A. Types

1. Chicken Pox
2. Scarlet Fever
3. Hand-Foot-and-Mouth Disease - cocksackievirus
4. Parvovirus B19 - Erythema Infectiosum or "Fifth Disease"
5. Measles
6. Rubella (German Measles)
7. Ruseola (Exanthum subitum) - human herpesviruses 6 and 7
8. Dengue Fever - flavivirus
9. Human Herpesvirus 8 (HHV-8)
10. Mumps

B. Chicken Pox

1. Symptoms
   1. Initial Mild to moderate fever and/or malaise x 2 days
   2. Eruption usually appears on day 2-3, begins on trunk, face and scalp with progression
   3. Generally proximal more affected than distal
   4. May involve mucous membrane
   5. Papular rash becomes vesicular over first 24 hours, then pustular, then crusted
   6. Multiple episodes of viremia lead to lesions of different ages on single host
2. Prognosis
   1. Generally mild in children
   2. Adults have more serious courses
   3. Immunocompromised patients may be severely affected
3. Diagnosis
   1. History, Physical Examination
   2. Recent contact
   3. Tzanck smear allows definitive diagnosis
   4. Smear is usually a Giemsa stained scraping from varicella vesicle base
   5. See multinucleated epithelial giant cells (identical in zoster and simplex)
4. Treatment
   1. Supportive care
   2. Acyclovir 800mg po 5x/day or IV
   3. Famciclovir also approved
   4. Immune Globulin specific for varicella zoster
5. Vaccination
   1. Varicella zoster virus vaccine recently approved in USA
   2. Effective and safe in patients with leukemia
   3. Over 25-years of followup in Japan suggests lasting efficacy and safety
   4. Currently recommended in older children and in special cases
   5. Eventually, vaccine may be more extensively used

C. Measles (Rubeola) [5]

1. Viral Properties
   1. Negative single-stranded, enveloped RNA virus (Paramyxoviridae)
   2. Infects only humans and other primates
   3. Uses CD150 (SLAM) and CD46 as receptors in humans
   4. Grouped into 8 classes (A through H) with 20 genotypes
2. Main Proteins
   1. H Protein - hemagglutinin protein
   2. F Protein - fusion protein, binds cell receptor CD46
   3. M protein - matrix protein
3. Mainly restricted to underdeveloped countries and/or areas of poor immunization rates
4. Clinical Disease
   1. Transmission through respiratory tract
   2. Incubation period is ~10 days
   3. Present with fever and upper respiratory tract symptoms
   4. Includes cough, conjunctivitis, nasal congestion
   5. Blue-white punctate leasions develop in buccal mucosa in 2-3 days (Koplik's spots)
   6. Red maculopapular rash begins on face, extends to trunk in 3-4 days
   7. In uncomplicated disease, symptoms abate in 4-5 days
   8. Desquamation of truncal lesions may occur
   9. Complications may occur including otitis media, croup, bronchitis, pneumonia
   10. Frank measles encephalitis occurs in 1 per 1000 children infected
5. Diagnosis
   1. Usually made clinically in unimmunized individuals
   2. Four-fold rise in antibody (peaks in 3-4 weeks)
   3. Virus can be isolated from throat during prodrome
   4. All suspected cases of measles in USA should be confirmed in laboratory
   5. Complications can be severe or life-threatening
6. Measles Pneumonia
   1. Most common fatal complication of measles
   2. Responsible for ~60% of measles deaths
   3. Secondary bacterial and occasionally viral coinfection is seen
   4. Mainly a problem in underdeveloped countries
   5. Vitamin A 200,000 U x 2 doses reduces duration and severity of complications
   6. Consider antibacterial coverage with antibiotics against pneumococcus and H. influenzae
   7. Oxygen should be given liberally
7. Measles CNS Disease
   1. Acute postinfectious measles encephalitis (APME)
   2. Subacute sclerosing panencephalitis (SSPE)
   3. Measles inclusion body encephalitis (MIBE)
8. APME
   1. Autoimmune process develops within 2 weeks
   2. Occurs in 0.1% of measles cases
   3. Probably due to T cell hyperactivity against myelin basic protein (MBP)
   4. Little or no virus production in brain
   5. No production of intrathecal anti-measles IgG
9. SSPE [6]
   1. Very unusual complication in <10 per 100,000 measles virus infections
   2. Progressive subcortical dementing encephalitis, nearly always fatal
   3. Subacute presentation 1-7 years after measles infection
   4. Insidious onset: mental retardation, motor dysfunction, coma, death
   5. Increased risk in boys and in persons with measles infection prior to age 2
   6. Due to failure to clear measles from the brain
   7. Intraventricular interferon alpha and inosiplex have been used experimentally
10. MIBE
    1. Subacute complication only in immunocompromised persons
    2. Usually within 6 months of measles infection
    3. Lack of cytotoxic T cells lead to failure to clear virus from body
11. Treatment
    1. Immune serum globulin is recommended for all suspected contacts age 4-12 months
    2. Rapid and complete vaccination of all persons in area of case is critical to reduce spread
    3. Measles immune globulin can also be given for severe disease (single dose)
    4. Treatment for measles pneumonia as above
12. MMR (measles, mumps, rubella) Vaccine [7,10]
    1. Live attenuated virus combination
    2. Two doses of vaccine should be given to all persons born after 1957
    3. First dose age >12 months; second dose >28 days later provokes lifelong immunity
    4. During outbreak, first dose may be given to children age 6-12 months, but 2 subsequent doses are still required to provide lifelong immunity []
    5. Single Dose MMR gives ~80% seroconversion for measles; 2 doses >98%
    6. Highly effective; has reduced number of infections considerably
    7. Should not be used for immunocompromised persons or during pregnancy
    8. Newer MMR do not contain egg proteins and are safe in persons with egg allergies
    9. Transient fever and/or rash can occur after vaccination

D. Rubella [9]

1. Also called German Measles
2. Caused by 60nm togavirus, single-stranded RNA virus (9762 bases), family Rubivurs
3. Well controlled in developed nations with MMR (measles-mumps-rubella) vaccination
4. In underdeveloped nations, congenital rubella syndrome continues to be a problem
5. Spread via aerosolization or transmission from mother to fetus
6. Detection with IgM (acute or recently acquired) or IgG (previous) serology
7. Clinical diagnosis is unreliable and laboratory confirmation required
8. Congenital Rubella
   1. Contraction of rubella during months 0-5 of gestation leads to congenital rubella
   2. The later the contraction, the less chance of defects
   3. Deafness is most common with up to 85% for infection acquired in first month
   4. Heart disease and CNS deficits are next most common
   5. Neonatal purpura peaks at 2 months (~40% of infections)
   6. Cataracts and glaucoma occur in 50% at 1 month, <5% by 4 months

E. Parvovirus B19 [1]

1. Single stranded DNA virus
2. Only member of Parvoviridae to infect humans
3. Associated Conditions
   1. Erythema infectiousum ("Fifth Disease") - "slapped cheak" appearance
   2. Immune thrombocytopenia
   3. Transient erythrobastopenia of childhood
   4. Aplastic crisis (especially in sickle cell disease, organ transplantation)
   5. Chronic Anemia and Blackfan-Diamond Anemia
   6. Relationship to chronic arthropathy is questionable [3]
   7. Others
4. Symptoms
   1. Children: classical "slapped cheek" rash
   2. Red maculopaupuar rash with lace-like reticular pattern, usually on extremities
   3. Anemia - pallor, shortness of breath
   4. Bleeding Diathesis - petechiae, purpura
5. Diagnosis
   1. ~50% of adults have IgG anti-parvovirus Ab
   2. Acute infection 3-4 weeks have IgM Ab
   3. Special concern: pregnancy, immunodeficiency, red cell disorder
6. Risk in Pregnancy
   1. Fetal hydrops may be fatal
   2. Low but definite risk to fetus in women exposed to virus
   3. Test for IgM
   4. Follw high risk patients with ultrasound, AFP levels (both unproven to affect outcome)
   5. Consider termination of pregnancy

F. HHV-8 Infection [2]

1. Cause of Kaposi Sarcoma and various lymphocytic neoplasms in immunocompromised
2. Primary infection in immunocompetent children now well documented
3. Maculopapular skin rash with fever
4. Patients are seropositive and HHV-8 titers should be evaluated
5. HHV-8 DNA found in saliva

G. Dengue Fever [4]

1. Mosquito-Transmitted Viral Disease
   1. ~75 million cases of dengue fever (DF) annually, worldwide
   2. ~250,000 cases of dengue hemorrhagic fever (DHF) annually
   3. ~25,000 deaths annually, mainly in DHF and dengue shock patients
   4. Typically transmitted by Aedes aegypti and Aedes albopictus mosquitos
   5. Southeast Asian travel is major risk factor (Thailand, Malaysia, Indonesia, Vietnam)
2. Flavivirus (Arbovirus) Infection
   1. Closely related set of Dengue Viruses (DEN)
   2. Four distinct viral serotypes, DEN 1 through 4
   3. Infection with one serotype provides lifelong immunity only to that serotype
3. Clinical Syndromes Overview
   1. Asymptomatic
   2. Dengue Fever (DF)
   3. Dengue Hemorrhagic Fever (DHF)
   4. Dengue Shock
   5. Majority of infections in children are asymptomatic
4. Diagnosis
   1. High clinical suspicion in endemic / epidemic areas
   2. Leukopenia and thrombocytopenia with elevated liver transaminases is fairly specific
   3. Diagnosis confirmed by rising serum antibody titers
   4. Probable disease: IgM Ab (ELISA) will become positive 4-5 days after symptom onset
   5. Single serum sample titer at least 1:1280 with hemagglutination or IgG test
   6. Confirm diagnosis with virus isolation, >4X increase in serum IgG/IgM, or PCR positive test
   7. Polymerase chain reaction (PCR) is available and is positive in 90% in early disease
   8. PCR test sensitivity rapidly declines 7 days after onset of illness
   9. PCR test is not routinely available
5. Differential Diagnosis
   1. Malaria
   2. Typhoid fever
   3. Leptospirosis
   4. Chikungunya
   5. West Nile Virus
   6. Measles
   7. Rubella
   8. Epstein-Barr Virus
   9. Viral hemorrhagic fevers
   10. Rickettsial diseases
   11. Early severe acute respiratory syndrome (SARS)
   12. Early acute HIV infection
6. Supportive therapy only is currently available

H. Mumps [8,9]

1. Main characteristic is childhood disease involving severe parotid gland swelling
   1. Cases in USA have been declining except for major outbreak in 2006
   2. In 2006, 6584 cases of mumps reported; 76% between March and May [3]
2. In most developed countries, is completely prevented by vaccination
3. Mumps Virus
   1. Enveloped RNA virus (Genus Rubulavirus in family Paramyxovifdae)
   2. Single negative stranded RNA of 15,384 nucleotides in length
   3. Six structural and two non-structural proteins including RNA polymerase
   4. Twelve mumps virus genotypes (A through L), differing by 2-6% of nucleotides, are known
4. Transmission
   1. Transmitted by dromlet or fomite exposure
   2. Incubation period typically 16-18 days
   3. >20% of cases asymptomatic
5. Symptoms
   1. Occur in >80% of cases
   2. Prodrome headache, malaise, anorxia, fever
   3. Within 24 hours of prodrome, unilateral or bilateral salivary gland (mainly parotid) swelling
   4. Oopheritis (5% postpubertal women), orchitis (25% postpubertal men) also occurs
   5. Usually benign meningitis (<10%)
   6. Transient high-frequency deafness (~4% of adults) can occur
6. Vaccination [8]
   1. Part of MMR vaccine; should be given at least once, and twice in high risk persons
   2. In 1990, two doses of mumps vaccine were recommended amongst schoolchildren
   3. During an outbreak, second dose should be considered for all adults and children 1-4 years old
   4. In 2006, a major outbreak of mumps occurred in midwestern US [3]
   5. This was despite 60-85% of persons having received two vaccines [3]

References

1. Kirchner JT. 1994. Am Fam Phys. 50(2):335
2. Andreoni M, Sarmati L, Nicastri E, et al. 2002. JAMA. 287(10):1295
3. Dayan GH, Quinlisk P, Parker AA, et al. 2008. NEJM. 358(15):1580
4. Halstead SB. 2007. Lancet. 370(9599):1644
5. Duke T and Mgone CS. 2003. Lancet. 361(9359):763
6. Gascon GG and Frosch MP. 1998. NEJM. 338(20):1448 (Case Record)
7. Poland GA, Jacobson RM, Thampy AM, et al. 1997. JAMA. 277(14):1156
8. Mumps Outbreak Recommendations. 2006. Med Let. 48(1236):45
9. Hviid A, Rubin S, Muhlemann K. 2008. Lancet. 371(9616):932
10. Measles Outbreak. 2008. Med Let. 50(1287):41