Thursday, February 23, 2017

respiratory tract infection drug that is safe for children

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♪ >>> hello. i'm anne schuchat,director of the national center for immunization and respiratorydiseases. i'm delighted to welcome you tothe 2011 edition of "surveillance ofvaccine-preventable diseases." disease surveillance is acritical element of public health.surveillance provides uswith information about where and when vaccine-preventable diseases are occurring. these data also help us toevaluate the impact of our

vaccination programs and suggestareas in which these programs might be improved. this program will provide you with current guidelines for the surveillance of vaccine-preventable diseases. the information we discuss inthis program should be especially helpful for those ofyou in local and state health departments and health careproviders who identify and report cases ofvaccine-preventable disease. your participation is critical. without you, there would be nonational surveillance.

in routine disease-controlprograms, routine disease surveillance systems are usuallyadequate to meet national program needs, despite theirlimitations. in contrast, in diseaseelimination or eradication programs, routine surveillanceactivities are often inadequate once the goal is near. this is the situation now in theunited states with diseases like measles and rubella. every case counts and must bethoroughly investigated and

reported. without adequate surveillance, we will be unable to achieve and sustain elimination ofvaccine-preventable diseases. we hope you will find theinformation in this course useful. your work in the rapididentification,investigation, and reporting ofvaccine-preventable diseases forms the foundation of ournational prevention and control programs.

because of you, our nationaldisease surveillance system works. thank you. >> as a result of effectiveimmunization programs, diseases that once were major causes ofdeath and morbidity among children in this country nowoccur so infrequently that many of us have never seen a case. our challenge now is to identifythe factors that allow the remaining cases to occur.

we also want to extend oursuccesses with the elimination of measles, rubella, and polioto other diseases, like pertussis, hepatitis "a," andvaricella. we do case investigations tohelp us figure out if we need to take public health action. if action is needed, exactlywhat do we need to do? at the local level, we needsurveillance information rapidly so we can start disease-controlactivities. an example is providingantibiotic prophylaxis for

contacts of a person withpertussis or vaccinating susceptible persons whenoutbreaks occur. before cases of any disease canbe counted, we must define what it is we're counting. this critical component of allsurveillance systems requires standardized case definitions. case definitions have beenestablished for vaccine-preventable diseases,and we'll mention many of them in the course of this program.

case definitions can be found inthe manual for the surveillance of vaccine-preventable diseases. we'll include a link to thesurveillance manual on the program web page. cdc also maintains a web pagethat contains the case definitions for all infectiousconditions under national public health surveillance, includingvaccine-preventable diseases. this is a very useful web page,and we'll also put a link to it on the resources web page for this program.

for each vaccine-preventabledisease, there are specific critical data that must becollected in order to plan and implement appropriatepublic-health action. for each case, we needdemographic information and relevant clinical data,vaccination history, and laboratory test results. this is the information neededto classify cases, and it's critical for the evaluation ofcases of vaccine-preventable diseases.

in addition to gatheringinformation about the case, you need to try to identify thepeople that the person may have transmitted the infection to. and you need to identify theperson the patient got the infection from. you need to find out whether thecase is linked to an outbreak or is an isolated, sporadic case. just because no other cases havebeen reported, you cannot assume that no other cases haveoccurred.

at the state level, surveillancedata on vaccine-preventable diseases is needed to evaluatethe effectiveness of disease-control programs. when there is a case of avaccine-preventable disease in someone for whom there is avaccination recommendation, it should serve as a warning topublic-health officials. there may be other susceptibleindividuals who should have been vaccinated but were not or theremay have been waning immunity in a vaccinated individual.

you need to find out, was theperson vaccinated? and if not, why not? were there missed opportunitiesto vaccinate? is there a more widespreadproblem? in addition to the evaluation ofdisease-control programs, states have other needs forsurveillance data. surveillance data are alsoneeded to formulate and evaluate immunization policy. at the national level, we usesurveillance data to formulate

national immunization policy andto evaluate the effectiveness of immunization programs. we also rely on surveillancedata to evaluate the effectiveness of the vaccinesthemselves and to document the impact of national immunizationefforts. this is especially importantwith relatively new vaccines, such as the meningococcalconjugate vaccine and the tetanus, diphtheria, andpertussis vaccine, or tdap, for adolescents and adults.

new vaccine schedules alsorequire careful surveillance and evaluation. an example of this is the 2007recommendation for the second dose of varicella vaccine. andrew? >> what we need from asurveillance system depends on where we are in ourdisease-control program. what we need early in theprogram or when there are large numbers of cases is quitedifferent than what we need when

the program is very far alongwith few cases. of course, we need to ensureadequate surveillance for vaccine adverse events for anyvaccine currently in use, regardless of the stage ofdisease control. before a vaccine is availablefor routine use, the information we need is pretty simple. we need to have a baseline ofreported disease. complete reporting is notessential, but we do need year-to-year consistency.

we need national data torepresent the epidemiology of the disease prior to theavailability of a vaccine. but during this phase, aggregatereporting of case counts is usually sufficient. when a new vaccine isrecommended for routine use and disease remains common, our goalshifts to monitoring the impact of the national vaccinationefforts. at this point, aggregatereporting of case counts is still sufficient.

when we have good diseasecontrol, as we have now with haemophilus influenzae type b,we need enhanced surveillance so we can document vaccine impact,evaluate effectiveness, and monitor progress toward diseaseelimination. we can use this information tofigure out why the cases that remain continue to occur. with good disease control, weneed detailed information from individual case investigations,including vaccination status and laboratory confirmation.

we also need highly specificcase definitions, because we really want to make sure thatthe cases we are counting are real cases of the disease. this is the phase when everycase counts. when disease incidence is verylow and we are striving for elimination, the completeness ofreporting and the quality of individual case investigationsare very important. at this point, the organism mayno longer even be circulating, and we can use molecular-typingmethods to help document that.

in summary, surveillanceactivities must be designed to fit the public-health need. we need baseline data fordiseases for which a new vaccine is available, but we needdetailed individual case investigations when we haveachieved higher levels of disease control throughvaccination programs. we rely on surveillance tomonitor the effectiveness of our immunization programs but how can we monitor theeffectiveness or quality of our

surveillance? surveillance is a challenge whenthe disease for which we are doing surveillance is rare. how do we know whether no caseswere reported because there really were no cases or becauseno one was looking? we rely on surveillanceindicators to monitor the quality of nationalsurveillance. certain critical elements needto be collected during investigation of cases ofvaccine-preventable diseases.

these include demographicinformation, relevant clinical and laboratory data, andvaccination status. monitoring whether or not thesedata are reported lets us track the quality of caseinvestigation, and we do this routinely. but that does not tell uswhether or not zero cases reported really means zerodisease or infection. we must ensure that we canidentify and respond to every case when disease rates are verylow.

for instance, between january 1,2011 and november 30, 2011, cdc was notified of 72 internationalmeasles importations and 17 measles outbreaks in the u.s. one of these 17 outbreaksinvolved 20 associated spread cases this illustrates that we mustmaintain our vigilance and surveillance forvaccine-preventable diseases. sandy? >> national surveillance forvaccine-preventable diseases

traditionally relies on passivereporting, which is often incomplete. in spite of this limitation,data from passive reporting are useful for routine nationalsurveillance because they are used primarily for monitoringtrends in disease occurrence rather than in response toindividual cases. however, for diseases with veryfew remaining cases, as with most of the vaccine-preventablediseases, surveillance data must be very complete.

every case counts. we need to know whether zeroreported cases mean that there is really no disease. surveillance indicators havebeen developed to assess the specifically, they can assessthe completeness of reporting -- that is, the ability of oursurveillance system to identify all cases, if and when they arepresent. remember that surveillance mustalso be specific enough to exclude non-cases by adequatecase investigation and

laboratory testing. surveillance indicators can alsobe used to assess investigative effort and the completeness ofepidemiologically important surveillance data. methods to monitor surveillancequality were first developed in 1988 by the pan american healthorganization as part of the polio-eradication effort in thewestern hemisphere. in the polio-eradication effort,surveillance was performed not just for paralytic poliomyelitisbut for a syndrome including

both paralytic polio and otherclinically compatible conditions. in the absence of polio, theseother conditions causing acute flaccid paralysis, or afp,remain constant through time. so if the reported afp rateremained constant without confirmed or compatible polio,there was confidence that the absence of reported cases ofpolio, in fact, meant the absence of polio the system was sensitive enoughto find afp and polio, if it

were present. this surveillance indicator usedan external standard -- afp -- to measure surveillance quality. surveillance indicators formeasles, mumps, and rubella are similar to each other. the indicators includecompleteness of data, timeliness of reporting, proportion ofcases that are laboratory confirmed, and proportion ofcases that have an imported source.

if our surveillance system canidentify even imported cases of measles and rubella, forexample, we have confidence that the system could also identifyindigenous cases, if they were present. for rubella, we also measure theproportion of cases among women of child-bearing age with knownpregnancy status. for measles, we measure theproportion of cases for which a clinical specimen is submittedfor virus isolation. we have also developedindicators for haemophilus

influenzae and pertussissurveillance. for haemophilus influenzae, wemeasure the timeliness and completeness of case informationfor children younger than 5 years of age, including vaccinehistory and serotype. we can also track the incidenceof non-type-b disease among children younger than 5 years ofage. the most recent nationalsurveillance indicator reports for measles, mumps, rubella,pertussis, and haemophilus influenzae are available on theresources web page for this

program. for pertussis, we measuretimeliness and completeness of epidemiologic data, especiallyvaccination history for children younger than 7 years of age. we also look at the proportionof clinically compatible cases that have laboratory testing. these are a few approaches tomonitoring the quality of surveillance. we do surveillance to monitorthe quality of our immunization

we use surveillance indicatorsto monitor the quality of our with the incidence of many ofthe vaccine-preventable diseases at all-time record lows, wecannot be sure that zero means zero unless we can document thatsomeone is looking. >> human papillomavirus, or hpv,is the most common sexually transmitted infection in theunited states, with an estimated 6.2 million new infections everyyear. more than 100 hpv types havebeen identified, and more than 40 of these types can infect thegenital area.

hpv types are classified bytheir association with cancer into either low-risk, ornon-oncogenic types, and high-risk, or oncogenic types. the oncogenic types areresponsible for many anogenital and oropharyngeal cancers. most hpv infections areasymptomatic and do not result in any clinical consequence. however, some persistentoncogenic hpv infections can cause certain associatedcancers.

it is impossible to distinguishwhich infections become persistent and may go on toproduce cancer years later. the prevention of hpv infectionthrough vaccination is important in order to prevent the canceroutcomes which may develop. high-risk hpv types are detectedin almost all cervical cancers, and 70% of cervical cancersworldwide are due to just two hpv types -- 16 and 18. while persistent infection withhigh-risk types is considered necessary for the development ofcervical cancer, it is not the

only factor, because the vastmajority of women with high-risk hpv infection do not developcancer. in addition to its associationwith cervical cancer, high-risk hpv infection is also associatedwith cancer of the vulva, vagina, penis, anus, andoropharynx -- that is, cancers in the back of the throat,including base of tongue and each of these is less commonthan cervical cancer, and unlike cervical cancer, not all casesof these less-common anogenital and oropharyngeal cancers arerelated to hpv infection.

low-risk, or non-oncogenictypes, such as hpv types 6 or 11, can cause anogenital wartsand a disease of the respiratory tract called recurrentrespiratory papillomatosis, or rrp. as of december 2011, there aretwo approved hpv vaccines in the united states. one is a quadrivalent vaccine,whose brand name is gardasil and is produced by merck. the second is a bivalentvaccine, brand name cervarix,

produced by glaxosmithkline. neither vaccine is a livevaccine. both vaccines contain capsidproteins of the targeted hpv types and are not infectious. the bivalent vaccine containsthe capsid proteins of two oncogenic hpv types -- 16 and18. the quadrivalent vaccinecontains the capsid proteins of the two oncogenic hpv types --16 and 18 -- and two non-oncogenic hpv types -- 6 and11.

both vaccines are highlyeffective against cervical pre-cancers due to hpv 16 or 18if administered prior to infection with the virus. the quadrivalent vaccine alsohas high efficacy against genital warts caused by hpv 6and 11. neither vaccine has atherapeutic effect on hpv-related disease or on riskof progression to disease in persons who have hpv infectionat the time of vaccination. the quadrivalent vaccine waslicensed by the food and drug

administration, or fda, in 2006for use in females and in 2009 for use in males. the bivalent vaccine waslicensed by the fda in 2009 for use in females. the advisory committee onimmunization practices, or acip, recommends routine vaccinationof 11- or 12-year-old girls with three doses of either thebivalent or the quadrivalent vaccine. vaccination can be startedbeginning at 9 years of age.

catch-up immunization of females13 through 26 years of age who have not been previouslyvaccinated or who have not completed the full series isalso recommended. the same hpv vaccine should beused for the complete vaccination series wheneverfeasible. acip also recommends routine hpvvaccination of males at 11 or 12 years of age, with catch-upvaccination of males through age 21 years. as with females, the vaccinationseries may be started at 9 years

of age catch-up vaccination through 26years of age is recommended for men who have sex with men andfor those who are immunocompromised. neither vaccine is currentlylicensed or recommended for persons older than 26 years. in considering surveillance forhpv, it is important to note that most sexually activeindividuals will acquire hpv infection at some point in theirlives.

most of these infections willnot result in clinical disease. it is for this reason thatroutine surveillance for hpv infection is not necessary. hpv infection and many otherhpv-associated clinical conditions are not nationallynotifiable, except for cancers. however, a variety of monitoringactivities are ongoing to help determine the impact of hpvvaccines in the u.s. on these outcomes. importantly, the burden fromcervical and other hpv-related

cancers will be monitored bycancer registries that cover 100% of the u.s. population. these registries are part of thecdc's national program of cancer registries, or npcr, and thenational cancer institute's surveillance, epidemiology andend results, or seer, program. the registries are designed tomonitor cancer trends over time, determine cancer patterns invarious populations, and guide planning and evaluation ofcancer-control programs, including vaccine, screening,and treatment.

data from the registries arecombined to estimate national cancer incidence and mortalityannually. surveillance data on cancer endpoints will be extremely useful in monitoring the impact of hpvvaccine on the u.s. population. but 20 or 30 years of cancersurveillance may be required before any impact can beaccurately measured. more quickly attainableend-point measures of vaccine impact include outcomes such ashpv prevalence, anogenital warts, and cervical-cancerprecursors.

monitoring the prevalence ofgenotype-specific hpv infection in a general population mayprovide the earliest evidence of vaccine impact. type-specific hpv infection hasbeen monitored nationally since 2002 as part of a researchprotocol conducted through the national health and nutritionexamination survey, or nhanes. nhanes is representative of thenon-institutionalized civilian u.s. population. nhanes data will provideinformation on trends in hpv

infection over time to determinevaccine impact at the national hpv genotype prevalence is alsobeing determined in young women undergoing routine pap screeningin a managed care organization. changes in hpv genotypes will befollowed as a measure of vaccine impact. decreases in genital-wartincidence could be one of the earliest impacts of thequadrivalent hpv vaccine. genital-wart surveillance isbeing conducted in a sentinel network of 41 sexuallytransmitted disease clinics

located in 12 states. data are being collected onnumbers of patients with genital warts by sex, age, sexualorientation, and wart treatment. genital-warts monitoring willalso be conducted using administrative and claims datain regional and national databases. in the u.s., women are routinelyscreened with the pap test for high-grade hpv-associatedcervical lesions that can progress to cervical cancer ifleft untreated.

pap screening is part of routinepreventive healthcare in the u.s. when high-grade abnormalitiesare found on pap testing, the woman is referred for cervicalbiopsy to determine if the abnormalities are due tocervical cancer or cervical-cancer precursors. two population-based projectshave been piloted to monitor hpv-vaccine impact onbiopsy-confirmed, high-grade cervical lesions

one system uses existinginfrastructure in select population-based cancerregistries to monitor high-grade cervical lesions in adultfemales. these areas are located inkentucky, louisiana, michigan, and los angeles county. one participating registry --the michigan central cancer surveillance program -- willalso be evaluating the feasibility of linking case datawith immunization registry records.

the second project also monitorshigh-grade lesions in a population of females 18 andolder residing in defined catchment areas in five states. data collected on all casesinclude age, race, ethnicity, and insurance status. an important part of thisproject is genotyping of the pre-cancerous lesions to monitortrends in specific hpv types. in addition, more detailedinformation, including hpv vaccine history, will bedetermined through a variety of

methods, including linkage withthe state immunization information systems. cervical-cancer screening in thegeneral population will be estimated to be able to accountfor changes in screening practices. other than the cancer-relateddata already being collected through cancer registries, thereis no recommendation for collection of routinehpv-associated surveillance data at the national level.

however, several states haveinitiated case reporting and other surveillance activities tomeasure the hpv-related-disease burden in their areas. the surveillance approachesbeing undertaken by cdc and states will help determine needsfor additional surveillance end points and measures ofhpv-related disease. >> the healthy people 2010objectives for the united states established a target ofelimination of indigenous cases of measles.

we have met that objective. in march 2000, a group ofexperts met in atlanta to review the current measles situation inthe united states. they concluded that measles wasno longer a year-round endemic disease in the u.s. they also warned that we shouldnot become complacent, because measles continues to be importedinto the u.s. from other parts of the world. endemic transmission could bere-established at any time.

we have experienced measlestransmission that was sustained for weeks or even monthsfollowing an imported case, so we must keep both immunizationlevels and surveillance quality high. in 2011, the u.s., inconjunction with the pan american health organization, orpaho, began the process of verifying and documenting thecontinued elimination of measles in the u.s. this is part of the pahoobjective to verify and document

elimination of measles, rubella,and congenital rubella syndrome, or crs, in all of the americas. this effort highlights the needfor high immunization levels and surveillance quality. typical measles disease includesa prodrome of fever and malaise, cough, coryza, and/orconjunctivitis, followed by a maculopapular rash. before a vaccine was available,measles was usually a moderately severe childhood illness, butsevere complications occurred,

and 1 to 3 cases per 1,000resulted in death. measles is highly contagious,and a single importation can lead to an outbreak if notquickly identified and contained. measles outbreaks can occur evenin the presence of high vaccination coverage whenpockets of susceptible persons are present or wheretransmission is facilitated by close living conditions. this graph shows the number ofmeasles cases reported in the

united states by year from 1950through september 2011. before the introduction of ameasles vaccine, there were more than 500,000 cases of measlesreported every year, although 3 to 4 million cases actuallyoccurred. these cases resulted in 48,000hospitalizations and 450 to 500 deaths every year on average. this disease burden spurreddevelopment of a vaccine to prevent measles. in the first five yearsfollowing licensure of the

vaccine -- 1963 through 1967 --the incidence of measles fell more than 90%. this graph shows the number ofreported cases of measles by year since 1980. in 1989 through 1991, there wasa major resurgence of measles in the united states. these epidemics highlighted therisks of measles among unvaccinated preschool-agedchildren. the epidemics led to majorefforts to improve immunization

coverage among young children,among whom coverage levels were quite low, especially inlow-income, urban populations. the outbreaks also acceleratedefforts to implement a routine second measles dose forschool-aged children, which was recommended in 1989. since 1992, immunizationcoverage among preschool-age children has increasedsubstantially and has been higher than 90% each year since1996. in addition, the immunizationcoverage for two doses of

measles vaccine among 13-through 17-year-olds is approximately 90%. as a result, measles virus nolonger continually circulates in this country. the cases that now occur are dueto importation and subsequent limited spread of the measlesvirus. 2011 has seen the mostimportations and recorded cases since 1996. through september 2011, therehave been 213 reported measles

cases in the u.s., including 72direct importations from between 19 and 22 source countries. 72% of the importations wereu.s. residents traveling abroad. another 32 cases were classifiedas imported-virus cases, meaning they had a virus genotypeidentified but no source of exposure. this means our surveillancesystem is missing a number of imported measles cases, so everyeffort should be made to maintain awareness for measlescases and educate clinicians on

the importance of reporting allsuspected measles cases. western europe has experienced alarge outbreak in 2011 and has been a major source ofimportations to the u.s. there have been more than 14,000cases in france alone and at least seven reported deaths inthe region. in the united states, with mmrvaccination coverage at sustained high levels, many ofthe people who remain susceptible are unvaccinatedbecause of religious or philosophical exemption.

they are likely to have closecontact with other persons who share these beliefs. this sets up a situation wherefurther spread is very likely. for example, in early 2005, anunvaccinated 16-year-old returned to the u.s. from amission trip in romania with measles. the single importation led to anoutbreak of 34 cases, mostly in her unvaccinated close contacts. in 2008, an intentionallyunvaccinated 7-year-old boy

returned to san diego afterbeing infected with measles in switzerland. 11 more cases resulted, one ofwhich was in a 10-month-old infant too young to have beenvaccinated, who was hospitalized for three days. cost of the outbreak wasestimated at $177,000, including public-sector expenditures,medical charges, and costs incurred by families inquarantine. the good news is that promptrecognition of the disease, with

appropriate control measures,can limit the spread of measles. so, let's move on to someguidelines that will help you recognize and contain measles,should you suspect it. the measles case definitionincludes a generalized rash for three days or more, atemperature of 101 degrees fahrenheit or higher, which is38.3 degrees celsius, and either a cough or coryza, orconjunctivitis. some persons with measles virusinfection, especially those who have received ameasles-containing vaccine in

the past, may have a milderdisease with fewer symptoms. these cases may not meet theclinical case definition and should be lab-tested in thecontext of an outbreak or if there is epidemiological linkageto a confirmed case. laboratory studies are criticalin the evaluation of a person with a febrile-rash illness. we asked dr. william bellini,chief of the cdc measles laboratory, to discuss thisissue. >> the laboratory evaluation ofa person in whom measles is

suspected involves collection ofspecimens for viral isolation or serum specimens for antibodytesting or both. the best way to confirm a caseof measles is isolation of measles virus from the person. viral isolates and determinationof virus genotype are essential for tracking the molecularepidemiology of measles now that we no longer have ongoingindigenous transmission in the united states virus identification, either byculture or by reverse

transcriptase polymerase chainreaction, or rt-pcr, should be attempted for all sporadic casesand from at least some cases in each outbreak. appropriate specimens for viralisolation, such as throat swabs or oral fluids, should becollected along with blood specimens, not after serologictest results are received. serologic testing for measlesantibody has been the cornerstone of measles diagnosisfor many years. generally, a susceptible personinfected with measles virus will

first develop an igm antibodyresponse. the igm response, shown here bythe purple line, is usually detectable in the first 48 to 72hours after onset of rash and peaks about two weeks later. igg antibody, shown by theyellow line, is usually not detectable until later in theillness. igg peaks later than igm andremains detectable for many years, probably for the rest ofthe person's life. for serologic confirmation ofmeasles, igm testing is the

method of choice. igg testing requires thedemonstration of a significant rise in measles antibody orseroconversion between the acute and convalescent specimens, sotwo specimens are necessary. because tests for igg requiretwo serum specimens and because a confirmed diagnosis cannot bemade until the second specimen is obtained, igm tests and viralisolation are preferred. the first serum specimen shouldbe obtained as soon as possible after rash onset and, at thelatest, within seven days after

rash onset. the second specimen should bedrawn 10 to 30 days after the first one. if the first blood specimen isdrawn too early in the course of the disease, it may be falselynegative and should be repeated after 72 hours of rash onset. 80% of infected persons will beigm-positive three days after rash onset, and 99% will beigm-positive at four days. a negative igm, even whenproperly drawn, does not rule

out measles in a previouslyvaccinated person, and acute and convalescent igg testing orvirologic testing will be necessary. the serologic test most commonlyperformed for measles antibody is an enzyme-linked immunoassay,which is also known as an elisa or eia. there are a number of commercialigm tests available, and the testing laboratories arewell-advised to run a panel of known igm-positive and -negativeserum specimens if using those

test kits for the first time. in general, most perform well indiagnostic laboratories, but large variations in sensitivityand specificity have been associated with some kits. cdc has developed a highlysensitive and specific igm-capture assay for measlesand accepts specimens for confirmation of igm testing. cdc no longer provides thecomponents of this assay to public-health laboratories.

contact information for themeasles laboratory will be provided on the resources webpage for this program. >> once a suspected case isidentified, contingency planning for public-health action shouldbegin. ideally, results from measlesigm antibody testing and molecular assays would beavailable quickly. but if they are not, it may benecessary to initiate public-health response in theabsence of laboratory confirmation.

control activities should not bedelayed pending the return or confirmation of laboratoryresults. a measles investigationworksheet like this one is included in the surveillancemanual. we will also put a link to themeasles and other worksheets on the web page for this program. there is specific informationthat is essential to collect during a measles caseinvestigation. in addition to collectingdemographic and clinical data,

laboratory confirmation isabsolutely essential for all outbreaks and for all isolatedor sporadic cases. as we mentioned, in theunited states, endemic measles has been eliminated, so measlesis now a rare disease compared with the past. most cases of measles-likeillness will not be measles. even in outbreaks, laboratoryconfirmation should be obtained on as many cases as possible. in the context of an outbreak, aperson meeting the measles

clinical case definition shouldbe considered to have measles for containment purposes,regardless of igm results. once community awareness isincreased during an outbreak, many cases of febrile-rashillness may be reported as suspected measles. the magnitude of the outbreakwill be exaggerated if these cases are classified asconfirmed in the absence of this is particularly importantas the outbreak is ending. at that point, laboratoryconfirmation should be sought on

all suspected cases. during a case investigation, itis important to obtain an accurate and completeimmunization history on all confirmed cases. measles case investigationsshould include complete immunization histories thatdocument all doses of measles-containing vaccine,including dates of vaccination. efforts should be made toidentify the source of infection for every confirmed case ofmeasles.

case patients or theircaregivers should be asked about contact with other known cases. when no history of contact witha known case can be elicited, opportunities for exposure tounknown cases should be sought. such exposures may occur inschools or childcare facilities, following contact withinternational visitors, while visiting tourist locations orsettings such as conventions, during air travel, including atairports, or, unfortunately, in healthcare settings.

unless there is a history ofexposure to a known person with measles, patients or theircaregivers should be closely questioned about all exposuresettings. al? >> thanks, jane. after determining the source ofinfection, you should assess the potential for transmission andidentify contacts. transmission is particularlylikely in households, schools, and other institutions, such ascolleges, prisons, and

contacts of the case patientduring the infectious period should be identified andevaluated for their evidence of immunity to measles -- that is,their vaccination and/or disease status. for measles, the infectiousperiod is from four days before to four days after rash onset. contacts without evidence ofmeasles immunity are at risk for infection and should bevaccinated as soon as possible after exposure, ideally within72 hours.

contacts who choose not to bevaccinated should be asked to quarantine themselves at homefor 21 days after their last exposure and to monitor theirsymptoms daily. immune globulin can beadministered within six days of immune globulin is indicated forhousehold or other close contacts of patients withmeasles who lack evidence of measles immunity, particularlycontacts younger than 1 year of age, pregnant women, andimmunocompromised persons for whom the risk of complicationsis highest.

now that measles is no longer anendemic disease in this country, importation of measles casesfrom outside the united states and subsequent transmission isthe only way cases can occur. among those cases classified asu.s.-acquired -- that is, persons infected within theunited states -- most can be linked to known importations. the cases that we are not ableto link are probably due to unrecognized importations. this situation will almostcertainly continue in the

future, until better measlescontrol is achieved worldwide. until measles is eradicated fromthe planet, our best defense is a well-vaccinated population,careful surveillance, and rapid public-health response tooutbreaks. >> rotavirus is the most commoncause of severe gastroenteritis in infants and young childrenworldwide. nearly every unvaccinated childin the u.s. is infected with rotavirus by age 5 years, andthe majority will have symptomatic gastroenteritis.

the clinical spectrum ofrotavirus illness ranges from mild, watery diarrhea of limitedduration to severe diarrhea with vomiting and fever. this can result in dehydrationwith shock, electrolyte imbalance, hospitalization, anddeath, although deaths are rare in the united states. following an incubation periodof one to three days, the illness often begins abruptly. vomiting often precedes theonset of diarrhea.

severe, dehydrating rotavirusinfection occurs primarily among children 3 to 35 months of age. gastrointestinal symptomsgenerally resolve in three to seven days. rotaviruses are shed in highconcentrations in the stool of infected children and aretransmitted primarily by the fecal-oral route, both throughclose person-to-person contact and through fomites. rotavirus is highlycommunicable, with an infectious

dose of less than 100 virusparticles. in the u.s., before use ofrotavirus vaccines, rotavirus caused marked winter seasonalpeaks of gastroenteritis. peak activity usually began inthe southwest during november or december and spread to thenortheast by april or may. since the widespread use ofrotavirus vaccines, this seasonality has shifted, andthis trend in rotavirus peak activity is no longerconsistently observed. two rotavirus vaccines arecurrently licensed in the

rv5, whose brand name isrotateq, is produced by merck. it is a live, oral, human-bovinereassortant rotavirus vaccine that was licensed in the u.s. in2006. the advisory committee on theimmunization practices recommends routine vaccinationof infants with three doses of this vaccine administered at 2,4, and 6 months of age. rv1, brand name rotarix, isproduced by glaxosmithkline. it was licensed in the u.s. in2008. this live oral vaccine containsan attenuated monovalent human

rotavirus strain. rv1 is recommended to beadministered in two doses to infants at ages 2 and 4 months. with the introduction ofrotavirus vaccines into the u.s. childhood immunization program,surveillance data are needed to monitor the impact ofvaccination in reducing the morbidity and mortality fromrotavirus disease. surveillance data will also benecessary to evaluate vaccine effectiveness in field use overtime and determine the causes of

possible vaccine failure,monitor possibly emerging rotavirus strains, identifypopulation groups that might not be adequately covered byvaccination, and continue to monitor the safety of rotavirusvaccines. since nearly every unvaccinatedchild develops rotavirus gastroenteritis by 5 years ofage and confirming a diagnosis of rotavirus requires laboratorytesting of fecal specimens, identification of every case ofrotavirus is not practical or necessary at this stage of therotavirus vaccination program.

instead, surveillance efforts atthe national level should focus on monitoring trends of severerotavirus disease, such as rotavirus hospitalizations oremergency department visits, and through more intensive effortsat some sentinel sites. in addition to surveillance forsevere disease, viral-strain surveillance is also essential. in the united states, rotavirussurveillance is conducted in several ways. the new vaccine surveillancenetwork, known as nvsn, conducts

active, prospective,population-based surveillance for rotavirus-associatedhospitalizations and emergency-room visits amongchildren. nvsn commenced rotavirussurveillance during the 2006 rotavirus season with threeoriginal sites. in 2011, the network includesseven surveillance sites at medical centers located intennessee, new york, ohio, texas, kansas, washington, andcalifornia. acute gastroenteritis cases areidentified and additional

epidemiological and clinicalinformation is collected from parental interviews and medicalchart reviews. stool specimens are tested forrotavirus antigen at each surveillance site, and cdclaboratories type all positive specimens. analyses are conducted toestimate disease burden and to assess rotavirus vaccineeffectiveness in field use. laboratory-based sentinelsurveillance systems that monitor temporal and geographicpatterns of rotavirus include

the national respiratory andenteric virus surveillance system and the nationalrotavirus strain surveillance system. data from national healthcareutilization data sets are also routinely analyzed to detectnational trends in rotavirus healthcare encounters. some important findings fromthese surveillance activities include the nearly real-timeobservation in 2008 that the u.s. rotavirus season hadshortened and that rotavirus

cases had dropped dramatically. in 2009, surveillance systemsempirically indicated that rotavirus reductions amongolder, largely unvaccinated children in 2008 likely resultedfrom indirect protection conferred by younger, vaccinatedchildren within the household and community. post-licensure rv5 vaccineeffectiveness studies have been conducted showing remarkablyconsistent findings of 86% to 95% protection against rotavirushospitalizations and

emergency-department visits. comparable estimates of vaccineeffectiveness were observed in the first and second years oflife and by rotavirus strain. rv1 vaccine was licensed twoyears later than rv5 in the u.s., and similar post-licensurevaccine effectiveness evaluations of rv1 vaccine areunder way. at this stage in the rotavirusvaccination program, case investigations are usually notwarranted. however, rotavirus outbreaksamong elderly adults in

residential communities continueto be important to investigate. in addition, outbreaks ofrotavirus among childcare or school settings could indicatewhere gaps in vaccine coverage occur and any possibleindication of waning immunity in older children. because diarrheal outbreaks canbe caused by many pathogens, a laboratory investigation for thecausative agent that includes viral, bacterial, and parasiticagents should be considered for gastroenteritis cases seekingmedical attention.

as the u.s. rotavirusvaccination program evolves and rotavirus ceases to be auniversal infection of childhood, our rotavirussurveillance will also need to evolve. >> mumps virus can cause illnesswith an acute onset of unilateral or bilateral tender,self-limited swelling of the parotid or other salivary gland,lasting two or more days. the combination measles, mumps,and rubella vaccine has contributed to the same highcoverage rate for mumps as we

have achieved for measles andrubella. since the start of the mumpsvaccination program in 1967, the number of reported mumps casesin the u.s. decreased more than 99% by 1999, when fewer than 500cases were reported for the first time. during 2000 to 2005, 200 to 400mumps cases were reported annually. most cases of mumps reported inthe u.s. are sporadic cases or result in very limited spread,even in close-contact settings

that may facilitatetransmission. however, larger outbreaks dooccasionally occur. since 2005, mumps outbreaks inhighly vaccinated communities have occurred in the u.s. andelsewhere. in 2006, the u.s. experienced the largest mumpsoutbreak in 20 years, with more than 6,500 cases reported from45 states and washington d.c. and with outbreaks reported onmany college campuses. eight midwest states accountedfor 85% of the reported cases.

the most-affected age group wasyoung adults 18 through 24 years of age, and the majority hadreceived two doses of the mmr reported mumps cases declined tofewer than 500 cases in 2008. however, during 2009 and 2010,reported mumps cases increased again. more than 3,500 outbreak-relatedcases of mumps were reported in orthodox jewish communities innew york city, two upstate new york counties, and onenew jersey county. students in middle and highschool had the highest mumps

incidence, and the vast majorityhad received two doses of mmr also in 2010, the island of guamexperienced a community outbreak resulting in over 500 reportedcases. we learned a lot from these andother outbreaks and made changes to the case definition,laboratory criteria, and case classifications, which went intoeffect beginning in january 2012. the language of the previousdefinition often resulted in inconsistent interpretations,especially for the probable

cases. the new language more clearlyoutlines the characteristics of a probable case and allows statehealth departments to define the group or community that shouldbe considered epidemiologically linked. finally, the updated languagerecognizes the improvements that have been made in mumpslaboratory diagnostics since 2008. the updated case definitionspecifies that, in addition to

certain clinical symptoms, acase must have positive laboratory results from eitherreverse transcriptase polymerase chain reaction, or rt-pcr, orcultures in order to be classified as confirmed. the cdc laboratory has made theprotocol for mumps rt-pcr, as well as control rna and practicepanels available to as a result, rt-pcr testing isbecoming increasingly available in state and local public-healthlaboratories. we will discuss mumps laboratorytesting in more detail in a

moment. jane? >> thanks, al. in the outbreaks in thenortheast united states in 2009 and 2010 and in guam in 2010, athird vaccine dose intervention was evaluated under irb-approvedprotocols. lessons learned from theseinterventions may help guide policies for responses to futureoutbreaks in vaccinated communities.

high vaccine coverage is stillthe best way to prevent and control mumps. acip recommendations for theprevention and control of mumps include two doses of mmr vaccinefor school-aged children kindergarten through high schooland for adults at high risk, such as those who work inhealthcare facilities, international travelers, andstudents at post-high-school educational institutions. routine vaccinationrecommendations for health care

personnel include those bornduring or after 1957 without evidence of immunity should havewritten documentation of having received two doses of live mumpsvirus vaccine. healthcare personnel bornbefore1957 without other evidence of immunity, should consider twodoses of mmr vaccine at the appropriate interval. in outbreak settings, if agegroups recommended for one vaccine dose are affected by theoutbreak, a second dose of mmr vaccine should be considered.

these groups are children 1through 4 years of age and adults not classified as highrisk. during an outbreak, two doses atthe appropriate interval should be recommended for health carepersonnel born before 1957 without other evidence ofimmunity. as we noted earlier, laboratorytesting for mumps virus infection has improved in thelast few years. we asked dr. william bellini,chief of the cdc mumps >> as with measles, laboratorystudies are very useful in the

evaluation of a person withsuspected mumps. however, some studies,particularly the results of antibody testing, can bedifficult to interpret. acute-mumps-virus infection canbe laboratory-confirmed by isolation of mumps virus ordetection of mumps virus by polymerase chain reaction, orpcr. laboratory confirmation can alsoinclude a significant rise in serum mumps igg antibody orseroconversion from igg-negative to igg-positive in acute andconvalescent specimens,

respectively. the latter scenario is rarelyencountered, since almost everyone has either beenvaccinated or has been previously infected with mumpsvirus. moreover, even in the case ofprimary mumps infection, it is not unusual for igg to appearvery early after onset of parotitis. finally, laboratory confirmationmay also be obtained by the detection of serum mumps igmantibody.

this test is quite variable andis most useful when the person has not been vaccinated and hasnot been previously infected with mumps virus. as with measles, mumps igm maybe transient or absent in individuals who previouslyreceived mumps vaccine. in highly vaccinatedpopulations, commercial mumps igm assays perform very poorly,detecting only between 10% and 30% of mumps cases. capture igm assays performbetter than indirect assays.

sera should be collected as soonas possible after symptom onset for igm testing or as acutespecimen for igg. convalescent sera should bedrawn two weeks later. the best specimen formumps-virus isolation is a swab from the parotid, or stensen'sduct. the parotid duct drains in thespace near the upper rear molars. fluid from the buccal area mayyield the best viral sample, particularly when theparotid-gland area just below

the ear is massaged for 30seconds prior to the collection of secretions. buccal swabs should ideally beobtained within three days of parotitis and not be attemptedafter more than seven days. urine samples are nowdiscouraged due to low viral yield. collection of viral samples frompersons suspected of having mumps is strongly recommended. the molecular characteristics ofmumps viruses provides important

information that will helpinform on importations of mumps and endemic mumps transmissionin the u.s. for sporadic cases, one shouldconsider also testing for other etiologies for the illnesses,such as influenza virus, epstein-barr virus, adenovirus,parainfluenza viruses types 1, 2, and 3, or bacteria, includingstaph aureus and alpha hemolytic streptococcus. >> the indicators we track tomonitor the quality of mumps surveillance show that there isa definite need for improvement

on the completeness ofcollection of some key variables during case investigations,including vaccination status. in addition to demographic andclinical data, it is important to obtain accurate and completeimmunization history so we can understand changes in mumpsepidemiology. recent outbreaks have includedmany cases who had already received one or two doses of amumps-containing vaccine. the source of infection shouldbe identified for each confirmed case of mumps.

if there is no history ofcontact with a known case, opportunities for exposure tounknown cases should be identified so that investigativeefforts can be directed to locations of possible exposure. finally, potential for furthertransmission should be assessed, and contacts of the case patientduring the infectious period should be identified. for contact investigations formumps, persons are considered infectious from one to two daysbefore, through five days after

the onset of parotitis. mumps vaccine should be given toall exposed persons who are unable to provide evidence ofimmunity. evidence of immunity is definedas appropriate vaccination status, physician-confirmeddisease history, serological evidence, or birth before 1957. note that physician-confirmedmumps disease history is no longer considered acceptableevidence of immunity for healthcare personnel.

although vaccine has not beenproven to prevent the occurrence of disease when administeredafter exposure, it will provide protection for future exposures. during an outbreak in a school,childcare center, or college, unvaccinated children orstudents should be excluded until 25 days after the lastcase or until they receive the first dose of mmr vaccine. the occurrence of mumpsoutbreaks in the united states, particularly among highlyvaccinated populations, is

challenging. however, careful investigationof recent outbreaks has provided useful information about theepidemiology of this disease. we hope that continuedinvestigations of mumps cases and outbreaks will provideinsights to help us achieve even better control. >> varicella, or chicken pox, isa highly infectious viral disease. before varicella vaccine waslicensed in the united states,

in 1995, about 4 million casesof varicella occurred each year, with more than 10,000varicella-related hospitalizations and about 100to 150 deaths. the good news is thatvaccination coverage among children has risen steadily, andfewer cases of chicken pox are occurring and being reported. in 2010, one-dose varicellavaccination coverage for u.s. children 19 to 35 months of age,as estimated by the national immunization survey, was 90%,and two-dose coverage among

adolescents was 58%. we need to continue efforts toprovide catch-up of the second dose of varicella vaccine forolder children and adolescents. with expanded varicellavaccination, further declines in varicella incidence areexpected. as the number of cases decrease,the need for more complete surveillance increases, andstate-wide case-based surveillance for varicellabecomes feasible. we are at a critical stage forvaricella surveillance.

in the past, most of thedetailed information about the change in varicellaepidemiology, including reduced disease incidence by age group,came from two active surveillance sites inantelope valley, california, and west philadelphia, pennsylvania. these sites were established in1995 to monitor the impact of vaccination program becausenational surveillance for varicella did not exist at thetime of vaccine licensure. however, due to the extremelylow numbers of varicella cases

now occurring, this surveillanceproject has ended, and beginning in 2012, we will be relyingentirely on surveillance through the national notifiable diseasessurveillance system, or nndss, to monitor the impact of ourvaccine policies, including changes in varicellaepidemiology in the u.s. reduction in varicella incidencehas been observed in all age groups. the overall reduction invaricella since implementation of the one-dose program is notunique to the active

surveillance sites. among the states that haveconsistently reported cases through nndss, there was asignificant reduction in cases compared to the pre-vaccine era. nationally, varicellahospitalizations and deaths have also declined substantially,especially among children, for whom there have been declines of90% or greater. extensive post-licensureexperience from outbreak investigations and studies hasshown that one dose of varicella

vaccine is, on average, about85% effective in preventing varicella and close to 100%effective in preventing severe varicella. this level of effectiveness hadconsiderable impact on varicella morbidity and mortality, but itwas not high enough to interrupt endemic disease transmission. outbreaks, though much smallerthan in the pre-vaccine era, continued to occur in schoolswith high one-dose varicella vaccine coverage among theirstudents.

these outbreaks were a majorimpetus behind the two-dose policy recommendation. to improve our control ofvaricella in the united states, in june 2006, the advisorycommittee on immunization practices, or acip, recommendeda routine two-dose schedule for children. the first dose should be givenat 12 to 15 months of age and the second dose at 4 to 6 yearsof age. a second dose is alsorecommended for all persons who

have previously received onlyone dose. in addition, acip recommendedthe use of school entry requirements for middle, highschool, and college to help increase varicella immunity. finally, a second dose wasrecommended for outbreak control. since implementation of theroutine two-dose varicella vaccination program in 2006,varicella incidence in the two active surveillance sitesdeclined 79% by 2010.

children and adolescents aged 5to 14 years continue to experience the greatestreduction in disease. among the states with adequateand consistent reporting through nndss, declines in incidence ofup to 72% have been noted since implementation of the two-dosevaccination program. a reduction of the number andsize of varicella outbreaks has also been noted in our activesurveillance sites and various states. >> thank you, adriana.

in 2002, the council of stateand territorial epidemiologists, or cste, recommended thatvaricella be included in the nndss. states were encouraged toconduct ongoing varicella surveillance to monitor vaccineimpact on morbidity. cste specifically recommendedthat states establish individual case-based reporting systems forvaricella surveillance by 2005. however, other forms ofsurveillance, such as case-based reporting in sentinel sites,were considered to be reasonable

interim steps toward statewidecase reporting. as of january 2011, 38 stateshave implemented either statewide or sentinel-site casereporting. case-based varicellasurveillance will allow us to monitor the impact of thevaricella vaccination program on varicella disease. systematic national case-basedvaricella surveillance will also allow us to continue evaluatingthe effectiveness of our vaccination program andpolicies.

as mentioned earlier, this isour sole source of varicella surveillance data beginning in2012. we are now more than five yearspast the date that cste set for all states to establishindividual case surveillance. states should now be conductingstatewide case-based for case-based surveillance,standard demographic, clinical, and epidemiological data shouldbe collected on each case. age of the person, vaccinationhistory, including number of doses, and the severity ofdisease based on lesion count

are key variables for monitoringimpact of the vaccination program on varicella incidence,including changes in varicella epidemiology and severeoutcomes. a varicella case, according tothe definition established in 1999, is an illness with acuteonset of a diffuse, generalized maculopapulovesicular rashwithout other apparent cause. breakthrough disease isvaricella that occurs in a vaccinated person more than 42days after vaccination. breakthrough disease occurs inabout 15% of persons vaccinated

with one dose who are exposed tovaricella and in less than 5% of persons vaccinated with twodoses. in about 70% to 80% ofbreakthrough cases, disease is mild, with fewer than 50 lesionsand has a shorter duration. the rash may also be atypical inappearance -- maculopapular with few or no vesicles. because of the increasinglikelihood of atypical rash, laboratory testing, wheneverpossible, or epidemiological linkage to a typical case orlaboratory-confirmed case should

be sought to confirm or rule outvaricella. here is dr. stephanie bialek,herpesvirus team lead in the cdc division of viral diseases, totell us more about laboratory testing for varicella. >> laboratory evaluation ofsuspected varicella cases is an important adjunct to varicellasurveillance, particularly in persons whose illness is nottypical. laboratory methods forconfirmation of varicella include virologic techniques,such as polymerase chain

reaction, or pcr, directfluorescent antibody, or dfa, and viral culture. serologic methods includevaricella igm antibody positivity, seroconversion forigg, or a significant rise between acute and convalescentigg antibody. virologic methods are preferredfor diagnosis, and among these, pcr is the best choice forconfirmation, because it is the most sensitive and specific. dfa, the other rapid detectionmethod, can be used if pcr is

unavailable. the preferred specimen for pcris material from skin lesions and scabs. many state public-healthlaboratories now have the capacity to do pcr testing toconfirm varicella. commercially available tests forigm antibody are not reliable and should not be used. in vaccinated persons, serologicmethods are not useful. igm may not be present, and afourfold rise in igg may not

occur. the national vzv laboratory atcdc has developed a reliable igm capture assay and can assistwith laboratory evaluation of unusual cases, if needed. contact information for thenational vzv laboratory is available on the resources webpage for this program. >> surveillance targeted attracking deaths continues to be important for determining theimpact of the vaccination varicella deaths becamenationally notifiable on january

1, 1999. states should investigate andreport every varicella death. each death represents apotential failure of our varicella vaccination program. an outbreak of varicella isdefined as five or more epidemiologically linked casesin one location, such as a school or childcare center. varicella outbreak controlstarts with the exclusion of persons with varicella, as wellas unvaccinated children from

the outbreak setting. persons receiving their firstdose as part of outbreak control may be readmitted to schoolimmediately. along with the second-doserecommendation, acip now recommends that persons who havereceived one dose of varicella vaccine receive a second doseduring a varicella outbreak for outbreak control. cdc guidelines for theinvestigation and management of varicella outbreaks areavailable on the cdc website.

as varicella outbreaks havebecome less common, it is increasingly important to makeevery effort to laboratory-confirm at least onecase in each outbreak and investigate the outbreak tounderstand why they are occurring. several states have alreadydeveloped their own outbreak guidelines. as of january 2011, 33 statesare conducting outbreak a worksheet for outbreaksurveillance and reporting has

been developed and is availableon the resource web page for this program. reporting of cases, deaths, andoutbreaks of varicella will provide evidence forprogrammatic changes that may be needed and will improvevaricella control. we cannot change policy orimprove our program for vaccine delivery without thisinformation. finally, we would like tocomment on surveillance for herpes zoster, also known asshingles.

following primary infection,varicella zoster virus remains in a latent state in human nervetissue. the virus reactivates inapproximately 15% to 30% of infected persons during theirlifetime, resulting in herpes zoster. zoster usually presents as avesicular rash with pain and itching in a dermatomaldistribution. herpes zoster incidenceincreases with increasing age, especially after age 50, and isincreased among

immunocompromised persons. a zoster vaccine is now licensedin the united states for persons 50 years of age and older andrecommended by acip for adults 60 years of age and older. herpes zoster is not nationallynotifiable, and there are currently no plans to recommendthat it be made nationally notifiable. at this stage of the herpeszoster vaccination program, data regarding the baseline incidenceof herpes zoster is important

for surveillance. for example, states could usedata from healthcare maintenance organizations or the behavioralrisk factor surveillance system to assess the incidence ofzoster. cdc is using some of thesemethods, such as national databases and hmo data, toconduct herpes zoster surveillance nationally. as the zoster vaccinationprogram develops, it will be important for us to find ways tomeasure its impact.

>> in 2009, about 3,400 cases ofacute hepatitis b were reported this is an incidence of 1.1cases per 100,000 population and is the lowest incidence ofhepatitis b ever reported in the the rate of hepatitis b hasdeclined 87% since 1990, due in large part to the implementationof universal childhood immunization. the greatest decline in ratesoccurred among children born since the recommendation ofuniversal childhood immunization was implemented in 1991.

but the impact of vaccinationhas also been seen in declining rates in older adolescents andyoung adults. the highest rate of acutehepatitis b are now among persons 30 through 39 years ofage. transmission of hepatitis bvirus, or hbv, occurs as a result of percutaneous orpermucosal exposure to blood of a person acutely or chronicallyinfected with hbv. modes of transmission vary byage. among infants, perinataltransmission of hbv from mother

to child can occur as a resultof blood exposure during birth. children can acquire infectionsvia transmission from infected family and household members. among adolescents and adults,common risk factors for acquiring infection withhepatitis b virus include sex with multiple partners andinjection drug use. other risk factors includeoccupational exposure to human blood or medical interventions,such as surgery, blood transfusion, or organtransplants.

the incubation period for acutehepatitis b averages 120 days, with a range of 45 to 160 days. infants, children younger than10 years of age, and immunosuppressed adults withnewly acquired hbv infection are usually asymptomatic. 30% to 50% of older children andadults are symptomatic. when present, clinical symptomsand signs include nausea, vomiting, abdominal pain, andjaundice. the fatality rate among personswith acute hepatitis b is about

0.5% to 1%. although the consequences ofacute hepatitis b can be severe, most of the serious sequelaeassociated with this disease occurs in person in whom chronicinfections develop. persons with chronic hbvinfection are often initially asymptomatic. however, chronic liver diseasedevelops in 15% to 25% of persons with chronic hbvinfection. 15% to 25% will die prematurelyfrom cirrhosis or liver cancer.

in infants, young children, andimmunosuppressed persons, most newly acquired hbv infectionsresult in chronic infection. 90% of infants with perinatalinfection develop chronic infection. in contrast, in persons withnormal immune systems who become infected as adults, almostall -- 94% to 98% -- recover completely from newly acquiredhbv infection. the high risk of chronicinfection with perinatal hbv infection is why prevention ofmaternal-to-infant transmission

is such a high priority in thehepatitis b elimination program. until recently, nationalsurveillance for hepatitis b included only acute symptomaticdisease and perinatal hepatitis b chronic hepatitis b viralinfection was added to the list of nationally notifiablediseases in 2003. suspected cases of acutehepatitis b, chronic hbv infection, and perinatal hbvinfection, identified by health departments, should beinvestigated to confirm that the

case meets the case definition,determine the characteristic of the case, and ensure thatrecommended interventions occur, including the vaccination ofsusceptible contacts. the case definition for acutehepatitis b includes having clinical compatible symptoms,jaundice, or an elevation in liver enzymes and laboratoryconfirmation. the preferred test forlaboratory confirmation of a case of acute hbv infection is apositive test for igm antibody to the hepatitis b core antigen.

igm antibody to core antigen isa good marker for acute hepatitis b because it isgenerally detectable for only the first six months afterinfection. if this test is not available, apositive test for hepatitis b surface antigen, or hbsag, witha negative test for acute hepatitis "a" viral infection,if done, is sufficient to confirm a diagnosis of acutehepatitis b in a symptomatic person. antibody to hepatitis b surfaceantigen indicates immunity to

hepatitis b virus. in investigating a confirmedcase of acute hepatitis b, in addition to collecting theappropriate demographic and clinical data to describe thecase, there are two additional priorities. first, you should identifywhether there are contacts to the patient at risk of becominginfected. second, you should determine, ifpossible, the source of infection for the index case.

critical data to be collectedfor an acute hepatitis case investigation should includedemographic and clinical data, laboratory data includingserologic testing and liver enzyme levels, risk-factorinformation, and vaccination pregnancy status of anyhbv-infected woman should be determined to make sure thataction is taken to prevent perinatal transmission to herinfant. if an hbv-infected woman ofchild-bearing age is identified, information on the patientshould be shared with the local

perinatal hepatitis bcoordinator. this will help to ensure thatinfants born to these women receive appropriatepost-exposure prophylaxis. contacts of a person with acutehepatitis b who are at risk of infection should be identifiedand given post-exposure prophylaxis as appropriate. for acute hepatitis b, thegeneral recommendation for post-exposure prophylaxis is togive hepatitis b immune globulin, or hbig, and to beginthe hepatitis b vaccine series

within 14 days of last exposure. contacts who requirepost-exposure prophylaxis include sexual contacts of thepatient and any infant younger than 12 months of age for whomthe patient is a primary caregiver. in addition, other persons withidentifiable percutaneous or permucosal exposure to the bloodof the patient should be given prophylaxis. providing hbig post-exposureprophylaxis to non-sexual

household contacts of thepatient or others with no clear exposure to blood of the personis not recommended. however, providing hepatitis bvaccine to non-sexual household contacts, especially childrenand adolescents, is highly recommended. in addition to contactinformation for post-exposure prophylaxis, it is alsoimportant to identify the source of the infection for acutecases. there may be other persons whocontinue to be at risk of

infection from the same source. to identify the source of acutehepatitis b infection, it is important to ask about exposureduring the previous six weeks to six months, including contactwith another person with acute or chronic hbv infection,occupational exposure to human blood, injection drug use,medical interventions such as dialysis, blood transfusion,organ transplants, or receipt of blood products. it is also important todetermine the sexual history of

the patient, including whetherthe individual has multiple sex partners or is a man who has hadsex with men. perinatal hepatitis b viralinfection is defined as the presence of hepatitis b surfaceantigen in an infant 1 to 24 months of age, born in the u.s. or u.s. territory to ahepatitis-b-surface-antigen- positive woman. since perinatal hbv infectionsare almost always asymptomatic, there are no clinical criteriafor these cases.

the identification of infectedinfants is dependent upon serologic testing of infantsborn to woman who are hbsag-positive. state-based perinatalhepatitis-b-prevention programs exist to follow up pregnantwomen known to be hbsag positive this activity helps to ensurethat their infants receive post-exposure prophylaxis. as part of their follow-up,exposed infants should be tested

for hbsag three months afterreceiving the third dose of when a perinatal case isidentified, the case should be reviewed and verified with thelocal perinatal hepatitis b coordinator. if the infant has been infected,it should be reported as a case of perinatal hbv infectionthrough the national notifiable disease surveillance system. although the implementation ofprograms for the prevention of perinatal hbv has considerablesuccess in preventing perinatal

and childhood transmission ofhbv, challenges remain. for example, although more than90% of pregnant women nationally are screened before delivery,cdc estimates that only about half of the expected births toinfected women are identified to state perinatalhepatitis-b-prevention programs for case management. case management of infants bornto hbv-infected women is needed to maximize on-time delivery ofpost-exposure prophylaxis. in addition, errors inmanagement of infants born to

hbsag-positive women and infantsborn to women with unknown hbsag status have kept many of theseinfants from receiving appropriate post-exposureprophylaxis to prevent hbv surveillance for hbv infectionis an important public-health tool. identification and reporting ofpersons with hbv infection assists public-healthprofessionals in reaching contacts of cases -- persons whoare at risk of infection -- so that vaccination andpost-exposure prophylaxis can be

provided, if appropriate. surveillance also helps usunderstand the risk of infection in order to provide theappropriate programmatic resources to reduce the risk ofhbv infection in the u.s. >> in february 2010, the foodand drug administration licensed the 13-valent pneumococcalconjugate vaccine, or pcv13. pcv13 was made a part of therecommended childhood immunization schedule soonthereafter, replacing the 7-valent pneumococcal conjugatevaccine, or pcv7, which was

originally introduced in 2000. national immunization surveydata for 2010 indicate that national coverage with fourdoses of pneumococcal conjugate vaccine is about 83%, withcoverage in states and metropolitan areas ranging from68% to 93%. as with othervaccine-preventable diseases, we need to establish surveillanceto monitor the impact of our vaccination program. before we talk about what such aprogram might look like, let's

review a little background onpneumococcal disease. streptococcus pneumoniae is agram-positive bacteria with more than 90 known serotypes. as with other encapsulatedorganisms, the polysaccharide capsule is an importantvirulence factor, and the capsular type-specific antibodyis protective. although all serotypes may causeserious disease, a relatively limited number of serotypescause the majority of invasive infections.

overall, six to 11 serotypes areestimated to account for more than 70% of invasive diseaseworldwide, but the ranking of serotype prevalence differs byage group and by geographic area. at the time of pcv7 introductionin 2000, the seven vaccine serotypes accounted for 80% ofisolates from blood or cerebrospinal fluid amongchildren younger than 5 years of age. in 2011, 11 years after vaccinelicensure, the seven vaccine

serotypes included in pcv7account for about 2% of cases in pneumococcus may be isolatedfrom the upper respiratory tract of about 10% of people at anygiven time. carriage rates among childrenare usually higher. all persons probably carrypneumococcus at some time during the course of a year. transmission can occur as longas the organism is present in respiratory secretions. we don't understand why somepeople go on to develop invasive

host factors, such as underlyingillness, are probably important. having a viral infection at thesame time pneumococcus is present in the upper airwaymight also make someone more likely to develop invasivedisease. but persons without anyunderlying illness may also develop invasive pneumococcaldisease. although pneumococcal infectionsoccur in healthy persons, there are factors that significantlyincrease the risk for invasive children with functional oranatomic asplenia, sickle cell

disease, and otherhemoglobinopathies, as well as children with hiv infection areat extremely high risk of invasive disease. some studies estimate rates morethan 50 times higher than the rates among children of the sameage without these conditions. out-of-home childcare has beenshown to increase the risk of invasive pneumococcal diseaseand acute otitis media. the risk for children in thesesettings is increased two- to three-fold among childrenyounger than 5 years of age.

finally, children of certainracial and ethnic groups have increased rates of invasivepneumococcal disease. these include alaska natives,certain american indian groups, and african-americans. the reasons for this increasedrisk is not clear. much of our knowledge of theincidence and risk factors for invasive pneumococcal diseasecomes from special studies and surveillance systems. one such surveillance system iscdc's active bacterial core

surveillance, or abcs. we asked dr. gayle langley, themedical director of abcs, to describe this system for us. >> cdc's active bacterial coresurveillance, or abcs, is an active laboratory andpopulation-based surveillance system for invasive disease dueto six bacterial pathogens. the pathogens include groups "a"and "b" streptococcus, haemophilus influenzae,neisseria meningitidis, streptococcus pneumoniae, andmethicillin-resistant

staphylococcus aureus, or mrsa. the principal objectives of abcsare to accurately measure the incidence of these six bacterialpathogens, to determine their epidemiologic characteristics,to track trends over time, and to provide an infrastructure forfurther public-health research. abcs is a core component of theemerging infections program network, or eip, and isconducted at 10 eip sites across these sites represent apopulation of more than 42 million persons.

abcs is managed by staff in thenational center for immunization and respiratory diseases. for each case of invasivedisease in the surveillance population, a case report formwith basic demographic and clinical information iscompleted. the bacterial isolate is sent tocdc and other reference laboratories for additionalevaluation. abcs also provides aninfrastructure for special studies, including ones aimed atidentifying risk factors for

disease, evaluatingpost-licensure vaccine effectiveness, and monitoringthe impact of prevention policies. for streptococcus pneumoniae,the main objectives of surveillance are to measure theburden of invasive pneumococcal disease among persons of allages, to track emerging antibiotic resistance, and tostudy the impact of pneumococcal vaccines. data from abcs has beenparticularly useful in

documenting the impact ofpneumococcal conjugate vaccine among children and the indirectbenefit of this vaccine for older persons. data for all six diseasesincluded in abcs, as well as estimates of disease burdenextrapolated to the u.s. population are available on theactive bacterial core surveillance website. >> data from abcs have beenvaluable for documenting the burden of invasive pneumococcaldisease, or ipd, among children

and for identifying groups ofchildren at increased risk of the abcs data have also beenvaluable in documenting the impact of pneumococcalvaccination of children. in fact, since implementation ofpneumococcal conjugate vaccines, abcs has documented that ratesof invasive pneumococcal disease have fallen significantly. this graph shows the rates ofinvasive pneumococcal disease among children less than 5 yearsof age, beginning in 1998 and continuing through 2010.

the vertical axis showsincidence, expressed as cases per 100,000 population. the blue line indicates rates ofinvasive disease due to the seven pneumococcal serotypescontained in pcv7. the gray line depicts rates ofdisease due to serotypes contained in pcv13, but not inpcv7. and the purple line depictsrates of disease due to non-vaccine serotypes. prior to introduction of thepneumococcal conjugate vaccine

in 2000, rates of invasivepneumococcal disease due to the seven vaccine serotypes werearound 90 cases per 100,000 population. after the introduction of pcv7in 2000, rates of disease due to these seven serotypes droppeddramatically to less than one case per 100,000 by 2007. however, during the last severalyears, rates of disease due to serotypes not covered by pcv7have increased. in order to provide increasedcoverage for these serotypes,

pcv-13 was introduced in 2010. with the introduction of pcv-13,it is anticipated that cases of invasive disease due to the sixadditional serotypes covered by the vaccine will decrease. abcs only operates in 10selected locations. we cannot rely on it to documentthe impact of each state's program for vaccination ofchildren with pneumococcal conjugate vaccine. to monitor this, each state mustevaluate invasive pneumococcal

disease through time and withinpopulations. national data, based on eachstate's surveillance, should be used to look at rates betweengroups to see if state programs are reaching individuals andgroups recommended for vaccination. fortunately, we have a goodmodel for how to do this from surveillance for haemophilusinfluenzae invasive disease. invasive disease due to eitherof these organisms is a laboratory-based diagnosis, andmany persons with these

infections are hospitalized. national reporting for invasivepneumococcal disease can be nearly complete withlaboratory-based reports. during 1994 through 2006,various changes were made to the case definition for invasivepneumococcal disease, especially as it relates toantibiotic-resistant infections. however, as of 2009, all casesof invasive pneumococcal disease are to be reported using asingle case definition -- that is, isolation of anypneumococcus from a normally

sterile site. additional information, such asinformation on antibiotic susceptibility testing, can beprovided as supplemental information. chad? >> thanks, gina. once we identify a case ofinvasive pneumococcal disease, or ipd, in a child younger than5 years old, what information should be collected?

we need the core data thatshould be collected for every case of vaccine-preventabledisease, including demographic information and clinical data,as well as risk factors for for pneumococcal disease, riskfactors include underlying medical conditions, such asasplenia or hiv infection and out-of-home childcare. and, of course, we areinterested in vaccination history. some cases of ipd will occuramong unvaccinated or

incompletely vaccinatedchildren, but there will be cases reported among fullyvaccinated children, as well. these fully vaccinated childrencould represent vaccine failures, defined as diseasecaused by a serotype included in the vaccine. a more likely possibility isthat they will represent disease caused by a serotypenotincluded in the vaccine. to facilitate the distinctionbetween vaccine failures and infection caused by non-vaccineserotypes, cdc has developed a

protocol for identifyingpneumococcal serotypes using this protocol is available onthe cdc website. we will include a link to thepcr-based serotyping protocol on the resources web page for thisprogram. pcr is used by most statepublic-health laboratories to detect a variety of infectiousdiseases. this technology should allowmost, if not all, state health departments to enhancesurveillance for invasive a key focus of state-basedsurveillance should be to

compare state rates to rateselsewhere to see if they are within the expected range and tocompare among populations within the state. importantly, rates of diseaseshould be considered in the context of pcv13 coverage rates. if rates of invasive disease areelevated, the next step would be to determine the cause. like any epidemiologicinvestigation, cases should be characterized in terms ofperson, place, and time.

these fundamental pieces of datacan shed light on whether an outbreak might be occurring in aparticular geographic location or in a specific population. clinical microbiologylaboratories should be contacted and asked to save allpneumococcal isolates or to ship them to the state public-healthlaboratory for storage. the pcr-based protocol forpneumococcal serotyping can be used to determine whether aspecific serotype is common to some or all of the cases.

this information can helpdetermine whether an outbreak is cdc is available to provideepidemiologic and laboratory support in outbreak situations. state health departments shouldcontact the respiratory diseases branch of the national centerfor immunization and respiratory diseases to discuss theirspecific situation. contact information for therespiratory diseases branch is included on the programresources web page. if you identify a child withinvasive pneumococcal disease,

you may consider asking thelaboratory to save the isolate. these stored isolates would thenbe available, if needed, in cases of outbreaks, unexplainedincrease in rates, or disparity in rates between the subsets ofstates' populations. remember, we will be relying onyour help in conducting national surveillance to understand theimpact of the 13-valent pneumococcal conjugate vaccine. >> among young children,invasive disease due to haemophilus influenzae type b,or hib, has virtually

disappeared in theunited states. with widespread use of conjugatehaemophilus influenzae type b vaccines since the early 1990s,this disease has changed from the most common cause ofbacterial meningitis in infants to a medical rarity. the bacterium haemophilusinfluenzae can either be encapsulated or unencapsulated. the capsule is composed ofpolysaccharide, of which there are six antigenically distincttypes.

the capsular types aredesignated by the letters "a" through "f." non-type-b encapsulated strainscan cause disease similar to type b infections. unencapsulated strains arereferred to as non-typable. non-typable strains are a commoncause of ear infections in children and bronchitis inadults, but may also cause invasive disease, such asbacteremia and pneumonia. before introduction of effectivevaccines, the type b

encapsulated strain accountedfor more than 95% of invasive haemophilus influenzae diseaseamong children. in the pre-vaccine era, therewere an estimated 20,000 cases of invasive hib disease annuallyamong children younger than 5 years of age in theunited states. hib was the leading cause ofbacterial meningitis in the united states among children inthat same age group. approximately 2/3 of cases wereamong children younger than 18 months of age.

conjugate vaccines against thehib bacterium were first licensed for use in infants inthe united states in 1990. invasive haemophilus influenzaeinfections in children younger than 5 years of age becamenationally notifiable in 1991. since then, vaccine coverageincreased rapidly, and hib disease decreased rapidly. this graph shows the incidenceof invasive type b disease among children younger than 5 years ofage since 1989, shown by the yellow line.

the rate fell rapidly afterintroduction of the conjugate by 1994, the incidence of hibamong children younger than 5 years of age had decreased by95% compared with the pre-vaccination era. by 2005, the incidence haddeclined by 99% or more, and the rate has remained very low sincethen. notice that the rates ofnon-type-b and non-typable disease, shown by the red andgreen lines, have remained basically unchanged.

chemoprophylaxis is onlyrecommended for hib cases, because disease among closecontacts has not been identified with other haemophilusinfluenzae strains. therefore, to make public-healthdecisions about whether chemoprophylaxis is needed, wemust serotype isolates from all haemophilus influenzae cases. on average, 40 cases of hib arereported each year in children younger than 5 years of age inthe united states. however, on average, 121haemophilus influenzae cases in

children younger than 5 years ofage have an unknown serotype each year. serotype data may be unknown ifisolate serotyping is not conducted or is misclassifiedduring data transmission from states to cdc. some of these cases with unknownserotype may be hib cases. we estimate that each year, sixto 12 cases of haemophilus influenzae with an unknownserotype are actually hib. for this reason, it is importantto serotype isolates of all

cases so that hib cases areidentified and appropriate chemoprophylaxis measures can betaken. gina? >> invasive haemophilusinfluenzae disease includes a number of clinical syndromes,including meningitis, epiglottitis, periorbital andbuccal cellulitis, septic arthritis, sepsis, andpneumonia. of course, these syndromes canbe caused by other bacterial and viral agents, as well, so caseconfirmation requires isolation

of haemophilus influenzae from anormally sterile body site. but isolation of the organism isnot the end of the laboratory investigation. the next step is serotyping. serotyping is an extremelyimportant laboratory procedure that should be performed onevery isolate of haemophilus influenzae from a normallysterile site. serotyping is the only way todetermine if an isolate is type b.

this is important because onlytype b is preventable by serotyping provides criticalinformation to those in public health who need to decidewhether or not the contacts of the patient requirechemoprophylaxis. the serotype can also help aphysician determine whether the immunological status of thepatient should be evaluated -- that is, hib disease in a personwho had already been vaccinated may indicate that the person maynot have responded normally to laboratory support forhaemophilus influenzae

serotyping should be readilyavailable through your state laboratory. for advice on serotypingcapability within your state, contact your state healthdepartment. other than getting the isolatefor serotyping, what else needs to be done for caseinvestigation? after you hear about a possiblecase, you need to review laboratory, hospital, and otherclinical records to obtain the critical information needed onevery case.

this includes demographicinformation and relevant clinical data. clinical data needed includesthe clinical syndrome, dates of hospitalization, date of firstpositive culture, and outcome of the illness. results of laboratory testingare critical. the serotype of the isolate,body-fluid source of the isolate, and antibioticsusceptibility are all important.

vaccination status should beobtained for every case. since there are several types ofhib vaccines, this means the date, manufacturer, and lotnumber of each hib vaccine dose. this information tells uswhether the case occurred as a result of vaccine failure orfailure to vaccinate. finally, we need information onrisk factors for hib disease. one of the most important ofthese is whether or not the child attended childcare. if the child attended childcare,control measures may be needed

for other center attendees. invasive haemophilus influenzaedisease is rare in the it is critical that every stateinvestigate, lab-confirm, serotype, and report every caseof invasive disease. how can surveillance for hibdisease be improved? hib is a laboratory-baseddiagnosis, and almost all cases are hospitalized for the firstfew days of the illness. as a result, reporting can benearly complete if all clinical microbiology laboratories andall hospitals report the cases

that they see. elizabeth? >> thank you, gina. with so few cases of hib diseasenow occurring, how can we be sure that our surveillance isgood enough to detect the few cases that may be still outthere? remember, only type b disease ispreventable by vaccination. that means that disease thatlooks like hib but is caused by non-type-b or non-typablestrains is still occurring.

although rates vary in differentpopulations, data from the active bacterial coresurveillance system, or abcs, suggest that each year, amongchildren younger than 5 years of age, non-b cases continue tooccur at a rate of less than one case per 100,000 children. non-typable cases occur at arate of 1.5 to 2 cases per 100,000 children. if cases of invasive haemophilusinfluenzae disease are being serotyped and reported amongchildren and you are not finding

type b cases, but you arefinding non-type-b or non-typable cases, that is goodevidence that surveillance is probably good enough to detecttype b cases. type b disease is probably notpresent in your community. this is an example of asurveillance indicator. a discussion of surveillanceindicators is included in a separate module of this program. >> high vaccination coverage hasled to all-time record low levels of manyvaccine-preventable diseases,

but not pertussis. pertussis remains endemic in theunited states. sporadic cases andcommunity-wide outbreaks continue to occur in spite ofrecord-high vaccine coverage among children. pertussis, or whooping cough, iscaused by the bacterium bordetella pertussis. classic pertussis illness ischaracterized by severe paroxysmal coughing, sometimesfollowed by an inspiratory

"whoop." illness can be milder and thetypical "whoop" absent, especially in those who havebeen vaccinated. pertussis occurs in a cyclicalpattern, with the number of cases peaking every three tofive years as immunity wanes and the bacteria begin circulatingagain. peak years occur when enoughsusceptible people are present in the population to allow forsustained transmission of pertussis.

before a vaccine was available,pertussis was a universal infection of childhood, withthousands of deaths each year. after the introduction ofpertussis vaccine in the late 1940s, the number of reportedcases began to drop. the lowest annual total was in1976, when about 1,000 cases were reported. since 1980, the number ofreported cases of pertussis has been gradually rising withperiodic peaks. reported cases of pertussispeaked in 2004 and 2005, with

more than 25,000 cases reportedeach year, and again in 2010, with more than 27,000 cases. most deaths occur among infantsyounger than 2 months of age, who are too young to bevaccinated. 27 pertussis-related deaths werereported during 2010. although we usually think ofpertussis as a disease of young children, there is increasingrecognition of pertussis in older children, adolescents, andadults. although infants typically havethe most severe cases of

pertussis, older children andadolescents can also have severe illness. here is a short video of anadolescent with pertussis. >> [ coughing, wheezing ] >> [ speaking french ] >> [ coughing and wheezingcontinues ] >> [ breathing deeply ]>> adolescents and adults accounted for an increasingproportion of reported pertussis cases during the early 2000s.

the proportion of cases reportedoccurring in persons 10 years of age and older increased from 20%in 1990 to 66% in 2006. more recently, increased ratesof disease have been observed among school-age children. outbreaks have been reported inelementary, middle, and high this is a reminder that fullyvaccinated persons of any age can become infected withpertussis, especially if pertussis is increasinglycirculating in the community. no vaccine is 100% effective,and protection afforded by the

vaccine wanes over time. however, when a vaccinatedperson gets pertussis, the infection is usually lesssevere. >> there are currently sixdiphtheria, tetanus, and acellular pertussis vaccineslicensed for use in infants and children through 6 years of age. we will refer to the pediatricvaccines as d-t-a-p. some of these vaccines areavailable in combination with other vaccines.

there are also two acellularpertussis vaccines approved for use in adolescents and adults. these vaccines are also combinedwith diphtheria and tetanus toxoids. we will refer to these vaccinesas tdap. the pediatric vaccines aredifferent from the adolescent and adult vaccines. there are also differences amongvaccines approved for the same age groups.

compared to tdap, the pediatricvaccines contain different components of the pertussisorganism, different amounts of these components, and thecomponents are made by different processes. diphtheria and tetanus toxoidsin the pediatric vaccines also differ in amounts. adolescent and adult versions ofthe vaccines have reduced quantities of pertussis,diphtheria, and tetanus components compared with thepediatric formulations.

routinely recommends a five-dosedtap vaccine series for all children, beginning at 2 monthsof age through 6 years of age. a single dose of tdap vaccine isrecommended for all adolescents at 11 or 12 years of age. tdap is also recommended forolder adolescents, 13 through 18 years of age, who have not yetreceived a dose of tdap. adults 19 through 64 years ofage are also recommended to receive a single dose of tdap toreplace the next dose of adult tetanus-diphtheria vaccine.

adults who are or anticipatebeing in close contact with an infant younger than 12 months ofage should be vaccinated. this includes adults 65 yearsand older. also, pregnant women should bevaccinated during the third or late second trimester ofpregnancy -- after 20 weeks gestation -- if they have notpreviously been vaccinated with tdap. collection of vaccine historyfor all cases is especially as you talk with vaccineproviders, encourage them to

remind adults to keep theirvaccination records. recording manufacturer, type ofvaccine, and lot number will make it easier to identify thetype of vaccine. this will be useful, both forsurveillance and for physicians providing vaccines for theiradult patients. at this time, we are not certainhow long protection will last from the booster dose inadolescents or adults. we will need good surveillancedata to help us address this issue.

tami? now let's talk about theinvestigation of a suspected pertussis case. pertussis should be suspected ina person who develops a cough illness that lasts more thanseven days and has fits, or paroxysms, of coughing. cough is the hallmark ofpertussis, but very young infants with pertussis maypresent with apnea, or long pauses in breathing.

when pertussis is clinicallysuspected, appropriate specimens should be obtained forlaboratory testing. for national reporting, thereare two different methods by which cases can belaboratory-confirmed. these methods are isolation ofbordetella pertussis from a clinical specimen or a positivepolymerase chain reaction, or pcr, assay. let me repeat that. for laboratory confirmation ofpertussis, we need either a

positive bordetella pertussisculture or a positive pcr test. commercial serological tests forpertussis infection are not standardized. results of serologic testing arenot used for case confirmation for national reporting, exceptin massachusetts, where a standardized serological assayhas been in use for many years. culture of a nasopharyngealaspirate is considered the gold standard for diagnosis. while culture is highlyspecific, sensitivity decreases

when patients have receivedantibiotics, have been vaccinated, or when there aredelays in specimen collection. culture results may not beavailable for seven to 14 days. optimal timing for diagnosingpertussis using culture is less than two weeks after coughonset. however, even in the bestcircumstances, the organism takes time to isolate. but you should try, especiallyin the setting of an outbreak. pcr is the most readilyavailable method for diagnosing

pertussis and is optimallysensitive less than three weeks after cough onset. while pcr is a sensitive andtimely diagnostic tool, signs and symptoms of the patientshould be consistent with pertussis to confirm diagnosis. a nasopharyngeal aspirate is thepreferred method of obtaining a specimen for pertussis cultureand pcr. however, nylon swabs may beused, as well. many epidemiologists andhealthcare providers have never

performed a nasopharyngealaspirate or swab. the quality of the specimen iscritical to obtaining an accurate result. since good technique inobtaining a nasopharyngeal specimen is such an importantpart of pertussis surveillance, we would like to show you ashort video that demonstrates the proper collection technique. >> ideally, you should collecttwo n.p. swabs -- one to be used for culture and one to be usedfor pcr.

one swab for culture and pcr isalso acceptable. the n.p. swab tips may becomposed of polyester, such as dacron or rayon or they may benylon-flocked. the swab shaft should bealuminum or flexible plastic. cotton-tipped or calciumalginate swabs are not acceptable, as residues presentin these materials may inhibit pcr assays. when collecting n.p. swabs,you'll also need a tube containing semi-solid regan-lowetransport agar.

once you have the necessarysupplies on hand, you can collect the specimen followingthese steps. first, put on your mask and eyeprotection. following hand-washing, put onyour gloves. ask the patient if he or she hasa deviated septum or nasal obstruction, and then ask themto blow their nose to remove any excess mucus from the nasalcavity. gently insert the swab straightback into a nostril, aiming posteriorly, along the floor ofthe nasal cavity, until reaching

the posterior wall of thenasopharynx, being careful not to insert it upwards. the distance from the nose tothe ear gives an estimate of the distance the swab should beinserted. do not force the swab. if an obstruction isencountered, try the other nostril. leave swab in place for up to 10seconds and then remove slowly. after collection, place one n.p.

swab in a regan-lowe transporttube for culture and the other n.p. swab in an empty tube forpcr. it is important to useregan-lowe transport agar, which contains the antibioticcephalexin, to prevent overgrowth of normalnasopharyngeal flora. depending on the brand of swabused for collection, the shaft may need to be bent slightly,cut, or broken off at score mark to fit the swab into thetransport tube. if only one swab can beobtained, place it in the

regan-lowe transport tube, whichcan be used for both culture and pcr. store tubes at 4 degrees celsiusand transport to the lab within 24 hours of collection in acooler with ice packs to maintain 4 degrees celsius. plating for culture will need tobe completed within 24 hours of specimen collection, so timelytransportation to the laboratory is essential. >> laboratory results,particularly cultures, are an

important part of theinvestigation of a suspected case of pertussis, but there isother information you will need to collect, as well. as always, we need demographicinformation like age and gender. we also need clinical data, suchas the duration of cough and the presence of paroxysms, whoop,and post-tussive vomiting. this information is important,because laboratory testing cannot always be obtained or maynot be conclusive. we use the clinical data todetermine if the person met the

clinical case definition forpertussis. we need to know how severe theillness is, which is why we ask about complications likepneumonia and whether or not the patient survived. and, of course, knowing thevaccination history is critical. a complete vaccination historyincludes the date, vaccine type, manufacturer, and lot number foreach dose of vaccine. this is important for all casesnow that vaccines are recommended for all ages.

a pertussis surveillanceworksheet is included in the surveillance manual. the worksheet will help youorganize your case investigation so you will not miss anycritical information. we will include a link to themanual on the resources web page for this program. how can you find out if yourpertussis surveillance system is working? one easy method is by using asurveillance indicator.

for pertussis, that meansfinding out if anyone is even considering the diagnosis. if laboratory testing is notbeing done, no cases will be reported because no one islooking. if you determine that no one islooking, there is a lot that can be done to improve pertussissurveillance at the community level. most importantly, cliniciansneed to know that pertussis is an important cause of coughillness in all persons,

regardless of age or vaccinestatus. many people undergo extensiveand unnecessary evaluations for prolonged cough without thediagnosis of pertussis even being considered. increasing awareness ofproviders about this infection and the appropriate diagnostictests is very important. with additional vaccinesavailable and changes in the recommended vaccinationschedules, surveillance will be essential to evaluate the impacton pertussis incidence in the

>> although the incidence ofmeningococcal disease is at a historic low, health departmentscontinue to play an important role in investigating cases toprevent secondary cases and to monitor disease trends. two quadrivalent meningococcalpolysaccharide-protein conjugate vaccines, which we will refer toas mcv4, are licensed by the food and drug administration. both vaccines provide protectionfor serogroups "a," "c," "y," and w-135.

both mcv4 vaccines are approvedfor use in persons 2 through 55 years of age. menactra brand mcv4 is alsoapproved by the food and drug administration as a two-doseseries in children aged 9 through 23 months. acip recommends routinevaccination at 11 or 12 years, with a booster dose at 16 years. routine vaccination is alsorecommended for college freshmen living in a dormitory and forother populations at increased

risk. examples of groups at increasedrisk include persons with anatomic or functional asplenia,military recruits, and certain international travelers. meningococcal vaccines that area four-dose series, starting at 2 months of age, may be licensedin 2012. national surveillance isimportant to identify outbreaks of meningococcal disease, tofollow disease trends, and to monitor the impact of thevaccination program.

before we discuss the componentsof surveillance, let's go through some backgroundinformation about neisseria meningitidis. neisseria meningitidis istransmitted through direct contact with respiratorysecretions from a person with invasive disease or, much morecommonly, from an asymptomatic carrier. meningococcal disease occurs inthree common clinical forms -- meningitis in about 50% ofcases, blood infection in about

30% of cases, and pneumonia inabout 10% of cases. other forms account for theremaining 10% of cases. 5% to 20% of patients developpurpura fulminans, also called meningococcemia, a severe andoverwhelming blood infection. approximately 800 to 1,200 casesof meningococcal disease are reported each year in theunited states, with a case-fatality ratio of 10% to14%. in addition, serious sequelae,including deafness, neurologic deficit, or limb loss, occur in11% to 19% of survivors.

serogroups "b," "c," and "y" arethe major causes of meningococcal disease in theu.s., each currently being responsible for about 1/3 ofcases. the proportion of cases causedby each serogroup changes with time and varies by age group. for example, serogroup "b"accounts for more than 50% of cases among infants younger than1 year of age. there is no serogroup "b"vaccine available in the u.s. at this time.

among persons 11 to 19 years ofage, 75% of cases are caused by serogroups "c," "y," or w-135,which are included in u.s.-licensed vaccines. the majority of these cases aresporadic single cases. although outbreaks causetremendous public concern and disruption, they account forvery few of cases. in the united states,meningococcal disease is seasonal, with cases peaking indecember and january. rates of meningococcal diseaseare currently the lowest since

the early 1990s, and these rateshave remained low for several years. this graph, from the activebacterial core surveillance system, or abcs, shows rates ofall reported meningococcal disease, not just vaccineserogroups, by single year of age during 2000 through 2009. the overall rate in theunited states is about 0.3 cases rates are highest in infancy, onthe left of the graphic. a second, lower peak occurs inadolescence, around 18 years of

it is this second peak amongadolescents that our current meningococcal vaccinationstrategy is intended to reduce. future vaccines licensed forinfants or that include serogroup "b" may give us a toolto also reduce the risk of meningococcal disease amonginfants. in the u.s., disease caused byneisseria meningitidis is nationally notifiable. states report cases to the cdcas part of the national notifiable diseases surveillancesystem, or nndss.

the nndss includes case reportsfrom healthcare providers and laboratories in all 50 states. in addition, active surveillancefor meningococcal disease is conducted by the abcs. abcs is a unique surveillancesystem that provides information for other bacterial pathogens,as well. describe the system for us. abcs is a core component of theremerging infections programrch. the principal objectives forneisseria meningitidis are to

provide baseline data related tothe meningococcal vaccine, to evaluate vaccine impact ondisease burden, herd immunity, and molecular epidemiology, andto determine appropriate verification and validationcriteria for current and potential serogrouping methods. >> because invasivemeningococcal disease is quite rare in the united states andbecause all cases need appropriate contactinvestigations and outbreaks need to be identified, we cannotrely on abcs surveillance alone.

it is critical that every stateinvestigate, confirm, serogroup, and report every case ofmeningococcal disease. meningococcal cases areconfirmed based on isolation of the organism from a normallysterile site, such as blood or cerebrospinal fluid or from skinscrapings from purpuric lesions. with national reporting,laboratory confirmation, and hospital staff reporting cases,reporting should be nearly complete. a diagnosis based on culture isquite specific, with infrequent

false-positives. but not all cases areculture-confirmed, especially in patients who already havereceived antibiotics. a probable case is defined as aclinically compatible illness and evidence of neisseriameningitidis dna, using a validated polymerase chainreaction, or pcr, obtained from a normally sterile site, orevidence of neisseria meningitidis antigen byimmunohistochemistry on formalin-fixed tissue, or latexagglutination of cerebrospinal

fluid. pcr and latex agglutinationtesting is available at some state health departments, aswell as cdc. immunohistochemistry testing isavailable only at cdc. information that should becollected for a case of neisseria meningitidis issimilar to other diseases we have discussed during thisprogram. report core data, includingdemographic, clinical, and risk-factor information.

serogroup and vaccinationhistory are also important data to report. testing should be performed todetermine the serogroup of the isolate, because vaccination canbe used to control outbreaks caused by serogroups in thevaccine. serogroup testing of neisseriameningitidis isolates is performed by hospital and statepublic-health laboratories. cases of serogroup "a," "c,""y," or w-135 in persons eligible for vaccination mayrepresent either a vaccine

failure or a failure tovaccinate. cases that are serogroup "b" arenot vaccine-preventable. the adolescent meningococcalvaccination program is now well under way. new vaccines to prevent infantdisease and serogroup "b" disease are on the horizon. surveillance will play animportant role as we monitor meningococcal disease trends andevaluate the best strategies for use of new vaccines.

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