bluuebunny/crossref_metadata_2025 huggingface dataset:
1664. Maternal Hookworm Infection and Its Effect on Maternal/Child Health: A Systematic Review and Meta-Analysis
Authors: Ness Tara , Bedard Kathryn R , Hotez Peter J , Weatherhead Jill
Published: October 2019

Background

Hookworm is an intestinal parasite that infects 500 million people, with another 5.1 billion at risk, especially in poverty-stricken, tropical and subtropical regions. In 2005, an estimated 6.9 million pregnant women living in Sub-Saharan Africa were infected with hookworm, despite efforts for mass drug administration (MDA) being recommended. This study aimed to investigate the health impact of hookworm infection in pregnant women in order to guide public health interventions.

Methods

A systematic review and meta-analysis were conducted using Medline OVID for the creation of MeSH terms, with subsequent translation to EMBASE and Cochrane Library. We performed a meta-analysis on the association between maternal hookworm and maternal anemia, as well as maternal hookworm co-infection with malaria. Other effects on maternal/child health were investigated and summarized without a meta-analysis due to the limited study numbers.

Results

Our search resulted in 471 studies for the meta-analysis, of which 23 met inclusion criteria. The prevalence of hookworm ranged from 1% to 67% in pregnant women, while malaria prevalence ranged from 11 to 81%. Pregnant women with anemia were more likely to have concurrent hookworm infection (combined odds ratio (cOR) 2.21 [1.94, 2.51], P < 0.001). Additionally, pregnant woman with malaria were more likely to have hookworm infection (cOR 1.71 [1.43, 2.03], P < 0.001). Our investigation also showed an association between maternal hookworm and infant cognitive development (one study), maternal co-infection with HIV (two studies), and infant birth weight (significant in three of four studies). Infant vaccine response did not show an association (four studies).

Conclusion

Hookworm infection in pregnant women is an important global health issue associated with significant maternal anemia and concurrent parasitic infections, such as malaria. Despite current MDA strategies in pregnant women, heavy hookworm burden, co-infection with malaria, and subsequent anemia persists. Further investigation on maternal-child outcomes of hookworm infection on maternal anemia, maternal malaria co-infection, and other areas, such as infant cognitive outcomes, will provide potential public health interventional targets to reduce morbidity.

Disclosures

All authors: No reported disclosures.
1668. No Impact of Nutritional Status on Oral Polio Vaccine shedding after Vaccination of Under 5 Children in Rural Mexico
Authors: Nino-Tapias Gianna J , Altamirano Jonathan , Sarnquist Clea , Behl Rasika , Leary Sean , Sommer Marvin , Maldonado Yvonne
Published: October 2019

Background

As wild poliovirus is nearing global eradication and countries switch from Oral Polio Vaccine (OPV) to Inactivated Polio Vaccine (IPV), preventing circulating vaccine-derived poliovirus is a top priority. However, the circulation of OPV serotypes remains a concern in undervaccinated communities. We sought to examine the relationship between pediatric nutritional status and OPV shedding based on length-for-age categorizations. Mexico provides a natural environment to study these patterns as it provides routine IPV immunization and bi-annual OPV campaigns.

Methods

We enrolled 466 households with children eligible for OPV before the February 2015 national health week from 3 semi-rural Indigenous communities near Orizaba, Mexico. In each community, a different proportion of eligible children received OPV (10%, 30%, 70%), with a total of 155 vaccinated children. OPV shedding was measured by RT-qPCR detection of OPV in samples collected serially over 10 weeks. Anthropometric measurements were collected and compared with the WHO Multicenter Growth Reference Study growth curves to assign stunting. Associations between stunting, OPV shedding, and shedding duration were tested by Fisher exact test and Wilcoxon-Man-Whitney Test (α = 0.05).

Results

Samples of fecal OPV isolates were collected over time and analyzed from 148 vaccinees. 25 (17%) of the vaccinees were stunted. There was no relationship between pediatric stunting and likelihood of ever shedding any serotype of OPV (P = 0.82). The mean duration of OPV shedding by stunted and non-stunted children differed, but not significantly (10.9 days vs. 9.3 days, respectively, P = 0.32). We did not find any statistically significant differences between stunting status and shedding of any individual OPV serotype.

Conclusion

Further understanding of factors related to OPV shedding is necessary to approach efficient worldwide poliovirus control. We found no relationship between stunting status and both OPV shedding and shedding duration post-vaccination, suggesting that nutritional status does not play a role in OPV shedding. The ongoing analysis includes longitudinal analysis of OPV shedding patterns by nutritional status, and the impact of stunting on viral load and reversion of OPV to vaccine-associated paralytic polio mutants.

Disclosures

All authors: No reported disclosures.
1669. Trends in Authorship for Infectious Disease Research Conducted in Low-Income Countries
Authors: Modlin Chelsea E , Powell Kimberly , Kempker Russell R
Published: October 2019

Background

Research capacity in low-income countries (LICs) plays an important role in strengthening national healthcare systems and addressing local health priorities. Research in infectious diseases is especially important as they comprise five of the top 10 causes of death in LICs. While academic collaborations between high-income countries (HICs) and LICs offer many benefits, they also risk structural and professional imbalances. This study explores research capacity as a function of first or last authorship and funding for research conducted in LICs that is published in high-impact infectious disease journals.

Methods

A literature search using the abstract database Scopus was completed for original research conducted within LICs or using samples collected from LIC subjects published between 1998 – 2017 in Clinical Infectious Diseases, Journal of Infectious Diseases, and Open Forum Infectious Diseases. Primary outcomes included the number of LIC first and last authors compared with HIC authors over time. Secondary outcomes included the geographic distribution of research and the proportion of research financed by LICs.

Results

A total of 1380 articles were identified of which 20% had LIC first authors and 21% had first authors with dual LIC/HIC affiliations. For last authors, 13% were affiliated with a LIC and 15% had dual LIC/HIC affiliation. HIC researchers compiled the majority of first and last authors regardless of geography (Figure 1). The number of studies conducted in LICs increased over the 20-year timeframe (Figure 2) but is attributed to an increase in articles with HIC authors. The number of LIC authors remained unchanged resulting in a decreasing proportion of LIC authors. Only 4% of articles received funding from a LIC; however, 79% of these studies were authored by LIC researchers vs. 39% of studies funded by HIC sources.

Conclusion

There is a growing appreciation for international HIC/LIC research collaborations with the objective to reduce the burden of infectious diseases that disproportionately affect low-income settings. However, with this increased attention comes the responsibility to improve LIC research capacity. This includes promoting LIC researchers via authorship and supporting sustainability with funding that highlights LIC priorities.

Disclosures

All authors: No reported disclosures.
1673. Gendered Patterns of HIV, TB, and Other Primary Care Referrals in Rural South Africa
Authors: Choi Koeun , Moll Anthony , Shenoi Sheela
Published: October 2019

Background

Men’s lack of engagement in healthcare hinders HIV efforts in sub-Saharan Africa. Masculine norms and lack of accessibility in a female-dominated healthcare system deter male health-seeking behavior. Community interventions combat the gender gap. In South Africa (SA), alcohol-based venues (ABV) are common locales for men. We created an ABV community health screening to determine the need.

Methods

Community Health Workers targeted ABV in rural SA, offering screenings for HIV, TB, Isoniazid Preventive Therapy, STI, hypertension, diabetes, circumcision, with referral to primary care services (PCS) for any positive screenings. Participants completed questionnaires, including socioeconomic (SE), healthcare use, and alcohol use evaluated by AUDIT scores. Multivariable logistic regression identified factors associated with referral to PCS.

Results

From July 2018 to March 2019, 1356 were screened, 74% were men, median age was 30 (IQR 22–46), 26% employed and 30% had running water. Men are more likely to have never gone to a PCS compared with women (15.9% vs. 9.7%, P = 0.004) and have lengthier time since the last clinic visit (1.4 years vs. 0.6 years, P < 0.001). Men are significantly more likely than women to report hazardous drinking (49% vs. 28%, P < 0.001) Overall, positive screenings were noted in 537 (53.9%) community members, and χ 2 analysis show men more likely to require referrals after screening (P = 0.08). Multivariate analysis shows among men, referrals were associated with older age, hazardous drinking, any health concerns; while higher SE was protective. For women, only age and health concerns were associated with referral. Similarly, alcohol contributed to HIV and TB referrals for men, while higher SE was protective of TB referrals for men (Table 1).

Conclusion

ABV males in this rural community, although disengaged from health care, required more referrals than women. HIV, TB, and any referrals for men screened at ABV in rural SA were associated with lower SE and hazardous drinking, highlighting the challenges that this population faces in seeking health care. Differentiated and targeted community-based services may facilitate care for these hard to reach men in sub-Saharan Africa. Next steps include determining clinical outcomes of referrals.

Disclosures

All authors: No reported disclosures.
1675. Implementation of Electronic Travel History Screening at an Urban Medical Center
Authors: de St. Maurice Annabelle M , Martinez Sandra , Sweeney Sarah , Genta Elizabeth , Walton Shaunte , Rubin Zachary A , Uslan Daniel
Published: October 2019

Background

Middle East Respiratory Syndrome (MERS), caused by a novel coronavirus, can lead to severe respiratory failure and death. CDC recommends screening patients who traveled to endemic countries for fever, respiratory symptoms, and exposure to MERS-positive contacts and healthcare facilities. UCLA is a large, academic, medical center located in a diverse city with frequent international travel. We implemented a travel screening (TS) questionnaire in our electronic medical record (EMR) (Figure 1) to identify high-risk patients in order to implement early isolation practices and testing. This study describes the use and performance of our TS for identifying suspect MERS cases.

Methods

An EMR-based tool prompts nurses to ask patients at triage or admission whether they have traveled out of the country in the past 30 days (Figure 1). If patients answer affirmatively, the EMR prompts nurses to inquire about travel to specific high-risk countries and to review symptoms and exposure risks. Upon notification of a potential MERS case, the EID physician on-call reviews the TS, clinical history, epidemiologic risks, and makes a determination whether further evaluation and/or isolation for suspect MERS is necessary. We reviewed travel history, demographics, and symptoms of patients who triggered a positive TS from April 2017 to September 2018.

Results

The ED completed 115,815 distinct TS on 81,197 individuals during this time period. The median time from ED arrival to TS completion was 6.4 minutes. 308 ED encounters triggered a positive TS; an additional 257 encounters in other units triggered a positive TS, resulting in 565 positive TS (Table 1). 122 (22%) expressed ≥1 MERS symptom and 29 (24%) expressed both fever and respiratory symptoms. Of these symptomatic patients, 0 had a history of contact with a MERS case; 3 had a history of contact with a healthcare facility while traveling; and 4 had a history of contact with camels. No patients were diagnosed with MERS (Table 2).

Conclusion

A history of travel to the MERS endemic countries is relatively common at a large urban hospital. Routine electronic screening of patients is an efficient way to identify high-risk travelers. This EMR tool could be modified for other emerging pathogens, such as measles or Ebola, to identify high-risk patients.

Disclosures

All authors: No reported disclosures.
1687. High-Rates of Candida auris Carriage and Co-Colonization with Multidrug-Resistant Organisms (MDROs)
Authors: Barza Ruby , Patel Parul , Patel Jignesh , Droske Lauren E , Schora Donna , Mangold Kathy , Lepinski Jeanette , Hines David , Lee Boeun , Singh Kamaljit
Published: October 2019

Background

Candida auris is an emerging multidrug-resistant pathogen that can persist in the environment and lead to healthcare-associated outbreaks. Residents of long-term acute care hospitals (LTACHs) are at particular risk for carriage of both MDROs and C. auris. However, there are few data on co-colonization rates of C. auris with other MDROs in LTACHs.

Methods

We conducted a point prevalence survey for MDROs, C. auris and C. difficile in a Chicago LTACH in March 2019. A combined axilla/groin E-swab (Copan) was collected and plated for C. auris isolation using CHROMagar Candida (Hardy). A rectal E-swab (Copan) was collected for C difficile PCR and MDRO detection including Carbapenem-resistant Enterobacteriaceae (CRE), Extended-spectrum B-lactamases (ESBLs) and Vancomycin-resistant Enterococci (VRE). Each swab was plated directly on VACC agar (Vancomycin, Amphotericin B, Ceftazidime, Clindamycin) and CHROMagar ESBL (Hardy). Bruker MALDI-TOF was used for bacterial and yeast identification and disc diffusion method for antimicrobial susceptibility testing. ESBL phenotypic confirmation was done using double-disc synergy method per CLSI guidelines. Carbapenemase production was confirmed using Xpert Carba-R assay (Cepheid). C. difficile PCR was performed using Xpert C. difficile/Epi assay (Cepheid).

Results

Of 38 patients 36 were eligible for the study (2 patients declined). Overall, 26/36 (72%) patients had an MDRO. Eight (22%) patients were positive for C. auris. Eight (22%) patients had ESBLs (2 P. mirabilis and 6 E. coli), six (17%) had CREs that were all blaKPC positive (4 K. pneumonia, 1 E. coli, and K. pneumoniae). Eight (22%) patients were positive for other gram-negative (GN)-MDROs including 1 A. baumanii, 3 P. aeruginosa, 2 E. cloacae, 1 E. asburiae and 1 P. aeruginosa, and A. baumanii. 20 patients (56%) had VRE colonization. Five (14%) were C. difficile PCR positive. 7/ 8 (87.5%) patients with C. auris were also colonized with another MDRO (2 VRE, 1 ESBL, 1 VRE, ESBL and KPC, 1 VRE and GN-MDRO, 1 VRE, ESBL and GN-MDRO, 1 VRE, KPC, and GN-MDRO).

Conclusion

We found a high rate of MDRO co-colonization among patients with C. auris carriage. Continuous active surveillance may be appropriate in LTACHs to limit the spread of C. auris and other MDROs.

Disclosures

All authors: No reported disclosures.
1700. A Rare Case of Candida glabrata Hemorrhagic Cystitis with Empagliflozin Use
Authors: Tran Ly , Thomas Mathew , Harvey Jeremy , Sampath Rahul , Rose Richard
Published: October 2019

Background

Hemorrhagic cystitis is an inflammatory condition of the bladder, infrequently seen after cancer chemotherapy, pelvic radiation, and viral infections in immunocompromised hosts.

Methods

We report a case of biopsy-proven Candida glabrata hemorrhagic cystitis in an immunocompetent host associated with empagliflozin use. Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, that increases urinary glucose excretion, and is associated with an increased risk of urogenital mycotic infections

Results

A 71-year-old man with a history type 2 diabetes, neurogenic bladder status post transurethral resection of the prostate, developed symptoms of pelvic pain and gross hematuria 3 months after the initiation of empagliflozin. The patient received multiple courses of empirical antibiotic therapy without any relief. Six months into the illness, the patient had significant weight loss, fatigue, progressive renal failure, and continued hematuria. Empagliflozin was self-discontinued by the patient secondary to a perceived relation between symptom onset and medication use. Urine cultures were negative. A CT scan showed mucosal thickening of the bladder wall with hydronephrosis. Cystoscopy was consistent with hemorrhagic cystitis. A bladder biopsy was negative for malignancy, stain and PCR negative for fungi, but culture positive for C. glabrata susceptible to Fluconazole. Mycobacterial stains, cultures, and PCR were negative. The patient was treated with Fluconazole for 4 weeks and experienced symptomatic improvement and resolution of hematuria one week into the therapy.

Conclusion

This is the first reported case of C. glabrata hemorrhagic cystitis in an immunocompetent host associated with empagliflozin. Invasive candida infections in the genitourinary system are rare in immunocompetent patients. We believe that empagliflozin-induced glycosuria may have been a predisposing factor.

Disclosures

All authors: No reported disclosures.
1701. Differences in Diagnostic Performance of β-d-Glucan Testing in Patients with Varying Degrees of Susceptibility to Invasive Fungal Infections
Authors: Nham Eliel , Kim Si-Ho , Lee Hyunjoo , Ko Jae-Hoon , Huh Kyungmin , Young Cho Sun , Kang Cheol-In , Ryeon Chung Doo , Ran Peck Kyong
Published: October 2019

Background

Usefulness of β-d-glucan (BDG) testing in high-risk patients for invasive fungal infection (IFI) diagnosis has been well demonstrated. However, data on its usefulness in patients without risk factors are limited. We evaluated differences in the diagnostic performance of BDG testing in patients with varying degrees of susceptibility to IFI.

Methods

From April 2017 to May 2018, all consecutive patients (≥18year-old) who were performed BDG testing (Beijing Gold Mountainriver Tech) were enrolled. Patients were classified into three groups: Group A for patients with host factors defined by 2008 European Organization for Research and Treatment of Cancer-Mycoses Study Group diagnostic (EORTC-MSG) criteria, Group B for patients with malignancy receiving recent chemotherapy within 1 month without host factors, and Group C for others. Cases of proven and probable IFI defined by EORTC-MSG criteria, Pneumocystis pneumonia and all fungemia were considered as true IFIs. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were calculated with a cut-off value for positivity ≥80 pg/mL.

Results

Among 473 eligible patients, 190, 142, and 141 patients were classified into group A, B, and C, respectively. Rates of true IFI were significantly different in each group (57/190, 19/142, and 10/141 in each group, P < 0.001). Sensitivities were 0.83, 0.68, and 0.70 and specificities were 0.62, 0.59, and 0.63 in group A, B, and C, respectively. PPVs were considerably different among three groups (PPV for 0.48, 0.20, and 0.12; NPV for 0.89, 0.92 and 0.97 in each group, respectively).

Conclusion

The BDG test is a useful assay for IFI diagnosis; however, the clinical interpretation should be different by patient risks. Whereas BDG testing could be considered as a tool for predicting IFI in high-risk patients, it only could be a tool for excluding IFI in patient without risk factors.

Disclosures

All authors: No reported disclosures.
1704. Geotrichum spp. Invasive Infection: Experience From a Third-Level Referral Center in Mexico
Authors: Rajme-López Sandra , Gonzalez-Lara María F , Rangel-Cordero Andrea , Ponce de Leon Alfredo
Published: October 2019

Background

Geotrichum spp has been recognized as an emergent pathogen that causes invasive infection in immunosuppressed hosts. There is no data in Latin America about invasive Geotrichum spp. infections. Our objective was to describe the epidemiology, clinical characteristics, and outcomes of patients with this infection.

Methods

We conducted a retrospective survey from 2001 to 2018, of all the Geotrichum spp. isolated from clinical samples at our institution. Data on demographic, clinical, laboratory findings, and imaging studies were obtained from medical records. All cases classified as proven or probable invasive fungal infections (IFI) according to the EORTC/MSG criteria were included. Isolates with unavailable clinical information were excluded. Descriptive analysis was made.

Results

We found 18 patients with a proven/probable Geotrichum spp. IFI. The mean age was 48.5 years and 55.5% were male. The most common predisposing condition was hematological malignancy (55.5%), autoimmune diseases (22.2%) and HIV, chronic granulomatous disease, and solid-organ malignancy in 1 case, respectively. Fifteen (83.3%) received immunosuppressors (cancer chemotherapy or steroids); 27.7% had neutropenia at the time of diagnosis. The most common clinical syndromes were lower respiratory tract infection and persistent fever (83.3%). Chest abnormalities were present in 15/16 CT scans, pulmonary nodules were the most common finding (62.5%). Geotrichum spp. was isolated from bronchoalveolar lavage, 77.7%; blood culture, 22.2%; and peritoneal dyalisis fluid, 5.6%. Seven patients were coinfected with other pathogens: 4 Aspergillus spp., 1 H. parainfluenzae, 1 P. aeruginosa, and 1 E. coli. Fifteen patients received antifungal treatment: 7 amphotericin B, 8 voriconazole, and 1 itraconazole. Among survivors (11), 72.7% received antifungal therapy at discharge: 4 voriconazole and 4 itraconazole. Three patients did not receive any antifungal: 1 was diagnosed postmortem and 2 were considered colonization (both were alive at 30 days). Overall mortality was 38.8%.

Conclusion

Eighteen cases of Geotrichum spp. were found. The majority had lower respiratory tract infection. Despite antifungal therapy 38.8% died. Geotrichum spp. should be recognized as an emerging pathogen in immunosuppressed hosts.

Disclosures

All authors: No reported disclosures.
1716. Baseline Serum C-Reactive Protein Level Predicts Mortality in Cryptococcal Meningitis
Authors: Chesdachai Supavit , Engen Nicole , Rhein Joshua , Tugume Lillian , kiiza. Kandole Tadeo , Abassi Mahsa , Williams Darlisha A , Skipper Caleb , Hullsiek Kathy H , kisekka. Musubire Abdu , Meya David , Boulware David
Published: October 2019

Background

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker widely used in various infections, particularly for following the progression and resolution of infection. We aimed to determine the association between baseline CRP level and cryptococcal meningitis outcome.

Methods

We reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline serum samples collected within 5 days from diagnosis had CRP levels measured and categorized into quartiles. We compared baseline serum CRP with 18-week survival using unadjusted time-to-event analysis.

Results

Of 168 participants, the first quartile of baseline serum CRP was 83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by quartile. Participants with CRP > 49.5 mg/L more likely presented with Glasgow Coma Scale <15 (P = 0.03). The 18-week mortality rate was 54.8% (46/84) in the highest two quartile CRP groups (49.5 mg/L), 40.5% (17/42) in the mid-range CRP group (29–49.5 mg/L), and 14.3% (6/42) in the low CRP group (<29 mg/L) (P < 0.001) (Figure 1).

Conclusion

Higher baseline serum CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. The serum CRP could be a surrogate marker for undiagnosed co-infections or may reflect immune dysregulation leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis. Additional studies investigating more specific inflammatory biomarkers and the longitudinal trend in CRP with effective therapy would be informative.

Disclosures

All authors: No reported disclosures.
1717. Cryptococcal Meningitis: A Comparison of Clinical Features and Outcomes by HIV Status
Authors: Pate Amy , Franco-Paredes Carlos , Henao-Martinez Andres
Published: October 2019

Background

Cryptococcal meningitis is an opportunistic fungal infection associated with HIV and other forms of immunosuppression. We lack a clear understanding of cryptococcal meningitis (CM) among HIV-negative patients in the United States. Our aim was to compare clinical features and outcomes across HIV status in patients with laboratory-confirmed cryptococcal meningitis.

Methods

We conducted a retrospective cohort study of patients with laboratory-confirmed (positive culture or antigen test) cryptococcal disease treated at a tertiary care center from January 2000 to September 2018. Patients were identified via local laboratory and TrinetX datasets. Data were gathered on demographics, HIV status, site of infection, clinical presentation, cerebrospinal fluid (CSF) profiles, hospital course, and mortality. Organ transplant recipients and/or non-meningeal infections were excluded.

Results

Seventy patients with cryptococcal disease were identified. Our final sample included 36 CM patients with a mean age of 48.8 ± 13.2 years; 66.7% (n = 24) had HIV. Median (IQR) absolute CD4 count for the HIV group was 35/μL (10–80/μL). Non-HIV patients were significantly older (P < 0.001) and had higher rates of altered mental status (AMS) on presentation (58.3% vs. 25%, P = 0.05). There was no significant variation in temperature, blood pressure, white blood cell count, serum sodium, or CSF opening pressure. Non-HIV patients had significantly higher CSF cell count (P = 0.02) and protein (P < 0.001), and lower glucose (P = 0.005) compared with HIV patients. There was no significant variation in length of stay or rates of intensive care unit admission. Overall, 90-day all-cause mortality was 19.4%: mortality rates were significantly higher in non-HIV patients at both 90 days (P = 0.017) and one year (P = 0.047).

Conclusion

Compared with individuals with HIV, non-HIV cryptococcal meningitis patients have a more inflammatory CSF profile at the time of diagnosis, higher rates of AMS on presentation, and higher rates of 90-day and 1-year all-cause mortality. We postulate that reversible immunosuppression among HIV patients may partially explain these findings. Further research is needed to identify hallmarks of cryptococcal meningitis in non-HIV patients to facilitate early intervention.

Disclosures

All authors: No reported disclosures.
1722. Histoplasmosis Acquired in Alberta, Canada, 2011–2018
Authors: Dingle Tanis , Fathima Sumana , Sonpar Ashlesha , Saxinger Lynora M , Schwartz Ilan S
Published: October 2019

Background

Histoplasmosis is a serious fungal infection caused by the geographically restricted, dimorphic fungus Histoplasma capsulatum. In Canada, the geographic range of H. capsulatum is classically thought to be restricted to southern parts of Ontario and Quebec. Over the past decade, histoplasmosis has occasionally been diagnosed in patients in Alberta without travel to areas of known geographic risk (Figure 1). We studied the epidemiology and geographic distribution of histoplasmosis in Alberta to assess evidence for locally-acquired infections.

Methods

We retrospectively reviewed all laboratory-confirmed (culture, antigen and/or immunodiffusion positive) cases of histoplasmosis diagnosed from January 1, 2011 to June 30, 2018. Data collected by public health and clinical charts were reviewed for clinical presentation, exposure and travel histories, and geographic distribution of cases. Cases of histoplasmosis in patients who had not left Alberta or associated with a local point source were classified as definite local acquisition; cases in patients with remote travel but with local exposures and appropriate timing of disease onset were deemed “probable” cases of local infection. University of Alberta’s Research Ethics Board approved this study.

Results

We identified 45 laboratory-confirmed cases of histoplasmosis, including 17 cases that were locally acquired. Among these, there were 12 cases of definite local acquisition, including 8 patients from 3 point-source outbreaks—all involving exposure to bats and/or their droppings in chimneys or attics of private dwellings or churches—and 4 sporadic cases in patients who had never traveled. Of the other 5 cases probably acquired in Alberta, patients had previously traveled (n = 4) or travel history was incomplete (n = 1) but local exposures preceding infection were considered compelling. The mean incidence rate of locally acquired infection was 0.062/100,000 population with incidence increasing since 2014. Table 1 shows features of locally acquired cases.

Conclusion

This study, for the first time, establishes Alberta as a region of geographic risk for histoplasmosis. The diagnosis should be considered in patients with compatible symptoms and exposure history, even in the absence of travel.

Disclosures

All authors: No reported disclosures.
1723. Human Serum Albumin Regulates the Growth of Candida auris in vitro
Authors: Sakai Jun
Published: October 2019

Background

Candida auris is commonly detected in human ear secretions. However, C. auris occasionally causes bloodstream infections even in immunocompetent patients resulting in poor prognosis. It was speculated that C. auris growth within the blood might be regulated by proteins in the bloodstream. Thus, in this study, the potential role of blood proteins in the regulation of C. auris growth was investigated.

Methods

Five Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis) were incubated overnight. Colony suspensions for each species were prepared and adjusted to OD 1.0 at absorbance 0.1. Then, human serum albumin (HSA) and bovine serum albumin (BSA) were diluted (2.5 g/dL–0.002 g/dL) and mixed with the suspensions. Mixed samples were adjusted to 100 μL and incubated on MHA plates at 35°C for 2 days. Then, 50 μL of the combined sample was extracted and streaked onto Yeast extract-Peptone-Dextrose (YPD) agar. The remaining 50 μL sample was analyzed using an XTT assay. Further testing was then conducted on the effects of a specific blood protein albumin on Candida. Thereby, C. albicans and C. auris were cultured following the procedure above and stained with Annexin V and PI.

Results

The growth of C. auris mixed with a high albumin concentration (2.5~0.15 g/dL) was regulated compared with that of other Candida species (P < 0.01) (Figures 1 and 2); however, the growth of C. auris mixed with a lower albumin concentration was similar to that of other species. The wash-out study showed that C. auris growth and survival in the high albumin concentration was not different than that of other species.

Conclusion

HSA and BSA regulated C. auris growth which led to increased necrosis of C. auris. Conversely, growth of the other Candida species was not regulated. Therefore, albumin might be involved in the growth and necrosis of C. auris. As the highest concentration at which albumin regulated C. auris growth was similar to that found in human serum, it is possible that serum albumin might help prevent C. auris from entering the bloodstream via the ear or skin.

Disclosures

All authors: No reported disclosures.
1724. Plasmid-free CRISPR-Cas9 System for Genetic Engineering of Rhizopus delemar
Authors: Gu Yiyou , Baldin Clara , Gebremariam Teklegiorgis , Alqarihi Abdullah , Mamouei Zeinab , Wang Ping , Nagy Gabor , Skory Christopher , Ibrahim Ashraf S
Published: October 2019

Background

Mucormycosis is a serious infection caused by fungi of the order Mucorales. Rhizopus delemar is the most common etiologic agent of mucormycosis. Pathogenesis studies of mucormycosis have been hampered by poor genetic trackability of the organism, owing to rare chromosomal integration events and multinucleated nature of the cells. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) system has been widely used in genetic manipulation through efficient homologous and non-homologous break points in a variety of organisms including R. delemar. However, plasmid-free CRISPR/Cas9 system has not been previously described in the fungus. Here, we introduce a rapid plasmid-free system for inducing orotidine 5’-phosphate decarboxylase (pyrF) gene mutation in R. delemar.

Methods

Protoplasts of R. delemar 99–880 strain were transformed with 20 nucleotide gRNA targeting the N-terminus of pyrF gene and the Cas9 enzyme. Screening for pyrF auxotrophy was carried out by plating transformed protoplasts on potato dextrose agar (PDA) plates containing 1 mg/mL 5-fluoroorotic acid (5-FOA) and 100 µg/mL uracil. Putative mutant strains were selected for uracil auxotrophy by plating simultaneously on media with or without uracil. pyrF disruption was verified by using PCR and qRT–PCR.

Results

Approximately100 transformants were generated through plating on 5-FOA plates. Only three transformants did not grow on minimal medium lacking uracil, indicating that they were true pyrF null mutants. PCR analysis showed that these three transformants have undergone nucleotide deletion events within the pyrF gene. The lack of pyrF gene expression was further verified by using qRT–PCR relative to wild-type R. delemar 99–880.

Conclusion

Similar to the plasmid-based genome manipulation strategy, the plasmid-free CRISPR/Cas9 system can induce gene editing in R. delemar. This rapid and simple approach adds an additional tool in our conquest to understand pathogenesis of mucormycosis.

Disclosures

All authors: No reported disclosures.
1730. Invasive Fusarium Species in Mayo Clinic Patients with Hematologic Malignancies
Authors: Harris Courtney , Tosh Pritish , Tande Aaron J
Published: October 2019

Background

The epidemiology of fungal infections in hematologic malignancies has changed in the past decade. Triazole prophylaxis has decreased Candida spp infections while infections due to other molds such as Aspergillus and Fusarium species have increased. Fusariosis has very poor prognosis, and after aspergillosis, is the most common invasive fungal infection in this patient population. We sought to describe fusariosis in patients with hematologic malignancy at the Mayo Clinic.

Methods

We performed a retrospective review of patients with culture-positive Fusarium infection from January 2003 to October 2016 at the Mayo Clinic, Rochester, MN. The records of patients were reviewed for demographics, diagnosis, treatment, and outcomes including mortality. Patients without a diagnosis of hematologic malignancy were excluded. Patients were classified with proven or probable Fusariosis based on the Revised Definitions of Invasive Fungal Disease from the EORTC/MSG Consensus Group.

Results

We identified 14 patients with hematologic malignancies (age range 17–76 years; median 60 years) with a confirmed culture diagnosis of Fusarium infection classified as proven (9 patients) or probable (5 patients). Two cases were isolated pulmonary infections, 3 extra-pulmonary, and 9 disseminated cases. Two patients had previously undergone stem cell transplantation. Eight patients (57%) were receiving antifungal prophylaxis at the time of diagnosis: 2 on voriconazole, 1 on posaconazole, 1 on fluconazole, 3 on echinocandins, and 1 on Amphotericin B. Nine patients (64%) were neutropenic at the time of diagnosis. Amphotericin was the initial treatment in 7 (50%) patients, with voriconazole added for 4 patients for combination therapy the first week. Voriconazole monotherapy was given initially in 5 patients. Seven patients (50%) were deceased at 6 weeks after culture positivity, with an additional 2 patients deceased by 12 weeks.

Conclusion

Fusarium infection outcomes in patients with hematologic malignancies are poor. Neutropenia was common in those diagnosed, and infections were more likely to be disseminated, with high mortality rates. Amphotericin was commonly used as initial treatment, with many physicians recommending combination therapy with two agents, commonly voriconazole.

Disclosures

All authors: No reported disclosures.
1731. Immune Dysregulation in Mucormycosis
Authors: Gupta Chhavi , Das Shukla , Rai Gargi , Singh Praveen K , Dar Sajad , Ansari Mohammad A
Published: October 2019

Background

Mucormycosis is a fatal fungal infection with unique predisposition to infect diabetics. Dysregulated adaptive immunity contributes to the pathogenesis in all fungal diseases, but activated Th17 cells have laid a new dimension to chronic inflammatory response which was previously attributed to uncontrolled Th1 response. We attempted to study the Th17 and T regulatory (Treg) immune response in diabetic patients with mucormycosis and compared the data with a healthy control and a T2DM case without fungal infection. In addition we could follow-up one patient post 6-month treatment and performed immunological studies.

Methods

2 mL of blood samples were collected in EDTA vial from two patients who were suffering from diabetes with mucormycosis for immunological investigations. Samples were also taken from age-matched T2DM patient without fungal infection and a healthy volunteer as controls for T-cell parameters. Repeat blood sample was taken to study immune parameters in one patient who was followed up after 6 months. The expression of various T-cell markers was analyzed by immunostaining with the antibodies against CD3, CD4, CD25, CD161, IL-23R [Becton Dickinson (BD) PharMingen]. Fluorescence profiles were analyzed using Flow Jo software (BD Biosciences). The results are expressed as a percentage of positive cells.

Results

The percentages of CD4+ cells were low in both patients when compared with and healthy control but it is much higher in diabetes case when compared with others. CD161+ cell population was higher in both patients when compared with healthy control and diabetic patient without fungal infection. The percentage of IL23R+ cells was significantly high in patient before treatment when compared with, healthy control and diabetics. and decline after treatment. The percentage positivity of CD25+ cells was highest in healthy control when compared with others. The profile of CD25+ cells was comparatively similar in patient before treatment and diabetics but we found a higher percentage, in patients after treatment.

Conclusion

The findings in this study imminently indicate the mechanism of immune dysregulation involving Th17 and Treg pathways in mucormycosis and provide evidence that restoration of Th17/Treg may be considered as a therapeutic option for long-term benefit in diabetics.

Disclosures

All authors: No reported disclosures.
1732. A Canine Target Species Challenge Model to Evaluate Efficacy of a Coccidioidomycosis Vaccine
Authors: Shubitz Lisa F , Bowen Richaard , Robb Edward J , Powell Daniel A , Bosco-Lauth Angela , Hartwig Airn , Trinh Hien , Lewis Maria L , Frelinger Jeffrey A , Galgiani John N
Published: October 2019

Background

The preferred efficacy design for licensing a vaccine for animal use (United States Department of Agriculture (USDA)) is a prospective, placebo-controlled, randomized, and double-blinded vaccination-challenge trial. In such studies, each subject receives the same exposure to the virulent pathogen by active challenge. To test a cps1, live avirulent canine coccidioidomycosis vaccine, an inhalation disease model was developed in beagle dogs.

Methods

6-month old male beagle dogs were housed according to PHS standards. All procedures, approved by the Institutional Animal Care and Use Committee for Colorado State University, were performed at ABSL3. Dogs were infected by nebulization with low, medium or high counts of arthroconidia of Coccidioides posadasii, strain Silveira, delivered via endotracheal tube under injectable anesthesia. Thoracic radiographs, CBC, and serum chemistries and body weights were obtained at 2- or 3-week intervals and dogs were euthanized 8 weeks p.i., or earlier if necessary. Approximately 1 gram lung specimens from each lobe were cultured for fungal burden. Fixed tissues were examined histologically. Serum was tested for antibodies.

Results

Ten of 11 dogs were successfully infected; 5 required early removal at 33 to 48-days p.i. Elevated globulin, decreased albumin, decreased A/G ratio, monocytosis and weight loss were present in all infected dogs. Radiographic and histopathological lesions were very extensive at the high challenge doses. Medium doses had the most consistent scoring and clinical findings, including some early removal, without overwhelming disease, while the low dose produced the least consistent quantifiable features. All dogs developed antibodies.

Conclusion

Nebulized aerosol delivery of spores reproducibly produced significant coccidioidomycosis in 10 of 11 dogs. Overall, the challenge model demonstrated consistent characteristic findings sufficient to assess vaccine efficacy in dogs during an 8-week period post challenge without producing a potentially overwhelming infection. The aerosol nebulization of arthroconidia in beagle dogs should provide a vaccination-challenge experimental design in line with Chapter 9 Code of Federal Regulations, parts 102.5 and 104.5.

Disclosures

All authors: No reported disclosures.
1739. Epidemiology of Invasive Fungal Infections in Allogenic Hematopoietic Stem Cell Transplant Recipients in Utah
Authors: Zurko Jessica , Webb Brandon J
Published: October 2019

Background

Invasive fungal infections are a leading cause of death in allo-HSCT (allogenic hematopoietic stem cell transplant) recipients. We describe the epidemiology of IFIs (invasive fungal infections) in allo-HSCT recipients at a single institution in Salt Lake City, Utah between 2006 and 2015.

Methods

We searched all encounters in the Intermountain Healthcare electronic medical record from 2006 to 2015 for clinical data associated with IFIs in allo-HSCT recipients. EORTC-MSG definitions were applied to categorize IFI as proven, probable, or possible. Linear regression was used to model the variation in incidence over time.

Results

326 unique allo-HSCT were performed; of these 114 episodes of IFI occurred in 105 patients. Mean incidence was 35.9 IFI per 100 transplants, and increased by 2.3 IFI cases/100 transplants per year. 25.4% of cases were classified as proven; 47.4% as probable and 19.3% as possible. Invasive Aspergillus represented the majority of cases (62.3%), followed by non-specified (in most cases positive imaging and a positive β-d-glucan, 18%), Candidiasis (10%), and Mucorales (3.5%). The median age was 50 years, range 22 to 73, with males representing 52.6% of cases. The most common non-hematologic comorbidities were chronic pulmonary disease (42.9%), chronic heart failure (32.4%), and hepatic disease (31.4%). 48.6% of patients received matched unrelated allo-HSCT, 34.3% received matched sibling donor allo-HSCT, 14.3% received haploidentical allo-HSCT, and 3% received cord allo-HSCT. 79% of transplants were myeloablative. Median time from transplant to onset of IFI was 145 days (95% CI 39–259). The median time to onset of Aspergillosis was 120 days (95% CI 34–241 days), Candidiasis was 130 days (95% CI 12–283 days), and Mucorales was 246 days (95% CI 126–338 days). Active GVHD was present in 60% of IFI cases. 63% of cases were on antifungal prophylaxis, most commonly an echinocandin. All-cause mortality was 30.5% at 42 days and 65.7% at 1 year. The median time to death from the onset of IFI was 68.5 days.

Conclusion

IFIs are common in allo-HSCT recipients and appear to be increasing in frequency. Further work is needed to risk-stratify patients, determine optimal prophylaxis and empiric treatment, and define resistance trends.

Disclosures

All authors: No reported disclosures.
1757. Hepatitis C-Infected Donors and Hepatitis C-Infected Recipients: Analysis of Renal Transplant Outcomes
Authors: Crossman Hayley , Tavakol Mehdi , Freise Chris , Chin-Hong Peter
Published: October 2019

Background

Increased utilization of hepatitis C virus (HCV)-infected organs could reduce the supply–demand mismatch in organ transplantation. It is important to determine precise outcomes of HCV-positive organs transplanted into HCV-positive recipients (HCV D+\R+) to quantify risk for patients and other stakeholders. Small studies have identified shorter wait times in HCV D+\R+ compared with HCV-negative donor and HCV-positive recipients (HCV D−\R+), but there is little information about survival and rejection in the era of effective direct-acting antivirals (DAA).

Methods

We performed a retrospective cohort study of all cases of renal transplantation involving HCV-positive recipients at an academic medical center from 2008 to 2019. We extracted data using the institutional electronic transplant database. Demographics, incidence of organ rejection, renal function and patient mortality data were compared between HCV D+\R+ and HCV D−\R+.

Results

Among 3,781 patients who received a kidney transplant between 2008–19, 139 were HCV D-\R+ and 51 were HCV D+\R+. Both groups had similar waiting list time (1,196 ± 889 days vs. 1,301 ± 1240 days, P > 0.20), donor mean age (37 ± 11 y vs. 39 ± 13 years, P > 0.20) and sex (female: 37% vs. 42%, P > 0.20). Follow-up time was similar between both groups (5.2 ± 4 years vs. 5.3 ± 3 years, P > 0.20). The incidence of mortality (16% vs. 17%, P > 0.20) [Figure 1] and rejection (18% vs. 19%, P > 0.20) [Figure 2] was similar between two groups. Using a Cox Hazards model, we found no association between HCV D+/R+ and increasing risk of rejection (HR 0.92, 95% CI 0.43–1.95, P > 0.20) or mortality (HR 0.93, 95% CI 0.42–2.1, P > 0.20). In a multivariate analysis, age was the only independent risk factor for HCV D+/R+ mortality (HR = 1.09, 95% CI 1.03–1.14, P < 0.001).

Conclusion

Patients who are HCV-positive did not have worse mortality or graft rejection if they received HCV-positive kidneys compared with HCV-negative kidneys. Providers can use these data to give specific risk information to HCV-positive patients about accepting an HCV-positive kidney for transplant, even perhaps encouraging it. Increasing the utilization of HCV-positive kidneys for transplantation in the era of effective DAA has the potential to offer life-saving treatment to substantially more patients.

Disclosures

All authors: No reported disclosures.