Cases Of Human Infection Research Articles

Re-identification and Characterization of Multidrug-Resistant Corynebacterium haemomassiliense-Like Organisms from Humans

Recently, non-diphtheriae Corynebacterium spp. have been increasingly reported in patients. In addition, several novel species of Corynebacterium isolated from humans. Here, we report two cases of human infections caused by Corynebacterium haemomassiliense-like organisms, which had not been identified at the species level by MALDI-TOF MS analysis. They were revealed to be closely related to C. haemomassiliense, a recently described species by three housekeeping genes (16S rRNA, rpoB, and gyrA) and phenotypic features. Both strains were multidrug-resistant but susceptible to vancomycin, meropenem, and linezolid. Our report suggests that human infections by the recently described Corynebacterium species may not be limited to a specific region, in addition to difficulty of classifying the genus Corynebacterium.

Classification and ranking of shigatoxin-producing Escherichia coli (STEC) genotypes detected in food based on potential public health impact using clinical data

Risk classification and management of shigatoxin-producing E. coli (STEC) isolated from food has been hampered by gaps in knowledge about the properties that determine the extent to which different subtypes of STEC can cause severe disease. Data on the proportion of infected human cases being affected by severe illness enables an evaluation of existing approaches for classifying STEC strains and the development of a new public health based approach. Evaluations show that existing approaches do not unequivocally classify different STEC variants according to their ability to cause severe disease. A new approach for ranking of STEC genotypes, combining the estimated probability of the strain to cause severe illness with the public health burden associated with the illness in terms of DALY per case, address these limitations. The result is a list of STEC genotypes in descending order of potential public health burden per case. The approach is risk based in considering the probability and consequences following infection (severe illness), and can support transparent risk management. This is illustrated by, arbitrarily, separating the ranked list of genotypes into classes based on the potential public health burden, and by characterising collections of strains isolated from different foods into different classes. Further, the classification of food samples as satisfactory or not based on the cost in terms of proportion of food being rejected and the benefit in terms of the proportion of strains causing severe illness (HUS) that are being captured is demonstrated using this approach.

Microvirgula curvata as a Cause of Ventriculoperitoneal Shunt Infection

Abstract Microvirgula curvata is a small Gram-negative, curved rod first isolated from hydrocarbon-contaminated soil in Kuwait (Subhash et al. Int J Syst Evol Microbiol 2016;66:5309–5313). We describe the first known case of human infection with M. curvata in a 65-year-old man with a ventriculoperitoneal shunt.

Epidemiological aspects of pediculosis in Astrakhan region

Objective. To study and describe the clinical and epidemiological aspects of pediculosis in residents of Astrakhan Region for 20162020.
 Materials and methods. In total, 1202553 cases of human infection with infectious and parasitic diseases were registered in Astrakhan Region during the analyzed period, of which pediculosis accounted for 0.4 % of all infectious diseases and 35.1 % (5380 cases) of all parasitic infestations. Cases of pediculosis were recorded in all age groups including children, who accounted for 74.6 % (4015 cases).
 Results. Considering the number of registered cases of pediculosis for the period of 20162020, the largest number of cases was noted in 20162019 and amounted to 89 % (4789 cases). Cases of pediculosis have been recorded in both urban and rural areas. In total, 41.3 % (2220) cases of pediculosis were registered in the rural areas of Astrakhan Region during the analyzed period, of which the proportion of children was 77.7 % (1724 cases) of all registered cases of pediculosis in the rural areas and 42.9 % of all cases of pediculosis registered in children. The incidence of the urban residents is 1.4 times higher than that of the rural ones and is 58.7 % (3160 cases), of which the child population is 72.5 % (2291 people) of all cases of pediculosis registered in the urban areas and 57.1 % of all cases of pediculosis in children.
 Conclusions. The epidemiological situation regarding pediculosis in Astrakhan Region remains very tense, as evidenced by the above indicators. The incidence of the urban residents is 1.4 times higher than that of the rural in Astrakhan Region. The most frequent cases of pediculosis are registered in children due to a large crowding of patients in various educational institutions, or epidemic outbreak in the class or school.
 The results of the study. Considering the number of registered cases of pediculosis for the period 2016-2020, the largest number of cases was noted in 2016-2019 and amounted to 89% (4789 cases).
 Cases of pediculosis have been recorded in both urban and rural areas. In total, 41.3% (2,220) cases of pediculosis were registered in rural areas of the Astrakhan region during the analyzed period, of which the proportion of children was 77.7% (1,724 cases) of all registered cases of pediculosis in rural areas and 42.9% of all cases of pediculosis registered in children.
 The incidence of urban residents is 1.4 times higher than that of rural residents and is 58.7% (3160 cases), of which the child population is 72.5% (2291 people) of all cases of pediculosis registered in urban areas and 57.1% of all cases of pediculosis in children.
 Conclusions. The epidemiological situation of pediculosis in the Astrakhan region remains very tense, as evidenced by the above indicators. The incidence of urban residents is 1.4 times higher than that of residents of rural areas of the Astrakhan region. The most frequent cases of pediculosis are registered in children, which may be due to a large crowding of patients in various educational institutions, or there may be an epidemic outbreak in the classroom or school.

Review of the epidemiological situation on Anthrax around the world and the Forecast for Kyrgyzstan

This review, prepared on the basis of WHO materials and from medical websites, and monographs by domestic and foreign researchers, provides information on cases of infection of humans and animals with anthrax in the world. The epidemiological situation for this especially dangerous infection remains quite complicated and is assessed as tense and does not tend to stabilize due to the existence of soil foci, which manifest themselves for many years as periodic outbreaks among farm animals and people. Cutaneous anthrax is an extremely preventable disease, yet still accounts for 95% of all anthrax cases, and has left many regions endemic. The objectives of this study was to review published outbreak investigations for cutaneous anthrax, while examining the current and new risk factors, as well as the present control measures and their effectiveness at preventing future outbreaks. A literature search of articles was performed using PubMed, Google Scholar, and New England Journal of Medicine, website of WHO, (HAW HamburgLibrary). Articles in English and pertaining to human subjects only, were retrieved. Seven articles included in this study examined sources of outbreak for cutaneous anthrax, investigated suspected cases using clinical diagnosis and surveys, and evaluated current control measures. Three studies reported relative risk, suggesting there is a likely association between butchering sick animals and infection. Further findings suggested a correlation between an individual's socioeconomic status and the likelihood of contracting anthrax. Additionally, the quality of livestock in the area can have a cyclical nature on cutaneous anthrax infections among humans. The cumulative evidence concludes that an improvement of surveillance and control measures is needed in endemic regions, and future investigation of new risk factors is required. Anthrax is a highly dangerous zoonotic infectious disease, the causative agent of which is the Gram-positive spore-forming bacterium Bacillus anthracis, which belongs to the pathogenicity group II. Almost all types of warm-blooded animals, including humans, are susceptible to anthrax. For herbivores, the source of infection is soil containing B. anthracis spores. The high resistance of anthrax spores to environmental factors, the ability to persist in the soil for a long time, and under certain conditions to pass into a vegetative form, makes the fight against this infection an extremely difficult task for medicine and veterinary medicine. A person becomes infected by household contact from contaminated objects of animal origin, and from 2,000 to 20,000 people fall ill every year in the world. Although anthrax is well controlled in the developed countries, anthrax remains of a global concern because B. anthracis spores can potentially be used as a biological weapon. On the other hand, some local anthrax outbreak has been recorded in western countries. For example, a case of naturallyacquired inhalation anthrax was reported in London, 2008 and another case was recorded in Scotland in 2006. Both cases were bongo drummers/drum makers who used imported animal hides. As of 14 January 2010, a total of 14 con- firmed cases of anthrax infection in Scotland were reported and 7 of these died. All cases were heroin user. Possible source of infection is said that heroin is transported in animal skin. In developed countries, there is also an infection risk after contact with a commercial product prepared from inadequately treated wool or leather. Products made from contaminated hair (e.g. shaving brush, wool coat), skins (e.g. drums, drumheads made from animal skin), and bone meal (e.g. fertilizer) may continue to be sources of infection for many years. A review of the epidemiological situation on anthrax in the world for 2021 was carried out. In Kyrgyzstan, eight cases of human infection with the cutaneous form of anthrax were registered in the Suzak district of the Jalal-Abad region and 7 cases in the Aksy district. Epizootics of anthrax among farm and wild animals have been identified mainly in the countries of Central Asia, with the largest number of confirmed human cases detected in Kyrgyzstan. Infection of people with the causative agent of anthrax is associated primarily with the ingestion of the meat of sick and dead anthrax animals, contact with animals during forced slaughter, skinning, and processing of contaminated meat. The level of incidence of anthrax in the territory of Kyrgyzstan in 2021 will be determined by a set of planned volumes of preventive measures and, subject to their proper implementation, will be limited to the detection of sporadic cases of infection that are potentially possible within certain regions of Kyrgyzstan.

Comprehensive Review of Emergence and Virology of Tickborne Bourbon Virus in the United States.

Abstract The emergence of SARS-CoV-2 and the worldwide COVID-19 pandemic triggered considerable attention to the emergence and evolution of novel human pathogens. Bourbon virus (BRBV) was first discovered in 2014 in Bourbon County, Kansas, USA. Since its initial discovery, several cases of BRBV infection in humans have been identified in Kansas, Oklahoma, and Missouri. BRBV is classified within the Thogotovirus genus; these negative-strand RNA viruses appear to be transmitted by ticks, and much of their biology remains unknown. In this review, we describe the emergence, virology, geographic range and ecology, and human disease caused by BRBV and discuss potential treatments for active BRBV infections. This virus and other emerging viral pathogens remain key public health concerns and require continued surveillance and study to mitigate human exposure and disease.

Human immunodeficiency virus infection in pregnant women and its correlation with socioeconomic determinants.

To analyze the spatial pattern of human immunodeficiency virus infection in pregnant women and its correlation with socioeconomic determinants. Ecological study, carried out with cases of human immunodeficiency virus infection in pregnant women in the state of Pará, Brazil, from 2010 to 2017. Rate analysis was performed using the empirical Bayesian method and univariate local Moran. Bivariate analyses were used to examine the correlation between infection and socioeconomic determinants. High rates of infection were observed in municipalities in the mesoregions of Southeast of Pará and Metropolitan area of Belém. A significant spatial correlation was found between human immunodeficiency virus infection rates in pregnant women and human development index indicators (I = 0.2836; p < 0.05), average income (I = 0.6303; p < 0.05), and illiteracy rate (I = 0.4604; p < 0.05). The spatial pattern of human immunodeficiency virus infection in pregnant women correlated to socioeconomic determinants highlights the need to restructure public policies for the control and prevention of AIDS virus that take into account the socioeconomic factors of this specific population and locoregional disparities in Pará.

Echinococcus granulosus. Клинический случай

Echinococcosis is a serious problem for modern mankind. This disease has no specific clinical manifestations, but its complications can be fatal. Echinococcus granulosus is endemic for the Astrakhan Region. Every year, the number of cases of human infection with Echinococcus granulosus is increasing on the Astrakhan Region territory. Most often Echinococcus granulosus cysts are found in the liver (85%) and lung (up to 15%). The heart (only 0.4–2%), spleen, kidneys, and brain are damaged much less frequently (1–5% for all locations). The article presents a clinical case of a patient with echinococcosis of the heart and aorta, brain caused by Echinococcus granulosus.

Entomological Surveillance Activities in Regions in Greece: Data on Mosquito Species Abundance and West Nile Virus Detection in Culex pipiens Pools (2019-2020).

Human cases of West Nile virus (WNV) infections have been recorded in Greece since 2010, with seasonal outbreaks (summer-autumn) on an almost annual basis, caused mainly by the WNV lineage 2 strain (Nea Santa-Greece-2010). National Public Health Organization (NPHO) in Greece is annually implementing enhanced surveillance of human WNV infection, in order to promptly identify human cases of WNV infection and monitor distribution in terms of time and place. Entomological surveillance activities were carried out on a national basis in 2019 and 2020, under NPHO coordination and the collaboration of several private subcontractors, along with the Unit of Medical Entomology, Laboratory for Surveillance of Infectious Diseases (LSID). The aim was to monitor mosquito species composition, abundance, and WNV circulation in mosquito pools of Culex pipiens s.l. species. Adult mosquito traps were placed in selected sites; collected samples were morphologically characterized and pooled by date of collection, location, and species types. Female Culex pipiens s.l. pools were tested for WNV and WNV infection rates (MIR and MLE) were estimated. Highest mean number of female Culex pipiens s.l. species was recorded in Central Macedonia both for 2019 and 2020. Six hundred and fifty-nine mosquito pools (147 in 2019 and 512 in 2020) of female Culex pipiens s.l. were examined for WNV presence. The highest MLE was detected in Western Macedonia in 2019 and in Thessaly in 2020. Here, we present data on the mosquito species composition in the studied areas and WNV detection in mosquitoes from areas in Greece where the specific national mosquito surveillance program was implemented, for two years, 2019 and 2020.

Severe Human Case of Zoonotic Infection with Swine-Origin Influenza A Virus, Denmark, 2021.

During routine surveillance at the National Influenza Center, Denmark, we detected a zoonotic swine influenza A virus in a patient who became severely ill. We describe the clinical picture and the genetic characterization of this variant virus, which is distinct from another variant found previously in Denmark.

Differential Impact of Specific Amino Acid Residues on the Characteristics of Avian Influenza Viruses in Mammalian Systems.

Avian influenza virus (AIV) H9N2 was declared to be endemic in birds of the Middle East, in particular in Egypt, with multiple cases of human infections. Despite concerns about the pandemic threat posed by H9N2 AIV, due to the fact that its receptor specificity is similar to that of human influenza viruses, its morbidity and mortality rates in humans are so far negligible. However, the acquisition of specific adaptive amino acid (aa) mutations in the viral polymerase can enhance cross-species transmission of the virus itself or of reassortants, which gained these changes. The polymerase basic protein 2 (PB2) is one of the key determinants for AIV adaptation towards mammals. Although mammalian pathogenicity-related mutations (MPMs) in PB2 genes were identified in different AIVs, the specific effect of single or multiple mutations on viral fitness has not been compared so far. Here, we studied the effect of the aa K at position 591, which was frequently reported in the PB2 of Egyptian H9N2 isolates, on the proliferation efficiency and polymerase activity of an H5N1 (clade 2.2.1.2) AIV already carrying the mammalian adaptive mutation 627K. Using reverse genetics, we generated a set of recombinant parental strains and H5N1 variants carrying the avian-like 591Q/627E or mammalian-like adaptive mutations 591K/627K (H5N1EGY, H9N2EGY, H5N1PB2-H9N2EGY, H5N1H9N2_PB2_K591Q, H5N1PB2_K627E, H5N1PB2_K627E/591K, H5N1PB2_627K/591K). Regardless of the avian-like 627E or the mammalian-adaptive 627K, both variants carrying the 591K (H5N1PB2_K627E/591K, H5N1PB2_627K/591K) and the reassortant H5N1PB2-H9N2EGY replicated to significantly higher levels in mammalian continuous MDCK and Calu-3 cell lines and primary normal human bronchial epithelial cells than the parental H5N1EGY virus (carrying solely the 627K adaptive mutation). Expectedly, the H5N1 variants carrying avian-like PB2 mutations (H5N1H9N2_PB2_K591Q, H5N1PB2_K627E) replicated to significantly lower levels than the parental H5N1EGY virus in the predefined primary and continuous mammalian cell line systems. Consistently, the activity of H5N1 subtype AIV polymerase complexes comprising PB2 segments with singular 591K or combined with 627K was significantly enhanced when compared to parental H5N1EGY and H9N2EGY. This study emphasizes the significant impact of 591K containing PB2 segments in the background of H5N1 polymerase on viral fitness in addition to the well-known MPM 627K in vitro.

Antiviral Treatment against Monkeypox: A Scoping Review.

During the COVID-19 pandemic, the increase in reports of human monkeypox virus infection cases spreading in many countries outside Africa is a major cause for concern. Therefore, this study aimed to explore the evidence of antiviral pharmacotherapy available for the treatment of adult patients with monkeypox. A scoping review of the literature was conducted using PubMed, Scopus, Web of Science, Embase, and CENTRAL databases until 12 September 2022. The key search terms used were "monkeypox" and "treatment". A total of 1927 articles were retrieved using the search strategy. After removing duplicates (n = 1007) and examining by title, abstract, and full text, 11 studies reporting case reports of monkeypox with antiviral treatment were included, detailing the number of monkeypox cases, clinical manifestations, number of participants with antiviral treatment, history of sexually transmitted diseases, method of diagnosis, location of skin lesions, drugs used in antiviral treatment, route of administration, and outcome. A total of 1281 confirmed cases of monkeypox have been reported, of which 65 monkeypox cases had antiviral treatment distributed most frequently in the United States (n = 30), the United Kingdom (n = 6), and Spain (n = 6). Of the total cases, 1269 (99.1%) were male with an age range of 18 to 76 years, and 1226 (95.7%) had a sexual behavior of being men who have sex with men. All confirmed cases of monkeypox were diagnosed by reverse transcriptase polymerase chain reaction (RT-PCR). The most frequent clinical manifestations were skin lesions, fever, lymphadenopathy, headache, fatigue, and myalgia. The most frequent locations of the lesions were perianal, genital, facial, and upper and lower extremities. The most commonly used drugs for antiviral treatment of monkeypox were: tecovirimat, cidofovir, and brincidofovir. All patients had a complete recovery. According to current evidence, the efficacy and safety of antiviral drugs against monkeypox is of low quality and scarce.

Immunological signature in human cases of monkeypox infection in 2022 outbreak: an observational study

An unprecedented global monkeypox outbreak started in May, 2022. No data are yet available about the dynamics of the immune response against monkeypox virus. The aim of this study was to describe kinetics of T-cell response, inflammatory profile, and pox-specific T-cell induction in patients with laboratory-confirmed monkeypox. 17 patients with laboratory-confirmed monkeypox admitted at the Lazzaro Spallanzani National Institute for Infectious Diseases (Rome, Italy), from May 19, to July 7, 2022, were tested for differentiation and activation profile of CD4 and CD8 T (expression of CD38, PD-1, and CD57 assessed by flow cytometry), frequency of pox-specific T cells (by standard interferon-γ ELISpot), and release of interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor (TNF) in plasma (by ELISA). All patients were tested 10-12 days after symptoms onset. In a subgroup of nine patients with a laboratory-confirmed monkeypox, the kinetics of the immune response were analysed longitudinally according to timing from symptoms onset and compared with ten healthy donors (ie, health-care workers recruited from the same institution). Among the 17 patients, ten were HIV negative and seven HIV positive, all with good viro-immunological status. On days 0-3 from symptom onset, patients with laboratory-confirmed monkeypox were characterised by a statistically significant reduction in CD4+ T cells (p=0·0011) and a concurrent increase of CD8+ T cells (p=0·0057) compared with healthy donors. A lower proportion of naive (CD45RA+CD27+) CD4+ T cells was observed in six (67%) of nine patients and a concomitant higher proportion of effector memory (CD45RA-CD27-) CD4+ T cells in all patients; this skewed immune profile tended to normalise over time. A similar differentiated profile was also observed in CD8+ T cells with a consistent expansion of terminally differentiated CD8+ T cells. Patients with monkeypox had a higher proportion of CD4+CD38+ and CD38+CD8+ T-cells than healthy donors, which normalised after 12-20 days from symptom onset. The expression of PD-1 and CD57 on CD4+ and CD8+ T-cells showed kinetics similar to that observed for CD38. Furthermore, the inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF) were higher in patients with monkeypox than in healthy donors and, although they decreased over time, they remained elevated after recovery. Almost all patients (15 [94%] of 16) developed a pox-specific Th1 response. No differences in immune cells profile were observed between patients with and without HIV, whereas paucysimptomatic patients (without systemic symptoms, with less than five skin lesions, and no other mucosal localisation of monkeypox) showed a less perturbed immune profile early after symptom onset. Our data showed the immunological signature of monkeypox virus infection, characterised by an early expansion of activated effector CD4+ and CD8+ T cells that persisted over time. Almost all patients, even regardless of HIV infection, developed a poxvirus-specific Th1 cell response. These results might have implications on the expected immunogenicity of monkeypox vaccination, suggesting that it might not be necessary to vaccinate people who have already been infected. Italian Ministry of Health. For the Italian translation of the abstract see Supplementary Materials section.

Rapid spread of a new West Nile virus lineage 1 associated with increased risk of neuroinvasive disease during a large outbreak in northern Italy, 2022: One Health analysis.

A new strain of WNV lineage 1 (WNV - 1) emerged in the Veneto Region, northern Italy, in 2021, eight years after the last outbreak of WNV - 1 in Italy. The virus, which co-circulates with WNV-2, has become endemic in the Region, where, in 2022, most human cases of neuroinvasive disease (WNND) reported in Europe have occurred. Comparative analysis of the epidemiology and clinical presentation of WNV-1 and WNV-2 infection in humans, as well as the temporal and geographic distribution of WNV-1 and WNV-2 among wild birds and Culex pipiens mosquitoes in Veneto, from May 16th to August 21st, 2022, to determine if the high number of WNND cases was associated with WNV-1. As of August 21st, 2022, 222 human cases of WNV infection were confirmed by molecular testing, including 103 with fever (WNF) and 119 with WNND. WNV lineage was determined in 201 (90.5%) cases, comprising 138 WNV-1 and 63 WNV-2 infections. During the same period, 35 blood donors tested positive, including 30 in whom WNV lineage was determined (13 WNV-1 and 17 WNV-2). Comparative analysis of the distribution of WNV-1 and WNV-2 infections among WNND cases, WNF cases and WNV-positive blood donors showed that patients with WNND were more likely to have WNV-1 infection than blood donors (odds ratio 3.44; 95% CI 95% 1.54 to 8.24; p = 0.0043). As observed in humans, in wild birds WNV-1 had higher infectious rate (IR) and showed a more rapid expansion than WNV-2. At variance, the distribution of the two lineages was more even in mosquitoes, but with a trend of rapid increase of WNV-1 IR over WNV-2. Comparative analysis of WNV-1 vs WNV-2 infection in humans, wild birds, and mosquitos showed a rapid expansion of WNV-1 and suggested that WNV-1 infected patients might have an increased risk to develop severe disease.

In planta Production and Validation of Neuraminidase Derived from Genotype 4 Reassortant Eurasian Avian-like H1N1 Virus as a Vaccine Candidate.

Influenza viruses are a major public health threat that causes repetitive outbreaks. In recent years, genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 (G4 EA H1N1) has garnered attention as a potential novel pandemic strain. The necessity of developing vaccines against G4 EA H1N1 is growing because of the increasing cases of human infection and the low cross-reactivity of the strain with current immunity. In this study, we produced a G4 EA H1N1-derived neuraminidase (G4NA) as a vaccine candidate in Nicotiana benthamiana. The expressed G4NA was designed to be accumulated in the endoplasmic reticulum (ER). The M-domain of the human receptor-type tyrosine-protein phosphatase C was incorporated into the expression cassette to enhance the translation of G4NA. In addition, the family 3 cellulose-binding module and Brachypodium distachyon small ubiquitin-like modifier sequences were used to enable the cost-effective purification and removal of unnecessary domains after purification, respectively. The G4NA produced in plants displayed high solubility and assembled as a tetramer, which is required for the efficacy of an NA-based vaccine. In a mouse immunization model, the G4NA produced in plants could induce significant humoral immune responses. The plant-produced G4NA also stimulated antigen-specific CD4 T cell activation. These G4NA vaccine-induced immune responses were intensified by the administration of the antigen with a vaccine adjuvant. These results suggest that G4NA produced in plants has great potential as a vaccine candidate against G4 EA H1N1.

Rhamnose-Positive Strains of Plague Agent: Virulence and Epidemiological Significance

The aim of the review is to show the groundlessness of the unconditional assessment of rhamnose-positive strains of plague pathogen as avirulent for most species of carriers and humans and having no epidemiological significance. The main carriers of rhamnose-positive strains are several species of voles and the Mongolian pika. The vast majority of experts are of the opinion that rhamnose-positive (“vole`s” and “pika`s”) strains of Yersinia pestis are avirulent or weakly virulent for many species of warm-blooded animals and humans, and therefore have no epidemiological significance. However, in a series of experiments on infecting marmots, ground squirrels, and large gerbils with rhamnose-positive strains, some of the experimental animals fell ill acutely and died from the plague. In nature, rhamnose-positive strains have been isolated from carcasses of relatively resistant red marmots. When evaluating the epidemiological significance of rhamnose-positive strains, such an important criterion as the presence or absence of effective factors and pathways of pathogen transmission in foci of the vole and pika types is omitted. Voles and pikas are not eaten; therefore, the contact route of infecting humans in these foci is impossible. The second way of transmission of the pathogen to humans – vector-borne – is difficult due to the lack of migration of vole fleas from burrows to the surface and their low efficiency as vectors. Nevertheless, cases of human infection with rhamnose-positive strains of the plague agent in the Caucasus and Mongolia give grounds to assert that at least some rhamnose-positive strains have a sufficiently high virulence and are capable of causing infectious process in humans as well. Therefore, epidemiological surveillance in the foci of plague of the vole and pika types cannot be totally abandoned. It can be conducted according to an abbreviated scheme.

Pseudorabies Virus Associations in Wild Animals: Review of Potential Reservoirs for Cross-Host Transmission.

Pseudorabies virus (PRV) has received widespread attention for its potential health effects on humans, wildlife, domestic animals, and livestock. In this review, we focus on PRV dynamics in wildlife, given the importance of wild-origin PRV transmission to domestic and farm animals. Wild boars, pigs, and raccoons can serve as reservoirs of PRV, with viral transmission to domestic livestock occurring via several routes, such as wild herd exposure, contaminated meat consumption, and insect vector transmission. Many endangered feline and canine species can be infected with PRV, with acute disease and death within 48 h. The first confirmed human case of PRV infection in mainland China was reported in 2017. Thus, PRV exhibits potentially dangerous cross-host transmission, which is likely associated with inappropriate vaccination, poor awareness, and insufficient biosecurity. Currently, no vaccine provides full protection against PRV in all animals. Here, we summarize the epidemiology and pathogenesis of PRV infection in wild, domestic, and farmed animals, which may facilitate the design of novel therapeutics and strategies for controlling PRV infection and improving wildlife protection in China.

Recurring Osteomyelitis Caused by Clostridium celerecrescens in an Adolescent After Motocross Trauma: The Importance of Multidisciplinary Care.

To the Editors: A 15-year-old male adolescent was presented to the emergency department of the trauma unit with a type II open fracture of the left lower arm caused by an accident during a cross-country motorcycle race (Fig. 1A,B). He had gotten off track and lost control of this motorcycle, thereby crashing on to dry meadow soil. The patient presented hemodynamically stable and was prepared for debridement and elastic stable intramedullary nailing. He was started on intravenous cefuroxime. White blood counts and C-reactive protein (CRP) were unremarkable, except for a brief postoperative increase in CRP. Microbiological cultures of the intraoperative swabs yielded Bacillus thuringiensis and Pseudomonas koreensis (both on an aerobic medium), upon which the treatment was changed to meropenem according to susceptibility results (Table S1, Supplemental Digital Content 1, https://links.lww.com/INF/E809). After 9 days, treatment was stopped, and the patient was discharged.FIGURE 1.: Radiographic and computed tomography findings of a left radius type II open fracture of a 15-year-old male adolescent; (A,B) before the first surgery; (C,D) after external fixation; (E) follow-up visit 15 months after discharge.After 5 weeks, he presented again with pain in the lower arm on rotation and with slight wound discharge. MR imaging of the left arm showed the presence of an inflammatory process of the radius with subperiostal abscess formation. The patient underwent surgical revision, including removal of the nailing, wound debridement and external fixation. Intravenous cefuroxime was re-initiated. Tissue and swab cultures revealed Clostridium celerecrescens and Clostridium sphenoides from an anaerobic medium, and Paenibacillus macerans from an aerobic medium. Clindamycin was added before susceptibility testing was finished. Upon final susceptibility results (Table S1, Supplemental Digital Content 1, https://links.lww.com/INF/E809), a multidisciplinary team consisting of trauma surgeons, pediatric infectious diseases specialists, and clinical microbiologists was formed to discuss the case. Based on the susceptibility testing results, the decision was made to start ampicillin-sulbactam and metronidazole. After 7 days, the patient underwent surgical revision and repeat sampling. Cultures again revealed C. celerecrescens. Three-dimensional reconstruction computed tomography of the left arm yielded a suspicious lesion compatible with bone sequestration (Fig. 1C,D), upon which the decision for another surgical revision was made, 7 days after the previous revision. Intraoperatively, two avital bone fragments of approximately 2.8 cm were removed. Follow-up cultures revealed no bacterial growth. Intravenous ampicillin-sulbactam and metronidazole were continued for a total of 5 weeks. On discharge, the patient was switched to oral sultamicillin and metronidazole for another 4 weeks. No side effects related to the antibacterial therapy were reported. After 2 months, the external fixator was removed after imaging confirmed sufficient fracture healing. On regular follow-up visits, the patient presented in a good general state without functional compromise, whereas radiologic findings showed a 17° axis deviation of the radius (Fig. 1E). Anaerobic osteomyelitis is a rare event in children and adolescents but can occur in the presence of predisposing factors such as decubital ulcers, vascular disease, peripheral neuropathy, bites or trauma.1 The most frequently described pathogens in pediatric anaerobic osteomyelitis are Peptostreptococcus spp., Prevotella spp., Fusobacterium spp., Bacteroides fragilis group and Clostridium spp.1 However, aerobic pathogens can be involved as well, for example, Staphylococcus aureus.2,3 Only a few cases of human infections caused by C. celerecrescens have been reported (Table S2, Supplemental Digital Content 1, https://links.lww.com/INF/E809).4–6 There are some features of our case that deserve discussion. First, cefuroxime was started initially and then changed to meropenem. The presence of microorganisms indicating contact with soil may have been suggestive of further pathogens, particularly spore-forming, ubiquitous bacteria. Therefore, meropenem may have been more appropriate than cefuroxime. However, the 9-day-course was longer than currently recommended for open fractures.7 Yet, apparently it did not suffice to prevent a relapse. Second, imaging turned out to be pivotal in showing the presence of bone sequestrations that prompted another revision and led to ultimately decisive source control, alongside the appropriate antibacterial therapy. Third, the detection of multiple bacteria should not be discarded per default as contamination in patients with open fractures and potential inoculation of soil microorganisms. Last, our case demonstrates the importance of a multidisciplinary approach in the care of patients with complicated post-traumatic bone and joint infections. In conclusion, relapses due to spore-forming bacteria such as Clostridium spp. can occur several weeks to months after the initial open fracture. Therefore, a high level of suspicion should be maintained in these patients even after a clinically inapparent follow-up interval. ACKNOWLEDGMENTS We thank the patient and his mother for their consenting to this report. Written informed consent was obtained from both the patient and the parent before any data was used for this case report. This case report has been presented at the 2021 annual meeting of the German Society for Pediatric Infectious Diseases.

AddaVax-Adjuvanted H5N8 Inactivated Vaccine Induces Robust Humoral Immune Response against Different Clades of H5 Viruses.

Since some cases of human infections with H5N8 avian influenza virus have been reported and caused great concern in recent years, it is important to develop an effective vaccine for human use to prevent a potential H5N8 pandemic. In the present study, a vaccine candidate virus based on newly human-infected A/Astrakhan/3212/2020 H5N8 virus was constructed by reverse genetics (RG) technology. The immunogenicity of H5N8 whole virion inactivated vaccine was evaluated by various doses of vaccine antigen formulated with squalene-based adjuvant (AddaVax), aluminum hydroxide (Al(OH)3) or without adjuvant in mice. The results showed AddaVax-adjuvanted H5N8 inactivated vaccine could stimulate the mice to produce a stronger protective immune response with higher titers of IgG antibodies, hemagglutination inhibition (HI), neuraminidase inhibition (NI) and microneutralization (MN) antibodies than vaccine formulations with Al(OH)3 adjuvant or without adjuvant, and achieve a dose-sparing effect. Moreover, the AddaVax-adjuvanted formulation also exhibited potent cross-reactive response in HI antibodies against different clades of H5 viruses. A significant correlation and a curve fitting among HI, NI and MN were found by the correlation analysis to predict the protective effect of the vaccine. With these findings, our study demonstrates that AddaVax adjuvant can enhance the immunogenicity of H5N8 inactivated vaccine remarkably, and proposes an effective strategy for dealing with a potential H5N8 virus pandemic.

Current Knowledge of Hepatitis E Virus (HEV) Epidemiology in Ruminants.

Hepatitis E virus (HEV) infection represents an emerging public health concern worldwide. In industrialized countries, increasing numbers of autochthonous cases of human HEV infection are caused by zoonotic transmission of genotypes 3 and 4, mainly through the consumption of contaminated raw or undercooked meat of infected pigs and wild boars, which are considered the main reservoirs of HEV. However, in the last few years, accumulating evidence seems to indicate that several other animals, including different ruminant species, may harbor HEV. Understanding the impact of HEV infection in ruminants and identifying the risk factors affecting transmission among animals and to humans is critical in order to determine their role in the epidemiological cycle of HEV. In this review, we provide a summary of current knowledge on HEV ecology in ruminants. A growing body of evidence has revealed that these animal species may be potential important hosts of HEV, raising concerns about the possible implications for public health.