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Home , Chikungunya, Filoviridae, Reston virus, Viral hemorrhagic fever

9/27/15

Emerging : &

Chikungunya

Elizabeth Race, MD, MPH Infectious / HIV Medicine AIDS Healthcare Foundation, Dallas,

Chikungunya Virus: A Newly Re-emergent Infectious Problem //

• originally identified in 1950s in E. Africa, in sylvatic cycle involving and forest mosquitoes -Triad of fever/rash/arthritis is characteristic of Chikungunya, O’nyong-nyong, Ross River, Mayaro, • Clinical descriptions first in 1970s in South Africa and Sindbis

• Limited outbreaks periodically in SE Asia, with a larger one -Symptoms generally appear after 2-3 days incubation in 2001-2003 in (after 20-year hiatus) a) fever, chills, b) polyarthralgia mainly affecting small joints • Explosive outbreak in 2005-present, in Indian Ocean c) islands & Indian subcontinent, involving millions of cases -Arthritis generally resolves in a few weeks, but may • Imported cases in Europe, North America among travelers persist for months, or years in some cases. to Indian Ocean sites

Aedes albopictus

• ; Family Togaviridae

• First isolated from the blood of a febrile patient in in 1952

• Identified repeatedly in west, central and southern Africa and many areas of Asia

• Transmitted by A. aegypti, A.albopictus, others; vertebrate hosts include primates Charrel R et al. N Engl J Med 2007;356:769-771

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World Distribution of the albopictus Togaviridae, genus Alphavirus

Charrel R et al. N Engl J Med 2007;356:769-771

Chikungunya

• chikungunya fever typically lasts a few days to a couple of weeks, but some patients have prolonged lasting several weeks

• Up to 10% may develop chronic joint symptoms • can cause a debilitating illness, most often characterized by fever, , • Death is very uncommon fatigue, , , muscle pain, rash, and joint pain. The term ‘chikungunya’ is • No or preventive drug; recommendation: Swahili for ‘that which bends up.’ control, vector avoidance

Skin manifestations in CHIKV in travelers

Hochedez P, Jaureguiberry S, Debruyne M, Bossi P, Hausfater P, Brucker G, et al. Chikungunya infection in travelers. Emerg Infect Dis. 2006 Oct From: Medicine 2007;86:123-137

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Chikungunya

tenosynovitis, arthritis

MRI: arthritis, tenosynovitis

From: Medicine 2007;86:123-137 Figure: WHO; http://www.who.int/csr/don/Regional_Chykungunya_largeb.jpg

Chikungunya Outbreaks: Chikungunya Infection in Travelers

• India (14 states), Malaysia, Indonesia, Sri Lanka, Maldives, Nicobar Islands • Imported cases reported in multiple countries: – Australia – Japan During 2005-’06, 12 cases of CHIK – Taiwan fever were dx’d serologically and virologically at CDC in travelers who – Europe: UK, France, Italy, Spain arrived in the US from areas known to – USA be epidemic or endemic for CHIKV

Hochedez P, Jaureguiberry S, Debruyne M, Bossi P, Hausfater P, Brucker G, et al. Chikungunya infection in travelers. Emerg Infect Dis. 2006 Oct

Chikungunya Virus: Summary • Caused by virus inoculated via bites – Increased risk May-October (rainy season) – Increased risk in urban and village areas African Tick-Bite Fever • Symptoms: Sudden onset of fever, rash on trunk and limbs, back pain, and severe joint pain / arthritis in multiple joints

• Treatment: , NSAIDS, ; has been used in a few refractory cases Rickettsia africae

• Countermeasures – Prevent mosquito bites – Use – Sleep under a permethrin-treated bed net

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Spotted Fever Group : African Tick-Bite Fever Mediterranean spotted fever - Rickettsia (R.) conorii • Rickettsial infections: R africae & R conorii Rickettsialpox - R. akari African tick bite fever - R. africae • Transmitted by ticks Queensland tick typhus - R. australis Japanese spotted fever - R. japonica • 1992: Kelly et al isolated R africae from a Flinders Island spotted fever - R. honei patient in Zimbabwe (Lancet 340:982-983) California flea rickettsiosis - R. felis Siberian tick typhus - R. sibirica • Exported from southern Africa [ & Israeli spotted fever - not named Guadeloupe] to US 1997 Astrakhan fever - not named

(Am J Trop Med Hyg1999;60(5):865-7; France 1998 (CID 1998;27(2): 316-23); France 2001 (NEJM 2001;344(20);1504-10) Italy 1999 (EJCMID 2002;21(2): 133-6) Norway 2003 (CID 2003;36(11):1411-7)

African Tick Bite Fever

• Seroprevalence of R. africae in ticks approx. 27-50% • Amblyomma ticks (found on cattle & ungulates) • Exposure: walking through brush/cattle areas • Usual 6-7d, varies, most in 2 wks • Fever, H/A, adenopathy, occ. RUQ pain, rash • Single or multiple eschars (vesicular) • Diagnosis: PCR, MIF, Western Blot, culture • Complications unusual • : doxycycline (possibly single-dose) Amblyomma variegatum (female). Parola P, Raoult D. et al. Am J Trop Med Hyg 1999;60:888-93. PHILIPPE PAROLA, GUY VESTRIS, DOMINIQUE MARTINEZ, BERNARD BROCHIER, VERONIQUE ROUX, DIDIER RAOULT. Am. J. Trop. Med. Hyg., 60(6), 1999, pp. 888–893

Four Eschars (Arrows) on the Legs of a Patient Who Presented with Tick Borne Rickettsial Lesions: African Tick-Bite Fever after Returning from a Safari in South Africa “Tache noire”

Raoult D et al. N Engl J Med 2001;344:1504-1510

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Figure 1. Fibrinoid necrosis of a vessel in the dermis (arrow) with Figure 3. Inoculation eschar from a patient with African tick-bite perivascular inflammatory infiltrates mainly composed of fever showing numerous dermal inflammatory infiltrates mainly polymorpho-nuclear leukocytes (hematoxylin-eosin-saffron; orig. composed of polymorphonuclear leukocytes (immunoperoxidase magnification ×250). staining with an anti-CD15 ; original magnification ×100). Hubert Lepidi,Pierre-Edouard Fournier,& Didier Raoult,Université de la Méditerranée, Marseille, France Vol.12,No. Hubert Lepidi,Pierre-Edouard Fournier,& Didier Raoult,Université de la Méditerranée, Marseille, France Vol.12,No. 9 Sept2006 9 Sept2006

Clinical Characteristics of R.africae infection

• Fever > 38.5 • 88% • Neck • 81% • Inoculation • 95% eschars • 54% • Multiple eschars • 43% • Lymphadenopathy • 46% (45%) • Rash (vesicular) Figure 5. Immunohistochemical detection of Rickettsia africae in • 0% the inoculation eschar of a pt with African tick-bite fever. Note • Death location of the bacteria in the endothelial and inflammatory cells of a blood vessel in the dermis (arrow);monoclonal rabbit anti-R. Raoult D, et al. NEJM 2001;344:1504-10. africae antibody used at a dilution of 1:1,000 & hematoxylin counterstain; orig. magnification ×250. Hubert Lepidi,Pierre-Edouard Fournier,& Didier Raoult,Université de la Méditerranée, Marseille, France Vol.12,No. 9 Sept2006

Rickettsial Disease in the Treatment of African Tick Bite Fever Returning Traveler (Lyme, RMSF, Ehrlichia)

• R.africae > murine typhus (R.typhae) > mediterranean spotted fever > scrub typhus • Also RMSF, epidemic typhus, N. Asian, doxycycline Queensland tick typhus • Approx. 3rd most likely etiology of fever in the returning traveler after and typhoid fever

Jensenius M, et al. Clin Infec Dis 2004;39:1493-9; Intl J Infec Dis 2004;8:139-46.

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Emerging Infections: Ebola Virus Disease Viral Hemorrhagic

Flaviviridae (dengue, , TBE encephalitides)

Arenaviridae (Lassa, Junin, Machupo, Guanarito)

Enveloped RNA viruses

Bunyaviridae (CCHF, RVF, (Ebola, ) Hantaviruses)

Ebola

Scientific Classification Order: Family: Filoviridae Genus: Ebola like viruses Species: Ebola Subtypes – Ebola-Zaire, Ebola-Sudan,Ebola-Ivory Coast Copyrighted Dr. Fre:derick A. Murphy, D.V.M., Ph.D. 1976. • disease in – Ebola-Reston • disease in nonhuman primates

• Ebola virus and are most well known and studied • Other viruses: Sudan virus, Bundibugyo virus, Tai Forest virus, , Ravn virus

Viruses without borders Ebola Virus

q Prototype Viral Hemorrhagic q >20 previous Ebola and Fever Marburg virus outbreaks § Filovirus: enveloped, q 2014 West Africa Ebola non-segmented, negative- stranded RNA virus outbreak caused by Zaire species § Severe disease with high case fatality (five known Ebola virus species) § Absence of specific treatment or vaccine

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Epidemiology and ecology are intimately linked Ebola Virus

q Zoonotic virus – the most likely reservoir, although species unknown

q Spillover event from infected wild animals (e.g., fruit bats, monkey, ) to humans, followed by -human transmission

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Current Ebola virus outbreak Figure. Ebola virus disease (EVD) cumulative incidence* — West Africa, October 18, 2014

* Cumulative number of reported EVD cases per 100,000 persons since December 22, 2013. MMWR 2014;63(43):978-981

(graphics: BBC) 40

2014 Ebola Outbreak, West Africa EVD Cases and Deaths*

Reporting Confirmed Total Cases Total Deaths Date Cases Guinea 27 Oct 14 1,906 1,391 997 Liberia 25 Oct 14 6,535 2,515 2,413 Sierra Leone 27 Oct 14 5,235 3,700 1,500 Nigeria** 15 Oct 14 20 19 8 Spain 27 Oct 14 1 1 0 Senegal** 15 Oct 14 1 1 0 United States 24 Oct 14 4 4 1 Mali 23 Oct 14 1 1 1 TOTAL 13,733 7,632 4,920

Updated case counts available at http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html. WHO Ebola Response Team. N Engl J Med 2014. DOI: 10.1056/NEJMoa1411100 *Reported by WHO using data from Ministries of Health http://www.nejm.org/doi/full/10.1056/NEJMoa1411100?query=featured_ebola#t=articleResults **The outbreaks of EVD in Senegal and Nigeria were declared over on October 17 and 19, respectively.

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EVD Cases (United States) EVD Cases (United States) q As of October 24, 2014, EVD has been diagnosed in the United States in four people, one (the index patient) who traveled to Dallas, q As of October 31, 2014, four U.S. health workers and one Texas from Liberia, two healthcare workers who cared for the index journalist who were infected with Ebola virus in West Africa patient, and one medical aid worker who traveled to from Guinea were transported to hospitals in the United States for care § Index patient – Symptoms developed on September 24, 2014 approximately four days after arrival, sought medical care at Texas Health Presbyterian Hospital § All the patients have recovered and have been released from the of Dallas on September 26, was admitted to hospital on September 28, testing hospital after laboratory testing confirmed that they no longer confirmed EVD on September 30, patient died October 8. have Ebola virus in their blood § TX Healthcare Worker, Case 2 – Cared for index patient, was self-monitoring and presented to hospital reporting low-grade fever, diagnosed with EVD on October 10, recovered and released from NIH Clinical Center October 24. § TX Healthcare Worker, Case 3 – Cared for index patient, was self-monitoring and reported low-grade fever, diagnosed with EVD on October 15, recovered and released from Emory University Hospital in Atlanta October 28.

§ NY Medical Aid Worker, Case 4 – Worked with Ebola patients in Guinea, was self-monitoring and reported fever, diagnosed with EVD on October 24, currently in isolation at Bellevue Hospital in New York City. Information on U.S. EVD cases available at http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html. 43 44

Modes of Transmission Ebola Virus Transmission

q Virus present in high quantity in blood, body fluids, and excreta of symptomatic EVD-infected patients

q Opportunities for human-to-human transmission 3 most common § Direct contact (through broken skin or unprotected mucous membranes) with an EVD-infected patient’s blood or body fluids modes of infection: § Sharps injury (with EVD-contaminated needle or other sharp) 1. Unsterilized needles § Direct contact with the corpse of a person who died of EVD 2. Suboptimal hospital § Indirect contact with an EVD-infected patient’s blood or body fluids via a contaminated object (soiled linens or used utensils) conditions 3. Personal contact q Ebola can also be transmitted via contact with blood, fluids, or meat of an infected animal § Limited evidence that dogs become infected with Ebola virus § No reports of dogs or cats becoming sick with or transmitting Ebola http://www.ecplanet.com/pic/2003/12/1071257871/ebola.jpg 45

Detection of Ebola Virus in Different Human Body Fluids over Time Human-to-Human Transmission

q Infected persons are not contagious until onset of symptoms

q Infectiousness of body fluids (e.g., ) increases as patient becomes more ill

§ Remains from deceased infected persons are highly infectious

q Human-to-human transmission of Ebola virus via inhalation (aerosols) has not been demonstrated

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Risks to healthcare workers Personal Protecve Equipment (PPE)

• Health workers treating patients with suspected/ • Updated guidance for hospital-based confirmed illness at higher risk of infection healthcare workers released 10/20/14 – Only time people transmit disease is when they • Guiding principles: are symptomatic – Rigorous training so all are practiced – Overwhelmingly viremic when symptomatic and competent with PPE, including taking on and off • General public is generally safe – No skin exposure when PPE is worn – Supervision by trained monitor when taking PPE on and off.

EVD Risk Assessment Ebola Virus Pathogenesis

q Direct infection of tissues

q Immune dysregulation

q Hypovolemia and vascular collapse

§ Electrolyte abnormalities

§ Multi-organ failure, septic shock

q Disseminated intravascular coagulation (DIC) and coagulopathy

**CDC Website to check current affected areas: www.cdc.gov/vhf/ebola Lancet. Mar 5, 2011; 377(9768): 849–862. 52

Ebola Pathogenesis Ebola Pathogenesis, cont

• Viral cores • Enters Bloodstream – stack up in – skin, membranes,open wounds – migrate to the cell surface • Cell Level – produce trans-membrane – docks with – push through cell surface – become enveloped by cell membrane • Viral RNA - – released into • ssRNA Mutations – production new viral proteins/ genetic material – capable of rapid mutation

Copyright: Russell Kightley Media, Australia – very adaptable to evade defenses and environmental change • New viral – rapidly coated in • Theory – create cores – virus evolved to occupy special niches in the wild

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Clinical Features Early Clinical Presentation q Nonspecific early symptoms progress to: q Acute onset; typically 8–10 days after exposure (range 2–21 days) § Hypovolemic shock and multi-organ failure § Hemorrhagic disease q § Death § Initial: Fever, chills, myalgias, malaise, anorexia

§ After 5 days: GI symptoms, such as nausea, vomiting, watery q Non-fatal cases typically improve 6–11 days after , abdominal pain symptoms onset § Other: Headache, , hiccups, rash, chest pain, shortness of breath, confusion, seizures q Fatal disease associated with more severe early § Hemorrhagic symptoms in 18% of cases symptoms q Other possible infectious causes of symptoms § Fatality rates of 70% have been reported in rural Africa § Malaria, typhoid fever, meningococcemia, and other § Intensive care, especially early intravenous and bacterial infections (e.g., pneumonia) – all very common in Africa electrolyte management, may increase the survival rate 55 56

Clinical Manifestations by Organ System Hemorrhagic Manifestations in West African Ebola Outbreak

Organ System Clinical Manifestation • Skin hemorrhages: General Fever (87%), fatigue (76%), (39%), myalgia (39%) petechiae, purpura, ecchymoses Neurological Headache (53%), confusion (13%), eye pain (8%), coma (6%) Cardiovascular Chest pain (37%), • Gingival Pulmonary Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%) • Nasal bleeding Gastrointestinal Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal pain (44%), dysphagia (33%), jaundice (10%) • Gastro-intestinal bleeding: Hematological Any unexplained bleeding (18%), melena/hematochezia (6%), , melena, hematochezia hematemesis (4%), vaginal bleeding (3%), gingival bleeding (2%), hemoptysis (2%), epistaxis (2%), bleeding at injection site (2%), hematuria (1%), petechiae/ecchymoses (1%) • Hematuria Integumentary Conjunctivitis (21%), rash (6%) • Increased menstrual flow

WHO Ebola Response team. NEJM. 2014 57

Examples of Hemorrhagic Signs

Hematemesis

Gingival bleeding

Bleeding at IV Site

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Laboratory Findings

q Thrombocytopenia (50,000–100,000/µL range)

q Leukopenia followed by neutrophilia

q Transaminase elevation: elevation aspartate amino- transferase (AST) > alanine transferase (ALT)

q Electrolyte abnormalities from fluid shifts

q Coagulation: PT and PTT prolonged

q Renal: proteinuria, increased creatinine

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EVD: Expected diagnostic test results over Diagnosis time

Critical information: Date of onset of fever/symptoms Timeline of infection Diagnostic tests available IgM IgG Within a few days after onset § -capture enzyme-linked immunosorbent assay (ELISA) testing § IgM ELISA § Polymerase chain reaction (PCR) 0 3 10 days post onset of symptoms § Virus isolation Fever Later in disease course or after § : IgM and IgG recovery RT-PCR Retrospectively in deceased § Immunohistochemistry testing ELISA IgM patients § PCR ELISA IgG § Virus isolation IgM: up to 3 – 6 months IgG: 3 – 5 years or more (life-long persistance?)

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Ebola Virus Diagnosis Other Ebola Virus Diagnostics

q Real Time PCR (RT-PCR) q Virus isolation § Used to diagnose acute infection § Requires 4 laboratory; § More sensitive than antigen detection ELISA § Can take several days § Identification of specific viral genetic fragments q Immunohistochemical staining and histopathology § Performed in select CLIA-certified laboratories § On collected tissue or dead wild animals; localizes viral antigen

q RT-PCR sample collection q Serologic testing for IgM and IgG (ELISA) § Volume: minimum volume of 4mL whole blood § Detection of viral antibodies in § Plastic collection tubes (not glass or heparinized tubes) specimens, such as blood, serum, or tissue suspensions § Whole blood preserved with EDTA is preferred § Monitor the immune response • Whole blood preserved with sodium polyanethol sulfonate (SPS), in confirmed EVD patients citrate, or with clot activator is acceptable

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Research on filoviruses requires maximum containment: laboratory designaons Laboratories

q CDC has developed interim Biosafety level 1 (BSL-1) guidance for U.S. laboratory Organisms (agents) not known to cause disease in healthy human adults. workers and other healthcare personnel who collect or handle Biosafety level 2 (BSL-2) specimens Agents known to pose a potentially moderate risk to health virus, virus q This guidance includes information about the appropriate steps for Biosafety level 3 (BSL-3) collecting, transporting, and Agents known to cause serious or potentially lethal disease as a result of exposure testing specimens from patients by inhalation , SARS who are suspected to be infected with Ebola Biosafety level 4 (BSL-4) q Specimens should NOT be Agents known to pose a high risk of lethal disease, which may be transmitted by the aerosol route, and for which there is not vaccine or therapy. shipped to CDC without Ebola virus consultation with CDC and local/ state health departments Information available at: http://www.cdc.gov/vhf/ebola/hcp/interim-guidance-specimen-collection-submission- patients-suspected-infection-ebola.html 68

Packaging & Shipping Clinical Specimens to CDC for Ebola Testing Interpreting Negative Ebola RT-PCR Result

q If symptoms started ≥3 days before the negative result

§ EVD is unlikely à consider other diagnoses § Infection control precautions for EVD can be discontinued unless clinical suspicion for EVD persists

q If symptoms started <3 days before the negative RT-PCR result

§ Interpret result with caution § Repeat the test at ≥72 hours after onset of symptoms § Keep in isolation as a suspected case until a repeat RT-PCR ≥72 hours after onset of symptoms is negative http://www.cdc.gov/vhf/ebola/hcp/packaging-diagram.html 69 70

Clinical Management of EVD: Investigational for EVD Patients Supportive, but Aggressive q No approved Ebola-specific prophylaxis or treatment

q Hypovolemia and sepsis physiology § has no in-vitro or in-vivo effect on Ebola virus § Aggressive intravenous fluid resuscitation § Therapeutics in development with limited human clinical trial § Hemodynamic support and critical care management if data necessary • Convalescent serum q Electrolyte and acid-base abnormalities • Therapeutic medications § Aggressive electrolyte repletion o Zmapp – chimeric human-mouse monoclonal antibodies

§ Correction of acid-base derangements o Tekmira – lipid nanoparticle small interfering RNA

q Symptomatic management of fever and gastrointestinal o – oral nucleotide analogue with antiviral activity symptoms § – in clinical trials § Avoid NSAIDS • Chimpanzee-derived adenovirus with an Ebola virus inserted q Multisystem organ failure can develop and may require • Attenuated vesicular stomatitis virus with an Ebola virus gene § Oxygenation and mechanical ventilation inserted § Correction of severe coagulopathy References: 1Huggins, JW et al. Rev Infect Dis 1989; 2Ignatyev, G et al. J Biotechnol 2000; 3Jarhling, P et al. JID 2007 S400; 4Mupapa, K et al. JID 1999 S18; 5Olinger, GG et al. PNAS 2012; 6Dye, JM et al. PNAS 2012; 7Qiu, X et al. Sci Transl § Renal replacement therapy Med 2013; 8Qiu, X et al. 2014; 9Geisbert, TW et al. JID 2007; 10Geisbert, TW et al. Lancet 2010; 11Kobinger, GP et Reference: Fowler RA et al. Am J Respir Crit Care Med. 2014 al. Virology 2006; 12Wang, D JV 2006; 13Geisbert, TW et al. JID 2011; and 14Gunther et al. JID 2011.

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Historical Vaccine Challenges: NEJM Webcast October 22, 2014 Strain Variation q Not effective: • In 2005, Jones & his colleagues, Dr. Heinz Feldmann of Winnipeg and Dr. Thomas Geisbert at , Maryland § Ribavirin announced that they had successfully vaccinated monkeys against the deadly Ebola virus § Corticosteroids § Activated Protein C • This was based on the 1976 strain of the Zaire species and protected from the 1995, but not the other 2 § Heparin species that affect humans.

Most promising agent: - small interfering RNA (“Tekmira”)

Hampton, Tracy. Vaccines Against Ebola and Marburg Viruses Show Promise in Primates Studies. Maedical News and Perspectives. JAMA. Vol. 294 No. 2 July 2005. Jones, Steven. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nature Medicine. Vol. 11 No. 7 July 2005.

NEJM Webcast October 22, 2014 NEJM Webcast October 22, 2014 • Homes of nurses who developed fever did not need special cleaning, only the home of patient zero • Infectivity is near zero on surfaces needed decontamination

• No airborne transmission; so N95 or PAC mask is adequate • There was no need to clean the plane the second infected nurse was traveling on, since she was feeling well when she boarded the plane • Cover all skin. Designate a supervisor to watch employees put on & take off PPE; stop & • Best to test by RT-PCR on or after 3rd day of decontaminate gown or gloves with bleach if gown visibly contaminated before removal symptoms

• Lifetime

Patient Recovery Practical Considerations for Evaluating Patients for EVD in the United States q Case-fatality rate 71% in the 2014 Ebola outbreak § Case-fatality rate is likely much lower with access to intensive care q CDC encourages all U.S. healthcare providers to § Ask patients with symptoms about a history of travel to West q Patients who survive often have signs of clinical Africa in the 21 days before illness onset improvement by the second week of illness § Know the signs and symptoms of EVD § Associated with the development of virus-specific antibodies § Know the initial steps to take if a diagnosis of EVD is suspected § Antibody with neutralizing activity against Ebola persists greater than 12 years after infection q CDC has developed documents to facilitate these evaluations q Prolonged convalescence § The EVD algorithm for the evaluation of a returned traveler § Includes arthralgia, myalgia, abdominal pain, extreme fatigue, and anorexia; many symptoms resolve by 21 months • Available at http://www.cdc.gov/vhf/ebola/pdf/ebola-algorithm.pdf § Significant arthralgia and myalgia may persist for >21 months § The checklist for evaluation of a patient being evaluated for EVD § Skin sloughing and hair loss has also been reported • Available at http://www.cdc.gov/vhf/ebola/pdf/checklist-patients-evaluated-us-

References: 1WHO Ebola Response Team. NEJM 2014; 2Feldman H & Geisbert TW. Lancet 2011; 3Ksiazek TG et al. JID evd.pdf 1999; 4Sanchez A et al. J Virol 2004; 5Sobarzo A et al. NEJM 2013; and 6Rowe AK et al. JID 1999.

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EVD Algorithm for Evaluation of the Returned Traveler

**CDC Website to check current affected areas: www.cdc.gov/vhf/ebola Algorithm available at http://www.cdc.gov/vhf/ebola/pdf/ebola-algorithm.pdf Checklist available at http://www.cdc.gov/vhf/ebola/pdf/checklist-patients-evaluated-us-evd.pdf 79

Interim Guidance for Monitoring and EVD Summary Movement of Persons with EVD Exposure q The 2014 Ebola outbreak in West Africa is the largest in q CDC has created guidance for monitoring people exposed history and has affected multiple countries to Ebola virus but without symptoms

RISK LEVEL PUBLIC HEALTH ACTION q Think Ebola: U.S. healthcare providers should be aware of Monitoring Restricted Restricted clinical presentation and risk factors for EVD Public Activities Travel q Human-to-human transmission by direct contact HIGH risk Direct Active Monitoring Yes Yes Case-by-case Case-by-case § No human-to-human transmission via inhalation (aerosols) SOME risk Direct Active Monitoring assessment assessment § No transmission before symptom onset Active Monitoring for some; q LOW risk No No Early case identification, isolation, treatment and effective Direct Active Monitoring infection control are essential to prevent Ebola for others transmission NO risk No No No www.cdc.gov/vhf/ebola/hcp/monitoring-and-movement-of-persons-with-exposure.html 82

Basic Research • The assembly of Ebola virus nucleocapsid requires virion- associated proteins 35 and 24 and posttranslational modification of

• Report describes distinct VP35 and VP24 proteins mechanism of regulation for filovirus assembly • suggests new approaches for viral therapies and vaccines for Ebola and related viruses

• Detection of antibodies against the four subtypes of Ebola virus in sera from any species using a novel antibody-phage For more information, please contact Centers for Disease Control and Prevention indicator assay 1600 Clifton Road NE, Atlanta, GA 30333 Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 • assesses the presence of specific antibodies in serum Visit: www.atsdr.cdc.gov | Contact CDC at: 1-800-CDC-INFO or www.cdc.gov/info • describes development of a novel assay for the detection of The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and seroconversion irrespective of Ebola virus subtype or animal Prevention. species Centers for Disease Control and Prevention CS252465 Office of the Director 83

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References

• Reemergence of Ebola Virus in Africa; Anthony Sanchez et al,EID Volume 1 * Number 3 July-September 1995 http://www.cdc.gov/ncidod/EID/vol1no3/sanchez.htm

• , Healthlink, Medical College of Wisconsin, 2000 http://healthlink.mcw.edu/article/955159073.html

• Isolation and Phylogenetic Characterization of Ebola Viruses Causing Different Outbreaks in Emerging Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention ,February 5, 1997 http://www.cdc.gov/ncidod/EID/vol3no1/courbot2.htm

• Hemorrhagic fevers; Julia Barrett, Gale Encyclopedia of Medicine, Gale Research, 1999 http://www.findarticles.com/cf_dls/g2601/0006/2601000652/p1/article.jhtm l Key Issues in the Prevention and Control of Viral Hemorrhagic Fevers Clarence J.Peters, MD, Special Branch/Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases/Centers for Disease Control and Prevention, 1997 http://www.cdc.gov/od/ohs/sympsium/symp43.htm

• Scientific Stock Images Library; Russell Kightley Media,Australia http://www.rkm.com.au/imagelibrary/index.html

• Outbreak of Ebola Hemorrhagic Fever ---Uganda, August 2000--January 2001, Morbidity and Mortality Weekly Report, Vol 50, No 05;73, 02/09/2001 / 50(05);73-7 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5005a1.htm

• Ebola-Reston Virus Infection Among Quarantined Nonhuman Primates -- Texas, 1996 Morbidity and Mortality Weekly Report, Vol 45, No 15;314 ,April 19, 1996 / 45(15);314-316 http://www.cdc.gov/mmwr/preview/mmwrhtml/00040920.htm The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein, Huang Y et al, Mol Cell. 2002 Aug;10(2):307-16. PMID: 12191476 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12191476&dopt=Abstract Detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.; Meissner F et al , PMID: 1235035 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12350354&dopt=Abstract

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