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Hot Topics in Infectious Diseases Penelope H. Dennehy, MD Director, Division of Pediatric Infectious Diseases Hasbro Children’s Hospital Professor and Vice Chair for Academic Affairs Department of Pediatrics Alpert Medical School of Brown University Disclosure Information • I do not have financial relationship(s) with the manufacturers(s) of any commercial product(s) and/or provider of commercial service(s) discussed in this CME activity. • I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation. • I acknowledge that today’s activity is certified for CME credit and thus cannot be promotional. I will give a balanced presentation using the best available evidence to support my conclusions and recommendations. Objectives • To discuss challenging issues and cases in infectious diseases representing the hot topics in infectious diseases for 2017 Case 1 • A mother calls you about her 18-year-old daughter, who is a student at a college where several students have been diagnosed with mumps • The mother does not know the immunization status of the infected individuals but states that her daughter is up to date on all her immunizations and, to the best of her knowledge, has received two doses of MMR • Her daughter has been asymptomatic, with no fever or other systemic complaint Case 1 Of the following, the MOST appropriate action is to: A. B. C. D. E. administer a dose of mumps immune globulin to her daughter confirm that her daughter has received two doses of MMR vaccine have her daughter stay out of classes for 9 days to observe for the development of symptoms vaccinate her daughter immediately with a monovalent mumps vaccine to prevent infection from this exposure vaccinate her daughter immediately with another dose of MMR to prevent infection from this exposure Mumps Cases by Year Mumps Cases in the United States Mumps Vaccine • MMR vaccine – routinely administered to children at 12 to 15 months, with a second dose given at 4 to 6 years • Monovalent mumps vaccine is not available • Mumps vaccine effectiveness – 78% for one dose – 88% for two doses Mumps in Vaccinated People • In highly vaccinated communities, the proportion of cases that occur among people who have been vaccinated may be high • People who have not been vaccinated against mumps usually have a much greater mumps attack rate than those who have been fully vaccinated Management of a Mumps Exposure • Ensure that the exposed person has received the recommended number of doses of MMR vaccine – If the individual has not received two doses, a second dose of MMR should be administered ASAP • Mumps vaccine is not effective in preventing infection after exposure • Immune globulin and mumps IG are not effective for post-exposure prophylaxis – Mumps IG no longer is available in the United States Management of a Mumps Exposure • Exclusion from school after exposure – Fully immunized persons do not need to be excluded – Students who are not fully immunized are excluded until they are immunized, then can be readmitted immediately – Students who refuse mumps vaccination should be excluded from school for at least 26 days after the onset of parotitis in the last person who has mumps in the affected school – Persons who have mumps are excluded from school for 9 days from the onset of their parotid swelling Mumps Outbreak Recommendations • Should you offer a third dose of MMR to persons who have two prior documented doses of MMR? – Consult with the local health department – Currently, data are insufficient to recommend for or against the routine use of a third dose of MMR vaccine – CDC has issued guidance for use of a third dose in specifically identified target populations along with criteria for public health departments to consider in decision making. – This information can be found at www.cdc.gov/vaccines/pubs/surv-manual/chpt09mumps.html. Case 2 • A 33-year old female is in the obstetric clinic for her 18th week check-up. She has no complaints. • She just got back from Brazil where she spent 3 weeks with her family. • She has not felt any fetal movements and a routine ultrasound reveals a moderate amount of microcephaly. Case 2 • Which of the following may be related to the fetal pathology? A. B. C. D. E. Chikungunya Dengue Yellow Fever Zika virus All of the above Case 2 • Which system is most often involved with congenital birth defects caused by the Zika virus infection? A. B. C. D. E. Cardiovascular system Central nervous system Joints Reproductive system Skin Zika Virus Zika virus (Zika) Single stranded RNA virus Genus Flavivirus, family Flaviviridae Closely related to dengue, yellow fever, Japanese encephalitis, and West Nile viruses Primarily transmitted through the bite of an infected Aedes species mosquito (Ae. aegypti and Ae. albopictus). Why do we worry about Zika Virus? • Many people infected with Zika virus won’t have symptoms or will only have mild symptoms. • Zika virus infection during pregnancy can cause microcephaly and other severe brain defects. Where has Zika been found? http://www.cdc.gov/zika/geo/index.html Zika in the United States • Zika Virus Disease Cases* – 5,359 • Pregnant Women with Any Lab Evidence of Zika Virus Infection# – 1,963 *Source: ArboNET data as of June 28, 2017 https://www.cdc.gov/zika/reporting/case-counts.html #Source: Pregnancy Registries as of June 13, 2017 https://www.cdc.gov/zika/geo/pregwomen-uscases.html Zika in the United States • Local mosquito-borne spread of Zika virus has been identified in Miami-Dade County, Florida, and Brownsville, Texas – Pregnant women should consider postponing travel to Brownsville, Texas (currently a yellow area) – CDC lifted the yellow area designation for Miami-Dade County on 6/2/17 Brownsville, Texas Miami-Dade County, Florida How is Zika spread? • Zika can be spread through – – – – Mosquito bites From a pregnant woman to her fetus Sex with an infected person Laboratory exposure • Zika may be spread through blood transfusion. • No reports of infants getting Zika through breastfeeding. What are the symptoms of Zika? • For people with symptoms, the most common symptoms of Zika are – – – – – – Fever Rash Headache Joint pain Conjunctivitis (red eyes) Muscle pain How can Zika affect pregnancies? • Zika virus can be transmitted during all trimesters of pregnancy • Mother may transmit even if she is asymptomatic • Most recent data from the Zika Pregnancy Registries suggest transmission rate is about 5% overall Shapiro-Mendoza CK, et al. Pregnancy Outcomes After Maternal Zika Virus Infection During Pregnancy — U.S. Territories, January 1, 2016–April 25, 2017. MMWR 2017;66:615-621. How can Zika affect pregnancies? • Infection during pregnancy can cause damage to the brain, microcephaly, and congenital Zika syndrome • Linked to other problems, such as miscarriage, stillbirth, and birth defects • No evidence that past infection will affect future pregnancies once the virus has cleared the body Congenital Zika Syndrome Distinct pattern of birth defects in fetuses and infants of women infected during pregnancy Associated with 5 types of birth defects not seen or rarely seen with other infections during pregnancy • severe microcephaly (>3 SD below the mean) with findings consistent with fetal brain disruption sequence including – • – – – partially collapsed skull, overlapping cranial sutures prominent occipital bone redundant scalp skin neurologic impairment – – – – – – – cerebral cortex thinning abnormal gyral patterns increased fluid spaces subcortical calcifications corpus callosum anomalies reduced white matter cerebellar vermis hypoplasia brain anomalies including • ocular findings such as – – – • • – – macular scarring focal pigmentary retinal mottling structural anomalies (microphthalmia, coloboma, cataracts, and posterior anomalies) chorioretinal atrophy optic nerve hypoplasia/atrophy – – unilateral or bilateral clubfoot arthrogryposis multiplex congenita – pronounced early hypertonia/spasticity with extrapyramidal symptoms motor disabilities cognitive disabilities Hypotonia irritability/excessive crying Tremors swallowing dysfunction vision impairment hearing impairment epilepsy congenital contractures, including neurological impairments such as – – – – – – – – – Assessing pregnant women for possible Zika exposure • At each prenatal care visit, all pregnant women should be asked if they – Traveled to or live in an area with risk of Zika – Had sex without a condom with a partner who lives in or traveled to an area with risk of Zika How is Zika diagnosed? • • A blood or urine test can confirm a Zika infection CDC has algorithms for testing pregnant women and infants – – • • – For pregnant women: https://www.cdc.gov/zika/pdfs/testing_algorithm.pdf At time of birth: https://www.cdc.gov/zika/hc-providers/test-specimens-attime-of-birth.html For infants: https://www.cdc.gov/mmwr/volumes/65/wr/mm6533e2.htm Healthcare providers should work closely with the state, local, or territorial health department to ensure that the appropriate test is ordered and interpreted correctly CDC maintains a 24/7 Zika consultation service for HCPs caring for pregnant women – To contact the service, call 770-488-7100 and ask for the Zika Pregnancy Hotline Who should be tested for Zika? • All pregnant women (regardless of symptoms) who – Live in or recently traveled to an area with risk of Zika that has a CDC Zika travel notice, or – Had unprotected sex with a partner who lives in or traveled to an area with risk of Zika that has a CDC Zika travel notice • Pregnant women who live in or recently traveled to an area with risk of Zika but without a CDC Zika travel notice – If they develop symptoms of Zika, or – If their fetus has abnormalities on an ultrasound that may be related to Zika infection Testing babies for Zika CDC recommends laboratory testing for • All infants born to mothers with laboratory evidence of Zika virus infection during pregnancy • Infants who have abnormal clinical or neuroimaging findings suggestive of congenital Zika syndrome and a mother with a possible exposure to Zika virus, regardless of maternal Zika virus testing results Reporting of Zika in the United States • • • Healthcare providers should report cases to their local, state, or territorial health department. State and territorial health departments are encouraged to report confirmed cases to CDC through ArboNET, the national surveillance system for arboviral diseases. Pregnant women with any lab evidence of possible Zika virus infection should be reported to the US Zika Pregnancy Registry. For the most recent case counts, visit https://www.cdc.gov/zika/geo/unitedstates.html. Zika Pregnancy Registries US Zika Pregnancy Registry • CDC established the US Zika Pregnancy Registry to collect information and learn more about pregnant women in the US with Zika and their infants. • Data will be used to – Update recommendations for clinical care – Plan for services for pregnant women and families affected by Zika – Improve prevention of Zika infection during pregnancy • Zika Active Pregnancy Surveillance System is used in Puerto Rico. https://www.cdc.gov/zika/hc-providers/registry.html https://www.cdc.gov/zika/public-health-partners/zapss.html Suggested Readings - Zika • General information about zika virus: http://www.cdc.gov/zika http://www.paho.org/hq/index.php?option=com_content&vi ew=article&id=11585&Itemid=41688&lang=en • Zika information for clinicians: http://www.cdc.gov/zika/hcproviders/index.html • Travel notices related to zika virus: http://wwwnc.cdc.gov/travel/page/zika-travelinformation • For information on where Zika virus is found: http://www.cdc.gov/zika/geo/index.html. • Information about zika for travelers and travel health providers: http://wwwnc.cdc.gov/travel/yellowbook/2016/i nfectious-diseases-related-to-travel/zika Case 3 • A previously healthy 10 year old girl presents to your office for her routine health maintenance visit in October 2017. • What influenza vaccine should she be given? A. B. C. D. E. Trivalent IIV Quadrivalent IIV Quadrivalent LAIV Either A or B Either A, B or C Influenza Vaccine Recommendations for 2017-2018 Influenza 2016-2017 Season • • • • As of early November 2016, only 37% of children aged 6 months–17 years had received vaccine Only 47% of pregnant women had been vaccinated by early November 2016 During the current flu season, 101 children died Vaccine effectiveness was 53% in children 6 mos to 8 years and 23% in older children Flannery B, et al. Interim Estimates of 2016–17 Seasonal Influenza Vaccine Effectiveness — United States, February 2017. MMWR 2017;66:167–171. Influenza 2016-2017 Season • Overall, flu activity was moderate, with peak incidence in mid-February • Influenza A (H3N2) viruses predominated overall, since late March, influenza B viruses have been reported more frequently than A viruses. Influenza Vaccine Recommendations for 2017-2018 • Core requirements for influenza immunization would remain the same for the 2017-18 flu season, under a recommendation approved by the Advisory Committee on Immunization Practices (ACIP) at the June meeting Influenza Vaccines for the 2017-2018 Season • 2017–18 trivalent vaccines contain: – an A/Michigan/45/2015 (H1N1) pdm09-like virus – an A/Hong Kong/4801/2014 (H3N2)-like virus – a B/Brisbane/60/2008-like virus (B/Victoria lineage) • 2017-2018 quadrivalent vaccines have two influenza B viruses and contain: – the viruses recommended for the trivalent vaccines – a B/Phuket/3073/2013-like virus (B/Yamagata lineage) Influenza Vaccine Recommendations for 2017-2018 • ACIP also recommended allowing any licensed, recommended and age-appropriate trivalent or quadrivalent inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV) for pregnant women. – The previous recommendation specified use of IIV for pregnant women. • Afluria (IIV3) now is indicated for people 5 years and older (down from 9 years and older). Influenza Vaccine Recommendations for 2017-2018 • ACIP reiterated that the quadrivalent live attenuated influenza vaccine (LAIV4) not be used in any setting during the upcoming flu season • In 2016 it was reported that in all pediatric age groups LAIV did not have any statistically significant benefit in preventing influenza during the 3 previous flu seasons • Additional data on LAIV4 is expected in October 2017 Prior Recommendations for Choice of Influenza Vaccine • Annual influenza vaccination for everyone ages 6 months and older has been recommended since 2011-2012 season • During 2014-2015 season – CDC/ACIP had a preferential recommendation for LAIV for young children – AAP had no preference • During the 2015-2016 season – CDC and AAP recommended influenza vaccination without any preference for vaccine Performance of Influenza Vaccine • Can range widely from season to season • Can be affected by a number of factors including: – characteristics of the person being vaccinated – the similarity between vaccine viruses and circulating viruses – which vaccine is used • While the protection offered by flu vaccines can vary, overall VE estimate was 48% against flu last season LAIV Vaccine Effectiveness • LAIV contains live, weakened influenza viruses • In general, vaccines containing live viruses can cause a stronger immune response than vaccines with inactivated virus • VE data before and soon after licensure of LAIV suggested it was either comparable to, or better than, IIV LAIV Vaccine Effectiveness In late May 2016, preliminary VE data on LAIV in children 2 through 17 years during 2015-2016 season became available from the U.S. Influenza Vaccine Effectiveness Network Vaccine VE against any flu virus 95% CI LAIV 3% -49 to 37% IIV 63% 52 to 72% Other non-CDC studies support the conclusion that LAIV worked less well than IIV during the 2015-2016 season LAIV Vaccine Effectiveness The data from 2015-2016 follows two previous seasons showing poor and/or lower than expected VE for LAIV in children 2 through 8 years 2013-2014 Vaccine LAIV IIV VE against influenza A (H1N1) 0 63% 2014-2015 Vaccine VE against influenza A H3N2 LAIV -23% (95% CI -90 to 21%) IIV 15% (95% CI -20 to 40%) The reason for the poor performance of LAIV is not known and is being investigated Influenza Vaccine Recommendations for 2017-2018 • The CDC director will review ACIP’s recommendations. Those that are approved will be published as official recommendations in the Morbidity and Mortality Weekly Report. • The AAP will review the CDC’s changes and make official policy recommendations of its own. Suggested Reading • Centers for Disease Control and Prevention. Vaccine effectiveness - How well does the flu vaccine work? • CDC’s seasonal influenza web page for health professionals, www.cdc.gov/flu/professionals/index.htm Post-Test Questions Question 1 • You are caring for a college student who is exposed to mumps on campus. The student received 2 prior doses of MMR at 12 months and 6 years of age. • You should administer a 3rd dose of MMR as soon as possible A. True B. False Question 2 • Zika is transmitted only during the first trimester of pregnancy A. True B. False Question 3 • An asymptomatically infected mother can not transmit Zika virus to her fetus A. True B. False Question 4 • Zika can be diagnosed with either blood or urine tests. A. True B. False Question 5 • LAIV is recommended for use during the 2017-2018 influenza season. A. True B. False