1. TOGAVIRIDAE

2. Introduction
The Togaviridae (togaviruses) can be classified into the following major genera: Alphavirus, Rubivirus, and Arterivirus.
No known arteriviruses cause disease in humans, so this genus is not discussed further.
Members of the Togaviridae are responsible for two very different kinds of human disease.
All alphaviruses are transmitted by arthropods, and cause encephalitis, arthritis, and rashes.

3. Introduction
Rubella virus is the only member of the Rubivirus group; it is discussed separately because its disease manifestation (German measles) and its means of spread differ from those of the alphaviruses.
Rubella virus is the agent of a mild rash disease but can also cause congenital abnormalities in the fetus when acquired by the mother early in pregnancy.

4. Rubella (German Measles)
Rubella is one of the five classic childhood exanthems, along with measles, roseola, fifth disease, and chickenpox.
Rubella, meaning “little red” in Latin, was first distinguished from measles and other exanthems by German physicians; thus the common name for the disease, German measles.
In 1941, an astute Australian ophthalmologist, Norman McAlister Gregg, recognized that maternal rubella infection was the cause of congenital cataracts.
Maternal rubella infection has since been correlated with several other severe congenital defects.
This finding prompted the development of a unique program to vaccinate children to prevent infection of pregnant women and neonates.

5. Characteristics Rubella virus is spherical and enveloped.
The diameter is from 40 to 90 nm.
Icosahedral nucleocapsid.
Genome is composed of a single molecule of positive RNA.
The envelope contains two E proteins that mediate fusion of viral and cellular membranes.
mRNA is translated into a single polyprotein.
The virus buds from cell membrane.
The virus contains hemagglutinin.

6. Epidemiology Humans are the only host for rubella.
The virus is spread in respiratory secretions and is generally acquired during childhood.
Spread of virus, before or in the absence of symptoms, and crowded conditions, such as those in day-care centers, promote contagion.
Approximately 20% of women of childbearing age escape infection during childhood and are susceptible to infection unless vaccinated.
Programs in many states in the United States test expectant mothers for antibodies to rubella.

7. Pathogenesis
Rubella virus is not cytolytic but does have limited cytopathologic effects in certain cell lines, such as Vero and RK13.
The prodromal period lasts approximately 2 weeks.
Rubella infects the upper respiratory tract and then spreads to local lymph nodes, which coincides with a period of lymphadenopathy.
This stage is followed by establishment of viremia, which spreads the virus throughout the body.

8. Pathogenesis
Infection of other tissues and the characteristic mild rash occur.
Recovery within 3-4 days after the appearance of rash.
The infected person can shed virus in respiratory droplets during the prodromal period and for as long as 2 weeks after the onset of the rash
Circulating antibody can block the transfer of virus at the indicated points (X).

9. Immune Response
Antibody is generated after the viremia, and its appearance correlates with the appearance of the rash.
The antibody limits viremic spread, but cell-mediated immunity plays an important role in resolving the infection.
Only one serotype of rubella exists, and natural infection produces lifelong protective immunity.
Most important, serum antibody in a pregnant woman prevents spread of the virus to the fetus.
Immune complexes most likely cause the rash and arthralgia associated with rubella infection.
Arthritis is joint pain with inflammation, whereas arthralgia is joint pain without inflammation

10. Congenital Infection
Rubella infection in a pregnant woman can result in serious congenital abnormalities in the child.
If the mother does not have antibody, the virus can replicate in the placenta and spread to the fetal blood supply and throughout the fetus.
Rubella can replicate in most tissues of the fetus.
The virus may not be cytolytic, but the normal growth, mitosis, and chromosomal structure of the cells of the fetus can be altered by the infection.
The alterations can lead to improper development of the fetus, small size of the infected baby, and the teratogenic effects associated with congenital rubella infection.
A teratogen is an agent that can disturb the development of the embryo or fetus. 
The nature of the disorder is determined by:
(1) the tissue affected and
(2) the stage of development disrupted

11. Congenital Infection
The virus may persist in tissues, such as the lens of the eye, for 3 to 4 years and may be shed up to a year after birth.
The presence of the virus during the development of the baby’s immune response may even have a tolerogenic effect on the system, preventing effective clearance of the virus after birth.
Immune complexes that produce further clinical abnormalities may also form in the neonate or infant.

12. Laboratory Diagnosis
Isolation of the rubella virus is difficult and rarely attempted.
The presence of the virus can be detected by RT-PCR detection of viral RNA.
The diagnosis is usually confirmed by the presence of antirubella-specific IgM.
A fourfold increase in specific IgG antibody titer between acute and convalescent sera is also used to indicate a recent infection.
Antibodies to rubella are assayed early in pregnancy to determine the immune status of the woman; this test is required in many states.
When isolation of the virus is necessary, the virus is usually obtained from urine and is detected as interference with replication of echovirus 11 in primary African green monkey kidney cell cultures (heterologous interference).

13. Treatment, Prevention, and Control
No treatment is available for rubella.
The best means of preventing rubella is vaccination with the live cold adapted RA27/3 vaccine strain of virus.
The live rubella vaccine is usually administered with the measles and mumps vaccines (MMR vaccine) at 15 months of age.
The primary reason for the rubella vaccination program is to prevent congenital infection by decreasing the number of susceptible people in the population, especially children.
As a result, there are fewer seronegative mothers and smaller chance that they will be exposed to the virus from contact with the children.
Because only one serotype for rubella exists, and humans are the only reservoir, vaccination of a large proportion of the population can significantly reduce the likelihood of exposure to the virus.

14. RHABDOVIRIDAE

15. Introduction
The members of the family Rhabdoviridae (from the Greek word rhabdos, meaning “rod”) include pathogens for a variety of mammals, fish, birds, and plants.
Rabies virus is the most significant pathogen of the rhabdoviruses.
Until Louis Pasteur developed the killed-rabies vaccine, a bite from a “mad” dog always led to the characteristic symptoms of hydrophobia and certain death.

16. Characteristics Bullet-shaped, RNA virus. Helical nucleocapsid.
Glycoprotein (G protein) spikes are responsible for viral attachment to cellular receptors.
The genome is single-stranded (-) RNA.
The virus contains virion-associated RNA transcriptase “the L protein”, which produces five viral mRNAs.
The M protein is the major structural protein, lies beneath the lipid membrane.
The nucleoprotein (N) protects RNA from degradation by RNase enzymes, NS “nucleocapsid small”

17. Characteristics
(Nucleocapsid Small)

18. Classification
Rhabdoviruses infecting mammals belong to two genera in Rhabdoviridae family
Lyssavirus
It contains rabies virus and related viruses (Lagos bat virus, Mokola, Duvenhage).
Genus vesiculovirus:
It contains vesicular stomatitis virus (VSV) and related viruses like Chandipur (arbelius)

19. Epidemiology Transmission At risk or risk factors Distribution
Bites of wild animals and unvaccinated dogs and cats
At risk or risk factors
Animal handlers, veterinarians
Those in countries with no pet vaccinations or quarantine
Distribution
Worldwide, except certain islands and U.K.
No seasonal incidence
Vaccines or antiviral drugs
Vaccines for pets and wild animals
Inactivated virus vaccine for at-risk personnel, post-exposure prophylaxis
No antiviral drugs

20. Pathogenesis Reproduces in muscle at bite site
Incubation period of weeks to months, depending on inoculum and distance of bite from central nervous system
Infects peripheral nerves and travels to brain
Reproduction in brain causes hydrophobia, seizures, hallucinations, paralysis, coma, and death
Spreads to salivary glands of nonhuman animals, from which it is transmitted
Post-exposure immunization can prevent disease due to long incubation period

22. Laboratory Diagnosis
The occurrence of neurologic symptoms in a person who has been bitten by an animal generally establishes the diagnosis of rabies.
Unfortunately, evidence of infection, including symptoms and the detection of antibody, does not occur until it is too late for intervention.
Laboratory tests are usually performed to confirm the diagnosis and to determine whether a suspected individual or animal is rabid (postmortem).
The hallmark diagnostic finding has been the detection of intracytoplasmic inclusions consisting of aggregates of viral nucleocapsids (Negri bodies) in affected neurons.

24. Laboratory Diagnosis
Several tests are necessary to diagnose rabies ante-mortem (before death) in humans; no single test is sufficient.
Tests are performed on samples of saliva, serum, spinal fluid, and skin biopsies of hair follicles at the nape of the neck.
Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR).
Serum and spinal fluid are tested for antibodies to rabies virus.
Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles.

25. Treatment and Prophylaxis
Clinical rabies is almost always fatal unless treated with post-rabies immunization.
Once the symptoms have appeared, little other than supportive care can be given.
Post-exposure prophylaxis is the only hope for preventing overt clinical illness in the affected person.
Prophylaxis should be initiated for anyone exposed by bite or by contamination of an open wound or mucous membrane to the saliva of an animal suspected to be infected with the virus, unless the animal is tested and shown not to be rabid.

26. Treatment and Prophylaxis
The first protective measure is local treatment of the wound.
Subsequently, immunization with vaccine in combination with administration of one dose of human rabies immunoglobulin (HRIG) or horsy antirabies serum is recommended.
Passive immunization with HRIG provides antibody until the patient produces antibody in response to the vaccine.
A series of five vaccinations is then administered over the course of a month.
The slow course of rabies disease allows active immunity to be generated in time to afford protection.

27. Treatment and Prophylaxis
The rabies vaccine is a killed-virus vaccine prepared through the chemical inactivation of rabies infected–tissue culture human diploid cells (HDCV) or fetal rhesus lung cells.
The HDCV is administered intramuscularly on the day of exposure and then on days 3, 7, 14, and 28 or intradermally with a lower dose of vaccine to multiple sites on days 0, 3, 7, 28, and 90.
Preexposure vaccination should be performed on animal workers, laboratory workers who handle potentially infected tissue, and people traveling to areas where rabies is endemic.
HDCV administered intramuscularly or intradermally in three doses is recommended and provides 2 years of protection.

28. Treatment and Prophylaxis
Ultimately the prevention of human rabies hinges on the effective control of rabies in domestic and wild animals.
Its control in domestic animals depends on the removal of stray and unwanted animals and the vaccination of all dogs and cats.