Mumps vaccine effectiveness of a 3rd dose of measles, mumps, rubella vaccine in school settings during a mumps outbreak -- Arkansas, 2016-2017.

Objectives: The largest mumps outbreak in the United States since 2006 occurred in Arkansas during the 2016-17 school year. An additional dose (third dose) of measles-mumps-rubella vaccine (MMR3) was offered to school children. We evaluated the vaccine effectiveness (VE) of MMR3 compared with two doses of MMR for preventing mumps among school-aged children during the outbreak. Study design: A generalized linear mixed effects model was used to estimate the incremental vaccine effectiveness (VE) of a third dose of MMR compared with two doses of MMR for preventing mumps. Methods: We obtained school enrollment, immunization status and mumps case status from school registries, Arkansas's immunization registry, and Arkansas's mumps surveillance system, respectively. We included students who previously received 2 doses of MMR in schools with ≥1 mumps case after the MMR3 clinic. We used a generalized linear mixed model to estimate VE of MMR3 compared with two doses of MMR. Results: Sixteen schools with 9272 students were included in the analysis. Incremental VE of MMR3 versus a two-dose MMR regimen was 52.7% (95% confidence interval [CI]: -3.6%‒78.4%) overall and in 8 schools with high mumps transmission it was 64.0% (95% CI: 1.2%‒86.9%). MMR3 VE was higher among middle compared with elementary school students (68.5% [95% CI: -30.2%‒92.4%] vs 37.6% [95% CI: -62.5%‒76.1%]); these differences were not statistically significant. Conclusion: Our findings suggest MMR3 provided additional protection from mumps compared with two MMR doses in elementary and middle school settings during a mumps outbreak.

Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis.

It has long been believed that methotrexate in therapeutic doses causes progressive liver injury resulting in advanced fibrosis and cirrhosis. Historically, this was a common indication for serial liver biopsy. However, new evidence suggests that methotrexate may not be a direct cause of liver injury; rather the injury and fibrosis attributed to methotrexate may be mediated by other mechanisms, specifically non-alcoholic fatty liver disease. The recent widespread use of non-invasive assessment of liver fibrosis has provided new evidence supporting this hypothesis. Thus, we conducted a meta-analysis and systematic review to determine whether methotrexate is indeed a direct cause of liver injury. For the meta-analysis portion, a comprehensive literature search was performed to identify manuscripts relevant to the topic. Of the 138 studies examined, 20 met our inclusion criteria. However, only 3 studies had sufficient homogeneity to allow aggregation. Thus, the remainder of the study was dedicated to a critical review of all studies relevant to the topic with particular attention to populations examined, risk factors, and assessment of injury and/or fibrosis. Meta-analysis did not show a statistically significant association between methotrexate dose and liver fibrosis. Individual studies reported fibrosis related to confounding factors such as diabetes, obesity, pre-existing chronic liver disease but not methotrexate exposure. In conclusion, existing evidence demonstrates that advanced liver fibrosis and cirrhosis previously attributed to methotrexate are in fact caused by metabolic liver disease or other chronic liver diseases, but not by methotrexate itself. This observation should direct the care of patients treated with long-term methotrexate.

Potential Association of Legionnaires' Disease with Hot Spring Water, Hot Springs National Park and Hot Springs, Arkansas, USA, 2018-2019.

Legionella pneumophila is the cause of Legionnaires' disease, a life-threatening pneumonia that occurs after inhalation of aerosolized water containing the bacteria. Legionella growth occurs in stagnant, warm-to-hot water (77°F-113°F) that is inadequately disinfected. Piped hot spring water in Hot Springs National Park, Arkansas, USA, has naturally high temperatures (>135°F) that prevent Legionella growth, and Legionnaires' disease has not previously been associated with the park or other hot springs in the United States. During 2018-2019, Legionnaires' disease occurred in 5 persons after they visited the park; 3 of these persons were potentially exposed in spa facilities that used untreated hot spring water. Environmental testing revealed Legionella bacteria in piped spring water, including 134°F stagnant pipe water. These findings underscore the importance of water management programs to reduce Legionella growth in plumbing through control activities such as maintaining hot water temperatures, reducing stored water age, and ensuring adequate water flow.

Repeated introductions and intensive community transmission fueled a mumps virus outbreak in Washington State.

In 2016/2017, Washington State experienced a mumps outbreak despite high childhood vaccination rates, with cases more frequently detected among school-aged children and members of the Marshallese community. We sequenced 166 mumps virus genomes collected in Washington and other US states, and traced mumps introductions and transmission within Washington. We uncover that mumps was introduced into Washington approximately 13 times, primarily from Arkansas, sparking multiple co-circulating transmission chains. Although age and vaccination status may have impacted transmission, our data set could not quantify their precise effects. Instead, the outbreak in Washington was overwhelmingly sustained by transmission within the Marshallese community. Our findings underscore the utility of genomic data to clarify epidemiologic factors driving transmission and pinpoint contact networks as critical for mumps transmission. These results imply that contact structures and historic disparities may leave populations at increased risk for respiratory virus disease even when a vaccine is effective and widely used.

2016-2017 Arkansas mumps outbreak in a close-knit community: Assessment of the economic impact and response strategies.

On August 8, 2016, a confirmed case of mumps was reported to the Arkansas Department of Health (ADH) in an adult resident of Springdale, Arkansas. By July 2017, nearly 3,000 cases of mumps were reported to ADH from 37 of the 75 counties in Arkansas. Over 50% of cases were in the Arkansas Marshallese community, a close-knit community characterized by large, and extended families sharing the same living space and communal activities. In a statewide effort, ADH collaborated with CDC, the Republic of the Marshall Island's (RMI) Ministry of Health, and the Arkansas Department of Education (ADE) to rapidly respond to and contain the outbreak. We assessed the economic burden to ADH of the outbreak response in terms of containment and vaccination costs, as well as response costs incurred by CDC, RMI, and ADE. The 2016-2017 Arkansas mumps outbreak was the second largest US mumps outbreak in over 30 years and was unique in size, spread, and population affected. Total public health response costs as a result of the outbreak were over $2.1 million, approximately $725 per case. The costs incurred to control this outbreak reflect the response strategies tailored to the affected populations, including consideration of social, cultural, and political factors in controlling transmission and requirements of distinctive strategies for public health outreach. Aside from the burden these outbreaks have on the affected population, we demonstrate the potential for high economic burden of these outbreaks to public health.

Bloodstream Infections With a Novel Nontuberculous Mycobacterium Involving 52 Outpatient Oncology Clinic Patients-Arkansas, 2018.

BACKGROUND: In July 2018, the Arkansas Department of Health (ADH) was notified by hospital A of 3 patients with bloodstream infections (BSIs) with a rapidly growing nontuberculous Mycobacterium (NTM) species; on 5 September 2018, 6 additional BSIs were reported. All were among oncology patients at clinic A. We investigated to identify sources and to prevent further infections. METHODS: ADH performed an onsite investigation at clinic A on 7 September 2018 and reviewed patient charts, obtained environmental samples, and cultured isolates. The isolates were sequenced (whole genome, 16S, rpoB) by the Centers for Disease Control and Prevention to determine species identity and relatedness. RESULTS: By 31 December 2018, 52 of 151 (34%) oncology patients with chemotherapy ports accessed at clinic A during 22 March-12 September 2018 had NTM BSIs. Infected patients received significantly more saline flushes than uninfected patients (P < .001) during the risk period. NTM grew from 6 unused saline flushes compounded by clinic A. The identified species was novel and designated Mycobacterium FVL 201832. Isolates from patients and saline flushes were highly related by whole-genome sequencing, indicating a common source. Clinic A changed to prefilled saline flushes on 12 September as recommended. CONCLUSIONS: Mycobacterium FVL 201832 caused BSIs in oncology clinic patients. Laboratory data allowed investigators to rapidly link infections to contaminated saline flushes; cooperation between multiple institutions resulted in timely outbreak resolution. New state policies being considered because of this outbreak include adding extrapulmonary NTM to ADH's reportable disease list and providing more oversight to outpatient oncology clinics.

Genomic characterization of mumps viruses from a large-scale mumps outbreak in Arkansas, 2016.

In 2016, a year-long large-scale mumps outbreak occurred in Arkansas among a highly-vaccinated population. A total of 2954 mumps cases were identified during this outbreak. The majority of cases (1676 (57%)) were school-aged children (5-17 years), 1536 (92%) of these children had completed the mumps vaccination schedule. To weigh the possibility that the mumps virus evaded vaccine-induced immunity in the affected Arkansas population, we established a pipeline for genomic characterization of the outbreak strains. Our pipeline produces whole-genome sequences along with phylogenetic analysis of the outbreak mumps virus strains. We collected buccal swab samples of patients who tested positive for the mumps virus during the 2016 Arkansas outbreak, and used the portable Oxford Nanopore Technology to sequence the extracted strains. Our pipeline identified the genotype of the Arkansas mumps strains as genotype G and presented a genome-based phylogenetic tree with superior resolution to a standard small hydrophobic (SH) gene-based tree. We phylogenetically compared the Arkansas whole-genome sequences to all publicly available mumps strains. While these analyses show that the Arkansas mumps strains are evolutionarily distinct from the vaccine strains, we observed no correlation between vaccination history and phylogenetic grouping. Furthermore, we predicted potential B-cell epitopes encoded by the Arkansas mumps strains using a random forest prediction model trained on antibody-antigen protein structures. Over half of the predicted epitopes of the Jeryl-Lynn vaccine strains in the Hemagglutinin-Neuraminidase (HN) surface glycoprotein (a major target of neutralizing antibodies) region are missing in the Arkansas mumps strains. In-silico analyses of potential epitopes may indicate that the Arkansas mumps strains display antigens with reduced immunogenicity, which may contribute to reduced vaccine effectiveness. However, our in-silico findings should be assessed by robust experiments such as cross neutralization assays. Metadata analysis showed that vaccination history had no effect on the evolution of the Arkansas mumps strains during this outbreak. We conclude that the driving force behind the spread of the mumps virus in the 2016 Arkansas outbreak remains undetermined.

Mumps in a highly vaccinated Marshallese community in Arkansas, USA: an outbreak report.

BACKGROUND: During 2000-15, Arkansas Department of Health, Little Rock, AR, USA, investigated between one and six cases of mumps each year. From Aug 5, 2016, to Aug 5, 2017, the department received notification of more than 4000 suspected mumps cases in the second largest outbreak in the USA in the past 30 years. METHODS: Arkansas Department of Health investigated all reported cases of mumps to ascertain exposure, travel, and vaccination histories and identify close contacts. Cases were classified as confirmed if the patient had laboratory confirmation of mumps virus or probable if they had clinical symptoms and either a positive serological test or a known epidemiological link to a confirmed case. FINDINGS: 2954 cases of mumps related to the outbreak were identified during the outbreak period: 1665 (56%) were laboratory confirmed, 1676 (57%) were in children aged 5-17 years, and 1692 (57%) were in Marshallese people. Among the 1676 school-aged cases, 1536 (92%) had previously received at least two doses of a vaccine containing the mumps virus. Although 19 cases of orchitis were reported, severe complications were not identified. Unusual occurrences, such as recurrent parotitis and prolonged viral shedding, were observed mostly in Marshallese individuals. Viral samples were characterised as genotype G. INTERPRETATION: This large-scale outbreak, primarily affecting a marginalised community with intense household crowding, highlights the need for coordinated, interdisciplinary, and non-traditional outbreak responses. This outbreak raises questions about mumps vaccine effectiveness and potential waning immunity. FUNDING: Council of State and Territorial Epidemiologists and US Centers for Disease Control and Prevention.

Influenza-Related Parotitis during a Large Mumps Outbreak - Arkansas, 2016-2017.

During August 2016-July 2017, Arkansas experienced a large mumps (parotitis) outbreak; however, mumps-negative cases of parotitis were also identified in this period. Nineteen of 215 samples (9%) randomly selected for influenza PCR testing were positive for influenza A virus. Practitioners should consider influenza as a cause of nonmumps parotitis.

Burkholderia thailandensis Isolated from Infected Wound, Arkansas, USA.

The bacterium Burkholderia thailandensis, a member of the Burkholderia pseudomallei complex, is generally considered nonpathogenic; however, on rare occasions, B. thailandensis infections have been reported. We describe a clinical isolate of B. thailandensis, BtAR2017, recovered from a patient with an infected wound in Arkansas, USA, in 2017.

Chagas Disease Surveillance Activities - Seven States, 2017.

Chagas disease, a potentially life-threatening disease caused by the protozoan parasite Trypanosoma cruzi, has become a concern in the United States as a result of human emigration from Latin America where Chagas disease is endemic (1). It is estimated that as many as 8 million people living in Mexico, and Central and South America have Chagas disease.* Most cases of Chagas disease in the United States are chronic infections; however, rare cases of acute congenital infections and autochthonous vectorborne transmission have been reported (2). To understand how data are collected and used, a review of state-level public health surveillance for Chagas disease was conducted through semistructured interviews with health officials in six states (Arizona, Arkansas, Louisiana, Mississippi Tennessee, and Texas) where Chagas disease is reportable and one (Massachusetts) where it was previously reportable. States implemented surveillance in response to blood donor screening for Chagas disease and to identify the route of disease transmission. Many states reported primarily chronic cases and had limited ability to respond to local transmission because acute cases were infrequently reported. Surveillance remains important in states with large populations of immigrants or frequent travelers from countries with endemic disease and for states with a risk for local transmission. Surveillance efforts can also help increase awareness among providers and assist in linking patients with Chagas disease to treatment to help prevent cardiac and gastrointestinal complications.

Multistate Epidemiology of Histoplasmosis, United States, 2011-2014

Histoplasmosis is one of the most common mycoses endemic to the United States, but it was reportable in only 10 states during 2016, when a national case definition was approved. To better characterize the epidemiologic features of histoplasmosis, we analyzed deidentified surveillance data for 2011-2014 from the following 12 states: Alabama, Arkansas, Delaware, Illinois, Indiana, Kentucky, Michigan, Minnesota, Mississippi, Nebraska, Pennsylvania, and Wisconsin. We examined epidemiologic and laboratory features and calculated state-specific annual and county-specific mean annual incidence rates. A total of 3,409 cases were reported. Median patient age was 49 (interquartile range 33-61) years, 2,079 (61%) patients were male, 1,273 (57%) patients were hospitalized, and 76 (7%) patients died. Incidence rates varied markedly between and within states. The high hospitalization rate suggests that histoplasmosis surveillance underestimates the true number of cases. Improved surveillance standardization and surveillance by additional states would provide more comprehensive knowledge of histoplasmosis in the United States.

Variation in Tularemia Clinical Manifestations-Arkansas, 2009-2013.

BACKGROUND: Francisella tularensis, although naturally occurring in Arkansas, is also a Tier 1 select agent and potential bioterrorism threat. As such, tularemia is nationally notifiable and mandatorily reported to the Arkansas Department of Health. We examined demographic and clinical characteristics among reported cases and outcomes to improve understanding of the epidemiology of tularemia in Arkansas. METHODS: Surveillance records on all tularemia cases investigated during 2009-2013 were reviewed. RESULTS: The analytic dataset was assembled from 284 tularemia reports, yielding 138 probable and confirmed tularemia cases during 2009-2013. Arthropod bite was identified in 77% of cases. Of 7 recognized tularemia manifestations, the typhoidal form was reported in 47% of cases, approximately double the proportion of the more classic manifestation, lymphadenopathy. Overall, 41% of patients were hospitalized; 3% died. The typhoidal form appeared to be more severe, accounting for the majority of sepsis and meningitis cases, hospitalizations, and deaths. Among patients with available antibiotic data, 88% received doxycycline and 12% received gentamicin. CONCLUSIONS: Contrary to expectation, lymphadenopathy was not the most common manifestation observed in our registry. Instead, our patients were more likely to report only generalized typhoidal symptoms. Using lymphadenopathy as a primary symptom to initiate tularemia testing may be an insensitive diagnostic strategy and result in unrecognized cases. In endemic areas such as Arkansas, suspicion of tularemia should be high, especially during tick season. Outreach to clinicians describing the full range of presenting symptoms may help address misperceptions about tularemia.

Possible Transfusion-Transmitted Babesia divergens-like/MO-1 Infection in an Arkansas Patient.

A patient with asplenia and multiple red blood cell transfusions acquired babesiosis infection with Babesia divergens-like/MO-1 organisms and not Babesia microti, the common United States species. He had no known tick exposure. This is believed to be the first transfusion-transmitted case and the fifth documented case of B. divergens-like/MO-1 infection.

Notes from the Field: Cluster of Tuberculosis Cases Among Marshallese Persons Residing in Arkansas - 2014-2015.

During early September 2014, the Arkansas Department of Health identified an increased number of tuberculosis (TB) cases among a unique population in a well-circumscribed geographical area in northwest Arkansas. The Compact of Free Association Act of 1985 (Public Law 99-239, amended in 2003 by Public Law 108-188) established the Republic of the Marshall Islands (RMI) as an independent nation, and persons from the RMI can travel freely (with valid RMI passport) to and from the United States as nonimmigrants without visas (1). Marshallese started settling in northwest Arkansas during the early 1990s because of employment and educational opportunities (2). According to the 2010 Census, an estimated 4,300 Marshallese resided in Arkansas (2), mostly within one county which ranked 6th in the United States for counties with the highest percentage of Native Hawaiians and Other Pacific Islanders (3). It is estimated that this number has been growing steadily each year since the 2010 Census; however, obtaining an accurate count is difficult. The RMI is a TB high-incidence country, with a case-rate of 212.7 per 100,000 persons for 2014, whereas the case-rate was 3.1 per 100,000 persons in Arkansas and 2.9 per 100,000 persons in the United States (4,5). Screening for either active TB or latent TB infection (LTBI) is not required for Marshallese entry to the United States (1).

A Clinical Review of Tick-Borne Diseases in Arkansas.

Tick-borne diseases are illnesses transmitted by ticks harboring wide variety of pathogens. Arkansas is reported as one of the states with a high incidence of tick-borne diseases. In Arkansas the four most frequently occurring tick-borne diseases are Rocky Mountain Spotted Fever (RMSF, also known as Spotted Fever Rickettsiosis), Ehrlichiosis, Tularemia and Anaplasmosis. Lyme disease, on the other hand, is not acquired in Arkansas and is only acquired by traveling to states where Lyme disease is endemic. The majority of tick-borne diseases are diagnosed based on a history of tick bite or exposure and the individual's clinical presentation. The recognition of specific symptoms requires prompt treatment to prevent long-term sequelae. Hence, knowledge of tick-borne diseases and preventive measures can help reduce the risks associated with the infection.

Impact of the 2012 extreme drought conditions on private well owners in the United States, a qualitative analysis.

BACKGROUND: Extreme hot and dry weather during summer 2012 resulted in some of the most devastating drought conditions in the last half-century in the United States (U.S.). While public drinking water systems have contingency plans and access to alternative resources to maintain supply for their customers during drought, little is known about the impacts of drought on private well owners, who are responsible for maintaining their own water supply. The purpose of this investigation was to explore the public health impacts of the 2012 drought on private well owners' water quality and quantity, identify their needs for planning and preparing for drought, and to explore their knowledge, attitudes, and well maintenance behaviors during drought. METHODS: In the spring of 2013, we conducted six focus group discussions with private well owners in Arkansas, Indiana, and Oklahoma. RESULTS: There were a total of 41 participants, two-thirds of whom were men aged 55 years or older. While participants agreed that 2012 was the worst drought in memory, few experienced direct impacts on their water quantity or quality. However, all groups had heard of areas or individuals whose wells had run dry. Participants conserved water by reducing their indoor and outdoor consumption, but they had few suggestions on additional ways to conserve, and they raised concerns about limiting water use too much. Participants wanted information on how to test their well and any water quality issues in their area. CONCLUSIONS: This investigation identified information needs regarding drought preparedness and well management for well owners.

Association of School-Based Influenza Vaccination Clinics and School Absenteeism--Arkansas, 2012-2013.

BACKGROUND: Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools and school absenteeism during the 2012-2013 influenza season. METHODS: The relationship between the percent of students vaccinated in Arkansas public schools during ADH-facilitated clinics and the average daily percent of students absent from school during the 2012-2013 influenza season was quantified using linear regression modeling. The effect of increasing vaccination coverage among students on absentee days in the Arkansas public school system was estimated. RESULTS: For every 1% higher vaccination coverage, 0.027% fewer absenteeism days were predicted. Larger school size was associated with higher absenteeism and predicted decreases in absenteeism were larger in magnitude for larger schools compared with smaller schools. Extrapolation of the model showed that a 10% higher vaccination level was associated with a reduction of 16-163 student absentee days per school over a 12-week influenza season. CONCLUSIONS: Influenza vaccination is an effective tool to reduce school absenteeism. School-based clinics are a feasible way to target influenza vaccinations to school-aged children.