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The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.
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PMID:Smallpox vaccination and adverse reactions. Guidance for clinicians. 1261 10

Japanese encephalitis (JE) is numerically one of the most important causes of viral encephalitis worldwide, with an estimated 50,000 cases and 15,000 deaths annually. About one-third of patients die and half of the survivors have severe neuropsychiatric sequelae. Three hundred patients clinically suspected of JE were tested in the present study. Laboratory confirmation of JE was on the basis of detection of antigen or presence of JE-specific IgM antibody and/or neutralizing antibody in a single CSF sample. The risk factors that were associated with fatal outcome were determined. Japanese encephalitis infection was confirmed in 70.7 per cent (212/300) of the patients. All patients were from rural areas and with low socioeconomic background. Prominent clinical findings were: fever in 100 per cent (212/212) patients, altered sensorium in 87.73 per cent (186/212), convulsion in 85.84 per cent (182/212), headache in 50 per cent (106/212), and vomiting in 47.64 per cent (101/212). The final clinical outcome was available for only 68.39 per cent (145/212) of patients, as children were taken home against medical advice. Of these, 35.86 per cent (52) died while 63.44 per cent (92) of patients survived. Correlations of investigative findings with the final outcome revealed that absence of virus-specific IgM and neutralizing antibodies in CSF were associated with fatal outcome. In patients diagnosed with Japanese encephalitis the presence of a virus-specific immune response is associated with a favourable outcome and an important parameter in recovery from illness.
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PMID:Japanese encephalitis in and around Pondicherry, South India: a clinical appraisal and prognostic indicators for the outcome. 1263 Jul 21

The December 2002 COM. A 19-year-old healthy male fell into stagnant water of the intercostal waterway (salt water of South Florida), following a jet ski accident. He sustained minor superficial injuries but engulfed significant quantities of water and sediment. A few days later he developed bifrontal headaches, vomiting, a stiff neck and a temperature of 102 degrees F. A CT scan on admission without contrast was negative. The CSF had markedly elevated white count but bacterial and fungal cultures were negative. He became progressively lethargic. On the fifth day he developed seizure activity. He expired the next day despite antibiotics. Gross examination of the brain at autopsy revealed edema, cerebellar tonsillar herniation and purulent meningitis. Microscopic examination revealed a massive leptomeningeal inflammatory infiltrate composed of neutrophils, lymphocytes, and numerous histiocyte-like cells. The inflammatory infiltrate extended into the cerebral parenchyma in numerous areas also involving the cerebellum, brainstem and ventricular system. Given the exposure to stagnant water (later confirmed to be a man-made fresh water lake), and the numerous histiocytic-like cells, suspicion for an amebic etiology of the disease process was raised and the CDC identified the ameba as Naegleria Fowleri. Infection by Naegleria Fowleri, a free-living ameba, occurs after exposure to polluted water in man-made fresh water lakes, ponds, swimming pools, particularly during the warm weather months when the thermophilic ameba grows well. The pathologic substrate of the infection is an acute hemorrhagic, necrotizing meningo-encephalitis mainly at the base of the brain, brainstem and cerebellum occurring in young, healthy individuals.
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PMID:December 2002: 19-year old male with febrile illness after jet ski accident. 1274 79

Clinical data adequate for analysis were available in 386 laboratory-confirmed cases of arthropod-borne encephalitis - 38 St. Louis and 348 western equine. Consistently observed symptoms varied with the age of the patient. Symptoms that occurred in a high proportion of patients in each age group were:LESS THAN ONE YEAR OF AGE: Fever and convulsions. (None had the St. Louis disease.)ONE THROUGH FOUR YEARS: Fever, headache, vomiting, drowsiness, irritability, restlessness, nuchal rigidity, tremor, and sometimes convulsions. FIVE THROUGH FOURTEEN YEARS: Headache, fever, and drowsiness. Sometimes the disease progressed no further, but if it did, nausea, vomiting, muscular pain, photophobia and limitation of neck and back flexion often were noted; and sometimes convulsions and intention tremors. FIFTEEN YEARS AND OLDER: Drowsiness, lethargy, malaise, fever, stiffness at the back of the neck and, almost always, severe intractable occipital headache associated with nausea, disturbance of vision, photophobia and vertigo. The extreme difficulty of differential diagnosis on the basis of clinical observation was indicated by the wide range of diagnoses made in these cases before the invading organism was identified by laboratory studies.
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PMID:The 1952 outbreak of encephalitis in California; differential diagnosis. 1306 16

We describe a case of Acanthamoeba encephalitis in a 45-year-old Caucasian male with acute myelogenous leukemia, who was 140 days status post partially mismatched related donor peripheral blood stem cell transplant. The patient had been transplanted with a highly T-cell-depleted graft, and was not taking any immunosuppressive drugs, and had no history of graft-versus-host disease. He complained of nausea, vomiting, and occasional episodes of confusion; he also had a chronic cough since transplantation. Physical examination was unremarkable except for orthostatic hypotension. Neurologic examination was within normal limits. Laboratory values including electrolytes, white blood cells and platelet counts were normal. Computed tomographic scan of the brain showed a pansinusitis and a hyperdense lesion along the corona radiata suggestive of a fungal abscess. Magnetic resonance imaging showed multifocal areas with mass effect in the posterior fossa and parietal and occipital lobes. The patient had worsening respiratory failure and died three days after admission. At autopsy, specific immunofluorescent staining identified Acanthamoeba castellani in the brain and lungs.
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PMID:Acanthamoeba castellani encephalitis following partially mismatched related donor peripheral stem cell transplantation. 1498 4

Autonomic seizures and autonomic status epilepticus in children have a high prevalence, manifest with dramatic clinical symptoms, and have important clinical and management implications. They probably affect approximately 13% of children aged 3-6 years with one or more nonfebrile seizures, or 6% in the age group 1-15. The primary cause is an idiopathic age-dependent epileptogenic susceptibility (Panayiotopoulos syndrome), but 10-20% are due to cerebral pathology. Autonomic seizures and autonomic status epilepticus have been best studied in Panayiotopoulos syndrome, which has been confirmed worldwide in more than 800 cases and recently recognized in the new classification scheme of the International League Against Epilepsy. Seizures start with autonomic symptoms, mainly emesis, while the child is usually fully conscious. Other more conventional seizure manifestations often ensue, but autonomic manifestations commonly predominate to the end of the seizure. Ictal syncope (transient loss of consciousness and postural tone) is an intriguing common symptom. Half of the seizures last longer than 30 minutes, constituting autonomic status epilepticus. Prognosis is invariably excellent except for the symptomatic cases. The interictal EEG shows great variability from normal to severely epileptogenic, often with multifocal spikes. Pathophysiology of Panayiotopoulos syndrome is unknown, but it is likely that they are due to diffuse maturation-related epileptogenicity activating susceptible-for-children emetic centers and the hypothalamus. Thus, Panayiotopoulos syndrome is not occipital epilepsy, with which it is often erroneously equated. Autonomic seizures and autonomic status epilepticus are frequently misdiagnosed and often treated as encephalitis, atypical migraine, cardiogenic syncope, or other unrelated medical conditions such as gastroenteritis. This review examines the existing evidence, provides a means of improving diagnostic yield, and proposes practice parameters and guidelines for the diagnosis and management of autonomic seizures and autonomic status epilepticus in children.
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PMID:Autonomic seizures and autonomic status epilepticus peculiar to childhood: diagnosis and management. 1514 96

Significant mortality, high incidences of complications and permanent neurological sequel are still noted in patients suffering fro herpetic encephalitis. They result mainly from delayed diagnosis and treatment of the specific cause. The aim of our paper was the analysis o a clinical course of patients with Herpes simplex encephalitis. From 1999 to 2001 7 patients aged 2 weeks to 15 years, treated in Children' Neurology Department of Silesian School of Medicine, were diagnosed to have herpetic encephalitis. Fever, headache, vomiting, as well as alteration of consciousness, all typical for neuroinfection were main clinical symptoms present on admission. Three children presented with respiratory distress requiring admission to Intensive Care Unit. On examination "cold sores" were found in 2 patients, in remaining 5 the history of exposition to herpes labialis was obtained. On neurological examination we found either right or left hemiparesis in all patients, motor aphasia in 2 and left sided central facial nerve palsy in 1. Lumbar puncture revealed lymphocytosis in 5 patients. Anti-HSV type IgG an IgM antibodies were found in serum of all 6 patients, while only in 2 of them were detected in cerebrospinal fluid (CSF). These were the 2 most severely ill children. In 2 patients DNA HSV using PCR (polymerase chain reaction) method was found in CSF and in serum. Magnetic resonance imaging (MRI) of the head confirmed diagnosis. Although herpetic encephalitis is an uncommon, sporadic disease, the diagnosis should be considered in any child with neuroinfection and early treatment started before laboratory confirmation.
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PMID:[Herpes encephalitis at children]. 1576 59

Metoclopramide is a dopamine antagonist that is widely used in gastroesophageal disease and chemotherapy-induced emesis in the paediatric population. It is also prescribed in nausea and vomiting caused by respiratory tract infections and enteritis in practice. The primary side-effect of the drug is extrapyramidal reactions with incidences as high as 25% in children. We report two cases, one of which was referred to our emergency department as encephalitis and the other as tetany, but which were just acute dystonic reactions caused by metaclopramide, even though the patients had used the drug in the recommended dosages. The adverse effects of the drug can be seen at normal doses. These dystonic reactions caused by metaclopramide can easily be confused with other diseases, because dystonia is not seen frequently in paediatric practice whatever the cause.
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PMID:Metoclopramide induced dystonia in children: two case reports. 1589 43

A 10-year-old boy presented with fever, headache, vomiting, and hypersomnolence. An akinetic-rigid syndrome with tremor, dysphagia, dysphonia, and sialorrhea, as well as pyramidal signs, developed. Slightly elevated protein content was found in the cerebrospinal fluid and serological investigations were suggestive of a primary Epstein-Barr virus infection. Magnetic resonance imaging (MRI) showed massive bilateral hyperintense striatal and punctiform periventricular lesions. After 2-month treatment with steroids and antiparkinsonian drugs, all features resolved without sequelae. Control MRI demonstrated only minimal residual lesions in both putamina. Strongly resembling the encephalitis lethargica-like syndrome, this case is an unusual presentation of parainfectious acute disseminated encephalitis.
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PMID:Acute reversible parkinsonism in Epstein-Barr virus-related encephalitis lethargica-like illness. 1625 20

Acute viral infections of the central nervous system (CNS) such as acute flaccid paralysis, meningitis, and encephalitis, are responsible for a high morbidity, particularly in children. Non-Polio enteroviruses (NPEV) are known to be responsible for over 80% of viral meningitis in which the etiologic agent is identified. In the present study, we show the frequency of enterovirus meningitis in Brazil from December 1998 to December 2003. Enterovirus were isolated from 162 (15.8%), of a total of 1,022 cerebrospinal fluid (CSF) specimens analyzed. Echovirus 30 was identified in 139 of these isolates (139/162-85.2%). Other identified enteroviruses were: Coxsackievirus B5 (3.7%), Echovirus 13 (3.7%), Echovirus 18 (3%), Echovirus 6 (1.2%), Echovirus 25 (1.2%), Echovirus 1 (0.6%), and Echovirus 4 (0.6%). Patients's age ranged from 28 days to 68 years old. The most frequent symptoms were fever (77%), headache (69.5%), vomiting (71.3%), neck stiffness (41.3%), convulsion (7.1%), and diarrhea (3.7%). Although, the majority of the patients recovered without any complication or permanent squeal, five deaths occurred. Throughout the surveillance period, five viral meningitis outbreaks were confirmed: four in the Southern Brazil and one in the Northeast Brazil. Echovirus 30 was responsible for four out of the five outbreaks while Echovirus 13 caused the fifth one. Besides the outbreaks, 734 sporadic cases were also identified during the study period and 59 of these were positive for virus isolation (8%). Echovirus 30 accounted for 70% of the isolates. Our results showed that Echovirus 30 was the most prevalent etiological agent of viral meningitis in Brazil, causing both outbreaks and sporadic cases.
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PMID:Enterovirus meningitis in Brazil, 1998-2003. 1629 28

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