Newcastle disease

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Jump to: navigation, search Newcastle disease virus Virus classification Group V
((-)ssRNA)

Group:

Order:

Mononegavirales

Family: Paramyxoviridae Genus: Avulavirus Newcastle disease virus

Species:

Newcastle disease is a contagious bird disease affecting many domestic and wild avian species. First found in Newcastle, United Kingdom in 1926, then by Burnet in 1943 in Australia in connection with laboratory infection where the virus was isolated from a ocular discharge of a patient to show the specific antibody titre in the patient's blood. Newcastle has a negative sense single stranded genome which codes for a RNA directed RNA polymerase, hemagglutininneuraminidase protein, fusion protein, matrix protein, phosphoprotein and nucleoprotein in the 5' to 3' direction. Its effects are most notable in domestic poultry due to their high susceptibility and the potential for severe impacts of an epizootic on the poultry industries. It is endemic to many countries. Newcastle disease was discovered in Newcastle upon Tyne, England in 1926 (Doyle), but also at this time slightly different strains were found in other parts of the world. Exposure of humans to infected birds (for example in poultry processing plants) can cause mild conjunctivitis and influenza-like symptoms, but the Newcastle disease virus (NDV) otherwise poses no hazard to human health. Interest in the use of NDV as an anticancer agent has arisen from the ability of NDV to selectively kill human tumour cells with limited toxicity to normal cells. No treatment for NDV exists, but the use of prophylactic vaccines and sanitary measures reduces the likelihood of outbreaks.

Contents
[hide]

1 Causal agent o 1.1 Description o 1.2 Strains o 1.3 Use as an anticancer agent 1.3.1 History of NDV in cancer therapy 1.3.2 NDV, pros and cons in cancer therapy 1.3.3 NDV-induced mechanisms leading to tumor cell death o 1.4 Use as a biological weapon 2 Transmission 3 Clinical findings o 3.1 Symptoms o 3.2 Postmortem lesions 4 Diagnosis o 4.1 Immunological tests o 4.2 Virus isolation 4.2.1 Samples 4.2.2 Handling 5 Prevention 6 References o 6.1 Footnotes 7 External links

[edit] Causal agent

[edit] Description
The causal agent, Newcastle disease virus, is a negative-sense single-stranded RNA virus. Transmission occurs by exposure to faecal and other excretions from infected birds, and through contact with contaminated feed, water, equipment and clothing.

[edit] Strains
NDV strains can be categorised as velogenic (highly virulent), mesogenic (intermediate virulence) or lentogenic (nonvirulent). Velogenic strains produce severe nervous and respiratory signs, spread rapidly and cause up to 90% mortality. Mesogenic strains cause coughing, affect egg quality and production and result in up to 10% mortality. Lentogenic strains produce mild signs with negligible mortality.

[edit] Use as an anticancer agent

In 1999, promising results were reported using an attenuated strain of the Newcastle virus, codenamed MTH-68, in cancer patients[1] by researchers who had isolated the strain in 1968.[2][3] It appears the virus preferentially targets and replicates in certain types of tumor cells, leaving normal cells almost unaffected. In 2006, researchers from the Hebrew University also succeeded in isolating a variant of the NDV, codenamed NDV-HUJ, which showed promising results in 14 glioblastoma multiforme patients.[4] [edit] History of NDV in cancer therapy Even if the oncolytic effect of the Newcastle Disease Virus (NDV) was documented already in the 1950-ies, the main advances of viruses in cancer therapy came with the advent of reverse genetics technologies (Flanagan et al 1955 in Mullen & Tanabe 2002[5], Vigil et al 2007[6]). With these new possibilities, studies of modified NDV strains with enhanced cancer treatment properties have been put on the agenda. This was demonstrated by Vigil et al (2007)[6] where the engineered Hitcher B1 NDV/F3aa strain was modified to express a highly fusogenic F-protein in combination with immunostimulatory molecules such as IFN-gamma, interleukin 2 or tumor necrosis factor alpha. Promising results was discovered with proteins associated to the adaptive immune system which paved the way for possibilities to use NDV to create a tumor-associated antigen. Another study showed how NDV/F3aa could be modified to express NS1, an influenza virus protein with capability to modulate with the innate immune response, for example, by suppressing the induction of the cellular interferons (Zamarin et al 2009b)[7]. [edit] NDV, pros and cons in cancer therapy NDV possesses many unique anti-cancer properties and thereby provides an excellent base in virotherapy research. NDV has selectivity on oncogenic cells, were it replicate without, or in a less pronounced way, harming normal cells (Elankumaran et al 2006[8], Fbin et al 2007[9]). It binds, fuse into and replicate within the infected cells cytoplasm independent of cell proliferation (Elankumaran et al 2006)[8]. One of the main issues using NDV in treatment is the host/patient immune response against the virus itself, which prior to the time of the reverse genetics technology decreased the applicability of NDV as a cancer treatment (Mullen & Tanabe 2002[5], Kuruppu & Tanabe 2005)[10]. [edit] NDV-induced mechanisms leading to tumor cell death The precise way in which the presence of NDV induce tumor cell death remains to be clarified and may show variation both regards strains of NDV and to which type of cancer is targeted. Elankumaran et al (2006)[8] showed that NDV triggers apoptosis in a wide range of cancer cell types via the mitochondrial/intrinsic pathway, through loss of membrane potential and thereby inducing release of cytochrome c in the tumor cell. The results of Elankumaran et al (2006)[8] also indicate that the extrinsic pathway is activated by TNF-related apoptosis-inducing ligand (TRIAL)induced NDV-mediated apoptosis in a late stage. Altomonte et al (2009)[11] studied a hyperfusogenic NDV/F3aa(L289A) with refined abilities to fusing into somatic cells. NDV has aggregating properties causing syncytia formations of tumor cell which, apart from amplifying immune based cell killing, also result in necrosis of cells. This pathway was believed to lead to a considerable boost of immune activation and potentially an antitumor response, which was

supported by observations of a significant accumulation of NK-cells and neutrophils following the infusion of NDV/F3aa(L289A) in Hepatocellular Carcinoma cells. In addition, Vigil et al (2008)[12] demonstrated an increase of CD4+ and CD8+ T-cells within the tumor cells when inducing NDV/F3aa recombined with the cytokine interleukin-2 (IL-2). Also Zamarin et al (2009a)[13] show that a NDV/F3aa-IL-2 strain induced the immune system, giving a cytotoxic effect on the tumor cells. A 15-year study on patient with malign melanoma showed increased numbers of oligoclonal CD8+ T-cells in the blood, suggesting that the vaccination with NDV oncolysates was associated with prolonged survival among the patients and that CD8+ T-cells played an important role (Batliwalla et al 1998)[14].

[edit] Use as a biological weapon

Newcastle disease was one of more than a dozen agents the United States researched as potential biological weapons before the nation suspended its biological weapons program[citation needed].

[edit] Transmission
NDV is spread primarily through direct contact between healthy birds and the bodily discharges of infected birds. The disease is transmitted through infected birds' droppings and secretions from the nose, mouth, and eyes. NDV spreads rapidly among birds kept in confinement, such as commercially raised chickens. High concentrations of the NDV are found in birds' bodily discharges; therefore, the disease can be spread easily by mechanical means. Virus-bearing material can be picked up on shoes and clothing and carried from an infected flock to a healthy one. NDV can survive for several weeks in a warm and humid environment on birds' feathers, manure, and other materials. It can survive indefinitely in frozen material. However, the virus is destroyed rapidly by dehydration and by the ultraviolet rays in sunlight. Smuggled pet birds, especially Amazon parrots from Latin America, pose a great risk of introducing NDV into the US. Amazon parrots that are carriers of the disease but do not show symptoms are capable of shedding NDV for more than 400 days.

[edit] Clinical findings

[edit] Symptoms

Egg drop after a (otherwise asymptomatic) Newcastle disease infection in a duly vaccinated broiler parent flock Signs of infection with NDV vary greatly depending on factors such as the strain of virus and the health, age and species of the host. The incubation period for the disease ranges from two to 15 days. An infected bird may exhibit the following signs: They can include respiratory signs (gasping, coughing), nervous signs (depression, inappetence, muscular tremors, drooping wings, twisting of head and neck, circling, complete paralysis), swelling of the tissues around the eyes and neck, greenish, watery diarrhea, misshapen, rough- or thin-shelled eggs and reduced egg production. In acute cases, the death is very sudden, and, in the beginning of the outbreak, the remaining birds do not seem to be sick. In flocks with good immunity, however, the signs (respiratory and digestive) are mild and progressive, and are followed after seven days by nervous symptoms, especially twisted heads.

Torticollis in a mallard

Same symptom in a broiler

PM lesions on proventriculus, gizzard and duodenum

[edit] Postmortem lesions

Petechiae in the proventriculus and on the submucosae of the gizzard are typical; there is also severe enteritis of the duodenum. The lesions are scarce in hyperacute cases (first day of outbreak).

[edit] Diagnosis
[edit] Immunological tests
Enzyme linked immunosorbent assay (ELISA), PCR, and sequence technology tests have been developed.

[edit] Virus isolation

[edit] Samples For routine isolation of NDV from chickens, turkeys, and other birds, samples are obtained by swabbing the trachea and the cloaca. Cotton swabs can be used. The virus can also be isolated from the lungs, brain, spleen, liver, and kidneys. [edit] Handling Prior to shipping, samples should be stored at 4 C (refrigerator). Samples must be shipped in a padded envelope or box. Samples may be sent by regular mail, but overnight is recommended.[15]

[edit] Prevention

Any animals that are showing symptoms of Newcastle disease should be quarantined immediately. New birds should also be vaccinated before being introduced to your flock. There is an inactivated viral vaccine available, as well as various combination vaccines.

Marek's disease
From Wikipedia, the free encyclopedia

Jump to: navigation, search Marek's disease Virus classification Group I

(dsDNA)

Group:

Family: Herpesviridae Genus: Mardivirus

Gallid Species: herpesvirus 2 (GaHV-2) Marek's disease is a highly contagious viral neoplastic disease in chickens. It is named after Jzsef Marek, a Hungarian veterinarian. Occasionally misdiagnosed as an abtissue pathology it is caused by an alphaherpesvirus known as 'Marek's disease virus' (MDV) or Gallid herpesvirus 2 (GaHV-2). The disease is characterized by the presence of T cell lymphoma as well as infiltration of nerves and organs by lymphocytes.[1] Viruses related to MDV appear to be benign and can be used as vaccine strains to prevent Marek's disease. For example, the related Herpesvirus of Turkeys (HVT), causes no apparent disease in turkeys and continues to be used as a vaccine strain for prevention of Marek's disease (see below). Birds infected with GaHV-2 can be carriers and shedders of the virus for life. Newborn chicks are protected by maternal antibodies for a few weeks. After infection, microscopic lesions are present after one to two weeks, and gross lesions are present after three to four weeks. The virus is spread in dander from feather follicles and transmitted by inhalation.[2]

Contents
[hide]

1 Syndromes 2 Diagnosis 3 Prevention 4 References

[edit] Syndromes

Left - normal chicken eye. Right - Eye of a chicken with Marek's disease There are five syndromes known to occur after infection with Marek's disease. These syndromes may overlap.

Classical Marek's disease or neurolymphomatosis causes asymmetric paralysis of one or more limbs. With vagus nerve involvement, difficulty breathing or dilation of the crop may occur. Besides lesions in the peripheral nerves, there are frequently lymphomatous infiltration/tumours in the skin, skeletal muscle, visceral organs. Organs that are commonly affected include the ovary, spleen, liver, kidneys, lungs, heart, proventriculus and adrenals. Acute Marek's disease is an epidemic in a previously uninfected or unvaccinated flock, causing depression, paralysis, and death in a large number of birds (up to 80 percent). The age of onset is much earlier than the classic form, birds are four to eight weeks old when affected. Infiltration into multiple organs/tissue is observed. Ocular lymphomatosis causes lymphocyte infiltration of the iris (making the iris turn grey), anisocoria, and blindness. Cutaneous Marek's disease causes round, firm lesions at the feather follicles.[2] Atherosclerosis is induced in experimentally infected chickens.[3] Immunosuppression Impairment of the T-lymphocytes prevent competent immunological response against pathogenic challenge and the affected birds become more susceptible to disease conditions such as coccidiosis and "Escherichia coli" infection .[4] Furthermore, without stimulation by cell-mediated immunity, the humoral immunity conferred by the B-cell lines from the Bursa of Fabricius also shuts down, thus resulting in birds that are totally immunocompromised.

[edit] Diagnosis

The demonstration of nerve enlargement, especially with the ischiatic nerve along with suggestive clinical signs in a bird that is around three to four months old is highly suggestive of Marek's Disease. The presence of nodules on the internal organs may also suggest Marek's disease but further testing is required for confirmation. This is done through histological demonstration of lymphomatous infiltration into the affected tissue. A range of leukocytes can be involved, including lymphocytic cell lines such as large lymphocyte, lymphoblast, primitive reticular cells and occasional plasma cells as well as macrophage and plasma cells. The T-cells are involved in the malignancy, showing neoplastic changes with evidence of mitosis. The lymphomatous infiltrates need to be differentiated with another condition that affects poultry known as Lymphoid Leukosis as well as an inflammatory event associated with hyperplastic changes of the affected tissue.

[edit] Prevention
Vaccination is the only known method to prevent the development of tumors when chickens are infected with the virus. However, administration of vaccines does not prevent transmission of the virus, i.e., the vaccine is non-sterilizing.[1] However, it does reduce the amount of virus shed in the dander and hence reduce horizontal spread of the disease. Marek's Disease does not spread vertically. The vaccine was introduced in 1970 and the scientist credited with its development is Dr. Benjamin Roy Burmester.[5] Before that, Marek's disease caused substantial revenue loss in the poultry industries of the United States and the United Kingdom. The vaccine can be administered to one day old chicks through sub-cutaneous inoculation or by in-ovo vaccination when the eggs are transferred from the incubator to the hatcher. In-ovo vaccination is the preferred method, as it does not require handling of the chicks and can be done rapidly by automated methods. Immunity develops within two weeks.[2] The vaccine originally contained the antigenically similar turkey herpesvirus, which is serotype 3 of MDV.[6] However, because vaccination does not prevent infection with the virus,[7] the Marek's Disease virus has evolved increased virulence and resistance to this vaccine. As a result, current vaccines use a combination of vaccines consisting of HVT and gallid herpesvirus type 3 or an attenuated MDV strain, CVI988-Rispens (ATCvet code: QI01AD03).[8]