Incidence and serotype distribution of invasive group B streptococcal disease in young infants: a multi-country observational study.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of serious infection in very young infants. Robust incidence data from many geographic regions, including Latin America and Asia, are however lacking. METHODS: A multicenter, hospital-based observational study was performed in Panama, Dominican Republic, Hong Kong and Bangladesh. All represented urban, tertiary referral hospitals, except Bangladesh. GBS cases (microbiological isolation from normally sterile sites in infants aged 0-89 days) were collected over 12 months. RESULTS: At 2.35 (95% CI: 1.74-3.18) cases per 1000 live births, the incidence of early onset GBS disease (EOD) was highest in the Dominican Republic, compared with 0.76 (95% CI: 0.41-1.39) in Hong Kong and 0.77 (95% CI: 0.44-1.35) in Panama, while no cases were identified in Bangladesh. Over 90% of EOD cases occurred on the first day of life, with case fatality ratios ranging from 6.7% to 40%, varying by center, age of onset and clinical presentation. Overall, 90% of GBS (EOD and late onset disease) was due to serotypes Ia, Ib and III. CONCLUSIONS: The incidence rate of early onset GBS infection reported in Dominican Republic was not dissimilar from that described in the United States prior to screening and intrapartum antibiotic prophylaxis, while the incidence in Hong Kong was higher than previously reported in the Asian region. The failure to identify GBS cases in Bangladesh highlights a need to better understand the contribution of population, healthcare and surveillance practice to variation in reported incidence. Overall, the identified disease burden and serotype distribution support the need for effective prevention methods in these populations, and the need for community based surveillance studies in rural areas where access to healthcare may be challenging.

Breastfeeding prevents severe disease in full term female infants with acute respiratory infection.

BACKGROUND: Breastfeeding is a well-known protective factor against severe respiratory tract infections. Recently, a gender specific role for human milk has been described in very low birth weight infants and neonates: breast milk protected girls but not boys. OBJECTIVE: To determine whether the protective effect of breastfeeding on the severity of acute respiratory infections in full term infants is different for girls and boys. METHODS: A prospective cross-sectional study of infants seeking medical care for acute respiratory infection. The protective role of breastfeeding against viral pneumonia and hospitalization were assessed by univariate and multivariate analyses. Analyses were adjusted for important confounders. RESULTS: A total of 323 patients were enrolled in this study. Breastfeeding protected girls against pneumonia and hospitalization, but did not protect boys. Nonbreastfeeding females were particularly susceptible to severe acute respiratory infections. CONCLUSIONS: Breastfeeding had a protective effect against severe disease in infant girls experiencing their first symptomatic respiratory infection. Nonbreastfeeding females are at significant risk for severe acute lung disease and should be targeted intensively by breastfeeding campaigns.

Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

BACKGROUND: The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. METHODS: Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. RESULTS: During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: <0-100) and 80.6% (95% CI: 51.4-93.2) against the pooled non-G1 rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. CONCLUSION: RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

Cytokine profiles in the respiratory tract during primary infection with human metapneumovirus, respiratory syncytial virus, or influenza virus in infants.

OBJECTIVES: We characterized the T helper cytokine profiles in the respiratory tract of infants infected with influenza virus, human metapneumovirus, and respiratory syncytial virus to examine whether these agents elicit similar cytokine responses and whether T helper type 2 polarization is associated with wheezing and severe disease. METHODS: A prospective study of infants who were seeking medical help for acute upper and/or lower respiratory tract infection symptoms for the first time and were found to be infected with influenza, human metapneumovirus, or respiratory syncytial virus was performed. Respiratory viruses were detected in nasal secretions with reverse transcriptase-polymerase chain reaction assays. The study was performed in emergency departments and outpatient clinics in Buenos Aires, Argentina. T cell cytokine responses were determined in nasal secretions with immunoassays and reverse transcriptase-polymerase chain reaction assays. RESULTS: Influenza elicited higher levels of interferon-gamma, interleukin-4, and interleukin-2 than did the other agents. Human metapneumovirus had the lowest interferon-gamma/interleukin-4 ratio (T helper type 2 bias). However, no association was found between T helper type 2 bias and overall wheezing or hospitalization rates. CONCLUSIONS: These findings show that viral respiratory infections in infants elicit different cytokine responses and that the pathogeneses of these agents should be studied individually.

Differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy.

Viral respiratory infections are the most frequent cause of hospital admission for infants and young children during winter. However, the mechanisms of illness that are associated with viral lower-respiratory-tract infection (LRI) are unclear. A widely accepted hypothesis attributes the pathogenesis of viral LRI in infants to the induction of innate inflammatory responses. This theory is supported by studies showing that Toll-like receptor 4 is activated by respiratory syncytial virus (RSV), leading to production of inflammatory cytokines. We prospectively examined previously naive infants in Buenos Aires, Argentina, who had either upper- or lower-respiratory-tract symptoms. Infection with human metapneumovirus (hMPV) was second only to RSV in frequency. Both viruses were associated with rhinorrhea, cough, and wheezing; however, hMPV elicited significantly lower levels of respiratory inflammatory cytokines than did RSV. Symptoms in infants infected with influenza virus were different from those in infants infected with RSV, but cytokine responses were similar. These findings suggest that hMPV and RSV either cause disease via different mechanisms or share a common mechanism that is distinct from innate immune activation.