Tuberculosis - United States, 2023.

After 27 years of declining U.S. tuberculosis (TB) case counts, the number of TB cases declined considerably in 2020, coinciding with the COVID-19 pandemic. For this analysis, TB case counts were obtained from the National TB Surveillance System. U.S. Census Bureau population estimates were used to calculate rates overall, by jurisdiction, birth origin, race and ethnicity, and age group. Since 2020, TB case counts and rates have increased each year. During 2023, a total of 9,615 TB cases were provisionally reported by the 50 U.S. states and the District of Columbia (DC), representing an increase of 1,295 cases (16%) as compared with 2022. The rate in 2023 (2.9 per 100,000 persons) also increased compared with that in 2022 (2.5). Forty states and DC reported increases in 2023 in both case counts and rates. National case counts increased among all age groups and among both U.S.-born and non-U.S.-born persons. Although TB incidence in the United States is among the lowest in the world and most U.S. residents are at minimal risk, TB continues to cause substantial global morbidity and mortality. This postpandemic increase in U.S. cases highlights the importance of continuing to engage communities with higher TB rates and their medical providers in TB elimination efforts and strengthening the capacity in public health programs to carry out critical disease control and prevention strategies.

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.

Investigation of Heartland Virus Disease Throughout the United States, 2013-2017.

BACKGROUND: Heartland virus (HRTV) was first described as a human pathogen in 2012. From 2013 to 2017, the Centers for Disease Control and Prevention (CDC) implemented a national protocol to evaluate patients for HRTV disease, better define its geographic distribution, epidemiology, and clinical characteristics, and develop diagnostic assays for this novel virus. METHODS: Individuals aged ≥12 years whose clinicians contacted state health departments or the CDC about testing for HRTV infections were screened for recent onset of fever with leukopenia and thrombocytopenia. A questionnaire was administered to collect data on demographics, risk factors, and signs and symptoms; blood samples were tested for the presence of HRTV RNA and neutralizing antibodies. RESULTS: Of 85 individuals enrolled and tested, 16 (19%) had evidence of acute HRTV infection, 1 (1%) had past infection, and 68 (80%) had no infection. Patients with acute HRTV disease were residents of 7 states, 12 (75%) were male, and the median age (range) was 71 (43-80) years. Illness onset occurred from April to September. The majority reported fatigue, anorexia, nausea, headache, confusion, arthralgia, or myalgia. Fourteen (88%) cases were hospitalized; 2 (13%) died. Fourteen (88%) participants reported finding a tick on themselves in the 2 weeks before illness onset. HRTV-infected individuals were significantly older (P < .001) and more likely to report an attached tick (P = .03) than uninfected individuals. CONCLUSIONS: Health care providers should consider HRTV disease testing in patients with an acute febrile illness with either leukopenia or thrombocytopenia not explained by another condition or who were suspected to have a tickborne disease but did not improve following appropriate treatment.

Transmission of Eastern Equine Encephalitis Virus From an Organ Donor to 3 Transplant Recipients.

BACKGROUND: In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. METHODS: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pretransplant organ donor evaluation and local EEEV surveillance. RESULTS: We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the 8 blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor's county of residence. Neuroinvasive EEEV infection directly contributed to the death of 1 organ recipient and likely contributed to death in another. CONCLUSIONS: Our investigation demonstrated EEEV transmission through SOT. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2017.

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC from U.S. states in 2017 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because, in the continental United States, these viruses are acquired primarily through travel. In 2017, 48 states and the District of Columbia (DC) reported 2,291 cases of domestic arboviral disease, including 2,097 (92%) WNV disease cases. Among the WNV disease cases, 1,425 (68%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national rate of 0.44 cases per 100,000 population. More Jamestown Canyon and Powassan virus disease cases were reported in 2017 than in any previous year. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct and promote prevention activities.

Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2012-2016.

BACKGROUND: In March 2009, the U.S. Food and Drug Administration licensed an inactivated Vero cell culture-derived Japanese encephalitis vaccine (JE-VC [IXIARO®]) for use in persons aged ≥17 years. In 2013, licensure was extended to include children aged ≥2 months. A previous analysis reviewed adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from May 2009 through April 2012. METHODS: We reviewed adverse events reported to VAERS following JE-VC administered from May 1, 2012 through April 30, 2016. Adverse event reporting rates were calculated using 802,229 doses distributed. RESULTS: During the 4-year period, 119 adverse event reports were received for a reporting rate of 14.8 per 100,000 doses distributed. Nine (8%) adverse events were classified as serious for a reporting rate of 1.1 per 100,000 distributed. The most commonly reported event was hypersensitivity (n = 24; 20%) for a rate of 3.0 per 100,000 doses distributed; 1 anaphylaxis event was reported. Ten (8%) neurologic events were reported for a rate of 1.2 per 100,000 doses distributed; 2 events were classified as seizures. Sixty-three (53%) adverse events occurred after a first dose of JE-VC. Eighty (67%) adverse events occurred after administration of JE-VC with other vaccines. Eleven (9%) adverse events were reported in children; 1 was considered serious. CONCLUSIONS: These data continue to support the generally favorable safety profile of JE-VC. Reporting rates of adverse events were similar to those of the previous analysis. Although reporting rates of adverse events in children could not be calculated, there were low numbers of reported events in this age group. Post-licensure adverse event surveillance for this relatively new vaccine continues to be important to monitor adverse event reporting rates and identify possible rare serious events.

Update: Noncongenital Zika Virus Disease Cases - 50 U.S. States and the District of Columbia, 2016.

Zika virus is a flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections also have been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-3). Most Zika virus infections are asymptomatic or result in mild clinical illness, characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis; Guillain-Barré syndrome, meningoencephalitis, and severe thrombocytopenia rarely have been associated with Zika virus infection (1). However, congenital Zika virus infection can result in fetal loss, microcephaly, and other birth defects (1,2). In 2016, a total of 5,168 noncongenital Zika virus disease cases were reported from U.S. states and the District of Columbia. Most cases (4,897, 95%) were in travelers returning from Zika virus-affected areas. A total of 224 (4%) cases were acquired through presumed local mosquitoborne transmission, and 47 (1%) were acquired by other routes. It is important that providers in the United States continue to test symptomatic patients who live in or recently traveled to areas with ongoing Zika virus transmission or had unprotected sex with someone who lives in or traveled to those areas. All pregnant women and their partners should take measures to prevent Zika virus infection during pregnancy. A list of affected areas and specific recommendations on how to prevent Zika virus infection during pregnancy are available at https://www.cdc.gov/pregnancy/zika/protect-yourself.html.

Zika Virus Disease Cases - 50 States and the District of Columbia, January 1-July 31, 2016.

Zika virus is a mosquito-borne flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections have also been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-5). Most Zika virus infections are asymptomatic (1,6). Clinical illness, when it occurs, is generally mild and characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. However, Zika virus infection during pregnancy can cause adverse outcomes such as fetal loss, and microcephaly and other serious brain anomalies (1-3). Guillain-Barré syndrome, a rare autoimmune condition affecting the peripheral nervous system, also has been associated with Zika virus infection (1). Following the identification of local transmission of Zika virus in Brazil in May 2015, the virus has continued to spread throughout the Region of the Americas, and travel-associated cases have increased (7). In 2016, Zika virus disease and congenital infections became nationally notifiable conditions in the United States (8). As of September 3, 2016, a total of 2,382 confirmed and probable cases of Zika virus disease with symptom onset during January 1-July 31, 2016, had been reported from 48 of 50 U.S. states and the District of Columbia. Most cases (2,354; 99%) were travel-associated, with either direct travel or an epidemiologic link to a traveler to a Zika virus-affected area. Twenty-eight (1%) cases were reported as locally acquired, including 26 associated with mosquito-borne transmission, one acquired in a laboratory, and one with an unknown mode of transmission. Zika virus disease should be considered in patients with compatible clinical signs or symptoms who traveled to or reside in areas with ongoing Zika virus transmission or who had unprotected sex with someone who traveled to those areas. Health care providers should continue to educate patients, especially pregnant women, about the importance of avoiding infection with Zika virus, and all pregnant women should be assessed for possible Zika virus exposure at each prenatal visit (2).

Staphylococcus aureus shedding pattern throughout lactation in dairy cows with naturally occurring intramammary infection.

OBJECTIVE: To evaluate shedding patterns of Staphylococcus aureus, specifically the association between clonal relatedness and shedding patterns of S aureus for cows with naturally occurring S aureus intramammary infection. DESIGN: Longitudinal field study. SAMPLE: Milk samples from 22 lactating cows (29 mammary glands) of varied numbers of lactations on 2 dairies. Procedures-Foremilk samples were collected weekly for 26 to 44 weeks during lactation from individual mammary glands. Milk samples were cultured bacteriologically with a 0.01-mL inoculum. Samples were considered culture positive for S aureus if ≥ 1 colony-forming units were obtained. Milk samples from known S aureus-positive mammary glands that were culture negative for S aureus or culture positive with a single colony of S aureus were cultured bacteriologically a second time with a 0.1-mL inoculum. Longitudinal shedding patterns of S aureus and the effect of strain type on ln(colony forming unit count) were examined. RESULTS: With the 0.01-mL inoculum, 914 of 1,070 (85%) samples were culture positive. After reculturing of negative samples with a 0.1-mL inoculum, 1,011 (95%) of the samples were culture positive. There was no significant difference in the detection of S aureus between genotypic clusters when either the 0.01- or 0.1-mL inoculum was used. There was no significant difference in the amount of shedding between mammary glands infected with isolates in genotypic cluster 1 or 2. No consistent shedding patterns were identified among or within cows. There was a significant difference in mammary gland linear score and test day (composite) linear score between mammary glands infected with isolates in genotypic clusters 1 and 2. CONCLUSIONS AND CLINICAL RELEVANCE: S aureus was shed consistently in cows with naturally occurring intramammary infection in cows, and regardless of the pulsotype, variations in the amount of S aureus shedding had no significant effect on the ability to detect S aureus with a 0.1-mL inoculum.

Variation in daily shedding patterns of Staphylococcus aureus in naturally occurring intramammary infections.

The goal of the current prospective field study was to examine the shedding patterns of naturally occurring Staphylococcus aureus intramammary infections and the association of pulsed field gel electrophoresis pulsotype with shedding. Milk samples from 5 multiparous and 2 primiparous cows identified with S. aureus intramammary infections were collected for 21 consecutive days, 3 times throughout the lactation (63 days total). Cyclicity of each quarter was evaluated using a locally weighted regression. Pulsed field gel electrophoresis was used for genotypic cluster comparisons to evaluate the association of strain type and shedding patterns. Although the amount of shedding varied greatly, 97.5% of the samples were culture positive. There were notable differences in S. aureus shedding patterns among cows as well as within cows; however, no consistent cyclic pattern was identified. Quarters infected with S. aureus isolates grouped in genotypic cluster 1 appeared to shed at consistently higher levels with a median cfu/0.01 ml of 154 (ln[cfu] = 5.0). In comparing ln(cfu)/0.01 ml between genotypic clusters over the first 21-day sample period, accounting for the effect of sample day, samples collected from quarters infected with S. aureus in genotypic cluster 1 had a 1.5 times greater ln(cfu) than those collected from quarters infected with strains in genotypic cluster 2. The ability to detect S. aureus from day to day was very consistent. The current study examining naturally occurring intramammary infections would support the conclusions of other studies suggesting that a single quarter sample would be adequate in determining S. aureus intramammary infections status.

A survey of reasons why veterinarians enter rural veterinary practice in the United States.

OBJECTIVE: To identify factors associated with interest in or choosing a career in rural veterinary practice (RVP). DESIGN: Cross-sectional descriptive study. SAMPLE POPULATION: Veterinarians and veterinary students in the United States. PROCEDURES: Veterinary students and veterinarians in any area of practice were solicited to participate in an online survey through invitation letters sent to various veterinary associations. Proportions of respondents assigning high importance to various factors were analyzed for differences among gender, age, and background groups. RESULTS: 1,216 responses were received. In general, survey respondents indicated that RVP could be characterized as the practice of veterinary medicine in any community where agriculture represented a significant part of the local economy. Responses also indicated that RVP should not be confused with large animal or food animal exclusive practice. Most respondents (38.9%) developed an interest in RVP early in life (before 8th grade), with 13.0% reportedly developing their interest in RVP during veterinary school. The most highly ranked factors with regard to influence on developing an interest in RVP were having relatives with a farm background, having a veterinarian in RVP as a mentor, and exposure to RVP during veterinary school. Gender, generational category, background (rural vs urban), and livestock experience were significantly associated with when respondents developed an interest in RVP and with factors important in developing that interest. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggested that various factors are associated with interest in and choosing a career in RVP. These factors should be considered when strategies for increasing interest and encouraging careers in RVP are planned.

A survey of reasons why veterinarians leave rural veterinary practice in the United States.

OBJECTIVE: To identify factors associated with veterinarians leaving a career in rural veterinary practice (RVP). DESIGN: Cross-sectional descriptive study. SAMPLE POPULATION: Veterinarians from the United States who no longer worked in RVP. PROCEDURES: Veterinarians in any area of practice were solicited to participate in an online survey through invitation letters sent to various veterinary associations. Those who indicated that they had left RVP were asked to rank the importance of various potential factors in their decision to leave RVP. RESULTS: 805 responses were obtained from veterinarians who had worked in RVP, of which 246 (30.6%) had left RVP. Most (231/246 [93.9%]) of those who reported leaving RVP had been in practice > 5 years, and 75.2% (185/246) had been in practice > 12 years. Eighty-three (33.7%) who left RVP pursued careers in urban areas, 72 (29.3%) entered academia, and 7 (2.8%) retired. Reasons for leaving RVP ranked by the highest proportions of respondents as being of high importance were emergency duty, time off, salary, practice atmosphere, and family concerns. Women ranked factors such as time off, mentorship, practice atmosphere, conflict with staff, and gender issues as being of high importance more often than men did. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the perceived shortage of veterinarians in RVP may be in part influenced by a lack of retention, particularly among experienced veterinarians. Targeted efforts to tackle issues related to emergency duty, time off, salary, practice atmosphere, and family issues could help alleviate the efflux from RVP.

Emergency and disaster planning at Ohio animal shelters.

Results of a cross-sectional study to determine the level of emergency and disaster response planning at Ohio nonhuman animal shelters and the role Ohio agencies have in emergency and disaster response planning in their communities indicated a lack of preparedness coupled with underutilization of the agencies as a resource. A total of 115 agencies (68%) responded to a standardized survey mailed to 170 Ohio agencies. Most (68%) agencies agreed that emergency and disaster response planning was important to their organization, although only 13% of agencies had completed a written emergency and disaster response plan. The majority (80%) of agencies indicated they would provide critical resources in an emergency or disaster in their community. Only 38 (33%) of the responding agencies were aware of the PETS Act of 2006. Although many agencies indicated the importance of an emergency and disaster plan, there may be insufficient resources, including time and proper training, available to ensure plans are developed. Improved coordination among veterinarians, local veterinary medical associations, emergency preparedness agencies, and animal shelters would enhance the relief efforts in a crisis.

Evidence of mnt-myc antagonism revealed by mnt gene deletion.

Myc proteins play a central role in promoting cell proliferation and contribute to a diverse array of cancers. My function appears completely dependent on heterodimerization with Max through related bHLHZip regions. Max interaction with Myc is required for DNA binding at so-called E-box sequences and Myc-dependent transcriptional activation. The repressor with similar DNA binding specificity raised the possibility that Mnt may serve a general role as a Myc antagonist.

Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis.

Mnt is a Max-interacting transcriptional repressor that has been hypothesized to function as a Myc antagonist. To investigate Mnt function we deleted the Mnt gene in mice. Since mice lacking Mnt were born severely runted and typically died within several days of birth, mouse embryo fibroblasts (MEFs) derived from these mice and conditional Mnt knockout mice were used in this study. In the absence of Mnt, MEFs prematurely entered the S phase of the cell cycle and proliferated more rapidly than Mnt(+/+) MEFs. Defective cell cycle control in the absence of Mnt is linked to upregulation of Cdk4 and cyclin E and the Cdk4 gene appears to be a direct target of Mnt-Myc antagonism. Like MEFs that overexpress Myc, Mnt(-/-) MEFs were prone to apoptosis, efficiently escaped senescence and could be transformed with oncogenic Ras alone. Consistent with Mnt functioning as a tumor suppressor, conditional inactivation of Mnt in breast epithelium led to adenocarinomas. These results demonstrate a unique negative regulatory role for Mnt in governing key Myc functions associated with cell proliferation and tumorigenesis.