Faculty Bibliography

Solid organ transplant (SOT) candidates and recipients are at risk of significant morbidity and mortality from infection, including those circulating in the community from unexpected outbreaks. In late 2018-summer of 2019, a measles outbreak occurred in the New York City area, with a total of 649 cases reported. We developed a systematic three-part approach to address measles risk in our adult SOT program through: 1) identification of non-immune adults living in outbreak ZIP codes, 2) education focused on risk reduction for patients from outbreak ZIP codes and 3) risk reduction for non-immune patients. All waitlisted or previously transplanted patients residing in outbreak areas received a measles patient education handout. The electronic medical record of patients born in or after 1957 was reviewed for serologic evidence of measles immunity. Measles immunity testing was performed in patients without documentation of immunity. Patients who tested non-immune were offered MMR vaccination or intravenous immunoglobulin depending on their transplant phase and risk profile. Thus, we demonstrate successful implementation of a systematic risk assessment during a large measles outbreak to identify and protect at-risk SOT patients. As vaccine hesitancy persists, our strategies may be increasingly relevant to transplant centers and those caring for immunocompromised patients.

Coronavirus disease 2019 (COVID-19) is associated with a high inflammatory burden that can induce severe respiratory disease among other complications; vascular and neurological damage has emerged as a key threat to COVID-19 patients. Risk of severe infection and mortality increases with age, male sex, and comorbidities including cardiovascular disease, hypertension, obesity, diabetes, and chronic pulmonary disease. We review clinical and neuroradiological findings in five patients with COVID-19 who suffered severe neurological disease and illustrate the pathological findings in a 7-year-old boy with COVID-19-induced encephalopathy whose brain tissue sample showed angiocentric mixed mononuclear inflammatory infiltrate. We summarize the structural and functional properties of the virus including the molecular processes that govern the binding to its membrane receptors and cellular entry. In addition, we review clinical and experimental evidence in patients and animal models that suggests coronaviruses enter into the central nervous system (CNS), either via the olfactory bulb or through hematogenous spread. We discuss suspected pathophysiological mechanisms including direct cellular infection and associated recruitment of immune cells and neurovirulence, at least in part, mediated by cytokine secretion. Moreover, contributing to the vascular and neurological injury, coagulopathic disorders play an important pathogenic role. We survey the molecular events that contribute to the thrombotic microangiopathy. We describe the neurological complications associated with COVID-19 with a focus on the potential mechanisms of neurovascular injury. Our thesis is that following infection, three main pathophysiological processes-inflammation, thrombosis, and vascular injury-are responsible for the neurological damage and diverse pathology seen in COVID-19 patients.

BACKGROUND AND PURPOSE/OBJECTIVE:Patients with the Coronavirus Disease of 2019 (COVID-19) are at increased risk for thrombotic events and mortality. Various anticoagulation regimens are now being considered for these patients. Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared. We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population. METHODS:Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study. Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist. Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications. RESULTS:We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37-83 years), 21.2% of whom were female. Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate. Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small- moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation. Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery. CONCLUSIONS:Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen.

Background. Staphylococcus aureus infection confers high mortality. S. aureus-colonized hospitalized patients are more likely to develop invasive infection and can transmit S. aureus to other patients in the absence of symptoms. Our health system has a baseline S. aureus colonization rate of 21% (MSSA and MRSA combined). To reduce risk of invasive S. aureus infection in our patients, we implemented an inpatient S. aureus screening and decolonization program. Methods. Interventions include universal S. aureus screening and targeted decolonization for all patients on the Medicine and Pediatrics inpatient services. Adult patients are screened at admission and change in the level of care; pediatric patients are screened weekly. S. aureus screening began incrementally by unit between 2016 and 2017, and extended to transplant units in 2018. All cultures are processed in the hospital microbiology lab for identification of MRSA and MSSA. S. aureus decolonization (mupirocin ointment in nares twice daily, chlorhexidine 2% wipes below the chin daily for 5 days) began in 2017 for patients with a central venous catheter, in intensive care unit or multibedded room. Decolonization was extended to all S. aureus-colonized patients beginning in June 2018, with involvement of a dedicated clinical nurse specialist. We compared compliance with screening and decolonization and the secondary outcome of MRSA bacteremia in the 6 month period before and after the addition of the clinical nurse specialist. Results. 21.5% of screened patients were colonized with S. aureus (82.4% MSSA, 17.6% MRSA). Screening compliance improved from 39.4% of eligible patients (N = 1805) to 52.1% (N = 2024) and decolonization increased from 18.6% of colonized patients to 41.2% comparing January-June 2018 with July-December 2018. The MRSA bacteremia rate fell from 0.2/1,000 patient-days in the first half of 2018 to 0.1/1,000 patient-days in the second half of 2018. Conclusion. A system-wide program that includes S. aureus screening and decolonization of hospitalized patients found that 21% of patients had S. aureus colonization. Screening and decolonization compliance increased with the introduction of a dedicated clinical nurse specialist, and the MRSA bloodstream infection rate fell

Background/UNASSIGNED:Asymptomatic Plasmodium falciparum infections are common in Malawi, however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Methods/UNASSIGNED:Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for two years. During follow-up visits, participants with malaria symptoms were tested and treated if positive. Samples from all visits were tested for parasites using both microscopy and PCR, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Results/UNASSIGNED:Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (HR 0.50, p < 0.001). When asymptomatic infections preceded malaria illness, newly acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly acquired infections (OR 1.4, 95%CI 1.3-1.5) than to persistent infections. Conclusions/UNASSIGNED:Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness but do not protect against disease when new infection occurs.

Few data exist on the incidence or duration of natural Plasmodium falciparum infections in high transmission settings. School-aged children (SAC) carry a disproportionate burden of infections, suggesting either increased incidence or duration. We estimated the incidence and duration of unique infections by age groups. The Mfera Cohort Study (2012-2017) had two years of follow-up with 120 participants tested monthly and during sick visits. Blood samples were collected to detect P. falciparum by microscopy and polymerase chain reaction. Positive samples underwent genotyping. Simulation was used to account for high non-detection of infection among low parasitemia infections, which increase in frequency with age. Adults had significantly fewer unique infections per person per year (median, 2.5) compared to SAC and under-five children (6.3 and 6.6, respectively). Over half of all genotypes were persistent. Infections lasted significantly longer in adults (median, 180 days) and SAC (median, 163 days) compared to under-five children (median, 97 days), after accounting for age-dependent, non-detection of infection. SAC acquired new infections at the same rate as under-five children, but maintained these infections for longer periods of time, similar to adults. This study provides new insights into P. falciparum infection dynamics that should be considered when designing malaria control strategies.

Background. The multiplex polymerase chain reaction respiratory pathogen panel (RPP) is used frequently in emergency departments (EDs) for the rapid identification of viruses and atypical bacteria of the respiratory tract. Its clinical value is unclear, as numerous studies have demonstrated that its use has a limited impact on antibiotic prescribing. We aimed to describe the relationship between RPP results and antibiotic prescribing rates for ED patients in our large academic medical center. Methods. We retrospectively analyzed the charts of 1,061 patients aged 18-90 who were treated and released from two EDs from January 1, 2015 to January 31, 2018 and underwent RPP testing. Patients with evidence of bacterial infection were excluded based on RPP detection of atypical bacteria and microbiological analysis of blood, urine, wound, and sputum specimens. The results of the RPP and the rates of subsequent respiratory pathogen-directed antibiotic prescribing (including ED and outpatient pharmacy orders) were compared. Results. Antibiotic prescription rates were 21.5% in patients who tested negative for any respiratory virus, compared with 14.5% in patients who tested positive (OR 0.70, P < 0.01). When positive RPPs were subdivided based on virus type (influenza and non-influenza) and compared with negative RPPs, only influenza-detection was associated with a significant reduction in antibiotic prescriptions (Table 1). Conclusion. In our study population, the presence of a respiratory virus detected by the RPP was correlated with a significant decrease in antibiotic prescribing. This effect was largely driven by influenza detection. This demonstrates that at our institution, the RPP may have a role in reducing unnecessary antibiotic utilization, but providers need further guidance in the interpretation of non-influenza respiratory virus positivity. (Table Presented)