Measles. "The primary targets of the virus are lymphoid tissue, skin, conjunctiva, kidney, lungs, GI tract and liver.

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1 Measles One of the most important viruses that cause childhood infections and diseases, but has been brought under control as a consequence of vaccination which was introduced late in the sixties. Measles is a typical paramyxo virus that lacks neuraminidase, it has the G glycoprotein on the surface which acts as a binding site for the receptor of measles, and the receptor is CD46. Measles is a virus that can fuse adjacent cells because it has the F (fusion) glycoprotein, so it can cause multinucleated giant cells formation. Measles is acquired by the respiratory route where individuals infected with the virus shed it in their saliva and respiratory droplets. Susceptible individuals acquire the infection where first the virus replicates locally in the oropharynx, and then it gain access to lymphoyid tissue where lymphocytes "as they are one of the primary targets to this virus" are infected to develop what s known as (Warthin-Finkeldey cells) in the lymphoid tissue itself, those cells are multinucleated giant cells rich with the virus. After this early phase of replication for 2-4 days, the virus causes primary (transient) viremia that seeds the virus into other lymph nodes "locally" and reticular system that s followed by secondary viremia, which disseminates the virus to a variety of organs. The virus can reach any organ: GI tract, respiratory tract, heart, liver, CNS, while measles's wide range of dissemination is reflected in its serious complications as If gaining access to lungs and causing pneumonia "regular or giant cell pneumonia" and might get complicated with diarrhea and hepatitis is possible to take place and post infectious encephalitis when disseminating the CNS and the fatal SSPE is to take place due to persistence of the virus in brain tissue. the virus in the SSPE case lacks M proteins so it is not able to get released, as result it persists and spreads by de-myelinating and causing severe damage to brain tissues "to be discussed next year". "The primary targets of the virus are lymphoid tissue, skin, conjunctiva, kidney, lungs, GI tract and liver. Primary replication takes place in endothelial cells which are believed to be very essential for the pathogenesis and spreading of the virus, The virus

2 reaches skin and mucous membrane s epithelium as a consequence of direct extension from endothelial cells to the overlying epithelial layer where they cause infections of the granular layers ; stratum granulosum is affected in the epithelium of the skin and mucus membranes. In skin, a maculopapular skin rash tend to coalesce causing large blotches of lesions developing in the skin, whereas the affected mucous membrane have a characteristic development of what is known as koplik s spots that can be detected at the buccal mucosa as small irregular bright red spot with bluish white specks at the center, they are similar to grains of salt on the buccal mucosa, as these spots are usually seen toward the end of the prodromal phase, that means with the end of the incubation period the prodromal phase develop for 2-3 days during which the koplik s spots are seen. ( look at the slides and note the spots on the buccal mucosa of the patient ). If children with measles are examined for it, it s easy to make a diagnosis immediately, but usually children are NOT examined for measles during this period of time because it precedes the appearance of the rash. SO there is an incubation period of 10 to 14 days, during which the virus replicates locally, then splits to cause transient ( primary) viremia, then secondary viremia then invasion of skin and mucous membranes being ended with the prodromal phase which lasts for 2-3 days. The prodrome of measles is characterized with: 1- Fever which could be very high 40 or more 2-the 3Cs : Conjunctivitis,Coreza (runny nose ) and Cough pointing to the involvement of the respiratory tract ;the whole of the respiratory tract is affected ; THE EYE is considered as an extension of the respiratory tract, the eye infection is as Conjunctivitis. The prodromal phase ends with the eruption of the rash, at this point the child is most sick; the fever is highest, and the respiratory manifestations are severe. that s why among the general public, among the elders, they make the child very warm under the belief that this will cause the eruption of skin rash, from heritage they think that rash helps in recovering (when rash

3 appear improvement) that s why they help the rash to appear by covering the child with heavy covering, this is not a proper management. But if the child is left naturally, the natural consequence of events (the high fever) is followed by eruption which is associated with improvement. IN uncomplicated measles, clinical recovery begins soon after the appearance of the rash. The rash which lasts for 5 to 6 days fades to a café au lait color (often called staining). In uncomplicated measles the rash is restricted to 3-4 days of progression then the child improves. The rash first appears on the face, then goes down to the trunk and the extremities then disappears in the same order; disappears first from the face then the two other parts. REMEMBER: koplick s spot are to fade at the end of incubation period, when the skin rash erupts. There s usually a generalized lymphadenopathy, the lymph nodes become enlarged, because the lymphoid tissue is a primary target for measles. Measles may be complicated with many complications, the most common of which are respiratory in nature like: pneumonia, giant cell pneumonia, croup and otitis media. Also measles can cause encephalitis which develop within short period after measles, usually 1 to 3 weeks, this is known as post infectious or Para infectious encephalitis thought to be caused by an immune mediated type of complications, also it can cause a very late complication known as SSPE subacute sclerosing panencephalitis which is inevitably fatal and develops several years after measles because of the persistence of the virus in the CNS. The virus can t leave the CNS because of the defect in the M protein production, so it cannot be released from the infected cells by budding as result it persists and spreads by de-myelinating and causing severe damage to brain tissues. It can also cause hepatitis, while In conditions of malnutrition : measles can be very serious because it has been reported to cause quisionco.in those children especially those with vitamin A deficiency they can develop keratitis and may lead to blindness, and this is commonly seen in India.

4 Measles is a major killer in the developing countries, so vaccination is indicated and recommended to control measles because of the serious complications that can take place especially in developing countries where the vaccination is given early in life. Pathogenesis of measles In brief : Infection primary viremia 2ndary viremia the dissemination of the virus with prodromal manifestations (virus shedding, koplick s spots, gaint cells in infected tissue ) then antibody appearance which coincides with the appearance of the rash recovery. Treatment: Because measles is a monotypic virus (of one type) natural infection is followed with lifelong immunity. There is no specific treatment for it; the treatment is symptomatic, but in some cases it s fatal because of encephalitis. Prevention : Vaccination, using the attenuated virus given with mumps and rubella so the vaccine is called The MMR vaccine. In developed countries, It s recommended to give the first dose after the age of one year (12-18 months) and a second dose before school or college to maintain a long life immunity. As measles take place during childhood, the vaccine is given in extra dose before the age of one year. In Jordan it s given at the age of 9 months because cases below one year still take place. "However, there s one drawback of this practice that must be taken into consideration, which is the persistence of maternal antibodies for 9-12 months; unlike all antibodies the maternal measles antibodies may persist for 12 months and may prevent immunity establishment to the vaccine." Measles vaccine is given in 2 doses; at the beginning one single dose of the vaccine where given, but after 20 years of experience outbreaks affecting those who were vaccinated were documented in 1989 to 1990;They affected college students in the United States who were immunized in late sixties or early seventies but immunity

5 fades with time. That s why a second dose is recommended for a longer time of protection, because the vaccine protects for 20 years or so. RUBELLA - German measles Belongs to the Togaviridae, and all toga viruses are arthropod borne except the rubella so it is related to paramyxovirus in pathogenesis (much like measles in pathogenesis ) enters through the respiratory tract replicates locally, targets the lymph nodes (lymphadenopathy is remarkable in rubella),this replication is followed by viremia dissemination of virus to the target organs ( skin is one of the most important targets, and manifestations are usually restricted to the skin ), but also, similar to measles, it can infect other organs like CNS and lungs. The appearance of the rash coincides with the appearance of antibodies which points to the possibility of the rash being immune mediated so the virus is cleared from the circulation, and this is followed by the appearance of the rash. * Infection takes place early in childhood, followed by life-long immunity. Rubella in Latin means little red to indicate the mild nature of the disease compared to measles. Manifestations of rubella include macuolopapular rash, lymphadenopathy, low-grade fever, conjunctivitis, sore throat and arthralgia (especially among females, but the most consistent is skin rash nearly in 95% of all symptomatic cases, sometimes with lymphadenopathy, the characteristic of it in rubella involve the posterior cervical and the suboccipital lymph nodes. The rash progress and fades rapidly within 3-4 days that s why it s called the 3 days illness. Also similar to measles, rubella can be associated with post infectious involvement with CNS and it can also develop a similar condition to that of progressive rubella panencephalitis that develop several years after rubella which also can be fatal, but most cases of rubella in children are benign,

6 Child bearing age among females is very serious because of the risk of congenital spread, trans-placentally spread to the fetus which is associated with congenital malformations "Heart problems, congenital cataract, deafness". Parvovirus B 19 Fifth disease Parvoviruses was the only member of parvoviruses that cause infection before the discovery of Boca viruses "that causes respiratory diseases " Parvovirus target immature erythrocytes, and cause their destruction, so it is dependent on actively dividing cells for its replication. The stage of development that can be detected is the giant pronormoblast that is detected in the bone marrow of infected individual. No reticulocytes and no mature erythrocytes because they are destroyed at the pronormoblast lamina, so individuals with infection develop anemia, and because the infection is transient that lasts for few day, the anemia is not significant and usually cause nothing "in normal individuals". However in children with underlying conditions(hemolytic disease) like thalasemia, sickle cell and enzyme deficiencies, stressed erythropoiesis; anemia maybe serious and causes a condition known as transient Aplastic crisis TAC, which is associated with significant anemia that could lead to heart failure and death, that s why in such conditions of underlying hemolytic disease, parvovirus B19 infections can be serious,but most cases of parvovirus b19 are limited to manifestations known as fifth disease or erythema infectiosum where skin rash with joint involvement particularly in females being the most common manifestation. The fifth disease is characterized by slapped cheek appearance because of the facial erythema and a lacyreticular maculopapular eruption over the trunk and proximal extremities

7 No available treatment nor vaccination to this disease The infection is associated "sometimes" with other complications of connective tissue disease like SLE, vasculitis, polyarteritis nodosa or neurological disease and cases of purpera, whether idiopathic thrombocytopenic purpera or Henoch Schönlein purpura, and the disease might be associated with arthritis. Rash of parvo B19 is immune mediated which is proved by the fact that those immune compromised patients don t develop this manifestation and don t produce anti-bodies to neutralize the viral particles Roseola Infantum ( Exanthem Subitum ) : Caused by human herpes virus 6, that spreads by saliva, most cases of infection takes place during childhood,that means 70-95% of children have antibodies to the virus, and the signs and symptoms are usually mild being composed of irritability, diarrhea, cough, fever can reach to 40 for 3 to 7 days,sometimes seizures and rash appears after the temp. falls down Replicates in the respiratory tract similarly in pathogenesis to Rubella and B19 with a high titer of virus to be produced, and associated to the high Temp. through the first few days of onset while rash appears as faint macules when Temp. falls down, and as the doctor said that Infectivity is associated to the incubation period When the disease is symptomatic : fever, diarrhea, cough, are to take place while seizures can develop and might get associated with necrotic type of lymphadenititis that mimic the kikuchi disease!!! Roseola Infantum effects on SKIN rash usually mild develop after the fever is gone in the form of faint macules develop on trunk and extremities that blanch upon pressure, and they last for hours or few days, and they might require no treatment, this rash is to be

8 differentiated from rubella measles and scarlet fever as it appears as rose colored maculu-papular rash!! clinically : Fever takes place for few days with upper respiratory symptoms as well as the rash on trunk and extremities Hand, foot and mouth disease Is caused by coxsackie virus A 16, but coxsackie virus B as well as another Enterovirus have been linked with it"a( ) B(2-5) enterovirus 71. Here we have both skin eruption (exanthema) and internal eruption of the mouth. The infection affects the palms which resolve in 2 to 7 days, the lesions are vesicular in nature, usually mild and self-limiting and involving the three sites "hand, foot, face" - "this virus transmits through the orofecal route" The involvement of muscles with certain viruses: The most important infection of muscles caused by coxsackie B virus and that is known as Pleurodynia, epidemic Myalgia, Bronholm disease, or Devil s grip. All enteroviral infections spread by oral-fecal routes; consumption of contaminated food or drink, the virus replicates in the GIT and causes viremia which disseminates the virus to the target organ (could be the heart, CNS, different muscles, pancreas, liver, etc). in this case the target organ is the chest muscle as well as the diaphragm, that s why this disease is associated with difficulty in breathing "might cause respiratory failure" because of the severe pain that is associated with the infection (devil grip). The intense pain is usually bilateral but sometimes it s unilateral and maybe confused with myocardial infarction, that s why fever is important to be distinguished.it resolves spontaneously leaving the patient weak with some tenderness in muscles but it may return. The currents can take place in the case pleural lung, but all cases are followed by full recovery. Echovirus 3 was reported to be the cause of wandering myoclonus, which was reported from china. This is a serious illness that maybe fatal and intend to

9 10% of cases. High mortality is associated with wandering myoclonus that effects young adults in china. Finally, Mycolonus and Rhabdomyolysis have been caused by West Nile Virus (they cause lysis of muscle). Adnan Tarawneh