Hepatitis E in South Africa. Tongai Maponga

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Hepatitis E in South Africa Tongai Maponga 7th FIDSSA CONGRESS 2017

This is what usually comes to mind

History of hepatitis E virus An ET-NANB hepatitis virus later named HEV was first suspected in 1980. This followed an outbreak of acute viral hepatitis in the Kashmir Valley, India, between November 1978 and April 1979. 275 clinical cases among 16 620 inhabitants, 11-40 years old in villages with common water source

History of hepatitis E virus The findings of HEV were supported by retrospective analysis of a large outbreak of hepatitis in New Delhi (1955 1956). Source: contaminated municipal water from flooded Yamuna river. 29 000 icteric cases. Pregnant women often had fulminant hepatic failure with high case-fatality rate.

Current epidemiology of HEV Approximately 20 million infections worldwide each year. 3.3 million symptomatic cases of hepatitis E/annum. 56 600 hepatitis E-related deaths/annum. Clinical attack rates highest in young adults aged 15 49 years.

Global distribution of HEV CDC: Pink Book

Transmission routes Overview of different routes of HEV transmission. Proven modes of transmission are indicated in solid arrows, whereas potential routes of spread are indicated with dashed arrows Sayed: Is Hepatitis E Virus an Emerging Problem in Industrialized Countries?

Virology of HEV Genus: Hepevirus. Family: Hepeviridae. Spherical particles measuring 27 34 nm in diameter. Genome consists of positive-sense, single-stranded RNA. Approximately 7.2-Kb long. Three discontinuous and partially overlapping ORFs.

Genomic variability HEV isolates from human and other mammals have been mostly divided into four genotypes, namely 1, 2, 3 and 4. Smith et al. Consensus proposals for classification of the family Hepeviridae

Genomic variability Each HEV genotype appears to have a specific geographic distribution. Genotypes 1 and 2 HEV isolated from human cases of epidemic and sporadic hepatitis E where the disease is highly endemic. HEV genotypes 3 and 4 appear in humans and animals- responsible for zoonotic infections. Camelid HEV genotype 7 also linked with zoonotic transmission.

Signs and symptoms of HEV infection Mean incubation period: 6 weeks (2 9 ). Symptomatic infection is most common in young adults aged 15 40 years. Hepatitis like signs and symptoms include: Jaundice, fever, loss of appetite, abdominal pain, lethargy, ALT Children often show no symptoms or only a mild illness without jaundice that goes undiagnosed. Hepatitis E is not clinically distinguishable from other types of acute viral hepatitis.

Diagnosis of HEV Diagnosis: presence of antibody against HEV or detection of HEV RNA. Viremia usually lasts for 2-4 weeks. Viruses are excreted into the bile and shed in the faeces for 4-6 weeks Virus is detected for longer in stool than from plasma.

The Lancet Infectious Diseases 2008 8, 698-709DOI: (10.1016/S1473-3099(08)70255-X) Copyright 2008 Elsevier Ltd Terms and Conditions

Treatment of HEV infection No specific treatment capable of altering the course of acute infection. Disease is usually self-limiting, hospitalization is generally not required. Hospitalization may be needed for patients with fulminant hepatitis. Immunosuppressed people with chronic hepatitis E benefit from specific treatment using ribavirin. Interferon has also been used successfully. Decreasing the dosage of immunosuppressive therapy in transplant recipients may also promote clearance of infection.

Prevention of HEV Vaccine (currently only licensed in China for use in people aged 16 years). Quality standards for public water supplies. Proper disposal systems of faecal waste. Hygienic practices such as hand-washing with safe water, particularly before handling food. Safe food practices.

HEV in South Africa The first case in SA was described in 1992 of a 34-year-old woman from Cape Town who presented at 32 weeks gestation with diarrhoea, jaundice, and episodic confusion. She had returned from holiday in India where she had also had a history of contact with hepatitis in India. She may have subsequently passed the infection to the referring physician and two theatre sisters in maternity unit, Groote Schuur Hospital. Robson et al. Lancet. 1992 Jun 6;339(8806):1424-5.

HEV in South Africa Most data is based on seroprevalence studies conducted using assays that were not as sensitive/specific compared to those currently available. Year Prevalence Reference 1996 10.7% (n=767) 407 urban adults (5.8%) 360 rural adults (19.1%) 1994 2.0% (n=782) 555 canoeists exposed to sewage contaminated water (1.8%). 227 medical students (2.6%) Tucker et al. J Med Virol. 1996 Oct;50(2):117-9. Grabow et al. J Med Virol. 1994 Dec;44(4):384-8.

HEV in South Africa Chronic HEV infection in an HIV-infected patient in Cape Town. Presented with persistently liver transaminases after starting ART.

Chronic HEV in HIV-infected male HEV Genotype 3 infection.

HEV in South Africa Transmission of HEV genotype 3 post-kidney transplant from consumption of pork. Taking immunosuppressive therapy at the time of acquisition of infection.

Phylogenetic analysis of Cape Town HEV cases

HEV in South Africa No evidence of viraemic HEV infection among blood donors in the Western Cape, HEV IgG prevalence of 26%.

HEV in South Africa Seroprevalence of 27.9% (n = 324/1161) No viraemic infections Greatest risk factors were being 30 years, followed by pork consumption Case report of a 54 yr old white male Death due to fulminant hepatic failure HEV genotype 3 detected from serum sample

HEV studies among humans in SA Evidence of viraemic HEV infections among humans within Cape Town. Evidence points to HEV genotype 3 as the main infecting genotype. Infections likely due to zoonotic transmission. There is a risk of chronic HEV infection developing in immunocompromised patients including organ transplant recipients. Serological evidence of HEV infection among blood donors likely points towards zoonotic(?) transmission as source of infection. No viraemic infections seen among 300 blood donors. Clinical suspicion may be warranted for patients with unexplained hepatitis after exclusion of the routine causes.

HEV in Western Cape South African pig herds Cross-sectional study of 16 commercial pig herds supplying pork to Cape Town. All 16 farms tested were seropositive for HEV. Seroprevalence median of 0.93 (range: 0.06 to 1). Viral RNA was detected in 3/45 serum samples tested.

HEV in Western Cape pig herds Sequence from pig clusters with HEV sequences obtained from human patients in Cape Town

Zoonotic transmission of HEV in SA Hepatitis E is present in South African pigs and may pose a zoonotic risk to local pork producers, farm workers, abattoir workers, butchers and pork consumers. Pork producers have a responsibility to protect the health of these groups of people, by putting in place measures not only serve to prevent the introduction and spread of HEV in pig herds. There is need to prevent environmental contamination by pig herds that are HEV infected. Avoid contamination of water sources by faecal material from piggeries.

.and this too!

Many thanks Prof Monique Andersson Prof Wolfgang Preiser Prof Richard Tedder Dr Samreen Ijaz Ms Tatum Lopes Mr Russell Cable Ms Charlotte Pistorius Dr Stephen Korsman Dr Piers Stead Dr Izak Heys