Morven S. Edwards

Group B Streptococcal Infections in Elderly Adults

Elderly adults account for >40% of persons with invasive group B streptococcal (GBS) disease and for >50% of GBS-associated deaths in the United States. The prevalence of colonization among healthy elderly adults (approximately 25%) is similar to that among women of childbearing age. Delineating contributions of comorbid conditions, altered integrity of anatomical barriers, and abnormalities in immune responses caused by immune senescence to pathogenesis require further investigation. Delayed clinical recognition of illness may contribute to poor outcome. Skin and soft-tissue infections and bacteremia with no identified focus are common manifestations of infection in elderly adults and younger nonpregnant adults. Urinary tract infection and pneumonia are presentations more often encountered in elderly persons than in younger adults. The safety and immunogenicity of GBS serotype V-tetanus toxoid conjugate vaccine in healthy elderly persons suggest the potential for vaccination as an approach to prevention of invasive GBS infections in elderly persons.

Immunization of Pregnant Women with a Polysaccharide Vaccine of Group B Streptococcus

Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus is a promising strategy for the prevention of perinatal infections caused by group B streptococci. To explore the feasibility of this strategy, we vaccinated 40 pregnant women at a mean gestation of 31 weeks with a single 50-microgram dose of the Type III capsular polysaccharide of group B streptococcus. The only adverse effect detected was a mild local reaction in nine women (22 percent). Of the 35 women with low or unprotective antibody levels before immunization (less than 2 micrograms per milliliter), 20 (57 percent) responded to the vaccine. The geometric mean antibody level rose from 1.3 to 7.1 micrograms per milliliter four weeks after vaccination (P less than 0.02), and these levels persisted at delivery and three months post partum. Sixty-two percent of the vaccine-induced immunoglobulin in the mothers was IgG, which readily crosses the placenta. Infant antibody levels in cord serum correlated directly with maternal antibody levels at delivery (r = 0.913, P less than 0.001). Of the 25 infants born to women who responded to the vaccine, 80 percent continued to have protective levels of antibody at one month of age and 64 percent had protective levels at three months. Serum samples from infants with greater than or equal to 2 micrograms of antibody to Type III group B streptococcus per milliliter uniformly promoted efficient opsonization, phagocytosis, and bacterial killing in vitro of Type III strains. This effect could be mediated exclusively by the alternative complement pathway. Although this vaccine with an overall response rate of 63 percent is not optimally immunogenic, we conclude that maternal immunization is feasible and can provide passive immunity against systemic infection with Type III group B streptococcus in the majority of newborns. Larger trials with better vaccines will be required to evaluate the safety and clinical effectiveness of this strategy.

Chagas disease: "the new HIV/AIDS of the Americas".

Endemic Chagas disease has emerged as an important health disparity in the Americas. As a result, we face a situation in both Latin America and the US that bears a resemblance to the early years of the HIV/AIDS pandemic.

Complications and sequelae of meningococcal infections in children.

Eight-six children with meningococcal meningitis or bacteremia were evaluated prospectively between 1977 and 1979 to determine the incidence of complications and features predictive of their development. The majority (83%) of these infections were caused by serogroup B strains. Twenty-seven percent of survivors experienced one or more suppurative, allergic, or neurologic complications. Hearing loss, noted in 9% of children, occurred significantly more often in patients with admission leukocytosis or leukopenia, or with CSF leukocytosis greater than 10,000/mm3 than in those with an uncomplicated course (P less than 0.01). Ten percent of survivors developed allergic complications manifested as cutaneous vasculitis or arthritis with onset five to eight days after admission. Shock, purpuric skin lesions, and fever persisting longer than five days occurred significantly more often in these children than in those who developed hearing loss or those with an uncomplicated course (P less than 0.05). Resolution of allergic complications occurred within 14 days of their onset. Compared to Neisseria meningitidis groups A and C, group B strains appear to be intermediate in their potential for allergic complications associated with childhood infection.

Group B streptococcal conjugate vaccines

Linkage of bacterial capsular polysaccharides to proteins to create conjugate vaccines has had a dramatic impact on the health of children. Although unconjugated polysaccharides are poorly immunogenic in infants and some older children and adults, their covalent coupling with proteins stimulates T cell dependent antigenic recognition that profoundly enhances immunogenicity. In the decade since the introduction and widespread use of Haemophilus influenzae type b polysaccharide conjugate vaccines in the United States, invasive H influenzae infections have become a rarity in childhood.1 Similarly, the conjugation of polysaccharides of Streptococcus pneumoniae to a derivative of diphtheria toxoid and the addition of pneumococcal conjugate vaccine to infant immunisation schedules carries with it promise for a similar decline in the incidence of invasive pneumococcal disease in paediatric patients.2

Long-term sequelae of group B streptococcal meningitis in infants*

The long-term outcome and admission features predictive of outcome were determined for 61 patients with group B streptococcal meningitis treated between 1974 and 1979. Infection was rapidly fatal in 13 patients (21%). Among the 48 survivors, 38 (79%) 3 years of age or older were available for comprehensive evaluation. Excluding five who had died before age 3 years, the mean age at evaluation was 6.0 years (range 3.3 to 9.0 years). Among survivors, 11 (29%) had severe neurologic sequelae, eight (21%) had mild to moderate deficits, and 19 (50%) were functioning normally. Analysis of predictive features revealed a significant risk of death or severe impairment among infants who at hospital admission were comatose or semicomatose, had decreased perfusion, total peripheral WBC less than 5,000/mm3, absolute neutrophil count less than 1000/mm3, and CSF protein greater than 300 mg/dl (P less than or equal to 0.05). These data indicate that, although mortality from group B streptococcal meningitis has declined, approximately half of the survivors of acute infection have some degree of morbidity when evaluated at ages permitting the detection of language delay and borderline or mild mental retardation.

Features of Invasive Staphylococcal Disease in Neonates

Objective. Most clinical descriptions of invasive staphylococcal disease (ISD) in neonates date from before the mid-1980s, when neonatal viability and intensive care differed substantially from current standards. We aimed to describe the contemporary incidence, clinical features, and outcome of infants with ISD in a neonatal intensive care unit. Methods. A retrospective cohort study was conducted of infants who had ISD and were in the neonatal intensive care unit of the Womans Hospital of Texas, Houston, from January 2000 to June 2002. Confirmed ISD was defined as clinical sepsis and Staphylococcus aureus (SA) isolated from ≥1 blood culture (BC) or a sterile body site excluding urine or coagulase-negative staphylococci (CoNS) isolated from ≥2 BC or from 1 BC and a sterile body site. Probable ISD was defined as CoNS isolated from 1 BC or a sterile body site for which clinical and laboratory data review by 3 infectious disease specialists indicated that antimicrobial treatment was appropriate. Confirmed and combined confirmed plus probable cases were analyzed. Results. A total of 149 episodes (83 confirmed [39 SA, 44 CoNS], 66 probable) in 137 infants (mean gestational age [GA]: 27.6 weeks [22.4–36.4]; mean birth weight: 981 g [350–2995]) were reviewed. Four (3%) infants had early-onset infection (2 SA, 2 CoNS). Median age at infection onset was similar (17 days SA; 18 days CoNS). Intravascular catheters (IVC) were in situ in a minority of infants with ISD episodes (38% SA, 43% CoNS). CoNS more than SA infections were associated with very low birth weight (<1500 g), lower GA, a history of more IVCs and concurrent total parenteral nutrition, but IVC and parenteral nutrition days were similar. By multivariate analysis correcting for birth weight and complications of prematurity, hypoxia at the time of sepsis evaluation was significantly associated with CoNS and hypotension with SA infections; other clinical features were similar. Methicillin-resistant SA caused 8% of SA infections. Among bacteremic infants, SA more frequently than CoNS involved ≥2 sites. Overall, SA had more focal complications (primarily bone and joint) than CoNS, resulting in a 2- to 3-fold higher SA-associated morbidity rate. Mortality directly attributable to either organism was similar (5% SA; 5% confirmed, 3% confirmed/probable CoNS). Conclusion. CoNS ISD occurred in smaller, more premature infants than SA and was IVC associated in a minority of cases. Hypoxia and hypotension were the only presenting features that differentiated CoNS and SA. SA-associated morbidity was substantial, but SA infection carried no greater risk of death (5%) than CoNS.

Opsonophagocytic killing antibody to Pseudomonas aeruginosa mucoid exopolysaccharide in older noncolonized patients with cystic fibrosis

The principal cause of morbidity and mortality in cystic fibrosis is persistent respiratory colonization with mucoid strains of Pseudomonas aeruginosa. To investigate possible mechanisms of resistance to this organism, we studied serum from 16 older (greater than or equal to 12 years) patients not colonized with mucoid P. aeruginosa, 11 older (greater than or equal to 14 years) colonized patients, 10 younger (less than or equal to 11 years) noncolonized patients, and 20 healthy adults. The samples from the older patients not colonized with mucoid P. aeruginosa contained antibody specific to the mucoid-exopolysaccharide antigen, which could mediate bacterial killing in conjunction with complement and white cells (titers of 4 to 80). These opsonophagocytic killing antibodies were not detected in samples from the 20 normal controls (P less than 0.0001 vs. noncolonized older patients) or 9 of 10 younger (less than or equal to 11 years) noncolonized patients (P = 0.0072 vs. noncolonized older patients). Although the patients with chronic colonization had higher titers of serum opsonophagocytic killing antibody than did the older noncolonized patients (P = 0.0005), these antibodies were not specific to the mucoid-exopolysaccharide antigen. We conclude that there is an association between mucoid-exopolysaccharide-specific opsonophagocytic killing antibody and a lack of detectable P. aeruginosa colonization in a subset of older, relatively healthy patients with cystic fibrosis.

A mouse model of chronic pulmonary infection with Pseudomonas aeruginosa and Pseudomonas cepacia

ABSTRACT. A mouse model of chronic pulmonary infection with either Pseudomonas aeruginosa or Pseudomonas cepacia was developed to compare bacteriologic and pathologic features of these infections. Experimental pneumonia was established in Swiss mice by transoral intratracheal inoculation of 103-104 colony-forming units of mucoid P. aeruginosa or P. cepacia enmeshed in agarose beads. Unilateral infection with either strain was tolerated without morbidity. By 10 days postinoculation, the mean colonyforming units per infected lung was 3.8 x 105 for P. aeruginosa and 1.0 x 105 for P. cepacia. Bacterial counts remained stable through 21 days with no significant difference between organisms. Acute and chronic inflammatory histopathologic changes similar to many found in the lungs of cystic fibrosis patients were present in 95% of lung specimens. The changes occurred with both organisms but were more extensive with mucoid P. aeruginosa. This model represents an important tool for study of the contribution of complement, antibody, and adoptive transfer of T cell-mediated immunity to the pathogenesis of chronic pneumonia with Pseudomonas species, and represents the first successful model of chronic pulmonary infection with P. cepacia.

Long-term Outcomes of Group B Streptococcal Meningitis

OBJECTIVE: Group B Streptococcus (GBS) is the leading cause of meningitis in young infants. We evaluated long-term outcomes among GBS meningitis survivors. We hypothesized that despite reduced mortality, GBS meningitis would remain a significant cause of morbidity among GBS survivors. METHODS: Ninety term and near-term infants diagnosed with GBS meningitis from 1998 through 2006 were identified from 2 children’s hospitals. Five died acutely, and 5 died at 6 months to 3 years of age. Forty-three survivors (54%; mean age 6.8, range 3–12 years) were consented for evaluation and underwent physical and neurologic examinations, hearing and vision screening, and standardized developmental assessments. Associations among presenting features, laboratory parameters, neurologic status at hospital discharge, and later developmental outcomes were explored by using descriptive statistics and logistic regression. RESULTS: Twenty-four of 43 (56%) children evaluated demonstrated age-appropriate development, 11 (25%) had mild-to-moderate impairment, and 8 (19%) had severe impairment. Admission features associated with death after hospital discharge or severe impairment included lethargy (P = .003), respiratory distress (P = .022), coma or semicoma (P = .022), seizures (P = .015), bulging fontanel (P = .034), leukopenia (P = .026), acidosis (P = .024), cerebrospinal fluid protein >300 mg/dL (P = .006), cerebrospinal fluid glucose <20 mg/dL (P = .026), and need for ventilator (P = .002) or pressor support (P < .001). Features at discharge associated with late death or severe impairment included failed hearing screen (P = .004), abnormal neurologic examination (P < .001), and abnormal end of therapy brain imaging (P = .038). CONCLUSIONS: Survivors of GBS meningitis continue to have substantial long-term morbidity, highlighting the need for ongoing developmental follow-up and prevention strategies such as maternal immunization.