ABSTRACT
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Liver/immunology , Malaria Vaccines/immunology , Malaria, Falciparum/prevention & control , Plasmodium falciparum/immunology , Sporozoites/immunology , Adolescent , Adult , Animals , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Humans , Injections, Intravenous , Injections, Subcutaneous , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Macaca mulatta , Malaria Vaccines/administration & dosage , Malaria Vaccines/adverse effects , Mice , Middle Aged , Rabbits , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology , Young AdultSubject(s)
Career Choice , Curriculum , Education, Medical/organization & administration , Health Workforce , Medically Underserved Area , Primary Health Care , Rural Health Services , Specialization , Clinical Competence , Georgia , Health Services Needs and Demand , Humans , Longitudinal Studies , Schools, MedicalABSTRACT
BACKGROUND: Many clinicians believe the radiographic expression of community-acquired pneumonia (CAP) is affected by the fluid volume status of the patient. However, there are very few data to support or refute this concept. With this study we began to examine the relationship between admission fluid volume status and the radiographic expression of CAP. METHODS: Using a retrospective chart review, we examined 376 consecutive inpatient encounters with the diagnosis of pneumonia at discharge from a community teaching hospital. Patients were evaluated by age, sex, admission serum sodium, blood urea nitrogen (BUN) level, creatinine, and fluid administered in the first 48 hours of treatment. We classified these patients as either showing radiographic progression (P) or no radiographic progression (NP) by comparison of admission and follow-up radiographs. RESULTS: A total of 125 patient encounters satisfied inclusion criteria for the study. Using the Student t test we noted a statistically significant difference between the P and NP groups for BUN level (P=.02), volume of fluid administered during the first 48 hours (P=.04), and marginally for age (P=.05). The P group had higher BUN levels (mean=34 vs 24), more 48-hour fluid intake (mean=5824 mL vs 4764 mL), and younger age (mean=59 years vs 66 years) than the NP group. Logistic regression poorly predicted which patients would have worsening infiltrate on the second radiograph. CONCLUSIONS: Elevated admission BUN level and higher fluid volume administered in the first 48 hours of admission were associated with worsening radiographic findings of pneumonia after hydration. Prospective studies are needed for confirmation of our results.
