10/13/2014. Ebola: filoviruses. Location of outbreaksdd. Some curious facts about Ebola. Ebola subtypes SCREENING AT AIRPORT
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1 SCREENING AT AIRPORT Ebola: filoviruses Location of outbreaksdd RNA viruses: Marburg and Ebola Marburg first identified in 1967, hemorrhagic fever, traced to African green monkeys Ebola recognized 9 years later near Ebola river First patient in Sudan outbreak was worker in batinfested cotton weaving factory Ebola Reston was found in 1989 in sick cynomoglus monkey from Philippines (no human cases) 4 th Ebola species (Cote d Ivorie) found in ethnologist doing necropsy on a chimp Now called Tau forest ebolavirus 5 th ebolavirus is Bundibugyo ebolavirus Ebola subtypes Ebola Zaire: 1995 Kikwat, DRC (325 cases, 81% fatal) Ebola Sudan: 2004 Sudan (17 cases) Ebola Reston: No human illness but Humans have shown evidence of infection Ebola Cote d Ivorie: sick ethnologist Ebola Zaire and needlesticks have highest mortality Some curious facts about Ebola Africansmay eat road kill : bats are probable carriers Some African specialty shops in the US may illegally import The current Ebola (Zaite) has multiple mutations Most early outbreaksof Ebola were local, associatedwith local burial customs and fairly easily contained The current outbreakis the most virulent, widespreadever Nigeria was able to contain spread because of a more efficient public health system and immediate mobilization There is significant resistancein some areas to health care workers attempting to control the epidemic Other hemorrhagicfevers (Lhassa) and diseases (malaria) can mimic Ebola 1
2 Challenges with Ebolavirus 340 documented mutations in virus, 8 constant African immigrants in US have been bringing in monkeys and monkey meat to sell in their shops Reston ebolavirus (lethal to monkeys) has already mutated into an airbourne disease In the past 2 months, there have been about 36,000 fliers out of Sierra Leone, Liberia and Guinea. WE allow flights Many other African countries disallow flights from epidemic countries Thomas Eric Duncan: the face of Ebola How do patients with Ebola virus present? Lied about contact with sick person in Liberia (carried sick woman to hospital) First visit with early signs of Ebola resulted in patient being sent home on antibiotics from Texas Health Presbyterian Hospital in Dallas 2 days later, brought in by ambulance Died on October 8 th Dr Thomas Freiden: questionnaires at 5 airports Incubation usually 4-10 days but can be 2-21 days Abrupt onset of severe headache, myalgia, abdominal pain, diarrhea, sore throat, vomiting, fever >101.5 Herpetic type lesions of mouth, throat Asthenia, conjunctival injection, gingival hemorrhage Possible maculopapillar rash Bleeding diathesis follows rash Neuro problems can include hemiplegia, psychosis, convulsions, coma What prognosticates outcome? Ebola: transmission - Initial leukopenia and lymphopenia - Later increase in leukocytes, large abnormal lymphocytes dark cytoplasm (virocytes) - Thrombocytopenia, abnormal platelet function - Elevation of serum transaminases - Tachypnea a poor prognostic sign - Death usually occurs about day 10 Natural reservoir not known, bats suspect Direct blood/bodily fluid contact Exposure to objects contaminated with infected secretions The dead can be contagious Healthcare personnel at increased risk Use standard, contact, and droplet precautions ALL persons in a healthcare setting (laundry, pharmacy etc etc) need full protection 2
3 Protective gear What can we as healthcare providers do? ASK EVERYONE presenting with fever, headache, weakness, myalgia, GI, hemorrhage if they have traveled in past 21 days, or had contact with, travelers from Africa (or Dallas) Ebola testing is done in symptomatic patients (4 cc blood) Blood test may need to be repeated 3 days after symptoms start* Acute infections confirmed with real-time RT-PCR In confirmed disease, serologic IgM and IgG can monitor immune response Information available on testing at CDC ( ) and Ebolavirus: hospital setting What patients presenting in USA are at risk? Single patient room, bathroom Log of all entering patient s room Wear gloves, gown (impermeable), eye protection, face mask, shoe coverings, leg coverings, consider double gloving Dedicated disposable medical equipment Instructions for gowning and removing PPE can be found at: /hicpac/2007ip/2007ip Travel to or coming from area with Ebola within 3 weeks Presenting with fever above 38.6 C Headache, myalgia, vomiting, diarrhea, hemorrhage Direct handling of bats, rodents or primates from endemic areas Contact with body fluids from victim of Ebolavirus Laboratory diagnosis The Future Virus isolation in Vero cells RT-pcr or antigen capture ELISA IgM and IgG by ELISA in those living long enough to make antibodies Scientists trying to understand genome and rate of evolution of these viruses Neutralizing human monoclonal antibody: protects guinea pigs but not macaque monkeys Convalescent serum and whole blood from survivors have helped some patients rnapc2(recombinant nematode anticoagulant protein inhibiting tissue factor initiated blood coagulation)helped macaque monkeys a bit Recombinant vesicular stomatitis virus based vaccine expressing Ebola virus glycoprotein protected macaques and small animals when given soon after exposure 3
4 Brincidofovir etc Middle East Respiratory Syndrome (MERS) Emergency Investigational New Drug Application just granted by FDA Oral nucleotide analog with broad spectrum activity against DNA viruses (Ebola is an RNA virus) In vitro testing at the CDC did show activity against Ebola Other possible drugs include Zmaxx (none left), Avagan and TKMebola MERS (Middle Eastern Respiratory Syndrome) Caused by coronavirus, an RNA virus which usually causes only mild URI SARS is a coronavirus however First isolated in 2012 in Saudi Arabia, victim died Case fatality rate is >50% (tip of iceberg?) Camels harbor virus MERS-CoV Symptoms Incubation period is probably 2-14 days (average 5 days) and presents with: Severe acute respiratory illness with cough Fever Shortness of breath Diarrhea, nausea and vomiting Occasional victims had very mild disease or NO symptoms Persons with pre-existing medical conditions or weakened immune systems get severe disease, 4
5 Coronavirus Transmission of MERS-CoA Appropriately named All cases so far linkedto countriesin/neararabian Peninsula Countrieswith lab confirmedcases include: Oman Kuwait Yemen United Arab Emirates Jordan Qatar Iran Saudi Arabia Lebanon Close contact with an ill person is required (6 feet) (Almost all cases are secondary, not tertiary, average of patient is 51) DO NOT: - Have contact with camelsif avoidable - Drink raw camel milk or urine - Eat undercookedcamel meat Increased risk of severe SARS Hajj and Umrah in Saudi Arabia Males Older individuals Chronic underlying medical conditions Outbreaks have occurred in hemodialysis units, CRD increases risk in secondary cases Secondary cases also increased in healthcare facilities Co-infection with other respiratory viruses can occur Hajj (10/2-7/14) draws 3 million Moslems yearly Saudi Ministry of Health suggests postponing IF: - Older than 65 or younger than 12 - Pregnant - Chronic diseases (heart, kidney, lung, DM) - Immune system suppression - Cancer/terminal * If people develop respiratory disease at the Hajj, they should wear a mask MERS: When to evaluate for MERS-CoV How to dress around a camel A fever and pneumonia or acute respiratory distress syndrome AND A history of travel to countries in/near Arabian Peninsula within 14 days of symptom onset OR Close contact to Arabian Peninsula traveler who developed fever and respiratory illness within 14 days of travel OR A member of cluster of patients with severe respiratory illness/pneumonia of unknown etiology 5
6 How to evaluate for MERS CoV MERS CoV therapy Call local health department or CDC under Reporting Patients Under Investigation CDC developed molecular diagnostics & assays for antibodies and health departments have MERS-CoV testing kits CDC recommends collecting multiple specimens from multiple sites at different times Multiple sites include lower respiratory where possible and naso or oropharyngeal, stool and serum specimens Hospitalized patients need infection isolation room, providers need to use standard, airborne and contact precautions, (N95 fitted respirator for provider) Supportive What doesn t seem to work too well or has side effects : ribavirin, oseltamivir, broad spectrum antibiotics In one study, interferon alpha may have helped?? Studies generally were of suboptimal quality or no controls or meds started at different times in the course of illness Enterovirus D68 (EV D68) Enterovirus D68 Epidemic of severe respiratory disease started in Missouri States with confirmed EV D68 infection EV D68 first identified in California in 1968 Causes infection mainly in children, rare in adults EV D68 is shed in respiratory secretions Most children who developed severe respiratory symptoms had history of wheezing One possible death (at home) being investigated Enterovirus D68 Unexplained paralysis? EV D68? Enterovirus D68 can cause very mild respiratory disease or can present as severe respiratory disease even in absence of fever Consider testing for EV D68 in clusters of severe respiratory disease of unclear etiology Laboratory testing of respiratory specimens for enterovirus can be done in such cases State health departments can help with diagnostic and molecular typing of enteroviruses Between Aug. 9 th and Sept.29 th, 2014, 10 children in Colorado were hospitalized with unexplained paralysis Symptoms coincided with increase in respiratory illness Focal limb weakness + spinal cord grey matter abnormalities on MRI were characteristic 4 of 9 children had airway presence EV D68 (CSF pending) Children s Mercy Hospital in Kansas City is also investigating similar cases 6
7 Anterior flaccid paralysis: CA Chikungunya Fever ( that which bends up in Kimakonde language) 23 cases, usually male, average age 10 URI or GI prodrome < 10 days before onset 2 had enterovorus D 68 isolated from respiratory source In general, specimens were collected VERY LATE in course of illness (only 9 at <7 days of paralysis) Poliovirus deemed unlikely per epidemiology/testing Aedes mosquito Distribution of Chikungunya fever Chikungunya Fever First identified in Kenya, spread to India in Can cause congenital disease Intrauterine transmission 50% late in pregnancy Usually causes pain, rash, fever, edema Intracerebral and GI hemorrhage seen in some babies Some infants have had vesiculobullous skin blistering Chikunggunya Fever Chikungunya RNA virus Transmitted thru mosquito bite Incubation is 3-7 days Acute onset of fever >39 degrees and polyarthralgia Joint symptoms usually bilateral and symmetric Symptoms: headache, myalgia, conjunctivitis, nausea/emesis and maculopapillar rash Labs: lymphopenia, thrombopenia, elevated creatinine/lft s Symptoms usually resolve in 7-10 days Severe disease can occur in neonates exposed intrapartum, adults > 65, those with underlying medical problems 7
8 Chikungunya advances! Chikungunya virus Local transmission in Florida In 2013, it emerged in almost every Caribbean island Continental UShas had 751 cases Aedes mosquitoesbite during the day stay inside Looks like Dengue in some cases (Dengue has more thrombocytopeniaand hemorrhage) Testing: IgM capture ELISA and IgG ELISA (>4 d) (CDC, some state labs and one commercial lab do test) Viral cultures can be done in 1 st 3 days of illness RT-PCR to detect viral RNA in 1 st 8 days of illness Vaccinesare under development Chikungunya fever: management Supportive care and hydration Make sure patient doesn t have look-alikes like dengue, malaria, bacterial infection) Use acetaminophen for fever and pain If patient possibly has dengue, don t use nonsteroidal unless afebrile for 48 hrs, having no warning sign of severe dengue For persistent joint pain consider physical therapy, NSAIDS, steroids 8
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