Flor M. Munoz

Prevalence of Pertussis Antibodies in Maternal Delivery, Cord, and Infant Serum

BACKGROUND Passively acquired maternal antibodies protect infants from many pathogens. With increasing reports of infant pertussis, we evaluated pertussis antibodies in maternal-infant paired sera from 1999-2000. METHODS Antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), and fimbrial proteins (FIM) were measured by validated IgG-specific enzyme-linked immunosorbant assay (ELISA) in 64 maternal-umbilical cord serum pairs and in 61 of 64 infant sera. Geometric mean concentrations (GMCs) of pertussis antibodies and cord : maternal GMC ratios were calculated. RESULTS Mean maternal age and gestation were 29.7 years (range, 19-42) and 39.3 weeks (range, 35.6-40.9), and 81% of mothers were white. GMCs of maternal antibodies at delivery (ELISA units/mL) were 2.4 for PT, 6.9 for FHA, and 13 for FIM. Cord GMCs were 169%, 178%, and 157% of maternal delivery values for PT, FHA, and FIM, respectively, demonstrating active placental transfer (P<.001). Pertussis-specific IgG values for each antigen decayed to below the threshold of detection by age 2 months. CONCLUSIONS Despite efficient placental transfer, low maternal pertussis antibody levels and their rapid decay in infant sera leave infants with little humoral protection against pertussis. These data support the rationale for maternal or neonatal immunization, with acellular pertussis vaccines, to prevent life-threatening pertussis in early infancy.

Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women.

A randomized, double-blind, placebo controlled study was carried out to determine the safety and immunogenicity of RSV PFP-2 vaccine (Wyeth-Lederle Vaccines, NY) in 35 healthy women in the third trimester of pregnancy and their offspring. Infants were followed during their first RSV season for occurrence and severity of respiratory illnesses. RSV-PFP-2 vaccine was safe and well tolerated by pregnant women. Mild pain at the site of injection occurred in 65% of PFP-2 and 13% of placebo recipients (P=0.005). There were no systemic reactions, fever, or serious adverse events associated with vaccine administration in mothers. All 35 infants were born healthy, and there were no differences among the groups in perinatal or neonatal outcomes, growth and development in the first year of life. During the RSV season, there was no increase in the frequency or morbidity associated with respiratory tract illnesses in infants of vaccine recipients. 15/20 (75%) vaccine recipients had a response to PFP-2 by Western blot vs. 0/15 placebo recipients (P<0.01). 19/20 (95%) vaccine recipients had a > or =4 fold rise in IgG ELISA Ab after immunization with PFP-2 vs. 0/15 placebo recipients (P<0.01). Geometric mean concentrations of IgG ELISA Ab were 4 fold higher in infants of vaccine recipients at birth, 2 and 6 months after delivery than in infants of placebo recipients (P<0.01). A modest (0.5log2) increase in neutralization Ab was observed in vaccine recipients and their infants. The half-life of maternal antibodies in infants was > or =3 weeks. There was no evidence of enhanced T-cell or cytokine activity in infants of vaccine recipients vs. infants of placebo recipients. Vaccine specific anti-F IgA and IgG concentrations in breast milk were higher in mothers who received RSV-PFP-2.

Disseminated Adenovirus Disease in Immunocompromised and Immunocompetent Children

A retrospective review of adenovirus infections at Texas Childrens Hospital during 1990-1996 was performed to evaluate the epidemiology, clinical course, management, and outcome of disseminated adenovirus disease (DAD) in children. DAD with multiorgan involvement occurred in 11 (2.5%) of 440 adenovirus-infected patients. Six (54%) of the 11 were immunocompromised and 5 (45%) were immunocompetent. Mortality was 83% among the immunodeficient, 60% in the immunocompetent, and 73% overall. Two (28%) of the 7 patients receiving immunoglobulins with or without antivirals and 3 (75%) of the 4 not treated died of DAD. DAD was caused by particular serotypes (3, 5, and 7) and occurred at a younger age in immunocompetent children. Viremia and prolonged viral excretion were more common in the immunocompromised. Clinical features and outcome were similar in both groups. Prospective studies addressing the use of new antiviral agents, combination antiviral therapy, and preventive strategies are necessary to determine the optimal therapeutic approach for patients with DAD.

Influenza A virus outbreak in a neonatal intensive care unit.

BACKGROUND Nosocomial infections with influenza virus are rarely recognized in neonatal intensive care units (NICU). An outbreak of influenza A virus infection in the NICU of an urban county hospital during the 1997 to 1998 influenza season is reported. METHODS Clinical and virologic data were recorded in all symptomatic NICU patients after influenza A infection was diagnosed in one infant in October, 1997. RESULTS Influenza A/H3N2 was isolated from two of four symptomatic infants. The application of rapid diagnostic techniques for the characterization of influenza virus infection allowed the timely institution of basic infection control measures, limiting this outbreak. Resistance to amantadine was documented for the first time in this patient population by reverse transcription-PCR within 48 h of treatment in one case. CONCLUSIONS Prevention by immunization is a priority in those caring for high risk NICU patients.

Impact of Maternal Postpartum Tetanus and Diphtheria Toxoids and Acellular Pertussis Immunization on Infant Pertussis Infection

BACKGROUND Mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention recommend tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine for postpartum women before hospital discharge. In January 2008, this recommendation was implemented in a predominantly Hispanic, medically underserved population at Ben Taub General Hospital (BTGH) in Houston (hereafter the intervention population). METHODS A cross-sectional study compared preintervention (July 2000 through December 2007) and postintervention (January 2008 through May 2009) periods. Pertussis diagnosis was determined using International Classification of Diseases, Ninth Revision (ICD-9) codes and microbiology reports from 4 major childrens hospitals in Houston. Only those infants ≤6 months of age with laboratory-confirmed pertussis illness were included. The proportions of pertussis-infected infants born at BTGH in the pre- and postintervention periods were compared. RESULTS Of 514 infants with pertussis, 378 (73.5%) were identified during preintervention and 136 (26.5%) during postintervention years. These groups were similar in age (mean, 79.3 vs 72 days; P = .08), sex (males, 55% vs 52%; P = .48), length of hospitalization (mean, 9.7 vs 10.7 days; P = .62), mortality (2 deaths each; P = .29) and hospital of pertussis diagnosis. After adjustment for age, sex, and ethnicity, the proportions of pertussis-infected infants born at BTGH and potentially protected through maternal postpartum Tdap immunization were similar for the 2 periods (6.9% vs 8.8%; odds ratio, 1.06; 95% confidence interval, 0.5-2.2; P = .87). CONCLUSIONS Immunizing only postpartum mothers with Tdap vaccine did not reduce pertussis illness in infants ≤6 months of age. Efforts should be directed at immunizing all household and key contacts of newborns with Tdap, not just mothers.

Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation

In a randomized, double blinded study, 23-valent pneumococcal polysaccharide vaccine (PSV) or conjugate Haemophilus influenzae type b (HbOC) vaccine was administered to 60 healthy women in the third trimester of gestation. Total IgG, IgG1, and IgG2 antibodies to pneumococcal serotypes 6B, 14, 19F and 23F were measured by ELISA in mothers prior to immunization, at delivery and 7 months after delivery, and in infants at birth (cord blood), 2 and 7 months after delivery. IgA was evaluated in breast milk at 2 and 7 months, and opsonophagocytic activity in cord blood. PSV was safe and immunogenic in pregnant women. Transplacental transmission of vaccine-specific antibodies was efficient. Maternal immunization with PSV resulted in significantly higher concentrations of pneumococcal antibodies in infants at birth and at 2 months of age, and greater functional opsonophagocytic activity of passively acquired IgG antibody.

Noroviruses: The Most Common Pediatric Viral Enteric Pathogen at a Large University Hospital After Introduction of Rotavirus Vaccination

We conducted an 8.5-year study examining enteric viruses at Texas Childrens Hospital (TCH) before and after rotavirus vaccine introduction. Norovirus prevalence was 10.9%. Rotavirus prevalence decreased 64% after vaccine licensure. Noroviruses are the most common TCH enteropathogen and will likely eclipse rotaviruses as the most important US pediatric gastroenteritis pathogen.

Immunogenicity of an Inactivated Monovalent 2009 H1N1 Influenza Vaccine in Pregnant Women

BACKGROUND Although pregnant women are at increased risk of severe illness following influenza infection, there is relatively little information on the immunogenicity of influenza vaccines administered during pregnancy. METHODS We conducted a clinical trial that enrolled 120 pregnant women in which participants were randomly assigned to receive an inactivated 2009 H1N1 influenza vaccine containing either 25 μg or 49 μg of hemagglutinin (HA) in a 2-dose series with a 21-day period between administration of the first and second doses. RESULTS Following the first vaccination, HA inhibition (HAI) titers of ≥1:40 were detected in 93% (95% confidence interval [CI], 82%-98%) of subjects who received the 25-μg dose and 97% (95% CI, 88%-100%) of subjects receiving the 49-μg dose. In cord blood samples, HAI titers of ≥1:40 were found in 87% (95% CI, 73%-96%) of samples from the 25-μg dose group and in 89% (95% CI, 76%-96%) from the 49-μg dose group. Microneutralization titers tended to be higher than HAI titers, but the patterns of response were similar. CONCLUSIONS In pregnant women, 1 dose of an inactivated 2009 H1N1 influenza vaccine containing 25 μg of HA elicited an antibody response typically associated with protection against influenza infection. Efficient transplacental transfer of antibody was also documented.

Vaccines in Pregnancy

The concept of maternal immunization to prevent infectious diseases during a period of increased vulnerability in the infant is supported by historical experience and carefully conducted studies of various viral and bacterial vaccines. Candidate vaccines should be minimally reactogenic, immunogenic, and safe. Health education and access to immunization should be a priority if maternal immunization is to succeed as a disease prevention strategy. The potential effect on the incidence of disease in the newborn and young infant can only increase as more candidate vaccines that could be administered during pregnancy become available. In the future, common infections and other, more dreaded diseases, such as herpes simplex virus infection, cytomegalovirus, and human immunodeficiency virus infection, could be prevented with this intervention. Further research on the safety and efficacy of maternal immunization must continue if the occurrence of serious infectious diseases in neonates and young infants is to be reduced.

Influenza virus infection in infancy and early childhood.

Infants and young children have the highest influenza infection and hospitalisation rates in paediatrics. The immaturity of the infants immune system and the absence of prior immunity and exposure to the virus are potential contributors. Although most children that suffer from influenza infection are otherwise healthy, an underlying chronic medical condition further increases the risk for complications. Annual immunisation with influenza vaccine is recommended for any child 6 months of age and older in whom prevention of disease is desirable, particularly for those with underlying medical conditions. Offering influenza vaccine to pregnant women who will deliver during the influenza season can potentially reduce the frequency and severity of influenza disease in infants less than 6 months of age. Family members, including other children and all other close contacts, should also receive influenza vaccine to reduce transmission to children at risk and infants in the first 6 months of life.