How the response to the epidemic of HIV infection has strengthened the public health system.

Since acquired immunodeficiency virus (AIDS) was first identified in 1981, it has become one of the leading causes of death in men and women 25-44 years of age in the United States. The urgent public health response to the human immunodeficiency virus (HIV) and AIDS epidemic has required the development of new prevention programs; these efforts have significantly strengthened the public health system itself. A major part of CDC's mission is to prevent HIV infection and reduce the incidence of HIV-associated illness. In fighting HIV infection and AIDS, as in all successful public health programs, CDC has four important goals: (a) to assess risks, (b) to develop prevention technologies, (c) to build prevention capacities, and (d) to implement prevention programs. The urgency of the need to prevent HIV infection and AIDS has in many instances added impetus or substance to programs already under way, as well as prompting the development of new initiatives to meet the four goals. Examples of ways in which the public health system has benefited from HIV-related programs and activities are detailed in this article. Although the HIV epidemic has created significant stresses in many areas of public health and medical services, the experience gained in dealing with this epidemic will strengthen the nation's response to other health crises that arise. Despite the huge challenges, lessons learned thus far provide direction and hope for the future.

Adsorption of fetal surfactant protein SP-B on the human amnion at term and on amniocytes incubated with fetal surfactant in vitro.

Fetal surfactant stimulates the synthesis of prostaglandins by slices of human amnion at term and by a human amnion cell line, and these effects are partly dependent upon surfactant apoproteins. In this paper, methods are described for the purification of surfactant from human amniotic fluid and from post-mortem human lung. A procedure is described for the purification of surfactant protein SP-B from human amniotic fluid, and the sequence of 20 amino acids at the N-terminal has been determined. A monoclonal antibody generated against human lung surfactant has been shown to react with SP-B from amniotic-fluid surfactant, and the presence of SP-B on the surface of the amnion at term has been demonstrated by immunohistochemical methods. It has also been shown that SP-B from surfactant is present on the surface of amniocytes incubated with surfactant in vitro.

Current CDC efforts to prevent and control human immunodeficiency virus infection and AIDS in the United States through information and education.

The human immunodeficiency virus (HIV) is estimated to have infected more than a million people in the United States and millions more in other countries. Even though there is no vaccine or effective treatment, HIV infection can be prevented through behavioral change. As the lead Public Health Service Agency for disease prevention, the Centers for Disease Control (CDC) has designed and implemented information and education activities with the ultimate goal of preventing HIV infection and AIDS in the United States. The target populations include the general public, school- and college-aged populations, persons infected or at increased risk of infection, minorities, and health workers. Because AIDS will be with us for a long time, CDC views educating the public as a long-term undertaking. The agency has initiated an intensive continuing national public information campaign, an informational brochure to be distributed to every U.S. household, a national AIDS information toll-free hotline, and a clearinghouse system that will maintain a comprehensive inventory of AIDS information resources and services. CDC also supports public information and education efforts by State and local health agencies. To reach school- and college-age youth, CDC, in consultation with governmental and national private sector organizations, developed guidelines for effective school health education to assist school health personnel in determining the scope and content of AIDS education. CDC also works with State and local education agencies to help carry out and evaluate educational efforts to prevent the spread of HIV among school- and college-age youth. The populations with the highest priority for AIDS information and education efforts are those who are at increased risk of acquiring or transmitting the AIDS virus because they use illicit intravenous drugs and share needles, engage in anal intercourse, have many sexual partners, practice prostitution, or engage in sex with those who practice these behaviors. Another high-priority population, because they can infect their offspring,is reproductive age women engaging in high-risk behavior and women infected with HIV who become pregnant. CDC programs targeted to these groups include community health education and risk reduction interventions, counseling and testing for HIV infection, AIDS community demonstration projects, perinatal AIDS prevention projects,and programs focused on preventing AIDS in minority populations. CDC is developing a variety of educational approaches for health workers in clinical settings because they are an important channel for providing accurate AIDS information, helping to assess risk, and counseling to actively reduce risk for the patient, sex partners of the patient, friends, and family members of the patient. CDC has conducted research and provided information and training on the use of HIV laboratory tests. CDC has also developed numerous scientific and technical guidelines and recommendations in consultation with practitioners, public health officials, and others and disseminated these through the Morbidity and Mortality Weekly Report. In addition,CDC has provided information about the risk of HIV transmission in the workplace and about methods of prevention. CDC will continue to evaluate these activities and support research in education and related interventions that may be necessary to prevent infection by the HIV virus. By providing educational support for behavior changes that decrease HIV transmission, we can contribute to AIDS prevention in the 1990s.

Acellular and whole-cell pertussis vaccines in Japan. Report of a visit by US scientists.

Since the introduction of acellular pertussis vaccines in Japan late in 1981, more than 20 million doses have been administered, mostly to children 2 years of age and older. Clinical studies indicate that mild local and febrile reactions are less frequent after administration of acellular pertussis vaccines than after whole-cell vaccines. Serious adverse events with sequelae occurred in 2-year-old children at approximately the same low rate during the period 1975 through August 1981, when whole-cell vaccines were used, and during August 1981 through 1984, when acellular vaccines were used exclusively. Five household contact studies have yielded vaccine efficacy estimates ranging from 78% to 92% in children 1 year of age or older. In addition, there has been a continuing decrease in reported pertussis incidence from the epidemic peak in 1979. Additional data on the safety and efficacy of acellular pertussis vaccines administered to infants would be useful in consideration of acellular pertussis vaccine licensure in the United States.

An immune response profile model for immunogenicity quantitation.

We propose an analytical model, which can simultaneously depict many fundamental characteristics of the immunogenicity of various vaccines. This model, the Immune Response (IR) profile, conveniently expresses the mathematical relation between pre- and post-vaccination titers. A vaccine's IR profile is antigen-specific, dose-dependent and post-vaccination interval-dependent. The maximal capability for serological response to a vaccine can be determined using this model irrespective of the dose administered, the post-vaccination assay interval, or the live or killed state of the vaccine. The IR profile obtained from analysis of booster vaccine responses in a limited number of seropositive study subjects can be used to predict maximal antibody titers which are expected after vaccination and can predict the geometric mean post-vaccination antibody titer of a cohort of subjects undergoing primary immunization. Using this model, it is anticipated that the immunoregulation implied by the IR profile may also prove to be correlated with cellular subpopulations and idiotypic antibody functions. Although derived from influenza vaccines analyses, the model successfully describes immune response characteristics following natural infection with malaria and following diphtheria and rubella vaccine administration.

Cytotoxic T-cell immunity to influenza.

In a study designed to determine whether cytotoxic T lymphocytes contribute to immunity against influenza virus infection, we inoculated 63 volunteers intranasally with live unattenuated influenza A/Munich/1/79 virus. Over the next seven days clinical observations were made, and the amount of virus shed was measured. The protective effects of preinfection serum antibody and of cytotoxic T-cell immunity against influenza A virus were assessed for each participant. All subjects with demonstrable T-cell responses cleared virus effectively. This response was observed in volunteers in all age groups, including those born after 1956, who did not have specific antibody and hence had probably not been exposed to this subtype of influenza A virus before. Cytotoxic T cells show cross-reactivity in their recognition of the different subtypes of influenza A virus, in contrast to the antibody response that is specific for each virus subtype. We conclude that cytotoxic T cells play a part in recovery from influenza virus infection.

Summary of clinical trials of inactivated influenza vaccine - 1978.

This report summarizes the clinical trials of the A/USSR/77 (H1N1) influenza vaccines performed in 1978. A total of 2,091 subjects participated in these trials. The results of these clinical trials indicated that two doses of H1N1 viral antigen were necessary to produce serum titers of hemagglutinin-inhibiting (HAI) antibody of greater than 1:40 in 80% or more of the test subjects younger than 25 years of age, who were unlikely to have experienced natural infection during the earlier period of prevalence of H1N1 virus (1947-1957). Only one dose of the A/Texas/77 (H3N2) or B/Hong Kong/72 antigen was necessary to stimulate equivalent titers of HAI antibody in serum. Thus, previous natural exposure to H1N1 viruses primed individuals 26 years of age or older to respond to H1N1 antigens. No major differences in antigenicity were noted between whole-virus and split-virus vaccines. No differences in reaction indexes measuring systemic reactions were noted when vaccine types were compared. Only one vaccine was associated with a reaction index appreciably higher than that of placebo. The relatively uniform antibody responses observed were attributed to the newer methods of vaccine standardization introduced after the clinical trials in 1976. No cases of vaccine-related neurological problems, including Guillain-Barré syndrome, were found during these trials. Vaccines containing 7-21 micrograms of each viral antigen were antigenic and were well tolerated.

An outbreak of influenza B in an elderly population.

An outbreak of influenza B occurred in an elderly population residing in a Minnesota nursing home between April 24 and May 21, 1979 and involved 129 (35.9%) of the 359 residents. Throat swabs from 11 and 19 acutely ill residents yielded influenza B virus similar to the B/Singapore/79 strain. Fourfold or greater increases in titer of complement-fixing or hemagglutination-inhibiting antibodies were detected in paired sera from 18 of the 19 persons affected and from three of 16 unaffected residents. Three hundred thirty-three (93%) of the 359 residents had received trivalent influenza virus vaccine in November 1978. The attack rate was age-specific and increased with age (z = 2.69; P = 0.007). Increasing susceptibility to influenza B with age in the elderly has not been previously demonstrated in this infrequently studied population. Increased risk for becoming ill was also found to be statistically associated with decreasing levels of care required and residence in closed wards and temporally associated with taking meals in the facility's dining areas.

Outbreak of influenza A/USSR/77 at Marquette University.

An outbreak of influenzalike illness occurred at Marquette University, Milwaukee, Wisconsin, in February 1978. Epidemiologic and laboratory data indicate that the outbreak was due to influenza A/USSR/77 (N1H1) virus. A self-administered questionnaire inquiring about the presence and spectrum of illness was given to faculty members, dental students, and residents of an undergraduate dormitory. Age-specific attack rates were 61.5% for persons less than or equal to 22 years of age, 24.7% for those 23 or 24 years of age, and 9.7% for those greater than or equal to 25 years of age. This pattern of age-specific attack rates paralleled the age distribution of persons without hemagglutination-inhibiting antibody to influenza A/USSR/77 virus found in independent serosurveys. Prior swine influenza (H1N1) immunization provided no protection from illness in this outbreak. Past epidemic antibody titers in undergraduates were only weakly associated with clinical illness. The data on disease impact gathered in this study indicate that in a university setting influenza A/USSR/77 virus produced a short-lived outbreak of respiratory illness with a very high attack rate in young adults.

Influenza vaccine in unprimed children: improved immunogenicity with few reactions following one high dose of split-product vaccine.

Thirty-one unprimed children and young adults received an influenza A/USSR/77 vaccine containing 43 microgram of hemagglutinin. Their HAI antibody response was compared to that in 92 age-matched individuals from the 1978 national influenza immunization trial who received 10 and 4 microgram HA vaccines. A dose-related antibody response was observed after the first vaccine doses in the 7- to 12- and 13- to 25-year-old groups. An HAI titer greater than or equal to 40 was present in 81% and 93% of 43 microgram HA recipients, in 38% and 43% of 10 microgram HA recipients, and in 24% and 12% of 4 micrograms HA recipients respectively. The antibody response to the 43 microgram HA dose was significantly higher than was the response to the 10 and 4 microgram HA doses. The local and systemic side effects were not significantly different among the three vaccine groups and the placebo group. Thus, a high dose of influenza A/USSR/77 split-product vaccine given to unprimed children and young adults stimulated presumably protective levels of antibody and was free of a significant incidence of side effects.

Sensitivity and specificity of enzyme immunoassay for serodiagnosis of influenza A virus infections.

Antibodies to influenza virus in sera from 40 patients infected with influenza A/USSR/90/77H1N1-like virus were measured by an enzyme immunoassay (EIA), and results were compared with those obtained by complement-fixation (CF) and hemagglutination-inhibition (HAI) tests. The sensitivity of EIA in detecting an increase in influenza antibody in sera from these 40 patients was intermediate (27 of 40) between the CF test (19 of 40) and the HAI test (35 of 40) when an ether-treater influenza A/USSR/77 virus was used as antigen in all three tests. In contrast with results from HAI tests, however, EIA did not reliably distinguish between infections caused by H1N1 and H3N2 viruses; EIA was thus most comparable in specificity to the CF test. It appears, therefore, that both EIA and CF tests measure antibodies directed to internal antigens common to all type A influenza strains, and that EIA with whole or ether-split influenza virus antigen may be a feasible alternative to the CF test for the type-specific serodiagnosis of influenza infections.

Laboratory-based surveillance of influenza virus in the United States during the winter of 1977-1978. I. Periods of prevalence of H1N1 and H3N2 influenza A strains, their relative rates of isolation in different age groups, and detection of antigenic variants.

Influenza A (H3N2) viruses were isolated from outbreaks and epidemics of disease during the period December 1977 to March 1978. For the last two months of this period, H1N1 strains of influenza A were also responsible for epidemics. In some regions (e.g., Hawaii) co-circulation of H1N1 AND H3N2 strains occurred, whereas in other regions (e.g., Wisconsin) isolation of H3N2 strains had almost ceased prior to isolation of H1N1 strains. Few influenza B isolates were reported. Analysis of the ages of patients from whom specimens were submitted for influenza virus isolation confirmed that, whereas H3N2 strains were isolated from persons of all ages, greater than 97 per cent of H1N1 isolates in six states analyzed were recovered from patients less than 26 years old, although specimens were tested from older persons who were ill during the period of prevalence of H1N1 influenza. The majority of H3N2 isolates tested by hemagglutinin-inhibition reaction were similar to A/Texas/1/77, and the majority of H1N1 isolates were similar to A/USSR/90/77. Antigenic analysis of isolates, however, identified a small number of variants of H3N2 and H1N1 strains.

Laboratory-based surveillance of influenza virus in the United States during the winter of 1977--1978. II. Isolation of a mixture of A/Victoria- and A/USSR-like viruses from a single person during an epidemic in Wyoming, USA, January 1978.

At a time when outbreaks and sporadic cases of influenza caused a A/Victoria/3/75-like and A/Texas/1/77-like H3N2 strain of influenza were occurring in the Rocky Mountain region of the USA, about 60% of the students of a high school in Cheyenne, Wyoming, were involved in an outbreak of influenza-like illness. Six influenza A(H1N1) virus isolates were obtained from throat swabs collected from 12 of these students. Virus isolated from a seventh student, however, contained a mixture of H1 and H3 (A/Victoria/3/75-like) hemagglutinins and N1 and N2 neuraminidases, as shown by the ability to clone from the mixture viruses with antigenic components H1N1, H3N1, and H3N2. An antigenic hybrid virus with H3N1 composition was re-isolated from the original throat swab. The results show that one student was shedding a mixture of A/Victoria/3/75(H3N2)-like and A/USSR/90/77(H1N1)-like viruses at the time his throat swab was taken.

Elevated titer of antibodies to Simian sarcoma virus envelope antigen (gp70) and normal response to influenza virus in untreated Danish Hodgkin's patients.

Untreated Danish Hodgkin's disease (HD) patients and paired age- and sex-matched controls were tested for serum antibodies to Epstein-Barr virus (EBV), six strains of influenza virus and Simian sarcoma virus/Simian sarcoma-associated virus [SSV(SSAV)] antigens. HD sera showed significantly elevated titers against EBV and both increased incidence and mean titer of antibodies to the envelope glycoprotein of SSV(SSAV), whereas testing against the influenza viruses revealed no differences between HD and controls. A focus reduction assay demonstrated a low incidence in HD and controls of sera with neutralizing effects against SSV(SSAV) and the "baboon" C-type virus component of the human HL-23 virus complex, which seemed coupled to HL-A type W19.