bluuebunny/crossref_metadata_2025_split huggingface dataset:
1393. Loss to Follow-up Rate in the Treatment of Latent Tuberculosis by Region of Origin
Authors: Yoshii Hikari , Bark Charles 
Published: December 2021

Abstract

Background
Adherence in the treatment of latent tuberculosis infection (LTBI) is closely related to reactivation and infection control in the population. However, there has been little research on which populations are at higher risk of loss to follow-up. The aim of this study is to investigate how the adherence of LTBI patients in the United States (US) differs by region of origin.

Methods
A retrospective, observational study was conducted from 2001 to 2020. LTBI patients were identified from the Cuyahoga County Tuberculosis Clinic in Cleveland, Ohio. Only patients who were informed of the diagnosis of LTBI were included. Patients were discharged from the Tuberculosis outpatient clinic upon completion of treatment or when the physician decided to discontinue treatment. We defined loss to follow-up as a case where LTBI was diagnosed but the patient was not formally discharged. Patients whose treatment was interrupted due to side effects were not considered loss to follow-up. Odds ratios were calculated using a multivariable regression model with patients from North America as the reference group.

Results
Of 4018 LTBI patients, 1171 (28.7%) were lost to follow-up, of which 950/2314 (41.0%) were from North America. Compared with LTBI patients from North America, significantly lower loss to follow-up rates were observed for those from Middle East and North Africa 30/170 (17.7% OR 0.52, 95% Confidence Interval (CI) 0.31-0.89), South Asia 60/692 (8.7% OR 0.41, 95% CI 0.21-0.78), and Sub-Saharan Africa 69/526 (13.1% OR 0.22, 95% CI 0.14-0.36).

Conclusion
The analysis showed that a high loss to follow-up rate was observed in the patient groups from North America, Europe and Central Asia, and Latin America & the Caribbean. LTBI patients from North America had a significantly higher loss to follow-up rate than those from Middle East and North Africa, South Asia, and Sub-Saharan Africa, respectively. Further research is needed to determine how to intervene in the poorly adherent patient population, such as LTBI patients from North America, Europe and Central Asia, and Latin America & the Caribbean.

Disclosures
All Authors: No reported disclosures
1394. Autochthonous Leprosy in Missouri
Authors: Patel Paragkumar , Rojas-Moreno Christian , Nelson Taylor , Zaesim Araya , Dyer Jon 
Published: December 2021

Abstract

Background
Introduction: Leprosy (Hansen’s disease) is a chronic granulomatous infection of the skin/peripheral nerves caused by Mycobacterium leprae. Of 216 new cases reported in the US in 2019, 70% were in FL, LA, TX, HI, CA, GA and NY. Leprosy is considered a zoonosis in the southern US with the nine-banded armadillo as a reservoir. There have been no reported autochthonous leprosy cases in Missouri.

Methods
Case: 55 y/o previously healthy male noted a new rash on his arm 2 years ago. Over time it spread to his extremities/torso. Skin biopsy showed a granulomatous infiltrate, suspected granuloma annulare, but it progressed despite appropriate therapy. He noted progressive numbness of the affected areas of skin and several regional nerve distributions. In the weeks prior to his initial visit he noted facial swelling, eyelid and ear induration, worsening fatigue, diffuse arthralgia, and some vision changes. His travel history is limited to Canada, Colorado and a brief vacation to the Texas/Mexico border (no notable outdoor exposure during the latter trip; no travel outside the country). He lives in rural Missouri where he is exposed to armadillos. His dogs frequently kill them and often bring them into the yard, rolling around on/in the dead carcasses which he disposes of. He typically wears gloves when handling them and has never consumed them. On exam he had diffuse purplish-red nummular infiltrated anesthetic papules and plaques diffusely distributed over the trunk and extremities. Distinct left ulnar neuropathy was noted. He exhibited leonine facies and infiltration of the bilateral helices. Repeat biopsy showed a granulomatous infiltrate with abundant acid-fast bacilli. DNA sequencing confirmed M. leprae. He was preventatively treated with prednisone and methotrexate to minimize immune reaction, and two weeks later began a regimen of monthly rifampin, minocycline, and moxifloxacin with an anticipated duration of 24 months.

Results

Diagnosis
lepromatous leprosy with pre-treatment immune reaction. This is potentially the first case of autochthonous leprosy in Missouri. Providers should include Hansen’s disease in the differential diagnosis of patients with dermal eruption and cutaneous neurological symptoms to avoid delays in diagnosis/care.

Disclosures
All Authors: No reported disclosures
1395. Epidemiology of Non-Tuberculous Mycobacteria Infection Among Immunocompromised Children: A Single Center Experience
Authors: Kang Ye jin , Sue Paul K , Filkins Laura , Chery Giselle S 
Published: December 2021

Abstract

Background
Nontuberculous mycobacteria (NTM) infection is associated with high rates of morbidity and mortality among immunocompromised adults. However, sparse data exists regarding clinical outcomes among immunocompromised (IC) children with NTM infection. We sought to characterize clinical features and outcomes among IC children at our institution with microbiologically confirmed NTM disease.

Methods
Retrospective review of cases of microbiologically confirmed NTM infection among IC children between January 2017 and December 2020. Children (≤21y.o) with microbiologically confirmed NTM disease and known primary or secondary immunodeficiency diagnosed between January 1, 2017 and December 20, 2020 were included in the study. All subjects with a positive NTM microbiologic stain or culture but no subsequent treatment for NTM infection were excluded. Demographic and clinical characteristics were assessed and risk factors for mortality were evaluated.

Results
Of 147 mycobacterial cultures sent during the study period, 72 subjects had a positive microbiologically confirmed NTM species, with 10 subjects meeting all inclusion and no exclusion criteria. Median age was 16 years old, with 40 percent being female and 50 percent of Hispanic ethnicity. NTM disease was distributed among patients with primary immunodeficiency (30%), solid organ transplantation (20%), hematopoietic stem cell transplant (20%), rheumatologic disease on immunosuppressive therapy (10%), and hematologic malignancy (10%). Bacteremia was common, with blood cultures positive in 70% of cases, and M. abscessus (50%) and M. avium complex (30%) the most frequently implicated pathogens. Hospital acquired infection was common (60%). 2 year mortality following invasive NTM infection was high at 40%.

Conclusion
While rare, NTM infections are associated with significant morbidity and mortality among immunocompromised children. Additional investigations are needed to assess for risk factors associated with NTM and severe NTM disease.

Disclosures
Laura Filkins, PhD, Avsana Labs (Board Member, Scientific advisory board member)Biofire Diagnostics (Grant/Research Support)
1397. Modern Lineages of Mycobacterium tuberculosis Were Recently Introduced in Western India and Demonstrate Increased Transmissibility
Authors: Dixit Avika , Kagal Anju , Ektefaie Yasha , Freschi Luca , Lokhande Rahul , Groeschel Matthias , Tornheim Jeffrey A , Gupte Nikhil , Pradhan Neeta N , Kadam Deelip , Gupta Amita , Golub Jonathan , Farhat Maha , Mave Vidya 
Published: December 2021

Abstract

Background
Mycobacterium tuberculosis (Mtb) transmissibility may vary between lineages (or variants) and this may contribute to the slow decline of tuberculosis incidence. The objective of our study was to compare transmissibility across four major lineages (L1-4) of Mtb in Pune, India.

Methods
We performed whole-genome sequencing (WGS) of Mtb isolated from sputum culture of adult patients with pulmonary TB. We performed genotypic susceptibility testing for both first- and second-line drugs using a previously validated random forest predictor. We identified single nucleotide polymorphisms and generated a multiple sequence alignment excluding drug resistance conferring mutations to avoid skewing the phylogeny due to convergent evolution in these regions. We used Bayesian molecular dating to generate phylogenies and compared tree characteristics using a two-sample Kolmogorov-Smirnov (KS) test.

Results
Of the 642 isolates from distinct study participants that underwent WGS, 612 met quality criteria. The median age of participants was 31 years (range 18-74), the majority were male (64.7%) and sputum smear-positive (83.3%), and 6.7% had co-infection with HIV (Table 1). There was no significant difference in baseline characteristics between lineages. The majority of isolates belonged to L3 (44.6%). The majority (61.1%) of multidrug-resistant (MDR, resistant to isoniazid and rifampin) isolates belonged to L2. In phylogenetic analysis, we found evidence of higher transmissibility of L2 as indicated by shorter branch lengths (i.e., less time had elapsed between transmission and sampling) and more genetic similarity (smaller pairwise single nucleotide polymorphism [SNP] distances) among L2 isolates as compared to other lineages (Figure 1). Branching times for L2 and L4 were smaller than L1 and L3 indicating recent introduction into the region (p &lt; 0.001 [KS test]).

Figure 1: Lineage-wise distribution of A) phylogenetic tree branch lengths (log) and B) pairwise single nucleotide polymorphism (SNP) distance, using 612 tuberculosis isolates from Pune, India. P values calculated using two-sample Kolmogorov-Smirnov test.

Table 1: Demographic characteristics of study participants included in the study, by lineage.

Conclusion
Modern Mtb lineages (L2 and L4) were relatively recently introduced in western India, as compared to older lineages (L1 and L3), with the more drug-resistant L2 showing higher transmissibility. These findings highlight the need for early detection and treatment initiation to interrupt transmission with important implications for antimicrobial stewardship and heightened surveillance of TB resistance rates.

Disclosures
All Authors: No reported disclosures
1398. Gland Tuberculosis: A Rare Localization of Tuberculosis
Authors: Hammami Fatma , Koubaa Makram , Chakroun Amal , Rekik Khaoula , Marrakchi Chakib , Smaoui Fatma , Jemaa Mounir Ben 
Published: December 2021

Abstract

Background
Tuberculosis (TB) is a multisystem disease that might affect all organs. Gland TB is characterized with a misleading clinical presentation which often mimic a neoplastic process. The aim of our work was to study the clinical, therapeutic and evolutionary features of gland TB.

Methods
We conducted a retrospective study including all patients hospitalized for gland TB in the infectious disease department between 1999 and 2020.

Results
We encountered 28 cases among which 24 were females (85.7%). The mean age was 39±14 years. A rural origin was noted in 15 cases (53.5%). Two patients were previously treated for TB (7.1%). Systemic symptoms of TB included fever (60.7%), asthenia (53.5%), loss of appetite (46.4%) and weight loss (25%). There were 18 cases of breast TB (64.3%), 4 cases of salivary gland TB (14.3%) and 3 cases of ovarian TB (10.7%). Two cases of pituitary TB (7.1%) and one case of adrenal TB (3.6%) were noted. Multifocal TB was noted in 7 cases (25%). Lymph node (17.8%), pulmonary (14.2%) and peritoneal (7.1%) TB were associated with gland TB. Tuberculin skin test was positive in 19 cases (67.8%). The diagnosis was based on histopathological proof in 23 cases (82.1%), microbiological proof in 4 cases (14.3%) and clinically confirmed in one case (3.6%). The median duration of antitubercular therapy was 10 [9-15] months. Patients received fixed-dose combination in 11 cases (39.2%). Adverse effects of antitubercular therapy were noted in 10 cases (35.7%) represented by gastrointestinal symptoms (14.3%), increase in hepatic enzyme levels (14.3%) and skin reactions (7.1%). The disease evolution was favorable in 26 cases (92.9%). Relapse was noted in two cases (7.1%).

Conclusion
Gland TB included different sites. The presence of systemic symptoms of TB and the diagnosis of TB elsewhere in the body helped through the diagnosis process which requires high index of suspicion. It was mainly based on histological evidence.

Disclosures
All Authors: No reported disclosures
1399. Clarithromycin–Rifampin-based Treatment for Non-tuberculous Mycobacterial Infections in Immunocompromised Patients Who Require Concomitant CYP-Metabolized Medications
Authors: Gonzalez-Bocco Isabel H , Aleissa Muneerah M , Cheng Matthew , Manne-Goehler Jennifer , Marty Francisco M 
Published: December 2021

Abstract

Background
Non-tuberculous mycobacteria (NTM) are causes of pulmonary and extrapulmonary disease that frequently affect immunocompromised hosts (ICH). Current treatment guidelines recommend a macrolide-based, multi-drug regimen that includes rifampin. Rifampin is a potent cytochrome P450 (CYP) 3A inducer, which often results in drug-drug interactions in ICH receiving multiple CYP substrates. One way to mitigate rifampin’s CYP induction is to utilize clarithromycin, a CYP inhibitor, as the accompanying macrolide. We evaluated the incidence of NTM treatment-related adverse events (AEs) in patients who received a clarithromycin-based regimen compared to patients who received an azithromycin-based regimen.

Methods
We conducted a retrospective review of NTM infection in 30 immunocompromised adults. All participants had a positive culture for a NTM and had received a rifamycin (rifampin or rifabutin) with a macrolide (azithromycin or clarithromycin) for treatment at Brigham and Women’s Hospital between 01/01/2011-10/18/2020 or Dana-Farber Cancer Institute between 06/03/2015-07/01/2020. The primary outcome was the incidence of NTM treatment-related AEs in patients who received a clarithromycin-based regimen compared to those who received an azithromycin-based regimen.

Results
There were no significant differences in the reasons for discontinuation of NTM treatment or 90-day mortality between groups. The number of AEs possibly related to NTM treatment were similar in patients who received a clarithromycin-based regimen and those who received an azithromycin-based one (10/13 vs. 14/17; p=0.73). The most common AE was liver function test abnormalities (Table 1). Additionally, the proportion of patients requiring dose adjustments for interacting medications and patients with out-of-range tacrolimus levels were similar between the two groups (23.1% vs. 29.4%; p=0.76 and 8.0% vs. 6.0%; p=1.00, respectively).
Table 1: Adverse events

Conclusion
A clarithromycin-based regimen for NTM treatment was safe and well tolerated in our patient population. This combination provides a good alternative for patients requiring medications that are CYP substrates, or those who cannot tolerate azithromycin.

Disclosures
Matthew Cheng, MD, GEn1E Lifesciences (Advisor or Review Panel member)Kanvas Biosciences (Board Member, Shareholder)nplex biosciences (Advisor or Review Panel member)
1401. Infliximab for Immune Reconstitution Inflammatory Syndrome (IRIS) in Tuberculous Meningitis; A Treatment Paradox
Authors: Azeem Ahad , Ahmad Faran , Velagapudi Manasa 
Published: December 2021

Abstract

Background
Tumor necrosis factor (TNF)-α inhibitors are known for the reactivation of latent tuberculosis (TB). As a paradox, it has been reported to have a role in the treatment of immune reconstitution inflammatory syndrome (IRIS) from anti-TB therapy.

Methods
We report a case of paradoxical worsening of central nervous system TB after initiation of anti-TB medications, which was treated successfully with infliximab (TNF-α inhibitor).

Results
A 34-year-old man from Nepal with a history of untreated latent TB presented with complaints of occipital headache, slurred speech, and witnessed seizure. His physical exam was consistent with hyperreflexia. MRI of the brain revealed multiple small contrast-enhancing lesions in cerebral hemispheres. CT Chest showed bilateral centrilobular nodules suggestive of miliary TB. Cerebrospinal fluid (CSF) analysis showed pleocytosis, high protein, and low glucose. He was started on isoniazid, rifampin, ethambutol, and pyrazinamide along with high-dose dexamethasone for TB meningitis. Later, MTB DNA probe from bronchioalveolar lavage and CSF detected Mycobacterium Tuberculosis which was pan-susceptible. Repeat MRI of the brain 6 months into therapy revealed worsening of brain lesions. Moxifloxacin and linezolid were added to the regimen given clinical progression on first-line therapy. 6-months into this enhanced regimen he started experiencing blurring of vision. Visual field mapping showed left homonymous hemianopia. Repeat MRI of the brain confirmed extensive changes of basilar meningitis completely enveloping the optic chiasm. IRIS from TB was suspected. His prednisone dose was increased, and 3-doses of infliximab infusion were, 2-weeks apart were administered which showed clinical and radiological improvement.
MRI Brain

MRI Brain (axial T2/flair sequence) shows hyperintensities in multiple locations including the involvement of the left optic nerve and the left occipital region.

Conclusion
Exacerbation of pre-existing clinical symptoms, formation of new lesions, or cavitation of prior pulmonary infiltrates is known as tuberculosis IRIS or paradoxical reaction. Despite the clinical and radiological exacerbation, mycobacterial cultures usually stay negative. Continuation of anti-TB medications and high-dose corticosteroids are the backbone of treatment but in refractory cases, immune modulation is needed with anti-TNF-α agents.

Disclosures
All Authors: No reported disclosures
1404. Tuberculosis and HIV Coinfection: A Review of 135 Cases Experience of the Infectious Diseases Department- CHU Mohamed VI- Marrakech
Authors: Alaoui Zahid Talibi , Raiteb Mohammed , Ihbibane Fatima , Soraa Nabila , Tassi noura 
Published: December 2021

Abstract

Background
Tuberculosis is a health problem in Morocco, which is increasingly indicative of human immunodeficiency virus (HIV) infection.

Objective
To determine the epidemiological, clinical and paraclinical, therapeutic and evolutionary aspects of tuberculosis and HIV co-infection.

Methods
we report 135 cases co-infected with HIV and tuberculosis, collected by the infectious diseases department at the Mohammed VI University Hospital in Marrakech. This is a 12-year retrospective study (2007 to 2020) that involved all HIV-infected patients hospitalized for tuberculosis regardless of its location.

Results
The mean age of the patients was 40 years (17-73 years). A male predominance was noted in 69% of cases. In 74.6% of cases, tuberculosis was indicative of HIV infection. Nine patients were receiving antiretroviral (ARV) treatment at the time of the discovery of tuberculosis. There were 24% pulmonary tuberculosis, 25.3% extrapulmonary tuberculosis and 49% disseminated tuberculosis. Tuberculosis was confirmed in 31.7% of cases. At the time of tuberculosis diagnosis, the average CD4 count was 86 cells / mm. Quadruple therapy with isoniazid, rifampicin, pyrazinamide and ethambutol was started in 83% of patients. The average time to start ARVs was 7 weeks. All patients who received ARVs received a combination therapy comprising the combination of 2 nucleoside analogs and one non-nucleoside analog. At the end of our work, the evolution was favorable in 53% of cases, death occurred in 25% of cases, 18.6% of patients were lost to follow-up, two cases of failure and another of relapse. Immune restoration syndrome was noted in 8 cases. Drug toxicity was observed in 24.5% of patients, 73% of which was related to hepato-toxicity of antibacillary drugs.

Conclusion
Tuberculosis is the most common opportunistic infection in people with HIV. Despite the advent of highly active triple therapy, tuberculosis is still a major cause of death in HIV positive people.

Disclosures
All Authors: No reported disclosures
1406. Hepatitis B and C Prevalence in Patients with Active and Latent Tuberculosis in an Ethnically Diverse Area of London, UK
Authors: Duret Amedine , Thorley Emma , Eni-Olotu Ayolola , Sikdar Oishi , Papineni Padmasayee 
Published: December 2021

Abstract

Background
North West London has one of the highest tuberculosis (TB) rates in the UK, at 24.8 per 10,000. The UK prevalence of hepatitis B virus (HBV) is 0.1-0.5% and for hepatitis C virus (HCV) is 0.5-1%. Chronic infection with HBV or HCV can lead to an increased risk of adverse treatment outcomes, such as drug-induced liver injury (DILI) in patients with active or latent TB. National guidelines recommend routinely screening for HBV/HCV prior to initiating TB treatment. Our objectives were to 1) evaluate the HBV/HCV screening practice in local TB clinics, 2) establish the prevalence of HBV/HCV in patients receiving TB treatment.

Methods
Retrospective analysis of laboratory and medical records of patients treated for active or latent TB identified from the London TB register and clinic records from 01/01/2018 to 31/12/2020 from London North West NHS Trust.

Results
1409 patients received treatment for TB during the time period of interest; 574 (40.7%) had active disease and 835 (59.3%) had latent infection. 966/1409 patients (68.56%) were screened for HBV and HCV. 55.9% of the active TB group and 77.2% of the latent infection group were tested. 66 (6.8%) patients had isolated anti-HBc positivity, 22 (2.3%) were HBV surface antigen positive and 8 (0.8%) were HCV-antibody positive. HBV surface antigens were more prevalent in active TB patients: 9/321 (2.80%) with active TB versus 13/645 (2.02%) with latent TB. 36/321 (11.21%) active TB patients had HBV core antibodies compared to 30/645 (4.65%) latent TB patients (p &lt; 0.001). Three patients started antiviral treatment following their viral hepatitis diagnosis (one with HBV, two with HCV).

Conclusion
The prevalence of chronic HBV in the study population was higher than the estimated UK prevalence. Fifteen diagnoses of hepatitis were new, allowing specialist referral for monitoring of fibrosis and development of hepatocellular carcinoma. Three patients required hepatitis treatment. 6.8% of patients were positive for anti-HBc and therefore identified as being at future risk of HBV reactivation if requiring immunosuppressive therapies.TB disproportionately affects marginalised communities; screening for viral hepatitis in TB clinic represents an opportunity to target these hard-to-reach groups to maximise the impact of public health interventions.

Disclosures
All Authors: No reported disclosures