Hepatitis E Infection

6,367 views
5,891 views

Published on

Hepatitis E Infection

Published in: Health & Medicine, Technology
1 Comment
5 Likes
Statistics
Notes
No Downloads
Views
Total views
6,367
On SlideShare
0
From Embeds
0
Number of Embeds
8
Actions
Shares
0
Downloads
595
Comments
1
Likes
5
Embeds 0
No embeds

No notes for slide

Hepatitis E Infection

  1. 1. HEPATITIS E INFECTION AN UPDATE Dr.T.V.Rao MDDR.T.V.RAO MD 1
  2. 2. HISTORY AS DOCUMENTED• In 1978 there was a vast epidemic of icteric viral hepatitis in the Kashmir Valley involving 52000 cases with 1650 fulminant forms and 1560 deaths. Since serology for hepatitis A and B in these patients was negative and the clinical course and the epidemic type of its spread were not those of post-transfusional non-A non-B hepatitis, MS Khuroo in 1980 suggested that this epidemic of hepatitis might have been caused by another virus.(Am J Med 68:818-23,1980).In 1983 Balayan demonstrated that this virus, at difference of non-A non-B virus, is transmitted by fecal-oral route. He himself ingested fecal suspensions from affected patients and contracted the disease.(Intervirology 20:23-31,1983).By transmitting the disease to monkeys the virus was recovered and its morphology and genome were identified only 12-13 years later in the early nineties.DR.T.V.RAO MD 2
  3. 3. Viral Hepatitis - Historical Perspectives “Infectious” A E Enterically transmittedViral hepatitis NANB Parenterall “Serum” B D C y transmitted F, G, TTV ? other DR.T.V.RAO MD 3
  4. 4. Type of Hepatitis A B C D ESource of feces blood/ blood/ blood/ fecesvirus blood-derived blood-derived blood-derived body fluids body fluids body fluidsRoute of fecal-oral percutaneous percutaneous percutaneous fecal-oraltransmission permucosal permucosal permucosalChronic no yes yes yes noinfectionPrevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior DR.T.V.RAO MD modification 4
  5. 5. DR.T.V.RAO MD 5
  6. 6. DR.T.V.RAO MD 6
  7. 7. STRUCTURE OF HEPATITIS E VIRUS• The virus is icosahedral and nonenveloped. It has a diameter of approximately 34 nanometers, and it contains a single strand of RNA approximately 7.5 kilobases in length. Four HEV genotypes exist, and genotype 1 causes human disease.DR.T.V.RAO MD 7
  8. 8. STRUCTURAL CHARACTER OF HEPATITIS E VIRUS• HEV is an icosahedral, nonenveloped single stranded RNA virus that is approximately 27 to 34 nm in diameter . It has been classified as the single member of the genus herpesvirus in the family Herpesviridae Three large opening reading frames (ORFs) of the positive-sense RNA of HEV have been described• The largest ORF consists of 1693 codons; it codes for nonstructural proteins that are responsible for the processing and replication of the virus.• The second ORF is composed of 660 codons and codes for structural proteins.• The third ORF consists of 123 codons; although it may encode for a structural protein, its function remains undetermined.DR.T.V.RAO MD 8
  9. 9. HEPATITIS E SHOWS DIFFERENT DISTINCT FEATURES• The genomic RNA of HEV exhibits several distinct features compared to the genomic RNA of caliciviruses, including a methylated cap at the 5-end and an ORF1 with functional domains arranged in a different order.DR.T.V.RAO MD 9
  10. 10. PHYLOGENETIC ANALYSIS• Phylogenetic analysis suggests that there are four genotypes (1 through 4) and up to 24 subtypes . The association of genotypes with clinical features is incompletely understood. However, genotype 1 and 2 appear to be confined to humans while genotype 3 and 4 infect humans and animals. Genotype 3 has been associated with less virulent diseaseDR.T.V.RAO MD 10
  11. 11. HEPATITIS E VIRUS INFECTION• Hepatitis E (HEV) was not recognized as a distinct human disease until 1980. Hepatitis E is caused by infection with the hepatitis E virus, a non- enveloped, positive-sense, single-stranded RNA virus.• Although man is considered the natural host for HEV, antibodies to HEV or closely related viruses have been detected in primates and several other animal speciesDR.T.V.RAO MD 11
  12. 12. UNHYGIENIC CONDITIONS INCREASE THE SPREAD OF HEPATITIS E INFECTIONS • The highest rates of infection occur in regions where low standards of sanitation promote the transmission of the virus. Epidemics of hepatitis E have been reported in Central and South-East Asia, North and West Africa, and in Mexico, especially where faecal contamination of drinking water is common. However, sporadic cases of hepatitis E have also been reported elsewhere and serological surveys suggest a global distribution of strains of hepatitis E of low pathogenicity.DR.T.V.RAO MD 12
  13. 13. HEPATITIS E INFECTION CAN BE UNEVENTFUL• In general, hepatitis E is a self-limiting viral infection followed by recovery. Prolonged viraemia or faecal shedding are unusual and chronic infection does not occur.• Occasionally, a fulminant form of hepatitis develops, with overall patient population mortality rates ranging between 0.5% - 4.0%. Fulminate hepatitis occurs more frequently in pregnancy and regularly induces a mortality rate of 20% among pregnant women in the 3rd trimester.DR.T.V.RAO MD 13
  14. 14. ANIMALS CAN BE RESERVOIRS OF INFECTION• Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs. Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well. The rate of transmission to humans by this route and the public health importance of this are however still unclear.• A number of other small mammals have been identified as potential reservoirs: the lesser bandicoot rat (Bandicota bengalensis), the black rat (Rattus rattus brunneusculus) and the Asian house shrew (Suncus murinus). A new virus designated rat hepatitis E virus has been isolated.DR.T.V.RAO MD 14
  15. 15. CAN WE CALL HEPATITIS E AN EMERGING ZOONOTIC INFECTION ???• The host range of HEV is ever- expanding. In addition to the animal species from which HEV strains have been genetically identified including domestic and wild pigs, chickens, deer, rabbits, and mongeese, antibodies to HEV have also been detected in many other animal species such as dogs, cats, sheep, goats, rodents, cattle, and non-human primates, suggesting that these animals have been exposed to HEV or a related agent.DR.T.V.RAO MD 15
  16. 16. COURSE OF INFECTION• The course of infection has 2 phases, the prodromal phase and the icteric phase. The infection is self-limited. Whether protective immunoglobulins develop against future reinfection remains unknown. The overall case fatality rate is 4%, though pregnant women and liver transplant recipients may be at substantially higher risk .DR.T.V.RAO MD 16
  17. 17. Transmission• HEV is spread by the oral-faecal route• Consumption of faecally contaminated drinking water has given rise to epidemic cases,• Ingestion of raw or uncooked shellfish has been the source of sporadic cases in endemic areas• Most outbreaks associated with faecally contaminated drinkingDR.T.V.RAO MD 17
  18. 18. Zoonotic transmission• Naturally acquired HEV antibodies have been detected in primates, rodents and swine• Swine HEV cross-reacts with antibodies to the human HEV• Human hepatitis E has been transmitted under laboratory conditions to various species of primates, pigs, lambs, ratsDR.T.V.RAO MD 18
  19. 19. Zoonotic transmission• Species specific HEV has been demonstrated in pigs with the identification of swine HEV• Swine HEV is distinct, but closely related to human HEV strains• Swine HEV raises a potential public health concern for zoonosis and xenozoonosis following xenotransplantation with pig organsDR.T.V.RAO MD 19
  20. 20. Zoonotic transmission• A zoonotic spread of HEV is not excluded• Monkeys, pigs, cows, rodents, sheep and goats are susceptible• Anti-HEV has been found in a significant proportion, up to 28% in some areas, of healthy individuals in industrialized countriesDR.T.V.RAO MD 20
  21. 21. Hepatitis E - Epidemiologic Features  Most outbreaks associated with faecally contaminated drinking water.  Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico.  In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (<2%) has been found in healthy populations. The source of infection for these persons is unknown.  Minimal person-to-person transmission.DR.T.V.RAO MD 21
  22. 22. Hepatitis E - Clinical Features  Incubation period: Average 40 days Range 15-60 days  Case-fatality rate: Overall, 1%-3% Pregnant women, 15%-25%  Illness severity: Increased with age  Chronic sequelae: None identifiedDR.T.V.RAO MD 22
  23. 23. PRODROMAL PHASE• The incubation period ranges from 15 days to 60 days. The course of infection has 2 phases, the prodromal phase and the icteric phase.• Prodromal-phase symptoms include the following:• Myalgia• Arthralgia• Fever with mild temperature elevations (25-97%)• Anorexia (66-100%)• Nausea/vomiting (30-100%)• Weight loss (typically 2-4 kg)• Dehydration• Right upper quadrant pain that increases with physical activity (abdominal pain is reported in 35-80% of patients)DR.T.V.RAO MD 23
  24. 24. ICTERIC-PHASE SYMPTOMS INCLUDE THE FOLLOWING:• Jaundice – This may be difficult to see with some patients’ natural skin color; the serum bilirubin level is higher than 3 mg/dL; scleral icterus is present• Dark urine• Light-colored stools (20-40%)• Pruritus (50%)• Other features include the following:• Urticarial rash• Diarrhea• Malaise (95-100%)DR.T.V.RAO MD 24
  25. 25. AGE-, SEX-, AND RACE-RELATED DEMOGRAPHICS• Hepatitis E predominantly affects persons aged 15-40 years. It may affect younger age groups, but it generally is not recognized and may be subclinical in these populations. No chronic cases have been described. Although hepatitis E is not known to have a predilection for either sex, pregnant women are prone to complications. Hepatitis E has no apparent racial predilection.DR.T.V.RAO MD 25
  26. 26. NO ESTABLISHED CHRONICITY IN HEPATITIS E INFECTIONS ??? • No chronic cases of acute hepatitis E have been reported. The infection is self-limited. Whether protective immunoglobulins develop against future reinfection remains unknown. The overall case fatality rate is 4%.DR.T.V.RAO MD 26
  27. 27. Diagnosis of hepatitis E • Hepatitis E should be suspected in outbreaks of waterborne hepatitis occurring in: • Developing countries, • Especially if the disease is more severe in pregnant women, • Or if hepatitis A has been excluded • If laboratory tests are not available, epidemiologic evidence can help in establishing a diagnosisDR.T.V.RAO MD 27
  28. 28. Diagnosis of hepatitis E • Acute hepatitis E is diagnosed when the presence of IgM anti-HEV is detected • Storage of serum samples is acceptable for several days at 4°C, • Anti-HEV will be preserved at – 20°C, • A temperature of #-70°C should be preferred when viremia is suspected.42DR.T.V.RAO MD 28
  29. 29. Hepatitis E Virus Infection Typical Serologic Course Symptoms ALT IgG anti-HEV IgM anti-HEVTiter Virus in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Weeks after Exposure DR.T.V.RAO MD 29
  30. 30. Diagnosis of Hepatitis E • HEV RNA can be detected in acute phase faeces by PCR in approximately 50% of cases • Immune electron microscopy is positive in only about 10% of cases • The viral proteins pORF2 and pORF3 have been expressed in various recombinant systems and form the basis for diagnostic tests and vaccine studiesDR.T.V.RAO MD 30
  31. 31. Diagnosis of hepatitis E • To confirm the results of EIA or ELISA tests, Western blot assays to detect IgM and IgG anti-HEV in serum can be used • PCR tests for the detection of HEV RNA in serum and stool, • Immunofluorescent antibody blocking assays to detect antibody to HEV antigen in serum and liver, • Immune electron microscopy to visualize viral particles in faecesDR.T.V.RAO MD 31
  32. 32. HIGHER FATALITIES IN PREGNANT WOMEN• Among pregnant women, the case fatality rate is 20%, and this rate increases during the second and third trimesters. Reported causes of death include encephalopathy and disseminated intravascular coagulation. The rate of fulminant hepatic failure in infected pregnant women is high.DR.T.V.RAO MD 32
  33. 33. LIVER TRANSPLANT PATIENTS AT RISK • Liver transplant recipients may be at a greater risk for HEV infection, which can lead to chronic hepatitis. However, if the patient has antibodies against HEV, the risk of reactivation is extremely lowDR.T.V.RAO MD 33
  34. 34. PREVALENCE OF HEPATITIS E INFECTION• Hepatitis E is prevalent in most developing countries, and common in any country with a hot climate. It is widespread in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly through fecal contamination of water supplies or food; person-to-person transmission is uncommon. Outbreaks of epidemic Hepatitis E most commonly occur after heavy rainfalls and monsoons because of their disruption of water supplies. Major outbreaks have occurred in New Delhi, India (30,000 cases in 1955-1956), Burma (20,000 cases in 1976-1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988).DR.T.V.RAO MD 34
  35. 35. Some of the Major Epidemics Place Year Number of cases India 1955 30000 Myanmar 1976 20000 Kashmir 1978 52000 China 1986 100000 Somalia 1988 11000 Mexico 1989 4000 Iran (Kermanshah) 1991 Hundreds Sudan 2004 4000 Chad 2004 1000 IraqDR.T.V.RAO MD 2004 hundreds 35
  36. 36. PREVENTION• Improving sanitation is the most important measure, which consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures and sanitary food preparation. Thus, prevention strategies of this disease are similar to those of many others that plague developing nations, and they require large-scale international financing of water supply and water treatment projects.DR.T.V.RAO MD 36
  37. 37. BEST OPTIONS TO PREVENT HEPATITIS E INFECTIONS• Ensuring a clean drinking water supply remains the best preventive strategy. Recombinant vaccines are being developed that may be particularly useful for travellers to disease-endemic areas and for pregnant women.DR.T.V.RAO MD 37
  38. 38. IMMUNOGLOBULINS IN 3 RD. TRIMESTER REDUCES MORTALITY • Protective antibodies after the infection are apparently effective to prevent reinfection even with strains from distant regions but the duration of this protection in humans is still questioned. Immune serum globulin will considerably reduce mortality in the 3rd trimester of pregnancy but will not block incidence of infection on contact. A vaccine is not yet available.DR.T.V.RAO MD 38
  39. 39. Vaccines• At present, no commercially available vaccines exist for the prevention of hepatitis E.• Several studies for the development of an effective vaccine against hepatitis E are in progress :1- Recombinant vaccines2- Subunit HEV vaccinesDR.T.V.RAO MD 39
  40. 40. A VACCINE ON TRAIL • A vaccine based on recombinant viral proteins has been developed and recently tested in a high- risk population (military personnel of a developing country).The vaccine appeared to be effective and safe, but further studies are needed to assess the long-term protection and the cost- effectiveness of hepatitis EDR.T.V.RAO MD vaccination. 40
  41. 41. Vaccines•Recombinant vaccines• A 55 kDa recombinant HEV-derived ORF2 protein has been used to vaccinate rhesus monkeys against different strains of hepatitis E.• Although primates could still be infected, the vaccine protected them from the symptoms of diseaseDR.T.V.RAO MD 41
  42. 42. Vaccines•Subunit HEV vaccines• The direct intramuscular injection of purified plasmid DNA containing the full-length ORF2 of HEV has induced a prolonged humoral immune response (>12 months)• To the expressed structural protein ORF2 in 80% and 100% of two separate groups of challenged mice, respectivelyDR.T.V.RAO MD 42
  43. 43. HEPATITIS CAN GO INTO CHRONIC PHASE IN IMMUNOSUPPRESSED • Recent studies indicate that chronic HEV infection may develop in immunosuppressed patients. Acute HEV infection in immunocompromised patients such as organ transplant recipients and cancer patients not only can evolve into chronic hepatitis E, but also can rapidly progress into cirrhosis as well. In some of these patients, anti- HEV antibodies were negative [56] probably because of immune suppression. The contribution of the deficiency of anti-HEV antibodies to the establishing of the chronic infection needs to be established.DR.T.V.RAO MD 43
  44. 44. HEPATITIS E INFECTION IS A CONCERN OF DEVELOPED NATIONS TOO• Hepatitis E is no longer just a disease of developing countries. Sporadic cases of human hepatitis E have been reported in both industrialized and developing countries, although epidemics only occur in developing countries of Asia, Africa, and in Mexico.[Recently, there has been an increased incidence of sporadic hepatitis E cases in industrialized countries, and most are caused by zoonotic genotypes 3 and 4 strains of HEV.DR.T.V.RAO MD 44
  45. 45. HYGIENIC HAND WASH CAN SAVE SEVERAL LIVES FROM HEPATITIS E INFECTIONSDR.T.V.RAO MD 45
  46. 46. MAJOR REFERENCES• CDC, Atlanta on Hepatitis E infections• WHO/CDS/CSR/EDC/2001.12, Hepatitis E World Health Organization, Department of Communicable Disease Surveillance and, Response• Control of communicable diseases, 2000DR.T.V.RAO MD 46
  47. 47. FOR ARTICLES OF ACADEMIC INTEREST ON INFECTIOUS DISEASES FOLLOW ME ONDR.T.V.RAO MD 47
  48. 48. • Created by Dr.T.V.Rao MD for ‘e’ learning resources for Medical Professionals in Developing World • Email • doctortvrao@gmail.comDR.T.V.RAO MD 48

×