Presentation on theme: "PART TWO SYSTEMIC VIROLOGY Prepared by Professor Dr Hassan J Hasony"— Presentation transcript:
1 PART TWO SYSTEMIC VIROLOGY Prepared by Professor Dr Hassan J Hasony Dept Med Microbiology, Basrah Medical College
2 OBJECTIVES:Viral infections attributed to each system will be discussed concentrating on :- properties of viral aetiologic agent- clinical finding and case presentation- Epidemiology of viral infections- prevention and control measures- Laboratory diagnosis and interpretation of lab. Test results
3 LEARNING OBJECTIVESstudent should be able to answer the questions attached to each lecture concerning the target system and having a skil to identify and interprept the results of any related investigations for linking the presented case to the viral aetioloigic agent(s)
4 THE FAMILY OF VIRUSES RNA VIRUSES Orthomyxoviridae Paramyxoviridae RhabdoviridaeFiloviridaeFlaviviridaePicornaviridaeReoviridaeTogaviridaeRetroviridae
7 Why so many? Constant exposure: 21,000 L of air/day RT is a favorable environment for viruses:Warm, moist, and darkPlenty of cell types (25), which are good “tissue culture media”Optimal temperatureEasy transmission via:Sneezing – aerosol m particles at 100 ft/secCough – disperses nasopharyngeal content at 850 ft/secIntimate and non-intimate contact
8 Determinants of Viral Respiratory Disease Viral FactorsTissue tropismRoute of infectionStability of the virusReplication and release of viruses into aerosolsHost FactorsAgeImmune statusUnderlying diseaseadaptationEnvironmental FactorsDosageExposureOccupationLife Style:Day care settingPublic transport
10 RNA VIRUSES Enveloped, Single-stranded RNA Viruses Orthomyxoviruses: Influenza- spherical particles with an average diameter of nm- contains 7 structural proteins :PB1, PB2, PA – bound to viral RNA ; responsible for RNAtranscription and replicationNucleoprotein ( NP ) – associates with viral RNA to form astructure 9 nm in diameter that assumes ahelical configurationMatrix ( M ) protein – forms a shell underneath the virallipid envelope; important in particle morphogenesisHA ( hemagglutinin ) } determines antigenic variationNA ( neuraminidase ) } of influenza viruses
11 ORTHOMYXOVIRUSES type A, B, C : NP, M1 protein helical nucleocapsid (RNA plusNP protein)HA - hemagglutininpolymerase complexlipid bilayer membraneNA - neuraminidasetype A, B, C : NP, M1 proteinsub-types: HA or NA protein
12 Influenza virus genome: - divided into eight separate segments reassortingduring viral assembly antigenic nature ofproteins change- antigenic drift : changes in a single amino acid- antigenic shift : the accumulation of enough changes tocreate a new subtype different from theoriginal strainH and 9 N ( H= 2 to the power 16 ,N=2 topower 9
13 Classification and nomenclature : - antigenic differences between NP and M proteins dividesinfluenza viruses into :type A : highly variable antigenically ; responsiblefor most cases of epidemic influenzatype B : may exhibit antigenic changes and sometimescauses epidemicstype C : antigenically stable ; causes only mild illness
14 Properties :- relatively stable; may be stored at 4 degrees C for a week- infectivity destroyed by heating at 56 degrees C for afew minutes, treatment with ether, formaldehyde,phenol and other protein denaturants- initial isolation best accomplished by amnioticinoculation of embryonated chicken eggs and monkeycell cultures
15 EPIDEMIOLOGY: Influenza A - acute, highly contagious , respiratory illness afflictingpeople of all ages marked by seasonal regularity andpandemics at predictable intervals- five pandemics in recorded history : the worst was in1918 where there were at least 50 million deaths- the most virulent among the three types of influenzaviruses
17 ( cont. epidemiology )- influenza A strains are also known for pigs, horses,ducksand chicken- antigenic changes in group A > B; group C appears to beantigenically stable- interpersonal spread due to formation of virus-ladenaerosol droplets when an infected patient sneezes or coughs if virus is not neutralized ( e.g. local IgA specific anti-hemagglutinin Ab ), initial replication occurs
18 Mode of influenza transmission: - inhalation of aerosol and droplets major route of infection- transmission greatly facilitated by crowding and poor ventilationusually in late fall and winter in temperate countriesthroughout the year in the tropics- occupational contact with ducks, other poultry,and swine constitutesa special high-risk category for disease- OVERALL MORTALITY FOR INFLUENZA A : 0.1 % of caseswith deaths occurring among the elderly and small childrenPathogenesis:Virus binds to ciliated columnar cells (respiratory mucosa)rapid shedding of mucosal cells together with a loadof viruses trachea and bronchial epithelia are stripped tothe basal layer leading to severe inflammation and irritationviruses remain in respiratory tract (viremia is rare);ciliated columnar epithelium restored w/in 1-2 wks
19 FACTORS AFFECTING EFFICIENCY OF AEROSOL SPREAD:1. direct proportion to the number of particles generated2. density of susceptibles3. physical and temporal contiguity to aerosols4. degree of stagnation of ambient atmosphere- high attack rates : nursing homes, classrooms, ships,barracks, aircraft- smokers : increased susceptibility to infection- young children ( pre-school or grade school ) : mosteffective disseminators of the disease- periodicity of influenza epidemics/pandemics:determined by the surface antigens of the virus and theantibodies induced within a population
20 Recovery from infection depends on: a. general health b. immunity from previousexposurec. vaccinationd. age
21 DIAGNOSIS:Virus isolation /detection of viral antigen in respiratorysecretions ( nasal/throat swabs; nasal washes ;combined nose-and-throat swab ; sputum ) which areinoculated into :a. rhesus monkey kidney or Madin-Darby caninekidney cell cultures CPE or hemadsorptionb. embryonated hens’ eggs ( allantoic or amniotic cavity )
22 2. Rapid diagnosisa. samples centrifuged directly onto cells in shellvials detection of viral antigens by IF orELISA* sensitivity higher in nasophrayngeal washes andswabsb. PCR
23 3. serologic testing- compares acute and convalescent sera ( daysapart ): 4 fold rise in titera. CFb. HAI4. epidemiologic diagnosis- when infection is confirmed within a region by thelocal health department
24 PREVENTION:- primary means of prevention : vaccines- vaccines not used much because:a. offers only a short duration of protectionb. possibility of sensitization or severe allergic reactions inpersons hypersensitive to eggs ( vaccine viurs grown in chickembryo )c. possibility of toxic reactions to the high concentration ofvirus material administered parenterallyd. uncertainty of protection because of the changing antigenicityof the circulating influenza strains- vaccination recommended for high-risk groups:a. the chronically illb. the elderly ( > 65 years old )c.persons with high degree of exposure to the public
25 standard vaccines containing viruses grown in embryonated eggs have an overall effectiveness of 70 %( accompanied by side effects of chills and fever)- newer subunit vaccines made by disrupting virus withdetergents or solvents have fewer side reactions but aremore limited in scope of protection- recent tests being done on influenza vaccine administeredintra-nasally ( greater potential for immunogenicity)
26 CONCEPT QUESTIONS -Mention the major groups of viruses causes RTI. - What are the determinants of viral respiratory diseases ?-What are the properties of orthomyxoviruses ?- What is the major characters of influenza virus genome ?- On what basis influenza viruse can be classified ?- What is the possible mechanism for influenza virus antigenic changes?- What is the mode of influenza virus trasmission ?- Illustrate the pathogenesis of influenza virus ?- What are the factors affecting efficiency of aerosole spread ?- Recovery from influenza virus infection depends on:- What are the diagnostic methods for influenza infections?- What are the strategies for influenza prevention ?- Who are the target for influenza virus vaccinatio ?-What are the types of influenza vaccines, giving the advantages of each ?
27 ENVELOPED, RNA VIRUSES PARAMYXOVIRUSES The important human paramyxoviruses:a. Paramyxovirus ( parainfluenza and mumps )b. Morbillivirus ( measles virus )c. Pneumovirus ( respiratory syncytial virus )- resembles the influenza virus but are largerall are transmitted thru respiratory dropletsenvelope has HN spikes and F glycoprotein spikes that allow thevirus to infect neighboring cells :HN ( hemaglutinin and neuraminidase ) : responsiblefor host cell attachmentF glycoprotein : mediates membrane fusion andhemolysin activity
28 Paramyxoviridae Properties of the Paramyxoviridae 2. Morphology & structural proteins
29 Paramyxoviridae Properties of the Paramyxoviridae 2. Morphology & structural proteins
30 PARAMYXOVIRUSES:Mechanism of infection:cell membrane of infected cell modified by insertion of spikesHN spikes immediately bind an uninfected neighboringcell in the presence of F spikes two cellspermanently fusechain reaction of multiple cell fusions produce a syncytium ora multinucleate giant cell (with cytoplasmic inclusion bodies)
31 2. Parainfluenza virus type 3 I. PARAINFLUENZA4 major serotypes :1. Parainfluenza virus types 1 and 2- usually infects infants and children2. Parainfluenza virus type 3- infects infants < 2 years- year round infections- more severe than types 1 and 23. Parainfluenza virus type 4- mild disease
32 Epidemiology and Pathology primary infection with virus occurs throughout theyear ( seasonal peaks in late fall and winter )droplets and respiratory secretions disseminate thevirus into the air and onto fomitesusual route of transmission: inhalation or inoculationof mucous membranes by contaminated handsusually seen most frequently in childrenNO transplacental immunity ; babies in firstyear are particularly susceptible ( more severesymptoms )
33 Characteristic symptoms of parainfluenza: a. minor upper respiratory tract disease (a cold)- causedby all typesb. bronchitis – usually caused by type 3c. bronchopneumonia – usually caused by type 3d. laryngotracheobronchitis ( croup)- afflicts larynx ofinfants and young children causing labored ,noisybreathing with hoarse cough; usually asso. with types1& 2* second only to RSV as a cause of lowerrespiratory tract infection* commonly cause croup
34 LABORATORY DIAGNOSIS : 1. Isolation and identification of the virus* specimens : throat and nasal swabs andnasal washes* inoculated on primary human and monkeykidney cells -> isolates typed byIF or hemadsorption inhibitionor HI2. Serology : uses paired sera
35 CONCEPT QUESTIONS Mention the important human paramyxoviruses . What is the mechanism of infections with paramyxoviruses ?Four serotypes of parainfluenza, mention the host range anddisease caused by each type .What are the epidemiologic feature and pathology ofparainfuenza virus infections?What are the characteristic symptoms of parainfluenza ?Mention the main laboratory diagnostic methods forparainfluenza.
47 CONCEPT QUESTIONS: Mention the main characteristic of adenoviruses . - Describe the pathogenesis of adenovirus infections.- What are the epidemiological feature of adenovirus infection?- What are the clinical significane of addenovirus infections?- What are the main clinical finding associated with acutefebrile pharyngitis?- In what ways adenovirus can evade host immune response?
48 II. MUMPS ( EPIDEMIC PAROTITIS ) : - self-limited, mildly epidemic illness associated with painfulat the angle of the jaw with occasional swelling of the testes- virus bears morphologic and antigenic characteristics similar tothe parainfluenza virus- has only one serological type- grows readily in embryonated eggs esp. in the amniotic sac- can be grown in cell culture to produce large multinucleated giantcells ( syncytia ) and a hemagglutinin- infectivity of virus destroyed by heating at 56 degrees C for 20 mins.
49 MumpsInflammation, parotitis in a child with mumps
51 Epidemiology and Pathology of Mumps: - humans are the exclusive natural hosts- occurs worldwide, epidemics occur in the late winter and earlyspring- high rate of infection among crowded populations- most cases occur in children under 15 years ( 40 % subclinical)- lasting immunity follows any form of mumps infection- communicated thru salivary and respiratory secretions( less contagious than measles or varicella )
52 incubation period : 2-3 weeks followed by symptoms of ( cont. epidemiology and pathology of mumps )incubation period : 2-3 weeks followed by symptoms offever, nasal discharge, muscle pain, and malaiseinflammation of salivary glands ( esp. the parotids) producethe classic “gopher-like” swelling of the cheeks on one orboth sidesviral multiplication in salivary glands viremia andinvasion of other organs ( e.g. testes, overies, thyroid gland,pancreas, meninges, heart, kidney)PROGNOSIS: most will have complete, uncomplicatedrecovery
53 Complications of Mumps: 1.Orchitis and epididymitis : occurs in 20-30% of young adult males: painful but no permanent damage occurs2. Pancreatitis : virus replicates in beta cells and pancreatic epithelialcells3. Viral meningitis : fever, headache, nausea, vomiting, and stiff neck: common in mumps: appears 2-10 days after onset of parotitis: lasts 3-5 days, dissipates with few or no adverseside effects4. Hearing loss : a rare occurrence: affects only one side: virus replicates in the organ of Corti causingpermanent deafness
54 ( cont. mumps )Diagnosis:1. history ( exposure ) and PE ( parotid swelling )2. serologic studies* IgM antibodies by ELISA or 4 fold increase betweenacute and convalescent sera3. viral isolation* virus present in saliva for about 1 week aftre onsetof parotitisTreatment : Symptomatic treatment usually adequatePrevention : a live, attenuated mumps vaccine given routinely as partof the MMR vaccine at 15 months of age ( powerful andeffective control agent ): protection often lasts a decade
55 CONCEPT QUESTIONS -What are the characteristic of mumps disease ? - What are the epidemiologic feature and pathology of mumps?- What are the major complication of mumps ?- What are the diagnostic methods for mumps?- What are the main method s for prevention & control ofmumps ?
56 III. MEASLES ( Morbillivirus Infection ) - also known as red measles and rubeola- entirely unrelated to rubella ( German MEASLES )- characterized by maculopapular eruption , URTI,conjunctivitisEpidemiology:one of the most contagious infectious diseases- rare under 6 months of age: transplacental IgGtransmitted principally by direct contact with respiratory aerosols- epidemic spread favored by crowding, a prevalence of nonimmunechildren, malnutrition1986 measles epidemic linked to lack of immunization in childrenor the failure of a single dose of vaccine in many childrenno reservoir other than humansperson considered infectious during period of incubation, prodrome,and skin rash- single attack confers lifelong immunity
60 ( The large syncytia, or multinucleated giant cells, result CPE typical of measles virus infection of Hela cells(Hematoxylin & Eosin staining)( The large syncytia, or multinucleated giant cells, resultfrom fusion of cell membranes bearing viral glycoproteins e syncytia, or multinucleated giant cells, resultfrom fusion of cell membranes bearing viral glycoproteins.)
61 Infection and Disease: * incubation period : 2weeks ( cont. Measles )Infection and Disease:* incubation period : 2weeks: invasion of mucosal lining ofrespiratory tract, followed by viremiaSymptoms : sore throat, dry cough, headache,conjunctivitis, lymphadenitis, and feverSigns : Koplik’s spots( on lateral buccal mucosa ) appearas a prelude to the red maculopapular exanthem thaterupts on the head which progresses to the trunk andextremities: rash gradually coalesce into red patches that fade tobrown
62 “Koplik’s spot” Patient who presented with Koplik’s spots on palate due to pre-eruptive measles on day 3 ofthe illness
63 Complications : in most instances, a self-limited infection : may be severe enough to cause death in about 1 in 500 children: laryngitis, bronchopneumonia, bronchitis,pneumonitis , bacterial secondary infections ,otitis media and sinusitis: children with leukemia predisposed topneumonia due to lack of natural T-celldefense: SSPE ( subacute sclerosing panencephalitis )( manifests 5-7 years after initial infection)
64 Diagnosis :1. Clinical- age, history of recent exposure to measles,( useful clues to diagnosis)- cough, coryza, conjunctivitis, Kopliks’ spots,a maculopapular rash beginning on the face2. Laboratorya. virus isolationb. identification of measles antigen in infectedtissues ( IF from nasal exudates/urine sedi-ments and RT-PCR )c. demonstration of specific serologic response( ELISA, HI on paired serum samples )
65 Treatment : symptomatic treatment for most cases : antibiotics may be given for bacterialcomplications: large doses of immune globulin may betherapeuticPrevention : vaccination is the most practical, economical,and enduring strategy to combat measles
66 - immunity persists for about 20 years - may cause atypical infection Measles vaccine :- attenuated virus given subcutaneously- immunity persists for about 20 years- may cause atypical infection- recommended for all healthy children at the age of 15months ( MMR vaccine , with mumps and rubella )and a booster prior to entering school- any person who received the vaccine prior to 1980 orwhose immunization history is in doubt should berevaccinated
67 CONCEPT QUESTIONSDefine measles.- What are the epidemiologic picture of measles.- What are the major sign and symptoms of measles.- What are the complications of measles ?- What are the basis for the diagnosis of measlesclinically or laboratory?What are the major preventive measures of measles?What is the schedule of measles vaccination andwhat type of vaccine ?
69 Rubella Epidemiology of Rubella Virus Disease / Viral Factors - Rubella infects only humans.- Virus can cause asymptomatic disease.- There is one serotype.
70 Rubella Epidemiology of Rubella Virus Transmission - Respiratory route Who Is at Risk?- Children: mild exanthematous disease.- Adults: more severe disease with arthritis /arthragia- Neonates younger than 20 weeks: congenital
71 Rubella Rash of rubella on skin of child's back.Distribution is similar to that of measles but the lesions are less intensely red.
72 Rubella Prenatal or congenital rubella The risk to a fetus is highest in the first fewweeks of pregnancy and then declines in term of bothfrequency and severity, although there is still somerisk in 2nd trimester.The virus infects the placenta and then spreadsto the fetus. If non-immune mothers are infectedin the 1st trimester, up to 80% of neonates mayhave sequelae.
73 Rubella The sequelae of congenital rubellar syndrome are: Hearing loss: This is the most common sequellaof congenital rubella infectionespecially when the latter occursafter 4 months of pregnancy.Congenital heart defectsNeurologic problems: psychomotor retardation: mental retardationOphthamic problems: cataract, glaucoma,retinopathy
74 Rubella Prominent Clinical Findings in congenital rubella Syndrome Cataracts & other ocular defectsHeart defectsDeafnessIntrauterine growth retardationFailure to thrive
75 Rubella Prominent Clinical Findings in congenital rubella Syndrome Mortality within the first yearMicrocephalyMental retardation
76 Rubella This infant has the rash of congenital rubella (German measles).These infants are at great risk forsevere mental retardation, deafness, blindness(atrophic eyes, cataracts and chorioretinitis)as well as congenital heart disease and other abnormalities..
77 Rubella Baby born with rubella: Thickening of the lens of the eye that causes blindness (cataracts)
78 Rubella * Humoral Immunity Immune response - Specific IgM antibody appears within a few daysof the rash, and is followed soon after by IgG.The titer of IgM increases rapidly, reaching apeak about 10 days after onset and thereafterdeclining to undetectable amounts over severalweeks or months.
79 Rubella * Humoral Immunity Immune response The rapid appearance of specific IgM antibodyis invaluable for diagnostic purposes.- IgG antibody peaks at about the same time asIgM, and persists for many years, as does IgAantibody, which appears in the serum andnasopharyngeal secretion.
80 Rubella * Cellular Immunity Immune response - The cell-mediated response precedes theappearance of antibody by a few days, reachesa peak at about the same time, and is alsodetectable for many years.
81 Rubella Diagnosis of rubella - Many (~ 50%) infections are apparently subclinical and many infections go unrecognized,even if symptoms develop (rash is not alwayspresent).- Infections with many other agents give similarsymptoms to rubella (e.g. infection with humanparvovirus, certain arboviruses, many of theenterovirus group of piconaviruses, someadenoviruses, EBV, scarlet fever, toxic drugreactions).
82 Rubella Diagnosis of rubella - Serological tests or isolation of virus (immunofluorescence) are needed to confirminfection of individualCord blood rubella- IgM
83 Rubella Epidemiology - Human is the only host and rubella occurs world wide.- Periodic epidemics occur in an unvaccinatedpopulation.- Natural infection protects for life(there is a single serotype).
84 Rubella Prevention - The best means of preventing rubella is vaccination with the live cold-adaptedRA27/3 vaccine strain of virus.- The live rubella vaccine is usually administeredwith the measles & mumps vaccines(MMR vaccine) at 24 months of age.
85 Rubella Prevention - A live vaccine (attenuated strain) is available. The vaccine virus is grown in human diploidfibroblasts. Since there is only 1 serotype,a univalent attenuated vaccine can providelifelong immunity.
86 Rubella Prevention - It is important that women are vaccinated prior to their 1st pregnancy.- United States recommendations are forchildhood vaccination to prevent epidemics,combined with vaccination of susceptible,non-pregnant adolescent and adult females.
87 Rubella Prevention - The vaccine is contraindicated for pregnant women, but when unwittingly used, no problemshave been seen.- If the patient is pregnant and seronegative, thepregnancy should be monitored carefully and thepatient vaccinated postpartum.
88 Rubella Treatment There is no specific treatment. Supportive care should be used.
89 CONCEPT QUESTIONS What is the epidemiologic feature of rubella ? - Who is at risk of rubella infections?- What are the differences between measles and rubella ?- What is CRS ?- Describe the consequences of congenital rubella ?- What are the sequellae of congenital rubella syndrome ?- What are the prominant clinical findings in CRS ?- Describe the humoral responses to rubella virus infection?- Describe the cellular responses to rubella virus infection?-Is the diagnosis of rubella virus infection always feasible ?- What are the diagnostic methods for rubella and CRS ?- What are the epidemiologic feature of rubella?- Mention the main methods for rubella prevention?- In what situations rubella vaccine can be contraindicated ?
90 IV. RESPIRATORY SYNCYTIAL VIRUS - Also called Pneumovirus- infects the respiratory tract and produces giant multinucleate cells- peak incidence in the winter and early spring- children 6 months or younger are especially susceptible to seriousdiseaseRSV Infection :- incidence of RSV in children < one year old is 5/1000 live births( most prevalent cause of respiratory infection in this age group)- mortality highest for children with complications ( e.g.,prematurity, congenital disease, and immunodeficiency )- immunity is partial or transient, hence, infection could be recurrent- manifests itself as a common cold in older children and adults
91 - portal of entry : epithelia of the nose and eye ( cont. RSV infections )Pathogenesis- transmission : respiratory route- portal of entry : epithelia of the nose and eye- main site of replication: nasopharynx- symptoms : ( 1o infection) fever that lasts for three days: rhinitis, pharyngitis, and otitis: infection of the bronchial tree and lungparenchyma gives rise to croup ( acute bouts ofcoughing, wheezing, dyspnea and rales )
92 - major cause of respiratory illness in young children Clinical Disease:- major cause of respiratory illness in young children- < 24 months : devastating disease-> 4 months : no protective maternal antibodyLower respiratory tract infections- pneumonia, bronchiolitis, tracheobronchitis2. Upper respiratory tract infections- presents as common cold3. Complications- otitis media: common
93 Diagnosis- critical in babies than in older children- positive identification of RSV must be made asrapidly as possibleViral isolation on nasal wash / naspharyngeal andthroat swab ( done ASAP since virus is labile )2. Direct and indirect fluorescent staining from a freshsample ( the virus is very fragile)3. ELISA testing and DNA probes
94 ( cont. RSV )Treatment : Ribavirin (virazole) appears beneficial sinceit interferes with the replication of the virus ininfected cells: Ribavirin is administered as an aerosol( cannot be given to persons whose ventilationis compromised): costly treatment with some adverse side effects: supportive measuresPrevention : intranasal live vaccine presently beingdeveloped
95 CONCEPT QUESTIONS-In what age groups the incidence of RSV is highest ?- Describe the pathogenesis of RSV .- Mention the clinical diseases caused by RSV andtheir complications .-What are the diagnostic methods of RSV infections?- What are the treatment of RSV and the methodsfor prevention?
96 HUMAN RHINOVIRUS (HRV ) an extremely large group of picornaviruses ( > 110 serotypes )associated with the common cold- characteristics which distinguish the rhinovirus from the otherpicornaviruses:1. Rhinoviruses are sensitive to acidic environments( e.g. stomach )2. Optimum temperature for multiplication is notnormal body temperature, but 33o C, the averagetemperature in the human nosestructure of the Rhinovirus:- the capsid units are of two types:a. protruberances (knobs), which are antigenically diverseamong the rhinovirusesb. indentations (pockets) of which there are two types
98 Pathogenesis and Clinical Manifestations Portal of entry: nose, mouth, eyesReplication: in the nosePrimarily infects upper airway common coldBinds to ICAM-1 as cellular receptorsCauses lysis of cellsInfected cells release bradykinin and histamine rhinitis & rhinorrheaSore throat, cough, headache, malaiseImmunity is serotype specific
99 Epidemiology and Infection of Rhinoviruses: the surface antigens are the only ones accessible to the immunesystem ( i.e. a successful vaccine would have to containhundreds of different antigens- not practical )-the indented antigens are too deeply situated for either immunesurveillance or antibody fitEpidemiology and Infection of Rhinoviruses:infection occurs in all areas, and all age groups at all times of theyear.- many strains circulate in the population at one time ( occasionallya single type may cause epidemics)- children are the most successful disseminators of colds, oftenintroducing the virus to the whole family- virus is shed from infected respiratory tract for several days – weeks- transmission is linked very closely to inoculation by hands andfomites ( to a lesser extent to droplet nuclei )
100 Rhinovirus Control of infection: - combined antiviral-antimediator treatment:In a trial using interferon-alpha 2 + ipratropium (both instilled into thenose) + oral naproxen - > viral shedding and progression ofillness were reduced in the treatment groupOther measures:a. hand washingb. avoiding finger-eye and finger-nose contactc. covering coughs and sneezes with disposable nasal tissues
101 Rhinovirus Symptomatic therapy: Combination of a 1st generation antihistamine and a non-steroidalanti-inflammatory compound effective treatment-Treatment started a early as symptoms are recognized andcontinued every 12 hours for 4-5 days-Antibiotics have no place in therapyAntiviral therapy:the most promising results have been obtained with recombinantinterferon-alpha 2 applied topically in the nose- interferon-alpha 2 is given prophylactically on doses ofapproximately 5 million units or greater per day highlyeffective in prevcnting experimental infection or illness- side effects of chronic topical interferon-alpha 2 include :nasal irritation, stuffiness, pinpoint mucosal ulcerations
102 CONCEPT QUESTION -What are the characteristics of Rhinoviruses ? - What are the pathogenesis and clinical manifestationof rhinoviruses?- what are the epidemiologic feature of Rhinoviruses?- How can we control rhinovirus infections?- mention the strategies for rhinovirus infection therapy: symptomatic therapy: antiviral therapy
104 SARS Cause: SARS-associated corona (RNA) virus Respiratory illness with onsetT > 100.5°F (>38° C)Cough, shortness of breath, difficulty breathing, hypoxia, or radiographic findings of either pneumonia or acute respiratory distress syndromeTravel within 10 days of onset of symptoms to an area with documented or suspected community transmission of SARSClose contact with a person with SARS within 10 days of onset
105 Define: Coronaviruses Define: SARS - Mention the main clinical feature of SARS - Mention the main routes of transmission.
106 RHABDOVIRUSES one end and flat on the other end ) Rabies virus ( Lyssavirus ):- have a distinctive bullet –like appearance ( round onone end and flat on the other end )- helical nucleocapsid with spikes that protrude thru theenvelope- family contains approximately 60 different viruses- only the rabies virus affect humans ( rarely, othermammalian lyssaviruses )- killed by UV irradiation or sunlight
108 - worldwide distribution in various mammals ( skunks, Epidemiology- slow , progressive zoonotic disease characterized by afatal meningitis- worldwide distribution in various mammals ( skunks,foxes, raccoons, wolves, mongooses, and badger )- humans become accidental hosts thru dog bites, catscratches and contact with sylvan animal reservoirs1.Sylvatic rabies- rabies in wild animals ( bats, skunks, racoons, foxes )- fruit and herbivorous bats are known to transmitrabies2. Urban rabies- rabies in domestic animals ( dogs, cats, horses, cattle)- vampire bats in S. America ( source of rabies in cattle)
109 TRANSMISSION- primarily affects wild animals- humans and animals : accidentally infectedanimal bite – majority2. via a scratch3. inhalation of contaminated aerosolized animal material4. transplantation of infected tissue ( cornea )inoculation through intact mucous membrane* virus found in saliva of infected animal few daysbefore clinical signs* bat infection : latent ( bats excrete virus in saliva formonths )
110 Note: no viremiaMurray et al., Medical Microbiology
111 site ( it may also be inhaled or inoculated orally) Infection and Disease- begins when an infected animal’s saliva enters a puncturesite ( it may also be inhaled or inoculated orally)- virus multiplies at the trauma site, up to a week upontransmission- virus gradually enters sensory nerve endings orneuromuscular junction and advances toward the sensoryganglia, spinal cord and brain- virus multiplies throughout the brain with migration toother sites ( eye, heart, skin, and oral cavity )- viral replicates in the salivary glands and is shed into thesaliva- considered a slow, progressive infection
112 Clinical phases of Rabies: Average incubation period: 1-2 months ( extremes of 1week to more than a year )Incubation period : depends on wound site, its severity, virusconcentration in inoculum, host’s age,host’s immune status: shorter in facial, neck and scalp woundsdue to their proximity to the brain: prodrome begins with fever, anorexia,nausea, vomiting, headache, fatigue,some may have pain, burning, prickingor tingling sensation at the site of thewound
113 Furious form – agitation, disorientation, seizures, and twitching Forms of Rabies:Furious form – agitation, disorientation, seizures, andtwitching- spasms in the neck and pharyngealmuscles lead to severe pain on swallowing ( even thesight of liquids can bring about hydrophobia )- the patient is fully coherent and alertDumb form – patient is paralyzed, disoriented andstuporous*Both forms eventually lead to coma and death from cardiacor respiratory arrest.*Only 3 patients have recovered from rabies with minimalresidua
114 Diagnosis- when symptoms appear after a rabid animal attack thediagnosis is readily made- often the diagnosis is made at autopsy- the laboratory criteria most diagnostic of rabies are :1. intracelllular inclusions ( Negri bodies )2. identification, isolation of rabies virus in saliva or braintissue3. demonstration of rabies virus antigens in brain, serum ,CSF
115 Section of brain showing rabies viruses Bullet-shapedRabies virusSection of brain showing rabies viruses
116 Rabies virus infected - Negri body - note dark blue basophilic granules (Sellers stain)
117 Rabies Prevention and Control: Measures that effectively prevent and limit rabies are:1. Postexposure vaccination2. Animal control3 IM injections of HDCV ( human diploid cell vaccine)are recommended for high risk groups ( veterinarians, animalhandlers, lab personnel, and travelers to endemic areas )other control measures such as vaccination of domestic animalselimination of strays, strict animal quarantine have reduced the virusreservoirA new genetically engineered vaccine made with a vaccinia virusthat carries the gene for rabies virus surface antigen have beenincorporated into bait placed in habitats of wild reservoir species.It is hoped eating this bait will render animals immune to rabies.
118 Postexposure Prophylaxis: 1. A wild animal especially a skunk, raccoon, fox, or coyotethat bites without provocation is considered to be rabid andtreatment is commencedIf the animal is captured, brain samples, and other tissuesare examined for verification of rabiesIn an apparently healthy dog or cat they are quarantined for10 days for observationFollowing an animal bite the wound should be scrupulouslywashed with soap or detergent and water, followed bydebridement and application of an antiseptic that inactivatesthe virus ( alcohol or peroxide )Combination of passive and active postexposure immunizationis very effective: wound is infused with ( HRIG) human rabiesimmunoglobulin to impede spread of virus , also injected IM-a full course of (HDCV) is given simultaneously
119 CONCEPT QUESTIONS - Is the rabies virus morphology distinctive ? -Define: rabies- Mention the epidemiologic feature of rabies virus.- What is sylvanic rabies, and whatis urban rabies ?- What are the of rabies virus transmission ?-Describe infection and disease development of rabies.- Mention the cliniocal phases of rabies .- Enumerate the forms of rabies .-Mention the lab. Criteria most diagnostic to rabies.- Define negri bodies.- What are the measures that effectively prevent rabies?- What are thew postexposure prophylaxis ?
120 OTHER ENVELOPED RNA VIRUSES Arboviruses: viruses spread by arthropod vectors: includes members of several virus families( see table): named according to place of discovery* rubella virus : only member of the genusRubiviridae that is also a member of theTogaviridae family: not an arbovirus because it istransmitted from person to person
121 FAMILY STRUCTURAL CHARACTERIS- TICS GENUS EXAMPLES ( virus ) Togviridae+ RNAenvelopedAlphavirusesEastern equine encephalitis;Western equineencephalitis;California equine encepha-litis; Venezeluan equine encephalitisFlaviviridaeFlavivirusesYellowfever ; Dengue;St. Louis encephalitis;Japanese B encephalitis;Central European ence-PhalitisBunyaviridae- RNABunyavirusesPhlebovirusesNairovirusesCalifornia encephalitis;Lacross encephalitis;Sandfly feverCrimean-Congo hemorrhagic feverReoviridaeSegmented, doubleStranded RNA, nakedOrbivirusesColorado tick fever
122 ArbovirusesThese viruses multiply inside the vertebrate host as well as the vector .The vector transmits the disease to human and other mammals , through the bite .Man generally plays no role in the natural history of arboviruses .Humans are not the natural reservoir for the virus .
123 Arboviruses associated with hemorrhagic fever . 1- Dengue virus . Family: Flaviviridae . 2- Yellow fever virus . family : Flaviviridae . 3- Rift valley fever virus . Family : Bunyaviridae . 4- Crimean congo hemorrhagic fever virus .
124 Arboviruses with hemorrhagic fever 2- yellow fever :Geographical distribution : Africa and South America .Vector : Mosquitoes .Vertebrate host : Human , monkeys.Symptoms: Most cases are mild or asymptomatic .The severe form of the disease is characterized by fever, myalgia, arthralgia, nausea, vomiting, jaundice, mucosal bleeding, bleeding under the skin, vomiting blood, seizures and coma .
125 Yellow fever cycle . 1- Jungle yellow fever : Involves transmission between mosquitoes and non-human primate, with human as accidental host.2- Urban yellow fever :Involves transmission between mosquitoes and human
127 Rift valley fever .3- Meningoencephalitis : fever, severe headache, stiffness of neck, back pain, hallucination. Mental confusion, lack of coordination, convulsions and coma .Transmission :By direct contact with infected animal blood or tissue .Through the bite of mosquitoes.Human to human transmission has not been documented..
128 Arboviruses associated with hemorrhagic fever 4- Crimean Congo H F :Geog. Dist. : Africa, Asia and middle east .Vector : Ticks .Vertebrate host : Sheep, goats , cattle and human .Symptoms : Most cases are mild or asymptomatic .In severe cases, the symptoms are : fever, headache, myalgia, artheralgia, nausea, vomiting, mucosal bleeding and bleeding under the skin .
129 The major arboviruses pathogenic to man: 1. Togaviruses ( Alphavirus)2. Flavivirus3. Bunyaviruses ( Bunyavirus and Phlebovirus )4. Reoviruses ( Orbivirus )The chief vectors ( bloodsucking arthropods ) :a. mosquitosb. ticksc. fliesd. gnats
130 Most types of illness caused by the virus: a. mild undifferentiated feversb. some would cause severe encephalitidesc. some would cause life-threatening hemorrhagic feversGeneral characteristics of Arbovirus Infections :sudden , unexpected epidemics, sometimes with previouslyunreported viruses are due to the uncertain nature of hostand viral cycles- travelers entering endemic areas are at special riskbecause, unlikethe natives of that region,they have no immunity to theviruses
131 Arboviruses ( con’t )The influence of the Vector:- activity and distribution of arboviruses closely tied toecology of vectors- factors to consider: a. longevity of the arthropodb. availability of breeding sitesc. climactic influence ( temp. &humidity )Epidemiology of arbovirus disease:- worldwide distribution ( being arthropod-borne )- vectors and viruses tend to be clustered in the tropics andsubtropics- many temperate zones report periodic epidemics- vertebrate host : recovers vector: carries virus for life
132 PATHOGENESIS :* infected vector bites -> virus injected into capillary circulation-> viral replication in vascular endothelium -> viremia ( precedes onsetof clinical symptoms ) -> circulating virus reaches the organ for whichit has special tropismex. liver ( yellow fever virus ) ; brain ( encephalitis virus )1. incubation period : short ( 1 week ) because virusesare introduced directly into the bloodstream2. morbilliform rash – secondary to :a. endothelial cell damage* if severe and disseminated : rash becomes hemorrhagicand involves the mucous membranes, GIT mucosaand skin* may lead to disseminated intravascular coagulation( DIC ) and thrombocytopeniab. increased vascular permeability
133 maculopapular rash and usually benign CLINICAL SYNDROMES:I. Febrile Illness :- of undifferentiated type with or without amaculopapular rash and usually benignA. infections typified by dengue fever and Colorado tickfever:( 1 ) mild, and self-limited, with no sequelae( 2 ) fever of up to 40o C, prostration, headache,myalgia , orbital pain, muscle aches, and jointstiffness( 3 ) midway thru the illness, a maculopapular orpetechial rash may erupt over trunk and limbs
134 II. Encephalitis:( invasion of brain, meninges and spinal cord ) - caused by alphaviruses, flaviviruses, bunyavirusesa). exemplified by Western equine, eastern equine, St. Louis,and California encephalitisb). viruses cycle between wild animals ( primarily birds )and mosquitos or ticks – humans are not the reservoir hostsc). begins with an arthropod bite release of virus intotissues replication in nearby lymphaticsprolonged viremia establishes virus in brain ->swelling and inflammation causes damage to various nucleiand tracts including the meningesd). symptoms : ( variable ), may include coma, convulsions,paralysis, tremors, rigidity, loss of coordination, palsies,memory deficits, changes in speech and personality,and heart damage.e). survivors may have permanent brain damage ( youngchildren and very old patients )
135 III. Hemorrhagic Fevers a. flu-like syndrome ( mild cases )- fever, chills, headache, backache, nausea,vomitingb. extensive hemorrhage ( severe cases ) in mucousmembranes of nose, GIT , bladder- melanemesis ( vomiting of digested blood )- decrease in pulse pressure accompanied by aparadoxical decrease in pulse rate- jaundice/proteinuria- certain arboviruses can disrupt vascular bed which can cause sudden localized bleeding in the tissues leading to shock or death ( e.g. yellow fever and dengue fever viruses )
136 exact mechanisms of pathology are obscure : the virus causes capillary fragility and disrupts the blood clottingmechanismsthese “ hemorrhagic syndromes” are caused by a variety ofviruses, carried by variety of vectors, and are distributedgloballyreservoir animals: small mammals: yellow fever and dengue fever can beharbored in human population
139 Single-stranded RNA, + strand, enveloped AlphavirusAlphaviruses are transmitted by arthropods; include EEE, WEERubivirus (rubella virus)
140 Single-stranded RNA, – strand, one RNA strand FilovirusEnveloped, helical virusesEbola and Marburg viruses
141 - transmitted by mosquitoes ( Aedes aegypti ) C. Dengue Fever ( DF) / Dengue Hemorrhagic Fever ( DHF ):- four serotypes ( Types 1-4 ) of dengue ( in tropics )- transmitted by mosquitoes ( Aedes aegypti )* principal mosquito vector which are adapted to breed around human dwellings ( in man made water-holding receptacles, around human habitation , in treeholes or plants close to human dwelling )( intensification of dengue transmission in tropical cities)* epidemics start often during rainy season whenAedes aegypti is most abundant
142 ( cont. Dengue )* viral replication in the mosquito takes about(1-2 weeks) then undergoes extrinsic incubation* extrinsic incubation period required before itcan transmit the virus on subsequent feedings* feeding attempts may number several times a daydepending on the availability of hosts* lifespan of mosquito is 1-4 weeks* mosquitoes sheltered indoors and bite during dayat 1-2 hour intervals in the morning and lateafternoon
143 PATHOGENESIS ( DF/ DHF ): - self-limited dengue is the usual outcome of infection- an immunopathologic response in some patientsusually in the setting of a heterologous immunityproduces the syndrome DHF-DSSInfectious mosquito bite viral replication inlocal lymph nodes disseminates via the blood tovarious tissues (w/in 2-3 days) virus circulates in bloodin infected monocytes , B cells, an T cells (for 4-5 days)nearly all patients are viremic at the point of clinicalpresentation with fever virus cleared from bloodwithin a day after defervescence local suppressionof erythrocytic, myelocytic, and thrombocyticpoeisis( within 4-5 days)
144 - shock in DHF-DSS follows sudden extravasation of plasma into extravascular sites including pleural andabdominal cavities usually with defervescence of fever- the increase vascular permeability may be due to:1. Increased levels of soluble tumor necrosis factor2. Interferon-gamma3. Activation of the complement system- rapid, predictive reversibility of syndrome within48 hours ( with paucity of histopathologic correlation)suggests an inflammatory response causing vasculopathies- the rise of levels of neutralizing antibodies correlateswith clearance of viremia
145 - asymptomatic in 80 % of infants and children CLINICAL FEATURES:1. Dengue Fever:- acute febrile illness with headaches, musculoskeletal painand rash- asymptomatic in 80 % of infants and children- cannot be distinguished from other common childhoodinfections- in adults more severe and acute incubation period ( 4-7days) of fever, chills, severe frontal headache, retroorbitalpain scarlatiniform rash develops within (3-4 days)- virtually all cases are uncomplicated- hepatitis frequently complicates dengue fever ( deathsare rare )- vertical transmission of virus to neonates where mothershad an onset of 1o or 2o dengue fever ( 0-8 days beforedelivery) resulted in acute neonatal dengue fever
146 - may occur in individuals with heterologous dengue 2. DHF-DSS:- may occur in individuals with heterologous dengueantibody ( possibly acquired as maternal antibody orendogenously produced )- hemorrhagic phenomena and hypovolemic shock due toincreased vascular permeability and plasma leakage- clinical signs similar to DF but with defervescence within2-7 dayscondition worsens with associated :1. hypoprotenemia2. thrombocytopenia3. prolonged bleeding time4. elevated prothrombin time
147 may lead to Dengue Shock Syndrome- cyanosis, restlessness, diaphoresis, cool,clammy skin- with support, spontaneous resolution of vasculopathy and circulatory problem within2-3 days with complete recovery
148 ( cont. Dengue ) Factors responsible for occurrence of DSS: poorly understood ( ? hypersensitivity reactions )secondary Dengue infectionformation of virus antibody complexesactivation of complement systemvascular dysfunction due to complement products* due to formation of large amounts of cross-reactingantibodies at the time of second dengue infection
149 Dengue Prevention:- relies on public health and community-based A. aegypticontrol programs to remove or destroy mosquito-breedingsitesinsecticidal fogging is considered unhelpfulin sealed houses, indoor insecticide sprays should beeffectualvaccines:The most advanced is a tetravalent combinationof attenuated dengue strains that is under phaseII clinical evaluation- travelers can protect themselves by using repellents andinsecticidal sprays indoors
150 DIAGNOSIS: 1. viral isolation ( most accurate ) - most sensitive is intracebrebral inoculation of suckling mice- successful recovery from blood only before an antibodyresponse develops2. PCR- identifies the presesnce of Dengue virus and serotypes( used in specialized lanoratories )3. serum IgM in dengue infection ( within 60 days ) bya. antibody capture ELISA- preferred techniqueb. indirect immunofluorescence for IgM and IgG antibodies4. Rapid immunochromatographic test- for dengue and JE IgM and IgG* high sensitivity and specificity
151 CONCEPT QUESTIONS -Define: Arboviruses - Name the major arboviruses pathoigenic to man .The chief vectors of arboviruses include:- Most types of illnesses caused by arboviruses include:- What are the general characteristicsa of arboviruses?- Activity and distribution of arboviruses closely tied to ecology ofvectors, what factors to be considered?- Mention the epidemiologic feature of arboviruses.- Describe the pathogenesis of arboviruse with an example to each.- What are the clinical syndrome associated with arboviral infections?- Mention the characters , members and mode of transmission of arbov.- Which viruses causing hemorrhagic and pulmonary syndrome associatedwith rodents?
152 What are the members of Togaviridae? - What are the characteristic of filoviruses? mention the diseases caused .-Define : Lassa fever, Ebola virus , Marburg HF, Dengue fever- What are the main epidemiologic characteristics of DHF ?- Describe the pathogenesis of DF/DHF.- In DF/DHF, what are the causes for increased vascular permeability?- What are the clinical feature of DF?-Dengue shock syndrome(DSS), how its caused ?- What are the factors responsible for occurrence of DSS?- What are the conditions that worsens DSS if associated?- What are the preventive measures of DF?- Mention the methods for diagnosis of DF/ DHF.
153 NONENVELOPED SINGLE-STRANDED RNA VIRUSES: PICORNAVIRUSES AND CALICIVIRUSES PICORNA viruses are named for their small ( pico )sizeand their RNA core.Important representatives include:1. Enterovirus2. Rhinovirus3. Cardiovirus ( infects the brain and heart in humansand other mammals)
154 Selected Characteristics of the human picornaviruses GenusRepresentative1o DiseaseEnterovirusPolioviruspoliomyeitisCoxsackievirus AFocal necrosis,myositisCoxsackievirus BMyocarditis of newbornEchovirusAseptic meningitis,enteritisEnterovirus 72Hepatitis ARhinovirusCommon ColdCardiovirusEncephalomyocarditisAphthovirusFoot and Mouth Disease
155 - an acute enteroviral infection of the spinal cord that may cause POLIOVIRUS:- an acute enteroviral infection of the spinal cord that may causeneuromuscular paralysisalso called infantile paralysis ( often affects small children)Properties :inactivated when heated at 55 degrees C for 30 minutespurified poliovirus is inactivated by chlorine concentration of0.1 ppmrequires primate-specific membrane receptor for infectionundergoes replication after attaching to viral receptors : servesboth as its own messenger RNA and as the source of geneticinformation
158 - respiratory droplets are only rarely involved Poliomyelitis:- transmission via mechanical vectors such as flies may occur- respiratory droplets are only rarely involved- has been virtually eliminated in North and South America- prevalence varies in Asia, Africa, and European countriesInfection and Disease:Ingestion of an infectious dose ( approx virions)polioviruses adsorb to receptors of mucosal cells in oropharynxand intestine viral multiplication ( preciselocation unknown but may be mucosal epithelia or lymphoidtissue) large numbers of viruses are shed into thethroat and feces and some leak into the blood
159 PolioIncubation period: 1-2 weeks4 types of infections:a. subclinical infection ( inapparent without symptoms)b. minor diseasec. aseptic, nonparalytic meningitisd. paralytic diseaseMost infections ( 95% ) are contained as a short-termasymptomatic viremiaa small number of persons will develop minor disease (withnonspecific symptoms of fever, headache, nausea, sorethroat, and myalgia )being neurotropic, it may gain access to the CNS via theblood-brain barrier -> infiltrate the motor neurons ofthe spinal cord -> invasion of nervous tissue withoutdestruction causes nonparalytic meningitis
160 Paralytic Disease:highly virulent virus + / or highly susceptible host = destructionof nervous tissue ( various degrees offlaccid paralysis )- flaccid paralysis ensue over a period of a few hours to several days- depending on the level of damage to the motor neurons of theanterior horn of the spinal cord ( occasionally, the spinal ganglia,cranial nerves,and motor nuclei) paralysis of the muscles of the legsabdomen, back, intercostals, diaphragm, pectoral girdle, and bladdermay occur.- bulbar poliomyelitis : less frequent: disintegration of the brain stem , medulla,cranial nerves: autonomic cardiorespiratory regulatorycenters, palate, pharynx, and vocal cordare affected
161 Epidemiology- has 3 serotypes; Types 1 and 3 cause the most severe formsof disease- protective capsid and lack of an envelope confer chemicalstability and resistance to acid and bile detergentsSIGNIFICANCE: the virus is capable of passing thru thegastric environment undamaged- incidence is more pronounced during the summer and fallin temperate- virus is passed within the population thru food, water, hands,and objects contaminated with feces
162 Paralytic Disease (con’t) antibodies to poliovirus: occur locally in the intestine and tonsils( secretory antibodies), and in the serumOne exposure confers lifelong immunityDIAGNOSIS:* suspected when epidemics of neuromuscular disease occurs inthe summer in temperate climates* must be differentiated from Guillain-Barre syndrome, infantbotulism, and encephalomyelitis caused by other enterovirusesCSF : increased leucocytes and proteins; glucose normal2. virus can be isolated by inoculating cell cultures with stool orthroat washings in the early part of the disease3. stage of infection demonstrated by testing serum samples forthe type and amount of antibody
164 Immune response- Infection induces antibodies with complement-fixing andneutralizing activities and they may be used retrospectivelyfor laboratory confirmation at polio infection.- There is the usually early specific IgM response, rapidlyfollowed by a much longer-lasting production of specificIgG.- Neutralizing antibodies—IgG in the blood and IgA atmucous surfaces—are important in protecting againstreinfection.- However, antibody against one of the 3 serotypes does notin general protect against the others, although there may besome cross-protection between types 1 and 2.
165 Treatment and Control of Polio: no specific therapy, treatment rests largely on alleviatingpain and sufferingrespiratory failure may require artificial ventilationsecondary pulmonary infection as a result of impairmentof swallowing and coughing may require antibioticsafter the acute febrile phase, prompt physical therapy todiminish crippling deformities and to retrain muscles
166 Prevention :vaccination is the mainstay of prevention.2 forms of vaccine currently in use:1. Salk Vacine – inactivated poliovirus vaccine ( IPV )2. Sabin Vaccine – oral poliovirus vaccine ( OPV )- both vaccines are prepared from animal cell cultures and aretrivalent ( combinations of 3 serotypes )- both vaccines are effectivein tropical countries where exposure of infants to wild virusis common, both vaccines may be givenpolio immunization must be instituted as early in life aspossible, usually four doses starting at about two months ofageadult candidates are travelers and members of the armedforces.
167 NONPOLIO ENTEROVIRUSES - commonly cause transient neonatal infections- Coxsackieviruses A and B, echoviruses, and nonpolioenteroviruses are like polioviruses in many epidemio-logic and infectious characteristics- spread thru fecal contamination- incidence is highest from late spring to early summerin temperate climates- 50 % to 80 % of enteroviral infections are subclinical,and the remainder fall into the category of“ undifferentiated febrile illness”- initial phase of infection is intestinal after which thevirus enters the lymph, blood and disseminates to otherorgans
169 Coxsackievirus & Echovirus Infection Coxsackie A virus :- Herpangina is caused by several types of Coxsackie A virus & is not related to aherpesvirus infection. Fever, sore throat, pain onswallowing, anorexia, & vomiting.The classic finding is vesicular ulcerated lesions around the soft palate & uvula
171 Coxsackievirus & Echovirus Infection Coxsackie A virus :- Hand-foot-and-mouth disease:a vesicular exanthem usually caused bycoxsackievirus A16.
172 Hand-foot-and-mouth disease caused by Coxsackie A virus.
173 Coxsackievirus & Echovirus Infection Coxsackie B virus :- Myocardial & pericardial infections(The symptoms resemble those of myocardial infarction with fever.)
174 Acute Hemorrhagic Conjunctivitis: caused by Enterovirus 70 ( responsible for tens ofmillions of cases since 1969 )a variant of coxsackie A24 causes a similar, but geographi-cally more restricted diseaseAHC first recognized in Ghana and Indonesia in 1969 andhas spread rapidly in different parts of the world ( inAfrica, some parts of Europe and Asia.)regions of Asia where it has caused epidemics include:Vietnam, Bangladesh, Thailand, Sri Lanka, Taiwan,The Philippines, Samoa, and Japanlarge-scale epidemics have occurred predominantly incrowded costal areas of tropical countries during the hot,rainy season
175 AHC:unlike most other enterovirus infections, transmission isprimarily from fingers or fomites directly to the eyeboth enterovirus 70 and coxsackie A24 can be isolatedfrom the conjunctiva early in the illnesshighly contagious and spreads rapidlycontagion is favored by crowding and unsanitary livingconditionsreuse of water for bathing and sharing of towels areimplicated as factors contributing to spread of infectionbegins abruptly, reaches its peak within 1 daymain symptoms: burning, foreign body sensation, ocularpain, photophobia, swelling of eyelids, and watery dischargesubconjunctival hemorrhage is the most distinctive featureof enterovirus infection ( much less with coxsackie)
176 more profuse in the young AHC:conjunctival edema more common in the elderly; hemorrhagemore profuse in the youngrecovery is noticeable on the 2nd or 3rd day and is completeby 10 daysComplications:1. Keratitis occasionally persists but no permanent scarringoccurs2. Motor paralysis similar to polio occurs in persons who haverecently recovered from AHC ( a rare occurrence consi-dering the number of AHC cases)* Bulbar paralysis can occur in half of the cases* CSF abnormalities are that of aseptic meningitis
177 Treatment: Symptomatic AHC:Diagnosis:- Diagnosed easily in major epidemics but may be confused withadenovirus infection causing epidemic keratoconjunctivitis insporadic cases- AHC has shorter incubation period ( 1 day) compared to 5-7 dayswith epidemic keratoconjunctivitis- Bacterial and chlamydial conjunctivitis do not cause extensiveoutbreaksLab:- Virus can be recovered from conjunctival swabs or scrapings ofpatients with AHC- Rising antibody titers in paired seraTreatment: SymptomaticPrevention: hand washing, use separate towels, sterilization of oph-thalmologic instruments
178 CONCEPT QUESTIONS-Show the main characteristics of human picornaviruses.- Mention the properties of polioviruses.- Define: poliomyelitis- Describe infection and disease of polioviruses .- Mention the 4 types of poliovirus infections.-What is the paralytic poliomyelitis ?-Mention the characters of bulbar poliomyelitis.- Show the epidemiologic feature of poliovirus.- The diagnosis of poliomyelitis include:- What are the clinical feature of poliomyelitis?- Describe the immune responses to poliovirus ionfection.- What are the steps for the treatment of poliomyelitis?-What are the prevention measures of poliomyelitis ?
179 NON-POLIO ENEROVIRUSES -What are the general properties of Coxsackie & Echo viruses?- Mention the types of infections associated with coxsackievirus A & B.- What is acute hemorrhagic conjunctivitis(AHC) ?- What are the complications associated with AHC ?Coxsackieviruses incriminated as a cause of:- What are the diagnostic methods and preventive measures of AHC?