bluuebunny/crossref_metadata_2025_split huggingface dataset:
1632. Comparing the epidemiology and clinical characteristics of childhood tuberculosis through active and passive case finding
Authors: Ikeda Saki , Cruz Andrea T , Starke Jeffrey R 
Published: January 2021

Abstract

Background
Childhood tuberculosis can be found via passive case finding (PCF), diagnosing a symptomatic child, and active case finding (ACF), discovering a child through contact tracing. Most high prevalence areas perform PCF, but as ACF is introduced, the clinical and radiologic findings may differ. We compare clinical, radiographic, microbiologic and epidemiological characteristics of children diagnosed through PCF and ACF.

Methods
A retrospective cohort study of all patients diagnosed with TB from 01/01/2012-12/31/2019 at Texas Children’s Hospital. ACF is TB in a child who had not previously sought care before identified via contact tracing, immigration screening, or screening for incarceration. Severity of disease was based on location of illness, imaging and bacteriology/histopathology. Associations between PCF/ACF and demographics, disease severity, and microbiology were analyzed.

Results
Of 178 patients, 80 (45%) were diagnosed via ACF. ACF patients were more likely to be US-born (OR: 2.29, [95% Confidence interval (CI): 1.12-4.67]) and younger (mean 6.18 vs 8.84 years, p= 0.016). Only 2.5% of ACF patients had extrapulmonary disease, compared to 45% of the PCF group (p&lt; 0.0001). All 14 severe extrathoracic cases were in the PCF group (10 central nervous system disease, 3 ocular disease, 1 spondylitis). Fewer patients in the ACF group had severe intrathoracic findings (11% vs 39%, p&lt; 0.001): miliary disease (0% vs 10%, p=0.006), cavity (1% vs 9%, p=0.04), and multilobar involvement (7.5% vs 22.4%, p=0.006). ACF patients had more hilar/mediastinal adenopathy (OR: 2.51, [CI: 1.34-3.72], p=0.004). ACF patients were less often cultured (38% vs 89%, p&lt; 0.0001) and had less microbiological confirmation by cultures or PCR (21% vs 52%, p=&lt; 0.0001).

Conclusion
Patients in the ACF group were younger, had less severe clinical manifestations, and had almost no extrathoracic disease. Clinicians need to be aware that the common clinical and radiographic presentations in children differ between PCF and ACF.

Disclosures
Jeffrey R. Starke, MD, Otsuka Pharmaceuticals (Other Financial or Material Support, Member, Data Safety Monitoring Board)
1638. Synchronous Video Observed Therapy for Monitoring Treatment of Tuberculosis: Experience in a Cases Series from Cali, Colombia, 2019
Authors: Tello-Cajiao Maria E , Mosquera Hernandez Juan Camilo C , Ardila-Giraldo Santiago , Romero-Rosas Nelson , Parra-Lara Luis , Niño Yessenia , Luna Lucy , García-Goez Jose 
Published: January 2021

Abstract

Background
In Directly Observed Treatment (DOT) monitoring strategy for the treatment of tuberculosis (TB), the patient has to travel daily to the health institution to take the TB medication. Although has been usefulness, this strategy increases the catastrophic costs of the disease, rising the probability of rejection, abandonment, and failure to treatment. Therefore, a monitoring strategy was implemented through video calls phone known as Synchronous Video Observed Therapy (S-VOT), to document the experience and its results in a series of patients from a low-middle income country.

Methods
A prospective case series study was conducted involving 23 TB patients managed with standard treatment, who were supervised through daily video call phone, during 2019, Cali-Colombia. Adherence to VOT strategy and treatment were evaluated, as well as patient characteristics, adverse drug effects, perception and costs. Categorical variable data were summarized in absolute and relative frequency tables. Quantitative variables were described with median and Interquartile range. Proportional differences were calculated with Z test, risk opportunities and difference of medians with Mann Whitney’s U test were performed. We take p values &lt; 0.05 as significant.

Results
Adherence to S-VOT monitoring strategy was 99.8% in first phase of treatment and 98.2% in second phase. All patients completed treatment, achieving 100% cure criteria in patients with pulmonary TB. Most adverse drug effects were reported on first month (31.6%, p=0.003). Skin changes were the most frequent complaint at the beginning of management (16.4%) and epigastralgia at the end (20%). The likelyhood of adverse effects was significantly reduced when patients started maintenance phase on third month (OR: 0.29, p = 0.0003). The experience of the strategy was generally positive for patients. Time savings was major advantage. Travel costs in S-VOT were lower than DOT for patients, as well as the daily time investment in TB treatment.

Conclusion
S-VOT strategy was well tolerated and accepted by all patients, allowing an excellent level of adherence, with reduction in travel costs and investment of time for treatment. S-VOT is proposed as a viable alternative to DOT in selected patients.

Disclosures
All Authors: No reported disclosures
1641. A Comparative Analysis Of Lymph Node Tuberculosis Between Children And Adults
Authors: Hammami Fatma , Koubaa Makram , Chakroun Amal , Rekik Khaoula , Smaoui Fatma , Elleuch Emna , Marrakchi Chakib , Jemaa Mounir Ben 
Published: January 2021

Abstract

Background
Lymph node tuberculosis (LNTB) represents the most common site of extrapulmonary tuberculosis. Among children, due to non-specific clinical features, the diagnosis is often delayed. We aimed to compare the clinical, therapeutic and evolutionary features of LNTB between adults and children.

Methods
We conducted a retrospective study including patients hospitalized for LNTB in the infectious diseases and pediatric department between 1993 and 2018. Children aged ≤18 years were included.

Results
Overall, we encountered 231 cases of LNTB. There were 40 children (17.3%) with a mean age of 11±4 years and 191 adults (82.7%) with a mean age of 42±16 years. As to gender, females were more affected (adults: 67% vs children: 70%), with no significant difference (p &gt;0.05). A family history of tuberculosis was significantly more frequent among children (20% vs 6.3%; p=0.01). Raw milk consumption (38.2% vs 30%; p &gt;0.05) and close contact with animals (29.8% vs 35%; p &gt;0.05) were noted among both adults and children. Fever (53.4% vs 32.5%; p=0.01), night sweats (35.8% vs 10%; p=0.001), loss of appetite (38.2% vs 17.5%; p=0.01) and weight loss (35.1% vs 15%; p=0.01) were significantly more frequent among adults. Tuberculin skin test was positive in 75.8% of the cases among adults and in 86.2% of the cases among children (p &gt;0.05). Multifocal tuberculosis was significantly more frequent among adults (23.8% vs 5.7%; p=0.01). Antitubercular therapy was prescribed for a mean duration of 10±4 months among adults and for 9±3 months among children, with no significant difference (p &gt;0.05). Side effects of antitubercular drugs were more frequent among adults (33% vs 10.3%), with a significant difference (p=0.004). Comparison of the disease evolution showed no significant difference between adults and children, regarding recovery (94.8% vs 90%), relapse (5.2% vs 5%) and death (0.5% vs 2.5%).

Conclusion
The clinical presentation of LNTB among children was less common and misleading. A family history of tuberculosis and a high index of suspicion might shorten the diagnostic delay.

Disclosures
All Authors: No reported disclosures
1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab)
Authors: Dousa Khalid M , Kurz Sebastian G , Bethel Christopher , Miller Alita , Bonomo Robert A 
Published: January 2021

Abstract

Background
Mab is a MDR nontuberculous mycobacterium that causes lung infections in patients with structural lung disease. Mab harbors a chromosomally encoded class A β-lactamase, BlaMab, able to hydrolyze penicillins, cephalosporins and carbapenems. L,D- and D,D-transpeptidases (L,D TP and D,D TP) shape peptidoglycan (PG) synthesis and contribute to cell wall structure. Select combinations of β-lactams that inhibit L,D TP and D,D TPs and BlaMab are desirable as they can potentially improve treatment outcomes. DUR is a novel DBO β-lactamase inhibitor (BLI) with broad-spectrum activity against Ambler class A, C, and D β-lactamases (Fig.). Here, we investigated the mechanism of action and efficacy of DUR alone and combined with select β-lactams in restoring susceptibility of Mab to β-lactam antibiotics

Methods
Minimum inhibitory concentrations (MICs) of cefuroxime (CEF), imipenem (IMI) and amoxicillin (Amox) with or without DUR were determined using microdilution. Approximately 5 x 105 colony-forming units per milliliter were inoculated into Middlebrook 7H9 Broth supplemented with 10% (vol/vol) oleic albumin dextrose catalase and 0.05% (vol/vol) Tween 80. When more than 2 drugs were combined, Amox was added at fixed concentration of 8 µg/ml to serial dilutions of CEF-DUR or IMI-DUR. Mab isolates were incubated with test agents at 30°C for 48 h, and MIC was defined as lowest antibiotic concentration that prevented visible bacterial growth. Reaction intermediates in the inactivation pathway of BlaMab, L,D-TP and D,D-TPs with DUR

Results
One hundred clinically derived and previously characterized isolates were tested in these assays. MIC50 and MIC90 of DUR alone was 4 and 8 µg/ml, demonstrating intrinsic activity. Combinations of DUR-IMI or DUR-CEF plus 8 µg/mL Amox lowered MIC50 to &lt; 0.06 µg/ml in all 100 clinical isolates (Table). Mass spectrometry analyses of BlaMab, L,D-TP and D,D-TPs Mab (2,4) inactivated by DUR showed formation of stable adducts of DUR to BlaMab, L,D-TP and D,D-TPs (Fig.)
Chemical composition of durlobactam (DUR) and mass spectrometry of BlaMab, L,D TP and D,D TPs incubated with DUR

MIC50 and MIC90 of 100 Mab clinical strains against DUR alone and in combination with Amox, CEF and IMI

Conclusion
We demonstrate that a novel DBO BLI, DUR, is an active agent with potent intrinsic activity against BlaMab and Mab L,D-TPs and D,D-TPs. We hypothesize that DUR improves b-lactam activity by protecting against the hydrolytic activity of BlaMab and by targeting multiple steps in PG synthesis

Disclosures
Alita Miller, PhD, Entasis Therapeutics (Employee) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)
1648. CD4 T Lymphocyte and Monocyte Activation within One Year After Treatment Completion for Pulmonary Tuberculosis: A Pilot Study
Authors: Huaman Moises A , Moussa Anissa , Orsborn Kris I , Ticona Eduardo , Sanchez Jorge , Zavaleta Milagros , Sterling Timothy , Chougnet Claire , Deepe George S , Fichtenbaum Carl 
Published: January 2021

Abstract

Background
Persons with active tuberculosis (TB) have increased immune activation, which declines with TB treatment. Whether residual immune activation is present after completion of TB treatment is unknown. We conducted immunophenotyping of T cells and monocytes from individuals who had completed TB treatment, and compared them to controls without history of active TB.

Methods
Cross-sectional study of HIV-uninfected individuals 40 to 70 years old recruited in Lima, Peru. For this analysis, we included 6 individuals who had completed treatment for pulmonary TB within the past year, and 10 healthy controls without history of active TB (6 QuantiFERON®-TB positive; 4 QuantiFERON®-TB negative). Participants provided blood for T cell and monocyte immunophenotyping using multi-parameter flow cytometry, including expression of cell surface activation markers.

Results
There were no significant differences in age, sex, or comorbidities between patients previously treated for TB and controls without history of active TB. Median time since TB treatment completion was 4 months (range, 2 – 9) for the previously treated group. Compared to controls, persons previously treated for TB had increased CD4+ to CD8+ ratio (2.4 vs. 1.3; p=0.03), increased proportion of CD4+ T cells co-expressing HLA-DR and CD38 activation markers (5.8% vs. 3.1%; p=0.02), increased CD4+ T cell ICAM-1 expression (56.3% vs. 33.2%; p=0.03), as well as increased density of HLA-DR in monocytes (HLA-DR MFI; 7572 vs. 3917; p=0.03).

Conclusion
In this pilot study, individuals who recovered from pulmonary TB exhibited increased CD4+ T cell and monocyte activation phenotypes within one year of TB treatment completion. These results suggest residual immune activation after clinical TB cure.

Disclosures
Carl Fichtenbaum, MD, Amgen (Grant/Research Support, outside the submitted work)Clinical Care Options (Other Financial or Material Support, outside the submitted work)Cytodyn (Grant/Research Support, outside the submitted work)Gilead Sciences (Grant/Research Support, outside the submitted work)Janssen (Grant/Research Support, outside the submitted work)Merck (Grant/Research Support, outside the submitted work)ViiV Healthcare (Research Grant or Support, outside the submitted work)
1649. Characterizing Factors Associated with Pediatric Latent Tuberculosis Infection in an Urban Health System to Improve Screening Practices
Authors: Hoekstra Nadia E , Anderson Mark , Gaensbauer James 
Published: January 2021

Abstract

Background
The epidemiology and risk factors informing current American Academy of Pediatrics (AAP) guidelines on screening for pediatric latent tuberculosis infection (LTBI) have evolved over the past decade. To improve pediatric LTBI screening efficiency, we sought to reevaluate characteristics associated with positive QuantiFERON-TB Gold Plus (QFT-Plus) at Denver Health (DH), an urban health system that includes a network of primary care clinics, a refugee clinic and a tuberculosis clinic.

Methods
We retrospectively analyzed all QFT-Plus tests performed on children aged 2-18 years from 1/2019 to 9/2019. To obtain additional variables we conducted chart review on all positive and indeterminate results, and a random 10% sample of negatives. Characteristics (age range, sex, region of birth, clinic setting, primary language) of patients with positive and negative QFT-Plus were compared using Chi2 or Fisher’s exact tests (Table 1). Using the 10% negative controls, we calculated odds ratios for each variable and included important or significant variables in a multivariable logistic regression model.

Results
Of 1063 QFT-Plus tests performed, 29 (2.7%) were positive. 76% of all positive tests and 83% of positive tests in primary care clinics occurred in patients age ≥10. 51.7% of all positive patients were born in the US. Among factors analyzed by logistic regression including birth region, reason for screening, sex, age, ordering location, insurance status, and language, only Spanish language (OR 5.0, CI 1.6-15.8) and non-English, non-Spanish language (OR 6.4, CI 1.4-28.5) were significant risk factors for positive testing.
Characteristics of Denver Health Patients with Positive and Negative QFT-Plus, January-September 2019.

Conclusion
Language was the only predictor of LTBI in this study, and may be a proxy for high risk travel and family exposure. Region of birth was not predictive, as half of positive tests occurred in US-born children. The majority of positive tests occurred in older children, suggesting they should be prioritized in screening programs, though occasional detection among younger children reinforces the importance of LTBI detection in ages where risk of progression to active TB is higher. Further studies are needed to better elucidate the details behind positive testing, including more detailed characterization of travel and potential family exposures.

Disclosures
All Authors: No reported disclosures
1650. Clinical Features and Risk Factors of Active Tuberculosis in Patients with Behçet’s Disease
Authors: Liu Yaxu , Zhang Lifan , Zhou Ziyue , Sun Luxi , Zhou Baotong , Liu Xiaoqing , Zheng Wenjie 
Published: January 2021

Abstract

Background
Understanding the clinical characteristics and risk factors of active tuberculosis (ATB) in Behçet’s disease (BD) is of great significance to improve the treatment efficacy and guide the preventive treatment. However, the relevant studies are very limited.

Methods
We retrospectively reviewed medical records of BD patients admitted to our institute from 2010 to 2019. BD patients with ATB were enrolled as the case group, and the control group was selected by random number sampling from the remaining BD patients. Multivariate logistic regression analysis was performed to explore the potential risk factors of ATB in BD patients.
Figure 1. Flowchart of the study

Results
Twenty-one ATB cases were identified from 386 BD patients, including four (19.0%) microbiologically confirmed and 17 (81.0%) clinically diagnosed. ATB patients can present with systemic symptoms (fever, night sweating, unexplained weight loss) and/or symptoms related to the infection site. Logistic regression analysis revealed that ESR&gt;60mm/h (OR=13.710, 95%CI (1.101, 170.702)), increased IgG (OR=1.226, 95%CI (1.001, 1.502)), and positive T-SPOT.TB (OR=7.793, 95%CI (1.312, 48.464), for 24-200 SFC/106PBMC; OR=17.705 (2.503, 125.260), for &gt;200 SFC/106PBMC) were potential risk factors for ATB in BD patients.
Table 1. Past medical history and medication of BD patients with and without ATB

Table 2. Clinical presentation and laboratory results of BD patients with and without ATB

Table 3. Potential risk factors for ATB in BD patients

Conclusion
When BD patients have fever, night sweating, unexplained weight loss, or manifestations rarely occurred in BD, the diagnosis of ATB should be considered. Significantly elevated T-SPOT.TB indicates a high risk of ATB in BD patients.

Disclosures
All Authors: No reported disclosures
1651. Describing the Tuberculosis Infection Cascade of Care Based on Electronic Health Record Data
Authors: Vonnahme Laura A , Todd Jonathan , Puro Jon , Oakley Jee , Jones Matthew , Rivera Pedro , Langer Adam J , Ayers Tracy 
Published: January 2021

Abstract

Background
Appropriate screening of individuals to detect latent tuberculosis infection (LTBI) is a critical step for achieving tuberculosis (TB) elimination in the US; &gt;80% of TB cases are attributed to LTBI reactivation. TB infection testing and treatment must engage community health clinics where populations at risk seek care. However, there are significant data knowledge gaps in the current LTBI cascade of care (CoC) in this setting. We used an electronic health record (EHR) database from OCHIN, Inc., to characterize the LTBI CoC and identify potential future interventions.

Methods
We extracted a cohort of patients from 2012–2016 EHR data; we stratified by whether patients were at risk for TB based on meeting at least one of the following criteria: non-US born or non-English language preference, homelessness, encounter at correctional facility, history of close contact with a TB case, or being immunocompromised. Along each step of the LTBI CoC, we determined the proportions with a test for TB infection, with available test results, with a positive test, with an LTBI diagnosis, and with LTBI treatment prescribed. We used Χ 2 tests to compare the LTBI CoCs among patients at risk with those classified as not at risk.

Results
Of nearly 2.2 million patient records, 701,467 (32.0%) met criteria for being at risk for TB; 84,422 at risk (12.0%) were tested; 65,562 (77.7%) had available results, of whom 9,624 (14.7%) were positive. Among those with positive results, 6,958 (72.3%) had an LTBI diagnosis, of whom 1,732 (24.9%) were prescribed treatment. Among those classified as not at risk, fewer were tested (66,773 [4.5%], p&lt; 0.001) and had positive results (2,500 [3.7%], p&lt; 0.0001). Among those with positive results, 1,998 (80.0%) had an LTBI diagnosis, of whom 395 (19.8%) initiated treatment.

Conclusion
This study highlights gaps in the LTBI CoC, and where interventions are most needed. The largest gaps were in testing patients at risk, as 88% were not tested, and treatment, as 75% diagnosed with LTBI were not treated. Just under half (44%) of all TB tests appeared to be performed in persons with little risk for TB; this is a substantial amount of testing given very few begin treatment. Resources could be redirected to increase screening and treatment among populations at risk.

Disclosures
All Authors: No reported disclosures
1655. Extrapulmonary Tuberculosis in a Large Healthcare System
Authors: Denmeade Travis , Smith William , Kooken Banks , Leonard Michael 
Published: January 2021

Abstract

Background
The US has seen a rise in the proportion of patients with extrapulmonary tuberculosis (TB) even though the yearly incidence of new TB cases has been in decline. The purpose of this study was to analyze incidence of extrapulmonary TB at Atrium Health, a large non-profit health system in the Southeastern US.

Methods
Retrospective chart review of 94 adult patients with culture confirmed extrapulmonary TB between 2008-2019. Individuals younger than 18 years were excluded from analysis. The primary objective was to examine incidence of extrapulmonary TB and compare it to that reported in the literature. Secondary objectives included determination of sites of extrapulmonary disease and associated patient characteristics including HIV status, race, ethnicity, and birthplace.

Results
237 patients were identified as having confirmed TB infection from 2008-2019 in a retrospective analysis within the Atrium Health System. 94 (40%) were found to have extrapulmonary disease; 42 (45%) with concomitant pulmonary disease. The patients were 55% male, 40% African American, 21% Hispanic or Latino, and 51% US-born. Median age was 44 years (range 20-62). The most common sites of extrapulmonary TB were lymphatic (35%), pleural (24%), GI/Peritoneal (12%), CNS (10%), and Bone/Joint (10%). Lymphatic involvement was 40% cervical, 19% intrathoracic, and 16% axillary. 66% of skeletal disease was vertebral. Other sites included GU, pericardial, skin, and disseminated disease (5%). 37% were HIV positive, 18% with unknown HIV status as they were never tested. Information regarding patient’s race, ethnicity, and birthplace were unknown for 2 patients. The percentage of extrapulmonary cases were 29% in 2008, 39% in 2012, 38% in 2016, and 49% in 2019.

Conclusion
Lymphatic and pleural involvement were the most common extrapulmonary sites. Of those tested, 37% were HIV positive but there was a significant portion never tested showing a need for increased testing. The proportion of extrapulmonary TB cases since 2008 is higher at 40% compared to the 31% reported in the United States. There has been a rise in the proportion of extrapulmonary TB within our healthcare system and deserves further analysis.

Disclosures
All Authors: No reported disclosures