Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.

Many organisms live in fragmented populations, which has profound consequences on the dynamics of associated parasites. Metapopulation theory offers a canonical framework for predicting the effects of fragmentation on spatiotemporal host–parasite dynamics. However, empirical studies of parasites in classical metapopulations remain rare, particularly for vector-borne parasites. Here, we quantify spatiotemporal patterns and possible drivers of infection probability for several ectoparasites (fleas, Ixodes trianguliceps and Ixodes ricinus) and vector-borne microparasites (Babesia microti, Bartonella spp., Hepatozoon spp.) in a classically functioning metapopulation of water vole hosts. Results suggest that the relative importance of vector or host dynamics on microparasite infection probabilities is related to parasite life-histories. Bartonella, a microparasite with a fast life-history, was positively associated with both host and vector abundances at several spatial and temporal scales. In contrast, B. microti, a tick-borne parasite with a slow life-history, was only associated with vector dynamics. Further, we provide evidence that life-history shaped parasite dynamics, including occupancy and colonization rates, in the metapopulation. Lastly, our findings were consistent with the hypothesis that landscape connectivity was determined by distance-based dispersal of the focal hosts. We provide essential empirical evidence that contributes to the development of a comprehensive theory of metapopulation processes of vector-borne parasites.

The dengue virus type 3 (DENV-3) homotypic outbreak cycles reported in Klang Valley, Malaysia in 1992–1995 and 2002 demonstrated different epidemic magnitude and duration. These outbreak cycles were caused by two closely related strains of viruses within the DENV-3 genotype II (DENV-3/II). The role of viral genotypic diversity and factors that could have influenced this phenomenon were investigated. The serum neutralisation sensitivity of DEN3/II strains responsible for the DENV-3 outbreak cycles in 1992–1995 and 2002 were examined. Representative virus isolates from the respective outbreaks were subjected to virus neutralisation assay using identified sera of patients with homotypic (DENV-3) or heterotypic dengue infections (DENV-1 and DENV-2). Results from the study suggested that isolates representing DENV-3/II group E (DENV-3/II-E) from the 1992–1995 outbreak and DENV-3/II group F (DENV-3/II-F) from the 2002 outbreak were neutralised at similar capacity (intergenotypic differences <2-fold) by sera of patients infected with DENV-3, DENV-1 and DENV-2/Asian genotypes. Sera of the DENV-2/Cosmopolitan infection efficiently neutralised DENV-3/II-F (FRNT50 = 508.0) at a similar neutralisation capacity against its own homotypic serotype, DENV-2 (FRNT50 = 452.5), but not against DENV-3/II-E (FRNT50 = 100.8). The different neutralisation sensitivities of DENV-3/II strains towards the cross-reacting DENV-2 heterotypic immunity could play a role in shaping the DENV-3 recurring outbreaks pattern in Malaysia. Two genetic variations, E-132 (H/Y) and E-479 (A/V) were identified on the envelope protein of DENV-3/II-E and DENV-3/II-F, respectively. The E-132 variation was predicted to affect the protein stability. A more extensive study, however, on the implication of the naturally occurring genetic variations within closely related DENV genotypes on the neutralisation profile and protective immunity would be needed for a better understanding of the DENV spread pattern in a hyperendemic setting.

From 1971 to 2012, in New York State, years with human Eastern equine encephalitis (EEE) were more strongly associated with the presence of Aedes canadensis, Coquillettidia perturbans and Culiseta melanura mosquitoes infected with the EEE virus (Fisher's exact test, one-sided P = 0.005, 0.03, 0.03) than with Culiseta morsitans, Aedes vexans, Culex pipiens-restuans, Anopheles quadrimaculatus or Anopheles punctipennis (P = 0.05, 0.40, 0.33, 1.00, 1.00). The estimated relative risk of a case in a year in which the virus was detected vs. not detected was 14.67 for Ae. canadensis, 6.38 for Cq. perturbans and 5.50 for Cs. morsitans. In all 5 years with a case, Cs. melanura with the virus was detected. In no year was there a case in the absence of Cs. melanura with the virus. There were 18 years with no case in the presence of Cs. melanura with the virus. Such observations may identify the time of increased risk, and when the methods may be used to prevent or reduce exposure to vector mosquito species in this geographic region.

Entomological indicators such as vector density, distribution, biology and bionomics and their vectorial attributes are important parameters for measuring the pattern and intensity of malaria transmission. Although published articles provide evidence for the existence of associations between entomological indices and malaria transmission dynamics, none of them is able to establish a strong correlation. In order to address this issue, the present study aims to assess how malaria transmission is influenced and can be predicted by local major vector dynamics. We carried out an entomological assessment of major Anopheline vector abundance, habit/habitat, resting and feeding behavior, infectivity rates, and other entomological parameters. Results suggest that malaria transmission was correlated with a vector control intervention and non-intervention scenario in a high endemic region of Kalahandi district of Odisha, India. Amongst all indices, infective anthropophagic vectors established a strong positive correlation with malaria morbidity in comparison to infective or anthropophagic vector species during both the study periods. Though other entomological parameters influenced the transmission intensity, little quantifiable association was detected among study sites. This study provides strong baseline evidence of an association between entomological indices and malaria transmission dynamics, which could be used as an early warning system for outbreak prediction.

Trypanosoma cruzi is the causative agent of Chagas disease, a vector-borne disease. The parasite molecules involved in vector interaction have been little investigated. Metallopeptidases and gp63 molecules have been implicated in parasite adhesion of several trypanosomatids to the insect midgut. Although gp63 homologues are highly expanded in the T. cruzi genome, and are implicated in parasite–mammalian host interaction, its role in the insect vector has never been explored. Here, we showed that divalent metal chelators or anti-Tcgp63-I antibodies impaired T. cruzi adhesion to Rhodnius prolixus midgut. Parasites isolated after insect colonization presented a drastic enhancement in the expression of Tcgp63-I. These data highlight, for the first time, that Tcgp63-I and Zn-dependent enzymes contribute to the interaction of T. cruzi with the insect vector.

Fleas have great medical relevance as vectors of the causative agents of several diseases in animals and humans and rodents are the principal reservoirs for these pathogens. Argentinian Patagonia has the highest diversity of rodent fleas in South America. However, parasitism rates of rodents by fleas, the factors that influence them and the ecological aspects that modulate geographical distributions of flea–host association remain unknown for this region. This is the first study to record the diversity, prevalence, abundance, geographical distributions and host ranges of fleas in Argentinian Patagonia. It also compares parasitism rates among Patagonian ecoregions and host species. We captured 438 rodents belonging to 13 species, which harboured 624 fleas from 11 species and subspecies (P = 46%; mean abundance = 1.44). The high parasitism rates obtained were consistent with previous records for other arid regions, suggesting that Patagonia favours the survival and development of Siphonaptera. Host geographic range and abundance were related to the parasitological indexes: host species with high-density populations had the highest mean flea abundance and prevalence, whereas widely distributed hosts had the highest richness and diversity of flea species. Our results contribute to the knowledge of the flea–host–environment complex. Our analysis of flea distributions and parasitism rate in Central Patagonia may be useful in epidemiological studies of flea-borne diseases and provide a basis for implementing surveillance systems for better risk assessment of emerging zoonoses in the region.

Water-holding tree holes are main larval habitats for many pathogen vectors, especially mosquitoes (Diptera: Culicidae). Along 3 years, the diversity and composition of mosquito species in tree holes of two neighbouring but completely different environments, a city and its adjacent forest, were compared using generalized linear mixed models, PERMANOVA, SIMPER and species association indexes. The city area (Northwest Argentina) is highly relevant epidemiologically due to the presence of Aedes aegypti L. (main dengue vector) and occurrence of dengue outbreaks; the Yungas rainforests are highly biologically diverse. In total seven mosquito species were recorded, in descending order of abundance: Ae. aegypti, Haemagogus spegazzinii Brèthes, Sabethes purpureus (Theobald), Toxorhynchites guadeloupensis Dyar and Knab, Aedes terrens Walker, Haemagogus leucocelaenus Dyar & Shannon and Sabethes petrocchiae (Shannon and Del Ponte). The seven mosquito species were recorded in both city sites and forested areas; however, their mosquito communities significantly diverged because of marked differences in the frequency and relative abundance of some species: Tx. guadeloupensis and Ae. aegypti were significantly more abundant in forest and urban areas, respectively. Positive significant associations were detected between Ae. aegypti, Hg. spegazzinii and Hg. leucocelaenus. The combined presence of Ae. aegypti, Haemagogus and Sabethes in the area also highlight a potential risk of yellow fever epidemics. Overall results show an impoverished tree hole mosquito fauna in urban environments, reflecting negative effects of urbanization on mosquito diversity.

A survey of publications and collections databases reveals a pattern of non-indigenous decapods distribution in the 13 seas around Russia and adjacent countries. No alien species were reported from Russian territorial waters and exclusive economic zone in the Japan, Okhotsk, west Bering and most of the Siberian shelf Seas. From the seas and their basins in East Europe, 13 alien species have been recorded, with seven of these yet to become established. Established or commonly occurring species can be categorized as: ‘global invaders’ (Chinese mitten crab, Eriocheir sinensis in the White, Baltic, Black, Azov and Caspian Seas; and Harris mud crab, Rhithropanopeus harrisii in all mentioned seas, except the White Sea); ‘regional aliens’ (Palaemon adspersus and P. elegans in the Caspian Sea and the latter species in the Baltic); and ‘Arctic invaders’ (Kamchatka king crab Paralithodes camtschaticus and snow crab Chionoecetes opilio). Eriocheir sinensis is the most widely occurring alien decapod species, but there are no indications of an established population in East Europe. For this and other mentioned crab species, invasion history, distribution and important biological data are reviewed. In the seas where few or no native crab species have been present, Harris mud crab (in the Azov and Caspian Seas), Kamchatka crab (in the Barents Sea) and snow crab (in the Barents and Kara Seas) have shown rapid establishment (within two decades) of an invasive population throughout an entire basis or its significant part.

Genetic connectivity directly shapes the demographic profile of marine species, and has become one of the most intensely researched areas in marine ecology. More importantly, it has changed the way we design and describe Marine Protected Areas across the world. Population genetics is the preferred tool when measuring connectivity patterns, however, these methods often assume that dispersal patterns are (1) natural and (2) follow traditional metapopulation models. In this short review, we formally introduce the phenomenon of cryptic dispersal, where multiple introductory events can undermine these assumptions, resulting in grossly inaccurate connectivity estimates. We also discuss the evolutionary consequences of cryptic dispersal and advocate for a cross-disciplinary approach that incorporates larval transport models into population genetic studies to provide a level of oceanographic realism that will result in more accurate estimates of dispersal. As globalized trade continues to expand, the rate of anthropogenic movement of marine organisms is also expected to increase and as such, integrated methods will be required to meet the inevitable conservation challenges that will arise from it.

Zika virus continues to pose a significant global health threat. While the outbreak pattern may seemingly mirror those of other arboviruses, unique transmission characteristics and clinical outcomes warrant a different approach to traditional public health practices. Sexual transmission and virus-associated fetal and nonfetal neurologic disorders specifically challenge conventional methods of disease protection and prevention with regard to vector control, disease surveillance, and health risk communication. The protocols for outbreak and case limitation led by the World Health Organization (in accordance with Public Health Emergency of International Concern declaration) may be augmented by localized risk categorization and assignment for Zika and future emergent outbreaks. There is currently a great deal of “behind the scenes” discussion about modifications to the formal process described in the International Health Regulations. A scalable, adaptable, and flexible process is needed that can be customized to a specific threat. (Disaster Med Public Health Preparedness. 2017;11:279–284)

The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.

Aedes aegypti (L.) (Diptera: Culicidae), the main vector of dengue and urban yellow fever in the world, is highly adapted to the human environment. Artificial containers are the most common larval habitat for the species, but it may develop in tree holes and other phytotelmata. This study assessed whether tree holes in San Ramón de la Nueva Orán, a city located in subtropical montane moist forest where dengue outbreaks occur, are relevant as larval habitat for Ae. aegypti and if the species may be found in natural areas far from human habitations. Water holding tree holes were sampled during 3 years once a month along the rainy season using a siphon bottle, in urban and suburban sites within the city and in adjacent forested areas. Larvae and pupae were collected and the presence and volume of water in each tree hole were recorded. Finding Ae. aegypti in forested areas was an isolated event; however, the species was frequently collected from tree holes throughout the city and along the sampling period. Moreover, larvae were collected in considerably high numbers, stressing the importance of taking into account these natural cavities as potential reinfestation foci within dengue control framework.