Faculty Bibliography

BACKGROUND:Osteoarticular infections (OAIs) account for 10%-20% of extrapulmonary Mycobacteria tuberculosis (MTB) complex infections in children and 1%-2% of all pediatric tuberculosis infections. Treatment regimens and durations typically mirror recommendations for other types of extrapulmonary MTB, but there are significant variations in practice, with some experts suggesting a treatment course of 12 months or longer. METHODS:We conducted a retrospective review of children diagnosed with MTB complex OAI and cared for between December 31, 1992, and December 31, 2018, at a tertiary care pediatric hospital near the United States-Mexico border. RESULTS:We identified 21 children with MTB complex OAI during the study period. Concurrent pulmonary disease (9.5%), meningitis (9.5%), and intra-abdominal involvement (14.3%) were all observed. MTB complex was identified by culture from operative samples in 15/21 children (71.4%); 8/15 (53.3%) cultures were positive for Mycobacterium bovis. Open bone biopsy was the most common procedure for procurement of a tissue sample and had the highest culture yield. The median duration of antimicrobial therapy was 52 weeks (interquartile range, 46-58). Successful completion of therapy was documented in 15 children (71.4%). Nine children (42.9%) experienced long-term sequelae related to their infection. CONCLUSION/CONCLUSIONS:Among the 21 children with MTB complex OAI assessed, 8 of 15 (53.3%) children with a positive tissue culture had M. bovis, representing a higher percentage than in previous reports and potentially reflecting its presence in unpasteurized dairy products in the California-Baja region. Bone biopsy produced the highest culture yield in this study. Given the rarity of this disease, multicenter collaborative studies are needed to improve our understanding of the presentation and management of pediatric MTB complex OAI.

OBJECTIVES/OBJECTIVE:This article is one of a series on acute, severe diseases of humans caused by emerging viruses for which there are no or limited licensed medical countermeasures. We approached this summary on South American Hemorrhagic Fevers (SAHF) from a clinical perspective that focuses on pathogenesis, clinical features, and diagnostics with an emphasis on therapies and vaccines that have demonstrated potential for use in an emergency situation through their evaluation in nonhuman primates (NHPs) and/or in humans. METHODS:A standardized literature review was conducted on the clinical, pathological, vaccine, and treatment factors for SAHF as a group and for each individual virus/disease. RESULTS:We identified 2 treatments and 1 vaccine platform that have demonstrated potential benefit for treating or preventing infection in humans and 4 other potential treatments currently under investigation. CONCLUSION/CONCLUSIONS:We provide succinct summaries of these countermeasures to give the busy clinician a head start in reviewing the literature if faced with a patient with South American Hemorrhagic Fever. We also provide links to other authoritative sources of information.

During the 2014-16 W. Africa outbreak of Ebola virus disease, the US had no mechanism to study investigational treatments rapidly, and individual institutions provided investigational products as emergency investigational new drugs (eINDs). Consequently, determining the optimum care for the disease was not achieved. The Special Pathogens Research Network (SPRN) was established to create the infrastructure to conduct multi-center clinical research to improve outcomes for emerging special pathogens. This included establishing a central IRB at the University of Nebraska Medical Center and 10 collaborative sites across the US. As the COVID-19 outbreak began, the SPRN quickly executed three protocols. We share efficiencies and ideas for future improvements. At the onset of the COVID-19 outbreak, the network established three clinical protocols: 1) a "natural history" protocol for collecting discarded specimens and patient data; 2) a NIAID-sponsored randomized placebo controlled trial with the antiviral drug Remdesivir; and 3) a prospective data and sample collection protocol. We evaluated the IRB approval timeline centrally and at partner sites and the rapidity of first subject enrollment. We assessed aspects that facilitated or hindered the adoption of the different protocols across the network. Central and other site IRB approvals occurred expeditiously. Subjects were enrolled within one day of site approval in all three studies. UNMC enrolled the first US patient in the Remdesivir RCT. IRB approval occurred at all 10 sites within 32 days of central IRB approval; however, contracts for data use and material transfer agreements (DUAs and MTAs) lagged. Consequently, some sites developed their own natural history protocols, rather than adopt a network protocol. In conclusion, the SPRN pre-existing network of 10 sites was able to enroll subjects rapidly at the start of the outbreak, functioning as one unit in many respects. Contracting for specimen collection protocols has proved challenging and thus has impacted the ability to organize and deliver. This continues to be addressed

Understanding the role that children play in the clinical burden and propagation of severe acute respiratory syndrome coronavirus 2, responsible for coronavirus disease 2019 (COVID-19) infections, is emerging. While the severe manifestations and acute clinical burden of COVID-19 have largely spared children compared with adults, understanding the epidemiology, clinical presentation, diagnostics, management, and prevention opportunities and the social and behavioral impacts on child health is vital. Foremost is clarifying the contribution of asymptomatic and mild infections to transmission within the household and community and the clinical and epidemiologic significance of uncommon severe post-infectious complications. Here, we summarize the current knowledge, identify resources, and outline research opportunities. Pediatric infectious diseases clinicians have a unique opportunity to advocate for the inclusion of children in epidemiological, clinical, treatment, and prevention studies to optimize their care as well as to represent children in the development of guidance and policy during pandemic response.

Background/UNASSIGNED:Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. Methods/UNASSIGNED:We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14. Results/UNASSIGNED: = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay. Conclusions/UNASSIGNED:In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

The human immune response to eastern equine encephalitis virus (EEEV) infection is poorly characterized due to the rarity of infection. We examined the humoral and cellular immune response to EEEV acquired from an infected donor via liver transplantation. Both binding and highly neutralizing antibodies to EEEV as well as a robust EEEV-specific IgG memory B cell response were generated. Despite triple-drug immunosuppressive therapy, a virus-specific CD4+ T cell response, predominated by interferon-γ production, was generated. T cell epitopes on the E2 envelope protein were identified by interferon-γ ELISpot. Although these results are from a single person who acquired EEEV by a non-traditional mechanism, to our knowledge this work represents the first analysis of the human cellular immune response to EEEV.