The clinical epidemiology, management, and outcomes of patients diagnosed with encephalitis in North Carolina, 2015-2020.

IMPORTANCE: Despite the relatively high mortality and the difficulty in diagnosis, nearly one-third of patients hospitalized with a documented diagnosis of encephalitis did not undergo a lumbar puncture (LP). When an LP was performed, pathogen-specific testing was greatly underutilized. Infectious etiologies were most common, but over 40% of cases were idiopathic at discharge. These findings suggest that there is a substantial opportunity to improve the quality of care through more accurate and timely diagnosis.

Global Landscape of Encephalitis: Key Priorities to Reduce Future Disease Burden.

Encephalitis affects people across the lifespan, has high rates of mortality and morbidity, and results in significant neurological sequelae with long-term consequences to quality of life and wider society. The true incidence is currently unknown due to inaccurate reporting systems. The disease burden of encephalitis is unequally distributed across the globe being highest in low- and middle-income countries where resources are limited. Here countries often lack diagnostic testing, with poor access to essential treatments and neurological services, and limited surveillance and vaccination programs. Many types of encephalitis are vaccine preventable, whereas others are treatable with early diagnosis and appropriate management. In this viewpoint, we provide a narrative review of key aspects of diagnosis, surveillance, treatment, and prevention of encephalitis and highlight priorities for public health, clinical management, and research, to reduce the disease burden.

Global magnitude of encephalitis burden and its evolving pattern over the past 30 years.

OBJECTIVE: We aimed to estimate the spatiotemporal patterns of the encephalitis burden along with its attributable risk factors at the national, regional, and global levels, which may be helpful in guiding targeted prevention and treatment programs. METHODS: Based on available data sources, the incidence, mortality, and disability-adjusted life years (DALYs) of encephalitis in 204 countries and regions from 1990 to 2019 were reconstructed by the Global Burden of Disease Study 2019 using the Cause of Death Ensemble model, spatiotemporal Gaussian process regression, and DisMod-MR 2.1. We conducted a systematic analysis on the epidemiological characteristics of encephalitis in detail by gender, region, and age over the past three decades. RESULTS: Globally, 1,444,720 incident cases, 89,900 deaths, and 4.80 million DALYs related to encephalitis were estimated in 2019. The age-standardized incidence rate and age-standardized mortality rate (ASMR) decreased from 23.17 and 2.18 to 19.33 and 1.19 per 100,000 person-years over the past 30 years, respectively. However, beginning in 2011-2013, the burden of encephalitis has shown an inflection point, with a further decline of the ASRs ceasing. Lower socio-demographic index (SDI) regions in South Asia, Western and Eastern Sub-Saharan Africa had the highest burden of encephalitis in 2019. During the past three decades, most countries of South Asia achieved significant control of the burden. In contrast, developed countries with a higher SDI have shown a notable increase in ASMR and age-standardized DALYs rate. Children and older adults have always been high-risk groups for encephalitis. CONCLUSION: Although the global burden of encephalitis has decreased in the past 30 years, a further decline stopped from 2011 to 2013. The diverse burden in different regions calls for differentiated management, and the persistent high burden in some low-SDI regions and the increased burden in developed countries with higher SDIs deserve more attention.

Impact of cerebrospinal fluid syndromic testing in the management of children with suspected central nervous system infection.

The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1 year, with possible CNS infection and CSF pleocytosis (> 15 cells/mm3). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value < 0.001). In aseptic meningitis cases a virus was detected in 27/61(44.2%) and in 11/66(16.7%) controls (P value < 0.001). Median (IQR) length of stay in cases and controls with aseptic meningitis was 5(4-8) and 8(6-10) days, respectively (P value < 0. 001). The median (IQR) duration of antimicrobials in cases and controls was 4(2-5.7) and 7(5-10) days, respectively (P value < 0.001). The hospitalization cost was calculated in cases and controls 1042€ (932-1372) and 1522€ (1302-1742), respectively (P value < 0.001). The use of FA-ME was able to reduce significantly the use of antimicrobials, the hospitalization days, and the total cost comparing to the control group in children with suspected CNS infection.

La Von Economo's encephalitis lethargica and the Spanish flu pandemic in Bogotá and Medellín (Colombia): An historic review one hundred years after / La encefalitis letárgica de von Economo y la pandemia de la gripe española en Bogotá y Medellín: reseña histórica cien años después.

Von Economo's encephalitis is a neuropsychiatric disorder of possible autoimmune origin, which affects basal ganglia. This reaction may occur secondary to infection by different viral or bacterial agents. Given that it appears after the acute episode has disappeared, molecular mimetism has been proposed to explain the autoimmune lesion. Several cases have been reported through time, but it was with the 1918 flu pandemic, known as the Spanish flu, that lethargic encephalitis reached epidemic levels with cases reported until 1923 in various countries. The Spanish flu pandemic appeared in Colombia at the end of 1918 in several cities but it affected especially Bogotá where the highest number of patients and deaths was reported. Our purpose with the present work was to commemorate the arrival of the Spanish flu to our country after one hundred years, as well as to reflect on its main complications, which included some lethargic encepahilitis cases.

La encefalitis letárgica de von Economo es un trastorno neuropsiquiátrico de posible origen autoinmunitario, en el cual se afectan los ganglios basales. Esta reacción puede ocurrir luego de una infección aguda por diversos agentes virales o bacterianos. Dado que aparece cuando ya se ha resuelto el cuadro agudo, se ha propuesto el mecanismo del mimetismo molecular para explicar la lesión autoinmunitaria. Se han reportado diversos casos a lo largo del tiempo, pero fue con la pandemia de influenza de 1918, conocida como la gripe española, que la encefalitis letárgica alcanzó niveles de epidemia, con casos reportados hasta 1923 en diversos países. La pandemia de la gripe española se extendió a Colombia durante los últimos meses de 1918 y afectó varias ciudades, principalmente Bogotá, donde se reportó el mayor número de enfermos y muertos. Con este trabajo se busca rememorar, cien años después, el ingreso de la gripe española a nuestro país y sus principales complicaciones, entre las que se describieron algunos casos de encefalitis letárgica.

A Population-based Observational Study of Childhood Encephalitis in Children Admitted to Pediatric Intensive Care Units in England and Wales.

BACKGROUND: Encephalitis is a serious neurologic condition that can result in admission to intensive care. Yet, there are no studies on pediatric intensive care unit (PICU) admission rates and usage of intensive care resources by children with encephalitis in England and Wales. The objectives of this study were to (1) define the PICU incidence and mortality rates for childhood encephalitis, (2) describe the usage of intensive care resources by children with encephalitis admitted to PICU and (3) explore the associated cost from PICU encephalitis admissions. METHODS: Retrospective analysis of anonymized data for 1031 children (0-17 years) with encephalitis admitted (January 2003 to December 2013) to PICU in England and Wales. RESULTS: The PICU encephalitis incidence was 0.79/100,000 population/yr (95% confidence interval [CI]: 0.74-0.84), which gives an annual total of 214 bed days of intensive care occupancy for children admitted with encephalitis and an estimated annual PICU bed cost of £414,230 (interquartile range: 198,111-882,495) for this cohort. PICU encephalitis admissions increased during the study period (annual percentage change = 4.5%, 95% CI: 2.43%-6.50%, P ≤ 0.0001). In total, 808/1024 (78.9%) cases received invasive ventilation while 216/983 (22.0%) and 50/890 (5.6%) cases received vasoactive treatment and renal support, respectively. There were 87 deaths (8.4%), giving a PICU encephalitis mortality rate of 0.07/100,000 population (0-17 years)/yr (95% CI: 0.05-0.08). CONCLUSIONS: These data suggest that encephalitis places a significant burden to the healthcare service. More work is needed to improve outcomes for children with encephalitis.

Prevention of epilepsy: Should we be avoiding clinical trials?

Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon. We review data to suggest that there is basis to do epilepsy prevention studies now with the current knowledge and available drugs, and that those studies are feasible with currently available tools. We suggest that a different approach is needed from the past in order to maximize chances of success, minimize the cost, and set up platform for future preventive treatment development. That approach should include close coordination of preclinical and clinical development programs in a combined PTE prevention strategy, consideration of polytherapy, and simultaneous, combined clinical development of preventive treatment and of biomarker discovery. We argue that the currently favored approach of eschewing clinical studies until biomarkers are available will delay the discovery of epilepsy prevention treatment by at least 10 years and significantly increase the cost of such discovery.

Hospitalized Children With Encephalitis in the United States: A Pediatric Health Information System Database Study.

OBJECTIVES: Given the paucity of data on resource utilization among children with encephalitis, the objective of this study was to describe the epidemiology and evaluate resource utilization and discharge data of children with encephalitis admitted to US hospitals from 2004 to 2013. METHODS: We conducted a retrospective cohort study utilizing the Pediatric Health Information System database of children aged 0 to 18 years with the International Classification of Diseases, Ninth Revision codes for encephalitis from 2004 to 2013. Only the initial admissions were included, and the age group analyzed was 0 to 18 years. RESULTS: Among 7298 children with encephalitis, 2933 (40%) were admitted to a pediatric intensive care unit. The median age was nine years, the overall median length of stay was 16 days, and children requiring critical care had a median length of stay of 25 days. Children in the pediatric intensive care unit were more likely to have seizures (P <0.001) and head magnetic resonance imaging (P <0.001) than children on the floor. Similarly, children requiring critical care were more likely to have a broad diagnostic evaluation sent including cerebrospinal fluid cultures, blood bacterial and fungal cultures, western equine encephalitis antibody, St. Louis equine encephalitis antibody, varicella-zoster serology, human immunodeficiency virus 1 antibody, human immunodeficiency virus DNA polymerase chain reaction, acid-fast stain, and Lyme disease serology. Seventeen percent of children were treated with intravenous immunoglobulin, and 4% underwent plasmapheresis. There was a trend of increasing use of intravenous immunoglobulin and plasmapheresis in children with encephalitis over the study period. A total of 5944 (81%) children were discharged home, and the mortality in this cohort was 3% (230). The mean charges for hospitalization for a child with encephalitis was $64,604 and for those requiring critical care was $260,012. CONCLUSIONS: Encephalitis is a significant cause of morbidity and mortality in children. Children with encephalitis admitted to the pediatric intensive care unit are more likely to have seizures and to undergo a more extensive evaluation to determine the cause of encephalitis. Use of plasmapheresis and intravenous immunoglobulin is on the rise in hospitalized children. Prospective studies are necessary to better understand treatment and intervention strategies for children with encephalitis and their impact on outcomes.

An integrated model of care for neurological infections: the first six years of referrals to a specialist service at a university teaching hospital in Northwest England.

BACKGROUND: A specialist neurological infectious disease service has been run jointly by the departments of infectious disease and neurology at the Royal Liverpool University Hospital since 2005. We sought to describe the referral case mix and outcomes of the first six years of referrals to the service. METHODS: Retrospective service review. RESULTS: Of 242 adults referred to the service, 231 (95%) were inpatients. Neurological infections were confirmed in 155 (64%), indicating a high degree of selection before referral. Viral meningitis (35 cases), bacterial meningitis (33) and encephalitis (22) accounted for 38% of referrals and 61% of confirmed neurological infections. Although an infrequent diagnosis (n = 19), neurological TB caused the longest admission (median 23, range 5-119 days). A proven or probable microbiological diagnosis was found in 100/155 cases (64.5%). For the whole cohort, altered sensorium, older age and longer hospital stay were associated with poor outcome (death or neurological disability); viral meningitis was associated with good outcome. In multivariate analysis altered sensorium remained significantly associated with poor outcome, adjusted odds ratio 3.04 (95% confidence interval 1.28-7.22, p = 0.01). CONCLUSIONS: A service of this type provides important specialist care and a focus for training and clinical research on complex neurological infections.

Burden of encephalitis-associated hospitalizations in the United States, 1998-2010.

OBJECTIVE: To estimate the burden of encephalitis-associated hospitalizations in the United States for 1998-2010. METHODS: Using the Nationwide Inpatient Sample, a nationally representative database of hospitalizations, estimated numbers and rates of encephalitis-associated hospitalizations for 1998-2010 were calculated. Etiology and outcome of encephalitis-associated hospitalizations were examined, as well as accompanying diagnoses listed along with encephalitis on the discharge records. Total hospital charges (in 2010 US dollars) were assessed. RESULTS: An estimated 263,352 (standard error: 3,017) encephalitis-associated hospitalizations occurred in the United States during 1998-2010, which corresponds to an average of 20,258 (standard error: 232) encephalitis-associated hospitalizations per year. A fatal outcome occurred in 5.8% (95% confidence interval [CI]: 5.6%-6.0%) of all encephalitis-associated hospitalizations and in 10.1% (95% CI: 9.2%-11.2%) and 17.1% (95% CI: 14.6%-20.0%) of encephalitis-associated hospitalizations in which a code for HIV or a tissue or organ transplant was listed, respectively. The proportion of encephalitis-associated hospitalizations in which an etiology for encephalitis was specified was 50.3% (95% CI: 49.6%-51.0%) and that for which the etiology was unspecified was 49.7% (95% CI: 49.0%-50.4%). Total charges for encephalitis-associated hospitalizations in 2010 were an estimated $2.0 billion. CONCLUSIONS: Encephalitis remains a major public health concern in the United States. Among the large number of encephalitis-associated hospitalizations for which an etiology is not reported may be novel infectious and noninfectious forms of encephalitis. Associated conditions such as HIV or transplantation increase the risk of a fatal outcome from an encephalitis-associated hospitalization and should be monitored.

The functional, social and economic impact of acute encephalitis syndrome in Nepal--a longitudinal follow-up study.

BACKGROUND: Over 133,000 children present to hospitals with Acute Encephalitis Syndrome (AES) annually in Asia. Japanese encephalitis (JE) accounts for approximately one-quarter of cases; in most cases no pathogen is identified and management is supportive. Although JE is known to result in neurological impairment, few studies have examined the wider impact of JE and AES on patients and their families. METHODOLOGY/PRINCIPAL FINDINGS: Children (aged 1 month-14 years) with AES were assessed 5-12 months after discharge from two Nepali hospitals. Assessment included clinical examination, the Liverpool Outcome Score (LOS) - a validated assessment of function following encephalitis, questionnaires about the child's social participation since discharge, and out-of-pocket costs to the family. Children were classified as JE or 'other AES' based on anti-JE virus antibody titres during acute illness. Contact was made with the families of 76% (73/96) of AES children. Six children had died and one declined participation. 48% (32/66) reported functional impairment at follow-up, most frequently affecting behaviour, language or limb use. Impairment was more frequent in JE compared to 'other AES' cases (68% [13/19] versus 40% [19/47]; p = 0.06). 49% (26/53) had improvement in LOS between discharge and follow-up. The median out-of-pocket cost to families, including medical bills, medication and lost earnings was US$ 1151 (10 times their median monthly income) for children with severe/moderate impairment and $524 (4.6 times their income) for those with mild/no impairment (P = 0.007). Acute admission accounted for 74% of costs. Social participation was limited in 21% of children (n = 14). CONCLUSIONS/SIGNIFICANCE: Prolonged functional impairment was common following AES. Economic impact to families was substantial. Encouragingly, almost half the children improved after discharge and most reported sustained social participation. This study highlights a need for long-term medical support following AES. Rationalisation of initial expensive hospital treatments may be warranted, especially since only supportive treatment is available.

Forecasting burden of long-term disability from neonatal conditions: results from the Projahnmo I trial, Sylhet, Bangladesh.

INTRODUCTION: The burden of disease resulting from neonatal conditions is substantial in developing countries. From 2003 to 2005, the Projahnmo I programme delivered community-based interventions for maternal and newborn health in Sylhet, Bangladesh. This analysis quantifies burden of disability and incorporates non-fatal outcomes into cost-effectiveness analysis of interventions delivered in the Projahnmo I programme. METHODS: A decision tree model was created to predict disability resulting from preterm birth, neonatal meningitis and intrapartum-related hypoxia ('birth asphyxia'). Outcomes were defined as the years lost to disability (YLD) component of disability-adjusted life years (DALYs). Calculations were based on data from the Projahnmo I trial, supplemented with values from published literature and expert opinion where data were absent. RESULTS: 195 YLD per 1000 neonates [95% confidence interval (CI): 157-241] were predicted in the main calculation, sensitive to different DALY assumptions, disability weights and alternative model structures. The Projahnmo I home care intervention may have averted 2.0 (1.3-2.8) YLD per 1000 neonates. Compared with calculations based on reductions in mortality alone, the cost-effectiveness ratio decreased by only 0.6% from $105.23 to $104.62 ($65.15-$266.60) when YLD were included, with 0.6% more DALYs averted [total 338/1000 (95% CI: 131-542)]. DISCUSSION: A significant burden of disability results from neonatal conditions in Sylhet, Bangladesh. Adding YLD has very little impact on recommendations based on cost-effectiveness, even at the margin of programme adoption. This model provides guidance for collecting data on disabilities in new settings.

The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project.

BACKGROUND: In 2007, the California Encephalitis Project (CEP), which was established to study the epidemiology of encephalitis, began identifying cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Increasing numbers of anti-NMDAR encephalitis cases have been identified at the CEP, and this form rivals commonly known viral etiologies as a causal agent. We report here the relative frequency and differences among encephalitides caused by anti-NMDAR and viral etiologies within the CEP experience. METHODS: Demographic, frequency, and clinical data from patients with anti-NMDAR encephalitis are compared with those with viral encephalitic agents: enterovirus, herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and West Nile virus (WNV). All examined cases presented to the CEP between September 2007 and February 2011 and are limited to individuals aged ≤30 years because of the predominance of anti-NMDAR encephalitis in this group. The diagnostic costs incurred in a single case are also included. RESULTS: Anti-NMDAR encephalitis was identified >4 times as frequently as HSV-1, WNV, or VZV and was the leading entity identified in our cohort. We found that 65% of anti-NMDAR encephalitis occurred in patients aged ≤18 years. This disorder demonstrated a predilection, which was not observed with viral etiologies, for females (P < .01). Seizures, language dysfunction, psychosis, and electroencephalographic abnormalities were significantly more frequent in patients with anti-NMDAR encephalitis (P < .05), and autonomic instability occurred exclusively in this group. DISCUSSION: Anti-NMDAR encephalitis rivals viral etiologies as a cause of encephalitis within the CEP cohort. This entity deserves a prominent place on the encephalitic differential diagnosis to avoid unnecessary diagnostic and treatment costs, and to permit a more timely treatment.

[Epidemiological, clinical, etiological features of neuromeningeal diseases at the Fann Hospital Infectious Diseases Clinic, Dakar (Senegal)]. / Profil épidémiologique, clinique et étiologique des affections cérébroméningées observées à la clinique des maladies infectieuses du CHU de Fann à Dakar.

OBJECTIVES: This retrospective study was carried out to determine the prevalence of cerebromeningeal diseases at the Fann Teaching Hospital Infectious Diseases Clinic, in Dakar, and to describe their epidemiological, clinical, and etiological features. PATIENTS AND METHODS: Data was collected for analysis from patients files recorded from January 1, 2001 to December 31, 2003. RESULTS: Four hundred seventy cases were identified (11.4% of total admissions) with a M/F sex ratio of 1.38 and a mean age of 33 years. Eighty-nine patients were infected by HIV and clinical presentations included fever (78%), meningeal syndrome (57.4%), coma (64.9%), convulsions (19%), focal neurological deficits (15.5%), and cranial nerves dysfunction (7.2%). Etiologies presented as cerebral malaria (85 cases), purulent meningitis (51 cases), neuromeningeal cryptococcosis (37 cases), tuberculous meningitis (11 cases), intracranial abscess (10 cases), toxoplasma encephalitis (4 cases), cerebrovascular attack (11 cases), and cerebromeningeal hemorrhages (3 cases). In as many as 248 cases (52.8%) no etiology could be found. The case fatality rate was 44.5% overall (209 deaths) and 68.5% among HIV-infected patients. Neurological sequels were found in 22 survivors (8.8%), consisting in focal neurological deficit (12 cases), deafness (5 cases), diplopia (2 cases), dementia (2 cases), postmeningitic encephalitis (1 case). CONCLUSION: These results show the need to improve our technical capacities in our diagnostic laboratories, the prevention of opportunistic infections in the course of HIV/AIDS infection, and the involvement of various specialists in the management of cerebromeningeal diseases.

Burden of encephalitis-associated hospitalizations in the United States, 1988-1997.

Analysis of the National Hospital Discharge Survey data for 1988-1997 revealed a substantial disease burden associated with encephalitis in the United States: on average, there were nearly 19,000 hospitalizations (7.3 hospitalizations per 100,000 population), 230,000 hospital days, and 1400 deaths annually. For most encephalitis-associated hospitalizations (59.5%), the etiologic agent was unknown or not recorded; the most common etiologic categories among known causes were "viral" (38.2%) and "other infectious" (34.1%). The most common individual diagnoses with known agents were herpetic and toxoplasmic encephalitides (each associated with an annual average of 2100 hospitalizations). Human immunodeficiency virus infection was listed among discharge diagnoses for 15.6% of hospitalizations. Rates of encephalitis-associated hospitalization were highest for children <1 year old and persons > or =65 years old. The etiology of encephalitis was unknown for persons > or =65 years old significantly more often than it was for younger persons. The average cost of an encephalitis-associated hospitalization, as determined by the Healthcare Cost and Utilization Project for 1997, was $28,151, for an annual national cost of hospitalization of $650 million.

Experimenting on the past: the enigma of von Economo's encephalitis lethargica.

Encephalitis lethargica (EL) was a complex and mysterious disease that appeared around the same time as the great influenza pandemic of 1918. The contemporaneous relationship of the 2 diseases led to speculation that they were causally related. Contemporary and subsequent observers conjectured that the influenza virus, directly responsible for the deaths of more than 20 million people, might also have been the cause of EL. A review of the extensive literature by observers of the EL epidemic suggests that most contemporary clinicians, epidemiologists, and pathologists rejected the theory that the 1918 influenza virus was directly responsible for EL. Disappearance of the acute form of EL during the 1920s has precluded direct study of this entity. However, modern molecular biology techniques have made it possible to examine archival tissue samples from victims of the 1918 pandemic in order to detect and study the genetic structure of the killer virus. Similarly, tissue samples from EL victims can now be examined for evidence of infection by the 1918 influenza virus.

Childhood coma in Ibadan. Relationship to socio-economic factors.

According to the literature, socio-economic factors may contribute more to geographic variations in the aetiology and prognosis of childhood coma than has previously been recognised. This prospective study involving 118 children with strictly defined coma demonstrated that the commonest causes of coma in Ibadan were cerebral malaria (55%), meningitis (13%) and encephalitis (10%). The prognosis was poor. Forty-three (36%) of 118 cases died and 75 (64%) survived, including 23 who showed neurologic deficits. Noteworthy prognostic indices of coma were the aetiology of the condition, the presence of severe anaemia, hypoglycaemia and pneumonia. The findings are discussed in the context of the socio-economic background of children in the tropics.

Impact of measles in the United States.

Measles has had a severe impact on children in the United States since colonial times. In the early decades of the 20th century, thousands of fatal measles infections were reported each year. During the 1950s an annual average of greater than 500,000 cases of measles and nearly 500 deaths due to measles were reported in the United States. Surveys indicated that 95% of the population had been infected with measles by the age of 15 years. The introduction of measles vaccine and its widespread use, which began in 1963, has had a major impact on the occurrence of measles in the United States. Reported numbers of cases, deaths due to measles, and complications of measles (e.g., encephalitis) have declined dramatically. Accompanying the decline in reported incidence of measles and following it by approximately seven years, has been a decline in the reported incidence of subacute sclerosing panencephalitis (SSPE). In recent years, the incidence of measles has dropped to levels that are less than 1% of those seen in the prevaccine era. In 1981, provisional figures indicated that only 10% of counties in the United States reported any cases of measles. The reported incidence in 1981 was 1.3 cases per 100,000 population, compared with an average incidence of 336.3 cases per 100,000 population in the decade 1950-1959. Thus, the impact of measles in the United States has been markedly reduced, and it is anticipated that indigenous transmission will be eliminated entirely from the country within the year.