Inferring the disruption of rabies circulation in vampire bat populations using a betaherpesvirus-vectored transmissible vaccine.

Transmissible vaccines are an emerging biotechnology that hold prospects to eliminate pathogens from wildlife populations. Such vaccines would genetically modify naturally occurring, nonpathogenic viruses ("viral vectors") to express pathogen antigens while retaining their capacity to transmit. The epidemiology of candidate viral vectors within the target wildlife population has been notoriously challenging to resolve but underpins the selection of effective vectors prior to major investments in vaccine development. Here, we used spatiotemporally replicated deep sequencing to parameterize competing epidemiological mechanistic models of Desmodus rotundus betaherpesvirus (DrBHV), a proposed vector for a transmissible vaccine targeting vampire bat-transmitted rabies. Using 36 strain- and location-specific time series of prevalence collected over 6 y, we found that lifelong infections with cycles of latency and reactivation, combined with a high R0 (6.9; CI: 4.39 to 7.85), are necessary to explain patterns of DrBHV infection observed in wild bats. These epidemiological properties suggest that DrBHV may be suited to vector a lifelong, self-boosting, and transmissible vaccine. Simulations showed that inoculating a single bat with a DrBHV-vectored rabies vaccine could immunize >80% of a bat population, reducing the size, frequency, and duration of rabies outbreaks by 50 to 95%. Gradual loss of infectious vaccine from vaccinated individuals is expected but can be countered by inoculating larger but practically achievable proportions of bat populations. Parameterizing epidemiological models using accessible genomic data brings transmissible vaccines one step closer to implementation.

Quantifying the effectiveness of betaherpesvirus-vectored transmissible vaccines.

Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is identifying viral vectors that can rapidly spread immunity through a reservoir population. Because they are broadly distributed taxonomically, species specific, and stable to genetic manipulation, betaherpesviruses are leading candidates for use as transmissible vaccine vectors. Here we evaluate the likely effectiveness of betaherpesvirus-vectored transmissible vaccines by developing and parameterizing a mathematical model using data from captive and free-living mouse populations infected with murine cytomegalovirus (MCMV). Simulations of our parameterized model demonstrate rapid and effective control for a range of pathogens, with pathogen elimination frequently occurring within a year of vaccine introduction. Our results also suggest, however, that the effectiveness of transmissible vaccines may vary across reservoir populations and with respect to the specific vector strain used to construct the vaccine.

Experimental Infections Reveal Acquired Zoonotic Capacity of Human Schistosomiasis Trough Hybridization.

We are currently witnessing the endemization of urogenital schistosomiasis in southern Europe. The incriminated parasite is a hybrid between a human parasite and a livestock parasite. Using an experimental evolutionary protocol, we created hybrid lines from pure strains of both parasite species. We showed that the host spectrum of the human parasite is enlarged to the livestock parasite after genomic introgression. We also evidenced that the tropism of the parasites within the host changes and that some hybrid lines are more virulent than the parental strains. These results engage a paradigm shift from human to zoonotic transmission of urogenital schistosomiasis.

Characterization of Mycobacterium orygis, Mycobacterium bovis, and Mycobacterium caprae Infections in Humans in Western Canada.

Epidemiologic research on zoonotic tuberculosis historically used Mycobacterium bovis as a surrogate measure, however, increased reports of human tuberculosis caused by other animal-associated Mycobacterium tuberculosis complex members like Mycobacterium orygis necessitates their inclusion. We performed a retrospective cohort study including persons infected with any animal-lineage M. tuberculosis complex species in Alberta, Canada, from January 1995 to July 2021, identifying 42 patients (20 M. bovis, 21 M. orygis, one M. caprae). Demographic, epidemiologic and clinical characteristics were compared against persons with culture-confirmed M. tuberculosis infection. The proportion of culture-positive infections caused by M. orygis increased continuously from 2016-2020. Significantly more females at a higher median age were impacted by M. orygis, with all patients originating from South Asia. M. bovis caused significantly more extra-pulmonary disease, and disproportionately impacted young females, particularly those pregnant or post-partum. All infections were acquired abroad. These findings can aid in developing targeted public health interventions.

Proteomic profiling of antibiotic-resistant Escherichia coli GW-AmxH19 isolated from hospital wastewater treated with physical plasma.

Microorganisms which are resistant to antibiotics are a global threat to the health of humans and animals. Wastewater treatment plants are known hotspots for the dissemination of antibiotic resistances. Therefore, novel methods for the inactivation of pathogens, and in particular antibiotic-resistant microorganisms (ARM), are of increasing interest. An especially promising method could be a water treatment by physical plasma which provides charged particles, electric fields, UV-radiation, and reactive species. The latter are foremost responsible for the antimicrobial properties of plasma. Thus, with plasma it might be possible to reduce the amount of ARM and to establish this technology as additional treatment stage for wastewater remediation. However, the impact of plasma on microorganisms beyond a mere inactivation was analyzed in more detail by a proteomic approach. Therefore, Escherichia coli GW-AmxH19, isolated from hospital wastewater in Germany, was used. The bacterial solution was treated by a plasma discharge ignited between each of four pins and the liquid surface. The growth of E. coli and the pH-value decreased during plasma treatment in comparison with the untreated control. Proteome and antibiotic resistance profile were analyzed. Concentrations of nitrite and nitrate were determined as long-lived indicative products of a transient chemistry associated with reactive nitrogen species (RNS). Conversely, hydrogen peroxide served as indicator for reactive oxygen species (ROS). Proteome analyses revealed an oxidative stress response as a result of plasma-generated RNS and ROS as well as a pH-balancing reaction as key responses to plasma treatment. Both, the generation of reactive species and a decreased pH-value is characteristic for plasma-treated solutions. The plasma-mediated changes of the proteome are discussed also in comparison with the Gram-positive bacterium Bacillus subtilis. Furthermore, no effect of the plasma treatment, on the antibiotic resistance of E. coli, was determined under the chosen conditions. The knowledge about the physiological changes of ARM in response to plasma is of fundamental interest to understand the molecular basis for the inactivation. This will be important for the further development and implementation of plasma in wastewater remediation.

Neuroinvasive Francisella tularensis Infection: Report of 2 Cases and Review of the Literature.

BACKGROUND: Neuroinvasive infection with Francisella tularensis, the causative agent of tularemia, is rare. Establishing clinical suspicion is challenging if risk factors or clinical features classically associated with tularemia are absent. Tularemia is treatable with antibiotics; however, there are limited data to inform management of potentially fatal neuroinvasive infection. METHODS: We collected epidemiologic and clinical data on 2 recent US cases of neuroinvasive F. tularensis infection, and performed a literature review of cases of neuroinvasive F. tularensis infection published after 1950. RESULTS: One patient presented with focal neurologic deficits and brain lesions; broad-range molecular testing on resected brain tissue detected F. tularensis. The other patient presented with meningeal signs; tularemia was suspected based on animal exposure, and F. tularensis grew in cerebrospinal fluid (CSF) culture. Both patients received combination antibiotic therapy and recovered from infection. Among 16 published cases, tularemia was clinically suspected in 4 cases. CSF often displayed lymphocytic pleocytosis. Among cases with available data, CSF culture was positive in 13 of 16 cases, and F. tularensis antibodies were detected in 11 of 11 cases. Treatment typically included an aminoglycoside combined with either a tetracycline or a fluoroquinolone. Outcomes were generally favorable. CONCLUSIONS: Clinicians should consider neuroinvasive F. tularensis infection in patients with meningitis and signs suggestive of tularemia or compatible exposures, lymphocyte-predominant CSF, unrevealing standard microbiologic workup, or lack of response to empiric bacterial meningitis treatment. Molecular testing, culture, and serologic testing can reveal the diagnosis. Favorable outcomes can be achieved with directed antibiotic treatment.

Tularemia From Veterinary Occupational Exposure.

Tularemia is a disease caused by Francisella tularensis, a highly infectious bacteria that can be transmitted to humans by direct contact with infected animals. Because of the potential for zoonotic transmission of F. tularensis, veterinary occupational risk is a concern. Here, we report on a human case of tularemia in a veterinarian after an accidental needlestick injury during abscess drainage in a sick dog. The veterinarian developed ulceroglandular tularemia requiring hospitalization but fully recovered after abscess drainage and a course of effective antibiotics. To systematically assess veterinary occupational transmission risk of F. tularensis, we conducted a survey of veterinary clinical staff after occupational exposure to animals with confirmed tularemia. We defined a high-risk exposure as direct contact to the infected animal's body fluids or potential aerosol inhalation without use of standard personal protective equipment (PPE). Survey data included information on 20 veterinary occupational exposures to animals with F. tularensis in 4 states. Veterinarians were the clinical staff most often exposed (40%), followed by veterinarian technicians and assistants (30% and 20%, respectively). Exposures to infected cats were most common (80%). Standard PPE was not used during 80% of exposures; a total of 7 exposures were categorized as high risk. Transmission of F. tularensis in the veterinary clinical setting is possible but overall risk is likely low. Veterinary clinical staff should use standard PPE and employ environmental precautions when handling sick animals to minimize risk of tularemia and other zoonotic infections; postexposure prophylaxis should be considered after high-risk exposures to animals with suspected or confirmed F. tularensis infection to prevent tularemia.

Human Passage of Schistosoma incognitum, Tamil Nadu, India, and Review of Autochthonous Schistosomiasis, South Asia.

A fecal survey in Tamil Nadu, India, revealed 2 persons passed schistosome eggs, later identified as Schistosoma incognitum, a parasite of pigs, dogs, and rats. We investigated those cases and reviewed autochthonous schistosomiasis cases from India and Nepal. Whether the 2 new cases represent true infection or spurious passage is undetermined.

Macacine alphaherpesvirus 1 (B Virus) Infection in Humans, Japan, 2019.

Two human patients with Macacine alphaherpesvirus 1 infection were identified in Japan in 2019. Both patients had worked at the same company, which had a macaque facility. The rhesus-genotype B virus genome was detected in cerebrospinal fluid samples from both patients.

Taenia martis Neurocysticercosis-Like Lesion in Child, Associated with Local Source, the Netherlands.

A neurocysticercosis-like lesion in an 11-year-old boy in the Netherlands was determined to be caused by the zoonotic Taenia martis tapeworm. Subsequent testing revealed that 15% of wild martens tested in that region were infected with T. martis tapeworms with 100% genetic similarity; thus, the infection source was most likely local.

Seasonal Patterns of Mpox Index Cases, Africa, 1970-2021.

Across 133 confirmed mpox zoonotic index cases reported during 1970-2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.

Emergence of Thelaziosis Caused by Thelazia callipaeda in Dogs and Cats, United States.

We report 2 autochthonous feline thelaziosis cases caused by the eyeworm Thelazia callipaeda and discuss the spread among dogs in the northeastern United States. Phylogenetic analysis suggests the parasite was introduced from Europe. Adopting a One Health approach is needed to limit further spread of T. callipaeda eyeworms in North America.

Delayed Diagnosis of Locally Acquired Lyme Disease, Central North Carolina, USA.

Healthcare providers in North Carolina, USA, have limited experience diagnosing and managing Lyme disease because few cases occur annually statewide. We outline the prolonged diagnostic course for a patient with locally acquired Lyme disease in North Carolina. This case highlights the need for greater awareness and professional education.

Crimean-Congo Hemorrhagic Fever Virus Diversity and Reassortment, Pakistan, 2017-2020.

Sporadic cases and outbreaks of Crimean-Congo hemorrhagic fever (CCHF) have been documented across Pakistan since 1976; however, data regarding the diversity of CCHF virus (CCHFV) in Pakistan is sparse. We whole-genome sequenced 36 CCHFV samples collected from persons infected in Pakistan during 2017-2020. Most CCHF cases were from Rawalpindi (n = 10), followed by Peshawar (n = 7) and Islamabad (n = 4). Phylogenetic analysis revealed the Asia-1 genotype was dominant, but 4 reassorted strains were identified. Strains with reassorted medium gene segments clustered with Asia-2 (n = 2) and Africa-2 (n = 1) genotypes; small segment reassortments clustered with the Asia-2 genotype (n = 2). Reassorted viruses showed close identity with isolates from India, Iran, and Tajikistan, suggesting potential crossborder movement of CCHFV. Improved and continuous human, tick, and animal surveillance is needed to define the diversity of circulating CCHFV strains in Pakistan and prevent transmission.

Nephropathia Epidemica Caused by Puumala Virus in Bank Voles, Scania, Southern Sweden.

In 2018, a local case of nephropathia epidemica was reported in Scania, southern Sweden, more than 500 km south of the previously known presence of human hantavirus infections in Sweden. Another case emerged in the same area in 2020. To investigate the zoonotic origin of those cases, we trapped rodents in Ballingslöv, Norra Sandby, and Sörby in southern Sweden during 2020‒2021. We found Puumala virus (PUUV) in lung tissues from 9 of 74 Myodes glareolus bank voles by screening tissues using a hantavirus pan-large segment reverse transcription PCR. Genetic analysis revealed that the PUUV strains were distinct from those found in northern Sweden and Denmark and belonged to the Finnish PUUV lineage. Our findings suggest an introduction of PUUV from Finland or Karelia, causing the human PUUV infections in Scania. This discovery emphasizes the need to understand the evolution, cross-species transmission, and disease outcomes of this newly found PUUV variant.

Case Management of Imported Crimean-Congo Hemorrhagic Fever, Senegal, July 2023.

We report an imported Crimean-Congo hemorrhagic fever case in Senegal. The patient received PCR confirmation of virus infection 10 days after symptom onset. We identified 46 patient contacts in Senegal; 87.7% were healthcare professionals. Strengthening border crossing and community surveillance systems can help reduce the risks of infectious disease transmission.

Detection of Rat Hepatitis E Virus in Pigs, Spain, 2023.

We identified rat hepatitis E virus (HEV) RNA in farmed pigs from Spain. Our results indicate that pigs might be susceptible to rat HEV and could serve as viral intermediaries between rodents and humans. Europe should evaluate the prevalence of rat HEV in farmed pigs to assess the risk to public health.

Autochthonous Ascariasis, Mississippi, USA.

We describe a case of a 2-year-old child who expelled a single adult female Ascaris lumbricoides worm. The patient is from a rural county in Mississippi, USA, with no reported travel outside of the United States. The caregivers in the home practice good sanitation. Exposure to domestic pigs is the likely source of infection.

Seroprevalence of Avian Influenza A(H5N6) Virus Infection, Guangdong Province, China, 2022.

In 2022, we assessed avian influenza A virus subtype H5N6 seroprevalence among the general population in Guangdong Province, China, amid rising numbers of human infections. Among the tested samples, we found 1 to be seropositive, suggesting that the virus poses a low but present risk to the general population.

Emergence of Bluetongue Virus Serotype 3, the Netherlands, September 2023.

Since 1998, notifiable bluetongue virus (BTV) serotypes 1-4, 6, 8, 9, 11, and 16 have been reported in Europe. In August 2006, a bluetongue (BT) outbreak caused by BTV serotype 8 began in northwestern Europe. The Netherlands was declared BT-free in February 2012, and annual monitoring continued. On September 3, 2023, typical BT clinical manifestations in sheep were notified to the Netherlands Food and Product Safety Consumer Authority. On September 6, we confirmed BTV infection through laboratory diagnosis; notifications of clinical signs in cattle were also reported. We determined the virus was serotype 3 by whole-genome sequencing. Retrospective analysis did not reveal BTV circulation earlier than September. The virus source and introduction route into the Netherlands remains unknown. Continuous monitoring and molecular diagnostic testing of livestock will be needed to determine virus spread, and new prevention strategies will be required to prevent BTV circulation within the Netherlands and Europe.