Immunocompromised Adults Research Articles

Downregulation of A20 Expression Increases the Immune Response and Apoptosis and Reduces Virus Production in Cells Infected by the Human Respiratory Syncytial Virus.

Human respiratory syncytial virus (HRSV) causes severe lower respiratory tract infections in infants, the elderly, and immunocompromised adults. Regulation of the immune response against HRSV is crucial to limiting virus replication and immunopathology. The A20/TNFAIP3 protein is a negative regulator of nuclear factor kappa B (NF-κB) and interferon regulatory factors 3/7 (IRF3/7), which are key transcription factors involved in the inflammatory/antiviral response of epithelial cells to virus infection. Here, we investigated the impact of A20 downregulation or knockout on HRSV growth and the induction of the immune response in those cells. Cellular infections in which the expression of A20 was silenced by siRNAs or eliminated by gene knockout showed increased inflammatory/antiviral response and reduced virus production. Similar results were obtained when the expression of A20-interacting proteins, such as TAX1BP1 and ABIN1, was silenced. Additionally, downregulation of A20, TAX1BP1, and ABIN1 increased cell apoptosis in HRSV-infected cells. These results show that the downregulation of A20 expression might contribute in the control of HRSV infections by potentiating the early innate immune response and increasing apoptosis in infected cells.

Measles: An Overview of a Re-Emerging Disease in Children and Immunocompromised Patients.

Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children under the age of 5 years and immunocompromised adults. The increase in measles incidence is caused by the ongoing reduction of vaccination coverage. This event has triggered public and scientific interest. For this reason, we reviewed the pathophysiology of measles infection, focusing on mechanisms by which the virus spreads systemically through the host organism. By reaching the lymphocytes from the airways through a “trojan horse” strategy, measles induces an immunosuppression status. H and F glycoproteins, both expressed in the envelope, ensure attachment of the virus to host cells and spreading from one cell to another by binding to several receptors, as described in detail. The severity of the disease depends both on the age and underlying conditions of patients as well as the social and health context in which epidemics spread, and is often burdened by sequelae and complications that may occur several years after infection. Particular attention was paid to special groups that are more susceptible to severe or atypical measles. An overview of microbiology, symptoms, diagnosis, prevention, and treatment completes and enriches the review.

Clinical, imaging, endoscopic findings, and management of patients with CMV colitis: a single-institute experience.

To evaluate clinical, laboratory, imaging, endoscopic findings, treatment, and outcomes of patients with CMV colitis. The electronic medical records of 652 patients who had an impression of colitis of unspecified etiology via endoscopic findings between 2011 and 2019 were retrospectively reviewed. There were 9 patients with biopsy-proven CMV colitis and associated CT imaging performed within 1month of diagnosis. Demographic data, past medical history, symptoms, laboratory, imaging, endoscopic and biopsy findings, colitis-related adverse events, treatment, and management were recorded. Within the group of 9 patients (2 men; median age, 60years), all were in an immunosuppressed state (8/9 on immunosuppressive medication regimen and 1/9 with untreated AIDS). Presenting symptoms of CMV colitis included bloody stools (9/9), abdominal pain (7/9), and diarrhea (7/9). The most common imaging findings were pericolonic stranding (9/9) and bowel wall thickening (9/9). Endoscopic evaluation noted inflammation (9/9), ulceration (9/9), and erythema (8/9) as the most prevalent impressions. As determined by both imaging and endoscopy, the sigmoid colon was most commonly affected. Patients were treated with valganciclovir alone (3/9) or ganciclovir followed by valganciclovir (6/9). Outcomes included perforated colon (1/9), persistent colitis (3/9), discharge to hospice (1/9), and resolution (4/9). CMV colitis is generally associated with an immunosuppressed state. Imaging and endoscopic findings can mimic inflammatory, ischemic, and infectious colitides. However, CMV colitis should be included in the differential diagnosis in immunocompromised adults who present to emergency department with bloody stools, acute abdominal pain or diarrhea, and have bowel wall thickening and pericolonic stranding on imaging.

Filament genes and biofilm formation in Streptococcus agalactiae

Streptococcus agalactiae is the prominent cause of bacterial sepsis and meningitis in neonates and is also the contributing agent of a number of serious infections in immunocompromised adults. S. agalactiae run into multiple niches through an infection, suggesting that regulatory mechanisms control the expression of specific virulence factors in this bacterium. Like other Gram-positive bacteria, Group B streptococcus (GBS) can create three-dimensional structures, such as biofilms that can increase their ability to colonize and maintain in the host. Biofilm formation has been investigated by GBS under laboratory conditions and is clearly controlled under environmental conditions. Significantly, antibodies that act against the proteins of the pili can prevent the creation of biofilms. The consequences of biofilm formation in the field of asymptomatic colonization and its dissemination remain invasive and its details are examined. The complex pathway leading to biofilm development in different species of microorganisms involves the contribution of both environmental conditions and genetic factors. Numerous genes or factors have been identified as being essential or required for biofilm formation. Such genes include those that regulate surface-exposed proteins, appendages, such as pili or fimbriae, and extracellular polymeric substance (EPS) matrix materials. Pilus seems to play a key role in adhesion and attachment to host cells both in Gram-negative and Gram-positive pathogens. Their involvement in the transition from planktonic growth to a surface-attached multicellular community has also been demonstrated in many studies. Three different types of pili have been characterized in GBS as potential virulence factors. For example, type 2a pili are involved in biofilm formation.

Outcome and prognostic factors of Pneumocystis jirovecii pneumonia in immunocompromised adults: a prospective observational study

BackgroundPneumocystis jirovecii pneumonia (PJP) remains a severe disease associated with high rates of invasive mechanical ventilation (MV) and mortality. The objectives of this study were to assess early risk factors for severe PJP and 90-day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis.MethodsWe prospectively enrolled all patients meeting pre-defined diagnostic criteria for PJP admitted at Nantes university hospital, France, from January 2012 to January 2017. Diagnostic criteria for PJP were typical clinical features with microbiological confirmation of P. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (PCR) assay. Severe PJP was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least 50% FiO2, non-invasive ventilation, or MV.ResultsOf 2446 respiratory samples investigated during the study period, 514 from 430 patients were positive for P. jirovecii. Of these 430 patients, 107 met criteria for PJP and were included in the study, 53 (49.5%) patients had severe PJP, including 30 who required MV. All patients were immunocompromised with haematological malignancy ranking first (n = 37, 35%), followed by solid organ transplantation (n = 27, 25%), HIV-infection (n = 21, 20%), systemic diseases (n = 13, 12%), solid tumors (n = 12, 11%) and primary immunodeficiency (n = 6, 8%). By multivariate analysis, factors independently associated with severity were older age (OR, 3.36; 95% CI 1.4–8.5; p < 0.05), a P. jirovecii microscopy-positive result from bronchoalveolar lavage (BAL) (OR, 1.3; 95% CI 1.54–9.3; p < 0.05); and absence of a BAL fluid alveolitis profile (OR, 3.2; 95% CI 1.27–8.8; p < 0.04). The 90-day mortality rate was 27%, increasing to 50% in the severe PJP group. Factors independently associated with 90-day mortality were worse SOFA score on day 1 (OR, 1.05; 95% CI 1.02–1.09; p < 0.001) whereas alveolitis at BAL was protective (OR, 0.79; 95% CI 0.65–0.96; p < 0.05). In the subgroup of HIV-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher 90-day mortality (OR, 1.25; 95% CI 1.02–1.55; p < 0.05).ConclusionsOlder age and P. jirovecii oocysts at microscopic examination of BAL were independently associated with severe PJP. Both initial PJP severity as evaluated by the SOFA score and viral co-infection predicted 90-day mortality. Alveolitis at BAL examination was associated with less severe PJP. The pathophysiological mechanism underlying this observation deserves further investigation.

The effect of pneumococcal immunization on total and antigen-specific B cells in patients with severe chronic kidney disease

BackgroundWhile the 23-valent pneumococcal polysaccharide vaccine (PPV23) is routinely used in Canada and some other countries to prevent pneumococcal infection in adults with chronic kidney disease (CKD), patients develop a suboptimal antibody response to PPV23 due to their immune dysfunction. The 13-valent pneumococcal conjugate vaccine (PCV13) has superior immunogenicity in some categories of immunocompromised adults; however, its effect on the immune response in CKD patients has only been addressed by two recent studies with conflicting results. The effect of PPV23 or PCV13 on B cells in these patients has not been previously studied. We studied the absolute numbers and proportions of B cells and subpopulations in two groups of adult patients with severe CKD pre- and 7 days post-immunization with PCV13: pneumococcal vaccine naïve and previously immunized with PPV23 (over one year ago).ResultsPPV23 immunized patients had significantly lower proportions and absolute numbers of class switched memory (CD19 + CD27 + IgM-), as well as lower absolute numbers of IgM memory (CD19 + CD27 + IgM+) and class switched B cells (CD19 + CD27-IgM-) compared to PPV23 naïve patients. Following PCV13 immunization, the differences in absolute numbers of B-cell subpopulations between groups remained significant. The PPV23 immunized group had higher proportions of CD5- B cells along with lower proportions and absolute numbers of CD5+ B cells compared to PPV23 naïve patients both pre- and post-immunization with PCV13. However, previous PPV23 immunization did not have a noticeable effect on the numbers of total IgG or serotype 6B and 14 specific antibody-secreting cells detected 7 days post-immunization with PCV13. Nevertheless, fold increase in anti-serotype 14 IgG concentrations 28 days post-PCV13 was greater in PPV23 naïve than in previously immunized patients.ConclusionsThe results suggest that immunization with PPV23 may result in long-term changes in B-cell subpopulations such as increased prevalence of CD5- B cells and decreased prevalence of class switched memory B cells in the peripheral blood. Because previous immunization with PPV23 in patients with CKD is associated with a significant decrease in the total class switched memory B cells in response to subsequent immunization with PCV13, this may reduce PCV13 immunogenicity in the setting of PPV23 followed by PCV13.Trial registrationRegistered February 24, 2015 at ClinicalTrials.gov (NCT 02370069).

Varicella-zoster virus post-exposure management and prophylaxis: A review.

Varicella-zoster virus causes both varicella (chickenpox) and herpes zoster (shingles). Although varicella incidence has dramatically declined since introduction of the live-attenuated varicella vaccine, vaccination rates are suboptimal, and outbreaks still occur. Additionally, herpes zoster incidence continues to rise. Severe or fatal complications may result from varicella transmission to at-risk individuals who are exposed to either varicella or herpes zoster. An increasing number of children and adults are receiving immunosuppressive therapies and are at high risk for severe varicella and other complications if exposed to the virus. Clinical management of individuals exposed to varicella-zoster virus should take into consideration the type of exposure, evidence of immunity, and host-immune status with regard to ability to receive varicella vaccination safely. Post-exposure varicella vaccination may prevent infection or mitigate disease severity in persons eligible for vaccination. Post-exposure prophylaxis with varicella zoster immune globulin is indicated for populations ineligible for vaccination, including immunocompromised children and adults, pregnant women, newborns of mothers with varicella shortly before or after delivery, and premature infants. Appropriate post-exposure management of individuals exposed to either varicella or herpes zoster-including assessment of immune status and rapid provision of optimal prophylaxis-can help avoid potentially devastating complications of varicella-zoster virus infection.

Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.

The primary reported risk factors for herpes zoster (HZ) include increasing age and immunodeficiency, yet estimates of HZ risk by immunocompromising condition have not been well characterized. We undertook a systematic literature review to estimate the HZ risk in immunocompromised patients. We systematically reviewed studies that examined the risk of HZ and associated complications in adult patients with hematopoietic cell transplants (HCT), cancer, human immunodeficiency virus (HIV), and solid organ transplant (SOT). We identified studies in PubMed, Embase, Medline, Cochrane, Scopus, and clinicaltrials.gov that presented original data from the United States and were published after 1992. We assessed the risk of bias with Cochrane or Grading of Recommendations Assessment, Development, and Evaluation methods. We identified and screened 3765 records and synthesized 34 studies with low or moderate risks of bias. Most studies that were included (32/34) reported at least 1 estimate of the HZ cumulative incidence (range, 0-41%). There were 12 studies that reported HZ incidences that varied widely within and between immunocompromised populations. Incidence estimates ranged from 9 to 92 HZ cases/1000 patient-years and were highest in HCT, followed by hematologic malignancies, SOT, and solid tumor malignancies, and were lowest in people living with HIV. Among 17 HCT studies, the absence of or use of antiviral prophylaxis at <1 year post-transplant was associated with a higher HZ incidence. HZ was common among all immunocompromised populations studied, exceeding the expected HZ incidence among immunocompetent adults aged ≥60 years. Better evidence of the incidence of HZ complications and their severity in immunocompromised populations is needed to inform economic and HZ vaccine policies.

1759. Incidence of Hospitalizations and Emergency Department Visits for Herpes Zoster in Immunocompromised and Immunocompetent Adults in Ontario, Canada, 2002–2016

BackgroundAdults with immunocompromising conditions are at increased risk of herpes zoster (HZ) infection and related complications. We aimed to assess the incidence of HZ seen in hospital or emergency department in immunocompromised populations and compare it to that of immunocompetent populations.MethodsUsing healthcare administrative data, we calculated incidence rates (IR) of HZ in Ontario, Canada between April 1, 2002 and August 31, 2016 in adults ≥18 years categorized as immunocompromised or immunocompetent. We repeated these analyses by type of immunocompromising condition and provided incidence rate ratios (IRR) comparing to immunocompetent adults. We also calculated IRs and IRRs of HZ complications by immunocompromised status.ResultsThere were 120,654 incident cases of HZ seen in hospital or emergency department during the study period. Immunocompromised adults accounted for 13% of these cases despite representing only 3% of the population. The risk of HZ was higher for immunocompromised adults compared with immunocompetent (IRR = 2.8, 95% CI 2.8–2.9) and ranged across type of immunocompromising condition (from 2.4 [95% CI 2.3–2.5] in those with a solid tumor malignancy to 11.0 [95% CI 10.0–12.0] in those who had undergone a hematopoietic stem cell transplant). The risk of any HZ complication was also higher in immunocompromised adults (IRR = 3.5, 95% CI 3.4–3.6) and was highest for disseminated zoster (IRR = 31.5, 95% CI 26.3–37.5).ConclusionThe risk of HZ and related complications was higher in immunocompromised populations compared with immunocompetent. Our findings underscore the high-risk nature of this population and the potential benefits that may be realized through HZ vaccination of this group.Disclosures All authors: No reported disclosures.

1629. Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review

BackgroundThe two known primary risk factors for herpes zoster (HZ) are age and immunodeficiency yet estimates of HZ risk by immunocompromising medical condition have not been well characterized. We undertook a systematic review of the literature to estimate HZ risk in six categories of immunocompromised patients.MethodsWe conducted a systematic review of evidence for HZ in patients with hematopoietic cell transplants (HCT), cancer (blood and solid tumor), HIV, and solid-organ transplant (SOT; kidney and other). We identified studies in Pubmed, Embase, Cochrane, Scopus and clinicaltrials.gov using the following outcome search terms: Herpes Zoster, Shingles, VZV, chickenpox, Varicella-zoster virus, or opportunistic infection. We included articles that presented original data from studies in the United States on risk of HZ in adults and were published after 1992 (1996 for HIV). Case reports and conference abstracts were excluded. We assessed risk of bias with Cochrane (clinical trials) or GRADE (observational) methods and categorized studies as high, medium, or low risk.ResultsWe identified and screened 3,765 records; 57 articles were abstracted and 34 deemed low or moderate risk of bias (Figure 1). All articles reported at least one estimate of HZ cumulative incidence, which ranged from 0% to 41%. Thirteen studies estimated HZ incidence, which varied widely within and between immunocompromised populations (Figure 2). The highest estimates were seen in HCT (median = 52 HZ cases/1000 patient-years), followed by blood cancers and SOT, and then solid tumor cancers and HIV (median = 13 HZ cases/1,000 patient-years). Among 17 studies of HCT patients, longer follow-up time and absent or <1 year of post-transplant antiviral prophylaxis were associated with higher HZ cumulative incidence (Figure 3).ConclusionHZ is common among all immunocompromised populations studied—exceeding expected HZ incidence in immunocompetent middle-age adults. Antiviral prophylaxis among HCT patients has an ameliorating effect but long-term HZ risk following discontinuation is unclear. Better evidence for incidence and severity of HZ in immunocompromised populations is needed to inform economic and HZ vaccine policy analyses. Disclosures All authors: No reported disclosures.

LB6. EDP-938, a Novel RSV N-Inhibitor, Administered Once or Twice Daily Was Safe and Demonstrated Robust Antiviral and Clinical Efficacy in a Healthy Volunteer Challenge Study

BackgroundRespiratory syncytial virus (RSV) represents an important global health challenge with significant morbidity and mortality in infants, elderly, and immunocompromised adults. No effective therapy is currently available. EDP-938 demonstrates potent in vitro activity against RSV Subtypes A and B. We report data from EDP 938-101, a double-blind, placebo-controlled, Phase 2a study that evaluated EDP-938 in adult volunteers inoculated with RSV-A Memphis 37b.MethodsSubjects were healthy volunteers, 18–45 years, who were sero-suitable (i.e., lower 25th percentile). After RSV inoculation on Study Day 0, subjects had 12 hourly nasal wash monitored for RSV infection by qualitative RSV RT–PCR. On Study Day 5 or previously if qualitative RT–PCR was RSV+, subjects were randomized to receive 5 days of EDP-938 600 mg once daily (QD arm) or 500 mg loading dose then 300 mg twice daily (BID arm), or placebo twice daily. Assessments included 12 hourly nasal wash for quantitative RSV viral load, 8 hourly RSV Total Symptom Scoring (TSS) and daily mucus weights. Safety assessments were continued though Day 28 (last follow-up). The primary endpoint was the RSV viral load area under the curve (AUC) from first dose through Day 12 among RSV-infected subjects, defined as the Intent To Treat-Infected (ITT-I) population. The study was fully powered for both RSV viral load and TSS endpoints.ResultsA total of 115 subjects were randomized and inoculated; 86 were included in the ITT-I analysis. The primary and secondary efficacy endpoints were achieved with high statistical significance in QD and BID arms (figure and table). Among EDP-938 recipients all adverse events (AEs) were mild except for a single AE of moderate dyspepsia in the BID arm and events of moderate headache (n = 2) and hypoacusis (n = 1) in the placebo arm. All AEs resolved in follow-up.ConclusionsIn the RSV Challenge study, EDP-938 administered once or twice daily achieved primary and key secondary endpoints with robust reductions in RSV viral load (by both qRT–PCR and plaque assays), symptom scores and mucus weights. These data support the further clinical evaluation of EDP-938 in populations at risk of severe RSV disease. DisclosuresEoin Coakley, MD, Enanta Pharmaceuticals (Employee), Alaa Ahmad, PhD, Enanta Pharmaceuticals (Employee), Kajal Larson, PhD, Enanta Pharmaceuticals (Employee), Ty McClure, PhD, Enanta Pharmaceuticals (Employee), Kai Lin, PhD, Enanta Pharmaceuticals (Employee), Kursten Tenhoor, n/a, Enanta Pharmaceuticals (Consultant), Kingsley Eze, n/a, hVIVO Services Ltd. (Employee), Nicolas Noulin, PhD, No financial relationships or conflicts of interest, Veronika Horvathova, MBChB, MSc, hVIVO Services Limited (Other Financial or Material Support, Employed by hVIVO during the conduct of the study), Bryan Murray, MBBS, No financial relationships or conflicts of interest, Mark Baillet, PhD, S-CUBED (Employee), Julie Mori, PhD, hVIVO (Employee, Shareholder) Nathalie Adda, MD, Enanta Pharmaceuticals (Employee).

1417. Detection of Human Herpesviruses DNA in Cerebrospinal Fluids of Patients Suspected with Central Nervous System Infection

BackgroundOf the nine human herpesviruses (HHVs), most viruses have neurovirulence. Clinical manifestations of central nervous system (CNS) complications caused by some of the HHVs are well examined in children and immunocompromised adults; however, information of EBV and β-herpesviruses in an immunocompetent adult is limited.MethodsBetween April 2013 and March 2018, 322 patients (median age; 51.6 years old, male/female; 196/126) suspected to CNS infection were enrolled in this study. Patients with unconsciousness or characteristic change lasting more than 24 hours and abnormal brain MRI or EEG were defined as encephalitis. Real-time PCRs for detection of the 7 HHVs DNA including HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, and HHV-7 were carried out in DNA extracted from 200 μL CSF. HHV-6 was discriminated between HHV-6A and HHV-6B using RFLP analysis.ResultsHerpesviruses DNA was detected in 33 (10.2%) of the 322 patients. The most frequently detected HHVs was VZV (19 cases) and followed by HHV-6B (4 cases), HSV-1 (3 cases), HSV-2 (3 cases), and EBV (2 cases). Multiple HHVs DNAs were detected from the 2 patients (case A; HSV-2, HHV-6, and EBV, case B; EBV and HHV-6B). No CMV and HHV-7 DNAs were detected in any of the samples. Eleven cases were assigned as encephalitis, and other 22 cases were non-encephalitis. Although all 3 patients with positive HSV-1 DNA were encephalitis, all 3 patients with positive HSV-2 DNA were meningitis. Fourteen (13 patients had zoster) of the 19 patients with positive VZV DNA were meningitis, and the remaining 5 patients (4 patients had zoster) were encephalitis. Two of the 4 HHV-6B-positive patients were non-encephalitis, one patient was diagnosed Orbital apex syndrome and another patient was myelitis. One of the 2 encephalitis patient was chromosomally integrated (ci) HHV-6. Additionally, case B was also ciHHV-6.ConclusionApproximately 10% of the samples were positive of HHVs DNA. VZV was the most frequently detected viral DNA in this cohort. Thirty-three percent of the patients were encephalitis, remaining patients were non-encephalitis such as meningitis and myelitis. As suggested, ciHHV-6 can cause miss-diagnosis of patients suspected with CNS infection.Disclosures All authors: No reported disclosures.

2716. Persistence of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Serotypes in Invasive Pneumococcal Disease in Adults in Southern Ontario Canada Despite Routine Pediatric Vaccination

BackgroundIn Ontario, Canada, PCV13 is covered for immunocompromised (IC) adults over 50y. PCV13 programs are thought not to be cost-effective in other adults because it is assumed that herd immunity from pediatric vaccination programs (PCV7 since 2005; PCV13 since 2010) will reduce PCV13 disease burden dramatically in adults. We analyzed data from the Toronto Invasive Bacterial Diseases Network (TIBDN) to ask whether PCV13-type invasive pneumococcal disease (IPD) in adults persists in our population.MethodsTIBDN performs population-based surveillance for IPD in Toronto+Peel Region, Ontario (pop4.1M). All microbiology laboratories receiving specimens from residents report cases of IPD and submit isolates to a central study lab for serotyping; annual audits are conducted. Demographic, medical and vaccination information are obtained from patients, families and physicians. Population data are from Statistics Canada.ResultsSince 1995, 10,365 episodes of IPD have been identified; detailed medical information was available for 9,801 (95%) and serotyping for 9411 (91%). Among 8658 adult cases, 4,273 (49%) were in those aged 15–64 years, and 4,285 (51%) in those aged >645 years. The most common diagnoses were pneumonia (5,978/8,025, 74%) and bacteremia without focus (1,030, 13%); 470 (4.6%) cases had meningitis; the case fatality rate (CFR) was 21%. The incidence of disease due to STs in PCV13 in adults declined from 7.0/100,000/year 2001 to 2.9/100,000/year in 2015–2018 and was stable from 2015–2018 (Figure 1). The incidence was > 5/100,000/year in non-IC patients over 65 years, and younger patients with cancer and kidney disease (Figure 2). In IPD from 2015 to 2018, adult patients with PCV13 ST disease were younger (median age 64 years vs. 67 years, P = .03) than other patients; there was no significant difference in the proportion with at least one underlying chronic condition (253, 69% PCV13ST, vs. 541,74% other ST, P = 0.08), or in CFR (59, 16% PCV13 vs. 145, 20% other, P = 0.13). The ST distribution of cases due to PCV13 STs is shown in Figure 3.ConclusionA significant burden of IPD due to PCV13 serotypes persists in adults in our population despite 8 years of routine pediatric PCV13 vaccination. This burden needs to be considered in assessing the value and cost-effectiveness of PCV programs for adults. Disclosures All authors: No reported disclosures.

2728. Proportion of Invasive Pneumococcal Disease Potentially Covered by Current and Next-Generation of Higher-Valency Pneumococcal Conjugate Vaccines in Canada, 2010–2016

BackgroundIn Canada, routine pediatric immunization with 7-valent pneumococcal conjugate vaccine (PCV7) was introduced between 2002 and 2006. Two of ten provinces transitioned to PCV10 in 2009; by mid-2011, following a national preferential recommendation, PCV13 replaced PCV7/PCV10 across Canada. PCV13 also has been recommended for immunocompromised adults since 2013, and immunocompetent adults aged ≥65 years on an individual basis since 2016. Immunization with 23-valent polysaccharide vaccine (PPV23) is recommended in adults with certain comorbidities, and routinely in those aged ≥65 years. Two higher-valency PCVs, PCV15, and PCV20 are currently under development.MethodsCase counts of invasive pneumococcal disease (IPD) by serotype and age group were obtained from published annual reports of passive laboratory-based national IPD surveillance conducted by the National Microbiology Laboratory (NML) since April 2010.ResultsIn all ages, the proportion of IPD due to PCV13 serotypes declined from 55% in 2010 to 31% in 2016 (Figure 1); in children age < 5 years, from 66% to 19%; in adults age 50–64 years, from 52% to 34%, and in adults age > 65 years from 51% to 25%. While most age groups have experienced declines in the proportion of PCV13-type IPD, this proportion has plateaued since 2014 in all age groups except 2–4 years old. During 2016, among all ages, the proportions of IPD due to PCV13, PCV15, and PCV20 types were 31%, 43%, and 58%, respectively; among children age < 5 years 19%, 35%, and 50%, respectively, among adults 50–64 years, 34%, 47%, and 61%, respectively, and among adults age ≥65 years, 25%, 38%, and 53%, respectively.ConclusionThe proportion of PCV13-type IPD has declined across all ages since the introduction of PCV13 in children. The plateau in this proportion observed across most age groups since 2014 suggests that herd effect may have been maximized, and additional reductions could be expected primarily from direct PCV13 adult immunization. PCV20 could potentially protect against a large proportion of the remaining IPD burden in Canada. Disclosures All authors: No reported disclosures.

2746. Effectiveness of Influenza Vaccine for Prevention of Influenza-associated Hospitalizations Among Immunocompromised Adults—2017–2018

BackgroundImmunocompromised (IC) individuals are at higher risk for severe complications of influenza. Little literature describes vaccine effectiveness (VE) in this population. We evaluated VE for prevention of influenza-associated hospitalization among IC adults.MethodsWe analyzed data from adults hospitalized with acute respiratory illness (ARI) during the 2017–2018 FLU season at 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Details of disease severity, underlying health status, and vaccination status were obtained through enrollment interviews and medical records. Prior year clinical encounter diagnoses and enrollment interviews were used to define IC groups. IC groups were mutually exclusive. VE was evaluated with a test-negative case–control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, race, and other factors, and stratifying by immunocompromising conditions.ResultsOf 3524 adults hospitalized with ARI, 1210 (34%) had an immunocompromising condition. Chronic steroid (n = 397), chemo/radiation therapy (n = 242), hematologic condition (n = 175), and organ transplant (n = 144) were most common. HIV (n = 45) and stem cell transplant (SCT) (n = 28) were least common. IC patients were more likely to be vaccinated than non-IC (60% vs. 55%, P = 0.002). Overall, vaccination reduced risk of influenza hospitalization by 36% (95% CI: 24,46). Among IC adults, VE was 9% (95% CI: −25,34). VE was 32% (95% CI: 5,51) for chemo/radiation therapy, 29% (95% CI: 6,47) for chronic steroids, 29% (95% CI: -6,52) for hematologic conditions, −1% (95% CI: −50,32) for organ transplant, −48% (95% CI: −190,25) for HIV, and −154% (95% CI = −458,−15) for SCT (Figure 1).ConclusionVaccination reduced risk of influenza hospitalization among adults with the most prevalent immunocompromising conditions in our cohort; however, it had little to no effect in other groups, such as in HIV and organ and stem cell transplant recipients. Results support using other preventative strategies in addition to vaccinating adults with immunocompromising conditions, such as vaccination of close contacts. Disclosures All authors: No reported disclosures.

Epidemiological characteristics and phylogenic analysis of human respiratory syncytial virus in patients with respiratory infections during 2011–2016 in southern China

BackgroundHuman respiratory syncytial virus (RSV) is one of the most important pathogens that cause acute respiratory infections in children and immunocompromised adults. This work was conducted to understand the epidemiological and phylogenetic features of RSV in southern China during 2011–2016. MethodsA total of 16 024 nasopharyngeal swabs were collected from patients with respiratory infections in 14 hospitals, and screened for RSV and seven other respiratory viruses using real-time PCR. Six hundred and twenty-three RSV-positive samples from 13 hospitals were further analyzed for subtypes. G gene sequencing and phylogenetic analysis were performed based on 46 RSV-A and 15 RSV-B strains. ResultsRSV was detected in 9.5% of the 16 024 specimens, the highest among the eight respiratory viruses screened. Most of these specimens came from inpatients and children under 3 years of age. The incidence of RSV-A (9.4%) was higher than that of RSV-B (4.4%) in children (<15 years), but not in adults (0.64% vs. 0.58%). A 2-year RSV-A dominance followed by a 1-year RSV-B dominance pattern was found. The co-detection rate of RSV was 25.1%. The main prevalent genotypes were NA1, ON1, and BA9. The prevalent RSV-A genotype in 2011–2012 was NA1, close to Chongqing and Brazil, but a new Hong Kong ON1 genotype was introduced and became the prevalent genotype in Guangzhou in 2014–2015. Deduced amino acid sequence analysis confirmed the ongoing evolution and a high selection pressure of RSV-A and B strains, especially in RSV-A ON1 and NA1 genotypes. ConclusionsThis study demonstrated the molecular epidemiological characteristics of RSV in patients with respiratory infections in southern China.

Complete Genome Sequence of Citrobacter freundii Myophage Maleficent.

Citrobacter freundii, a member of the Enterobacteriaceae family, has been linked to opportunistic infections in neonates and immunocompromised adults. Here, we report the complete genome sequence of a T4-like myophage, Maleficent, which infects C. freundii.

A CLAW TO THE LUNG: A PULMONARY MANIFESTATION OF DISSEMINATED BARTONELLA HENSELAE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Infection from Bartonella henselae typically produces a localized cutaneous lymphadenitis. However, disseminated disease may occur and can be life-threatening. Pulmonary manifestations of Bartonella range from solitary nodules to pneumonia and ARDS. CASE PRESENTATION: A 44-year-old man with type 2 diabetes presented with 3 weeks of fever, weight loss, and nonproductive cough. He was otherwise healthy, used no illicit substances, had not traveled recently, but he owned several cats. On arrival, he was afebrile, hypotensive, and mildly hypoxic on room air. His lung exam revealed diffuse fine inspiratory crackles and diminished breath sounds at the bases. His spleen was enlarged and there were no skin lesions. Notable labs included white blood count 2,700/mm3, hemoglobin 9 g/dl, platelets 50,000 /mm3. Chest X-ray showed diffuse bilateral opacities and effusions and testing for HIV was negative. CT chest/abdomen further demonstrated marked splenomegaly, 2.7 cm splenic lesion, a 1.9 cm left upper lobe pulmonary nodule, and prominent mesenteric, mediastinal, and hilar lymph nodes. Bone marrow biopsy revealed normocellular marrow with erythroid hyperplasia, no abnormal B-cell clones or blasts. Subsequently, wedge resection of the pulmonary nodule and sampling of the mediastinal lymph nodes was performed via video assisted thoracoscopic surgery. Post-operatively, despite Vancomycin, Meropenem, Doxycycline, and Rifampin, fevers persisted, and he developed ARDS, ultimately necessitating veno-venous ECMO. Despite these measures, he died one week after admission. All cultures remained negative, however serologies returned positive for Bartonella henselae IgG at a titer >1:1024 and IgM of 1:128. The mediastinal lymph node biopsy demonstrated microorganisms on Warthin-Starry stain consistent with Bartonella. DISCUSSION: Bartonella henselae is a fastidious and fragile organism, thus very difficult to isolate in cultures. Patients are typically diagnosed with disseminated bartonellosis based on serologies or special stains in the context of typical clinical features such as our patient’s lymphadenopathy, splenic lesions, pancytopenia, and cat exposure. Most reports of disseminated bartonellosis occur in those immunocompromised after solid organ transplant or with advanced HIV, in whom mortality rates are 10-40% even with appropriate anti-microbials. Disseminated disease in immunocompetent hosts occurs rarely and does not commonly involve the lungs. Of 16 cases of Bartonella infections with pulmonary manifestations, 80% occurred in immunocompromised adults in whom nodules were more common manifestations than pneumonia or effusions, and only one individual developed ARDS (1). CONCLUSIONS: Because of its rarity, there are no previous reports describing ECMO to treat Bartonella-associated ARDS, emphasizing the importance of further studies. Reference #1: 1. Bandyopadhyay, Anuja, et al. “Pulmonary Nodules in an Immunocompetent Child with Cat Scratch Disease.” The Pediatric Infectious Disease Journal, U.S. National Library of Medicine, Dec. 2013, www.ncbi.nlm.nih.gov/pubmed/24030347. DISCLOSURES: No relevant relationships by Thomas Baudendistel, source=Web Response No relevant relationships by Tess Knudson-Fitzpatrick, source=Web Response

2227 Herpes Simplex Virus - 1 Related Acute Fulminant Liver Failure Successfully Treated With Medical Therapy

INTRODUCTION: Herpes simplex virus (HSV 1&amp;2) is an uncommon cause of asymptomatic hepatitis and acute liver failure. Fatal disease often occurs in immunocompromised adults but is a rare event in immunocompetent patients. Early suspicion of infection is imperative as late diagnosis and treatment carries poor prognosis and high mortality. We describe a case of acute hepatic failure from HSV-1 virus in an immunocompetent adult successfully treated with medical therapy without need for liver transplantation. CASE DESCRIPTION/METHODS: A 55-year-old diabetic male with recent hospitalization for necrotizing fasciitis of the groin (discharged on amoxicillin/clavulanate 5 days ago) presented to the hospital with fever, vomiting, abdominal pain and was found to have severe elevation in liver enzymes. Patient denied prior history of liver disease. Physical exam was notable for fever: 102 degree F, tachycardia, multiple small circular lesions on the oral mucosa and tender hepatomegaly. Liver tests at baseline were normal and on admission showed: AST 1317 U/L (normal:&lt; 32 U/L), ALT 966 U/L (normal:&lt; 36 U/L), total bilirubin 0.4mg/dL (normal:0.2-1.2 mg/dL), alkaline phosphatase 86 U/L (normal:45-117 U/L) and INR 1.7 (normal:0.8-1.2). Urine drug screen was negative of acetaminophen. Imaging excluded hepatic venous thrombosis. Laboratory tests for viral and autoimmune hepatitis, wilson’s disease were negative. Patient was empirically started on IV acyclovir given concern for herpes hepatitis based on oral exam. Diagnosis was confirmed with a positive blood and oral swab HSV DNA PCR and a liver biopsy (Figures 1 and 2) showing herpes simplex viral inclusions. Due to progressive worsening of liver tests and patient’s condition while on treatment, intravenous immunoglobulin (IVIG) therapy was added eventually leading to clinical and laboratory signs of improvement (Table 1). He was discharged on an oral course of valganciclovir and continues to do well on follow up visit. DISCUSSION: Fulminant liver failure from herpes virus has been infrequently reported in immunocompetent adults and usually represents disseminated infection. It is a potentially treatable condition that requires high degree of diagnostic suspicion as presenting symptoms can be non-specific. Early empiric treatment with acyclovir while awaiting HSV PCR or liver biopsy has been shown to improve outcomes and decrease need for liver transplantation. We herein describe a novel approach to treat HSV hepatic failure with combination therapy of acyclovir and IVIG.

2614 Astrovirus Enteritis in an Immunocompetent Adult in the Setting of Chronic Proliferative Synovitis

INTRODUCTION: Astrovirus enteritis is a clinical entity seen mainly in children and immunocompromised adults resulting in severe diarrheal episodes. It is quite rarely implicated in acute gastroenteritis in immunocompetent adults with only few cases reporting its incidence. Here, we report a case of Astrovirus enteritis in an immunocompetent adult with chronic proliferative synovitis and positive ANA titers. CASE DESCRIPTION/METHODS: We present a 38-year-old woman with history of chronic proliferative synovitis who presented with acute nausea, crampy mid abdominal pain, and profuse non-bloody diarrhea after 12 hours of eating from a restaurant. The diarrheal episodes were associated with fevers up to 103oF with chills and rigors. The patient reported to have two recent sick contacts with similar diarrheal episodes and a course of amoxicillin 1 month ago for a dental indication. However, she denied any vomiting, recent meat, dairy or egg consumption or travel history. She had no past medical history of gastrointestinal complaints, immunosuppression or any new medications. Clinical examination only revealed mild abdominal diffuse tenderness. Initial clinical workup was remarkable for a mild leukocytosis, newly increasing AST and ALT, but normal total bilirubin, ALP and lipase levels. Microbiological investigation revealed positive Astrovirus in GI PCR, negative C. difficile assay and negative HIV status. An autoimmune workup revealed positive ANA titers of 1:80 in the setting chronic proliferative synovitis. The patient underwent supportive treatment for her diarrhea with Loperamide and IV fluids following which she improved clinically. DISCUSSION: Astrovirus is a positive single stranded RNA virus implicated in acute gastroenteritis in children and immunocompromised individuals. However, it has a low prevalence among healthy adults which is hypothesized to be due to acquired immunity gained from a prior childhood infection. In this patient, her chronic proliferative synovitis with raised ANA titers seems to have increased her predisposition to acquiring Astrovirus enteritis. Patients with chronic inflammatory conditions like SLE or synovitis seem to be more prone to viral infections due to their pro-inflammatory condition, making them more susceptible to infections that are otherwise cleared by the adult immune system. Hence, it is important to consider this clinical entity when assessing severe gastroenteritis in patients with pro-inflammatory status.