Viral Acute Lower Respiratory Tract Infections (ALRI) in Rural Bangladeshi Children Prior to the COVID-19 Pandemic.

Background: Acute lower respiratory tract infections (ALRIs) remain the leading infectious cause of death among children < 5 years, with viruses contributing to a large proportion of cases. Little is known about the epidemiology and etiology of viral ALRI in rural Bangladesh.

Methods: We enrolled 3- to 23-month-old children with ALRIs attending a subdistrict hospital outpatient clinic in Sylhet district in Bangladesh.

Emerging Tick-borne Infections in the Upper Midwest and Northeast United States Among Patients With Suspected Anaplasmosis.

Background: Emerging tick-transmitted illnesses are increasingly recognized in the United States (US). To identify multiple potential tick-borne pathogens in patients from the Upper Midwest and Northeast US with suspected anaplasmosis, we used state-of-the-art methods (polymerase chain reaction [PCR] and paired serology) to test samples from patients in whom anaplasmosis had been excluded.

Methods: Five hundred sixty-eight patients without anaplasmosis had optimal samples available for confirmation of alternative tick-borne pathogens, including PCR and/or paired serology (acute-convalescent interval ≤42 days).

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics.

RADx-UP Testing Core: Access to COVID-19 Diagnostics in Community-Engaged Research with Underserved Populations.

Research on the COVID-19 pandemic revealed a disproportionate burden of COVID-19 infection and death among underserved populations and exposed low rates of SARS-CoV-2 testing in these communities. A landmark National Institutes of Health (NIH) funding initiative, the Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program, was developed to address the research gap in understanding the adoption of COVID-19 testing in underserved populations. This program is the single largest investment in health disparities and community-engaged research in the history of the NIH.

Use of Structured Electronic Health Records Data Elements for the Development of Computable Phenotypes to Identify Potential Adverse Events Associated with Intravenous Immunoglobulin Infusion.

Introduction: Detection of adverse reactions to drugs and biologic agents is an important component of regulatory approval and post-market safety evaluation. Real-world data, including insurance claims and electronic health records data, are increasingly used for the evaluation of potential safety outcomes; however, there are different types of data elements available within these data resources, impacting the development and performance of computable phenotypes for the identification of adverse events (AEs) associated with a given therapy.

Objective: To evaluate the utility of different types of data elements to the performance of computable phenotypes for AEs.

Effectiveness of the 10-valent pneumococcal conjugate vaccine against radiographic pneumonia among children in rural Bangladesh: A case-control study.

Background: Pneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh.

Previously Derived Host Gene Expression Classifiers Identify Bacterial and Viral Etiologies of Acute Febrile Respiratory Illness in a South Asian Population.

Background: Pathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI in cohorts of European and African descent. We determined classifier performance in a South Asian cohort.

Rickettsioses as Major Etiologies of Unrecognized Acute Febrile Illness, Sabah, East Malaysia.

Orientia tsutsugamushi, spotted fever group rickettsioses, and typhus group rickettsioses (TGR) are reemerging causes of acute febrile illness (AFI) in Southeast Asia. To further delineate extent, we enrolled patients >4 weeks of age with nonmalarial AFI in Sabah, Malaysia, during 2013-2015. We confirmed rickettsioses (past or acute, IgG titer >160) in 126/354 (36%) patients.

Optimization and Evaluation of a Multiplex Quantitative PCR Assay for Detection of Nucleic Acids in Human Blood Samples from Patients with Spotted Fever Rickettsiosis, Typhus Rickettsiosis, Scrub Typhus, Monocytic Ehrlichiosis, and Granulocytic Anaplasmosis.

Spotted fever group rickettsioses (SFGR), typhus group rickettsioses (TGR), scrub typhus (caused by ), ehrlichiosis, and anaplasmosis often present as undifferentiated fever but are not treated by agents (penicillins and cephalosporins) typically used for acute febrile illness. Inability to diagnose these infections when the patient is acutely ill leads to excess morbidity and mortality. Failure to confirm these infections retrospectively if a convalescent blood sample is not obtained also impairs epidemiologic and clinical research.

Geospatial analysis of dengue emergence in rural areas in the Southern Province of Sri Lanka.

Background: Dengue is a major cause of acute febrile illness in Sri Lanka. Dengue has historically been considered an urban disease. In 2012-2013, we documented that acute dengue was surprisingly associated with self-reported rural residence in the Southern Province of Sri Lanka.

Chest radiograph reading panel performance in a Bangladesh pneumococcal vaccine effectiveness study.

Introduction: To evaluate WHO chest radiograph interpretation processes during a pneumococcal vaccine effectiveness study of children aged 3-35 months with suspected pneumonia in Sylhet, Bangladesh.

Methods: Eight physicians masked to all data were standardised to WHO methodology and interpreted chest radiographs between 2015 and 2017. Each radiograph was randomly assigned to two primary readers.

Respiratory Viral Infection: An Underappreciated Cause of Acute Febrile Illness Admissions in Southern Sri Lanka.

The contribution of respiratory viruses to acute febrile illness (AFI) burden is poorly characterized. We describe the prevalence, seasonality, and clinical features of respiratory viral infection among AFI admissions in Sri Lanka. We enrolled AFI patients ≥ 1 year of age admitted to a tertiary care hospital in southern Sri Lanka, June 2012-October 2014.

Development and Clinical Validation of a Multiplex Real-Time Quantitative PCR Assay for Human Infection by Anaplasma phagocytophilum and Ehrlichia chaffeensis.

Background: Human granulocytic anaplasmosis (HGA), caused by , and human monocytic ehrlichiosis (HME), caused by , often present as undifferentiated fever but are not treated by typical empiric regimens for acute febrile illness. Their role as agents of vector-borne febrile disease in tropical regions is more poorly studied than for other rickettsial infections. Limitations in diagnosis have impaired epidemiologic and clinical research and needless morbidity and mortality occur due to untreated illness.

Evaluation of the WHO 2009 classification for diagnosis of acute dengue in a large cohort of adults and children in Sri Lanka during a dengue-1 epidemic.

Background: Dengue is a leading cause of fever and mimics other acute febrile illnesses (AFI). In 2009, the World Health Organization (WHO) revised criteria for clinical diagnosis of dengue.

Methodology/principal Findings: The new WHO 2009 classification of dengue divides suspected cases into three categories: dengue without warning signs, dengue with warning signs and severe dengue.

Estimated seroprevalence of Anaplasma spp. and spotted fever group Rickettsia exposure among herders and livestock in Mongolia.

Background: To better understand the epidemiology of tick-borne disease in Mongolia, a comprehensive seroprevalence study was conducted investigating exposure to Anaplasma spp. and spotted fever group (SFG) Rickettsia spp. in nomadic herders and their livestock across three provinces from 2014 to 2015.

Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka.

In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI).

Analysis of Dengue Serotype 4 in Sri Lanka during the 2012-2013 Dengue Epidemic.

The four serotypes of dengue virus (DENV-1, -2, -3, and -4) have had a rapidly expanding geographic range and are now endemic in over 100 tropical and subtropical countries. Sri Lanka has experienced periodic dengue outbreaks since the 1960s, but since 1989 epidemics have become progressively larger and associated with more severe disease. The dominant virus in the 2012 epidemic was DENV-1, but DENV-4 infections were also commonly observed.

First Identification and Description of Rickettsioses and Q Fever as Causes of Acute Febrile Illness in Nicaragua.

Background: Rickettsial infections and Q fever present similarly to other acute febrile illnesses, but are infrequently diagnosed because of limited diagnostic tools. Despite sporadic reports, rickettsial infections and Q fever have not been prospectively studied in Central America.

Methodology/principal Findings: We enrolled consecutive patients presenting with undifferentiated fever in western Nicaragua and collected epidemiologic and clinical data and acute and convalescent sera.

Unsuspected Dengue as a Cause of Acute Febrile Illness in Children and Adults in Western Nicaragua.

Background: Dengue is an emerging infectious disease of global significance. Suspected dengue, especially in children in Nicaragua's heavily-urbanized capital of Managua, has been well documented, but unsuspected dengue among children and adults with undifferentitated fever has not.

Methodology/principal Findings: To prospectively study dengue in semi-urban and rural western Nicaragua, we obtained epidemiologic and clinical data as well as acute and convalescent sera (2 to 4 weeks after onset of illness) from a convenience sample (enrollment Monday to Saturday daytime to early evening) of consecutively enrolled patients (n = 740) aged ≥ 1 years presenting with acute febrile illness.

Emergence of Epidemic Dengue-1 Virus in the Southern Province of Sri Lanka.

Background: Dengue is a frequent cause of acute febrile illness with an expanding global distribution. Since the 1960s, dengue in Sri Lanka has been documented primarily along the heavily urbanized western coast with periodic shifting of serotypes. Outbreaks from 2005-2008 were attributed to a new clade of DENV-3 and more recently to a newly introduced genotype of DENV-1.

Use of Peptide-Based Enzyme-Linked Immunosorbent Assay followed by Immunofluorescence Assay To Document Ehrlichia chaffeensis as a Cause of Febrile Illness in Nicaragua.

Ehrlichia chaffeensis, the etiologic agent of human monocytic ehrlichiosis (HME), has been extensively studied as a cause of acute febrile illness and an emerging tick-borne zoonosis in the United States. Limited data suggest its presence in other regions, including Central and South America but not Nicaragua to date. Diagnosis of E.

Use of Rapid Influenza Testing to Reduce Antibiotic Prescriptions Among Outpatients with Influenza-Like Illness in Southern Sri Lanka.

Acute respiratory tract infections (ARTIs) are a common reason for unnecessary antibiotic prescriptions worldwide. Our objective was to determine if providing access to rapid influenza test results could reduce antibiotic prescriptions for ARTIs in a resource-limited setting. We conducted a prospective, pre-post study from March 2013 to October 2014.

An under-recognized influenza epidemic identified by rapid influenza testing, southern Sri Lanka, 2013.

Influenza accounts for a large burden of acute respiratory tract infections in high-income countries; data from lower-income settings are limited due to lack of confirmatory testing. Consecutive outpatients presenting to the largest tertiary care hospital in southern Sri Lanka were surveyed for influenza-like illness (ILI), defined as acute onset of fever ≥ 38.0°C and cough.