Dangerous Viral Infections Research Articles

Plant viruses in the system of seed potato production

Solanum tuberosum L. is susceptible to 40 different virus species and 2 viroids. To prevent plant viruses from spreading in field conditions, it is necessary to have reliable data on the species composition of plant reservoirs of viral infection, the total activity of insect vectors, and possible ways of virus transmission in a particular territory of seed material production. Attention should be paid to the factors that facilitate and hinder the disease development in crops and to disease symptoms in different potato varieties. Manifestations of viral infections were monitored on every plant from the sample at the stages of initial growth, bud formation, and flowering and before the removal of potato haulms. Insects were collected using standard entomological method. The total RNA was isolated employing commercial kits for the extraction of nucleic acids from plant material “PhytoSorb” (Syntol Llc) and the benchtop automated extraction instrument KingFisher Flex (ThermoScientific) with magnetic particles. Plant viral infection was observed to accumulate if potato planting material was not renewed. The tested potato plants contained mixed viral infection, which consisted of viruses from mosaic group: PVY, PVX, PVM, PVS PVA, as well as PSTVd and PLRV. Without the renewal of seed potatoes, the concentration of plant viruses in an agroecosystem rises and causes secondary infections in potato plants. The research identified the main insect-vectors in the agroecosystem of potato fields: insects from genera Cicadella, Henosepilachna vigintioctomaculata, Dolycoris baccarum, Mythimna separata, Lygus pratensis, and Rhopalosiphum padi. Many wild weeds serve as fodder plants for insect vectors facilitating the accumulation of plant viruses in agroecosystems. It was established that perennial weeds were the main plant reservoirs of dangerous viral infections, e.g. Sonchus arvensis and Taraxacum officinale. We determined that Trifolium pratense typus L., Chenopodium album L., Plantago major L., Barbarea vulgaris W.T. Aiton, and Ambrosia artemisiifolia L. were the reservoirs of PVY. All these factors can lead to an epiphytotic situation.

Porcine reproductive and neonatal infections: Importance and threats of bacterial virophoria

The provisions of the doctrine of transfer the epizootic process of dangerous viral infections to the enzootic process and their rooting in pig production through the integration of their pathogen into the pig microbiome in the form of comorbid viral and bacterial infections are substantiated. The aim of the study is to systematize the bacterial virophoria in the epizootology of porcine reproductive and neonatal infections (PRNI) as a component of the enzootic cycle of emergent infections in the pig industry of Ukraine. Classical swine fever (CSF) virus: attenuated strain ‘IECVM 03’; Aujeszky’s disease (AD) virus: epizootic strains of Ukrainian origin of AD virus ‘18v UNDIEV’; Teschen disease (TD) virus: epizootic strain ‘Bucha’. Epizootic strains: pasteurella bacteria, streptococcus, lacto- and bifidobacteria. According to the results of the study, it was found that the rotating magnetic field of the right direction promoted the adsorption of the CSF virus on pasteurella cells. The Aujeszky’s disease virus was adsorbed on the bacteria Salmonella choleraesuis No. 34, Bacterium bifidum and Lactobacillus casei with an efficiency of 15–45% in the pH range of 8.5–9.5, at neutral pH (7.4) no more than 1.5% of the virus was adsorbed, and at acidic pH (3.0) the AD virus was not adsorbed et all. On bacteria Pasteurella multocida No. 7, AD virus was adsorbed in the pH range of 8.5–9.5 with an efficiency of no more than 1.5%; at neutral pH (7.4), up to 50% of the virus was adsorbed, and at acidic pH (3.0), no more than 1.5% of AD virus was adsorbed. The interaction of TD virus with bifidobacteria inhibited viral reproduction in the body of infected polecats, but preserved the reproductive activity of teschovirus in the presence of streptococci. The rooting of dangerous viral infections (AD and TD, circovirus and parvovirus infections, reproductive and respiratory syndrome, and endemic porcine diarrhea) in pig production has always been accompanied by the ‘engraftment’ of their pathogens in the microbiome of pig production facilities in the form of comorbid (i. e. clinically manifested) and/or associated infections (i. e. similar to the group of Minimal Residual Human Diseases — Maladie Résiduelle Minimale, MRD). A key role in the establishment of these diseases and the formation of their stationary centers in pig production is played by the virophoria of bacteria synergistic with their pathogens, in particular as part of the etiologic microflora of reproductive and neonatal infections in pigs

ЗОНИРОВАНИЕ КАК ИНСТРУМЕНТ ПРЕДУПРЕЖДЕНИЯ И КОНТРОЛЯ БОЛЕЗНЕЙ SUIDAE

Dangerous viral infections (ASF, CSF, PRRS, etc.) are putting unprecedented pressure on food security in pig industry. In connection with the infectious threat, measures aimed at preventing the penetration of Suidae pathogens into new territories, as well as preventing their further rooting and spread, are of paramount importance. One of the effective preventive tools of the risk assessment system in the fight against especially dangerous animal diseases is zoning. The use of zoning makes it possible to contain the spread of the pathogen, minimize the imposed trade restrictions and, as a result, reduce economic losses. However, differences in the mechanisms for allocating zones and the lack of specific scientifically based recommendations on their size in a number of regulatory documents lead to the impossibility of uniformity of algorithms for implementing the zoning principle and makes it difficult to introduce the experience of foreign countries into domestic practice. This review describes the experience of using zoning in different countries to control the spread of the most significant viral diseases for swine breeding, and provides recommendations for possible zone sizes to be introduced when outbreaks of CSF and PRRS are confirmed.

STAT1 and Its Crucial Role in the Control of Viral Infections.

The signal transducer and activator of transcription (STAT) 1 protein plays a key role in the immune response against viruses and other pathogens by transducing, in the nucleus, the signal from type I, type II and type III IFNs. STAT1 activates the transcription of hundreds of genes, some of which have been well characterized for their antiviral properties. STAT1 gene deletion in mice and complete STAT1 deficiency in humans both cause rapid death from severe infections. STAT1 plays a key role in the immunoglobulin class-switch recombination through the upregulation of T-bet; it also plays a key role in the production of T-bet+ memory B cells that contribute to tissue-resident humoral memory by mounting an IgG response during re-infection. Considering the key role of STAT1 in the antiviral immune response, many viruses, including dangerous viruses such as Ebola and SARS-CoV-2, have developed different mechanisms to inhibit this transcription factor. The search for drugs capable of targeting the viral proteins implicated in both viral replication and IFN/STAT1 inhibition is important for the treatment of the most dangerous viral infections and for future viral pandemics, as shown by the clinical results obtained with Paxlovid in patients infected with SARS-CoV-2.

Categorizing white blood cells by utilizing deep features of proposed 4B-AdditionNet-based CNN network with ant colony optimization

White blood cells, WBCs for short, are an essential component of the human immune system. These cells are our body's first line of defense against infections and diseases caused by bacteria, viruses, and fungi, as well as abnormal and external substances that may enter the bloodstream. A wrong WBC count can signify dangerous viral infections, autoimmune disorders, cancer, sarcoidosis, aplastic anemia, leukemia, tuberculosis, etc. A lot of these diseases and disorders can be extremely painful and often result in death. Leukemia is among the more common types of blood cancer and when left undetected leads to death. An early diagnosis is necessary which is possible by looking at the shapes and determining the numbers of young and immature WBCs to see if they are normal or not. Performing this task manually is a cumbersome, expensive, and time-consuming process for hematologists, and therefore computer-aided systems have been developed to help with this problem. This paper proposes an improved method of classification of WBCs utilizing a combination of preprocessing, convolutional neural networks (CNNs), feature selection algorithms, and classifiers. In preprocessing, contrast-limited adaptive histogram equalization (CLAHE) is applied to the input images. A CNN is designed and trained to be used for feature extraction along with ResNet50 and EfficientNetB0 networks. Ant colony optimization is used to select the best features which are then serially fused and passed onto classifiers such as support vector machine (SVM) and quadratic discriminant analysis (QDA) for classification. The classification accuracy achieved on the Blood Cell Images dataset is 98.44%, which shows the robustness of the proposed work.

Comparative analysis of existing platforms for the development of vaccines against dangerous and extremely dangerous viral infections with pandemic potential

The main triggers of new infectious diseases, including those with pandemic potential, are: spontaneous emergence of infectious strains which are more virulent for humans and contribute to transmission of pathogenic microorganisms, environmental changes, social and economic factors, increased contact rates between different regions. A successful pandemic response requires mass immunisation against a specific disease, aimed at the development of herd immunity which is based on the concept of indirect protection of the whole of the population by immunising a part of it. A well-grounded choice of the vaccine platform is central to dealing with this problem. The aim of the study was to compare characteristics of vaccine platforms (attenuated, inactivated, subunit, recombinant vector, DNA, and RNA vaccines) intended for mass immunisation against dangerous and extremely dangerous viral infections with pandemic potential. The study focused on the members of Poxviridae, Orthomyxoviridae and Coronaviridae families as potential pathogens. The vaccine platforms were compared in terms of the following parameters: capability of producing a robust immune response; protective efficacy; time required for vaccine development and testing; ability to produce vaccine in volumes required for mass immunisation; potential obstacles associated with the intended use of the vaccine. It is expected that in the next few decades DNA and RNA vaccine platforms will be most widely used for development of products against dangerous and extremely dangerous viral infections with pandemic potential, regardless of taxonomic groups of pathogens.

Glycyrrhizic Acid Derivatives as New Antiviral and Immune Modulating Agents

The search for new drugs to treat viral infections and immune deficiencies of various etiologies is still one of the most important tasks of medicinal chemistry, pharmacy, and medicine due to the widespread prevalence of a number of socially dangerous viral infections. This review focuses on the chemical modification of Glycyrrhizic acid (Gl), the main component of licorice root, which is currently a leading natural glycoside that is considered to be promising for the development of new antiviral agents. The review presents the results of studies conducted over the past 15 years to obtain a library of Gl acid derivatives for biological studies and to search for leader compounds. The synthesis of new biologically active derivatives and analogues (conjugates with amino acids and dipeptides, amino sugars, licorice triterpene acids conjugates with amino sugars, saponins and mono glycosides, and heterocyclic amides) was conducted, and their antiviral and immune modulating properties were studied. Potent inhibitors of HIV, SARS CoV, Epstein-Barr, and influenza A/H1N1 viruses and the stimulators of primary immune response were found among the Gl derivatives and analogues that were produced.

Epizootic situation concerning especially dangerous viral infections among birds of South Ukraine

Aim of the work was monitoring of especially dangerous and economically significant poultry infections in the South of Ukraine. The research was conducted at the Odessa Research Station of the National Scientific Center “Institute of Experimental and Clinical Veterinary Medicine” and in the Testing Center of the Odessa Regional State Laboratory of the State Service of Ukraine on Food Safety and Consumer Protection. The corpses of dead birds were subjected to autopsy; meanwhile biological material was picked up for research. Serological tests for Newcastle disease were performed in HIT with a virus dose of 4 UHA in a titer of 1:8 and higher. In addition to common bacteriological studies the presence of bacterial associates was determined. Serological tests of 365 samples of blood from poultry from 73 settlements, 16 samples from wild and 18 samples from synanthropic birds of Odessa Region, did not reveal antibodies to avian influenza virus of subtype H5. The presence of the formed group immunity against the causative agent of Newcastle disease was detected in the farmsteads of 118 settlements and in 10 industrial poultry farms (seropositivity is 80–100%). Antibodies against the pathogen of Newcastle disease in the blood sera from wild birds from Odessa Region were not detected. In the summer-autumn season, some outbreaks of the Newcastle disease among ornamental pigeons were detected in three farms of two settlements. Mortality was 50–70%. Studying of 15 blood samples from pigeons detected antibodies to Newcastle disease virus (antibody titer 4.0–7.1 log2). Autopsy of 28 poultry carcasses revealed changes characteristic of infectious laryngotracheitis of chickens, as well as some diseases of bacterial (tuberculosis, pasteurellosis, escherichiosis) and protozoan (trichomoniasis of chickens) etiology. Monitoring data on particularly dangerous viral infections of poultry in the South of Ukraine indicate the stability of the epizootic situation. The absence of hemagglutinating antibodies to avian influenza virus of the H5 subtype in the populations of the studied birds of different species and the presence of the formed group immunity against the Newcastle disease pathogen were established; seropositivity is 80–93 %. The circulation of Newcastle disease virus among ornamental pigeons has been established

Recombinant Retroviral Particles: Technology of Poduction and Application as Positive Controls for PCR Diagnostics of Dangerous Viral Infections

Objective. Construction of positive control samples based on recombinant retroviral particles and their application in RT-PCR diagnostic assays for RNA detection of agents of dangerous and particularly dangerous viral infections.Materials and methods. Molecular biological, genetic engineering, and immunological methods were used: polymerase chain reaction, restriction, ligation, cloning, transformation, transfection, flow cytometry.Results and discussion. Technology of positive control samples producing based on recombinant virions has been developed and tested. It includes construction of retroviral vector with cloned diagnostic sequence of the viral genome; obtaining a packaging cell line producing chimeric retroviral particles; determination of recombinant virions titer by flow cytometry and polymerase chain reaction; application of the obtained preparation as a control sample for PCR diagnostics of infectious agents. Positive controls based on retroviral vectors as carriers of genomic RNA fragments of pathogenic viruses were used in the development of PCR diagnostic kits for dangerous and particularly dangerous viral infections. Their application increased the kits quality and made it possible to exclude the work with concentrated hazardous infectious agents (Lassa virus, tick-borne encephalitis virus, lymphocytic choriomeningitis virus, Puumala virus).

Prevalence of Hepatitis C Virus in Iranian Prisoners: An Updated Systematic Review and Multilevel Meta-Analysis Study

Context: Hepatitis C is one of the most dangerous viral infections causing chronic liver disease. Objectives: The current study aimed to estimate the pooled prevalence of hepatitis C in Iranian prisoners. Evidence Acquisition: Articles were identified through searching international databases, including PubMed, Scopus, Elsevier, Google Scholar, and Web of Science and Iranian databases, including Scientific Information Database (SID), Health.barakatkns, IranDoc, Civilica, and MagIran. We systematically reviewed all studies reporting the prevalence of HCV in Iranian prisoners. All studies conducted ELISA tests for the evaluation of HCV antibodies. In this study, a multilevel meta-analysis method was used to estimate the pooled prevalence. Results: The electronic search identified 147 records, 33 of which were relevant papers used for the pooled meta-analysis of HCV prevalence. Overall, the prevalence of HCV using a multilevel meta-analysis approach was 24.88% (95% CI = 19.12 - 31.69). The highest pooled HCV rate was related to Markazi province (59.47% [95% CI = 51.70 - 67.25]), while the lowest pooled HCV rate belonged to North Khorasan province (5.00% [95% CI = 2.44 - 7.55]). A decreasing HCV prevalence trend was observed between 1995 and 2018. Conclusions: The results of the study showed that the prevalence of HCV is significantly high among prisoners in Iran. An enhanced training program is needed for prisoners and prison staff to improve the prisoners’ health status.

COVID-19 and emerging viral infections: The case for interferon lambda.

With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.

Getting to Know the Neighbours with GTM: The Case of Antiviral Compounds.

Recent outbreaks of dangerous viral infections, such as Ebola virus disease, Zika fever, etc., are forcing the search for new antiviral compounds. Preferably, such compounds should possess broad-spectrum antiviral activity, as the development of drugs for the treatment of dozens of viral infections lacking specific treatment would require significant resources. Antiviral activity data present in public resources are very sparse and further investigation of structure-activity relationships is necessary. One of the strategies could be the investigation of chemical space around known active compounds and assessment of activity against closely related viruses in order to fill in the antiviral activity matrix. Here we present an investigation of antiviral activity using universal maps built with generative topographic mapping (GTM) algorithm. The GTM-based maps were used to find commercially available compounds in close proximity to already known compounds with anti-flaviviral and anti-enteroviral activities. Selected compounds were then assessed in cell-based assays against tick-borne encephalitis virus (TBEV) and a panel of enteroviruses. This approach allowed us to identify 23 new compounds showing anti-TBEV activity with EC50 values in micromolar and submicromolar range.

Future Developments and Applications of the Vaccines against Dangerous Viral Infections, RNA-Replicon-Based, Obtained from the Venezuelan Equine Encephalomyelitis Virus

The members of the Filoviridae (Marburg and Ebola viruses) and Arenaviridae (Lassa, Lujo, Machupo, Junin, Guanarito, Sabia viruses) families are the etiological agents of particularly dangerous viral hemorrhagic fevers. These agents pose a potential threat to public health care in view of the possibility of their unintended import into the non-endemic regions, and thus construction of specific medical protectors as regards induced by them diseases is a pressing issue. According to leading experts, vaccination of the cohorts that fall in the risk groups is the most effective and least expensive method to prevent the development of epidemics. The review contains information on a new prospective line of protective preparations development as regards particularly dangerous viral infections - construction of alphavirus-replicon-based vaccine. Elaboration of recombinant replicons does not require cultivation of pathogenic microorganisms. RNA-replicons are distinguished by their incapacity to produce infective progeny, which is of a great importance for the development of vaccines against particularly dangerous viral hemorrhagic fevers. Advantages of alphaviral replicons over other RNA-replicons are as follows: high levels of heterologous gene expression and resistance to anti-vector immunity. RNA-replicons of alphaviruses combine the safety of inactivated, and immunogenicity of live attenuated vaccines. Alphaviruses-based replicons are suitable for express vaccine development with the purpose of specific prophylaxis of viral infectious diseases.

Future Developments and Applications of the Vaccines against Dangerous Viral Infections, RNA-Replicon-Based, Obtained from the Venezuelan Equine Encephalomyelitis Virus

The members of the Filoviridae (Marburg and Ebola viruses) and Arenaviridae (Lassa, Lujo, Machupo, Junin, Guanarito, Sabia viruses) families are the etiological agents of particularly dangerous viral hemorrhagic fevers. These agents pose a potential threat to public health care in view of the possibility of their unintended import into the non-endemic regions, and thus construction of specific medical protectors as regards induced by them diseases is a pressing issue. According to leading experts, vaccination of the cohorts that fall in the risk groups is the most effective and least expensive method to prevent the development of epidemics. The review contains information on a new prospective line of protective preparations development as regards particularly dangerous viral infections - construction of alphavirus-replicon-based vaccine. Elaboration of recombinant replicons does not require cultivation of pathogenic microorganisms. RNA-replicons are distinguished by their incapacity to produce infective progeny, which is of a great importance for the development of vaccines against particularly dangerous viral hemorrhagic fevers. Advantages of alphaviral replicons over other RNA-replicons are as follows: high levels of heterologous gene expression and resistance to anti-vector immunity. RNA-replicons of alphaviruses combine the safety of inactivated, and immunogenicity of live attenuated vaccines. Alphaviruses-based replicons are suitable for express vaccine development with the purpose of specific prophylaxis of viral infectious diseases.

Physicochemical properties of high-molecular-weight plant polysaccharide of hexose glycoside class (Panavir) with antiviral activity

A high-molecular-weight plant polysaccharide belonging to the hexose glycoside (HG) class and composed of rhamnose (2–10%), arabinose (3–15%), glucose (10–67%), galactose (2–27%), xylose (0.1–3%), and mannose (0.1–5%) monosaccharides, as well as uronic acids (2–5%), had been isolated previously. It has high antiviral activity, as is proven by experimental models using hazardous and extremely dangerous viral infections such as herpes, cytomegalovirus, influenza, encephalitis, measles, rabies, and hepatitis C. The antiviral drug Panavir developed on its basis has an extremely low toxicity (LD50 = 3000) and is an antiviral and immunomodulatory agent. There has been no microscopic (instead of phenomenological) model of its biological or pharmacological activity because of a lack of knowledge about its physicochemical nature. In the present work, the results of a study on the physicochemical properties of the HG macromolecules which makes it possible to qualitatively explain the biological activity and pharmacological properties of Panavir are presented.

Sanitary Protection of the Territory from Importation and Spread of Particularly Dangerous Infections. Communication 6. Argentine and Bolivian Hemorrhagic Fevers

Presented are the results of examination of Argentine and Bolivian hemorrhagic fevers in accordance with previously proposed categories, signs and criteria of particularly dangerous viral infections (PDVI), actual for sanitary protection of the territory. Argentine and Bolivian hemorrhagic fevers are contagious PDVI of pathogenicity group I, capable of epidemic spread. Anti-epidemic measures are necessary in case of Argentine and Bolivian hemorrhagic fevers importation onto non-endemic territory to prevent the epidemiologic complications.

Multilocus PCR in real time for detection of highly dangerous and dangerous viral infections

Multilocus PCR in real time for detection of highly dangerous and dangerous viral infections

Sanitary Protection of a Territory from Importation and Dissemination of Particularly Dangerous Viral Infections. Communication 5. Lassa Fever

Analysis of the situation with Lassa fever (LF) in accordance with the previously offered signs and characters, criteria and categories, actual for sanitary protection of territories from particularly dangerous viral infections (PDVI), showed LF to be a contagious PDVI classified as pathogenicity group I, capable of epidemic expansion. In case of LF import to a non-endemic territory, the maximal volume of anti-epidemic measures is recommended to be accomplished because epidemiologic complications may emerge even with the advent of an individual case of the disease.

Gene mutations and pedigrees

Research into haemophilia has resulted in important advances in both the theory and practice of human genetics. In 1935, Haldane showed that haemophilia, an X-linked recessive condition, was maintained in the population by an equilibrium between the loss of haemophilia genes, due to the reduced chance that affected males have of reproducing, and the gain of new haemophilia genes, due to mutation. This scenario results in allelic heterogeneity and explains why disease severity varies, patients are frequently sporadic, and mutations are usually different and of independent origin in every family. The small size of modern western families allows haemophilia mutations to go undetected for some generations, and artificially increases the proportion of sporadic patients. In 1952, locus heterogeneity was discovered. Thus, deficiency of coagulation factor VIII was called haemophilia A and that of factor IX named haemophilia B. This knowledge eventually led to treatments based on the administration of specific gene products missing in patients. These substances were provided by networks of haemophilia centres, and the mean life expectancy of haemophilia patients in the UK seemed to approach that of the general population. Unfortunately, however, blood-derived therapeutic agents were later shown to be the vehicle of dangerous viral infections, such as HIV-1 and hepatitis, a situation that is now compounded by concerns about transmission of prions for bovine spongiform encephalopathy. Investigators should learn from these adversities, and new therapies should be preceded and accompanied by thorough risk assessment. A proportion of patients with either haemophilia A or B become refractory to treatment because of an immune reaction against the therapeutic coagulant factor. The occurrence of this reaction, called inhibitor formation, is strongly affected by the patient’s gene defect. Thus, large gene deletions or nonsense mutations cause strong predisposition, presumably because they prevent the synthesis in the patient’s cells of any immunologically recognisable factor IX protein. Therefore, the normal gene product, absent in the patient, seems foreign to their immune system. Direct or indirect replacement therapy can result in adverse immune reactions in patients who have had no chance of developing immune tolerance to the therapeutic agent. Research is needed to learn how to prevent or overcome such reactions. The relatives of patients with haemophilia are often worried about having the disease, for although haemophilia is, by and large, manageable, treatments often cause adverse reactions. There is, therefore, demand for genetic screening, which usually involves general genetic counselling, carrier diagnosis, and, more rarely, prenatal diagnoses. Carrier tests are usually required by patients’ sisters or more distant female relatives, but in 50% of families the mother of an apparently sporadic patient will want to know if she is a carrier, and hence at high risk of having more sons with haemophilia. Concern about haemophilia depends on individual circumstances, including severity of disease in the family—some patients bleed excessively only after major trauma, whereas others bleed frequently and spontaneously. In patients with haemophilia B there is good correlation between phenotype and gene defect, so that information about the gene defect has prognostic value. So far, the phenotypic consequences of 750 different mutations have been recorded. Mutations that seriously affect the structure of factor IX result in a large reduction in the amount of circulating factor IX, whereas mutations that alter its catalytic centre or its ability to interact with factor VIII and factor X (the substrate of the complex formed by factors VIII and IX) tend to cause pronounced loss of factor IX coagulant activity. The large variety and recent origin of most haemophilia mutations complicates the genetic screening process. The best way to diagnose carriers is to test for the gene defect specific to their family. Thus, in order to provide a good screening service for those with haemophilia B, a new strategy has been introduced. This is based on the construction of a national, confidential database of gene mutations and pedigrees. The mutations are identified in one patient or carrier in every family and recorded. Thus, a family member can be screened quickly, accurately, and at a reduced cost, since only a small part of the haemophilia gene needs to be checked, dependent on which family the individual belongs to. This strategy is now in full use in the UK and in Sweden, and it represents a model for the screening of other inherited diseases characterised by a varied spectrum of genetic defects, including haemophilia A. In the UK the construction of a confidential database of haemophilia A mutations and pedigrees is well on the way. Descendants of Queen Victoria (arrow), showing inheritance of haemophilia Patients are shown as red squares, and known carriers as purple circles.