bluuebunny/crossref_metadata_2025_split huggingface dataset:
797. Tuberculosis Treatment: Combined Forms vs. Dissociated Forms
Authors: Trigui Maroua , Koubaa Makram , Ayed Houda Ben , Marrakchi Chakib , Hammami Fatma , Jemaa Tarak Ben , Dammak Jamel , Jemaa Mounir Ben 
Published: November 2018

Abstract

Background
Tuberculosis treatment is based on the regular and concomitant intake of several antibiotics. The goal of this multidrug therapy is to prevent the selection of mutants resistant. This combination drug comes in two regimens with dissociated forms (DF) and combined forms (CF). Our study aimed to compare both forms of anti-tubercular treatment.

Methods
We retrospectively collected data from the regional registry of tuberculosis in the government of Sfax as a part of the National Tuberculosis Program. We included all new cases of tuberculosis from January 1995 to December 2016.

Results
We counted 2,771 cases of tuberculosis. There were 59.5% cases with extra-pulmonary (n = 1,650) forms and 40.5% with pulmonary forms (n = 1,121). The median age was 38 years (IQR = [25–55 years]) with a male predominance (n = 1,508; 54.4%). We noted that 72.9% of patients (n = 1,985) received the DF, 26.2% (n = 714) received the CF and 0.8% (n = 23) received both forms of treatment. DF was significantly more prescribed in patients with extra-pulmonary tuberculosis (75.4% vs. 72%; OR = 0.837; P = 0.043) whereas CF was significantly prescribed in patients with pulmonary tuberculosis (28% vs. 24.6%; OR = 0.837; P = 0.043). DF was more used in patients with primary tuberculosis infection (30.3% vs. 21.6%; OR = 0.632; P &lt; 0.001). The duration of treatment was significantly higher in patients who received DF (9 months vs. 8 months; P &lt; 0.001). We did not find a difference in the evolution between patients treated with DF and those treated with CF.

Conclusion
CF are of a great importance to ensure better compliance and synergistic effects of different antibiotics with a reduced duration.

Disclosures
All authors: No reported disclosures.
799. Genetic Diversity of Mycobacterium tuberculosis Strains Causing Drug-Resistant Tuberculosis in Central Region of Mozambique: The Whole-Genome Sequencing
Authors: Namburete Evangelina 
Published: November 2018

Abstract

Background
Knowing the genetic diversity of M. tuberculosis strains causing drug-resistant tuberculosis (DR-TB) in high burden TB and low resources countries such as Mozambique is a key factor to TB disease spread control and world TB epidemic control. Whole-genome sequencing (WGS) better describes molecular diversity, lineages and sub lineages, relationship between strains, underline mutations conferring drug-resistant TB, which may not be shown by molecular and phenotypic tests. As far as we know this is the first study that describes genetic diversity of M. tuberculosis strains causing DR-TB and using WGS in central region of Mozambique.We aim to describe genetic diversity of M. tuberculosis strains causing DR-TB in central Mozambique.

Methods
A total of 35 strains from Beira Mozambique were evaluated with genotypic tests (Genotype MTBDRplus™, and MTBDRsl™); phenotypic (MGIT-SIRE™) and DST. All isolates resistant to isoniazid (H) or rifampicin (R) or both were submitted to WGS Illumina HiSeq 2000 and analyzed with TB profiler database and phylogenetic tree was done using Figtree tool. This was a descriptive cross-sectional study.

Results
WGS shown that strains analyzed, belongs to three of six major lineages, with Lineage 4: 25(71.4%); Lineage 1: 5(14.3%); and Lineage 2 Beijing family: 5(14.3%)]. All pre-XDR strains 3(8.6%) were from lineage 4.3. By WGS, all 35 strains had any mutations conferring DR-TB while in one strain, mutation was not shown by genotypic neither phenotypic DST. Compared with genotypic tests, WGS had best performance in showing mutation conferring resistance to etambutol 12/35 (34.3%) and 7/35 (20%).

Conclusion
The DR-TB disease in Beira Mozambique is mainly caused by M. tuberculosis strains of Lineage 4, sub-lineage 3 although lineage 1 and 2 are also present. WGS shows underline mutations causing DR–TB that are not detected by genotypic and phenotypic DST test.

Disclosures
All authors: No reported disclosures.
801. Emergence of Multi-Drug Resistance Tuberculosis During the Treatment Course of Pan-Susceptible TB: A Case Series
Authors: Ford Mary , Lago Kathryn , Kizilbash Quratulain , Vasquez Adriana 
Published: November 2018

Abstract

Background
Successful treatment of tuberculosis (TB) requires monitoring for clinical, radiographic, and microbiologic improvement. Even after negative cultures are obtained, there should be continued monitoring of sputa. If cultures become positive during treatment of drug susceptible TB (DS-TB), there should be concern for multi-drug-resistant tuberculosis (MDR-TB). We present two cases diagnosed with DS-TB who developed MDR-TB during treatment. Case Report: Case 1 is a 33-year-old male who was incarcerated in Peru. During incarceration in 2008, three of his cellmates had MDR-TB and he was diagnosed with DS-TB and treated with directly observed therapy (DOT) for 7 months. In Texas in 2015 he was diagnosed with DS-TB and was initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). Five months into DOT, his sputa became culture positive with molecular detection of drug resistance (MDDR) and drug susceptibility testing (DST) revealing resistance to all of RIPE. Repeat MDDR and DST of the 2015 isolate showed no resistance. Genotyping of the two isolates were identical by mycobacterial interspersed repetitive units (MIRU) and spoligotyping. However, whole genome sequencing showed two different isolates. Case 2 is a 63-year-old female diagnosed with DS-TB in Saipan and started on RIPE in April 2017. She was on DOT until July when she moved to Texas and was lost to follow-up until September. She claims adherence with rifampin and isoniazid during this time. All sputa collected between diagnosis and September were smear and culture negative. Six months into therapy, she had sputa that was culture positive with MDDR and DST showing MDR-TB. Her isolates from Saipan and Texas were sent for genotyping. The MIRU and spoligotyping showed two different isolates.

Conclusion
These cases show the importance of following cultures throughout treatment. Traditionally, MDR-TB is thought to be due to poor adherence. However, in high prevalence areas, heterogeneous infection with two different strains is an important consideration for the cause of MDR-TB. Concomitant infection of DS and MDR-TB can occur with MDR-TB not being detected until far into therapy. These cases represent heterogeneous exogenous infection of DS and MDR-TB—only discovered after meticulous culture monitoring.

Disclosures
All authors: No reported disclosures.
802. Use of N-Acetylcysteine for Prevention and Treatment of Isoniazid Induced Liver Injury During Treatment of Mycobacterial Infections
Authors: Diaz Heidi Torres , Serrano Ruth , Bowling Jason E , Anstead Gregory , Javeri Heta 
Published: November 2018

Abstract

Background
Hepatotoxicity secondary to therapy for Mycobacterium tuberculosis (MTB) is a common complication that may lead to treatment interruption. N-Acetylcysteine (NAC) exerts a hepatoprotective effect by repleting glutathione stores and enhancing the cellular antioxidant defense mechanism. NAC has been found to be protective against liver toxicity in animals treated for MTB infection. Randomized controlled trials have shown that its use in humans also decreases the risk of hepatotoxicity associated with anti-MTB treatment but there is minimal data regarding its utility for treatment of liver toxicity.

Methods
Patients who received NAC from January 2012 to March 2018 for prophylaxis and treatment of increasing liver function tests (LFTs) while on isoniazid (INH) were included. A retrospective review of the medical record system was performed.

Results
Nineteen patients were included. Eight received NAC for treatment. The average age was 49 years. Seventy percent of patients were male. The mean BMI was 25. Five patients had underlying liver cirrhosis and two had hepatic steatosis. Eleven patients had Hepatitis C (HCV) and one had active Hepatitis B infection. Ten patients had MTB pulmonary infection, thee had latent TB infection, two meningitis, and three had disseminated disease. One patient was treated for atypical mycobacterial infection. The dose of NAC used was 600 mg oral twice daily and the duration was variable.
The prophylaxis group had stable LFTs during treatment, except for two patients whose enzymes increased more than three times the upper limit of normal. These two patients had underlying HCV and liver cirrhosis. Only one required discontinuation of INH. This group received NAC for an average of 47 days. The treatment group had a favorable trend of liver enzymes after NAC initiation, with levels significantly improving by day 14 (Figures 1 and 2). Three patients did not require discontinuation of antibiotics. INH was stopped prior to NAC initiation in four patients. No side effects of NAC were documented in any patient.

Conclusion
NAC is a safe and effective measure to prevent and treat hepatotoxicity secondary to INH therapy. More studies are needed to determine its optimal dose and duration for this indication.

Disclosures
All authors: No reported disclosures.
806. 2013–2015 Nationwide Tuberculosis Contact Investigation in Childcare Centers and Schools in Korea
Authors: Suh Woosuck , Kim Jong-Hyun , Hwang Ji Hyen , Lee Sodam , Lee Kang-Hee , Park Misun 
Published: November 2018

Abstract

Background
The Republic of Korea has the highest incidence rate of tuberculosis (TB) among members of the OECD, reported as 78.8/100,000 population in 2016. In response, a state-run intensive contact investigation for TB is being conducted. More effective TB control requires an epidemiologic emphasis on the diagnosis and treatment of latent TB infections in children and adolescents, compared with other age groups. Here we present an analysis of data from the childcare center and school contact investigation by the Korea Centers for Disease Control and Prevention (CDC) in 2013–2015.

Methods
Data collected from index patients included age, sex, occupation, disease status, results of AFB smear/culture, and chest x-ray. Data collected from contacts included age, sex, results of serial tuberculin skin test (TST), and chest x-ray. Congregate settings included childcare centers, kindergartens, elementary and secondary schools, and age groups were stratified as follows: 0–4 years, 5–12 years, and 13–18 years. TSTs were considered positive if induration ≥10 mm on the first test (TST1) or demonstrated an increase ≥6 mm over the induration of TST1 on repeat testing after 8 weeks (TST2).

Results
Of the 197,801 subjects with data collected, 173,998 were eligible and included in our analysis. TST1 results were available for 159,346 (91.6%) and when results were positive, induration was 10–14 mm in 7.6% and ≥15 mm in 1.5%. TST2 results were available for 119,797 (82.7%) of the 144,904 with negative TST1, and conversion rate was 9.0%. Altogether considering TST1 and TST2, 17.3% contacts had latent TB infections. Positive rates of TST significantly decreased with age: 20.3% in 0–4 years, 18.8% in 5–12 years, 17.1% in 13–18 years.

Conclusion
In this 3-year school-setting contact investigation, 17.3% contacts were diagnosed with latent TB infection, as demonstrated by TST reactions. Positive rates of TST significantly but mildly decreased with age.

Disclosures
All authors: No reported disclosures.
807. A Risk-Stratified Approach to Healthcare-Associated Tuberculosis Exposures Following the “Stone in the Pond” Principle
Authors: Pepe Dana E , Aniskiewicz Michael , Paci George , Sullivan Linda , Dembry Louise-Marie , Martinello Richard , Advani Sonali 
Published: November 2018

Abstract

Background
Large-scale tuberculosis (TB) exposure investigations cause anxiety to healthcare personnel (HCP) and patients, in addition to being resource and time intensive. TB contact tracing in England and Singapore follow the “stone in the pond” principle. We propose a similar risk-stratified approach to TB exposure investigations in an area of low incidence.

Methods
This retrospective study was conducted at a 1,541 bed academic medical center in New Haven, CT between January 14 and 11, 2017. Microbiology records, patient charts, and infection prevention databases were reviewed to find TB exposures. A scoring system adapted from CDC’s “Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis” was developed to predict infectivity (two points for laryngeal TB, one point each for: cavitary TB, ≥1 positive respiratory acid fast bacilli smear or Xpert MTB/RIF, multi-drug-resistant (MDR) TB, foreign-born status, immunocompromised status, cough/hemoptysis, or procedure associated with positive TB culture). Using the “stone in the pond” principle, contacts were graded based on the type of exposure (Figure 1). Based on high, medium, and low risk, our new risk-stratified approach was applied to contact tracing.

Results
During the study period, 17 of 29 patients with pulmonary TB led to exposures. A subset of seven TB patients with complete exposure data was selected for further analysis. The original exposure investigations led to contact tracing of 586 HCP and 72 patients. No active or latent TB cases were identified among these exposed contacts. Using our scoring system, these seven patients were categorized into three high, two medium, and two low infectivity risk groups. On applying our new risk-stratified approach, contact tracing could be reduced by 42% and 84% for medium and low-risk exposures, respectively, by excluding these HCP groups from investigation (Figure 2).

Conclusion
We recommend a risk-stratified approach to healthcare-associated TB exposure investigations similar to the “stone in the pond” principle, based on index patient’s infectivity risk and type of exposure. This has potential to optimize resources and possibly reduce anxiety in medium and low-risk TB exposures in an area of low TB incidence.

Disclosures
All authors: No reported disclosures.
808. Perinatal Depression Among HIV- and TB-Infected and Uninfected Women in an Urban Slum in India: Prevalence and Associated Birth Outcomes
Authors: Grossman Tracy , Mathad Jyoti S 
Published: November 2018

Abstract

Background
In low- and middle-income countries, depression during pregnancy is three times more common than in the United States and is more common than postpartum depression. There have been few studies on the prevalence of antepartum and postpartum depression in India. The objective of this study was to describe the prevalence of antepartum and postpartum depression among HIV-infected and uninfected pregnant women in an urban slum in India, and to evaluate associated pregnancy and birth outcomes.

Methods
This study was a longitudinal cohort study of HIV-infected and HIV-uninfected pregnant women at Sassoon General Hospital in Pune, India. Enrolled women answer questions about sociodemographics and medical history, including obstetric history. The PHQ-9 depression scale is administered during pregnancy and at 6 months postpartum.

Results
Of the 189 pregnant women enrolled, 113 (60 %) exhibited at least one symptom of depression on the PHQ-9 scale with 23 (12%) women having moderate or severe depression. However, significantly fewer postpartum women had evidence of depression (60% antepartum vs. 26% postpartum, P &lt; 0.001). Of the 77 women who had a postpartum visit, 20 (26%) also had symptoms of depression prior to delivery, but only 2 (10%) had more severe depression scores while 18 (90%) had improved scores. Thirty (39%) women with antepartum depression had resolution of symptoms postpartum and no women developed incident depression in the postpartum period. There was a trend toward increased rates of antenatal depression among HIV-infected vs. uninfected women (69% vs. 57%, P = 0.13). Both depressed and nondepressed pregnant women experienced low rates of intrauterine fetal demise, intrapartum hypertension, and preterm delivery. However, women with depression had 3-fold higher incidence of intrauterine growth restriction on prenatal ultrasound (4.4% vs. 1.5%).

Conclusion
We found that the majority of pregnant women in our population experience some form of depression during pregnancy. Most women with antepartum depression experienced improvement in their mood postpartum, which contrasts with patterns of perinatal depression in developed countries. We are planning qualitative studies to understand the social contributors for antepartum depression in India, and to identify potential solutions.

Disclosures
All authors: No reported disclosures.
813. Combination of N-Acetyl-Cysteine With Clarithromycin Against Mycobacterium avium Infection
Authors: Shiozawa Ayako , Kajiwara Chiaki , Ishii Yoshikazu , Tateda Kazuhiro 
Published: November 2018

Abstract

Background
N-Acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases. In previous studies, its antimicrobacterial and antimycobacterial effects have been reported. Among its effect in Mycobacteria, it has been mainly studied in Mycobacterium tuberculosis. Here, we examined whether NAC has antibiotic activity against M. avium.

Methods
The antimycobacterial effect of NAC was assessed in JCM 15430 M. avium strain infected A-549 (human lung epithelial cells) and MH-S (mouse alveolar macrophages). These cells were infected with M. avium at multiplicity of infection of 10 for 1 hours, washed and then cultivated for 5 days. Bacterial uptake was evaluated at 0 days and 5 days of cultivation. For the NAC treatment group, 5% FBS medium with 10 mM NAC was used as culture medium. We also tested its effect in combination with clarithromycin in vivo. BALB/c mice were infected intranasally with M. avium, and were given NAC (400 mg/kg) or clarithromycin (100 mg/kg) or both by gavage daily for 6 days. On day 7 of infection, lungs were harvested and CFU, cytokines and antimicrobial peptides were measured.

Results
NAC treatment of M. avium-infected A-549 and MH-S resulted in a significant reduction of mycobacterial loads (P = 0.014 and P = 0.014). In vivo, NAC treatment resulted in a significant reduction of mycobacterial loads in the lungs of M. avium-infected mice (P = 0.007). When in combination with clarithromycin, we also had an additional reduction (vs. clarithromycin monotherapy; P = 0.001). Several antimicrobial peptides significantly increased when treated with NAC and clarithromycin combination therapy.

Conclusion
NAC exhibits potent anti-mycobacterial effects and may limit M. avium infection. In addition with clarithromycin, it showed an additive effect in reduction of mycobacterial loads. Interestingly, in our study, several antimicrobial peptides increased significantly which may be one of the possibility on how NAC is involved in antimycobacterial effects. These results indicate that NAC may be an additional option in treating M. avium-infected patients in future, along with its classical drug regimens containing clarithromycin.

Disclosures
All authors: No reported disclosures.
985. Safety of Guidelines Recommending LAIV for Routine Use in Children and Adolescents With Asthma
Authors: Nordin James , Vazquez-Benitez Gabriela , Olsen Avalow , Kuckler Leslie , Kharbanda Elyse 
Published: November 2018

Abstract

Background
Asthma is the most common chronic medical condition in children. Prior observational studies of live attenuated influenza vaccine (LAIV) safety in asthmatic children have been limited due to confounding by indication, with LAIV restricted to patients with mild asthma. To minimize bias, we evaluated safety of LAIV in children with asthma using a natural experiment in which two medical groups, within a single health system, serving similar populations, differed in vaccination guidelines. Prior to 2010 both groups recommended inactivated influenza vaccine (IIV). Starting in 2010, one group recommended LAIV for children with asthma.

Methods
Asthmatic children age 2–18 years with visits to two large medical groups in the upper Midwest from 2007 to 2015 were identified and classified by severity and control using validated algorithms. Primary outcomes were lower respiratory events (LRE) occurring within 21 and 42 days after influenza immunization. Multiple records per subject were included when children received influenza vaccines in more than one season. The analysis was intention to treat with each medical group’s subjects analyzed as a group. A pre-/post-ratio of ratios (ROR) approach was used to estimate the LAIV guideline impact using a generalized linear model with a Poisson distribution, accounting for multiple records per subject and adjusting for age and asthma classification. Analyses were for the overall population, and stratified by age group: 2–4 and 5–18 years.

Results
A total of 7,959 observations from 4,824 unique asthmatic children were analyzed, with 1,896 from the IIV guideline and 6,061 from the LAIV guideline medical groups. Postimplementation, 67% received LAIV. Age and asthma classification adjusted ROR showed no increase in LREs using the LAIV guideline: overall ROR (95% CI): 0.79 (0.46–1.37) for LRE 21 days and 0.82 (0.56–1.20) for 42 days; age 2–4: 1.07 (0.40–2.83) for 21 days and 1.0 (0.53–1.90) for 42 days; and age 5–18: 0.72 (0.37–1.41) for 21 days and 0.75 (0.46–1.21) for 42 days.

Conclusion
A guideline recommending LAIV rather than IIV for asthmatic children did not result in more LREs following vaccination in children age 2–18. Guidelines for influenza vaccination in asthmatic children should be based on effectiveness studies.

Disclosures
All authors: No reported disclosures.