An update on primary care management for tuberculosis in children.

PURPOSE OF REVIEW: Tuberculosis (TB) is still a significant cause of mortality and morbidity among children worldwide. Recent advances in scientific and clinical research have looked into the epidemiology, diagnostic, therapeutic and preventive interventions in order to provide insights into more effective control. RECENT FINDINGS: The risk of infection has been shown to be related to the duration and proximity of exposure to an infectious case, usually an adult or adolescent, rising with increased exposure in toddlers, associated with school entry, and in the teen years and early adulthood. Initial primary exposure to TB disease plays a significant role in the development of a latent TB infection, which may serve as a reservoir for future reactivation in adulthood. Diagnosis remains a dilemma for the clinician due to the lack of a gold standard. T-cell assays measuring production of interferon gamma have proven to be more specific than the Tuberculin Skin Test but are unable to distinguish between latent and active disease. SUMMARY: Recent findings have shown the importance of addressing not only active TB disease in children but also latent TB infection. Advances in understanding TB in children provide insights to enhance efforts to control this disease.

Antibody Persistence up to 3 Years After Primary Immunization With Inactivated Japanese Encephalitis Vaccine IXIARO in Philippine Children and Effect of a Booster Dose.

BACKGROUND: An inactivated Vero cell culture derived Japanese encephalitis virus vaccine (IXIARO) requires a booster dose 1 year after primary schedule for long-term antibody persistence in adults. The aim of this study is to evaluate immunogenicity and safety of a booster dose in children 2 months to <18 years of age. METHODS: This is a randomized, controlled open-label study in the Philippines. Three hundred children vaccinated with IXIARO in a previous trial were randomized 1:1 to receive either no booster or a booster 12 months after initiation of the primary series. Neutralizing antibody titers were assessed before and after the booster and up to 3 years after primary series. Safety endpoints included the rate of subjects with solicited adverse events (AEs), unsolicited AEs and serious AEs within 1 month after the booster. RESULTS: Geometric mean titer declined by 1 year after the primary series, but titers remained above the established protective threshold in 85%-100% of children depending on age group. The booster led to a pronounced increase in geometric mean titer and 100% seroprotection rate in all age groups. The booster was well tolerated, with AE rates lower compared with the primary series. Most AEs were mild. CONCLUSIONS: A booster dose of IXIARO administered 12 months after the primary immunization was well tolerated and highly immunogenic.

Safety of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children: An Open-label, Randomized, Active-controlled, Phase 3 Study.

BACKGROUND: Japanese encephalitis remains a serious health concern in Asian countries and has sporadically affected pediatric travelers. In the present study, we monitored the safety profile of the Japanese encephalitis virus vaccine IXIARO (Valneva Austria GmbH, Vienna, Austria) in a pediatric population. METHODS: We randomized 1869 children between 2 months and 17 years of age in an age-stratified manner to vaccination with IXIARO or one of the control vaccines, Prevnar (formerly Wyeth Pharmaceuticals Inc., now Pfizer Inc., Kent, United Kingdom) and HAVRIX 720 (GlaxoSmithKline Biologicals, Rixensart, Belgium). Adverse events (AEs) (unsolicited and solicited local and systemic AEs), serious AEs and medically attended AEs were assessed up to day 56 and month 7 after the first dose. RESULTS: Incidences of AEs, serious AEs or medically attended AEs did not differ significantly between the groups in any age stratum. AEs were most frequent in children <1 year of age and decreased with age. AEs of special interest, predefined as AEs associated with potential hypersensitivity/allergy or neurologic disorders up to day 56, were reported in 4.6% (IXIARO) versus 6.3% (Prevnar) in the ≥2 months to <1 year age group and 3.4% (IXIARO) versus 3.3% (HAVRIX) in the ≥1 to <18 years age group. Fever, the most frequent systemic reaction in 23.7% of infants to 3.8% of adolescents, decreased with age and did not differ between groups. CONCLUSIONS: The safety profile of IXIARO was comparable to the control vaccines in terms of overall AE rates, serious AEs and medically attended AEs.

Demonstration of safety and enhanced seroprotection against hepatitis B with investigational HBsAg-1018 ISS vaccine compared to a licensed hepatitis B vaccine.

Adults 40 years of age and older have been shown to be hypo-responsive immunologically to the currently available hepatitis B virus (HBV) vaccines. Three intramuscular doses of a Toll-like receptor 9 agonist, 1018 immunostimulatory sequence (1018 ISS) adjuvant, combined with recombinant hepatitis B surface antigen (HBsAg) demonstrated faster, superior, and more durable seroprotection than three doses of a licensed comparator HBV vaccine (Engerix-B(®)). This investigational vaccine, HBsAg-1018 ISS, was well tolerated with a safety profile similar to the comparator vaccine. These results suggest that HBsAg-1018 may be more effective in this hypo-responsive population.

Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children.

Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).

Multinational study of major breast milk carotenoids of healthy mothers.

BACKGROUND: Carotenoids in serum vary between countries and within populations with evidence suggesting a qualitative relationship to diet. Breast milk carotenoids furnish a source of vitamin A and potentially provide immunoprotection and other health benefits for infants. There have been numerous studies of milk carotenoid concentrations in undernourished populations; however, carotenoid concentrations have not previously been compared in populations of well-nourished mothers. AIM OF STUDY: To compare concentrations of five major carotenoid groups: alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene in breast milk of healthy women from Australia, Canada, Chile, China, Japan, Mexico, the Philippines, the United Kingdom, and the United States, and to qualitatively compare patterns of dietary intake with milk carotenoid concentrations. METHODS: Breast milk collected from healthy lactating women was analyzed for concentrations of five carotenoids and retinol and quantitated relative to total milk lipid. All determinations were performed in a single research laboratory using standardized methodology. Mothers consumed their usual diets and provided a single 24-h dietary recall. RESULTS: Breast milk carotenoid concentrations varied greatly among countries, with the greatest differences in beta-cryptoxanthin (approximately 9-fold) and the least in alpha-carotene and lycopene (approximately 3-fold). Breast milk retinol concentrations varied approximately 2-fold across countries. The provitamin A carotenoids alpha-carotene, beta-carotene, and beta-cryptoxanthin as a group accounted for > 50 % of the carotenoids measured. Total breast milk carotenoids were highest in Japanese and lowest in Philippine mothers. Breast milk beta-carotene concentrations were highest in Chile and lowest in the Philippines. CONCLUSIONS: Patterns of breast milk carotenoids were unique to each country and qualitative patterns reflected the dietary carotenoid supply.