Inter-epizootic Periods Research Articles

Natural foci of plague in Kazakhstan in the space-time continuum

The relevance of the problem of the stated topic lies in the fact that the causative agent of the plague infection demonstrates high survival while maintaining high virulence in the territories, which are enzootic in terms of the plague. The study aimed to investigate the geographic distribution and genetic diversity of the plague pathogen in endemic regions through molecular genetic research. The work included the results of laboratory studies of 3058 samples, including soil – 1154, burrow substrates – 549, the contents of the feeding chamber – 349, bone remains – 18, biological objects – 988 samples of sera and suspensions from carriers and vectors of plague infection collected from 14 autonomous plague foci of Kazakhstan for the period 2021–2022. The leading method in the study was a laboratory experiment, thanks to which, using a new advanced technology on a microbiological analyser VITEK 2 COMPACT 30, it was possible to study pathogenic and non-pathogenic strains of the genus Yersinia isolated during field experiment. As a result of experimental work, it was shown that during a long inter-epizootic period, the plague pathogen can persist in the soil in symbiosis with soil microorganisms, and in this area, it chooses soil with a low-quality index of 10 points, where soils with a low total microbial number and species landscape prevail.

Long-Term Persistence of <i>Yersinia pestis</i> in Association with Acanthamoeba castellanii in Experiment

The aim of the study was to test the feasibility of long-term survival and preservation of the properties of Yersinia pestis in association with soil amoeba Acanthamoeba castellanii. Materials and methods. Y. pestis strains and acanthamoeba isolated in the common area of the Gorno-Altai high-mountain plague focus were used for the study. The systematic affiliation of protozoa was determined through analyzing the 18S rRNA gene fragment sequencing data, followed by alignment with amoeba sequences from the NCBI GenBank database. A fluorescent Y. pestis strain was obtained by electroporation using the pTurboGFP-B plasmid. Co-cultivation was carried out in saline buffer in the absence of nutrients for the cells of plague pathogen. The influence of co-culturing with protozoa on Y. pestis properties was determined using microbiological, biological, and molecular-genetic methods. Results and discussion. The cell viability preservation for 22 months of the experiment in Y. pestis strain belonging to the main subspecies of the antique biovar, the 4.ANT phylogenetic line in co-culture with amoeba cells in the absence of additional nutrients has been established. Co-cultivation with amoebae did not lead to a change in the cultural, morphological, genetic and virulent properties of the plague pathogen strain. The data obtained confirm the possibility of using Acanthamoeba castellanii by the plague microbe to persist in soil biocenoses and open up the prospect of studying the mechanisms of plague pathogen surviving during extended inter-epizootic periods.

Caspian Sandy Natural Focus: Phylogenetic History and Origin of <i>Yersinia pestis</i> Strains

The purpose of the work was to analyze the phylogenetic relations and origin of Yersinia pestis strains isolated in different periods of epizootic activity of the Caspian sandy natural focus (CSNF) of plague in the XX–XXI centuries.Materials and methods. We used 40 Y. pestis strains from CSNF and adjacent plague foci, isolated in 1922–2015. Carried out was whole genome sequencing of 19 Y. pestis strains from CSNF. Phylogenetic analysis was performed using whole genome SNP analysis based on 1914 identified SNPs. The search for marker SNPs was conducted using the Snippy 4.6 software. The phylogenetic tree was constructed using the Maximum Likelihood algorithm, the GTR nucleotide substitution model.Results and discussion. The whole genome SNP analysis has revealed that Y. pestis strains of the medieval biovar from CSNF belong to 2.MED1 phylogenetic lineage and fall into two major branches. One of them circulated in the focus in the first half of the XX century, and the other – in the second half of the XX – early XXI centuries. It is shown that strains of the first branch were the cause of outbreaks and individual cases of plague in the CSNF in the first half of the XX century. They are closely related to strains from the Caspian North-Western steppe and Volga-Ural sandy natural plague foci, which caused numerous outbreaks with high mortality rate in the same period. Y. pestis strains from the CSNF of the second half of the XX and early XXI centuries belong to the second phylogenetic branch of the 2.MED1 line, at the node of which the strains from the Northern Aral Sea region of 1945 lay. The latter were the predecessors of all strains isolated in the CSNF after a long inter-epizootic period that occurred in the middle of the XX century. There can also be traced a genetic relation between the strains from CSNF and the Dagestan plain-foothill focus.

An unusually long Rift valley fever inter-epizootic period in Zambia: Evidence for enzootic virus circulation and risk for disease outbreak.

Rift valley fever (RVF) is a mosquito-borne disease of animals and humans. Although RVF outbreaks are usually reported at 5-15-year intervals in sub-Saharan Africa, Zambia has experienced an unusually long inter-epizootic/-epidemic period of more than three decades. However, serological evidence of RVF virus (RVFV) infection in domestic ruminants during this period underscores the need for comprehensive investigation of the mechanisms of virus perpetuation and disease emergence. Mosquitoes (n = 16,778) captured from eight of the ten provinces of Zambia between April 2014 and May 2019 were pooled (n = 961) and screened for RVFV genome by a pan-phlebo RT-PCR assay. Aedes mosquito pools (n = 85) were further screened by nested RT-PCR assay. Sera from sheep (n = 13), goats (n = 259) and wild ungulates (n = 285) were screened for RVFV antibodies by ELISA while genome detection in pooled sera (n = 276) from domestic (n = 248) and wild ungulates (n = 37) was performed by real-time RT-PCR assay. To examine the association between the long inter-epizootic period and climatic variables, we examined El Niño-Southern Oscillation indices, precipitation anomalies, and normalized difference vegetation index. We then derived RVF risk maps by exploring climatic variables that would favor emergence of primary RVFV vectors. While no RVFV genome could be detected in pooled mosquito and serum samples, seroprevalence was significantly high (OR = 8.13, 95% CI [4.63–14.25]) in wild ungulates (33.7%; 96/285) compared to domestic ruminants (5.6%; 16/272). Retrospective analysis of RVF epizootics in Zambia showed a positive correlation between anomalous precipitation (La Niña) and disease emergence. On risk mapping, whilst northern and eastern parts of the country were at high risk, domestic ruminant population density was low (< 21 animals/km2) in these areas compared to low risk areas (>21 animals/km2). Besides evidence of silent circulation of RVFV and the risk of disease emergence in some areas, wildlife may play a role in the maintenance of RVFV in Zambia.

Detection of West Nile Virus in Overwintering Mosquitoes in the Volgograd Region

Introduction: West Nile fever is a zoonotic, vector-borne viral infection caused by West Nile virus. The possibility of persistence of West Nile virus in overwintering mosquitoes in regions with a temperate climate is of great importance for understanding the mechanisms of pathogen circulation. Objective: To detect West Nile virus in mosquitoes during the inter-epizootic period in the Volgograd Region. Materials and methods: In 2013–2021, we collected overwintering mosquitoes in different locations of the Volgograd Region using a battery-powered aspirator with a Krishtal’s trap to detect West Nile virus RNA in them using a real-time reverse transcription polymerase chain reaction. An isolate (WNV Volgograd_o16/19) was obtained from sample o16/19 (Cx. pipiens, collected on April 2, 2019) with detected West Nile virus RNA using a VERO cell culture. After that, total RNA was isolated from the filtered cell supernatant of that isolate. Metagenomic sequencing of the sample was performed using a high-throughput Illumina MiSeq sequencer, Illumina Inc., USA. Results: In total, we collected 4,070 mosquitoes in wintering shelters and tested 157 pools of the insects for West Nile virus RNA. The latter was detected in two pools of Culex pipiens and in one pool of Anopheles maculipennis complex. The phylogenetic analysis showed that the WNV Volgograd_о16/19 strain isolated from the pool of wintering mosquitoes belonged to lineage 2 of West Nile virus. We also established its belonging to the monophyletic clade of West Nile virus strains isolated in the Volgograd, Astrakhan, and Rostov regions in the years 2007 and 2018–2020. Conclusions: We were first to detect West Nile virus in overwintering mosquitoes in the Volgograd Region. Our findings confirm the hypothesis that lineage 2 strains of encephalitic West Nile virus persist in mosquitoes during the inter-epizootic period and can be transmitted from mosquito to bird in springtime as one of the mechanisms of forming autochthonous foci in WNV endemic areas of the Russian Federation in the absence of the annual import of this infection.

Prevention of rabies in Southern Siberia

Aim. To substantiate the need for coordinating measures to prevent rabies in adjacent territories with similar conditions for the spread of this infection.Materials and Methods. We retrospectively analyzed spatiotemporal trends in rabies spread during 1950-2020 by studying available statistics from nine Siberian territories (Altai Republic, Altai Region, Tyva Republic, Khakassia, Buryatia, Krasnoyarsk Region, Transbaikal Region, Irkutsk Region and Kemerovo Region). Mapping of rabies cases in humans (n = 124) and animals (n = 1648) was carried out using QGIS 3.16.3, ArcMap 10.8.1 and ArcScene 10.8.1 software and open electronic landscape maps Natural Earth and OpenStreetMap.Results. We revealed two periods of intensive rabies spread in southern Siberia: 1) from 1950 to 1983; 2) from 2002 to the present time. However, human rabies was recorded only during the first period. In all studied territories, inter-epizootic periods lasted from 10 to &gt; 40 years. Geographical analysis identified a mosaic localization pattern and a relative isolation of the affected areas. After 2002, there has been a connection between location of animal rabies cases with agricultural lands and a consistent advance of epizootics from west to east and north-east in all territories, excepting Irkutsk Region. The identified regional features of the spatial distribution of rabies were due to a mountainous terrain and a connection of some forest-steppe areas with similar landscapes of neighboring countries.Conclusions. Southern Siberia is characterized by long rabies-free periods and by the infection foci isolated from other areas as a result of periodic viral invasions from adjacent territories. These features determine the common approaches to the organization of preventive measures across the territories, suggesting their increased efficiency due to the numerous natural barriers and the possibility to concentrate the resources within the small areas. Our results indicate the feasibility of a regional approach to rabies control.

Evolution and circulation of Yersinia pestis in the Northern Caspian and Northern Aral Sea regions in the 20th-21st centuries.

According to the whole genome SNP analysis of 38 Yersinia pestis strains isolated in the foci of the Northern Caspian and Northern Aral Sea regions in the 20th–early 21st centuries, between 1912 and 2015, the spatial and temporal structure of the 2.MED population of a medieval biovar in this region was determined. A phylogenetic branch 2.MED4 was identified which preceded the 2.MED1 branch that diverged later. 2.MED1 strains became the etiological agent of high-mortality plague outbreaks that occurred in the Northern Caspian region at the beginning of the 20th century. Later in the 20th century, the 2.MED1 branch became widespread in the Caspian Sea region, Caucasus, and vast areas of Central Asia. Based on the data of phylogenetic analysis, as well as epidemiological and epizootiological data, we reconstructed the paths of spread of the 2.MED1 branch in the Northern Caspian Sea region and in the Northern subzone of the Central Asian deserts. It is shown, that the reason for the activation of plague foci in the Northern Caspian region in the second half of the 20th century after a long inter-epizootic period caused by cyclical climate warming was the return of 2.MED1 from the foci of the Northern Aral Sea region. This led to the formation of stable plague foci in the Northern Caspian Sea region and Pre-Caucasus, which manifested epizootic activity in the second half of the 20th and early 21st centuries.

Recombinant Rift Valley fever viruses encoding bluetongue virus (BTV) antigens: Immunity and efficacy studies upon a BTV-4 challenge

Many ruminant diseases of viral aetiology can be effectively prevented using appropriate vaccination measures. For diseases such as Rift Valley fever (RVF) the long inter-epizootic periods make routine vaccination programs unfeasible. Coupling RVF prophylaxis with seasonal vaccination programmes by means of multivalent vaccine platforms would help to reduce the risk of new RVF outbreaks. In this work we generated recombinant attenuated Rift Valley fever viruses (RVFVs) encoding in place of the virulence factor NSs either the VP2 capsid protein or a truncated form of the non-structural NS1 protein of bluetongue virus serotype 4 (BTV-4). The recombinant viruses were able to carry and express the heterologous BTV genes upon consecutive passages in cell cultures. In murine models, a single immunization was sufficient to protect mice upon RVFV challenge and to elicit a specific immune response against BTV-4 antigens that was fully protective after a BTV-4 boost. In sheep, a natural host for RVFV and BTV, both vaccines proved immunogenic although conferred only partial protection after a virulent BTV-4 reassortant Morocco strain challenge. Though additional optimization will be needed to improve the efficacy data against BTV in sheep, our findings warrant further developments of attenuated RVFV as a dual vaccine platform carrying heterologous immune relevant antigens for ruminant diseases in RVF risk areas.

Nipah virus dynamics in bats and implications for spillover to humans.

Nipah virus (NiV) is an emerging bat-borne zoonotic virus that causes near-annual outbreaks of fatal encephalitis in South Asia-one of the most populous regions on Earth. In Bangladesh, infection occurs when people drink date-palm sap contaminated with bat excreta. Outbreaks are sporadic, and the influence of viral dynamics in bats on their temporal and spatial distribution is poorly understood. We analyzed data on host ecology, molecular epidemiology, serological dynamics, and viral genetics to characterize spatiotemporal patterns of NiV dynamics in its wildlife reservoir, Pteropus medius bats, in Bangladesh. We found that NiV transmission occurred throughout the country and throughout the year. Model results indicated that local transmission dynamics were modulated by density-dependent transmission, acquired immunity that is lost over time, and recrudescence. Increased transmission followed multiyear periods of declining seroprevalence due to bat-population turnover and individual loss of humoral immunity. Individual bats had smaller host ranges than other Pteropus species (spp.), although movement data and the discovery of a Malaysia-clade NiV strain in eastern Bangladesh suggest connectivity with bats east of Bangladesh. These data suggest that discrete multiannual local epizootics in bat populations contribute to the sporadic nature of NiV outbreaks in South Asia. At the same time, the broad spatial and temporal extent of NiV transmission, including the recent outbreak in Kerala, India, highlights the continued risk of spillover to humans wherever they may interact with pteropid bats and the importance of limiting opportunities for spillover throughout Pteropus's range.

Rift Valley Fever - epidemiological update and risk of introduction into Europe.

Rift Valley fever (RVF) is a vector‐borne disease transmitted by a broad spectrum of mosquito species, especially Aedes and Culex genus, to animals (domestic and wild ruminants and camels) and humans. Rift Valley fever is endemic in sub‐Saharan Africa and in the Arabian Peninsula, with periodic epidemics characterised by 5–15 years of inter‐epizootic periods. In the last two decades, RVF was notified in new African regions (e.g. Sahel), RVF epidemics occurred more frequently and low‐level enzootic virus circulation has been demonstrated in livestock in various areas. Recent outbreaks in a French overseas department and some seropositive cases detected in Turkey, Tunisia and Libya raised the attention of the EU for a possible incursion into neighbouring countries. The movement of live animals is the most important pathway for RVF spread from the African endemic areas to North Africa and the Middle East. The movement of infected animals and infected vectors when shipped by flights, containers or road transport is considered as other plausible pathways of introduction into Europe. The overall risk of introduction of RVF into EU through the movement of infected animals is very low in all the EU regions and in all MSs (less than one epidemic every 500 years), given the strict EU animal import policy. The same level of risk of introduction in all the EU regions was estimated also considering the movement of infected vectors, with the highest level for Belgium, Greece, Malta, the Netherlands (one epidemic every 228–700 years), mainly linked to the number of connections by air and sea transports with African RVF infected countries. Although the EU territory does not seem to be directly exposed to an imminent risk of RVFV introduction, the risk of further spread into countries neighbouring the EU and the risks of possible introduction of infected vectors, suggest that EU authorities need to strengthen their surveillance and response capacities, as well as the collaboration with North African and Middle Eastern countries.

Forecasting of epizootic Activity of the Central Caucasian natural High-Mountain Plague Focus

Central-Caucasian natural plague focus was permanently epizootically active since its discovering in 1971 till 2007. Inter-epizootic period has been in progress since 2008. It was not possible to isolate agent strains from field material. Therefore a forecast for focus activation is a relevant task, especially against the background of registered plague cases in humans in 2014–2016. Objective of the study was to create a forecasting model for quantitative prediction of possible activation or maintenance of inter-epizootic period. Materials and methods. We used archival data of Kabardino-Balkar Plague Control Station: journals of rodents’ autopsy, annual reports on epizootiological surveillance, meteorological data from meteostation “Kislovodsk” over the period of 1989–2017, and our epidemiological data for the period 2010 to 2017. We applied Spearman nonparametric correlation analysis, regression analysis, including principal component method, quarterly analysis, and inhomogeneous sequential pattern recognition procedures for statistical processing. Results and discussion. We have designed statistical model which provides for forecasting of plague focus epizootic activity proactively, a year in advance and 99 % probability or higher. The model was tested on retrospective data over the course of 7 years. All predictions were correct. The operational forecasts from 2015 to 2017 proved right too. However there is a possibility of fast changes in the ecology system conditions of the Central-Caucasian natural plague focus because of the global warming. Thereby the forecasting model will be annually checked for informative value of the predictors and, if necessary, adjusted accordingly.

Genetic heterogeneity of dolphin morbilliviruses detected in the Spanish Mediterranean in inter-epizootic period

BackgroundIn the last 20 years, Cetacean Morbillivirus (CeMV) has been responsible for many die-offs in marine mammals worldwide, as clearly exemplified by the three dolphin morbillivirus (DMV) epizootics of 1990–1992, 2006–2008 and 2011 that affected Mediterranean striped dolphins (Stenella coeruleoalba). Systemic infection caused by DMV in the Mediterranean has been reported only during these outbreaks.ResultsWe report the infection of five striped dolphins (Stenella coeruleoalba) stranded on the Spanish Mediterranean coast of Valencia after the last DMV outbreak that ended in 2011. Animal 1 stranded in late 2011 and Animal 2 in 2012. Systemic infection affecting all tissues was found based on histopathology and positive immunohistochemical and polymerase chain reaction positive results. Animal 3 stranded in 2014; molecular and immunohistochemical detection was positive only in the central nervous system. Animals 4 and 5 stranded in 2015, and DMV antigen was found in several tissues. Partial sequences of the DMV phosphoprotein (P), nucleoprotein (N), and hemagglutinin (H) genes were identical for Animals 2, 3, 4, and 5, and were remarkably different from those in Animal 1. The P sequence from Animal 1 was identical to that of the DMV strain that caused the epizootic of 2011 in the Spanish Mediterranean. The corresponding sequence from Animals 2–5 was identical to that from a striped dolphin stranded in 2011 on the Canary Islands and to six dolphins stranded in northeastern Atlantic of the Iberian Peninsula.ConclusionsThese results suggest the existence of an endemic infection cycle among striped dolphins in the Mediterranean that may lead to occasional systemic disease presentations outside epizootic periods. This cycle involves multiple pathogenic viral strains, one of which may have originated in the Atlantic Ocean.

Current Epizootic Condition of Natural Plague Foci in Kyrgyz Republic and Measures Aimed at Provision of Epidemiological Welfare as regards Plague

Objective of the study is to characterize the mountain plague foci in Tien Shan and Pamir-Alai, to assess the results of the performed field disinsection activities, to describe the current epizootic condition of natural foci in Kyrgyz Republic and measures aimed at provision of epidemiological welfare as regards plague. Materials and methods. Archival epizootic and epidemiological data from the Republican Center of Quarantine and Particularly Dangerous Infections, Ministry of Health of Kyrgyz Republic, as well as copyright author’s materials were used for the analysis. Results and Conclusions. It is noted that following sanitation activities in 1971–1989, using deep disinsection of marmot burrows, epizootic activity of Tien Shan and Alai natural foci significantly decreased, up to long inter-epizootic periods. In the light of revitalization of high-mountain plague foci in Kyrgyz Republic, epizootiological monitoring of enzootic territories has been considerably strengthened, control over the state of populations of main agent carriers and vectors has been improved. In order to lower the risk of infection, 1750 km2 of the focal territories were treated twice, using deep disinsection of marmot burrows applying ecologically safe insecticides, in particular “Absolute-dust”.

Study of Interactions of Microscopic Fungi Isolated from Burrow Microbiotopes of Great Gerbil and Little Souslik with Plague Agent and its Vectors

At present there is strong evidence of the long-term persistence of Yersinia pestis in soil during interepizootic period in nonculturable and L-forms of bacteria. This information helps to reveal the mechanisms of emergence, establishment and extinction of plague foci. Deciphering causes of transformation of plague microbe in rodent burrows is possible only under condition of detailed study of biocenotic relations of plague causative agent with each of the multiple biocenosis components, including microorganisms -permanent inhabitants of the burrow microbiotopes in natural plague foci. Purpose of the study: Study of interactions of microscopic fungi-micromycetes iso-lated from burrow microbiotopes of great gerbil and little souslik in the Ural-Emba interfluve and in Nogai steppe with plague agent and its vectors. Materials and methods: The effect of 74 micromycete species, isolated in natural plague foci, on Yersinia pestis virulent strains was studied in vitro and in vivo (in organisms of X. skrjabini fleas). In the experiments in vitro fungi metabolites were applied on the lawns of Y. pestis test-cultures with subsequent recording of the size of lysed zones. Fleas were challenged in tubes with filtering-paper strips impregnated by fungal cultural liquid and then LT100 value was calculated. In the experiments in vivo fungus conidia were applied on the surface of insect cuticle; flea challenging with plague was carried out on agonizing white mice infected by plague microbe. Insect challenge with plague and fungal conidia was alternated in different succession. Results and discussion: Of 74 micromycete strains 78.4% produced antagonistic effect in relation to 1-5 Y. pestis strains. Ashergillus versicolor, A. clavatus, A. sulfereus, Mucor racematus, Penicillium baarnensens, P. sp. relative to P. charlesii, P. sp. relative to P. martensii, P. insectus, P. chrysogenum fungi induced growth suppression of all five test strains of Y. pestis. High antibiotic activity of fungi metabolites was accompanied by insecticidal activity against Xenopsylla skrjabini fleas. Microscopic fungi P. funiculosum, P. cyclopium, P. chrisogenum, P. charlesii. P. canescens, A. versicolor induced 100% flea death on 4-6 day. As a result of insect pretreatment by conidia of P. funiculosum with subsequent challenging with plague microbe block formation in fleas decreased 14 times, and the number of Y. pestis cells after 12 days was 25-33 times less independent of succession, in which insects were challenged with microorganisms. Conclusion. It is supposed that micromycetes could play an important role in natural plague foci, adjusting epizootic activity of plague vectors and causative agent.

Yersinia pestis Resists Predation by Acanthamoeba castellanii and Exhibits Prolonged Intracellular Survival.

Plague is a flea-borne rodent-associated zoonotic disease caused by Yersinia pestis The disease is characterized by epizootics with high rodent mortalities, punctuated by interepizootic periods when the bacterium persists in an unknown reservoir. This study investigates the interaction between Y. pestis and the ubiquitous soil free-living amoeba (FLA) Acanthamoeba castellanii to assess if the bacterium can survive within soil amoebae and whether intracellular mechanisms are conserved between infection of mammalian macrophages and soil amoebae. The results demonstrate that during coculture with amoebae, representative Y. pestis strains of epidemic biovars Medievalis, Orientalis, and Antiqua are phagocytized and able to survive within amoebae for at least 5 days. Key Y. pestis determinants of the intracellular interaction of Y. pestis and phagocytic macrophages, PhoP and the type three secretion system (T3SS), were then tested for their roles in the Y. pestis-amoeba interaction. Consistent with a requirement for the PhoP transcriptional activator in the intracellular survival of Y. pestis in macrophages, a PhoP mutant is unable to survive when cocultured with amoebae. Additionally, induction of the T3SS blocks phagocytic uptake of Y. pestis by amoebae, similar to that which occurs during macrophage infection. Electron microscopy revealed that in A. castellanii, Y. pestis resides intact within spacious vacuoles which were characterized using lysosomal trackers as being separated from the lysosomal compartment. This evidence for prolonged survival and subversion of intracellular digestion of Y. pestis within FLA suggests that protozoa may serve as a protective soil reservoir for Y. pestisIMPORTANCEYersinia pestis is a reemerging flea-borne zoonotic disease. Sylvatic plague cycles are characterized by an epizootic period during which the disease spreads rapidly, causing high rodent mortality, and an interepizootic period when the bacterium quiescently persists in an unknown reservoir. An understanding of the ecology of Y. pestis in the context of its persistence in the environment and its reactivation to initiate a new epizootic cycle is key to implementing novel surveillance strategies to more effectively predict and prevent new disease outbreaks. Here, we demonstrate prolonged survival and subversion of intracellular digestion of Y. pestis within a soil free-living amoeba. This suggests the potential role for protozoa as a protective soil reservoir for Y. pestis, which may help explain the recrudescence of plague epizootics.

Rift Valley fever virus: strategies for maintenance, survival and vertical transmission in mosquitoes.

Rift Valley fever virus (RVFV) is a mosquito-borne arbovirus causing severe disease in humans and ruminants. Spread of RVFV out of Africa has raised concerns that it could emerge in Europe or the USA. Virus persistence is dependent on successful infection of, replication in, and transmission to susceptible vertebrate and invertebrate hosts, modulated by virus-host and vector-virus interactions. The principal accepted theory for the long-term maintenance of RVFV involves vertical transmission (VT) of virus to mosquito progeny, with the virus surviving long inter-epizootic periods within the egg. This VT hypothesis, however, is yet to be comprehensively proven. Here, evidence for and against the VT of RVFV is reviewed along with the identification of factors limiting its detection in natural and experimental data. The observations of VT for other arboviruses in the genera Alphavirus, Flavivirus and Orthobunyavirus are discussed within the context of RVFV. The review concludes that VT of RVFV is likely but that current data are insufficient to irrefutably prove this hypothesis.

Reconstruction of Rift Valley fever transmission dynamics in Madagascar: estimation of force of infection from seroprevalence surveys using Bayesian modelling

The force of infection (FOI) is one of the key parameters describing the dynamics of transmission of vector-borne diseases. Following the occurrence of two major outbreaks of Rift Valley fever (RVF) in Madagascar in 1990–91 and 2008–09, recent studies suggest that the pattern of RVF virus (RVFV) transmission differed among the four main eco-regions (East, Highlands, North-West and South-West). Using Bayesian hierarchical models fitted to serological data from cattle of known age collected during two surveys (2008 and 2014), we estimated RVF FOI and described its variations over time and space in Madagascar. We show that the patterns of RVFV transmission strongly differed among the eco-regions. In the North-West and Highlands regions, these patterns were synchronous with a high intensity in mid-2007/mid-2008. In the East and South-West, the peaks of transmission were later, between mid-2008 and mid-2010. In the warm and humid northwestern eco-region favorable to mosquito populations, RVFV is probably transmitted all year-long at low-level during inter-epizootic period allowing its maintenance and being regularly introduced in the Highlands through ruminant trade. The RVF surveillance of animals of the northwestern region could be used as an early warning indicator of an increased risk of RVF outbreak in Madagascar.

Genetic diversity of Venezuelan alphaviruses and circulation of a Venezuelan equine encephalitis virus subtype IAB strain during an interepizootic period.

Several species of alphaviruses have been previously described in the Americas, some of which are associated with encephalitis and others are associated with arthralgia. Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are endemic to Venezuela, with the former being responsible for major outbreaks of severe and often fatal disease in animals and humans. The aim of this study was to analyze the genetic diversity of Venezuelan alphaviruses isolated during two decades (1973-1999) of surveillance in northern Venezuela. Phylogenetic analysis indicated the circulation of a VEEV subtype IAB strain 8 years after the last reported outbreak. Thirteen strains within two subclades of South American lineage III of EEEV were also found in Venezuela. Considerable genetic variability was observed among Venezuelan Una virus strains, which were widely distributed among the clades. The first Venezuelan Mayaro sequence was also characterized.

Single-Nucleotide Polymorphisms Reveal Spatial Diversity Among Clones of Yersinia pestis During Plague Outbreaks in Colorado and the Western United States.

In western North America, plague epizootics caused by Yersinia pestis appear to sweep across landscapes, primarily infecting and killing rodents, especially ground squirrels and prairie dogs. During these epizootics, the risk of Y. pestis transmission to humans is highest. While empirical models that include climatic conditions and densities of rodent hosts and fleas can predict when epizootics are triggered, bacterial transmission patterns across landscapes, and the scale at which Y. pestis is maintained in nature during inter-epizootic periods, are poorly defined. Elucidating the spatial extent of Y. pestis clones during epizootics can determine whether bacteria are propagated across landscapes or arise independently from local inter-epizootic maintenance reservoirs. We used DNA microarray technology to identify single-nucleotide polymorphisms (SNPs) in 34 Y. pestis isolates collected in the western United States from 1980 to 2006, 21 of which were collected during plague epizootics in Colorado. Phylogenetic comparisons were used to elucidate the hypothesized spread of Y. pestis between the mountainous Front Range and the eastern plains of northern Colorado during epizootics. Isolates collected from across the western United States were included for regional comparisons. By identifying SNPs that mark individual clones, our results strongly suggest that Y. pestis is maintained locally and that widespread epizootic activity is caused by multiple clones arising independently at small geographic scales. This is in contrast to propagation of individual clones being transported widely across landscapes. Regionally, our data are consistent with the notion that Y. pestis diversifies at relatively local scales following long-range translocation events. We recommend that surveillance and prediction by public health and wildlife management professionals focus more on models of local or regional weather patterns and ecological factors that may increase risk of widespread epizootics, rather than predicting or attempting to explain epizootics on the basis of movement of host species that may transport plague.

Evaluation of the effect of host immune status on short-term Yersinia pestis infection in fleas with implications for the enzootic host model for maintenance of Y. pestis during interepizootic periods.

Plague, a primarily flea-borne disease caused by Yersinia pestis, is characterized by rapidly spreading epizootics separated by periods of quiescence. Little is known about how and where Y. pestis persists between epizootics. It is commonly proposed, however, that Y pestis is maintained during interepizootic periods in enzootic cycles involving flea vectors and relatively resistant host populations. According to this model, while susceptible individuals serve as infectious sources for feeding fleas and subsequently die of infection, resistant hosts survive infection, develop antibodies to the plague bacterium, and continue to provide bloodmeals to infected fleas. For Y. pestis to persist under this scenario, fleas must remain infected after feeding on hosts carrying antibodies to Y. pestis. Studies of other vector-borne pathogens suggest that host immunity may negatively impact pathogen survival in the vector. Here, we report infection rates and bacterial loads for fleas (both Xenopsylla cheopis (Rothschild) and Oropsylla montana (Baker)) that consumed an infectious bloodmeal and subsequently fed on an immunized or age-matched naive mouse. We demonstrate that neither the proportion of infected fleas nor the bacterial loads in infected fleas were significantly lower within 3 d of feeding on immunized versus naive mice. Our findings thus provide support for one assumption underlying the enzootic host model of interepizootic maintenance of Y. pestis.