By H. Ines. Ohio Valley College. 2019.
The visualization of the presence and location (length) of the analyzed fragments is done autoradiography probe exposes photographic emulsion (e discount super p-force 160 mg amex. In this disease one of the 146 amino acids is exchanged inside the beta-globin strand of hemoglobin buy 160 mg super p-force amex. In an effected individual the glutamic acid in the th 6 position is replaced by valine buy super p-force 160mg. Mutated fragment (S) is cleaved in another position (palindrome) and has length 1 buy 160 mg super p-force with amex. The detection of fragments is done by electrophoresis and obtained fragment are compared with a length marker. In the human genome there are dozens of such regions there, and each of them, because of the variability in the number of motif repeats, has in different persons different lengths. The autoradiographic image is made up of several strands and is therefore individually more specific then the prints of papillary lines of the fingers. Besides the identification of individuals (in forensic practice), this method is also used in fatherhood justice (Fig. Nowadays it is one of the most significant and perspective method in molecular genetics. On the base of complementarity with a target sequence, primers hybridize with complementary sequences (sc. The growing number of repetitions leads to an exponential multiplication of the amplified sequence. In practice, by 25-35 cycles of 4 repetitions it is possible to achieve a 10 – 6 10 fold amplification (multiplication) of a specified sequence (Fig. Its optimal working temperature is 37° C, so, in each step of denaturation it was inactivated and was necessary to supply it again, for each new cycle. For ensuring of the temperature changes during the each step, three water baths were used with different temperature and the tubes containing reaction mixture had to be replaced after each step. It was time consuming and it didn’t allow following an exact time and temperature regime. The development of the thermal cycler, neither quickened and simplified the whole process, nor increase accuracy of procedure – since it allowed an automatic adjustment of temperature and followed an exact time and temperature regime necessary for a successful amplification (Fig. Theoretically one copy of a given sequence is enough 78 for undergoing the amplification. They are chosen in a way, to ensure a specific hybridization of primer with a unique sequence in the genome – not to bind on to multiple places. It is also necessary to choose such sequence of primers bases, which prevents their mutual pairing and the formation of primer dimers. To fulfill all mentioned conditions for successful amplification, the accurate primers are chosen in computer databases of human genome. The amount of Taq polymerase per one reaction depends on the volume of the reaction mixture. That is why its constitution depends on the used polymerase and is usually supplied by the manufacturer together with the polymerase. Hybridization takes place under the o o temperature 55 C - 65 C, lasting between 30 seconds and 1 minute. The alleles are inherited from parents to offspring (one allele from the mother and one from the father). These fluorochromes have a specific affinity to intercalation compounds - for example their avidin constituent to biotin). They are used mainly in prenatal and preimplantational diagnostics, for instance in determining the number of a certain chromosome (in aneuploidia there is one, three or more signals instead of two) and the origin of a certain chromosome. They are used mainly for determining the amplification of alleles of a certain gene (for instance oncogenes), finding of translocations and micro-deletions (for example with malignant and microdeletion syndromes). Whole chromosomal (painting) – probes hybridize with the whole (specific) chromosome or with its important part. They are used for example in diagnostics of chromosomal remodeling and during the diagnostics of aneuploidies – in mitotic figures. After the implication of the probe, the slide is covered by a glass and is placed into a humid chamber; • the clearance of a non-specifically bonded probe (with the help of formamide, under the temperature of 72°C) from places where the probe is not completely complementary bonded; • addition of antibody against avidin; • the observation of the slide in a fluorescent microscope – the number of colored signals in 100 nuclei or mitotic figures are recorded. Sequencing arises from two standard methods which are G A independent from each other – Sanger and Maxam-Gilbert. A C By this a series of fragments of different length are formed in each test-tube. The samples from the test-tubes are deposited G (each in independent path) into the polyacrylamide gel and are separated by Thelectrophoresis. After autoradiography the order of bases is subtracted in the A sequenced sector (gradually – in each column there is only one band in the A row) – Fig. In each test-tube only one type of the nitrogen base is damaged chemically (by methylation). The conditions of the reaction are constructed so they are not entirely destroyed, only their small part. Many fragments arise which have 83 different sizes, depending on how far was the damaged base located from the end of the molecule. Electrophoresis, autoradiography, and the evaluation are all done in the same way as in the Sanger method. The name came about because the technology used during their manufacture is the same as with computer chips. With the coming of the biochips, the membrane was substituted by a silanized glass plate with a size of a post stamp. It can be attached by more then 100 000 different probes and it can identify many different parameters during one examination – for instance all the known polymorphisms and mutations of a certain gene. It is not only used in diagnostics (for example the genetic predisposition to tumours of the mammary gland), in farmacogenetics, but also for determining phylogenetical consequences. Introduction to the genetics of viruses Viruses are the most simple forms of life on earth. The name virus was formed as the description of an originator of an infectious (transferable) disease which could not be detected by a light microscope. The virion (basically) consists of a protein capsule (capsid) which contains a nucleic acid (genome of the virus). The shape and reproductive properties of the virus is influenced by the proteins, from which the virion is formed. Viral proteins are of two types – the ones which form the subunits of the capsid (capsomeres) and the ones which are located under the capsid (sc. A capsid of a virus is made up of two types of proteins, which have two main functions: • They enable a specific connection of the virion to the membrane (receptors) of the target host cell and by this the start of the life (reproduction) cycle of the virus. In most cases it concerns glycoproteins and are distinguished according to their molecular weight. In laboratories they are used for determining the originator of the disease; • for the imune system of the host, the structures which project out from the capsid represent antigenes which it can recognize. It has a large importance for the formation of specific antibodies against them, and so for the survival of target cells and the host. In certain virions the capsid contain, besides the genomic nucleic acids, different proteins (core proteins), which fulfill specific functions. Besides different stabilizing and functional (regulatory) proteins, it contains three enzymes (reverse transcriptase, integrase and protease) which are also important for its reproduction cycle. In most cases the capsomeres assemble into a polyhedral crystal which slightly resembles a globe (Fig. Virions can also have two bizarre shapes, either a hollow spiral shape of a mosaic disease of plants or the typical shape of a bacteriophage. In an infected cell the capsomeres accumulate in a predetermined locality (packaging site), were the viruses are „assembled“ and which is typical for different kinds of viruses, since it largely relates to the way in which the virions are released from the infected cell. An example of a virion capsid Virions leaving the host cells by exocytosis (budding), take the remains of the cytoplasmic membrane of the host cell on the surface of the capsid. This lipoid covering, simplifies the process of viral entrance into the host cells and partly protects the virus against the immunity system of the host. Except this, there is also an interspecies barrier, an occurrence as in the case of the measles virus, which only infects humans and not animals. At the same time, unless the viruses are located inside the host cell, they don’t show any life manifestations.
Eosinophils are not as efficient as killers but are more important in parasitic infections effective super p-force 160 mg. Basophils contain granules of chemical factors that enhance inflammation; basophils are found in the blood and probably have a function similar to that of tissue-bound mast cells cheap super p-force 160mg. In contrast to poly- morphonuclear phagocytes purchase super p-force 160mg overnight delivery, mononuclear phagocytes tend to remain con- fined to their local area discount 160mg super p-force fast delivery. Macrophages process foreign material and present antigen to the specific immune system. Macrophages process antigens and provide a link between general and targeted immune responses. Neutrophils, monocytes, and lymphocytes adhere to the vascular endothelium and migrate into the surrounding tissue. Interaction between leukocytes and the endothelial cells lining the blood vessels, leading to the migration of cells into damaged areas, involves the following: ● Thethering: Circulating cells are slowed. Selectins recog- nize specific carbohydrate sequences on either leukocytes or endothelial cells. These cells eliminate can- cer- or virus-infected cells by nonspecifically targeting the cell membrane and releasing cytolytic enzymes. Mononuclear and polymorphonuclear phagocytes participate in the inflammatory response, generating free radicals as they attempt to eliminate foreign or dead cells. Triggers of phagocytosis are opsonized bacteria and diverse stimuli that acti- vate cell membrane receptors (e. Enzymes in the primary granules of phagocytic cells such as proteases, lysozyme, and myeloperoxidase facili- tate destruction of ingested material. Bacteria and viruses are destroyed by phagocytic cells with an oxidative burst that produces nitric oxide, super- oxide, hydrogen peroxide, and halide anions (I–, Cl–, Br–). Unless adequately contained, the cellular products that are toxic to bacteria can result in untoward cellular destruction. Reduced nicotinamide adenine dinucleotide phosphate oxidase reduces oxygen to superoxide. Superoxide dismutase rapidly converts superoxide to hydrogen peroxide, which is detoxified by catalase and oxidative reduction of glutathione (see Figure 3-7). Imprecise control of this and other physiologic processes that generate energy and render microbes innocuous can have pathologic consequences. Chronic hepatitis carries an increased risk of liver cancer; schistosomiasis carries the risk of colon or bladder cancer, depending on the Schistosoma species responsible for the infection. Although a positive feedback system is necessary to enhance the inflam- matory response, an uncontrolled response can result in excess tissue damage. Eosinophils contain enzymes that dampen the vascular effects of inflammatory response by various mechanisms including degradation of histamine and leukotrienes. Inflammation is augmented by chemical mediators such as serotonin, histamine, kinins, eicosanoids, complement, and lym- phokines. These chemicals enhance inflammation, aid phagocytosis, and interact with the specific immune system to achieve cytolysis. Inflammatory mediators may circulate, in an inactive form, in plasma or be produced by a diversity of cells. It is chemotactic for and activates neutrophils and nonhematopoeitic cells involved in wound healing. A number of chemicals in plasma, when activated, participate in the inflammatory process. The kinin system generates bradykinin, which augments inflammation- enhancing vasodilation, vascular permeability, and pain. The complement system may be activated by the classical pathway involv- ing an antibody-antigen (microbe) complex or by the alternate pathway after exposure to microbial polysaccharide. The consequences of complement activation are increased vascular permeability, neutrophil chemotaxis and activation, and opsonization of foreign cells followed by cytolysis. Chapter 3 / Self-Regulation 63 Common triggers for diverse interacting positive or negative feedback systems can make clinical outcomes difficult to predict. Inflammatory Response: A Fine Balance Between Healing and Harming The body mounts an inflammatory response to tissue injury. The inflam- matory process localizes cellular damage, removes cell debris and pathogens, and provides a framework for tissue repair and healing. Acute inflammation is dominated by a vascular response characterized by neu- trophils and mast cells, whereas chronic inflammation is characterized by a proliferative response with macrophages and lymphocytes. When inflam- mation is exaggerated or prolonged, instead of healing, tissue destruction can result. Although a humoral response is required to achieve local inflammation and healing, the chemical mediators of inflammation may have pathologic repercussions. Histamine improves perfusion but also increases permeability of local capillaries and promotes exudation. Histamine is stored in an inactive bound form in mast cells, basophils, and platelets. H1 recep- tors are found mainly in smooth muscles and exocrine glands of the respira- tory tract. The concentration and site of histamine release determine the repercussions of histamine release. Activation of H1 receptors increases the cellular level of cyclic guanosine monophosphate, which enhances contraction in smooth muscle and endothelial cells, chemotaxis in neutrophils, and prostaglandin synthesis in mast cells. Other cyclic guanosine monophosphate stimulants are biotin, ginseng, vitamin C in high doses, and leukotrienes. Histamine stimulation of H1 receptors mediates the following: ● Muscle contraction of the bronchi, intestine, and uterus. Potential adverse consequences of smooth muscle contraction are bronchospasm, colic, and dysmenorrhea. Other consequences are receptor stimulation (resulting in itching, pain, and sneezing), prostaglandin generation, and a positive chronotropic effect increasing heart rate. In classic allergies, histamine and other mediators are released from mast cells after cross-linkage between two immunoglobulin E molecules on the mast cell membrane. H2 receptors stimulate mucus production in the bronchial tree and aug- ment gastric acid production. Other consequences are increased production of cyclic adenosine monophosphate; inhibition of the release of lym- phokines, basophil histamine, neutrophil enzymes, eosinophil migration; and T-lymphocyte–mediated cytotoxicity. Stimulation of H2 receptors dampens lymphocyte, eosinophil, neutrophil, and mast cell activity. Lifestyle choices can modulate the balance between the interacting systems controlling the acute inflammatory response. Dietary Modulation of Inflammation The polyunsaturated fatty acids, linoleic (ω-6) and α-linolenic acid (ω-3), are essential for normal cellular function. Chapter 3 / Self-Regulation 65 Eicosanoids are involved in cell regulation; among their functions is modu- lation of inflammation. Two important groups of eicosanoids involved in inflammation are the leukotrienes and prostaglandins. The nature of the eicosanoid produced is influenced both by the unsaturated fatty acid sub- strate and the oxygenase enzyme system present. Although leukotrienes are more potent inflammatory mediators than prostaglandins,11 the essential fatty acids from which the eicosanoid is generated determines its relative potency. Leukotrienes produced from the ω-6 series of fatty acids are 10 to 30 times more potent inflammatory agents than leukotrienes produced from the ω-3 fatty acids. Exercise and com- pounds in fruit and vegetables stimulate production of cyclic adenosine monophosphate. Box 3-1 illustrates the protean effect of a single dietary change on the inflammatory process, and Box 3-2 shows how such dietary changes influence physiologic processes in other body systems. Leukotriene B4 attracts leukocytes, enhances their adhesion to endothelial cells, and activates them to secrete reactive oxygen species and degradation enzymes. Leukotrienes C4, D4, and E4 stimulate smooth muscle contraction, which may result in vasoconstriction and bronchospasm.
The definitive hosts are domestic dogs or wild canids such as coyotes quality 160 mg super p-force, foxes generic super p-force 160 mg without a prescription, and jackals purchase super p-force 160mg with amex, which harbor the tapeworms in their small intestines buy 160 mg super p-force otc. It is believed that goats can develop this coenurus in the subcuta- neous or intermuscular tissue or in other organs. The life cycle starts with the expulsion of gravid proglottids or eggs with the feces of the definitive host. Intermediate hosts are infected by ingesting the eggs deposited in grass or in water. The oncospheres (embryos) penetrate the wall of the small intes- tine and, through the blood vessels, are distributed to different tissues and organs. The cycle is completed when a dog or wild canid ingests tissue or an organ containing coenuri. Each coenurus can give rise to numerous tapeworms, which develop in the small intestine of the canids. There is no reliable morphologi- cal criterion for distinguishing the species in the adult stage. While up until 1950 just five cases of infection with the larva were recog- nized in man, by 1990, some 55 human cases of cerebral coenurosis had been recorded in the world, most in Africa or South America. A study carried out in Ethiopia found that 37 of 37 sheep (100%) that were apparently sick with coenurosis and 5 of 183 sheep (2. In 96% of the cases, the larvae were in the brain, and in the rest of the cases they were in the cerebellum. Prediction of the local- ization of the coenurus based on the direction of the parasite’s circular movements or gid or the deviation of the head were accurate in just 62% of the cases. A retrospec- tive study showed that the local prevalence of coenurosis in sheep was 2. Seventy-two percent of infections in sheep occurred when the animals were between the ages of 6 and 24 months (Achenef et al. Human infection is rare; about 10 cases have been recognized, mostly in Africa (Faust et al. In central Africa, where this is the only species found, about 25 human cases of coenurosis in connective tissue have been described, as well as one case with ocular localization. The Disease in Man: Most human infections are located in the brain, less fre- quently, they are subcutaneous, and, in rare cases, they are ocular or peritoneal. Several years may pass between infection and the appearance of symptoms, and the symptomatology varies with the neuroanatomic localization of the coenurus: cerebral coenurosis is manifested by signs of intracranial hypertension, and the disease is very difficult to distinguish clinically from neurocysticercosis or cerebral hydatidosis. Symptoms that may be observed consist of headache, vomiting, paraplegia, hemiplegia, aphasia, and epilep- tiform seizures. The degree of damage to vision depends on the size of the coenurus and the extent of the choroidoretinal lesion. The prognosis for coenurosis of the nervous tis- sue is always serious and the only treatment is surgery, although recently, the test- ing of treatment with praziquantel or albendazole has begun. Interestingly, researchers have discovered that coenuri produce certain compo- nents that interfere with the host’s immunity and may be responsible for the host’s relative tolerance of the larva (Rakha et al. The Disease in Animals: Cerebral coenurosis occurs primarily in sheep, although it may also occur in goats, cattle, and horses. Two phases can be distinguished in the symptomatology of cerebral coenurosis in sheep. Massive numbers of larva can migrate simultaneously and cause meningoencephalitis and the death of the animal. The second phase corre- sponds to the establishment of the coenurus in the cerebral tissue. In general, symp- toms are not observed until the parasite reaches a certain size and begins to exert pressure on the nervous tissue. Symptoms vary with the location of the parasite and may include circular movements or gid, incoordination, paralysis, convulsions, excitability, and prostration. This change occurs most often in young animals and when the coenuri are situated on the surface of the brain. Source of Infection and Mode of Transmission: The transmission cycle of infection by T. Man is an accidental host and does not play any role in the epidemiology of the disease. The main factor in maintaining the parasitosis in nature is access by dogs to the brains of dead or slaughtered domestic herbivores that were infected with coenuri. The life cycle of the other two species of Taenia that form coenuri depends on predation by dogs on leporids and rodents. Taenia eggs expelled in the feces of infected dogs or other canids are the source of infection for man and for the other intermediate hosts. Since these dry out rapidly and are destroyed outside the host, the eggs are released and dispersed by the wind, rain, irrigation, and waterways. Diagnosis: Diagnosis in the definitive hosts can be made only by recovery and examination of the parasite; even so, identification of the species is doubtful. Neither the proglottids nor the eggs are distinguishable from those of other species of Taenia. Diagnosis in the intermediate hosts can be made only by recovery and exam- ination of the parasite. The presumptive diagnosis in man is generally made by establishing the existence of a lesion that occupies space; however, since coenurosis is much less common than hydatidosis, coenurosis is rarely considered before the parasite is recovered (Pierre et al. However, the tests that are currently available indicate that cross-reactions with other cestodes are common (Dyson and Linklater, 1979). Control: For man, individual prophylaxis consists of avoiding the ingestion of raw food or water that may be contaminated with dog feces. General preventive measures for cestodiases consist of preventing infection in the definitive host so that it cannot contaminate the environment, preventing infection in the intermediate host so that it cannot infect the definitive host, or changing the environment so that both actors are not found in nature. Some details on the application of these measures for the control of coenurosis can be found in the chapter on Hydatidosis, which has a similar epidemiology. Coenurus cerebralis infection in Ethiopian highland sheep: Incidence and observations on pathogenesis and clinical signs. Intestinal parasites of the grey fox (Pseudalopex culpaeus) in the central Peruvian Andes. Metacestodes of sheep with special reference to their epidemiological status, pathogenesis and economic implications in Fars Province, Iran. Immunological activities of a lymphocyte mitogen isolated from coenurus fluid of Taenia multiceps (Cestoda). Before the rela- tionship between taeniae and their cysticerci was understood, the larval stages were described with their own scientific names, as if they were separate species. These cysticerci are also occasionally found in dogs, cats, sheep, deer, camels, monkeys, and humans. In the past, cases of human infection by cysticerci with unarmed rostella—identified as T. Currently, this is not considered a valid criterion for identifying the species because the hooks can detach due to the host’s reaction. Current expert opinion holds that there is no reliable proof of human parasitism caused by the larval stages of T. The eggs remain near the droppings or are disseminated by the wind, rain, or other climatic phenomena, con- taminating water or food which may be consumed by pigs or man (for further details, see the chapter on Taeniasis). When a pig or a person ingests them, the hexacanth embryo is activated inside the egg then released from it; it then penetrates the intestinal mucosa, and is spread via the bloodstream. Once lodged in its preferred tissue, the embryo is trans- formed into a cysticercus which looks like an ovoid vesicle approximately 5 mm by 8–10 mm and contains the scolex of the invaginated adult taenia. The scolex of the cysticercus, like that of the adult taenia, has four suckers and two different-sized rows of hooks. In pigs, the cysticerci preferentially locate in striated or cardiac muscle; in man, the majority of cysticerci found are located in the nervous system or subcuta- neous tissue, although they have also been found in the eye socket, musculature, heart, liver, lungs, abdominal cavity, and almost any other area. Rarely, a multilobular larva that resem- bles a bunch of grapes has been found, but with vesicles that have no scolices, at the base of the infected person’s brain; it has been designated Cysticercus racemosus. The histology of the parasite indicates that it is a taenia larva, and most authors believe it is a degenerative state of C.
That the condition is widely known as ‘ulcera de los chicleros’ (ulcer developed Overview in gatherers of ‘chicle’ discount super p-force 160mg mastercard, a gummy latex from the forest tree Manilkara zapota) in Mexico and is designated ‘guerrilla’s Phlebotomine sandﬂies are involved in the transmission of sore’ in Venezuela and Colombia reﬂects the historically close several viral agents super p-force 160mg discount, among which the most important are contact of humans with a sylvatic environment that maintains grouped into the Phlebovirus genus (family Bunyaviridae) 160 mg super p-force, several species of phlebotomine vectors among wild species of which includes the sandﬂy fever Sicilian and Toscana viruses 160mg super p-force, mammalian reservoirs. Hence, hunting, lumbering and mining and the Vesiculovirus genus (family Rhabdoviridae), which activities have been associated with the disease. Since the includes vesicular stomatitis, and the Chandipura and Isfahan 1960s, transmission has increasingly spread to peridomestic viruses. Massive migration from the high plateau to low tropical The risk for infection with sandﬂy-transmitted phleboviruses areas in the Andean region, intensive deforestation and the has been shown to pertain to very large areas of the Old World establishment of new settlements have greatly contributed to (southern Europe, Africa, the Middle East, central and western the increase in numbers of cases (Desjeux, 2001; Aagaard- Asia) in association with the presence of sandﬂy vectors (Thesh Hansen et al. Recent investigations have indicated that virus on the behaviour of vectors has been exhaustively reviewed diversity in the Mediterranean basin is higher than initially by Rangel & Lainson (2009) in Brazil, and by Gonzalez suspected, and that populations living south and east of the et al. Deforestation and the replacement Mediterranean Sea have a high risk for infection during their of primary forest by monocultures (e. Although deforestation was predicted The International Committee for Taxonomy of Viruses to reduce human contact with wild reservoirs and sandﬂies, currently recognizes several phleboviruses associated with © 2012 The Authors Medical and Veterinary Entomology © 2012 The Royal Entomological Society, Medical and Veterinary Entomology, doi: 10. These caused signiﬁcant morbidity among non-native populations in include two virus species: (a) sandﬂy fever Naples virus, Mediterranean regions (Pick, 1886). An Austrian commission which includes the Naples virus, Thehran virus, Karimabad in 1909 reported that the illness was caused by a ﬁlterable agent virus and Toscana virus, (b) and Salehabad virus, which found in the blood of infected soldiers and that the vector was includes the Salehabad and Arbia viruses. In addition, recent ﬁeld stationed in the Mediterranean and Middle East reported tens and clinical studies have provided increasing evidence that of thousands of cases and attack rates of 3–10% (locally up the number of known viruses in the genus Phlebovirus to 80%) (Sabin, 1951; Hertig & Sabin, 1964). In August 1943, after the Allied Among the viral agents belonging to the genus Vesiculovirus, landing in southern Italy, sandﬂy fever accounted for at least at least 28 infect invertebrates and vertebrates (Wunner et al. Those infecting humans and domestic animals, for sandﬂy fever occurred repeatedly in the former U. Vesicular stomatitis viruses causing stomatitis The observation of two or more attacks in the same in humans and domestic livestock are largely endemic in individual resulted in the early suggestion that sandﬂy the New World, whereas Chandipura encephalitis virus and fever might be caused by distinct viruses (Livschitz, 1937). Isfahan virus are endemic in the Old World in some parts However, it was almost impossible to distinguish these of India (Basak et al. Sabin (1951) conﬁrmed the existence of more than Turkmenistan and other central Asian republics (Gaidamovich one strain of sandﬂy fever virus. Volunteers to human illness and has been found to be non-pathogenic in inoculated with Naples virus developed the typical symptoms, horses, cattle and other ruminants (Marriott, 2005). The Naples virus was ﬁrst isolated from a Sandﬂy fever, also known as Phlebotomus fever, pappataci febrile patient in Italy in 1944 (Sabin, 1955). Additional fever or three-day fever, has been an important cause of recoveries have been made in Egypt, India, Iran, Pakistan, febrile disease during military operations since at least the Serbia and the former Soviet Union (Gaidamovich et al. In 1976, a founding study extended © 2012 The Authors Medical and Veterinary Entomology © 2012 The Royal Entomological Society, Medical and Veterinary Entomology, doi: 10. Most common vesiculoviruses infecting domestic animals and humans (from Letchworth et al. Antibodies to the Naples The clinical pictures corresponding to infections with the virus have been found in residents of Turkmenia, Tajikistan, Naples and Sicilian viruses are virtually identical. Seroepidemiological studies conducted in areas around by the sudden onset of fever, headache, retro-orbital pain, pho- the Mediterranean indicate that Naples virus infections have tophobia, generalized aching, malaise and chills. The face can decreased during the last 30 years (Thesh & Papaevangelou, be suffused, with injection of the conjunctivas and scleras, and 1977). Although the renewed interest in phlebotomine sandﬂy- photophobia is accompanied by intense ocular pain on move- transmitted phleboviruses has produced numerous studies ment of the eyes. This may suggest that the Naples virus 85% of cases, but may extend to 11 days in extreme cases. The prototype strain of Sicilian virus was the onset of fever and during the ﬁrst 24 h thereafter. Other isolates ian and Naples viruses are not recovered from the cerebrospinal were subsequently obtained in Egypt, India, Iran, Pakistan and ﬂuid and, by contrast with Toscana virus, have not been asso- Afghanistan (R. Complica- is also present in Bangladesh, Greece, Cyprus, Iraq, Morocco, tions have not been noted but convalescence is occasionally Saudi Arabia, Somalia, Sudan, Tunisia, Turkey, the southern prolonged for weeks (Sabin, 1955; Bartelloni et al. Hannoun, per- Summer meningitis caused by Toscana virus sonal communication, 2005; Filipe, 1974; Thesh et al. Cases of sandﬂy fever begin to appear in and neurotropism of Toscana virus was reported more than April and gradually build to a peak in September. The viruses that cause sandﬂy fever (Naples and it was suggested that this phlebovirus might cast the vectors Sicilian viruses) have a wide geographical distribution, which themselves in the role of reservoirs because male sandﬂies were parallels that of P. In addition, venereal transmission eradicate malaria and dengue fever (Dunlap, 1981), as well as from infected P. Later reports of virus isolation and to generation in sandﬂy colonies suggested that this virus serologic studies indicate that phleboviruses are still present in could not be maintained indeﬁnitely by vertical or venereal the Mediterranean coastal regions of Europe and North Africa, transmission. Consequently, the existence of a reservoir was © 2012 The Authors Medical and Veterinary Entomology © 2012 The Royal Entomological Society, Medical and Veterinary Entomology, doi: 10. Serological studies showed no evidence of viral leishmaniasis and phleboviral infections, which has been circulation among domestic or wild animals, although a assumed for a long time, was statistically established in south- Toscana virus strain was isolated from the brain of a bat, east France between L. The ﬁrst large Italian study showed that Toscana virus was a Moreover, recent studies indicate that in relation to pre- prominent cause of summer meningitis in central Italy (Nico- viously accepted parameters: (a) the geographic distribution letti et al. Until recently, its known distribution was of sandﬂy-associated phleboviruses is much larger; (b) the limited to Italy and Portugal (Charrel et al. More number of phleboviruses infecting sandﬂies is higher; (c) the recently, as indicated by virus isolation or serological surveys, number of sandﬂy species involved in transmission may be the geographical distribution of the virus has been extended more important, and (d) the relationship between sandﬂy-borne to include France, Spain, Slovenia, Greece, Cyprus, Elba and phleboviruses and Leishmania parasites is tighter. Some studies have reported the presence of among sandﬂy-borne phleboviruses, Leishmania parasites and Toscana virus based on serological evidence using immunoﬂu- sandﬂies. This is particularly relevant because of the recent report of novel viruses that are closely related to but distinct from Toscana virus in Tunisia (Punique virus), France (Mas- Infections in humans. When symptomatic, the disease in humans is a severe, but uniformly non-fatal, inﬂuenza-like illness. In New phleboviruses patients with clinical manifestations, the initial symptom is high fever that is often biphasic. Subsequent symptoms are ﬂu- Recently, virological and molecular evidence for the pres- like and include severe malaise, headaches, myalgia, arthralgia, ence of a phlebovirus closely related to but distinct from retrosternal pain, eye aches and nausea. Adria virus (a relative of Arbia residents do not have easy access to medical care and are virus) was detected, but not isolated, in phlebotomine sandﬂies unlikely to seek attention for such relatively minor complaints, collected in Albania and subsequently in a human case (Papa and thus their aetiology is never determined. Massilia virus was iso- true incidence of clinical illness caused by infection with these lated from P. Granada virus was isolated from sandﬂies (unidentiﬁed) than is indicated by the relatively few viral isolations obtained in Spain (Collao et al. Punique virus was isolated in from sick persons and from the limited serosurveys that have northern Tunisia from P. To date, there are no data mya1gia, headache and malaise of 3–5 days in duration to support the suggestion that they cause disease in humans. Vesicular stomatitis virus dis- sandﬂy-associated phleboviruses occur (Thesh et al. Clin- Very recently, the epidemiological link between human ical disease presents severe vesiculation and/or ulceration of © 2012 The Authors Medical and Veterinary Entomology © 2012 The Royal Entomological Society, Medical and Veterinary Entomology, doi: 10. Although Chandipura virus was later identiﬁed as the is clinically indistinguishable from foot-and-mouth disease. It cause of mild dengue-like symptoms in human patients, and occurs seasonally every year in the southeastern U. In 2004, a second outbreak with a fatality rate activity in the region has been focal and limited to isolated of >75% was reported in the eastern state of Gujarat (Chadha wildlife populations. Chandipura virus was reported to have been isolated from pools of wild-caught Phlebotomus spp. Strong evidence supports the role of bit- sandﬂy specimens belonging to the genus Sergentomyia ing arthropods as vectors of vesiculoviruses and indeed the (Geevarghese et al. Among arthropods, midges [Culicoides and domiciliary species prevalent in several parts of India. However, phlebotomine sandﬂies seem to from a hedgehog (Atelerix spiculus) in Nigeria, suggesting a be the only vectors to have been conﬁrmed biologically. In humans, it causes a probable that phlebotomine sandﬂies are the only biological disease known as Carrion’s´ disease, which has two clinically vectors because they have been found infected in the absence distinct phases: an acute or haematic phase, known as ‘Oroya of clinical cases in humans or domestic animals.