Heterologous prime-boost strategy to immunize very young infants against measles: pre-clinical studies in rhesus macaques.

Infants in developing countries are at high risk of developing severe clinical measles if they become infected during the "window of vulnerability" (age 4-9 months), when declining maternal antibodies do not protect against wild virus, yet impede successful immunization by attenuated measles vaccine. We developed two Sindbis replicon-based DNA vaccines expressing measles virus hemagglutinin and fusion protein with the goal of priming young infants to respond safely and effectively to subsequent boosting with attenuated measles vaccine. Intradermal prime with DNA vaccines by needle-free injection followed by aerosol or parenteral boost with licensed measles vaccine was well tolerated by juvenile and young infant rhesus macaques, and protected against clinical measles and viremia on wild-type virus challenge. A proteosome-measles vaccine administered alone (three doses) or as a boost following DNA vaccine priming was also safe and protective. These promising results pave the way for clinical trials to assess this prime-boost strategy.

Immune responses to measles and measles vaccine: challenges for measles control.

Most strategies for reducing global measles morbidity and mortality and eliminating measles are based on the ability to enhance immune responses to measles virus. Challenges to measles elimination and eradication are based in part on the need to sustain high levels of population immunity to interrupt transmission of measles virus. We review aspects of the immunology of measles and measles vaccination with the aim of demonstrating how knowledge of the immune responses is essential to furthering the goals of reducing measles morbidity and mortality and the elimination of measles. Better understanding of the mechanisms of immune suppression after measles, the potential for alternative vaccination strategies to induce immunity in young infants, and the immunologic basis of atypical measles, increased mortality after high-titer measles vaccine, and waning immunity will lead to improved strategies for measles control and elimination.

Colonization by Streptococcus penumoniae in human immunodeficiency virus-infected children.

OBJECTIVE: Children with HIV infection are particularly susceptible to invasive pneumococcal disease, yet the effect of HIV infection and its medical management on colonization and resistance to antibiotics are poorly described. To provide a basis for medical practice, we determined the prevalence of nasopharyngeal colonization and antibiotic resistance of Streptococcus pneumoniae in children with HIV infection. METHODS: Cross-sectional prevalence sample of children attending the pediatric HIV and pulmonary clinics to examine nasopharyngeal colonization with S. pneumoniae and antibiotic resistance to beta-lactams and trimethoprim-sulfamethoxazole (T/S). Subjects were matched by age and date of clinic visit. RESULTS: The colonization rate with S. pneumoniae of HIV-infected and -indeterminate children was equal to that of controls (20% vs. 19%). HIV infection, CDC staging or receipt of oral antibiotic therapy did not affect colonization. Isolates from HIV-infected and -indeterminate children were less likely to be penicillin-resistant than those from controls (18% vs. 50%). There was no difference in pneumococcal resistance to T/S among isolates from subjects and controls, despite 72% T/S use in the HIV clinic. CONCLUSION: Colonization with S. pneumoniae in HIV disease is no different from that of comparable children. The high incidence of pneumococcal disease and prophylaxis with T/S are not related to nasopharyngeal colonization. Antibiotic prophylaxis of HIV-infected children does not necessarily lead to increased resistance of S. pneumoniae.

Successful DNA immunization against measles: neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles.

Measles remains a principal cause of worldwide mortality, in part because young infants cannot be immunized effectively. Development of new vaccines has been hindered by previous experience with a formalin-inactivated vaccine that predisposed to a severe form of disease (atypical measles). Here we have developed and tested potential DNA vaccines for immunogenicity, efficacy and safety in a rhesus macaque model of measles. DNA protected from challenge with wild-type measles virus. Protection correlated with levels of neutralizing antibody and not with cytotoxic T lymphocyte activity. There was no evidence in any group, including those receiving hemagglutinin-encoding DNA alone, of 'priming' for atypical measles.

Production of atypical measles in rhesus macaques: evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody.

The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and fusion-inhibiting antibodies, but no cytotoxic T-cell response. Subsequent infection with measles virus caused an atypical rash and pneumonitis, accompanied by immune complex deposition and an increase in eosinophils. Fusion-inhibiting antibody appeared earlier in these monkeys than in non-immunized monkeys. These data indicate that atypical measles results from previous priming for a nonprotective type 2 CD4 T-cell response rather than from lack of functional antibody against the fusion protein.

Changing partners: the dance of infant formula changes.

The purpose of the study was to establish the frequency of, reasons for, and outcome of formula changes in infants. In this survey, we interviewed a convenience sample of 100 parents in our pediatric outpatient clinic and 75 parents in private pediatric office practices regarding their baby's initial formula, changes in formula, age at change, reason for change, initiator of the change, and outcome. The infants were 30-210 days old. Sixteen of the 175 infants (9%) were started on nonstandard formulas at birth. Fifty-eight of the remaining 159 infants (36%) were changed from regular to nonstandard formulas. After using nonstandard formulas, only seven infants (4%) were ever challenged subsequently with regular formula and all did well. Colic and regurgitation were the main reasons for switching formulas. In 47% the decision to change the formula was made by the mother and in 44% by the pediatrician. Following the formula change, mothers reported improvement or complete resolution of symptoms in 80% of infants. Although published estimates of formula intolerance range from 2% to 7.5%, one in three infants experiences a formula change, suggesting that nonstandard formulas are used excessively by both mothers and physicians. Nevertheless, in the vast majority of cases, parents report that the changes result in improvement or resolution of symptoms. Thus, while this practice appears to be a simple and effective intervention, it produces a significant population of soy and other nonstandard formula-fed babies who should be drinking regular formulas. Such changes encourage a belief by parents that their infants are allergic or otherwise abnormal and could have a negative impact on subsequent child development.

Transient elevation of sweat chloride concentration in a malnourished girl with the Mauriac syndrome.

Elevated sweat chloride concentration in a patient with Mauriac syndrome has been reported only once. The authors of that report regarded their patient's underlying malnutrition, and not Mauriac syndrome per se, as the cause of the elevated sweat chloride concentration. We describe a second example of transient elevation of sweat chloride concentration, which confirms that the malnutrition intrinsic to Mauriac syndrome, rather than the syndrome itself, was the probable cause of elevated sweat chloride values.