9. At the end of session you will learnAt the end of session you will learn
• MumpsMumps has many complicationshas many complications
• Epidemic/2–5yEpidemic/2–5y
• It is preventableIt is preventable
• CongenitalCongenital RubellaRubella is dangerousis dangerous
• It is also preventableIt is also preventable
• Non gestational rubella is mildNon gestational rubella is mild
• Cl.Cl. RabiesRabies is always lethal. It is also preventableis always lethal. It is also preventable
10. IntroductionIntroduction
Mumps is a contagious d. c/by a pleomorphic RNA:Mumps is a contagious d. c/by a pleomorphic RNA:
paramyxovirusparamyxovirus
Single strainSingle strain
Incidence: 100–1k/100k/yIncidence: 100–1k/100k/y
Anyone non-immune can get itAnyone non-immune can get it
Before vax., it was common inBefore vax., it was common in
children and young adultschildren and young adults
No specific Rx: supportiveNo specific Rx: supportive
EM: Mumps virus is enveloped;EM: Mumps virus is enveloped;
variable shape. Size: 120–450 nmvariable shape. Size: 120–450 nm
11. TransmissionTransmission
• Worldwide.Worldwide. HumansHumans are theare the onlyonly hosthost
• Direct contact/droplets (coughs, sneezes or talks), fomites;Direct contact/droplets (coughs, sneezes or talks), fomites;
cups or soft drink cans, contaminated handscups or soft drink cans, contaminated hands
• IPIP ~17d (12-25d)~17d (12-25d)
• PI:PI: 2d before salivary swelling to 5d after start2d before salivary swelling to 5d after start
In immunized people most parotitis are not MIn immunized people most parotitis are not M
12. CL. FEATURESCL. FEATURES
• A multi-system viremiaA multi-system viremia
• 50%50% subclinicalsubclinical
Typical:Typical: a few days F (≥38°C), HA, myalgia, arthralgia,a few days F (≥38°C), HA, myalgia, arthralgia,
tiredness, dry mouth, anorexia: followed by swelling oftiredness, dry mouth, anorexia: followed by swelling of
salivary g.: parotids the commonest (pain, tenderness,salivary g.: parotids the commonest (pain, tenderness,
dysphagia).dysphagia). 70% unilateral; 30% bilateral70% unilateral; 30% bilateral
• 1/3 without swelling: as URTI1/3 without swelling: as URTI
• Many do not feel very illMany do not feel very ill
13. MostlyMostly mildmild in children,in children, more severe in adults with moremore severe in adults with more
complicationscomplications
PPeak:eak: aged 5–9yaged 5–9y
InIn >50%: CSF pleocytosis>50%: CSF pleocytosis but <10% have CNS symptomsbut <10% have CNS symptoms
Encephalitis and permanent neurological sequelae rareEncephalitis and permanent neurological sequelae rare
11stst
TM of preg:TM of preg: ⇑⇑ abortionabortion
Crosses placenta but no cong. malformationCrosses placenta but no cong. malformation
CL. FEATURES ..CL. FEATURES ..
14. Parotitis. Edematous swelling extends below the angle of mandibleParotitis. Edematous swelling extends below the angle of mandible
Normal
Full recess
19. SupportiveSupportive
• Analgesic, antipyretic, hot moist compressAnalgesic, antipyretic, hot moist compress
OUTBREAK CONTROLOUTBREAK CONTROL
• Exclude affected students forExclude affected students for 9d9d
• Immunize all susceptibleImmunize all susceptible
• Vax., Ig/Mumps Ig not effective in the exposedVax., Ig/Mumps Ig not effective in the exposed
• Immunization during IP: noImmunization during IP: no ⇑⇑ riskrisk
TREATMENTTREATMENT
20. ISOLATIONISOLATION
Droplet precautions untilDroplet precautions until 5d5d after onsetafter onset
• No close contact to esp. babies and weak immunityNo close contact to esp. babies and weak immunity
• Stay home for 5d. Cover mouth and nose with a tissueStay home for 5d. Cover mouth and nose with a tissue
when cough/sneeze; cough/sneeze into your upper sleevewhen cough/sneeze; cough/sneeze into your upper sleeve
or elbow, not handsor elbow, not hands
• Wash hands well and frequentlyWash hands well and frequently
• Don’t share drinks or eating utensilsDon’t share drinks or eating utensils
• Regularly clean surfaces that are touched with soap waterRegularly clean surfaces that are touched with soap water
21. MUMPS VACCINEMUMPS VACCINE
• Live-attenuated,Live-attenuated, monovalent. MMR preferredmonovalent. MMR preferred
• >95% with 1 shot.>95% with 1 shot. Outbreaks may occur:Outbreaks may occur: 22ndnd
dose for:dose for:
• primary vax. failureprimary vax. failure
• permanent immunitypermanent immunity
• MMR at 9mo. 2MMR at 9mo. 2ndnd
dose at least 1mo-1y laterdose at least 1mo-1y later
• ImmunizeImmunize beforebefore puberty.puberty. No mumps vax. after ≥50yNo mumps vax. after ≥50y
22. Adverse ReactionsAdverse Reactions
• Rare:Rare: orchitis, parotitis, LGF, allergy,orchitis, parotitis, LGF, allergy, rashrash
• Very rare:Very rare: febrile fitfebrile fit, nerve deafness, rash, aseptic, nerve deafness, rash, aseptic
meningitis, encephalitis, pruritus, purpurameningitis, encephalitis, pruritus, purpura
Precautions and C.I.Precautions and C.I.
• None in minor illnesses. IfNone in minor illnesses. If seriousserious: defer: defer
• Mild allergy to components may occur. Anaphylaxis rareMild allergy to components may occur. Anaphylaxis rare
• Children with egg allergy can be immunized but not thoseChildren with egg allergy can be immunized but not those
with anaphylaxis to eggwith anaphylaxis to egg
• Immunocompromised (HIV, cancer, steroids)Immunocompromised (HIV, cancer, steroids)
23. PregnancyPregnancy
• NoNo conception for 4w. Avoid in pregnancyconception for 4w. Avoid in pregnancy
• Vax. virusVax. virus cancan infect placenta, but not fetus; vax. in preg.infect placenta, but not fetus; vax. in preg.
has not been associated with cong. malform.has not been associated with cong. malform.
Altered ImmunityAltered Immunity
AvoidAvoid in Ca, steroid Rx., chemo-, radiation etc.in Ca, steroid Rx., chemo-, radiation etc.
Exception is HIVException is HIV
Risk of M in altered immunity isRisk of M in altered immunity is ⇓⇓ by vaccinating closeby vaccinating close
contactscontacts
Immune people do not transmit M vax. virusImmune people do not transmit M vax. virus
24. • IVIgIVIg (Kawasaki D, GBS)(Kawasaki D, GBS) can inhibit response.can inhibit response. PushPush
2 w before/3 mo after Ig or BT2 w before/3 mo after Ig or BT
CorticosteroidsCorticosteroids
• 1 mo after stopping steroids (2 mg/kg/d or >201 mo after stopping steroids (2 mg/kg/d or >20
mg/day formg/day for ≥≥14 d)14 d)
• Immunosuppression: wait 3 mo after stoppingImmunosuppression: wait 3 mo after stopping
Ig Administration
26. EPIDEMIOLOGYEPIDEMIOLOGY
• An RNA virus of Togaviridae familyAn RNA virus of Togaviridae family
• Humans only. 50% asymptomaticHumans only. 50% asymptomatic
• Direct/droplet contactDirect/droplet contact
• Mostly mildMostly mild
• Immunity from infx/vax is prolongedImmunity from infx/vax is prolonged
• IP: 2-3w (16-18 d)IP: 2-3w (16-18 d)
• PI: a few days before to 7d after rashPI: a few days before to 7d after rash
• Some CRS shed virus in NP secretions and urine for 1ySome CRS shed virus in NP secretions and urine for 1y
27. CL. MANIFESTATIONSCL. MANIFESTATIONS
Postnatal RubellaPostnatal Rubella
• MildMild
• GeneralizedGeneralized MPR, GLAPMPR, GLAP (occipital, postauricular, cx.), LGF(occipital, postauricular, cx.), LGF
• Transient polyarthritis is common in adolescents,Transient polyarthritis is common in adolescents,
especially femalesespecially females
• Encephalitis, thrombocytopenia are rareEncephalitis, thrombocytopenia are rare
28. Adenovirus and enterovirus can cause exanthem that mimics rubella. Serologic testing isAdenovirus and enterovirus can cause exanthem that mimics rubella. Serologic testing is
important if the patient is pregnantimportant if the patient is pregnant
32. Cong. Rubella Syndrome (CRS)Cong. Rubella Syndrome (CRS)
• R. in preg. can cause abortion, IUD, or a many cong.R. in preg. can cause abortion, IUD, or a many cong.
anomalies. Risk:anomalies. Risk:
• 85%85% in the first moin the first mo
• 30%30% in the 2ndin the 2nd
• 5%5% in the 3in the 3rdrd
– 4– 4thth
38. Longitudinal sclerotic striae (celeryLongitudinal sclerotic striae (celery
stalk) at metaphyses which arestalk) at metaphyses which are
irregular with dense bandsirregular with dense bands
(20%); most evident around(20%); most evident around
knees. Medulla is narrow (20%).knees. Medulla is narrow (20%).
Epiphyseal centers absentEpiphyseal centers absent
43. DIAGNOSISDIAGNOSIS
• Virus from nose, blood, urine, CSF, TSVirus from nose, blood, urine, CSF, TS
• Sp. IgM may beSp. IgM may be falsefalse--positivepositive;; confirm byconfirm by
stable/rising RIgG over several mo. (4-foldstable/rising RIgG over several mo. (4-fold ⇑⇑))
• Dx ofDx of CRSCRS after >1y of age is difficult: serology isafter >1y of age is difficult: serology is
not diagnostic, viral isolation is impossiblenot diagnostic, viral isolation is impossible
• ELISA, IFA, and latex agglutination can be doneELISA, IFA, and latex agglutination can be done
44. Exposure in PregnancyExposure in Pregnancy
• Immediate Ab test. RIgG indicates immunityImmediate Ab test. RIgG indicates immunity
• If negative do 2If negative do 2ndnd
test 3w latertest 3w later
• If negative, do 3If negative, do 3rdrd
test 3w after 2test 3w after 2ndnd
::
• still negative: no infx.still negative: no infx.
• positive 2positive 2ndnd
/3/3rdrd
: recent infx.: recent infx.
• Routine Ig is not recommendedRoutine Ig is not recommended
• Ig is given if termination is not wanted:Ig is given if termination is not wanted:
∀⇓⇓ clinical infx.clinical infx.
• but does not guarantee prevention of CRSbut does not guarantee prevention of CRS
48. ISOLATION OF HOSP. PT.ISOLATION OF HOSP. PT.
• Standard droplet precautions for 7d of rashStandard droplet precautions for 7d of rash
• Contact isolation from CRS until 1y of age, or till nose,Contact isolation from CRS until 1y of age, or till nose,
throat and urine are repeatedly negative after 3 mo of agethroat and urine are repeatedly negative after 3 mo of age
School and Child CareSchool and Child Care
• All R. are excluded for 7 d of rashAll R. are excluded for 7 d of rash
• Caregivers should avoid pregnant contactsCaregivers should avoid pregnant contacts
49. VaccineVaccine
• Live attenuated; MMR preferred. 2 shots:Live attenuated; MMR preferred. 2 shots:
• prevents primary vax. failureprevents primary vax. failure
• ~ 100% seroconversion~ 100% seroconversion
• No conception within 28 d of vax.No conception within 28 d of vax.
• Can be given with other vax.Can be given with other vax.
• H/o R is not an evidence of immunityH/o R is not an evidence of immunity
ContraindicationsContraindications:: F is not a CI. Defer in serious illnessF is not a CI. Defer in serious illness
• Administration of IG:Administration of IG:
• Altered immunity :Altered immunity :
• Corticosteroids:Corticosteroids:
50. PrecautionsPrecautions in vaccinationin vaccination
• Pregnancy.Pregnancy. Avoid. If given or preg. within 28d:Avoid. If given or preg. within 28d:
• 2% fetuses develop asymptomatic R. infx., but no cong.2% fetuses develop asymptomatic R. infx., but no cong.
defects.defects. No terminationNo termination
• Immunizing children whose contacts are pregnant isImmunizing children whose contacts are pregnant is
not a risknot a risk
• Immunized people may shed vax. virus for 28d, but noImmunized people may shed vax. virus for 28d, but no
evidence of transmissionevidence of transmission
51. Adverse Reactions of vaccioneAdverse Reactions of vaccione
• Mild LAP common. F: 5-15%Mild LAP common. F: 5-15%
• Arthralgia 25% and reactive arthritis 10% 1-3w later; moreArthralgia 25% and reactive arthritis 10% 1-3w later; more
in femalesin females
• Rash 5%Rash 5%
• ThrombocytopeniaThrombocytopenia
52. IVIGIVIG
• mmay interfere immune response. R. vax. may beay interfere immune response. R. vax. may be
given to women along with anti-Rh (D) or bloodgiven to women along with anti-Rh (D) or blood
products, but testedproducts, but tested ≥≥8 w later to see8 w later to see
seroconversionseroconversion
Altered immunityAltered immunity
• No live-virus vaccine except in HIVNo live-virus vaccine except in HIV
• Immunize the close contactsImmunize the close contacts
CorticosteroidsCorticosteroids
• 1 month after HD steroids for1 month after HD steroids for ≥≥14 days14 days
53. FDA: Indications of IVIgFDA: Indications of IVIg
• Kawasaki disease, GBS, CIDPKawasaki disease, GBS, CIDP
• ITP, Pediatric HIVITP, Pediatric HIV
• Allogeneic BM transplant, CLLAllogeneic BM transplant, CLL
• ImmunodeficienciesImmunodeficiencies
• Kidney transplant with a high Ab recipient or with an ABOKidney transplant with a high Ab recipient or with an ABO
incompatible donorincompatible donor
54. Reactive ArthritisReactive Arthritis
autoimmune A. in response to an infx. in non-articular part ofautoimmune A. in response to an infx. in non-articular part of
the body, GU or GITthe body, GU or GIT (cross-reactivity)(cross-reactivity) usually by ausually by a
bacterium ("trigger”) which is cured (commonly salmonella,bacterium ("trigger”) which is cured (commonly salmonella,
shigella, campylobacter,shigella, campylobacter, C. trachomatisC. trachomatis oror N. gonorrheae)N. gonorrheae)
• <5 joints: commonly knees or sacroiliacs; may be “additive”<5 joints: commonly knees or sacroiliacs; may be “additive”
or “migratory”or “migratory”
• It is seronegative, HLA-B27-linkedIt is seronegative, HLA-B27-linked
• Age: 20–40 y, men more. More in HIVAge: 20–40 y, men more. More in HIV
55. • RA often is coupled withRA often is coupled with Reiter's Syn. ofReiter's Syn. of arthritis,arthritis,
conjunctivitis/uveitis, and urethritis in men or cervicitis inconjunctivitis/uveitis, and urethritis in men or cervicitis in
womenwomen
• +/- mucocutaneous lesions, psoriasis-like lesions like+/- mucocutaneous lesions, psoriasis-like lesions like
circinate balanitis, and keratoderma blennorrhagicacircinate balanitis, and keratoderma blennorrhagica
• Enthesitis of Achilles T can cause heel painEnthesitis of Achilles T can cause heel pain
• Features can be incompleteFeatures can be incomplete
56.
57.
58. Man’s best friend but not vaccinatedMan’s best friend but not vaccinated
63. World Rabies Day (Sept. 28)
• …… to reduceto reduce
the sufferingthe suffering
from rabiesfrom rabies
64. At the end of session you will learnAt the end of session you will learn
• Rabies: an invariably fatalRabies: an invariably fatal encephalitisencephalitis. Only. Only
mammals affected.mammals affected. Always endemic in the wildAlways endemic in the wild
• VirusVirus descendsdescends from brain to salivary glandsfrom brain to salivary glands
• 90% are from rabid dog; bats spread it by aerosol90% are from rabid dog; bats spread it by aerosol
• It can be preventedIt can be prevented
• Bangladesh stands 2Bangladesh stands 2ndnd
in mortalityin mortality
• 100% preventable100% preventable
65. Key factsKey facts
• Globally >Globally >60,000 deaths/60,000 deaths/yy in >150 countriesin >150 countries
• 95% in Asia Africa95% in Asia Africa
• 50% children50% children
• India: (~30,000)India: (~30,000)
• Wound cleansing and immunization can prevent itWound cleansing and immunization can prevent it
• Bangladesh: mBangladesh: most people are unprotectedost people are unprotected
• Rabies costs the world $124 billion/yRabies costs the world $124 billion/y
66. What is Rabies?What is Rabies?
• .. a zoonosis c/by.. a zoonosis c/by rabiesrabies virusvirus
• Infects both domestic and wild animalsInfects both domestic and wild animals
• Causes ac. EncephalitisCauses ac. Encephalitis
Symptomatic rabies:Symptomatic rabies: 100% fatal100% fatal
67. Rhabdo/lyssa viruses
• Bullet shaped.Bullet shaped. RNARNA
• EnvelopedEnveloped
• Killed by ethanol ether,Killed by ethanol ether,
iodine, soap/detergents,iodine, soap/detergents,
chloroform, acetone,chloroform, acetone,
heat (60heat (6000
c x5 min)c x5 min)
Lyssa means rageLyssa means rage
68. Fixed and Street VirusFixed and Street Virus
• Fixed virusFixed virus (lab virus)(lab virus):: Rabies virus after serial passageRabies virus after serial passage
through rabbits to stabilize its virulence and IPthrough rabbits to stabilize its virulence and IP
• Street virus:Street virus: wild viruswild virus
IP: incubation periodIP: incubation period
69. EpidemiologyEpidemiology
• Primary reservoirs:Primary reservoirs: wild mammalswild mammals
• OnlyOnly mammalsmammals affected; exceptaffected; except mice !mice !
• ManMan, dogs, raccoons, skunks, foxes, bats, cats, cattle, dogs, raccoons, skunks, foxes, bats, cats, cattle
commonlycommonly affectedaffected
• It is endemic in many countries except Australia, Malaysia,It is endemic in many countries except Australia, Malaysia,
Japan, Bhutan, NepalJapan, Bhutan, Nepal
77. Pathogenesis ..Pathogenesis ..
• RV replicates in muscles: enters nerves and ascends toRV replicates in muscles: enters nerves and ascends to
CNS (CNS (3 mm/h)3 mm/h)
• Spread within CNS is rapidSpread within CNS is rapid
• Then spreads centrifugally by nerves to salivary g., eyes,Then spreads centrifugally by nerves to salivary g., eyes,
kidneys, breastskidneys, breasts
• This time the classic CF developThis time the classic CF develop
RV: rabies virusRV: rabies virus
82. Furious rabiesFurious rabies
• anxiety, confusion, insomnia, nervousness, seizure,anxiety, confusion, insomnia, nervousness, seizure,
aggressivenessaggressiveness, hallucinations, delirium, fear of death, hallucinations, delirium, fear of death
• biting, delusions, HGF, hyperhydrosis, goose skin, priopism,biting, delusions, HGF, hyperhydrosis, goose skin, priopism,
hypersalivation, dysphagia, hydrophobia (50%),hypersalivation, dysphagia, hydrophobia (50%),
aerophobia, photophobiaaerophobia, photophobia
• a few days later coma and deatha few days later coma and death
83. Dumb/paralytic rabiesDumb/paralytic rabies
• S/of partial/full paralysisS/of partial/full paralysis usually begins in the limbs andusually begins in the limbs and
spreads all overspreads all over
• Hydrophobia isHydrophobia is unusualunusual
• Progress to coma and death (heart or lung failure)Progress to coma and death (heart or lung failure)
84. A rabid dog displayingA rabid dog displaying
the classic form ofthe classic form of
paralytic R, cranial-paralytic R, cranial-
nerve deficits andnerve deficits and
hypersalivationhypersalivation
85. Routine rabies tests:Routine rabies tests:
• Direct fluorescent antibody test (dFA:) (only postDirect fluorescent antibody test (dFA:) (only post
mortem)mortem)
• Histopathology:Histopathology: NegriNegri bodies. Immunohistochemistrybodies. Immunohistochemistry
(IHC). EM(IHC). EM
Importance:Importance:
• For timely post-exposure prophylaxis (PEP)For timely post-exposure prophylaxis (PEP)
• Save a pt. from unnecessary physical and psycho. traumaSave a pt. from unnecessary physical and psycho. trauma
if the animal is not rabidif the animal is not rabid
Diagnosis in AnimalsDiagnosis in Animals
86. dFAdFA detects RVdetects RV
• Ideal tissue is nerve (brain)Ideal tissue is nerve (brain)
• Fl. anti-rabies Ab incubated with brain tissue fixes RV; seenFl. anti-rabies Ab incubated with brain tissue fixes RV; seen
by Fl. MC. Unbound Ab can be washed awayby Fl. MC. Unbound Ab can be washed away
IHCIHC
• Like dFA, IHC uses sp. Ab to detect RV inclusions in tissues.Like dFA, IHC uses sp. Ab to detect RV inclusions in tissues.
More sensitive than histopathologyMore sensitive than histopathology
Fl: fluorescence. MC: microscopeFl: fluorescence. MC: microscope
88. • Negri bodiesNegri bodies are pathognomonic incl. bodies in theare pathognomonic incl. bodies in the
cytoplasm of certain nerves (cytoplasm of certain nerves (only in 20%)only in 20%)
89. Rabies Dx in HumansRabies Dx in Humans
• No test available before cl. diseaseNo test available before cl. disease
• Confirmed pre- and post mortem by detecting RV, viral Ag inConfirmed pre- and post mortem by detecting RV, viral Ag in
brain, skin, urine, salivabrain, skin, urine, saliva
• Saliva is tested by reverse transcription followed by PCR (RT-Saliva is tested by reverse transcription followed by PCR (RT-
PCR)PCR)
• Antibody: serum, CSFAntibody: serum, CSF
Ag: antigenAg: antigen
90. PreventionPrevention
• Vaccinating pet and killing stray dogsVaccinating pet and killing stray dogs
• Vaccine for at risk personsVaccine for at risk persons
• No contact with stray/wild animalsNo contact with stray/wild animals
• Not touching animal carcassesNot touching animal carcasses
• Don’t capture or provoke stray animalsDon’t capture or provoke stray animals
• Secure garbageSecure garbage
• Cover chimneys and other entrancesCover chimneys and other entrances
91. • If bitten by bats, skunks, foxes, other carnivoresIf bitten by bats, skunks, foxes, other carnivores
• regard as rabid unless the area is R free or until animalregard as rabid unless the area is R free or until animal
is negative by lab testingis negative by lab testing
• immediate immunization and HRIGimmediate immunization and HRIG
• Bites by squirrels, gerbils, hamsters, G. pigs, rats, mice,Bites by squirrels, gerbils, hamsters, G. pigs, rats, mice,
other rodents, rabbits, hare almost never require anti-Rother rodents, rabbits, hare almost never require anti-R
RxRx
HRIG: human rabies immunoglobulinHRIG: human rabies immunoglobulin
PreventionPrevention
93. Who should get the vaccine?Who should get the vaccine?
Pre-exposurePre-exposure
• High-risk people:High-risk people: vets., animal handlers, R lab. workers,vets., animal handlers, R lab. workers,
spelunkers (cave explorer), forestry workers, wildspelunkers (cave explorer), forestry workers, wild
explorers,explorers, travelers in endemic areastravelers in endemic areas
• Also for: Also for: people having frequent contact with R virus,people having frequent contact with R virus,
travelers to endemic areastravelers to endemic areas
• 3 doses: 0-7-21/283 doses: 0-7-21/28thth
d d
94. Benefits of pre-exposure VaxBenefits of pre-exposure Vax
• No need of HRIGNo need of HRIG
• Less post-expo. vax. dosesLess post-expo. vax. doses
• Post exposure Rx might be delayedPost exposure Rx might be delayed
• Protects from inapparent exposures to RProtects from inapparent exposures to R
• For repeated exposure screen for boosterFor repeated exposure screen for booster
95. Post-exposurePost-exposure
• bitten by an animal, or contactbitten by an animal, or contact
• 4 doses: 0-3-7-144 doses: 0-3-7-14thth
daysdays
• They should also get HRIG with first dose vax.They should also get HRIG with first dose vax.
• Pre-vaccinated person get 2 doses: 0-3Pre-vaccinated person get 2 doses: 0-3rdrd
d; no HRIGd; no HRIG
• Should the animal be kept for 10 d?Should the animal be kept for 10 d?
98. Future Rabies VaccinesFuture Rabies Vaccines
• Vaccines under development may be safe, potent andVaccines under development may be safe, potent and
cheapercheaper
• DNA vaccinesDNA vaccines, recombinant vaccines, recombinant vaccines
• Plant biotechnology for making AgPlant biotechnology for making Ag
• Neutralizing monoclonal antibodyNeutralizing monoclonal antibody
99. Adverse ReactionsAdverse Reactions
• Less in childrenLess in children
• Adults: local reactions (25%), systemic- (20%)Adults: local reactions (25%), systemic- (20%)
• HA, nausea, AP, aches and dizziness (5-40%)HA, nausea, AP, aches and dizziness (5-40%)
• Very rare:Very rare: illness like GBSillness like GBS
• Immune-complex with boosters: hives, arthralgia, F (6%)Immune-complex with boosters: hives, arthralgia, F (6%)
• Different brands differDifferent brands differ
• Anaphylaxis, if any, occurs within a min- to an hr. withAnaphylaxis, if any, occurs within a min- to an hr. with
dyspnoea, hoarseness, wheeze, throat swelling, hives,dyspnoea, hoarseness, wheeze, throat swelling, hives,
pallor, weakness, tachycardia, or dizzinesspallor, weakness, tachycardia, or dizziness
100. Human Rabies IG (HRIG)Human Rabies IG (HRIG)
• Category iii bite: 20iu/kgCategory iii bite: 20iu/kg
with vax. but different siteswith vax. but different sites
• ½ at the site (infiltrate the½ at the site (infiltrate the
wound); ½ IMwound); ½ IM
101. Basic Care in Animal BitesBasic Care in Animal Bites
• Immediate thorough toileting x15min with soapImmediate thorough toileting x15min with soap
water, detergent, povidone iodine.water, detergent, povidone iodine. Don't suture!Don't suture!
• Categorize the bite:Categorize the bite:
• Post- exposure prophylaxisPost- exposure prophylaxis
102.
103. CategoryCategory -- WHOWHO
• Category I: 1.Category I: 1. touching/feeding suspect animalstouching/feeding suspect animals
2.2. licks on intact skinlicks on intact skin
• Category II: 1.Category II: 1. nibbling of skinnibbling of skin
2.2. scratches/abrasionsscratches/abrasions, but no hge., but no hge.
3.3. licks on broken skinlicks on broken skin
• Category III:Category III: 1 or more1 or more bites/scratches, licks with hge.;bites/scratches, licks with hge.;
contamination of m. membrane with saliva, contactscontamination of m. membrane with saliva, contacts
with batswith bats
104. Category ICategory I
no treatmentno treatment
Category IICategory II
wound disinfection, vaccine onlywound disinfection, vaccine only
105. Category IIICategory III
wound cleansing, HRIG and vaccinewound cleansing, HRIG and vaccine
• Animal observation in our country is not practical:Animal observation in our country is not practical:
frequent bitesfrequent bites
• Delay Rx only ifDelay Rx only if
• Species unlikely to be infectedSpecies unlikely to be infected
• Lab Dx in 48hrLab Dx in 48hr
• Dog >1yr old with current vaccination (observe forDog >1yr old with current vaccination (observe for
10d)10d)
109. • To date only 6 cases survivedTo date only 6 cases survived
• Once clinical, rabies is always fatal, Rx is only supportiveOnce clinical, rabies is always fatal, Rx is only supportive
• Rabies typically ends after 2-10 d (6d)Rabies typically ends after 2-10 d (6d)
No danger of nursing R pts with precautionsNo danger of nursing R pts with precautions
PrognosisPrognosis
111. Shots for Dogs Would Save People in DCsShots for Dogs Would Save People in DCs
• Mass vaccination for dogs could eliminate it in humanMass vaccination for dogs could eliminate it in human
• R is rare in HICs (widespread vaccination of dogs)R is rare in HICs (widespread vaccination of dogs)
• Lack of international commitment is among the reasonsLack of international commitment is among the reasons
why rabies in people persistswhy rabies in people persists
112. MCQMCQ
• Most rabies are from bite by rabid dogsMost rabies are from bite by rabid dogs
• Most of rabid-dog bites develop into rabiesMost of rabid-dog bites develop into rabies
• HDCV is at present the best ARVHDCV is at present the best ARV
• Rabies is not transmitted by contaminated corneal graftRabies is not transmitted by contaminated corneal graft
• Rabies is always endemic in the forestRabies is always endemic in the forest
113. MCQMCQ
• Vaccinating pet dogs is essential to control rabiesVaccinating pet dogs is essential to control rabies
• Everyone should be vaccinated against rabiesEveryone should be vaccinated against rabies
• Rabies virus spread to CNS via bloodRabies virus spread to CNS via blood
• It can be transmitted by foodIt can be transmitted by food
• Saliva contains R virus after brain involvementSaliva contains R virus after brain involvement
• Rabies can be eradicatedRabies can be eradicated
Most viral meningitis are c/by enteroviruses; but only a small number of enterovirus cause it. Others include mumps, EBV, HSV, VZV, measles, influenza, arboviruses. In rare cases LCMV, which is spread by rodents, can cause viral meningitis
Mikulicz syn: a chr. enlarged salivary and lachrymal glands with xerostomia, dry eyes. The tonsils and LN may be involved. Almost always benign but always occurs with another d like TB, leukemia, syphilis, Hodgkin‘s, lymphoma, Sjogren , SLE. Pts. are at risk for lymphomas. Some may have recurring F and uveitis. Cause unknown. It may be a form of Sjogren. SS may be persistent or frequently recurrent; are v similar to those of Sjögren. It may be autoimmune with excessive accumulation of lymphocytes into affected glands.Affects more F and mostly in middle adult years. DD: Mumps, Heerfordt&apos;s Syn, aka Uveoparotid F, Sarcoidosis. and paralysis of one or more of the CN. The nerves of the face are most commonly affected.Sjogren Syndrome is an autoimmune disorder characterized by the progressive degeneration of mucous secreting glands, especially those of the mouth (salivary) and eyes (lacrimal). The symptoms of Sjogen Syndrome usually begin suddenly and may include inflammation of the membranes that surround the eyes and the corneas (keratoconjunctivitis). Varying degrees of dryness in the mouth (sicca xerostomia) may cause difficulty swallowing and/or dental disease. (For more information on this disorder, choose &quot;Sjogren&quot; as your search term in the Rare Disease Database.)Swelling of the glands in front of the ears (parotid swelling) may occur for many different reasons. Painless swelling on both sides of the face may occur without fever and in association with other disorders such as Laennec&apos;s Cirrhosis, chronic alcoholism, malnutrition, diabetes mellitus, pregnancy, lactation, and/or Hypertriglyceridemia. Malignant and benign salivary gland tumors can also cause swelling of the salivary glands. Parotid gland enlargement may also be related to the use of certain drugs (e.g., guanethidine or iodine). Obstruction of the duct from the parotid gland to the mouth (Stensen&apos;s duct) by a stone (calcification) can also cause swelling of the parotid gland.
Standard Therapies
Biopsy of one of the swollen glands is key to the diagnosis of Mikulicz syndrome. An ultrasound examination of the area may help to rule out other reasons for gland swelling. Treatment of this disorder is symptomatic. Medical therapies are more productively directed toward the treatment of any underlying disease. Artificial tears may be used to maintain moisture in the eyes, and artificial saliva may be used to treat oral symptoms.Some individuals with Mikulicz syndrome may be instructed to follow a soft moist diet. This may help to reduce the pain caused by chewing and swallowing. Other treatment is symptomatic and supportive..
Investigational Therapies
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
Synonyms: Dacryosialoadenopathia
Dacryosialoadenopathy
Mikulicz Syndrome
Mikulicz-Radecki Syndrome
Mikulicz-Sjogren Syndrome
von Mikulicz
Usually clinical, in particular the swelling of parotids. If you have mumps, your GP can see and feel the swelling. By looking inside your mouth, they may be able to see that your tonsils have been pushed out of their usual position.
Your GP can also check your temperature to see if it is higher than normal.
If your GP suspects mumps, they should notify your local health protection unit (HPU). The HPU will arrange for a sample of your saliva to be tested to confirm or rule out the diagnosis
PI: period of infectivity
Young adult with post-rubella thrombocytopenic purpura with large &quot;blueberry muffin&quot; skin lesions
BM: bone marrow. MR: mental retardation
HSM: hepatosplenomegaly. BM: bone marrow
CXR: mild cardiomegaly and slightly enlarged P arteries. The cardiac apex points downward and laterally, suggesting LV enlargement. Note inhomogeneous density of the proximal metaphyses of both humeri
XR of the lower limbs: longitudinal striation of sclerotic and radiolucent areas (celery stalk appearance) at the metaphyses. The changes are most pronounced around the knees. The epiphyseal centers are not seen. Note dense metaphyseal bands, irregularity of the metaphyses, and narrowing of the medullary cavities
4-y boy with CRS with unilateral microphthalmos and cataract in the L eye
CXR of an infant with CRS pneumonia with HSM
Infant boy with CRS with microcephaly.
Vaccine
Live vax.: RA 27/3 strain grown in human diploid cell cultures
Pushed s.c. 0.5 ml preferably as MMR
Can be given with other vax
Seroconversion: &gt;95% after 1 dose
As 2 doses needed for measles, 2 doses for rubella vax. (as MMR) given. This safeguards against primary vax. failure
Live rubella vax. theoretically could prevent illness if pushed within 3 days of exposure
Immunization of a person who is incubating rubella or immune does not adverse effects
Keratoderma Blenorrhagicum are skin lesions commonly found on the palms and soles but which may spread to the scrotum, scalp and trunk, resembling psoriasis. KB is commonly seen as an additional feature of reactive arthritis in 15% of male. The lesions are yellow-brown vesico-pustular and waxy. They may coalesce to form larger crusty plaques with desquamating edges
Bats possible source of rabies
The R virus can infect all mammals except mice
The reservoirs vary based on geographic location; commonly dogs, bats, raccoons, foxes, cats, and skunks.
The primary cause of human rabies worldwide is from dogs
In the US, dogs are vaccinated, the primary c/of R in humans is from wildlife (particularly bats)
Transmission
Transmission of rabies virus usually begins when infected saliva of a
host is passed to an uninfected animal. Various routes of transmission
have been documented and include contamination of mucous membranes (i.e.,
eyes, nose, mouth), aerosol transmission, and corneal transplantations.
The most common mode of rabies virus transmission is through the bite
and virus-containing saliva of an infected host.
Following primary infection (see Figure, numbers 1 & 2), the virus enters an
eclipse phase in which it cannot be easily detected within the host. This
phase may last for several days or months. Investigations have shown both
direct entry of virus into peripheral nerves at the site of infection
and indirect entry after viral replication in nonnervous tissue (i.e.,
muscle cells). During the eclipse phase, the host immune defenses may
confer cell-mediated immunity against viral infection because rabies virus
is a good antigen . The uptake of virus into peripheral nerves is important
for progressive infection to occur (see Figure, number 3).
After uptake
into peripheral nerves, rabies virus is transported to the central nervous
system (CNS) via retrograde axoplasmic flow. Typically this occurs via
sensory and motor nerves at the initial site of infection. The incubation
period (see figure, number 4) is the time from exposure to onset of clinical
signs of disease. The incubation period may vary from a few days to several
years, but is typically 1 to 3 months. Dissemination of virus within the
CNS is rapid, and includes early involvement of limbic system neurons
(see Figure, number 5). Active cerebral infection is followed by passive
centrifugal spread of virus to peripheral nerves. The amplification of
infection within the CNS occurs through cycles of viral replication and
cell-to-cell transfer of progeny virus. Centrifugal spread of virus may
lead to the invasion of highly innervated sites of various tissues, including
the salivary glands. During this period of cerebral infection, the classic
behavioral changes associated with rabies develop.
Pathology
Pathology of rabies infection is typically defined by encephalitis and
myelitis. Perivascular infiltration with lymphocytes, polymorphonuclear
leukocytes, and plasma cells can occur throughout the entire CNS. Rabies
infection frequently causes cytoplasmic eosinophilic inclusion bodies
(Negri bodies) in neuronal cells, especially pyramidal cells of the hippocampus
and Purkinje cells of the cerebellum. These inclusions have been identified
as areas of active viral replication by the identification of rabies viral
antigen.
Several factors
may affect the outcome of rabies exposure. These include the virus variant,
the dose of virus inoculum, the route and location of exposure,as well
as individual host factors, such as age and host immune defenses.
Hydrophobia is a set of symptoms in later stages of R: difficulty swallowing, panic when presented with liquids to drink, and the pt. can&apos;t quench its thirst
Aerophobia: pathological aversion or sensitivity to air or its movement, especially as a symptom of R.
Rabies diagnosis in humans
The importance of routine rabies tests
Essential characteristics for routine rabies tests
Laboratory tests for rabies
Direct fluorescent antibody test (dFA)
Antigen detection by dFA
General histopathology
Negri bodies
Immunohistochemistry (IHC)
Ultrastructure Amplification methods
New standard DFA protocol for rabies
Rabies diagnosis in animals
The direct fluorescent antibody test (dFA) is the test most frequently used to diagnose rabies. This test requires brain tissue from animals suspected of being rabid. The test can only be performed post-mortem
Rabies diagnosis in humans
Several tests are necessary to diagnose rabies ante-mortem (before death) humans; no test sufficient. Tests are performed on samples of saliva, serum, CSF, and skin biopsies of hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and spinal fluid are tested for antibodies to rabies virus. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles.
The importance of routine rabies tests
Rapid and accurate laboratory diagnosis of rabies in humans and other animals are essential for timely administration of postexposure prophylaxis.
Within a few hours, a diagnostic laboratory can determine whether or not
an animal is rabid and inform the responsible medical personnel. The laboratory
results may save a patient from unnecessary physical and psychological
trauma, and financial burdens, if the animal is not rabid.
In addition, identification of positive rabies cases may aid in defining current epidemiologic patterns of disease and provide appropriate information
for the development of rabies control programs.
Essential characteristics for routine rabies test
The nature of rabies disease dictates that laboratory tests be standardized,
rapid, sensitive, specific, economical, and reliable.
Laboratory tests for rabies
The standard test for rabies testing is dFA. This test has been thoroughly
evaluated for more than 40 years, and is recognized as the most rapid
and reliable of all the tests available for routine use. All rabies laboratories
in the United States perform this test (post-mortem) on animals suspected
of having rabies. Other tests for diagnosis and research, such as electron microscopy (EM), histologic examination, immunohistochemistry (IHC), RT-PCR, and isolation in cell culture are useful tools for studying the virus structure, histopathology, typing, and virulence of rabies viruses.
Direct fluorescent antibody test (dFA)
The dFA test is based on the observation that animals infected by rabies virus
have rabies virus proteins (antigen) present in their tissues. Because
rabies is present in nervous tissue (and not blood like many other viruses),
the ideal tissue to test for rabies antigen is brain. The most important
part of a dFA test is flouresecently-labelled anti-rabies antibody.
When labelled antibody is incubated with rabies-suspect brain tissue,
it will bind to rabies antigen. Unbound antibody can be washed away and
areas where antigen is present can be visualized as fluorescent-apple-green
areas using a fluorescence microscope. If rabies virus is absent there
will be no staining.
Antigen detection by dFA
The rabies antibody used for the dFA test is primarily directed against
the nucleoprotein (antigen) of the virus (see The Virus section on viral structure). Rabies virus replicates in the cytoplasm of cells, and infected cells may contain large round or oval inclusions containing collections of nucleoprotein (N) or smaller collections of antigen that appear as dust-like fluorescent particles if stained by
the dFA procedure.
Rabies diagnosis in humans
The importance of routine rabies tests
Essential characteristics for routine rabies tests
Laboratory tests for rabies
Direct fluorescent antibody test (dFA)
Antigen detection by dFA
General histopathology
Negri bodies
Immunohistochemistry (IHC)
Ultrastructure Amplification methods
New standard DFA protocol for rabies
Rabies diagnosis in animals
The direct fluorescent antibody test (dFA) is the test most frequently used to diagnose rabies. This test requires brain tissue from animals suspected of being rabid. The test can only be performed post-mortem
Rabies diagnosis in humans
Several tests are necessary to diagnose rabies ante-mortem (before death) humans; no test sufficient. Tests are performed on samples of saliva, serum, CSF, and skin biopsies of hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and spinal fluid are tested for antibodies to rabies virus. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles.
The importance of routine rabies tests
Rapid and accurate laboratory diagnosis of rabies in humans and other animals are essential for timely administration of postexposure prophylaxis.
Within a few hours, a diagnostic laboratory can determine whether or not
an animal is rabid and inform the responsible medical personnel. The laboratory
results may save a patient from unnecessary physical and psychological
trauma, and financial burdens, if the animal is not rabid.
In addition, identification of positive rabies cases may aid in defining current epidemiologic patterns of disease and provide appropriate information
for the development of rabies control programs.
Essential characteristics for routine rabies test
The nature of rabies disease dictates that laboratory tests be standardized,
rapid, sensitive, specific, economical, and reliable.
Laboratory tests for rabies
The standard test for rabies testing is dFA. This test has been thoroughly
evaluated for more than 40 years, and is recognized as the most rapid
and reliable of all the tests available for routine use. All rabies laboratories
in the United States perform this test (post-mortem) on animals suspected
of having rabies. Other tests for diagnosis and research, such as electron microscopy (EM), histologic examination, immunohistochemistry (IHC), RT-PCR, and isolation in cell culture are useful tools for studying the virus structure, histopathology, typing, and virulence of rabies viruses.
Direct fluorescent antibody test (dFA)
The dFA test is based on the observation that animals infected by rabies virus
have rabies virus proteins (antigen) present in their tissues. Because
rabies is present in nervous tissue (and not blood like many other viruses),
the ideal tissue to test for rabies antigen is brain. The most important
part of a dFA test is flouresecently-labelled anti-rabies antibody.
When labelled antibody is incubated with rabies-suspect brain tissue,
it will bind to rabies antigen. Unbound antibody can be washed away and
areas where antigen is present can be visualized as fluorescent-apple-green
areas using a fluorescence microscope. If rabies virus is absent there
will be no staining.
Antigen detection by dFA
The rabies antibody used for the dFA test is primarily directed against
the nucleoprotein (antigen) of the virus (see The Virus section on viral structure). Rabies virus replicates in the cytoplasm of cells, and infected cells may contain large round or oval inclusions containing collections of nucleoprotein (N) or smaller collections of antigen that appear as dust-like fluorescent particles if stained by
the dFA procedure.
Despite evidence that control of dog rabies through programs of animal vaccination and elimination of stray dogs can reduce the incidence of human rabies, exposure to rabid dogs is still the cause of over 90% of human exposures to rabies and of over 99% of human deaths worldwide.
Spelunkers: cave explorers
Purpose of PrEP: First, although it does not eliminate the need for additional medical attention after a exposure, it simplifies therapy by eliminating the need for HRIG and decreasing the number of vaccine doses needed – a point of particular importance for persons at high risk of being exposed to rabies in areas where immunizing products may not be available, and it minimizes SE to multiple doses of vaccine.
Second, it may enhance immunity in persons whose postexposure Rx might be delayed.
Finally, it may provide protection to persons with inapparent exposures to rabies.
It consists of 3 doses: on days 0, 7, and 21 or 28
RIG: Rabies Immune Globulin
Vero cells are used in cell cultures; first isolated from kidney epith cells from an African green monkey in 1962
They are used for: screening toxin of E coli (&quot;Vero toxin“ or &quot;Shiga-like toxin“), for growing virus; testing for rabies virus, growth of viral stocks for research purposes, host cells for eukaryotic parasites. The Vero cell lineage is continuous and aneuploid meaning an abnormal number of chromosomes. Vero cells are interferon-deficient; they do not secrete interferon when infected by viruses though they have Interferon receptor
Local treatment of the wound: Removing the RV at the site by chemical or physical means is an effective means of protection, prompt local treatment of all bite wounds and scratches that may be contaminated with RV is important. Immediate and thorough flushing and washing of the wound for a minimum of 15 min with soap and water, detergent, povidone iodine or other substances that kill the rabies virus
Signs and symptoms
The first symptoms of rabies may be nonspecific flu-like signs —
malaise, fever, or headache, which may last for days. There may be discomfort
or paresthesia at the site of exposure (bite), progressing within days
to symptoms of cerebral dysfunction, anxiety, confusion, agitation, progressing
to delirium, abnormal behavior, hallucinations, and insomnia. The acute
period of disease typically ends after 2 to 10 days (6). Once clinical
signs of rabies appear, the disease is nearly always fatal, and treatment
is typically supportive. Disease prevention is entirely prophylactic and
includes both passive antibody (immune globulin) and vaccine. Non-lethal
exceptions are extremely rare. To date only six documented cases of human
survival from clinical rabies have been reported and each included a history
of either pre- or postexposure prophylaxis.