Charles R. Newton

We have improved the "polymerase chain reaction" (PCR) to permit rapid analysis of any known mutation in genomic DNA. We demonstrate a system, ARMS (Amplification Refractory Mutation System), that allows genotyping solely by inspection of reaction mixtures after agarose gel electrophoresis. The system is simple, reliable and non-isotopic. It will clearly distinguish heterozygotes at a locus from homozygotes for either allele. The system requires neither restriction enzyme digestion, allele-specific oligonucleotides as conventionally applied, nor the sequence analysis of PCR products. The basis of the invention is that unexpectedly, oligonucleotides with a mismatched 3'-residue will not function as primers in the PCR under appropriate conditions. We have analysed DNA from patients with alpha 1-antitrypsin (AAT) deficiency, from carriers of the disease and from normal individuals. Our findings are in complete agreement with allele assignments derived by direct sequencing of PCR products.

PURPOSE: To estimate the burden of lifetime epilepsy (LTE) and active epilepsy (AE) and examine the influence of study characteristics on prevalence estimates. METHODS: We searched online databases and identified articles using prespecified criteria. Random-effects meta-analyses were used to estimate the median prevalence in developed countries and in urban and rural settings in developing countries. The impact of study characteristics on prevalence estimates was determined using meta-regression models. RESULTS: The median LTE prevalence for developed countries was 5.8 per 1,000 (5th-95th percentile range 2.7-12.4) compared to 15.4 per 1,000 (4.8-49.6) for rural and 10.3 (2.8-37.7) for urban studies in developing countries. The median prevalence of AE was 4.9 per 1,000 (2.3-10.3) for developed countries and 12.7 per 1,000 (3.5-45.5) and 5.9 (3.4-10.2) in rural and urban studies in developing countries. The estimates of burden for LTE and AE in developed countries were 6.8 million (5th-95th percentile range 3.2-14.7) and 5.7 million (2.7-12.2), respectively. In developing countries these were 45 (14-145) million LTE and 17 (10-133) million AE in rural areas and 17 (5-61) million LTE and 10 (5-17) million AE in urban areas. Studies involving all ages or only adults showed higher estimates than pediatric studies. Higher prevalence estimates were also associated with rural location and small study size. CONCLUSIONS: This study estimates the global burden of epilepsy and the proportions with AE, which may benefit from treatment. There are systematic differences in reported prevalence estimates, which are only partially explained by study characteristics.

BACKGROUND: About 90 percent of the deaths from malaria are in African children, but criteria to guide the recognition and management of severe malaria have not been validated in them. METHODS: We conducted a prospective study of all children admitted to the pediatric ward of a Kenyan district hospital with a primary diagnosis of malaria. We calculated the frequency and mortality rate for each of the clinical and laboratory criteria in the current World Health Organization (WHO) definition of severe malaria, and then used logistic-regression analysis to identify the variables with the greatest prognostic value. RESULTS: We studied 1844 children (mean age, 26.4 months) with a primary diagnosis of malaria. Not included were 18 children who died on arrival and 4 who died of other causes. The mortality rate was 3.5 percent (95 percent confidence interval, 2.7 to 4.3 percent), and 84 percent of the deaths occurred within 24 hours of admission. Logistic-regression analysis identified four key prognostic indicators: impaired consciousness (relative risk, 3.3; 95 percent confidence interval, 1.6 to 7.0), respiratory distress (relative risk, 3.9; 95 percent confidence interval, 2.0 to 7.7), hypoglycemia (relative risk, 3.3; 95 percent confidence interval, 1.6 to 6.7), and jaundice (relative risk, 2.6; 95 percent confidence interval, 1.1 to 6.3). Of the 64 children who died, 54 were among those with impaired consciousness (n = 336; case fatality rate, 11.9 percent) or respiratory distress (n = 251; case fatality rate, 13.9 percent), or both. Hence, this simple bedside index identified 84.4 percent of the fatal cases, as compared with the 79.7 percent identified by the current WHO criteria. CONCLUSIONS: In African children with malaria, the presence of impaired consciousness or respiratory distress can identify those at high risk for death.

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.