Date: Fri, 1 Mar 1996 10:47:04 +0500 From: ghmcleaf{CONTRACTOR/ASPEN/ghmcleaf}%NAC-GATEWAY.ASPEN@ace.aspensys.com Subject: MMWR 03/01/96 MORBIDITY AND MORTALITY WEEKLY REPORT ****************************************** Centers for Disease Control and Prevention March 1, 1996 Vol. 45, No. 8 Articles included: * Mortality Patterns --- United States, 1993 * Animal Rabies --- South Dakota, 1995 * Outbreak of Primary and Secondary Syphilis --- Baltimore City, Maryland, 1995 * Notice to Readers: Availability of Case Definitions for Public Health Surveillance on Internet Mortality Patterns -- United States, 1993 In 1993, a total of 2,268,553 deaths were registered in the United States--92,940 more than in 1992 and the highest number ever recorded (1). In addition, life expectancy at birth declined for the first time since 1980. This report characterizes mortality patterns in 1993 (the most recent year for which complete data were available) (1) and compares these with patterns in 1992. National mortality statistics are based on information from death certificates filed in state vital statistics offices as required by state law and are compiled by CDC into a national database. Cause-of-death statistics are based on the underlying cause of death*, which is recorded on the death certificate by the attending physician, medical examiner, or coroner in a manner specified by the World Health Organization (WHO) and endorsed by CDC. Data are presented only for blacks and whites because of inconsistent reporting of other racial/ethnic groups on death certificates. From 1992 to 1993, the crude death rate increased 3.2% (from 852.9 to 880.0 deaths per 100,000 population); the age-adjusted death rate** increased 1.7% (from 504.5 to 513.3 per 100,000 population). The 10 leading causes of death and their rankings were unchanged during this period; mortality decreased only for cancer (-0.4%) (Table 1)***. The largest increase in age-adjusted death rate (9.5%) was for human immunodeficiency virus (HIV) infection (International Classification of Diseases, Ninth Revision [ICD-9], codes 042-044****); this rate (13.8) was the highest ever recorded for HIV infection (1). From 1992 to 1993, age-adjusted death rates increased 1.6% for whites***** (from 477.5 to 485.1) and 2.3% for blacks (from 767.5 to 785.2). Rates were higher for blacks than for whites for eight of the 10 leading causes (Table 2). Race-specific ratios were greatest for homicide (6.8) and HIV infection (4.0). Death rates for blacks were lower for chronic obstructive pulmonary diseases and allied conditions (COPD) (ICD-9 codes 490-496; 0.8) and suicide (ICD-9 codes E950-E959; 0.6). From 1992 to 1993, age-adjusted death rates increased 1.3% for males (from 656.0 to 664.9) and 2.1% for females (from 380.3 to 388.3). Rates were higher for males than females for all 10 leading causes (Table 2). Sex-specific ratios were greatest for HIV infection (6.3), suicide (4.4), and homicide (3.8). Compared with 1992, sex-specific ratios decreased for HIV infection and homicide. The sex-specific ratio was lowest for diabetes mellitus (ICD-9 code 250; 1.2). In 1993, a total of 302 women were reported to have died from causes associated with pregnancy and childbirth (i.e., deaths assigned to complications of pregnancy, childbirth, and the puerperium [ICD-9 codes 630-676]). The overall maternal mortality rate was 7.5 deaths per 100,000 live-born infants. However, this rate was approximately four times higher for blacks than for whites (20.5 versus 4.8). From 1992 to 1993, overall life expectancy (LE) at birth declined from 75.8 years to 75.5 years. As in 1992, LE at birth continued to be highest among white females (79.5 years), followed by black females (73.7 years), white males (73.1 years), and black males (64.6 years). Although LE declined for all four racial-sex groups during 1992-1993, the overall race-specific difference in LE for blacks and whites increased slightly, from 6.9 years in 1992 to 7.1 years in 1993. Reported by: Mortality Statistics Br, Div of Vital Statistics, National Center for Health Statistics, CDC. Editorial Note: LE summarizes death rates by age into a single measure used as an indicator of the nation's health. Death rates and LE can be used to monitor health status and progress toward national health objectives and to identify groups at increased risk for specific diseases and injuries. The findings in this report indicate that, in 1993, crude and age-adjusted death rates increased and LE decreased from 1992. The decline in LE most likely reflects increases in death rates for 1) chronic diseases during the two influenza outbreaks of 1993, 2) pneumonia and influenza, and 3) HIV infection and unintentional injuries. Race-specific variation in death rates are accounted for, in part, by differences in factors such as socioeconomic status, access to medical care, and risk behaviors. The increases in both the crude and age-adjusted rates in 1993 are the first since 1988 and 1975, respectively; however, preliminary analysis of provisional data for 1994 suggest small, but statistically significant, decreases in these rates (3). In 1993, death rates for some chronic diseases--heart disease, stroke, COPD, and diabetes--and for pneumonia and influenza accounted for nearly 75% of all deaths during the year. This analysis especially highlights the role of heart disease and cancer as leading causes of death in the United States; these two causes accounted for approximately 56% of deaths in 1993. Although increases in the rates for HIV infection and unintentional injuries among younger persons contributed to the decline in LE, most increases in mortality were among persons aged greater than or equal to 65 years. References 1. NCHS. Advance report of final mortality statistics, 1993. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, CDC, 1996. (Monthly vital statistics report; vol 44, no. 7, suppl). 2. NCHS. Vital statistics of the United States, 1988. Vol 2, mortality, part A. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, CDC, 1991; DHHS publication no. (PHS)91-1101. 3. NCHS. Annual summary of births, marriages, divorces, and deaths: United States, 1993. Hyattsville, Maryland: US Department of Health and Human Services, Public Health Service, CDC, 1994. (Monthly vital statistics report; vol 43, no. 13). *Defined by the World Health Organization's International Classification of Diseases, Ninth Revision, as "(a) the disease or injury which initiated the train of morbid events leading directly to death, or (b) the circumstances of the accident or violence which produced the fatal injury." **Age-adjusted to the 1940 U.S. population. Age-adjusted death rates indicate the risk for death relative to a standard population and are more effective than crude death rates for comparing mortality of population groups with different age structures. ***"Motor-vehicle accidents" and "all other accidents and adverse effects" are not included as causes of death for which the rate has decreased because these causes are subcategories of the leading cause "accidents and adverse effects." When a death occurs under "accidental" circumstances, the preferred term within the public health community is "unintentional injury." ****These codes are from addenda to the ICD-9 (2). *****Hispanics and non-Hispanics are included in totals for both whites and blacks. Animal Rabies -- South Dakota, 1995 On July 28, 1995, the South Dakota Public Health Laboratory diagnosed rabies in an 8-week-old puppy; on July 23, the puppy had had onset of neurologic signs (e.g., head tilt, ataxia, and somnolence) that culminated in seizures, and the puppy was euthanized. A clinically normal littermate owned by a neighboring family was euthanized on July 31 and tested positive for rabies. This report summarizes the epidemiologic investigation and follow-up management by the South Dakota Department of Health (SDDH), with assistance from CDC, of persons and domestic animals potentially exposed to rabies. On July 8, the neighboring families acquired the two puppies from a private owner near Summit, South Dakota. The puppies were from a litter of nine born on May 29. On June 13 or 14, a skunk attacked the litter in a garage where they were kept. The skunk was killed by the owner of the puppies but was not tested for rabies. All the puppies were free of clinical signs consistent with rabies when given away between July 8 and July 27. However, the original owner of the puppies was uncertain of the identity of all the persons who had adopted them. Through announcements in the local news media and distribution of flyers door-to-door by the Aberdeen Area Indian Health Service in Sisseton, by August 4 the remaining seven puppies were identified to be in private residences located throughout eastern South Dakota. Six of the puppies tested negative for rabies at the South Dakota Public Health Laboratory; the seventh puppy had been killed by the owner because it was part of the exposed litter, and it was unavailable for testing. The dam of the litter and another contact dog--neither of which were currently vaccinated against rabies--were euthanized and tested negative for rabies. Two other potentially exposed pet dogs, past due for rabies vaccination, were identified; they were managed by home quarantine and booster vaccination according to the 1995 animal rabies compendium (1) and remained symptom-free. The SDDH initiated efforts to identify persons with potential exposure to the two puppies and determine their risk for rabies infection. In response to the alert, the state health department and four major health-care facilities screened by phone or personal interview approximately 150 persons possibly exposed during July 13-31 (the established period of potential rabies transmission). In addition, SDDH conducted town meetings and provided briefings to health-care providers, the news media, and animal-control authorities. Of the 150 persons, 22 (15%) (including nine persons from the veterinary clinic in which the ill puppy had been treated and euthanized and seven persons who had had contact with the puppy that had been destroyed and was unavailable for rabies testing) met the criteria used to determine the need for rabies postexposure treatment (PET) for either a bite or nonbite exposure as defined by the Immunization Practices Advisory Committee (2). Specific antirabies treatment was initiated for 31 persons; the other nine persons requested and received PET despite reassurance they were at low risk for rabies infection. Reported by: K Peterson, DVM, Milbank Veterinary Clinic, K Vanadurongvan, MD, Milbank Medical Clinic, Milbank; H Burrish, DVM, Sisseton Veterinary Clinic, Sisseton; F Zambrana, MD, J Leith, Aberdeen Area Indian Health Service, Sisseton; S DeCoteau, Sisseton-Wahpeton Sioux Tribe, Sisseton; G Larson, MD, H Nipe, MD, K Peterson, MD, C Gerrish, MD, R Peshek, MD, M Preys, MD, L Danforth, Brown Clinic, Watertown; J Ostby, MD, C Breske, MD, M Jergenson, Bartron Clinic, Watertown; L Volmer, L Schaefer, G Welch, S Lance, DVM, State Epidemiologist, South Dakota Dept of Health; R Steece, PhD, South Dakota Public Health Laboratory. Viral and Rickettsial Zoonoses Br, and Special Pathogens Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC. Editorial Note: In the United States, the most frequently reported rabid wild animals are raccoons, skunks, bats, and foxes (3). Although the exposure for the two rabid puppies in this report was not confirmed, the skunk that attacked the litter in mid-June was probably the source of infection. Measures for preventing pets from contacting wild animals include keeping them indoors, on leashes, or in fenced outdoor areas. If pets are wounded by wild animals, wounds should be washed immediately with soap and water, and the pet should be evaluated by a veterinarian. Wildlife that attacks persons or pets should be apprehended by trained personnel, euthanized, and tested for rabies. Wild and stray domestic animals exhibiting signs of neurologic illness or of abnormal behavior (signs of rabies among wild animals cannot be interpreted reliably) should be reported to appropriate local health authorities, especially if the animal bites or scratches a person. Only trained personnel should attempt to trap or capture these animals and submit them for rabies testing. The economic burden of the exposures in South Dakota was minimized because of the small number of persons requiring PET and as a result of efforts to inform and reassure persons who unnecessarily were seeking medical services for exposures not associated with true risk (e.g., petting a rabid puppy, handling a noninfected littermate, or having contact with a human who had been exposed to a rabid puppy). Nonetheless, substantial resources were required to educate potentially exposed persons about rabid animals and to conduct the prompt and standardized assessment of persons who received PET (4). The estimated cost associated with the public health response, assessment, and PET was $115,000: $97,900 for chemoprophylaxis and provider services, $16,500 for the investigation by public health officials, and $600 for laboratory testing of animals. In South Dakota, from 1990 through 1995, an estimated $1.4 million was spent for PET for 632 persons exposed to approximately 704 rabies-positive animals. Although this estimate is for a 5-year period, it is similar to the cost ($1.5 million) associated with the single-point source exposure to a rabid kitten in New Hampshire, in which PET was initiated for 665 persons (5). To facilitate efforts to investigate rabies exposures such as those described in this report, persons involved in the private sale or adoption of pets are encouraged to maintain records of buyers' or adoptees' names and addresses. References 1. CDC. Compendium of animal rabies control, 1995: National Association of State Public Health Veterinarians, Inc. MMWR 1995;44(no. RR-2). 2. CDC. Rabies prevention--United States, 1991: recommendation of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(no. RR-3). 3. Krebs JW, Strine TW, Smith JS, Rupprecht CE, Childs JE. Rabies surveillance in the United States during 1993. J Am Vet Assoc 1994:205:1695-709. 4. Childs JE, Noah DL, Rupprecht CE. Rabies. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious diseases. 2nd ed. Philadelphia, Pennsylvania: Saunders (in press). 5. CDC. Mass treatment of humans exposed to rabies--New Hampshire, 1994. MMWR 1995; 44:484-6. Outbreak of Primary and Secondary Syphilis -- Baltimore City, Maryland, 1995 From 1993 to 1995, the number of primary and secondary syphilis cases reported in Baltimore City (1990 population: 736,014) increased 97%, from 179 to 352 cases per year (Figure 1). To identify potential reasons for this increase, CDC, in collaboration with the Baltimore City Health Department (BCHD) and the Maryland Department of Health and Mental Hygiene, analyzed data about primary and secondary syphilis cases during 1992-1995 and about temporal trends in factors that may affect syphilis rates (e.g., partner-notification results, access to medical care, and community illicit-drug use). In addition, data were analyzed from the two public sexually transmitted disease (STD) clinics in Baltimore City. BCHD collects demographic data for all cases of reported syphilis among patients who reside in Baltimore City and attempts to interview and provide partner notification and treatment for these patients. This report summarizes the results of the analysis, which suggest the outbreak has been associated with decreases in partner notification and health department clinical services and a substantial increase in community cocaine use. Epidemiology Of 344 patients with primary or secondary syphilis reported in 1995 and for whom demographic information was available, 196 (57%) were non-Hispanic black males; 120 (35%), non-Hispanic black females; 16 (5%), non-Hispanic white males; nine (3%), non-Hispanic white females; and three (1%), Hispanic (two males and one female). The mean age of males was 37.3 years (range: 13-69 years) and of females, 30.3 years (range: 14-58 years). Among persons with primary or secondary syphilis reported in 1995 and for whom self-reported sexual orientation was known, 16 (8%) of 206 men and nine (7%) of 123 women reported same-sex sexual contact since 1978; in addition, 56 (27%) men and 18 (15%) women reported exchanging money or drugs for sex. During 1995 at one of the two STD clinics, cocaine use was reported by 18 (26%) of 70 male patients with a presumptive diagnosis of primary or secondary syphilis, compared with 663 (14%) of 4780 without a presumptive diagnosis (p less than 0.01). Among female patients, cocaine use was reported by 27 (28%) of 97 with a presumptive diagnosis of primary or secondary syphilis, compared with 299 (13%) of 2281 without a presumptive diagnosis (p less than 0.01). In addition, among female patients with a presumptive diagnosis of primary or secondary syphilis, prostitution was reported by nine (35%) of 26 who reported cocaine use, compared with one (1%) of 69 who did not use cocaine (p less than 0.01). During January-September 1995, tests for human immunodeficiency virus (HIV) were positive for 22 (8%) of 265 STD clinic patients with early syphilis (i.e., primary, secondary, or early latent) who were tested for HIV at the time syphilis was diagnosed; in comparison, HIV-antibody tests were positive for 243 (3%) of 7079 STD clinic patients without early syphilis (p less than 0.01). Based on analysis of interview records, of 293 persons with early syphilis in 1995 for whom current HIV serostatus was known (including persons who were HIV-infected before their syphilis infection), 54 (18%) were HIV-infected. From 1993 to 1994, the number of clinicians at the two BCHD STD clinics decreased from 12 to eight and, from 1993 to 1995, the number of public health workers conducting partner notification decreased from 14 to eight. The contact index (i.e., the number of sex partners for whom information was sufficient to initiate efforts to locate that person divided by the number of persons with early syphilis interviewed), progressively declined from 1.3 in 1992 to 1.0 in 1995. The treatment index (i.e., the number of persons treated as a result of partner notification divided by the number of persons interviewed) declined from 0.6 in 1992 and 1.0 in 1993 to 0.4 in 1995. From 1993 to 1995, the number of self-referred patients that visited the two public STD clinics declined 12% (from 17,190 to 15,197). In comparison, during each year from 1990 through 1994, the proportion of gonorrhea cases reported from private health-care providers, a potential marker for access to private provider STD care, remained nearly constant (57% to 59%). Community Cocaine Use Based on data from the Drug Abuse Warning Network (DAWN), from 1990 through 1994, the annual number of listings of cocaine by medical examiners in drug-abuse-death cases in Baltimore City increased 737% (1) (Figure 2), and the annual number of cocaine-related emergency department episodes increased 239% (from 3023 to 10,243) (2). In addition, DAWN data indicated that the crack cocaine epidemic began in Baltimore City later than in other east coast cities. From 1990 through 1995, annual listings of crack cocaine use by Baltimore City residents entering drug treatment increased 196% (from 2131 to 6312) (Maryland Alcohol and Drug Abuse Administration, unpublished data). Reported by: P Beilenson, MD, A Garnes, MD, W Brathwaite, K West, K Becker, DVM, Baltimore City Health Dept; E Israel, MD, K Seechuk, D Dwyer, MD, State Epidemiologist, Maryland Dept of Health and Mental Hygiene. Epidemiology and Surveillance Br, Statistics and Data Management Br, Program Development and Support Br, Div of Sexually Transmitted Disease Prevention, National Center for Prevention Svcs, CDC. Editorial Note: During 1990, the rate for primary and secondary syphilis in the United States (20.3 per 100,000 population) was the highest since the 1940s and approximately 10-fold higher than in other industrialized countries (3). Use of crack cocaine and the exchange of sex for drugs were identified as major contributors to this epidemic (4). Although the national rate had declined to 8.1 by 1994, endemic disease at high rates persists in some communities and outbreaks continue to occur. The investigation of primary and secondary syphilis in Baltimore City identified epidemiologic patterns consistent with other urban areas of the United States: most cases occurred among blacks, and cocaine use and the exchange of money or drugs for sex were frequently reported risk behaviors; the predominance of cases among blacks may reflect factors including area of residence, socioeconomic status, and access to health services. A communitywide expansion in crack cocaine use preceded the increase in Baltimore City and most likely was the primary contributing factor. In addition, a decline in clinical and partner-notification service staffing may have limited the public health response to the increase in cases, although cocaine-associated syphilis outbreaks may be characterized by lower partner notification indices independent of available personnel (5). At least three potential intersecting epidemics may be associated with the increased occurrence of early syphilis in Baltimore City, including crack-cocaine use, congenital syphilis, and HIV infection. Because the numbers of syphilis-infected pregnant women in Baltimore City may increase, efforts to prevent congenital syphilis must be intensified (6). HIV transmission in Baltimore City may be increasing because HIV infection is associated with the use of crack cocaine (7) and because genital ulcers directly facilitate HIV transmission (8). In a previous syphilis epidemic, 18% of all documented HIV seroconversion in STD clinic patients was attributable to syphilis infection (9). Because of the duration of the incubation period of HIV and its effect on recognition of HIV transmission patterns, additional efforts should assess whether early syphilis rates are useful indicators of risk for HIV transmission. To control the increase in syphilis cases, BCHD is alerting the medical community about the syphilis outbreak (e.g., letters to and teleconferences with health-care providers), filling STD program personnel vacancies, and expanding case-finding and surveillance activities. References 1. Office of Applied Studies, Substance Abuse and Mental Health Services Administration. Annual medical examiner data, 1994: data from the Drug Abuse Warning Network. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, Substance Abuse and Mental Health Services Administration, 1995. 2. Office of Applied Studies, Substance Abuse and Mental Health Services Administration. Preliminary estimates from the Drug Abuse Warning Network: 1994 preliminary estimates of drug-related emergency department episodes. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, Substance Abuse and Mental Health Services Administration, 1995. (Advance report no. 11). 3. Nakashima AK, Rolfs RT, Flock ML, Kilmarx P, Greenspan JR. Epidemiology of syphilis in the United States, 1941-1993. Sex Transm Dis 1996;23:16-23. 4. Rolfs RT, Goldberg M, Sharrar RG. Risk factors for syphilis: cocaine and prostitution. Am J Public Health 1990;80:853-7. 5. Andrus JK, Fleming DW, Harger DR, et al. Partner notification: can it control epidemic syphilis? Ann Intern Med 1990;112:539-43. 6. CDC. Guidelines for the prevention and control of congenital syphilis. MMWR 1988;37(suppl no. S-1). 7. Edlin BR, Irwin KL, Faruque S, et al. Intersecting epidemics: crack cocaine use and HIV infection among inner-city young adults. N Engl J Med 1994;331:1422-7. 8. Plummer FA, Simonsen JN, Cameron DW, et al. Cofactors in male-female sexual transmission of HIV. J Infect Dis 1991;163:233-9. 9. Otten MW, Zaidi AA, Peterman TA, Rolfs RT, Witte JJ. High rate of HIV seroconversion among patients attending urban sexually transmitted disease clinics. AIDS 1994;8:549-53. Notice to Readers Availability of Case Definitions for Public Health Surveillance on Internet In response to high demand from state and local health departments, the 1990 MMWR Recommendations and Reports entitled Case Definitions for Public Health Surveillance (1) is now available electronically on the Internet. This document provides case definitions for use by health-care providers, laboratories, and other public health personnel who report the occurrences of notifiable diseases to state and local health departments. The reported numbers of cases of selected notifiable diseases are printed each week in Tables I-III of MMWR. Case definitions for specific conditions can be accessed individually as World-Wide Web (WWW) pages. To access these pages, use WWW browser software to connect to the CDC home page at http://www.cdc.gov/, then select MMWR -- Morbidity and Mortality Weekly Reports; go to the "new" item titled Case Definitions for Public Health Surveillance. To access the Case Definitions directly, connect to http://www.cdc.gov/epo/mmwr/other/case_def/about.html. Users can download the complete document as a .pdf file (Adobe[Registered] Acrobat[Registered]* portable document format) from the Case Definitions for Public Health Surveillance WWW page and from CDC's file transfer protocol server at ftp.cdc.gov/. When prompted for user name enter anonymous, and give your Internet e-mail address when prompted for the password. Select pub/publications/mmwr/rr/rr3913.pdf and download the file (309,488 bytes). Because of changes in software used for processing the file, the page numbers for this file do not correspond to those in the original document. Case definitions for conditions recently made nationally reportable and newly revised case definitions will be included in a supplement to this 1990 publication, which will be added to this website at a later date. The Council of State and Territorial Epidemiologists and CDC are revising the entire case definitions document for publication in late 1996. Reference 1. CDC. Case definitions for public health surveillance. MMWR 1990;39(no. RR-13). * Use of trade names and commercial sources is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services. Date: Sat, 16 Mar 1996 11:02:16 +0500 From: ghmcleaf{CONTRACTOR/ASPEN/ghmcleaf}%NAC-GATEWAY.ASPEN@ace.aspensys.com Subject: MMWR Rpts & Rcmdtns 03/01/96 MORBIDITY AND MORTALITY WEEKLY REPORT ****************************************** Centers for Disease Control and Prevention March 1, 1996 Vol. 45, No. RR-2 Recommendations and Reports U.S. Public Health Service Guidelines for Testing and Counseling Blood and Plasma Donors for Human Immunodeficiency Virus Type 1 Antigen The MMWR series of publications is published by the Epidemiology Program Office, Centers for Disease Control and Prevention (CDC), Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA 30333. SUGGESTED CITATION Centers for Disease Control and Prevention. U.S. Public Health Service guidelines for testing and counseling blood and plasma donors for human immunodeficiency virus type 1 antigen. MMWR 1996;45(No. RR-2):[inclusive page numbers]. Centers for Disease Control and Prevention............................ David Satcher, M.D., Ph.D. Director The material in this report was prepared for publication by: National Center for Prevention Services ....................... Helene D. Gayle, M.D., M.P.H. Director Division of HIV/AIDS Prevention................................. Helene D. Gayle, M.D., M.P.H. Acting Director The production of this report as an MMWR serial publication was coordinated in: Epidemiology Program Office.................................... Stephen B. Thacker, M.D., M.Sc. Director Richard A. Goodman, M.D., M.P.H. Editor, MMWR Series Scientific Information and Communications Program Recommendations and Reports................................... Suzanne M. Hewitt, M.P.A. Managing Editor Rachel J. Wilson Project Editor Morie M. Higgins Visual Information Specialist Use of trade names and commercial sources is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services. Copies can be purchased from Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402-9325. Telephone: (202) 783-3238. Contents Introduction P24-Antigen-Test Algorithm and Interpretation of Test Results Donor Counseling, Follow-up, and Deferral Implications for Other HIV Test Sites Conclusions References Single copies of this document are available from the Centers for Disease Control and Prevention, National AIDS Clearinghouse, P.O. Box 6003, Rockville, MD 20850. Telephone: (800) 458-5231. Consultants Celso Bianco, M.D. Council of Community Blood Centers New York, NY Michael Busch, M.D., Ph.D. Irwin Memorial Blood Center San Francisco, CA Richard Davey, M.D. American Red Cross Arlington, VA Steven Kleinman, M.D. American Association of Blood Banks Los Angeles, CA Susan Stramer, Ph.D. American Red Cross Atlanta, GA The following CDC staff members prepared this report: Eve M. Lackritz, M.D. Robert S. Janssen, M.D. Helene D. Gayle, M.D., M.P.H. Division of HIV/AIDS Prevention National Center for Prevention Services Charles A. Schable, M.S. Harold W. Jaffe, M.D. Division of AIDS, STD, and TB Laboratory Research National Center for Infectious Diseases in collaboration with Jay S. Epstein, M.D. Paul A. Mied, Ph.D. Sharon J. Geyer, Ph.D. Office of Blood Research and Review Center for Biologics Evaluation and Research Food and Drug Administration U.S. Public Health Service Guidelines for Testing and Counseling Blood and Plasma Donors for Human Immunodeficiency Virus Type 1 Antigen Summary The Public Health Service (PHS) has recommended a multifaceted approach to blood safety in the United States that includes stringent donor selection practices and the use of screening tests. Blood donations in the United States have been screened for antibody to human immunodeficiency virus type 1 (HIV-1) since March 1985 and type 2 (HIV-2) since June 1992. An estimated one in 450,000 to one in 660,000 donations per year (i.e.,18 27 donations) are infectious for HIV but are not detected by currently available screening tests. Because maintaining a safe blood supply is a public health priority, the Food and Drug Administration (FDA) recommended in August 1995 that all donated blood and plasma also be screened for HIV-1 p24 antigen, effective within 3 months of licensure of a test labeled for such use. Donor screening for p24 antigen is expected to reduce the number of otherwise undetected infectious donations by approximately 25% per year. Routine testing for p24 antigen in settings other than blood and plasma centers as a method for diagnosing HIV infection is discouraged because the estimated average time from detection of p24 antigen to detection of HIV antibody is 6 days, and not all recently infected persons have detectable levels of p24 antigen. Among children >= 18 months of age and adults, diagnostic testing for HIV infection, including confirmatory testing, should routinely be performed with FDA-licensed assays for antibodies to HIV-1; p24-antigen tests alone should not be used for diagnosing HIV infection. This report provides PHS guidelines for a) interpreting p24-antigen assay results, b) counseling and follow-up of blood donors who have positive or indeterminate p24-antigen-test results, and c) using p24-antigen testing in settings other than blood banks. INTRODUCTION In the United States, the implementation of antibody testing in 1985 of all donated blood for human immunodeficiency virus type 1 (HIV-1) resulted in a substantial decrease in the transmission of HIV through blood transfusions (1,2). To further decrease the risk for transmission of HIV by transfusion, the testing of all blood donations with a combination antibody test for HIV-1 and HIV type-2 (HIV-2) was implemented by June 1992. The risk for HIV transmission by transfusion of screened blood is minimal. Nearly all cases of transfusion-associated HIV transmission are now caused by blood donated during the infectious window period (i.e., when recently infected donors are infectious but have not yet developed detectable levels of HIV antibody). When whole-virus lysate enzyme immunosorbent assays (EIAs) were used to screen blood donations from 1985 through 1990, the average length of the window period was 45 days (95% confidence interval [CI]=34 55 days) (3). The average window period of the most sensitive contemporary recombinant protein-based EIA for HIV-1 and HIV-2 antibodies is now 20 days less (4), yielding an average infectious window period of 25 days (95% CI=9 41 days) (5). The increased sensitivity of contemporary HIV-antibody EIAs, improved donor interviewing about behaviors associated with risk for HIV infection, and deferral of donors who test positive for HIV, hepatitis, human T-cell leukemia virus type 1 (HTLV-I), or syphilis have considerably improved the safety of the U.S. blood supply. In 1993, only approximately six per 100,000 blood donations collected by the American Red Cross tested positive for HIV antibody (6). In addition, only an estimated one in 450,000 to one in 660,000 donations per year (i.e., 18 27 donations) were infectious for HIV but were not detected by current screening tests (5). During the acute period of infection, tests for p24 antigen can detect HIV infection earlier than antibody tests. P24 antigen, the core structural protein of HIV, is detectable 2 3 weeks after HIV infection during the initial burst of virus replication associated with high levels of viremia (7,8). During this time, the blood of infected persons is highly infectious, and tests for p24 antigen are usually positive (9 11). On average, p24 antigen is detected an estimated 6 days before antibody tests become positive (4,9). When antibodies to HIV become detectable, p24 antigen is often no longer detectable because of antigen-antibody complexing and viral clearance (9 11). In August 1995, the Food and Drug Administration (FDA) recommended that all blood and plasma donations be screened for p24 antigen, effective within 3 months of licensure of a test labeled for such use (12). FDA recommended p24 screening as an additional safety measure because a) recent studies indicated that p24 screening reduces the infectious window period (4), b) implementation of p24-antigen testing had become logistically feasible for mass screening, and c) such testing would reduce the risk for HIV infection for persons who receive donated blood or blood products. Among the 12 million annual blood donations in the United States, p24-antigen screening is expected to detect four to six infectious donations that would not be identified by other screening tests. If each of these units were divided into an average of 1.8 blood components (13), antigen testing would result in removal of an estimated seven to 11 infectious components each year that would otherwise be available for transfusion. FDA regards donor screening for p24 antigen as an interim measure pending the availability of technology that would further reduce the risk for HIV transmission from blood donated during the infectious window period. This report provides guidelines for a) interpreting p24-antigen assay results, b) counseling and follow-up of blood and plasma donors who have positive or indeterminate antigen-test results, and c) using p24-antigen testing in settings other than blood banks. These guidelines may be modified when additional information concerning antigen testing under mass screening conditions is collected and analyzed. Definitions used in interpreting HIV-1 p24-antigen tests according to FDA recommendations: * Initially reactive Initial p24 EIA test is reactive. * Repeatedly reactive One or both duplicate p24 EIA retests is (are) reactive. * Negative Initial p24 EIA test is not reactive; or, initial p24 EIA test is reactive and both duplicate p24 EIA retests are not reactive. * Positive P24 EIA test is repeatedly reactive and the neutralization test is positive (i.e, neutralizing). * Indeterminate P24 EIA test is repeatedly reactive and the neutralization test is either negative (i.e., non-neutralizing) or invalid. P24-ANTIGEN-TEST ALGORITHM AND INTERPRETATION OF TEST RESULTS The p24-antigen screening assay is an EIA performed on serum or plasma. If the first screening test is nonreactive, the test result is reported as negative (see Definitions used in interpreting HIV-1 p24-antigen tests according to FDA recommendations). If the first screening test is reactive, the p24 EIA is repeated in duplicate. If both duplicate tests are nonreactive, the test result is reported as negative. If at least one of the repeated p24 EIA tests is reactive, the test is considered repeatedly reactive; the donation is then discarded, the donor is deferred from donating blood, and a more specific assay (the neutralization assay) is performed to verify the presence of p24 antigen. The neutralization assay should be performed before informing donors of test results. As specified by FDA (12), donations collected within 3 months of a repeatedly reactive p24-antigen test (regardless of neutralization-assay results) should be quarantined pending results of repeat donor testing for antigen and antibody to HIV. Sample storage requirements and time restrictions specified in the test kit package insert should be closely followed to prevent sample deterioration, and thus, invalid test results. FDA recommends that units of whole blood, blood components, source leukocytes, and source plasma obtained from donors whose blood samples are repeatedly reactive on p24-antigen screening tests be destroyed or quarantined and not used for transfusion or for manufacturing into injectable products. Available data indicate that the p24-antigen assay is sensitive and specific. The specificity of the p24-antigen test was calculated by two test-kit manufacturers to be 99.95% and 99.93% (Table 1) (14). Additionally, in one study of 514,000 donations, 225 were repeatedly reactive on the screening test. Of these donations, neutralization tests were negative for 220 (98%). Five (2%) donations were negative on neutralization tests and had detectable HIV antibodies. Testing by the polymerase chain reaction (PCR) for HIV DNA and RNA was performed on 120 of these non-neutralizing blood donations, all of which were negative for HIV. Follow-up samples were obtained from 79 of these donors, all of which were negative for HIV-1 antibody (15). In a pro-spective study conducted from September 1993 through September 1995, a total of 305,989 donations were tested for p24 antigen; three donors had both repeatedly reactive p24-antigen EIA screening-test results and positive neutralization results (two of whom were also HIV-antibody positive), and 223 donors had repeatedly reactive p24-antigen EIA screening-test results and negative neutralization results. Of those donors who had negative neutralization results, 81 later returned to donate blood again. Sixty-five of these donors had negative test results for HIV-1/HIV-2 antibody and for antigen EIA and neutralization. However, 16 donors who were HIV-1/HIV-2 antibody negative on subsequent donations continued to have repeatedly reactive p24-antigen EIA screening tests that did not neutralize (16). A recent study of 51 seroconversion panels has yielded an estimate of clinical sensitivity of the p24-antigen screening test in detecting blood donated during the infectious window period. An analysis of 69 preseroconversion samples that were positive for HIV-1 RNA by PCR demonstrated that the antigen test was reactive for 51 (74%) of those samples (M.P. Busch, personal communication, 1995). To assess sensitivity of the neutralization test, two antigen-test-kit manufacturers also performed neutralization testing on samples of blood from persons seroconverting to HIV. One manufacturer tested 102 repeatedly reactive specimens from 30 seroconverting plasma donors; 100% were positive on the neutralization assay. Similarly, a second manufacturer found that all 52 repeatedly reactive specimens from 25 seroconverting plasma donors were positive on the neutralization test (14). DONOR COUNSELING, FOLLOW-UP, AND DEFERRAL Counseling blood and plasma donors who have positive or indeterminate HIV-test results is an essential adjunct to HIV testing. Counseling in the bloodbank setting a) provides information about follow-up diagnostic evaluation and available medical, preventive, and psychosocial services and b) assists infected persons in preventing transmission to others. HIV counseling should be conducted in accordance with PHS standards and guidelines (17,18). TABLE 1. Specificity of HIV-1 p24 antigen for use in screening blood and plasma donors (14) Repeatedly Manu- Study No. of Initially Repeatedly reactive & facturer Pop. specimens reactive (%) reactive (%) neutralized (%*) A Blood donors 301,699 1,348 (0.45) 144 (0.05) 3 (2.10) B Blood and 10,270 47 (0.46) 8 (0.08) 1  (12.50) plasma donors *Percentage of specimens that were repeatedly reactive. Two of three specimens were also antibody positive. The third specimen was from a donor who subsequently showed no other evidence of HIV infection. The specificity of Manufacturer A's antigen assay is approximately 99.95% (301,555 per 301,697) based on a) an assumed zero prevalence of HIV-1 p24 antigen in random blood donors who have no other evidence of HIV-1 infection and b) additional testing using the neutralization test and Western blot analysis for HIV-1 antibodies.  The repeatedly reactive specimen was confirmed as being HIV-1 p24-antigen positive; the donor subsequently seroconverted to antibodies to HIV-1. When the HIV-1 p24-antigen positive donor was removed from the calculation, the specificity of Manufacturer B's test was 99.93% (10,262 per 10,269; 95% confidence interval=99.86%-99.97%). PHS guidelines for notification and counseling of donors who have repeatedly reactive antigen-test results are based on available data. These guidelines may be modified after the collection and analysis of additional information concerning antigen testing under mass screening conditions. Donors Who Have Positive P24-Antigen-Test Results Donors whose HIV-antibody-test results are negative, but whose screening-test results for HIV antigen are repeatedly reactive and neutralization-assay results are positive, should be counseled that they are probably infected with HIV (Figure 1). Donors who have such test results should be notified promptly after a positive neutralization test. Prompt notification is important because persons who are newly infected with HIV and do not have HIV antibodies often have high viral titers and may be at high risk for transmitting HIV infection (7). According to FDA recommendations, donors who have repeatedly reactive and neutralizing p24-antigen tests should be advised that they are permanently deferred from future blood and plasma donation. Donors who have repeatedly reactive EIA and neutralizing HIV antigen tests should have their results confirmed by follow-up antibody testing; diagnosis of HIV infection should not be made on the basis of p24-antigen-test results alone. Arrangements for follow-up antibody testing should be incorporated into routine counseling. Because the time between detection of antigen and antibody is estimated to be an average of 6 days, donors who have positive p24-antigen-test results can be offered repeat antigen and antibody testing at any follow-up visit. If repeat antigen tests remain reactive and antibody tests remain negative, antibody testing should be repeated after a minimum of 8 weeks to allow time for antibodies to develop. Pending repeat testing to confirm the initial positive antigen-test result, strategies to reduce transmission should be implemented immediately by the donor (e.g., abstaining from sexual intercourse and using condoms consistently and correctly). If follow-up antibody tests are positive thus confirming HIV infection infected persons should be referred for medical care; sex and needle-sharing partners of such persons should be advised to seek HIV testing at clinical sites. Some donors repeatedly have positive p24-antigen and negative HIV-antibody-test results, although such an occurrence is unusual. If after 8 weeks such persons still have negative antibody-test results, they should be referred for further medical evaluation, including determining CD4+ T-lymphocyte cell count or percentage. Testing for HIV by PCR or culture also may be helpful in determining HIV status; however, neither test is licensed for diagnosis of HIV infection. Donors Who Have Repeatedly Reactive P24-Antigen Screening-Test Results but Negative or Invalid Neutralization-Test Results In the blood- and plasma-donor population, which has a low prevalence of HIV infection, most repeatedly reactive p24-antigen screening-test results are expected to be false-positive reactions. Donors who have repeatedly reactive p24-antigen screening tests but have negative neutralization and HIV-antibody tests are probably not infected with HIV. Donors who have negative neutralization results should be counseled that their antigen screening tests were reactive but that their supplementary tests were negative, which likely represents a false-positive test. Although donors who have negative neutralization results should be reassured that their test result probably does not represent infection, they should be counseled to take HIV risk-reduction precautions until repeat testing has confirmed their HIV-infection status. An invalid neutralization result occurs when a sample is repeatedly reactive in the initial screening test, but in the neutralization assay, the neutralized sample and unneutralized control both fall below the cutoff level. Most frequently, invalid results occur when a screening-test value is low or borderline reactive in an uninfected person; however, invalid results can also occur when a screening-test value is low or borderline reactive in an infected person (15). An invalid result may also be the result of sample deterioration or antigen-antibody complex formation during storage. Donors who have invalid neutralization results should be counseled that their antigen screening tests were reactive but their supplementary tests were inconclusive because the neutralization-test results were invalid. These donors are probably not infected with HIV, but infection cannot be excluded. Donors who have invalid neutralization-test results should be counseled to take HIV risk-reduction precautions until their HIV-infection status is confirmed. Retesting a fresh sample may clarify the result. To exclude HIV infection, donors who have repeatedly reactive p24-antigen screening-test results, invalid or negative neutralization-test results, and negative HIV-antibody-test results can be offered repeat antigen and antibody testing at any follow-up visit. Negative antigen- and antibody-test results at the time of follow-up indicate the donor was not infected with HIV at the time of the initial test. For donor reentry purposes, or for diagnostic purposes among donors who continue to have reactive antigen screening-test results and negative antibody-test results, repeat antigen and antibody testing should be performed a minimum of 8 weeks after the initial repeatedly reactive antigen screening test. Negative antigen and antibody tests performed >=8 weeks after the initial repeatedly reactive antigen screening tests indicate the donor was not infected with HIV at the time of the initial test. If the donor's screening antigen test remains repeatedly reactive, neutralization test remains negative, and HIV-antibody tests are negative or indeterminate, the donor is probably not infected with HIV. Further follow-up and additional tests (i.e., CD4+ T-lymphocyte cell count or percentage, HIV PCR, and culture) may clarify infection status, although these tests are not licensed for diagnosis of HIV infection. FDA recommendations indicate that donors whose blood samples are repeatedly reactive by the p24 screening test and negative or invalid on the neutralization test should be temporarily deferred from donating blood or plasma for a minimum of 8 weeks. These persons should be counseled that donor deferral does not indicate infection, because the screening test on which the deferral was based was most likely a false-positive result. If, after 8 weeks, samples from such donors test negative by screening tests for p24 antigen and antibodies to HIV, the donors are not infected and can be reinstated as blood or plasma donors. However, if, after 8 weeks, samples test repeatedly reactive on the screening test for HIV antigen or are positive for antibody, the donors should be permanently deferred from donating blood or plasma-regardless of HIV-antigen neutralization-test results. IMPLICATIONS FOR OTHER HIV TEST SITES Initiation of p24-antigen screening of the blood supply may motivate some persons who are at high risk for HIV infection to donate blood to determine HIV status. Such an unintended inducement could offset the benefits of p24-antigen screening (19). Since 1983, PHS has discouraged persons at high risk for HIV infection from donating blood (20). Such persons should be discouraged from donating blood and plasma and encouraged to be tested for HIV antibody at other sites. Initiation of routine testing for p24 antigen in publicly funded HIV counseling and testing sites, physicians' offices, or other nonbloodbank settings is not recommended. Few additional infected persons would be identified by routine antigen testing in such settings, because the estimated average time from detection of p24 antigen to detection of antibody is only 6 days. In addition, recently infected persons may not have detectable levels of p24 antigen. However, antigen testing may be appropriate in certain circumstances, such as diagnosis of perinatally exposed children (21,22). Diagnostic testing for HIV infection in children >=18 months of age and adults should routinely consist of an HIV-1 antibody screening test and Western blot or immunofluorescent assay for confirmation of antibodies to HIV-1. CONCLUSIONS PHS is committed to maintaining a safe blood supply. To further promote this goal, FDA has recommended that all blood and plasma donations be screened with tests for HIV-1 p24 antigen because these test results frequently become positive before assays for HIV antibodies. Screening blood donors for p24 antigen is expected to remove four to six infectious donations from the blood supply each year that would not be removed by other screening tests. After implementation of p24-antigen screening, CDC will collaborate with blood-and plasma-collection agencies to evaluate the sensitivity, specificity, and positive predictive value of the p24-antigen test. As a result, the p24-antigen testing algorithm and counseling guidelines may be modified after additional data are collected and analyzed. References 1. Ward JW, Holmberg SD, Allen JR, et al. Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody. N Engl J Med 1988;318:473 8. 2. Selik RM, Ward JW, Buehler JW. Trends in transfusion-associated acquired immune deficiency syndrome in the United States, 1982 through 1991. Transfusion 1993;33:890 3. 3. Petersen LR, Satten GA, Dodd R, et al. Duration of time from onset of human immunodeficiency virus type 1 infectiousness to development of detectable antibody. Transfusion 1994;34:283 9. 4. Busch MP, Lee LLJ, Satten GA, et al. Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors. Transfusion 1995;35:91 7. 5. Lackritz EM, Satten GA, Aberle-Grasse J, et al. Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med 1995;333: 1721 5. 6. CDC. National HIV serosurveillance summary: results through 1992. Vol. 3. Atlanta, GA: US Department of Health and Human Services;1994. 7. Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med 1991;324:961 4. 8. Clark SJ, Saag MS, Decker WD, et al. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med 1991;324:954 60. 9. Gallarda JL, Henrard DR, Liu D, et al. Early detection of antibody to human immunodeficiency virus type 1 by using an antigen conjugate immunoassay correlates with the presence of immunoglobulin M antibody. J Clin Microbiol 1992;30:2379 84. 10. Zaaijer HL, v. Exel-Oehlers P, Kraaijeveld T, Altena E, Lelie PN. Early detection of antibodies to HIV-1 by third-generation assays. Lancet 1992;340:770 2. 11. Henrard DR, Phillips J, Windsor I, et al. Detection of human immunodeficiency virus type 1 p24 antigen and plasma RNA: relevance to indeterminate serologic tests. Transfusion 1994;34:376 80. 12. Food and Drug Administration, Center for Biologics Evaluation and Research. Recommendations for donor screening with a licensed test for HIV-1 antigen [memorandum]. August 8, 1995. 13. Surgenor DM, Wallace EL, Hao SHS, Chapman RH. Collection and transfusion of blood in the United States, 1982 1988. N Engl J Med 1990;322:1646 51. 14. Workshop on Implementation of HIV-1 P24 Antigen. Bethesda, MD: November 7, 1995. 15. Alter HJ, Epstein JS, Swenson SG, et al. Prevalence of human immunodeficiency virus type 1 p24 antigen in U.S. blood donors an assessment of the efficacy of testing in donor screening. N Engl J Med 1990;323:1312 7. 16. Gilcher R, Smith J, Belcher l, Chandler R. Prospective HIV antigen (p24 antigen) testing: donor detection [S-168]. 48th Annual Meeting of the American Association of Blood Banks, New Orleans, November 11-15, 1995. 17. CDC. HIV counseling, testing, and referral standards and guidelines. Atlanta, GA: US Department of Health and Human Services, Public Health Service, CDC, 1994. 18. CDC. Recommendations for HIV testing services for inpatients and outpatients in acute-care hospital settings; and Technical guidance on HIV counseling. MMWR 1993;42(No. RR-2):11 6. 19. Korelitz JJ, Busch MP, Williams AE. Antigen testing for human immunodeficiency virus (HIV) and the magnet effect: will the benefit of a new HIV test be offset by the numbers of higher-risk, test-seeking donors attracted to blood centers? Transfusion 1996 (in press). 20. CDC. Prevention of acquired immune deficiency syndrome (AIDS): a report of inter agency recommendations. MMWR 1983;32:101 3. 21. Early HIV infection Guideline Panel. Clinical Practice Guideline Number 7: evaluation and management of early HIV infection. Washington, DC: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1994;DHHS publication no. (AHCPR)94-0572. 22. CDC. 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR 1994;43(No. RR-12):1 10. 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