains a major cause of morbidity in developing countries with poor sanitation conditions that enable fecal contamination of water distribution systems. Historical evidence has shown that contamination of water systems used for household consumption or agriculture are key transmission routes for Salmonella Typhi and Salmonella Paratyphi A. The World Health Organization now recommends that typhoid conjugate vaccines (TCV) be used in settings with high typhoid incidence; consequently, governments face a challenge regarding how to prioritize typhoid against other emerging diseases. A key issue is the lack of typhoid burden data in many low- and middle-income countries where TCV …

The Surveillance For Enteric Fever In Asia Project (Seap), Severe Typhoid Fever Surveillance In Africa (Seta), Surveillance Of Enteric Fever In India (Sefi), And Strategic Typhoid Alliance Across Africa And Asia (Strataa) Population-Based Enteric Fever Studies: A Review Of Methodological Similarities And Differences, Megan E. Carey, William R. Macwrigh, Justin Im, James E. Meiring, Malick M. Gibani, Se Eun Park, Ashley Longley, Hyon Jin Jeon, Caitlin Hemlock, Mohammad Tahir Yousafzai, Farah Qamar

Department of Paediatrics and Child Health

Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to …

Developing A Virus-Like Particle (Vlp)-Based Vaccine For Neisseria Gonorrhoeae, Ashvini Vaidya

Biomedical Sciences ETDs

Neisseria gonorrhoeae (Ng) is a sexually transmitted bacterium that infects human reproductive mucosal surfaces. Due to the risk of complications in untreated cases and evolving antibiotic resistance, a prophylactic vaccine is critical for preventing infection. There are four Ng outer-membrane proteins that contribute to Ng survival and resistance: PorB, BamA, TbpA, and MtrE. Each protein contains surface-exposed loops that are targets of bactericidal antibodies. Vaccines were developed by displaying Ng epitopes on the surface of bacteriophage virus-like particles (VLP). VLPs are immunogenic, multivalent, self-assembling complexes composed of viral structural proteins. Antigenic peptide sequences can be displayed on the surface …

A Race Against Time: Reduced Azithromycin Susceptibility In Salmonella Enterica Serovar Typhi In Pakistan, Junaid Iqbal, Irum Fatima Dehraj, Megan E. Carey, Zoe A. Dyson, Denise Garrett, Jessica C. Seidman, Furqan Kabir, Senjuti Saha, Stephen Baker, Farah Naz Qamar

Department of Paediatrics and Child Health

Antimicrobial resistance is an ongoing issue in the treatment of typhoid fever. Resistance to first-line antimicrobials and extensively drug resistant (XDR) Salmonella Typhi isolates in Pakistan have left azithromycin as the only remaining effective oral treatment. Here, we report the emergence of organisms with a single point mutation in acrB gene, implicated in azithromycin resistance, in a S. Typhi isolate from Pakistan. The isolation of this organism is worrisome and highlights the significance of the introduction of typhoid conjugate vaccine in South Asia.
Importance: The emergence of XDR Salmonella Typhi in Pakistan has left azithromycin as the only viable oral …