Poxviruses

Dr. Ali Hashemi

Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Introduction Structure and Composition

 Poxviruses are the largest and most complex of infecting humans.

 Poxviruses are large enough to be seen as featureless particles by light microscopy.

 By electron microscopy, they appear to be brick-shaped or ellipsoid particles.

 An outer lipoprotein membrane,or envelope, encloses a core and two structures of unknown function called lateral bodies Cont….

 The core contains the large viral genome of linear double- stranded DNA.

 The DNA contains inverted terminal repeats of variable length, and the strands are connected at the ends by terminal hairpin loops.

 The chemical composition of a poxvirus resembles that of a bacterium. is composed predominantly

of protein (90%), lipid (5%), and DNA (3%).

Classification

 Poxviruses are divided into two subfamilies based on whether they infect vertebrate or insect hosts.

 Most of the poxviruses that can cause disease in humans are contained in the genera and ; there are also several that are classified in the genera and Molluscipoxvirus. Cont… Cont…

 The have a broad host range affecting

several vertebrates. They include ectromelia (mousepox),

camelpox, , , vaccinia, and variola () viruses.

 Some poxviruses have a restricted host range and infect

only rabbits (fibroma and myxoma) or only birds. Others

infect mainly sheep and goats (sheeppox, goatpox) or cattle

(pseudocowpox, or milker’s nodule). Poxvirus replication

 Poxviruses are unique among DNA viruses in that the entire multiplication cycle takes place in the cytoplasm of infected cells.

 Poxviruses are further distinguished from all other animal

viruses by the fact that the uncoating step requires a newly synthesized, virus-encoded protein. Cont…

 A. Virus Attachment, Penetration, and uncoating

Virus particles establish contact with the cell surface and fuse

with the cell membrane. Some particles may appear within

vacuoles. Viral cores are released into the cytoplasm.

Poxviruses inactivated by heat can be reactivated either by viable poxviruses or by poxviruses inactivated by nitrogen mustards (which inactivate the DNA). Cont…

 This process is called nongenetic reactivation and is caused by the action of the uncoating protein. Heat-inactivated virus alone cannot cause second-stage uncoating because of the heat lability of the RNA polymerase. Apparently, the heat-killed virus provides the template and the second virus provides the enzymes needed for transcription. Cont…

B. replication of Viral DNA and Synthesis of Viral Proteins Among the early proteins made after vaccinia virus infection are enzymes involved in DNA replication, including a DNA polymerase and thymidine kinase.

C. Maturation

An antiviral drug affects the morphogenesis of poxvirus particles. Rifampin can block the formation and assembly of the vaccinia virus envelope. Cont…

 D. Virus-Encoded Host Modifier Genes

Several poxvirus genes resemble mammalian genes for proteins that would inhibit host defense mechanisms.

Examples include tumor necrosis factor receptor, interferon-γ receptor, interleukin-1 receptor, and a complement-binding protein.

POXVIRUS INFECTIONS IN HUMANS: VACCINIA AND VARIOLA

 Edward Jenner introduced vaccination with live cowpox virus in 1798. Comparison of Vaccinia and Variola Viruses

 Vaccinia virus, the agent used for smallpox vaccination, is a

distinct species of Orthopoxvirus.

 Vaccinia virus may be the product of genetic recombination, a new species derived from cowpox virus or variola virus by serial passage, or the descendant of a now extinct viral genus. Pathogenesis and Pathology of Smallpox

 The portal of entry of variola virus was the mucous membranes of the upper respiratory tract. In the preeruptive phase, the disease was barely infective. By the sixth to ninth day, lesions in the mouth tended to ulcerate and discharge virus. Thus, early in the disease, infectious virus originated in lesions in the mouth and upper respiratory tract. Later, pustules broke down and discharged virus into the environment of the smallpox patient.

Clinical Findings

 The incubation period of variola (smallpox) was 10–14 days.The onset was usually sudden. One to 5 days of and malaise preceded the appearance of the , which began as macules, then papules, then vesicles, and finally pustules. These formed crusts that fell off after about 2 weeks, leaving pink scars that faded slowly. In each affected area, the lesions were generally found in the same stage of development (in contrast to ).

Immunity

 Vaccination with vaccinia induced immunity against variola virus for at least 5 years and sometimes longer.

 Production of interferon is another possible immune mechanism. Laboratory Diagnosis

 The tests depend on identification of viral DNA or antigen from the lesion, direct microscopic examination of material from skin lesions, recovery of virus from the patient, and, least importantly, demonstration of antibody in the blood.

Virus isolation can also be carried out by inoculation of

vesicular fluid onto the chorioallantoic membrane of chick embryos. The , virus, and tanapoxvirus do not grow on the membrane. Treatment

 Vaccinia immune globulin is prepared from blood from persons vaccinated with the vaccinia virus.

 Methisazone

 Cidofovir, a nucleotide analog Epidemiology

 Transmission of smallpox occurred by contact between cases.Smallpox was highly contagious.

 The virus was stable in the extracellular environment but was most commonly transmitted by respiratory spread.

 Patients were most highly infectious during the first week of rash after the fever had begun. Respiratory droplets were infectious earlier than skin lesions. Cont…

 There was no known nonhuman reservoir. There was one stable serotype. There was an effective vaccine.

 Vaccinia virus for vaccination is prepared from vesicular

lesions (“lymph”) produced in the skin of calves, or it can

be grown in chick embryos. The final vaccine contains 40%

glycerol to stabilize the virus and 0.4% phenol to destroy

bacteria.

 vector for introducing foreign genes for immunization purposes and as oncolytic viral therapy for cancer. Time of Vaccination  Vaccinating between 1 and 2 years

 Primary take

 Revaccination

 Adverse reactions of Vaccination:

 Inadvertent autoinoculation-Contact transmission

-

-Fetal vaccinia

 Postvaccinial central nervous system disease

MONKEYPOX INFECTIONS

 zoonosis

 It is probably acquired by direct contact with wild animals killed for food and skins. The primary reservoir host is not known, but squirrels and rodents can be infected. COWPOX INFECTIONS

 The natural reservoir of cowpox seems to be a rodent, and both cattle and humans are only accidental hosts. Domestic cats also are susceptible to cowpox virus. INFECTIONS

 There is some concern that human-to-human transmission may also occur. VIRUS INFECTIONS

 The virus of orf is a species of Parapoxvirus. It causes a disease in sheep and goats that is prevalent worldwide.

 Orf is transmitted to humans by direct contact with an

infected animal.

 Infection of humans occurs usually as a single lesion on a finger, hand, or forearm but may appear on the face or neck.

MOLLUSCUM CONTAGIOSUM

 Only in humans.

 The virus has not been transmitted to animals and has not been grown in tissue culture.

 The lesions of this disease are small, pink, -like tumors on the face, arms, back, and buttocks.

TANAPOX AND YABA MONKEY TUMOR POXVIRUS INFECTIONS

 They do not grow on the chorioallantoic membrane of embryonated eggs.

Rabies, Slow Virus Infections, and Prion Diseases

Dr. Ali Hashemi

Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran RABIES

 Rabies is an acute infection of the central nervous system that is almost always fatal.

 The virus is usually transmitted to humans from the bite of a rabid animal.

 Single-stranded RNA, linear, nonsegmented, negative-Sense.

 Virions contain an RNA-dependent RNA polymerase.

Classification

 The viruses are classified in the family Rhabdoviridae .

 Rabies viruses belong to the genus Lyssavirus, whereas the vesicular stomatitis-like viruses are members of the genus Vesiculovirus.

 The Rhabdoviruses are very widely distributed in nature,infecting vertebrates, invertebrates, and plants. Rabies is the only medically important rhabdovirus. Many of the animal rhabdoviruses infect insects, but rabies virus does not. Reactions to Physical and Chemical Agents

 Rabies virus survives storage at 4°C for weeks and at –70°C for years. It is inactivated by CO2 , so on dry ice it must be stored in glass-sealed vials.

 Rabies virus is killed rapidly by exposure to ultraviolet radiation or sunlight, by heat (1 hour at 50°C), by lipid solvents (ether, 0.1% sodium deoxycholate),by trypsin, by detergents, and by extremes of pH. Virus replication Animal Susceptibility and Growth of Virus

 The virus is widely distributed in infected animals, especially in the nervous system, saliva, urine, lymph, milk, and blood. Recovery from infection is rare except in certain bats, where the virus has become peculiarly adapted to the salivary glands.  There is a single serotype of rabies virus.

Pathogenesis and Pathology

 Rabies virus multiplies in muscle or connective tissue at the site of inoculation and then enters peripheral nerves at neuromuscular junctions and spreads up the nerves to the central nervous system.

 However, it is also possible for rabies virus to enter the nervous system directly without local replication.

 It multiplies in the central nervous system and progressive encephalitis develops. Cont…

 The virus then spreads through peripheral nerves to the salivary glands and other tissues. The organ with the highest titers of virus is the submaxillary salivary gland.

 Other organs where rabies virus has been found include pancreas, kidney, heart, retina, and cornea.

 Rabies virus has not been isolated from the blood of infected persons.

Cont…

 There is a higher attack rate and shorter incubation period in persons bitten on the face or head; the lowest mortality occurs in those bitten on the legs.

 Rabies virus produces a specific eosinophilic cytoplasmic inclusion,the Negri body, in infected nerve cells. Negri bodies are filled with viral nucleocapsids.

Clinical Findings

 Bites of rabid animals

 The incubation period in humans is typically 1–3 months but may be as short as 1 week or more than a year.

 It is usually shorter in children than in adults.

 The clinical spectrum can be divided into three phases: a short prodromal phase, an acute neurologic phase, and coma. Cont…

 The prodrome, lasting 2–10 days, may show any of the following nonspecific symptoms: malaise, anorexia, headache, photophobia, nausea and vomiting, sore throat, and fever. Usually there is an abnormal sensation around the wound site. Cont… During the acute neurologic phase, which lasts 2–7 days, patients show signs of nervous system dysfunction such as nervousness, apprehension, hallucinations, and bizarre behavior.

General sympathetic overactivity is observed, including lacrimation, pupillary dilatation, and increased salivation and perspiration.

A large fraction of patients will exhibit hydrophobia (fear of water) or aerophobia (fear when feeling a breeze). Cont…

 This phase is followed by convulsive seizures or coma and death.

 The major cause of death is cardiorespiratory arrest.

 Paralytic rabies occurs in about 30% of patients, most frequently in those infected with bat rabies virus.

Laboratory Diagnosis

 A definitive pathologic diagnosis of rabies can be based on the finding of Negri bodies in the brain or the spinal cord. Immunity and Prevention

 Only one antigenic type of rabies virus is known. More than 99% of infections in humans and other mammals that develop symptoms end fatally.

 Postexposure rabies prophylaxis consists of the immediate and thorough cleansing of all wounds with soap and water, administration of rabies immune globulin, and a vaccination regimen. Types of Vaccines

 Human diploid cell vaccine (HDCV)

 Purified chick embryo cell vaccine (PCEC)

 Rabies vaccine, adsorbed (RVA)

 Nerve tissue vaccine

 Duck embryo vaccine

 Live attenuated viruses: NO Types of rabies Antibody

 Rabies immune globulin, human (HRIG)

 Antirabies serum, equine Epidemiology

 Rabies is believed to be the tenth most common cause of death in humans due to infections.

 Worldwide, at least 50,000 deaths due to human rabies occur each year.

 Almost all rabies deaths (>99%) occur in developing countries, with Asia accounting for over 90% of all rabies fatalities. Cont…

 Human-to-human rabies infection is very rare. The only documented cases involve rabies transmitted by corneal and organ transplants.

 Transmission likely occurred via neuronal tissue in the transplanted organs, as rabies virus is not spread in the blood. Treatment and Control

 There is no successful treatment for clinical rabies.  An 11-year-old boy was brought to a hospital in California after falling; his bruises were treated, and he was released. The following day, he refused to drink water with his medicine, and he became more anxious. That night he began to act up and hallucinate. he also was salivating and had difficulty breathing. Two days later, he had a fever of 40.8° C (105.4° F) and experienced two episodes of cardiac arrest. Although rabies was suspected, no remarkable data were obtained from a computed tomographic image of the brain or cerebrospinal fluid analysis. A skin biopsy from the nape of the neck was negative for viral antigen on day 3 but was positive for rabies on day 7. The patient’s condition continued to deteriorate, and he died 11 days later. When the parents were questioned, it was learned that 6 months earlier, the boy had been bitten on the finger by a dog while on a trip to India. Arthropod-Borne and Rodent-Borne Viral Diseases

 The arboviruses are transmitted by bloodsucking arthropods from one vertebrate host to another.

 The vector acquires a lifelong infection through the ingestion of blood from a viremic vertebrate.

 The viruses multiply in the tissues of the arthropod without evidence of disease or damage. Cont…

 Some arboviruses are maintained in nature by transovarian transmission in arthropods.

 The major arbovirus diseases worldwide are yellow fever, dengue, Japanese B encephalitis, St. Louis encephalitis, western equine encephalitis, eastern equine encephalitis, tick-borne encephalitis, West Nile fever, and sandfly fever. Cont…

 Rodent-borne viral diseases are maintained in nature by direct intraspecies or interspecies transmission from rodent to rodent without participation of arthropod vectors.

 Transmission occurs by contact With body fluids or excretions. Cont…

 Major rodent-borne viral diseases include hantavirus infections, Lassa fever, South American hemorrhagic and Colorado tick fever.

 Marburg and Ebola. Their reservoir hosts are unknown but are suspected to be rodents or bats. HUMAN ARBOVIRUS INFECTIONS

 There are several hundred arboviruses, of which about 100 are known human pathogens.

 Diseases produced by arboviruses may be divided into three clinical syndromes: (1) fevers of an undifferentiated type with or without a maculopapular rash and usually benign; (2) encephalitis (inflammation of the brain), often with a high case-fatality rate; and (3) hemorrhagic fevers,also frequently severe and fatal.  TOGAVIRUS AND FLAVIVIRUS ENCEPHALITIS Classification and Properties of Togaviruses and Flaviviruses

 In the Togaviridae family, the genus consists of about 30 viruses and a single-stranded, positive-sense RNA genome.

often establish persistent infections in mosquitoes and are transmitted between vertebrates

 by mosquitoes or other blood-feeding arthropods. Cont…

 The viruses are inactivated by acid pH, heat, lipidsolvents, detergents, bleach, phenol, 70% alcohol, and formaldehyde.

 Arboviruses are in the Flavivirus genus in the Flaviviridae family.

 The Flaviviridae family consists of about 70 viruses that have a single-stranded, positive-sense RNA genome. Cont…

 Some flaviviruses are transmitted among vertebrates by mosquitoes and ticks, but others are transmitted among rodents or bats without any known insect vectors.

 Hepatitis C virus, classified in a separate genus in the Flaviviridae family, has no arthropod vector and is not an arbovirus. Pathogenesis and Pathology

 susceptible vertebrate hosts, primary viral multiplication occurs either in myeloid and lymphoid cells or in vascular endothelium. Multiplication in the central nervous system depends on the ability of the virus to pass the blood–brain barrier and to infect nerve cells.

Clinical Findings

 Incubation periods of the encephalitides are between 4 and 21 days. Some infected persons develop mild flu-like illness, and others develop encephalitis. There is a sudden onset with severe headache, chills and fever, nausea and vomiting, generalized pains, and malaise. Within 24–48 hours, marked drowsiness develops, and the patient may become stuporous. Cont…

 Mental confusion, tremors, convulsions, and coma develop in severe cases. Fever lasts 4–10 days. The mortality rate in encephalitides varies. With Japanese B encephalitis, the mortality rate in older age groups may be as high as 80%. Laboratory Diagnosis

 The blood only early in the infection, usually before the onset of symptoms. Virus can also be found in cerebrospinal fluid and tissue specimens, depending on the agent. Alphaviruses and flaviviruses are usually able to grow in common cell

 lines, such as Vero, BHK, HeLa, and MRC-5. Mosquito cell lines are useful. Intracerebral inoculation of suckling mice or hamsters may also be used for virus isolation. Cont…

 Antigen detection and polymerase chain reaction (PCR) assays are available for direct detection of viral RNA or proteins in clinical specimens for some arboviruses.

 B. Serology Immunity

 Both humoral antibody and cellular immune responses are thought to be important in protection and recovery from

 infection. Because of common antigens, the response to immunization or to infection with one of the viruses of a group

 may be modified by prior exposure to another member of the

 same group (eg, no Japanese B encephalitis in areas endemic

 for West Nile fever). Epidemiology

 A. Eastern and Western Equine Encephalitis  Eastern equine encephalitis is the most severe of the arboviral encephalitides, with the highest case-fatality rate.  B. St. Louis Encephalitis  St. Louis encephalitis virus is the most important cause of  epidemic encephalitis of humans in North America.  C. West Nile Fever  The 2002 West Nile virus epidemic included the first  documented cases of person-to-person transmission through  organ transplantation, blood transfusion, in utero, and perhaps breastfeeding. Cont…

 D. Japanese B Encephalitis

 Japanese B encephalitis is the leading cause of viral encephalitis in Asia.

 E. Virus

 This mosquito-borne alphavirus is a member of the Semliki

 Forest antigenic complex. The disease is characterized by high fever and severe joint pain; infections are rare. There is no vaccine available. ArbovirusHost–Vector Transmission Cycles

 Infection of humans by mosquito-borne encephalitis viruses occurs when a mosquito or another arthropod bites first an infected animal and later a human.

 The equine encephalitides—eastern, western, and Venezuelan—are transmitted by culicine mosquitoes to horses or humans from a mosquito–bird–mosquito cycle. Cont…

 A mosquito–bird–mosquito cycle also occurs in St. Louis encephalitis, West Nile virus, and Japanese B encephalitis. Swine are an important host of Japanese B encephalitis.

YELLOW FEVER

 Yellow fever virus is the prototype member of the Flaviviridae family. It causes yellow fever, an acute, febrile, mosquito- borne illness that occurs in the tropics and subtropics of Africa and South America. Severe cases are characterized by liver and renal dysfunction and hemorrhage, with a high mortality rate. Pathogenesis and Pathology

The virus is introduced by a mosquito through the skin, where it multiplies. It spreads to the local lymph nodes, liver, spleen, kidney, bone marrow, and myocardium, where it may persist for days. It is present in the blood early during infection. Clinical Findings

The incubation period is 3–6 days. At the abrupt onset, the patient has fever, chills, headache, dizziness, myalgia, and backache followed by nausea, vomiting, and bradycardia.

During this initial period, which lasts several days, the patient is viremic and a source of infection for mosquitoes. Cont…

Most patients recover at this point, but in about 15% of cases, the disease progresses to a more severe form, with fever, jaundice, renal failure, and hemorrhagic manifestations.

The vomitus may be black with altered blood. Cont…

When the disease progresses to the severe stage (hepatorenal failure), the mortality rate is high (20% or higher), especially among young children and elderly adults. Death occurs on day

7–10 of illness. Encephalitis is rare. Laboratory Diagnosis

 A. Virus Detection or Isolation

 B. Serology Immunity

Neutralizing antibodies develop about 1 week into the illness and are responsible for viral clearance. Neutralizing antibodies endure for life and provide complete protection from disease. Demonstration of neutralizing antibodies is the only useful test for immunity to yellow fever. Epidemiology

Two major epidemiologic cycles of transmission of yellow fever are recognized: (1) urban yellow fever and (2) jungle yellow fever.Urban yellow fever involves person-to-person transmission by domestic Aedes mosquitoes.Jungle yellow fever is primarily a disease of monkeys. In South America and Africa, it is transmitted from monkey to monkey by arboreal mosquitoes (ie, Haemagogus, Aedes).

It is estimated that annually, yellow fever strikes 200,000 persons,of whom about 30,000 die. Treatment, Prevention, and Control

 There is no antiviral drug therapy.

 The 17D strain of yellow fever virus is an excellent attenuated live-virus vaccine.

 Vaccination is contraindicated for infants younger than

9 months of age, during pregnancy, and in persons with egg allergies or altered immune systems (eg, human immunodeficiency virus infection with low CD4 T cell counts, malignancy,organ transplantation). DENGUE

Dengue (breakbone fever) is a mosquito-borne infection caused by a flavivirus that is characterized by fever, severe headache, muscle and joint pain, nausea and vomiting, eye pain, and rash. Severe forms of the disease, dengue hemorrhagic fever and dengue shock syndrome, principally affect children. Cont… Clinical disease begins 4–7 days (range, 3–14 days) after an infective mosquito bite. The onset of fever may be sudden or there may be prodromal symptoms of malaise, chills, and headache. Pains soon develop, especially in the back, joints,muscles, and eyeballs. Fever lasts from 2 to 7 days, corresponding to peak viral load. The temperature may subside on about the third day and rise again about 5–8 days after onset (“saddleback” form). Myalgia and deep bone pain (breakbone fever) are characteristic. A rash may appear on the third or fourth day and last for 1–5 days. Laboratory Diagnosis

Reverse transcriptase PCR (RT-PCR)-based methods are available for rapid identification and serotyping of dengue virus in acute-phase serum, roughly during the period of fever. Isolation of the virus is difficult.

Analysis of paired acute and convalescent sera to show a significant rise in antibody titer is the most reliable evidence of an active dengue infection. Treatment and Control

 There is no antiviral drug therapy. Dengue hemorrhagic fever can be treated by fluid replacement therapy. There is no vaccine. BUNYAVIRUS ENCEPHALITIS

 The Bunyaviridae family contains more than 300 viruses,mostly transmitted by arthropods. Spherical particles measuring 80–120 nm contain a single-stranded, negative- sense or ambisense, triple-segmented RNA genome 11–19 kb in total size. Several member viruses produce mosquito-borne encephalitides of humans and animals; others cause hemorrhagic fevers. Transovarial transmission occurs in some mosquitoes. Cont…

La Crosse virus, a significant human pathogen in the United States.La Crosse virus is a major cause of encephalitis and aseptic in children.

The viruses are transmitted by various woodland mosquitoes, primarily Aedes triseriatus. Principal vertebrate hosts are small mammals such as squirrels, chipmunks, and rabbits. Human infection is tangential. Overwintering can occur in eggs of the mosquito vector. Cont…

 The onset of California encephalitis viral infection is abrupt, typically with severe headache, fever, and in some

 cases vomiting and convulsions. About half of patients develop seizures, and the case-fatality rate is about 1%. Less

 frequently, patients have only aseptic meningitis. The illness lasts from 10 to 14 days, although convalescence may be prolonged. SANDFLY FEVER

Sandfly fever is a mild, insect-borne disease that occurs commonly in countries bordering the Mediterranean Sea and in

Russia, Iran, Pakistan, India, Panama, Brazil, and Trinidad.Sandfly fever (also called Phlebotomus fever) is caused by a bunyavirus in the Phlebo virus genus.The disease is transmitted by the female sandfly,Phlebotomus papatasii. RIFT VALLEY FEVER

The agent of this disease, a bunyavirus of the Phlebovirus genus, is a mosquito-borne zoonotic virus pathogenic primarily for domestic livestock. Humans are secondarily infected during the course of epizootics in domesticated animals. Transmission to humans is primarily by contact with infected animal blood and body fluids and mosquito bites. COLORADO TICK FEVER

Colorado tick fever is classified in the genus Coltivirus. African horse sickness and bluetongue viruses are in the genus Orbivirus. Rotaviruses and orthoreoviruses have no arthropod vectors. Colorado tick fever, also called mountain fever or tick fever, is transmitted by a tick. The disease is limited to areas where the wood tick Dermacentor andersoni is distributed RODENT-BORNE HEMORRHAGIC FEVERS The zoonotic rodent-borne hemorrhagic fevers include Asian

(eg, Hantaan and Seoul viruses), South American (eg, Junin and Machupo viruses), and African (Lassa virus) fevers.

Hantaviruses also cause a hantavirus pulmonary syndrome in the Americas (eg, Sin Nombre virus). The natural reser voirs of Marburg and Ebola viruses (African hemorrhagic fever) are not known but are suspected to be rodents or bats.

Causative agents are classified as bunyaviruses, arenaviruses, and filoviruses. BUNYAVIRUS DISEASES

Hantaviruses are classified in the Hantavirus genus of the

Bunyaviridae family. The viruses are found worldwide and cause two serious and often fatal human diseases: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Cont…

 Transmission among rodents seems to occur horizontally, and transmission to humans occurs by inhaling aerosols of rodent excreta (urine, feces, saliva). ARENAVIRUS DISEASES

Arenaviruses are typified by pleomorphic particles that contain a segmented RNA genome; are surrounded by an envelope with large, club-shaped peplomers. Multiple arenaviruses cause human disease, including Lassa, Junin, Machupo, Guanarito, Sabia, Whitewater Arroyo, and lymphocytic choriomeningitis. Lassa Fever

The first recognized cases of Lassa fever occurred in 1969 among Americans stationed in the Nigerian village of Lassa.

The incubation period for Lassa fever is 1–3 weeks from time of exposure. The disease can involve many organ systems, although symptoms may vary in the individual patient. Cont…

Onset is gradual, with fever, vomiting, and back and chest pain. The disease is characterized by very high fever, mouth ulcers, severe muscle aches, skin rash with hemorrhages, pneumonia, and heart and kidney damage. Deafness is a common complication, affecting about 25% of patients during recovery;hearing loss is often permanent. Cont…

Lassa virus infections cause fetal death in more than 75% of pregnant women. South American Hemorrhagic Fevers

 Junin, Machupo, Guanarito, and Sabia viruses. FILOVIRUS DISEASES

 Filoviruses are pleomorphic particles, appearing as long filamentous. Threads or as odd-shaped forms.

 The four subtypes of Ebola virus (Zaire, Sudan, Reston, Ivory Coast). Cont…

Filoviruses are highly virulent and require maximum containment facilities (Biosafety Level 4) for laboratory work.

Filovirus infectivity is destroyed by heating for 30 minutes at

60°C, by ultraviolet and γ-irradiation, by lipid solvents, and by bleach and phenolic disinfectants. African Hemorrhagic Fevers (Marburg and Ebola Viruses)

Marburg and Ebola viruses are highly virulent in humans and nonhuman primates, with infections usually ending in death.

The incubation period is 3–9 days for Marburg disease and

2–21 days for Ebola. Cont…

Fever, headache, sore throat, and muscle pain followed by abdominal pain, vomiting, diarrhea, and rash, with both internal and external bleeding, often leading to shock and death. Filoviruses have a tropism for cells of the macrophage system, dendritic cells, interstitial fibroblasts, and endothelial cells. Very high titers of virus are present in many tissues, including the liver, spleen, lungs, and kidneys, and in blood and other fluids. Cont…

These viruses have the highest mortality rates (25–90%) of all the viral hemorrhagic fevers. Viral antigens in serum can be detected by ELISA, providing a rapid screening test of human samples. RT-PCR can also be used on clinical specimens.

REPLICATION

The VP1 proteins at the vertices of the virion contain a canyon structure to which the receptor binds.The receptors for , some , and rhinoviruses are members of the immunoglobulin superfamily of proteins.

At least 80% of the rhinoviruses and several serotypes of bind to the intercellular adhesion molecule-1 (ICAM-1) expressed on epithelial cells, fibroblasts, and endothelial cells.

Transmitted by the fecal-oral route.

The upper respiratory tract, the oropharynx, and the intestinal tract are the portals of entry for enteroviruses. The virions are impervious to stomach acid, proteases, and bile. Viral replication is initiated in the mucosa and lymphoid tissue of the tonsils and pharynx, and the virus later infects M cells and lymphocytes of the Peyer patches and enterocytes in the intestinal mucosa.

Clinical Syndromes

The clinical syndromes produced by the enteroviruses are determined by several factors, including (1) viral serotype; (2) infecting dose; (3) tissue tropism; (4) portal of entry; (5) patient’s age, gender, and state of health; and (6) pregnancy. Infections

Poliovirus may cause one of the following four outcomes in unvaccinated people, depending on the progression of the infection :

1. Asymptomatic illness results if the viral infection is limited to the oropharynx and the gut. At least 90% of poliovirus infections are asymptomatic.

2. Abortive poliomyelitis, the minor illness, is a non 5% of infected people. Cont… Fever, headache, malaise, sore throat, and vomiting occur in such persons within 3 to 4 days of exposure.

3. Nonparalytic poliomyelitis or aseptic meningitis occurs in 1% to 2% of patients with poliovirus infections. In this disease, the virus progresses into the central nervous system and the meninges, causing back pain and muscle spasms in addition to the symptoms of the minor illness.

4. Paralytic polio, the major illness, occurs in 0.1% to 2.0% of persons with poliovirus infections and is the most severe outcome. Cont…

Paralytic poliomyelitis

Bulbar poliomyelitis

Postpolio syndrome Coxsackievirus and Echovirus Infections

Coxsackie A viruses are associated with diseases involving vesicular lesions (e.g., ), whereas Coxsackie B viruses (B for body) are most frequently associated with myocarditis and pleurodynia. Cont…

Herpangina is caused by several types of Coxsackie A virus and is not related to a herpesvirus infection.

Fever, sore throat, pain on swallowing, anorexia, and vomiting characterize this disease. Cont…

Hand-foot-and-mouth disease is a vesicular usually caused by Coxsackievirus A16.

Pleurodynia (), also known as the devil’s grip Cont…

Myocardial and pericardial infections caused by Coxsackie occur sporadically in older children and adults but are most threatening in newborns.

Vira Outbreaks of meningitis (echovirus 11) occur each year during the summer and autumn. Cont…

Fever, rash, and common cold like symptoms may occur in patients infected with echoviruses or Coxsackie viruses.

Coxsackie viruses A21 and A24 and echoviruses 11 and 20 can cause rhinovirus-like symptoms resembling the common cold. Other Diseases

Enterovirus 70 and a variant of Coxsackie virus A24 have been associated with an extremely contagious ocular disease, acute hemorrhagic .

Coxsackie B virus infections of the beta cells of the pancreas can cause insulin-dependent diabetes as a result of the destruction of the islets of Langerhans. Laboratory Diagnosis

Clinical Chemistry

Cerebrospinal fluid (CSF) from enterovirus aseptic meningitis can be distinguished from bacterial meningitis. The CSF lacks neutrophils, and the glucose level is usually normal or slightly low. The CSF protein level is normal to slightly elevated. The CSF is rarely positive for the virus.  Culture  Genome and Serology Studies Treatment, Prevention, and Control

A new antiviral drug, pleconaril, is available on a limited basis.

The two types of poliovirus vaccine are (1) inactivated polio vaccine (IPV), developed by Jonas Salk, and (2) live attenuated oral polio vaccine (OPV).

RHINOVIRUSES

 Rhinoviruses are the most important cause of the common cold and upper respiratory tract infections. Treatment, Prevention, and Control

Pleconaril and similar experimental antiviral drugs (e.g., arildone, rhodanine,disoxaril) contain a 3-methylisoxazole group that inserts into the base of the receptor-binding canyon and blocks uncoating of the virus.

Adenoviruses

Adenoviruses were first isolated in 1953 in a human adenoid cell culture.

Adenoviruses can replicate and produce disease in the respiratory, gastrointestinal, and urinary tracts and in the eye.

Cont… The E1A early gene is especially important; it must be expressed for the other early regions to be transcribed. Modulation of the cell cycle is accomplished by the E1A gene products. The E1B early region encodes proteins that block cell death (apoptosis) that occurs as a result of E1A functions; this is necessary to prevent premature cell death that would adversely affect virus yields. Cont…

The E1A and E1B regions contain the only adenovirus genes involved in cell transformation; those gene products bind cellular proteins (eg, pRb, p300,p53) that regulate cell cycle progression.

The penton base carries a toxin-like activity that causes rapid appearance of cytopathic effects and detachment of cells from the surface on which they are growing. Cont…

The capsid comprises 240 capsomeres, which consist of hexons and pentons. The 12 pentons, which are located at each of the vertices, have a penton base and a fiber. The fiber contains the viral attachment proteins and can act as a hemagglutinin. The penton base and fiber are toxic to cells. The pentons and fibers also carry type-specific antigens. Classification

Cont…

The histologic hallmark of adenovirus infection is adense, central intranuclear inclusion (that consists of viral DNA and protein) within an infected epithelial cell. These inclusions may resemble those seen in cells infected with , but adenovirus does not cause cellular enlargement (cytomegaly). EPIDEMIOLOGY

Adenovirus virions resist drying, detergents, gastrointestinal tract secretions(acid, protease, and bile),and even mild chlorine treatment Cont…

Adenoviruses 1 through 7 are the most prevalent serotypes. From 5% to 10% of cases of pediatric respiratory tract disease is caused by adenovirus types 1, 2, 5, and 6, and the infected children shed virus for months after infection. CLINICAL SYNDROMES

Acute Febrile Pharyngitis and Pharyngoconjunctival Fever

Adenovirus causes pharyngitis, which is often accompanied by conjunctivitis and pharyngoconjunctival fever. Pharyngitis alone occurs in young children, particularly those younger than 3 years, and may mimic streptococcal infection. Cont…

Acute Respiratory Disease

Other Respiratory Tract Diseases

Adenoviruses cause cold like symptoms, laryngitis, croup, and bronchiolitis.

They can also cause a pertussis-like illness in children and adults that consists of a prolonged clinical course and true viral pneumonia. Cont…

Conjunctivitis and Epidemic

Keratoconjunctivitis

Swimming pool conjunctivitis

Epidemic keratoconjunctivitis

Gastroenteritis and Diarrhea:40,42

Systemic Infection in

Immunocompromised Patients

TREATMENT, PREVENTION, AND CONTROL

Live oral vaccines have been used to prevent infections with adenovirus types 4 and 7 in military recruits but are not used in civilian populations. gene Therapy

Adenoviruses are being used as gene delivery vehicles for cancer therapy, gene therapy, and genetic immunization studies.