Hasil untuk "Infectious and parasitic diseases"

Anja Wolpers, Johannes Ponge, Adelinde M. Uhrmacher

Non-pharmaceutical interventions (NPIs) are commonly used tools for controlling infectious disease transmission when pharmaceutical options are unavailable. Yet, identifying effective interventions that minimize societal disruption remains challenging. Agent-based simulation is a popular tool for analyzing the impact of possible interventions in epidemiology. However, automatically optimizing NPIs using agent-based simulations poses a complex problem because, in agent-based epidemiological models, interventions can target individuals based on multiple attributes, affect hierarchical group structures (e.g., schools, workplaces, and families), and be combined arbitrarily, resulting in a very large or even infinite search space. We aim to support decision-makers with our Agent-based Infectious Disease Intervention Optimization System (ADIOS) that optimizes NPIs for infectious disease simulations using Grammar-Guided Genetic Programming (GGGP). The core of ADIOS is a domain-specific language for expressing NPIs in agent-based simulations that structures the intervention search space through a context-free grammar. To make optimization more efficient, the search space can be further reduced by defining constraints that prevent the generation of semantically invalid intervention patterns. Using this constrained language and an interface that enables coupling with agent-based simulations, ADIOS adopts the GGGP approach for simulation-based optimization. Using the German Epidemic Micro-Simulation System (GEMS) as a case study, we demonstrate the potential of our approach to generate optimal interventions for realistic epidemiological models

Samara Alves Stocki, Mísia Beatriz Bueno Alvarenga, Davi de Souza Pinheiro et al.

Introduction: Severe Acute Respiratory Syndrome (SARI) became one of the main causes of hospitalization and death among older adults during the coronavirus pandemic (COVID-19), especially due to the greater severity of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this group. With the start of COVID-19 vaccination in Brazil in January 2021, prioritizing older adults, a reduction in severe outcomes was expected. This study aimed to assess the trend in hospital lethality from SARI caused by COVID-19 among Brazilian older adults between 2020 and 2023, and its relationship with vaccination coverage against SARS-CoV-2. Methods: This is a retrospective ecological study that analyzed public data from 2020 to 2023 on hospitalizations for SARI caused by SARS-CoV-2 among older adults (≥60 years). Lethality by age group was calculated and related to vaccination coverage (complete primary series and booster doses) obtained from OpenDataSUS. A descriptive analysis of the annual evolution of lethality and vaccination was performed. Results: In 2020, before vaccination, lethality from COVID-19–related SARI among older adults was 47.2%. In the following year, with the start of immunization, the rate dropped to 35.6%. In 2022 and 2023, with expansion of vaccine schedules and boosters, stabilization was observed between 24% and 26%. Vaccination coverage with complete primary series reached 87% of older adults in 2021, increasing to more than 95% in 2022. The introduction of booster doses coincided with the maintenance of lower levels of lethality, even with circulation of the Delta and Omicron variants. The data suggest an inverse association between vaccination coverage and hospital lethality from SARI among older adults over the years analyzed. Conclusion: COVID-19 vaccination significantly reduced lethality from SARI among older adults in Brazil between 2020 and 2023. The findings confirm its effectiveness against severe forms, even in the face of new variants, especially with the administration of booster doses. High vaccination coverage, together with surveillance and hospital strengthening, contributed to the decline in mortality. Despite the limitations of aggregated data, standardization of SIVEP-Gripe strengthens the analysis. Continued vaccination and surveillance are essential to prevent new outbreaks.

Juliana Gonzaga Cardoso, Áurea Angélica Paste

Visceral leishmaniasis (VL), caused by Leishmania infantum, is endemic in Brazil. In people living with HIV (PLHIV), coinfection may present with atypical manifestations, severe course, and higher risk of relapse. Among the rare presentations is post- or para-kala-azar dermal leishmaniasis (PKDL), characterized by a maculopapular or nodular rash predominantly on the face, upper limbs, and trunk that occurs during or shortly after the visceral disease. Most cases described in the literature come from areas with higher prevalence of L. donovani; presentation with L. infantum is rare. We report the case of a 50-year-old Black woman from Chapada Diamantina (Bahia), diagnosed with VL in 2000 and treated with meglumine antimoniate. In 2013, she was diagnosed with HIV, with CD4 count 102 cells/mm³ and viral load 470,717 copies/mL. Initially with poor ART adherence, she had virologic failure and was later rescued with a new regimen. In 2019, with undetectable viral load and CD4 134 cells/mm³, she presented bicytopenia and gastrointestinal symptoms. Amastigotes were identified on duodenal biopsy, confirming the first VL relapse, treated with liposomal amphotericin B. She then started biweekly secondary prophylaxis with amphotericin. In 2020, during the COVID-19 pandemic, prophylaxis became irregular. In 2021, a new relapse occurred with pancytopenia and hepatosplenomegaly, confirmed by bone-marrow examination. In 2023, even on regular secondary prophylaxis, she developed epistaxis and bicytopenia associated with multiple cutaneous nodules on the face, limbs, and back. Workup for VL relapse was undertaken. Bone-marrow examination showed Leishmania spp. amastigotes. Histopathology of skin lesions revealed a nodular hypodermal lesion with epithelioid macrophages containing Leishmania spp. amastigotes, compatible with PKDL. She received liposomal amphotericin B (40 mg/kg) plus miltefosine, with clinical resolution of lesions within three months. She currently remains on biweekly prophylaxis, without further relapses. HIV/VL coinfection is a clinical challenge, particularly in patients with CD4 < 200 cells/mm³. PKDL is rare in areas with L. infantum and is more prevalent in PLHIV. This case underscores the importance of continuous prophylaxis, ART adherence, and recognition of PKDL as a manifestation of VL relapse.

Ying Qian, Kui Zhang, Éric Marty et al.

Accurate forecasting of contagious diseases is critical for public health policymaking and pandemic preparedness. We propose a new infectious disease forecasting model based on physics-informed neural networks (PINNs), an emerging scientific machine learning approach. By embedding a compartmental model into the loss function, our method integrates epidemiological theory with data, helping to prevent model overfitting. We further enhance the model with a sub-network that accounts for covariates such as mobility and cumulative vaccine doses, which influence the transmission rate. Using state-level COVID-19 data from California, we demonstrate that the PINN model accurately predicts cases, deaths, and hospitalizations, aligning well with existing benchmarks. Notably, the PINN model outperforms naive baseline forecasts and several sequence deep learning models, including Recurrent Neural Networks (RNNs), Long Short-Term Memory (LSTM) networks, Gated Recurrent Units (GRUs), and Transformers. It also achieves performance comparable to a sophisticated Gaussian infection state forecasting model that combines compartmental dynamics, a data observation model, and parameter regression. However, the PINN model features a simpler structure and is easier to implement. In summary, we systematically evaluate the PINN model's ability to forecast infectious disease dynamics, demonstrating its potential as an efficient computational tool to strengthen forecasting capabilities.

Xavier Didelot, David Helekal, Ian Roberts

When an infectious disease outbreak is of a relatively small size, describing the ancestry of a sample of infected individuals is difficult because most ancestral models assume large population sizes. Given a set of infected individuals, we show that it is possible to express exactly the probability that they have the same infector, either inclusively (so that other individuals may have the same infector too) or exclusively (so that they may not). To compute these probabilities requires knowledge of the offspring distribution, which determines how many infections each infected individual causes. We consider transmission both without and with superspreading, in the form of a Poisson and a Negative-Binomial offspring distribution, respectively. We show how our results can be incorporated into a new lambda-coalescent model which allows multiple lineages to coalesce together. We call this new model the omega-coalescent, we compare it with previously proposed alternatives, and advocate its use in future studies of infectious disease outbreaks.

Mengyao Tang, Lanlan Chen

Abstract Mendelian Randomization (MR) is increasingly used in cancer research to infer causal relationships by leveraging genetic variants as instrumental variables. While the growth of genome-wide association studies and biobank data has expanded the utility of MR, this surge—particularly pronounced in China—raises concerns about methodological rigor. The widespread adoption may be partly driven by the Chinese translation of key MR literature. Recent advances such as multivariable MR, mediation analysis, and integration with AI and omics data have enhanced the robustness and biological interpretability of MR studies. However, challenges persist, including horizontal pleiotropy, weak instrument bias, and misinterpretation of biomarkers as causal exposures. To improve MR study credibility, frameworks like STROBE-MR and MR-GRADE are being adopted. This article reviews methodological improvements and persistent pitfalls in MR, especially within cancer epidemiology, and highlights strategies for ensuring validity in this rapidly evolving field.

P. Gazzinelli-Guimarães, S. Jones, David Voehringer et al.

Eosinophils, traditionally associated as central innate effector cells with type-2 immunity during allergic and helminth parasitic diseases, have recently been revealed to have important roles in tissue homeostasis as well as host defense in a broader variety of infectious diseases. In a dedicated session at the 2023 biennial conference of the International Eosinophil Society titled "Eosinophils in Host Defense", the multifaceted roles eosinophils play against diverse pathogens ranging from parasites to fungi, bacteria, and viruses was presented. In this review, the session speakers offer a comprehensive summary of recent discoveries across pathogen classes, positioning eosinophils as pivotal leukocytes in both host defense and pathology. By unraveling the intricacies of eosinophil engagement in host resistance, this exploration may provide valuable insights not only to understand specific underpinnings of the eosinophil functions related to each class of pathogens, but also to develop novel therapeutics effective against a broad spectrum of infectious diseases.

Suyanpeng Zhang, Sze-chuan Suen

Repeated decision-making problems under uncertainty may arise in the health policy context, such as infectious disease control for COVID-19 and other epidemics. These problems may sometimes be effectively solved using Markov decision processes (MDPs). However, the continuous or large state space of such problems for capturing infectious disease prevalence renders it difficult to implement tractable MDPs to identify the optimal disease control policy over time. We therefore develop an algorithm for discretizing continuous states for approximate MDP solutions in this context. We benchmark performance against a uniform discretization using both a synthetic example and an example of COVID-19 in Los Angeles County.

Thien-Minh Le, Jukka-Pekka Onnela

Infectious disease modeling is used to forecast epidemics and assess the effectiveness of intervention strategies. Although the core assumption of mass-action models of homogeneously mixed population is often implausible, they are nevertheless routinely used in studying epidemics and provide useful insights. Network models can account for the heterogeneous mixing of populations, which is especially important for studying sexually transmitted diseases. Despite the abundance of research on mass-action and network models, the relationship between them is not well understood. Here, we attempt to bridge the gap by first identifying a spreading rule that results in an exact match between disease spreading on a fully connected network and the classic mass-action models. We then propose a method for mapping epidemic spread on arbitrary networks to a form similar to that of mass-action models. We also provide a theoretical justification for the procedure. Finally, we show the advantages of the proposed methods using synthetic data that is based on an empirical network. These findings help us understand when mass-action models and network models are expected to provide similar results and identify reasons when they do not.

Shuanglin Jing, Ling Xue, Jichen Yang

Decline of immunity is a phenomenon characterized by immunocompromised host and plays a crucial role in the epidemiology of emerging infectious diseases (EIDs) such as COVID-19. In this paper, we propose an age-structured model with vaccination and reinfection of immune individuals. We prove that the disease-free equilibrium of the model undergoes backward and forward transcritical bifurcations at the critical value of the basic reproduction number for different values of parameters. We illustrate the results by numerical computations, and also find that the endemic equilibrium exhibits a saddle-node bifurcation on the extended branch of the forward transcritical bifurcation. These results allow us to understand the interplay between the decline of immunity and EIDs, and are able to provide strategies for mitigating the impact of EIDs on global health.

Chaitya Shah, Kashish Gandhi, Javal Shah et al.

Many uncontrollable disease outbreaks of the past exposed several vulnerabilities in the healthcare systems worldwide. While advancements in technology assisted in the rapid creation of the vaccinations, there needs to be a pressing focus on the prevention and prediction of such massive outbreaks. Early detection and intervention of an outbreak can drastically reduce its impact on public health while also making the healthcare system more resilient. The complexity of disease transmission dynamics, influence of various directly and indirectly related factors and limitations of traditional approaches are the main bottlenecks in taking preventive actions. Specifically, this paper implements deep learning algorithms and LLM's to predict the severity of infectious disease outbreaks. Utilizing the historic data of several diseases that have spread in India and the climatic data spanning the past decade, the insights from our research aim to assist in creating a robust predictive system for any outbreaks in the future.

Fernando Rodriguez Avellaneda, Jorge Mateu, Paula Moraga

Understanding the spread of infectious diseases such as COVID-19 is crucial for informed decision-making and resource allocation. A critical component of disease behavior is the velocity with which disease spreads, defined as the rate of change between time and space. In this paper, we propose a spatio-temporal modeling approach to determine the velocities of infectious disease spread. Our approach assumes that the locations and times of people infected can be considered as a spatio-temporal point pattern that arises as a realization of a spatio-temporal log-Gaussian Cox process. The intensity of this process is estimated using fast Bayesian inference by employing the integrated nested Laplace approximation (INLA) and the Stochastic Partial Differential Equations (SPDE) approaches. The velocity is then calculated using finite differences that approximate the derivatives of the intensity function. Finally, the directions and magnitudes of the velocities can be mapped at specific times to examine better the spread of the disease throughout the region. We demonstrate our method by analyzing COVID-19 spread in Cali, Colombia, during the 2020-2021 pandemic.

Henry Zakumumpa, Adolf Alinaitwe, Marjorie Kyomuhendo et al.

Abstract Introduction Long-acting injectable antiretroviral treatment (LAI-ART) has emerged as a novel alternative to the burden of daily oral pills. The bi-monthly intramuscular injectable containing cabotegravir and rilpivirine holds the promise of improving adherence to ART. The perspectives of potential users of LAI-ART, the majority of whom reside in Eastern and Southern Africa, are still largely unexplored. We set out to understand the experiences of people with HIV (PWH) who received LAI-ART at Fort Portal Regional Referral Hospital in mid-Western Uganda for at least 12 months. Methods This qualitative study, conducted between July and August 2023, was nested within a larger study. We conducted four focus groups with 32 (out of 69) PWH who received intramuscular injections of cabotegravir and rilpivirine. In-depth interviews were held with six health workers who delivered LAI-ART to PWH. Data were analyzed by thematic approach broadly modeled on the five domains of the Consolidated Framework for Implementation Research (CFIR). Results There was high acceptability of LAI-ART (30 /32 or 94%) participants requested to remain on LAI-ART even after the end of the 12-month trial. Adherence to ART was reportedly improved when compared to daily oral treatment. Participants credited LAI-ART with; superior viral load suppression, redemption from the daily psychological reminder of living with HIV, enhanced privacy in HIV care and treatment, reduced HIV-related stigma associated with taking oral pills and that it absolved them from carrying bulky medication packages. Conversely, nine participants reported pain around the injection site and a transient fever soon after administering the injection as side effects of LAI-ART. Missed appointments for receiving the bi-monthly injection were common. Providers identified health system barriers to the prospective scale-up of LAI-ART which include the perceived high cost of LAI-ART, stringent cold chain requirements, physical space limitations, and workforce skills gaps in LAI-ART delivery as potential drawbacks. Conclusion Overall, PWH strongly preferred LAI-ART and expressed a comparatively higher satisfaction with this treatment alternative. Health system barriers to potential scale-up are essential to consider if a broader population of PWH will benefit from this novel HIV treatment option in Uganda and other resource-limited settings. Trial registration Trial Registry Number PACTR ID PACTR202104874490818 (registered on 16/04/2021).

Tatiana P. Ospelnikova, O. A. Svitich, F. I. Ershov

Among respiratory viruses, the most serious complications are caused by influenza A and B viruses, as well as coronaviruses. Most studies determined the absolute content of interferons (IFNs) of different types in blood serum. However, serum IFN protein concentrations do not always reflect the level of antiviral protection. The purpose of this study was a comparative assessment of interferon status in patients with ARVI: influenza and the acute stage of COVID-19. Materials and methods. We used biomaterial in the form of whole blood samples from 113 patients with influenza and 110 patients in the acute phase of moderate COVID-19. The body’s antiviral defense during ARVI was assessed by determining the activity of type I and II interferons produced by blood leukocytes using the “Interferon status” method in a cell-virus system simulated in vitro. Results. This work reveals a statistically significant decrease in the biological activity of interferons produced by blood leukocytes in influenza and a deficiency of IFN activity in COVID-19, compared with reference values, and also shows possible prospects for the treatment of these nosologies with such immunoactive drugs as IFN inducers (cycloferon, Kagocel) and immunomodulators (ingavirin, multicomponent vaccine Immunovac-VP-4). Conclusion. The results of IFN activity are necessary to assess the antiviral potential of the body, especially with COVID-19, given the “novelty” of the infection, the severity and variety of its clinical manifestations. Today it is known that the SARS-CoV-2 virus is capable of penetrating not only into the epithelial cells of the upper respiratory tract, epithelial cells of the stomach and intestines, but also into the cells of the esophagus, heart, adrenal glands, bladder, brain, as well as into the vascular endothelium and macrophages. Coronavirus SARS-CoV-2 inhibits the expression of cellular genes, including innate immune genes, and has a negative effect on the IFN system. The use of IFN inducers and immunomodulators for influenza and COVID-19 has shown immunological feasibility and clinical promise.

Maria Luisa Beraldi Mestriner, Cacilda Tezelli Junqueira Padovani, Greizielle Barroso et al.

Introdução/objetivo: O Papilomavírus humano (HPV) é causador de infecção sexualmente transmissível, a qual pode evoluir para o câncer, a depender do potencial de oncogenicidade viral. O início sexual cada vez mais precoce propicia alta vulnerabilidade das adolescentes às ISTs. O déficit do conhecimento entre os adolescentes acerca da infecção por HPV apresenta relevância e deve ser analisado. A vacinação é o método de prevenção mais eficaz e a cobertura vacinal ainda está abaixo da meta preconizada. A pesquisa teve como objetivo analisar o conhecimento sobre o HPV em estudantes da rede pública e promover ação educativa. Métodos: Trata-se de uma pesquisa descritiva, transversal, quantitativa, com coleta de dados primários, mediante entrevista estruturada com aplicação de questionário e atividades educativas (palestras, rodas de conversa, distribuição de cartilha e folders) a 194 estudantes do 6° ao 9° ano das escolas municipais Professor Luiz Cavallon e Domingos Gonçalves Gomes, no município de Campo Grande – MS (CEP/UFMS, Parecer n.: 5.596.389, 22/agosto/2022). Resultados: Os estudantes estavam na faixa etária de 10 a 15 anos, sendo a maioria do sexo feminino (63,4%). A maioria já ouviu falar sobre o HPV (70,1%; 136/194), no entanto, somente 38,1% (74/194) afirmaram que o HPV é um vírus que causa câncer e 11,3% (22/194) responderam que é um vírus que causa verrugas. Alguns deles (17,5%; 34/194) afirmaram que o HPV se referia diretamente ao termo câncer e 16,5% (32/194) apontaram que o HPV é a vacina. Cerca de um terço (61/194) demonstrou não ter conhecimento algum sobre o significado da sigla HPV e 10,8% (21/194) fizeram associação com o vírus herpes. Quando questionados sobre o que é o colo do útero, a maioria (73,2%; 142/194) respondeu que não sabia. A maioria 84,5% (164/194) sabem da existência da vacina contra o HPV e 57,7% (112/194) sabiam que a vacina está disponível de forma gratuita. Entre os participantes, 49% (95/194) afirmaram ter tomado a vacina, no entanto, quando consultados os dados referentes à vacinação no sistema e-SUS encontrou-se uma cobertura vacinal superior ao informado, onde 62,3% (121/194) dos alunos estavam vacinados e 40,7% (79/194) com esquema completo. Conclusão: Concluiu-se que há um déficit de conhecimento entre os participantes sobre a infecção por HPV, principalmente sobre a sua relação com o desenvolvimento do câncer e que há necessidade de intensificação de ações educativas e promoção da vacina

Jonathan Hammond, Katherine Checkland, Igor Francetic et al.

Introduction Primary care networks (PCNs) are claimed to be an effective model to organise and deliver primary healthcare through collaborative relationships and effective coordination of primary care activities. Though increasingly implemented in different contexts, there is limited evidence on the effectiveness of PCNs in low-income and lower middle-income countries (LLMICs).Objective Our scoping review aims to understand how PCNs in LLMICs have been conceptualised, implemented and analysed in the literature and further explores the evidence of the effectiveness of these networks.Methods We structured our review using Arksey and O’Malley’s framework for scoping reviews and recommendations by Levac et al. We also used the population, concept and context (PCC) guide of the Joanna Briggs Institute (JBI) methodology for scoping reviews to define the search strategy. The identified documents were then mapped, using Cunningham’s evaluation framework for health networks, to understand how PCNs are conceived in LLMIC settings.Results We identified 20 documents describing PCNs in five LLMICs. The selected documents showed differing forms and complexities of networks, with a majority resourced by government, non-governmental and donor entities. Most networks were mandated, and established with defined goals, although these were not always understood by stakeholders. Unlike PCNs in developed settings, the scoping review did not identify integration of care as a major goal for the establishment of PCNs in LLMICs. Network evaluation relationships, outputs and outcomes also varied across the five networks in the identified documents, and perceptions of effectiveness differed across stakeholder groups.Conclusion PCNs in LLMICs benefit from clearly stated goals and measurable outcomes, which facilitates evaluation. In order to maximise the benefits, careful attention to the aspects of network design and operation is required. Future research work could shed light on some of the missing pieces of evidence on their effectiveness by, for example, considering differential consequences of modes of network establishment and operation, including unintended consequences in the systems within which they reside, and evaluating long-term implications.

Alison C Hale, Jonathan M Read, Christopher P Jewell

In regard to infectious diseases socioeconomic determinants are strongly associated with differential exposure and susceptibility however they are seldom accounted for by standard compartmental infectious disease models. These associations are explored here with a novel compartmental infectious disease model which, stratified by deprivation and age, accounts for population-level behaviour including social mixing patterns. As an exemplar using a fully Bayesian approach our model is fitted, in real-time if required, to the UKHSA COVID-19 community testing case data from England. Metrics including reproduction number and forecasts of daily case incidence are estimated from the posterior samples. From this UKHSA dataset it is observed that during the initial period of the pandemic the most deprived groups reported the most cases however this trend reversed after the summer of 2021. Forward simulation experiments based on the fitted model demonstrate that this reversal can be accounted for by differential changes in population level behaviours including social mixing and testing behaviour, but it is not explained by the depletion of susceptible individuals. In future epidemics, with a focus on socioeconomic factors the approach outlined here provides the possibility of identifying those groups most at risk with a view to helping policy-makers better target their support.

Gantasala E, Bhat S, Saralaya V et al.

Elizabeth Gantasala,1 Sevitha Bhat,2 Vishwas Saralaya,2 Madhumitha Jayaram,1 Jeppu Udayalaxmi2 1Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India; 2Department of Microbiology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, IndiaCorrespondence: Jeppu Udayalaxmi, Department of Microbiology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India, Tel +91 824-2423452, Email udayalaxmi68@gmail.comAim: To determine the antibiotic resistance patterns, detection of carbapenemase genes in uropathogenic bacilli belonging to the Enterobacteriaceae family and to correlate it with clinical data.Materials and Methods: Identification and antibiotic sensitivity testing of the uropathogenic Enterobacteriaceae was done by using VITEK2 Compact (C) system. Multiplex PCR was used to detect blaIMP, blaKPC, blaNDM1, blaOXA − 48, and blaVIM genes.Results: Out of 1602 urine samples, 417 (26%) showed significant growth, and in these 311 (74.6%) belonged to the Enterobacteriaceae family. Escherichia coli showed a relatively low rate of resistance to nitrofurantoin (17/205; 8.3%), with the majority of the isolates showing a MIC value of ≤ 16 μg/mL when compared to Klebsiella spp. (55/86; 64%), with MIC values for the majority of isolates being 128 μg/mL. Klebsiella spp. showed a relatively low rate of resistance to nalidixic acid (48/86; 55.8%) when compared with E. coli isolates (179/205; 87.3%). Out of 145 isolates tested, we found blaNDM in 11 (7.58%), bla OXA − 48 in 8 (5.51%), bla VIM in 4 (2.75%), bla KPC in one (0.6%) and blaIMP in none of the isolates. Of these 3 isolates were carbapenem sensitive, the rest were resistant.Conclusion: Most of the isolates were sensitive to fosfomycin, carbapenems and resistant to cephalosporins and nalidixic acid. We detected carbapenemase genes in 13 (59%) out of 22 carbapenem resistant isolates and 3 (2.4%) out of 123 carbapenem sensitive isolates.Keywords: antibacterial agents, drug resistance, multiplex polymerase chain reaction, urinary tract infection

Yu-Ke Liu, Guo-Hua Liu, Lei Liu et al.

Abstract Background Haemaphysalis flava is a hematophagous ectoparasite that acquires the nutrition needed for development and reproduction by sucking blood and digesting the blood meal. During blood-sucking and blood-meal digestion, the prevention of blood coagulation is important for this tick. Previous studies have shown that heat shock cognate 70 (HSC70) protein has certain anticoagulant activities, but its immunogenicity remains unclear. Also, whether the mutation of individual bases of the TKD-like peptide of HSC70 through the overlap extension method can change its anticoagulant activities and immunogenicity remains to be investigated. Methods The gene encoding the HSC70 protein was cloned from a complementary DNA library synthesized from H. flava. The coding gene of the TKD-like peptide of HSC70 was mutated into a TKD peptide coding gene (HSC70TKD) using the overlap extension method. Escherichia coli prokaryotic expression plasmids were constructed to obtain the recombinant proteins of HSC70 (rHSC70) and HSC70TKD (rHSC70TKD). The purified rHSC70 and rHSC70TKD were evaluated at different concentrations for anticoagulant activities using four in vitro clotting assays. Emulsifying recombinant proteins with complete and incomplete Freund’s adjuvants were subcutaneously immunized in Sprague Dawley rats. The serum antibody titers and serum concentrations of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected using an indirect enzyme-linked immunosorbent assay to assess the immunogenicity of rHSC70 and rHSC70TKD. Results The open reading frame of HSC70 was successfully amplified and found to have a length of 1958 bp. The gene encoding the TKD-like peptide of HSC70 was artificially mutated, with the 1373-position adenine (A) of the original sequence mutated into guanine (G), the 1385-position cytosine (C) mutated into G and the 1386-position G mutated into C. rHSC70 and rHSC70TKD that fused with His-tag were obtained using the expression plasmids pET-28a-HSC70 and pET-28a-HSC70TKD, respectively. rHSC70 and rHSC70TKD prolonged the thrombin time (TT) and reduced the fibrinogen (FIB) content in the plasma, but did not affect the prothrombin time (PT) or activated partial thromboplastin time (APTT) when compared to the negative control. Interestingly, the ability of rHSC70TKD to prolong the TT and reduce the FIB content in the plasma was better than that of rHSC70. The specific antibody titers of both rHSC70 and rHSC70TKD in rat serum reached 1:124,000 14 days after the third immunization. The serum concentration of IFN-γ in the rHSC70TKD group was higher than that in the rHSC70 group. The rHSC70 group has the highest serum concentration of IL-4, and the serum concentration of IL-4 in the rHSC70TKD group was higher than that in the negative group. Conclusions rHSC70 and rHSC70TKD exhibited anticoagulant activities by prolonging the TT and reducing the FIB content in vitro. rHSC70TKD had better anticoagulant activities than rHSC70. Both rHSC70 and rHSC70TKD had good immunogenicity and induced humoral and cellular immunity.

Kerry E. Rolph, Ryan P. Cavanaugh

In recent years, growing attention has been paid to the influence/role of infectious diseases in tumour development and progression. Investigations have demonstrated that some infectious organisms can have a direct role in the development of neoplasia, whereas others can predispose to neoplasia by alterations in the immune response, or by creating a pro-inflammatory environment. Feline leukaemia virus was one of the first infectious agents recognised as an oncogenic organism, and along with feline immunodeficiency virus has received the most attention. Since the discovery of this retrovirus, several other organisms have been associated with neoplastic processes in cats, these include gammaherpes virus, mouse mammary tumour virus, papillomaviruses, hepadnavirus, <i>Helicobacter</i> species, and the parasitic infections <i>Platynosomum fastosum</i> and <i>Opisthorchis viverrini</i>. This review summarises the findings to date.