Disease Transmission To Humans Research Articles

The Dual Resistance Mechanism of CYP325G4 and CYP6AA9 in Culex pipiens pallens Legs According to Transcriptome and Proteome Analysis.

Mosquitoes within the Culex pipiens complex play a crucial role in human disease transmission. Insecticides, especially pyrethroids, are used to control these vectors. Mosquito legs are the main entry point and barrier for insecticides to gain their neuronal targets. However, the resistance mechanism in mosquito legs is unclear. Herein, we employed transcriptomic analyses and isobaric tags for relative and absolute quantitation techniques to investigate the resistance mechanism, focusing on Cx. pipiens legs. We discovered 2346 differentially expressed genes (DEGs) between deltamethrin-resistant (DR) and deltamethrin-sensitive (DS) mosquito legs, including 41 cytochrome P450 genes. In the same comparison, we identified 228 differentially expressed proteins (DEPs), including six cytochrome P450 proteins. Combined transcriptome and proteome analysis revealed only two upregulated P450 genes, CYP325G4 and CYP6AA9. The main clusters of DEGs and DEPs were associated with metabolic processes, such as cytochrome P450-mediated metabolism of drugs and xenobiotics. Transcription analysis revealed high CYP325G4 and CYP6AA9 expression in the DR strain at 72 h posteclosion compared with that in the DS strain, particularly in the legs. Mosquitoes knocked down for CYP325G4 were more sensitive to deltamethrin than the controls. CYP325G4 knockdown reduced the expression of several chlorinated hydrocarbon (CHC)-related genes, which altered the cuticle thickness and structure. Conversely, CYP6AA9 knockdown increased CHC gene expression without altering cuticle thickness and structure. P450 activity analysis demonstrated that CYP325G4 and CYP6AA9 contributed to metabolic resistance in the midgut and legs. This study identified CYP325G4 as a novel mosquito deltamethrin resistance factor, being involved in both metabolic and cuticular resistance mechanisms. The previously identified CYP6AA9 was investigated for its involvement in metabolic resistance and potential cuticular resistance in mosquito legs. These findings enhance our comprehension of resistance mechanisms, identifying P450s as promising targets for the future management of mosquito vector resistance, and laying a theoretical groundwork for mosquito resistance management.

Parasitology ‒ As an Important Scientific Field of Medicine

Abstract Medical parasitology is the science that studies human parasites, diseases caused by them, and measures to combat these diseases. Medical parasitology is an important part of the science of parasitology (which includes zooparasitology and phytoparasitology) and studies the causes, transmission, pathogenesis, clinic, epidemiology, immunology and treatment of parasitic diseases in humans, as well as ways of prevention and control of these diseases. Traditionally, parasitic diseases include diseases caused by protozoa (protozoa), diseases caused by helminths (helminthoses) and diseases caused by arthropods. One of the most important tasks facing parasitology is the development and implementation of scientific-based measures against diseases caused by parasites in order to protect people's health, protect agricultural animals and plants from various diseases.

Prevalence and diversity of enteric Helicobacter spp. in healthy and diarrheic cats.

Helicobacters are gastric and enterohepatic and live in the gut. The role of enterohepatic Helicobacters as intestinal pathogens is uncertain, while stomach Helicobacters are well-known. The prevalence of Helicobacter species in cat feces helps us understand their impact on cat health and human disease transmission. This study used PCR to identify Helicobacter spp. in feces samples from healthy and diarrhoeic cats, independent of the reason. The study also compared intestinal and stomach Helicobacter species. PCR analysis was performed on fecal samples from 40 cats, with 20 cats having diarrhea and 20 cats showing no symptoms. The PCR analysis aimed to detect Helicobacter's presence using a method that identifies the bacteria through the 16S rRNA gene. The diarrhoeic group had a greater prevalence of infection (17:9 ratio), with an overall 65% infection rate detected. Cats that were older than 2 years showed a higher incidence of disease. H. canis had the highest occurrence rate (69.2%), followed by H. bilis, H. bizzozeronii, and H. salomonis. Significantly, H. pylori, H. felis, and H. heilmannii were not reported. H. canis was the predominant species found in both healthy and diarrheic cats, indicating the need for more investigation. The detection of the gastric species H. salomonis and H. bizzozeronii further complicates the classification. This highlights the complex nature of Helicobacter infections in cats, emphasizing the need for further investigation to guide the development of preventative measures and treatment techniques for both veterinary and public health purposes.

Optimal control strategies for toxoplasmosis disease transmission dynamics via harmonic mean-type incident rate

Toxoplasma infection in humans is considered due to direct contact with infected cats. Toxoplasma infection (an endemic disease) has the potential to affect various organs and systems (brain, eyes, heart, lungs, liver, and lymph nodes). Bilinear incidence rate and constant population (birth rate is equal to death rate) are used in the literature to explain the dynamics of Toxoplasmosis disease transmission in humans and cats. The goal of this study is to consider the mathematical model of Toxoplasma disease with harmonic mean type incident rate and also consider that the population of humans and cats is not equal (birth rate and the death rate are not equal). In examining Toxoplasma transmission dynamics in humans and cats, harmonic mean incidence rates are better than bilinear incidence rates. The disease dynamics are first schematically illustrated, and then the law of mass action is applied to obtain nonlinear ordinary differential equations (ODEs). Analysis of the boundedness, positivity, and equilibrium points of the system has been analyzed. The reproduction number is calculated using the next-generation matrix technique. The stability of disease-free and endemic equilibrium are analyzed. Sensitivity analysis is also done for reproduction number. Numerical simulation shows that the infection is spread in the population when the contact rate βh\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta_{h}$$\\end{document} and βc\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta_{c}$$\\end{document} increases while the infection is reduced when the recovery rate δh\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\delta_{h}$$\\end{document} increases. This study investigates the impact of various optimal control strategies, such as vaccinations for the control of disease and the awareness of disease awareness, on the management of disease.

PREVALENCE AND SUSCEPTIBILITY OF BACTERIA FROM USED TOOTHBRUSHES OF STUDENTS RESIDING IN HALL I AND II UNIVERSITY OF BENIN

Used toothbrushes are reservoirs for varieties of bacteria that are implicated in human disease transmission. Personal oral hygiene and removal of plaque are important roles played by the use of toothbrushes in an act endorsed for oral hygiene resolution and ubiquitously practiced in developing and developed Nations. The study aims to evaluate the prevalence and susceptibility of bacteria present in used toothbrushes of students residing in Halls I and II, University of Benin. New toothbrushes ninety (90) were bought and forty-five (45) each were distributed to students in each hall of residence, these toothbrushes were used for one month and collected for bacteria analysis. Standard bacteriological procedures were observed for the analysis. Data were analyzed using the SPSS 22.0 computer software package. Independent t-test was used to find the differences between the two variables. The value of p< 0.05 was taken to be statistically significant. Heavy bacteria contamination was associated with used toothbrushes while no bacteria contamination in the unused ones, which serves as a control. Klebsiella species 16 (35.53 %), and 19 (42.2 %) were more prevalent than coagulase-negative staphylococci species 2 (4.4 %) and 2(4.4 %) respectively from both halls. All the toothbrushes analyzed in this study had bacteria contaminates that are known to harm human health, contributing significantly to the spread of diseases, and increasing infection risks. Establishing a high aseptic protocol, storage, and management be encouraged in tertiary institution halls of residence as the incidence of these oral bacteria and individual health risks will be minimized.

Detection of pathogenic bacteria in ticks from Isiolo and Kwale counties of Kenya using metagenomics.

Ticks are arachnid ectoparasites that rank second only to mosquitoes in the transmission of human diseases including bacteria responsible for anaplasmosis, ehrlichiosis, spotted fevers, and Lyme disease among other febrile illnesses. Due to the paucity of data on bacteria transmitted by ticks in Kenya, this study undertook a bacterial metagenomic-based characterization of ticks collected from Isiolo, a semi-arid pastoralist County in Eastern Kenya, and Kwale, a coastal County with a monsoon climate in the southern Kenyan border with Tanzania. A total of 2,918 ticks belonging to 3 genera and 10 species were pooled and screened in this study. Tick identification was confirmed through the sequencing of the Cytochrome C Oxidase Subunit 1 (COI) gene. Bacterial 16S rRNA gene PCR amplicons obtained from the above samples were sequenced using the MinION (Oxford Nanopore Technologies) platform. The resulting reads were demultiplexed in Porechop, followed by trimming and filtering in Trimmomatic before clustering using Qiime2-VSearch. A SILVA database pretrained naïve Bayes classifier was used to classify the Operational Taxonomic Units (OTUs) taxonomically. The bacteria of clinical interest detected in pooled tick assays were as follows: Rickettsia spp. 59.43% of pools, Coxiella burnetii 37.88%, Proteus mirabilis 5.08%, Cutibacterium acnes 6.08%, and Corynebacterium ulcerans 2.43%. These bacteria are responsible for spotted fevers, query fever (Q-fever), urinary tract infections, skin and soft tissue infections, eye infections, and diphtheria-like infections in humans, respectively. P. mirabilis, C. acnes, and C. ulcerans were detected only in Isiolo. Additionally, COI sequences allowed for the identification of Rickettsia and Coxiella species to strain levels in some of the pools. Diversity analysis revealed that the tick genera had high levels of Alpha diversity but the differences between the microbiomes of the three tick genera studied were not significant. The detection of C. acnes, commonly associated with human skin flora suggests that the ticks may have contact with humans potentially exposing them to bacterial infections. The findings in this study highlight the need for further investigation into the viability of these bacteria and the competency of ticks to transmit them. Clinicians in these high-risk areas also need to be appraised for them to include Rickettsial diseases and Q-fever as part of their differential diagnosis.

Investigating the Status of Contamination With Pulex irritans and Xenopsylla cheopis in Pets, Guard and Stray Dogs in Tabriz, Iran

Introduction: Fleas are the most prevalent ectoparasites indoors and outdoors due to their high reproductive rate, ability to feed on different hosts, and the unpleasant effects of their bites. Methods: This study was conducted on 360 dogs in and around Tabriz to find the rate and type of human flea contamination in these dogs, which were divided into three categories: pets, guards, and stray dogs. After fleas were identified in the dogs’ skin, they were taken with glue and fixed on the slide with glue. When the number of fleas was large, the captured fleas were transported to a test tube and treated with 70% alcohol. Dehydration of fleas was performed with ascending percentages of ethanol from 50 to 100% absolute and was kept inside each alcohol percentage for 10 to 20 minutes. Results: Regarding the dogs studied in this research, the rate of actual contamination in guard dogs was 76.67% (92 dogs were contaminated with flea feces). However, 74 dogs (about 15%) were infested with different fleas. Unfortunately, the rate of contamination in stray dogs was 100%. The rate of real contamination based on the separation of fleas and flea excrement from the body of this group of dogs was equal. The rate of flea infestation in pet dogs was 14 out of 100 dogs, representing 14% contamination. Conclusion: It should be acknowledged that, unfortunately, flea infestation is expected in the region’s dogs, depending on the type of dogs kept. Infestation with these insidious skin parasites with varying rates and symptoms is common, which, in addition to the economic damage of spending time and money on medicine for disease in animals, causes environmental pollution, increases the likelihood of disease transmission by these parasites, and increases the possibility of human infection and disease transmission from them to humans, as well as environmental pollution.

Impacts of Changing Climate on Arthropod Vectors and Diseases Transmission

Climate change stands as a burgeoning global concern with profound implications. The present review seeks to present the projected impacts of climate change on disease vectors and their transmission of various human and animal diseases. The impact of climate on the prevalence of vector-borne diseases (VBDs), which significantly affect human and animal populations, is notable. The occurrence of VBDs, influenced by local epidemiological and ecological factors alongside specific climatic conditions, may exhibit fluctuations due to climate change. Particularly affected are exothermic arthropod vectors, responsible for transmitting most vectorborne diseases. The intricate interplay of temperature, precipitation, humidity, and other environmental factors significantly shapes the reproduction, development, behavior, and population dynamics of arthropod disease vectors. Also, climate change can alter the spread of pathogens within vectors, influence population dynamics, and impact the range of nonhuman vertebrate reservoirs for numerous vector-borne diseases. Predicting the precise impact of sustained climate change on these diseases poses a considerable challenge, necessitating comprehensive long-term research. These researches must encompass the effects of climate change while considering the contributions of other global change agents, including increased trade and travel, demographic shifts, civil unrests, alterations in land use, water availability, and related factors. The association between climate change and the emergence of specific diseases has been established. However, for certain diseases, the risk of local transmission is significant, while for others, pinpointing the exact influence remains elusive. Therefore, strategic adaptation and preparedness for the shifting distribution patterns of VBDs are imperative, especially in the context of Nigeria and Africa as a whole.

Earliest records of the Asian longhorned tick (Acari: Ixodidae) in Staten Island, New York, and subsequent population establishment, with a review of its potential medical and veterinary importance in the United States.

Three Asian longhorned ticks (Haemaphysalis longicornis) were collected on Staten Island, Richmond County, New York, in 2014-2015 as part of a tick-borne disease surveillance program conducted by the New York City Department of Health and Mental Hygiene and the Defense Centers of Public Health - Aberdeen Tick-Borne Disease Laboratory. These records mark the earliest known occurrence of H. longicornis in New York State outside of quarantine areas, predating previously reported detections by several years. Robust populations of H. longicornis were collected in subsequent years at the Staten Island site where these few ticks were found, demonstrating that small infestations have the potential to proliferate quickly. Haemaphysalis longicornis is a 3-host ixodid tick native to eastern Asia but now established in the United States, as well as Australasia and several Pacific islands. Although H. longicornis has not yet been associated with human disease transmission in the United States, it warrants attention as a potential vector, as it is demonstrated to harbor various pathogens of medical and veterinary interest across its native and introduced range.

Scenario analysis of COVID-19 dynamical variations by different social environmental factors: a case study in Xinjiang.

With the rapid advancement of the One Health approach, the transmission of human infectious diseases is generally related to environmental and animal health. Coronavirus disease (COVID-19) has been largely impacted by environmental factors regionally and globally and has significantly disrupted human society, especially in low-income regions that border many countries. However, few research studies have explored the impact of environmental factors on disease transmission in these regions. We used the Xinjiang Uygur Autonomous Region as the study area to investigate the impact of environmental factors on COVID-19 variation using a dynamic disease model. Given the special control and prevention strategies against COVID-19 in Xinjiang, the focus was on social and environmental factors, including population mobility, quarantine rates, and return rates. The model performance was evaluated using the statistical metrics of correlation coefficient (CC), normalized absolute error (NAE), root mean square error (RMSE), and distance between the simulation and observation (DISO) indices. Scenario analyses of COVID-19 in Xinjiang encompassed three aspects: different population mobilities, quarantine rates, and return rates. The results suggest that the established dynamic disease model can accurately simulate and predict COVID-19 variations with high accuracy. This model had a CC value of 0.96 and a DISO value of less than 0.35. According to the scenario analysis results, population mobilities have a large impact on COVID-19 variations, with quarantine rates having a stronger impact than return rates. These results provide scientific insight into the control and prevention of COVID-19 in Xinjiang, considering the influence of social and environmental factors on COVID-19 variation. The control and prevention strategies for COVID-19 examined in this study may also be useful for the control of other infectious diseases, especially in low-income regions that are bordered by many countries.

The chromosome-scale genome assembly for the West Nile vector Culex quinquefasciatus uncovers patterns of genome evolution in mosquitoes

BackgroundUnderstanding genome organization and evolution is important for species involved in transmission of human diseases, such as mosquitoes. Anophelinae and Culicinae subfamilies of mosquitoes show striking differences in genome sizes, sex chromosome arrangements, behavior, and ability to transmit pathogens. However, the genomic basis of these differences is not fully understood.MethodsIn this study, we used a combination of advanced genome technologies such as Oxford Nanopore Technology sequencing, Hi-C scaffolding, Bionano, and cytogenetic mapping to develop an improved chromosome-scale genome assembly for the West Nile vector Culex quinquefasciatus.ResultsWe then used this assembly to annotate odorant receptors, odorant binding proteins, and transposable elements. A genomic region containing male-specific sequences on chromosome 1 and a polymorphic inversion on chromosome 3 were identified in the Cx. quinquefasciatus genome. In addition, the genome of Cx. quinquefasciatus was compared with the genomes of other mosquitoes such as malaria vectors An. coluzzi and An. albimanus, and the vector of arboviruses Ae. aegypti. Our work confirms significant expansion of the two chemosensory gene families in Cx. quinquefasciatus, as well as a significant increase and relocation of the transposable elements in both Cx. quinquefasciatus and Ae. aegypti relative to the Anophelines. Phylogenetic analysis clarifies the divergence time between the mosquito species. Our study provides new insights into chromosomal evolution in mosquitoes and finds that the X chromosome of Anophelinae and the sex-determining chromosome 1 of Culicinae have a significantly higher rate of evolution than autosomes.ConclusionThe improved Cx. quinquefasciatus genome assembly uncovered new details of mosquito genome evolution and has the potential to speed up the development of novel vector control strategies.

Efficient transmission of human prion diseases to a glycan-free prion protein-expressing host.

It is increasingly evident that the association of glycans with the prion protein (PrP), a major post-translational modification, significantly impacts the pathogenesis of prion diseases. A recent bioassay study has provided evidence that the presence of PrP glycans decreases spongiform degeneration and disease-related PrP (PrPD) deposition in a murine model. We challenged (PRNPN181Q/197Q) transgenic (Tg) mice expressing glycan-free human PrP (TgGlyc-), with isolates from sporadic Creutzfeldt-Jakob disease subtype MM2 (sCJDMM2), sporadic fatal insomnia and familial fatal insomnia, three human prion diseases that are distinct but share histotypic and PrPD features. TgGlyc- mice accurately replicated the basic histotypic features associated with the three diseases but the transmission was characterized by high attack rates, shortened incubation periods and a greatly increased severity of the histopathology, including the presence of up to 40 times higher quantities of PrPD that formed prominent deposits. Although the engineered protease-resistant PrPD shared at least some features of the secondary structure and the presence of the anchorless PrPD variant with the wild-type PrPD, it exhibited different density gradient profiles of the PrPD aggregates and a higher stability index. The severity of the histopathological features including PrP deposition appeared to be related to the incubation period duration. These findings are clearly consistent with the protective role of the PrP glycans but also emphasize the complexity of the conformational changes that impact PrPD following glycan knockout. Future studies will determine whether these features apply broadly to other human prion diseases or are PrPD-type dependent.

A Perspective on Monkeypox Related LGBT Phobia Among the General Public

Due to an upsurge in imported cases in the Western Pacific Region, the World Health Organization has proclaimed monkeypox a Public Health Emergency of International Concern on July 23rd, 2022. The worldwide transmission of human monkeypox disease presents substantial healthcare concern. Similar to previous infectious disease outbreaks, conspiracy theories have also emerged in relation to the 2022 monkeypox outbreak, undermining health behaviors and amplifying the outbreak's impact. Fake news on social media worsens the monkeypox outbreak, silencing healthcare experts. The outbreak has stigmatized monkeypox, putting LGBTQI+ communities at increased risk. Unsurprisingly, the present outbreak is impacting a large number of homosexuals, bisexuals, and men who have sex with men, which may lead to increased discrimination and stigma towards this group, along with increased LGBT phobia among the general population. Such stigmatization lead to healthcare disengagement, increasing morbidity and mortality, significant physical, socio-economic, and psychological consequences for LGBTQ+ community. Monkeypox is manageable if transmission chains are broken, aided by accurate information to dispel outdated myths rooted in fear and sexual bias. A holistic, culturally-sensitive approach is vital to combat current monkeypox-related stigma, requiring government interventions and multi-stakeholder collaboration for a multidisciplinary strategy.

Zoonotic diseases transmitted from the camels.

Zoonotic diseases, infections transmitted naturally from animals to humans, pose a significant public health challenge worldwide. After MERS-CoV was discovered, interest in camels was raised as potential intermediate hosts for zoonotic viruses. Most published review studies pay little attention to case reports or zoonotic epidemics where there is epidemiological proof of transmission from camels to humans. Accordingly, any pathogen found in camels known to cause zoonotic disease in other animals or humans is reported. Here, zoonotic diseases linked to camels are reviewed in the literature, focusing on those with epidemiological or molecular evidence of spreading from camels to humans. This review examines the risks posed by camel diseases to human health, emphasizing the need for knowledge and awareness in mitigating these risks. A search of the literature revealed that eight (36.4%) of the 22 investigations that offered convincing evidence of camel-to-human transmission involved MERS, five (22.7%) Brucellosis, four (18.2%) plague caused by Yersinia pestis, three (13.6%) camelpox, one (4.5%) hepatitis E, and one (4.5%) anthrax. The reporting of these zoonotic diseases has been steadily increasing, with the most recent period, from 2010 to the present, accounting for 59% of the reports. Additionally, camels have been associated with several other zoonotic diseases, including toxoplasmosis, Rift Valley fever, TB, Crimean-Congo hemorrhagic fever, and Q fever, despite having no evidence of a transmission event. Transmission of human zoonotic diseases primarily occurs through camel milk, meat, and direct or indirect contact with camels. The above-mentioned diseases were discussed to determine risks to human health. MERS, Brucellosis, plague caused by Y. pestis, camelpox, hepatitis E, and anthrax are the main zoonotic diseases associated with human disease events or outbreaks. Transmission to humans primarily occurs through camel milk, meat, and direct contact with camels. There is a need for comprehensive surveillance, preventive measures, and public health interventions based on a one-health approach to mitigate the risks of zoonotic infections linked to camels.

Patterns of genetic differentiation imply distinct phylogeographic history of the mosquito species Anopheles messeae and Anopheles daciae in Eurasia.

Detailed knowledge of phylogeography is important for control of mosquito species involved in the transmission of human infectious diseases. Anopheles messeae is a geographically widespread and genetically diverse dominant vector of malaria in Eurasia. A closely related species, An. daciae, was originally distinguished from An. messeae based on five nucleotide substitutions in its ribosomal DNA (rDNA). However, the patterns of phylogeographic history of these species in Eurasia remain poorly understood. Here, using internal transcribed spacer 2 (ITS2) of rDNA and karyotyping for the species identification we determined the composition of five Anopheles species in 28 locations in Eurasia. Based on the frequencies of 11 polymorphic chromosomal inversions used as genetic markers, a large-scale population genetics analysis was performed of 1932 mosquitoes identified as An. messeae, An. daciae and their hybrids. The largest genetic differences between the species were detected in the X sex chromosome suggesting a potential involvement of this chromosome in speciation. The frequencies of autosomal inversions in the same locations differed by 13%-45% between the species demonstrating a restricted gene flow between the species. Overall, An. messeae was identified as a diverse species with a more complex population structure than An. daciae. The clinal gradients in frequencies of chromosomal inversions were determined in both species implicating their possible involvement in climate adaptations. The frequencies of hybrids were low ~1% in northern Europe but high up to 50% in south-eastern populations. Thus, our study revealed critical differences in patterns of phylogeographic history between An. messeae and An. daciae in Eurasia. This knowledge will help to predict the potential of the malaria transmission in the northern territories of the continent.

What about Current Diversity of Mycolactone-Producing Mycobacteria? Implication for the Diagnosis and Treatment of Buruli Ulcer.

The identification of an emerging pathogen in humans can remain difficult by conventional methods such as enrichment culture assays that remain highly selective, require appropriate medium and cannot avoid misidentifications, or serological tests that use surrogate antigens and are often hampered by the level of detectable antibodies. Although not originally designed for this purpose, the implementation of polymerase-chain-reaction (PCR) has resulted in an increasing number of diagnostic tests for many diseases. However, the design of specific molecular assays relies on the availability and reliability of published genetic sequences for the target pathogens as well as enough knowledge on the genetic diversity of species and/or variants giving rise to the same disease symptoms. Usually designed for clinical isolates, molecular tests are often not suitable for environmental samples in which the target DNA is mixed with a mixture of environmental DNA. A key challenge of such molecular assays is thus to ensure high specificity of the target genetic markers when focusing on clinical and environmental samples in order to follow the dynamics of disease transmission and emergence in humans. Here we focus on the Buruli ulcer (BU), a human necrotizing skin disease mainly affecting tropical and subtropical areas, commonly admitted to be caused by Mycobacterium ulcerans worldwide although other mycolactone-producing mycobacteria and even mycobacterium species were found associated with BU or BU-like cases. By revisiting the literature, we show that many studies have used non-specific molecular markers (IS2404, IS2606, KR-B) to identify M. ulcerans from clinical and environmental samples and propose that all mycolactone-producing mycobacteria should be definitively considered as variants from the same group rather than different species. Importantly, we provide evidence that the diversity of mycolactone-producing mycobacteria variants as well as mycobacterium species potentially involved in BU or BU-like skin ulcerations might have been underestimated. We also suggest that the specific variants/species involved in each BU or BU-like case should be carefully identified during the diagnosis phase, either via the key to genetic identification proposed here or by broader metabarcoding approaches, in order to guide the medical community in the choice for the most appropriate antibiotic therapy.

MOSQUITO RESISTANCE TO INSECTICIDES IN BULGARIA

Mosquitoes are a group of blood-sucking insects that plays a major role in disease transmission in both humans and animals. They can pose a heavy nuisance, or serve as vectors of numerous viruses and parasites on most continents, including Europe. The strategy for successful control of the mosquito populations relies on the use of insecticides of five different categories: organochlorines, organophosphates, carbamates, pyrethroids, and biopesticides. The extensive use of the first four classes has resulted in the development of resistance originating in various mechanisms. The main ones are metabolic resistance and genetic resistance, manifested by point mutations in the insecticide targets, resulting in limited binding of neurotoxic substances. Much data is available on mosquito insecticide resistance in Bulgaria between 1948 and 1990, but only regarding organochlorines, organophosphates and carbamates. There is no data on pyrethroid resistance, which should raise an alarm for both public health authorities and private pest control companies since the only insecticides registered for professional mosquito control nowadays are pyrethroids. Therefore, there is an urgent need for the use of modern multidisciplinary approaches to study the resistance of native and invasive species of mosquitoes to insecticides, which should be a key contribution to elucidating their role in the circulation of pathogens of humans and animals and optimizing methods for controlling their populations.

Insecticide resistance: Status and potential mechanisms in Aedes aegypti

Aedes aegypti, an important vector in the transmission of human diseases, has developed resistance to two commonly used classes of insecticides, pyrethroids and organophosphates, in populations worldwide. This study examined sensitivity/resistance to chlorpyrifos, fenitrothion, malathion, deltamethrin, permethrin, and β-cyfluthrin, along with possible metabolic detoxification and target site insensitivity, in three Aedes aegypti mosquito strains. The resistant strain (PR) had developed high levels of resistance to all three pyrethroid insecticides compared to a susceptible population, with 6, 500-, 3200- and 17,000-fold resistance to permethrin, β-cyfluthrin, and deltamethrin, respectively. A newly emerged Ae. aegypti population collected from St. Augustine, Florida (AeStA) showed elevated levels of resistance to malathion (12-fold) and permethrin (25-fold). Synergists DEF (S,S,S,-tributyl phosphorotrithioate) and DEM (diethyl maleate) showed no or minor effects on insecticide resistance in both the AeStA and PRG20strains, but PBO (piperonyl butoxide) completely abolished resistance to both malathion and permethrin in AeStA and partially suppressed resistance in PR. The voltage-gated sodium channel sequences were examined to explore the mechanism that only partially inhibited the suppression of resistance to PBO in PR. Two mutations, V1016G/I and F1534C substitutions, both of which are associated with the development of pyrethroid resistance, were identified in the PRG20 strain but not in AeStA. These results suggest that while cytochrome P450 mediated detoxification may not be solely responsible, it is the major mechanism governing the development of resistance in AeStA. Both P450 mediated detoxification and target site insensitivity through the mutations in the voltage-gated sodium channel contribute to the high levels of resistance in the PRG20 strain.

Evolutionary potential ofthe monkeypox genome arising from interactions with human APOBEC3 enzymes.

APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational 'hotspots', can drive viral mutagenesis with host-specific preferential hotspot mutations contributing to pathogen variation. While previous analysis of viral genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown a high frequency of C>T mutations at TC motifs, suggesting recent mutations are human APOBEC3-mediated, how emerging monkeypox virus (MPXV) strains will evolve as a consequence of APOBEC3-mediated mutations remains unknown. By measuring hotspot under-representation, depletion at synonymous sites, and a combination of the two, we analyzed APOBEC3-driven evolution in human poxvirus genomes, finding varying hotspot under-representation patterns. While the native poxvirus molluscum contagiosum exhibits a signature consistent with extensive coevolution with human APOBEC3, including depletion of TC hotspots, variola virus shows an intermediate effect consistent with ongoing evolution at the time of eradication. MPXV, likely the result of recent zoonosis, showed many genes with more TC hotspots than expected by chance (over-representation) and fewer GC hotspots than expected (under-representation). These results suggest the MPXV genome: (1) may have evolved in a host with a particular APOBEC GC hotspot preference, (2) has inverted terminal repeat (ITR) regions-which may be exposed to APOBEC3 for longer during viral replication-and longer genes likely to evolve faster, and therefore (3) has a heightened potential for future human APOBEC3-meditated evolution as the virus spreads in the human population. Our predictions of MPXV mutational potential can both help guide future vaccine development and identification of putative drug targets and add urgency to the task of containing human Mpox disease transmission and uncovering the ecology of the virus in its reservoir host.

Epidemic thresholds and human mobility

A comprehensive view of disease epidemics demands a deep understanding of the complex interplay between human behaviour and infectious diseases. Here, we propose a flexible modelling framework that brings conclusions about the influence of human mobility and disease transmission on early epidemic growth, with applicability in outbreak preparedness. We use random matrix theory to compute an epidemic threshold, equivalent to the basic reproduction number R_{0}, for a SIR metapopulation model. The model includes both systematic and random features of human mobility. Variations in disease transmission rates, mobility modes (i.e. commuting and migration), and connectivity strengths determine the threshold value and whether or not a disease may potentially establish in the population, as well as the local incidence distribution.