Infectious Diseases in the Media. Anna-Kathryn Rye Burch, MD Palmetto Health USC DHEC Division of Acute Disease Epidemiology

Transcription

1 Infectious Diseases in the Media Anna-Kathryn Rye Burch, MD Palmetto Health USC DHEC Division of Acute Disease Epidemiology

2 I have nothing to disclose. Disclosures

3 I had good intentions of summarizing infectious diseases recently seen in the media, to include Ebola, Zika, Naegleria fowleri and Enterovirus D-68. I quickly realized, there was too much information on Zika virus which eventually took up my entire presentation (and it is the infectious disease with the most media attention currently). So

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5 Zika Virus Zika Virus is a flavivirus the same family as Dengue, Yellow Fever, West Nile and Japanese Encephalitis viruses. Vectors: Ae. aegypti or Ae. Albopictus mosquito Also transmits Dengue and Chikungunya Aggressive daytime biters Live in and around households Lay eggs in domestic water-holding containers

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8 Zika Routes of Transmission Maternal Fetal Transmission Intrauterine perinatal transmission Other Transmission Sexual Transmission from infected men Laboratory exposure Blood transfusion Plausible modes of transmission Tissue transplantation Breast milk

9 Zika Epidemiology Discovered in the Zika forest in Uganda in 1947 in monkeys Before 2007, sporadic human disease case reports from Africa and southeast Asia In 2007, first outbreak reported in Micronesia , >28,000 suspected cases reported from French Polynesia* Western Hemisphere: Brazil s first reports were May 2015 cases of microcephaly potentially associated with ZIKA infection were identified in November 2015 SO.was Zika Virus imported to Brazil during the 2014 World Cup or 2014 World Sprint Championship Canoe Race????? *

10 Zika Importation to Brazil Zika virus in the Americas: Early epidemiological and genetic findings Science April 2016, Faria et al. Phylogenetic analysis Suggests single introduction of Zika to the Americas (brought to Brazil by just one person) Estimated introduction date to be about May to December 2013 approximately 12 months earlier than the virus was initially reported estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands Science 15 Apr 2016: Vol. 352, Issue 6283, pp DOI: /science.aaf5036

11 Active Transmission of Zika as of 6/29/2016

12 US Cases of Zika There are currently NO reports of active Zika virus transmission along the U.S.-Mexico border

13 US Zika Numbers US States (Majority NY, FL, CA, TX) Locally acquired mosquito-borne cases reported: Travel-associated cases reported: 819 Laboratory acquired cases reported: 1 Total: 820 Sexually transmitted: 11 Guillain-Barré syndrome: 4 US Territories (American Samoa, Puerto Rico, US Virgin Islands) Locally acquired cases reported: 1,854 Travel-associated cases reported: 6 Total: 1,860 ZERO SC has had one confirmed case of Zika (6/29/2016) Guillain-Barré syndrome: 7 ArboNET for January 01, 2015 June 22, 2016.

14 Zika Clinical Presentation Illness usually mild with symptoms lasting from several days to a week Most common symptoms: fever, rash, joint pain, and conjunctivitis Severe disease and hospitalization is uncommon 90% of infections are asymptomatic Deaths are rare and are associated with other underlying conditions.

15 Differential Diagnosis for Zika Dengue Chikungunya Malaria Leptospirosis Rickettsial Diseases Rubella Measles Parvovirus Enterovirus Adenovirus Group A streptococcus

16 Zika vs. Dengue vs. Chikungunya Dengue and chikungunya viruses are transmitted by same mosquitoes Dengue and chikungunya can circulate in the same area and rarely cause coinfections Diseases have similar clinical features Important to rule out dengue, as proper clinical management can improve outcome

17 Zika Incubation and Viremia Incubation Period: Evidence from case reports and experience from related flavivirus infections indicate that the incubation period for Zika virus disease is likely 3 14 days Viremic Period: After symptom onset, the duration of Zika viremia may range from a few days to 1 week the longest duration of viremia in the published literature was 11 days Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016 Weekly / April 1, 2016 / 65(12);

18 Treatment Currently, no medication or vaccine exists to prevent or treat the virus Treatment is supportive for symptoms: rest, fluids, antipyretics and analgesics Aspirin and NSAIDs are not recommended until dengue is ruled out due to the risk of hemorrhage with dengue. Education for suspect cases: avoid mosquito bites for the first week of illness to prevent spread to mosquitoes prevention of sexual transmission

19 Sexual Transmission of Zika Virus

20 Sexual Transmission of Zika (Men) Zika can be transmitted via MEN vaginal and anal sex, and fellatio (most likely) To date, sexually transmitted cases have only been from symptomatic men Can asymptomatic men sexually transmit Zika???? Zika virus RNA has been detected in semen up to 62 days after the onset of symptoms Men who have possible Zika virus exposure without clinical illness should wait at least EIGHT weeks after possible exposure before attempting conception Men diagnosed with Zika should abstain from sex or use condoms for SIX months, especially before attempting conception Any man who has traveled to a country with ongoing Zika transmission who has a pregnant partner should abstain from sex or use condoms for the ENTIRE duration of the pregnancy Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016 Weekly / April 1, 2016 / 65(12);

21 Sexual Transmission/Conception Summary Situation Men who have traveled, are ASYMPTOMATIC and want to conceive Men who have traveled, are SYMPTOMATIC and want to conceive Men who have traveled and have a pregnant partner Women who have traveled, are SYMPTOMATIC and want to conceive Duation of Absinence/Condom Use 8 Weeks 6 Months from symptom onset Entire Rest of Pregnancy 8 Weeks from symptom onset Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016 Weekly / April 1, 2016 / 65(12);

22 Sexual Transmission of Zika (Men) Testing a man s blood, urine or semen is not recommended to determine his potential risk of sexually transmitting Zika virus for the following reasons: A negative blood test or antibody test could be falsely reassuring. This can happen when: The blood test is performed after the virus is no longer in the blood (detected by RT-PCR), but Zika virus remains in the semen. The antibody test is performed early after infection when the antibody levels are not yet high enough to be detected, or later after infection when the antibody levels have fallen to undetectable levels. The test is falsely negative. CDC has limited understanding of how to interpret the results of semen testing. Zika shedding in semen may be intermittent Studies are underway Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016 Weekly / April 1, 2016 / 65(12);

23 Sexual Transmission of Zika (Women) NO current evidence that a woman with Zika can transmit the virus to her sex partner(s) during vaginal sex or cunnilingus Available studies have detected Zika in saliva, urine, and breast milk, but not in vaginal swabs collected from women with Zika NO evidence that Zika virus will cause congenital infection in pregnancies conceived after the resolution of maternal Zika viremia Women with possible Zika virus exposure during the 8 weeks before conception (6 weeks before the last menstrual period) can be offered serologic testing within 2 12 weeks of this exposure Any pregnant woman who has traveled to a country with ongoing Zika transmission while pregnant can be offered serologic testing within 2 12 weeks of this exposure Routine testing is not currently recommended for women who are attempting conception who have possible exposure to Zika virus but no clinical illness Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016 Weekly / April 1, 2016 / 65(12);

24 Pregnant Women with Zika Exposure

25 Call DHEC A negative immunoglobulin M test result obtained 2 12 weeks after known exposure would suggest that a recent Zika virus infection did not occur and could obviate the need for serial ultrasounds Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure United States, 2016 Weekly / April 1, 2016 / 65(12);

26 Zika Testing

27 Clinical Criteria for Zika Testing Travel to area of known ongoing Zika transmission, OR sexual contact with a traveler who has visited an area of ongoing Zika transmission AND One or more of the following symptoms: Acute onset of fever (measured or reported) Maculopapular rash Arthralgia Conjunctivitis OR Complication of pregnancy Fetal loss in a mother with compatible illness and/or epidemiologic risk factors; OR In utero findings of microcephaly and/or intracranial calcifications with maternal risk factors OR Guillain-Barré syndrome not known to be associated with another diagnosed etiology

28 Zika Virus Testing Real-time reverse transcription polymerase chain reaction (rrt-pcr) is the preferred test for Zika virus infection Serum PCR testing within 7 days of onset of symptoms IgM 4 days after onset of symptoms Potential cross reaction with related flaviviruses (dengue, yellow fever, vaccination history) Urine (currently only performed by CDC) CDC Trioplex rrt-pcr assay is the only diagnostic tool authorized by the FDA for Zika virus testing of urine PCR testing within 14 days of onset of symptoms Confirmatory testing of any positive results performed by CDC Plaque reduction neutralizing test (PRNT)

29 Serology Cross-Reactions with Other Flaviviruses Zika serology (IgM) can be positive due to antibodies against related flaviviruses Dengue, Yellow Fever (even after vaccination), etc PRNT may discriminate between cross-reacting antibodies in primary flavivirus infections, and is needed to confirm positive Zika IgM. Difficult to distinguish infecting virus in people previously infected with or vaccinated against a related flavivirus Healthcare providers should work with DHEC to ensure test results are interpreted correctly

30 Urine vs. Serum Zika PCR Comparison of Test Results for Zika Virus RNA in Urine, Serum, and Saliva Specimens from Persons with Travel-Associated Zika Virus Disease Florida, 2016 Weekly / May 13, 2016 / 65(18) Overall, urine specimens from 65 of 70 cases (93%) obtained within 20 days after symptom onset were rrt- PCR-positive. Of the 55 cases with specimens obtained on the same date and within 5 days of illness onset, urine was rrt- PCR-positive in 95%, but serum rrt-pcr was positive in only 56%. 82 percent (9/11) of urine specimens obtained more than 5 days after illness onset were rrt-pcr-positive, but none of the serum specimens were positive. Florida Department of Health Bureau of Public Health Laboratories performed Zika virus testing on specimens from 913 people who met criteria for testing. Previous data demonstrate detection of the virus by rrt-pcr of urine, saliva, and semen; therefore, the Florida Department of Health obtained multiple specimen types from people with suspected acute disease.

31 Zika Testing Information Days from Illness Onset Specimen Type Testing Available <4 days Serum and Urine Urine PCR; Serum -- PCR 4-7 days Serum and Urine Urine PCR; Serum PCR and IgM 8-14 days Serum and Urine Urine PCR; Serum IgM >14 days to ~12 weeks Serum IgM Asymptomatic, pregnant within 2-12 weeks of travel to Zikaaffected area or sexual contact with a person confirmed to have Zika virus infection Serum IgM only

32 Zika Virus Commercial Testing Focus Diagnostics Zika Virus RNA Qualitative Real-Time RT-PCR Emergency Use Authorization issued on April 28, 2016 Testing limited to Quest Diagnostics laboratories Serum only Detects Zika only Must meet criteria for testing developed by CDC/DHEC

33 Complications of Zika Virus

34 Complications of Zika Virus Infection Zika infection during pregnancy Causes microcephaly and other severe fetal brain defects Linked to eye defects, hearing loss and impaired growth in infants Research being done to better understand the extent of Zika virus impact on infants Post-infection complications Guillain-Barré syndrome

35 Zika Virus and Microcephaly Reports of a substantial increase in number of babies born with microcephaly in 2015 in Brazil True baseline is unknown Zika virus infection identified in several infants born with microcephaly (including deaths) and in early fetal lossses Some of the infants with microcephaly have tested negative for Zika virus Incidence of microcephaly among fetuses with congenital Zika infection is unknown

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37 Zika Virus and Microcephaly Rasmussen SA et al. Zika Virus and Birth Defects Reviewing the Evidence for Causality. N Eng J Med 2016; 374: Use of Shepard s Criteria for Proof of Teratogenicity in Humans and Bradford Hill criteria as framework to infer a causal relationship between prenatal Zika virus infection and microcephaly and other severe brain abnormalities Based on epidemiologic studies from Brazil and French Polynesia Evidence that Zika virus infects neural progenitor cells and produces cell death and abnormal growth Evidence of Zika virus in brains of fetuses and infants with microcephaly

38 Zika Virus and Microcephaly If a pregnant woman is infected: What we don t know how the virus will affect her or her pregnancy. when in pregnancy the infection might cause harm to the fetus. how likely the virus will pass to a fetus. if the fetus is infected, if it will develop birth defects. if sexual transmission of Zika virus poses a different risk of birth defects than mosquito-borne transmission.

39 Zika Virus and Guillain-Barré CDC is tracking GBS cases associated with Zika As of June 8, 2016, 2 cases in US states and 7 in US territories Case control study, French Polynesia, Zika outbreak in patients diagnosed with GBS during the study period 100% had neutralizing antibodies against Zika 93% had positive Zika IgM and 88% had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurologic symptoms (suggesting recent Zika virus infection) Conclusion: Serologic evidence for recent Zika infection causing Guillain-Barré syndrome No evidence of contribution of past dengue history to development of GBS Cao-Lormeau V et al. Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016:387:

40 Infants with Possible Congenital Zika

41 Recommended Clinical Eval and Lab Testing for Infants with Possible Congenital Zika For all infants with possible congenital Zika virus infection, perform the following: Comprehensive physical examination, including careful measurement of occipitofrontal circumference, length, weight, and assessment of gestational age. Evaluation for neurologic abnormalities, dysmorphic features, splenomegaly, hepatomegaly, and rash or other skin lesions. Full body photographs and photographic documentation of any rash, skin lesions, or dysmorphic features should be performed. If an abnormality is noted, consultation with an appropriate specialist is recommended. Cranial ultrasound, unless prenatal ultrasound results from third trimester demonstrated no abnormalities of the brain. Evaluation of hearing by evoked otoacoustic emissions testing or auditory brainstem response testing, either before discharge from the hospital or within 1 month after birth. Infants with abnormal initial hearing screens should be referred to an audiologist for further evaluation. Ophthalmologic evaluation, including examination of the retina, either before discharge from the hospital or within 1 month after birth. Infants with abnormal initial eye evaluation should be referred to a pediatric ophthalmologist for further evaluation. Staples, JE, Dziuban EJ, Fischer M, et al. Interim guidelines for the evaluation and testing of infants with possible congenital Zika virus infection United States, MMWR Morb Mortal Wkly Rep 2016;65:63 7.

42 Recommended Clinical Eval and Lab Testing for Infants with Possible Congenital Zika Other evaluations specific to the infant s clinical presentation: For infants with microcephaly or intracranial calcifications, additional evaluation includes the following: Consultation with a clinical geneticist or dysmorphologist. Consultation with a pediatric neurologist to determine appropriate brain imaging and additional evaluation (e.g., ultrasound, computerized tomography scan, magnetic resonance imaging, and electroencephalogram). Testing for other congenital infections such as syphilis, toxoplasmosis, rubella, cytomegalovirus infection, lymphocytic choriomeningitis virus infection, and herpes simplex virus infections. Consider consulting a pediatric infectious disease specialist. Complete blood count with platelet count and liver function and enzyme tests, including alanine aminotransferase, aspartate aminotransferase, and bilirubin. Consideration of genetic and other teratogenic causes based on additional congenital anomalies that are identified through clinical examination and imaging studies. Adapted from: Staples, JE, Dziuban EJ, Fischer M, et al. Interim guidelines for the evaluation and testing of infants with possible congenital Zika virus infection United States, MMWR Morb Mortal Wkly Rep 2016;65:63 7.

43 Zika Virus Laboratory Testing of Infants Recommended for: Infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant Infants born to mothers with positive or inconclusive ve test results for Zika virus infection Staples, JE, Dziuban EJ, Fischer M, et al. Interim guidelines for the evaluation and testing of infants with possible congenital Zika virus infection United States, MMWR Morb Mortal Wkly Rep 2016;65:63 7.

44 Recommended Zika Virus Testing for Infants Recommended tests: Serum Zika RT-PCR, serum Zika IgM, urine Zika RT-PCR Dengue virus IgM Clinical specimens: Serum (within 2 days of birth if possible) CSF if obtained Consider histopathologic evaluation of placenta and umbilical cord Immunohistochemical staining Zika virus RT-PCR on specimen If not already perfomed, test mom for Zika IgM and Dengue IgM Staples, JE, Dziuban EJ, Fischer M, et al. Interim guidelines for the evaluation and testing of infants with possible congenital Zika virus infection United States, MMWR Morb Mortal Wkly Rep 2016;65:63 7.

45 Staples, JE, Dziuban EJ, Fischer M, et al. Interim guidelines for the evaluation and testing of infants with possible congenital Zika virus infection United States, MMWR Morb Mortal Wkly Rep 2016;65:63 7.

46 Recommended Long-term Follow-up for Infants with Possible Congenital Zika Virus For all infants with possible congenital Zika virus infection, recommended longterm follow-up: Report case to state, territorial, or local health department and monitor for additional guidance as it is released. Consider conducting additional hearing screen at age 6 months. Refer any child with developmental delay for an audiologic evaluation. Ensure that appropriate follow-up of abnormal newborn hearing screening has occurred. Carefully evaluate occipitofrontal circumference and developmental characteristics and milestones throughout the first year of life, in consultation with appropriate medical specialists (e.g., pediatric neurology, developmental and behavioral pediatrics, physical and speech therapy).

47 Zika Prevention

48 Zika Prevention Zika infection can be prevented by elimination of mosquito vectors and avoiding mosquito exposure to prevent ongoing Zika transmission Prevention of sexual transmission Individuals with suspected mosquito-borne illnesses are advised to avoid mosquitoes during the viremic period to prevent local infection of mosquitoes. Survey household members and neighbors of travel-associated cases Blood donor screening

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50 What to do If You Suspect Zika First, call Health Department where patient lives. Lowcountry: Berkeley, Charleston, Dorchester; Phone: (843) Beaufort, Colleton, Hampton, Jasper; Phone: (843) Allendale, Bamberg, Calhoun, Orangeburg; Phone: (803) Nights/Weekends; Phone: (843) Midlands: Kershaw, Lexington, Newberry, Richland; Phone: (803) Chester, Fairfield, Lancaster, York; Phone: (803) Aiken, Barnwell, Edgefield, Saluda; Phone: (803) Nights/Weekends; Phone: (888) Pee Dee: Upstate: Chesterfield, Darlington, Dillon, Florence, Marion, Marlboro; Phone: (843) Clarendon, Lee, Sumter; Phone: (803) Georgetown, Horry, Williamsburg; Phone: (843) Nights/Weekends; Phone: (843) Anderson, Oconee; Phone: (864) Abbeville, Greenwood, Laurens, McCormick; Phone: (864) Cherokee, Greenville, Pickens, Spartanburg, Union; Phone: (864) Nights/Weekends; Phone: (866)