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Prospects for vaccine research, development, and use over the next decade are extraordinarily optimistic. Innovative investigative programs promise new vaccines with reduced numbers of injections, combinations of multiple antigens, and confinement of administration to the early weeks or months of life. Enhanced attention to the infrastructure and support of immunization programs should rapidly augment coverage to more than 90% of the US infant population in the first 2 years of life with all the recommended vaccines. Programs of the WHO and CVI should extend protection from morbidity and mortality of diseases preventable with vaccine to children of all nations. Adjustments and realignments of the Vaccine Injury Compensation Program should reduce to realistic dimensions the finances of benefits for children who suffer the rare, true adverse responses to required immunizations. In order to maintain familiarity and leadership in childhood immunization, pediatricians will need to maintain careful attention to and familiarity with all these emerging developments.

The history of the elimination of polio from the United States began in 1949 with the landmark achievement by Enders, Robbins, and Weller of the isolation and growth of polioviruses in cell culture systems. Within 5 years, Jonas Salk had developed and successfully tested his inactivated polio virus vaccine (IPV) incorporating all three serotypes in a formalin-heat inactivated preparation. After the successful Francis Field trial in April 1955, widespread programs for immunization were begun throughout the United States. Over the succeeding 4 years the success in marked reduction of polio each summer and autumn resulted in annual totals of fewer than 2000 paralytic patients in contrast to the previous tolls of 25 000 each year.

Virologic and CD4 Response to Treatment with Nelfinavir in Therapy Experienced, Protease Inhibitor Naive HIV-Infected Children: 48 Week Follow-Up

Plasma virus load measurements, CD4 counts, and clinical evaluations were performed on 63 HIV infected children in the Fall of 1994, and follow-up assessments were performed in the Fall,1996. At baseline, the median age was 5.54 years [Range 0.36 to 13.4 years], median log RNA copy number: 4.78(60,256 copies/ml) [1.7-6.34], median CD4 percent: 23% [0-50]. At the time of follow-up, the medians were: Age 7.58 years, CD4 18%, and log viral RNA copy number 4.32 (20,892). 8 Patients died during the period of follow-up, 13 others developed a new CDC Category C diagnosis, 42 had neither. A comparison of the median baseline values for those who died /had a new category C Dx/ neither showed: Age [5.10 / 4.25 / 6.08 years] CD4% [2 / 7 / 27.5%] Log RNA[5.63 / 5.07 / 4.46]. 17 of the 21 children with a new category C or death had an initial RNA PCR >4.6 logs (50,000 copies/ml). Three of the 4 with bad outcomes and

Drs Terry and Schneider raise legitimate questions regarding changes in polio immunization recommendations. In response to the former, although two doses of inactivated polio vaccine provide humoral immunity that will protect an individual against central nervous system invasion by wild or revertant attenuated polioviruses, they do not provide intestinal immunity, a valued asset of oral polio vaccine (OPV). Because we live in a global community where jet transportation enables one to move from a polio-endemic area to a polio-free area in less than one day, the introduction of wild polio viruses from sub-Saharan Africa or Southeast Asia poses a legitimate threat and concern to those who wish to maintain community protection, in addition to individual protection, against possible reintroduction of wild virus to the United States.

In the August 1995 issue of theArchives, Woodin et al 1 presented an interesting survey of physicians and parents regarding multiple immunizations given by separate injections at health visits. This is interesting information and should be used accordingly by those who are working on the technology to combine many antigens, so that a single injection would be polyvalent. Until that time, however, if one uses the already available diphtheria-tetanuspertussis toxoids (DTP) plus Haemophilus influenzae type b (Hib) conjugate combination, there is no need for more than two injections per visit, with the sole exception of that after the first birthday, when one might administer the combination of DTP and Hib conjugate vaccine (DTP-Hib) with measles-mumps-rubella (MMR) and varicella-zoster vaccine (VZV). Our neighbors in Canada already have available to them a combined vaccine that includes DTP, Hib conjugate, and inactivated polio (IPV). With the demonstrated success in overseas trials of

In Reply.— The immediate problem of cost is certainly a barrier to the acceptability of the hepatitis B universal infant and adolescent immunization program. Whereas I agree that the mechanism of sole purchase may result in the detrimental and devastating effects you suggest, is it not possible to suggest that various groups of physicians or clinics combine to seek bulk purchase rates from all manufacturers? Could we encourage the various manufacturers to offer lowered bulk purchase rates, concurrently encouraging and sustaining commercial competitiveness? My assumption would be that the lowered bulk purchase price would not be detrimental to the manufacturer and their needed resources for production and research, as costs could be saved in distribution, sales, and greater use of the vaccines.

In Reply .—Dr Slater writes of the unending debate between the proponents of OPV and those favoring the addition or substitution of the new E-IPV. The exchange of commentaries by Drs Marcuse and me was not such a debate but a presentation of positions both favoring the addition of E-IPV. The question was a matter of timing; whether to make the addition now for the private sector only or to introduce it later when all infants and children would benefit, and when E-IPV could be integrated into our immunization schedule to include DTP and conjugate Haemophilus influenza B for infants. We agree with his conclusion that the need exists for "harnessing the special virtues of both of these excellent products." The combined schedule that eventually will be used in the United States will probably differ from that initiated in Israel (E-IPV at 2, 4, and 12 months; trivalent OPV at

In Reply .—Dr Bader's thoughtful comments merit consideration now and for the future. If, indeed, the state of Washington has a vaccine-associated paralytic polio rate of 1 per 100 000, it differs markedly from the rest of the nation where careful surveillance and annual review of reported alleged cases by an expert committee have consistently disclosed an overall rate of 1 per 2.7 million poliovirus vaccine live oral trivalent (TOPV) doses or 1 per 560 000 first doses of TOPV. From 1975 to 1986, 107 cases were labeled vaccine-associated paralytic disease, of which 37 were in recipients and 48 in contacts. If Washington has a higher rate, it may resemble the unexplained geographic (or possibly genetic) aberrations observed in some other infectious diseases studies such as the unusual results in Minnesota with the initial studies of Haemophilus influenzae type B polyribose phosphate vaccines in contrast to the efficacy studies in

During the first half of this decade, much new information about the acquired immunodeficiency syndrome (AIDS) became available, including landmark reports of the syndrome in children from Oleske et al, Rubinstein et al, and Scott et al; descriptions of AIDS in pregnancy by Wetli et al, Rawlinson et al, and Minkoff et al; and discovery of the agent that causes AIDS, the human immunodeficiency virus (HIV, formerly called HTLV-III/LAV). The first sets of health guidelines pertaining to HIV-infected children and adolescents in school, day-care and foster care settings were published by the American Academy of Pediatrics' Committee on Infectious Diseases in March 1986 and 1987. In 1987, the Surgeon General's Workshop on Children With HIV Infection and Their Families provided the first comprehensive set of recommendations relevant to the provision of pediatric and obstetrical care to infected mothers, infants, children, and adolescents. Most recently, during February 1988, the Secretary of Health and Human Services formed the Secretary's Work Group on Pediatric HIV Infection and Disease that consisted of members from each of the health and human services agencies, including the Social Security Administration and the Health Care Financing Administration. The broad mandate of this group was to make recommendations to facilitate the removal of barriers to care, treatment, and financial burdens of children and adolescents with HIV infection and their families. In contrast, HIV infection has not received sufficiently widespread attention from the obstetric, pediatric, or adolescent research communities. The uneven geographic distribution of the disease; its associated social, legal, and ethical complexities; and the lack of sufficient research monies all have contributed to this problem.

Varicella is usually a well-tolerated disease in normal children. Pyogenic infections involving the skin are the commonest complications and their potential severity is emphasized by our recent experience with two children who suffered from gangrene as a result of cutaneous superinfection with group A β-hemolytic streptococci. We present the recognition and management of these patients in an effort to reacquaint physicians with this potentially fatal infection.

Patients with agammaglobulinemia are particularly susceptible to chronic enteroviral infections of the central nervous system. Data on 42 patients were obtained by literature review, communications with other physicians, and personal experiences. Thirty-eight patients had congenital immunodeficiencies, most frequently X-linked agammaglobulinemia. Most patients who could be assessed were receiving maintenance therapy with intramuscular gamma-globulin before their enteroviral infection. Seven patients had not been recognized as hypogammaglobulinemic before the onset of infection. The commonest pathogens were echoviruses (37 of 41 cases), especially type 11 (11 cases). Thus far, four patients have had sequential or simultaneous infections with a second enteroviral serotype. Other features of the disease have included weakness, lethargy or coma, headaches, hearing loss, seizures, ataxia, and paresthesias. Some patients have also had nonneurologic manifestations of chronic enteroviral infection, including fever, the dermatomyositis-like syndrome, edema, rashes, and hepatitis. Treatment has consisted primarily of antibody administration, either in intravenous immunoglobulin preparations or in immune plasma. Twelve patients have received intraventricular immunoglobulin through reservoir devices; six of these 12 have improved substantially, as judged by clinical criteria.

Sixteen patients who fit the diagnostic criteria of endocardial fibroelastosis were investigated by means of mumps skin tests and serum assays of mumps hemagglutination-inhibiting antibodies. No relationship was found between the clinical entity, endocardial fibroelastosis, and either mumps-specific antibodies or delayed cutaneous hypersensitivity to the mumps virus.

Presentation of Case* A six-month-old boy was admitted to the hospital because of fever and dyspnea. The child was the product of a normal pregnancy and delivery and weighed 7 pounds, 14 ounces, at...

IN the first seven reports of this series the development and mode of preparation of an avianized attenuated measles-virus vaccine together with observations on the clinical and immunologic responses induced by this vaccine in susceptible monkeys and children are described. This vaccine will be referred to as "measles vaccine (attenuated)." In a final communication the data obtained by the various investigators collaborating in these studies will be summarized and critically evaluated. Preliminary accounts of the first trial in children have been published.1 , 2 Introduction Numerous attempts have been made to devise an effective and harmless means for the artificial induction in . . .

RAPIDLY accumulating knowledge, as yet incomplete and only partially understood, of the varied effects on host cells and tissues of infectious agents renders increasingly difficult a dispassionate and judicious evaluation of the benefits and risks inherent in any vaccine. Great strides have been made in the development and application of technics ensuring consistent and reliable production of large quantities of such antigens, both live and killed, that satisfy existing standards for safety and efficacy. Unfortunately, but understandably, these advances in methodology have been achieved more rapidly than the acquisition of information pertinent to those effects, other than immunologic, of such . . .

Presentation of Case A thirty-one-year-old mother of two children was admitted to the hospital because of dyspnea and cyanosis. Five days before entry a rash developed over the trunk, associated wi...

A retrospective study of 280 nephrotic admissions from 1963 through 1967 at Children's Hospital Medical Center in Boston revealed that gram-negative bacilli have caused the majority of infections in hospitalized nephrotic children. The organisms isolated during this period included pneumococci, E. coli, proteus, klebsiella-enterobacter species, pseudomonas, and Serratia marcescens. This information is recorded to aid physicians in the selection of initial antibiotic therapy in the septic nephrotic patient.

Consent must be obtained prior to the institution of medical or surgical treatment. Pediatricians should keep informed concerning court decisions and statutes relative to consent and minors.

Should children in day-care facilities receive rifampin chemoprophylaxis after the occurrence of invasive Hemophilus influenzae b disease in a day-care contact? The magnitude of uncertainty regardi...

Although the total number of reported cases of the acquired immunodeficiency syndrome (AIDS) in children in the United States is less than 2 percent of the number in adults, the seriousness of the problem of pediatric AIDS threatens to grow in the coming years, as increasing numbers of women of childbearing age become infected with the human immunodeficiency virus (HIV) through intravenous drug use or heterosexual transmission. The epidemiology of pediatric AIDS is, of course, strikingly different from that of its adult counterpart. At present, approximately 80 percent of the children who have AIDS were infected through perinatal transmission, whereas . . .

In 1984 fewer than 3000 cases of measles were reported in the United States. This reflected more than a 99.9 per cent reduction from the numbers of cases that occurred annually in this country before the licensure of measles vaccine in 1963. Young American parents and health professionals are no longer familiar with this illness — its misery, complications, and sequelae. In 1984 more than 1.5 million children in less-developed countries died of measles and its complications. Through its Expanded Programme on Immunization (EPI) the World Health Organization has struggled to reduce the terrible mortality and morbidity of this and . . .

We observed persistent ECHOvirus infection of the central nervous system, as defined by continued presence of isolatable virus in cerebrospinal fluid, in five patients with agammaglobulinemia. The immunologic deficit in each was characterized by absence of surface-immunoglobulin-bearing B lymphocytes and of lymph-node cortical follicles, but normal T-cell function. ECHOviruses 30, 19, 9 and 33 were recovered from cerebrospinal fluid for periods varying from two months to three years. The patients had few signs of acute central-nervous-system infection. Three of the five patients had a dermatomyositis-like syndrome, with peripheral lymphocytes that reacted with anti-human leukemia-specific primate and rabbit serums in a cytotoxicity assay. These data suggest that intact B-cell function is essential for eradication of ECHOvirus infection of the central nervous system.

The rate of nasal colonization with group B Streptococcus in infants cultured at the time of discharge from the nursery rose significantly during a four-month interval. Investigation of this trend resulted in detection of group B streptococci in the domes of two intrauterine pressure transducers (IPTs). Subsequent routine sterilization of IPT domes after each maternal use was associated with a decline in infant group B streptococcal colonization to the usual endemic rate in the nursery. Retrospective evaluation demonstrated that colonization in infants born to IPT-monitored women had increased significantly during the study interval and that no increase in colonization occurred in infants born to non-IPT-monitored women. From epidemiologic evidence it appears that use of contaminated IPTs during labor was a nosocomial source of group B streptococcal colonization.

Ninety-two children received single doses of one of 13 monovalent vaccines derived from influenza virus strain A/New Jersey/8/76 (A/NJ), and 18 children received placebo. Five influenza virus vaccines were whole-virus vaccines, and eight were split-product vaccines. Samples of sera were taken once three weeks after vaccination. All of the 29 children receiving whole-virus vaccines developed a titer of antibody to A/NJ virus of greater than or equal to 1:20, and the geometric mean titers were 1:14-1:45. One of the 60 children who received split-product vaccines developed a titer of antibody to A/NJ of greater than or equal to 1:20, and geometric mean titers were all less than 1:10. There was a trend toward correlation between titers of hemagglutination-inhibiting (HAI) antibody to A/NJ and titers of HAI antibody to A/Victoria/3/75 viruses, with a correlation coefficient of 0.40 for children who received whole-virus vaccines. Three of 60 recipients of split-product vaccines and two of 20 recipients of whole virus developed a fever of greater than or equal to 38 C. One of the two febrile children who had received whole-virus vaccine had otitis media. Therefore, reactogenicity of whole-virus vaccines and split-product vaccines appeared to be similar in these children.

Preceding reports at this conference have already considered many aspects of the question of markers for the measles virus. Table 1 recapitulates some of these markers that have already been discussed. Two more will have to be added in the light of the report by Dr. Buynak, Dr. Hilleman, and co-workers 1 describing the plaques produced by the attenuated Edmonston strain in cultures of chick embryo and grivet kidney cells and the neuropathology produced by the virulent Edmonston strain after thalamic inoculation in the monkey. Virulent early kidney-cell-passage virus does not seem to grow in chick cells, where as the attenuated does. In one stable amnion cell line, developed at the Sterling-Winthrop Company laboratories, the 20th passage of the human kidney line induces few or no cytopathic effects. Virus from the 30th passage level in this medium does, however, cause extensive changes. The attenuated agent grows well in this line