Use of US Public Health Travel Restrictions during COVID-19 Outbreak on Diamond Princess Ship, Japan, February-April 2020.

Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.

Factoring Prior Treatment into Tuberculosis Infection Prevalence Estimates, United States, 2011-2012.

To refine estimates of how many persons in the United States are candidates for treatment of latent tuberculosis, we removed from analysis persons who self-reported prior treatment on the National Health and Nutrition Examination Survey 2011-2012. We estimate that 12.6 million persons could benefit from treatment to prevent active tuberculosis.

US Federal Travel Restrictions for Persons with Higher-Risk Exposures to Communicable Diseases of Public Health Concern.

Published guidance recommends controlled movement for persons with higher-risk exposures (HREs) to communicable diseases of public health concern; US federal public health travel restrictions (PHTRs) might be implemented to enforce these measures. We describe persons eligible for and placed on PHTRs because of HREs during 2014-2016. There were 160 persons placed on PHTRs: 142 (89%) involved exposure to Ebola virus, 16 (10%) to Lassa fever virus, and 2 (1%) to Middle East respiratory syndrome coronavirus. Most (90%) HREs were related to an epidemic. No persons attempted to travel; all persons had PHTRs lifted after completion of a maximum disease-specific incubation period or a revised exposure risk classification. PHTR enforced controlled movement and removed risk for disease transmission among travelers who had contacts who refused to comply with public health recommendations. PHTRs are mechanisms to mitigate spread of communicable diseases and might be critical in enhancing health security during epidemics.

Tuberculosis Disease Among Nonimmigrant Visa Holders Reported to US Quarantine Stations, January 2011-June 2016.

US-bound immigrants and refugees undergo a mandatory overseas medical examination that includes tuberculosis screening; this exam is not routinely required for temporary visitors applying for non-immigrant visas (NIV) to visit, work, or study in the United States. US health departments and foreign ministries of health report tuberculosis cases in travelers to Centers for Disease Control and Prevention Quarantine Stations. We reviewed cases reported to this passive surveillance system from January 2011 to June 2016. Of 1252 cases of tuberculosis in travelers reported to CDC, 114 occurred in travelers with a long-term NIV. Of these, 83 (73%) were infectious; 18 (16%) with multidrug-resistant tuberculosis (MDR TB) and one with extensively drug-resistant tuberculosis (XDR TB). We found evidence that NIV holders are diagnosed with tuberculosis disease in the United States. Given that long-term NIV holders were over-represented in this data set, despite the small proportion (4%) of overall non-immigrant admissions they represent, expanding the US overseas migration health screening program to this population might be an efficient intervention to further reduce tuberculosis in the United States.

Using Electronic Health Record Data to Measure the Latent Tuberculosis Infection Care Cascade in Safety-Net Primary Care Clinics.

Introduction: Prevention of tuberculosis disease through diagnosis and treatment of latent tuberculosis infection is critical for achieving tuberculosis elimination in the U.S. Diagnosis and treatment of latent tuberculosis infection in safety-net primary care settings that serve patients at risk for tuberculosis may increase uptake of this prevention effort and accelerate progress toward elimination. Optimizing tuberculosis prevention in these settings requires measuring the latent tuberculosis infection care cascade (testing, diagnosis, and treatment) and identifying gaps to develop solutions to overcome barriers. We used electronic health record data to describe the latent tuberculosis infection care cascade and identify gaps among a network of safety-net primary care clinics. Methods: Electronic health record data for patients seen in the OCHIN Clinical Network, the largest network of safety-net clinics in the U.S., between 2012 and 2019 were extracted. electronic health record data were used to measure the latent tuberculosis infection care cascade: patients who met tuberculosis screening criteria on the basis of current recommendations were tested for tuberculosis infection, diagnosed with latent tuberculosis infection, and prescribed treatment for latent tuberculosis infection. Outcomes were stratified by diagnostic test and treatment regimen. Results: Among 1.9 million patients in the analytic cohort, 43.5% met tuberculosis screening criteria, but only 21.4% were tested for latent tuberculosis infection; less than half (40.4%) were tested using an interferon-gamma release assay. Among those with a valid result, 10.5% were diagnosed with latent tuberculosis infection, 29.1% of those were prescribed latent tuberculosis infection treatment, and only 33.6% were prescribed a recommended rifamycin-based regimen. Conclusions: Electronic health record data can be used to measure the latent tuberculosis infection care cascade. A large proportion of patients in this safety-net clinical network are at high risk for tuberculosis infection. Addressing identified gaps in latent tuberculosis infection testing and treatment may have a direct impact on improving tuberculosis prevention in primary care clinics and accelerate progress toward elimination.

Impact of Targeted Local Interventions on Tuberculosis Awareness and Screening Among Persons Experiencing Homelessness During a Large Tuberculosis Outbreak in Atlanta, Georgia, 2015-2016.

OBJECTIVES: Tuberculosis (TB) outbreaks disproportionately affect persons experiencing homelessness (PEH) in the United States. During 2014-2016, a resurgent TB outbreak occurred among PEH in Atlanta, Georgia. To control the outbreak, citywide policies and educational interventions were implemented in January 2015. Policy changes standardized and enforced TB screening requirements for PEH in homeless shelters. Educational campaigns informed PEH of the outbreak and encouraged TB screening. We evaluated factors associated with, and the effect policy changes and educational interventions had on, TB screening and awareness among PEH in Atlanta. METHODS: Questions related to TB screening and awareness of the outbreak were added to an annual US Department of Housing and Urban Development survey of PEH in Atlanta in 2015 (n = 296 respondents) and 2016 (n = 1325 respondents). We analyzed the 2016 survey data to determine characteristics associated with outcomes. RESULTS: From 2015 to 2016, reported TB screening increased from 81% to 86%, and awareness of the TB outbreak increased from 68% to 75%. In 2016, sheltered PEH were significantly more likely than unsheltered PEH to report being evaluated for TB in the previous 6 months (prevalence odds ratio [pOR] = 3.18; 95% confidence interval [CI], 2.28-4.47) and to report being aware of the TB outbreak (pOR = 4.00; 95% CI, 2.89-5.55). CONCLUSIONS: Implementation of required TB screening and educational interventions may reduce the incidence and severity of TB outbreaks among PEH in other communities. Furthermore, the annual survey of PEH offers an opportunity to collect data to better inform practices and policies.

Inhibition of geranylgeranyl diphosphate synthase induces apoptosis through multiple mechanisms and displays synergy with inhibition of other isoprenoid biosynthetic enzymes.

Inhibitors of isoprenoid synthesis are widely used for treatment of human diseases, including hypercholesterolemia and osteoporosis, and they have the potential to be useful for treatment of cancer. Statin drugs inhibit the enzyme HMG-CoA reductase, whereas nitrogenous bisphosphonates have more recently been shown to inhibit farnesyl disphosphate synthase. In addition, our laboratory has recently developed several potent and specific bisphosphonate inhibitors of geranylgeranyl diphosphate synthase, including digeranyl bisphosphonate. Because all three enzymes fall in the same biosynthetic pathway and many of the biological effects are due to depletion of downstream products, we hypothesized that simultaneous inhibition of these enzymes would result in synergistic growth inhibition. In this study, we show that inhibition of geranylgeranyl diphosphate synthase induces apoptosis in K562 leukemia cells. This induction of apoptosis is in part dependent upon both geranylgeranyl diphosphate depletion and accumulation of farnesyl diphosphate. Combinations of either lovastatin or zoledronate with digeranyl bisphosphonate synergistically inhibited growth and induced apoptosis. These combinations also potently inhibited cellular geranylgeranylation. These results support the potential for combinations of multiple inhibitors of isoprene biosynthesis to inhibit cancer cell growth or metastasis at clinically achievable concentrations.

Federal travel restrictions to prevent disease transmission in the United States: An analysis of requested travel restrictions.

BACKGROUND: Individuals with certain communicable diseases may pose risks to the health of the traveling public; there has been documented transmission on commercial aircraft of tuberculosis (TB), measles, and severe acute respiratory syndrome (SARS). Federal public health travel restrictions (PHTR) prevent commercial air or international travel of persons with communicable diseases that pose a public health threat. METHODS: We described demographics and clinical characteristics of all cases considered for PHTR because of suspected or confirmed communicable disease from May 22, 2007, to December 31, 2015. RESULTS: We reviewed 682 requests for PHTR; 414 (61%) actions were completed to place 396 individuals on PHTR. The majority (>99%) had suspected (n = 27) or confirmed (n = 367) infectious pulmonary TB; 58 (16%) had multidrug-resistant-TB. There were 128 (85%) interceptions that prevented the initiation or continuation of travel. PHTR were removed for 310 (78%) individuals after attaining noninfectious status and 86 (22%) remained on PHTR at the end of the analysis period. CONCLUSIONS: PHTR effectively prevent exposure during commercial air travel to persons with potentially infectious diseases. In addition, they are effective tools available to public health agencies to prevent commercial travel of individuals with certain communicable diseases and possibly reconnect them with public health authorities.

Factors Associated with Symptoms of Depression Among Bhutanese Refugees in the United States.

Refugees are at risk for psychiatric morbidity, yet little is known about their mental health conditions. We identified factors associated with depression symptoms among Bhutanese refugees in the US. We randomly selected adult Bhutanese refugees (N = 386) to complete a cross-sectional survey concerning demographics, mental health symptoms, and associated risk factors. The case definition for depression symptoms was ≥1.75 mean depression score on the Hopkins Symptom Checklist-25. More women (26%) than men (16%) reported depression symptoms (p = 0.0097). Higher odds of depression symptoms were associated with being a family provider, self-reported poor health, and inability to read and write Nepali (OR 4.6, 39.7 and 4.3, respectively) among men; and self-reported poor health and inability to read and write Nepali (OR 7.6, and 2.6 respectively) among women. US-settled Bhutanese refugees are at risk for depression. Providers should be aware of these concerns. Culturally appropriate mental health services should be made more accessible at a local level.