bluuebunny/crossref_metadata_2025_split huggingface dataset:
745. Combination Treatment of Liposomal Amphotericin B and Isavuconazole is Synergistic in Treating Experimental Mucormycosis
Authors: Gebremariam Teclegiorgis , Gu Yiyou , Singh Shakti , Kitt Therese , Ibrahim Ashraf S 
Published: January 2021

Abstract

Background
Mucormycosis is a life-threatening infection that predominantly occurs in immunocompromised hosts. Liposomal amphotericin B (L-AMB) and isavuconazole (ISAV) are commonly used antifungal drugs to treat mucormycosis. However, the efficacy of combination therapy of L-AMB + ISAV compared to monotherapy is unknown. We used an immunosuppressed mouse model of pulmonary mucormycosis to compare the efficacy of L-AMB + ISAV vs. either drug alone.

Methods
ICR mice were immunosuppressed with cyclophosphamide (200 mg/kg) and cortisone acetate (500 mg/kg) on Days -2, +3, and +8 relative to intratracheal infection with 2.5 x 105 cells of Rhizopus delemar 99-880, or 2.5 x 106 cells of Mucor circinelloides. Treatment with L-AMB (10 mg/kg, given intravenously qd), ISAV (56 mg/kg, by oral gavage TID), or a combination of both started 8 h post-infection and continued through day +4. Placebo mice received vehicle control. Survival studies through day +21 and tissue fungal burden (by conidial equivalent [CE] using qPCR) on Day +4, served as primary and secondary endpoints.

Results
For mice (n=20) infected with R. delemar, L-AMB and ISAV equally prolonged median survival time and enhanced survival vs. placebo (19 and 16 days for L-AMB and ISAV, respectively, and overall survival of 50% for either drug alone, vs. 9 days and 5% overall survival for placebo, P&lt; 0.002 for either drug vs. placebo by Log Rank test). Importantly, combination treatment enhanced median survival time (&gt;21 days) and resulted in an overall survival of 80% (P&lt; 0.05 vs. all treatments). Both antifungal drugs reduced tissue fungal burden of mice (n=10) lungs and brain by ~1.0-2.0 log vs. placebo-treated mice (P&lt; 0.02 by Wilcoxon Rank Sum). Consistent with the survival data, treatment with combination therapy resulted in 2.0-3.5 log reduction in fungal burden of either organ vs. placebo and 1.0 log reduction vs. either drug alone (P&lt; 0.005). Similar results were obtained using mice infected with M. circinelloides.

Conclusion
L-AMB + ISAV demonstrate greater activity vs. monotherapy treatment in immunosuppressed mice infected with either of two common causes of mucormycosis. These studies warrant further investigation of LAmB + ISAV combination therapy as an optimal therapy of human mucormycosis.

Disclosures
Therese Kitt, MD, Astellas Pharma (Employee) Ashraf S. Ibrahim, PhD, Astellas Pharma (Research Grant or Support)
753. Performance Characteristics of Diagnostic Assays in Blastomycosis
Authors: O’Dowd Timothy , McHugh Jack , Wengenack Nancy , Theel Elitza , Vergidis Paschalis 
Published: January 2021

Abstract

Background
Blastomycosis has historically been a difficult diagnosis to establish, often initially misdiagnosed as bacterial pneumonia. Serologic assays and polymerase chain reaction (PCR) tests are available, but their performance is not well defined. The objective of this study was to characterize their performance.

Methods
Subjects were identified via chart review of patients diagnosed with blastomycosis from 2005 to 2020. A definitive diagnosis was based on fungal culture, histopathology, or cytology. Performance characteristics of the Blastomyces antibody enzyme linked immunosorbent assay (ELISA), immunodiffusion (ID), complement fixation (CF), urine and serum antigen ELISAs, and PCR were evaluated in patients with confirmed blastomycosis. Data on patient demographics, location of disease, and mortality was also collected.

Results
We identified 193 patients with blastomycosis. The mean age was 51.8 years (range, 11-84) and 73.6% of patients were male. 42.5% resided in Minnesota, 18.1% in Wisconsin, and 12.9% in Iowa. Diagnosis was based on culture in 142 (73.2%) or histopathology/cytology in 67 (34.7%) patients. Granulomatous inflammation was present in 73.1% (38/52) while 21.2% (41/193) had evidence of extrapulmonary dissemination.
The antibody, ID, and CF assays were positive in 43.5% (37/85), 35.1% (33/94) and 20.5% (8/39) of patients, respectively. Sensitivity of Blastomyces PCR was 40% (4/10) in sputum and 75% (21/28) in bronchoalveolar lavage (BAL) fluid. Blastomyces urine and serum antigen tests were positive in 68% (34/50) and 50% (9/18) of cases, respectively, while the urine antigen was positive in 63.6% (7/11) of disseminated cases. Patients had a positive Histoplasma urine antigen test in 54.1% (20/37) and Aspergillus galactomannan in BAL in 34.8% (8/23) of cases. Serum beta-D-glucan test was positive in 16.7% (2/12). 90-day mortality was 21/193 (10.9%) and median time from diagnosis to death was 18 days.

Conclusion
In this cohort, Blastomyces urine antigen was the most sensitive noninvasive test, with similar performance in pulmonary and disseminated disease. However, its utility is limited by poor specificity due to cross-reactivity. Blastomyces PCR from BAL fluid demonstrated the highest sensitivity. Blastomyces antibody, ID, and CF had poor sensitivity.

Disclosures
All Authors: No reported disclosures
758. Epidemiology of Tick-Borne Encephalitis (TBE): A Traveler′s Perspective
Authors: Pugh Sarah , Erber Wilhelm , Pilz Andreas , Schmitt Heinz-Josef 
Published: January 2021

Abstract

Background
Tick-borne Encephalitis (TBE) is a CNS infection caused by the TBE virus (TBEV), transmitted by ticks or by ingestions of unpasteurized dairy products. Persisting sequelae occur in up to 50% of patients and case fatality rates are 0.4-6% (up to 20% in Russia). There is no specific treatment, but prevention exists. New areas of TBEV circulation were recently identified. Here the current distribution of the TBEV by the end of 2019 is summarized.

Methods
Data were obtained from solicitation of local expert data from countries in Europe and Asia on TBEV isolation, type of surveillance/reporting, past/current case counts, and vaccine uptake, supplemented by literature searches. Countries were classified as suggested by the European Centers for Disease Prevention and Control (ECDC) as TBE- “predisposed” (competent ticks present), “imperiled” (TBEV isolated), “affected” (sporadic autochthonous cases) or “endemic” (annually autochthonous cases).

Results
TBE has now been diagnosed in Eurasia from the United Kingdom, Norway and France in the west, northern Italy in the south, central/eastern Europe, Russia, China on to Japan in the east. “New endemic” countries in the last five years include the United Kingdom, the Netherlands, as well as “new endemic regions”, e.g. in France, Norway, Germany, Finland and Poland. Six countries are considered as predisposed only, three as imperiled, five as affected and 29 as endemic. Misclassification is likely as some countries have no testing (no test), incomplete testing and/or underreporting.

Conclusion
The main considerations of TBEV risk for oversea travelers to Eurasia are: 1) the exact region and terrain within a country; 2) the planned type of (outdoor) activity; 3) the reliability of within country TBEV surveillance. TBE incidences per region may fluctuate log-fold over just a few years and low reported case counts may reflect a lack of testing, and/or preventive measures including vaccine uptake, and underreporting. As the incidence of TBE is unpredictable, prevention measures should be considered for any person traveling or residing in a recognized TBE “risk area”.

Disclosures
Sarah Pugh, PhD, Pfizer (Employee, Shareholder) Wilhelm Erber, PhD, Pfizer (Employee, Shareholder) Andreas Pilz, PhD, Pfizer (Employee, Shareholder) Heinz-Josef Schmitt, MD, Pfizer (Employee, Shareholder)
760. A Silent Threat: Seroprevalence of Chagas Disease in Latin Americans Living in Long Island, New York
Authors: Michelen Yamil E , Milla Lucia , Sin Eric , Taub Erin , Saldivar Miguel A , Marcos Luis 
Published: January 2021

Abstract

Background
Chagas Disease (CD), a neglected tropical disease of Latin America (LA) is caused by the parasite Trypanosoma cruzi, transmitted by the triatomine insect (kissing bug), and known to cause cardiomyopathy (CMP), megacolon or achalasia. Despite the population of Latin Americans, by birth or descent, in Long Island (LI), New York (NY) approximating 20%, information regarding prevalence of CD in this region is scarce. This study aims to determine the seroprevalence and risk factors for T. cruzi infection among hispanics in LI.

Methods
This is a cross-sectional study. Inclusion criteria included, birth or living in LA for &gt; 3 years, mother born or lived in LA for ≥3 years, and residency in Suffolk County, LI. Patients were screened by Chagas Detect™ Plus Rapid Test (immunochromatographic strip assay for the qualitative detection of human IgG antibodies to T. cruzi; InBios Rapid test). Seropositivity was confirmed by enzyme immune assay and immunoblot. Participants answered a questionnaire regarding demographics and risk factors of CD.

Results
A total of 121 subjects (55.4% male) were tested from February 2018 to February 2020. Twelve were seropositive confirmed cases (9.9%; 66.7% male), with 9 cases from El Salvador (75%, p=0.06). Factors associated with infection were living in a palm house (OR=14.1, CI 2.7-74.7), history of triatomine bite (OR=9.5 CI=1.75–51.7), living in a house with triatomine (OR= 9.02, CI=1.9 – 42.8), and having relatives diagnosed with Chagas (OR= 7.6, CI=1.4 – 39.2). T. cruzi infected were most likely to have donated blood (OR=9.4, 95% CI=2.3–3.6). Two cases (16.6%) had CMP and did not qualify for treatment. One had gastrointestinal disease (8.3%). Eight started treatment with benznidazole.

Conclusion
In conclusion, we found a prevalence of 9.9% of T. cruzi infection in this high-risk population of LI. Two cases were diagnosed with CMP during this screening study highlighting that there are unrecognized cases of CD in this region where 20% are Hispanics. Such high prevalence and unrecognized disease, highlights the importance of raising awareness among providers of early screening and to prevent potential deadly outcomes.

Disclosures
All Authors: No reported disclosures
761. Antimicrobial Resistance Trends at a Pediatric Hospital in Guatemala City, 2005-2019
Authors: Graff Kelly E , Windsor W Jon , Calvimontes Mirella , Toledo Mario Augusto Melgar , Rivera Jose , Santos Lucy , Dominguez Samuel , Asturias Edwin J , Mata Maria Remei Gordillo 
Published: January 2021

Abstract

Background
Antimicrobial resistance (AMR) is an increasing global threat to public health, particularly in Latin America. Most published data are based on adults with limited pediatric reports regarding resistance trends. Our study evaluated AMR rates in a large tertiary pediatric hospital in Guatemala City and the association with clinical outcomes.

Methods
We analyzed AMR rates for six bacterial species (Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus) identified from blood cultures from the WHONET database between 2005-2019. Resistance was determined using CLSI cut-offs on the VITEK and Sensititre systems. Student’s t tests and simple linear regression models were performed. A retrospective review was performed on 99 pediatric patient charts with positive blood cultures (June 2018-May 2019) to assess clinical outcomes.

Results
Klebsiella and Acinetobacter were the most prevalent organisms throughout the 15 years of surveillance, with 2019 sensitivities demonstrating carbapenem-resistance in 99 (57%) and 57 (91%) of isolates, respectively. Increased resistance rates were noted for all Gram-negative organisms evaluated, with particular clinical and statistical significance noted for K. pneumoniae with imipenem (4.3% average resistance increase per year (PARPY), p-value &lt; 0.0001), ciprofloxacin (4.5 PARPY, &lt; 0.0001), and piperacillin-tazobactam (3.4 PARPY, &lt; 0.0001), as well as A. baumannii with imipenem (2.9 PARPY, p-value &lt; 0.0001), cefepime (1.7 PARPY, &lt; 0.0001), and ciprofloxacin (2.5 PARPY, 0.0002). In contrast, resistance rates decreased for S. aureus with oxacillin (-2.7 PARPY, 0.0015). A mortality rate of 20% among our 99-patient cohort was detected. Of the 37% who received optimal therapy, the median time to optimal therapy was 90 hours.
Acinetobacter baumannii resistance to imipenem, 2005-2019

Klebsiella pneumoniae resistance to imipenem, 2005-2019

Staphylococcus aureus resistance to oxacillin, 2005-2019

Conclusion
Significant rises in AMR among pediatric patients in a large tertiary hospital in Guatemala City have occurred over 15 years. This likely contributed to delays in optimal antimicrobial therapy, increased exposure to broad spectrum antibiotics, and potentially increased mortality. Improved antimicrobial stewardship, infection prevention, and rapid diagnostic testing are needed in order to combat this growing problem.

Disclosures
Kelly E. Graff, MD, BioFire Diagnostics, LLC (Grant/Research Support) Samuel Dominguez, MD, PhD, BioFire (Consultant, Research Grant or Support)
764. Correlates of Lost to Follow-up Among Newly Diagnosed Older People with HIV in Ukraine
Authors: Allen Amy J , Zeziulin Oleksandr , Postnov Oleksandr , Rozanova Julia , Litz Taylor , Zaviryukha Irina , Kiriazova Tetiana , Shenoi Sheela 
Published: January 2021

Abstract

Background
Ukraine has the second largest HIV epidemic in Eastern Europe and Central Asia. Older People with HIV (OPWH) are at increased risk of poor outcomes compared to younger patients. We examined the prevalence and correlates of loss to follow-up (LTFU) among newly diagnosed patients in Ukraine.

Methods
Retrospective chart review was conducted of 400 patients newly diagnosed with HIV July 1, 2017 - Dec 1, 2018. Data was collected from clinics in the city of Odessa and surrounding regions. OPWH were ≥50 years old at diagnosis and LTFU was defined as no contact with the HIV clinic for 90 days. Demographic, clinical characteristics, and follow-up outcomes were examined, and multivariate logistic regression was used to estimate the adjusted odds ratios at 95% confidence intervals.

Results
Of the 400 people living with HIV, median age was 50 (IQR35-55), 196 (49%) were women, and 177 (44%) had CD4&lt; 200cell/mm3 at diagnosis. Overall, 65 (16.5%) were LTFU from diagnosis and 54/65 (83%) were lost after their first appointment at the HIV clinic. Among those lost to follow-up, 49 (75%) were ≥50 at the time of diagnosis. Multivariate analysis showed LTFU was associated with age &gt;50years (aOR 3.6, CI 1.8-7.3, p=0.001), lack of ART prescription (aOR 16.4, CI 8.5-31.8, p= 0.001), and living outside the city of Odessa (aOR 2.9, CI 1.5-5.7, p=0.002). Figure 1 shows the breakdown of lost to follow-up for OPWH.
Figure 1. Retainment in HIV Care for OPWH compared to those &lt;50 years old.

Conclusion
LTFU among OPWH is significantly greater than younger people with HIV, and associated with lack of ART and living in nonurban settings. OPWH may benefit from differentiated HIV service delivery to reduce loss to follow up and interventions tailored to improving HIV outcomes for OPWH in resource-limited settings are urgently needed.

Disclosures
All Authors: No reported disclosures
765. Epidemiological And Clinical Features Of Rickettsiosis
Authors: Hammami Fatma , Koubaa Makram , Chakroun Amal , Rekik Khaoula , Smaoui Fatma , Elleuch Emna , Marrakchi Chakib , Jemaa Mounir Ben 
Published: January 2021

Abstract

Background
Rickettsiosis is a common tick-borne disease in tropical regions. The treatment is usually delivered in front of high index of suspicion, since the diagnosis confirmation might be delayed. We aimed to study the epidemiological and clinical features of rickettsiosis in our region.

Methods
We conducted a retrospective study including all patients hospitalized in the infectious diseases and pediatric department for confirmed rickettsiosis between 1995 and 2017. The diagnosis was confirmed by serological tests (seroconversion) or a positive polymerase chain reaction assays for Rickettsia.

Results
There were 424 patients among whom 232 (54.7%) were male. The mean age was 39 ±18 years. There were 62 children aged ≤18 years (14.6%). During six months period, from May to October, 360 patients were diagnosed with the disease (84.9%). In total, 334 patients had a close contact with animals (78.7%). The revealing symptoms were fever (100%), arthralgia (77.6%), cephalalgia (72.4%) and vomiting (44.8%). Physical examination showed maculopapular skin rash in 350 cases (82.5%), inoculation eschar in 105 cases (24.8%) and meningeal syndrome in 43 cases (10.1%). There were 43 cases (10.1%) of meningitis, 6 cases of meningoencephalitis (1.4%) and 5 cases of myocarditis (1.2%). Laboratory investigations revealed liver cytolysis (60%) and thrombocytopenia (57.5%). Doxycycline was used in 288 cases (68%), fluoroquinolones in 113 cases (26.6%) and macrolide in 23 cases (5.4%). The mean duration of antibiotics was 8 ±4 days. The disease evolution was favourable in 418 cases (98.6%). Four patients (1%) were dead and 2 patients (0.4%) were transferred to intensive care unit.

Conclusion
Rickettsiosis is not a rare disease. Careful clinical and laboratory investigations guide the diagnosis process, which is confirmed with serological tests.

Disclosures
All Authors: No reported disclosures
767. Identification and Management of Diarrhea in Children Under Five in Bamako, Mali
Authors: Cuttin Karen , Dupont Elizabeth , Keita Adama Mamby , Sow Samba , Kotloff Karen 
Published: January 2021

Abstract

Background
Diarrhea is a leading cause of death for Children Under Five Years Old (CUFYO) worldwide, and Mali has the second highest diarrhea-related case fatality rate among African countries. The World Health Organization’s Integrated Management for Childhood Illness (IMCI) handbook provides recommendations for management of acute watery diarrhea (AWD), including: increased fluids, continued feeding, and zinc supplementation. It restricts antibiotics to dysentery. The 2018 Malian Demographic and Health Survey noted low rates of rehydration and zinc use. This study aimed to evaluate how provider knowledge, beliefs, and practices (KBPs) align with IMCI recommendations for diagnosis and management of diarrhea in Mali.

Methods
This qualitative cross-sectional study interviewed 136 providers who manage diarrhea in CUFYO in Bamako, Mali from July - August 2017. Providers included: doctors (D), pharmacists (P), market vendors of allopathic medications (MV), traditional healers (TH), and vendors of traditional medicines (TV). Participants were randomly selected and presented with scenarios depicting diarrheal syndromes. They provided a diagnosis, etiology of illness, and management recommendations. Providers were surveyed on KBPs regarding IMCI recommendations.

Results
Only 43% of providers provided the IMCI definition of AWD. Participant-IMCI concordant diagnosis varied by provider group for AWD (D-73%, P-67%, MV-31%, TH-18%, TV-40%), Dysentery (D-38%, P-75%, MV-38%, TH-61%, TV-40%), and Some Dehydration (D-31%, P-4%, MV-4%, TH-7%, TV-40%). Only 41% of all providers identified dehydration as a sequela of AWD; 18% noted mortality. Etiologies of AWD cited included: infection, teething, diet, hygiene, and many others. Participants volunteered treatment of AWD with fluids (D-52%, P-8%, MV-0%, TH-0%, TV-0%), but not zinc (0%). MK alone offered inappropriate use of antibiotics for AWD (23%).

Conclusion
Provider identification and management of diarrheal syndromes in CUFYO remain largely inconsistent with IMCI recommendations across all sectors of providers interviewed, specifically for rehydration therapy and zinc supplementation.

Disclosures
All Authors: No reported disclosures
769. Mortality Among Inpatients After the Initiation of ‘Treat All’ With Dolutegravir in Botswana
Authors: Klinger Amanda E , Kronen Ryan J , Barak Tomer , Mophuthegi Patricia , Makhema Joseph , Zash Rebecca , Shapiro Roger 
Published: January 2021

Abstract

Background
Botswana was the first African country to implement a ‘treat all’ dolutegravir (DTG)-based treatment program for all adults. We studied whether this transition made a short-term impact on inpatient mortality among people living with HIV (PLWHIV).

Methods
From Dec 2015-Nov 2017, data were collected prospectively on all patients admitted to the medical wards of a district hospital in Botswana. Tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) was the first-line recommended antiretroviral treatment (ART) regimen for all ART-naïve adults with CD4 &lt; 350 until May 2016, when it was replaced by TDF/FTC/DTG without CD4 restriction (‘treat all’). Multivariable logistic regression was used to compare mortality by ART regimen.

Results
Of 1,969 patients admitted, 41.5% were PLWHIV and of these 62.9% were on ART prior to admission. Before ‘treat all’, 160 (58.0%) of 276 PLWHIV were on ART prior to admission, and post-implementation 354 (65.4%) of 541 PLWHIV were on ART prior to admission (p=0.01). Among 315 patients on EFV-based ART and 85 on DTG-based ART prior to admission, demographics were similar (Table 1), except for more recent ART initiation with DTG, and lower median CD4 cell count with DTG (256 vs. 339 cells/mm3). Tuberculosis (TB) and community acquired pneumonia were the leading causes of hospitalization for both regimens. Death occurred in 178 (21.8%) PLWHIV, including 29% not on ART and 19% on any ART (p=0.003). Overall, 38% who initiated ART &lt; 3 months prior to admission died (23.7% DTG, 48.8% EFV), and 36% with CD4 cell count &lt; 50 cells/mm3 died (42.9% DTG, 30.8% EFV). Fewer deaths occurred among those on EFV (18%) compared with those on DTG (27%). However, controlling for CD4 count and timing of ART start, the risk of mortality among those on DTG and EFV was similar (aRR 1.08, 95% CI 0.62, 1.87). TB was the leading cause of death (40.1% off ART, 31.8% on DTG, 22.2% on EFV).
Table 1. Demographics, clinical characteristics, and outcomes of people living with HIV (PLWHIV) admitted to Scottish Livingstone Hospital, stratified by ART regimen prior to admission.

Conclusion
We found no improvement in inpatient mortality among PLWHIV during the shift to ‘treat all’ with DTG-based ART in Botswana. Decreasing high inpatient HIV mortality will require increased testing in the community to detect and treat PLWHIV prior to disease progression, and improved screening for opportunistic infections.

Disclosures
All Authors: No reported disclosures