1713 1713 AD AD to to Smallpox 1796 Smallpox 1796 AD to Measles AD AD to Measles AD 1963-What 1963-What to do or not to do and if to do or not to do and if given, how to do given, how to do it safely it safely . . James M. Oleske, MD, MPH James M. Oleske, MD, MPH François-Xavier Bagnoud Professor François-Xavier Bagnoud Professor of Pediatrics of Pediatrics Director, Division of Pediatrics Director, Division of Pediatrics Allergy, Immunology & Infectious Allergy, Immunology & Infectious Diseases Diseases Peter Wenger MD FAAP, FIDSA Peter Wenger MD FAAP, FIDSA Department of Pediatrics, New Department of Pediatrics, New
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The History of Prevention of The History of Prevention of EpidemicsEpidemics: : RinderpestRinderpest 17131713 ADAD toto Smallpox 1796 AD to Smallpox 1796 AD to Measles ADMeasles AD 1963-What to 1963-What to
do or not to do and if given, do or not to do and if given, how to do it safelyhow to do it safely. .
James M. Oleske, MD, MPHJames M. Oleske, MD, MPH
François-Xavier Bagnoud Professor of François-Xavier Bagnoud Professor of PediatricsPediatrics
Director, Division of Pediatrics Allergy, Director, Division of Pediatrics Allergy, Immunology & Infectious Diseases Immunology & Infectious Diseases
Peter Wenger MD FAAP, FIDSA Peter Wenger MD FAAP, FIDSA
Department of Pediatrics, New Jersey Department of Pediatrics, New Jersey Medical School, Newark, New Jersey Medical School, Newark, New Jersey
Eradication of Rinderpest-Eradication of Rinderpest-95% Infection fatality Rate 95% Infection fatality Rate
in cloven-footed beastsin cloven-footed beasts 17131713• Pope Clement XI asked Dr. Giovanni Lancisi to stop Pope Clement XI asked Dr. Giovanni Lancisi to stop
outbreak in papal herdsoutbreak in papal herds Charlatan cures bannedCharlatan cures banned Priests ordered to preach from their pulpitsPriests ordered to preach from their pulpits
• All herds with sick members slaughtered and buried All herds with sick members slaughtered and buried in limein lime
• Isolate healthy herdsIsolate healthy herds Laymen found resistant or cheatingLaymen found resistant or cheating
• Hanged and drawn and quarteredHanged and drawn and quartered Disobeying priests were imprisoned for lifeDisobeying priests were imprisoned for life
• Within 9 months the outbreak ended in Papal statesWithin 9 months the outbreak ended in Papal states It persisted for 100 years with >200 million dead cattle It persisted for 100 years with >200 million dead cattle
in Protestant sectorsin Protestant sectors
Eradication of Eradication of Rinderpest : A Costly Rinderpest : A Costly
SuccessSuccess By the 1750’s crude “vaccine” used in By the 1750’s crude “vaccine” used in England and Netherlands: 50 years England and Netherlands: 50 years before Jenner !before Jenner !
1761 first school of veterinary 1761 first school of veterinary medicine founded in Lyon, Francemedicine founded in Lyon, France
1924 creation of the World 1924 creation of the World Organization for Animal Health in Organization for Animal Health in response to a devastating European response to a devastating European outbreakoutbreak
1950’s Rinderpest was eradicated in 1950’s Rinderpest was eradicated in China utilizing Lancisi’s measures: China utilizing Lancisi’s measures: Uncooperative farmers were “only” Uncooperative farmers were “only” imprisoned !imprisoned !
single-stranded RNA single-stranded RNA virusvirus• Six identified Six identified
structural proteins: 3 structural proteins: 3 complexed with RNA complexed with RNA to form nucleocapsid to form nucleocapsid P, L, N protein and 3 P, L, N protein and 3 complexed with viral complexed with viral envelope (F, H, and M envelope (F, H, and M proteins)proteins)
immunization protects against all strainsimmunization protects against all strains Molecular sequencing can distinguish Molecular sequencing can distinguish between wild-type and vaccine-virusbetween wild-type and vaccine-virus
Measles Epidemiology Measles Epidemiology 11 Humans are the only natural hostsHumans are the only natural hosts
• No animal reservoirsNo animal reservoirs Highly contagiousHighly contagious
• Attack rate in susceptible household Attack rate in susceptible household contacts: 75%-90%contacts: 75%-90%
• Direct contact with infectious respiratory Direct contact with infectious respiratory secretionssecretions Large respiratory droplets and droplet Large respiratory droplets and droplet nucleinuclei•Lingers for at least 2 hoursLingers for at least 2 hours•Requires airborne precautionsRequires airborne precautions
Nasopharynx and conjunctivaNasopharynx and conjunctiva Most infectious in prodromal period Most infectious in prodromal period
•Before rash onsetBefore rash onset
Measles Epidemiology 2Measles Epidemiology 2 Incubation period: 8-12 daysIncubation period: 8-12 days Contagious period: 1-2 days before symptom onset (3-Contagious period: 1-2 days before symptom onset (3-
5 days before rash) to 4 days after rash appearance 5 days before rash) to 4 days after rash appearance • Immunocompromised patients may demonstrate Immunocompromised patients may demonstrate
prolonged excretion of virusprolonged excretion of virus Peak incidence in temperate regions is late winter and Peak incidence in temperate regions is late winter and
Pre-vaccine eraPre-vaccine era• Pre-school and young school age childrenPre-school and young school age children• Few susceptible by 20 years of ageFew susceptible by 20 years of age
Immunity appears to be lifelongImmunity appears to be lifelong• Wild-type infection or vaccine-inducedWild-type infection or vaccine-induced• Primary vaccine failure (≥12 months) ~5%Primary vaccine failure (≥12 months) ~5%
Most infections in previously immunized children Most infections in previously immunized children viewed as primary vaccine failuresviewed as primary vaccine failures
Measles PathophysiologyMeasles Pathophysiology Infects epithelial, reticuloendothelial, and white blood Infects epithelial, reticuloendothelial, and white blood
cellscells• Multiple organ systemsMultiple organ systems
Multinucleated giant cells found throughout the Multinucleated giant cells found throughout the respiratory and GI tracts and in most lymphoid respiratory and GI tracts and in most lymphoid tissue on autopsy tissue on autopsy
Onset of rash coincides with appearance of serum Onset of rash coincides with appearance of serum antibodiesantibodies•Skin and mucous membrane manifestations may Skin and mucous membrane manifestations may
represent a hypersensitivity reaction to the represent a hypersensitivity reaction to the virus*-virus*-
• Decline in CD4 cellsDecline in CD4 cells Prior to rash onset and lasting up to 1 monthPrior to rash onset and lasting up to 1 month
•Suppression of delayed-type hypersensitivitySuppression of delayed-type hypersensitivityPerry RT, Halsey NA. The clinical significance of measles: a review. JID. 189 (Suppl 1) S4-S16. May 1, 2004
Prodromal (2-4 days)Prodromal (2-4 days)• Fever (39°C–40.5°C), cough, coryza, and Fever (39°C–40.5°C), cough, coryza, and
conjunctivitisconjunctivitis Symptoms intensify and usually peak Symptoms intensify and usually peak on first day of rashon first day of rash
• Appearance of Koplik spots appear 1 Appearance of Koplik spots appear 1 day prior to rash onset and last 2-3 daysday prior to rash onset and last 2-3 days Buccal mucosa opposite 1Buccal mucosa opposite 1stst molar molar Soft palate, conjunctiva, vaginal Soft palate, conjunctiva, vaginal mucosamucosa
Perry RT, Halsey NA. The clinical significance of measles: a review. JID. 189 (Suppl 1) S4-S16. May 1, 2004
Measles Clinical Measles Clinical Presentation 2Presentation 2 Rash first appears on face and neckRash first appears on face and neck
• Discrete erythematous patches (3-8 mm)Discrete erythematous patches (3-8 mm) Lesions increase and spread downwards to trunk Lesions increase and spread downwards to trunk
and extremities (including palms in 25%-50%) and extremities (including palms in 25%-50%) • Most intense over face and trunkMost intense over face and trunk
Frequently become confluentFrequently become confluent Rash persists for 3-7 daysRash persists for 3-7 days
• Desquamation may appear but not pronouncedDesquamation may appear but not pronounced• Severe desquamation seen in malnourished Severe desquamation seen in malnourished
childrenchildren Immunocompromised patients may demonstrate Immunocompromised patients may demonstrate
an atypical presentationan atypical presentation• Without rashWithout rash
Perry RT, Halsey NA. The clinical significance of measles: a review. JID. 189 (Suppl 1) S4-S16. May 1, 2004
• <5 years and ≥20 years<5 years and ≥20 years• Immunocompromised Immunocompromised
T-cell suppression: Congenital or acquired T-cell T-cell suppression: Congenital or acquired T-cell deficiencies: 60% of all measles-associated deaths in deficiencies: 60% of all measles-associated deaths in NJ in 1990-1991 occurred in HIV-infected children*NJ in 1990-1991 occurred in HIV-infected children*
•Chemotherapy for cancer or steroid therapyChemotherapy for cancer or steroid therapy•Bone marrow transplantationBone marrow transplantation
• MalnourishedMalnourished Protein losing enteropathy, increased metabolic Protein losing enteropathy, increased metabolic
demand, decreased food intakedemand, decreased food intake Vitamin A deficiencies: Measles infection lowers Vitamin A deficiencies: Measles infection lowers
serum retinol levelsserum retinol levels• Crowded living conditionsCrowded living conditions
Developing countriesDeveloping countries
*Palumbo P, Hoyt L, et al. Population-based study of measles and measles immunization in HIV-infected children. PIDJ. 11:1008-14. 1992
PNEUMONIA: PNEUMONIA: Most common severe complication, Most common severe complication, responsible for most measles-associated deaths due responsible for most measles-associated deaths due to: to:
ViralViral: Measles or Secondary infection with : Measles or Secondary infection with adenovirus or HSV,adenovirus or HSV,
BacterialBacterial: : Streptococcus pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, H. influenzaeStaphylococcus aureus, H. influenzae
ImmunocompromisedImmunocompromised Host: Host: DDiffuse iffuse PProgressive rogressive MMeasles easles PPneumonitis (neumonitis (DPMPDPMP) ) most most common cause of death=Hecht’s giant cell pneumonia common cause of death=Hecht’s giant cell pneumonia
OTITIS MEDIA: OTITIS MEDIA: Most common complication in US 14% Most common complication in US 14% of children under 5 years of ageof children under 5 years of age
LARYNGOTRACHEOBRONCHITIS:LARYNGOTRACHEOBRONCHITIS: “measles croup” “measles croup” the cause of 9%-32% of US children hospitalized and the cause of 9%-32% of US children hospitalized and 22ndnd most common cause of death after pneumonia most common cause of death after pneumonia
Perry RT, Halsey NA. The clinical significance of measles: a review. JID. 189 (Suppl 1) S4-S16. May 1, 2004
Measles: Neurological Measles: Neurological ComplicationsComplications Febrile Seizures: Febrile Seizures: 0.3%-2.3% in hospitalized children 0.3%-2.3% in hospitalized children
in US and UK (benign, with no long term residual in US and UK (benign, with no long term residual damage) damage)
Encephalitis:Encephalitis: a. a. PPost ost IInfectious nfectious EEncephalomyelitis ncephalomyelitis ((PIEPIE); 1-3/1000 infections; onset 3-10 days post rash ); 1-3/1000 infections; onset 3-10 days post rash onset ; Highest incidence in adolescents and onset ; Highest incidence in adolescents and adults;~25% case fatality rate &~33% have adults;~25% case fatality rate &~33% have neurological sequelae; b. neurological sequelae; b. SSubacute ubacute SSclerosing clerosing PPan-an-EEncephalitis (ncephalitis (SSPESSPE), persistence of measles virus in ), persistence of measles virus in CNS, slowly progressive infection and demyelization to CNS, slowly progressive infection and demyelization to Vegetative state, 1/8.5 million US cases, onset 7-10 Vegetative state, 1/8.5 million US cases, onset 7-10 years post acute infection ( years post acute infection ( Disappeared in the US since Disappeared in the US since advent of measles immunizationadvent of measles immunization) c. ) c. MMeasles easles IInclusion nclusion BBody ody EEncephalitis (ncephalitis (MIBEMIBE) in ) in IImmunocompromised mmunocompromised hhosts with mental status changes, seizures without osts with mental status changes, seizures without fever.fever.
Perry RT, Halsey NA. The clinical significance of measles: a review. JID. 189 (Suppl 1) S4-S16. 5/1/04
Measles Complications-GI Measles Complications-GI and Ocularand Ocular DiarrheaDiarrhea
• Most common in people <5 years and >30 yearsMost common in people <5 years and >30 years• 30%-70% of hospitalized patients with measles in 30%-70% of hospitalized patients with measles in
USUS• Typical onset just before rashTypical onset just before rash• Dehydration commonDehydration common
BlindnessBlindness• Keratitis (inflammation of the cornea)Keratitis (inflammation of the cornea)
CommonCommon Secondary infections with viruses (adenovirus, Secondary infections with viruses (adenovirus,
HSV) and bacteria (HSV) and bacteria (Pseudomonas Pseudomonas spp. and spp. and staph)staph)
Scarring and blindnessScarring and blindness• Vitamin A deficiencyVitamin A deficiency• Cortical damage secondary to encephalitis Cortical damage secondary to encephalitis
Perry RT, Halsey NA. The clinical significance of measles: a review. JID. 189 (Suppl 1) S4-S16. May 1, 2004
Global SituationGlobal Situation** In 2008, ~83% of the world’s children received In 2008, ~83% of the world’s children received
one dose of measles-containing vaccine (MCV) one dose of measles-containing vaccine (MCV) by their first birthdayby their first birthday• Up from 72% in 2000Up from 72% in 2000
In 2008 there were an estimated 164,000 In 2008 there were an estimated 164,000 deaths due to measlesdeaths due to measles• A 78% decrease (733,000 deaths) since 2000A 78% decrease (733,000 deaths) since 2000• >95% of deaths in low-income countries with >95% of deaths in low-income countries with
weak health infrastructuresweak health infrastructures• Mainly seen in children <5 years of ageMainly seen in children <5 years of age
*WHO estimates. See http://www.who.int
United States- United States- Stable MiseryStable Misery
• Pre-vaccine era ( befor1963 Licensure)Pre-vaccine era ( befor1963 Licensure) ~500,000 cases annually~500,000 cases annually
• In reality, ~4 million infected/yearIn reality, ~4 million infected/year ~500 deaths~500 deaths ~150,000 with respiratory complications~150,000 with respiratory complications ~48,000 hospitalizations~48,000 hospitalizations 7,000 seizure episodes7,000 seizure episodes 4,000 cases of encephalitis4,000 cases of encephalitis Up to 25% of people with measles-Up to 25% of people with measles-
associated encephalitis were associated encephalitis were permanently brain damaged or deafpermanently brain damaged or deaf
United States …United States …Going…Going..Going…Going..
• Since 1963 (vaccine licensure)Since 1963 (vaccine licensure) 99% decrease in measles incidence99% decrease in measles incidence
• Most pronounced decrease seen with Most pronounced decrease seen with enactment of laws requiring vaccination for enactment of laws requiring vaccination for school entry in early 1980’sschool entry in early 1980’s
From 1985 – 1992From 1985 – 1992• Children with exemptions were 35x more likely Children with exemptions were 35x more likely
to contract measles than nonexempt children*to contract measles than nonexempt children*• 1989-1991 resurgence1989-1991 resurgence
• Estimated 55,000 measles cases with >130 Estimated 55,000 measles cases with >130 deathsdeaths
• Controlled by:Controlled by: Increased rate of immunizationIncreased rate of immunization Institution of 2-dose regimen in childrenInstitution of 2-dose regimen in children
*Omer SB, Salmon DA, Orenstein WA, et al. Vaccine refusal, mandatory immunization, and the risks of vaccine-preventable diseases. NEJM2009;360:1981-88
United States …Going…United States …Going…Going..Going..…Gone??…Gone??
• Measles elimination (i.e., interruption of Measles elimination (i.e., interruption of endemic measles transmission) was endemic measles transmission) was declared in the US in 2000 !declared in the US in 2000 ! No sustained transmission for ≥1 yearNo sustained transmission for ≥1 year
• Median of 56 cases from 2001 – 2008Median of 56 cases from 2001 – 2008** Range: 37 - 140Range: 37 - 140 Associated with imported infectionAssociated with imported infection
• January – June 17, 2011*January – June 17, 2011* 156 cases reported156 cases reported
•More than reported for 2010More than reported for 2010•Highest number reported for this Highest number reported for this
period since 1996period since 1996*http://emergency.cdc.gov/HAN/han00323.asp; Accessed June 23, 2011
MeaslesMeaslesPrevention-Immunization of Prevention-Immunization of
ChildrenChildren Two dose scheduleTwo dose schedule
• All childrenAll children First dose : 12-15 months of ageFirst dose : 12-15 months of age Second dose: 4-6 years of ageSecond dose: 4-6 years of age May get 2May get 2ndnd dose ≥28 days after 1 dose ≥28 days after 1stst dose dose
• If traveling abroadIf traveling abroad 6-12 months of age, prior to travel6-12 months of age, prior to travel Then follow standard schedule (see Then follow standard schedule (see above)above)
Intramuscular immune globulin (IG) can be Intramuscular immune globulin (IG) can be given up to 6 days post-exposuregiven up to 6 days post-exposure• Delay giving children MMR 5-6 months after Delay giving children MMR 5-6 months after
receiving IG depending on the dosereceiving IG depending on the dose
IVIG preparations usually contain adequate IVIG preparations usually contain adequate amount of measles antibodies amount of measles antibodies • For those receiving IVIG regularly, 400mg/kg For those receiving IVIG regularly, 400mg/kg
should be adequate for prophylaxis for should be adequate for prophylaxis for exposures occurring within 3 weeks of exposures occurring within 3 weeks of receiving IVIGreceiving IVIG
The Dilemma The Dilemma Measles remains endemic in many parts of the worldMeasles remains endemic in many parts of the world
• The world is a villageThe world is a village Measles is highly contagiousMeasles is highly contagious
• Airborne transmissionAirborne transmission• Most contagious prior to presentation of rashMost contagious prior to presentation of rash
Resembles upper respiratory tract infectionResembles upper respiratory tract infection Low index of suspicion in regions where control has Low index of suspicion in regions where control has
been most successfulbeen most successful• Diagnosis and institution of infection control Diagnosis and institution of infection control
interventions commonly delayedinterventions commonly delayed On reintroduction into regions of low endemicity or On reintroduction into regions of low endemicity or
where elimination has been achieved where elimination has been achieved • Serious consequences of disease especially in Serious consequences of disease especially in
vulnerable populationsvulnerable populations• Great expense in time and money to public health Great expense in time and money to public health
and medical entities as well as to society as a and medical entities as well as to society as a wholewhole
In 1736 I lost one of my Sons, a fine Boy of 4 Years old, by the Smallpox taken in the common way. I long regretted bitterly and still regret that I had not given it to him by Inoculation. This I mention for the Sake of Parents who omit that Operation on the Supposition that they should never forgive themselves if a Child died under it; my Example showing that the Regret may be the same either way, and that therefore the safer should be chosen.
Benjamin FranklinAutobiography[Part III, p. 83]
SMALLPOXSMALLPOX
SMALLPOXSMALLPOX EPIDEMIOLOGYEPIDEMIOLOGY
• Once worldwide in distribution ; Eradicated in Once worldwide in distribution ; Eradicated in 1977 in Somalia driven by vaccine campaign1977 in Somalia driven by vaccine campaign
• 2 principal forms Variola major 2 principal forms Variola major >>30% case-fatality 30% case-fatality andandVariola minor Variola minor <<1% case-fatality rate1% case-fatality rate
TRANSMISSIONTRANSMISSION• Person to person by Droplet nucleiPerson to person by Droplet nuclei• Fomite Contaminated clothing/bed linensFomite Contaminated clothing/bed linens• No known animal or insect reservoirs/vectors No known animal or insect reservoirs/vectors
SMALLPOX AS A BIO-WEAPONSMALLPOX AS A BIO-WEAPON High infectivity, high secondary attack rate of10-High infectivity, high secondary attack rate of10-
20 2ed generation cases and Susceptible 20 2ed generation cases and Susceptible population (wide spread civilian vaccination population (wide spread civilian vaccination ceased around 1980), no known cureceased around 1980), no known cure
VACCINIAVACCINIALength of ProtectionLength of Protection
Primary VaccinationPrimary Vaccination• > 95% primary vaccines have neutralizing > 95% primary vaccines have neutralizing
antibody at titer antibody at titer >>1:10 within 1-2 weeks1:10 within 1-2 weeks 7 days after revaccination7 days after revaccination
• Evidence of cell-mediated response by day 8 Evidence of cell-mediated response by day 8 • High level immunityHigh level immunity
3 to 5 years3 to 5 years Decreasing afterwardsDecreasing afterwards
RevaccinationRevaccination• Some level of immunity – 30 years or longer?Some level of immunity – 30 years or longer?
Efficacy in prevention – 95%Efficacy in prevention – 95%
CONTRAINDICATIONS TO CONTRAINDICATIONS TO SMALLPOX IMMUNIZATIONSMALLPOX IMMUNIZATION
In Vaccines and Household ContactsIn Vaccines and Household Contacts• History of eczema, atopic dermatitis, Darier’s disease irrespective of History of eczema, atopic dermatitis, Darier’s disease irrespective of
disease severity or activity and other acute or chronic exfoliative skin disease severity or activity and other acute or chronic exfoliative skin conditions (burns, impetigo, zoster, herpes, severe acne, or psoriasis) conditions (burns, impetigo, zoster, herpes, severe acne, or psoriasis) should not receive vaccine until the condition resolvesshould not receive vaccine until the condition resolves
• Pregnancy or women trying to become pregnant (4 weeks post-vac.) Pregnancy or women trying to become pregnant (4 weeks post-vac.) In Vaccines onlyIn Vaccines only
• Breastfeeding mothersBreastfeeding mothers• All children < 1 year of age, ACIP advises against non-emergency use of All children < 1 year of age, ACIP advises against non-emergency use of
smallpox vaccine in children < 18 years of age, Concurrent moderate or smallpox vaccine in children < 18 years of age, Concurrent moderate or severe short-term illnesssevere short-term illness
• Severe allergic reaction to past smallpox vaccination or to one of the Severe allergic reaction to past smallpox vaccination or to one of the vaccine componentsvaccine components
(Polymyxin B sulfate, Streptomycin sulfate, Chlortetracyline (Polymyxin B sulfate, Streptomycin sulfate, Chlortetracyline hydrochloride, Neomycin sulfate, phenolhydrochloride, Neomycin sulfate, phenol
VACCINIA COMPLICATIONSVACCINIA COMPLICATIONS
IncidenceIncidence**• 164.6 per million primary vaccinations164.6 per million primary vaccinations• 10.0 per million revaccinations 10.0 per million revaccinations
Erythema MultiformeErythema Multiforme Stevens Johnson SyndromeStevens Johnson Syndrome Eczema VaccinatumEczema Vaccinatum Generalized VacciniaGeneralized Vaccinia Vaccinia Necrosum (Progressive Vaccinia)Vaccinia Necrosum (Progressive Vaccinia) Postvaccinial Encephalopathy and EncephalomyelitisPostvaccinial Encephalopathy and Encephalomyelitis TreatmentTreatment
• Supportive careSupportive care• AntipruriticsAntipruritics• Vaccinia immune globulin (VIG) : Used only in severe Vaccinia immune globulin (VIG) : Used only in severe
progressive casesprogressive cases*Lane, M.L., et al. Complications of Smallpox Vaccination, 1968: Results of Ten Statewide Surveys. JID. 122;4:303-309. October 1970
VACCINIA PERIOCULAR AUTOINOCULATIONVACCINIA PERIOCULAR AUTOINOCULATION Consider VIG In More Serious Cases Consider VIG In More Serious Cases
GENERALIZED VACCINIA GENERALIZED VACCINIA Consider VIG In More Serious Cases Consider VIG In More Serious Cases
ECZEMA VACCINATUMECZEMA VACCINATUM* * Early treatment with VIGEarly treatment with VIG * Treatm * Treatment of secondary bacterial / ent of secondary bacterial /
fungal infectionsfungal infections* Lesions contain virus mandating * Infection control * Lesions contain virus mandating * Infection control
Occurs in people with compromised immune Occurs in people with compromised immune systems; systems; Poorer prognosis especially in CMI deficitsPoorer prognosis especially in CMI deficits
Vaccinia lesion fails to heal, secondary lesions may Vaccinia lesion fails to heal, secondary lesions may appear and gradually spreadappear and gradually spread
Mortality rate Mortality rate ~ 25-33%~ 25-33%• Management includes ; Aggressive VIG therapy, Management includes ; Aggressive VIG therapy,
Surgical debridement, Treatment of secondary Surgical debridement, Treatment of secondary bacterial or fungal infectionbacterial or fungal infection
• Second line treatment Cidofovir ; No studied in Second line treatment Cidofovir ; No studied in humans, only available under Investigational New humans, only available under Investigational New Drug (IND) protocol from CDC and Department of Drug (IND) protocol from CDC and Department of DefenseDefense
Lesions contain virus, and needs strict Infection Lesions contain virus, and needs strict Infection control precautionscontrol precautions
