Paediatric dental outcomes among children exposed to chemotherapy in utero.

AIM: Our study prospectively evaluated dental development in children exposed to chemotherapy in utero compared with unexposed controls. DESIGN: Women who received chemotherapy while pregnant were enrolled in a research registry. After age two, each child's dentist was asked to complete a questionnaire about dental abnormalities and malformations, as well as for their unexposed siblings. Multivariate linear regression adjusting for age was used to compare the groups. RESULTS: Dental information was received for 67 exposed children and 59 controls. The majority of mothers were treated for breast cancer (79.1%) and primarily received doxorubicin (89.6%) and cyclophosphamide (80.6%). Mean gestational age at first exposure was 20.7 (±5.7) weeks. Mean age at dental evaluation was 8.0 (±4.3) years for exposed and 10.4 (±5.1) years for controls (P < .01). Missing teeth, tooth size, shape, and color did not differ significantly between groups. There was no statistical difference in dental caries, facial abnormalities, or abnormalities of enamel or gingiva. There was no association between any chemotherapy agent or regimen and increased risk of dental abnormalities. CONCLUSIONS: Overall, there was no difference in dental abnormalities between groups. These negative findings may be because no one received chemotherapy prior to 14 weeks when formation of primary teeth was beginning.

Full-length Plasmodium falciparum circumsporozoite protein administered with long-chain poly(I·C) or the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and CD4+ T cell immunity and protection in mice.

The Plasmodium falciparum circumsporozoite (CS) protein (CSP) is a major vaccine target for preventing malaria infection. Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here, we compare four distinct full-length P. falciparum CS proteins expressed in Escherichia coli or Pichia pastoris for their ability to induce immunity and protection in mice when administered with long-chain poly(I · C) [poly(I · C)LC] as an adjuvant. CS proteins expressed in E. coli induced high-titer antibody responses against the NANP repeat region and potent CSP-specific CD4(+) T cell responses. Moreover, E. coli-derived CS proteins in combination with poly(I · C)LC induced potent multifunctional (interleukin 2-positive [IL-2(+)], tumor necrosis factor alpha-positive [TNF-α(+)], gamma interferon-positive [IFN-γ(+)]) CD4(+) effector T cell responses in blood, in spleen, and particularly in liver. Using transgenic Plasmodium berghei expressing the repeat region of P. falciparum CSP [Pb-CS(Pf)], we showed that there was a 1- to 4-log decrease in malaria rRNA in the liver following a high-dose challenge and ~50% sterilizing protection with a low-dose challenge compared to control levels. Protection was directly correlated with high-level antibody titers but not CD4(+) T cell responses. Finally, protective immunity was also induced using the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) as the adjuvant, which also correlated with high antibody titers yet CD4(+) T cell immunity that was significantly less potent than that with poly(I · C)LC. Overall, these data suggest that full-length CS proteins and poly(I · C)LC or GLA-SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection.