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Rainbow trout Oncorhynchus mykiss were infiltrated with either saline or lidocaine adjacent to the dorsal fin to assess histopathological changes. Infiltration was done as if it were being used as a local anaesthetic. Tissue lesions and associated tissue healing were examined over a period of 30 days. Most changes occurred at the cranial site of where the solution was first infiltrated. The infiltration of a dose of 10 mg kg−1 of lidocaine appears to have damaged the skeletal muscle and connective tissues more than a similar volume of saline, especially during the first 15 days. The primary changes included haemorrhage, inflammation and muscle degeneration and necrosis. By day 30 post‐infiltration inflammatory lesions were either nearly or completely absent, signs of myofibre regeneration were noted in only one fish. This experiment shows local anaesthetics and saline can produce localized tissue damage, especially during the first 2 weeks post infiltration. Care should be taken to allow the fish to heal for at least 30 days and probably more, no matter the solution administered, especially if giving repeated injections or infiltrations at the same site. [ABSTRACT FROM AUTHOR]

Approximately 8 weeks after a chlorine insult associated with the city water supply, shortnose sturgeon, Acipenser brevirostrum (L.), from one group presented with small (3-4 mm) irregular foci of cutaneous pallor that involved the dorsocranial integument with progressive ulceration of the nascent lesions. Various bacterial organisms were isolated from the cutaneous lesions, but not from the internal viscera. Histologically, the nuclei of the intralesional and perilesional epidermal cells often exhibited margination of the chromatin that resulted in a homogenous, pale, amphophilic, tinctorial quality of the nucleoplasm consistent with a herpesvirus infection. In addition, rare lamellar epithelial cells were prominently enlarged due to an abundant, dense, basophilic cytoplasm characteristic of an iridovirus infection. Inoculation of cutaneous lesion and kidney, spleen, liver sample pools from affected shortnose sturgeon onto white sturgeon spleen ( WSS-2) cell line induced cytopathic effect characterized by syncytia formation. Ultrastructural analysis of infected WSS-2 cells revealed viral particles with a characteristic herpesvirus morphology. Intranuclear hexagonal capsids had a diameter of 95-108 nm, and enveloped particles present in the cytoplasm of infected cells had a diameter of 176-196 nm. This is the first report of a herpesvirus and a possible iridovirus-like infection in shortnose sturgeon. [ABSTRACT FROM AUTHOR]

Lepeophtheirus salmonis infections in Atlantic salmon, Salmo salar, have been characterized by little to no hyperplastic response and a biphasic immune response that results in chronic inflammation with tissue repair as the infection progresses. We hypothesized that Cp G administration with prior lice exposure would enhance epithelial inflammatory mechanisms and boost the Atlantic salmon immune response to L. salmonis, leading to greater protection against infection. We administered multiple exposures of L. salmonis to two groups of Atlantic salmon and compared responses against first-time exposed Atlantic salmon. Following re-exposure, Cp G fed fish exhibited increased skin expression of interleukin ( IL)-1β and IL-12 β compared to control previously exposed ( CPE) and control first-time exposed ( CFE) animals, respectively. This inflammatory enhancement occurred with significantly lower expression of matrix metalloproteinase-9 ( MMP 9), both systemically (spleen) and locally (skin). Reduced MMP 9 expression was a hallmark of the re-infected fish (occurred in both tissues at both times). When significant differences were present in the skin or spleen, the two re-exposed groups showed greater similarity than with the first exposure group. Lice numbers on Cp G fed fish were significantly lower than CFE fish at 7 days post-re-infection (dpri), and although they were not significantly different at 17 dpri, the trend of lower lice levels remained. CpG fed fish also showed nearly twofold greater protection than CPE when compared to the CFE group (48.5% vs. 27.0% reductions at 7 dpri and 27.2% vs. 13.1% reductions at 17 dpri, respectively). The enhanced protection of Cp G oligodeoxynucleotide administration to previous exposure was consistent across all body surfaces and suggests that Cp G can not only enhance innate responses to L. salmonis in Atlantic salmon, but also further stimulate adaptive responses. [ABSTRACT FROM AUTHOR]

A systemic infection of a Rickettsia-like organism (RLO) in cultured sea bass is described for the first time. In hatcheries, clinical signs were lethargy, inappetence and discoloration. Twenty days after transfer to sea cages from hatcheries where the disease existed, fish showed erratic and abnormal swimming behaviour, loss of orientation, and lethargy. Cumulative mortality in colder months of the year reached 30% in hatcheries and 80% in cages. Surviving fish in cages did not show any clinical signs of RLO infection in the subsequent year. Evidence for a systemic distribution of RLO was supported by histolopathological lesions in both infected hatchery and caged fish, where the lesion profile included cranial sensory, central nervous, integumental and alimentary organ systems. Intracranial lesions were primarily characterized by an ascending histiocytic perineuritis and necrotizing congestive meningoencephalitis, with evidence for transfer of infective agents across the blood-brain barrier confirmed by the presence of RLOs within capillary end othelium and histiocytes in inflamed regions of the optic tectum and the cerebellum. In the most severe cases, infection spread to the statoacoustical (semicircular) canal system and the ependymal lining of ventricles, with marked rickettsia-laden histiocytic infiltration of the canal lumen. Integumental lesions were restricted to the oral submucosa, nares and integumental dermis of the cranium. Alimentary lesions were noted in both the liver parenchyma and mucosa/submucosa of the stomach. In all affected organs the RLOs were found by immunohistochemistry to be related to Pisirickeusia salmonis. [ABSTRACT FROM AUTHOR]

Abstract Background Infectious salmon anaemia (ISA) is a viral disease of marine-farmed Atlantic salmon (Salmo salar) caused by ISA virus (ISAV), which belongs to the genus Isavirus, family Orthomyxoviridae. The virus is considered to be carried by marine wild fish and for over 25 years has caused major disease outbreaks in marine-farmed Atlantic salmon in the Northern hemisphere. In the Southern hemisphere, ISAV was first detected in Chile in 1999 in marine-farmed Coho salmon (Oncorhynchus kisutch). In contrast to the classical presentation of ISA in Atlantic salmon, the presence of ISAV in Chile until now has only been associated with a clinical condition called Icterus Syndrome in Coho salmon and virus isolation has not always been possible. During the winter of 2007, unexplained mortalities were registered in market-size Atlantic salmon in a grow-out site located in Chiloé in Region X of Chile. We report here the diagnostic findings of the first significant clinical outbreak of ISA in marine-farmed Atlantic salmon in Chile and the first characterization of the ISAV isolated from the affected fish. Results In mid-June 2007, an Atlantic salmon marine farm site located in central Chiloé Island in Region X of Chile registered a sudden increase in mortality following recovery from an outbreak of Pisciricketsiosis, which rose to a cumulative mortality of 13.6% by harvest time. Based on the clinical signs and lesions in the affected fish, and laboratory tests performed on the fish tissues, a confirmatory diagnosis of ISA was made; the first time ISA in its classical presentation and for the first time affecting farmed Atlantic salmon in Chile. Rapid sequencing of the virus-specific RT-PCR products amplified from the fish tissues identified the virus to belong to the European genotype (Genotype I) of the highly polymorphic region (HPR) group HPR 7b, but with an 11-amino acid insert in the fusion glycoprotein, and ability to cause cytopathic effects (CPE) in CHSE-214 cell line, characteristics which make it distinct from common European Genotype ISAV isolates from Europe and North America. Conclusion In conclusion, the present work constitutes the first report of a case of ISA in farmed Atlantic salmon in Chile. The clinical signs and lesions are consistent with the classical descriptions of the disease in marine-farmed Atlantic salmon in the Northern hemisphere. The outbreak was caused by ISAV of European genotype (or Genotype I) of HPR 7b but distinct from common European Genotype ISAV isolates.

Abstract Background Infectious salmon anaemia (ISA) virus (ISAV), which causes ISA in marine-farmed Atlantic salmon, is an orthomyxovirus belonging to the genus Isavirus, family Orthomyxoviridae. ISAV agglutinates erythrocytes of several fish species and it is generally accepted that the ISAV receptor destroying enzyme dissolves this haemagglutination except for Atlantic salmon erythrocytes. Recent work indicates that ISAV isolates that are able to elute from Atlantic salmon erythrocytes cause low mortality in challenge experiments using Atlantic salmon. Previous work on ISAV-induced haemagglutination using the highly pathogenic ISAV strain NBISA01 and the low pathogenic ISAV strain RPC/NB-04-0851, showed endocytosis of NBISA01 but not RPC/NB-04-0851. Real-time RT-PCR was used to assess the viral RNA levels in the ISAV-induced haemagglutination reaction samples, and we observed a slight increase in viral RNA transcripts by 36 hours in the haemagglutination reaction with NBISA01 virus when the experiment was terminated. However, a longer sampling interval was considered necessary to confirm ISAV replication in fish erythrocytes and to determine if the infected cells mounted any innate immune response. This study examined the possible ISAV replication and Type I interferon (IFN) system gene induction in Atlantic salmon erythrocytes following ISAV haemagglutination. Results Haemagglutination assays were performed using Atlantic salmon erythrocytes and one haemagglutination unit of the two ISAV strains, NBISA01 and RPC/NB-04-0851, of differing genotypes and pathogenicities. Haemagglutination induced by the highly pathogenic NBISA01 but not the low pathogenic RPC/NB-04-0851 resulted in productive infection as evidenced by increased ISAV segment 8 transcripts and increase in the median tissue culture infectious dose (TCID50) by 5 days of incubation. Moreover, reverse transcription (RT) quantitative PCR used to compare mRNA levels of key Type I IFN system genes in erythrocyte lysates of haemagglutination reactions with the two ISAV strains showed a higher relative fold increase of IFN-α in NBISA01 haemagglutinations compared to RPC/NB-04-085-1 haemagglutinations (33.0 – 44.26 relative fold increase compared to 11.29). Erythrocytes exposed to heat-inactivated virus or to polyinosinic:polycytidylic acid (polyI:C) or to L-15 medium alone (negative control assays) had minimal late induction ( Conclusion ISAV-induced haemagglutination by a highly pathogenic virus strain results in virus uptake and productive infection of Atlantic salmon erythrocytes accompanied by significant induction of IFN-α. This study also highlights the critical role of ISAV strain variation in the initial stages of the virus-cell interaction during haemagglutination, and possibly in the pathogenesis of ISA. Moreover, the study shows for the first time that fish erythrocytes immunologically respond to ISAV infection.

There is tremendous variation in life-history strategies among anadromous salmonids. Species that enter the ocean environment at small sizes (< 20 g) are likely under more physiological pressure from pathogens; however, little data is available on responses at these early stages. With this in mind, we performed salmon louse challenges with Coho salmon either immediately after seawater entry (SW; ca. 10 g) or after 30 days in SW (ca. 20 g). Irrespective of size or time in SW, parasites were rapidly rejected by the host, with > 90% of all parasites lost by 16 days post-infection (dpi). Rejection was concomitant with host epithelial granulomatous infiltrations that initially targeted the embedded frontal filament (4 dpi) and the entire parasite by 10 dpi. Illumina sequencing, followed by functional enrichment analysis, revealed a concerted defense response in the fin within 1 dpi that included multiple innate and adaptive immunity components. Strikingly, early indications of an allergic-type inflammatory response were associated with chitin sensing pathways orchestrated by early overexpression of the IgE-receptor, fcer1g. Additionally, there was profound overexpression of several classes of c-type lectin receptors, including dectin-2, mincle, and dc-sign at 1 dpi onward. These profiles and upregulation of cellular effector markers were corroborated by histopathological evaluation, revealing the simultaneous presence of mast cell/eosinophilic granular cells, sacciform cells, macrophages/histiocytes, and granulocytes in fin. At 10 dpi and concurrent with parasite expulsion, there was evidence of immunoregulation in addition to tissue remodelling pathways. At 16 dpi, the response was effectively abrogated. Simultaneous profiling of the parasite transcriptome revealed early induction of chitin metabolism and immunomodulation, toxin production and ECM degradation; however, after 7 dpi, these were replaced with overexpression of stress and immune defense genes. These data present the first evidence for Coho salmon demonstrating chitin- and sugar moiety-sensing as key drivers of salmon louse rejection., (© 2023. The Author(s).)

Background: The genus Huffmanela Moravec, 1987 (Nematoda, Trichosomoididae, Huffmanelinae), represents a group of nematodes that infect both marine and freshwater fish, and the main gross feature of infection with different species of the genus is the presence of noticeable dark spots or tracks within the parasitized tissues. The purpose of this study was to describe morphologically and morphometrically the eggs of a new marine species of Huffmanela (Huffmanela persica sp. nov.), which was found in the form of black spots in the ovary and the tunica serosa of the stomach of the daggertooth pike conger (Muraenesox cinereus). The new species differs from Huffmanela hamo, another species reported from musculature of this host in Japan, in egg metrics, eggshell features and targeted organ. Molecular identification and pathological examination of the lesions caused by the new species are also reported., Methods: Nematode eggs with varying degrees of development were separated from the infected tissues (ovary and tunica serosa of stomach) and investigated using light and scanning electron microscopy. Different species-specific markers (small subunit ribosomal DNA, 18S; large subunit ribosomal DNA, 28S; internal transcribed spacer, ITS) were used for molecular identification and phylogenetic study of the new species. Infected tissues were fixed in buffered formalin for pathological investigations., Results: The fully developed eggs of H. persica sp. nov. are distinguished from those previously described from this host on the basis of their measurements (size, 54-68 × 31-43 µm; polar plugs, 6.4-9.7 × 8.4-12 µm; shell thickness, 3.5-6.1 µm) and a delicate but ornate uterine layer (UL) covering the entire eggshell including the polar plugs. Histopathological examination revealed a fibro-granulomatous inflammation in the ovary and the serosal layer of the stomach of infected fish. Maximum-likelihood (ML) phylogenetic analysis recovered a sister relationship between the new species of marine origin and Huffmanela species previously collected from freshwater hosts., Conclusions: The present study is the first to report the molecular characterization and phylogenetic position of a teleost-associated marine species of the genus Huffmanela. A comprehensive list of nominal and innominate populations of Huffmanela is also provided., (© 2023. The Author(s).)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows rapid and reliable identification of microorganisms. The accuracy of bacterial identification using MALDI-TOF MS depends on main spectral profiles (MSPs) provided in a quality-assured commercial reference library, which requires ongoing improvement. This study aimed to develop and validate an in-house MALDI-TOF MS MSP to rapidly identify Yersinia ruckeri isolated from Atlantic salmon ( Salmo salar ). The novel MSP was prepared using an isolate of Y. ruckeri recovered from Atlantic salmon and confirmed by 16S rRNA gene sequencing. Subsequently, a validation set which comprises 29 isolates of Y. ruckeri were examined from three fishes: Atlantic salmon ( Salmo salar ) ( n = 26), American eel ( Anguilla rostrata ) ( n = 1), and Atlantic cod ( Gadus morhua ) ( n = 2). These isolates were randomly selected from the Atlantic Veterinary College, Aquatic Diagnostic Services Bacteriology Laboratory's culture collection to validate the novel MSP. Analytical sensitivity of MALDI-TOF MS using the novel MSP to identify the validation set was 86.2%. Repeatability was assessed by acquiring spectra from 30 different spots of a randomly-selected isolate of Y. ruckeri , and analyzed spectra from each spot were compared against the novel MSP. The coefficient of variation was 3.3%. The novel MSP clustered with Bruker MSPs ( n = 3) of Y. ruckeri in the reference library and did not falsely identify any closely related bacteria to Y. ruckeri . This study reports the development of a novel MSP of high analytical sensitivity and specificity for rapid identification of Y. ruckeri using MALDI-TOF MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ojasanya, Gardner, Groman, Saksida, Saab and Thakur.)

An incursion of infectious salmon anaemia virus (ISAV) was detected in 2020 in southern Newfoundland, Canada. This resulted in an outbreak affecting four marine farms stocking Atlantic salmon (Salmo salar L.) vaccinated against ISAV. This study provides the first description of epidemiologic characteristics of an ISAV outbreak in 2020 and 2021, and detected ISAV variants at the population level. Fish kidneys were screened for ISAV by real-time RT-PCR and non-negative samples were submitted for genotyping and further diagnostic testing. Nine distinct ISAV variants were identified: five European and three North American (NA) HPRΔ ISAV, and one NA-HPR0 ISAV variant. A notable finding was the concurrent detection of both an HPR0 and an HPRΔ ISAV variant in one individual fish. In two farms, both European and NA variants were simultaneously detected, while in the other two farms either NA or European variants were identified, but not both together. Generally, mortality increases followed rises in ISAV prevalence and cycle threshold values on RT-PCR decreased with time. Epidemiologic descriptions of ISAV outbreaks in Atlantic Canada contributes to the understanding of local disease dynamics and identification of changes thereof. Such insights are essential for the strengthening of disease management plans., (© 2022 John Wiley & Sons Ltd.)

Introduction: Cervical cancer is a leading cause of cancer among women in Mongolia with an age-standardized incidence rate of 23.5 per 100,000. HPV vaccination has not been introduced nationally and Gavi co-financing support is not available in Mongolia. Extended Gavi pricing for HPV vaccine may be available from vaccine manufacturers for a number of years. To inform introduction decision-making, we evaluated the potential cost-effectiveness of HPV vaccination among girls and young women in Mongolia., Methods: We used UNIVAC (version 1.4), a static decision model, to evaluate the health and economic outcomes of single-cohort vaccination among females from the government perspective compared to no vaccination. We modeled vaccine introduction over 10 birth cohorts starting in 2022 comparing quadrivalent or bivalent vaccine selection and vaccine pricing variations. We used locally-specific data for cancer incidence, mortality, treatment and costs. Model outcomes included cancer cases, hospitalizations, deaths, disability-adjusted life years (DALY), and costs presented in 2018 USD. Incremental costs and health outcomes were discounted at 3% and aggregated into an Incremental Cost-Effectiveness Ratio (ICER)., Results: The base-case scenario of HPV vaccination among 9 year-old girls was projected to avert 5,692 cervical cancer cases, 3,240 deaths, and 11,886 DALYs and incur $2.4-3.1M more costs compared to no vaccination. At prices of ($4.50-$4.60/dose), we estimated an ICER of $166-$265/DALY averted among 9-year-olds. When price per dose was increased to reported mean vaccine purchase price for non-Gavi LMICs ($14.17/dose), the ICER ranged from $556-820/DALY averted., Conclusion: HPV vaccination among girls is highly likely to be a cost-effective investment in Mongolia compared to no vaccination with projected ICERs less than 20% of the 2018 GDP per capita of $3,735., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

In an increasingly crowded vaccine landscape, global and country decision-makers will require evidence-based and disease-specific information when prioritizing new public health interventions. The Advancing Maternal Immunization collaboration (AMI) was designed to develop a cross-program strategy to advance respiratory syncytial virus (RSV) maternal immunization (MI) availability and accessibility in low- and middle-income countries by completing a comprehensive RSV MI gap analysis and developing an actionable roadmap report. By engaging and coordinating key stakeholders using a web-based communication platform and developing standardized tools, AMI was able to facilitate interaction and consensus between members. This paper describes the methodology used to create and manage AMI's work. We share lessons learned from our approach to inform other groups conducting similar work requiring cross-sectoral engagement. This approach could be adapted to efficiently conduct gap analyses for other health interventions that require input and coordination across a variety of topic areas, disciplines, geographies, and stakeholders., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Groman D et al.)

With respect to salmonid aquaculture, one of the most important bacterial pathogens due to high mortality and antibiotic usage is the causative agent of typical furunculosis, Aeromonas salmonicida spp. salmonicida ( Asal ). In Atlantic salmon, Salmo salar , the host response during infections with Asal is well-documented, with furunculosis outbreaks resulting in significant mortality in commercial settings. However, less is known about the host-pathogen interactions in the emerging aquaculture species, Arctic charr Salvelinus alpinus . Furthermore, there is no data on the efficacy or response of this species after vaccination with commonly administered vaccines against furunculosis. To this end, we examined the immunological response of S. alpinus during infection with Asal , with or without administration of vaccines (Forte Micro®, Forte Micro® + Renogen®, Elanco Animal Health). Artic charr (vaccinated or unvaccinated) were i.p.-injected with a virulent strain of Asal (10 6 CFUs/mL) and tissues were collected pre-infection/post-vaccination, 8, and 29 days post-infection. Unvaccinated Arctic charr were susceptible to Asal with 72% mortalities observed after 31 days. However, there was 72-82% protection in fish vaccinated with either the single or dual-vaccine, respectively. Protection in vaccinated fish was concordant with significantly higher serum IgM concentrations, and following RNA sequencing and transcriptome assembly, differential expression analysis revealed several patterns and pathways associated with the improved survival of vaccinated fish. Most striking was the dramatically higher basal expression of complement/coagulation factors, acute phase-proteins, and iron hemostasis proteins in pre-challenged, vaccinated fish. Remarkably, following Asal infection, this response was abrogated and instead the transcriptome was characterized by a lack of immune-stimulation compared to that of unvaccinated fish. Furthermore, where pathways of actin assembly and FcγR-mediated phagocytosis were significantly differentially regulated in unvaccinated fish, vaccinated fish showed either the opposite regulation (ForteMicro®), or no impact at all (ForteMicro®Renogen®). The present data indicates that vaccine-induced protection against Asal relies on the pre-activation and immediate control of humoral immune parameters that is coincident with reduced activation of apoptotic (e.g., NF-κB) and actin-associated pathways.

Introduction: Rotavirus disease in Mongolia is estimated to cause more than 50 deaths yearly and many more cases and hospitalizations. Mongolia must self-finance new vaccines and does not automatically access Gavi prices for vaccines. Given the country's limited resources for health, it is critical to assess potential new vaccine programs. This evaluation estimates the impact, cost-effectiveness, and budget implications associated with a nationwide rotavirus vaccine introduction targeting infants as part of the national immunization program in Mongolia, in order to inform decision-making around introduction., Methods: The analysis examines the use of the two-dose vaccine ROTARIX®, and three-dose vaccines ROTAVAC® and RotaTeq® compared to no vaccination from the government and the societal perspective. We use a modelling approach informed by local data and published literature to analyze the impact and cost-effectiveness of rotavirus vaccination over a ten-year time period starting in 2019, using a 3% discount rate. Our main outcome measure is the incremental cost-effectiveness ratio (ICER) expressed as US dollar per DALY averted. We assessed uncertainty around a series of parameters through univariate sensitivity analysis., Results: Rotavirus vaccination in Mongolia could avert more than 95,000 rotavirus cases and 271 deaths, over 10 years. Averted visits and hospitalizations represent US$2.4 million in health care costs saved by the government. The vaccination program cost ranges from $6 to $11 million depending on vaccine choice. From the governmental perspective, ICER ranged from $412 to $1050 and from $77 to $715 when considering the societal perspective. Sensitivity analysis highlights vaccine price as the main driver of uncertainty., Conclusion: Introduction of rotavirus vaccination is likely to be highly cost-effective in Mongolia, with ICERs estimated at only a fraction of Mongolia's per capita GDP. From an economic standpoint, ROTAVAC® is the least costly and most cost-effective product choice., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Despite progress made in child survival in the past 20 years, 5.9 million children under five years died in 2015, with 9% of these deaths due to diarrhea. Rotavirus is responsible for more than a third of diarrhea deaths. In 2013, rotavirus was estimated to cause 215,000 deaths among children under five years, including 89,000 in Asia. As of April 2017, 92 countries worldwide have introduced rotavirus vaccination in their national immunization program. Afghanistan has applied for Gavi support to introduce rotavirus vaccination nationally. This study estimates the potential impact and cost-effectiveness of a national rotavirus immunization program in Afghanistan., Methods: This study examined the use of Rotarix® (RV1) administered using a two-dose schedule at 6 and 10 weeks of age. We used the ProVac Initiative's UNIVAC model (version 1.2.09) to evaluate the impact and cost-effectiveness of a rotavirus vaccine program compared with no vaccine over ten birth cohorts from 2017 to 2026 with a 3% annual discount rate. All monetary units are adjusted to 2017 US$., Results: Rotavirus vaccination in Afghanistan has the potential to avert more than one million cases; 660,000 outpatient visits; approximately 50,000 hospital admissions; 650,000 DALYs; and 12,000 deaths, over 10 years. Not accounting for any Gavi subsidy, rotavirus vaccination can avert DALYs at US$82/DALY from the government perspective and US$80/DALY from the societal perspective. With Gavi support, DALYs can be averted at US$29/DALY and US$31/DALY from the societal and government perspective, respectively. The average yearly cost of a rotavirus vaccination program would represent 2.8% of the total immunization budget expected in 2017 and 0.1% of total health expenditure., Conclusion: The introduction of rotavirus vaccination would be highly cost-effective in Afghanistan, and even more so with a Gavi subsidy., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Diarrhea causes about 10% of all deaths in children under five years globally, with rotavirus causing about 40% of all diarrhea deaths. Ghana introduced rotavirus vaccination as part of routine immunization in 2012 and it has been shown to be effective in reducing disease burden in children under five years. Ghana's transition from low to lower-middle income status in 2010 implies fewer resources from Gavi as well as other major global financing mechanisms. Ghana will soon bear the full cost of vaccines. The aim of this study was to estimate the health impact, costs and cost-effectiveness of rotavirus vaccination in Ghana from introduction and beyond the Gavi transition., Methods: The TRIVAC model is used to estimate costs and effects of rotavirus vaccination from 2012 through 2031. Model inputs include demographics, disease burden, health system structure, health care utilization and costs as well as vaccine cost, coverage, and efficacy. Model inputs came from local data, the international literature and expert consultation. Costs were examined from the health system and societal perspectives., Results: The results show that continued rotavirus vaccination could avert more than 2.2 million cases and 8900 deaths while saving US$6 to US$9 million in costs over a 20-year period. The net cost of vaccination program is approximately US$60 million over the same period. The societal cost per DALY averted is US$238 to US$332 with cost per case averted ranging from US$27 to US$38. The cost per death averted is approximately US$7000., Conclusion: The analysis shows that continued rotavirus vaccination will be highly cost-effective, even for the period during which Ghana will assume responsibility for purchasing vaccines after transition from Gavi support., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Diarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners., Methods: This analysis used Pan American Health Organization's TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates., Results: Over ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to $142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from $615/DALY to $1514/DALY averted., Conclusion: The discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rainbow trout (average weight of 2 g) in fresh water experienced high mortality and were infected with a diplomonad intestinal parasite. Tanks of fish experienced an immediate reduction in mortality after an in-feed treatment with 3% Epsom salts for 2 d. Treatments had to be applied several times, but in each case there was a similar reduction in mortality.

Filamentous black yeasts from the genus Exophiala are ubiquitous, opportunistic pathogens causing both superficial and systemic mycoses in warm- and cold-blooded animals. Infections by black yeasts have been reported relatively frequently in a variety of captive and farmed freshwater and marine fishes. In November 2012, moribund and recently dead, farm-raised Atlantic Halibut Hippoglossus hippoglossus were necropsied to determine the cause of death. Histopathology revealed that three of seven fish were affected by a combination of an ascending trans-ductual granulomatous mycotic nephritis, necrotizing histiocytic encephalitis, and in one fish the addition of a fibrogranulomatous submucosal branchitis. Microbial cultures of kidney using selective mycotic media revealed pure growth of a black-pigmenting septated agent. Application of molecular and phenotypic taxonomy methodologies determined that all three isolates were genetically consistent with Exophiala angulospora. This is the first report of E. angulospora as the causal agent of systemic mycosis in Atlantic Halibut.

Lepeophtheirus salmonis infections in Atlantic salmon, Salmo salar, have been characterized by little to no hyperplastic response and a biphasic immune response that results in chronic inflammation with tissue repair as the infection progresses. We hypothesized that CpG administration with prior lice exposure would enhance epithelial inflammatory mechanisms and boost the Atlantic salmon immune response to L. salmonis, leading to greater protection against infection. We administered multiple exposures of L. salmonis to two groups of Atlantic salmon and compared responses against first-time exposed Atlantic salmon. Following re-exposure, CpG fed fish exhibited increased skin expression of interleukin (IL)-1β and IL-12 β compared to control previously exposed (CPE) and control first-time exposed (CFE) animals, respectively. This inflammatory enhancement occurred with significantly lower expression of matrix metalloproteinase-9 (MMP 9), both systemically (spleen) and locally (skin). Reduced MMP 9 expression was a hallmark of the re-infected fish (occurred in both tissues at both times). When significant differences were present in the skin or spleen, the two re-exposed groups showed greater similarity than with the first exposure group. Lice numbers on CpG fed fish were significantly lower than CFE fish at 7 days post-re-infection (dpri), and although they were not significantly different at 17 dpri, the trend of lower lice levels remained. CpG fed fish also showed nearly twofold greater protection than CPE when compared to the CFE group (48.5% vs. 27.0% reductions at 7 dpri and 27.2% vs. 13.1% reductions at 17 dpri, respectively). The enhanced protection of CpG oligodeoxynucleotide administration to previous exposure was consistent across all body surfaces and suggests that CpG can not only enhance innate responses to L. salmonis in Atlantic salmon, but also further stimulate adaptive responses., (© 2012 Blackwell Publishing Ltd.)

This case report provides pathologic and confirmatory diagnostic documentation of the first reported clinical epizootic of infectious pancreatic necrosis (IPN) in farmed rainbow trout Oncorhynchus mykiss from central Mexico. Both the gross and microscopic pathology were consistent with IPN. A virus was isolated in cell culture with the cytopathic effect typical of the IPN virus (IPNV). Positive identification as IPNV was achieved by means of an IPNV-specific indirect fluorescent antibody test and reverse transcription-polymerase chain reaction. Further genotyping identified this isolate as the Buhl strain of IPNV, which is a member of the West Buxton (A1) serotype of aquatic birnavirus serogroup A.

The phenotypic correlates of pathogenicity for Infectious salmon anemia virus (ISAV) in salmonid fishes have not been thoroughly studied to date. In this study, a comparison was made of 13 different strains of ISAV, isolated from different geographical regions between 1997 and 2004, for their infectivity in three fish species [Atlantic salmon (Salmo salar), coho salmon (Oncorhynchus kisutch) and rainbow trout (Oncorhynchus mykiss)]. When the different virus isolates were used at an approximate inoculum dose of 10(6) TCID(50) in 0.2 ml per fish, it was found that the most virulent strains had an acute mortality phase in Atlantic salmon that started at 10-13 days post-inoculation and lasted for 9-15 days with a cumulative mortality of >/=90 %. These highly pathogenic strains also caused low mortality in rainbow trout, albeit later in infection. Viruses with a more delayed or protracted mortality phase resulting in cumulative mortalities of 50-89 % in Atlantic salmon were considered to be of intermediate pathogenicity and isolates with cumulative mortalities of

Current understanding of the etiopathogenesis of infectious salmon anemia (ISA) virus (ISAV) infection in fish comes mostly from virus detection in homogenized tissues taken from ISA-suspected mortalities. This study combined in situ hybridization (ISH) and histology to demonstrate viral RNA transcripts in different fish cell lines infected with ISAV and in tissues collected during the clinical phase of ISAV infection in Atlantic salmon. For this, a riboprobe to mRNA transcripts of ISAV RNA segment 8 was shown to detect viral mRNA in ISAV-infected TO, CHSE-214, and SHK-1 cell cultures. Specific hybridization was initially detected exclusively in the nuclei of infected cells, which is consistent with the nuclear transcription of orthomyxoviruses. For use of the riboprobe on fish tissues fixed in paraformaldehyde or formalin, the conditions used to permeabilize tissues before ISH (Proteinase K or Tween 20) were first optimized. Tissues were collected 15-20 days after challenge from 7 fresh mortalities of Atlantic salmon parr (approximately 20 g) showing severe gross and microscopic lesions, consistent with ISAV infection. Reverse transcription-polymerase chain reaction on tissue pools confirmed the presence of ISAV in each of the 7 fish. Of the tissues examined in each fish, the heart and liver consistently showed the strongest hybridization signal and, therefore, the most in situ virus, which was located in the endothelium of small blood vessels and in macrophage-like cells.

This case report provides pathologic and confirmatory diagnostic documentation of the first reported clinical epizootic of infectious pancreatic necrosis (IPN) in farmed rainbow trout Oncorhynchus mykiss from central Mexico. Both the gross and microscopic pathology were consistent with IPN. A virus was isolated in cell culture with the cytopathic effect typical of the IPN virus (IPNV). Positive identification as IPNV was achieved by means of an IPNV-specific indirect fluorescent antibody test and reverse transcription-polymerase chain reaction. Further genotyping identified this isolate as the Buhl strain of IPNV, which is a member of the West Buxton (A1) serotype of aquatic birnavirus serogroup A.

A large-scale mortality of larval and juvenile halibut Hippoglossus hippoglossus occurred at a semi-commercial halibut farm in Atlantic Canada. Investigation of the cause revealed aquareovirus particles in necrotic liver tissue of affected fish. Cytopathic effect on CHSE-214 cell lines occurred from all fish cultured for viruses, and the viral morphology of the particles in culture was consistent with that observed in necrotic host tissue. The virus was placed in the family of Reoviridae, genus Aquareovirus based on morphology and RT-PCR results. Multifocal hepatocellular necrosis was a consistent finding in all fish as well as acute necrosis of proximal renal tubules. Concurrent bacterial infections were present in some specimens. Fish experimentally treated with oxytetracycline or a combination of oxytetracycline and chloramine-T had a significantly lower mortality rate than untreated fish. Fish treated with chloramine-T alone had a significantly elevated mortality rate compared to controls. Despite supportive medical therapy, mortality levels in treated and untreated groups remained elevated, supporting the hypothesis that the primary pathogen was of viral origin. This is the first report of elevated mortalities in Atlantic halibut associated with an aquareovirus.