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Discriminant analysis: a method of identifying foci of vector-borne diseases.

Identification of foci of vector-borne diseases does not require knowledge of exact abundances of vectors and pathogens; rather, a focus is defined by the presence, or some minimal level of abundance, of a vector and pathogen. Stepwise discriminant analysis (DA) was applied to data on free-ranging adult wood ticks (the vector) and to data on isolations of Colorado tick fever virus from small mammals. Trap stations were grouped on the basis of relative abundance of wood ticks for one set of analyses and on the presence or absence of virus for another set of analyses. Additional data consisted of easily measured environmental variables. It is concluded that DA provides a useful tool for analysis of ecosystem structure and an effective means of identifying foci of infection.

Animals

Vectors of dengue fever/dengue haemorrhagic fever with advances in their control.

The most important vector of dengue in the Western Pacific Region is Ae. aegypti. On some occasions, Ae. albopictus, Ae. polynesiensis and several other species of the Ae. scutellaris complex have been suspected vectors in localities where Ae. aegypti was not found. Long-term vector control by the use of insecticides has been expensive and difficult to achieve. However, spray equipment and ULV insecticides have been obtained in many places for emergency use during outbreaks, and Abate larviciding also has been used in high-risk localities to help prevent outbreaks. Obtaining greater community participation supported by intensified health education and other acceptable measures is considered an important approach for achieving improved long-term control. Developing an acceptable and effective cover for domestic water storage containers is also recognized as a potentially important tool for suppressing vector populations.

Aedes

[The dynamic ecology of virus-vector system (author's transl)].

The phenomenon of arbovirus transmission by their vectors is based upon the constitution of virus-vector systems, not only at the species level, but also at an infra-specific level. The study of such systems leads to consider some particular aspects of their ecology which can have important epidemiological consequences (selection of viral clones by the vector, transovarial and sexual transmissions). Finely the authors approach the question of evolution of virus-vector systems, which appear as adaptative, functional and temporary associations.

Aedes

Bacteriophage lambda-E. coli K12 vector-host system for gene cloning and expression under lactose promoter control. II. DNA fragment insertion at the vicinity of the lac UV5 promoter.

Bacteriophage vectors derived from lambda plac5 have been constructed. Their genomes have one EcoRI restriction site which is located at the very beginning of the lac Z gene. The major part of this gene was deleted by an in vivo intramolecular recombination. These vectors allow the fusion of a gene or an operon with the beginning of the lac Z gene, placing them under the control of the lac promoter, which carries the UV5 mutation. Some of these vectors (lambda Y) also include the lac Y gene and it too is under the control of the lac promoter. The lambda YEQS, which carries the Qam73 and Sam7 mutations, as safety mutations, has been certified as a B2 (EK2) vector by the French control commission "recombinaison génétique in vitro".

Coliphages

Construction of a hybrid bacteriophage-plasmid recombinant DNA vector.

A phage-plasmid hybrid was constructed for use as a recombinant DNA vector, allowing the propagation of cloned EcoRI restriction endonuclease fragments of about 2 X 10(6) to 11 X 10(6) daltons. The colicin E1 plasmid replicon was fused to the left arm of a lambdagt generalized transducing phage with a thermolabile repressor, yielding a genome which could be replicated either by phage lambda functions or via the colicin E1 plasmid replicon. At the nonpermissive temperature, phage functions were derepressed and phage growth occurred lytically. Alternatively, at the permissive temperature, lambda functions were repressed and the vector replicated as a covalently closed circular plasmid. The phage-plasmid hybrid vector could be maintained at a copy number determined by the colicin E1 plasmid replicon and was also sensitive to amplification after chloramphenicol treatment. An EcoRI fragment of Escherichia coli DNA encoding genes of the arabinose operon also was inserted into the central portion of the vector.

Chloramphenicol

[Importance of space analysis of U-moment-vectors concerning ageing people and chronical heart and blood circulation diseases (author's transl)].

U-vectors are a stabil component of electric activity of the heart repolarisation. The examinations of the space sizes and direction of the U-moment-vectors give an idea about the character of repolarisation of Purkinje's fibres and papillar muscles in old age and in chronical heart and blood circulation diseases. Pathological alteration of the U-vectors appear sooner and are more explicit than the T-vectors.

Adult

Genomic profiling of digestion related enzymes in Anopheles aquasalis a major coastal neotropical malaria vector.

Digestive genes are fundamental for the development and survival of mosquitoes and can serve as a target for the development of strategies for mosquito control or vector-borne disease prevention. Genes related to digestion were identified in the genome of the neotropical malaria vector Anopheles aquasalis by similarity. We used reciprocal BLAST with annotated digestion proteins for Anopheles gambiae. Orthology and evolutionary analyses were performed using MEGA with a bootstrapped phylogenetic tree constructed by the neighbor-joining method, and copy number variation was measured by the standard deviation of the average copy number in each gene family. We identified 241 genes related to digestion in An. aquasalis: 56 genes related to carbohydrate digestion, 51 genes for lipid digestion, and 134 genes for protein digestion. Phylogenetic relationships with other anophelines show that An. aquasalis genes are closely related to those of neotropical mosquitoes Anopheles darlingi and Anopheles albimanus. Orthologous gene clusters are conserved in important families of all four species. Some of these conserved genes are of interest for studies on controlling mosquito vectors, such as larvicidal toxin receptor genes, alpha-amylase, alpha-glucosidase, and maltase; important target genes for transmission-blocking vaccines, such as aminopeptidase N1 and carboxypeptidase B; and the major intestinal serine proteases, such as trypsins and chymotrypsins, which can positively or negatively affect Plasmodium development in the midgut. These data provide a better understanding of digestion-related genes in American anopheline mosquitoes and may support further fundamental and applied studies aimed at malaria control.

Animals

New vectors and optimal conditions for allelic exchange in hypervirulent Klebsiella pneumoniae.

The emergence of antibiotic-resistant Klebsiella pneumoniae is a significant global health threat that has led to increased morbidity and mortality. This resistance also hinders basic research, as many strains are no longer susceptible to antibiotics commonly used in microbial genetics. Addressing this requires the development of new genetic tools with alternative selective markers. In this report, we introduce new allelic exchange vectors for use in drug-resistant strains. These vectors feature a conditional R6K origin of replication, an origin of transfer, SacB counter-selection, and alternative selectable markers. We validated the vectors by generating unmarked deletions in the K. pneumoniae KPPR1S bla (β-lactamase) and lacZ (β-galactosidase) genes. During this process, we defined optimized conditions for SacB-mediated allelic exchange in KPPR1S, significantly enhancing the efficiency of mutant generation. Furthermore, we demonstrated that lacZ is dispensable for virulence and that the lacZ mutant can serve as a surrogate for wild-type strains in competition assays using the Galleria mellonella infection model. Our findings provide new tools for the efficient genetic manipulation of K. pneumoniae and other drug-resistant bacteria.

Klebsiella pneumoniae

Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors.

Despite increasingly widespread use of recombinant adeno-associated virus (AAV) and lentiviral (LV) vectors for transduction of neurons in a wide range of brain structures and species, the diversity of cell types within a given brain structure is rarely considered. For example, the ability of a vector to transduce neurons within a brain structure is often assumed to indicate that all neuron types within the structure are transduced. We have characterized the transduction of mouse somatosensory cortical neuron types by recombinant AAV pseudotyped with serotype 1 capsid (rAAV2/1) and by recombinant lentivirus pseudotyped with the vesicular stomatitis virus (VSV) glycoprotein. Both vectors used human synapsin (hSyn) promoter driving DsRed-Express. We demonstrate that high titer rAAV2/1-hSyn efficiently transduces both cortical excitatory and inhibitory neuronal populations, but use of lower titers exposes a strong preference for transduction of cortical inhibitory neurons and layer 5 pyramidal neurons. In contrast, we find that VSV-G-LV-hSyn principally labels excitatory cortical neurons at the highest viral titer generated. These findings demonstrate that endogenous tropism of rAAV2/1 and VSV-G-LV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively.

Animals

Application of mutated miR-206 target sites enables skeletal muscle-specific silencing of transgene expression of cardiotropic AAV9 vectors.

Insertion of completely complementary microRNA (miR) target sites (miRTS) into a transgene has been shown to be a valuable approach to specifically repress transgene expression in non-targeted tissues. miR-122TS have been successfully used to silence transgene expression in the liver following systemic application of cardiotropic adeno-associated virus (AAV) 9 vectors. For miR-206-mediated skeletal muscle-specific silencing of miR-206TS-bearing AAV9 vectors, however, we found this approach failed due to the expression of another member (miR-1) of the same miR family in heart tissue, the intended target. We introduced single-nucleotide substitutions into the miR-206TS and searched for those which prevented miR-1-mediated cardiac repression. Several mutated miR-206TS (m206TS), in particular m206TS-3G, were resistant to miR-1, but remained fully sensitive to miR-206. All these variants had mismatches in the seed region of the miR/m206TS duplex in common. Furthermore, we found that some m206TS, containing mismatches within the seed region or within the 3' portion of the miR-206, even enhanced the miR-206- mediated transgene repression. In vivo expression of m206TS-3G- and miR-122TS-containing transgene of systemically applied AAV9 vectors was strongly repressed in both skeletal muscle and the liver but remained high in the heart. Thus, site-directed mutagenesis of miRTS provides a new strategy to differentiate transgene de-targeting of related miRs.

Base Pairing

Chlorfenapyr-pyrethroid nets for pyrethroid-resistant malaria vectors: efficacy, resistance risks, and policy implications.

The Global Technical Strategy for Malaria 2016-2030 aims to reduce malaria incidence and mortality by 90%, yet widespread pyrethroid resistance among major malaria vectors in sub-Saharan Africa threatens this goal. Thus, the World Health Organization recommends chlorfenapyr-pyrethroid combination nets as a priority intervention where pyrethroid resistance undermines vector control. This systematic review synthesizes evidence on the performance, emerging resistance risks, and policy implications of these next-generation insecticide-treated nets. A structured search of literature from 2010 to 2024 across PubMed, Embase, WHO IRIS, and Google Scholar identified 31 eligible studies from 113 records. Evidence shows that chlorfenapyr-pyrethroid nets consistently outperform pyrethroid-only nets against resistant Anopheles populations, demonstrating a 1.8-fold increase in mosquito mortality (95% CI: 1.5-2.1). Community trials report 40-60% reductions in malaria infection incidence and entomological inoculation rates following deployment. However, early signs of chlorfenapyr resistance have emerged in Anopheles gambiae populations in Central Africa (RR: 2.4, p&#x2009;=&#x2009;0.01), linked to CYP6P4 metabolic overexpression. A significant correlation was also observed between agricultural pesticide use and vector resistance patterns (r&#x2009;=&#x2009;0.62, p&#x2009;<&#x2009;0.05). Although chlorfenapyr-pyrethroid nets provide an important short-term tool for managing pyrethroid resistance, their long-term effectiveness depends on integrated resistance management. Rotational deployment with other insecticide classes, strengthened genetic and phenotypic surveillance, and a coordinated 'One Health' approach involving both public health and agriculture are essential to sustain gains and advance progress toward the 2030 malaria targets.

Pyrethrins

Systemic and Persistent Muscle Gene Expression in Rhesus Monkeys with a Liver De-Targeted Adeno-Associated Virus Vector.

The liver is a major off-target organ in gene therapy approaches for cardiac and musculoskeletal disorders. Intravenous administration of most of the naturally occurring adeno-associated virus (AAV) strains invariably results in vector genome sequestration within the liver. In the current study, we compared the muscle tropism and transduction efficiency of a liver de-targeted AAV variant to AAV9 following systemic administration in newborn rhesus monkeys. In vivo bioluminescence imaging was performed to monitor transgene expression (firefly luciferase) post administration. Results indicated comparable and sustained levels of systemic firefly luciferase gene expression in skeletal muscle over a period of two years. Quantitation of vector biodistribution in harvested tissues post-administration revealed widespread recovery of vector genomes delivered by AAV9 but markedly decreased levels in major systemic organs from the AAV variant. These studies validate the translational potential and safety of liver de-targeted AAV strains for gene therapy of muscle-related diseases.

Animals

A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.

BACKGROUND: This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B). METHODS: This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50&#xa0;IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (&#x2265;1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated. RESULTS: In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or &#x2265;1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs &#x2265;10&#xa0;mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors. CONCLUSIONS: Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.

Humans

Emergence and phylogeography of the dengue vector Aedes aegypti in Southeastern Iran.

BACKGROUND: Aedes (Stegomyia) aegypti (Linnaeus) is the primary vector of dengue, chikungunya, Zika, and yellow fever viruses. Its recent detection in southeastern Iran raises public health concerns about arbovirus spread to new regions. This study provides the first genetic and phylogeographic analysis of Ae. aegypti populations from Sistan and Baluchistan Province (SBP), Iran, to infer their origin and invasion pathways. METHODS: Mitochondrial COI and ND4 genes were analysed in newly collected Ae. aegypti specimens from border areas, ports, and urban centres of SBP. Haplotype network analyses were constructed using the TCS method in PopART, and phylogenetic analyses were conducted using global reference sequences. RESULTS: Iranian specimens comprised 7 COI haplotypes (n&#x2009;=&#x2009;18) and 10 ND4 haplotypes (n&#x2009;=&#x2009;17). COI phylogeny placed Iranian specimens into two main clades, while ND4 analysis distributed them across several derived clades, mostly clustering with lineages from Latin America (Brazil, Mexico) or Africa. One Iranian specimen showed a close relationship with a Saudi Arabian sequence (bootstrap: 98%) near the basal region. Combined COI&#x2009;+&#x2009;ND4 analysis revealed a monophyletic clade of Iranian specimens with a Sri Lankan specimen, distinct from other global lineages. The global COI network (n&#x2009;=&#x2009;47) showed a star-like topology with a dominant haplotype 1 shared among 10 Iranian specimens. The ND4 network (n&#x2009;=&#x2009;31) revealed a complex topology with 18 haplotypes, where a Saudi Arabian and one Iranian specimen (~30 mutational steps) possibly represented the peripheral root. CONCLUSIONS: Detection of diverse Ae. aegypti clades confirm establishment of this vector in southeastern Iran. Results support multiple introductions and genetic connectivity with Latin America, Africa, and South Asia, pointing to an emerging invasion corridor. Continued genomic surveillance and integrated vector monitoring are urgently needed to guide prevention strategies.

Animals

A longitudinal study of schistosome vector snail populations in Liberia.

Seasonal changes in populations of Biomphalaria pfeifferi and Bulinus globosus were observed at 62 locations in Liberia, West Africa. All varieties of water in both urban and rural locations were sampled. A wet season decrease and dry season increase of B. globosus populations in both urban and rural locations, similar to that reported elsewhere in West Africa, was observed. Similar fluctuations of B. pfeifferi populations were noted. The prevalence of schistosome infected vector snails varied markedly between rural and urban locations. At rural sites parasite prevalence followed the appropriate vector snail prevalence. At urban sites a portion of the vector snail population appeared relatively unaffected by seasonal changes. This stable population harbors a reservoir of infected snails that sustain year round transmission. Human infection was sampled in school children in the study area and prevalence of approximately 50% was found for both Schistosoma mansoni and S. haematobium. Added to the malacologic information this suggests less than hyperendemic transmission. The data suggest that urban environments should receive priorities for control programs.

Animals

Bacteriophage lambda-E. coli K12 vector-host system for gene cloning and expression under lactose promoter control: I. DNA fragment insertion at the lacZ EcoRI restriction site.

Bacteriophage lambda vectors, derived from lambda plac5 were constructed. Their genomes have only one EcoRI restriction site, located near the end of the beta-galactosidase gene. Recombinants, constructed in vitro, having a DNA fragment inserted in the EcoRI site, are lac- and can be easily recognized. Expression of such foreign genes is then under the control of the lac promoter. Mutations Qam73 and Sam7 greatly increase the amount of beta-galactosidase synthesized by the vector bacteriophage. The lambda ZEQS vector has been certified B2 (EK2) by the French control commission "Recombinaisons génétiques in vitro".

Coliphages

The natural decline of Wuchereria bancrofti infection in a vector control situation in the Solomon Islands.

In a situation where filariasis and malaria are transmitted by the same vector, as seen here in the Solomon Islands, the Malaria Eradication Programme aimed at controlling the vector, was found to have an effect on both diseases. In an area of Choiseul island first surveyed by the author in 1970, three follow-up surveys were conducted--in 1974, 1975 and 1976. These showed a progressive decrease in persons infected. When the densities, especially the median microfilarial counts, were expressed as percentage values of the pre-spray survey, there was found to be a proportional decrease over eight years. It is possible that the Anopheline vector needs to be reduced less for the cessation of transmission of filariasis than for malaria. A theoretical ratio was calculated and supporting field evidence presented.

Age Factors