Sandra J. Holmes

Prospective Evaluation of Hearing Impairment as a Sequela of Acute Bacterial Meningitis

As part of a prospective study of acute bacterial meningitis in children, we studied for five years the hearing of 185 infants and children who had acute bacterial meningitis when they were more than one month of age. Nineteen (10.3 per cent) of the patients had persistent bilateral or unilateral sensorineural hearing loss. The incidence of hearing loss as determined by electric-response audiometry and conventional tests was 31 per cent with Streptococcus pneumoniae, 10.5 per cent with Neisseria meningitidis, and 6 per cent with Hemophilus influenzae infections. Transient conductive hearing impairment was found in 16 per cent of the sample, but in no case was there apparent improvement in a sensorineural deficit over time. The site of disease resulting in impaired hearing cannot be stated with certainty, but involvement of the inner ear or auditory nerve was suspected. The number of days of illness (symptoms) before hospitalization and institution of antibacterial treatment was not correlated with the development of sensorineural deafness.

Seizures and Other Neurologic Sequelae of Bacterial Meningitis in Children

BACKGROUNDnAlthough the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy.nnnMETHODSnWe followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter.nnnRESULTSnOne month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001).nnnCONCLUSIONSnAfter bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy.

The Role of Parental Disciplinary Practices in the Development of Depression and Alcoholism

Awareness of child abuse has been growing over the past several decades as more cases have come to the attention of medical personnel and school and police authorities. Information-gathering systems have become more effective, and the long-term deleterious effects of abusive treatment have been brought into focus (American Humane Association 1981; Strauss et al. 1980). Cases which come to the attention of the authorities probably represent only the most blatant and severe instances of abuse. However, since Kempke and colleagues (1962) originally described the battered child syndrome, descriptions of child abuse have been broadened to include maltreatment other than physical abuse resulting in injury (Martinez-Roig et al. 1983; Smith and Hanson 1974; Wolff 1981). Indeed, Strauss and colleagues contend that even mild forms of physical punishment should be considered abusive because they would be illegal if directed toward adults or strangers. The current paper examines retrospectively the relationship between disciplinary practices experienced in childhood, both mild and severe, and the experience of major depressive episodes and alcoholism in adulthood in a general population sample, in whom disorder tends to be untreated and mild.

EARLY HOME ENVIRONMENT AND RETROSPECTIVE RECALL: A Test for Concordance Between Siblings With and Without Psychiatric Disorders

Case control studies are a reasonably rapid and inexpensive method of developing causal hypotheses concerning the role of early environment on the development of psychiatric pathology. The current study tested an interview designed to assess early home environment on a group of patients with alcoholism or depression, on a control group free of psychiatric disorder, and on close-in-age siblings in each group. Findings demonstrated substantial agreement, suggesting that interviews requiring recall of childhood environment may be reasonably valid; patient status did not appear to influence agreement or, presumably, validity.

Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants

OBJECTIVEnTo compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas.nnnDESIGNnA multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age.nnnSUBJECTSnA convenience sample of 458 infants recruited largely from private pediatric practices.nnnMEASUREMENTS AND RESULTSnAt each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine.nnnCONCLUSIONSnIn infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown.

Effect of immunity to the carrier protein on antibody responses to Haemophilus influenzae type b conjugate vaccines

The anticapsular antibody responses to some Haemophilus influenzae type b (Hib) conjugate vaccines may be enhanced by prior or simultaneous administration of the carrier protein used in the conjugate. Currently, there are two Hib conjugate vaccines licensed in the USA for use in infants beginning at 2 months of age: Hib polysaccharide coupled to an outer membrane protein complex of Neisseria meningitidis (PRP-OMPC), and Hib oligosaccharides conjugated to CRM197, a non-toxic mutant diphtheria toxin (HbOC). The PRP-OMPC conjugate vaccine is immunogenic in infant monkeys and infant humans in the absence of carrier priming or additional carrier vaccination. The mechanism responsible for this immunogenicity is unknown but may relate to the adjuvanticity of the OMPC carrier. In contrast, data from infant rhesus monkeys and infant humans suggest that there may be a need for vaccination with diphtheria toxoid in order to maximize anti-PRP antibody responses to the HbOC conjugate. In addition, immunization with HbOC alone appears to be insufficient to elicit an antibody response to diphtheria toxoid. Thus, the need for additional vaccination with diphtheria toxoid in order to generate consistent anti-PRP antibody responses to HbOC may be a result of failure of the CRM197 protein carrier to elicit T-cell help. In infants in whom diphtheria-tetanus-pertussis (DTP) vaccination is deferred because of medical contraindications, vaccination with the PRP-OMPC conjugate would appear to be preferable to HbOC because of the ability of the former to elicit antibody responses in the absence of diphtheria toxoid vaccination.

Comparative immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugate vaccines

There are only minor differences in the immunogenicity of the three Haemophilus b polysaccharide-protein conjugate vaccines licensed in the US when tested in children 17 to 19 months of age. In contrast, there are much greater differences in immunogenicity in 2-month-old infants. At this age, a single dose of PRP-OMPC evokes a strong primary antibody response, whereas repeated doses of HbOC or PRP-D are required to evoke an antibody response. These differences in immunogenicity are noteworthy, but they are not necessarily correlated with differences in the ability of different conjugate vaccines to confer protection against disease. Vaccination with all three of the conjugate vaccines primes infants for the ability to make a booster antibody response to reimmunization with unconjugated PRP vaccine and, possibly, to exposure to the encapsulated bacteria. Although unproven, this priming may be sufficient to confer protection against disease even in the absence of a protective level of serum antibody.

Psychometric Testing in Bacterial Meningitis: Results of a Long-Term Prospective Study of Infants and Children Treated Between 1973 and 1977

Acute bacterial meningitis can result in structural damage to the nervous system with associated functional derangements. Neurologic abnormalities can be transient, although some sequelae, including lasting impairment in cognition and behavior, may be permanent. 1,2 In this brief report, we present the results of psychometric testing of patients conducted over a 5-year period in our prospective study of acute bacterial meningitis begun in 1973.