Outbreak of Mycobacterium orygis in a Shipment of Cynomolgus Macaques Imported from Southeast Asia - United States, February-May 2023.

Nonhuman primates (NHP) can become infected with the same species of Mycobacteria that cause human tuberculosis. All NHP imported into the United States are quarantined and screened for tuberculosis; no confirmed cases of tuberculosis were diagnosed among NHP during CDC-mandated quarantine during 2013-2020. In February 2023, an outbreak of tuberculosis caused by Mycobacterium orygis was detected in a group of 540 cynomolgus macaques (Macaca fascicularis) imported to the United States from Southeast Asia for research purposes. Although the initial exposure to M. orygis is believed to have occurred before the macaques arrived in the United States, infected macaques were first detected during CDC-mandated quarantine. CDC collaborated with the importer and U.S. Department of Agriculture's National Veterinary Services Laboratories in the investigation and public health response. A total of 26 macaques received positive test results for M. orygis by culture, but rigorous occupational safety protocols implemented during transport and at the quarantine facility prevented cases among caretakers in the United States. Although the zoonotic disease risk to the general population remains low, this outbreak underscores the importance of CDC's regulatory oversight of NHP importation and adherence to established biosafety protocols to protect the health of the United States research animal population and the persons who interact with them.

Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells - United States, 2023.

During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed.

Decrease in Tuberculosis Cases during COVID-19 Pandemic as Reflected by Outpatient Pharmacy Data, United States, 2020.

We analyzed a pharmacy dataset to assess the 20% decline in tuberculosis (TB) cases reported to the US National Tuberculosis Surveillance System (NTSS) during the coronavirus disease pandemic in 2020 compared with the 2016-2019 average. We examined the correlation between TB medication dispensing data to TB case counts in NTSS and used a seasonal autoregressive integrated moving average model to predict expected 2020 counts. Trends in the TB medication data were correlated with trends in NTSS data during 2006-2019. There were fewer prescriptions and cases in 2020 than would be expected on the basis of previous trends. This decrease was particularly large during April-May 2020. These data are consistent with NTSS data, suggesting that underreporting is not occurring but not ruling out underdiagnosis or actual decline. Understanding the mechanisms behind the 2020 decline in reported TB cases will help TB programs better prepare for postpandemic cases.

Association between Birth Region and Time to Tuberculosis Diagnosis among Non-US-Born Persons in the United States.

Approximately 90% of tuberculosis (TB) cases among non-US-born persons in the United States are attributable to progression of latent TB infection to TB disease. Using survival analysis, we investigated whether birthplace is associated with time to disease progression among non-US-born persons in whom TB disease developed. We derived a Cox regression model comparing differences in time to TB diagnosis after US entry among 19 birth regions, adjusting for sex, birth year, and age at entry. After adjusting for age at entry and birth year, the median time to TB diagnosis was lowest among persons from Middle Africa, 128 months (95% CI 116-146 months) for male persons and 121 months (95% CI 108-136 months) for female persons. We found time to TB diagnosis among non-US-born persons varied by birth region, which represents a prognostic indicator for progression of latent TB infection to TB disease.

Factors Associated With Latent Tuberculosis Infection Treatment Failure Among Patients With Commercial Health Insurance-United States, 2005-2016.

CONTEXT: Approximately 80% of US tuberculosis (TB) cases verified during 2015-2016 were attributed to untreated latent TB infection (LTBI). Identifying factors associated with LTBI treatment failure might improve treatment effectiveness. OBJECTIVE: To identify patients with indicators of isoniazid (INH) LTBI treatment initiation, completion, and failure. METHODS: We searched inpatient and outpatient claims for International Classification of Diseases (Ninth and Tenth Revisions), National Drug, and Current Procedural Terminology codes. We defined treatment completion as 180 days or more of INH therapy during a 9-month period. We defined LTBI treatment failure as an active TB disease diagnosis more than 1 year after starting LTBI treatment among completers and used exact logistic regression to model possible differences between groups. Among treatment completers, we matched 1 patient who failed treatment with 2 control subjects and fit regression models with covariates documented on medical claims paid 6 months or less before INH treatment initiation. PARTICIPANTS: Commercially insured US patients in a large commercial database with insurance claims paid during 2005-2016. MAIN OUTCOME MEASURES: (1) Trends in treatment completion; (2) odds ratios (ORs) for factors associated with treatment completion and treatment failure. RESULTS: Of 21 510 persons who began LTBI therapy during 2005-2016, 10 725 (49.9%) completed therapy. Treatment noncompletion is associated with those younger than 45 years, living in the Northeast or South Census regions, and women. Among persons who completed treatment, 30 (0.3%) progressed to TB disease. Diagnoses of rheumatoid arthritis during the 6 months before treatment initiation and being aged 65 years or older (reference: ages 0-24 years) were significantly associated with INH LTBI treatment failure (adjusted exact OR = 5.1; 95% CI, 1.2-28.2; and adjusted exact OR = 5.1; 95% CI, 1.2-25.3, respectively). CONCLUSION: Approximately 50% of persons completed INH LTBI therapy, and of those, treatment failure was associated with rheumatoid arthritis and persons 65 years or older among a cohort of US LTBI patients with commercial health insurance.

US Tuberculosis Rates among Persons Born Outside the United States Compared with Rates in Their Countries of Birth, 2012-20161.

The US Centers for Disease Control and Prevention recommends screening populations at increased risk for tuberculosis (TB), including persons born in countries with high TB rates. This approach assumes that TB risk for expatriates living in the United States is representative of TB risk in their countries of birth. We compared US TB rates by country of birth with corresponding country rates by calculating incidence rate ratios (IRRs) (World Health Organization rate/US rate). The median IRR was 5.4. The median IRR was 0.5 for persons who received a TB diagnosis <1 year after US entry, 4.9 at 1 to <10 years, and 10.0 at >10 years. Our analysis suggests that World Health Organization TB rates are not representative of TB risk among expatriates in the United States and that TB testing prioritization in the United States might better be based on US rates by country of birth and years in the United States.

Tuberculosis - United States, 2019.

Since 1989, the United States has pursued a goal of eliminating tuberculosis (TB) through a strategy of rapidly identifying and treating cases and evaluating exposed contacts to limit secondary cases resulting from recent TB transmission (1). This strategy has been highly effective in reducing U.S. TB incidence (2), but the pace of decline has significantly slowed in recent years (2.2% average annual decline during 2012-2017 compared with 6.7% during 2007-2012) (3). For this report, provisional 2019 data reported to CDC's National Tuberculosis Surveillance System were analyzed to determine TB incidence overall and for selected subpopulations and these results were compared with those from previous years. During 2019, a total of 8,920 new cases were provisionally reported in the United States, representing a 1.1% decrease from 2018.* TB incidence decreased to 2.7 cases per 100,000 persons, a 1.6% decrease from 2018. Non-U.S.-born persons had a TB rate 15.5 times greater than the rate among U.S.-born persons. The U.S. TB case count and rate are the lowest ever reported, but the pace of decline remains slow. In recent years, approximately 80% of U.S. TB cases have been attributed to reactivation of latent TB infection (LTBI) acquired years in the past, often outside the United States (2). An expanded TB elimination strategy for this new decade should leverage existing health care resources, including primary care providers, to identify and treat persons with LTBI, without diverting public health resources from the continued need to limit TB transmission within the United States. Partnerships with health care providers, including private providers, are essential for this strategy's success.

Bacillus Calmette-Guérin Cases Reported to the National Tuberculosis Surveillance System, United States, 2004-2015.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is used as a vaccine to protect against disseminated tuberculosis (TB) and as a treatment for bladder cancer. We describe characteristics of US TB patients reported to the National Tuberculosis Surveillance System (NTSS) whose disease was attributed to BCG. We identified 118 BCG cases and 91,065 TB cases reported to NTSS during 2004-2015. Most patients with BCG were US-born (86%), older (median age 75 years), and non-Hispanic white (81%). Only 17% of BCG cases had pulmonary involvement, in contrast with 84% of TB cases. Epidemiologic features of BCG cases differed from TB cases. Clinicians can use clinical history to discern probable BCG cases from TB cases, enabling optimal clinical management. Public health agencies can use this information to quickly identify probable BCG cases to avoid inappropriately reporting BCG cases to NTSS or expending resources on unnecessary public health interventions.

Effect of an Electronic Health Record Decision Support Alert to Decrease Excess Cervical Cancer Screening.

OBJECTIVE: Cervical cancer screening is often conducted in excess of current screening guidelines. The objective of this study was to evaluate the effect of an electronic health record (EHR) clinical decision support alert to decrease guideline-nonadherent cervical cancer screening beyond the age limits of screening or posthysterectomy. MATERIALS AND METHODS: The proportion of guideline-nonadherent Pap tests in women younger than 21 years or older than 65 years or posthysterectomy were compared 4 months before and 3 months after implementation of an EHR clinical decision support alert warning providers that a Pap test is not indicated. Providers could cancel the Pap test or override the alert and place the order. Provider characteristics and Pap test indications were summarized by preintervention/postintervention period using descriptive statistics. The proportions of nonindicated Pap tests were compared by intervention period and provider characteristics using generalized estimating equation models. RESULTS: In women beyond the screening age limits or posthysterectomy, a total of 388 Pap tests were ordered before intervention, and 313 tests were ordered after intervention. Proportion of guideline-nonadherent tests was similar before (62%) and after intervention (63%); thus, implementation of the clinical decision support alert did not change the proportion of guideline-nonadherent Pap tests ordered (OR = 1.08, 95% CI = 0.77-1.52). It is notable that 52% of guideline-nonadherent tests were ordered by 11 providers. Even when controlling for providers who ordered more than 1 test during the study period, multivariate analysis showed that male providers were more likely to order guideline-nonadherent Pap tests (OR = 2.30, 95% CI = 1.36-3.89); no other differences by provider characteristics were observed. CONCLUSIONS: An EHR clinical decision support alert does not decrease guideline-nonadherent cervical cancer screening. These data suggest efforts to optimize clinical decision support should be focused on other aspects of cervical cancer prevention.

Tuberculosis - United States, 2017.

In 2017, a total of 9,093 new cases of tuberculosis (TB) were provisionally* reported in the United States, representing an incidence rate of 2.8 cases per 100,000 population. The case count decreased by 1.8% from 2016 to 2017, and the rate declined by 2.5% over the same period. These decreases are consistent with the slight decline in TB seen over the past several years (1). This report summarizes provisional TB surveillance data reported to CDC's National Tuberculosis Surveillance System for 2017 and in the last decade. The rate of TB among non-U.S.-born persons in 2017 was 15 times the rate among U.S.-born persons. Among non-U.S.-born persons, the highest TB rate among all racial/ethnic groups was among Asians (27.0 per 100,000 persons), followed by non-Hispanic blacks (blacks; 22.0). Among U.S.-born persons, most TB cases were reported among blacks (37.1%), followed by non-Hispanic whites (whites; 29.5%). Previous studies have shown that the majority of TB cases in the United States are attributed to reactivation of latent TB infection (LTBI) (2). Ongoing efforts to prevent TB transmission and disease in the United States remain important to continued progress toward TB elimination. Testing and treatment of populations most at risk for TB disease and LTBI, including persons born in countries with high TB prevalence and persons in high-risk congregate settings (3), are major components of this effort.

Tuberculosis - United States, 2016.

In 2016, a total of 9,287 new tuberculosis (TB) cases were reported in the United States; this provisional* count represents the lowest number of U.S. TB cases on record and a 2.7% decrease from 2015 (1). The 2016 TB incidence of 2.9 cases per 100,000 persons represents a slight decrease compared with 2015 (-3.4%) (Figure). However, epidemiologic modeling demonstrates that if similar slow rates of decline continue, the goal of U.S. TB elimination will not be reached during this century (2). Although current programs to identify and treat active TB disease must be maintained and strengthened, increased measures to identify and treat latent TB infection (LTBI) among populations at high risk are also needed to accelerate progress toward TB elimination.

Tuberculosis Among Foreign-Born Persons Diagnosed ≥10 Years After Arrival in the United States, 2010-2015.

The majority of tuberculosis (TB) cases in the United States are attributable to reactivation of latent TB infection (LTBI) (1). LTBI refers to the condition when a person is infected with Mycobacterium tuberculosis without signs and symptoms, or radiographic or bacteriologic evidence of TB disease. CDC and the U.S. Preventive Services Task Force (USPSTF) recommend screening populations at increased risk for LTBI, including persons who have lived in congregate settings at high risk and persons who were born in, or are former residents of countries with TB incidence ≥20 cases per 100,000 population (2-4). In 2015, foreign-born persons constituted 66.2% of U.S. TB cases (5). During the past 30 years, screening of persons from countries with high TB rates has focused on overseas screening for immigrants and refugees, and domestic screening for persons who have newly arrived in the United States (6,7). However, since 2007, an increasing number and proportion of foreign-born patients receiving a diagnosis of TB first arrived in the United States ≥10 years before the development and diagnosis of TB disease. To better understand how this group of patients differs from persons who developed TB disease and received a diagnosis <10 years after U.S. arrival, CDC analyzed data for all reported TB cases in the United States since 1993 in the National TB Surveillance System (NTSS). After adjusting for age and other characteristics, foreign-born persons who arrived in the United States ≥10 years before diagnosis were more likely to be residents of a long-term care facility or to have immunocompromising conditions other than human immunodeficiency virus (HIV) infection. These findings support using the existing CDC and USPSTF recommendations for TB screening of persons born in countries with high TB rates regardless of time since arrival in the United States (2,3).

Leveling of Tuberculosis Incidence - United States, 2013-2015.

After 2 decades of progress toward tuberculosis (TB) elimination with annual decreases of ≥0.2 cases per 100,000 persons (1), TB incidence in the United States remained approximately 3.0 cases per 100,000 persons during 2013-2015. Preliminary data reported to the National Tuberculosis Surveillance System indicate that TB incidence among foreign-born persons in the United States (15.1 cases per 100,000) has remained approximately 13 times the incidence among U.S.-born persons (1.2 cases per 100,000). Resuming progress toward TB elimination in the United States will require intensification of efforts both in the United States and globally, including increasing U.S. efforts to detect and treat latent TB infection, strengthening systems to interrupt TB transmission in the United States and globally, accelerating reductions in TB globally, particularly in the countries of origin for most U.S.

Rabies in a Dog Imported from Egypt with a Falsified Rabies Vaccination Certificate--Virginia, 2015.

Canine rabies virus variant has been eliminated in the United States and multiple other countries. Globally, however, dogs remain the principal source for human rabies infections. The World Health Organization recommends that when dogs cross international borders, national importing authorities should require an international veterinary certificate attesting that the animal did not show signs of rabies at the time of shipment, was permanently identified, vaccinated, or revaccinated, and had been subjected to a serologic test for rabies before shipment. On June 8, 2015, an adult female dog that had recently been picked up from the streets of Cairo, Egypt, and shipped by a U.S. animal rescue organization to the United States was confirmed to have rabies by the Virginia Department of General Services Division of Consolidated Laboratory Services (DCLS). This dog was part of a large shipment of dogs and cats from Egypt that rescue organizations had distributed to multiple states for adoption. During the investigation, public health officials learned that the rabies vaccination certificate used for entry of the rabid dog into the United States had intentionally been falsified to avoid exclusion of the dog from entry under CDC's current dog importation regulations. This report underscores the ongoing risk posed by U.S. importation of domestic animals that have not been adequately vaccinated against rabies.

Salmonella typhimurium infections associated with peanut products.

BACKGROUND: Contaminated food ingredients can affect multiple products, each distributed through various channels and consumed in multiple settings. Beginning in November 2008, we investigated a nationwide outbreak of salmonella infections. METHODS: A case was defined as laboratory-confirmed infection with the outbreak strain of Salmonella Typhimurium occurring between September 1, 2008, and April 20, 2009. We conducted two case-control studies, product "trace-back," and environmental investigations. RESULTS: Among 714 case patients identified in 46 states, 166 (23%) were hospitalized and 9 (1%) died. In study 1, illness was associated with eating any peanut butter (matched odds ratio, 2.5; 95% confidence interval [CI], 1.3 to 5.3), peanut butter-containing products (matched odds ratio, 2.2; 95% CI, 1.1 to 4.7), and frozen chicken products (matched odds ratio, 4.6; 95% CI, 1.7 to 14.7). Investigations of focal clusters and single cases associated with nine institutions identified a single institutional brand of peanut butter (here called brand X) distributed to all facilities. In study 2, illness was associated with eating peanut butter outside the home (matched odds ratio, 3.9; 95% CI, 1.6 to 10.0) and two brands of peanut butter crackers (brand A: matched odds ratio, 17.2; 95% CI, 6.9 to 51.5; brand B: matched odds ratio, 3.6; 95% CI, 1.3 to 9.8). Both cracker brands were made from brand X peanut paste. The outbreak strain was isolated from brand X peanut butter, brand A crackers, and 15 other products. A total of 3918 peanut butter-containing products were recalled between January 10 and April 29, 2009. CONCLUSIONS: Contaminated peanut butter and peanut products caused a nationwide salmonellosis outbreak. Ingredient-driven outbreaks are challenging to detect and may lead to widespread contamination of numerous food products.

Vaginal Calculus Formation on Exposed Midurethral Sling Mesh.

The presence of a vaginal calculus is a rare clinical entity which may develop in the setting of vaginal urinary stagnation. Numerous factors contribute to stone formation, and management can be complicated by variations in size, location of the stone, and location of adjacent structures. Generally, once diagnosed, vaginal calculi should be removed and surrounding anatomy should be evaluated thoroughly for secondary fistula, erosion, or presence of an instituting foreign body. This report presents a case of vaginal calculus formation on exposed midurethral sling mesh in an elderly patient with hemorrhagic cystitis. This report emphasizes contributing pathophysiology, diagnostic factors, and treatment.

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.

Tracking COVID-19 in the United States With Surveillance of Aggregate Cases and Deaths.

Early during the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) leveraged an existing surveillance system infrastructure to monitor COVID-19 cases and deaths in the United States. Given the time needed to report individual-level (also called line-level) COVID-19 case and death data containing detailed information from individual case reports, CDC designed and implemented a new aggregate case surveillance system to inform emergency response decisions more efficiently, with timelier indicators of emerging areas of concern. We describe the processes implemented by CDC to operationalize this novel, multifaceted aggregate surveillance system for collecting COVID-19 case and death data to track the spread and impact of the SARS-CoV-2 virus at national, state, and county levels. We also review the processes established to acquire, process, and validate the aggregate number of cases and deaths due to COVID-19 in the United States at the county and jurisdiction levels during the pandemic. These processes include time-saving tools and strategies implemented to collect and validate authoritative COVID-19 case and death data from jurisdictions, such as web scraping to automate data collection and algorithms to identify and correct data anomalies. This topical review highlights the need to prepare for future emergencies, such as novel disease outbreaks, by having an event-agnostic aggregate surveillance system infrastructure in place to supplement line-level case reporting for near-real-time situational awareness and timely data.

Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Nonpasteurized dairy products, disease outbreaks, and state laws-United States, 1993-2006.

Although pasteurization eliminates pathogens and consumption of nonpasteurized dairy products is uncommon, dairy-associated disease outbreaks continue to occur. To determine the association of outbreaks caused by nonpasteurized dairy products with state laws regarding sale of these products, we reviewed dairy-associated outbreaks during 1993-2006. We found 121 outbreaks for which the product's pasteurization status was known; among these, 73 (60%) involved nonpasteurized products and resulted in 1,571 cases, 202 hospitalizations, and 2 deaths. A total of 55 (75%) outbreaks occurred in 21 states that permitted sale of nonpasteurized products; incidence of nonpasteurized product-associated outbreaks was higher in these states. Nonpasteurized products caused a disproportionate number (≈150× greater/unit of product consumed) of outbreaks and outbreak-associated illnesses and also disproportionately affected persons <20 years of age. States that restricted sale of nonpasteurized products had fewer outbreaks and illnesses; stronger restrictions and enforcement should be considered.