Measles Introduction Background: Measles virus (MV), a negative-sense enveloped RNA virus, is a member of the Morbillivirus genus in the

Paramyxoviridae family Measles is a highly !ommuni!able a!ute disease mar"ed by prodromal fever, !ough, !ory#a, !on$un!tivitis, and pathognomoni! enanthem (ie, %opli" spots), follo&ed by an erythematous ma!ulopapular rash on the third to seventh day 'nfe!tion !onfers lifelong immunity A generali#ed immunosuppression that follo&s a!ute measles fre(uently predisposes patients to ba!terial otitis media and bron!hopneumonia 'n approximately ) *+ of !ases, measles !auses a!ute en!ephalitis ,uba!ute s!lerosing panen!ephalitis (,,P-) is a rare !hroni! degenerative disease that o!!urs several years after measles infe!tion .e!ause of a failure to deliver at least * dose of measles va!!ine to all infants in !ertain industriali#ed and developing nations, measles remains a !ommon disease in !ertain regions and !ontinues to a!!ount for nearly /)+ of the * 0 million deaths !aused ea!h year by va!!ine-preventable !hildhood diseases Maternal antibodies play a signifi!ant role in prote!tion against infe!tion in infants younger than * year and may interfere &ith liveattenuated measles va!!ination A single dose of measles va!!ine administered to a !hild older than *1 months indu!es prote!tive immunity in 2/+ of re!ipients .e!ause MV is highly !ontagious, a /+ sus!eptible population is suffi!ient to sustain periodi! outbrea"s in other&ise highly va!!inated populations A se!ond dose of va!!ine, no& re!ommended for all s!hool-aged !hildren in the 3nited ,tates, indu!es immunity in about 2/+ of the /+ &ho do not respond to the first dose ,light genotypi! variation in re!ently !ir!ulating strains has not affe!ted the prote!tive effi!a!y of live-attenuated measles va!!ines 3nsubstantiated !laims that suggest an asso!iation bet&een measles va!!ine and autism have led to redu!ed va!!ine use and a re!ent resurgen!e of measles in !ountries &here immuni#ation rates have fallen to belo& the level needed to maintain herd immunity

4onsidering that for industriali#ed !ountries su!h as the 3nited ,tates, endemi! transmission of measles may be reestablished if measles immunity falls to less than 25-2/+, efforts to ensure high immuni#ation rates among people in both developed and developing !ountries must be sustained Vitamin A supplementation during a!ute measles signifi!antly redu!es ris"s of morbidity and mortality Pathophysiology: MV is spread by aerosol and enters the sus!eptible host by the respiratory route 'nitial infe!tion and viral repli!ation o!!ur lo!ally in tra!heal and bron!hial epithelial !ells After 1-6 days, MV infe!ts lo!al lymphati! tissues, perhaps !arried by pulmonary ma!rophages 7ollo&ing the amplifi!ation of MV in regional lymph nodes, a predominantly !ell-asso!iated viremia disseminates the virus to various organs prior to the appearan!e of rash 'n individuals &ith defi!ien!ies in !ellular immunity, MV !auses a progressive and often fatal giant !ell pneumonia Measles !auses an immunosuppression mar"ed by de!reases in delayed-type hypersensitivity, interleu"in-*1 produ!tion, and antigen-spe!ifi! lymphoproliferative responses that persist for &ee"s to months after the a!ute infe!tion 'mmunosuppression may predispose individuals to severe ba!terial infe!tion, parti!ularly bron!hopneumonia, a ma$or !ause of measles-related mortality among younger !hildren Frequency:

In the US: 8he pra!ti!e of administering 1 doses of liveattenuated measles va!!ine to !hildren to prevent s!hool outbrea"s of measles &as implemented after the last ma$or 3, outbrea" in *22* 8his pra!ti!e interrupted the transmission of indigenous MV in the 3nited ,tates by *225 and redu!ed in!iden!e of measles to an histori! lo& (9) / !ases per million persons) by *22:-*222 ;espite the highest re!orded immuni#ation rates in history, young !hildren &ho are not appropriately va!!inated may experien!e more than a 0)-fold in!rease in ris" of disease due to exposure to imported measles !ases in the 3nited ,tates

Internationally: Approximately 5) million measles !ases are reported annually Most reported !ases are from Afri!a 'n *22<, the reported !ases of measles per *)),))) total population reported to the =orld >ealth ?rgani#ation &as * 0 in the Ameri!as, < 1 in -urope, ** * in the -astern Mediterranean region, 6 1 in ,outh -ast Asia, / ) in the =estern Pa!ifi! region, and 0* : in Afri!a

Mortality/Morbidity:

Morbidity@ 4ommon infe!tious !ompli!ations in!lude otitis media, bron!hopneumonia, laryngotra!heobron!hitis (ie, !roup), and diarrhea Rare !ompli!ations in!lude hepatitis, en!ephalitis, and ,,P- 8ransient hepatitis may o!!ur during an a!ute infe!tion Approximately * of every *))) patients develops a!ute en!ephalitis, &hi!h often results in permanent brain damage ,,P-, a degenerative 4N, disease, !an result from a persistent measles infe!tion ,,P- is !hara!teri#ed by the onset of behavioral and intelle!tual deterioration and sei#ures years after an a!ute infe!tion (the mean in!ubation period for ,,P- is approximately *) < y) Mortality@ Measles-related mortality, most often due to respiratory and neurologi! !ompli!ations, o!!urs in ) *-) 5+ of reported 3, !ases =orld&ide, measles !auses approximately <<),))) deaths ea!h year An estimated </+ of these deaths o!!ur in Afri!a and ,outheast Asia 4ase-fatality rates are higher among !hildren younger than / years >ighest fatality rates are among infants aged 6-*1 months and in !hildren &ho are immuno!ompromised be!ause of >'V infe!tion or other !auses

Race: Measles affe!ts people of all ra!es Sex:

-x!ess mortality follo&ing a!ute measles has been observed among females at all ages, but it is most mar"ed in adoles!ents and young adults

-x!essive nonAmeasles-related mortality has also been observed among female re!ipients of high-titer measles va!!ines in ,enegal, Buinea .issau, and >aiti

ge: Age-spe!ifi! atta!" rates may be highest in sus!eptible infants younger than *1 months, s!hool-aged !hildren, or young adults, depending on lo!al immuni#ation pra!ti!es and in!iden!e of the disease 4ompli!ations su!h as otitis media, bron!hopneumonia, laryngotra!heobron!hitis (ie, !roup), and diarrhea o!!ur more !ommonly in young !hildren !linical "istory: 8he in!ubation period from exposure to onset of symptoms ranges from <-*1 days 8he prodromal phase is mar"ed by malaise, fever, anorexia, !on$un!tivitis, !ough, and !ory#a 8he entire !ourse of un!ompli!ated measles, from late prodrome to resolution of fever and rash, is :-*) days 4ough may be the final symptom to appear Physical:

7ever@ A temperature ex!eeding *)*C7 begins &ith the prodrome and persists :-*) days -nanthem@ %opli" spots (ie, bluish-gray spe!"s or Dgrains of sandD on a red base) appear on the bu!!al mu!osa opposite the se!ond molars near the end of the prodrome, $ust prior to appearan!e of rash (see 'mage *) 8his enanthem begins to slough as the rash appears Rash@ An erythematous and ma!ulopapular rash that be!omes !onfluent begins on the fa!e, then pro!eeds to the trun", extremities, palms, and soles and lasts for about / days Patients appear most ill during the first or se!ond day of the rash ;es(uamation, &hi!h spares the palms and soles, may o!!ur after * &ee" 8he rash may be absent in patients &ith underlying defi!ien!ies in !ellular immunity

Eymphoid involvement@ Benerali#ed lymphadenopathy, mild hepatomegaly, and appendi!itis may o!!ur be!ause of generali#ed involvement of lymphoid tissue

!auses:

Ris" fa!tors for infe!tion

4hildren &ith immunodefi!ien!y due to >'VFA';,, leu"emia, al"ylating agents, or !orti!osteroid therapy, regardless of immuni#ation status 8ravel to areas &here measles is endemi! or !onta!t &ith travelers to endemi! areas 'nfants &ho lose passive antibody prior to the age of routine immuni#ation

Ris" fa!tors for severe measles and its !ompli!ations

Malnutrition 3nderlying immunodefi!ien!y Pregnan!y Vitamin A defi!ien!y Section ( o) **

#IFF$R$%&I 'S #i))erentials

;engue -nteroviral 'nfe!tions %a&asa"i ;isease Parvovirus .*2 'nfe!tion Ro!"y Mountain ,potted 7ever Rubella 8oxi! ,ho!" ,yndrome

+ther Proble,s to be !onsidered: ;rug eruption Roseola -uick Find Related ;engue rticles

-nteroviral 'nfe!tions %a&asa"i ;isease Parvovirus .*2 'nfe!tion Ro!"y Mountain ,potted 7ever Rubella 8oxi! ,ho!" ,yndrome uing $ducation Patient $ducation .orkup 'ab Studies:

4onfirmation of MV infe!tion
o

8he MV sand&i!h-!apture immunoglobulin M ('gM) antibody assay is the (ui!"est method to !onfirm a!ute measles .e!ause 'gM may not be dete!table during the first 1 days of rash, obtain blood for measles-spe!ifi! 'gM on the third day of the rash or on any subse(uent day up to * month after onset to avoid a false-negative 'gM result Among persons &ith !onfirmed measles infe!tion, the seropositivity rate for first samples is about ::+ &hen !olle!ted &ithin :1 hoursG the rate rises to *))+ &hen !olle!ted 6-** days after rash onset Although the measles serum 'gM level remains positive 5)-0) days

after the illness in most individuals, the 'gM titer may be!ome undete!table in some sub$e!ts at 6 &ee"s after rash onset 8he assay is offered through many lo!al health departments and through the 4enters for ;isease 4ontrol and Prevention
o

Eaboratories !an !onfirm measles by demonstrating more than a 6-fold rise in immunoglobulin B ('gB) antibodies bet&een a!ute and !onvales!ent sera 'gB antibodies may be dete!table 6 days after the onset of the rash, although most !ases have dete!table 'gB antibodies by about a &ee" after rash onset 8hus, ta"e spe!imens on the seventh day after rash onset and repeat *)-*6 days later to !onfirm the !ase as soon as possible Patients &ith ,,P- have unusually high titers of measles antibody in their serum and !erebrospinal fluid 8he earliest !onfirmation of measles using 'gB antibodies ta"es about 5 &ee"s from the onset of illness, a delay too long to permit implementation of effe!tive !ontrol measures MV !an be isolated from nasopharyngeal s&abs Viral genotyping in a referen!e laboratory may determine &hether an isolate is endemi! or imported 'n immuno!ompromised patients, &ho may have poor antibody responses that pre!lude serologi! !onfirmation of measles, virus isolation from infe!ted tissue or identifi!ation of measles antigen by immunofluores!en!e may be the only method to !onfirm the diagnosis

?ther diagnosti! tests

A leu"openia o!!urs in the late stages of viremia -levated hepati! transaminase levels may be dete!ted in patients &ith MV hepatitis

I,aging Studies:

Perform !hest radiography if ba!terial pneumonia is suspe!ted 8he fre(uent o!!urren!e of measles pneumonia, even in

un!ompli!ated !ases, limits the predi!tive value of !hest radiography for ba!terial bron!hopneumonia +ther &ests:

Perform a lumbar pun!ture if en!ephalitis is suspe!ted

"istologic Findings: Eymphoid multinu!leated giant !ells (up to *)) nm in diameter) !an be identified in biopsies of %opli" spots, in dermal or epithelial rashes, and in lung or lymphoid tissue .rain biopsies of patients &ith measles en!ephalitis !an reveal demyelination, vas!ular !uffing, gliosis, and infiltration of fatladen ma!rophages near blood vessel &alls

&R$ &M$%& &reat,ent Medical !are:

Section / o) **

4onsider administration of antibioti!s (if eviden!e exists of otitis media or ba!terial pneumonia), vitamin A supplements (parti!ularly for !hildren aged 0-16 mo), or ribavirin (experimental) 8o prevent or modify measles in exposed sus!eptible individuals, !onsider administering MV va!!ine or human immunoglobulin

!onsultations: 4onsult publi! health or infe!tious disease spe!ialists for re!ommendations and guidelines for diagnosti! !onfirmation of !ases and prophylaxis of sus!eptible !onta!ts #iet: Medi!ation ;rug 4ategory@ Vitamins -- Vitamin A treatment for !hildren &ith measles in developing !ountries has been asso!iated &ith a mar"ed redu!tion in morbidity and mortality 8he =orld >ealth ?rgani#ation re!ommends vitamin A administration to all !hildren &ith measles in !ommunities &here vitamin A defi!ien!y is a re!ogni#ed problem and &here the MV-related mortality rate ex!eeds *+ ?f note, lo& serum !on!entrations of vitamin A are found in !hildren &ith severe measles in the 3nited ,tates 8hus, !onsider supplemental vitamin A in patients aged 0 months to 1 years &ho are hospitali#ed &ith measles and its !ompli!ations (eg, !roup, pneumonia, diarrhea) Also !onsider vitamin A supplementation for any patient &ho meets the follo&ing !riteria@ * 's older than 0 months and has measles 1 's not already re!eiving vitamin A supplementation 5 's immunodefi!ient 4onsider vitamin A supplementation

6 >as !lini!al eviden!e of vitamin A defi!ien!y / >as moderate-to-severe malnutrition 0 >as re!ently emigrated from an area &ith high mortality rates due to measles #rug %a,e Vitamin A (A(uasol A) -- 7at-soluble vitamin needed for gro&th of s"in, bones, and male and female reprodu!tive organs Pediatric #ose 90 months@ Not established 0 months to * year@ *)),))) '3 P? as a single doseG repeat dose the next day and at 6 &" for ophthalmologi! eviden!e of vitamin A defi!ien!y H* year@ 1)),))) '3 P? as a single doseG repeat dose the next day and at 6 &" for ophthalmologi! eviden!e of vitamin A defi!ien!y !ontraindications ;o!umented hypersensitivityG large doses may be teratogeni! and, thus, !ontraindi!ated in pregnan!y Interactions 4holestyramine or neomy!in retard absorption Pregnancy 4 - ,afety for use during pregnan!y has not been established Precautions A 1)),))) '3 dose may be asso!iated &ith vomiting and heada!heG patients &ith hepati! dysfun!tion have in!reased sus!eptibility to vitamin A toxi!ity ;rug 4ategory@ Antivirals -- MV is sus!eptible to ribavirin in vitro Although ribavirin (either 'V or aerosoli#ed) has been used to treat severely affe!ted and immuno!ompromised adults &ith a!ute measles or ,,P- ('V plus intrathe!al high-dose interferon-alfa), no !ontrolled trials have been !ondu!tedG ribavirin is not approved by the 7ood and ;rug Administration (7;A) for this indi!ation, and su!h use should be !onsidered experimental #rug %a,e Ribavirin (Vira#ole) -- 7or experimental use only A guanosine analog, the me!hanism of a!tion is not fully defined but relates to alteration of !ellular nu!leotide pools and of viral messenger RNA information dult #ose 1)-5/ mgF"gFd 'V for : d Pediatric #ose Not established !ontraindications ;o!umented hypersensitivity Interactions 'ntera!ts &ith thymidine-phosphorylated nu!leoside analogs (eg, #idovudine, d68), de!reasing their effe!ts Pregnancy I - 4ontraindi!ated in pregnan!y

Precautions 4losely monitor patients &ith 4?P; and asthma for deterioration of respiratory fun!tionG asso!iated &ith a dose-dependent hemolyti! anemia ;rug 4ategory@ Vaccines -- 8hese agents are available in the 3nited ,tates &ith attenuated rubella and mumps viruses as measlesmumps-rubella (MMR) va!!ine 4laims that suggest an asso!iation bet&een measles va!!ine and pervasive developmental or other neurologi! disorders have not been substantiated Va!!ines are used for universal immuni#ation of !hildren older than *1 months in the 3nited ,tates or in !hildren at age 2 months in developing !ountries &ith high endemi!ity 'n the 3nited ,tates, a se!ond dose !an be administered as soon as 1 months later but is generally administered at age 6-0 years All adults born after *2/: should re!eive a se!ond dose of MMR unless they are do!umented as seropositive for measles 'gB antibody by en#yme immunoassay (-'A) 'f administered &ithin :1 hours of exposure to measles-naive individuals, MMR may prevent or attenuate disease ('n a sus!eptible household !onta!t, !onsider immunoglobulin instead ) 'n the 3nited ,tates, 6< states and the ;istri!t of 4olumbia re(uire a se!ond dose of measles va!!ine for s!hool enrollment Rates of sero!onversion average </+ after a single dose at age 2 months (the re!ommended strategy for routine immuni#ation in developing !ountries), 2/+ after a single dose at *1 months, 2<+ after a single dose at age */ months, and greater than 22+ after 1 doses after age *1 months #rug %a,e Measles virus va!!ine (Attenuvax) -- 7or anyone born in or after *2/: &ho la!"s do!umentation of live va!!ine immuni#ation on or after his or her first birthday dult #ose ) / mE ,4 in outer aspe!t of upper arm Pediatric #ose H*1 months@ Administer as in adults !ontraindications ;o!umented hypersensitivityG pregnan!yG immunodefi!ien!y or immunosuppression (eg, se!ondary to >'V infe!tion &ith very lo& 4;6J 8-lympho!yte !ount, high-dose !orti!osteroids for H*6 d, leu"emia)

Interactions ;rugs that suppress the immune system may diminish response to immuni#ationG live-attenuated measles va!!ines may indu!e general suppression of !ellular immunity that lasts for several &"G therefore, interpretation of purified tuber!ulin test for tuber!ulosis infe!tion may be altered (if 8. test is indi!ated, pla!e on day of measles immuni#ation) Pregnancy I - 4ontraindi!ated in pregnan!y Precautions 4ontra!eption in females is advised for 5 mo follo&ing immuni#ation ;rug 4ategory@ Immunoglobulins -- >uman immunoglobulin prevents or modifies measles in sus!eptible individuals if administered &ithin 0 days of exposure #rug %a,e 'mmunoglobulin -- 'ndi!ated for all sus!eptible !onta!ts of patients &ith measles &ho reside in the same household &ho are pregnant, immuno!ompromised, or aged 0-*1 moG also indi!ated for all !hildren and adoles!ents &ith >'V infe!tion &ho are exposed to measles, regardless of measles immuni#ation status, unless they have re!eived 'B'V (6)) mgF"g as part of routine immunoprophylaxis) &ithin 5 &" of exposure dult #ose */ mE 'M Pediatric #ose ) 1/ mEF"g 'M () / mEF"g for patients &ith >'V)G not to ex!eed */ mEFdose 'M !ontraindications ;o!umented hypersensitivityG 'gA defi!ien!yG anti-'g-F'gB antibodies Interactions May ina!tivate live virus va!!ines (eg, MMR, Varivax)G do not administer &ithin /-0 mo of va!!ine Pregnancy 4 - ,afety for use during pregnan!y has not been established Precautions 4he!" serum 'gA before 'V'B (use an 'gAdepleted produ!t, eg, Bammagard ,F;)G infusions may in!rease serum vis!osity and thromboemboli! eventsG infusions may in!rease ris" of migraine atta!"s, asepti! meningitis (*)+), urti!aria, pruritus, or pete!hiae (1-/ d postinfusion to 5) d)G in!reases ris" of renal tubular ne!rosis in elderly people and in those &ith diabetes, volume depletion, and preexisting "idney diseaseG laboratory result !hanges asso!iated &ith infusions in!lude elevated antiviral or antiba!terial antibody titers for * mo, 0-fold in!rease in -,R for 1-5 &ee"s, and apparent hyponatremia

F+''+.0UP

Section 1 o) **

Follo20up Further Inpatient !are:

>ospitali#ation may be indi!ated for treatment of !ompli!ations (eg, ba!terial superinfe!tion, pneumonia, dehydration, !roup)

In/+ut Patient Meds:

Perform timely !onta!t tra!ing and institute prophylaxis or immuni#ation, if indi!ated

#eterrence/Pre3ention:

Prevention re(uires va!!ination &ith live-attenuated measles va!!ine (per routine) or earlier immuni#ation (ie, no younger than age 0 mo) during epidemi!s >uman immunoglobulin prevents or modifies disease in sus!eptible !onta!ts if administered &ithin 0 days of exposure

Prognosis:

Most !hildren re!over uneventfully >igh !ase-fatality rates may be observed among !hildren &ho are malnourished or immunodefi!ient, parti!ularly in developing nations

Special !oncerns:

.e!ause the transmission of indigenous measles has been interrupted in the 3nited ,tates and all re!ent 3, epidemi!s have been lin"ed to imported !ases, immediately reporting any suspe!ted !ase of measles to a lo!al or state health

department is imperative, as is obtaining serum for 'gM antibody testing as soon as possible (ie, on or after the third day of rash)

Airborne pre!autions are indi!ated for hospitali#ed !hildren during the period of !ommuni!ability (ie, up to 6 d after the rash develops in healthy !hildren and for the duration of illness in patients &ho are immuno!ompromised) ,us!eptible health !are &or"ers should be ex!used from &or" from the fifth to the 1*st day after exposure A syndrome !alled atypi!al measles has been des!ribed in individuals &ho &ere infe!ted &ith &ild MV several years after immuni#ation &ith a "illed measles va!!ine (a va!!ine used in the 3nited ,tates from *205-*20:) 8he disease tends to be more prolonged and severe than regular measles and is mar"ed by a prolonged high fever, pneumonitis, a rash that begins peripherally and may be urti!arial, ma!ulopapular, hemorrhagi!, andFor vesi!ular 8he assumed pathogenesis is hypersensitivity to MV in a partially immune host Eaboratory tests reveal a very lo& measles antibody titer early in the !ourse of the disease, follo&ed soon thereafter by the appearan!e of an extremely high measles 'gB antibody titer (eg, *@*,))),)))) in the serum PI!&UR$S Section *4 o)