Jennifer Adjemian

Murine Typhus in Austin, Texas, USA, 2008

Physicians should be alert for possible cases in this area.

Zoonotic Infections Among Employees from Great Smoky Mountains and Rocky Mountain National Parks, 2008–2009

U.S. National Park Service employees may have prolonged exposure to wildlife and arthropods, placing them at increased risk of infection with endemic zoonoses. To evaluate possible zoonotic risks present at both Great Smoky Mountains (GRSM) and Rocky Mountain (ROMO) National Parks, we assessed park employees for baseline seroprevalence to specific zoonotic pathogens, followed by evaluation of incident infections over a 1-year study period. Park personnel showed evidence of prior infection with a variety of zoonotic agents, including California serogroup bunyaviruses (31.9%), Bartonella henselae (26.7%), spotted fever group rickettsiae (22.2%), Toxoplasma gondii (11.1%), Anaplasma phagocytophilum (8.1%), Brucella spp. (8.9%), flaviviruses (2.2%), and Bacillus anthracis (1.5%). Over a 1-year study period, we detected incident infections with leptospirosis (5.7%), B. henselae (5.7%), spotted fever group rickettsiae (1.5%), T. gondii (1.5%), B. anthracis (1.5%), and La Crosse virus (1.5%) in staff members at GRSM, and with spotted fever group rickettsiae (8.5%) and B. henselae (4.3%) in staff at ROMO. The risk of any incident infection was greater for employees who worked as resource managers (OR 7.4; 95% CI 1.4,37.5; p=0.02), and as law enforcement rangers/rescue crew (OR 6.5; 95% CI 1.1,36.5; p=0.03), relative to those who worked primarily in administration or management. The results of this study increase our understanding of the pathogens circulating within both parks, and can be used to inform the development of effective guidelines and interventions to increase visitor and staff awareness and help prevent exposure to zoonotic agents.

Epidemiologic Investigation of Immune-Mediated Polyradiculoneuropathy among Abattoir Workers Exposed to Porcine Brain

Background In October 2007, a cluster of patients experiencing a novel polyradiculoneuropathy was identified at a pork abattoir (Plant A). Patients worked in the primary carcass processing area (warm room); the majority processed severed heads (head-table). An investigation was initiated to determine risk factors for illness. Methods and Results Symptoms of the reported patients were unlike previously described occupational associated illnesses. A case-control study was conducted at Plant A. A case was defined as evidence of symptoms of peripheral neuropathy and compatible electrodiagnostic testing in a pork abattoir worker. Two control groups were used - randomly selected non-ill warm-room workers (n = 49), and all non-ill head-table workers (n = 56). Consenting cases and controls were interviewed and blood and throat swabs were collected. The 26 largest U.S. pork abattoirs were surveyed to identify additional cases. Fifteen cases were identified at Plant A; illness onsets occurred during May 2004–November 2007. Median age was 32 years (range, 21–55 years). Cases were more likely than warm-room controls to have ever worked at the head-table (adjusted odds ratio [AOR], 6.6; 95% confidence interval [CI], 1.6–26.7), removed brains or removed muscle from the backs of heads (AOR, 10.3; 95% CI, 1.5–68.5), and worked within 0–10 feet of the brain removal operation (AOR, 9.9; 95% CI, 1.2–80.0). Associations remained when comparing head-table cases and head-table controls. Workers removed brains by using compressed air that liquefied brain and generated aerosolized droplets, exposing themselves and nearby workers. Eight additional cases were identified in the only two other abattoirs using this technique. The three abattoirs that used this technique have stopped brain removal, and no new cases have been reported after 24 months of follow up. Cases compared to controls had higher median interferon-gamma (IFNγ) levels (21.7 pg/ml; vs 14.8 pg/ml, P<0.001). Discussion This novel polyradiculoneuropathy was associated with removing porcine brains with compressed air. An autoimmune mechanism is supported by higher levels of IFNγ in cases than in controls consistent with other immune mediated illnesses occurring in association with neural tissue exposure. Abattoirs should not use compressed air to remove brains and should avoid procedures that aerosolize CNS tissue. This outbreak highlights the potential for respiratory or mucosal exposure to cause an immune-mediated illness in an occupational setting.

Epidemiology of Nontuberculous Mycobacterial Lung Disease and Tuberculosis, Hawaii, USA

Previous studies found Hawaiians and Asian-Americans/Pacific Islanders to be independently at increased risk for nontuberculous mycobacterial pulmonary disease (NTMPD) and tuberculosis (TB). To better understand NTM infection and TB risk patterns in Hawaii, USA, we evaluated data on a cohort of patients in Hawaii for 2005–2013. Period prevalence of NTMPD was highest among Japanese, Chinese, and Vietnamese patients (>300/100,000 persons) and lowest among Native Hawaiians and Other Pacific Islanders (50/100,000). Japanese patients were twice as likely as all other racial/ethnic groups to have Mycobacterium abscessus isolated (adjusted odds ratio 2.0, 95% CI 1.2–3.2) but were not at increased risk for infection with other mycobacteria species. In contrast, incidence of TB was stable and was lowest among Japanese patients (no cases) and highest among Filipino, Korean, and Vietnamese patients (>50/100,000). Substantial differences exist in the epidemiology of NTMPD by race/ethnicity, suggesting behavioral and biologic factors that affect disease susceptibility.

A Clustering of Immune-mediated Polyradiculoneuropathy among Swine Abattoir Workers Exposed to Aerosolized Porcine Brains, Indiana, United States

Abstract In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28–52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005–December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.

Serological Survey for Antibodies to Mosquito-Borne Bunyaviruses Among US National Park Service and US Forest Service Employees

Serum samples from 295 employees of Great Smoky Mountains National Park (GRSM), Rocky Mountain National Park (ROMO), and Grand Teton National Park with adjacent Bridger-Teton National Forest (GRTE-BTNF) were subjected to serological analysis for mosquito-borne bunyaviruses. The sera were analyzed for neutralizing antibodies against six orthobunyaviruses: La Crosse virus (LACV), Jamestown Canyon virus (JCV), snowshoe hare virus (SSHV), California encephalitis virus, and Trivittatus virus (TVTV) belonging to the California serogroup and Cache Valley virus (CVV) belonging to the Bunyamwera serogroup. Sera were also tested for immunoglobulin (Ig) G antibodies against LACV and JCV by enzyme-linked immunosorbent assay (ELISA). The proportion of employees with neutralizing antibodies to any California serogroup bunyavirus was similar in all three sites, with the prevalence ranging from 28% to 36%. The study demonstrated a seroprevalence of 3% to CVV across the three parks. However, proportions of persons with antibodies to specific viruses differed between parks. Participants residing in the eastern regions had a higher seroprevalence to LACV, with 24% (18/75) GRSM employees being seropositive. In contrast, SSHV seroprevalence was limited to employees from the western sites, with 1.7% (1/60) ROMO and 3.8% (6/160) GRTE-BTNF employees being positive. Seroprevalence to JCV was noted in employees from all sites at rates of 6.7% in GRSM, 21.7% in ROMO, and 15.6% in GRTE-BTNF. One employee each from ROMO (1.7%) and GRTE-BTNF (1.9%) were positive for TVTV. This study also has illustrated the greater sensitivity and specificity of plaque reduction neutralization test compared to IgG ELISA in conducting serosurveys for LACV and JCV.

Epidemiology of Nontuberculous Mycobacterial Pulmonary Disease (NTM PD) in the USA

Population-based studies of pulmonary nontuberculous mycobacterial disease in the USA indicate increasing prevalence. Prevalence is higher among women, older populations, and persons of Asian ancestry. The most frequent species is Mycobacterium avium complex, although the proportion varies geographically, with high rates of Mycobacterium abscessus in areas including the Southeast. Both host and environmental factors modulate disease risk. Environmental risk factors include high vapor pressure and low soil pH, while host risk factors include structural lung disease, thoracic skeletal abnormalities, and immunomodulatory medications.

Relative risk of all-cause mortality in patients with nontuberculous mycobacterial lung disease in a US managed care population

RATIONALE The risk of all-cause mortality of nontuberculous mycobacterial lung disease (NTMLD) in the United States (US) population is not well established. OBJECTIVES This study aims to assess the public health burden of NTMLD in the US by comparing the relative risk of all-cause mortality in the NTMLD population with an age- and sex-matched cohort from the general population. METHODS Patients with physician claims for NTMLD (ICD-9 0.031; ICD-10 A31.0) were identified between 2007 and 2016 from a large US national managed care insurance plan covering approximately 15-18 million members annually. A control group with no NTMLD ICD-9 or 10 codes was randomly selected from the general population and matched 3:1 to the NTMLD sample according to birth year, gender, and insurance benefit coverage. The date of first NTMLD diagnosis of each patient was assigned to the matched controls as the index date. The Cox proportional hazard method compared survival between cohorts, adjusting for demographic factors and baseline comorbidities. RESULTS A total of 2005 patients with NTMLD and 6014 controls were identified, with a mean follow-up duration of 3.4 years and 3.7 years, respectively. The NTMLD group had substantially higher proportions of patients with asthma (23.3% versus 3.5%), bronchiectasis (36.5% versus 0.1%), COPD (52.0% versus 5.9%), arrhythmia (22.6% versus 6.5%), coronary artery disease (18.5% versus 6.6%), heart failure (11.9% versus 4.1%), and cancer (18.5% versus 5.0%). The unadjusted rate of all-cause mortality from the index date was 20.7 per 1000 person-years in the NTMLD group vs 5.6 per 1000 person-years in the control group (rate ratio = 3.73; 95% CI: 2.93-4.75). Multivariable Cox regression, adjusted for the above variables as well as all other important baseline covariates, showed a doubling risk of all-cause mortality (hazard ratio [HR] = 2.06; CI: 1.52-2.79; P < 0.001) in the NTMLD vs control group. CONCLUSIONS All-cause mortality, adjusted for other factors, more than doubled with NTMLD compared with an age-sex-matched control group in a large US national managed care insurance plan.

Treatment Regimens Prescribed for Mycobacterium avium complex Infections Diagnosed in Hospitalized Patients throughout the United States, 2008-2013

Abstract Background Nontuberculous mycobacteria (NTM) are associated with human lung disease, with 80% of cases caused by Mycobacterium avium complex (MAC). American Thoracic Society (ATS)-led treatment guidelines exist for MAC (macrolide/ethambutol/rifamycin), although studies suggest poor concordance with clinician practice. Using a national database of hospitalized patients with MAC isolated, we sought to characterize US treatment practices and trends. Methods Linked demographic and microbiologic data from PremierTM Healthcare Database were extracted for all inpatient encounters from 2009 to 2013. Patients with ≥1 positive MAC culture were identified as cases; concomitant pathogens were also identified. Antibiotics ordered within 3-months post-positive culture were evaluated. Regression models were used to estimate the relative risk (RR) for factors associated with receiving an ATS regimen or macrolide monotherapy. Results Of 3629 MAC cases, 2285 (63%) received an evaluated antibiotic regimen. Most (59%) were treated with a quinolone-based regimen, and 481 (21%) received an ATS regimen. Concordance with ATS guidelines improved over time from 12% in 2009 to 20% in 2013, peaking in 2012(23%). Concordance was highest at facilities in the South (24%) and lowest in the Midwest (13%). Regimens associated with macrolide resistance were given to 160 (7%) cases, including macrolide monotherapy (4%). Guideline concordance was 60% more likely in the South (RR: 1.6, P < 0.01) and 5-fold greater among those who received initial tuberculosis-specific therapy (isoniazid/pyrazinamide, RR: 4.7, P < 0.01). Cases in the Northeast (RR: 2.3, P = 0.02) and without co-infection (only MAC isolated) (RR: 1.7, P = 0.05) were more likely to receive macrolide monotherapy. Conclusion Prescribing concordance with ATS guidelines increased over time. However, regimens associated with macrolide-resistance are still ordered nationally. Clinicians managing hospitalized patients with suspected MAC infections should avoid use of regimens associated with macrolide resistance, which can result in worse clinical outcomes. This work was supported in part by the Division of Intramural Research, NIAID, NIHFigure 1. Treatment regimens prescribed among a national cohort of inpatients with MAC isolated by co-infection status. Disclosures All authors: No reported disclosures.

Drug Treatment Pathways 2 Years Following Clinical Diagnosis of Nontuberculous Mycobacterial Lung Disease in a Large US Managed Care Population

in a Large US Managed Care Population A.E. O’Donnell,1 K.N. Olivier,2 T.K. Marras,3 J. Adjemian,4 G. Eagle,5 X. Li,6 P. Wang,5 R. Zhang,7 and Q. Zhang5 1Georgetown University Hospital, Washington, DC; 2Cardiovascular and Pulmonary Branch/National Heart, Lung, and Blood Institute, Bethesda, MD; 3Toronto Western Hospital, Toronto, ON, Canada; 4National Institutes of Health, Bethesda, MD; 5Insmed Inc., Bridgewater, NJ; 6KMK Consulting Inc., Morristown, NJ; 7Orbis Data Solutions, Woburn, MA