Racial and Ethnic Disparities in Tuberculosis Incidence, Arkansas, USA, 2010-2021.

We conducted an epidemiologic assessment of disease distribution by race/ethnicity to identify subpopulation-specific drivers of tuberculosis (TB). We used detailed racial/ethnic categorizations for the 932 TB cases diagnosed in Arkansas, USA, during 2010-2021. After adjusting for age and sex, racial/ethnic disparities persisted; the Native Hawaiian/Pacific Islander (NHPI) group had the highest risk for TB (risk ratio 173.6, 95% CI 140.6-214.2) compared with the non-Hispanic White group, followed by Asian, Hispanic, and non-Hispanic Black. Notable racial/ethnic disparities existed across all age groups; NHPI persons 0-14 years of age were at a particularly increased risk for TB (risk ratio 888, 95% CI 403-1,962). The risks for sputum smear-positive pulmonary TB and extrapulmonary TB were both significantly higher for racial/ethnic minority groups. Our findings suggest that TB control in Arkansas can benefit from a targeted focus on subpopulations at increased risk for TB.

Disease phenotypic and geospatial features vary across genetic lineages for Tuberculosis within Arkansas, 2010-2020.

Tuberculosis (TB) elimination in the United States remains elusive, and community-specific, localized intervention strategies may be necessary to meet elimination goals. A better understanding of the genotypic diversity of Mtb, the population subgroups affected by different TB strains, and differences in disease presentation associated with these strains can aid in identifying risk groups and designing tailored interventions. We analyze TB incidence and genotype data from all Arkansas counties over an 11-year time span from 2010 through 2020. We use statistical methods and geographic information systems (GIS) to identify demographic and disease phenotypic characteristics that are associated with different Mtb genetic lineages in the study area. We found the following variables to be significantly associated with genetic lineage (p<0.05): patient county, patient birth country, patient ethnicity, race, IGRA result, disease site, chest X-ray result, whether or not a case was identified as part of a cluster, patient age, occupation risk, and date arrived in the US. Different Mtb lineages affect different subpopulations in Arkansas. Lineage 4 (EuroAmerican) and Lineage 2 (East Asian) are most prevalent, although the spatial distributions differ substantially, and lineage 2 (East Asian) is more frequently associated with case clusters. The Marshallese remain a particularly high-risk group for TB in Arkansas.

Tuberculosis Outbreak Associated With Delayed Diagnosis and Long Infectious Periods in Rural Arkansas, 2010-2018.

OBJECTIVES: During 2010-2018, the Arkansas Department of Health reported 21 genotype-matched cases of tuberculosis (TB) among residents of a rural county in Arkansas with a low incidence of TB and in nearby counties. The Arkansas Department of Health and the Centers for Disease Control and Prevention investigated to determine the extent of TB transmission and provide recommendations for TB control. METHODS: We reviewed medical and public health records, interviewed patients, and reviewed patients' social media posts to describe patient characteristics, identify epidemiologic links, and establish likely chains of transmission. RESULTS: We identified 21 cases; 11 reported during 2010-2013 and 10 during 2016-2018. All case patients were US-born non-Hispanic Black people. Eighteen case patients had the outbreak genotype, and 3 clinically diagnosed (non-culture-confirmed) case patients had epidemiologic links to patients with the outbreak genotype. Social media reviews revealed epidemiologic links among 10 case patients not previously disclosed during interviews. Eight case patients (38%) had ≥1 health care visit during their infectious period, and 7 patients had estimated infectious periods of >12 months. CONCLUSIONS: Delayed diagnoses and prolonged infectiousness led to TB transmission in this rural community. TB education and awareness is critical to reducing transmission, morbidity, and mortality, especially in areas where health care providers have limited TB experience. Use of social media can help elucidate people at risk, especially when traditional TB investigation techniques are insufficient.

Hansen's Disease and Complications among Marshallese Persons Residing in Northwest Arkansas, 2003-2017.

Persons from the Republic of the Marshall Islands have among the highest rates of Hansen's disease (HD) in the world; the largest Marshallese community in the continental United States is in northwest Arkansas. In 2017, the HD Ambulatory Care Clinic in Springdale, Arkansas, informed the Arkansas Department of Health (ADH) that Marshallese persons with HD had severe disease with frequent complications. To characterize their illness, we reviewed ADH surveillance reports of HD among Marshallese persons in Arkansas treated during 2003-2017 (n = 42). Hansen's Disease prevalence among Marshallese in Arkansas (11.7/10,000) was greater than that in the general U.S. population. Complications included arthritis (38%), erythema nodosum leprosum (21%), and prolonged treatment lasting > 2 years (40%). The majority (82%) of patients treated for > 2 years had documented intermittent therapy. Culturally appropriate support for therapy and adherence is needed in Arkansas.

Hansen Disease (Leprosy) and Armadillo Exposure in Arkansas: A Case Series.

BACKGROUND: Although most cases of Hansen disease (HD) in the United States are imported from endemic areas, a subset of cases are relate to exposure to nine-banded armadillos. Several recent cases of HD in Arkansas occurred in patients who had not traveled to endemic areas and who reported variable degrees of armadillo exposure. OBJECTIVE: The purpose of this study was to report 6 cases of HD diagnosed in Arkansas between 2004 and 2016. The secondary purpose was to explore the correlation between exposure to the nine-banded armadillo as it pertains to transmission of the disease. METHODS: The referring clinician of each patient was contacted to gather information regarding the patient's clinical presentation, armadillo exposure, and travel history. In addition, the Arkansas Department of Health was consulted to review the demographics of individuals diagnosed with HD in the past 15 years and to review the distribution of HD throughout the state of Arkansas. RESULTS: Six domestic cases of HD were associated with both direct and indirect exposure to armadillos. LIMITATIONS: Armadillo exposure may be underreported in patients with HD because of fear of stigmatization and/or lack of access to care. CONCLUSIONS: Direct exposure to armadillos does not appear to be required for transmission of HD making a soil-mediated mechanism of indirect exposure plausible.

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection.

Background: Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

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).

Tuberculosis and leprosy infections in the Marshallese population of Arkansas, USA.

The cross-immunity between tuberculosis and leprosy is unknown. The aim of this pilot study was to evaluate the occurrence of Mycobacterium tuberculosis and M. leprae infection in Marshallese adult volunteers in Springdale, Arkansas, U.S.A., a population that experiences high rates of leprosy and tuberculosis. We used immunodiagnostic testing for tuberculosis and leprosy infection and found significant prevalence of latent tuberculosis infection (19.0%), and asymptomatic Mycobacterium leprae infection (22.2%). We found a negative association between presence of antibodies to Mycobacterium leprae and a positive interferon-γ release assay for Mycobacterium tuberculosis infection, prevalence odds ratio = 0.1 (95% CI = 0.0, 0.9). Although these findings require confirmation on a larger scale, they are supportive of the existence of cross-immunity.

Effectiveness of contact investigations for tuberculosis control in Arkansas.

Comprehensive assessment of the effectiveness of contact investigations for tuberculosis (TB) control is still lacking. In this study, we use a computational model, calibrated against notification data from Arkansas during the period 2001-2011, that reproduces independent data on key features of TB transmission and epidemiology. The model estimates that the Arkansas contact investigations program has avoided 18.6% (12.1-25.9%) of TB cases and 23.7% (16.4-30.6%) of TB deaths that would have occurred during 2001-2014 if passive diagnosis alone were implemented. If contacts of sputum smear-negative cases had not been included in the program, the percentage reduction would have been remarkably lower. In addition, we predict that achieving national targets for performance indicators of contact investigation programs has strong potential to further reduce TB transmission and burden. However, contact investigations are expected to have limited effectiveness on avoiding reactivation cases of latent infections over the next 60 years.

Pulmonary Tuberculosis in a Patient with Cystic Fibrosis.

CONTEXT: Mycobacterium tuberculosis (MTB) infection is rarely seen in cystic fibrosis (CF) patients. CASE REPORT: We report a 24-year-old CF patient with fever, cough, hemoptysis, and weight loss of 1week duration prior to admission. Past sputum cultures grew methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The patient was treated with broad spectrum antibiotics based on previous culture data, but failed to improve. Chest radiograph and computed tomography (CT) chest revealed chronic collapse of the anterior subsegment of right upper lobe and multiple bilateral cavitary lesions which were worse compared to prior films. MTB was suspected and was confirmed by positive acid-fast bacilli (AFB) smears and cultures. After receiving first-line antituberculous drugs, the patient's condition markedly improved. CONCLUSION: MTB is an infrequent finding, but considered a potential pathogen in CF patients, and may lead to serious pulmonary complications if there is a delay in diagnosis and treatment.

Tuberculosis reinfection in a pregnant cystic fibrosis patient.

Cystic Fibrosis (CF) is a multisystem disease predominantly affecting the airways and predisposing patients to recurrent infections with various multidrug resistant organisms. Mycobacterium tuberculosis (MTB) infection is rarely seen, but considered a potential pathogen in CF patients. We report a 26 year old pregnant CF patient on Ivacaftor who was admitted with symptoms suggestive of tuberculosis. Three years prior to the current admission, she had completed four drug anti- MTB therapy for pulmonary tuberculosis and was considered cured as her sputum cultures after six months of treatment were negative. Genotype analysis revealed the current MTB strain to be different from the strain causing the previous infection. After receiving first line anti-tuberculous regimen for nine months, the patient's condition markedly improved culminating in an uneventful pregnancy and delivery. To our knowledge, this is the only reported case of reinfection tuberculosis in a CF patient.

Initial experience with GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.

BACKGROUND: Mycobacterium tuberculosis remains one of the most significant causes of death from an infectious agent. Rapid and accurate diagnosis of pulmonary and extra-pulmonary tuberculosis (TB) is still a great challenge. The GeneXpert MTB/RIF assay is a novel integrated diagnostic system for the diagnosis of tuberculosis and rapid detection of Rifampin (RIF) resistance in clinical specimens. In 2012, the Arkansas Tuberculosis Control Program introduced GeneXpert MTB/RIF assay to replace the labour-intensive Mycobacterium Tuberculosis Direct (MTD) assay. AIMS: To rapidly diagnose TB within two hours and to simultaneously detect RIF resistance. OBJECTIVES: Describe the procedure used to introduce GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.Characterise the current gap in rapid M. tuberculosis diagnosis in Arkansas.Assess factors that predict acid fast bacilli (AFB) smearnegative but culture-positive cases in Arkansas.Illustrate, with two case reports, the role of GeneXpert MTB/RIF assay in reduction of time to confirmation of M. tuberculosis diagnosis in the first year of implementation. METHOD: Between June 2012 and June 2013, all AFB sputum smearpositive cases and any others, on request by the physician, had GeneXpert MTB/RIF assay performed as well as traditional M. tuberculosis culture and susceptibilities using Mycobacteria Growth Indicator Tube (MGIT) 960 and Löwenstein-Jensen (LJ) slants. Surveillance data for January 2009-June 2013 was analysed to characterise sputum smear-negative but culture-positive cases. RESULTS: Seventy-one TB cases were reported from June 2012- June 2013. GeneXpert MTB/RIF assay identified all culture-positive cases as well as three cases that were negative on culture. Also, this rapid assay identified all six smear-negative but M. tuberculosis culture-positive cases; two of these cases are described as case reports. CONCLUSION: GeneXpert MTB/RIF assay has made rapid TB diagnosis possible, with tremendous potential in determining isolation of TB suspects on one hand, and quickly ruling out TB whenever suspected.

The road to tuberculosis (Mycobacterium tuberculosis) elimination in Arkansas; a re-examination of risk groups.

OBJECTIVES: This study was conducted to generate knowledge useful for developing public health interventions for more effective tuberculosis control in Arkansas. METHODS: The study population included 429 culture-confirmed reported cases (January 1, 2004-December 31, 2010). Mycobacterium tuberculosis genotyping data were used to identify cases likely due to recent transmission (clustered) versus reactivation (non-clustered). Poisson regression models estimated average decline rate in incidence over time and assessed the significance of differences between subpopulations. A multinomial logistic model examined differences between clustered and non-clustered incidence. RESULTS: A significant average annual percent decline was found for the overall incidence of culture-confirmed (9%; 95% CI: 5.5%, 16.9%), clustered (6%; 95% CI: 0.5%, 11.6%), and non-clustered tuberculosis cases (12%; 95% CI: 7.6%, 15.9%). However, declines varied among demographic groups. Significant declines in clustered incidence were only observed in males, non-Hispanic blacks, 65 years and older, and the rural population. CONCLUSIONS: These findings suggest that the Arkansas tuberculosis control program must target both traditional and non-traditional risk groups for successful tuberculosis elimination. The present study also demonstrates that a thorough analysis of TB trends in different population subgroups of a given geographic region or state can lead to the identification of non-traditional risk factors for TB transmission. Similar studies in other low incidence populations would provide beneficial data for how to control and eventually eliminate TB in the U.S.

TB or not TB; don't miss the obvious.

Tuberculosis (TB) is one of the leading causes of morbidity and mortality in the world. Its classic forms include cavitary and miliary TB. The non-specific clinical presentation of TB and similarity of its signs and symptoms with other pulmonary diseases makes its diagnosis difficult, especially in low burden settings like Arkansas. We emphasize the importance of early diagnosis and describe two cases where a delay resulted in complications and a prolonged treatment plan for the patients.

Identification of factors for tuberculosis transmission via an integrated multidisciplinary approach.

It was reported previously that the major fraction of the recent decrease of tuberculosis incident cases in Arkansas had been due to a decrease in the reactivated infections. Preventing transmission of Mycobacterium tuberculosis is the key to a continued decline in tuberculosis cases. In this study, we integrated epidemiological data analysis and comparative genomics to identify host and microbial factors important to tuberculosis transmission. A significantly higher proportion of cases in large clusters (containing >10 cases) were non-Hispanic black, homeless, less than 65 years old, male sex, smear-positive sputum, excessive use of alcohol, and HIV sero-positive, compared to cases in small clusters (containing 2-5 cases) diagnosed within one year. However, being non-Hispanic black and homeless within the past year were the only two host characteristics that were identified as independent risk factors for being in large clusters. This finding suggests that social behavioral factors have a more important role in transmission of tuberculosis than does the infectiousness of the source. Comparing the genomic content of one of the large cluster strains to that of a non-clustered strain from the same community identified 25 genes that differed between the two strains, potentially contributing to the observed differences in transmission.

Cross-jurisdictional transmission of Mycobacterium tuberculosis in Maryland and Washington, D C, 1996-2000, linked to the homeless.

From 1996 to 2000, 23 Maryland and Washington, D.C., tuberculosis cases were identified in one six-band DNA cluster. Cases were clustered on the basis of their Mycobacterium tuberculosis isolates. Medical record reviews and interviews were conducted to identify epidemiologic linkages. Eighteen (78%) of the 23 case-patients with identical restriction fragment length polymorphism patterns were linked to another member; half the patients were associated with a Washington, D.C., homeless shelter. Molecular epidemiology defined the extent of this large, cross-jurisdictional outbreak.

Molecular epidemiology of tuberculosis in a low- to moderate-incidence state: are contact investigations enough?

To assess the circumstances of recent transmission of tuberculosis (TB) (progression to active disease <2 years after infection), we obtained DNA fingerprints for 1172 (99%) of 1179 Mycobacterium tuberculosis isolates collected from Maryland TB patients from 1996 to 2000. We also reviewed medical records and interviewed patients with genetically matching M. tuberculosis strains to identify epidemiologic links (cluster investigation). Traditional settings for transmission were defined as households or close relatives and friends; all other settings were considered nontraditional. Of 436 clustered patients, 115 had recently acquired TB. Cluster investigations were significantly more likely than contact investigations to identify patients who recently acquired TB in nontraditional settings (33/42 vs. 23/72, respectively; p<0.001). Transmission from a foreign-born person to a U.S.-born person was rare and occurred mainly in public settings. The time from symptom onset to diagnosis was twice as long for transmitters as for nontransmitters (16.8 vs. 8.5 weeks, respectively; p<0.01). Molecular epidemiologic studies showed that reducing diagnostic delays can prevent TB transmission in nontraditional settings, which elude contact investigations.