Changes in tuberculosis epidemiology, United States, 1993-2017.

BACKGROUND: After 20 years of steady decline, the pace of decline of tuberculosis (TB) incidence in the United States has slowed.METHODS: Trends in TB incidence rates and case counts since 1993 were assessed using national US surveillance data. Patient characteristics reported during 2014-2017 were compared with those for 2010-2013.RESULTS: TB rates and case counts slowed to an annual decline of respectively 2.2% (95%CI -3.4 to -1.0) and 1.5% (95%CI -2.7 to -0.3) since 2012, with decreases among US-born persons and no change among non-US-born persons. Overall, persons with TB diagnosed during 2014-2017 were older, more likely to have combined pulmonary and extra-pulmonary disease than extra-pulmonary disease alone, more likely to be of non-White race, and less likely to have human immunodeficiency virus infection, or cavitary pulmonary disease. During 2014-2017, non-US-born persons with TB were more likely to have diabetes mellitus, while the US-born were more likely to have smear-positive TB and use non-injecting drugs.CONCLUSION: Changes in epidemiologic trends are likely to affect TB incidence in the coming decades. The Centers for Disease Control and Prevention has called for increased attention to TB prevention through the detection and treatment of latent tuberculous infection.

Incidence and prevalence of recurrent respiratory papillomatosis among children in Atlanta and Seattle.

The incidence and prevalence of recurrent respiratory papillomatosis (RRP) for children aged <18 years were estimated in 2 US cities, Atlanta and Seattle, in 1996. All otolaryngologists in a 24-county area in metropolitan Atlanta (101 physicians) and an 8-county area in metropolitan Seattle (139 physicians) agreed to participate in the study. Medical record chart abstraction was performed only for children with documented current residence in the study area (21 patients in Atlanta and 14 patients in Seattle). The incidence rate for juvenile RRP was 1.11/100,000 population in Atlanta and 0.36/100, 000 in Seattle. The prevalence rate was 2.59/100,000 population in Atlanta and 1.69/100,000 in Seattle. In neither city did prevalences differ significantly when stratified by sex or race. Extrapolation of these estimates to the US population suggests that 80-1500 incident cases and 700-3000 prevalent cases of juvenile RRP will occur in the United States during 1999.

Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. RRP Task Force.

OBJECTIVE: To characterize the spectrum of juvenile-onset recurrent respiratory papillomatosis (RRP) in the United States and to obtain data about the natural course of the disease and its response to treatment. SETTING: Twenty tertiary-care pediatric otolaryngology centers throughout the United States. PATIENTS: All patients with active RRP aged less than 18 years at the participating sites. MAIN OUTCOME MEASURES: Number of surgical procedures performed per year, progression of papillomas to previously nondiseased anatomical sites, drug interventions and other adjuvant therapy, and need for tracheostomy. RESULTS: Data were collected from 399 children enrolled from January, 1, 1997, through December 31, 1998. There were 51.9% male; 62.7% white, 28.3% black, 9.0% other or unknown racial group; 10.8% Hispanic ethnicity. Mean age at diagnosis was 3.8 years (range, 0.1-16.3 years) and mean duration of disease was 4.4 years (range, 0.03-18.9 years). The mean number of surgical procedures per child was 4.4 per year (range, 0.2-19.3 per year). Children whose RRP was diagnosed at younger ages (<3.0 years) were 3.6 times more likely to have more than 4 surgical procedures per year (P=.001) and almost 2 times more likely to have 2 or more anatomical sites affected (P=.008) than were children whose RRP was diagnosed at later ages (> or =3.0 years), after adjusting for sex, race, and years of treatment. CONCLUSIONS: Children whose disease was diagnosed before age 3 years were more likely than children aged 3 years or older to have more severe disease as measured by the mean number of surgical procedures performed and by the number of anatomical sites affected. The registry will form the basis for future analysis on the outcome of disease, natural course of RRP under management strategies, prevention strategies, and public health importance.

Management of a Sabiá virus-infected patients in a US hospital.

OBJECTIVE: To describe the hospital precautions used to isolate a Sabiá virus (arenavirus: Arenaviridae)-infected patient in a US hospital and to protect hospital staff and visitors. DESIGN: Investigation of a single case of arenavirus laboratory-acquired infection and associated case-contacts. SETTING: A 900-bed, tertiary-care, university-affiliated medical center. PATIENTS OR OTHER PARTICIPANTS: The case-patient became ill with Sabiá virus infection. The case-contacts consisted of healthcare workers, coworkers, friends, and relatives of the case-patient. INTERVENTION: Enhanced isolation precautions for treatment of a viral hemorrhagic fever (VHF) patient were implemented in the clinical laboratory and patient-care setting to prevent nosocomial transmission. The enhanced precautions included preventing aerosol spread of the virus from the patient or his clinical specimens. All case-contacts were tested for Sabiá virus antibodies and monitored for signs and symptoms of early disease. RESULTS: No cases of secondary infection occurred among 142 case-contacts. CONCLUSIONS: With the frequency of worldwide travel, patients with VHF can be admitted to a local hospital at any time in the United States. The use of enhanced isolation precautions for VHF appeared to be effective in preventing secondary cases by limiting the number of contacts and promoting proper handling of laboratory specimens. Patients with VHF can be managed safely in a local hospital setting, provided that appropriate precautions are planned and implemented.

Hantavirus transmission in the United States.

In 1996, investigation of a hantavirus pulmonary syndrome (HPS) outbreak in southern Argentina found evidence of person-to-person transmission of a hantavirus. The infection control ramifications of this finding led to this review of hantavirus epidemiology in the United States; the review suggests that Sin Nombre virus infection is rarely, if ever, transmitted from person to person and that existing guidelines for prevention of HPS remain appropriate for North America.

Hantavirus pulmonary syndrome: the first 100 US cases.

In the spring of 1993, hantavirus pulmonary syndrome (HPS) "emerged" in the southwestern United States, where a multiagency investigation led to the rapid description of this new clinical entity and its etiology. Analysis of the first 100 US cases identified showed that the disease was distributed in 21 states, had gone unrecognized since at least 1959, and had a distinct spring-early summer seasonality. Of the infected persons, 54% were male; 63% were Caucasian, 35% were Native American, and 2% were African American. The average age of case-patients was 34.9 years, and 8 were children or adolescents aged < or = 16 years. The overall case-fatality rate was 52%. There was a 91% concordance among serologic, immunohistochemical, and molecular results. HPS in the United States is caused by at least three newly described pathogenic hantaviruses, each of which has a distinct rodent host, and cases of HPS have been recently recognized in Canada and South America. National surveillance of this sporadic disease remains essential for further defining the epidemiology and clinical spectrum.

Utility of emergency, telephone-based national surveillance for Hantavirus pulmonary syndrome. Hantavirus Task Force.

On May 27, 1993, in response to the outbreak investigation of newly recognized Hantavirus pulmonary syndrome (HPS) in the Four Corners states (New Mexico, Arizona, Utah, and Colorado), the Centers for Disease Control and Prevention established a national surveillance case definition for severe, unexplained respiratory disease to determine the extent of HPS throughout the United States. A toll-free telephone hotline number was instituted to provide updated information about unexplained respiratory illness and to serve as a passive mechanism for reporting suspected cases. Clinical information was obtained from callers reporting suspected cases, and diagnostic specimens and medical record reviews were requested from health care providers. From June 3 through December 31, 1993, the hotline received 21,443 telephone inquiries; callers identified 280 suspected cases living outside the Four Corners states with at least one specimen available for diagnostic testing. By December 31, 1993, 21 confirmed cases (age range, 14 to 58 years) residing in 11 states outside the Four Corners region had been identified. This passive surveillance system was successful in rapidly identifying the widespread sporadic geographic distribution for HPS cases throughout the United States and could serve as a model for similar emergencies. Expanding and coordinating surveillance systems for the early detection, tracking, and evaluation of emerging infections is a critical component of disease prevention.

Retrospective diagnosis of hantavirus pulmonary syndrome, 1978-1993: implications for emerging infectious diseases.

OBJECTIVE: To investigate the occurrence of unrecognized cases of hantavirus pulmonary syndrome preceding the detection of the 1993 outbreak in the southwestern United States and the initial description of the syndrome. DESIGN: Retrospective clinicopathologic and immunohistologic study. PATIENTS: Eighty-two patients who died prior to April 1993 with histologically unexplained noncardiogenic pulmonary edema. METHODS: Clinicopathologic review and immunohistochemical evaluation of autopsy tissues for evidence of hantaviral infection. RESULTS: Twelve retrospective fatal cases of hantavirus pulmonary syndrome were identified through clinicopathologic review and immunohistochemical testing of tissues. Patients' ages ranged from 16 to 49 years. The earliest identified case occurred in 1978, 15 years prior to the outbreak of hantavirus pulmonary syndrome in the southwestern United States. Immunohistochemical testing showed widespread deposition of hantaviral antigens, primarily within endothelial cells, similar to the pattern observed with current hantavirus pulmonary syndrome cases. CONCLUSIONS: Although hantavirus pulmonary syndrome was first recognized in 1993, the findings from this study document the earlier existence of this disease. These findings underscore the need for systematic archiving and analysis of clinical information and specimens from patients with diseases of unknown etiology to facilitate the study of new clinical entities and their associated etiologic agents.

Hantavirus pulmonary syndrome in Florida: association with the newly identified Black Creek Canal virus.

Hantavirus pulmonary syndrome (HPS) is a recently recognized viral zoonosis. The first recognized cases were caused by a newly described hantavirus. Sin Nombre virus (previously known as Muerto Canyon virus), isolated from Peromyscus maniculatus (deer mouse). We describe a 33-year-old Floridian man who resided outside the ecologic range of P maniculatus but was found to have serologic evidence of a hantavirus infection during evaluation of azotemia associated with adult respiratory distress syndrome. Small mammal trapping conducted around this patient's residence demonstrated the presence of antihantaviral antibodies in 13% of Sigmodon hispidus [cotton rat). Serologic testing using antigen derived from the Black Creek Canal hantavirus subsequently isolated from this rodent established that this patient was acutely infected with this new pathogenic American hantavirus. HPS is not confined to the geographical distribution of P maniculatus and should be suspected in individuals with febrile respiratory syndromes, perhaps associated with azotemia, throughout the continental United States.

Regulation of rat pulmonary dendritic cell immunostimulatory activity by alveolar epithelial cell-derived granulocyte macrophage colony-stimulating factor.

The presentation and recognition of foreign antigen is the critical initial event in the development of local immunity. In the lung, antigen-presenting cell activity is largely attributable to pulmonary dendritic cells (DC) that are distributed along the airways and throughout the pulmonary interstitium in close proximity to overlying alveolar epithelial cells. To test the hypothesis that DC immunostimulatory activity might be locally regulated by overlying alveolar epithelial cells, we evaluated the ability of rat type II alveolar epithelial cells to influence the capacity of purified rat pulmonary DC to stimulate T-cell proliferation in an allogeneic, mixed leukocyte reaction. We found that alveolar epithelial cells greatly enhanced the ability of dendritic cells to induce T-cell proliferation. This effect on DC immunostimulatory activity was mediated by a soluble factor preferentially secreted from the basolateral epithelial cell surface. Alveolar epithelial cultures were found to express mRNA for granulocyte macrophage colony-stimulating factor (GM-CSF), and blocking antibodies against GM-CSF partially neutralized the effect of epithelial cell-conditioned media on DC stimulatory activity, indicating that the effect was due at least in part to alveolar epithelial cell-derived GM-CSF. Through the polar secretion of GM-CSF, alveolar epithelial cells may play an important role in creating distinct immunologic environments within the lung.

Regulation of the immunostimulatory activity of rat pulmonary interstitial dendritic cells by cell-cell interactions and cytokines.

Pulmonary dendritic cells (DC) are potent antigen-presenting cells that are thought to play a critical role in the initiation of immune responses within the lung. Because the lung is both a site of entry into the body for microbial pathogens and the organ of gas exchange, pulmonary immune responses must be meticulously regulated to achieve a balance between host defense and respiration. The initial interaction of DC with T cells in the lung is an excellent point at which to control local immune responses. Studies of the regulation of DC accessory cell function have been greatly hampered by difficulties in obtaining pure populations of pulmonary DC that have not been subjected to prolonged incubations during which the DC may undergo functional alteration. We now describe a method for isolating pulmonary DC from the rat that yields 1 x 10(5) cells/rat with > 90% purity. These cells are potent accessory cells, inducing T cell proliferation in a mixed leukocyte reaction (MLR) at a stimulator-to-responder ratio of 1:1,000. This method, which involves flow cytometric separation of nonphagocytic cells that stain brightly for class II MHC (OX6) from a population of low-density pulmonary interstitial cells, avoids extended incubations at 37 degrees C and thus allows study of a relatively pure population of cells that have functional capacities resembling those of naive cells from the normal lung. With these cells, we demonstrate that the functional capacity of pulmonary DC as stimulator cells in an MLR is significantly increased by exposure to the cytokines interleukin-1 or granulocyte/macrophage colony-stimulating factor (GM-CSF) and by culture with interstitial, but not alveolar, macrophages. Furthermore, DC are heterogeneous with respect to the cell surface expression of receptor for GM-CSF, and this expression is subject to modulation in cell culture. From these studies, we conclude that the immunostimulatory capacity of pulmonary DC is a function of local interactions with cytokines and other parenchymal cells. This suggests that DC function may be an important regulatory point for the local control of pulmonary immune responses.

Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro.

Cryptococcus neoformans, a pathogenic fungus usually acquired by inhalation, causes the most common lethal mycosis in AIDS. The resident lung phagocytes, alveolar macrophages (AM phi), inhibit growth of C. neoformans poorly unless activated by cytokines such as IFN-gamma. In this study, we examined the effect of rat AM phi of the potent hematopoietic and M phi-activating cytokine, granulocyte-macrophage CSF (GM-CSF), alone and in combination with other cytokines. Rat AM phi monolayers were preincubated with 0.1 to 1000 U/ml GM-CSF without or with other recombinant cytokines, and then were incubated with viable C. neoformans (strain H99/C3D). Growth inhibition was assessed by counting cryptococcal CFU at 24 and 48 h of coculture; AM phi proliferation was assessed by measuring both uptake of [3H]TdR and AM phi numbers. AM phi preincubated with GM-CSF for 5 days (but not for shorter periods) inhibited growth of C. neoformans. Anticryptococcal activity required direct contact of AM phi with C. neoformans, but once induced by preincubation, did not require continued exposure to GM-CSF. Induction of anticryptococcal activity by GM-CSF was dose dependent (maximal induction at 250 U/ml), and was due to both increased ingestion and killing. GM-CSF induced AM phi proliferation, but anticryptococcal activity was not due totally to increases in AM phi numbers, indicating AM phi activation by GM-CSF. GM-CSF-induced AM phi proliferation was increased by IL-6, unchanged by IL-8, and abolished by LPS or IFN-gamma. However, IL-6 did not increase GM-CSF-induced anticryptococal activity. The combination of GM-CSF and IFN-gamma showed rapid and sustained anticryptococcal activity, unlike either cytokine alone. Our in vitro data suggest that the combination of GM-CSF and IFN-gamma may have beneficial effects on host defense against C. neoformans in vivo.

The enteric immune response to shigella antigens.

Mucosal immunity to some enteropathogens occurs naturally following infection. By learning how to optimize initiation of the mucosal immune response it will be possible to develop vaccines against a wide variety of enteropathogens and their toxic products. In the past few years, we have examined stimulation of the mucosal response to Shigella antigens. We have found that the mucosal memory response to Shigella LPS can be stimulated by oral immunization with live, but not with killed Shigella. This primes specific B lymphocytes which, following rechallenge, quickly migrate from the Peyer's patches to mesenteric lymph nodes, the spleen, and back to the Peyer's patches. We have found that the uptake of S. flexneri is the initial step in developing a mucosal immune response to Shigella. Whereas there is little difference between the initial uptake of virulent and avirulent bacteria by M cells, pathogenic strains of Shigella are able to replicate following their uptake by the specialized M cells located in the follicle-associated epithelium of the gut. This likely serves as the source of the ulcerative lesions found in dysentery. Lastly, we have detected a vigorous secretory IgA response to Shiga toxin. The titer of IgA activity to Shiga toxin from these loop secretions correlated well with the ability to prevent Shiga toxin cytotoxin effects in vitro. The extremely vigorous mucosal immune response to Shiga toxin makes this an attractive alternative to cholera toxin to potentiate the secretory IgA immune response.