Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease.

Background: Q fever, brucellosis, and leptospirosis are zoonoses typically associated with terrestrial animal reservoirs. These bacterial agents are now known to infect marine mammal species, though little is known about potential human health risks from marine mammal reservoir species. We investigated potential risks of these bacteria in humans associated with marine mammal exposure. Methods: The Marine Mammal Center (TMMC) in Sausalito, California, requested a Health Hazard Evaluation by the National Institute for Occupational Safety and Health. In June 2011, an investigation occurred, which included a written questionnaire and serosurvey among workers for Coxiella burnetii, Brucella spp., and Leptospira spp., and an environmental assessment for C. burnetii. Results: Serologic evidence of past exposure was detected in 4% (C. burnetii), 0% (Brucella), and 1% (Leptospira) of 213 participants, respectively. One of 130 environmental samples tested positive for C. burnetii. No significant marine mammal-specific risk factors were identified, but some safety deficiencies were noted that could lead to a higher risk of exposure to zoonotic diseases. Conclusion: Although this study did not identify disease exposure risks associated with marine mammals, additional studies in different settings of other groups with frequent exposure to marine mammals are warranted. Some deficiencies in safety were noted, and based on these, TMMC modified protocols to improve safety. © 2024 The Authors. Public Health Challenges published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

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.

On November 7, 2022, dengue virus (DENV), which is not endemic in the continental United States (1), was identified in a Maricopa County, Arizona resident by reverse transcription–polymerase chain reaction (RT-PCR) testing at Arizona State Public Health Laboratory (ASPHL). The patient (patient A) was admitted to a hospital on October 19 for a dengue-like illness, 7 days after traveling to and remaining in Mexicali, Mexico for <4 hours. Patient A was hospitalized for 3 days and subsequently recovered. Maricopa County Environmental Services Department (MCESD) conducted retrospective testing for DENV in samples collected from 21 mosquito pools located within 5 miles (8 km) of patient A’s residence during October 1–November 3. A sample collected from one mosquito pool (pool A) on October 5 was positive for DENV. Whole genome sequencing by CDC’s Dengue Branch later revealed that closely related DENV-3 strains not known to be circulating in the patient’s travel region were identified in both patient A and pool A, suggesting local DENV transmission.

In 2020, Montana, USA, reported a large increase in Colorado tick fever (CTF) cases. To investigate potential causes of the increase, we conducted a case-control study of Montana residents who tested positive or negative for CTF during 2020, assessed healthcare providers' CTF awareness and testing practices, and reviewed CTF testing methods. Case-patients reported more time recreating outdoors on weekends, and all reported finding a tick on themselves before illness. No consistent changes were identified in provider practices. Previously, only CTF serologic testing was used in Montana. In 2020, because of SARS-CoV-2 testing needs, the state laboratory sent specimens for CTF testing to the Centers for Disease Control and Prevention, where more sensitive molecular methods are used. This change in testing probably increased the number of CTF cases detected. Molecular testing is optimal for CTF diagnosis during acute illness. Tick bite prevention measures should continue to be advised for persons doing outdoor activities.

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus which is endemic throughout most of Asia and parts of the Western Pacific [1,2]. Since the availability of a JE vaccine in the United States (U.S.) in 1993, a total of 13 JE cases in U.S. travelers or expatriates have been reported [[3], [4], [5], [6]]. We describe a case of severe JE in an unvaccinated returning traveler. | | A 37-year-old woman presented to Cleveland Clinic in Abu Dhabi, United Arab Emirates with 4 days of headache, fever and confusion. The patient is a U.S. citizen and had been living in Abu Dhabi for the past 2 years. She had returned from a 2-week vacation to Vietnam, where she primarily stayed in urban locales. However, she did participate in a 2-day hike within the Sa Pa region of Northern Vietnam, where she stayed in unscreened lodging and sustained multiple mosquito bites despite using preventive measures. She had not received the JE vaccine prior to travel. Her symptoms began while still in country on day 13 of the 14-day trip.

Coxiella burnetii is a gram-negative bacterium that is the etiologic agent of the zoonotic disease Q fever. Common reservoirs of C. burnetii include sheep, goats, and cattle. These animals shed C. burnetii into the environment, and humans are infected by inhalation of aerosols. A survey of 1622 environmental samples taken across the United States in 2006-2008 found that 23.8% of the samples contained C. burnetii DNA. To identify the strains circulating in the U.S. environment, DNA from these environmental samples was genotyped using an SNP-based approach to derive sequence types (ST) that are also compatible with multispacer sequence typing methods. Three different sequence types were observed in 31 samples taken from 19 locations. ST8 was associated with goats and ST20 with dairy cattle. ST16/26 was detected in locations with exposure to various animals and also in locations with no direct animal contact. Viable isolates were obtained for all three sequence types, but only the ST20 and ST16/26 isolates grew in acidified citrate cysteine medium (ACCM)-2 axenic media. Examination of a variety of isolates with different sequence types showed that ST8 and closely related isolates did not grow in ACCM-2. These results suggest that a limited number of C. burnetii sequence types are circulating in the U.S. environment and these strains have close associations with specific reservoir species. Growth in ACCM-2 may not be suitable for isolation of many C. burnetii strains.

Coxiella burnetii is a zoonotic pathogen that causes Q fever in humans and is transmitted primarily from infected goats, sheep, or cows. Q fever typically presents as an acute febrile illness; however, individuals with certain predisposing conditions, including cardiac valvulopathy, are at risk for chronic Q fever, a serious manifestation that may present as endocarditis. In response to a cluster of Q fever cases detected by public health surveillance, we evaluated C. burnetii infection in a community that operates a large-scale cow and goat dairy. A case was defined as an individual linked to the community with a C. burnetii phase II IgG titer ≥ 128. Of 135 participants, 47 (35%) cases were identified. Contact with or close proximity to cows, goats, and their excreta was associated with being a case (relative risk 2.7, 95% confidence interval 1.3-5.3). Cases were also identified among individuals without cow or goat contact and could be related to windborne spread or tracking of C. burnetii on fomites within the community. A history of injection drug use was reported by 26/130 (20%) participants; follow-up for the presence of valvulopathy and monitoring for development of chronic Q fever may be especially important among this population.

Valvular endocarditis has been well described in northern sea otters Enhydra lutris kenyoni of Alaska and in many cases no cause has been identified. It is also one of the most common conditions observed in people with chronic Coxiella burnetii infection. Given the high levels of C. burnetii exposure in marine mammals distributed throughout the same geographic range as the northern sea otter, and the presence of valvular lesions seen in otters, the objective of this study was to determine the level of C. burnetii exposure in otters and investigate any association between exposure, infection and valvular disease in this species. Archived serum from 75 live captured, apparently healthy otters (25 from each of 3 stocks) and 30 dead otters were tested for C. burnetii antibodies by indirect florescent antibody assay (IFA). Archived bone marrow and heart valves were tested for C. burnetii DNA by real-time PCR (qPCR). Overall, the seroprevalence in live otters was 17%, with significantly more exposed animals in the south central (40%) stock relative to the southwest (8%) and southeast (4%). The seroprevalence of animals sampled post mortem was 27%, although none of the bone marrow or heart valve samples were positive by qPCR. Results of this study failed to demonstrate a significant association between C. burnetii infection and valvular endocarditis in sea otters; however, the differing seroprevalence suggests that exposure opportunities vary geographically.

Coxiella burnetii, a Gram-negative intracellular bacterium, can give rise to Q fever in humans and is transmitted mainly by inhalation of infected aerosols from animal reservoirs. Serology is commonly used to diagnose Q fever, but the early cellular immune response-i.e., C. burnetii-specific interferon gamma (IFN-gamma) production in response to antigen challenge-might be an additional diagnostic. Detection of IFN-gamma responses has been used to identify past and chronic Q fever infections, but the IFN-gamma response in acute Q fever has not been described. By challenging immunocompetent BALB/c mice with aerosols containing phase I C. burnetii, the timing and extent of IFN-gamma recall responses were evaluated in an acute C. burnetii infection. Other cytokines were also measured in an effort to identify other potential diagnostic markers. The data show that after initial expansion of bacteria first in lungs and then in other tissues, the infection was cleared from day 10 onwards as reflected by the decreasing number of bacteria. The antigen-induced IFN-gamma production by splenocytes coincided with emergence of IgM phase II antibodies at day 10 postinfection and preceded appearance of IgG antibodies. This was accompanied by the production of proinflammatory cytokines including interleukin (IL) 6, keratinocyte-derived cytokine, and IFN-gamma-induced protein 10, followed by monocyte chemotactic protein 1, but not by IL-1beta and tumor necrosis factor alpha, and only very low production of the anti-inflammatory cytokine IL-10. These data suggest that analysis of antigen-specific IFN-gamma responses could be a useful tool for diagnosis of acute Q fever. Moreover, the current model of C. burnetii infection could be used to give new insights into immunological factors that predispose to development of persistent infection.

Little is known about the prevalence of zoonotic infections among laboratory animal care technicians (LAT). Q fever, a disease caused by Coxiella burnetii, is a known occupational hazard for persons caring for livestock. We sought to determine the seroprevalence of C. burnetii antibodies among LAT and to identify risk factors associated with C. burnetii seropositivity. A survey was administered and serum samples collected from a convenience sample of 97 LAT. Samples were screened by using a Q fever IgG ELISA. Immunofluorescent antibody assays for phase I and phase II IgG were used to confirm the status of samples that were positive or equivocal by ELISA; positive samples were titered to endpoint. Antibodies against C. burnetii were detected in 6 (6%) of the 97 respondents. In our sample of LAT, seropositivity to C. burnetii was therefore twice as high in LAT as compared with the general population. Age, sex, and working with sheep regularly were not associated with seropositivity. Risk factors associated with seropositivity included breeding cattle within respondent's research facility, any current job contact with waste from beef cattle or goats, and exposure to animal waste during previous jobs or outside of current job duties. Only 15% of responding LAT reported being aware that sheep, goats, and cattle can transmit Q fever. Research facilities that use cattle or goats should evaluate their waste-management practices and educational programs in light of these findings. Additional efforts are needed to increase awareness among LAT regarding Q fever and heightened risk of exposure to infectious materials. Physicians should consider the risk of infection with C. burnetii when treating LAT with potential occupational exposures.

Q fever is a zoonotic disease caused by inhalation of the bacterium Coxiella burnetii. Ruminant livestock are common reservoirs for C. burnetii, and bacteria present in aerosols derived from the waste of infected animals can infect humans. The significance of infection from material deposited in the environment versus transmission directly from infected animals is not known. In 2011 an outbreak of Q fever cases on farms in Washington and Montana was associated with infected goats. A study was undertaken to investigate the quantity and spatial distribution of C. burnetii in the environment of these goat farms. Soil, vacuum, and sponge samples collected on seven farms epidemiologically linked to the outbreak were tested for the presence of C. burnetii DNA by quantitative PCR. Overall, 70.1% of the samples were positive for C. burnetii. All farms had positive samples, but the quantity of C. burnetii varied widely between samples and between farms. High quantities of C. burnetii DNA were in goat housing/birthing areas, and only small quantities were found in samples collected more than 50 meters from these areas. Follow-up sampling at one of the farms one year after the outbreak found small quantities of C. burnetii DNA in air samples, and high quantities of C. burnetii persisting in soil and vacuum samples. The results suggest that highest concentrations of environmental C. burnetii are found in goat birthing areas and contamination of other areas is mostly associated with human movement.

Q fever is a zoonotic disease caused by infection with the bacterium Coxiella burnetii. Infection with C. burnetii results in humoral and cellular immune responses, both of which are thought to contribute to protection against subsequent infection. Whole-cell formalin-inactivated vaccines have also been shown to induce both humoral and cellular immunity and provide protection. Whether measurement of cellular or humoral immunity is a better indicator of immune protection is not known, and the duration of immunity induced by natural infection or vaccination is also poorly understood. To better understand the measurement and duration of C. burnetii immunity, sixteen people vaccinated against Q fever (0.2 to 10.3 years before analysis) and 29 controls with low risk of Q fever exposure were tested for immune responses to C. burnetii by an indirect fluorescent antibody test (IFA) to measure circulating antibody and by an interferon gamma release assay (IGRA) to measure cellular immunity. In vaccinated subjects, the IFA detected antibodies in 13/16, and the IGRA also detected positive responses in 13/16. All of the vaccinated subjects had a positive response in at least one of the assays, whereas 8/29 control subjects were positive in at least one assay. There was not a correlation between time since vaccination and responses in these assays. These results show that IFA and IGRA perform similarly in detection of C. burnetii immune responses, and that Q fever vaccination establishes long-lived immune responses to C. burnetii.

In 2010, Coxiella burnetii was identified at a high prevalence in the placentas of Northern fur seals (Callorhinus ursinus) collected at a single rookery on St. Paul Island Alaska; an area of the United States where the agent was not known to be present. As contamination was hypothesized as a potential cause of false positives, but nothing was known about environmental C. burnetii in the region, an environmental survey was conducted to look for the prevalence and distribution of the organism on the island. While environmental prevalence was low, two strains of the organism were identified using PCR targeting the COM1 and IS1111 genes. The two strains are consistent with the organism that has been increasingly identified in marine mammals as well as a strain type more commonly found in terrestrial environments and associated with disease in humans and terrestrial animals. Further work is needed to elucidate information regarding the ecology of this organism in this region, particularly in association with the coastal environment.

The decline in the number of northern fur seal (NFS; Callorhinus ursinus) pups on St. Paul Island, Alaska, has led to multidisciplinary research, including investigation into issues of reproductive health and success. Given the recent identification of Coxiella burnetii in the placenta of two other marine mammal species, NFS placentas were collected from Reef rookery on St. Paul Island, Alaska, during the 2010 pupping season, examined histologically, and tested for C. burnetii using polymerase chain reaction (PCR). Of 146 placentas examined, gram-negative intratrophoblastic bacteria that were positive for C. burnetii on immunohistochemistry were observed in 5 (3%) placentas. Placental infection was usually devoid of associated inflammation or significant ancillary pathology. One hundred nine (75%) of the placentas were positive for C. burnetii on PCR. C. burnetii is globally distributed and persists for long periods in the environment, providing ample opportunity for exposure of many species. The significance of this finding for the declining fur seal population, potential human exposure and infection, and impact on other sympatric marine mammal or terrestrial species is unclear; further investigation into the epidemiology of Coxiella in the marine ecosystem is warranted.

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Humans are commonly exposed via inhalation of aerosolized bacteria derived from the waste products of domesticated sheep and goats, and particularly from products generated during parturition. However, many other species can be infected with C. burnetii, and the host range and full zoonotic potential of C. burnetii is unknown. Two cases of C. burnetii infection in marine mammal placenta have been reported, but it is not known if this infection is common in marine mammals. To address this issue, placenta samples were collected from Pacific harbor seals (Phoca vitulina richardsi), harbor porpoises (Phocoena phocoena), and Steller sea lions (Eumetopias jubatus). Coxiella burnetii was detected by polymerase chain reaction (PCR) in the placentas of Pacific harbor seals (17/27), harbor porpoises (2/6), and Steller sea lions (1/2) collected in the Pacific Northwest. A serosurvey of 215 Pacific harbor seals sampled in inland and outer coastal areas of the Pacific Northwest showed that 34.0% (73/215) had antibodies against either Phase 1 or Phase 2 C. burnetii. These results suggest that C. burnetii infection is common among marine mammals in this region.

Coxiella burnetii is a gram-negative bacterium that causes the zoonotic disease Q fever. Traditionally considered an obligate intracellular agent, the requirement to be grown in tissue culture cells, embryonated eggs, or animal hosts has made it difficult to isolate strains and perform genetic studies on C. burnetii. However, it was recently demonstrated that the attenuated Nine Mile Phase 2 (NM2) C. burnetii strain will grow axenically in acidified citrate cysteine medium (ACCM) in a 2.5% oxygen environment. The current study was undertaken to determine whether more virulent C. burnetii strains could be grown in ACCM, and whether virulence would be maintained after passage. The ACCM medium supported an approximately 1000-fold expansion of Nine Mile Phase 1 (NM1), NM2, M44, and Henzerling strains of C. burnetii, whereas the Priscilla (Q177) strain expanded only 100-fold, and the K strain (Q154) grew poorly in ACCM. To determine if passage in ACCM would maintain the virulence of C. burnetii, the NM1 strain was grown for up to 26 weekly passages in ACCM. C. burnetii maintained in ACCM for 5 or 8 passages maintained full virulence in a mouse model, but NM1 passaged for 23 or 26 times was somewhat attenuated. These data demonstrate that virulent strains of C. burnetii can be successfully passaged in ACCM; however, some strains can lose virulence after extended passage, and other strains grow poorly in this medium. The loss of virulence in axenic culture was associated with some truncation of lipopolysaccharide chains, suggesting a possible mechanism for attenuation.

Coxiella burnetii is an obligate intracellular bacterium that causes the zoonotic disease Q fever. Because C. burnetii is highly infectious, can survive under a variety of environmental conditions, and has been weaponized in the past, it is classified as a select agent and is considered a potential bioweapon. The agent is known to be present in domestic livestock and in wild animal populations, but the background levels of C. burnetii in the environment have not been reported. To better understand the amount of C. burnetii present in the environment of the U.S., greater than 1,600 environmental samples were collected from 6 geographically diverse U.S. states in the years 2006-2008. DNA was purified from these samples, and the presence of C. burnetii DNA was evaluated by quantitative PCR of the IS1111 repetitive element. Overall, 23.8% of the samples were positive for C. burnetii DNA. The prevalence in the different states ranged from 6 to 44 percent. C. burnetii DNA was detected in locations with livestock and also in locations with primarily human activity (post offices, stores, schools, etc.). This study demonstrates that C. burnetii is fairly common in the environment in the U.S., and any analysis of C. burnetii after a suspected intentional release should be interpreted in light of these background levels. It also suggests that human exposure to C. burnetii may be more common than what is suggested by the number of reported cases of Q fever.

Methods for the extraction of PCR-quality DNA from environmental soil samples using pairs of commercially available kits were evaluated. Coxiella burnetii DNA was detected in spiked soil samples at <1,000 genome equivalents per gram of soil, and in 12 (16.4%) of 73 environmental soil samples.