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BAB 195

INFEKSI POXVIRUS
Wynnis Tom
Sheila Fallon Friedlander

POXVIRUS

Poxvirus adalah virus DNA beruntai ganda yang bereplikasi dalam sitoplasma sel
induk(Tabel 195-1). Mereka adalah virus hewan terbesar dan dapat dilihat dengan mikroskop
cahaya. Poxvirus yang menyebabkan penyakit yang signifikan pada manusia ditinjau di sini.
Efek mereka pada host berkisar dari penyakit sistemik sampai infeksi lokal ke proliferasi sel
epitel saja.

INFEKSI ORTHOPOXVIRUS

Smallpox (Variola)
Virus variola adalah patogen yang bertanggung jawab untuk cacar, penyakit yang
menghancurkan umat manusiadalam wabah selama lebih dari 30 tahun. Poxvirus ini
membunuh dan memberi bekas luka pada jutaan orang baik di dunia Lama dan Dunia Baru,
mempengaruhi seluruhpopulasi di setiap benua.

Penemuan penting vaksinasi oleh Edward Jenner mengubah sejarah penyakit ini.Sekarang
penyakit ini bisa dicegah, dan upaya global yang intensif dalam vaksinasi dan pelacakan
kasus menghasilkan pemberantasan pada tahun 1980. Cacar dianggap telah menjadi penyakit
kepentingan sejarah. Ancaman bioterorisme dalam beberapa tahun terakhir, bagaimanapun,
telah memperbaharui kebutuhan pengetahuan tentang cacar dan fitur-fiturnya, serta
pengembanganvaksin dan pengobatanyang digunakan harus ditingkatkan untuk penyakit jika
timbul lagi.

EpidemiologiTidak seperti penyakit lain yang disebabkan oleh anggota keluarga Poxviridae,
smallpox hanya mempengaruhi manusia dan dengan demikian tidak dapat diperoleh dari
spesies lain. Transmisi dalam sebagian besar kasus adalah melalui droplet pernapasan dan
membutuhkan kontakdekat.Wabah terjadi pada musim dingin dan awal musim semi ketika
kondisi kelembabandan suhu yang rendah mendukungkelangsungan hidup virus aerosol
ini.Smallpox kurang menular dari penyakit lainnya yang menyebar melalui rute pernapasan,
termasuk campak, varicella, dan influenza.Tingkat serangan sekunder untuk kontak yang
tidak divaksinasi diperkirakan berkisar dari 37 persen hingga 38 persen.Kasus sekunder
sering terbatas pada anggota keluarga atau petugas kesehatan. Penyebaran cacar meningkat
ketika ada jumlah besar virus dalam tetesan aerosol, peningkatan jumlah dan tingkat pajanan
antara individu yang terinfeksi dan kontak, dan kepadatan penduduk yang lebih tinggi. Para
wanita yang sangat muda, tua, dan hamil lebih rentan terhadap infeksi. Individu dengan
penyakit klinis yang lebih berat dilaporkan lebih menular, tetapi orang-orang yang sama juga
cenderung toxemic dan dikurungdi tempat tidur.

dengan 30 persen atau lebih kematian tinggi terkait dengan jenis mayor dan kurang dari 1 persen kematian terkait dengan jenis minor. melalui konjungtiva. Yang memprihatinkan adalah bahwa stok virus lain yang tidak dilaporkan mungkin ada di tangan negara atau kelompok dengan hubungan teroris dan bisa saja diaerosol untuk digunakan sebagai senjata biologis (lihat Bab.Jarang melalui plasenta dan dengan partikel virus jarak jauh di udara atau yang disuspensikan di area tertutup. Portal masuk biasanya adalah oropharyngeal atau saluran pernapasan. Virus menyebar ke kulit dan mukosa. dan sakit kepala beratterjadi dalam waktu 7 sampai 17 hari dari pajanan.Paling menular selama 7 sampai 10 haripertama setelah onset ruam virus dan tetap menular sampai keropeng jatuh dari lesi kulit. Manusia merupakan satu-satunya reservoir alami virus variola yang diketahui. virus menempel pada sel-sel epitel pernapasan. Virus variola ditularkan mulai pada fase prodromal akhir melalui aerosolisasi partikel virus dari orofaring. virulensi mereka nyata berbeda. telah divaksinasi sejak saat itu untuk melayani sebagai responden lini pertama dalam wabah yang mungkin terjadi. Proses penyakit dimulaidari kontakdekat. Virus variola ini jarang menyebar melalui inokulasi tak disengaja di kulit. Viremia primer sementara dengan penyerapan virus oleh makrofag terjadi. ETIOLOGIDAN PATOGENESISSmallpox disebabkan oleh virus variola. yang terlalu lama dengan individu yang terinfeksi. bersama dengan personil militer.2F hingga 15. pemberantasan menjadimemungkinkan dan dicapai pada tahun 1980. mialgia. dan bereplikasi di daerah tersebut.Individu yang terinfeksi tetap asimtomatik selama masa inkubasi replikasi virus.Karena tidak ada carrier sub-klinis yang signifikan. virus yang bertanggung jawab seharusnya terbatas pada dua laboratorium di Amerika Serikat dan Uni Soviet. Strain virus jatuh ke dalam dua kelompok utama. baik dengan menghirup tetesan aerosol atau kontak langsung dengan membran mukosa yang terinfeksi. dan melalui kontak dengan cairan tubuh yang terinfeksi atau bentuk yang sangat terkontaminasi. bersama dengan organ dan jaringan lain seperti hati dan ginjal. GEJALA KLINISRiwayat. berjalan ke kelenjar getah bening regional. Mereka yang v divaksinasi sebelum 1972 memiliki tingkat imunitas yang tidak tentu.Viremia sekunder besar mengikuti dan menyebabkan timbulnya gejala (masa prodromal).Setelah masuk. Hanya sekelompok kecil warga sipil AS. Setelah pemberantasannya. dan virus variola menyebar ke organ-organ retikuloendotelial. di mana replikasi tanpa gejala terus berlanjut. mayoritas penduduk akan rentan terhadap penyakit smallpox. Meskipun genom mereka berbagi sekitar 98 persen homolog. Ukuran virus variola sekitar 300 x 250 x 200 nm dan memiliki penampilanberbentuk oval atau bata pada mikroskop elektron (lihat 19 di edisi on-line). Vaksinasi rutin warga sipil dihentikan di Amerika Serikat pada tahun 1972 dan di seluruh dunia pada 1980-an. variola mayor dan minor. Mengingat ini. virus DNAlinear.8F). menggigil. beruntai ganda dari genus Orthopoxvirus. Gejala prodromal demam tinggi 39C hingga 41C (102. . 213).Kemungkinan mengubah smallpox atau virus yang mirip secara genetikuntuk meningkatkan virulensi lebih lanjut mempertinggi kekhawatiran tentang penyalahgunaan virus ini.

Smallpox yang berubahbisa separah penyakit prodromal seperti smallpox biasa. Bentuk variola mayor lebih sering daripada variola minor. sama-sama sering terjadi pada orang yang tidak divaksinasi dan divaksinasi. Mereka yang terkena menjadi sakit parah dengan demam beracun. Anak-anak dapat mengalami kejang. Orang biasanya sakit parah dan terbaring di tempat tidur selama periode prodromal. dan orofaring yang kemudian menjadi vesikulasi dan ulserasi. Lesiurtikaria atau morbiliformis non-spesifik yang cepat hilang dapat terjadi selama prodromal.Wabah dikategorikan menjadi dua bentuk klinis. Lesi lebih sedikit jumlahnya dan cenderung tidak menjadi vesikel atau pustula. Salah satu klasifikasi membagi variola mayor menjadi lima jenis klinis. Hal ini dibagi menjadi dua bentuk.Rata-rata inkubasi adalah 12 hari untuk variola mayor dan beberapa hari lebih lama untuk variola minor.Melibatkan seluruh bagian tubuh. menjadi krusta di hari 10. Jenis variola mayor yang hemoragik. Lesi kulit mulai sebagai makula pada wajah dan ekstremitas atas yang kemudian menyebar dengan cepat ke badan dan ekstremitas bawah. lidah. Bentuk ini terjadi terutama pada orang yang divaksinasi dan tidak menyebabkan kematian. Demam berulang saat lesi menjadi pustul berbatas tegas sekitar hari 7 (Gambar. sering dengan umbilikasi. 195-2).Keropeng terpisah 3 sampai 4 minggu setelah timbulnya ruam. yang berlangsung 2 sampai 4 hari. terjadi dalam waktu 24 sampai 48 jam.Makula tumbuh menjadi papula dalam waktu 1 hari dan kemudian membentuk vesikel. variola mayor dan variola minor. 195-1) dan berlanjut sampai semua lesi telah berkulit dan berkeropeng pada hari ke 14 (Gambar. melepaskan konsentrasi tinggi partikel virus menular di sekresi pernapasan. Ini biasanya terjadi pada anak-anak dan individu yang tidak divaksinasi kurang imunitas seluler. termasuk telapak tangan dan kaki. 195-3).Demam biasanya menurun dengan munculnya ruam. namun perjalanan klinis lesi kulit dipercepat.The early form consists of Petedhiall hemorrhages into the skin or mucous membranes during the prodromal period. bekas luka (bopeng) sering tertinggal dan dapat menodai (Gbr. Lesi viral awal adalah makula merah pada mulut. Ruam kulit (exanthem) muncul dua sampai beberapa hari setelah timbulnya demam. Lesi Kulit. Massive hemorrhage from mucosal . Smallpox datar (juga disebut smallpox ganas) adalah bentuk umum dari variola mayor di mana makula nyaris mengangkat. Smallpox biasa adalah jenis yang paling umum dan menyumbang lebih dari 90 persen kasus smallpox pada individu yang tidak divaksinasi dan 70 persen pada mereka yang telah divaksinasi. Sekitar 1 hari setelah timbulnya demam. dengan semua lesi di salah satu daerah yang menunjukkan morfologi yang sama. akan ada enanthem muncul. dan pangkal paha. dini dan laten. dan sebagian besar mati dengan lesi hemoragik dan pneumomia. Fitur utama dari lesi kulit smallpoxpenonjolannyasecara perifer pada wajah dan ekstremitas dan kemajuan simultan mereka dalam pola sentrifugal. setelah 4 sampai 5 hari (lihat eFig. tingkat kekebalan. status vaksinasi. Jaringan parut ini biasanya pada wajah. di mana ada kelenjar sebasealebih banyak dan lebih besar. Setelah sembuh. pada waktu yang sama lesi mukosa berulserasi.2 dalam edisi on-line). poplitea. atau fulminan. dan status gizi.Exanthem bervariasi tergantung pada dosis virus dan strain. yang sangat rentan terhadap infeksi dan kerusakan oleh virus variola.Terjadi terutama pada individu yang sebelumnya divaksinasi di tempat vaksinasi dan daerah aksila. 195-0.

. For diagnosis. In the late form. in which vaccinated individuals come in contact vith affected individuals and develop fever and other symptoms (e. It can infect the metaphysis of growing bones and lead to arthritis in up to 2 percent of affected children. Severe thrombocytopenia occurs in both early and late hemorrhagic smallpox. blood. Molecular virologic differentiation between major and minor viral strains is now available.surfaces leads to death within 8 days of onset. the cells of the epidermisbecome vacuolated and svollen andundergo ballooning degeneration. the diagnosis of variola minor was given only after assessment of the severity of an outbreak. These vesicles have characteristic intracytoplasmic inclusion bodies called Garrier edies. The late form has a smaller degree of these coagulation disturbances Histopathology. with new epithelium growing to repair the surface. are more susceptible to this form. Cough and bronchitis may be seen in some cases of smallpox A degree of en cephalopathy often occurs. tonsillar swab. but no rash. and plasma cells Next. especially if pregnant. Mucous membrane lesions show similar changes but also have extensive necrosis of the epithelial cells leading to rapid ulceration rather than vesiculation. the lesions are non umbilicated in the pre-eradication period. histocytes. conjunctivitis. headache. the illiness |lastis 48 hours or less Serologic studies do show a rise in antibody titlers against smallpox virus' variola minor is clinically indistinguishable from cases of modified smallpoc and from cases of ordinary smallpook in which lesions are discrete rather than confluent. Skin biopsy specimens from early papirules show edema and dilation of the capillaries of the Papillary demis vith a perivascular inittate of lymphocytes. swelling of the eyelids and a mild conjunctivitis are common indings. and men and women are equally afFected. skin biopsy) should be collected by someone recently vaccinated and sent to designated high-containment facilities. *** Special Tests. scrapings of skinlesions can be examined . death occurs by 12 days after onset. In this case.g. specimens skinlesions. if the case fatality rate was low (1 percent or less). likely from disseminated intravascular coagulation. At times. with a case fatality of 100 percent women. related Physical Findings. with symptoms ranging from headache and hallucinations to delirium and psychosis Gross hematuria cancecurvith the hemorrhagic type of varioli majot' Laboratory tests the white hicell count may increase as the skin lesons ofsmalpoche come pustules. A marked decrease in the level of factorv accelerator globulin and increase in thrombin time are noted in the early form. Osteomyelitis occurs less frequently than arthritis. Pustules form with migration of polymorphonuclear cels into the vesides eventually the pustule becomes a crust. variola virus spreads via the blood to affect other non- cutaneous systems. The last type of variola major is variola sine erruption. before any appearance of the typical rash of smallpox. hemorrhage appears after onset of the typical rash.

to 2- day prodrome and with all lein a to 6 days from their initial appearance. and lesions are present at different stages varicella also has a shorter disease course. result in blindness in percent of cases. Differentalolacoss the earthern of smallpox is most often confused with that of varicells (chickenpox. The morbidiform prodromarash of smallpox can be confused with measles or coxsackievirus infections secondary syphilis should be considered. The lesions of hemorrhagic smallpox can be similar to those of meningococcemia.Externemouseumcomanosum human immunicodificiencius nacion Drugeroon | * Bullos pertigo | Pinas chanaces et actions − Fra e Henatagelects ar | ml/ reelers . It is a zoonotic disease and is not spread as easily between persons. Smallpox lesions are centrifugal with simultaneous progression of allesions.οι . this identifies the presence of a member of the genus but is noe specific for variola virus Polymerase chain reaction (PCR) methods are used to definitively identify variola virus and dan also characterize the viral strain Variola virus can be cultured in several commonly used cell lines and can be identified by the formation of characteristic pocks on chonioallamitolice membranes of chicken embryos. a eruptoi | • Vancala Disseminated use « .Druge upon Essen Manngococcam Diseminated na mascular coagullor celescore harlet-and-mouth sease . In con trast.Starsitas ini COMPLICATIONS secondary bacterial infection occurs commonly at skinlesions 5 percent of affected individuals) as well as at regional lymph nodes a temperature spike occurrings to 5 days after the start of the prodrome may indicate secondary infection keratitis and corneal ulceration common in malnourished individuals.апарева през always Rule Out Pano. but these lesions do not progress." Human monkeypoor clinically resembles smallpox but often manifests lymphadenopathy. Either variola virus or . the vesicles are more superficial. severe acute leukemia. Prodomainterto . Other eruptions in the differential diagnosis are listed in to . மம 1951 Diferenta Dagross of Smallipo and Monkeypox Most likely Pano. varicella lesions have a more truncal centripetal distribution.via electron microscopy to assess for the typical oval or brickshape of or thopoxviruses serologic testing for or thopoxviruses with paired samples can be performed. with only a 1. and other acute hemorrhagic eruptions such as those associated with coagulopathies. especially when there are lesions on the Palms and soles. a eruptoi * Secoоагувph= Hemorrhagesossmallpoon Accredicoagulo Μι .apara itu --.Steve en are are .

" Vaccination does not give lifelong immunity. Atlanta. This process of variolation did reduce morbid ity and mortality but also caused full in fection and spread in some cases. There is no specific treatment for smallpox a patient suspected of having the disease should be isolated in a negative-pressure room and given supportive care. including pneumonia.bacterial superinfection can lead to respiratory complications. Death often occurs between days 10 and 16 of illness. is associated with a mortality rate ranging from less than 10 percent when lesions are discrete to 50 percent to 75 percent when lesions are confluent. including bone shortening sublueation. PREVENTION Because of the development of lifelong immunity after recovery from natural smallpox infection. In 1796. The duration and degree of protection over time are subjects of debate. fait smalpox has a case fatality rate of over 90 percent. Encephalitis is an important factor in death from variola minor but not from variola major *** TREATMENT. Both arthritis and osteomyelitis can lead to limb deformties. smallpox vaccination within2 to 3 days of exposure can protect against se vere disease. Vaccination within 4 to 5 days may protect against death. GA through an Investigational New Drug protocol. Edvard Jenner developed viaccination. Orchitis is less common and usually unilateral Encephalies is reported in 0. a nucleotide analog approved for treatment of cytomegalovirus infection. at day 8 to 10 of illness. is available from the Centers for Disease Control and Prevention (CDC. vaccinia. using the cowpox virus to introl duce cross-immunity against the variola virus vaccinia virus later became the wirus used vaccination is 90 percent to 9 percent effective in preventing smallpox disease when given before exposure to variola virus For post-exposure prophy laxis. and hemorrhagic forms have nearly 100 percent mortality. Precautions should be taken to prevent secondary infection and appropriate antibiotics administered should it occur. but clinical data are not yet available Topical idoxuridine may be used to treat corneatlesions. although its efficacy has not been proven. Modified smallpox is associated with less than 10 percent mortality incontrast. common smallpox.2 percent of cases prognossano Clinical course the most common form of variola major. The overall montality rate for variola major is 30 percent compared to less than percent for variola minor. and laid joints. and other orthopoxviruses in in vitro and animal studies. the first efforts at prevention were to introduce crusts or fluid from lesions to unaffected individuals to induce mild disease. Dr. It has been found to have activity against variola. Most estimates suggest that primary vaccination gives full protection for 3 to 5 years and some but declining immunity at 10 years and after Revaccina tion may give protection for at least 30 years' . Those who survive either disease have lifetime immunity Death from smallpox is thought to be secondary to toxemia associated with immune complexes and variola antigens along with hypotension shock and mutiorean failure. Research on antiviral agents is ongoing Intravenous cidofovir. however.

with the less pathogenic New York City Board of Health and Lister- Elstreestrains being used during che globalsmall pox eradication campaign. calflymph vaccine (Dryvax. In the nineteenth century. CLICAL FINDINGS history. Most adverse events can occur at any age. either by transfer or a hostinability to contain the response. camelpox. it replaced cowpox as the virus for smal poxvaccination. Routine vaccination of civilians was discontinued in the United States in 1972 and worldwide in the 1980s. with the Postal anthrax and world Trade Center attacks in 2001 and other threats of bioterorism. PA) produced from the New York City Board of Health vaccinia strain after injection of vaccine into the skin by a bifurcated needlesee 1931 in on-line edition. the virus rapidly multiplies locally and occasionally in regionallymph nodes viable. transmissible vaccinia virus is present at the resulting skin lesion until the lesion scabs and separates. and cowpox. Marietta." EPIDEMIOLOGY Eradication of smalpox was made possible by intensive tracking of cases of infection with ring vaccination of primary and secondary contacts The last known case of natural infection was one of variola minor in Somalia in 1977. because it is not known to cause natural infection. Soreness is almost universal at the vaccination site . from contacts more often than from direct vaccination.Vaccinia and Smallpox Vaccination The vaccinia virus is also of the genus Orthopoxvirus. Because of its significant homology with other poevilruses vaccinia virus provides not only protection against smallpox but also cross-protection against closely related orthopoxviruses such as monkeypox.S. but given that vaccinia is a live virus. Its origins are unknown. One final case of accidentallabor ratory infection occurred in 1978. it does carry its own set of adverse effects. Adverse events and complications occur when the virus spreads outside of the local area. There are many strains of the virus. and the World Health Organization declared eradication in 1980. Discussion here focuses on its features as the smallpox vaccine. military personnel ceased in 1990. but it is most similar to the cowpoxvirus in this family. eczema vaccinatum. The currently licensed vaccine in the United States is a yophilized.' EtOLOGY AND PATHOGENESIs smallpox vaccination involves the introduction of vaccinia virus into the outer layers of the intact skin. It is usually limited by the host response with the development of antibody and cell-mediated immunity. vaccination of U. Wyeth Laboratories. but infants and children younger than the age of 5 years are particularly affected Adverse reactions are 10 times more common in primary vaccination than in revaccination individuals with atopic dermatitis can ac quire a severe eruption. vaccination was reinitiated in the United States in late 2002 for the military and a small group of voluntary public health and health care workers who would be first-line responders in a possible outbreak vaccination made eradication of smallFox possible. The infection heals with scarring at the injection site.

7°C 99. Those with substantial residual immunity may have only erythem with revaccination.三프 se 1904 Smallpox Vaccination . They generally peak at days 8 to 10 and last to 3 days. Minor local reactions that can occur near the primary site include nearby satellite lesions that progress at the same rate.Primary Response Multiple Pressure . more common in children. but it occurs 8 to 10 days after vaccination and self-improves without antibiotic therapy in 24 tio. in which the local reaction is 10 centimeters or larger in diameter. headsche myalgas and malsise. and intense surrounding erythema or edema vaccinia dan be indvertently inoculated into other body sitessee in online edition. occurs in 2 percent to 16 percent of first-time viaccinees (see –Fi.systemic symptoms can occur and are considered normal reactions. Adverse reactions. with the scab detaching at day 17 to 21 and leaving a residual scari is a robust take. Previously vaccinated individuals have a milder reaction with an accelerated time course. 9-4 in om-line edition. Approximately 30 percent of vaccinees feel todo il to carry out normal activities Cutaneous lesians. The normal local skin reaction to vaccination begins 3 to 5 days after administration with a rapule that then develops into a vesicle Jennerian vesicle followed by apustule around day 7 to 9. These include fever higher than 37. usually by staphylococci and group a streptococci. This can be mistaken for bacterial cellulits. . can occur at the primary site. lymphadencopathyymphangitis.Patient AA009 Day 0 Day 4 Day 7 Day 14 S LLLL 000S0 LL LL LLL LLSLLLL LLS LL LLL LLLL L LLLLL LL LLLLLL LL LSL LLSLSS L L L L L L L L L L L LS usually occur within the first 5 days or 30 days after vaccination. chills. adverse cutaneous reactions associated vich smallipox viaccination can be localized or generalized secondary bacterial infection. secondary bacterial infections 1903 초 = . 72 hours* lin contrast.9°F). It crusts and scabs over at day 10 to 14. and secondary reactions such as e ima multiforme can occur (see his in on-line edition) (see next section.

the most serious cases result in substantial loss of the skin barrier. It is thought be caused by spread of vaccinia virus via the bloodstream and usually occurses to 9 days after primary vaccination. GA. The individual feels ill with fever. also called ui nerosa and vain ansa. and genitalia lesions are seen at these areas to 10 days after vaccination. keratitis. nose. Generalized adverse eruptions can be non- specific. including morbilliform and roseola-like rashes. Hypersensitivity reactions such ss erythema multiforme an als develop (see — 19-4 in on-line edition). immune-mediated reactions. and they usually follow the time course of the original primary leson. malaise. In these individuals.Accidental vaccinia is the autoinoculation of vaccinia virus from the vaccination site to another area. and/or viscera. papular." Accidental inoculation to the eyes can lead to conjunctivitis. The severity of eczema vaccinatum is independent of the severity or activity of the atopic demaritis or other underlying skin disease. Papules. but cases have also been described in those with humoral defects. These rashes typically self-resolve over several days. and lymphadenopathy. The most common sites of transfer are the eyelids (see his 1942 in on-line edition). and contributed . or. the primary lesion at the site of vaccination does not heal but instead enlarges and progresses to a painless ulcer with central necross (see 11 in on-line edition) viral replication is not halted and virenia ccurs with similar metastatic lesions developing at distant sites on the skin. usually by children in contact with a recently vaccinated family members) Vaccination of individuals with sewere impairment of the immune system leads to progressive vaccinia. oririts. From the Centers for Disease Control and Preventon Public health image Library Atlanta. Most cases have occurred in individuals with defective cell-mediated immunity. pustules. other chronic dematoses. In rare cases StevensJohnson syndrome dan develop and requite hospitalization and supportive are vaccination can also lead to generalized vaccinia in which macular. The condition is self-limited in immunocompetent individuals but is often more severe in the setting of immunodeficiency *** Earlema vaccinatum is the localized or generalized spread of vaccinia virus in individuals affected with atopie dermaritis or less frequently. or vesicles can occur anywhere on the body but have a predilection for areas with prior lesions of atopic dematitis lesions can range from several to hundreds. bone. but the precise protective level is figure 195-5 Generalled acclaimanmonth-octant. Generalized vaccinia can be limited or extensive and can occur anywhere on the body ( 1955). It is the most common adverse event seen and accounts for about half of all such events. Thellesions progres as do other vaccinial lesons. The degree of immune impairment may correlate with the risk for development of progresive vaccinia. mouth. It can occur in the primary vaccinee with onset usually at the same time corsoon after the appearance of Illesons at the vaccination site. less commonly vesicular lesions can be disseminated to normal skin without evidence of autoinoculation. The lesions may be more attenuated if autoinoculation occus more than 5 days after vaccinations the host immune response is developing. It can also be acquired by secondary transmisson.

eczema vacciniatum. Individual vith postvacinal encephalopathy. vaccinia. fected by smallpox vaccination Central nervous system complications occur in previously helichy individual. spinal cord signs. mmunization Branch|| Related physical Findings. and polyneuritis. Postvaco cinial en cephalopathy most commonly affects children younger than 2 years of age.by Allen W. malaise. but one-fourth of survivors are left with residual sequelze (mental impaiment. and progress complications vaccina certies can cause corneal ulceration with scarring and visual loss Ecrema vaccinatum can be so severe that the affected individual loses a substantial amount of the cutaneous barrier much like a burn victim. or encephalomyelitis may recover in approximately 2 weeks. Higher rates of central nervous system complications are seen with non-New York City Board of Health vaccinia strains. vomiting. Postvaccinalencephalitis and encephalomyelitis occur 11 to 15 days after vaccination. aphasia. hemiplegia. In addition to the skin. and headache that progress to confuson. vhich su gestis but does not prove causality. seizures. other organ systems can be af. encephalits. les consin a = 0 acters diomyopathy conditions are caused by smal poxvaccination orare coincidental occurrences is not yet clear LABORATORY TESTS Neutralizing antibodies and cellular immunity start to become detectable around day7 ofvaccination vaccinia virus can be detected at the primary vaccination site and sites of accidental vaccinia. including myopercarditis. These complications are thought to be autoimmune reactions. but causality has not been established Cardiac events. of the California Emergency Preparades Otca. generalized viaccinia. and placental the appearance can be similar to that of generalited vaccinia or progressive vaccinia. 1 in on-line edition. or conszemi tali. paralysis) * smallpox vaccination of a woman during pregnancy can rarely lead to fetali. seizures. The rate of myopericarditis among US military vaccinees is ellewated 35-fold compared to the rate in unvaicinated personnel. causing cerebral edema without in flammation symptoms develop abruptly 6 to 10 days after vaccination and can include fever. seizures. and coma. and transient amnesia. Other neurologic events reported to occur in temporal association with smallpox vaccination include transverse myelits.* Whether the ischemic and dilated car FIGURE 195-6 m ac calmuth. can also occur since reinitiation of smallpox vaccination in the United States in 2002 schemic cardiac events as well as nomischemic dilated cardiomyopathy have been reported for the first time. headache. paralysis. It is unknown whether infection is through . because vaccinia virus is not found in sampled cerebrospinal fluid or tissue. with about 50 cases reported in the literature Transmission to the fetus can occur at any time during the pregnancy and results in lesions on the skin mucous membranes. MD. starties. and lesions can be extensive (see e. with fever. amnesia.

but if it is severe. lymphangitis. and postvaccinial centralnervous system disease Progres sive vaccinia i universally fatal fun treated Central nervous system complications have a 15 percent to 25 percent case fatality rate. because it can cause a reversible superficial punctate keratopathy. Generalized vaccinia usually requires only symptomatic treatment. Given the rarity offetal viaccinia. Fetal viaccinia often results in fetal or neonatal death My opercarditis was reported in the pre-eradication era and was thought to cause the rare cases of cardisc- associated deaths after vaccination. inadvertent vaccination during pregnancy is not ordinarily a reason for termination there is also no indication for prophylactic administration of wo to the pregnant woman. VC an exacerbate vaccinia keratitis and should not be used in cases of isolated keratitis. Triuridine eye drops can be tried. but it might be considered for a viable infant born with vacciniesions *** . No reliable intrauterine diagnostic test exists to confirm fetal infection prognossanoclinical course Potentially fatal adverse reactions from smallpox vaccination include eczema vaccinatum. Most fatal cases from secondary transmission occur in infants younger than year of age and are from contacteczemia vaccinatum. It has also been reported since reinstitution of vaccination in the United States in 2002. but there are no clinical data regarding successful treatment. such as in those with immunodeficiency VIG may be of benefit with severe eczema vacciniatum in which there is significant loss of the skin barniet meticulousskineare with volume and electrolyte repletion is needed. but no deaths have occurred to date severalischemic cardiac deaths have occurred TREATMENT symptomatic treatmentalone is needed for the normal systemic symptoms and minor local events robust take. Un complicated cases of accidental vaccinia do not require therapy. Extensive cases on be treated by administration ofovacdinia imune globulin V10 orcidofovir to speed recovery VIG is a sterile solution of the immunoglobulin fraction of plasma from persons vaccinated with the smallpox vaccinia vaccine Topical antiviral medications can be used in moderate to severe cases of ocular vaccinia. Widarabine ointment has been effective in the past. but supplies are likely very limited because it is no longer manufactured. Early trement with Vig has ben shown to reduce mortality from eczema vaccinatum (fatality rate was reduced From 30 percent to 40 percent to 7 percent VIG administration and are in 1905 1906 an intensive care unit also reduced the case fatality rate of progressive vaccinia from too percent to 20 percent to so percent Treatment for neurologic complications is supportive care. there SS S LLLLL LLLL LS S SSS S LLL L LSL LSL S the cases. It should not beadministered for konger than 14 days. progressive vaccinia. intense erythema or edema) occur after vaccination secondary infections should be treated with appropriate antimicrobaltherap.the blood or by direct contact with inFected amniotic fluid.

the . There are no absolute contraindications to vaccination should un actual outbreak occur. however. More detalled guidelines are available from the cool safer vaccines are under research and development to preven the adverse ef fects and complications of mal po viaccination issue and cell-culture vaccines. ef hay gainst actual diseuse. hove. etc. smallpox vaccination in the United states is currently limited to the select groups discussed earlier (see Epidemiology. Frederick.cephalitic and cardiac reactions because they are similar in immunogenicity to Dryva. MD. they are not necessar ily safer with regard to vaccina-associstedadverse events" a second strategy is the development of vaccines using strains of vaccinia at tenuated by serial passage through nonhuman tissue. By in creasin purity and reducing contamin tion. are in clinical trial Produc tion involves the sterile growth of cell lines that host the vaccinia virus. with passage of the lister vaccinia strain through rabbit kidney cells studies in lapan in the 1960s and 1970s foundit to haveles local and systemie reatogenicity but similar protective immunity to conventional smallpox vaccines. The Clems vaccine also uses an attenuated vaccinia strain. The modified vaccinia ankara strain is produced by pessage through ehek embro hibriohas no significant complications were reported with its use in Germany and turkey in the 1970s to help people at high risk for side effects (such as these with atopic demartisecrema. and p-i-. This leads to a reduced capacity for replication and potentially vaccination Against Smallpousing Woma V ots --------. durina re commodation hereanada elease | (non heart d = or sur le a racters Se tipo autonomy to charters Agungariano Prancourtean these | clased an actuals malo outurak reduced adverse effects. tolerate the standardsmallpox vaccine. these vaccines may help avoid the alerec and autoimmune reactions thought toistem from the nominaccinia materian callymph vaccines these reactions in dude hypersensitivity reations eryehema multifarre.LLLLLL LLLLL S SS S S S S S S S S be covered with gauze and an overlying semi- permeable membrane bandage Taking contact precautions and washing the hands frequently when caring for the site should be emphasized a higher proportion of persons are at risk for adverse vaccine reactions today than during the era of routine smallpox vaccination atopic dermatitis as well as immunocompromise have increased in prevalence to reduce the incidence of adverse events. further clinical study of modified vaccinia ankara and Leleims vaccines is under vay" Finally. Ma and cellcultured smallpox vaccine (Dymfort. advances in modemme lecular immunology have introduced the idea of subunit vaccines with . was never proven.Post pour unhas aaster a ATS as the release the | suppression. including AC AM 1000 and ACAM2000 acambis. Cuimrent nec ommendations and contraindications in the absence of a known exposure risk te listed in . Cambridge.

where . These are underlaboratory investigationa fu tur c id Monkeypox In contrast to smallpox. but usually in a limited manmet Outbreaksinthe Democratic Republic of the Congo in 1996 to 1997 showed sustained human-to-human transmission for the first time this may reflect decreased immunity with the discontinuation of smallpox vaccination in spring 2003. a zoomotic virus Like varola and viaccinia viruses. chimpanzees. which was described in writing as far back as so al moneypoincisamore recentrecinited disease it was first identified in 1958 as an illness of cynomalous mankeys. when an illness similar to smallpox was noted after etadation of the latter." In addition to humans hosts for monkeypox include cynomous and other monkeys. guinea pigs. however etology and pathoceness Monkeypor is caused by the monkeypoxvirus. It is endemic in the rain forest countries of central and west africal cecurring in sporade outbreaks the maority of cases are in children. a laboratory confirmed. then is rapidly transported to regonal lymph nodes. and nonprimate animals such as rabbits. All cases are thought to be sociated with contact with lipet prarie dogs previously housed with African rodents imported from Ghana The longest documented chain of per son-to-person transmission is eighteenerations. mice. it is also of the genus or thopoxvirus and hans un oval or brek shape om electron mer-py The monkeypox viral genome is is percent identical to that of the variola virus at the central region which encodes essential enzymes and structural proteins the end regions that encode virulence and host-range factors are substantially different. which suggests that monkeyrea has little rential for the type of epidemic spread seen with smallpox fossible genetic alteration to produce greater virulence or transmissibility is a concern. and the range af heats for the monkeypox virus is much wider than that for variola virus. EpioEMIOLOGY Human monkeypo is a disease acquired mainly from infected animals. The virus multiplies locally at the site of injury. orangutans). gorrillas. monkeypad has presumably caused illness for thousands for years. Despite its recent recognition.genes or proteins from vaccinia virus. Transmission is mainly during handling of infected animals or contact with the animals body fluids Person-toperson spread via respiratory dreplets and close contact can occur as with smallpox. hence its name Monkeypox was first documented to cause human illness in 1970 in Zaire the present Democratic Republic of the Congo). and giant anteaters. the first cases of human monkeyrock in the western hemisphere occurred in the Midwest region of the United states (72 reported cases. other primates apes. The natural reservoir is unknown but is thought to be wild redents such as the squirrel Monkeypox is mainly transmitted through abraded skin after a bite or scratch from an infected animal or by contact with their infected body fluids.

dengan penyebaran lesi secara sentrifugal dan menjadi generalisata. hanya satu kasus.3 dan 195-6. krusta. LESI KULIT Biasanya 1 sampai 3 hari setelah timbulnya demam. ruam berkembang. Kebingungan dan kejang jarang terjadi. . Hal ini mungkin mencerminkan infeksi dengan strain virus yang kurang ganas dari yang di Afrika TEMUAN FISIK TERKAIT Limfadenopat secara signifikan berkembang 1-2 hari sebelum timbul ruam. Kemudian berkembang lebih dari 14 sampai 21 hari menjadi vesikel dan pustula yang mengalami umbilikasi. Dispigmentasi dan parut yang cekung bisa dihasilkan. Gejala prodromal berupa demam. berlangsung 2 sampai 3 hari. Umumnya. servikal atau daerah inguinal (gambar 195-8). Tidak ada bentuk hemoragik dari monkeypox seperti smallpox telah dijelaskan pada manusia. dan sesak napas. dan deskuamasi (lihat gambar 195-6. Konjungtivitis dan keratitis mungkin terjadi. Dalam wabah di Amerika Serikat. dan tingkat nitrogen urea darah rendah sering terlihat. Limfositosis dan trombositopenia terjadi dengan frekuensi yang kecil.multiplication continues. Lesi monkeypox dapat melibatkan membran mukosa mulut dan alat kelamin. erupsi dimulai pada wajah dan / atau tubuh. awalnya terdiri dari makula dan papula monomorfik. Invasion of the bloodstream disseminates the virus to distant sites.1 dalam edisi online). Beberapa individu mengalami sakit tenggorokan. gejala bermanifestasi 10 sampai 14 hari setelah masa inkubasi. terutama pada tangan terkait dengan kontak langsung dengan hewan yang terinfeksi dan (gambar 195-7 dan lihat gambar 195-7. tingkat transaminase meningkat. menggigil. Individu lainnya yang terkena hanya lesi lokalisata. malaise. The monkeypox virus is also transmissible from person to person via aerosalization of the virus or contact with lesions or body fluids during the first week of the rash. memiliki ruam generalisata segencar yang terlihat dalam kasus-kasus di Afrika. batuk. biasanya pada submandibular. sakit kepala. PEMERIKSAAN LABORATORIUM Leukositosis. mialgia. Diare dan sakit perut juga dilaporkan. dan nyeri punggung bisa terjadi. Mereka dengan penyakit.4 pada edisi online). It may rarely be transmitted by contaminated formites TEMUAN KLINIS SEJARAH kasus sub-klinis monkeypoX bisa terjadi pada individu dengan dan tanpa vaksinasi smallpox sebelumnya. seorang anak.

Tes untuk antibodi spesifik terhadap monkeypox dapat membedakannya dari poxvirus lainnya. Ada edema papil di lapisan dermal yang serupa. termasuk jaringan parut dengan lesi kornea. TES KHUSUS Mikroskopis elektron dari bahan scabs atau cairan dari lesi kulit dapat digunakan untuk menentukan adanya suatu Orthopoxvirus. dengan lesi pleomorfik dan distribusi yang sentripetal. . dapat menghasilkan lesi kulit serupa tetapi lokalisata. Isolasi virus pada kultur sel mamalia dan karakterisasi dengan PCR dan pengurutan secara definitif dapat mengidentifikasi virus monkeypox. dan degenerasi keratinosit ballooning (gambar. eczema herpeticum. Hal ini mungkin diperparah dengan gizi buruk dan tidak dapat diaksesnya perawatan medis. rentang mortalitas dari 1%-10 % dan sebagian besar terjadi pada anak- anak. KOMPLIKASI Infeksi sekunder kulit dan jaringan lunak mungkin terjadi (sekitar 20% dari kasus). Varicella memiliki gejala prodromal virus yang lebih ringan dan lebih sebentar. Di Afrika. dan komplikasi okular. 195-9). PROGNOSIS DAN PERJALANAN KLINIS Jaringan parut yang ditinggalkan oleh ruam mungkin membaik seiring waktu. Diagnosa banding yang lain adalah erupsi obat. Sitoplasma eosinofilik inclusion bodies (Guamier bodies) juga terlihat (lihat gambar 195-9. Kematian umumnya pada minggu kedua dari penyakit dan merupakan superinfeksi sekunder bakteri. limfadenopati adalah ciri khas utama dari monkeypox yang biasanya tidak terlihat pada monkeypox. Semua individu yang terkena pulih tanpa kematian selama wabah di Amerika Serikat pada 2003.individu yang terkena mungkin juga terjadi pneumonitis (12 persen) ensefalitis (kurang dari 1 persen). Orang dengan infeksi human immunodeficiency virus dapat menjadi lesi moluskum luas yang dapat terlihat serupa. komplikasi gastrointestinal atau complikasi pulmonar. Hal ini diamati pada 90 persen kasus di mana individu tidak pernah menerima vaksin smallpox dan sekitar 53 persen dari mereka sudah tervaksinasi. peradangan akut.HISTOPATOLOGI Pada pemeriksaan spesimen biopsi kulit ciri-cirinya tidak bisa dibedakan dari smallpox. dan rickettsialpox (lihat tabel 195-1). Limfadenopati juga jarang terjadi dengan varicella. DIAGNOSA BANDING Ciri-ciri dari monkeypox secara klinis mirip tapi tidak separah smallpox biasa (variola mayor).1 pada edisi online). disebabkan oleh poxvirus dari genus Parapoxviridae. Stomatitis orf dan bovin. tetapi tidak dapat membedakan antara mereka. Virus Monkeypox tumbuh dengan baik dalam sel RK13 dan menyebabkan pocks dalam membran korioalantois pada 39C (102 F). Nekrosis fokal mungkin terjadi.

namun disarankan bagi mereka yang dalam waktu 4 hari dari kontak langsung dengan virus monkeypox dan harus dipertimbangkan sampai 14 hari setelah paparan. . vaksinasi terhadap Human Monkevpox menggunakan virus accinia indikasi  vaksinasi pre-exposure untuk peneliti binatang atau kasus human monkeypox dan petugas kesehatan yang merawat dan berkontak dekat dengan pasien monkeypox. PENCEGAHAN Eradikasi global nonkeypox lebih sulit daripada eradikasi cacar. namun belum ada data mengenai manfaat secara klinis pada manusia. termasuk pada anak-anak di bawah usia 12 bulan. Pengamatan kasus di Afrika menunjukkan 85 persen perlindungan terhadap monkeypox. Vaksinasi dengan calf-lymph derived smallpox vaccines terbaru (vaccinia virus) telah ditemukan efektif dalam mencegah human monkeypox. Pemberian VIG juga bisa dipertimbangkan pada kasus berat. Mereka dengan sistem kekebalan yang terganggu atau alergi yang mengancam nyawa terhadap lateks atau komponen vaksin tidak boleh menerima vaksin Dryvax meskipun terpapar oleh monkeypox. Cidofovir dapat dipertimbangkan untuk kasus yang berat. namun VIG dapat dipertimbangkan untuk profilaksis post-exposure. Pengobatan simptomatik harus diberikan. dan orang-orang dengan keadaan kulit tertentu. karena berbagai host untuk virus monkeypox memungkinkan untuk mempertahankan reservoir binatang sementara secara sporadis menyebabkan penyakit pada manusia. asalkan mereka tidak memiliki kontraindikasi untuk vaksinasi cacar (tabel 195-3). Vaksin smallpox yang lebih baru masih dalam penelitian dan pengembangan juga sedang dipelajari manfaatnya terhadap virus monkeypox dan di masa yang akan datang bisa mencegah human monkeypox dengan efek samping yang lebih sedikit.PENGOBATAN Tidak ada pengobatan khusus untuk monkeypox. Peran vaksinasi post- exposure kurang jelas. wanita hamil. Kasus monkeypox lebih ringan dan bahkan sub-klinis ketika mereka terjadi pada orang yang divaksinasi CDC saat ini merekomendasikan vaksinasi pre-exposure untuk peneliti hewan atau kasus human monkeypox dan petugas kesehatan yang merawat atau berada dalam kontak dekat dengan pasien monkeypox. namun manfaatnya belum diketahui.

termasuk HIV/AIDS. terjadi di seluruh dunia namun biasanya hanya terjadi pada individu yang berkontak dekat dengan sapi. imunodefisiensi selular akuisita dan herediter. Tidak ada kasus secara alamiah transmisi dari manusia ke manusia yang pernah dilaporkan. Usia lebih muda dari 12 bulan 6. streptomycin. dan penyakit autoimun yang berat 3. streptomycin. . dokter hewan. hanya pada kasus transmisi percobaan di laboratorium.  Vaksinasi post-exposure untuk mereka yang selama 4 hari terpapar langsung dengan virus monkeypox.sebagian besar kasus adalah sporadik namun sebagian kecil epidemik pernah dilaporkan. anggota genus Parapacirile cenderung menyebabkan penyakit lokalisata pada individu yang sehat. Ini merupakan penyakit akibat kerja dari pemerah susu. Sebagian besar kasus baru terjadi pada pemerah susu yang baru bekerja karena belum terbentuk imunitas. termasuk infeksi HIV/AIDS. Kehamilan atau menyusui  Kontraindikasi pada keadaan post-exposure 1. Alergi serius terhadap komponen pengencer vaksin (polymyxin. harus dipertimbangkan sampai dengan 14 hari setelah terpapar Kontraindikasi  Kontraindikasi pada keadaan pre-exposure 1. Penyakit jantung yang diketahui atau faktor risiko kardio yang signifikan 4. Muncul dermatitis atopik atau erupsi kulit lainnya dengan gangguan sawar kulit 2. NODUL MIKER epidemiologi nodul mikker juga disebut paravaccinia dan pseudocowpox. chlortetracycline) 5. Imunosupresi. dan penyakit autoimun yang berat 2. imunodefisiensi selular akuisita dan herediter. Imunosupresi. dan pekerja di industri daging. chlortetracycline) INFEKSI VIRUS PARAPOX Tidak seperti orthopoxviruses. Alergi serius terhadap komponen pengencer vaksin (polymyxin. neomycin. neomycin.