Slide 1 ______

EBOLA 2014 ______WEST AFRICA

Hosted by: ______Bhagavatula Ramakrishna, M.D. ______

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Slide 2 ______CENTRAL AND EAST AFRICA ______

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______Slide 4 IN WEST AFRICA ______2014 ______

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Slide 5 ______

“It is a disease of poverty and neglect of health systems. It is an infection that causes epidemics only if basic ______hospital hygiene is not respected.”

Dr. Peter Piot (one of the first ______researchers to identify Ebola Virus in 1976) ______

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Slide 6 Ebola Hemorrhagic Fever ______Ebola hemorrhagic fever (Ebola HF) is one of numerous Viral Hemorrhagic Fevers. It is a severe, often fatal ______disease in humans and nonhuman primates (such as monkeys, gorillas, and chimpanzees).

Ebola HF is caused by infection with a virus of the ______family , genus Ebola virus. When infection occurs, symptoms usually begin abruptly. The first Ebola virus species was discovered in 1976 in what is now the Democratic Republic of the Congo near the . Since then, outbreaks have appeared ______sporadically.

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______Slide 7 ______ There are five species of Ebola virus--a negative single-stranded RNA virus in the family of Filoviridae. ______

 The three species: Bundibugyo ______Zaire Sudan Ebola viruses Responsible For all the Outbreaks ______

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Slide 8 ______There are two other Ebola viruses:

 The which is limited to ______the Philippines and has not caused human disease; ______ The Tai Forest Ebola virus caused disease in a scientist doing an autopsy on a chimpanzee. ______

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Slide 9 Ebola Cycle ______

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______Slide 10 ______The First Outbreak

 September 1976 ______ Injection of Chloroquine for malaria leads to a febrile hemorrhagic illness in a patient and then spreads to healthcare workers. ______ In two months, 318 cases of viral hemorrhagic fever with 88% mortality in 55 villages in Congo ______(now Democratic Republic of Congo) (DRC). ______

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Slide 11 ______EBOLA VIRUS OUTBREAK

 The virus was identified and named after the Ebola River that traverses ______the affected regions.

 Since then there have been 20 ______outbreaks of Ebola Virus Disease (EVD). ______

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Slide 12 ______ These were all sporadic, mostly in Central and Eastern Africa. ______ The 2014 EVD was the first outbreak to occur in West Africa. ______ From 1979 to 1994, there were no cases reported. ______

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______Slide 13 Transmission ______How do you get the Ebola virus? Direct contact with: ______1. Bodily fluids of a person who is sick with or has died from Ebola (blood, vomit, urine,faeces sweat, semen, spit and other fluids). 2. Objects contaminated with the virus ______(needles, medical equipment). 3. Infected animals (by contact with blood or body fluids or infected meat). ______

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Slide 14 Reservoir and vectors of Ebola virus ______are not understood well.

 Ebola virus is a zoonotic disease. ______Fruit bats were implicated as the virus replicates in these bats and the virus was isolated from the guano. ______

 Monkeys and other non-human primates may serve as intermediate ______hosts.

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Slide 15 ______Transmission (Continued)

Because the natural reservoir of has not yet been proven, the ______manner in which the virus first appears in a human at the start of an outbreak is unknown. However, researchers have hypothesized that the first patient becomes ______infected through contact with an infected animal. ______

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______Slide 16 ______Transmission (Continued)

Healthcare workers and the family and friends in close contact with Ebola patients are at the highest risk of getting sick because they may come in ______contact with infected blood or body fluids.

During outbreaks of Ebola HF, the disease can spread quickly within healthcare settings (such as a ______clinic or hospital). Exposure to Ebola viruses can occur in healthcare settings where hospital staff are not wearing appropriate protective equipment, such as masks, gowns, and gloves. ______

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Slide 17 ______Clinical Course

 Incubation period 2-21 days  Most patients develop symptoms ______between day 8-10.  Abrupt onset of fever, chills, myalgia, sometimes macules, papules, rash ______ Watery diarrhea, nausea, vomiting  Hemorrhagic sequela such as  Petechiae and ecchymosis ______

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Slide 18 Signs & Symptoms ______

Symptoms of Ebola HF Typically Include: Some Patients May Experience:  Fever  A Rash  Headache  Red Eyes ______ Joint and muscle aches  Hiccups  Weakness  Cough  Diarrhea  Sore throat  Vomiting  Chest pain ______ Stomach pain  Difficulty breathing  Lack of appetite  Difficulty swallowing  Bleeding inside & outside of the body ______

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______Slide 19 ______Clinical Course (cont’d) ______ Death usually occurs 6-16 days after onset of symptoms.  Recovered patients have prolonged weakness, poor appetite, and failure ______to gain weight. ______

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Slide 20 VIRAL PERSISTENCE ______

 Dr. J. B. Varken, an American Physician, who survived Ebola in September 2014 (Sierra Leone): ______- Developed posterior uveitis 14 weeks after recovery - Aqueous humor sample positive for ______EBOV-RNA, but conjunctival and tear samples were negative. - There is a report of sexually transmitted Ebola because of persistence of the virus ______in the testes.

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Slide 21 Pathogenesis ______ The virus causes multi-organ system failure.  It invades endothelium and causes ______endothelial damage.  Causes a cytokine storm by attacking macrophages that leads to intense ______inflammation, hepatic necrosis, severe sepsis leading to death.  Hepatic necrosis plus thrombo- ______cytopenia, etc., lead to hemorrhage and death.

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______Slide 22 ______Pathogenesis of Ebola Virus (Cont’d)

Reason for Hemorrhagic Fever 1) Macrophages leak cytokines (IL-1beta, nitric ______oxide, TNF alpha) cause fever and inflammation and hypotension

2) Endothelial cell damage causes capillary (vascular) leak, hypotension and shock ______

3) Coagulopathy triggered by macrophage synthesized cell-surface tissue factor that triggers extrinsic coagulation pathway and ______DIC.

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Slide 23 Pathogenesis of Ebola ______

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Slide 24 ______Diagnosis

Diagnosis Ebola HF in an individual who has been infected for only a few days is difficult, because the ______early symptoms, such as red eyes and a skin rash, are nonspecific to Ebola virus infection and are seen often in patients with more commonly occurring diseases. ______However, if a person has the early symptoms of Ebola HF, and there is reason to believe that Ebola HF should be considered, the patient should be isolated and professionals notified. ______Samples from the patient can then be collected and tested to confirm infection.

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______Slide 25 ______Diagnosis (Continued)

Laboratory tests used in diagnosis include: Timeline of Infection Diagnostic Tests Available ______Within a few days after - Antigen-capture enzyme-linked symptoms begin immunosorbent assay (ELISA) testing - IgM ELISA - Polymerase chain reaction (PCR) - Virus isolation ______

Later in disease course or after - IgM and IgG antibodies recovery

Retrospectively in deceased - Immunohistochemistry testing ______- PCR - Virus isolation New Rapid Bedside tests Approved by the FDA ______

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Slide 26 Treatment ______Supportive:  Blood product transfusion ______ Electrolyte replacement  Fluid resuscitation  Vasopressors ______ Ventilator support

Evaluate for any concurrent infections, such as malaria, typhoid fever, etc. ______

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Slide 27 Investigational Drugs: ______ Z.Mapp. (Mapp. Biopharmaceutical) a combination of 3 different monoclonal antibodies that bind to the protein of ______Ebola Virus.  Bricidofovir  Blood and Serum from persons who ______have recovered from Ebola Virus Disease Have been used. ______

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______Slide 28 VACCINES ______PHASE I STUDIES Two vaccines being studied (New ______England Journal of Medicine (NEJM), April 2015).

A recombinant chimpanzee adenovirus ______and a vesicular stomatitis virus. These express Ebola surface glycoprotein. ______

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Slide 29 How Trials will Work ______for Ebola Vaccines (by Bonnie Berkowitz & Patterson Clark, Published February 8, 2015)

Two promising Ebola vaccines have begun ______clinical trials in West Africa. A different type of trial is planned for each of the three countries hit hardest by the epidemic. This phase could take a year or more, said Anthony ______Fauci, director of the National Institute of Allergy and Infectious Diseases. A trial’s length depends on the spread of the epidemic, and this one is subsiding. ______

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Slide 30 The Vaccines ______

Chimp adenovirus—made by GlaxoSmithKline A chimpanzee cold virus is ______used as a carrier to deliver a gene that makes the outer protein for the Zaire strain of Ebola. The virus is not alive and not able to replicate, but it can still express a protein. Once ______injected into the body, it makes a protein that triggers an immune response. It cannot cause infection. ______

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______Slide 31 ______The Vaccines (Cont’d.)

VSV-Zebov—made by NewLink and Merck

The vesicular stomatitis virus ______vaccine works similarly to the adenovirus vaccine, except that the virus is alive and replicates itself so that it makes more and more of the Ebola protein. It cannot cause an Ebola infection. One of several earlier trials ______was stopped because some participants developed joint pain, but the side effect was determined to be mild enough to restart the trial. A few tens of millions of doses will ______be available in 2015, according to the World Health Organization.

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Slide 32 ______Prevention

The prevention of Ebola HF presents many challenges. Because it is still unknown how exactly people are infected with Ebola HF, there are few ______established primary prevention measures.

When cases of the disease do appear, there is increased risk of transmission within healthcare ______settings. Therefore, healthcare workers must be able to recognize a case of Ebola HF and be ready to employ practical viral hemorrhagic fever isolation precautions or barrier nursing techniques. They should also have the capability to request ______diagnostic tests or prepare samples for shipping and testing elsewhere.

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Slide 33 Prevention (Continued) ______Barrier nursing techniques include:  wearing of protective clothing (such as masks, gloves, gowns, and goggles). ______ the use of infection control measures (such as complete equipment sterilization and routine use of disinfectant).  isolation of Ebola HF patients from contact with unprotected persons. ______The aim of all of these techniques is to avoid contact with the blood or secretions of an infected patient. If a patient with Ebola HF dies, it is equally important that direct contact with the body of the deceased patient be ______prevented.

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______Slide 34 ______Prevention (Continued)

Centers for Disease Control and Prevention (CDC), in conjunction with the World Health Organization, has developed a set of guidelines to help prevent ______and control the spread of Ebola HF. Entitled Infection Control for Viral Hemorrhagic Fevers in the African Healthcare Setting, the manual describes how to: ______ recognize cases of viral hemorrhagic fever (such as Ebola HF).  prevent further transmission in healthcare setting by using locally available materials and minimal financial resources. ______

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Slide 35 Travel ______If you must travel to an area with known Ebola cases, make sure to do the following:  Practice careful hygiene. Avoid contact with blood and body fluids.  Do not handle items that may have come in contact with an infected ______person’s blood or body fluids.  Avoid funeral or burial rituals that require handling the body of someone who has died from Ebola.  Avoid contact with bats and nonhuman primates or blood, fluids, and raw meat prepared from these animals. ______ Avoid hospitals where Ebola patients are being treated. The U.S. embassy or consulate is often able to provide advice on facilities.  After you return, monitor your health for 21 days, and seek medical care immediately if you develop symptoms of Ebola (/vhf/ebola/symptoms/index.html). ______

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Slide 36 ______2014 Ebola Outbreak in Context

 A two-year-old toddler died from the ______disease (Guéckédou Prefecture, Guinea) in December 2013. ______ 2014 outbreak started in Meliandou, Guinea. ______

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______Slide 37 ______ In March, Medicins' sans Frontières (MSF), Doctors without Borders, reported a mysterious illness that killed 59 of first 86 cases. ______

 Then the disease spreads to Liberia, , Nigeria, Sierra Leone, and ______Mali—all from infected travelers crossing borders. ______

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Slide 38 ______OUT SIDE AFRICA Outside Africa ______ September 30, 2014—The first case of EVD was diagnosed in the United States in a patient from Liberia to Dallas, Texas. ______

 Healthcare workers also were infected. ______

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Slide 39 ______ Similar transmission from a repatriated nun to a healthcare worker occurred in Spain. ______ Nigeria very quickly controlled the outbreak with a team of dedicated doctors and healthcare workers who died taking care of the patients and ______government policies that helped.  In DRC (Congo), another unrelated outbreak is going on at the same ______time; this was a different strain of Ebola.

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______Slide 40 WEST AFRICA ______EBOLA OUTBREAK CASE COUNTS ______Total Cases

Updated: ▪ From March 3,2014 to June 19 ,2015 ▪ Cases : 27,352 ______▪ Deaths : 11,193 ______

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Slide 41 ______What Caused this Large Outbreak?

 Previous outbreaks occurred in rural isolated villages with limited access ______to medical care resulting in high mortality, but limited transmission. ______ With industrialization and globalization of commerce, there is now increased travel from isolated areas to densely populated urban ______areas.

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Slide 42 ______

 Increased access to healthcare helped increase nosocomial ______transmission and spread of the disease. ______

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______Slide 43 ______ Nigeria’s healthcare system and brave doctors contained the disease quickly (2 doctors died in this ______outbreak).

 Outside of West Africa,the United ______States reported a case—a traveler from Liberia. died from the illness. ______

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Slide 44 ______

 All but three cases were acquired out of West Africa, and all were healthcare workers (2 in the USA and ______a Spanish nurse, Teresa Romero).

 Second person to die on U.S. soil ______was Martin Salia, a surgeon from Sierra Leone (treated in Nebraska). ______

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Slide 45 ______ Note: Nobody in Mr. Duncan’s family or contacts in the community contracted Ebola. ______

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______Slide 46 Why this Outbreak Continued ______Cultural and Societal Factors:  Family members often take care of the patients (relatives) putting ______themselves at risk.  Family members are fearful that the hospitals themselves are causing the ______infections.  People hiding the patients and their contacts from health authorities. ______

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Slide 47  Poor hygiene and sanitation and poor ______public health system.

 Burial practices in several parts of ______West Africa include close contact of the family members with the deceased. ______

 Illegal bushmeat trade.

 Increased contact between animals ______and humans.

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Slide 48 ______The Current Policy to Deal with EBOLA

 Screening Travelers from The ______Affected Countries at one of the five  International Airports  Monitoring the persons for symptoms for 21 days ______ Symptomatic Patients are Referred to Acute Health care Facility immediately ______

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______Slide 49 ______Acute Health Care Facilities

 Front Line Hospitals. ______ Ebola Assessment Hospitals.  Ebola Treatment Centers.  There are 55 Designated Ebola ______Treatment Centers in the Country.  Three Bio containment centers also Serve as Treatment Centers.(NIH,EMORY and Nebraska). ______)

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Slide 50 ______Lessons Learned

 Response to an Outbreak in Africa, (Dr. Stan Deresinski, Editor, ______Infectious Disease Alert): - Cable news and politicians spread panic and chaos in public health ______policy. - Enormous efforts put forth and money wasted for activities in the ______country to prevent Ebola here.

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Slide 51 ______Public Health Issues  Bill Gates (in NEJM) - The world response was not ______adequate to Ebola outbreak. - A more virulent virus, such as influenza and measles could cause ______10 million deaths. - The WHO has a Global Outbreak Alert and Response Network, but it is severely underfunded. ______

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______Slide 52 ______Bill Gates (Cont’d.) What could be done?  Build a warning and response system ______for outbreaks.  This system should: - be coordinated by a global ______institution that is given enough authority and funding to be effective. - enable fast decision-making at a ______global level.

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Slide 53 ______Bill Gates (Cont’d.) What could be done? - expand investment in research and development and clarify ______regulatory pathways for developing new tools and approaches. ______- improve early warning and detection systems, including scalable everyday systems that can be expanded during an ______epidemic.

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Slide 54 Bill Gates (Cont’d.) ______What could be done? - involve a reserve corps of travel personnel and volunteers. ______- strengthen healthcare systems in low and middle income countries. - incorporate preparedness ______exercises to study how to improve the response system. ______

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______Slide 55 ______

 Dr. Gregg Gonsalves, NEJM 2014

“We all have to become activists if ______we were to protect the public health from being used as a tool to serve primarily political purposes as it has ______been over the past few weeks in the U.S.” ______

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Slide 56 ______

 Dr. Craig Spencer, Ebola Treater in Africa and a Patient in the USA ______“We all lose when we allow irrational fear fueled in part by prime time ratings and political expediency to ______supersede pragmatic public healthcare policy.” ______

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Slide 57 ______ Centers for Disease Control and Prevention (CDC) ______Dr. Thomas Friedman came under a lot of criticism because of the way he communicated with the media during ______Ebola outbreak.

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______Slide 58 ______ The American Psychiatric Association Annual meeting in Toronto, Dr. Daniel Witter, M.D., Ph.D., discussed this issue. ______

He recommended the following: - Do not over-reassure. ______- Acknowledge uncertainty. - Do not ridicule the public’s emotions. ______

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Slide 59 ______

- Tell people what to expect. - Offer people things to do. ______- Acknowledge errors, deficiencies, and misbehaviors. ______

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