Immunology and Infectious Disease Commons^™

Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino

Pediatrics Faculty Publications

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that ( …

Interleukin-17a Promotes Cd8 T Cell Cytotoxicity To Facilitate West Nile Virus Clearance, Amber M. Paul, Dhiraj Acharya, Penghua Wang, Jianfeng Dai, David Gate

Publications

CD8 T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a/) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 T cells isolated from Il17a/ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in …

Hiv-1 Integrates Widely Throughout The Genome Of The Human Blood Fluke Schistosoma Mansoni., Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H. Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I. Bukrinsky, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein. The appearance of strong stop and positive strand cDNAs indicated that virions fused to schistosome cells, the nucleocapsid internalized and the …

The Nih-Niaid Schistosomiasis Resource Center At The Biomedical Research Institute: Molecular Redux., James J Cody, Wannaporn Ittiprasert, André N Miller, Lucie Henein, Margaret M Mentink-Kane, Michael H. Hsieh

Urology Faculty Publications

Schistosomiasis remains a health burden in many parts of the world. The complex life cycle of Schistosoma parasites and the economic and societal conditions present in endemic areas make the prospect of eradication unlikely in the foreseeable future. Continued and vigorous research efforts must therefore be directed at this disease, particularly since only a single World Health Organization (WHO)-approved drug is available for treatment. The National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases (NIAID) Schistosomiasis Resource Center (SRC) at the Biomedical Research Institute provides investigators with the critical raw materials needed to carry out this important research. …

The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Even though human hookworm infection is highly endemic in many countries throughout the world, its global economic and health impact is not well known. Without a better understanding of hookworm's economic burden worldwide, it is difficult for decision makers such as funders, policy makers, disease control officials, and intervention manufacturers to determine how much time, energy, and resources to invest in hookworm control.

METHODOLOGY/PRINCIPLE FINDINGS: We developed a computational simulation model to estimate the economic and health burden of hookworm infection in every country, WHO region, and globally, in 2016 from the societal perspective. Globally, hookworm infection resulted in …

Microfluidic Platform For Electrophysiological Recordings From Host-Stage Hookworm And Ascaris Suum Larvae: A New Tool For Anthelmintic Research, Janis Weeks, William Roberts, Kristin Robinson, Melissa Keaney, Jon Vermiere, Joseph Urban, Shawn Lockery, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device (‘chip’) that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels. Microfluidic technologies have transformedC. elegans research and the goal of the current study was to validate hookworm andAscaris …

An Ultrasensitive Electrogenerated Chemiluminescence-Based Immunoassay For Specific Detection Of Zika Virus, Amber M. Paul, Dhiraj Acharya, Pradip Bastola, Linda Le, Estenfani Fernandez, Michael S. Diamond, Wujian Miao, Fengwei Bai

Publications

Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV-PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs …

Global Assessment Of Schistosomiasis Control Over The Past Century Shows Targeting The Snail Intermediate Host Works Best., Susanne H Sokolow, Chelsea L Wood, Isabel J Jones, Scott J Swartz, Melina Lopez, Michael H. Hsieh, Kevin D Lafferty, Armand M Kuris, Chloe Rickards, Giulio A De Leo

Urology Faculty Publications

BACKGROUND: Despite control efforts, human schistosomiasis remains prevalent throughout Africa, Asia, and South America. The global schistosomiasis burden has changed little since the new anthelmintic drug, praziquantel, promised widespread control.

METHODOLOGY: We evaluated large-scale schistosomiasis control attempts over the past century and across the globe by identifying factors that predict control program success: snail control (e.g., molluscicides or biological control), mass drug administrations (MDA) with praziquantel, or a combined strategy using both. For data, we compiled historical information on control tactics and their quantitative outcomes for all 83 countries and territories in which: (i) schistosomiasis was allegedly endemic during the …

Data Correlations Between Gender, Cytomegalovirus Infection And T Cells, Nk Cells, And Soluble Immune Mediators In Elderly Humans, Ahmad Al-Attar, Steven R. Presnell, Charlotte A. Peterson, D. Travis Thomas, Charles T. Lutz

Pathology and Laboratory Medicine Faculty Publications

We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56^dim NK cell responses to a variety of stimuli and with CD56^bright/CD56^dim NK cell ratio. We also present the correlation of retinol binding protein (RBP)−4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56^dim NK cell responses. These data are discussed in Al-Attar et al. (2016)

Is Aerosalization A Problem With Carbapenem-Resistant Acinetobacter Baumannii In Thailand Hospital?, Anucha Apisarnthanarak, Ploenpit Tantajina, Pornpimol Laovachirasuwan, David J. Weber, Nalini Singh

Pediatrics Faculty Publications

We evaluated the presence of air contamination with carbapenem-resistant Acinetobacter baumannii (CRAB) in medical units where patients with CRAB pneumonia were hospitalized, and in Obstetrics and Gynecology units with open-air ventilation in-patient settings. There was no evidence of CRAB contamination in either of the units.

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Norovirus Infection And Acquired Immunity In 8 Countries: Results From The Mal-Ed Study, Furqan Kabir, Adil Kalam, Pascal Bessong Pascal Bessong, Zulfiqar Ahmed Bhutta, Anita K. M. Zaidi, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Shahida Qureshi, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Paediatrics and Child Health

Background: Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life.
Methods: A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity.
Results: Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was …

A Single Exercise Bout Enhances The Manufacture Of Viral-Specific T-Cells From Healthy Donors: Implications For Allogeneic Adoptive Transfer Immunotherapy, Guillaume Spielmann, Catherine Bollard, Hawley Kunz, Patrick J. Hanley, Richard J. Simpson

Pediatrics Faculty Publications

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and …

Hiv/Aids Care And Prevention Infrastructure In The U.S. Deep South, Susan S. Reif, Kristen Sullivan, Elena Wilson, Miriam Berger, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

Effect Of Mobile Phone Text Messages Reminders On Uptake Of Routine Immunization Among Children In Pakistan- Study Protocol For A Randomized Clinical Trial, Abdul Momin Kazi, Murtaza Ali, Khurram Zubair, Hussain Kalimuddin, Syed Asad Ali

Department of Paediatrics and Child Health

Introduction: Routine Immunization (RI) is considered one of the best public health interventions to decrease child morbidity and mortality. The RI coverage in Pakistan is still well below the desired level, leading to continued polio transmission, large measles outbreaks and thousands of deaths from vaccine-preventable illnesses. Different innovative and cost effective strategies are required to look into for enhancement in vaccination uptake and coverage. We plan to test the effectiveness of reminders to parents/caregivers on cell phones through short messaging system (SMS) in improving vaccine uptake and on-time routine immunization for children in Pakistan.
Methods and Analysis: A parallel-randomized controlled …