Assessing the spatial distribution of elemental concentrations in surface sediments of Lake Victoria, Kenya: implications for ecological health and management.

Lacustrine sediment quality indicates the effects of both natural and anthropogenic activities on the ecosystem and communities. Despite its ecological importance, myriad complexities, and potential contaminant sources, the spatial distribution of surficial sediments in Lake Victoria's Winam Gulf has never been comprehensively documented. The purpose of this study was to assess the spatial distribution, pathways, and ecological risk of metal elements in the lake using a sediment matrix. Sediment samples were collected throughout the gulf in November 2022. The concentrations of Al, As, Cd, Co, Cr, Cu, Fe, K, Mn, Mo, Ni, P, Pb, Sb, Sn, Ti, Tl, U, and Zn were compared to different contamination metrics and ecological risk assessment indices. The average concentrations were in the following decreasing order: Zn > > > Cr > > Cu > Ni > Pb > Co > As > Cd with mean (± SD) of 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1, 0.30 ± 0.09 mg kg-1, respectively, with strong indications of anthropogenic sources. Average concentrations were in the following decreasing order: Zn > > > Cr, Cu, Ni, Pb, Co, As, and Cd levels (mean ± SD) were 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1 and 0.30 ± 0.09 mg kg-1 with strong indications of anthropogenic sources. The geo-accumulation index (Igeo) and enrichment factor categorisation schemes, respectively, classified these as uncontaminated (level 0) and depletion to minimal enrichment (level 1), while the ecological risk analysis classified them as "low risk". The mouth of the Nyando River, as well as Kisumu, Kendu, and Homa bays, were the most element-enriched and should be prioritised for focused monitoring and remediation. As a result, targeted land management of urban, industrial, transportation, and agricultural areas offers the opportunity to reduce sediment inputs into the lake ecosystem.

Dirofilariasis mouse models for heartworm preclinical research.

Introduction: Dirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug research. Methods: As a refined alternative in vivo heartworm preventative drug screen, we assessed lymphopenic mouse strains with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase of Dirofilaria immitis. Results: Non-obese diabetic (NOD) severe combined immunodeficiency (SCID)γc-/- (NSG and NXG) and recombination-activating gene (RAG)2-/-γc-/- mouse strains yielded viable D. immitis larvae at 2-4 weeks post-infection, including the use of different batches of D. immitis infectious larvae, different D. immitis isolates, and at different laboratories. Mice did not display any clinical signs associated with infection for up to 4 weeks. Developing larvae were found in subcutaneous and muscle fascia tissues, which is the natural site of this stage of heartworm in dogs. Compared with in vitro-propagated larvae at day 14, in vivo-derived larvae had completed the L4 molt, were significantly larger, and contained expanded Wolbachia endobacteria titres. We established an ex vivo L4 paralytic screening system whereby assays with moxidectin or levamisole highlighted discrepancies in relative drug sensitivities in comparison with in vitro-reared L4 D. immitis. We demonstrated effective depletion of Wolbachia by 70%-90% in D. immitis L4 following 2- to 7-day oral in vivo exposures of NSG- or NXG-infected mice with doxycycline or the rapid-acting investigational drug, AWZ1066S. We validated NSG and NXG D. immitis mouse models as a filaricide screen by in vivo treatments with single injections of moxidectin, which mediated a 60%-88% reduction in L4 larvae at 14-28 days. Discussion: Future adoption of these mouse models will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround, and reduced costs and may simultaneously decrease the need for experimental cat or dog use.

Considerations for environmental biogeochemistry and food security for aquaculture around Lake Victoria, Kenya.

The impact of population expansion through economic growth and development has been identified as one of the key drivers of both water and sediment contamination from potentially harmful elements (PHEs). This presents a major hazard not only to aquatic ecosystems but local riparian communities and beyond who rely heavily on this natural resource for drinking water and fish-a valuable source of dietary micronutrients and protein. The present study measured biogeochemical concentration of PHEs in water, sediment and fish from locations pooled into four zones within Winam Gulf and Lake Victoria area of Kenya. Captured fish were used as a sentinel receptor of lake health to evaluate potential risks to fisheries and aquaculture food security. In water, concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu) and lead (Pb) were observed above the United States Environmental Protection Agency (US EPA) maximum contamination level drinking water guidelines (MCL), with aluminium (Al) observed above the Aquatic Life Criteria in all four zones. Similarly, sediment concentrations in all four zones exceeded the US EPA Effects range low (ERL) threshold guidelines for Cu, nickel (Ni), zinc (Zn) and Pb, with Cu, Zn and Pb classed at moderate contamination levels using the contamination factor. Fish tissue concentrations from the four zones were calculated using recommended daily intakes (RDI) and for PHEs as provisional maximum tolerable intakes (PMTIs) and indicated most macro- and micronutrients were at or below 10% RDI from aquaculture and wild fish, with Se indicating a greater RDI (16-29%) in all the zones. Contributions of PHEs to PMTIs were below threshold guidelines for both aquaculture and wild fish with only Cd, Cr and Pb levels being above the PMTI thresholds. There is a need to assess the long-term effects of persistent anthropogenic PHE input into Winam Gulf and the wider Lake Victoria basin. Continued monitoring of PHEs using both historical and more recent data will enable future management policies to be implemented through improved mitigation strategies to reduce their impact on water quality, fish health and subsequent human health.

Developments in Pb-210 methodologies to provide chronologies for environmental change.

Chronologies generated from core profiles to apply dates to environmental changes commonly use the measurement of the activity of radionuclides deposited and stratified with physical environmental material. The most commonly reported nuclide to define chronologies covering the last 150 years is Pb-210, for which accepted data processing methodologies in the literature have focussed on the constant rate of supply (CRS) model and the more recently published Bayesian Plum model. This short communication describes a validation approach using defined sediment layers referred to as 'varve' counting, which provide known points of reference to account for uncertainty between generated dates from each model using published Pb-210 measurements. A significant improvement in the chronologies was observed when applying reference date corrections to the models. This was shown to be essential in providing confidence in reported datasets and accuracy of predicted chronologies, which will better inform the interpretation of environmental change, e.g. sedimentation rates, climate change, pollution pathways and land degradation. Generated chronologies from both the CRS and Plum methods showed good agreement with the established varve dates (typically < 4-year difference).

The willingness of UK adults with intellectual disabilities to take COVID-19 vaccines.

BACKGROUND: Given the much greater COVID-19 mortality risk experienced by people with intellectual disabilities (ID), understanding the willingness of people with ID to take a COVID-19 vaccine is a major public health issue. METHOD: In December 2020 to February 2021, across the United Kingdom, 621 adults with ID were interviewed remotely and 348 family carers or support workers of adults with ID with greater needs completed an online survey, including a question on willingness to take a COVID-19 vaccine if offered. RESULTS: Eighty-seven per cent of interviewees with ID were willing to take a COVID-19 vaccine, with willingness associated with white ethnicity, having already had a flu vaccine, gaining information about COVID-19 from television but not from social media, and knowing COVID-19 social restrictions rules. A percentage of 81.7% of surveyed carers of adults with ID with greater needs reported that the person would be willing to take a COVID-19 vaccine, with willingness associated with white ethnicity, having a health condition of concern in the context of COVID-19, having had a flu vaccine, being close to someone who had died due to COVID-19, and having shielded at some point during the pandemic. CONCLUSIONS: Reported willingness to take the COVID-19 vaccine is high among adults with ID in the United Kingdom, with factors associated with willingness having clear implications for public health policy and practice.

Lysyl-tRNA synthetase produces diadenosine tetraphosphate to curb STING-dependent inflammation.

Inflammation is an essential part of immunity against pathogens and tumors but can promote disease if not tightly regulated. Self and non-self-nucleic acids can trigger inflammation, through recognition by the cyclic GMP-AMP (cGAMP) synthetase (cGAS) and subsequent activation of the stimulator of interferon genes (STING) protein. Here, we show that RNA:DNA hybrids can be detected by cGAS and that the Lysyl-tRNA synthetase (LysRS) inhibits STING activation through two complementary mechanisms. First, LysRS interacts with RNA:DNA hybrids, delaying recognition by cGAS and impeding cGAMP production. Second, RNA:DNA hybrids stimulate LysRS-dependent production of diadenosine tetraphosphate (Ap4A) that in turn attenuates STING-dependent signaling. We propose a model whereby these mechanisms cooperate to buffer STING activation. Consequently, modulation of the LysRS-Ap4A axis in vitro or in vivo interferes with inflammatory responses. Thus, altogether, we establish LysRS and Ap4A as pharmacological targets to control STING signaling and treat inflammatory diseases.

Elemental composition of aquaculture fish from West Bengal, India: nutrition versus food safety.

Aquaculture production continues to grow in West Bengal, where on average people consume 8.2 kg capita-1 of fish each year, and an extensive mosaic of aquaculture ponds has developed along the River Hugli as clay pits are repurposed. The adjacent brickworks and industry (especially tanneries) are a source of environmental pollution, with potential for bioaccumulation of potentially harmful elements (PHEs) in fish farmed in these ponds. Fish from aquaculture present an opportunity to meet food sufficiency in West Bengal; however, an investigation to assess their effectiveness for micronutrient supply balanced against food safety is required. Five ponds close to industrial brick manufacture (urban) and three from rural areas were assessed for the degree of pollution within their pond sediments and waters. Fish were also sampled from each location including a subset from the market in Kolkata to determine the concentrations of PHEs in their fish muscle tissue. Dietary intake and PHE loading were calculated for four fish species to evaluate their nutrient content with respect to recommended daily intakes for adults, e.g. calcium (Ca), potassium (K), magnesium (Mg), iron (Fe), zinc (Zn) and selenium (Se), and to establish whether the provisional maximum tolerable intakes (PMTIs) are exceeded for PHEs, e.g. aluminium (Al), arsenic (As), mercury (Hg), chromium (Cr), tin (Sn), copper (Cu) and lead (Pb). Preliminary results suggest that aquaculture is making an important contribution to nutrition, with fish being a good source of Se. However, in contrast to small wild-caught fish, aquaculture fish in the present study were poor sources of Fe, Ca and Zn. The fish also made substantial contributions (> 10%) to the PMTI of Hg and As. Therefore, there is an urgent need for ongoing monitoring and an expanded sampling programme, as well as research into approaches which might improve the nutritional quality of the farmed fish.

Acquired immune responses to the seasonal trivalent influenza vaccination in COPD.

Epidemiological data suggest that influenza vaccination protects against all-cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell-mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty-seven subjects were enrolled into the study; 23 COPD patients, 13 age-matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre-TIV vaccination and at days 7 and 28 and 6 months post-vaccine for haemagglutinin inhibition (HAI) titre, antigen-specific T cell and antibody-secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post-vaccine. As we observed no disease-dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = -0·4253, P = 0·0036) and influenza B (r = -0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1-specific CD4+ T helper cells (r = -0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management.

Comparison of a novel microcrystalline tyrosine adjuvant with aluminium hydroxide for enhancing vaccination against seasonal influenza.

BACKGROUND: Vaccination against seasonal influenza strains is recommended for "high risk" patient groups such as infants, elderly and those with respiratory or circulatory diseases. However, efficacy of the trivalent influenza vaccine (TIV) is poor in many cases and in the event of an influenza pandemic, mono-valent vaccines have been rapidly developed and deployed. One of the main issues with use of vaccine in pandemic situations is the lack of a suitable quantity of vaccine early enough during the pandemic to exert a major influence on the transmission of virus and disease outcome. One approach is to use a dose-sparing regimen which inevitably involves enhancing the efficacy using adjuvants. METHODS: In this study we compare the use of a novel microcrystalline tyrosine (MCT) adjuvant, which is currently used in a niche area of allergy immunotherapy, for its ability to enhance the efficacy of a seasonal TIV preparation. The efficacy of the MCT adjuvant formulation was compared to alum adjuvanted TIV and to TIV administered without adjuvant using a ferret challenge model to determine vaccine efficacy. RESULTS: The MCT was found to possess high protein-binding capacity. In the two groups where TIV was formulated with adjuvant, the immune response was found to be higher (as determined by HAI titre) than vaccine administered without adjuvant and especially so after challenge with a live influenza virus. Vaccinated animals exhibited lower viral loads (as determined using RT-PCR) than control animals where no vaccine was administered. CONCLUSIONS: The attributes of each adjuvant in stimulating single-dose protection against a poorly immunogenic vaccine was demonstrated. The properties of MCT that lead to the reported effectiveness warrants further exploration in this and other vaccine targets - particularly where appropriate immunogenic, biodegradable and stable alternative adjuvants are sought.

Source, distribution and ecotoxicological assessment of multielements in superficial sediments of a tropical turbid estuarine environment: A multivariate approach.

The work examined the distribution, possible sources and ecotoxicological assessment of 51 trace elements covering 13 sampling stations in surface sediments of coastal regions of Sundarban mangrove wetland and adjacent Hugli river estuary. The element concentrations exhibited an increasing trend towards downstream of the estuary (except lanthanides) with maximum enrichment for 22 elements at Gangadharpur (Sundarban region). According to Sediment Quality Guidelines (SQGs), the concentrations of Cu, As, Cr and Cd exceeded the Effects-Range-Low values, while Ni at certain stations exceeded the Effects-Range-Medium suggesting adverse effects on the sediment-dwelling organisms. The geoaccumulation index revealed that the stations were unpolluted to moderately polluted. Risk Index (357.61) and Enrichment factor (11.42) depicted that Nimtala station (upstream) was at high ecological risk zone. The result of PCA endorsed that organic carbon and clay fraction play crucial role in accumulating the elements in sediments. This pilot study contributes to a better understanding of the geochemistry of this complex deltaic ecosystem.

Performance and learning curve of a surgical care practitioner in completing hip aspirations.

INTRODUCTION The roles of non-medically trained practitioners within the NHS are expanding; they are now being employed by many specialties, including surgery, to relieve pressures on healthcare teams. AIMS To investigate the learning curve and competence of an orthopaedic surgical care practitioner (SCP) in performing hip aspirations. METHODS Data were retrospectively collected on 510 orthopaedic hip aspirations, of which 360 were completed by a single SCP and 150 were completed by surgeons before the SCP took over routine aspiration. The 360 aspirations completed by an SCP were separated into groups of 30 by date, so any trend in failure rate could be analysed. Ordinal χ2 analysis was used to analyse this trend and Pearson χ2 analysis was used to analyse differences in failure rates between professionals. RESULTS The hip aspiration failure rate for the SCP was significantly lower than for the surgeons; 8.6% vs 20.7% (P<0.001). With the experience gained in completing the first 210 procedures, the failure rate of the SCP dropped to 3.3% for the remaining 150 procedures. This downward trend in hip aspiration failure rate, with advancing experience of the SCP, was shown to be statistically significant (P=0.006). DISCUSSION SCPs who complete hip aspirations on a regular basis have significantly lower failure rates than surgeons, probably as a result of the learning curve, which this study demonstrated. Other trusts should consider delegating routine hip aspiration work to a designated SCP to lower failure rates.

Combined heart-liver transplantation with extended cardiopulmonary bypass.

We report a case of combined heart and liver transplantation for familial amyloid polyneuropathy. This is the first such combined transplant performed in Asia, and differs from previously described cases, in that cardiopulmonary bypass was continued at partial flow during liver transplantation in our case. This was done in order to provide haemodynamic support to the cardiac graft and to protect it from the impending reperfusion insult that frequently accompanies liver transplantation. The utility of this management course is discussed, along with its actual and potential complications. We also describe the impact of a lung-protective ventilation strategy employed during cardiac transplantation.

Establishment of an aerosol challenge model of tuberculosis in rhesus macaques and an evaluation of endpoints for vaccine testing.

The establishment of an aerosol challenge model in nonhuman primates (NHPs) for the testing of vaccines against Mycobacterium tuberculosis would assist the global effort to optimize novel vaccination strategies. The endpoints used in preclinical challenge studies to identify measures of disease burden need to be accurate and sensitive enough to distinguish subtle differences and benefits afforded by different tuberculosis (TB) vaccine regimens when group sizes are inevitably small. This study sought to assess clinical and nonclinical endpoints as potentially sensitive measures of disease burden in a challenge study with rhesus macaques by using a new protocol of aerosol administration of M. tuberculosis. Immunological and clinical readouts were assessed for utility in vaccine evaluation studies. This is the first example of TB vaccine evaluation with rhesus macaques where long-term survival was one of the primary endpoints. However, we found that in NHP vaccine efficacy studies with maximum group sizes of six animals, survival did not provide a valuable endpoint. Two approaches used in human clinical trials for the evaluation of the gamma interferon (IFN-gamma) response to vaccination (enzyme-linked immunospot [ELISpot] assay and enzyme-linked immunosorbent assay [ELISA]) were included in this study. The IFN-gamma profiles induced following vaccination were found not to correlate with protection, nor did the level of purified protein derivative (PPD)-specific proliferation. The only readout to reliably distinguish vaccinated and unvaccinated NHPs was the determination of lung lesion burden using magnetic resonance (MR) imaging combined with stereology at the end of the study. Therefore, the currently proposed key markers were not shown to correlate with protection, and only imaging offered a potentially reliable correlate.

Defective interfering viruses and their potential as antiviral agents.

Defective interfering (DI) virus is simply defined as a spontaneously generated virus mutant from which a critical portion of the virus genome has been deleted. At least one essential gene of the virus is deleted, either in its entirety, or sufficiently to make it non-functional. The resulting DI genome is then defective for replication in the absence of the product(s) of the deleted gene(s), and its replication requires the presence of the complete functional virus genome to provide the missing functions. In addition to being defective DI virus suppresses production of the helper virus in co-infected cells, and this process of interference can readily be observed in cultured cells. In some cases, DI virus has been observed to attenuate disease in virus-infected animals. In this article, we review the properties of DI virus, potential mechanisms of interference and progress in using DI virus (in particular that derived from influenza A virus) as a novel type of antiviral agent.

The effects of glucose ingestion and glucose regulation on memory performance in older adults with mild cognitive impairment.

BACKGROUND/OBJECTIVES: Previous research investigating the impact of glucose ingestion and/or improvements in glucose regulation has found selective cognitive facilitation on episodic memory tasks in successful ageing and dementia. The present study aimed to extend this research to mild cognitive impairment (MCI). SUBJECTS/METHODS: In a repeated-measures design, 24 older adults with and 24 older adults without MCI performed a battery of memory and attention tasks after 25 g of glucose or a sweetness matched placebo. In addition, to assess the impact of individual differences in glucose regulation, blood glucose measurements were taken throughout the testing session. RESULTS: Consistent with previous research, cognitive facilitation was observed for episodic memory tasks only in both successful ageing and MCI. Older adults with MCI had a similar glucose regulatory response as controls but their fasting levels were elevated. Notably, higher levels of blood glucose were associated with impaired memory performance in both the glucose and placebo conditions. Importantly, both blood glucose and memory performance indices were significant predictors of MCI status. CONCLUSIONS: The utility of glucose supplementation and the use of glucose regulation as a biological marker are discussed in relation to these data.

FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3.

Fanconi anemia (FA) is a human disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. Thirteen complementation groups and genes are identified, including BRCA2, which is defective in the FA-D1 group. Eight of the FA proteins, including FANCG, participate in a nuclear core complex that is required for the monoubiquitylation of FANCD2 and FANCI. FANCD2, like FANCD1/BRCA2, is not part of the core complex, and we previously showed direct BRCA2-FANCD2 interaction using yeast two-hybrid analysis. We now show in human and hamster cells that expression of FANCG protein, but not the other core complex proteins, is required for co-precipitation of BRCA2 and FANCD2. We also show that phosphorylation of FANCG serine 7 is required for its co-precipitation with BRCA2, XRCC3 and FANCD2, as well as the direct interaction of BRCA2-FANCD2. These results argue that FANCG has a role independent of the FA core complex, and we propose that phosphorylation of serine 7 is the signalling event required for forming a discrete complex comprising FANCD1/BRCA2-FANCD2-FANCG-XRCC3 (D1-D2-G-X3). Cells that fail to express either phospho-Ser7-FANCG, or full length BRCA2 protein, lack the interactions amongst the four component proteins. A role for D1-D2-G-X3 in homologous recombination repair (HRR) is supported by our finding that FANCG and the RAD51-paralog XRCC3 are epistatic for sensitivity to DNA crosslinking compounds in DT40 chicken cells. Our findings further define the intricate interface between FANC and HRR proteins in maintaining chromosome stability.

Clustering of behavioural and psychological symptoms in dementia (BPSD): a European Alzheimer's disease consortium (EADC) study.

OBJECTIVES: This cross-sectional study investigated the relationships between behavioural and psychological symptoms of dementia (BPSD). METHODS: We recruited 194 patients with dementia from the memory clinic practice of six European Alzheimer's Disease Consortium centres. BPSD were assessed using a pre-designed questionnaire comprising the Neuropsychiatric Inventory (NPI). BPSD scores were analysed by Spearman's correlation analysis and principal components factor analysis. Results were confirmed by performing Varimax rotation of the factors. RESULTS: The NPI symptoms occurred very frequently: 96% of the patients displayed at least one symptom. Among them, apathy (59.6%) and depression (58.5%) were the most common abnormalities, followed by irritability (44.6%), anxiety (44%) and agitation (41.5%). Four NPI-based factors were identified (58% of the common variance): psychosis factor (irritability, agitation, hallucinations and anxiety), psychomotor factor (aberrant motor behaviour and delusions), mood liability factor (disinhibition, elation and depression) and instinctual factor (appetite disturbance, sleep disturbance and apathy). CONCLUSION: Psychosis, psychomotor factor, mood liability factor and instinctual factor form four distinct behavioural syndromes in dementia. We report the novel observation that depression clusters together with disinhibition and elation within a mood liability factor. This finding highlights the nature of mood, and mood oscillations, from depression to disinhibition within the cluster, and has implications for treatment by taking into consideration the poles of the mood scale and any oscillation between them.

Interfering vaccine (defective interfering influenza A virus) protects ferrets from influenza, and allows them to develop solid immunity to reinfection.

Defective interfering (DI) virus RNAs result from major deletions in full-length viral RNAs that occur spontaneously during de novo RNA synthesis. These RNAs are packaged into virions that are by definition non-infectious, and are delivered to cells normally targeted by the virion. DI RNAs can only replicate with the aid of a coinfecting infectious helper virus, but the small size of DI RNA allows more copies of it to be made than of its full-length counterpart, so the cell produces defective virions in place of infectious progeny. In line with this scenario, the expected lethal disease in an influenza A virus-mouse model is made subclinical by administration of DI virus, but animals develop solid immunity to the infecting virus. Hence DI virus has been called an 'interfering vaccine'. Because interfering vaccine acts intracellularly and at a molecular level, it should be effective against all influenza A viruses regardless of subtype. Here we have used the ferret, widely acknowledged as the best model for human influenza. We show that an interfering vaccine with defective RNAs from an H3N8 virus almost completely abolished clinical disease caused by A/Sydney/5/97 (H3N2), with abrogation of fever and significant reductions in clinical signs of illness. Animals recovered fully and were solidly immune to reinfection, in line with the view that treatment converts the otherwise virulent disease into a subclinical and immunizing infection.