COVID-19

In response to the COVID-19 pandemic, IDCRP researchers activated an observational, longitudinal cohort study (Epidemiology, Immunology and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential [EPICC]) at six military treatment facilities within the United States and are expanding to others.  This study is capturing clinical and laboratory data from patients with confirmed COVID-19, as well as persons under investigation to better understand the natural history of SARS-CoV-2 infection, including the clinical, virologic, and immunologic determinants of severe disease. Findings from this observational study will address numerous gaps in the current understanding of COVID-19 and support the development of treatment and prevention strategies that will not only benefit military personnel, but also civilian populations.   

In addition, IDCRP clinical research sites are participating in a adaptive, randomized-controlled trial to evaluate the efficacy of Remdesivir (ACTT-1) and of Remdesivir + Baricitinib vs. Remdesivir (ACTT-2) among individuals hospitalized with COVID-19, sponsored by the National Institute of Allergy and Infectious Diseases. Preliminary results from the ACTT-1 trial have been published in the New England Journal of Medicine (NEJM).  For more information, please follow the links below.

Links

NEJM Preliminary Results from ACTT-1 

ACTT-1 ClinicalTrials.gov: NCT04280705 

ACTT-2 ClinicalTrials.gov: NCT04401579

Antibiotic Resistance

In September 2014, the White House released an Executive Order to establish a national task force to oversee efforts to control antimicrobial resistance. This document emphasized the rise of antibiotic-resistant bacteria as they become an increasingly serious threat to public health and the economy.  The President’s Council of Advisors on Science and Technology also issued the National Strategy for Combating Antimicrobial-Resistant Bacteria.

Infections related to antimicrobial resistance (such as Acinetobacter and carbepenem-resistant Enterobacteriaceae) in the traumatic wounds of our injured service members have been a major source associated with the spread of drug- resistant bugs within the Military Health System. Fifty percent or more of the skin and soft tissue infections that affect our troops training at Fort Benning, or serving on ships or submarines, are methicillin-resistant Staphylococcus aureus (MRSA).  Strains of the gonorrhea bacteria infecting service members may be resistant to many of the oral antibiotics previously used to control them, now requiring intramuscular shots for a cure.

"Health Policy Brief: Antibiotic Resistance," Health Affairs, May 21, 2015.

 

Diarrheal Diseases

Diarrhea, a scourge upon humanity since preliterate times, has been the particular nemesis of military forces. The Armed Forces of the United States have been in the forefront in the diagnosis, treatment, and prevention of diarrheal illness. U.S. military scientists and physicians implemented the first mandatory typhoid inoculation program, contributed to advances in water chlorination, and pioneered the use of antibiotics for typhoid fever. U.S. Navy physicians refined the intravenous treatment of cholera, reducing the death rate from 20% to less than 1%. Their studies of electrolyte and fluid balance in cholera, and the subsequent development of oral rehydration therapy for cholera and other diarrheal illness, have saved millions of lives worldwide. U.S. Army researchers refuted the desquamation theory of cholera pathogenesis, isolated the cholera exotoxin, and developed improved cholera vaccines. U.S. Army and Navy researchers pioneered the use of antibiotics for the treatment of typhoid fever, made major contributions to the treatment of dysentery, developed algorithms for the treatment of traveler’s diarrhea, and continue active development of traveler’s diarrhea and dysentery vaccines. U.S. military diarrheal research has directly contributed to the welfare of hundreds of millions of people.

Flu

Recent Findings from the IDCRP Acute Respiratory Infections Research Area:

Beigel JH, Tebas P, Elie-Turenne MC, Bajwa E, Bell TE, Cairns CB, Shoham S,Deville JG, Feucht E, Feinberg J, Luke T, Raviprakash K, Danko J, O'Neil D, Metcalf JA, King K, Burgess TH, Aga E, Lane HC, Hughes MD, Davey RT; IRC002 Study Team. Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study. Lancet Respir Med. 2017 Jun;5(6):500-511.

Background: Influenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports sugget that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza. 

Fairchok M, Schofield C, Chen WJ, et al. Inverse correlation between 25-OH Vitamin D levels and severity of viral respiratory illness in infants. Journal of Infectious Disease and Epidemiology. 2017, 2(1): 1-7

Background: 25-OH vitamin D levels above 30 ng/mL activate HCAP-18, which impacts the immune response to respiratory viruses. While emerging data suggests a link between low levels of 25-OH vitamin D and an increased incidence of respiratory infections, the relationship between these levels and severity of infection is unknown. We hypothesized that infants with insufficient 25-OH vitamin D levels would have more severe viral respiratory infections.

Powers J, Bacci E, Guerrero, M, et al. Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients Evaluation of the performance properties of the Influenza patient-reported outcomes instrument (Flu-PRO) in patients with Influenza-like Illness (ILI). Value in Health.  (In press)  2017

Gonorrhea

Gonococcal Resistance

Gonococcal (GC) infections have re-emerged as a significant global public health problem. The IDCRP Sexually Transmitted Infections (STI) Research Area (RA) is leading a global effort to identify the prevalence and risk factors of drug resistant GC infections among US military seeking care in a wide variety of geographic settings, currently from several sites across the globe. The IDCRP is the Coordinating Center for the DoD Gonococcal Repository & Reference Laboratory (GC-RRL)  in Dr. Ann Jerse’s lab at USU. An IDCRP protocol outlines the Program's role as Coordinating Center for a global GC Repository, with efforts including study site development; human subjects protection assistance; comparison protocols for GC microbiology and antimicrobial resistance testing technical support; standard operating procedures for isolate and data management and transfer; utilization of repository; and interfacing of microbiology and clinical research. This effort also aims to test the sensitivity of early stream urine culture and identify the prevalence of Chlamydia by urine nucleic acid amplification test (NAAT) testing among symptomatic and asymptomatic US military service members. This project is supported as an AFHSB GEIS Sustainment 3-year workplan.

HIV

Due to mandatory routine HIV testing, the active duty force in the US is a screened population.  This unique aspect of the military setting allows understanding of early events and the time course of HIV disease. Because this population is also healthy, racially diverse, and educated, with open access to healthcare and medications, IDCRP is able to conduct investigations without many confounders that plague other cohort studies, such as drug abuse, non-compliance, and poor follow-up.  Combined, these assets have resulted in hundreds of published manuscripts that have advanced the fields of HIV science and care.  At present, these aspects are being leveraged in many studies, including toward understanding and predicting individual risk of non-AIDS complications.

Identify, treat, and prevent HIV associated neurocognitive disorders in the US military health care system

The principal objective of IDCRP’s human immunodeficiency virus (HIV) research program is to build evidence toward maintaining the health, function, and longevity of HIV+ active duty service members and beneficiaries. This is primarily accomplished through our 28-year U.S. Military HIV Natural History Study, a resource hailed as a “national treasure,” having been leveraged to address contemporary HIV/AIDS-related issues. 

As individuals live longer with HIV, thanks to antiretroviral therapy, attention has turned to conditions other than AIDS. HIV-associated neurocognitive disorder (HAND) has emerged as an important concern for the military and the broader population, where it affects up to 50% of HIV+ individuals. In a recent IDCRP study, nearly 20% of HIV+ military members met criteria for HAND. Neurocognitive domains affected by HAND (motor function/dexterity, memory, learning, recall, and executive function) are highly relevant to military duties, and concern over impairment has been a key factor in restricting duty status of HIV+ personnel. This affects not only the individual service member, but is a significant loss to the military of a trained asset; our study may help inform the revision of this policy through an improved understanding of HAND.

In collaboration with the Walter Reed National Military Medical Center Bethesda, the Naval Medical Center San Diego, the National Institute of Neurologic Disorders and Stroke, and five other NIH institutes and centers, IDCRP have undertaken a 5-year study of military HIV+ individuals to better understand the causes and development of HAND, improve diagnosis and screening, and form the basis for studies of treatment and prevention.  Partnerships with other DoD and HJF programs, including the U.S. Military HIV Research Program (MHRP) and USU Center for Neuroscience and Regenerative Medicine (CNRM), as well as Veterans Affairs (VA) investigators, are being built and strengthened.

The military HIV+ population, comprised of young, healthy, racially diverse individuals with little illicit drug use and fewer mental health illnesses than other studied populations, offers an exciting opportunity to better understand HAND.  IDCRP will extensively characterize the cognitive health of volunteers over time through comprehensive neuropsychiatric testing supplemented by neuroimaging and analysis of cerebrospinal fluid. Initial investigations will include validation of a HAND screening tool developed from our prior study and evaluation of potential biomarkers to improve the objective diagnosis of HAND. With far-reaching goals, IDCRP’s study will benefit both the military and broader population.

Invasive Fungal Infections

Beginning in 2009, physicians at military hospitals that received combat-wounded individuals noted an increasing frequency of blast trauma patients with penetrating wounds sustained in southern Afghanistan diagnosed with the unexpected complication of invasive fungal wound infections (IFIs). These infections are characterized by recurrent wound tissue necrosis and often result in significant morbidity (e.g., limb amputations) and/or mortality. The Infectious Disease Clinical Research Program (IDCRP) at the Uniformed Services University of the Health Sciences (USU) led the Department of Defense outbreak investigation of these cases through their Trauma Infectious Disease Outcomes Study (TIDOS) in conjunction with orthopedic, trauma, and infectious disease services. During periods in 2010-2012, the IFI incidence rates were as high as 10-12% for intensive care unit admissions at Landstuhl Regional Medical Center in Germany (hospital where patients received care after medical evacuation from combat zone prior to transfer back to the United States), coincident with high blast casualty rates.  Based upon information from the initial outbreak investigation, the Joint Trauma System developed clinical practice guidelines (CPG) on IFI prevention and management. TIDOS analyses have since confirmed the independent IFI risk factors cited in the JTS CPG, including blast injuries sustained while on foot patrol, traumatic above knee amputations, and large-volume (>20 units) blood transfusions within first 24 hours after injury. In addition, through collaboration by TIDOS and hospital clinicians, a local CPG was implemented at Landstuhl, which greatly reduced the time to diagnosis and treatment initiation. Furthermore, a recent TIDOS analysis demonstrated the significant negative impact of IFIs on the timing of wound closure and healing. Aggressive surgical debridements remain the primary therapy accompanied by empiric systemic antifungal therapy when there is strong suspicion of an IFI. Other recommendations include: 1) early tissue sampling for wound histopathology and fungal cultures, 2) early consultation with infectious disease specialists and 3) coordination with surgical pathology and clinical microbiology.

Publications

Warkentien TE, Shaikh F, Weintrob AC, Rodriguez CJ, Murray CK, Lloyd BA, Ganesan A, Aggarwal D, Carson ML, and Tribble DR on behalf of the IDCRP TIDOS Group.  Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections. Journal of Clinical Microbiology. 2015.

Warkentien T, Rodriguez C, Lloyd B, et al. Invasive Fungal Infections following Combat-related InjuriesClinical Infectious Diseases. 2012; 55(11):1441-1449.

Rodriguez C, Weintrob AC, Shah J, et al. Risk factors associated with invasive fungal infections in combat traumaSurgical Infections. 2014; 15(5):521-526.

Lloyd BA, Weintrob AC, Rodriguez C, et al. Effect of early screening for invasive fungal infections in U.S. service members with explosive blast injuriesSurgical Infections. 2014; 15(5):619-626.

Tribble DR and Rodriguez CJ. Combat-related invasive fungal wound infectionsCurrent Fungal Infection Reports. 2014; 8(4):277-286.

Rodriguez CJ, Weintrob AC, Dunne JR, et al. Clinical Relevance of Mold Culture Positivity With and Without Recurrent Wound Necrosis Following Combat-Related InjuriesJournal of Trauma. 2014; 77(5):769-773.

Weintrob AC, Weisbrod AB, Dunne JR, et al. Combat trauma-associated invasive fungal wound infections: Epidemiology and clinical classificationEpidemiology and Infection. 2015; 143(1):214-224.