Pathology Commons^™

Exploration Of The Implementation Of An Integrated Electronic Laboratory Information Management System On Quality Diagnostics Service Indicators At A County Level Public Hospital In Western Kenya., Kelly Allen

Capstone Collection

Underinvestment in pathology and laboratory capacity caused by low visibility in research and in prioritization by public health leaders results in limited effective healthcare coverage and an estimated 1.1 million premature deaths annually in Low-and-Middle-Income Countries. Kenya’s public health laboratories provide a median 41% of the Essential Diagnostic List to their patients and in Kisumu County, as much as 44.2% of the population has little to no access to essential diagnostics. The government of Kisumu implemented the county Health Laboratory Strategic Plan 2018-2022 to address this public health challenge. Little information exists on the effectiveness of these initiatives and the …

Conflict Of Interests Driven By Pharmaceutical Incentivisation: Risks To The Medical Fraternity In Pakistan, Muhammad Naveed Noor, Afifah Rahman Shepherd, Amna Rehana Siddiqui

Department of Pathology and Laboratory Medicine

No abstract provided.

Equine Bronchial Epithelial Cells Are Susceptible To Cell Entry With A Sars-Cov-2 Pseudovirus But Reveal Low Replication Efficiency, Rebecca M Legere, Angelica R Allegro, Yvonne Affram, Bibiana Petri Da Silveira, Jennifer L Fridley, Kelsey M Wells, Numan Oezguen, Robert C Burghardt, Gus A Wright, Jeroen Pollet, Angela I Bordin, Paul De Figueiredo, Julian L Leibowitz, Noah D Cohen

Faculty, Staff and Students Publications

Objective: To examine the susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus relative to human bronchial epithelial cells (HBECs).

Sample: Primary EBEC cultures established from healthy adult horses and commercially sourced human bronchial epithelial cells (HBECs) were used as a positive control.

Methods: Angiotensin-converting enzyme 2 (ACE2) expression by EBECs was demonstrated using immunofluorescence, western immunoblot, and flow cytometry. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were transduced …

Stratification Of Pediatric Covid-19 Cases Using Inflammatory Biomarker Profiling And Machine Learning., Devika Subramanian, Aadith Vittala, Xinpu Chen, Christopher Julien, Sebastian Acosta, Craig Rusin, Carl Allen, Nicholas Rider, Zbigniew Starosolski, Ananth Annapragada, Sridevi Devaraj

Faculty, Staff and Students Publications

While pediatric COVID-19 is rarely severe, a small fraction of children infected with SARS-CoV-2 go on to develop multisystem inflammatory syndrome (MIS-C), with substantial morbidity. An objective method with high specificity and high sensitivity to identify current or imminent MIS-C in children infected with SARS-CoV-2 is highly desirable. The aim was to learn about an interpretable novel cytokine/chemokine assay panel providing such an objective classification. This retrospective study was conducted on four groups of pediatric patients seen at multiple sites of Texas Children's Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of …

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In A Rat Model, Mark Stoll

Annual Research Symposium

Would you like to know what happens to the immune system during opioid drug withdrawal?

Socioecological Factors Linked With Pharmaceutical Incentive-Driven Prescribing In Pakistan, Muhammad Naveed Noor, Afifah Rahman-Shepherd, Amna Rehana Siddiqui, Wafa Aftab, Sadia Shakoor, Rumina Hasan, Mishal Khan

Department of Pathology and Laboratory Medicine

Pharmaceutical marketing through financial incentivisation to general practitioners (GPs) is a poorly studied health system problem in Pakistan. Pharmaceutical incentivisation is seen to be distorting GPs prescribing behaviour that can compromise the health and well-being of patients. We draw on a conceptual framework outlined in the ecological system theory to identify multiple factors linked with pharmaceutical incentivisation to GPs in Pakistan. We conducted qualitative interviews with 28 policy actors to seek their views on the health system dynamics, how they sustain pharmaceutical incentivisation and their effect on the quality of care. Our analysis revealed four interlinked factors operating at different …

Metabolomics Of A Neonatal Cohort From The Alliance For Maternal And Newborn Health Improvement Biorepository: Effect Of Preanalytical Variables On Reference Intervals, Lena Jafri, Aysha Habib Khan, Muhammad Ilyas, Muhammad Imran Nisar, Javairia Khalid, Hafsa Majid, Aneeta Hotwani, Fyezah Jehan

Department of Pathology and Laboratory Medicine

Background: The study was conducted to determine reference interval (RI) and evaluate the effect of preanalytical variables on Dried blood spot (DBS)-amino acids, acylcarnitines and succinylacetone of neonates.
Methodology: DBS samples were collected within 48-72 hours of life. Samples were analyzed for biochemical markers on tandem mass spectrometer at the University of Iowa. Comparison of RI across various categorical variables were performed.
Results: A total of 610 reference samples were selected based on exclusion criteria; 53.2% being females. Mean gestational age (GA) of mothers at the time of delivery was 38.7±1.6 weeks; 24.5% neonates were of low birth weight and …

Uncovering The Role Of Fat-Infiltrated Axillary Lymph Nodes In Obesity-Related Diseases With Statistical And Machine Learning Analyses, Qingyuan Song

Dartmouth College Ph.D Dissertations

The link between obesity and pathogenesis is a complex and multifaceted area of research that is yet to be fully understood. Ample evidence exists to demonstrate the direct relationship between excessive internal fat and various health conditions such as cancer, and metabolic and cardiovascular diseases. The infiltration of ectopic fat into axillary lymph nodes, observable on breast cancer screening images, has been shown to be correlated with body mass index (BMI) in women undergoing screening. This study aimed to explore the relationship between fat-infiltrated axillary lymph nodes (FIN) and obesity-related diseases, with the goal of evaluating the clinical value of …

From Concept To Delivery: A Yeast-Expressed Recombinant Protein-Based Covid-19 Vaccine Technology Suitable For Global Access, Peter J Hotez, Rakesh Adhikari, Wen-Hsiang Chen, Yi-Lin Chen, Portia Gillespie, Nelufa Y Islam, Brian Keegan, Rakhi Tyagi Kundu, Jungsoon Lee, Zhuyun Liu, Jason T Kimata, Numan Oezguen, Jeroen Pollet, Cristina Poveda, Kay Razavi, Shannon E Ronca, Ulrich Strych, Syamala R Thimmiraju, Leroy Versteeg, Maria Jose Villar-Mondragon, Junfei Wei, Bin Zhan, Maria Elena Bottazzi

Faculty, Staff and Students Publications

Introduction: The development of a yeast-expressed recombinant protein-based vaccine technology co-developed with LMIC vaccine producers and suitable as a COVID-19 vaccine for global access is described. The proof-of-concept for developing a SARS-CoV-2 spike protein receptor-binding domain (RBD) antigen as a yeast-derived recombinant protein vaccine technology is described.

Areas covered: Genetic Engineering: The strategy is presented for the design and genetic modification used during cloning and expression in the yeast system. Process and Assay Development: A summary is presented of how a scalable, reproducible, and robust production process for the recombinant protein COVID-19 vaccine antigen was developed. Formulation and Pre-clinical Strategy: …

Randomized Placebo-Controlled Trial Of Oral Tannin Supplementation On Covid-19 Symptoms, Gut Dysbiosis And Cytokine Response, Silvia Molino, Andrea Pisarevsky, Shyam Badu, Qinglong Wu, Fabiana López Mingorance, Patricia Vega, Juan Pablo Stefanolo, Julieta Repetti, Guillermina Ludueña, Pablo Pepa, Juan Ignacio Olmos, Marcelo Rodriguez Fermepin, Tatiana Uehara, Elisa Viciani, Andrea Castagnetti, Tor Savidge, María Marta Piskorz

Faculty, Staff and Students Publications

The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction …

Drug-Resistant Bacterial Infections: We Need Urgent Action And Investment That Focus On The Weakest Link, Christiane Dolecek, Sadia Shakoor, Buddha Basnyat, Tochi Okwor, Benn Sartorius

Department of Pathology and Laboratory Medicine

Despite high mortality and morbidity, drug-resistant bacterial infections remain the forgotten pandemic. We argue for strengthening of diagnostics, WASH (water, sanitation, and hygiene) and infection prevention and control to reduce drug-resistant infections, as an integral part of sustainable high-quality health services, particularly in low- and middle-income countries.

Exploring Stakeholders' Experiences And Perceptions Regarding Barriers To Effective Surveillance Of Communicable Diseases In A Rural District Of Pakistan: A Qualitative Study, Imran Naeem Abbasi, Sameen Siddiqi, Mmna Rehana Sididiqui, Rumina Hasan

Community Health Sciences

Objective: To explore the experiences and perceptions of health system stakeholders of a rural district of Sindh, Pakistan regarding the barriers to effective surveillance of communicable diseases.
Design: This qualitative descriptive exploratory design comprised in-depth interviews. Both inductive and deductive thematic analysis was applied to identify key themes from the data.
Settings: The study was conducted in public sector healthcare facilities and the district health office of the rural district of Thatta, in Sindh province, Pakistan.
Participants: Fifteen healthcare managers and healthcare providers working in the eight public sector primary and secondary healthcare facilities were interviewed using an open-ended in-depth …

Informing Healthcare Operations With Integrated Pathology, Clinical, And Epidemiology Data: Lessons From A Single Institution In Kenya During Covid-19 Waves, Allan Njau, Jemimah Kimeu, Jaimini Gohil, David Nganga

Pathology, East Africa

Pathology, clinical care teams, and public health experts often operate in silos. We hypothesized that large data sets from laboratories when integrated with other healthcare data can provide evidence that can be used to optimize planning for healthcare needs, often driven by health-seeking or delivery behavior. From the hospital information system, we extracted raw data from tests performed from 2019 to 2021, prescription drug usage, and admission patterns from pharmacy and nursing departments during the COVID-19 pandemic in Kenya (March 2020 to December 2021). Proportions and rates were calculated. Regression models were created, and a t-test for differences between …

Covid-19 And Blood Clots: A Report Of Massive Pulmonary Embolism In Covid-19 Patient Supported On Veno-Venous Ecmo And The Utility Of Thrombolysis, Bindu Akkanti, Joseph Zwischenberger, Mark T Warner, Kha Dinh, Rahat Hussain, Farah Kazzaz, Pascal Kingah, Lisa M Janowiak, Biswajit Kar, Igor D Gregoric

Faculty, Staff and Student Publications

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our …

Igg Antibodies To Sars-Cov-2 In Asymptomatic Blood Donors At Two Time Points In Karachi, Muhammad Hasan, Bushra Moiz, Shama Qaiser, Kiran I. Masood, Zara Ghous, Areeba Hussain, Natasha Bahadur Ali, Syed Hani Abidi, Kulsoom Ghias, Erum Khan, Zahra Hasan

Department of Pathology and Laboratory Medicine

Introduction: An estimated 1.5 million cases were reported in Pakistan until 23 March, 2022. However, SARS-CoV-2 PCR testing capacity has been limited and the incidence of COVID-19 infections is unknown. Volunteer healthy blood donors can be a control population for assessment of SARS-CoV-2 exposure in the population. We determined COVID-19 seroprevalence during the second pandemic wave in Karachi in donors without known infections or symptoms in 4 weeks prior to enrollment.
Materials and methods: We enrolled 558 healthy blood donors at the Aga Khan University Hospital between December 2020 and February 2021. ABO blood groups were determined. Serum IgG reactivity …

Case Report: Axilla Fibroadenoma - An Atypical Presentation, Safna Naozer Virji, Lubna Mushtaque Vohra, Syeda Sakina Abidi, Romana Idress

Department of Surgery Docs

No abstract provided.

Foci Of Idc In Phyllodes Tumors: Should We Be Worried?: A Systematic Review Of The Literature, Kathryn Eckert, Victoria Tiedemann, Linda Szczurek

Rowan-Virtua Research Day

Phyllodes tumors are rare, fast growing fibroepithelial tumors of the breast that account for less than 1% of all breast tumors globally. They were first characterized by Johannes Muller in 1838 and most often present in the 5th decade of life. Phyllodes tumors are histologically composed of a stromal component and an epithelial component. The stromal component has a widely accepted malignant potential in up to 30% of cases. Grading of the stromal malignant potential of phyllodes tumors has been defined by the World Health Organization (WHO) as benign, borderline, or malignant based on the presence and degree of stromal …

A Streptococcus Pneumoniae Lineage Usually Associated With Pneumococcal Conjugate Vaccine (Pcv) Serotypes Is The Most Common Cause Of Serotype 35b Invasive Disease In South Africa, Following Routine Use Of Pcv, Kedibone M. Ndlangisa, Mignon Du Plessis, Stephani Lo, Linda De Gouveia, Chrispin Chaguza, Martin Antonio, Brenda Kwambana-Adams, Jennifer Cornick, Dean B. Everett, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in …

Spatially Resolved Transcriptomics Of High-Grade Serous Ovarian Carcinoma, Elaine Stur, Sara Corvigno, Mingchu Xu, Ken Chen, Yukun Tan, Sanghoon Lee, Jinsong Liu, Emily Ricco, Daniel Kraushaar, Patricia Castro, Jianhua Zhang, Anil K Sood

Faculty, Staff and Students Publications

Bulk and single-cell RNA sequencing do not provide full characterization of tissue spatial diversity in cancer samples, and currently available in situ techniques (multiplex immunohistochemistry and imaging mass cytometry) allow for only limited analysis of a small number of targets. The current study represents the first comprehensive approach to spatial transcriptomics of high-grade serous ovarian carcinoma using intact tumor tissue. We selected a small cohort of patients with highly annotated high-grade serous ovarian carcinoma, categorized them by response to neoadjuvant chemotherapy (poor or excellent), and analyzed pre-treatment tumor tissue specimens. Our study uncovered extensive differences in tumor composition between the …

Variants Associated With Bedaquiline (Bdq) Resistance Identified In Rv0678 And Efflux Pump Genes In Mycobacterium Tuberculosis Isolates From Bdq Naïve Tb Patients In Pakistan, Dania Khalid Saeed, Sadia Shakoor, Safina Abdul Razzak, Zahra Hasan, Saba Faraz Sabzwari, Zahida Azizullah, Akber Kanji, Asghar Nasir, Samreen Shafiq, Najia Karim Ghanchi, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Mutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.
Methods: Based on convenience sampling, we studied 48 MTB clinical isolates …

Sars-Cov-2 Anti-Spike Antibodies After Vaccination In Pediatric Heart Transplantation: A First Report, Joseph A Spinner, Christopher L Julien, Lily Olayinka, William J Dreyer, Claire E Bocchini, Flor M Munoz, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.

METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.

RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a …

Clinical Influenza Testing Practices In Hospitalized Children At United States Medical Centers, 2015-2018., Mark W. Tenforde, Angela P. Campbell, Marian G. Michaels, Christopher J. Harrison, Eileen J. Klein, Janet A. Englund, Rangaraj Selvarangan, Natasha B. Halasa, Laura S. Stewart, Geoffrey A. Weinberg, John V. Williams, Peter G. Szilagyi, Mary A. Staat, Julie A. Boom, Leila C. Sahni, Monica N. Singer, Parvin H. Azimi, Richard K. Zimmerman, Monica M. Mcneal, H Keipp Talbot, Arnold S. Monto, Emily T. Martin, Manjusha Gaglani, Fernanda P. Silveira, Donald B. Middleton, Jill M. Ferdinands, Melissa A. Rolfes

Manuscripts, Articles, Book Chapters and Other Papers

At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

D-Dimer Testing In Covid-19: From Basics To Clinical Application, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

Sarscov-2 Serostatus Amongst Vaccinated Employees At A Pediatric Hospital System, Sridevi Devaraj, Izmarie Poventud-Fuentes, Matthew Girotto, Jermaine Monroe, Julie Boom, George Delclos, James Versalovic

Faculty, Staff and Students Publications

To gain insights on the heterogeneity of immune responses to vaccination against SARS-CoV-2 and to identify factors that could make individuals vulnerable to infection due to lack of response to vaccination, our hospital started offering free voluntary post-antibody testing against the spike protein IgG for all fully vaccinated employees.

Post-vaccination response against SARS-CoV-2 was assessed using the FDA-EUA approved VITROS anti-SARS-CoV-2 IgG immunometric assay specific to the spike protein.

Out of a total of 3266 antibody tests performed in fully vaccinated Texas Children’s, 99.4% had a positive antibody response to the spike protein. From the 21 employees (0.6%) that had …

Association Of Body Composition With Odds Of Breast Cancer By Molecular Subtype: Analysis Of The Mechanisms For Established And Novel Risk Factors For Breast Cancer In Nigerian Women (Mend) Study, Tomi Akinyemiju, Kelley Jones, Anjali Gupta, Taofik Oyekunle, Veeral Saraiya, April Deveaux, Omolola Salako, Allison Hall, Olusegun Alatise, Gabriel Ogun, Adewale Adeniyi, Omobolaji Ayandipo, Thomas Olajide, Olalekan Olasehinde, Olukayode Arowolo, Adewale Adisa, Oludolapo Afuwape, Aralola Olusanya, Aderemi Adegoke, Trygve O. Tollefsbol, Donna K. Arnett, H3 Africa Kidney Research Network, Adetola Daramola

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women.

METHODS: We estimated odds ratios (ORs) and 95% confidence intervals …

Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo

Biostatistics Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …

Prevalence And Determinants Of Inappropriate Antibiotic Dispensing At Private Drug Retail Outlets In Urban And Rural Areas Of Indonesia: A Mixed Methods Study, Luh Putu Lila Wulandari, Mishal Khan, Marco Liverani, Astri Ferdiana, Yusuf Ari Mashuri, Ari Probandari, Tri Wibawa, Neha Batura, Gill Schierhout, John Kaldor

Department of Pathology and Laboratory Medicine

Introduction: The aim of this mixed-method study was to determine the extent and determinants of inappropriate dispensing of antibiotics by licensed private drug retail outlets in Indonesia.
Methods: Standardised patients (SPs) made a total of 495 visits to 166 drug outlets (community pharmacies and drug stores) between July and August 2019. The SPs presented three clinical cases to drug outlet staff: parent of a child at home with diarrhoea; an adult with presumptive tuberculosis (TB); and an adult with upper respiratory tract infection (URTI). The primary outcome was the dispensing of an antibiotic without prescription, with or without the client …

Orofacial Manifestations Of Lyme Disease: A Systematic Review, Brenda Bradshaw, Kelsey M. Jones, Joleen M. Westerdale-Mcinnis, Holly Gaff

Dental Hygiene Faculty Publications

Purpose: Orofacial manifestations of Lyme disease can affect head and neck anatomical structures that are frequently examined by dental professionals. The purpose of this systematic review was to examine the literature for types and frequencies of orofacial manifestations documented in populations in the United States (US) with Lyme disease.

Methods: Four electronic databases (Dentistry and Oral Sciences, PubMed, Cinahl Plus, and Medline) were systematically searched during the summer of 2019 using keywords and MeSH terms to identify relevant studies. Search term alterations and synonyms were cross-checked using the US National Library of Medicine Unified Medical Language System Metathesaurus. Full-text, English …

Gut Integrity And Duodenal Enteropathogen Burden In Undernourished Children With Environmental Enteric Dysfunction, Zehra Jamil, Najeeha Talat Iqbal, Romana Idress, Zubair Ahmad, Kamran Sadiq, Junaid Iqbal, Sana Syed, Aneeta Hotwani, Furqan Kabir, Kumail Ahmed, Sheraz Ahmed, Fayyaz Umrani, Fatima Aziz, Adil Kalam, Syed Asad Ali

Department of Biological & Biomedical Sciences

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > -1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = -0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25th, 75th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.

The Role Of Interspecies Recombination In The Evolution Of Antibiotic-Resistant Pneumococci, Joshua C. D'Aeth, Mark Pg Van Der Linden, Lesley Mcgee, Herminia De Lencastre, Paul Turner, Jae-Hoon Song, Stephanie W. Lo, Rebecca A. Gladstone, Gps Consortium, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking …