Ebola, Japanese encephalitis and Dengue vaccine

Submitted by

Ajay Singh

Ph.D biotechnology

College of biotechnology, DUVASU, Mathura

Ebola virus

Ebola virus disease

• Ebola is a severe and often deadly disease caused by a virus.

• Ebola can occur in humans and other primates (gorillas, monkeys, and chimpanzees).

• The 2014 Ebola outbreak in West Africa is the largest in history. About 70% of the people who have gotten Ebola in this outbreak have died.

• The virus poses a very low risk to people in the United States.

Causes

• Ebola was discovered in 1976 near the Ebola River in the Democratic Republic of the Congo. Since then, several small outbreaks have occurred in Africa. The 2014 outbreak is the largest. Countries affected in this recent outbreak include:

Guinea Liberia Sierra Leone• Ebola has also been reported in: Nigeria Senegal United States Spain Mali

• Most of these cases are due to people traveling from a country where Ebola is present.

• In October 2014, the World Health Organization (WHO) declared both Nigeria and Senegal free of Ebola virus transmission.

• As of November 2014, there have been 4 people diagnosed with Ebola in the United States.

HOW EBOLA CAN SPREAD

• ONLY spread between humans by direct contact with infected body fluids including but not limited to urine, saliva, sweat, feces, vomit, breast milk, and semen. The virus can enter the body through a break in the skin or through mucous membranes, including the eyes, nose, and mouth.

• Ebola may also be spread by:• Handling infected wild animals hunted for

food (bushmeat)• Contact with blood or body fluids of infected

animals• Contact with infected bats

• Ebola does NOT spread through:• Air• Water• Food• Insects (mosquitoes)

Symptoms

• The time between exposure and when symptoms occur (incubation period) is 2 to 21 days. On average, symptoms develop in 8 to 10 days.

Early symptoms of Ebola include:• Fever greater than 101.5°F (38.6°C)• Chills• Headache• Muscle pain

• Weakness• Fatigue• Rash • Abdominal (stomach) pain• Diarrhea• Vomiting Late symptoms include:• Bleeding from the mouth and rectum• Bleeding from eyes, ears, and nose• Organ failure• A person who does not have symptoms 21 days after being exposed

to Ebola will not develop the disease.

Treatment• There is no known cure for Ebola. Experimental treatments have

been used, but none have been fully tested to see if they work well and are safe.

• People with Ebola must be treated in a hospital. There, they can be isolated so the disease cannot spread. Health care providers will treat the symptoms of the disease.

Treatment for Ebola includes:• Fluids given through a vein (IV)• Oxygen• Blood pressure management• Treatment for other infections• Blood transfusions

Investigational Therapies for EVD Patients 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 • Therapeutic medications

• Zmapp – three chimeric human-mouse monoclonal antibodies • Tekmira – lipid nanoparticle small interfering RNA• Favipiravir – oral RNA-dependent RNA polymerase inhibitor

• 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; 2Jarhling, P et al. JID 2007; 3Mupapa, K et al. JID 1999 S18; 4Olinger, GG et al. PNAS 2012; 5Dye, JM et al. PNAS 2012; 6Qiu, X et al. Sci Transl Med 2013; 7Qiu, X et al. Nature 2014; 8Geisbert, TW et al. JID 2007; 9Geisbert, TW et al. Lancet 2010; 10Kobinger, GP et al. Virology 2006; 11Wang, D et al. J Virol 2006; 12Geisbert, TW et al. JID 2011; 13Gunther et al. JID 2011; 14Oestereich, L et al. Antiviral Res. 2014.

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EVD Summary

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

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

• Human-to-human transmission by direct contact

• No human-to-human transmission via inhalation (aerosols)

• No transmission before symptom onset

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

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Japanese encephalitis (JE)

Japanese encephalitis (JE)

A disease of public health importance:

- Epidemic potential - High case fatality - Complications leading to life long sequel

Previously disease of East Asia - Japan, Korea and ChinaRecent years spread to SEA - Thailand, Indonesia, India,

Vietnam, Myanmar and Sri Lanka.Estimated 43,000 cases with 11,000 deaths and 9,000

disabilities occur / year globally

JE OUTBREAK INDIA

• Nagpur (1954-1955)• Madras (1955)• Agra, (U.P)- 1958• W. Bengal – 1973• TN, KA, WB, AP, Bihar, Assam & U.P - 1977-1979• Goa, Kerala, Haryana (samuel et.al. 2000) .• 1145 cases of Japanese encephalitis have been reported

from 14 districts of Uttar Pradesh Province, India from 29 July to 30 August 2005. About one-fourth of these (n=296) have died. 90 cases from the adjoining districts of Bihar have also been admitted to the hospitals in Uttar Pradesh.

• The virus was isolated for the first time in the world from a post-mortem human brain in Japan in 1933

• JE was clinically diagnosed for the first time in India in 1955 at Vellore, Tamil Nadu.

• Approximately 3 billion people and 60% of the world's population live in endemic region

• 50,000 cases with 10,000 deaths were notified annually from a wide geographic range.

• In India there was a rise of JE incidence in 1980s and has dropped significantly and maintained till 1995.

JE endemic areas in India

Uttar PradeshAndhra PradeshAssamBiharGoaKarnatakaMaharashtraTamilnaduWest BengalKeralaJharkhandOrissaManipurPunjabHaryana

• The viruses responsible for these diseases are classified as arbovirus and these diseases are collectively called as arbovirus encephalitis.

• JEV is related to St. Louis encephalitis virus, Murray Valley virus and West Nile virus.

• The virus is antigenically related to several other flaviviruses including dengue virus.

• JE virus is a member of the family Flaviviridae. • It is a single stranded RNA virus.• It has three proteinsa) Envelope proteinb) Core proteinc) Membrane protein

Vectors: Culex tritaeniorhynchus, C. vishnui and C. pseudovishnui. Breeding habit: Irrigated rice fields, shallow ditches and pools etc. Resting habit: Exophilic but may rest indoor in extreme summer Feeding habit: Zoophilic and outdoor as well as indoor feeders The average life span of mosquito is about 21 days Flight Range: long distance (1 - 3 kms or even more) Environment: Mainly prevalent in rural areas Outbreak is a seasonal phenomenon Mosquito vector prefers large and clean water collections for breeding -

paddy cultivation areas offer typical favorable situation Rural setting offers the amplifier hosts in abundance Occurrence in monsoon and post-monsoon season: in north India from May-

October, in southern part from August to November

• Transmission is usually seasonal • In temperate zones of China, Japan, Korea and

northern areas of Southeast Asia, Japanese encephalitis is transmitted during summer and early autumn; May to September.

• In north India and Nepal transmission occurs from June to November

• In south India and Sri Lanka epidemics are found from September to January.

JE VACCINE•INACTIVATED MOUSE BRAIN VACCINE

•It is expensive vaccine, complicated dosing schedule or side effect of this vaccine.

•Inactivated Mouse brain vaccine

•3-5 US dollars/dose

•9 – 15 US dollars/per child

•The ‘mouse brain vaccine’ manufactured by killing populations of mice was being manufactured by Central Research Institute, Kasauli.

•LIVE ATTENUATED VACCINE

•SA 14 - 14-2 (Chinese live attenuated vaccine at affordable cost, safe, effective).

•This vaccine was developed in China and has been used there since 1988.

•it has been licensed and used in South Korea and Nepal and licensed in Sri Lanka.

•It also appears feasible that a single dose of vaccine will provide life-long protection.

Inactivated Vero Cell Culture-Derived JE Vaccine (IXIARO [JE-VC])

• What are the risks from Japanese encephalitis vaccine?

A vaccine, like any medicine, there is a chance of side effects. When side effects happen, they are usually mild and go away on their own.

• Mild Problems

Pain, tenderness, redness, or swelling where the shot was given (about 1 person in 4).

Fever (mainly in children).

Headache, muscle aches (mainly in adults).

Moderate or Severe Problems• Studies have shown that severe reactions to JE vaccine are very rare.

Problems that can happen after any vaccine• Brief fainting spells can happen after any medical procedure, including

vaccination. Sitting or lying down for about 15 minutes can help prevent fainting, and injuries caused by a fall. Tell your doctor if you feel dizzy, or have vision changes or ringing in the ears.

• Lasting shoulder pain and reduced range of motion in the arm where the shot was given can happen, very rarely, after a vaccination.

• Severe allergic reactions from a vaccine are very rare, estimated at less than 1 in a million doses. If one were to occur, it would usually be within a few minutes to a few hours after the vaccination.

• This information was taken directly from the JE-Ixiaro VIS (This information taken from Japanese Encephalitis Ixiaro VIS dated 1/24/14. If the actual VIS is more recent than this date, the information on

this page needs to be updated.)

• Inactivated Vero cell culture–derived JE vaccine (manufactured as IXIARO) is the only JE vaccine that is licensed and available in the United States. In 2009, the Food and Drug Administration (FDA) licensed IXIARO for use in adults ≥17 years of age. In May 2013, FDA licensed IXIARO for use in children 2 months through 16 years of age. On June 19, 2013, CDC’s Advisory Committee on Immunization Practices (ACIP) voted to extend existing recommendations for use of JE vaccine to include use of IXIARO in children aged 2 months through 16 years. 

Vaccine Administration• The primary series for IXIARO is 2 doses administered 28 days apart:• For adults and children aged ≥3 years, each dose is 0.5 mL.• For children aged 2 months through 2 years, each dose is 0.25 mL. To

administer a 0.25-mL dose, health care providers must expel and discard half of the volume from the 0.5-mL prefilled syringe before injection. To enable this, the manufacturer is developing a prefilled syringe with a red line on the barrel to indicate the 0.25-mL point.

• Studies are being conducted on the need for a booster dose for children following a primary series of IXIARO, but data are not yet available.

Dengue virus

What is the Dengue Virus?

• Arbovirus – Arthropod, Mosquito, born

• (Aedes aegypti)• It is a pathogen that causes – Dengue fever (DF)– Dengue hemorrhagic fever (DHF)Can lead to Dengue shock syndrome (DSS)

• Has four different serotypes (DEN-1,2,3,4)• First reported epidemics in 1780 in Asia, Africa, and

North America

Target tissues

Dengue induces cytokine production in cells Cytotoxic factor effects endothelial cells involved in most of

the following:• Heart• Liver• Kidneys• Lungs• Intestines• Spleen• Lymph nodes• Brain• Skin (inflammatory rashes)

Diagnostic tests

• Virus isolation by infection of mice using infected mosquitoes

• Detection of IgM antibodies in the blood by PCR or Viral isolation (Serology)

• ELISA (Enzyme-Linked Immunoabsorbent assay)• Thrombopenia

Pathogenesis and infection process of Dengue

• Humans are initially infected through a mosquito vector• Initial interaction with cell occurs with the viruses ability to

infect cell– Phagocytes

• Virus uses cell receptor molecule to enter cell• Cell receptor molecules include:– Glycosaminoglycan– Heparan Sulfate (Expressed in almost all cell types)

• Virus replicates in target organs• Infects white blood cells and lymphatic tissues• Virus is released and circulates in blood• Alternate mosquito then bites host and receives virus

Prevention:

There is no specific treatment

Relieving symptoms and complications:

• Plasma volume replacement

• Sedatives for restless patients

• Blood transfusion with patients with significant blood loss

• Aspirin should be avoided

• All efforts of control are aimed against mosquitoes

– Elimination of breeding areas

– Actions to prevent mosquito bites (repellant, nets, and vapors)

• Vaccinations are pending

– Problem is that the vaccination needs to prevent all four serotypes

Treatment:

Recent research on vaccine

• “Dengue vaccine tested on Indian adults, found safe” by Kounteya Sinha, Nov 2, 2014.

• The Sanofi Pasteur vaccine research and development laboratory in Lyon, France. The world's first, dengue vaccine CYD-TDV has passed the crucial India test and could be available in the country as early as by the end of next year.

• “Indian scientists break dengue code Progress” at ICGEB New Delhi in the search for a dengue vaccine September 2013 by Dr. Navin khanna.

Reference• http://www.path.org/projects/JE_in_depth.php• http://www.pon.nic.in/vcrc/jemanag.html•

http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/japanese-encephalitis.aspx.

• 1Huggins, JW et al. Rev Infect Dis 1989; 2Jarhling, P et al. JID 2007; 3Mupapa, K et al. JID 1999 S18; 4Olinger, GG et al. PNAS 2012; 5Dye, JM et al. PNAS 2012; 6Qiu, X et al. Sci Transl Med 2013; 7Qiu, X et al. Nature 2014; 8Geisbert, TW et al. JID 2007; 9Geisbert, TW et al. Lancet 2010; 10Kobinger, GP et al. Virology 2006; 11Wang, D et al. J Virol 2006; 12Geisbert, TW et al. JID 2011; 13Gunther et al. JID 2011; 14Oestereich, L et al. Antiviral Res. 2014.

Thankyou