9th of June 2020

Dra. Nerea García BenzaquénHead of the Neglected and Emerging Unit

VISAVET-UCMngarciab@visavet.ucm.es

HIV +§ Discomfort§ Diarrhea§ Jaundice§ Vomiting§ Fever§ liver enzyme alteration

HEPATITIS SEROLOGY: HEPATITIS A, B, C, E (ELISA)

HEPATITIS E VIRUS IN SERUM (PCR)

October 2015. Hospital Reina Sofía Córdoba.

HEV PCR

FAMILY MEMBERS

EPIDEMIOLOGY RESEARCH

FOOD

ANIMALS HEV PCR

EPIDEMIOLOGY RESEARCH: GENOTYPING

SAME STRAIN

GENOTYPE 3

HEPATITIS E : FOOD-BORNE ZOONOSIS

• Main cause of acute viral hepatitis worldwide• Public Health problem in developing countries. • Emerging zoonotic disease in industrializated countries. • Subestimated (Not notifiable disease)• Unknown to many health professionals• Increase description of animal hosts• Increase transmission pathways

Balayan et al. 1983. Intervirology 20: 23-31

• RNA single-stranded (27-34 nm) • quasi-enveloped virus

Hepatitis E Virus

Family Hepeviridae

Genus Hepevirus

Stable in the environment for prolonged periods of time

§ Resists freezing

§ Inactivation: 56°C 1h, 71°C 20 min or 80°C 1 min.

Ø1 and 2: humansØ3 and 4: humans and animals (pigs, wild boars, deers, etc).Ø5 and 6 : wild boars (Asia)Ø7 and 8: camelids (Asia)

8 genotypes

Nimgaonkar et al., 2018

Chapuy-Regaud et al., 2017

Genotypes 1 and 2

Genotype 3

Ø Asymptomatic

ANIMALS

HUMANS

Ø Majority asymptomatic (>70%)

Ø Incubation period: 15-60 days

Ø Acute self-limited hepatitis (fatigue, fever, abdominal pain, hepatosplenomegaly, etc.)

Ø Chronic hepatitis in patients with previous liver disease (genotype 3)

Ø Extrahepatic symptoms: neurological disorders (Guillain-Barré), kidney dysfunction, pancreatitis, etc.

Ø High mortality rate (25%) in pregnant women (genotype 1)

§ No specific treatment

§ Ribavirin in chronic infections

§ Vaccine only available in China

Gráfica de PCR en tiempo real (VISAVET-UCM).Jothikumar et al., 2016

ELISA (VISAVET-UCM)

ELISA: IgM and IgG.

PCR: serum, faeces, liver, food, water, etc.GENOTYPING: Phylogenetic studies

SEROLOGICAL METHODS

MOLECULAR METHODS

ANIMAL MODELSCELL CULTURE LINES

VERY DIFFICULT EVALUATE INFECTIVITY, QUNATIFY VIRAL LOAD, EFFECTIVITY OF INACTIVATION TREATMENTS

Ø Every year: 20 million HEV infections worldwide, estimated 3.3 million symptomatic cases of hepatitis E (WHO)

Ø Mortality rate in pregnant woman 20-25%Ø Refugee camps (Niger, South Sudan, Kenya, etc.)

10 fold increase in the last ten years

First case of acute hepatitis in Escocia

2015: 5617 cases

>95% autochtonous cases

2005: 514 cases

Ø Main reservoir of the virusØ Seroprevalence HEV in Europe 30-98%.Ø Target organ: liverØ Also in the intestine, bile, lymph nodes, colon, muscle, blood, semen, etc.Ø Vertical and horizontal transmission

64,90%

46,10%

66,70%

83,50%

Huesca Zaragoza Teruel Toledo

PREVALENCIA HEV EN SUERO DE CERDO GRANJA

Farm Prevalence: 65,3% Slaughterhouse prevalence: 71,4%

Ø seroprevalence very variable (2-68%)Ø Genotypes 3, 4, 5 and 6Ø In all EuropeØ High zoonotic potential

© Wageningen University

Ø Very variable seroprevalence (1-13%)Ø Genotype 3 Ø In all Europe Ø Zoonotic potential

ØRabbitsØCamelidsØRodentsØAquatic mammalsØRuminantsØEquinesØetc.

Epidemiology HEV in France

• National seroprevalence: 22,4%

• 3 hiperendemic regions

• Estimations:ü 60,000 acute cases/yearü 500 hospitalizationsü 20 deaths

Mansuy et al, Hepatology 2016

Van Cauteren et al, 2018

Figatellu consumption

• Liver and derivates• meat

• Milk

• Moluscs

• Fruits and vegetables

- Mainly pigs and wild boars- Raw or poorly cooked

- Genotipes 1, 3, 4- Asia- cows, goats, sheep, camels, donkeys, humans

Water-borne contamination

- MANAGEMENT- BIOSECURITY

- CONTACT WITH WILDLIFE

-NEW RESERVOIRS

- WASTEWATER TREATMENT- MANURE

- BIOSECURITY

-COOKED (71ªC 20 MIN)

-CROSS CONTAMINATION

- HYGIENE MANIPULATORS and

UTENSILS

- HEALTHCARE PROFESSIONALS

- RISK PERSONNEL-CONSUMERS

-

- REAL PREVALENCE- TRANSMISSION ROUTES

- CELL CULTURES- ANIMAL MODELS

- PATHOGENY- INACTIVATION

METHODS- VACCINES-…

ANIMALS ENVIRONMENT FOOD INFORMATION RESEARCH

HEPATITIS E