DescriptorName: Polymerase Chain Reaction. DescriptorName: Republic of Korea. DescriptorName: Tick Bites. DescriptorName: Tick-BorneDiseases. DescriptorName: Treatment Outcome. Abstract: Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium. Until now, the utility of tick-bite site samples for HGA diagnosis has not been reported.
DescriptorName: Phlebotomus Fever. DescriptorName: Phlebovirus. DescriptorName: Thrombocytopenia. DescriptorName: Tick-BorneDiseases. DescriptorName: Ticks. DescriptorName: Zoonoses. Abstract: Severe fever with thrombocytopenia syndrome (SFTS) is a newly recognized hemorrhagic fever disease found throughout Asia with a case fatality rate between 12% and 30. Since 2009, SFTS has been reported in China throughout 14 Chinese Provinces.
Thrombocytopenia (3), Tick-Borne Diseases (1), Communicable Diseases (1), more mentions
The structural risk of West Nile Disease results from the usual functioning of the socio-ecological system, which may favour the introduction of the pathogen, its circulation and the occurrence of disease cases. Its geographic variations result from the local interactions between three components: (i) reservoir hosts, (ii) vectors, both characterized by their diversity, abundance and competence, (iii) and the socio-economic context that impacts the exposure of human to infectious bites. We developed a model of bird-borne structural risk of West Nile Virus (WNV) circulation in Europe, and analysed the association between the geographic variations of this risk and the occurrence of WND human cases between 2002 and 2014. A meta-analysis of WNV serosurveys conducted in wild bird populations was performed to elaborate a model of WNV seropositivity in European bird species, considered a proxy for bird exposure to WNV. Several eco-ethological traits of bird species were linked to seropositivity and the statistical model adequately fitted species-specific seropositivity data (area under the ROC curve: 0.85). Combined with species distribution maps, this model allowed deriving geographic variations of the bird-borne structural risk of WNV circulation. The association between this risk, and the occurrence of WND human cases across the European Union was assessed. Geographic risk variations of bird-borne structural risk allowed predicting WND case occurrence in administrative districts of the EU with a sensitivity of 86% (95% CI: 0.79-0.92), and a specificity of 68% (95% CI: 0.66-0.71). Disentangling structural and conjectural health risks is important for public health managers as risk mitigation procedures differ according to risk type. The results obtained show promise for the prevention of WND in Europe. Combined with analyses of vector-borne structural risk, they should allow designing efficient and targeted prevention measures.
West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized ex vivo spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in ex vivo CNS tissue.IMPORTANCE West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available. Antiviral inflammatory responses are a crucial component of WNV pathology, and understanding how they are regulated is important for tailoring effective treatments. Proinflammatory responses during WNV infection have been extensively studied, but anti-inflammatory responses (and their potential protective and reparative capabilities) following WNV infection have not been investigated. Minocycline induced the expression of genes associated with the anti-inflammatory (M2) activation of CNS macrophages (microglia) in WNV-infected SCSC while inhibiting the expression of genes associated with proinflammatory (M1) macrophage activation and was protective for multiple CNS cell types, indicating its potential use as a therapeutic reagent. This ex vivo culture system can uniquely address the ability of CNS parenchymal cells (neurons, astrocytes, and microglia) to respond to minocycline and to modulate the inflammatory environment and cytotoxicity in response to WNV infection without peripheral immune cell involvement.
Neuroscience (1), Immune System Diseases (1) Infections (9), West Nile Fever (1), more mentions
West Nile Virus (WNV) first arrived in Ontario, Canada in 2001 and has since spread throughout most of the province, causing disease in humans. The provincial government established a province-wide surveillance program to monitor WNV transmission throughout the 36 regional health units. Here we have acquired records of WNV human and mosquito surveillance from 2002 to 2013 to describe seasonal and geographic trends in WNV activity in southern Ontario. Additionally, we obtained climate data from seven municipalities to investigate how temperature and precipitation affect WNV transmission dynamics. We identified a strong quadratic relationship between the number of confirmed human cases and positive Culex mosquito pools recorded at the end of each year (R2 = 0.9783, p < 0.001). Using Spearman rank correlation tests, we identified that the minimum infection rate of Culex pipiens/restuans pools are the strongest predictor of human cases at a 1 week lag period. We also identified positive correlations between minimum infection rates, temperature, vector abundance, and cumulative precipitation. Global Moran's I index indicates strong positive autocorrelation and clustering of positive Culex pool counts in southern Ontario. Local indicators of spatial association tests revealed a total of 44 high-high and 1 high-low trap locations (n = 680). In the current work we have identified when and where hot spots of WNV activity have occurred in southern Ontario. The municipalities surrounding the western shore of the Lake Ontario and Windsor-Essex County have the largest records of positive mosquitoes and human cases. We identified that positive mosquitoes are a strong indicator of human cases to follow in the coming weeks. An epidemic action threshold of cumulative positive Culex pools was established, allowing Ontario public health officials to predict an epidemic at epidemiological week 34 (rho = 0.90, p < 0.001). These data have the potential to contribute to more efficient larvicide programs and awareness campaigns for the public.
... will respond to defaunation and climate change in proportion to total tick abundance. These findings demonstrate interacting effects of defaunation and aridity that increase disease risk, and they highlight the need to incorporate ecological context when predicting effects of wildlife loss on zoonotic disease dynamics Keyword: Coxiella burnetii. Keyword: climate. Keyword: defaunation. Keyword: exclosure. Keyword: tick-bornedisease. Keyword: ticks.
DescriptorName: Sciuridae. Abstract: Lyme borreliosis is the most common tick-bornedisease in the northern hemisphere... Moreover, the density and tickinfection were investigated according to the tree species found in various patches of Sénart forest. For this purpose, ticks were sampled during 3 years. In the Sénart forest, the density of nymph and adult ticks showed no significant difference ...
Infections (5), Lyme Disease (4), Tick-Borne Diseases (1), more mentions
BACKGROUND: With an increasing number of recognized transfusion-transmitted (TT) babesiosis cases, Babesia microti is the most frequently TT parasite in the United States. We evaluated the inactivation of B. microti in red blood cells (RBCs) prepared in Optisol (AS-5) using amustaline and glutathione (GSH) and in platelet components (PCs) in 100% plasma using amotosalen and low-energy ultraviolet A (UVA) light.
STUDY DESIGN AND METHODS: Individual RBCs and apheresis PCs were spiked with B. microti-infected hamster RBCs (iRBCs) to a final concentration of 10(6) iRBCs/mL and treated with the respective inactivation systems according to the manufacturer's instruction. Samples were collected before (control) and after (test) each treatment. Dilutions of the control samples to 10(-6) were inoculated into hamsters, while the test samples were inoculated neat or at 10(-1) dilution. At 3 and 5 weeks postinoculation, hamsters were evaluated for B. microti infection by microscopic observation of blood smears and 50% infectivity titers (ID50 ) were determined. Log reduction was calculated as control log ID50 minus test log ID50 .
RESULTS: Parasitemia was detected in hamsters injected with as low as 100,000-fold diluted control samples, while no parasites were detectable in the blood smears of any hamsters receiving neat test samples. Mean log reduction was more than 5 log/mL by amustaline/GSH for RBCs and more than 4.5 log/mL by amotosalen/UVA for PCs.
CONCLUSION: B. microti was inactivated to the limit of detection in RBCs and PCs after the respective inactivation treatment. Complete inactivation of B. microti was achieved in this animal infectivity model, and pathogen reduction treatment inhibited transmission of infection.
INTRODUCTION: Lyme borreliosis (LB) is the most common tick transmitted disease in Europe. The diagnosis of LB today is based on the patient´s medical history, clinical presentation and laboratory findings. The laboratory diagnostics are mainly based on antibody detection, but in certain conditions molecular detection by polymerase chain reaction (PCR) may serve as a complement.
AIM: The purpose of this study was to evaluate the analytical sensitivity, analytical specificity and concordance of eight different real-time PCR methods at five laboratories in Sweden, Norway and Denmark.
METHOD: Each participating laboratory was asked to analyse three different sets of samples (reference panels; all blinded) i) cDNA extracted and transcribed from water spiked with cultured Borrelia strains, ii) cerebrospinal fluid spiked with cultured Borrelia strains, and iii) DNA dilution series extracted from cultured Borrelia and relapsing fever strains. The results and the method descriptions of each laboratory were systematically evaluated.
RESULTS AND CONCLUSIONS: The analytical sensitivities and the concordance between the eight protocols were in general high. The concordance was especially high between the protocols using 16S rRNA as the target gene, however, this concordance was mainly related to cDNA as the type of template. When comparing cDNA and DNA as the type of template the analytical sensitivity was in general higher for the protocols using DNA as template regardless of the use of target gene. The analytical specificity for all eight protocols was high. However, some protocols were not able to detect Borrelia spielmanii, Borrelia lusitaniae or Borrelia japonica.
Orientia tsutsugamushi is a major cause of vector-borne infection in Asia. Prompt recognition and appropriate treatment are crucial because of its potentially fatal complications and lack of response to beta-lactam antibiotics. The present study retrospectively evaluated the clinical characteristics and laboratory findings of 16 patients with scrub typhus-related central nervous system (CNS) infections. Single titers ≥ 1:40 of total serum antibodies against O. tsutsugamushi detected by an indirect immunofluorescent assay were considered as positive results. The median age was 35.5 (range, 14-72) years, and 10 (62.5%) patients were female. The most common symptoms were headache (81.3%) and fever (81.3%). Eschar formation was found in three (18.8%) patients. Among patients with encephalitis, seizures and altered consciousness occurred in five (83.3%) and four (66.7%) patients, respectively. An abnormal liver function was noted in seven (43.8%) patients. The median antibody titer was 1:120 (range, 1:40-1:2,560). Typical cerebrospinal fluid profiles were lymphocytic pleocytosis, mild protein elevations, and normal glucose levels. All patients received an empirical treatment with doxycycline and most (93.8%) of them recovered without neurological sequelae. None of the patients reported side effects of the doxycycline treatment. An empirical treatment with doxycycline is needed in patients with CNS infections in scrub typhus endemic areas.
Infectious Diseases (1) Infections (3), Scrub Typhus (3), Central Nervous System Infections (2), more mentions
The rapid pace of bacterial evolution enables organisms to adapt to the laboratory environment with repeated passage and thus diverge from naturally-occurring environmental ("wild") strains. Distinguishing wild and laboratory strains is clearly important for biodefense and bioforensics; however, DNA sequence data alone has thus far not provided a clear signature, perhaps due to lack of understanding of how diverse genome changes lead to convergent phenotypes, difficulty in detecting certain types of mutations, or perhaps because some adaptive modifications are epigenetic. Monitoring protein abundance, a molecular measure of phenotype, can overcome some of these difficulties. We have assembled a collection of Yersinia pestis proteomics datasets from our own published and unpublished work, and from a proteomics data archive, and demonstrated that protein abundance data can clearly distinguish laboratory-adapted from wild. We developed a lasso logistic regression classifier that uses binary (presence/absence) or quantitative protein abundance measures to predict whether a sample is laboratory-adapted or wild that proved to be ~98% accurate, as judged by replicated 10-fold cross-validation. Protein features selected by the classifier accord well with our previous study of laboratory adaptation in Y. pestis. The input data was derived from a variety of unrelated experiments and contained significant confounding variables. We show that the classifier is robust with respect to these variables. The methodology is able to discover signatures for laboratory facility and culture medium that are largely independent of the signature of laboratory adaptation. Going beyond our previous laboratory evolution study, this work suggests that proteomic differences between laboratory-adapted and wild Y. pestis are general, potentially pointing to a process that could apply to other species as well. Additionally, we show that proteomics datasets (even archived data collected for different purposes) contain the information necessary to distinguish wild and laboratory samples. This work has clear applications in biomarker detection as well as biodefense.
RATIONALE: We report the rare case of a 74-year-old man with anti-Ma2-associated paraneoplastic neurologic syndrome (PNS), and review and analyze the clinical manifestations, diagnosis, and treatment of the disease.
PATIENT CONCERNS: The patient presented with a 5-month history of muscle weakness, progressive body aches, and weakness and numbness in both lower extremities. Before his hospitalization, he had experienced cognitive function decline; ptosis, inward gaze, and vertical gaze palsy in the right eye; and occasional visual hallucinations. Brain and spinal cord magnetic resonance imaging (MRI) yielded normal results. Anti-Ma2 antibodies were detected in both serum and cerebrospinal fluid. A 4-hour electroencephalogram showed irregular sharp slow waves and δ waves in the temporal region. Electromyography showed peripheral nerve demyelination. Positron-emission tomography/computed tomography (PET-CT) examination revealed hypermetabolism in the lymph nodes of the whole body. Biopsy of the lymph nodes showed non-Hodgkin lymphoma.
DIAGNOSIS: A clinical diagnosis of lymphoma and PNS was made.
INTERVENTIONS: The patient was treated with intravenous dexamethasone (15 mg/day) for 3 days.
LESSONS: We have presented a rare case of a PNS involving both the central and peripheral nervous systems. The clinical features of this case indicated anti-Ma2-associated encephalitis and chronic inflammatory demyelinating polyneuropathy. PET-CT played a critical role in enabling early diagnosis and prompt treatment in this case.
The identification of mosquito vector species present at arboviral enzootic transmission foci is important to understand transmission eco-epidemiology and to propose and implement prevention and control strategies that reduce vector-borne equine encephalitis transmission. The goal of this study was to identify mosquito species potentially involved in the transmission of enzootic equine encephalitis, in relation to their abundance and diversity at three endemic regions in the República de Panamá. We sampled adult mosquitoes during the dry and rainy season of Panamá. We employed CDC light traps with octanol, EV traps with CO2 and Trinidad 17 traps baited with live hamsters. Traps were deployed in the peridomicile and extradomicile of houses from 18:00 to 6:00 h. We estimated the abundance and diversity of sampled species. We collected a total of 4868 mosquitoes, belonging to 45 species and 11 genera, over 216 sampling nights. Culex (Melanoconion) pedroi, a major Venezuelan equine encephalitis vector was relatively rare (< 2.0% of all sampled mosquitoes). We also found Cx. (Mel) adamesi, Cx. (Mel) crybda, Cx. (Mel) ocossa, Cx. (Mel) spissipes, Cx. (Mel) taeniopus, Cx. (Mel) vomerifer, Aedes scapularis, Ae. angustivittatus, Coquillettidia venezuelensis, Cx. nigripalpus, Cx. declarator, Mansonia titillans, M. pseudotitillans and Psorophora ferox all species known to be vectorially competent for the transmission of arboviruses. Abundance and diversity of mosquitoes in the sampled locations was high, when compared with similar surveys in temperate areas. Information from previous reports about vectorial competence / capacity of the sampled mosquito species suggest that sampled locations have all the elements to support enzootic outbreaks of Venezuelan and Eastern equine encephalitides.
The lifecycle of Rickettsia rickettsii includes infection of both mammalian and arthropod hosts, with each environment presenting distinct challenges to survival. As such, these pathogens likely have distinctive transcriptional strategies for infection of each host. Herein, we report the utilization of next generation sequencing (RNAseq) and bioinformatic analysis techniques to examine the global transcriptional profile of R. rickettsii within an infected animal, and to compare that data to transcription in tissue culture. The results demonstrate substantial R. rickettsii transcriptional alteration in vivo, such that the bacteria are considerably altered from cell culture. Identification of significant transcriptional changes and validation of RNAseq by quantitative PCR are described with particular emphasis on known antigens and suspected virulence factors. Together, these results suggest that transcriptional regulation of a distinct cohort of genes may contribute to successful mammalian infection.
BACKGROUND: An association between tick bites, the development of immunoglobulin E (IgE) antibodies to galactose-α-1, 3-galactose (α-Gal) and red meat allergy has recently been reported. Here we wanted to elucidate the relation between tick exposure, IgE antibodies to α-Gal and Lyme borreliosis (LB).
METHODS: In the highly LB endemic area of Kalmar County, Sweden, serum samples and health inquiries from 518 blood donors were included. All sera were investigated for multiple IgG anti-Borrelia antibodies using a multiplex assay (recomBead, Mikrogen). In addition, three serially collected sera over a six month period from 148 patients with clinically defined erythema migrans (EM) were included. IgE antibodies against α-Gal were determined using ImmunoCAP (Thermo Fisher Scientific).
RESULTS: In blood donors reporting previous LB (n = 124) IgE to α-Gal was found in 16%, while in donors denying previous LB but with multiple anti-Borrelia antibodies (n = 94; interpreted as asymptomatic LB) 10% were IgE α-Gal-positive. Finally, in donors without Borrelia antibodies denying previous LB (n = 300) 14% showed IgE to α-Gal. No significant difference in proportions among the groups were found. In EM patients, IgE to α-Gal was found in 32/148 (22%) at diagnosis, 31/148 (21%) after two-three months and 23/148 (16%) after six months. A significant reduction of proportion and level of IgE to α-Gal was found between the second and third sample (p<0.01). A positive IgE anti α-Gal was more common among men compared with women both in blood donors and in EM patients (p≤0.01).
CONCLUSIONS: IgE to α-Gal reactivity was common in a tick endemic area but showed no significant relation to previous LB. IgE anti-α-Gal reactivity in EM patients peaked within three months of diagnosis of EM, after which it waned indicating that recent tick exposure is of importance in α-Gal sensitization. Furthermore, IgE anti α-Gal was more common in men compared with women.
Background: The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days following infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection.
Methods: Gene arrays were utilized to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls.
Results: The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included three transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells.
Conclusion: This is the first study to globally assess the human skin transcriptional response during early Lyme disease. B. burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression.
Laboratory networks were established to provide accurate and timely laboratory confirmation of infections, an essential component of disease surveillance systems. The World Health Organization (WHO) coordinates global laboratory surveillance of vaccine-preventable diseases (VPDs), including polio, measles and rubella, yellow fever, Japanese encephalitis, rotavirus, and invasive bacterial diseases. In addition to providing high-quality laboratory surveillance data to help guide disease control, elimination, and eradication programs, these global networks provide capacity-building and an infrastructure for public health laboratories. There are major challenges with sustaining and expanding the global laboratory surveillance capacity: limited resources and the need for expansion to meet programmatic goals. Here, we describe the WHO-coordinated laboratory networks supporting VPD surveillance and present a plan for the further development of these networks.
Vaccines (3) Measles (4), Rubella (4), Poliomyelitis (4), more mentions
Tapping mode atomic force microscopy (AFM) in solution was used to analyze the role of the internally located periplasmic flagella (PFs) of the Lyme disease spirochete Borrelia burgdorferi in withstanding externally applied cellular stresses. By systematically imaging immobilized spirochetes with increasing tapping forces, we found that mutants that lack PFs are more readily compressed and damaged by the imaging process compared to wild-type cells. This finding suggest that the PFs, aside from being essential for motility and involved in cell shape, play a cytoskeletal role in dissipating energy and maintaining cellular integrity in the presence of external stress.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory syndrome predominantly affecting the brainstem, cerebellum, and spinal cord. Following its initial description, the salient features of CLIPPERS have been confirmed and expanded upon, but the lack of formalized diagnostic criteria has led to reports of patients with dissimilar features purported to have CLIPPERS. We evaluated clinical, radiological and pathological features of patients referred for suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from non-CLIPPERS aetiologies. Thirty-five patients were evaluated for suspected CLIPPERS. Clinical and neuroimaging data were reviewed by three neurologists to confirm CLIPPERS by consensus agreement. Neuroimaging and neuropathology were reviewed by experienced neuroradiologists and neuropathologists, respectively, both of whom were blinded to the clinical data. CLIPPERS was diagnosed in 23 patients (18 male and five female) and 12 patients had a non-CLIPPERS diagnosis. CLIPPERS patients' median age of onset was 58 years (interquartile range, 24-72) and were followed a median of 44 months (interquartile range 38-63). Non-CLIPPERS patients' median age of onset was 52 years (interquartile range, 39-59) and were followed a median of 27 months (interquartile range, 14-47). Clinical symptoms of gait ataxia, diplopia, cognitive impairment, and facial paraesthesia did not discriminate CLIPPERS from non-CLIPPERS. Marked clinical and radiological corticosteroid responsiveness was observed in CLIPPERS (23/23), and clinical worsening occurred in all 12 CLIPPERS cases when corticosteroids were discontinued. Corticosteroid responsiveness was common but not universal in non-CLIPPERS [clinical improvement (8/12); radiological improvement (2/12); clinical worsening on discontinuation (3/8)]. CLIPPERS patients had brainstem predominant perivascular gadolinium enhancing lesions on magnetic resonance imaging that were discriminated from non-CLIPPERS by: homogenous gadolinium enhancing nodules <3 mm in diameter without ring-enhancement or mass effect, and homogenous T2 signal abnormality not significantly exceeding the T1 enhancement. Brain neuropathology on 14 CLIPPERS cases demonstrated marked CD3-positive T-lymphocyte, mild B-lymphocyte and moderate macrophage infiltrates, with perivascular predominance as well as diffuse parenchymal infiltration (14/14), present in meninges, white and grey matter, associated with variable tissue destruction, astrogliosis and secondary myelin loss. Clinical, radiological and pathological feature define CLIPPERS syndrome and are differentiated from non-CLIPPERS aetiologies by neuroradiological and neuropathological findings.