Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 99 Records) |
Query Trace: Ritter T [original query] |
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ORF virus causes tumor-promoting inflammation in sheep and goats
Pintus D , Cancedda MG , Puggioni G , Scivoli R , Rocchigiani AM , Maestrale C , Coradduzza E , Bechere R , Silva-Flannery L , Bullock HA , Macciocu S , Montesu MA , Marras V , Dore S , Ritter JM , Ligios C . Vet Pathol 2024 3009858241241794 ORF virus (ORFV) causes contagious ecthyma ("ORF"), a disease of sheep and goats characterized by lesions ranging from vesicles and pustules to atypical papilloma-like and angiomatous lesions in the skin and mucosae. The authors investigated the molecular factors leading to the ORF-associated atypical tumor-like changes. Fifteen lambs, 15 kids, and an adult ram clinically affected by natural ORFV infection were enrolled in the study and examined by several methods. ORFV was detected by viral culture or real-time polymerase chain reaction (RT-PCR) in the lesioned tissues and in the blood of the clinically affected sheep and goats. Surprisingly, ORFV was also detected in the blood of healthy goats from an affected herd. Microscopically, they found a pseudo-papillomatous proliferation of the epithelium, while the dermis and lamina propria were expanded by a proliferating neovascular component that highly expressed the viral vascular endothelial growth factor (vVEGF) and its host receptor vascular endothelial growth factor receptor 2 (VEGFR2). Immunohistochemistry, immunofluorescence, and in situ hybridization for mRNA showed that epidermal growth factor receptor (EGFR) was expressed in the fibrovascular component, in the infiltrating CD163+ macrophages, and in the basal stratum of the epidermis. Confocal immunofluorescence microscopy demonstrated that CD163+ macrophages were associated with VEGF and VEGFR2. Finally, they found by quantitative RT-PCR the overexpression of the interleukin-6 and VEGFR2 genes in the lesioned tissues. These findings suggest that ORFV activates an inflammatory reaction characterized by CD163+ macrophages expressing EGFR and VEGFR2, which might play an oncogenic role through synergistic action with vVEGF signaling. |
Mortality associated with SARS-CoV-2 in nondomestic felids
Drozd M , Ritter JM , Samuelson JP , Parker M , Wang L , Sander SJ , Yoshicedo J , Wright L , Odani J , Shrader T , Lee E , Lockhart SR , Ghai RR , Terio KA . Vet Pathol 2024 3009858231225500 Between September and November 2021, 5 snow leopards (Panthera uncia) and 1 lion (Panthera leo) were naturally infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) and developed progressive respiratory disease that resulted in death. Severe acute respiratory syndrome coronavirus 2 sequencing identified the delta variant in all cases sequenced, which was the predominant human variant at that time. The time between initial clinical signs and death ranged from 3 to 45 days. Gross lesions in all 6 cats included nasal turbinate hyperemia with purulent discharge and marked pulmonary edema. Ulcerative tracheitis and bronchitis were noted in 4 cases. Histologically, there was necrotizing and ulcerative rhinotracheitis and bronchitis with fibrinocellular exudates and fibrinosuppurative to pyogranulomatous bronchopneumonia. The 4 cats that survived longer than 8 days had fungal abscesses. Concurrent bacteria were noted in 4 cases, including those with more acute disease courses. Severe acute respiratory syndrome coronavirus 2 was detected by in situ hybridization using probes against SARS-CoV-2 spike and nucleocapsid genes and by immunohistochemistry. Viral nucleic acid and protein were variably localized to mucosal and glandular epithelial cells, pneumocytes, macrophages, and fibrinocellular debris. Based on established criteria, SARS-CoV-2 was considered a contributing cause of death in all 6 cats. While mild clinical infections are more common, these findings suggest that some SARS-CoV-2 variants may cause more severe disease and that snow leopards may be more severely affected than other felids. |
Pathology and monkeypox virus localization in tissues from immunocompromised patients with severe or fatal mpox
Ritter JM , Martines RB , Bhatnagar J , Rao AK , Villalba JA , Silva-Flannery L , Lee E , Bullock HA , Hutson CL , Cederroth T , Harris CK , Hord K , Xu Y , Brown CA , Guccione JP , Miller M , Paddock CD , Reagan-Steiner S . J Infect Dis 2024 BACKGROUND: Pathology and monkeypox virus (MPXV) tissue tropism in severe and fatal human mpox is not thoroughly described but can help elucidate the disease pathogenesis and the role of coinfections in immunocompromised patients. METHODS: We analyzed biopsy and autopsy tissues from 22 patients with severe or fatal outcomes to characterize pathology and viral antigen and DNA distribution in tissues by immunohistochemistry and in situ hybridization. Tissue-based testing for coinfections was also performed. RESULTS: Mucocutaneous lesions showed necrotizing and proliferative epithelial changes. Deceased patients with autopsy tissues evaluated had digestive tract lesions, and half had systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs. Half also had bronchopneumonia, and one-third had acute lung injury. All cases had MPXV antigen and DNA detected in tissues. Coinfections were identified in 5/16 (31%) biopsy and 4/6 (67%) autopsy cases. DISCUSSION: Severe mpox in immunocompromised patients is characterized by extensive viral infection of tissues and viremic dissemination that can progress despite available therapeutics. Digestive tract and lung involvement are common and associated with prominent histopathological and clinical manifestations. Coinfections may complicate mpox diagnosis and treatment. Significant viral DNA (likely correlating to infectious virus) in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings. |
Clinical manifestations of an outbreak of monkeypox virus in captive chimpanzees in Cameroon, 2016
Brien SC , LeBreton M , Doty JB , Mauldin MR , Morgan CN , Pieracci EG , Ritter JM , Matheny A , Tafon BG , Tamoufe U , Missoup AD , Nwobegahay J , Takuo JM , Nkom F , Mouiche MMM , Feussom JMK , Wilkins K , Wade A , McCollum AM . J Infect Dis 2024 Monkeypox virus (MPXV) is a re-emerging virus of global concern. An outbreak of Clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, peri-laryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures. |
Large community outbreak of legionnaires disease potentially associated with a cooling tower - Napa County, California, 2022
Grossmann NV , Milne C , Martinez MR , Relucio K , Sadeghi B , Wiley EN , Holland SN , Rutschmann S , Vugia DJ , Kimura A , Crain C , Akter F , Mukhopadhyay R , Crandall J , Shorrock M , Smith JC , Prasad N , Kahn R , Barskey AE , Lee S , Willby MJ , Kozak-Muiznieks NA , Lucas CE , Henderson KC , Hamlin JAP , Yang E , Clemmons NS , Ritter T , Henn J . MMWR Morb Mortal Wkly Rep 2023 72 (49) 1315-1320 Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11 and 12, 2022, Napa County Public Health (NCPH) in California received reports of three positive urinary antigen tests for Legionella pneumophila serogroup 1 in the town of Napa. By July 21, six Legionnaires disease cases had been confirmed among Napa County residents, compared with a baseline of one or two cases per year. NCPH requested assistance from the California Department of Public Health (CDPH) and CDC to aid in the investigations. Close temporal and geospatial clustering permitted a focused environmental sampling strategy of high-risk facilities which, coupled with whole genome sequencing results from samples and investigation of water system maintenance, facilitated potential linking of the outbreak with an environmental source. NCPH, with technical support from CDC and CDPH, instructed and monitored remediation practices for all environmental locations that tested positive for Legionella. The investigation response to this community outbreak illustrates the importance of interdisciplinary collaboration by public health agencies, laboratory support, timely communication with the public, and cooperation of managers of potentially implicated water systems. Timely identification of possible sources, sampling, and remediation of any facility testing positive for Legionella is crucial to interrupting further transmission. |
Effects of exogenous erythropoietin on rabbit (Oryctolagus cuniculus) hematological and biochemical parameters
Levine JK , Nascimento Seixas J , Ritter JM , Liew AY , Tansey CM . Comp Med 2023 73 (6) 439-45 Rabbits can develop anemia due to serial phlebotomy or secondary to induced disease states. This study evaluated theeffects of a single injection and three consecutive injections of erythropoietin in rabbits at 150 IU/kg and 1,000 IU/kg in orderto determine whether these dosages produce a sustained increase in hematocrit. Analysis of CBC and chemistry parametersshowed significant elevation in hematocrit one week after administration of 1,000 IU/kg erythropoietin for three consecutivedays. These results indicate that this dosage regimen can increase hematocrit in apparently healthy, nonanemic rabbits forone week. |
Fatal invasive mold infections after transplantation of organs recovered from drowned donors, United States, 2011-2021
Wu K , Annambhotla P , Free RJ , Ritter JM , Leitgeb B , Jackson BR , Toda M , Basavaraju SV , Gold JAW . Emerg Infect Dis 2023 29 (7) 1455-1458 Drowned organ donors can be exposed to environmental molds through the aspiration of water; transplantation of exposed organs can cause invasive mold infections in recipients. We describe 4 rapidly fatal cases of potentially donor-derived invasive mold infections in the United States, highlighting the importance of maintaining clinical suspicion for these infections in transplant recipients. |
Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: Report of an investigation
Gould CV , Free RJ , Bhatnagar J , Soto RA , Royer TL , Maley WR , Moss S , Berk MA , Craig-Shapiro R , Kodiyanplakkal RPL , Westblade LF , Muthukumar T , Puius YA , Raina A , Hadi A , Gyure KA , Trief D , Pereira M , Kuehnert MJ , Ballen V , Kessler DA , Dailey K , Omura C , Doan T , Miller S , Wilson MR , Lehman JA , Ritter JM , Lee E , Silva-Flannery L , Reagan-Steiner S , Velez JO , Laven JJ , Fitzpatrick KA , Panella A , Davis EH , Hughes HR , Brault AC , St George K , Dean AB , Ackelsberg J , Basavaraju SV , Chiu CY , Staples JE . Lancet Microbe 2023 4 (9) e711-e721 BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases. |
Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination
Welch SR , Spengler JR , Genzer SC , Coleman-McCray JD , Harmon JR , Sorvillo TE , Scholte FEM , Rodriguez SE , O'Neal TJ , Ritter JM , Ficarra G , Davies KA , Kainulainen MH , Karaaslan E , Bergeron É , Goldsmith CS , Lo MK , Nichol ST , Montgomery JM , Spiropoulou CF . Sci Adv 2023 9 (31) eadh4057 Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease. |
Canine leproid granuloma caused by a member of the Mycobacterium tuberculosis complex
Giannitti F , Dorsch MA , Fernández-Ciganda S , Rabaza A , Vázquez S , César D , Hurtado J , Greif G , Rabeneck DB , Bhatnagar J , Ritter JM . J Vet Diagn Invest 2023 35 (4) 10406387231176816 Canine leproid granuloma (CLG) is a chronic form of dermatitis that has been associated with nontuberculous mycobacterial infections in Africa, Oceania, the Americas, and Europe. We report here a case of CLG associated with a member of the Mycobacterium tuberculosis complex (MTBC), which could be of public health concern. An 8-y-old pet dog developed 0.5-1-cm diameter, raised, firm, nonpruritic, alopecic, painless skin nodules on the external aspects of both pinnae. Histologic examination revealed severe pyogranulomatous dermatitis with intracellular Ziehl-Neelsen-positive bacilli that were immunoreactive by immunohistochemistry using a polyclonal primary antibody that recognizes tuberculous and nontuberculous Mycobacterium species. DNA extracted from formalin-fixed, paraffin-embedded skin sections was tested by a Mycobacterium genus-specific nested PCR assay targeting the 16S rRNA gene. BLAST sequence analysis of 214-bp and 178-bp amplicons showed 99.5% identity with members of the MTBC; however, the agent could not be identified at the species level. Although CLG has been associated traditionally with nontuberculous mycobacterial infections, the role of Mycobacterium spp. within the MTBC as a cause of this condition, and the role of dogs with CLG as possible sources of MTBC to other animals and humans, should not be disregarded given its zoonotic potential. |
Fatal Human Rabies Infection with Suspected Host-mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.
Holzbauer SM , Schrodt CA , Prabhu RM , Asch-Kendrick RJ , Ireland M , Klumb C , Firestone MJ , Liu G , Harry K , Ritter JM , Levine MZ , Orciari LA , Wilkins K , Yager P , Gigante CM , Ellison JA , Zhao H , Niezgoda M , Li Y , Levis R , Scott D , Satheshkumar PS , Petersen BW , Rao AK , Bell WR , Bjerk SM , Forrest S , Gao W , Dasheiff R , Russell K , Pappas M , Kiefer J , Bickler W , Wiseman A , Jurantee J , Reichard RR , Smith KE , Lynfield R , Scheftel J , Wallace RM , Bonwitt J . Clin Infect Dis 2023 77 (8) 1201-1208 BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise. |
Fatal systemic fungal infection in eastern bongo antelope (Tragelaphus eurycerus isaaci): Six cases
Garner MM , Fredholm DVE , Citino SB , Keating MK , Ritter JM , Lockart S , Lysen C , Bradway DS , Koons AR , Newton J . J Zoo Wildl Med 2023 54 (1) 102-110 Over a span of 6 yr, six adult eastern bongo antelope (Tragelaphus eurycerus isaaci) from a single institution died due to systemic mycotic infections. All animals were of the same genetic lineage and in good body condition at the time of death. Gross findings in all cases included multifocal white-to-tan nodules up to 10 cm in diameter that were most numerous in the heart, lung, and kidney. Histologic examination identified these nodules as foci of granulomatous inflammation containing branching, septate, broad, undulating fungal elements. Identification of the fungal species was pursued using PCR with sequencing, immunohistochemistry, and culture. Multiple fungal species were identified using the various modalities, and commonality of species identification was limited to Cladosporium sp. in four of the cases. The clinical and postmortem findings in these cases were identical and were considered to be the same infectious disease. The Cladosporium sp. was considered a candidate as an emerging fatal infectious agent in this population of bongo antelopes. In all of these cases, death was attributed to conduction abnormalities associated with the cardiac lesions or euthanasia. |
Prevalence of Platynosomum spp infection and its association with biliary lithiasis and secondary bacterial infections in free-ranging marmosets (Callithrix spp) of the Brazilian Atlantic Forest
Oliveira AR , Ritter JM , Santos DO , Lucena FP , Carvalho TP , Moreira LGA , Vasconcelos IM , Costa FB , Paixão TA , Santos RL . J Comp Pathol 2023 200 59-66 Platynosomosis is a parasitic disease caused by a trematode of the genus Platynosomum, a bile duct and gallbladder fluke that has been described in captive neotropical primates (New World primates; NWPs) and causes high morbidity and variable mortality. Although it is a major concern for ex-situ conservation of these animals, there are only a few studies of platynosomosis in free-ranging NWPs. Therefore, the aim of this study was to characterize platynosomosis in a free-ranging population of marmosets (Callithrix spp) from the Brazilian Atlantic Forest, focusing on the epidemiological and pathological aspects of the disease. A total of 1,001 marmosets were evaluated and on the basis of clinicoepidemiological data, histopathology, histochemistry and immunohistochemistry, we concluded that Platynosomum spp infection has a prevalence of 8.9% (confidence interval: 7.3-10.8%) in free-ranging marmosets, with a higher frequency in the Metropolitan Region of Rio de Janeiro. Infection was associated with fibrosing and proliferative cholangiohepatitis associated with biliary lithiasis (3.0% of cases) and secondary bacterial infections (14.6% of cases). |
Mouse models of Ebola virus tolerance and lethality: Characterization of CD-1 mice infected with wild-type, guinea pig-adapted, or mouse-adapted variants
Spengler JR , Welch SR , Ritter JM , Harmon JR , Coleman-McCray JD , Genzer SC , Nascimento Seixas J , Scholte FEM , Davies KA , Bradfute SB , Montgomery JM , Spiropoulou CF . Antiviral Res 2022 210 105496 Development of lethal models of Ebola virus disease has been achieved by the serial passage of virus isolates from human cases in mice and guinea pigs. Use of mice infected with non-adapted virus has been limited due to the absence of overt clinical disease. In recent years, newly recognized sequelae identified in human cases has highlighted the importance of continued investigations of non-lethal infection both in humans and animal models. Here, we revisit the use of rodent-adapted and non-adapted Ebola virus (EBOV) variants in mice to investigate infection tolerance and future utility of these models in pathogenesis and therapeutic intervention studies. We found that like non-adapted wild-type EBOV, guinea pig-adapted EBOV results in widespread tissue infection, variably associated with tissue pathology, and alterations in clinical and immunological analytes in the absence of overt disease. Notably, infection with either non-lethal variant does not greatly differ from lethal mouse-adapted EBOV until near the time end-point criteria are reached in these mice, supporting use of these models of virus tolerance for continued investigations of non-lethal infection and sequelae. |
Tissue replication and mucosal swab detection of Sosuga virus in Syrian hamsters in the absence of overt tissue pathology and clinical disease
Welch SR , Ritter JM , Schuh AJ , Genzer SC , Sorvillo TE , Harmon JR , Coleman-McCray JD , Jain S , Shrivastava-Ranjan P , Seixas JN , Estetter LB , Fair PS , Towner JS , Montgomery JM , Albariño CG , Spiropoulou CF , Spengler JR . Antiviral Res 2022 209 105490 Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. We demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues. |
Severe monkeypox in hospitalized patients - United States, August 10-October 10, 2022
Miller MJ , Cash-Goldwasser S , Marx GE , Schrodt CA , Kimball A , Padgett K , Noe RS , McCormick DW , Wong JM , Labuda SM , Borah BF , Zulu I , Asif A , Kaur G , McNicholl JM , Kourtis A , Tadros A , Reagan-Steiner S , Ritter JM , Yu Y , Yu P , Clinton R , Parker C , Click ES , Salzer JS , McCollum AM , Petersen B , Minhaj FS , Brown E , Fischer MP , Atmar RL , DiNardo AR , Xu Y , Brown C , Goodman JC , Holloman A , Gallardo J , Siatecka H , Huffman G , Powell J , Alapat P , Sarkar P , Hanania NA , Bruck O , Brass SD , Mehta A , Dretler AW , Feldpausch A , Pavlick J , Spencer H , Ghinai I , Black SR , Hernandez-Guarin LN , Won SY , Shankaran S , Simms AT , Alarcón J , O'Shea JG , Brooks JT , McQuiston J , Honein MA , O'Connor SM , Chatham-Stephens K , O'Laughlin K , Rao AK , Raizes E , Gold JAW , Morris SB . MMWR Morb Mortal Wkly Rep 2022 71 (44) 1412-1417 As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority. |
Ocular Monkeypox - United States, July-September 2022
Cash-Goldwasser S , Labuda SM , McCormick DW , Rao AK , McCollum AM , Petersen BW , Chodosh J , Brown CM , Chan-Colenbrander SY , Dugdale CM , Fischer M , Forrester A , Griffith J , Harold R , Furness BW , Huang V , Kaufman AR , Kitchell E , Lee R , Lehnertz N , Lynfield R , Marsh KJ , Madoff LC , Nicolasora N , Patel D , Pineda R2nd , Powrzanas T , Roberts A , Seville MT , Shah A , Wong JM , Ritter JM , Schrodt CA , Raizes E , Morris SB , Gold JAW . MMWR Morb Mortal Wkly Rep 2022 71 (42) 1343-1347 As of October 11, 2022, a total of 26,577 monkeypox cases had been reported in the United States.* Although most cases of monkeypox are self-limited, lesions that involve anatomically vulnerable sites can cause complications. Ocular monkeypox can occur when Monkeypox virus (MPXV) is introduced into the eye (e.g., from autoinoculation), potentially causing conjunctivitis, blepharitis, keratitis, and loss of vision (1). This report describes five patients who acquired ocular monkeypox during July-September 2022. All patients received treatment with tecovirimat (Tpoxx)(†); four also received topical trifluridine (Viroptic).(§) Two patients had HIV-associated immunocompromise and experienced delays between clinical presentation with monkeypox and initiation of monkeypox-directed treatment. Four patients were hospitalized, and one experienced marked vision impairment. To decrease the risk for autoinoculation, persons with monkeypox should be advised to practice hand hygiene and to avoid touching their eyes, which includes refraining from using contact lenses (2). Health care providers and public health practitioners should be aware that ocular monkeypox, although rare, is a sight-threatening condition. Patients with signs and symptoms compatible with ocular monkeypox should be considered for urgent ophthalmologic evaluation and initiation of monkeypox-directed treatment. Public health officials should be promptly notified of cases of ocular monkeypox. Increased clinician awareness of ocular monkeypox and of approaches to prevention, diagnosis, and treatment might reduce associated morbidity. |
Bovine Polyomavirus-1 (Epsilonpolyomavirus bovis): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans.
Giannitti F , daSilvaSilveira C , Bullock H , Bern M , Fernndez-Ciganda S , Bentez-Galeano MJ , Rodrguez-Osorio N , Silva-Flannery L , Perdomo Y , Cabrera A , Puentes R , Colina R , Ritter JM , Castells M . Viruses 2022 14 (9) Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1-associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed. |
Comparative Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Variants in the Ferret Model.
Pulit-Penaloza JA , Belser JA , Sun X , Pappas C , Brock N , Kieran TJ , Ritter JM , Seixas JN , Jones J , BasuThakur P , Pusch E , Wang L , Tumpey TM , Wentworth DE , Zhou B , Maines TR . mBio 2022 13 (5) e0242122 The continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans necessitates evaluation of variants for enhanced virulence and transmission. We used the ferret model to perform a comparative analysis of four SARS-CoV-2 strains, including an early pandemic isolate from the United States (WA1), and representatives of the Alpha, Beta, and Delta lineages. While Beta virus was not capable of pronounced replication in ferrets, WA1, Alpha, and Delta viruses productively replicated in the ferret upper respiratory tract, despite causing only mild disease with no overt histopathological changes. Strain-specific transmissibility was observed; WA1 and Delta viruses transmitted in a direct contact setting, whereas Delta virus was also capable of limited airborne transmission. Viral RNA was shed in exhaled air particles from all inoculated animals but was highest for Delta virus. Prior infection with SARS-CoV-2 offered varied protection against reinfection with either homologous or heterologous variants. Notable genomic variants in the spike protein were most frequently detected following WA1 and Delta virus infection. IMPORTANCE Continued surveillance and risk assessment of emerging SARS-CoV-2 variants are critical for pandemic response and preparedness. As such, in vivo evaluations are indispensable for early detection of variants with enhanced virulence and transmission. Here, we used the ferret model to compare the pathogenicity and transmissibility of an original SARS-CoV-2 isolate (USA-WA1/2020 [WA1]) to those of a panel of Alpha, Beta, and Delta variants, as well as to evaluate protection from homologous and heterologous reinfection. We observed strain-specific differences in replication kinetics in the ferret respiratory tract and virus load emitted into the air, revealing enhanced transmissibility of the Delta virus relative to previously detected strains. Prior infection with SARS-CoV-2 provided varied levels of protection from reinfection, with the Beta strain eliciting the lowest level of protection. Overall, we found that ferrets represent a useful model for comparative assessments of SARS-CoV-2 infection, transmission, and reinfection. |
Pathology and epidemiology of fatal toxoplasmosis in free-ranging marmosets (Callithrix spp.) from the Brazilian Atlantic forest
Rodrigues Oliveira A , Ritter JM , Oliveira Dos Santos D , Pizzolato de Lucena F , Aquino de Mattos S , Parente de Carvalho T , Bullock H , Giannini Alves Moreira L , Magalhães Arthuso Vasconcelos I , Barroso Costa F , Alves da Paixão T , Santos RL . PLoS Negl Trop Dis 2022 16 (9) e0010782 Toxoplasmosis is an important zoonotic disease that affects a wide range of warm-blooded host species. Neotropical primates (New World Primates; NWP) are highly susceptible, developing a lethal acute systemic disease. Toxoplasmosis in free-ranging NWP is poorly described, with only a few studies based on serosurveys. Herein we performed a retrospective study focusing on the epidemiology and pathology of toxoplasmosis among 1,001 free-ranging marmoset (Callithrix spp.) deaths from the Brazilian Atlantic Forest. This study included marmosets necropsied at the Instituto Municipal de Medicina Veterinária Jorge Vaitsman (IJV) from January 2017 to July 2019, which were found dead from all regions in the State of Rio de Janeiro. Histopathology, immunohistochemistry, and transmission electron microscopy were performed to better characterize toxoplasmosis in this free-ranging population. All samples were also tested for Yellow Fever Virus (YFV) RT-qPCR by the official diagnostic service. A total of 1,001 free-ranging marmosets were included in this study, with 16 (1.6%) cases of lethal Toxoplasma gondii infections identified both as individual cases and in outbreaks. Presence of infection was not associated with sex, age, geographical distribution, or year of death, and no co-infection with YFV was observed. The main pathological feature in these cases was random necrotizing hepatitis with detection of intralesional T. gondii zoites in all infected cases. Interstitial pneumonia rich in alveolar foamy macrophages and fibrin deposition, necrotizing myocarditis and necrotizing splenitis were also pathological features in affected marmosets. Therefore, toxoplasmosis was considered the cause of death in 1.6% of free-ranging marmosets in this retrospective series, including some cases associated with outbreaks. Necrotizing random hepatitis was a consistent pathological finding in affected cases and sampling of liver should be ensured from Callitrichid post mortem cases. |
Volume-Associated Clinical and Histopathological Effects of Intranasal Instillation in Syrian Hamsters: Considerations for Infection and Therapeutic Studies.
Forero C , Ritter JM , Seixas JN , Coleman-McCray JD , Brake M , Condrey JA , Tansey C , Welch SR , Genzer SC , Spengler JR . Pathogens 2022 11 (8) Syrian hamsters are a key animal model of SARS-CoV-2 and other respiratory viruses and are useful for the evaluation of associated medical countermeasures. Delivery of an infectious agent or intervention to the respiratory tract mirrors natural routes of exposure and allows for the evaluation of clinically relevant therapeutic administration. The data to support instillation or inoculation volumes are important both for optimal experimental design and to minimize or avoid effects of diluent alone, which may compromise both data interpretation and animal welfare. Here we investigate four intranasal (IN) instillation volumes in hamsters (50, 100, 200, or 400 µL). The animals were monitored daily, and a subset were serially euthanized at one of four pre-determined time-points (1, 3, 7, and 14 days post-instillation). Weight, temperature, oxygen saturation, CBC, radiographs, and respiratory tissue histopathology were assessed to determine changes associated with instillation volume alone. With all the delivery volumes, we found no notable differences between instilled and non-instilled controls in all of the parameters assessed, except for histopathology. In the animals instilled with 200 or 400 µL, inflammation associated with foreign material was detected in the lower respiratory tract indicating that higher volumes may result in aspiration of nasal and/or oropharyngeal material in a subset of animals, resulting in IN instillation-associated histopathology. |
Community outbreak of legionellosis associated with an indoor hot tub, New Hampshire, 2018
Daly ER , Talbot EA , Smith JC , Ritter T , McCormic ZD , Fay K , Raphael BH , Kozak-Muiznieks NA , Levinson KJ , Bean CL , Wilson RT , Morse D , Scacheri A , Linxweiler J , Chan BP . J Environ Health 2022 84 (10) 16-25 Legionellosis is an infection acquired through inhalation of aerosolized water droplets containing Legionella bacteria. In August 2018, public health officials in New Hampshire launched an investigation into a legionellosis outbreak. They identified 49 illnesses likely associated with the outbreak and implicated an improperly maintained hot tub at a hotel. The same strain of Legionella pneumophila serogroup 1 was found in both the hot tub and in samples from two patients with Legionnaires disease. The indoor hot tub vented to the outdoors, which is how some patients with confirmed legionellosis likely acquired the infection despite not entering the hotel during the incubation period. This outbreak is notable for 1) likely illness acquisition through the exterior vent of the hot tub room and 2) use of whole genome sequencing to link environmental and patient specimens. Collaboration among public health and environmental officials, laboratorians, and building managers was essential to determining the source of the outbreak and preventing further illness. 2022, National Environmental Health Association. All rights reserved. |
Influenza A virus infection and pathology in nasal and periocular tissues after ocular inoculation in ferrets
Gary JM , Ritter JM , Sun X , Maines TR , Belser JA . Vet Pathol 2022 59 (6) 3009858221109103 Influenza A viruses (IAV) cause mammalian infections following several transmission routes. Considering the anatomic proximity and connection between the nasopharynx and periocular tissues, there is a need to understand the dynamics of virus spread between these sites following both respiratory and nonrespiratory viral transmission. We examined virus distribution and associated inflammation within nasal and periocular tissues during the acute phase of H1N1 IAV infection in ferrets following intranasal or ocular inoculation. Ocular and intranasal inoculations with IAV caused comparable viral antigen distribution and inflammation in the nasal passages, though infection kinetics and magnitude differed by inoculation route. Ocular inoculation was associated with inflammation in the conjunctiva and lacrimal glands. Although intranasal inoculation was also associated with periocular inflammation, the onset was delayed relative to ocular inoculation. This work underscores the importance of investigating extrapulmonary tissues following mammalian infection with respiratory pathogens, even after intranasal inoculation. |
Multistate outbreak of Salmonella mbandaka infections linked to sweetened puffed wheat cereal-United States, 2018
Keaton AA , Schwensohn CA , Brandenburg JM , Pereira E , Adcock B , Tecle S , Hinnenkamp R , Havens J , Bailey K , Applegate B , Whitney P , Gibson D , Manion K , Griffin M , Ritter J , Biskupiak C , Ajileye K , Golwalkar M , Gosciminski M , Viveiros B , Caron G , McCullough L , Smith L , Vidyaprakash E , Doyle M , Hardy C , Elliot EL , Gieraltowski LB . Epidemiol Infect 2022 150 1-14 In May of 2018, PulseNet, the national molecular subtyping network for enteric pathogens, detected a multistate cluster of illnesses caused by an uncommon molecular subtype of Salmonella serovar Mbandaka. A case was defined as an illness in a person infected with the outbreak strain of Salmonella Mbandaka with illness onset on or after 3 March 2018 and before 1 September 2018. One-hundred thirty-six cases from 36 states were identified; 35 hospitalisations and no deaths were reported. Ill people ranged in age from <1 year to 95 years (median: 57 years). When standardised questionnaires did not generate a strong hypothesis, opened-ended interviews were performed. Sixty-three of 84 (75%) ultimately reported consuming or possibly consuming a specific sweetened puffed wheat cereal in the week before illness onset. Environmental sampling performed at the cereal manufacturing facility yielded the outbreak strain. The outbreak strain was also isolated from open cereal samples from ill people's homes and from a sealed retail sample. Due to these findings, the brand owner of the product issued a voluntary recall of the cereal on 14 June 2018. Additional investigation of the manufacturing facility identified persistent environmental contamination with Salmonella Mbandaka that was closely genetically related to other isolates in the outbreak. This investigation highlights the ability of Salmonella to survive in low-moisture environments, and the potential for prolonged outbreaks linked to products with long shelf lives and large distribution areas. |
Transmission of SARS-CoV-2 Delta variant (B.1.617.2) from a fully vaccinated human to a canine in Georgia, July 2021.
Wendling NM , Carpenter A , Liew A , Ghai RR , Gallardo-Romero N , Stoddard RA , Tao Y , Zhang J , Retchless AC , Ahmad A , Bunkley P , Godino C , Mauldin MR , Varela K , Ritter JM , Hennebelle J , Feldpausch A , Gabel J , Kainulainen MH , Herzegh O , Tong S , Spengler JR , Barton Behravesh C . Zoonoses Public Health 2022 69 (5) 587-592 SARS-CoV-2 infection has been described in a wide range of species, including domestic animals such as dogs and cats. Illness in dogs is usually self-limiting, and further diagnostics may not be pursued if clinical signs resolve or they respond to empirical treatment. As new variants emerge, the clinical presentation and role in transmission may vary in animals. This report highlights different clinical presentations and immunological responses in two SARS-CoV-2 Delta-variant-positive dogs with similar exposure to the same fully vaccinated human with a SARS-CoV-2 infection and emphasizes the need for active surveillance and additional One Health research on SARS-CoV-2 variant infections in companion animals and other species. |
Fatal human alphaherpesvirus 1 infection in free-ranging black-tufted marmosets in anthropized environments, Brazil, 2012-2019
Wilson TM , Ritter JM , Martines RB , Bullock HA , Fair P , Radford KW , Macedo IL , Sousa DER , Goncalves AAB , Romano AP , Passsos PHO , Ramos DG , Costa GRT , Cavalcante KRLJ , de Melo CB , Zaki SR , Castro MB . Emerg Infect Dis 2022 28(4) (4) 802-811 Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals. Copyright © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved. |
Multistate Outbreak of Melioidosis Associated with Imported Aromatherapy Spray.
Gee JE , Bower WA , Kunkel A , Petras J , Gettings J , Bye M , Firestone M , Elrod MG , Liu L , Blaney DD , Zaldivar A , Raybern C , Ahmed FS , Honza H , Stonecipher S , O'Sullivan BJ , Lynfield R , Hunter M , Brennan S , Pavlick J , Gabel J , Drenzek C , Geller R , Lee C , Ritter JM , Zaki SR , Gulvik CA , Wilson WW , Beshearse E , Currie BJ , Webb JR , Weiner ZP , Negrón ME , Hoffmaster AR . N Engl J Med 2022 386 (9) 861-868 Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area. |
Histopathology and localization of SARS-CoV-2 and its host cell entry receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison vison).
Ritter JM , Wilson TM , Gary JM , Seixas JN , Martines RB , Bhatnagar J , Bollweg BC , Lee E , Estetter L , Silva-Flannery L , Bullock HA , Towner JS , Cossaboom CM , Wendling NM , Amman BR , Harvey RR , Taylor D , Rettler H , Barton Behravesh C , Zaki SR . Vet Pathol 2022 59 (4) 3009858221079665 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans. |
Fatal Toxoplasma gondii myocarditis in an urban pet dog
Dorsch MA , Cesar D , Bullock HA , Uzal FA , Ritter JM , Giannitti F . Vet Parasitol Reg Stud Reports 2022 27 100659 A 70-day-old Boxer dog from a household in Montevideo, Uruguay, died after presenting neurologic, respiratory, and gastrointestinal signs for 6 days. Autopsy findings included lymphadenomegaly, ascites and hepatomegaly. Histopathology revealed severe widespread lymphohistiocytic and plasmacytic myocarditis with cardiomyocyte necrosis, mineralization and numerous intrasarcoplasmic protozoa immunoreactive with anti-Toxoplasma gondii antisera on immunohistochemistry. The protozoa were ultrastructurally confirmed as T. gondii by transmission electron microscopy. Other lesions included diffuse centrilobular hepatocellular necrosis, multifocal lymphohistiocytic portal hepatitis and interstitial nephritis. Other causes of myocarditis, including Neospora caninum, Trypanosoma cruzi, Sarcocystis neurona, canine distemper virus, and canine parvovirus were ruled out by immunohistochemistry. Toxoplasma gondii infections in dogs are usually subclinical; however, clinical disease with fatal outcome can occur. To our knowledge, this is the first report of fatal toxoplasmosis in a dog in Uruguay. This case raises awareness for dogs as sentinels and possible sources of human toxoplasmosis in urban settings in Uruguay. |
Potential Association of Legionnaires' Disease with Hot Spring Water, Hot Springs National Park and Hot Springs, Arkansas, USA, 2018-2019
James AE , Kesteloot K , Paul JT , McMullen RL , Louie S , Waters C , Dillaha J , Tumlison J , Haselow DT , Smith JC , Lee S , Ritter T , Lucas C , Kunz J , Miller LA , Said MA . Emerg Infect Dis 2022 28 (1) 44-50 Legionella pneumophila is the cause of Legionnaires' disease, a life-threatening pneumonia that occurs after inhalation of aerosolized water containing the bacteria. Legionella growth occurs in stagnant, warm-to-hot water (77°F-113°F) that is inadequately disinfected. Piped hot spring water in Hot Springs National Park, Arkansas, USA, has naturally high temperatures (>135°F) that prevent Legionella growth, and Legionnaires' disease has not previously been associated with the park or other hot springs in the United States. During 2018-2019, Legionnaires' disease occurred in 5 persons after they visited the park; 3 of these persons were potentially exposed in spa facilities that used untreated hot spring water. Environmental testing revealed Legionella bacteria in piped spring water, including 134°F stagnant pipe water. These fi ndings underscore the importance of water management programs to reduce Legionella growth in plumbing through control activities such as maintaining hot water temperatures, reducing stored water age, and ensuring adequate water flow. © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved. |
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