1. RUBELLA

2. What is Rubella
Rubella is a disease caused by the rubella virus. Rubella is usually a mild illness. Most people who have had rubella or the vaccine are protected against the virus for the rest of their lives. Because of routine vaccination against rubella since 1970 , rubella is now rarely reported.

3. Rubella ( German Measles )
Rubella is also called as 3 day Measles or German Measles.
Family – Togaviridae
Genus - Rubivirus
In general belong to Togavirus group

4. Rubella Virus Rubella virus are ss +ve RNA virus Diameter 50 – 70 nm
Enveloped Spherical
Virus carry hemagglutinin
Virus multiply in the cytoplasam of infected cell.

5. Prevailing Genotypes

6. Culturing the Virus
The virus can be cultured and adopted to continuous cell lines Rabbit kidney cells (RK 13 ) and Vero cells

7. Main Clinical Events
The clinical events occuring in the neonatal age is more important and divided into two major groups
1 Post Natal Rubella
2 Congenital Rubella

8. How Adults acquire Infection
Acquired, (i.e. not congenital), rubella is transmitted via airborne droplet emission from the upper respiratory tract of active cases. The virus may also be present in the urine, feces and on the skin. There is no carrier state: the reservoir exists entirely in active human cases. The disease has an incubation period of 2 to 3 weeks.

9. Systemic events of Rubella Infection

10. Post natal Rubella Occurs in Neonates and Childhood
Adult infection occurs through mucosa of the upper respiratory tract spread to cervical lymphnodes
Viremia devlops after 7 – 9 day
Lasts for 13 – 15 days
Leads to development of antibodies
The appearance of antibodies coincides the appearance of suggestive immulogic basis for the rash
In 20 – 50 % cases of primary infections are subclinical

11. Clinical findings Malaise Low grade fever Morbilliform rash
Rash starts on Face Extremities
Rarely lasts more than 5 days
No features of the rash give clues to definitive diagnosis of Rubella.

12. Rubella Rashes
When epidemics occur with similar features it is more suggestive of Rubella epidemics
Other Enterovirus infections can produce similar manifestations.

13. Other manifestations and complications
May produce transient Arthritis, in women in particular.
Serious complications are
Thrombocytopenia
Purpura
Encephalits

14. Immunity - Rubella
Antibodies appear in serum as rash fades and antibody titers raise
Rapid raise in 1 – 3 weeks
Rash in association with detection of IgM indicates recent infection.
IgG antibodies persist for life

15. Immunity - Protects One attack of Rubella infection, protects for life
Immune mothers transfer antibodies to off springs who are in turn are protected for 4 – 6 months.

16. Diagnosis of Rubella in Adults
Clinical Diagnosis is unreliable
Many viral infections mimic Rubella
Specif diagnosis of infection with
1 Isolation of virus
2 Evidence of seroconversion

17. Isolation and Identification of virus
Nasopharyngeal or throat swabs taken 6 days prior or after appearance of rash is a good source of Rubella virus
Using cell cultured in shell vial antigens can be detected by Immunofluresecentet mehods

18. Serology In Rubella
Hemagglutination inhibition test for Rubella is of Diagnostic significance
ELISA tests are greater importance
A raise in Antibody titers must be demonostrated between two serum samples taken at least 10 days apart.
Or Detection of Rubella specific IgM must be detected in a single specimen.

19. Epidemiology Rubella is world wide in distribution
Occurs round the year,
Epidemics occur every 20 – 25 years
Infection is transmitted by respiratory route
The use of Rubella vaccine has now eliminated both epidemic and endemic Rubella in USA and several developed countries

20. Treatment and Prevention
Rubella is a mild self limited illness.
No specific treatment or Antiviral treatment is indicated.
However Laboratory proved and clinically missed Rubella in the Ist 3-4 months of pregnancy is associated with fetal infections.

21. Congenital Rubella Syndrome
Maternal viremia with Rubella infection during pregnancy may result in infection of placenta and fetus.
The growth rate of fetal cells are reduced.
Results in fewer number of cells after the birth.
Lead to deranged and hypo plastic organ development.
Results in structural damage and abnormalities

22. Rubella infection – At various trimesters
Ist trimester infections lead to abnormalities in 85 % of cases. and greater damage to organs
2nd trimester infections lead to defects in 16 %
> 20 weeks of pregnancy fetal defects are uncommon
However Rubella infection can also lead to fetal deaths, and spontaneous abortion.
The intrauterine infections lead to viral excretion in various secretion in newborn upto months.

23. Clinical Findings ( Congenital Rubella Syndrome )
May be transient effects in infants.
Permanent manifestations may be apparent at birth, become recognized during the first year.
Developmental abnormalities appear during childhood and adolescents.

24. Classical Triad of Rubella
Cataract
Cardiac abnormalities
Deafness
Other manifestations
Growth retardation
Rash
Hepatosplenomegaly
Jaundice
Meingoencephalitis
CNS defects lead to moderate to profound mental retardation

25. Other Neurological manifestions
Problems in balance
Motor skills in preschool children altered.
A rare complication of Pan encephalitis can occur in second decade with Congenital rubella syndrome may progress to death.

26. Diagnosis of Congenital Rubella Syndrome
Demonstration of Rubella antibodies of IgM in a new born is diagnostic value. As IgM group donot cross the placenta and they are produce in the infected fetus,

27. Treatment, Prevention, Control
No specific treatment is available
CRS can be prevented by effective immunization of the young children and teenage girls, remain the best option to prevent Congenital Rubella Syndrome.
The component of Rubella in MMR vaccine protects the vaccinated

28. MMR Vaccine
The MMR vaccine is a mixture of three live attenuated viruses, administered via injection for immunization against measles, mumps and rubella. It is generally administered to children around the age of one year, with a second dose before starting school (i.e. age 4/5). The second dose is not a booster; it is a dose to produce immunity in the small number of persons (2-5%) who fail to develop measles immunity after the first dose. In the United States, the vaccine was licensed in 1963 and the second dose was introduced in the mid 1990s. It is widely used in all National, Universal Immunization programmes

29. Hepatitis C Virus Non A, non B Hepacivirus
Hepatitis C Infection
Hepatitis C Virus
Non A, non B
Hepacivirus

30. What is Hepatitis C Virus
Hepatitis C virus also known as Non A or Non B virus found while doing experiments on Chimpanzees.
HCV infections are seen only in humans
The epidemiology is like HBV infection.

31. HCV Virology The virus is not been grown in culture
The virus is nm with linear +ve single stranded RNA genome surrounded by an enveloped carrying glycoprotein spikes
Now classified as Hepacivirus in the family of Flaviviridae
Six genotypes are identified, with high mutability

32. Hepatitis C Virus capsid envelope protein protease/helicase
RNA-dependent
RNA polymerase
c22
33c
c-100 5’ 3’
core E1 E2
NS2
NS3
NS4
NS5
hypervariable
region 7 7 7

33. Hepatitis C Virus
Genome resembled that of a flavivirus positive stranded RNA genome of around 10,000 bases
1 single reading frame, structural genes at the 5' end, the non-structural genes at the 3' end. enveloped virus, virion thought to 30-60nm in diameter
Morphological structure remains unknown

34. Terminology
Family
Genus
Species
Genotype
Subtype
Quasispecies

35. Pathogenesis

36. Hepatitis C - Clinical Features
Incubation period: Average 6-7 wks
Range 2-26 wks
Clinical illness (jaundice): % (20-30%)
Chronic hepatitis: 70%
Persistent infection: %
Immunity: No protective antibody
response identified 8 8 8

37. How HCV transmitted Blood transfusions Transplantation of organs
Injectable drug abusers
Immunocompromised
Sexual transmission ?
Vertical transmission is possible

38. Clinical features Overt Jaundice is seen in 5% of patients
About 50 – 80% patients progress to chronic hepatitis
May progress to Cirrhosis, or Hepatocellular carcinoma

39. Chronic Hepatitis C Infection
The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.
All the manifestations of chronic hepatitis B infection may be seen, although with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.

40. Transmission of HCV Percutaneous IV drugs
Clotting factors before viral inactivation
Transfusion, transplant from infected donor
Therapeutic (contaminated equipment, unsafe injection practices)
Occupational (needle stick)
Per mucosal
Perinatal
Sexual

41. HCV - Occupational Transmission
Inefficiently transmitted
Average incidence 1.8% following needle stick from HCV-positive source
10 times lower than HBV infection
Hollow-bore needles
Case reports from blood splash to eye
No reports from skin exposures to blood
Prevalence 1-2% among health care workers
Lower than in the general population

42. Risk Factors Associated with Transmission of HCV
Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-positive contact
Multiple sex partners 11 11 11

43. Biochemical Indicators of Hepatitis C Virus Infection
In chronic hepatitis C, increases in the alanine and aspartate aminotransferases range from zero to 20 times (but usually less than five times) the upper limit of normal.
Alanine aminotransferase (ALT) levels are usually higher than aspartate aminotransferase (AST) levels, but that finding may be reversed in patients who have cirrhosis.
Alkaline phosphatase and gamma glutamyl transpeptidase are usually normal. If elevated, they may indicate cirrhosis.
Low platelet and white blood cell counts and raised levels of serum globulins (including immunoglobulins and rheumatoid factor) are frequent in patients with severe fibrosis or cirrhosis, providing clues to the presence of advanced disease.
The enzymes lactate dehydrogenase and creatine kinase are usually normal.
Albumin levels, bilirubin, and prothrombin time are normal until late-stage disease.
Iron and ferritin levels may be slightly elevated.

44. Hepatitis C Virus Infection
Typical Serologic Course
anti-HCV
Symptoms
Titre
ALT
alanine aminotransferase
Normal 1 2 3 4 5 6 1 2 3 4
Months
Years
Time after Exposure 10 10 10

45. 14 14 14

46. Laboratory Diagnosis
HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
ELISA test results to be confirmed with Immunoblotting assay

47. Molecular Methods in Diagnosis
HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.
HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.

48. Prognostic Tests
Genotyping – genotype 1 and 4 have a worse prognosis overall and respond poorly to interferon therapy. A number of commercial and in-house assays are available.
Genotypic methods – DNA sequencing, PCR-hybridization e.g. INNO-LIPA.
Serotyping – particularly useful when the patient does not have detectable RNA.
Viral Load – patients with high viral load are thought to have a poorer prognosis. Viral load is also used for monitoring response to IFN therapy.

49. INNO-LIPA

50. HCV Treatment α-Interferon Ribavirin Effective in about 50% of cases
No vaccine

51. Treatment
Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment.
Ribavirin - there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.

52. Prevention of Hepatitis C
Screening of blood, organ, tissue donors
High-risk behavior modification
Blood and body fluid precautions 15 15 15

53. Hepatitis E infection

54. Hepatitis E Virus Calicivirus-like viruses
unenveloped RNA virus, nm in diameter
+ve stranded RNA genome, 7.6 kb in size.
very labile and sensitive
Can only be cultured recently

55. Hepatitis E Virus 26 26 26

56. Hepatitis E - Clinical Features
Incubation period: Average 40 days
Range days
Case-fatality rate: Overall, 1%-3% Pregnant women, %-25%
Illness severity: Increased with age
Chronic sequelae: None identified 27 27 27

57. Hepatitis E Virus Infection
Typical Serologic Course
Symptoms
ALT
IgG anti-HEV
Titer
IgM anti-HEV
Virus in stool 1 2 3 4 5 6 7 8 9 10 11 12 13
Weeks after Exposure 28 28 28

58. Epidemiologic Features
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. 29 29 29

60. Prevention and Control Measures for Travelers to HEV-Endemic Regions
Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler.
IG prepared from donors in Western countries does not prevent infection.
Unknown efficacy of IG prepared from donors in endemic areas.
Vaccine? 31 31 31

61. Hepatitis G virus A new virus recently identified in Humans.
Not grown in culture lines
RNA genome is cloned
Its role still for debate
HGV RNA was found in acute, chronic, fulminant hepatitis , hemophiliacs, patients with multiple transfusions
It resembles HCV In all other aspects

62. Protect yourself
Medical and Paramedical staff can reduce, avoid the incidences of accidental infection with HBV,HCV,HDV,and Hepatitis G infections with, safe handling of needles

63. Prevent needle stick injuries

64. Report your needle stick injuries to higher authorities