Cases Of Human Disease Research Articles

Genome-scale analysis of Mycobacterium avium complex isolates from Portugal reveals extensive genetic diversity

Opportunist infections caused by nontuberculous mycobacteria (NTM) have emerged as a significant public health problem. Among these, species of the Mycobacterium avium complex (MAC) are the main responsible for the increase in the number of human disease cases. In order to address the current needs in the detection and surveillance of MAC disease cases, we evaluated different species classification methodologies (BLASTn-based marker-gene approach, Kraken v2, rMLST and MLST databases) and their congruence with a core-SNP phylogenetic approach, based on whole genome sequencing (WGS) data. For this purpose, we used a collection of 142 MAC isolates from Portuguese patients diagnosed between 2014 and 2022. The marker-gene approach (based on the rpoB, hsp65 and groEL genes), showed the best results, allowing the identification of the 142 MAC isolates to the species/subspecies level (M. avium subsp. hominissuis, M. intracellulare, M. intracellulare subsp. chimaera, M. intracellulare subsp. yongonense, M. marseillence and M. colombiense). Additionally, we performed drug susceptibility testing that confirmed clarithromycin efficacy as a first-line treatment for MAC disease, as 93 % of the Portuguese isolates were susceptible. Using a core-SNP approach we also performed an in-depth phylogenetic analysis within each identified species group, and despite the high genetic diversity within the MAC species, we were able to clearly distinguish all the species/subspecies and identify genetic clusters with epidemiological potential.We highlight not only the need for the standardization of an appropriate genotyping approach for species identification and management of MAC disease, but also a more robust large-scale WGS data analysis, in a One Health perspective, in order to identify potential routes of transmission.

Convergent generation of atypical prions in knockin mouse models of genetic prion disease.

Most cases of human prion disease arise due to spontaneous misfolding of WT or mutant prion protein, yet recapitulating this event in animal models has proven challenging. It remains unclear whether spontaneous prion generation can occur within the mouse lifespan in the absence of protein overexpression and how disease-causing mutations affect prion strain properties. To address these issues, we generated knockin mice that express the misfolding-prone bank vole prion protein (BVPrP). While mice expressing WT BVPrP (I109 variant) remained free from neurological disease, a subset of mice expressing BVPrP with mutations (D178N or E200K) causing genetic prion disease developed progressive neurological illness. Brains from spontaneously ill knockin mice contained prion disease-specific neuropathological changes as well as atypical protease-resistant BVPrP. Moreover, brain extracts from spontaneously ill D178N- or E200K-mutant BVPrP-knockin mice exhibited prion seeding activity and transmitted disease to mice expressing WT BVPrP. Surprisingly, the properties of the D178N- and E200K-mutant prions appeared identical before and after transmission, suggesting that both mutations guide the formation of a similar atypical prion strain. These findings imply that knockin mice expressing mutant BVPrP spontaneously develop a bona fide prion disease and that mutations causing prion diseases may share a uniform initial mechanism of action.

Usutu virus and West Nile virus use a transcellular route of neuroinvasion across an in vitro model of the human blood–brain barrier

West Nile virus (WNV) leads to thousands of cases of severe neurological disease in humans each year. Usutu virus (USUV) is closely related to WNV, but rarely induces disease in humans. We hypothesised that USUV is less able to cross the blood-brain barrier (BBB) and, consequently, is less likely to infect the brain. Therefore, we developed an in vitro BBB model consisting of primary human brain microvascular endothelial cells, pericytes and astrocytes. Both USUV and WNV invaded across the in vitro BBB via a transcellular mechanism in the absence of barrier disruption. USUV replicated to lower titres than WNV but induced a comparable cytokine and chemokine response, with modulation of key factors associated with barrier function and immune-cell migration. In conclusion, USUV appears attenuated in its ability to replicate at this interface compared with WNV, but further work must be done to identify key determinants underlying the differing clinical presentations.

Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease.

Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of the prion protein (PrP), encoded by the PRNP gene. Of human prion disease cases,<1% were transmitted by misfolded PrP, ~ 15% are inherited, and ~ 85% are sporadic (sCJD). While familial cases are inherited through germline mutations in PRNP, the cause of sCJD is unknown. Somatic mutations have been hypothesized as a cause of sCJD, and recent studies have revealed that somatic mutations accumulate in neurons during aging. To investigate the hypothesis that somatic mutations in PRNP may underlie sCJD, we performed deep DNA sequencing of PRNP in 205 sCJD cases and 170 age-matched non-disease controls. We included 5 cases of Heidenhain variant sporadic CJD (H-sCJD), where visual symptomatology and neuropathology implicate localized initiation of prion formation, and examined multiple regions across the brain including in the affected occipital cortex. We employed Multiple Independent Primer PCR Sequencing (MIPP-Seq) with a median depth of > 5000× across the PRNP coding region and analyzed for variants using MosaicHunter. An allele mixing experiment showed positive detection of variants in bulk DNA at a variant allele fraction (VAF) as low as 0.2%. We observed multiple polymorphic germline variants among individuals in our cohort. However, we did not identify bona fide somatic variants in sCJD, including across multiple affected regions in H-sCJD, nor in control individuals. Beyond our stringent variant-identification pipeline, we also analyzed VAFs from raw sequencing data, and observed no evidence of prion disease enrichment for the known germline pathogenic variants P102L, D178N, and E200K. The lack of PRNP pathogenic somatic mutations in H-sCJD or the broader cohort of sCJD suggests that clonal somatic mutations may not play a major role in sporadic prion disease. With H-sCJD representing a localized presentation of neurodegeneration, this serves as a test of the potential role of clonal somatic mutations in genes known to cause familial neurodegeneration.

Neuropathologically-directed profiling of PRNP somatic and germline variants in sporadic human prion disease.

Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of the prion protein (PrP), encoded by the PRNP gene. Of human prion disease cases, ~1% were transmitted by misfolded PrP, ~15% are inherited, and ~85% are sporadic (sCJD). While familial cases are inherited through germline mutations in PRNP, the cause of sCJD is unknown. Somatic mutations have been hypothesized as a cause of sCJD, and recent studies have revealed that somatic mutations accumulate in neurons during aging. To investigate the hypothesis that somatic mutations in PRNP may underlie sCJD, we performed deep DNA sequencing of PRNP in 205 sCJD cases and 170 age-matched non-disease controls. We included 5 cases of Heidenhain variant sporadic CJD (H-sCJD), where visual symptomatology and neuropathology implicate focal initiation of prion formation, and examined multiple regions across the brain including in the affected occipital cortex. We employed Multiple Independent Primer PCR Sequencing (MIPP-Seq) with a median depth of >5,000X across the PRNP coding region and analyzed for variants using MosaicHunter. An allele mixing experiment showed positive detection of variants in bulk DNA at a variant allele fraction (VAF) as low as 0.2%. We observed multiple polymorphic germline variants among individuals in our cohort. However, we did not identify bona fide somatic variants in sCJD, including across multiple affected regions in H-sCJD, nor in control individuals. Beyond our stringent variant-identification pipeline, we also analyzed VAFs from raw sequencing data, and observed no evidence of prion disease enrichment for the known germline pathogenic variants P102L, D178N, and E200K. The lack of PRNP pathogenic somatic mutations in H-sCJD or the broader cohort of sCJD suggests that clonal somatic mutations may not play a major role in sporadic prion disease. With H-sCJD representing a focal presentation of neurodegeneration, this serves as a test of the potential role of clonal somatic mutations in genes known to cause familial neurodegeneration.

Rickettsia africae infections in sub-Saharan Africa: A systematic literature review of epidemiological studies and summary of case reports.

Rickettsia africae is a tick-borne bacteria known to cause African tick bite fever (ATBF). While the disease was first described more than 100 years ago, knowledge of transmission risk factors and disease burden remain poorly described. To better understand the burden of R. africae, this article reviewed and summarized the published literature related to ATBF epidemiology and clinical management. Using a systematic approach, consistent with the PRISMA guidelines, we identified more than 100 eligible articles, including 65 epidemiological studies and 41 case reports. Most reports described R. africae in ticks and livestock, while human studies were less common. Human disease case reports were exclusively among returning travellers from non-endemic areas, which limits our disease knowledge among at-risk populations: people living in endemic regions. Substantial efforts to elucidate the ATBF risk factors and clinical manifestations among local populations are needed to develop effective preventative strategies and facilitate appropriate and timely diagnosis.

Epidemiological Aspects and Basic Directions of the Protective Medications against Monkeypox Development

Relevance. After smallpox eradication, in conditions of population immunity to orthopoxviruses absence, Monkeypox virus became most significant orthopoxvirus, pathogenic for humans. Therefore the generalization of data on the areas of infection outbreaks, human diseases and methods of prevention and treatment of monkey pox is important task. Aim. To characterize the problem of monkeypox in the world based on an analysis of foreign scientific publications over the past 20 years. Materials and methods. The work used publications presented in the main international medical information databases PubMed, Web of Science, Embase, etc. To analyze the publications, the analytical epidemiological method was used. Results and discussion. Monkeypox virus, obtained and identified in 1958, by genetic and phenotypic differences divides on two clades: West-African with lethality 3.6% and Central-African (Congo Basin) with lethality 10%. Monkeypox virus transmission to men happens in two ways, either from animal-to-human or human-to-human. Monkey pox is endemic only on African continent, but In 2003 year the first outbreak, numbering 47 confirmed cases, was occurred in non-endemic country – USA and the largest monkeypox outbreak began in Nigeria in September 2017 year and continue to the present. Comparison of the genome sequences of strains, isolated from patients in non-endemic countries, showed, that it genetically close to West-african strains, belong to II clades and were descended from a common ancestor. Many cases of disease in humans in the current outbreak have been traced to sexual transmission especially among men, who identify ourselves as gay or bisexual. The basis method for identification of agent in present time is PCR-RT targeting on the tumor necrosis factor (TNF) receptor gene. Usually monkeypox of human is mild, self-limiting disease. The symptoms of monkeypox are varied and non-specific. One of the most frequently observed clinical symptoms is lymphadenopathy. Most patients recover during some weeks. However, specific antiviral treatment – tecovirimat (S-246) and brincidofovir (CMX-001) – may be used for seriously ill or immunocompromised individuals. For prophylactic disease in present time are use vaccines JYNNEOSTM, ACAM2000R and Aventis Pasteur (APSV). Conclusion. General vaccination against monkeypox don't develop accordingly to modern recommendations WHO. Ring vaccination is recommended to conduct for suppression of spread virus in nidus of infection among population. Timely international coordination is needed to prevent the global spread of a disease with epidemic potential.

Impacts of ground ultra-low volume adulticide applications on Culex pipiens and Culex restuans (Diptera: Culicidae) abundance, age structure, and West Nile virus infection in Cook County, Illinois.

Since the introduction of West Nile virus (WNV) to the United States over 20 years ago, thousands of cases of human disease and death have been reported. Yearly seasonal outbreaks continue to persist, and the city and suburbs of Chicago, Illinois, is considered a "hot spot" for WNV activity. To interrupt WNV transmission, ground ultra-low volume (ULV) adulticide applications are regularly used to reduce Culex pipiens L. and Culex restuans Theobold (Diptera: Culicidae) abundance and infection. The real-world effectiveness of adulticide applications has not been comprehensively assessed, and prior studies, including our own investigation, have yielded inconclusive or conflicting results. Therefore, we expanded our prior work and evaluated the effects of 5 sequential weekly truck-mounted ULV adulticide applications in large residential areas in the northern suburbs of Chicago, Illinois, in 2019 and 2020. Each day, Cx. pipiens and Cx. restuans host-seeking and gravid mosquitoes were collected to assess abundance, age structure, and WNV infection rates. Adulticide applications resulted in significant reductions of both host-seeking and gravid abundance on the night of treatment. The reduction in host-seeking mosquitoes was followed by a reduction in gravid mosquitoes trapped 3 and 4 days after adulticide application and an increase in the proportion of nulliparous mosquitoes. WNV infection rates were significantly reduced in treatment sites as compared to untreated sites when infection rates were higher in 2020. This large-scale study provides comprehensive evidence that ground ULV adulticide applications are an effective tool in an integrated mosquito management program for combating WNV vectors and infection risk.

SUCCESSFUL EXPERIENCE IN THE TREATMENT OF NEUROBRUCELLOSIS IN KAZAKHSTAN

Brucellosis is a zoonotic infection and therefore an important public health problem in the world. More than 0.5 million cases of brucellosis in humans are registered annually. Endemic areas for brucellosis include countries with developed animal husbandry. Kazakhstan is among the twenty-five countries with the highest incidence of brucellosis. Among the post-Soviet countries, Kazakhstan ranks second after Kyrgyzstan in the incidence of brucellosis. In recent years, 2500-3500 cases of human disease have been registered annually in the country, of which about 600 are children under the age of 14. The problem of brucellosis in Kazakhstan is caused by the agricultural orientation and prevalence of small cattle, which is the carrier of the most pathogenic Brucella melitensis. 42.2% of Kazakhstanis live in rural areas, and their main income is animal care. More than 85% of human brucellosis cases have been registered in 4 southern regions where animal husbandry (sheep breeding) is developed. Despite the long history of campaigns to combat brucellosis, Kazakhstan has not overcome this threat to public health. Brucellosis can affect many organs and systems. Complications of brucellosis are usually about 30 percent. Neurological damage occurs in up to 10% of cases. Manifestations include meningitis (acute or chronic), encephalitis, brain abscess, myelitis, sciatica and/or neuritis (with damage to cranial or peripheral nerves). The article presents rare clinical cases of neurobrucellosis on the background of concomitant diseases.

Characterization of tularemia foci in the Republic of Kazakhstan from 2000 to 2020.

The wide distribution of tularemia in the territory of Kazakhstan is associated with landscape and geographical characteristics. This is explained by a combination of natural factors: the presence of certain types of rodents-reservoirs and sources, ectoparasites-carriers of the causative agent of tularemia. The study of the current spatial and temporal characterization of tularemia in Kazakhstan from 2000 to 2020 will determine the epidemiological status of tularemia and improve the monitoring system in Kazakhstan. In this work we demonstrated the results of a retrospective survey of natural foci of tularemia: analysis of vector, small mammal and human data. The spatial and temporal characteristics of tularemia from 2000 to 2020 in the territory of Kazakhstan were studied in comparison with historical data, including the description of tularemia outbreaks, the clinical picture, and the source of infection, transmission factors, and geographical coordinates of outbreak registration. Sampling was carried out by trapping rodents on snap traps and collecting ticks by rodent combing and by "flagging" methods. For the last 20 years, 85 human cases of tularemia have been reported. During the period from 2000 to 2020, more than 600 strains of F. tularensis were isolated from field rodents and ticks in the natural foci of tularemia. MLVA typing of F. tularensis strains isolated from natural foci of tularemia in Kazakhstan over the past 20 years. The results of retrospective monitoring indicate that currently active foci of tularemia include the Aktobe, West Kazakhstan, Almaty, East Kazakhstan, and Pavlodar regions. Low-activity natural foci are located in the territory of the Akmola, Karaganda, North Kazakhstan, Kostanay, Atyrau, Zhambyl, and Kyzylorda regions. There are no active natural foci of tularemia in the Mangystau and Turkestan regions. The widespread occurrence of tularemia in the country is associated with landscape and geographical features that contribute to the circulation of the pathogen in the natural focus. An analysis of natural foci of tularemia showed that it is necessary to continue monitoring studies of carriers and vectors for the presence of the causative agent of the F. tularensis, in order to prevent mass cases of human disease.

An acetyltransferase effector conserved across Legionella species targets the eukaryotic eIF3 complex to modulate protein translation.

The survival of Legionella spp. as intracellular pathogens relies on the combined action of protein effectors delivered inside their eukaryotic hosts by the Dot/Icm (defective in organelle trafficking/intracellular multiplication) type IVb secretion system. The specific repertoire of effector arsenals varies dramatically across over 60 known species of this genera with Legionella pneumophila responsible for most cases of Legionnaires' disease in humans encoding over 360 Dot/Icm effectors. However, a small subset of "core" effectors appears to be conserved across all Legionella species raising an intriguing question of their role in these bacteria's pathogenic strategy, which for most of these effectors remains unknown. L. pneumophila Lpg0103 effector, also known as VipF, represents one of the core effector families that features a tandem of Gcn5-related N-acetyltransferase (GNAT) domains. Here, we present the crystal structure of the Lha0223, the VipF representative from Legionella hackeliae in complex with acetyl-coenzyme A determined to 1.75 Å resolution. Our structural analysis suggested that this effector family shares a common fold with the two GNAT domains forming a deep groove occupied by residues conserved across VipF homologs. Further analysis suggested that only the C-terminal GNAT domain of VipF effectors retains the active site composition compatible with catalysis, whereas the N-terminal GNAT domain binds the ligand in a non-catalytical mode. We confirmed this by in vitro enzymatic assays which revealed VipF activity not only against generic small molecule substrates, such as chloramphenicol, but also against poly-L-lysine and histone-derived peptides. We identified the human eukaryotic translation initiation factor 3 (eIF3) complex co-precipitating with Lpg0103 and demonstrated the direct interaction between the several representatives of the VipF family, including Lpg0103 and Lha0223 with the K subunit of eIF3. According to our data, these interactions involve primarily the C-terminal tail of eIF3-K containing two lysine residues that are acetylated by VipF. VipF catalytic activity results in the suppression of eukaryotic protein translation in vitro, revealing the potential function of VipF "core" effectors in Legionella's pathogenic strategy.IMPORTANCEBy translocating effectors inside the eukaryotic host cell, bacteria can modulate host cellular processes in their favor. Legionella species, which includes the pneumonia-causing Legionella pneumophila, encode a widely diverse set of effectors with only a small subset that is conserved across this genus. Here, we demonstrate that one of these conserved effector families, represented by L. pneumophila VipF (Lpg0103), is a tandem Gcn5-related N-acetyltransferase interacting with the K subunit of human eukaryotic initiation factor 3 complex. VipF catalyzes the acetylation of lysine residues on the C-terminal tail of the K subunit, resulting in the suppression of eukaryotic translation initiation factor 3-mediated protein translation in vitro. These new data provide the first insight into the molecular function of this pathogenic factor family common across Legionellae.

Trypanosomatid diversity in a bat community of an urban area in Campo Grande, Mato Grosso do Sul, Brazil

Bats have a long evolutionary history with trypanosomatids, but the role of these flying mammals on parasite transmission cycles in urban areas, especially for Trypanosoma and Leishmania species, remains poorly known. The objective of this study was to evaluate the species richness of trypanosomatids parasitizing a bat community in Campo Grande (CG), a state capital within the Cerrado of the Brazilian Midwest. We evaluated 237 bats of 13 species by means of hemoculture and molecular detection in spleen samples. The bat community of CG appears to participate in the transmission cycles of various species of trypanosomatids. We report an overall trypanosomatid detection rate of 34.2% (n = 81), involving 11 out of 13 sampled bat species. We identified six species of trypanosomatids from 61 bats by analyzing SSU rRNA and/or kDNA: Trypanosoma cruzi DTU TcI, T. c. marinkellei, T. dionisii, Leishmania infantum, L. amazonensis, and T. janseni, with this latter being detected by hemoculture for the first time in a bat species. We also detected a Molecular Operational Taxonomic Unit, Trypanosoma sp. DID, in the phyllostomids Glossophaga soricina and Platyrrhinus lineatus. The highest trypanosomatid richness was observed for Sturnira lilium, which hosted three species: L. infantum, T. dionisii and T. janseni. Given that visceral leishmaniasis is endemic in CG, special focus should be placed on L. infantum. Moreover, L. amazonensis and T. cruzi warrant attention, since these are zoonotic parasites responsible for human cases of tegumentary leishmaniasis and Chagas disease, respectively. In this respect, we discuss how bat communities may influence the Leishmania spp. transmission in endemic areas.

Genomic epidemiology of the clinically dominant clonal complex 1 in the Listeria monocytogenes population in the UK.

Listeria monocytogenes is a food-borne pathogen, typically affecting the elderly, immunocompromised patients and pregnant women. The aim of this study was to determine the population structure of L. monocytogenes clonal complex 1 (CC1) in the UK and describe the genomic epidemiology of this clinically significant CC. We interrogated a working dataset of 4073 sequences of L. monocytogenes isolated between January 2015 and December 2020 from human clinical specimens, food and/or food-production environments. A minimum spanning tree was reconstructed to determine the population structure of L. monocytogenes in the UK. Subsequent analysis focused on L. monocytogenes CC1, as the cause of the highest proportion of invasive listeriosis in humans. Sequencing data was integrated with metadata on food and environmental isolates, and information from patient questionnaires, including age, sex and clinical outcomes. All isolates either belonged to lineage I (n=1299/4073, 32%) or lineage II (n=2774/4073, 68%), with clinical isolates from human cases more likely to belong to lineage I (n=546/928, 59%) and food isolates more likely to belong to lineage II (n=2352/3067, 77%). Of the four largest CCs, CC1 (n=237) had the highest proportion of isolates from human cases of disease (CC1 n=160/237, 67.5 %; CC121 n=13/843, 2 %; CC9 n=53/360, 15 %; CC2 n=69/339, 20%). Within CC1, most cases were female (n=95/160, 59%, P=0.01771) and the highest proportion of cases were in people >60 years old (39/95, 41%, P=1.314×10-6) with a high number of them aged 20-39 years old (n=35/95, 37%) most linked to pregnancy-related listeriosis (n=29/35, 83%). Most of the male cases were in men aged over 60 years old (40/65, 62%), and most of the fatal cases in both males and females were identified in this age group (42/55, 76%). Phylogenetic analysis revealed 23 5 SNP single linkage clusters comprising 80/237 (34 %) isolates with cluster sizes ranging from 2 to 19. Five 5 SNP clusters comprised isolates from human cases and an implicated food item. Expanding the analysis to 25 SNP single linkage clusters resolved an additional two clusters linking human cases to a potential food vehicle. Analysis of demographic and clinical outcome data identified CC1 as a clinically significant cause of invasive listeriosis in the elderly population and in women of child-bearing age. Phylogenetic analysis revealed the population structure of CC1 in the UK comprised small, sparsely populated genomic clusters. Only clusters containing isolates from an implicated food vehicle, or food processing or farming environments, were resolved, emphasizing the need for clinical, food and animal-health agencies to share sequencing data in real time, and the importance of a One Health approach to public-health surveillance of listeriosis.

Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis.

Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, no studies have assessed their roles in mammalian meiosis of females, whose abnormality accounts for over 80% of the cases of gamete-originated human reproductive disease. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of KL2 significantly reduced chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. Importantly, we demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, eliminated KL2 from chromosomes completely. KL2 also interacted with phosphorylated eukaryotic elongation factor-2 kinase; they competed for chromosome binding. We also observed that the phosphorylated KL2 was localized at spindle poles, and that KL2 phosphorylation was regulated by extracellular signal-regulated kinase 1/2. In summary, our study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.

Usutu virus, an emerging arbovirus with One Health importance.

Usutu virus (USUV, Flaviviridae) is an emerging arbovirus that has led to epizootic outbreaks in birds and numerous human neuroinvasive disease cases in Europe. It is maintained in an enzootic cycle with Culex mosquitoes and passerine birds, a transmission cycle that is shared by West Nile virus (WNV) and St. Louis encephalitis virus (SLEV), two flaviviruses that are endemic in the United States. USUV and WNV co-circulate in Africa and Europe, and SLEV and WNV co-circulate in North America. These three viruses are prime examples of One Health issues, in which the interactions between humans, animals, and the environments they reside in can have important health impacts. The three facets of One Health are interwoven throughout this article as we discuss the mechanisms of flavivirus transmission and emergence. We explore the possibility of USUV emergence in the United States by analyzing the shared characteristics among USUV, WNV, and SLEV, including the role that flavivirus co-infections and sequential exposures may play in viral emergence. Finally, we provide insights on the importance of integrated surveillance programs as One Health tools that can be used to mitigate USUV emergence and spread.

Pantoea agglomerans: A rare infectious outbreak affecting maintenance hemodialysis patients in a tertiary care hospital.

Pantoea agglomerans is an environmental pathogen known to cause infection in immunocompromised individuals, particularly after thorn injuries. However, previous data showed few cases of human disease caused by contaminated medical products such as parenteral nutrition, anesthetic agents, blood, and peritoneal dialysis solutions. Infection in hemodialysis patients is rare. In this study, we presented a detailed account of several hemodialysis patients infected with this contagious pathogen and compared them with noninfected dialysis patients. We retrospectively reviewed the hospital records of 105 hemodialysis patients. Seventeen of 105 patients were diagnosed with P. agglomerans infection. We carefully analyzed their entire in-hospital course. Among infected patients, 52.9% were male with a median age of 49 (IQR: 32-66) years. Compared to the noninfected patients, age below 50 years, prior kidney transplantation, prior immunosuppression and antibiotics use, and dialysis via a tunneled vascular catheter were the significant epidemiological features. Despite negative microbiological investigations, we suspect the possible infectious spread via infected central venous catheter was the likely infectious source. Most importantly, all patients responded well to intravenous antibiotics. Only two patients required the removal of the tunneled catheter. Their mortality rate was 0%. P. agglomerans infection, although considered rare, is becoming increasingly prevalent among dialysis patients. Its occurrence must be appraised as an infectious outbreak rather than mere contamination. Prompt treatment, source identification, and early implementation of preventive strategies should always be the goal to curtail this infection at an early stage.

Prevalence of five human pathogens in host-seeking Ixodes scapularis and Ixodes pacificus by region, state, and county in the contiguous United States generated through national tick surveillance

The majority of vector-borne disease cases reported in the United States (U.S.) are caused by pathogens spread by the blacklegged tick, Ixodes scapularis. In recent decades, the geographic ranges of the tick and its associated human pathogens have expanded, putting an increasing number of communities at risk for tick-borne infections. In 2018, the U.S. Centers for Disease Control and Prevention (CDC) initiated a national tick surveillance program to monitor changes in the distribution and abundance of ticks and the presence and prevalence of human pathogens in them. We assessed the geographical representativeness of prevalence data submitted to CDC as part of the national tick surveillance effort. We describe county, state, and regional variation in the prevalence of five human pathogens (Borrelia burgdorferi sensu stricto (s.s.), Borrelia mayonii, Borrelia miyamotoi, Anaplasma phagocytophilum, and Babesia microti) in host-seeking I. scapularis and I. pacificus nymphs and adults. Although I. scapularis and I. pacificus are widely distributed in the eastern and western U.S., respectively, pathogen prevalence was estimated predominantly in ticks collected in the Northeast, Ohio Valley, and Upper Midwest regions, where human Lyme disease cases are most commonly reported. Within these regions, we found that state and regional estimates of pathogen prevalence generally reached predictable and stable levels, but variation in prevalence estimates at the sub-state level was considerable. Borrelia burgdorferi s.s. was the most prevalent and widespread pathogen detected. Borrelia miyamotoi and A. phagocytophilum shared a similarly broad geographic range, but were consistently detected at much lower prevalence compared with B. burgdorferi s.s. Babesia microti was detected at similar prevalence to A. phagocytophilum, where both pathogens co-occurred, but was reported over a much more limited geographic range compared with A. phagocytophilum or B. burgdorferi s.s. Borrelia mayonii was identified at very low prevalence with a focal distribution within the Upper Midwest. National assessments of risk for tick-borne diseases need to be improved through collection and testing of ticks in currently under-represented regions, including the West, South, Southeast, and eastern Plains states.

Fatal Case of Heartland Virus Disease Acquired in the Mid-Atlantic Region, United States.

Heartland virus (HRTV) disease is an emerging tickborne illness in the midwestern and southern United States. We describe a reported fatal case of HRTV infection in the Maryland and Virginia region, states not widely recognized to have human HRTV disease cases. The range of HRTV could be expanding in the United States.

Unprecedented Outbreak of West Nile Virus — Maricopa County, Arizona, 2021

West Nile virus (WNV) is a mosquitoborne disease primarily transmitted through bites of infected Culex species mosquitos (1). In the United States, WNV is the leading domestically acquired arboviral disease; it can cause severe illness affecting the brain and spinal cord with an associated case fatality rate of 10% (2,3). On September 2, 2021, Maricopa County Environmental Services Department, Vector Control Division (MCESD-VCD) notified the Maricopa County Department of Public Health (MCDPH) and the Arizona Department of Health Services (ADHS) that the WNV vector index (VI), a measure of infected Culex mosquitoes, was substantially elevated. By that date, at least 100 WNV cases had already been reported among Maricopa County residents to MCDPH by health care providers and laboratories. Within 2 weeks, the VI reached its highest ever recorded level (53.61), with an associated tenfold increase in the number of human disease cases. During 2021, a total of 1,487 human WNV cases were identified; 956 (64.3%) patients had neuroinvasive disease, and 101 (6.8%) died. MCESD-VCD conducted daily remediation efforts to mitigate elevated VI and address mosquito-related complaints from residents (i.e., large numbers of outdoor mosquitoes from an unknown source and unmaintained swimming pools potentially breeding mosquitoes). MCDPH increased outreach to the community and providers through messaging, education events, and media. This was the largest documented focal WNV outbreak in a single county in the United States (4). Despite outreach efforts to communities and health care partners, clinicians and patients reported a lack of awareness of the WNV outbreak, highlighting the need for public health agencies to increase prevention messaging to broaden public awareness and to ensure that health care providers are aware of recommended testing methods for clinically compatible illnesses.

Transcriptomics in serum and culture medium reveal shared and differential gene regulation in pathogenic and commensal Streptococcus suis.

Streptococcus suis colonizes the upper respiratory tract of healthy pigs at high abundance but can also cause opportunistic respiratory and systemic disease. Disease-associated S. suis reference strains are well studied, but less is known about commensal lineages. It is not known what mechanisms enable some S. suis lineages to cause disease while others persist as commensal colonizers, or to what extent gene expression in disease-associated and commensal lineages diverge. In this study we compared the transcriptomes of 21 S. suis strains grown in active porcine serum and Todd-Hewitt yeast broth. These strains included both commensal and pathogenic strains, including several strains of sequence type (ST) 1, which is responsible for most cases of human disease and is considered to be the most pathogenic S. suis lineage. We sampled the strains during their exponential growth phase and mapped RNA sequencing reads to the corresponding strain genomes. We found that the transcriptomes of pathogenic and commensal strains with large genomic divergence were unexpectedly conserved when grown in active porcine serum, but that regulation and expression of key pathways varied. Notably, we observed strong variation of expression across media of genes involved in capsule production in pathogens, and of the agmatine deiminase system in commensals. ST1 strains displayed large differences in gene expression between the two media compared to strains from other clades. Their capacity to regulate gene expression across different environmental conditions may be key to their success as zoonotic pathogens.