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Emerging Infections: Ebola & Chikungunya

Elizabeth Race, MD, MPH Infectious Diseases / HIV Medicine

AIDS Healthcare Foundation, Dallas, Texas

Chikungunya Virus

Chikungunya Virus: A Newly Re-emergent Infectious Problem

•  Arbovirus originally identified in 1950s in E. Africa, in sylvatic cycle involving primates and forest mosquitoes

•  Clinical descriptions first in 1970s in South Africa

•  Limited outbreaks periodically in SE Asia, with a larger one in 2001-2003 in Indonesia (after 20-year hiatus)

•  Explosive outbreak in 2005-present, in Indian Ocean islands & Indian subcontinent, involving millions of cases

•  Imported cases in Europe, North America among travelers to Indian Ocean sites

-Triad of fever/rash/arthritis is characteristic of Chikungunya, O’nyong-nyong, Ross River, Mayaro, and Sindbis viruses -Symptoms generally appear after 2-3 days incubation

a) fever, chills, myalgia b) polyarthralgia mainly affecting small joints c) maculopapular rash

-Arthritis generally resolves in a few weeks, but may persist for months, or years in some cases.

Fever/Rash/Arthritis

•  Genus Alphavirus; Family Togaviridae

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

Aedes albopictus

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

World Distribution of the Aedes albopictus Togaviridae, genus Alphavirus

•  Infection can cause a debilitating illness, most often characterized by fever, headache, fatigue, nausea, vomiting, muscle pain, rash, and joint pain. The term ‘chikungunya’ is Swahili for ‘that which bends up.’

Chikungunya

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

• Up to 10% may develop chronic joint symptoms

• Death is very uncommon

•  No vaccine or preventive drug; recommendation: vector control, vector avoidance

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

Skin manifestations in CHIKV in travelers

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:

•  India (14 states), Malaysia, Indonesia, Sri Lanka, Maldives, Nicobar Islands

•  Imported cases reported in multiple countries: – Australia – Japan – Taiwan – Europe: UK, France, Italy, Spain – USA

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

Chikungunya Infection in Travelers

During 2005-’06, 12 cases of CHIK fever were dx’d serologically and virologically at CDC in travelers who arrived in the US from areas known to be epidemic or endemic for CHIKV

Chikungunya Virus: Summary

•  Caused by virus inoculated via mosquito bites –  Increased risk May-October (rainy season) –  Increased risk in urban and village areas

•  Symptoms: Sudden onset of fever, rash on trunk and limbs, back pain, and severe joint pain / arthritis in multiple joints

•  Treatment: analgesics, NSAIDS, corticosteroids; chloroquine has been used in a few refractory cases

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

African Tick-Bite Fever

Rickettsia africae

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Spotted Fever Group Mediterranean spotted fever - Rickettsia (R.)

conorii Rickettsialpox - R. akari African tick bite fever - R. africae Queensland tick typhus - R. australis Japanese spotted fever - R. japonica Flinders Island spotted fever - R. honei California flea rickettsiosis - R. felis Siberian tick typhus - R. sibirica Israeli spotted fever - not named Astrakhan fever - not named

Disease: African Tick-Bite Fever

•  Rickettsial infections: R africae & R conorii

•  Transmitted by ticks

•  1992: Kelly et al isolated R africae from a patient in Zimbabwe (Lancet 340:982-983)

•  Exported from southern Africa [ & Guadeloupe] to US 1997

(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 incubation period 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 •  Therapy: doxycycline (possibly single-dose)

Parola P, Raoult D. et al. Am J Trop Med Hyg 1999;60:888-93. Amblyomma variegatum (female).

PHILIPPE PAROLA, GUY VESTRIS, DOMINIQUE MARTINEZ, BERNARD BROCHIER, VERONIQUE ROUX, DIDIER RAOULT. Am. J. Trop. Med. Hyg., 60(6), 1999, pp. 888–893

Tick Borne Rickettsial Lesions: “Tache noire”

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

Four Inoculation Eschars (Arrows) on the Legs of a Patient Who Presented with African Tick-Bite Fever after Returning from a Safari in South Africa

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Figure 1. Fibrinoid necrosis of a vessel in the dermis (arrow) with perivascular inflammatory infiltrates mainly composed of polymorpho-nuclear leukocytes (hematoxylin-eosin-saffron; orig. magnification ×250). Hubert Lepidi,Pierre-Edouard Fournier,& Didier Raoult,Université de la Méditerranée, Marseille, France Vol.12,No.9 Sept2006

Figure 3. Inoculation eschar from a patient with African tick-bite fever showing numerous dermal inflammatory infiltrates mainly composed of polymorphonuclear leukocytes (immunoperoxidase staining with an anti-CD15 antibody; original magnification ×100). Hubert Lepidi,Pierre-Edouard Fournier,& Didier Raoult,Université de la Méditerranée, Marseille, France Vol.12,No.9 Sept2006

Figure 5. Immunohistochemical detection of Rickettsia africae in the inoculation eschar of a pt with African tick-bite fever. Note location of the bacteria in the endothelial and inflammatory cells of a blood vessel in the dermis (arrow);monoclonal rabbit anti-R. 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

Clinical Characteristics of R.africae infection

•  Fever > 38.5 •  Neck myalgias •  Inoculation

eschars •  Multiple eschars •  Lymphadenopathy •  Rash (vesicular) •  Death

•  88% •  81% •  95% •  54% •  43% •  46% (45%) •  0%

Raoult D, et al. NEJM 2001;344:1504-10.

Rickettsial Disease in the Returning Traveler

•  R.africae > murine typhus (R.typhae) > mediterranean spotted fever > scrub typhus

•  Also RMSF, epidemic typhus, N. Asian, Queensland tick typhus

•  Approx. 3rd most likely etiology of fever in the returning traveler after malaria and typhoid fever

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

Treatment of African Tick Bite Fever (Lyme, RMSF, Ehrlichia)

doxycycline

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Emerging Infections: Ebola Virus Disease

Filoviridae (Ebola, Marburg)

Arenaviridae (Lassa, Junin, Machupo, Guanarito)

Bunyaviridae (CCHF, RVF,

Hantaviruses)

Viral Hemorrhagic Fevers

Flaviviridae (dengue, yellow fever, TBE encephalitides)

Enveloped RNA viruses

Ebola Taxonomy Scientific Classification

Order: Mononegavirales Family: Filoviridae Genus: Ebola like viruses Species: Ebola Subtypes

–  Ebola-Zaire, Ebola-Sudan,Ebola-Ivory Coast •  disease in humans

–  Ebola-Reston •  disease in nonhuman primates

Copyrighted Dr. Fre:derick A. Murphy, D.V.M., Ph.D. 1976.

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

Ravn virus

Viruses without borders Ebola Virus

q  Prototype Viral Hemorrhagic Fever Pathogen §  Filovirus: enveloped,

non-segmented, negative-stranded RNA virus

§  Severe disease with high case fatality

§  Absence of specific treatment or vaccine

q  >20 previous Ebola and Marburg virus outbreaks

q  2014 West Africa Ebola outbreak caused by Zaire ebolavirus species (five known Ebola virus species)

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Ebola Virus q  Zoonotic virus – bats the most likely reservoir, although

species unknown

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

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Epidemiology and ecology are intimately linked

Current Ebola virus outbreak

(graphics: BBC)

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 40

2014 Ebola Outbreak, West Africa

WHO Ebola Response Team. N Engl J Med 2014. DOI: 10.1056/NEJMoa1411100 http://www.nejm.org/doi/full/10.1056/NEJMoa1411100?query=featured_ebola#t=articleResults 41

EVD Cases and Deaths* Reporting

Date Total Cases Confirmed Cases Total Deaths

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. *Reported by WHO using data from Ministries of Health **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) 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, Texas from Liberia, two healthcare workers who cared for the index patient, and one medical aid worker who traveled to New York City from Guinea §  Index patient – Symptoms developed on September 24, 2014 approximately

four days after arrival, sought medical care at Texas Health Presbyterian Hospital of Dallas on September 26, was admitted to hospital on September 28, testing confirmed EVD on September 30, patient died October 8.

§  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.

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Information on U.S. EVD cases available at http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html.

EVD Cases (United States) q  As of October 31, 2014, four U.S. health workers and one

journalist who were infected with Ebola virus in West Africa were transported to hospitals in the United States for care

§  All the patients have recovered and have been released from the hospital after laboratory testing confirmed that they no longer have Ebola virus in their blood

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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

§  Direct contact (through broken skin or unprotected mucous membranes) with an EVD-infected patient’s blood or body fluids

§  Sharps injury (with EVD-contaminated needle or other sharp) §  Direct contact with the corpse of a person who died of EVD §  Indirect contact with an EVD-infected patient’s blood or body

fluids via a contaminated object (soiled linens or used utensils)

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

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Modes of Transmission

3 most common modes of infection:

1.  Unsterilized needles 2.  Suboptimal hospital

conditions 3.  Personal contact

http://www.ecplanet.com/pic/2003/12/1071257871/ebola.jpg

Detection of Ebola Virus in Different Human Body Fluids over Time

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Human-to-Human Transmission q  Infected persons are not contagious until onset of

symptoms

q  Infectiousness of body fluids (e.g., viral load) 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 •  Health workers treating patients with suspected/

confirmed illness at higher risk of infection – Only time people transmit disease is when they

are symptomatic – Overwhelmingly viremic when symptomatic

•  General public is generally safe

•  Updated guidance for hospital-based healthcare workers released 10/20/14

•  Guiding principles: –  Rigorous training so all are practiced

and competent with PPE, including taking on and off

–  No skin exposure when PPE is worn –  Supervision by trained monitor when

taking PPE on and off.

Personal  Protec,ve  Equipment  (PPE)  

EVD Risk Assessment

**CDC Website to check current affected areas: www.cdc.gov/vhf/ebola

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

Lancet. Mar 5, 2011; 377(9768): 849–862.

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Ebola Pathogenesis

•  Enters Bloodstream –  skin, membranes,open wounds

•  Cell Level –  docks with cell membrane

•  Viral RNA –  released into cytoplasm –  production new viral proteins/ genetic material

•  New viral genomes –  rapidly coated in protein –  create cores

Copyright: Russell Kightley Media, Australia

Ebola Pathogenesis, cont

•  Viral cores –  stack up in cell –  migrate to the cell surface –  produce trans-membrane proteins –  push through cell surface –  become enveloped by cell membrane

•  ssRNA- Genome Mutations –  capable of rapid mutation –  very adaptable to evade host defenses and environmental change

•  Theory –  virus evolved to occupy special niches in the wild

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Early Clinical Presentation q  Acute onset; typically 8–10 days after exposure

(range 2–21 days)

q  Signs and symptoms §  Initial: Fever, chills, myalgias, malaise, anorexia §  After 5 days: GI symptoms, such as nausea, vomiting, watery

diarrhea, abdominal pain §  Other: Headache, conjunctivitis, hiccups, rash, chest pain,

shortness of breath, confusion, seizures §  Hemorrhagic symptoms in 18% of cases

q  Other possible infectious causes of symptoms §  Malaria, typhoid fever, meningococcemia, Lassa fever and other

bacterial infections (e.g., pneumonia) – all very common in Africa

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Clinical Features q  Nonspecific early symptoms progress to:

§  Hypovolemic shock and multi-organ failure §  Hemorrhagic disease §  Death

q  Non-fatal cases typically improve 6–11 days after symptoms onset

q  Fatal disease associated with more severe early symptoms

§  Fatality rates of 70% have been reported in rural Africa §  Intensive care, especially early intravenous and

electrolyte management, may increase the survival rate

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Clinical Manifestations by Organ System in West African Ebola Outbreak

Organ System Clinical Manifestation

General Fever (87%), fatigue (76%), arthralgia (39%), myalgia (39%)

Neurological Headache (53%), confusion (13%), eye pain (8%), coma (6%)

Cardiovascular Chest pain (37%),

Pulmonary Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%)

Gastrointestinal Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal pain (44%), dysphagia (33%), jaundice (10%)

Hematological Any unexplained bleeding (18%), melena/hematochezia (6%), hematemesis (4%), vaginal bleeding (3%), gingival bleeding (2%), hemoptysis (2%), epistaxis (2%), bleeding at injection site (2%), hematuria (1%), petechiae/ecchymoses (1%)

Integumentary Conjunctivitis (21%), rash (6%)

WHO Ebola Response team. NEJM. 2014

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Hemorrhagic Manifestations

•  Skin hemorrhages: petechiae, purpura, ecchymoses

•  Gingival bleeding •  Nasal bleeding •  Gastro-intestinal bleeding:

hematemesis, melena, hematochezia •  Hematuria •  Increased menstrual flow

Examples of Hemorrhagic Signs

Bleeding at IV Site

Hematemesis

Gingival bleeding

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Laboratory Findings

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

q  Leukopenia followed by neutrophilia

q  Transaminase elevation: elevation serum 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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viremia

3

IgM

ELISA IgM

0 10

IgG

IgM: up to 3 – 6 months

ELISA IgG

IgG: 3 – 5 years or more (life-long persistance?)

days post onset of symptoms

RT-PCR

Critical information: Date of onset of fever/symptoms

Fever

EVD: Expected diagnostic test results over time

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Diagnosis

Timeline of infection   Diagnostic tests available  

Within a few days after onset  

§  Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing

§  IgM ELISA §  Polymerase chain reaction

(PCR) §  Virus isolation

Later in disease course or after recovery  

§  Serology: IgM and IgG  

Retrospectively in deceased patients  

§  Immunohistochemistry testing §  PCR §  Virus isolation  

Ebola Virus Diagnosis q  Real Time PCR (RT-PCR)

§  Used to diagnose acute infection §  More sensitive than antigen detection ELISA §  Identification of specific viral genetic fragments §  Performed in select CLIA-certified laboratories

q  RT-PCR sample collection §  Volume: minimum volume of 4mL whole blood §  Plastic collection tubes (not glass or heparinized tubes) §  Whole blood preserved with EDTA is preferred

•  Whole blood preserved with sodium polyanethol sulfonate (SPS), citrate, or with clot activator is acceptable

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Other Ebola Virus Diagnostics q  Virus isolation

§  Requires Biosafety Level 4 laboratory; §  Can take several days

q  Immunohistochemical staining and histopathology §  On collected tissue or dead wild animals; localizes viral antigen

q  Serologic testing for IgM and IgG antibodies (ELISA) §  Detection of viral antibodies in

specimens, such as blood, serum, or tissue suspensions

§  Monitor the immune response in confirmed EVD patients

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Research  on  filoviruses  requires  maximum  containment:  biocontainment  laboratory  designa,ons  

Biosafety level 1 (BSL-1) Organisms (agents) not known to cause disease in healthy human adults.

Biosafety level 2 (BSL-2) Agents known to pose a potentially moderate risk to health Herpes simplex virus, rabies virus

Biosafety level 3 (BSL-3)

Agents known to cause serious or potentially lethal disease as a result of exposure by inhalation

West Nile virus, SARS Biosafety level 4 (BSL-4)

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.

Ebola virus

Laboratories q  CDC has developed interim

guidance for U.S. laboratory workers and other healthcare personnel who collect or handle specimens

q  This guidance includes information about the appropriate steps for collecting, transporting, and testing specimens from patients who are suspected to be infected with Ebola

q  Specimens should NOT be shipped to CDC without 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

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Packaging & Shipping Clinical Specimens to CDC for Ebola Testing

http://www.cdc.gov/vhf/ebola/hcp/packaging-diagram.html

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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

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Clinical Management of EVD: Supportive, but Aggressive

q  Hypovolemia and sepsis physiology §  Aggressive intravenous fluid resuscitation §  Hemodynamic support and critical care management if

necessary q  Electrolyte and acid-base abnormalities

§  Aggressive electrolyte repletion §  Correction of acid-base derangements

q  Symptomatic management of fever and gastrointestinal symptoms §  Avoid NSAIDS

q  Multisystem organ failure can develop and may require §  Oxygenation and mechanical ventilation §  Correction of severe coagulopathy §  Renal replacement therapy

Reference: Fowler RA et al. Am J Respir Crit Care Med. 2014

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Investigational Therapies for EVD Patients q  No approved Ebola-specific prophylaxis or treatment

§  Ribavirin has no in-vitro or in-vivo effect on Ebola virus §  Therapeutics in development with limited human clinical trial

data •  Convalescent serum •  Therapeutic medications

o  Zmapp – chimeric human-mouse monoclonal antibodies o  Tekmira – lipid nanoparticle small interfering RNA o  Brincidofovir – oral nucleotide analogue with antiviral activity

§  Vaccines – in clinical trials •  Chimpanzee-derived adenovirus with an Ebola virus gene inserted •  Attenuated vesicular stomatitis virus with an Ebola virus gene

inserted 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 Med 2013; 8Qiu, X et al. Nature 2014; 9Geisbert, TW et al. JID 2007; 10Geisbert, TW et al. Lancet 2010; 11Kobinger, GP et 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: Strain Variation

•  In 2005, Jones & his colleagues, Dr. Heinz Feldmann of Winnipeg and Dr. Thomas Geisbert at Fort Detrick, Maryland announced that they had successfully vaccinated monkeys against the deadly Ebola virus

•  This Ebola vaccine was based on the 1976 strain of the Zaire species and protected from the 1995, but not the other 2 species that affect humans.

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

q  Not effective: § Ribavirin § Corticosteroids §  Activated Protein C § Heparin

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

NEJM Webcast October 22, 2014

•  Infectivity is near zero on surfaces

•  No airborne transmission; so N95 or PAC mask is adequate

•  Cover all skin. Designate a supervisor to watch employees put on & take off PPE; stop & decontaminate gown or gloves with bleach if gown visibly contaminated before removal

NEJM Webcast October 22, 2014 •  Homes of nurses who developed fever did not need

special cleaning, only the home of patient zero needed decontamination

•  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

•  Best to test by RT-PCR on or after 3rd day of

symptoms

•  Lifetime immunity

Patient Recovery q  Case-fatality rate 71% in the 2014 Ebola outbreak

§  Case-fatality rate is likely much lower with access to intensive care

q  Patients who survive often have signs of clinical improvement by the second week of illness §  Associated with the development of virus-specific antibodies §  Antibody with neutralizing activity against Ebola persists greater

than 12 years after infection

q  Prolonged convalescence §  Includes arthralgia, myalgia, abdominal pain, extreme fatigue,

and anorexia; many symptoms resolve by 21 months §  Significant arthralgia and myalgia may persist for >21 months §  Skin sloughing and hair loss has also been reported

References: 1WHO Ebola Response Team. NEJM 2014; 2Feldman H & Geisbert TW. Lancet 2011; 3Ksiazek TG et al. JID 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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Practical Considerations for Evaluating Patients for EVD in the United States

q  CDC encourages all U.S. healthcare providers to §  Ask patients with symptoms about a history of travel to West

Africa in the 21 days before illness onset §  Know the signs and symptoms of EVD §  Know the initial steps to take if a diagnosis of EVD is suspected

q  CDC has developed documents to facilitate these evaluations §  The EVD algorithm for the evaluation of a returned traveler

•  Available at http://www.cdc.gov/vhf/ebola/pdf/ebola-algorithm.pdf

§  The checklist for evaluation of a patient being evaluated for EVD •  Available at

http://www.cdc.gov/vhf/ebola/pdf/checklist-patients-evaluated-us-evd.pdf

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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

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Interim Guidance for Monitoring and Movement of Persons with EVD Exposure

q  CDC has created guidance for monitoring people exposed to Ebola virus but without symptoms

www.cdc.gov/vhf/ebola/hcp/monitoring-and-movement-of-persons-with-exposure.html

RISK LEVEL PUBLIC HEALTH ACTION

Monitoring Restricted Public Activities

Restricted Travel

HIGH risk Direct Active Monitoring Yes Yes

SOME risk Direct Active Monitoring Case-by-case assessment

Case-by-case assessment

LOW risk

Active Monitoring for some; Direct Active Monitoring for others

No No

NO risk No No No

EVD Summary

q  The 2014 Ebola outbreak in West Africa is the largest in history and has affected multiple countries

q  Think Ebola: U.S. healthcare providers should be aware of clinical presentation and risk factors for EVD

q  Human-to-human transmission by direct contact §  No human-to-human transmission via inhalation (aerosols)

§  No transmission before symptom onset

q  Early case identification, isolation, treatment and effective infection control are essential to prevent Ebola transmission

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For more information, please contact Centers for Disease Control and Prevention

1600 Clifton Road NE, Atlanta, GA 30333 Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348

Visit: www.atsdr.cdc.gov | Contact CDC at: 1-800-CDC-INFO or www.cdc.gov/info

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

Prevention.

CS252465 Centers for Disease Control and Prevention Office of the Director 83

Basic Research •  The assembly of Ebola virus nucleocapsid requires virion-

associated proteins 35 and 24 and posttranslational modification of nucleoprotein •  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 indicator assay

•  assesses the presence of specific antibodies in serum •  describes development of a novel assay for the detection of

seroconversion irrespective of Ebola virus subtype or animal species

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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

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

•  Isolation and Phylogenetic Characterization of Ebola Viruses Causing Different Outbreaks in Gabon

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 Pathogens 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