bluuebunny/crossref_metadata_2025 huggingface dataset:
715. Evaluation of Four Chromogenic Selective Media for the Isolation of Candida auris
Authors: Phee Lynette , Kwang Lee Ling , Ng Tong Yong
Published: December 2021

Background

Candida auris is an emerging healthcare-associated multi-drug resistant pathogen able to cause severe invasive infections. Public health agencies have emphasized the need for active surveillance of C. auris to enable prompt infection control measures in healthcare institutions. Four commercially available chromogenic selective media were evaluated for the isolation of C. auris in this study.

Methods

Four chromogenic selective media (Brilliance Candida (BC), CHROMagar Candida (CC), CHROMagar Candida Plus (CCP) and chromID Candida (CAN2)) were evaluated with 52 fungal and 20 bacterial strains. Isolates were identified with Vitek matrix-assisted laser desorption/ionization mass spectrometry (MS). 1 µL spots of broth subcultures of each organism were inoculated onto chromogenic media and incubated as per manufacturer’s instructions. Plates were read at 24, 36 and 48 hours. Sabouraud Dextrose agar (fungi) or blood agar (bacteria) were inoculated to obtain viable counts. All reads were categorized into color groups. Sensitivity and specificity were determined based on phenotypic characteristics after 48h of incubation. Additionally, spots of serially diluted C. auris type strain CDC B11903 were assessed for expression of the expected C. auris phenotype at 36, 48 and 72 h. Probit regression model (R version 3.6.3) was used to estimate limit of detection (LOD) for each medium at each time-point.

Results

A minimum of 36h incubation (optimally > 48 h) was required for observation of distinct color and colony morphology. CCP performed best overall, with 100% sensitivity and 96% specificity. Sensitivity was 100% across all 4 media, but specificity was reduced (BC – 66%, CAN2 – 83%, CC – 81%). The lowest LOD was observed with CCP at 4 colony-forming units (CFU). See figure 1 for details.

Figure 1. Comparison of limit of detection for C. auris by type of chromogenic selective media across various time-points.

Conclusion

Rapid isolation and accurate identification of C. auris from samples, including those from non-sterile sites, are crucial for the management of C. auris infections and in curtailing nosocomial transmission. Chromogenic media are simple to use, inexpensive and scalable; ideal for routine diagnostics and high volume screening samples. Of the 4 media evaluated, CCP is best suited to screen for C. auris, with subsequent confirmation of identification using MS or genotypic methods.

Disclosures

Lynette Phee, MD PhD, Creative Life Science Co. Ltd (Creative Media Plate) (Other Financial or Material Support, Provided some of the CHROMagar Candida and CHROMagar Candida Plus plates free-of-charge for evaluation purposes.)Fort Richard Laboratories (Other Financial or Material Support, Provided some of the CHROMagar Candida Plus plates free-of-charge for evaluation purposes.)
716. Characterization of Azole Susceptibility Profiles of Aspergillus spp. Isolates Obtained From Immunocompromised Patients in Cali, Colombia
Authors: Rosso Fernando
Published: December 2021

Background

Aspergillus spp. are opportunistic filamentous fungi causing a spectrum of diseases described aspergillosis. Aspergillosis is treated with triazole antifungals of second-generation, mostly voriconazole or itraconazole, which inhibit the ergosterol synthesis, an important component of the fungal membrane. However, the efficacy of these drugs has been affected by the presence of resistance found in different Aspergillus spp. species, as a mutations in CYP51 gene We describe the azole susceptibility profiles of Aspergillus spp., isolated from clinical samples in a hospital in Cali, Colombia.

Methods

A total of 63 Aspergillus spp. clinical isolates were identified at a phenotypic and protein level through matrix-assisted laser ionization (MALDI-TOF-MS), susceptibility profiles against voriconazole and itraconazole were subsequently characterized. Following the guidelines for susceptibility determination issued by EUCAST, 96-well plates were prepared with the azole antifungals itraconazole (ITZ) and voriconazole(VCZ), using concentrations ranging from 0.06 to 32 mg/L. Each well was then inoculated with 100μL of the fungal inoculum previously diluted in distilled water and 20% tween adjusted to a concentration of 0.5 on the Mcfarland scale. The plates were incubated at 37 °C and readings were taken after 48 hours of incubation.

Results

A total of 63 clinical isolates of Aspergillus spp were collected, of these 44% corresponded to isolates of A. fumigatus, 25% A. flavus/oryzae, 18% A. niger, 5% A. parasiticus, 3% A. terreus and 3% A. versicolor. In vitro characterization of the susceptibility profiles revealed variable phenotypes, with a predominance of susceptible strains for the two antifungals tested, however, of the total isolates, 8% (5/63) were resistant to itraconazole (ITZ), and 6% (4/63) to voriconazole (VRZ).

Figure 1. Distribution or Frequency of Aspergillus spp. Species and Their Resistance Profiles

Conclusion

Azole resistance was low 6-8% . Susceptibility profiles of the strains isolated from clinical samples is important to carry out an accurate identification of each one of the agents involved in infections caused by Aspergillus spp in order to differentiate common species from cryptic ones, since these have increasingly acquired importance at the clinical level,.

Disclosures

All Authors: No reported disclosures
718. Posaconazole Versus Standard of Care for Treatment of Invasive Mold Infections
Authors: Idusuyi Ann-Marie , McCoy Christopher , Gold Howard
Published: December 2021

Background

Invasive mold infections (IMIs) including Aspergillus spp. are a significant cause of morbidity and mortality in immunocompromised patients. Voriconazole is recommended as first line treatment for primary IA. Liposomal amphotericin B and isavuconazole are also recommended alternative therapies. Posaconazole has activity against mold species including those not covered by voriconazole, is available as an IV and oral formulation with a distinct adverse effect profile making it a potential effective alternative for treatment. This study investigated the clinical outcomes of treatment of invasive mold infections (IMIs) with posaconazole compared to standard of care (voriconazole, isavuconazole, liposomal amphotericin B).

Methods

A retrospective, single center, cohort study was completed to evaluate patients with IMIs treated with posaconazole versus those treated with standard of care therapy. Medication orders for posaconazole or standard of care therapy between January 2012 and December 2020 were identified from a clinical data repository. Only patients with antifungal orders with a listed indication for “treatment of fungal infection” were included. Data collected for each group included baseline demographics, underlying conditions, site of infection, type of mold, therapeutic drug monitoring and classification of IMI.

Results

A total of 120 patients met inclusion criteria, with 35 patients in the posaconazole group and 85 patients in the SOC group. Baseline characteristics were similar except for increased severe neutropenia in the posaconazole group (p< 0.0001), more probable IMIs in the SOC group (p=0.009) and more possible IMIs in the posaconazole group (p=0.043). In the posaconazole group 37.1% (13/35) of patients were treatment experienced vs. 29.4% (25/85) of patients in the SOC group. More patients achieved a complete/partial response in the SOC group compared to the posaconazole group (p=0.0001) and more patients experienced treatment failure in the posaconazole group (p=0.01). A higher proportion of patients experienced adverse effects in the SOC group compared to the posaconazole group (p=0.0001).

Conclusion

Posaconazole was not as effective as SOC in treating invasive mold infections but patients experienced comparatively fewer adverse events.

Disclosures

All Authors: No reported disclosures
719. Susceptibility Testing of Oteseconazole (VT-1161) Against Clinical Isolates from Phase 3 Clinical Studies in Subjects with Recurrent Vulvovaginal Candidiasis
Authors: Ghannoum Mahmoud , Degenhardt Thorsten , Person Karen , Brand Stephen
Published: December 2021

Background

Oteseconazole (VT-1161) is a novel, investigational oral therapy that is currently under FDA review for the treatment of recurrent vulvovaginal candidiasis (RVVC). Susceptibility testing was performed on all viable clinical isolates collected from three Phase 3 studies to determine the susceptibility of causative pathogens to oteseconazole versus the current treatment standard of care, fluconazole.

Methods

Vaginal cultures were obtained at screening and at all subsequent study visits throughout the duration of the studies (approx. 48 Weeks) and submitted to a central mycology laboratory for fungal species identification and storage. Susceptibility testing was conducted in accordance with the CLSI Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast M27-Ed4.

Results

Candida albicans was identified as the primary causative pathogen in 87% of women with RVVC presenting with an acute infection, followed by C. glabrata (8%). Other non-albicans species including; C. parapsilosis, C. tropicalis, C. krusei, C. dubliniensis, C. kefyr and Saccharomyces cerevisiae were responsible for < 1% of infections. A total of 1910 isolates were collected. The MIC range, MIC50 and MIC90 values against all isolates for oteseconazole were ≤ 0.0005 to > 0.25, 0.002 and 0.06 µg/mL, respectively. In comparison, the MIC range, MIC50 and MIC90 values for fluconazole were, ≤ 0.06 to > 32, 0.25 and 8 µg/mL respectively. The MIC range, MIC50 and MIC90 values against all C.glabrata isolates for oteseconazole were 0.002 to > 0.25, 0.03 and 0.125 µg/mL, respectively. In comparison, the MIC range, MIC50 and MIC90 values for fluconazole were, ≤ 0.06 to 32, 2 and 8 µg/mL respectively.

Conclusion

Oteseconazole demonstrated very low MIC values against most Candida strains, including fluconazole resistant isolates, aligning with clinical study outcomes. Oteseconazole MICs against C. glabrata strains were approximately 6-fold lower than fluconazole.

Disclosures

Mahmoud Ghannoum, PhD, Mycovia Pharmaceuticals (Grant/Research Support, Research Grant or Support) Thorsten Degenhardt, Ph.D, Mycovia Pharmaceuticals (Employee, Shareholder) Karen Person, M.S., Mycovia Pharmaceuticals, Inc. (Employee)Mycovia Pharmaceuticals, Inc. (Employee) Stephen Brand, Ph.D, Mycovia Pharmaceuticals (Employee)
720. Efficacy of Nifurtimox + Eflornithine in the Treatment of African Trypanosomiasis. Systematic Review
Authors: Hidalgo Jessica , Tirupathi Raghavendra , Ortiz Juan Fernando , Fabara Stephanie P , Reddy Dinesh , Rabaan Ali A , Al-Tawfiq Jaffar A
Published: December 2021

Background

Sleeping sickness is an infectious disease transmitted mainly by the Trypanosoma Brucei, with the tsetse fly as a vector. The condition has two stages: The hemolymphatic and the meningo-encephalitic stage. The second stage is caused mainly by the Trypanosoma Brucei Gambiense. The treatment of the second stage has changed from melarsoprol, eflornithine, to now nifurtimox-eflornithine (NECT). This systematic review will focus on the efficacy and the toxicity of the medication.

Methods

We use PRISMA and MOOSE protocol for this review. On figure 1, we detail the methodology used for the extraction of information from the systematic review. To assess the study's bias, we used Cochrane Collaboration’s tool for risk assessment of the clinical trials and the Robins I tool for the observational studies.

Results

We collected four clinical trials and two observational studies after an extensive search. Three clinical trials showed that NECT was non-inferior to eflornithine with the following cure rates (NECT VS eflornithine): 1) 96.3% vs. 94.1% ; 2) 90.9% vs. 88.9%; 3) 91.6% vs. 96.5%. An additional clinical trial revealed that the proportion of patient discharge from the hospital was 98.4% (619/629); 95% CI [97.1%; 99.1%]). The two observational studies discussed the pharmacovigilance of the drug and toxicity related to NECT. In one study, patients treated with NECT, 589 (86%) experienced at least one adverse effect (AE) during treatment, and 70 (10.2%) experience serious AE. On average, children experienced fewer AEs than adults. In the other study at least one AE was described in 1043 patients (60.1%), and Serious AE was reported in 19 patients (1.1% of treated), leading to nine deaths (case fatality rate of 0.5%). The major limitations of the studies were the lack of blinding because most of them were open-label. Also, there was heterogenicity in the definition of the outcomes in the observational studies.

PRISMA Flow Chart

Conclusion

NECT is not inferior to eflornithine, and the proportion of patients discharged from the hospital alive showed favorable results. The observational studies revealed a high frequency of AE. However, NECT is more convenient and safe than Eflornithine and Melarsoprol.

Disclosures

All Authors: No reported disclosures
721. Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay; A Multicenter Study
Authors: Abdallah Wassim , Myint Thein , LaRue Richard W , Minderman Melissa , Gunn Suphansa , Wheat Lawrence J , Hage Chadi A
Published: December 2021

Background

Accurate and timely methods for the diagnosis of histoplasmosis in endemic resource-limited settings are largely lacking. Histoplasma galactomannan antigen detection by enzyme immunoassay (EIA) is the most widely used method for the diagnosis of acute pulmonary and disseminated histoplasmosis in the United States (USA). EIA methods have constraints in resource-limited settings including cost, turnaround time, and the need for large reference laboratories, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFA) are practical methods that can be used in this setting for Histoplasma antigen detection.

Methods

Frozen urine specimens were submitted to MiraVista (MVista) for Histoplasma antigen EIA testing from three academic medical centers in highly endemic areas of the USA. They were also blinded and tested for the MVista Histoplasma LFA by skilled MVista technologists. Medical records were reviewed for clinical information. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable, pulmonary, or disseminated, immune competent or immune suppressed, and mild, moderate, or severe.

Results

352 subjects were enrolled, including 66 cases of histoplasmosis (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (68%). 76% had disseminated histoplasmosis. 6% were mild, 66% moderate, and 28% severe. A high degree of concordance was found between LFA and EIA results (kappa 0.837, OR 372.7, LR 204, p< 0.001). Overall, the sensitivity and specificity of the LFA were 78.8% and 99.3% respectively (kappa 0.84, p< 0.001). The sensitivity was higher in proven cases (93.2%), in patient with disseminated (94.7%), moderate (80%) and severe disease (94%), and those with galactomannan levels ≥ 2 ng/mL (97.7%). Specificity was 99.3% in proven cases, 99.3% in patient with moderate and severe disease, and 96.4% in those with galactomannan levels ≥ 2 ng/mL.

Table 1. Statistical characteristics of the LFA test for histoplasmosis in different categories. PPV: Positive Predictive Value. NPV: Negative Predictive Value. EIA: Enzyme Immunoassay.

The LFA test for histoplasmosis is more accurate in patients with high burden of infection.

Conclusion

The MVista Histoplasma galactomannan LFA may meet the need for accurate rapid diagnosis of histoplasmosis in resource-limited settings, especially in patients with relatively high disease burden, potentially reducing morbidity and mortality.

Disclosures

Melissa Minderman, Bachelor's Degree, Molecular Biology, MiraVista Diagnostics (Employee) Suphansa Gunn, Bachelor's Degree, psychology, MiraVista Diagnostics (Employee) Lawrence J. Wheat, MD, MiraVista Diagnostics (Employee)
722. Parasitic and Non-Parasitic Causes of Eosinophilia in Children Presenting to a Tertiary Care Center in the United States
Authors: Ness Tara , Erickson Timothy , Diaz Veronica , Hajjar Joud , Anvari Sara , Weatherhead Jill E
Published: December 2021

Background

Peripheral eosinophilia can be caused by many underlying conditions, including infectious pathogens, allergic disorders, neoplastic disorders, and immunological disorders. However, uncovering the cause of eosinophilia in children can be challenging due to the wide differential diagnosis.

Methods

To identify causes and risk factors of eosinophilia in children, we performed a retrospective chart review of children presenting to Texas Children’s Hospital in Houston, TX with peripheral eosinophilia from January 1, 2011 to December 31, 2019. Eosinophilia was classified as mild (absolute eosinophilia count or AEC >500 and < 1500), moderate (AEC >1500 and < 5000) and severe (AEC > 5000). Demographic information in addition to travel history, co-morbid conditions, and diagnostic workup were collected.

Results

A total of 773 patients under 18 years of age were evaluated. The most common cause of eosinophilia in children was atopy (N=343, 44%), followed by eosinophilia of unknown etiology (N=227, 29%). Infectious pathogens were the etiology in 8% of cases of which all were parasitic pathogens. Helminthic (n=48, 79% of parasitic diseases in total) pathogens were more common than protozoan (n=13, 21% of parasitic diseases in total) and patients with parasitic infections had higher median eosinophilia compared to other subgroups (median = 1661, range 512-17,501) with the majority having moderate to severe eosinophilia (57%). The most common helminth was Toxocara (n=31), followed by Strongyloides (n=15), and, more rarely, pinworms (n=4). The most common protozoa identified was Dientamoeba fragilis (n=9), followed by Giardia species (n=5), Endolimax nana (n=4), Blastocystis species (n=3), and Iodamoeba butschlii (n=1). Many unknown cases had limited workup that did not include investigations for common parasites.

Conclusion

While atopy and unknown etiology were the most common diagnoses for children presenting with eosinophilia, parasites were relatively common and should be considered in the differential when investigating etiologies for peripheral eosinophilia.

Disclosures

Joud Hajjar, MD, MS, Baxalta (Grant/Research Support)Horizon (Advisor or Review Panel member)Pharming (Advisor or Review Panel member)
723. Cryptosporidium Detection in Preserved Stool Specimens: A Comparison Study of EIA, DFA, and Direct Microscopic Method
Authors: Bao Jian R , Master Ronald N , Jones Robert S , Clark Richard B , Shier Kileen L
Published: December 2021

Background

Cryptosporidium is an intestinal parasite that may cause diarrhea. Laboratory diagnosis largely relies on microscopic or immunology-based antigen detection. Direct fluorescent antibody (DFA) is considered the gold standard. Enzyme immunoassay (EIA) is an attractive alternative, but direct comparison studies for the performance together with the impact from different specimen preservation media are limiting.

Methods

We compared these three methods for the detection of Cryptosporidium oocysts (direct microscopic) or antigen (DFA or EIA) from stool samples preserved in either 10% buffered formalin, Cary-Blair/C&S, or Total Fix (MCC, Torrance, CA). The DFA from Meridian Bioscience (Cincinnati, OH) and the EIA using CRYPTOSPORIDIUM II (TechLab®, Blacksburg, VA) were performed according to the manufacturer’s instructions. The direct microscopic method was performed according to laboratory protocols, including direct wet mount, modified acid-fast stain, or permanent trichrome stain.

Results

A total of 140 samples, including 116 clinical specimens, 20 validation panel samples and 4 proficiency survey specimens, were examined (Table 1). The DFA and EIA methods produced 100% concordant results using all three preservatives, while the microscopic method had decreased sensitivity. All microscopic positives remained positive for both the DFA and EIA. Cross-reactivity from other parasites, such as Giardia, of the two immunoassays was not observed.

Conclusion

While the two immunological methods both outperformed the microscopic method, the EIA has the advantages of being objective, simple to perform, has less hands-on time, and thus makes it an attractive option for high throughput Cryptosporidium detection.

Disclosures

Kileen L. Shier, PhD, D(ABMM), MLS(ASCP)CM, Quest Diagnostics (Employee)
726. Operational Impact of Infectious Disease Threats During Military Travel
Authors: Boatwright Michael A , Utz Gregory , Kunz Anjali , Colombo Rhonda E , Fraser Jamie , Kuo Huai-Ching , Tribble David , Lalani Tahaniyat
Published: December 2021

Background

We evaluated the incidence and operational impact of travelers’ diarrhea (TD), influenza-like illness (ILI) and undifferentiated febrile illness (FI) in US active duty (AD) personnel traveling outside the continental U.S for deployment (DEP), joint military training exercises (EXR) or other military travel (e.g. Temporary Duty Travel) (TDY).

Methods

AD personnel traveling for ≤ 6.5 months were prospectively enrolled between 2010-2019. Participants completed a post-travel survey regarding risk behaviors, illnesses and impact on daily activities. Trip purpose was categorized into DEP, EXR, TDY and syndromic definitions were used to identify cases of TD, ILI and FI based on symptoms. A multivariate logistic regression model with backward selection was used to determine the odds ratio associated with partial or complete incapacitation due to infections (a composite endpoint of either TD, ILI or FI).

Results

1822 servicemembers were enrolled: 36.2% traveled on DEP, 36.2% for EXR and 27.7% for TDY (Table 1). 83.5% of personnel traveling for DEP were Special Operations and Marine units, and 82% of the EXR group participated in Pacific Pathways. Overall, 19% of US personnel experienced infections associated with partial or complete incapacitation (median duration of incapacitation- TD: 1 day; ILI: 4 days; FI: 3 days). DEP personnel had a longer travel duration and the highest rate of partial or complete incapacitation due to TD, ILI or FI (Figure 1 and 2). Risk factors associated with partial or complete incapacitation due to infections were non-adherence with malaria chemoprophylaxis (OR: 1.7 [95%CI:1.2-2.4]), close contact with locals (OR:1.7 [95%CI:1.3-2.2]), inability to clean hands regularly before meals (OR: 1.7 [95%CI: 1.3-2.3]), fresh water or rodent exposure OR: 1.4 (95%CI:1.1-1.9) and consuming street vendor food (OR:1.8 [95%CI:1.3-2.4]).

Table 1. Demographic and travel characteristics of AD personnel traveling outside the continental US.

Proportion of AD servicemembers that experienced TD, ILI or undifferentiated febrile illness during DEP, EXR, TDY (p<0.05 for the comparison of each illness between DEP, EXR and TDY).

Figure 2.

Proportion of AD personnel with partial or complete incapacitation due to TD, ILI or FI during DEP, EXR or TDY (p < 0.05 for the comparison of each illness between DEP, EXR and TDY).

Conclusion

Infectious disease syndromes are common during overseas military travel. TD had the highest negative impact on military travel especially among DEP personnel. We identified several modifiable risk factors associated with incapacitating infections which can be used to inform preventive and treatment strategies.

Disclosures

All Authors: No reported disclosures
729. Lassa Fever Associated Hearing Loss
Authors: Ficenec Samuel , Grant Donald , Emmett Susan , Schieffelin John
Published: December 2021

Background

Hearing loss (HL) is the second leading cause of disability affecting approximately 19% of the world’s population. Despite well known social, economic, and neurologic consequences this condition receives little attention. Lassa Fever (LF) was noted to be associated with HL shortly after its discovery in the 1970’s. However, the true burden of this sequelae is likely underestimated due to a lack of standardized measurement and reporting.

Methods

We performed a cross-sectional study of LF survivors and household controls in Kenema, Sierra Leone. Upon recruitment, survivors and controls were screened for HL by determining Pure Tone Averages (PTA) of air conduction thresholds using an AMBCO audiometer, according to WHO standards. Individuals found to have elevated PTAs were referred to confirmatory testing measuring both air and bone thresholds using a SHOEBOX audiometer to differentiate sensorineural and conductive HL. All subjects completed symptom questionnaires and physical exams to understand the full spectrum of viral sequelae.

Results

94 LF survivors and 281 controls were recruited. The average age of LF survivors was higher than controls (32.9 vs 28.7, p=0.008). Of these 94 LF survivors, 40 (43%) were found to have HL in comparison to 40 (14%) of controls (p< 0.001). Lassa fever survivors were also found to have significantly worse HL with 16 (40%) found to have profound HL compared to only 2 (5%) of controls (p< 0.001). Logistic regression of this cohort found that LF infection (OR = 1.30, p< 0.001), any inner or middle ear symptoms (OR = 1.20, p=0.041), or pharyngeal symptoms (OR = 1.23, p=0.012) were significant risk factors of developing HL (p< 0.001). Interestingly the development of any pulmonary symptoms was protective of HL (OR = 0.86, p=0.039). Animal model studies suggested that LF infection may result in the development of an ANCA vasculitis which may be causative of LF sequelae. A subset of LF survivors (n=80) and IgG negative controls (n=9) were tested for ANCA proteins, of these 20 (25%) survivors vs 5 (55%) tested positive with mean concentrations of 202.4 µg/ml and 135.7 µg/ml (p=0.449), respectively.

Conclusion

This data further characterizes the sequelae of LF and suggests mechanisms of pathogenesis of symptoms.

Disclosures

All Authors: No reported disclosures
731. Puerperal Sepsis Among Women with In-facility Births in Western Tanzania
Authors: Smith Rachel , Ruiz Alicia , Westercamp Matthew , Maro Godson , Serbanescu Florina
Published: December 2021

Background

Puerperal sepsis is an important cause of maternal mortality worldwide. As access to emergency obstetric services expands in resource-limited settings, rapid recognition and treatment of sepsis, and prevention of nosocomial infections that might lead to sepsis, is critical. We describe puerperal sepsis cases among women with in-facility births in the Kigoma region of Tanzania.

Methods

Demographic, obstetric history, pregnancy complication and outcome, as well as mortality data were collected for women who delivered in hospitals, health centers and dispensaries in the Kigoma region, Tanzania 2016 – 2018. Up to 3 maternal complications were recorded as free text. Puerperal sepsis included women where ‘sepsis’ was recorded as a complication during hospitalization. We calculated rates of puerperal sepsis and completed a descriptive analysis of patients.

Results

203,604 women delivered infants in 197 participating facilities during the data collection period. Of these, 2228 (1.1%) had sepsis recorded, for an overall rate of 10.9 sepsis cases per 1000 deliveries. Although 48% of births occurred in dispensaries, sepsis complications were reported almost exclusively in hospitals and health centers (37.7 and 10.3 per 1000 deliveries, respectively). Sepsis rates varied across individual facilities, from 15.5 to 45.2 cases per 1000 deliveries in hospitals and 0 to 38.6 cases per 1000 deliveries in health centers. Women who developed sepsis had a median age of 25 (IQR 22 – 30) years and 1113 (56%) were nulliparous. 1763 (90%) of women who had sepsis delivered by caesarian delivery. Obstructed labor (827; 42%) was a common co-complication of sepsis; obstetric hemorrhage and uterine rupture were seen in 93 (5%) and 77 (4%) women with sepsis, respectively. 49 women with sepsis (3%) died prior to hospital discharge. Stillbirths and pre-discharge neonatal deaths complicated 107 (5%) and 74 (4%) deliveries to women with sepsis.

Conclusion

In the Kigoma region of Tanzania puerperal sepsis frequently occurs in women with obstructed labor and caesarian delivery. Further evaluation of both facility-level and individual factors that contribute to the incidence of sepsis in this population, particularly those related to invasive procedures, is critical for early recognition and prevention. issue

Disclosures

All Authors: No reported disclosures
732. Sensitivity and Specificity of Point of Care Lung Ultrasound vs. Chest X-Ray for the Diagnosis of Pediatric Pneumonia in Limited resource settings: The Zambia Experience
Authors: Camelo Ingrid Y , Pieciak Rachel , castro-aragon Ilse , Setty Bindu , Etter Lauren , Wang Kaihong , Gill Christopher
Published: December 2021

Background

Pediatric pneumonia is the leading cause of child mortality in low-income countries. Pneumonia diagnosis is a challenge. Chest x-ray (CXR) is considered the gold standard, but it exposes children to ionizing radiation, and access to CXR is limited to hospital settings. Lung Point of Care Ultrasound (POCUS) is a portable and non-radiating alternative to CXR.

Methods

We enrolled 200 children aged 1-59 months from the University Teaching Hospital (UTH) Emergency Department (ED) in Lusaka, Zambia who met the WHO (World Health Organization) case definition for severe pneumonia. From each child, we collected demographic and clinical data, a CXR, and a set of ultrasound images using a Butterfly ultrasound probe. Images were independently interpreted by two radiologists blinded to the results of the other imaging modality. Using CXR as the gold standard, we determined the sensitivity and specificity, positive and negative predictive values, and likelihood ratios for pneumonia using lung POCUS.

Results

This preliminary analysis included 50 children seen between May-October 2020. Median age (9 months) (Range 4-15). 58% were male, (29/50). Median temperature was 37.3⁰C (range 36.5-38.0); median respiratory and pulse rates were 41 breaths/min (range 31-50) and 139 beats/min (range 124-160) respectively; median SpO2 on RA was 91% (range 89-95). 50% of cases had difficulty breathing (82%, 41/50); chest retractions (70%, 35/50) and grunting (62%, 31/50). Ultrasound images for 49/50 (98%) cases and CXRs for 50/50 (100%) of cases we analyzed. Sensitivity of lung POCUS in the detection of CAP was 61% (95% Cl: 0.52-0.84). The specificity was 77% (95% Cl: 0.56-0.91). Positive predictive value (PPV) 70% (95% CI: 0.62-0.94) and negative predictive value (NPV) 69% (95% CI: 0.56-0.79).

Conclusion

Preliminary findings of this study demonstrated the lower diagnostic accuracy of lung POCUS versus CXR in the detection of pneumonia in children 1- 59 months. The high specificity of the test will aid in ruling out severe pneumonia in children. Due to its availability, ease of interpretation, and absence of radiation exposure, lung POCUS should still be considered as an important initial imaging tool for the diagnosis of CAP in children in limited-resource settings.

Disclosures

All Authors: No reported disclosures
733. Carbapenem-Resistant Enterobacterales (CRE) Colonization Prevalence in Botswana: an Antibiotic Resistance in Communities and Hospitals (ARCH) Study
Authors: Mannathoko Naledi , Mosepele Mosepele , Smith Rachel , Gross Robert , Glaser Laurel , Alby Kevin , Richard-Greenblatt Melissa , Sharma Aditya , Jaskowiak Anne , Sewawa Kgotlaetsile , Reesey Emily , Cowden Laura , Cressman Leigh , Otukile Dimpho , Paganotti Giacomo , Mokomane Margaret , Lautenbach Ebbing
Published: December 2021

Background

Although CRE are a global threat, data in low- and middle-income countries are scarce. Colonization data are vital for informing antibiotic resistance strategies. We characterized the colonization prevalence of CRE in various settings in Botswana.

Methods

This study was conducted in 3 districts in Botswana (1 hospital and 2 clinics per district). Adult inpatients and clinic patients were randomly selected for enrollment. Community subjects were enrolled by inviting each enrolled clinic subject to refer up to 3 adults. Each adult clinic or community subject was also asked to refer their children. All subjects had rectal swabs obtained and inoculated on selective chromogenic media for preliminary identification of CRE. Final identification and susceptibility testing were performed using MALDI-TOF MS and VITEK-2, respectively. CRE underwent genotyping for carbapenemase genes.

Results

Subjects were enrolled from 1/15/20-9/4/20 with a pause from 4/2/20-5/21/20 due to a countrywide COVID lockdown. Of 5,088 subjects approached, 2,469 (49%) participated. Enrollment by subject type was: hospital – 469 (19%); clinic – 959 (39%); community adult – 477 (19%); and community child – 564 (23%). Of 2,469 subjects, the median (interquartile range) age was 32 years (19-44) and 1,783 (72%) were female. 42 (1.7%) subjects were colonized with at least one CRE; 10 subjects were colonized with multiple strains. E. coli (n=17), K. pneumoniae (n=20), and E. cloacae complex (n=11) were most common. CRE colonization prevalence was 6.8% for hospital subjects, 0.7% for clinic subjects, 0.2% for adult community subjects, and 0.5% for child community subjects (p< 0.001)). CRE prevalence varied across regions (Figure 1) and was significantly higher pre- vs post-lockdown (Figure 2). VIM and NDM were the most common carbapenemase genes (Figure 3).

Figure 1. CRE Colonization - Study Sites

Figure 2. CRE Colonization - Temporal Trends

FIgure 3. CRE Genotypic Analyses

Conclusion

CRE colonization was significantly higher in hospital vs community settings in Botswana. CRE prevalence varied by region and decreased significantly following a countrywide lockdown. With CRE prevalence still modest, elucidating risk factors for CRE colonization holds promise in developing strategies to curb further emergence of CRE. Additional investigation of the CRE isolates without identified resistance genes is warranted.

Disclosures

Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))
734. Abnormal Lipid Profiles in Human Babesiosis
Authors: Mann Inderjit , pham Sophia , Spector Rachel , Papamanoli Aikaterini , Garry Evan , Lamba Pooja , Krivacsy Sara , Lum Michael D , Zahra Aleena , Hou Wei , Spitzer Eric , Marcos Luis A
Published: December 2021

Background

Babesiosis has gained attention as an emerging protozoal zoonotic disease with an expanding known incidence and geographical range in the US. The infection is caused by Babesia microti in the US and is transmitted by the bite of Ixodes ticks, and occasionally by blood transfusion. The diagnosis is usually established by microscopic examination of a stained blood smear to see intraerythrocytic organisms. The level of parasitemia is only loosely correlated with clinical severity. Anecdotal reports suggest that HDL cholesterol levels decline during acute babesiosis. In this study, we report cholesterol levels in a series of patients with acute babesiosis with the hypothesis that HDL levels may be a potential biomarker for more severe infections.

Methods

A retrospective chart review was performed at Stony Brook University Hospital and Stony Brook Southampton Hospital between 2013 and 2018. Inclusion criteria was defined as a case of acute Babesia infection proven by peripheral blood smear microscopy and who had a lipid profile drawn during presentation to the emergency department. Cholesterol levels that were measured either before or after the infection (at least 1 month apart) were also recorded to compare to the levels reported during acute infection.

Results

A total of 40 patients (27.5% female) met criteria for acute Babesia infection. Fifteen (37.5%) had a history of splenectomy. The patients were divided into two groups for comparisons based on the treating physician’s clinical decision: 32 patients who were admitted to the hospital and 8 patients who were not-admitted. History of hypertension was more common in admitted than non-admitted patients (37% vs. 17%, Chi-square test p=0.02); the median levels of LDL and HDL were more reduced in admitted than non-admitted patients (46 vs 76 mg/dL, p=0.04 and 9 vs 28.5 mg/dL, p=0.03, based on t-test respectively)

Conclusion

LDL and HDL levels are significantly reduced in acute babesiosis, and LDL levels are inversely proportional to the parasitemia, suggesting that low levels of LDL may predict worsening disease in babesiosis. The mechanism of this phenomenon is unknown. Further prospective studies are needed.

Disclosures

All Authors: No reported disclosures
735. Malaria Chemoprophylaxis Adherence Among U.S. Active Duty Service Members during Deployment to Endemic Regions
Authors: Collier Ryan P , Lindholm David A , Lalani Tahaniyat , Telu Kalyani , Kuo Huai-Ching , Fraser Jamie , Ganesan Anuradha , Kunz Anjali , Geist Charla , Yun Heather , Yun Heather , Tilley Drake
Published: December 2021

Background

Military members frequently deploy to malaria-endemic regions. Most cases of travel-related malaria occur due to prophylaxis non-adherence, impacting mission readiness. Factors assessing adherence are described in outbreak settings; we prospectively assess adherence in military travelers.

Methods

TravMil is a prospective, observational cohort study of US military beneficiaries traveling outside the US (2010-2019). Our analysis includes only active-duty service members traveling with a military purpose to malaria-endemic regions, who were prescribed malaria prophylaxis, and who completed a pre- and post-deployment survey; they could also enroll after return from deployment. All travelers received pre-travel counseling. Survey responses were assessed using descriptive statistics and multivariate regression to determine risk factors for adherence.

Results

1504 travelers were included (85% male; median age 28 years; 73% white). Median duration of travel was 77 days (12% traveled ≤ 14 days). Africa was the most common destination (33%). Primary prophylaxis included doxycycline (54%) and atovaquone/proguanil (43%). 969 (64%) were fully adherent to their regimen. The frequency of prophylaxis did not match expected values, as 3.6% of subjects reported taking prophylaxis weekly, and 2.9% did not know how often they took it. 103 (6.9%) did not take any of the prescribed regimen. On multivariate analysis, deployers were more likely to adhere if they traveled for ≤ 14 days or to Africa or practiced other mosquito-avoidance behaviors. Study enrollment post-deployment was associated with decreased odds of adherence, as was use of a tent. The use of daily versus weekly prophylaxis was not associated with a difference in adherence, though we had limited subjects prescribed weekly regimens.

Figure 1. Reasons for not taking any of the prescribed chemoprophylaxis (n = 103)

Table 1. Odds of full adherence to malaria chemoprophylaxis on multivariate logistic analysis

Conclusion

Short-duration travel, travel to highly endemic regions, and mosquito-avoidance behaviors were associated with increased adherence to prophylaxis. The lower rate of adherence in post-deployment enrollees may be a surrogate for inadequate counseling or recall bias. Our study highlights potential holes in counseling regarding malaria prophylaxis and the importance of ongoing provider and patient education on malaria.

Disclosures

Heather Yun, MD, American Board of Internal Medicine (Individual(s) Involved: Self): Board Member
736. Delays in Malaria Recognition and Door to Anti-malarial Time in a South London Hospital
Authors: Patel Nisha , Materski Tomasz , Gonzalez Elisa , Russom Solomon , Sandhu Gurjinder
Published: December 2021

Background

The prompt recognition and treatment of Plasmodium falciparum is necessary to prevent death. We reviewed data from a cohort of patients presenting with malaria to Kings College Hospital NHS Trust, London.

Methods

Retrospective review of electronic records and drug charts of patients diagnosed with malaria from Jan 2019- March 2021.

Results

109 cases of malaria were identified representing travellers from 11 Sub-Saharan African countries: Nigeria(38%), Sierra Leone(33%), Ivory Coast(10%). The age range varied from 4 to 76 years with a mean of 44, 66% of the cohort was male. 22 cases occurred during the COVID-19 Pandemic. The commonest symptoms were Fever (97%), Headache (92%) and malaise (72%). P. falciparum was present in 99% cases. A travel history was taken in 94% of cases. Malaria was considered by the first clinician in 82% of cases with the second highest differential being a viral illness. In 6 cases, it took 4 to 11 medical reviews before malaria was considered. 29 patients met the UK criteria for severe malaria. Door to antimalarial time varied from 1 to 128 hours, with a median of 7.4 hours. 46% of the cohort received intravenous Artesunate as their first antimalarial. Extreme delays occurred were clinicians did not consider malaria, patients had negative films or a patient did not declare a travel history when asked. 1 patient died of cerebral malaria with a door to needle time of 2hr 3min. Where a reason for delay is documented, drug availability represented the highest cause with mean delay from prescribing antimalarial to giving antimalarial of 2.7 hours. There was no difference in door to antimalarial administration during the COVID-19 Pandemic, but patients did have a delay in presentation to hospital from onset of symptoms, mean 6.2 days pre-pandemic, 10.5 days during pandemic, this was not statistically significant (P= 0.198). 3 patients presenting during the Pandemic had covid-19 swabs prior to admission and 10 had attended primary care services. Number of days between onset of malaria symptoms and presentation to the Emergency Department

Box plot demonstrating that patients were waiting longer post symptom onset to access care in the Emergency Department. 3 patients had covid swabs in the community and 10 accessed care through their primary care physician.

Conclusion

Our data show that malaria is being considered early in the emergency department however there remain significant delays in administration of treatment. In 6 cases where malaria was not considered early there were delays in diagnosis of up to 5 days. An audit cycle will be completed with the aim of reducing door to antimalarial time.

Disclosures

All Authors: No reported disclosures
739. Self-Reported Prevalence of Insect Bites During International Travel
Authors: Shoemaker Holly , Graves Michael , Ahmed Sharia , Birich Holly K , Benson Scott , Contreras John R , McAfee Colette , Leung Daniel T
Published: December 2021

Background

Vector borne diseases are responsible for almost one fifth of global infectious disease burden. International travelers are at risk for potentially life-threatening conditions when visiting areas with endemic vector borne disease, but this risk can be mitigated when proper insect precautions are taken. This study sought to evaluate the prevalence of insect precaution use and subsequent insect bites among Utah travelers who have attended pre-travel consultations.

Methods

A cross-sectional study at the University of Utah and Salt Lake County travel clinics was analyzed. Descriptive statistics and multivariable logistic regression were used to explore factors associated with insect repellant use, and reporting bug bites despite insect repellant use.

Results

A total of 463 individuals completed the survey and were included in our analytic sample. The majority of respondents (80%) reported using insect repellent, and close to half (45%) reported bug bites. Insect repellent use was positively associated with visiting rural/countryside (OR 2.78, 95% CI 1.50 – 5.15), and traveling to South East Asia (OR 3.16, 95% CI 1.40 – 7.26), or Americas regions (OR 3.34, 95% CI 1.45 – 7.92). Being of male gender (OR 0.37, 95% CI 0.21 – 0.64) or traveling to high altitude locations (OR 0.37, 95% CI 0.18 – 0.74) was negatively associated with using insect repellent. Longer trip duration (OR 1.01, 95% CI 1.00 – 1.02) was positively associated with reporting insect bites, while male gender (OR 0.51, 95% CI 0.33 – 0.80), older age (OR 0.96, 95% CI 0.95 – 0.98), and having an advanced degree (OR 0.47, 95% CI 0.22 – 0.99) were negatively associated.

Estimated Risk Factors of Insect Bites and Insect Repellent Use

Characteristics of international travelers were self-reported in a cross-sectional study. Use of insect repellent and reporting bug bites despite repellant use was examined through multivariate logistic regression and used to calculate odds ratios and 95% confidence intervals. Due to multicollinearity and data skewness, the following variables were omitted from the insect repellent model: Accommodation: Hotel/other enclosed structure, Location: European, Location: and Western Pacific. Reference categories are Gender: Female, Education: High school diploma/GED or less, Group size: 1 (Traveled alone), Location type: Urban, and Malaria region: No. All other categories are not mutually exclusive and evaluated as separate binary variables.

Conclusion

We show that gender, age, trip duration, and education level were associated with self-reported bug bites during travel abroad. Given the number of vector-borne diseases affecting health of travelers, our findings will contribute towards strategies to advise travelers for disease prevention.

Disclosures

All Authors: No reported disclosures
740. Elucidation of the Mode of Clostridioides difficile Transmission Based on One Health Approach
Authors: Yoshizawa Sadako , Sawa Tomoka , Komori Kohji , Sasaki Masakazu , Mori Nobuaki , Aoki Kotaro , Ishii Yoshikazu , Tateda Kazuhiro
Published: December 2021

Background

Community-onset Clostridioides difficile (C. difficile) infection (CACDI) has been increasing in recent years. To explore the transmission route of CACDI, we performed the whole-genome sequencing of C. difficile isolated from CACDI patients and compared it to the isolates from livestock, companion animals, and soil.

Methods

From October 2020 until April 2021, fecal specimens of cattle, poultry, swine, felines, canines, CACDI patients, their families, and soil from the CACDI patients' living environment were applied for isolation of C.difficile. Whole-genome sequencing of C. difficile was performed on the MiSeq system (Illumina). Using the draft genome obtained from these analyses, the house-keeping gene (tpi), MLST, toxin genes (tcdA, tcdB, cdtA, cdtB), and resistance genes (gyrA, gyrB, rpoA, rpoB, rpoC) were comprehensively analyzed.

Results

As of March 31, 2021, 275 specimens were collected. Forty-five fecal specimens of companion animal origin (23 feline and 22 canines) were collected and the positive rate of C.difficile was 28.9% (2 felines, 11 canines). In MLST analysis, ST 15 (4 strains), ST 26 (2 strains), ST 42, ST 3, ST 28, ST 100, and ST 185 were detected in canines, and ST 203 and ST 297 strains were detected in felines. Samples of livestock origin were collected from 135 cattle, 41 poultries, and 20 swine. The detection rate in cattle was 11%, toxin-gene positivity was 60%. MLST analysis of 9 strains revealed ST 11 (5 strains), ST 2, ST 15, ST 58, and ST 101. No isolates were found from poultry or swine. Patient-derived strains of CACDI were collected from 14 patients at 2 sites. MLST analysis revealed ST42, ST37, ST100, and ST203(two isolates, respectively), ST 224, ST 81, ST 28, and ST 47. 2 isolates were unclassifiable. One case was a healthy 1-year-old girl, whose family revealed no isolation of C.difficile. Impressively, the soil in the parks (A and B) related to the child detected C.difficile from 4/4 samples (toxin-gene positivity; 75%) in Park A and 1/4 samples (toxin-gene positive) in Park B. MLST analysis demonstrated ST 42, the same as that in the affected child and core-genome single-nucleotide polymorphisms(SNPs) analysis suggested closely related strain.

Conclusion

Our results suggest one health approach is fundamental to prevent the transmission of C.difficile.

Disclosures

All Authors: No reported disclosures