Infant Schedule Research Articles

Pneumococcal Polysaccharide Protein D-Conjugate Vaccine (Synflorix™; PHiD-CV)

The pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) contains ten capsular polysaccharide serotypes from the bacterium Streptococcus pneumoniae, eight of which are conjugated to a nonlipidated cell-surface liporotein (protein D) of non-typeable Haemophilus influenzae (NTHi) and two of which are conjugated to either tetanus or diphtheria toxoid. In a three-dose primary vaccination schedule in infants aged <6 months, PHiD-CV elicited high immune responses against all pneumococcal serotypes contained in the vaccine and was noninferior to an approved 7-valent pneumococcal conjugate vaccine (7vCRM) for eight of the ten serotypes (five of the seven common to both vaccines). Moreover, functional antibodies were elicited against all vaccine serotypes in an opsonophagocytic activity (OPA) assay. A fourth booster dose of PHiD-CV during the second year of life elicited an anamnestic response against all ten pneumococcal serotypes, as determined by both antibody concentrations and OPA titers. There were no clinically relevant changes in the immunogenicity of PHiD-CV when coadministered with meningococcal serogroup C conjugate or pentavalent whole cell pertussis combination vaccines, and polio vaccines using two different primary vaccination schedules. 11Pn-PD, an 11-valent prototype of PHiD-CV, demonstrated protection against episodes of acute otitis media (AOM) caused by S. pneumoniae and NTHi in infants aged <27 months. The first occurrence of an episode of AOM caused by pneumococcal vaccine serotypes was reduced by 52.6% in 11Pn-PD vaccinees compared with recipients of a control vaccine (primary endpoint). The tolerability profile of PHiD-CV was generally similar to that of 7vCRM.

Randomized Clinical Trial Comparing Hepatitis B Vaccine Administered by 0, 6 and 14 Week versus 6, 10 and 14 Week Schedule in Healthy Infants

This randomized, single-blinded trial was carried out to compare the sero-efficacy of hepatitis B vaccine administered to healthy infants by either of two schedules-birth, 6, 14 weeks or 6, 10 and 14 weeks. The 74 infants born to HbsAg-negative mothers were randomized to receive recombinant hepatitis B vaccine at 0, 6 and 14 weeks (Group A) or 6, 10 and 14 weeks (Group B). Serum anti-HBs antibody titer was measured before the first dose and 6 months after the third dose by laboratory personnel blinded to the intervention. All participants received other vaccines as per the national immunization schedule. At 6 months after the third dose sero-conversion was 100% in both groups. A total of 97.3% of subjects in Group A were sero protected (>10 mIUml(-1)) with geometric mean titer (GMT) of 113.78 mIUml(-1) and 94.6% in Group B (GMT 107.04 mIUml(-1)) [p = 0.8]. Hepatitis B vaccination by 0, 6 and 14 weeks and 6, 10 and 14 weeks schedules are comparable in terms of sero-efficacy.

Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants

The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants. In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives. At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P=0.01). The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. (ClinicalTrials.gov number, NCT00289185.)

Anthroposophic paediatric care in a public service. A 15 years’ experience

Having worked as anthroposophy-oriented paediatric consultant in a preventive care unit (the so-called Consultorio Familiare), in Sestu (Cagliari, Sardinia, Italy) for 15 years, the author provides a number of examples to how an integrative approach is possible to care in a suburb area public service. The types of requests a non-conventional paediatrician is exposed to in a public service are synthetically outlined. They range from daily pedagogical problems, to vaccinations, to preventive care in order to better face the common upper and lower airway infections of the first years of life, to common pathological problems. Nutrition , rhythmic day activity schedule for infants , toddlers and pre-school age children , a sound sense of authority, the practice of arts (music), age-related manual work and intense open air activities during the school age period are the cornerstone of anthroposophic preventive care. The author concludes underlining how anthroposophic paediatrics encompasses both a medical and a pedagogical approach. Some hints are also given about anthroposophic paediatric pharmacological treatment.

Clinical assessment of autism in high-risk 18-month-olds

Earlier intervention improves outcomes for children with autism spectrum disorders (ASDs), but existing identification tools are at the limits of standardization with 18-month-olds. We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD. Prospective data were collected using the Autism Diagnostic Observation Schedule (ADOS) and Autism Observation Scale for Infants (AOSI) on 155 infant siblings and 73 low-risk controls at 18 months. Infants were classified into three groups (ASD sibs, non-ASD sibs, controls) based on blind best-estimate diagnosis at age 3. Fisher's exact tests, followed by discriminant function analyses, revealed that the majority of informative ADOS items came from the social and behavioural domains, and AOSI items measuring behavioural reactivity and motor control contributed additional information. Findings highlight the importance of considering not only social-communication deficits, but also basic dimensions of temperament including state regulation and motor control when assessing toddlers with suspected ASD.

Progress in vaccination against Haemophilus influenzae type b in the Americas.

Worldwide, Haemophilus influenzae type b (Hib) causes at least 3 million cases of severe disease each year. Approximately 400,000 children die annually due to pneumonia or meningitis caused by Hib [1]. Severe neurological sequelae occur in 15% to 30% of those who survive Hib meningitis [2]. Other, less frequent, manifestations of Hib are epiglottitis, septic arthritis, osteomyelitis, and septicemia [1–3]. Current polysaccharide–protein conjugate Hib vaccines are highly efficacious and safe. Primary series of two or three doses protect approximately 95% of infants [4–8]. Universal infant Hib immunization has proven to dramatically reduce Hib invasive disease [9–13] through direct vaccine protection and an important herd effect related to the reduction in Hib nasopharyngeal carriage in the community [12,14–16]. Adverse events are rare, and Hib vaccine is contraindicated only for persons with hypersensitivity to any of the vaccine's components [8,17]. The World Health Organization (WHO) recommends the introduction of Hib vaccines worldwide [1]. Furthermore, the Global Alliance for Vaccines and Immunization (GAVI Alliance)—an organization that aligns public and private resources in a global effort to create greater access to the benefits of immunization—considers Hib vaccine introduction in the world's poorest countries to be a top priority [18]. Prior to vaccine introduction, an estimated 20,000 cases of Hib meningitis were estimated to occur in countries of Latin America and the Caribbean (LAC) annually, based on an overall Hib meningitis incidence of 35 per 100,000 children aged 0–4 years [19]. Another 20,000 cases of invasive Hib disease were estimated to occur in the United States annually [20]. Most cases occurred in children aged less than 24 months, with at least 60% of cases occurring in children aged 0–11 months in half of the studies. The annual mortality rate for Hib meningitis in children aged less than five years was estimated to be around two per 100,000 in the Western Hemisphere [21]. Summary Points Hib vaccine introduction in countries of Latin America and the Caribbean has substantially reduced morbidity and mortality due to invasive Hib infections. All Latin American and Caribbean countries but one include Hib vaccine in their routine immunization schedule for infants. Factors that favored this region-wide Hib vaccine adoption include strong political will, data supporting Hib disease burden and impact in early adopting countries, and experience exchange among countries. Financial sustainability when introducing the more expensive Hib vaccine was critical for ensuring successful vaccine introduction in all countries. Efforts are still needed to improve vaccination coverage and to strengthen invasive bacterial disease surveillance in developing countries. In this article, we review the progress of vaccine introduction, lessons learned, and remaining challenges regarding Hib vaccination in the Americas, with emphasis on LAC countries. We expect that this updated and summarized information on Hib vaccination will serve as a useful reference to public health officials and policy makers from other regions who face the challenge of introducing Hib and other new or underutilized vaccines.

Two versus three doses of a meningococcal C conjugate vaccine concomitantly administered with a hexavalent DTaP-IPV-HBV/Hib vaccine in healthy infants

The immunogenicity and reactogenicity of a meningococcal serogroup C (MenC) conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib vaccine according to a two- or three-dose schedule in healthy infants was evaluated. At 1 month post-vaccination, 98% (two doses) and 100% (three doses) of subjects had serum bactericidal antibody using human complement assay (hSBA) titres > or =1:8; at 12 months of age > or =89% of subjects in each group remained seroprotected. Induction of immunological memory, as evaluated by administration of a meningococcal serogroup A/C polysaccharide vaccine challenge dose, was similar for both regimens and no interference was observed in the immune response to MenC or hepatitis B virus antigens. Reactogenicity was similar in each group. MenC conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib to healthy infants in the first year of life using a two-dose schedule is as safe and immunogenic as a three-dose regimen.

A Review of Thimerosal (Merthiolate) and its Ethylmercury Breakdown Product: Specific Historical Considerations Regarding Safety and Effectiveness

Thimerosal (Merthiolate) is an ethylmercury-containing pharmaceutical compound that is 49.55% mercury and that was developed in 1927. Thimerosal has been marketed as an antimicrobial agent in a range of products, including topical antiseptic solutions and antiseptic ointments for treating cuts, nasal sprays, eye solutions, vaginal spermicides, diaper rash treatments, and perhaps most importantly as a preservative in vaccines and other injectable biological products, including Rho(D)-immune globulin preparations, despite evidence, dating to the early 1930s, indicating Thimerosal to be potentially hazardous to humans and ineffective as an antimicrobial agent. Despite this, Thimerosal was not scrutinized as part of U.S. pharmaceutical products until the 1980s, when the U.S. Food and Drug Administration finally recognized its demonstrated ineffectiveness and toxicity in topical pharmaceutical products, and began to eliminate it from these. Ironically, while Thimerosal was being eliminated from topicals, it was becoming more and more ubiquitous in the recommended immunization schedule for infants and pregnant women. Furthermore, Thimerosal continues to be administered, as part of mandated immunizations and other pharmaceutical products, in the United States and globally. The ubiquitous and largely unchecked place of Thimerosal in pharmaceuticals, therefore, represents a medical crisis.

Surveillance for Invasive Pneumococcal Disease During 2000–2005 in a Population of Children Who Received 7-Valent Pneumococcal Conjugate Vaccine

To assess the incidence of invasive pneumococcal disease (IPD) in all children younger than 5 years of age in the Northern California Kaiser Permanente (NCKP) health care system during a 5-year surveillance period (2000-2005) after the introduction in April 2000 of routine use of 7-valent pneumococcal conjugate vaccine (PCV7). This was a laboratory-based surveillance study of all children younger than 5 years of age in the NCKP health care system from April 2000 to March 2005. The comparison group was all children younger than 5 years of age in the NCKP health care system from April 1996 to March 2000. Data obtained from clinical databases included microbiologic identification and susceptibility testing; serotyping of isolates; immunization records; and IPD diagnoses for inpatients and outpatients. IPD was defined as a positive culture of Streptococcus pneumoniae from a normally sterile body site. For all serotypes, the mean annual incidence of IPD during the postlicensure surveillance period was 15.3 cases/100,000 person-years (10(5) p-y) compared with 62.5 cases/10(5) p-y in the prelicensure years of 1996-2000. The average incidence of IPD caused by vaccine serotypes was reduced from 50.1 cases/10(5) p-y during the prelicensure years to 4.9 cases/10(5) p-y during the postlicensure period. The average incidences of IPD caused by cross-reactive and by nonvaccine serotypes were 5.8 and 5.3 cases/10(5) p-y, respectively, during the prelicensure years and 2.5 and 6.2 cases/10(5) p-y, respectively, during the postlicensure period. Of the 131 IPD cases observed during the postlicensure surveillance period, bacteremia (50.4%) and pneumonia (31.3%) were the most common diagnoses. During the 5-year postlicensure surveillance period, only 3 subjects who were identified to be fully vaccinated for age with PCV7 (3 doses by 7 months of age or 4 doses by 18 months of age) developed vaccine-serotype IPD. The incidence of IPD has significantly decreased in a large population of children after the introduction of PCV7. Vaccine-type IPD was rare in patients who received full 4-dose immunization with PCV7. There is no clear evidence of a significant increase in nonvaccine-serotype IPD. Introduction of a 4-dose infant schedule of PCV7 into this population has resulted in a marked and sustained reduction of IPD in children.

Reliability and validity of the fear survey schedule for infants-preschoolers

The aim of this research was to examine the reliability and validity of a new questionnaire to measure fears in young children. One hundred and thirty-three parents of children 18 months to 5 years of age completed the Fear Survey Schedule for Infants-Preschoolers (FSSIP). Parents and other caregivers were interviewed and completed questionnaires concerning child fearfulness, and child fearful behavior was observed. The FSSIP demonstrated high internal consistency, low-to-moderate test-retest correlations over an average of 6 months, and good convergent and discriminant validity. With further research, the FSSIP could aid in the investigation of the duration and consequences of fears in young children.

Bacterial Meningitis

Acute bacterial meningitis remains an important cause of morbidity and mortality in children. Children <2 years of age are particularly susceptible to infection with encapsulated bacteria due to their immature response to polysaccharide antigens. Conjugate vaccines, which induce T cell memory, can provide immunological protection for these children. The Haemophilus influenzae type b (Hib) conjugate vaccine was the first such vaccine to become available. The efficacy of the vaccine has been quoted as being 98%. Its introduction was followed by a dramatic decrease in the incidence of all invasive Hib disease, including meningitis. This reduction was in part due to the ability of these vaccines to reduce nasopharyngeal carriage of the organism and thereby induce herd immunity. Different Hib vaccines use a variety of protein carriers and differ in their immunogenicity and efficacy. The most suitable vaccine needs to be determined according to the local epidemiology of Hib disease. Commercial combination vaccines may lead to lower antibody levels. A recent increase in the incidence of Hib disease in the UK highlights the importance of continued surveillance and the need for booster vaccinations to ensure continued protection. Conjugate vaccines to Streptococcus pneumoniae and Neisseria meningitidis have been developed. The introduction of a pneumococcal conjugate vaccine in the US has led to a decrease in the rate of infection by nearly 60% in children <5 years of age. A reduction in pneumococcal carriage may also modify disease epidemiology. The UK introduced the conjugate meningococcal C vaccine into its infant schedule with a corresponding reduction in N. meningitidis group C disease. A recent decrease in the effectiveness of the vaccine, however, suggests a booster may be necessary in the future. Our present understanding of the immunology of conjugate vaccines is far from complete. Developed countries have introduced conjugate vaccines into their immunisation schedules to prevent bacterial meningitis; however, their high cost precludes their use in many developing countries. Progress needs to be made in order to get these highly effective vaccines to those areas that need them.

Vaccination du prematuré

Premature infants have an increased risk of experiencing infectious diseases, some of which are vaccine preventable diseases. Maturation of immune responses begins with exposition to environmental antigens and in premature infants as fast as in term-infants. Premature infants must be vaccinated at 2 months of age, whatever the gestational age. Acellular Pertussis vaccine and pneumococcal conjugate vaccine must be given as early as possible, at two months of age. Immunization schedule in premature infants is the same as in full-term infants : three injections one month apart with a pentavalent vaccine : Diphteria, Tetanus, Poliomyelitis, Pertussis and Haemophilus type b. First injection of hepatitis B vaccine must not be taken in account when this vaccine is given at birth to infants under 2 kg birth weight. Premature infants 6 months of age or older and experiencing chronic lung disease have to be vaccinated against influenza. In all cases, surroundings have to be vaccinated. Apnea and/or bradycardia have been reported within the 48 hours following vaccination in premature infants before 32 weeks of gestational age and justify giving their first injection of vaccine under cardiorespiratory monitoring. These injections will be given before discharge as often as possible.

Varicella and zoster vaccines

The varicella vaccine (OKA strain) first used in Japan in 70's was introduced into the routine infants immunisation schedule of United States in 1995. Two other new varicella vaccines have been just licensed: a tetravalent measles-mumps-rubella-varicella vaccine (MMRV) and a zoster vaccine for more than 60 years old adults. In Europe varicella vaccine is not introduced in routine infant schedule, except in Germany, and only used for targeted aims. This reluctance is justified by several considerations: the fear of a shift of varicella to adults by low vaccine coverage, the risk of increasing zoster in adults by a mass vaccination. Several recent varicella outbreaks in highly vaccinated children stress the possible need for a routine second dose of vaccine in infants. The cost-effectiveness studies results are not similar in different countries and the benefits are indirect (time off work).Varicella is often considered as a mild disease, in spite of a better knowledge of complications and health benefits in United-States, where vaccination has resulted in a dramatic decline of deaths, hospitalisations and varicella-related complications. The new tetravalent MMRV vaccine could stimulate Europe to implement routine vaccination, provided that an efficient surveillance for varicella and shingles be instituted.

Immunogenicity and Boosting After a Reduced Number of Doses of a Pneumococcal Conjugate Vaccine in Infants and Toddlers

The minimum number of doses of pneumococcal conjugate vaccine required for protection is not known. We studied the immunogenicity of a reduced schedule in infants and toddlers. U.K. infants were given either 2 or 3 doses (at 2 and 4 or 2/3/4 months of age) of a 9-valent pneumococcal conjugate vaccine (9VPCV) followed by boosting at 12 months of age. In a separate study, toddlers (12 months) received 1 or 2 doses (2 months apart) of 9VPCV followed by pneumococcal polysaccharide vaccine at 18 months of age. For infants, serotype-specific IgG geometric mean concentrations were similar post-primary immunization between the groups with both showing avidity maturation and similar booster responses. For toddlers, the primary response to 4 of the 9 serotypes was lower in the 1- compared with the 2-dose group (type 6B, 0.77 versus 7.1; type 14, 4.67 versus 14.98; type 19F, 5.05 versus 7.75; type 23F, 2.48 versus 5.05), although for all serotypes booster responses were similar between groups, and the postprimary responses in the 1-dose group were at least as high as those after infant immunization. The 2-dose infant priming schedule of 9VPCV is comparable with the 3-dose schedule and may thus be equally protective, whereas 1 dose in toddlers may suffice for a catch-up.

Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants

Background To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). Methods Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12–15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each dose and compared between groups. Blood was obtained prior to dose 1, one month after dose 3, immediately prior to and 1 month following the booster dose to measure antibody responses to each of the antigens. Results Two hundred and fifty-three subjects (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226 subjects for the primary immunization and 212 for the booster dose (per-protocol (PP) population). Although there were some differences in geometric mean concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series, GMCs for all antigens after the booster dose were similar in both groups, except for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41 IU/mL; Control, 5.78 IU/mL). Reactogenicity and safety data were compared in 252 infants receiving primary immunization and 235 children receiving the booster dose. Site reactions were similar in both groups. Fever ≥38.0 °C following each vaccination was reported more frequently in the PCV7 group (28.3–50.0%) than in the Control group (15.6–33.6%) whereas fever >39.0 °C occurred only in a few cases and to the same extent in both groups (PCV7, 0.8–2.7%; Control, 1.6–4.1%). Only one reported serious adverse event was characterized as being related to the study vaccines: control subject was hospitalized with a fever. Conclusion DTPa-HBV-IPV/Hib and PCV7 were highly immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of age with a booster dose at 12–15 months of age. These results support the coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine immunization schedule for infants and children.

Immunogenicity of one, two or three doses of a meningococcal C conjugate vaccine conjugated to tetanus toxoid, given as a three-dose primary vaccination course in UK infants at 2, 3 and 4 months of age with acellular pertussis-containing DTP/Hib vaccine

Reduction of the number of injections necessary to confer protection in the infant schedule would reduce discomfort, improve cost-effectiveness and create space for the addition of new vaccinations in the future. This study assessed the immunogenicity of one, two or three doses of meningococcal C conjugate vaccine conjugated to tetanus toxoid (MCC-TT) [Neis-VacC ®] given concomitantly with a combined diphtheria/tetanus/acellular pertussis/ Haemophilus influenzae type b -TT conjugate (DTaP-Hib-TT) [Infanrix-Hib ®] vaccine at 2, 3 and 4 months of age. A total of 106 healthy UK infants were enrolled and randomised into two groups, one in which blood was taken after the first and third dose and the other after the second and third dose. The meningococcal serogroup C serum bactericidal antibody (SBA) geometric mean titre (GMT) rose significantly from post-first dose (491, 95% CI 275, 877) to post-second dose (1052, 95% CI 774, 1433) ( p = 0.03), with no significant change after the third dose (1024, 95% CI 768, 1366). An SBA titre of ≥8 was achieved by 92% after the first dose and 100% after the second and third doses. The Hib IgG geometric mean concentration (GMC) rose significantly after each dose: post-first (0.14 μg/ml 95% CI 0.10, 0.18), post-second (0.54 μg/ml, 95% CI 0.33, 0.90), post-third (2.04 μg/ml, 95% CI 1.52, 2.74). The Hib GMC after the third dose was higher than reported previously when this DTaP/Hib was given either on its own or concomitantly with a MCC-CRM conjugate vaccine according to the UK 2, 3 and 4 month schedule. This suggests some enhancement of the response to a Hib-TT vaccine by concomitant administration of MCC-TT. These results suggest that a reduced number of doses of MCC-TT would be adequate in infancy if given concomitantly with an acellular pertussis-containing vaccine.

An Intervention Program for Families With Irritable Infants

To describe and evaluate a home-based nursing intervention program, the REST routine, which incorporates the use of infant behavior assessment, pattern recognition, individualized infant schedules, specific management strategies, and parent education and support. A two-site clinical trial was conducted on 164 healthy full-term infants with excessive unexplained irritability or colic. Infants between the ages of 2 to 6 weeks were randomized to routine care or a home-based intervention program (n = 121). A third group (n = 43) of infants too old at entry for randomization (mean age = 10.4 weeks) were entered into a posttest-only group. Infants in the REST routine treatment group cried 1.3 hours per day on average following the intervention program as compared to the control group crying 3 hours per day (p = .02). Infant irritability was resolved (< 1 hour) in 62% of the treatment group while only in 29% of the control group at the time of the 8-week follow-up visit (p = .04). Families in both the treatment and control groups reported benefiting from a nurse visiting in their home to inquire about their infant and their well-being. Options for individualizing the program for those most in need of intensive home visiting and other delivery modes for the intervention are areas for further investigation.

One for all: newer combination vaccines in practice.

As new combination vaccines are approved, practices must consider whether to switch. The decision is likely to be complex, involving everything from re-education of staff to recalculating the bottom line. At some point, however, change will be inevitable, driven principally by the need to add new vaccines to the schedule. In fall 2004, practitioners will be adding two doses of inactivated influenza vaccine to the infant schedule. More communities will be adding two doses of hepatitis A vaccine, which may become routine for all children at some point. We can hope as well for a meningococcal conjugate vaccine series, which, like Hib and PCV-7, would be administered by an infant's first birthday. In addition, there's the pentavalent bovine reassortant rotavirus vaccine (Rotateq) which, although given orally, will further crowd the schedule. The sooner we become comfortable with combination vaccines, the better.

Pediatricians' self-reported clinical practices and adherence to national immunization guidelines after the introduction of pneumococcal conjugate vaccine.

Little is known about whether pneumococcal conjugate vaccine (PCV) has altered pediatricians' practices regarding well-child and acute care. To (1) describe whether PCV caused pediatricians to move other routine infant vaccines and/or add routine visits; (2) characterize adherence to national immunization recommendations; and (3) determine whether PCV altered pediatricians' planned clinical approach to well-appearing febrile infants. One year after PCV was added to the pediatric immunization schedule, we mailed a 23-item survey to 691 randomly selected pediatricians in Massachusetts. The adjusted response rate was 77%. After PCV introduction, 39% of pediatricians moved other routine infant vaccines to different visits and 15% added routine visits to the infant schedule. The self-reported immunization schedules of 36% were nonadherent to national immunization guidelines for at least 1 vaccine. Nonadherence rates were significantly higher among pediatricians who had been in practice longer, moved another vaccine because of PCV introduction, and/or offered to give shots later when multiple injections were due. For a hypothetical febrile 8-month-old girl who had received 3 doses of PCV, pediatricians reported they were significantly less likely to (1) perform both blood and urine testing and (2) prescribe antibiotics than in the pre-PCV era. The introduction of PCV may have had unintended effects on pediatric primary care, including decreased adherence to national recommendations for the timing of immunizations and decreased urine testing for well-appearing febrile infants. Special efforts may be warranted to ensure that pediatricians remain current with changing recommendations.

Should the Centers for Disease Control and Prevention's childhood lead poisoning intervention level be lowered?

The US Centers for Disease Control and Prevention (CDC) in 1991 chose 10 micro g/dL as an initial screening level for lead in children's blood. Current data on health risks and intervention options do not support generally lowering that level, but federal lead poisoning prevention efforts can be improved by revising the follow-up testing schedule for infants aged 1 year or less with blood lead levels of 5 micro g/dL or higher; universal education about lead exposure risks; universal administration of improved, locally validated risk-screening questionnaires; enhanced compliance with targeted screening recommendations and federal health program requirements; and development by regulatory agencies of primary prevention criteria that do not use the CDC's intervention level as a target "safe" lead exposure.