Lewis B. Lefkowitz

Bacterial Meningitis in the United States in 1995

BACKGROUND Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.

Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis.

BACKGROUND Group B streptococcal infections are a leading cause of neonatal mortality, and they also affect pregnant women and the elderly. Many cases of the disease in newborns can be prevented by the administration of prophylactic intrapartum antibiotics. In the 1990s, prevention efforts increased. In 1996, consensus guidelines recommended use of either a risk-based or a screening-based approach to identify candidates for intrapartum antibiotics. To assess the effects of the preventive efforts, we analyzed trends in the incidence of group B streptococcal disease from 1993 to 1998. METHODS Active, population-based surveillance was conducted in selected counties of eight states. A case was defined by the isolation of group B streptococci from a normally sterile site. Census and live-birth data were used to calculate the race-specific incidence of disease; national projections were adjusted for race. RESULTS Disease in infants less than seven days old accounted for 20 percent of all 7867 group B streptococcal infections. The incidence of early-onset neonatal infections decreased by 65 percent, from 1.7 per 1000 live births in 1993 to 0.6 per 1000 in 1998. The excess incidence of early-onset disease in black infants, as compared with white infants, decreased by 75 percent. Projecting our findings to the entire United States, we estimate that 3900 early-onset infections and 200 neonatal deaths were prevented in 1998 by the use of intrapartum antibiotics. Among pregnant girls and women, the incidence of invasive group B streptococcal disease declined by 21 percent. The incidence among nonpregnant adults did not decline. CONCLUSIONS Over a six-year period, there has been a substantial decline in the incidence of group B streptococcal disease in newborns, including a major reduction in the excess incidence of these infections in black infants. These improvements coincide with the efforts to prevent perinatal disease by the wider use of prophylactic intrapartum antibiotics.

Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997.

OBJECTIVES This study examined epidemiologic factors affecting mortality from pneumococcal pneumonia in 1995 through 1997. METHODS Persons residing in a surveillance area who had community-acquired pneumonia requiring hospitalization and Streptococcus pneumoniae isolated from a sterile site were included in the analysis. Factors affecting mortality were evaluated in univariate and multivariate analyses. The number of deaths from pneumococcal pneumonia requiring hospitalization in the United States in 1996 was estimated. RESULTS Of 5837 cases, 12% were fatal. Increased mortality was associated with older age, underlying disease. Asian race, and residence in Toronto/Peel, Ontario. When these factors were controlled for, increased mortality was not associated with resistance to penicillin or cefotaxime. However, when deaths during the first 4 hospital days were excluded, mortality was significantly associated with penicillin minimum inhibitory concentrations of 4.0 or higher and cefotaxime minimum inhibitory concentrations of 2.0 or higher. In 1996, about 7000 to 12,500 deaths occurred in the United States from pneumococcal pneumonia requiring hospitalization. CONCLUSIONS Older age and underlying disease remain the most important factors influencing death from pneumococcal pneumonia. Mortality was not elevated in most infections with beta-lactam-resistant pneumococci.

Homotypic antibody responses to fresh clinical isolates of human immunodeficiency virus

Human immunodeficiency virus type 1 (HIV-1) exhibits extensive genomic and antigenic diversity, which is thought to contribute to the failure of the hosts immune response to control infection and prevent clinical progression. Part of this failure may be due to utilization by the virus of antigenic variation as a means to escape protective immune responses. Antibody-escape variants of HIV-1 were studied here using fresh clinical isolates and autologous plasmas. HIV-1 was isolated from the plasma of seven people who were all seropositive for at least 2 years, and symptomatic sometime during that period. Isolated viruses were confirmed as HIV-1 by the presence of reverse transcriptase activity in infected culture supernatants, and by positive immunofluorescence using human monoclonal antibody to HIV-1 core protein. Plasma from these people were positive by Western immunoblot (DuPont) for most major HIV-1 (strain IIIB) antigens. These plasmas neutralized three laboratory strains of HIV-1 (i.e., IIIB, RF, and MN) but did not neutralize the homotypic strain in five cases, and had greatly reduced neutralizing titers against the homotypic strain in two cases. Homotypic neutralizing antibodies were absent in autologous plasma obtained 3 months later. When antibody titers were measured by fixed-cell indirect immunofluorescence assays (IFAs), high titers of IgG (1:6400 to 1:25,600) were detected against HIV-1 IIIB, while low titers of only 1:20 to 1:160 were detected against homotypic viral antigens at the time of virus isolation, and remained low 12 and 16 weeks later. No class IgA, IgD, IgE, or IgM antibodies to homotypic viral antigens, as possible IgG-blocking antibodies, were detected by fixed-cell IFAs. Cross-reactions with heterologous donors plasmas were observed in some cases, and in these cases the cross-reactions were unidirectional. Live-cell IFAs detected IgG in patients plasma to HIV-1 IIIB-infected cells but not to cells infected with homotypic isolates. These results suggest that it is common for neutralization-resistant HIV-1 variants to appear during the course of infection, and that all or most antigens of these variants are capable of escaping antibody recognition.

Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site.

OBJECTIVE To assess the extent of nosocomial transmission and risk factors associated with tuberculin skin test (TST) conversions among healthcare workers (HCWs) exposed to a patient with genitourinary Mycobacterium tuberculosis. DESIGN Retrospective cohort study of exposed HCWs. SETTING A 275-bed community hospital in Middle Tennessee. PARTICIPANTS A total of 128 exposed HCWs and the index patient, who required drainage of a prostatic abscess and bilateral orchiectomy and expired after a 27-day hospitalization. Disseminated tuberculosis was diagnosed at autopsy. METHODS Contact tracing was performed on exposed HCWs. Logistic regression was used to identify independent risk factors associated with TST conversion. RESULTS A total of 128 HCWs were exposed to the index patient. There was no evidence of active pulmonary tuberculosis throughout the patients hospitalization; TST conversions occurred only among HCWs who were exposed to the patient during or after his surgical procedures. A total of 12 (13%) of 95 exposed HCWs who were previously nonreactive had newly positive TST: 6 of 28 nurses, 3 of 3 autopsy personnel, 2 of 17 respiratory therapists, and 1 of 12 surgical staff. By logistic regression, irrigation or packing of the surgical site was the only independent risk factor associated with TST conversion among nurses (odds ratio, 9; 95% confidence interval, 1.2-67; P=.03). CONCLUSION Manipulation of infected tissues of the genitourinary tract can result in nosocomial transmission of tuberculosis.

Absence of a clinical correlation for complement-mediated, infection-enhancing antibodies in plasma or sera from HIV-1-infected individuals

Neutralizing and complement-mediated infection-enhancing antibodies to HIV-1 were measured in sera or plasma from 54 HIV-1-positive individuals at various stages of disease, and from an additional 36 HIV-1-positive individuals for whom no clinical data were available. Antibodies were measured in microtiter infection assays utilizing MT-2 cells and the IIIB strain of HIV-1. The frequency of detection of both types of antibodies was identical, being 77 out of 90 cases (86%). Neutralizing and infection-enhancing antibodies were not always found together, and in four cases both were undetectable. No correlation was found between liters of either type of antibody and stage of disease. Furthermore, liters of infection-enhancing antibodies at early stages of disease did not predict rate of disease progression.

A Controlled Family Study of Live, Attenuated Rubella-Virus Vaccine

Abstract In a family study of live, attenuated rubella-virus vaccine (HPV80), 85 susceptible placebo recipients were exposed to siblings with evidence of infection with the vaccine strain of rubella virus after inoculation. Of these placebo recipients a rise in titer of hemagglutination-inhibiting antibody developed in one. The type of antibody response and her clinical course indicated that vaccine virus infection had occurred. Although this response might have resulted from her having received vaccine by mistake, the possibility of intrafamilial spread of vaccine-strain virus must be seriously considered.

A survey of 251 patients with acute syphilis treated in the collaborative penicillin study of 1943-1950.

The dramatic and apparently curative effect of penicillin for the treatment of acute syphilis led to follow-up studies for only comparatively brief periods, and the acceptance of the long-term benefit of penicillin has rested on uncontrolled clinical impressions. More certainty about the efficacy of penicillin was sought by a follow-up review of 251 patients treated between March 1944 and December 1950 under the Penicillin Study of the Office of Scientific Research and Development (OSRD) and continued under the U. S. Public Health Service after World War II. Eighty-eight patients were interviewed and examined. Telephone conversation or correspondence was had with 43 subjects; an additional nine are known to be living but did not respond to letters. Thirty-two patients died ≥20 years after treatment, and 21 patients died within < 20 years of treatment. Fifty-eight patients could not be found. Treatment failures were documented. Syphilis was not shown to be the cause of disability or death, except for a patient with meningo-vascular syphilis who died soon after initial treatment. Disabilities recorded and deaths documented revealed only diseases common to any middle-aged population. The outcomes of 17 pregnancies of women treated for acute syphilis were documented. Blood samples obtained from the 88 subjects examined were tested at the Center for Disease Control (Atlanta, Ga.); the results are recorded and discussed. Methods for locating the patients are described, and the psychosocial findings for the 88 patients interviewed are presented. The study has confirmed the clinical impressions of the therapeutic effectiveness of penicillin, which have been accepted for 30 years.

GESTATIONAL EXPOSURE TO RUBELLA VACCINEES.A POPULATION SURVEILLANCE STUDY

Over a two-year period an attempt was made to identify instances of transmission of rubella vaccine virus from rubella vaccinees to pregnant women in Nashville-Davidson County, Tennessee. Approximately 24,000 children were immunized in a mass campaign at the outset of the study. Several prospective surveillance methods of 11,635 women and their new babies were employed. Attempts were made to recover rubella virus from throat swabs of 10,951 newborns. No rubella vaccine virus was recovered. Wild rubella virus was isolated from a single infant with the congenital rubella syndrome whose mother had natural rubella during the first month of pregnancy. Rubella virus was not isolated from the products of 240 abortions. There were no seroconversions among 3990 women who had paired sera available for study. Clinical and serologic follow-ups of infants judged to be a high risk because of intimate maternal exposure to vaccine virus revealed no late manifestations of congenital rubella infection. A history of close maternal contact with vaccinees during the three months before and the three months following conception was not associated with an increased incidence of congenital anomalies or clinical features seen with congenital rubella infection. Thus, no evidence of vaccine virus transmission was found, providing further evidence of the safety of rubella vaccine under field conditions. A seroepidemiologic study of 8824 pregnant women revealed the expected decline in rubella susceptibility with increasing age. When age was controlled, the variables of race, parity, and educational achievement produced no major influence on immunity.