bluuebunny/crossref_metadata_2025 huggingface dataset:
715. Increase in Reported Respiratory Syncytial Virus Cases Among Adults in the Minneapolis-St. Paul Metropolitan Area, 2014–2018
Authors: Como-Sabetti Kathryn , Bye Erica , Strain Anna , McMahon Melissa , Lynfield Ruth
Published: November 2018

Background

Respiratory syncytial virus (RSV) is a common cause of respiratory infection, typically causing severe disease in young children. We were interested in evaluating trends of severe RSV infections in adults.

Methods

The Minnesota Department of Health conducts active surveillance for laboratory-confirmed RSV in hospitalized patients in the Minneapolis-St. Paul metropolitan area as part of the CDC Emerging Infections Program. Adults (≥18 years) cases identified during the RSV season (10/1–4/30) from 2014 through 2018 were analyzed and surveys of catchment-area hospital laboratories were conducted regarding respiratory virus panel (RVP) testing.

Results

Twenty-three catchment area hospitals serve adults. Four hospitals offered RVP during the 2014–2015 and 2015–2016 seasons; eight offered RVP during the 2016–2017 and 2017–2018 seasons. Three hundred and fifty-five cases were identified. Three hundred and nine (87%) were reported from four hospitals where RVP was offered throughout the study period. Case increases were observed at three hospitals; all of these hospitals offered RVP throughout the surveillance period; increases were not observed at hospitals where RVP was added for the 2016–2017 and 2017–2018 seasons. Cases increased from 42 in 2014–2015 to 198 in 2017–2018 (χ2 = 125.51, P < 0.01), the proportion of cases reported by year was 12%, 15%, 17% and 56% during consecutive seasons. Cases by age groups over time generally did not differ; however, cases ≥85 years increased from 7% of total cases in 2014–2015 to 19% in 2017–2018 (χ2 = 6.14, P = 0.01). Overall, 23% of cases were admitted to the ICU and 7% died during hospitalization. The proportion of ICU admissions and deaths did not change over time.

Conclusion

We found an increase in adult RSV hospitalizations from 2014 to 2018, especially among the oldest age group. This increase was observed only at hospitals where RVP testing was offered throughout the surveillance period. It is unclear if this represents a true increase in RSV or a change in testing practices. However, it does illustrate that RSV should be considered as a cause of severe respiratory illness (SARI) in adults, particularly among the elderly. A more systematic approach in identifying the causes of SARI in adults would be informative, particularly as RSV vaccines and antivirals approach licensure.

Disclosures

All authors: No reported disclosures.
718. Viral Coinfection and Nasal Cytokines in Children with Acute Bacterial Sinusitis (ABS)
Authors: Lopez Santiago , Martin Judith M , Johnson Monika , Williams John V , Shaikh Nader
Published: November 2018

Background

ABS is one of the most common infections in childhood leading to antibiotic prescriptions, but remains a clinical diagnosis. Laboratory testing does not aid diagnosis and there are no predictors to identify those who will respond to therapy or develop complications. Thus, the tools to diagnose and manage ABS remain limited. Initial viral infection predisposes to development of ABS. However, there is poor understanding of the contribution of viral infection to pathogenesis, rate of complications, or the immune response to ABS. The objective of this study was to define bacterial upper airway colonization, viral co-infection and cytokine response in the upper airway during ABS.

Methods

In the context of an ongoing larger prospective clinical study, children were enrolled who were diagnosed with ABS using standardized clinical criteria. Nasopharyngeal (NP) samples were processed for bacterial culture for S. pneumoniae, H. influenzae, S. pyogenes and M. catarrhalis; real-time PCR viral testing and cytokine measurement by qPCR. We correlated these findings with clinical symptoms at the time of presentation.

Results

Of 184 enrolled children (median age 4.9 years), 134 (72.8%) had a positive bacterial culture for potentially pathogenic bacteria and 50 (27.2%) had growth of normal flora. A total of 129 (70.4%) subjects tested positive for a virus. The most common virus detected was rhinovirus (n = 86) followed by influenza virus (n = 23) and adenovirus (n = 21). A total of 102 patients (70.4%) had both a positive pathogenic bacterial culture and viral detection. Patients who had a bacterial pathogen plus a viral detection had a significantly higher expression of IL-6, IL-8 and IL-25 (P < 0.001). Univariable analysis found no correlation between clinical presentation with viral and/or cytokine expressions.

Conclusion

Children meeting clinical criteria for ABS and a NP swab with a pathogenic bacteria plus viral detection demonstrated higher expression of inflammatory cytokines compared with subjects whose culture had normal respiratory flora.

Disclosures

J. V. Williams, Quidel: Board Member, Consulting fee. GlaxoSmithKline: Consultant, Consulting fee.
723. Validation of a Wild-Type Influenza A/Texas-Like H3N2 Human Challenge Model with Comparison to the Validated A(H1N1)pdm09 Model
Authors: Han Alison , Czajkowski Lindsay , Donaldson Amanda , Baus Holly Ann , Reed Susan , Athota Rani , Bristol Tyler , Rosas Luz Angela , Cervantes-Medina Adriana , Taubenberger Jeffery K , Memoli Matthew J
Published: November 2018

Background

Healthy volunteer challenge studies provide an opportunity to better understand influenza pathogenesis and correlates of protection. The development of vaccines and therapeutics has relied on these studies as will future universal vaccine candidates. The first fully validated wild-type human infection model with A(H1N1)pdm09 was developed at the NIH Clinical Center (CC) in 2012 and this study represents the first validation of a wild-type seasonal H3N2 human infection model. The objective of this study was to characterize a wild-type Influenza A/Texas-like H3N2 challenge virus in healthy volunteers.

Methods

Healthy volunteers were isolated at the NIH CC for a minimum of 9 days. Subjects received a single dose of a reverse genetics, cell-based, GMP, wild-type A H3N2 virus intranasally. Dose escalation was performed from 104 to 107 TCID50. Viral shedding and clinical disease were evaluated daily, including clinician assessments and a validated patient-reported outcome tool, FLU-PRO©.

Results

A total of 37 subjects were challenged. Sixteen (43%) subjects had viral shedding and 27 (73%) developed influenza symptoms, with 12 subjects (32%) experiencing mild-to-moderate influenza disease (MMID) defined as symptoms and shedding. Only subjects receiving the 106 and 107 TCID50 doses experienced MMID at 44% and 40%, respectively. Nose and throat symptoms were most common and peaked by Days 2–3 post-challenge. Although serum antibody responses were observed, many of these responses were limited in a significant number of subjects.

Conclusion

The A/Texas-like H3N2 Influenza challenge virus safely induced MMID in healthy volunteers, but was less effective than the A(H1N1)pdm09 challenge virus. This lower MMID rate of 40% was observed at the 107 TCID50 dose and was driven by less detection of shedding as the incidence of symptoms was similar to A(H1N1)pdm09. The limited serum antibody responses observed demonstrate that preexisting immunity in healthy volunteers against the seasonal H3N2 lineage may limit shedding compared with the more recently emerged seasonal A(H1N1)pdm09 lineage. The successful characterization of this H3N2 model makes future studies using this model to explore viral pathogenesis or evaluate vaccines possible.

This research was supported by the Intramural Research Program of the NIH, NIAID.

Disclosures

All authors: No reported disclosures.
724. Neurologic Complications in Hospitalized Pediatric Patients with Influenza Infection, A Multicenter Retrospective Study in Korea
Authors: Choi Gwang-Jun , Park Ji Young , Choi Joon-Sik , Kim Bitna , Choi Sae Rom , Kim Dong Sub , Kang Ji-Man , Lee Jun Wha , Woo Young-Jong , Lee Jeehun , Kim Yae-Jean
Published: November 2018

Background

The aim of the study was to evaluate the incidence and characteristics of influenza associated neurologic complications (IANCs) in hospitalized pediatric patients in Korea.

Methods

We performed retrospective review of hospitalized cases of confirmed influenza infection from October 2010 to April 2017. Patient’s data were collected from three referral hospitals in different regions of the country.

Results

A total 2,002 laboratory confirmed influenza cases were identified. The median age was 3.3 years old (range 0.0–18.9 years) and 1,003 patients were male (54%). Influenza A was diagnosed in 1,357 cases (68%), influenza B in 624 (31%) and both influenza A and B in 21 (1%). Other combined respiratory virus infection was detected in 104 (5.2%) cases. Out of 2,002 cases, IANCs were identified in 167 cases (8.3%); influenza virus A was detected in 116 (69.4%), B in 50 (29.9%) and both A and B in one case (0.6%). Of 167 cases with IANCs, 25 patients (15%) had underlying neurologic diseases. Eleven patients (11/167, 6.5%) had combined respiratory viral infection (Rhinovirus = 5; respiratory syncytial virus = 3; coronavirus = 2; and bocavirus = 1). The most common diagnosis was a simple febrile seizure (112/167, 67.1%), followed by other seizures (26/167, 15.6%), encephalopathy/encephalitis (17/167, 10.2%), meningitis (7/167, 4.2%), meningism (4/167, 2.4%) and acute ataxia (1/167, 0.6%). In two patients with encephalitis/meningitis, one patient had influenza A and the other patient had influenza B detected by PCR in cerebrospinal fluid. Most of the patients were fully recovered (162/167, 97%) and no neurologic complication occurred in patients who had only initial manifestation of simple febrile seizure. Ten patients (10/167, 6.0%) required hospitalization in intensive care unit. Three patients (3/167, 1.8%) died of encephalopathy (n = 1) and combined encephalopathy/myocarditis (n = 2). Pre-existing neurologic disease was a risk factor of IANCs with an odds ratio of 3.94 (95% confidence interval 2.37 to 6.56, P < 0.0001).

Conclusion

IANCs is not rare and may cause serious outcome including death. Clinicians should be aware of the increased risk for IANCs in certain patients with neurologic diseases.

Disclosures

All authors: No reported disclosures.
730. Hospital Readmissions Following Laboratory-Confirmed Influenza
Authors: Dobrzynski David , Ndi Danielle , Markus Tiffanie , Zhu Yuwei , Schaffner William , Talbot H Keipp
Published: November 2018

Background

Further understanding of hospital readmissions after influenza illness could reduce readmissions. The aim of our study was to characterize the morbidity associated with laboratory confirmed influenza hospitalizations.

Methods

This was a retrospective study using data from 2006 to 2016 from the Tennessee (TN) Emerging Infections Program Influenza Surveillance Network, which prospectively identifies laboratory-confirmed influenza hospitalizations in Nashville, TN and surrounding counties. Using the TN Hospital Discharge Data System, which collects information on all hospitalizations and discharges in TN, cases were linked to subsequent hospitalizations up to 1 year. The International Classification of Diseases was used to define the primary diagnosis associated with each hospitalization. Demographic characteristics and outcomes were compared by using χ2 tests for categorical variables. Multivariable logistic regression was used to compare study outcomes.

Results

Of the 2,897 patients with a laboratory-confirmed influenza hospitalization, 1,364 (47%) had a hospital readmission during the subsequent year (figure). Multiple readmissions occurred in 740 patients (54%). The readmission group was older, female predominant, and had more comorbidities than patients not re-hospitalized. Acute COPD/asthma exacerbation, pneumonia, septicemia, and acute renal failure were the most common causes for readmission. Underlying cardiovascular disease (OR 1.6), lung disease (OR 1.6), kidney disease (OR 1.7), diabetes (OR 1.3), immunosuppression (OR 1.6), and liver disease (OR 2.1) were associated with increased risk of readmission (table).

Conclusion

An influenza hospitalization is associated with increased hospital readmissions. Approximately 47% of patients hospitalized with influenza are readmitted within 1 year. Patient comorbidities could be an important link to influenza readmissions.

Disclosures

W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee. Pfizer: Member, Data Safety Monitoring Board, Consulting fee. Dynavax: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. SutroVax: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.
742. “Troponin Leaks” in Patients with Acute Respiratory Viral Infections Enrolled in SUPERNOVA: A Marker of Worse Clinical Outcomes
Authors: Ruiz Ernesto , Lengi Bashir , Gray Tiffany , Mushtaq Mahwish , Musher Daniel , Rodriguez-Barradas Maria
Published: November 2018

Background

Cardiac troponin I (cTnI) is a specific marker of cardiac muscular injury. Many patients hospitalized with acute respiratory illness (ARI) have elevated cTnI levels but do not meet EKG criteria for an acute ischemic cardiac event. Troponin leaks could be due to demand ischemia or acute inflammation of the myocardium. We hypothesized that patients with viral ARI and elevated cTnI have worse cardiopulmonary outcomes than those with viral ARI and normal cTnI.

Methods

From November 11, 2016–September 30, 2017 nasopharyngeal swabs from patients enrolled in SUPERNOVA ARI Study, a CDC/2-VA site, active surveillance platform to evaluate the incidence of viral infection in patients hospitalized with symptoms and/or signs of ARI, were tested using a FilmArray Respiratory Panel. Based on detection of any virus, patients were categorized as positive (vPCR+) or negative (vPCR−). Patient enrolled at the Houston site with cTnI obtained <48 hours of admission were included in the analysis. cTnI above upper limit of normal (>0.03 ng/dL) was defined as elevated. Demographic and clinical data were abstracted from chart review. Outcomes were myocardial infarction (MI) on admission, 30- and 90-day re-admissions due to cardio-respiratory illness and 30- and 90-day all-cause mortality. For the univariable analysis of baseline factors and outcomes we used unpaired t-tests for continuous variables and χ2 or Fisher exact test for categorical variables as appropriate.

Results

Ninety-four of 332 cases were vPCR positive and cTnI levels on admission were available in 86. Demographics and comorbidities were all similar for the high (N = 42) and normal (N = 44) cTnI groups. Compared with normal cTnI group, those with high cTnI had similar 30- and 90-day readmission rates (14% vs. 9%, P = 0.4 and 26% vs. 16%, respectively, P = 0.2). However, 30- and 90-day mortality rates were higher for high cTnI patients (10% vs. 0% and 19% vs. 5%, P < 0.03).

Conclusion

Troponin elevation on patients with a documented viral respiratory infection is associated with higher 30- and 90-day mortality rates. Troponin leaks should not be dismissed as a trivial finding in this group of patients. Further work on its pathogenesis is warranted.

Disclosures

All authors: No reported disclosures.
744. Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine and Influenza Vaccine Against Pneumococcal Pneumonia Among Elderly Patients Aged 65 Years and Older in the Republic of Korea: A Case–Control Study
Authors: Kim Jong Hun , Chun Byung Chul , Song Joon Young , Kim Hyo Youl , Bae In-Gyu , Kim Dong-Min , Choi Won Suk , Jeong Y H , Choi Young Hwa , Kang Seong Hui , Yoon Young Kyung , Sohn Jang-Wook , Kim Min-Ja
Published: November 2018

Background

The national immunization program (NIP) of annual influenza vaccination to the elderly population (≥65 years of age) in the Republic of Korea (ROK) has been implemented since 1987. Recently, the 23-valent pneumococcal polysaccharide vaccine (PPV23) through the NIP has been provided to the elderly population in the ROK since May 2013. The aim of this study was to assess PPV23 and influenza vaccine (IV) effectiveness in preventing pneumococcal pneumonia (PP) among elderly patients ≥65 years of age.

Methods

A case–control study using a hospital-based cohort was conducted. Cases of PP including bacteremic PP and nonbacteremic PP were collected from 14 hospitals in the pneumococcal diseases surveillance program from March 2013 to October 2015. Controls matched by age and sex in the same hospital were selected. Demographic, clinical information, and vaccination histories were collected. Previous immunization was categorized into “vaccinated” if a patient had received vaccines as follows: PPV23 (4 weeks to 5 years) and IV (2 weeks to 6 months) prior to the diagnosis of PP for case patients and prior to the hospital admission for control patients. Adjusted odds ratio (OR) was calculated, controlling for underlying medical conditions. Vaccine effectiveness was defined as (1 – OR) × 100.

Results

During the study period, a total of 661 cases (104 bacteremic PP cases and 557 nonbacteremic PP cases) and 661 controls were enrolled for analyses. For overall patients ≥65 years of age, there was no significant vaccine effectiveness against PP. For young elderly patients with 65–74 years, IV alone (1.2%, [95% confidence interval (CI) −95.3% to 50.0%]) and PPV23 alone (21.9%, [95% CI −39.0% to 56.1%]) were not effective. However, significant vaccine effectiveness of PPV23 plus IV against PP was noted (54.4%, [95% CI 6.9–77.7%], P = 0.031). For older elderly patients ≥75 years of age, no significant vaccine effectiveness was observed.

Conclusion

Our study indicates that PPV23 plus IV may be effective in preventing PP among young elderly patients with 65–74 years, suggesting additive benefits of influenza plus PPV23 vaccination. Further studies are required to confirm the persistent additive protective effectiveness.

Disclosures

All authors: No reported disclosures.
766. Migration Flows and Increase of Extrapulmonary Tuberculosis in a Low Prevalence Setting: A Retrospective Analysis in Two Italian Centers
Authors: Compagno Mirko , Campogiani Laura , Coppola Luigi , Sarmati Loredana , Andreoni Massimo , Francisci Daniela , Saraca Lavinia , Baldelli Franco
Published: November 2018

Background

Extrapulmonary tuberculosis (EPTB) represents 25% of Worldwide tuberculosis and it is more commonly associated with immunodepression. The purpose of this study was to determinate the burden of EPTB in a low TB prevalence setting.

Methods

A retrospective evaluation of patients treated for TB at Tor Vergata Hospital and Terni Hospital (Italy) from January 2013 to November 2017 was done. Clinical charts, laboratory tests and radiological findings were reviewed and analysed. Data were elaborated using Yates’ method analysis, Fisher test and Pearson’s chi-square test.

Results

A total of 171 patients were enrolled from 2013 to 2017 in two Italian centers (Rome and Terni); 71% were males, with a mean age of 41.5 years. The number of TB diagnosis increased among the study period (6.6% in 2013 vs. 56% in 2017) and an increase of EPTB (23% in 2013 vs. 44% in 2017) was seen. Most commonly EPTB presented as generalized lymphadenitis (34%), osteomyelitis and spondylodiscitis (28%) and other sites localizations (31%). Statistical analysis revealed a significant correlation between geographical provenience and TB localization (P = 0.004). Extra European immigrants (76% Africans) resulted at higher risk of EPTB (OR 2.31; CI 95% 0.63–8.46), while being Caucasian showed a protective role toward EPTB development (P = 0.001). The risk of EPTB doubled in 2015–2017 respect 2013–2014.

Conclusion

From 2013 to 2017 an increase in TB admissions was documented with a significant higher number of EPTB cases, particularly in extra-European immigrants. The doubled risk in 2015–2017 was likely the consequence of the recent ongoing escalating levels of migration from African countries and may result as an emerging Public Health problem.

Disclosures

All authors: No reported disclosures.
768. Epidemiological and Clinical Profile of Miliary Tuberculosis in Southern of Tunisia
Authors: Jemaa Maissa Ben , Koubaa Makram , Ayed Houda Ben , Marrakchi Chakib , Trigui Maroua , Hammami Fatma , Hmida Mariem Ben , Jemaa Tarak Ben , Dammak Jamel , Jemaa Mounir Ben
Published: November 2018

Background

Miliary tuberculosis (MT) is a severe rare form of tuberculosis (TB). It is often due to lymphohaematogenous dissemination of tubercle bacilli. Although the global incidence of TB has been slowly decreasing with globally conducted program, MT incidence is relatively increasing owing mainly to widespread use of immunosuppressive drugs and HIV/AIDS pandemicity. Few reports were found regarding epidemiological data of MT in developing countries. We aim to evaluate epidemiological characteristics of MT in the region of Sfax Southern Tunisia.

Methods

We conducted a retrospective study of all new cases of MT of all ages between January 1995 and December 2016. Data were collected from the regional register of tuberculosis implanted in the anti-tuberculosis center of Sfax.

Results

We analyzed 22 patients with MT accounting for 0.8 of all cases of tuberculosis. Incidence rates of MT were stable over the 22-year study period. Their median age was of 41 years (IQR= [17–63.5]) and a half of them were females. MT was significantly more common in patients less than 15 years (2.4% vs. 0.7%; OR=3.5; P = 0.04). Six patients (27.3%) had extra-pulmonary locations with lymph nodes (n = 1), meninges (n = 2), bones and joints (n = 1), abdominal cavity (n = 1), and pleura (n = 1). One patient (4.5%) died within 8 months after a confirmed diagnosis. Median duration of treatment was 10 months (IQR = [6–15 months]). The outcome was favorable in 19 cases (86.4%) and three patients received a combined-drug regimen (13.6%).

Conclusion

MT remains a serious form of tuberculosis which may compromise the life-threatening. It was mainly seen in young nonvaccinated children but currently, except among HIV-infected persons, it is more common among older persons who experience more an endogenous reactivation. These findings emphasize the high efficacy of BCG vaccination in developing countries to prevent MT.

Disclosures

All authors: No reported disclosures.
772. Factors Associated With Healthcare Delay of Active Pulmonary Tuberculosis After Hospitalization
Authors: Han Jaijun , Park Se Yoon , Park Jebyung , Lee So Young , Kim Gil Eun , Jeong Yeon Su , Kim Jin Hwa , Lee Eunyoung , Lee Eun Jung , Yu Shi Nae , Kim Tark , Jeon Min Hyok , Choo Eun Ju , Kim Tae Hyong
Published: November 2018

Background

Hospitals are undesirable reservoirs for a respiratory outbreak. Active pulmonary tuberculosis (TB) can be readily transmitted among hospitalized patients. Early recognition of pulmonary TB is an essential priority against transmission. The aim of this study was to evaluate factors associated with delayed identification of pulmonary TB in hospital settings.

Methods

Medical records of newly diagnosed TB patients admitted to a referral hospital from January 2015 through December 2017 were reviewed. Delayed recognition of pulmonary TB was defined as failure to initiate airborne isolation within the first 3 days after admission. We analyzed clinical, microbiological, radiological, and healthcare factors associated with delayed recognition of pulmonary TB. Patients who were not suspected of having active pulmonary TB had no remarks about TB on their initial chest radiograph interpretation by radiologists. Multivariate logistic regression analysis was performed with significant factors included.

Results

A total of 136 patients were analyzed who had positive sputum acid-fast bacilli (AFB) cultures. Of these, 45 (33%) patients were isolated 3 days after admission and had longer days of exposure before isolation (median 9, interquartile range [IQR] 6–14, P < 0.001) in comparison to others (median 0, IQR 0–1). Patients with older age (odds ratio [OR] = 1.04, 95% confidence interval [CI] 1.01–1.08, P = 0.01), patients who were admitted to departments other than infectious diseases or pulmonology (OR = 6.23, 95% CI 2.17–17.89, P = 0.001) and patients who were not suspected of having active pulmonary TB by radiologists (OR = 11.36, 95% CI 4.11–31.39, P < 0.001) were more likely to have delayed recognition of pulmonary TB.

Conclusion

In a country with intermediate TB prevalence, better awareness for pulmonary TB is required for all hospitalized patients who are admitted to departments other than infectious diseases or pulmonology. Although active pulmonary TB is not suspected by a radiologist, sputum AFB smear, and culture are necessary when new lesions are present in chest radiographs.

Disclosures

All authors: No reported disclosures.
775. An Epidemiological Analysis of Patients With Multidrug-Resistant Tuberculosis Among Tibetan Refugees in India
Authors: Desel Tenzin , Tsuda Naonori , Tsundue Tenzin , Lingtsang Rangjung , Topgyal Sonam , Sako Akahito , Yanai Hidekatsu , Sadutshang Tsetan
Published: November 2018

Background

Globally, refugee populations face an increased risk for tuberculosis (TB) due to malnutrition, overcrowding, and poor living conditions. Compared with the general Indian population, Tibetan refugees in India display a higher incidence rate of both TB and multidrug-resistant TB (MDR-TB). The high incidence of MDR-TB in younger population is a serious public health concern.

Methods

We retrospectively reviewed the medical records of patients with MDR-TB treated from January 2010 to December 2013 in Tibetan Delek Hospital, which is the center of TB control among Tibetan refugees. Patients were classified into either new cases (supposed infection by exposure to MDR-TB) or previously treated MDR-TB cases (suspected acquirement of MDR-TB through anti-TB treatment or by MDR-TB exposure after treatment). We compared patients’ age, sex, birthplace, residence type, occupation, contact history, and treatment outcome.

Results

Of 749 patients with TB, we enrolled 134 patients with MDR-TB [median age, 26 (interquartile range: 22–35) years; males, 55%]. The Tibetan ethnicity comprised 96% of the study population, whereas Indians (trans-Himalayan) comprised 4%. The birthplace was Tibet for 22% patients, India for 75%, and Nepal for 2%. New MDR-TB cases were 28% and previously treated MDR-TB cases were 72%. Failure was observed in 42% patients and cured and completed in 54% patients, during their previous TB treatment. The median age was significantly lower in new cases than in previously treated MDR-TB cases (24 vs. 28.5 years; P < 0.01). Tibet was the birthplace of 34% new cases and 18% in previously treated cases (P = 0.04). The residence was of the congregated type in 58% of new cases and 30% in previously treated MDR-TB cases (P = 0.01). The occupation was “student” and “unemployed” in 58% and 8% in new cases and 33% and 24% in previously treated cases, respectively (P = 0.03). Contact history with TB type and treatment outcome were not considerably different, although the rates of cured and completed were high in both new (82%) and previously treated (84%) MDR-TB cases.

Conclusion

This study shows that new MDR-TB correlates with younger age, birth in Tibet, congregated residence, and student occupation. Targeting the above-listed characteristics could be effective in further reducing the MDR-TB transmission among Tibetan refugees in India.

Disclosures

All authors: No reported disclosures.
776. Tuberculosis Screening Among People Living With HIV in Arkansas: A Ryan White Program Evaluation
Authors: Gu Mofan , Patil Naveen , Fischbach Lori , Vance Tiffany , Bedell Charles , Mukasa Leonard
Published: November 2018

Background

The current TB screening practice among people living with HIV in the United States is understudied. In our preliminary study, we found that only 6 (12%) US states recommended TB screening in their HIV guidelines; and only half of the Ryan White Programs capture client TB status. In this ongoing project, we aim to determine the prevalence of TB screening among people living with HIV in Arkansas, inform policy revisions, and ultimately reduce the burden of TB-HIV comorbidity.

Methods

We generated a sample of patients who received Ryan White service during the last grant year (April 1, 2016 to March 31, 2017) from CAREWare (Ryan White client database). We reviewed these patient files in multiple site visits and collected data on TB screening practice. We then performed descriptive analysis and multivariate logistic regression to analyze TB screening patterns in Arkansas.

Results

To date, we reviewed 728 patient records from 22 clinics across Arkansas during a 6-month study period. Three hundred sixty-seven (50%) patients have baseline (HIV diagnosis) TB status. On the basis of the multivariate logistic regression model (adjusting for age, gender, race, and patient residence), TB screening among Ryan White patients vary significantly by clinical regions in Arkansas (P < 0.0001). As compared with the central region, HIV patients in the North Central clinical region are more likely to be screened for TB (OR, 23.28; 95% CI, 5.29, 102.49); and HIV patients in the Northeast clinical region are less likely to be screened (OR, 0.05; 95% CI, 0.01, 0.30).

Conclusion

We observed in Arkansas (1) low adherence to recommendations for TB screening among people living with HIV and (2) insufficient HIV surveillance infrastructure to capture TB status, and (3) geographic variations in TB screening practice among people with HIV, indicating the need for (1) clearer guidelines, (2) stronger TB education among providers, and (3) program collaboration and service integration between TB and HIV. In our next steps, we want to explore further into the regional variations in TB screening among people with HIV, in order to tailor interventions to different geographic regions. We also want to examine changes in TB screening practice after implementation of the new contract, and to determine the optimal frequency of TB screening among people living with HIV.

Disclosures

All authors: No reported disclosures.
782. Risk Factors, Clinical Characteristic, and Treatment Outcomes for Nontuberculous Mycobacterial Disease in Mexico
Authors: Luis Bruno Ali Lopez , Perez-Gutierrez Ma Teresa , Bobadilla-Del-Valle Miriam , Ponce-De-Leon Alfredo , Sifuentes-Osornio José
Published: November 2018

Background

Nontuberculous Mycobacteria (NTM) cause diverse clinical manifestations in multiples clinical setting, and in the past years, there has been an increasing prevalence and variability among geographic regions, this associated with a diversity of hosts and clinical manifestations. We objective was evaluated the clinical and microbiologic characteristic, and the treatment outcomes related to slowly growing mycobacteria (SGM) and rapidly growing mycobacteria (RGM).

Methods

When conducting a retrospective study between January 2001 and December 2017, retrospectively their medical records were reviewed for obtainments of site of isolation or infection, comorbidities or predisponent condition, clinical and radiographic presentation, and treatment outcomes.

Results

A total of 90 patients with isolated of RGM and 87 within SGM were evaluated among these M. avium and M. fortuitum were the most predominant species. HIV infection was the predominat risk factor for SGM infections (P < 0.001); the conditions associated to RGM infections were cancer (P = 0.02787); diabetes mellitus (DM) (P = 0.01418), chronic kidney disease (CKD)(P = 0.04662), use of immunosuppressive medication (P < 0.001), and use of invasive device only were present in the RGM group. In the RGM group, lung infection was the most common site of infection (43%); in the SGM group, the disseminated disease was the most common (54%). The time of treatment was more prolonged in the SGM group (196 vs. 229 days, P = 0.0309). In the RGM group, the rate of cure was higher in the subgroup of Mycobacterial stream infections and disseminated disease (15 vs. 5, P = 0.0146). In the analysis of lung infection who meet the IDSA/ATS criteria were divided into the group with treatment and the group without treatment, the outcomes were not significative in both groups.

Conclusion

The NTM infections are an important cause of disease in patients with chronic conditions such as cancer, immunosuppressive medication, CKD, use of invasive device, and DM. HIV infection persist as the first risk factor for M. avium disseminated disease, the treatment for this latter condition in spite of more prolonged, it had a lower rate of cure. The treatment of lung infections for NTM must be individualized although the IDSA/ATS criteria are met.

Disclosures

All authors: No reported disclosures.
783. Characterization of Non-tuberculous Mycobacteria Isolates in a National Mycobacterial Laboratory in Panama: 2012–2015
Authors: Zavala Sofia , Rosas Samantha , Calvo Arlene , Sosa Nestor , Henostroza German , Rodriguez Ana Belen Arauz
Published: November 2018

Background

Nontuberculous mycobacteria (NTM) are becoming more frequently isolated in microbiology laboratories. There is no standardized diagnosis, treatment, and/or monitoring of patients with NTM disease. We described the experience of the Panama National Mycobacterial Laboratory in isolating NTM in patients suspected to have active tuberculosis in Panama.

Methods

Data registries of the National TB Program Laboratory of Panama between 2012 and 2015 were reviewed. Demographic information, relevant history, sample source, and isolate identified for each specimen obtained at the time of specimen submission was extracted. Identification of mycobacterial species were made using culture and PCR. Data were exported to an Excel workbook and a descriptive analysis was performed using STATA.

Results

A total of 4,545 samples were received during this period. Of these, 288 (6.3%) were not processed. From the remaining 4,257 samples, 705 (16.5%) were negative, 2,783 (65.3%) were positive for M. tuberculosis, and 769 (18%) were confirmed NTM. NTM species identification was achieved in 715 (93%) using PCR. Median age was 55 years (0 – 92); 49.4% were male. The most frequent NTM isolate was M. avium complex in 172 (22.3%) samples, followed by M. fortuitum in 131 (17%). M. chelonae was isolated in 98 (12.7%) samples, M. gordonae in 50 (6.5%), M. scrofulaceum in 20 (2.6%), and M. triviale in 16 (2.0%). NTM isolation steadily rose over the study period with 490 (63.7%) of the samples being from 2015 and 465 (94.5%) of these typified by PCR. Specimens mainly originated from the Panama metropolitan area (88.2%) and were mostly sputum samples (70.8%).

Conclusion

Nontuberculous mycobacteria represented an important proportion of isolates among TB suspects in Panama. The implementation of more sensitive diagnostic techniques is increasing the recovery of NTM. Further evaluation of the clinical significance of these finding is required for appropriate guideline implementation.

Disclosures

G. Henostroza, Aeras: Investigator, Grant recipient.
791. Hyponatremia Incidence and Its Association With Mortality in Patients With Tuberculosis
Authors: Llamas-Lopez Andrea , Vargas Tania , Morales-Garza Luis , Maya Rogelio
Published: November 2018

Background

In 2014, 26,000 new cases of tuberculosis were reported in Mexico. TB infection can cause hyponatremia which has a strong association with mortality. The objective of this study was to determine the association of mortality with hyponatremia in patients with tuberculosis infection.

Methods

Patients were collected from a 2-year period in the Hospital Dr. Bernardo Sepœlveda in Nuevo Leon, Mexico. Inclusion criteria were patients >18 years of age, with positive tuberculosis tests, and sodium and serum glucose values upon admission.

Clinical data from the electronic file were collected and analyzed by descriptive statistics; Student’s t-test and chi-square test were used to compare categorical variables, and Kaplan–Meier to estimate survival curves.

Results

There were 314 patients with suspected TB, 77 patients were included (Table 1).

Mean follow-up was 6.5 ± 7.1 months. Overall mortality rate was 36.3%. Analysis of mortality is presented in Fig 2, and in severe hyponatremia in Figure 3.

Conclusion

Overall mortality was higher than previously reported, but there was no statistical association between hyponatremia and mortality compared with patients with normal sodium, or by severity. Within the limitations of this study, we must consider that 92% of patients were hospitalized patients at the time of diagnosis, implying that they were patients with complications and may be the reason why both mortality and the incidence of hyponatremia were higher.

Disclosures

All authors: No reported disclosures.
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

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 < 0.001). The duration of treatment was significantly higher in patients who received DF (9 months vs. 8 months; P < 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

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

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

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.