4/8/2017 EUREKA ZIKA: THAT DENGUE MOSQUITO IS AT IT AGAIN! HISTORY OF THE ZIKA VIRUS HISTORY OF THE ZIKA VIRUS

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1 EUREKA ZIKA: THAT DENGUE MOSQUITO IS AT IT AGAIN! LUCIA JOHNSON, MEd., MT(ASCP)SBB HISTORY OF THE ZIKA VIRUS 1 st identified in 1947 in Zika Forest in Uganda, Africa Found in a monkey with mild fever Transmitted by Aedes africanus, a mosquito found primarily in forested areas 1 st human cases in 1952 in Africa in Uganda and Tanzania; then periodic outbreaks in tropical areas in Africa, SE Asia, and Pacific Islands 14 documented cases before 2007 but many more likely but not reported Flavivirus HISTORY OF THE ZIKA VIRUS 1st large outbreak in 2007 Yap Island in remote area of Pacific Ocean ~ 5,000 mild cases Next large outbreak in French Polynesia, also in remote area of Pacific Ocean ~ 20,000 cases; large # of Guillain-Barre syndrome cases identified Aedes aeqypti and Aedes albopictus species of mosquitoes implicated in transmission Since 2007, 72 countries have reported Zika infections In 2012, researchers identified two distinct lineages of the virus: African and Asian 1

2 ZIKA VIRUS OUTBREAK Began in Brazil and rapidly spread to other countries in South America, Central America, and the Caribbean Brazil was most affected with more than 500,000 cases; Colombia followed with about 20,000 cases Puerto Rico had about 2,000 people/week becoming infected; CDC estimated ¼ of the island s 3.5 million people were likely to be infected if outbreak could not be slowed WHO predicted 3-4 million people infected in 2016 in the Americas (South America, Central America, the Caribbean) if outbreak could not be slowed OUTBREAK Mosquito species implicated Aedes aeqypti African species; Yellow Fever mosquito Arrived in colonial North America & Caribbean in slave trade ships from West Africa In 2001, identified in California; imported from China in tires on ships Lives/breeds close to human populations OUTBREAK Mosquito species implicated Aedes albopictus Asian tiger mosquito Considered most invasive mosquito in world 1 st documented in US in Texas in 1985 (shipment of tires from SE Asia) Identified in Florida in 1986 and California in 2001 Breeds in more rural areas Breeds/eggs survive in cooler temps; has potential to spread into US in Midwest and East Cost 2

3 OUTBREAK Mosquito species implicated Aedes species mosquitoes also transmit Chikungunya Dengue Yellow Fever Some types of filariasis (parasitic roundworm) MOSQUITOES IN GENERAL Only females bite Mouthparts of females designed to piece skin and suck blood; need protein to help eggs develop; protein obtained from blood Lay eggs about 2 days later Prefer to lay eggs in stagnant water such as ponds, marshes, swamps, other types of wetlands; will lay eggs in any area of standing non-moving water (cracks in cement), flowerpot saucers, birdbaths, gutters, discarded tires When female bites, injects saliva into the wound Saliva contains anticoagulant to prevent blood from clotting while they ingest Saliva also serves as a carrier of any infectious diseases the mosquito is carrying 3,500 species of mosquitoes worldwide; 176 species in US Typically found in humid hot environments in tropics/semi-tropics Some species inhabit areas as far north as the Artic Circle Most species tend to bite at dusk, night, or dawn OTHER METHODS OF ZIKA TRANSMISSION Mother to fetus: pregnant woman can transmit Zika virus to fetus during pregnancy or at the time of birth Sexual activity: virus can be found in vaginal fluids, urine, and semen; lives up to 6 months in semen Blood transfusion: multiple unconfirmed reports from Brazil In French Polynesia outbreak, 2.8% of blood donors tested positive for Zika virus On August 16, 2016 the FDA issued guidelines for universal testing of donated whole blood and components for Zika virus Blood donors are asked to postpone donations for at least 4 weeks if they believe they have been exposed to the virus or traveled to an area with an ongoing outbreak 3

4 OTHER METHODS OF ZIKA TRANSMISSION Laboratory exposure 1 reported case in US as of 6/26/2016 from outbreak Before outbreak, 4 reports of laboratory-acquired infection Transmission of these cases not clearly determined Possible body fluid exposure not related to sexual activity Caregiver of elderly Zika-infected man developed infection Caregiver had no travel or sexual history that could have resulted in infection Caregiver came into contact with infected man s sweat and tears Infected man had traveled to a Zika-outbreak area and had more than 100,000 times the normal amount of virus in his blood than other infected people Patient did pass away; had underlying health condition which has not been disclosed TYPICAL ZIKA ILLNESS Many people infected with Zika have no symptoms Others may have mild symptoms such as fever, rash, joint pain, conjunctivitis, muscle pain, and headache Symptoms last several days to a week Infected people generally do not seek treatment People rarely die No specific treatment; rest, fluids, acetaminophen ZIKA SEQUELAE Guillain-Barre Syndrome (GBS) Occurs when immune system attacks peripheral nervous system Occurs few days-weeks after bacterial or viral infection Increased occurrence worldwide following Zika virus infection Early symptoms are weakness and abnormal sensations in arms and upper body Body can become entirely paralyzed, requiring ventilator-assisted breathing Also have abnormal heart rhythms, blood clots, hypo- or hypertension Treatment = plasmapheresis, high dose immunoglobulin therapy, high dose steroids Most recover; many continue to have physical/emotional difficulties 4

5 ZIKA SEQUELAE Microcephaly A birth defect in which a baby s head is smaller than expected when compared to babies of the same sex and age Babies with microcephaly often have smaller brains that might not have developed properly During pregnancy, a baby s head grows because the baby s brain grows; microcephaly can occur because a baby s brain has not developed properly during pregnancy or has stopped growing after birth In US, microcephaly occurs in about 7 in 10,000 live births ZIKA SEQUELAE Congenital Zika Syndrome Pattern of birth defects found among fetuses and babies infected with Zika virus during pregnancy The following five features: Severe microcephaly where the skull has partially collapsed Decreased brain tissue with a specific pattern of brain damage Damage to the back of the eye Joints with limited range of motion, such as clubfoot Too much muscle tone restricting body movement soon after birth ZIKA SEQUELAE Not all babies born with congenital Zika infection will have all of these problems Some infants with congenital Zika virus infection who do not have microcephaly at birth may later experience slowed head growth and develop postnatal microcephaly Not all women infected with Zika during pregnancy will have a baby with a birth defect; infection with Zika during pregnancy increases the chances for these problems In Brazil between 10/2014-1/2016, 3,500 microcephaly cases 5

6 ZIKA VIRUS IN THE UNITED STATES Travel-associated infections were identified in all states but Alaska between 1/1/2016 and 3/29/2017 Florida reported the most infections (1,114) with 216 locally acquired infections; the locally-acquired infections were all in a 4.5 square mile area of Miami Beach On 12/14/2017, Brownsville, Texas reported a locally-acquired infection; to date, there have been 6 locally-acquired infections ZIKA VIRUS IN THE UNITED STATES - SUMMARY In the United States 1/1/2015 3/29/2017 5,182 Zika virus disease cases reported 4,886 cases in travelers returning from affected areas 222 cases acquired through presumed local mosquito-borne transmission in Florida (216) and Texas (6) 74 cases acquired through other routes, including sexual transmission (45), congenital infection (27), laboratory transmission (1), and person-to-person through an unknown route (1) ZIKA VIRUS IN THE US TERRITORIES- SUMMARY 1/1/2015 3/29/2017 US territories primarily: American Samoa, Guam, Northern Marina Islands, Puerto Rico, US Virgin Islands 38,303 Zika virus disease cases reported 147 cases in travelers returning from affected areas 38,156 cases acquired through presumed local mosquito-borne transmission 0 cases acquired through other routes* *Sexually transmitted cases are not reported for US territories because with local transmission of Zika virus it is not possible to determine whether infection occurred due to mosquito-borne or sexual transmission. 6

7 PREGNANCY OUTCOMES IN US Evidence of Possible Zika Virus Infection During Pregnancy- 1/2016 2/2017: 1,228 completed pregnancies 54 live born infants with birth defects* 7 pregnancy losses with birth defects* *microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from damage to brain that affects nerves, muscles and bones, such as clubfoot or inflexible joints, and confirmed hearing loss DIAGNOSIS As symptoms similar to chikungunya and dengue, and the three viruses are often found in the same areas, diagnostic lab testing is necessary Only CDC, certain qualified reference laboratories, and some state/local health departments do testing Testing is recommended If individual becomes ill within 2 weeks of travel to Zika outbreak area For pregnant women who have traveled to Zika outbreak area within 2 weeks of travel even if they do not feel sick or develop symptoms If living in Zika outbreak area, pregnant women should be tested At 1 st prenatal visit AND again in 2 nd trimester Any time during pregnancy if symptoms of infection occur DIAGNOSIS Testing is recommended Infants born to mothers with lab evidence of Zika infection during pregnancy Infants who have abnormal clinical findings of congenital Zika syndrome and maternal risk factors regardless of maternal Zika test results; maternal risk factors include Travel or residence in Zika outbreak area Sexual activity with partner who has traveled or resided in Zika outbreak area Specimens for testing Adults: serum, plasma, urine Newborns: serum, urine, umbilical cord, placenta, fetal membranes 7

8 TESTING METHODOLOGIES Serologic IgM Antibody Capture Enzyme Linked Immunosorbent Assay or Zika MAC-ELISA (anti-zika IgM antibodies): antibodies usually detectable 1 week after exposure and for up to 12 weeks Zika plaque-reduction neutralization test (Zika PRNT); use if MAC- ELISA is negative Molecular Real-time reverse transcription-polymerase chain reaction (Zika rrt-pcr): Zika RNA usually detectable in first two weeks of person with symptoms) WHAT S HAPPENING NOW? WHO reports the overall global health risk has not changed Continues to spread in areas where vectors are present 84 countries, territories, or subnational areas with vector-borne ZIKA 13 countries have reported person-to-person transmission 31 countries reported microcephaly and other CNS malformations suggestive of congenital infection 23 countries reported increased incidence of Guillian-Barre syndrome and/or lab confirmation of ZIKA infection in someone with Guillain-Barre 8

9 WHAT S HAPPENING NOW? WHO classifies into 4 categories Category 1: New introduction or reintroduction with ongoing transmission (South America, Central America, Caribbean primarily; *US* Category 2: Evidence of virus circulation before 2015 with ongoing transmission: ex - some of West Africa, Indonesia, Thailand, Cambodia, Viet Nam, Malaysia, Philippines Category 3: Interrupted transmission and potential for future transmission: ex - Chile, French Polynesia Category 4: Areas with vector but no known documented past or current transmission: ex - Egypt, Saudi Arabia, India, Australia WHAT ABOUT THE US? Soon it will be mosquito breeding season Florida officials are preparing for mosquito control and communication about outbreaks Miami-Dade Public Works and Waste Management has added 42 positions including a medical entomologist Already monitoring mosquito traps to identify infected female mosquitoes so areas can be sprayed California has concerns as Aedes aegypti and Aedes albopictus have been found in 129 cities in the state; California Department of Public Health is preparing for a pandemic WHAT ABOUT THE US? Map showing the reported occurrence of Ae. aegypti by county between 1 January 1995 and March 2016 in the United States. Counties shown in yellow had Ae. aegypti presence records for 1 year within the specified time period, those shown in orange had 2 years of presence records within the specified time period, and those shown in red had 3 or more years of presence records within the specified time period. CDC/ Journal of Medical Entomology 9

10 WHAT ABOUT THE US? Blood Supply FDA implemented investigational screening of donors in Puerto Rico n April 2016 and the entire US by the end of 2016 Evaluated 17 Zika assays in 11 laboratories 2 screening assays documented excellent sensitivity (>99.99%) : Roche cobas Zika (358,786 donations screened) and Grifols Procleix Zika (466,834 donations screened) Both are rrt-pcr tests Research is also looking at pathogen reduction of Zika virus in blood components and inactivation of Zika virus during the manufacturer of plasma derivatives INTERESTING RESEARCH Studies have shown that prior infection with West Nile virus or dengue can make Zika symptoms worse (research done in mice) This can explain the severity of the Zika infections in Brazil where dengue is common; pre-existing immunity to dengue is associated with increased Zika viremia and clinical symptoms including microcephaly Raises concerns about experimental dengue vaccines as they could inadvertently make Zika infections worse INTERESTING RESEARCH Studies have identified that the Zika virus dramatically changes the cell s architecture during the viral replication stage inside the cell Zika has a unique way of rearranging endoplasmic reticulum and cytoskeletal architecture of host cell, especially in human liver and neural stem cells This damages these cells and alters their natural functions Zika nucleic acid can be detected for a median of 14 days in serum, 8 days in urine, and 81days in semen; few infected people have detectable RNA in saliva or vaginal secretions 10

11 PREVENTION OF ZIKA Do not travel to areas with outbreaks if pregnant or if trying to get pregnant Control mosquito populations Keep mosquitoes out of indoors Screens on windows/doors Use air conditioning whenever possible Sleep under a mosquito net if sleeping outdoors or in place without screens At least once a week empty and scrub, discard, or cover anything that could hold water such as birdbaths, flower pots, buckets, tires, swimming pools, etc. Prevent mosquito bites Use EPA-registered insect repellent Wear long-sleeved shirts and long pants Avoid outdoors at dawn, dusk PREVENTION OF ZIKA If pregnant or trying to get pregnant and partner has traveled to area with outbreak, use safe sex practices or avoid sex for at least 6 months If traveled to area with outbreak, take precautions to prevent mosquito bites for at least 3 weeks so mosquitoes do not pick up and spread to others Seek diagnostic testing if develop symptoms within 2 weeks of return from travel to an area with outbreak PREVENTION OF ZIKA Brazil and Florida have used genetically-engineered mosquitoes in an attempt to reduce mosquito populations Lab-grown mosquitoes are engineered with a lethal gene that when passed to their offspring cause the mosquitoes to die Only the male mosquitoes are released, and when they mate with the native female mosquitoes, the majority of the offspring die before they can mature into adult mosquitoes 11

12 PARALLELS BETWEEN ZIKA & RUBELLA VIRUSES Zika is not the 1 st virus associated with infection in pregnant women and birth defects In , a rubella (aka German measles) pandemic began in Europe and spread to the US In an estimated 12.5 million rubella cases occurred in the US Rubella infection is generally mild: mild fever, headache, inflamed eyes, runny nose, enlarged cervical lymph nodes, fine pink rash that begins on face, spreads to trunk, and then to arms and legs PARALLELS BETWEEN ZIKA & RUBELLA VIRUSES Rubella infection in pregnant woman, especially in the 1 st trimester, can result in fetal death or serious multiple birth defects called congenital rubella syndrome (CRS) In in the US, there were 11,000 miscarriages and 20,000 cases of CRS Of those with CRS 2,100 died as neonates 12,000 were deaf 3,580 were blind 1,800 had intellectual disabilities Many were also deaf and blind Others had growth retardation, heart defects, and defects of other organs PARALLELS BETWEEN ZIKA & RUBELLA VIRUSES Maternal infection in 2 nd and 3 rd trimesters also caused birth defects but the highest risk is in the 1 st trimester Rubella parties given when a young girl was infected; all female classmates invited to house as it was important for females to be infected and become immune before they were of child-bearing age Rubella vaccine was licensed in 1969 and most children now receive vaccine When CRS is seen it is usually in foreign-borne females who have not received vaccine Great concern in US over this virus if parents/guardians fail to vaccinate; the greater the number of non-immune people, the higher the risk for an outbreak 12

13 OTHER IMPORTANT MOSQUITO-BORNE DISEASES Malaria Responsible worldwide for more death and illness than any other infectious disease WHO estimates that in 2015 there were 214 million cases of malaria with 438,000 deaths 88% of infections/deaths occur in sub-saharan Africa Recent years has shown some malarial mosquitoes (Anopheles) have developed resistance to insecticides No licensed vaccine but a research vaccine is being evaluated in 7 African countries Factoid: 1 st book published west of the Mississippi was in Malaria in Missouri OTHER IMPORTANT MOSQUITO-BORNE DISEASES Dengue 50 million-100 million infections occur worldwide each year Most infections are mild but several hundred thousand cases of dengue viral hemorrhagic fever occur yearly, with estimated 22,000 deaths Aedes mosquitoes are vector Endemic in Puerto Rico, many parts of South America, the Caribbean, Southeast Asia, and Pacific Islands About 200 suspected cases per year in continental US; Hawaii had outbreak of 264 cases 9/2015-3/2016 Has been transmission in Florida; last reported case 6/1/2016 Symptoms: fever up to 105, severe headache, retro-orbital pain, severe joint and muscle pain ( break bone fever ), rash, nausea, vomiting Can develop bleeding, shock, multiple organ failure, death (hemorrhagic fever) Licensed vaccine available for 6 countries with large ongoing outbreaks: Philippines, Brazil. Paraguay, Singapore, El Salvador, Mexico OTHER IMPORTANT MOSQUITO-BORNE DISEASES Yellow Fever Aedes aegypti mosquitoes are the vector; can be transmitted via sharps injuries Found primarily in South America and Africa; Brazil has current outbreak CDC identified 45 countries with possible transmission of yellow fever, mostly in tropical regions Initial symptoms fever, chills, myalgia, headache, vomiting About 15% develop viral hemorrhagic fever with jaundice, hepatitis, hemorrhage, vomiting, multiple organ failure, often death There is a vaccine for those who live in or travel to countries with a known risk of infection; some countries require proof of vaccination before entering country Historically, the worst urban disaster in US was in the summer/fall of 1878 when yellow fever caused 100, ,000 deaths in southern Mississippi River area (Memphis, New Orleans, Savannah, Charleston, and Mobile No US acquired infections since 1950s 13

14 OTHER IMPORTANT MOSQUITO-BORNE DISEASES West Nile Normal infection between mosquitoes and birds In 1999, infection between mosquitoes and humans (and other mammals) occurred Humans/mammals are dead end hosts as uninfected mosquitoes cannot become infected by biting infected humans/mammals Most people infected with West Nile have no symptoms; some develop fever with headache, body aches, joint pains, rash, vomiting, diarrhea About 1% can develop meningitis or encephalitis; about 10% of these individuals die In 2016, California had 33 infections and one death Can be transmitted via blood transfusion and organ donation No vaccine OTHER IMPORTANT MOSQUITO-BORNE DISEASES Chikungunya Spread by Aedes aegypti and Aedes albopictus Like Zika, first identified in Africa in forested area; now found in more urban areas in Africa, Asia, Pacific/Indian Ocean islands, South America, Central America, Mexico, Caribbean As of 10/2016, 102 cases reported in 32 US states since 1/1/2016; all occurred in travelers returning from areas with outbreaks Symptoms include fever, severe joint pain, rash, headache, muscle pain, and fatigue Most people fully recover in about 1 week to 10 days Can have complications such as inflammation of the heart, liver, brain, kidneys, and vision-threatening eye problems No vaccine OTHER IMPORTANT MOSQUITO-BORNE DISEASES Viral Encephalitis Widespread number of viruses, including West Nile Also includes La Crosse Virus, St. Louis Encephalitis, Western Equine Encephalitis, and Eastern Equine Encephalitis Normally the viruses cycle between mosquitoes and birds or other mammals Humans can become infected if bitten by infected mosquito; as with West Nile, humans are dead-end hosts Mosquito vectors are primarily Culex sp. Symptoms include headache, fever, muscle/joint pain, fatigue; develop neurological symptoms such as seizures, paralysis, double vision, loss of consciousness; may result in death Recovery may take weeks to months and may have permanent neurological complications such as paralysis, memory problems, and more About cases per year in US 14

15 OTHER IMPORTANT MOSQUITO-BORNE DISEASES Filariasis Tiny roundworm parasites spread by Culex, Anopheles, and Aedes mosquitoes 3 types of filarial parasites: Wuchereria bancrofti, Brugia malayi, and Burgia timori WHO estimates 947 million people in 54 countries require preventative treatment to stop the spread of filariasis Majority of people at risk live in Angola, Cameroon, Côte d Ivoire, Democratic Republic of the Congo, India, Indonesia, Mozambique, Myanmar, Nigeria, and Tanzania Adult filarial live in lymphatic system and produce microfilaria that circulate in the blood Adult worm damage the structures of the lymphatic system, blocking the flow of lymph resulting in lymphedema Causes elephantiasis or enlargement of breasts and lower portions of the body Estimated 25 million men suffer from genital disease and another 15 million has other forms of lymphedema Physical disabilities result in social stigma, financial losses, and poverty WHAT WILL BE THE NEXT ZIKA? Mayaro virus Transmitted by Aedes sp Indistinguishable from chikungunya Over 100,00 confirmed cases in Central and South America as of 9/2016, many in large Brazilian cities In 9/2016, identified in Haiti Rift Valley Fever virus Found in parts of eastern and southern Africa, and in sub-saharan Africa and Madagascar Primarily affects livestock but humans can become infected when bitten by mosquitoes Thousands of human cases have been identified; about 10% develop hemorrhagic fever disease, and about 50% of those die 19 species of mosquitoes in US capable of transmitting; infected mosquitoes could easily arrive on trade ships or planes WHAT WILL BE THE NEXT ZIKA? Crimean-Congo Hemorrhagic Fever Transmitted by tick Found in the Congo, India, Middle East, central Asia, eastern Europe, and northwestern China Current ongoing outbreak in Turkey that has infected 100,000 Has up to a 40% fatality rate so it is a dangerous virus Tick species have been found in Germany and United Kingdom; thought to have hitchhiked on birds migrating from areas with outbreaks Usutu (USE-u-to) virus Similar disease to West Nile Transmitted by Culex sp mosquitoes Originally in Africa; recently reported in Croatia and Italy 15

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