RESUMEN
Infection with Coxiella burnetii, the causative agent of Q fever, can result in life-threatening persistent infection. Reactogenicity hinders worldwide implementation of the only licensed human Q fever vaccine. We previously demonstrated long-lived immunoreactivity in individuals with past symptomatic and asymptomatic Coxiella infection (convalescents) to promiscuous HLA class II C. burnetii epitopes, providing the basis for a novel T-cell targeted subunit vaccine. In this study, we investigated in a cohort of 22 individuals treated for persistent infection (chronic Q fever) whether they recognize the same set of epitopes or distinct epitopes that could be candidates for a therapeutic vaccine or aid in the diagnosis of persistent infection. In cultured enzyme-linked immunosorbent spot (ELISpot) assays, individuals with chronic Q fever showed strong class II epitope-specific responses that were largely overlapping with the peptide repertoire identified previously for convalescents. Five additional peptides were recognized more frequently by chronic subjects, but there was no combination of epitopes uniquely recognized by or nonreactive in subjects with chronic Q fever. Consistent with more recent/prolonged exposure, we found, however, stronger ex vivo responses by direct ELISpot to both whole-cell C. burnetii and individual peptides in chronic patients than in convalescents. In conclusion, we have validated and expanded a previously published set of candidate epitopes for a novel T-cell targeted subunit Q fever vaccine in treated patients with chronic Q fever and demonstrated that they successfully mounted a T-cell response comparable to that of convalescents. Finally, we demonstrated that individuals treated for chronic Q fever mount a broader ex vivo response to class II epitopes than convalescents, which could be explored for diagnostic purposes.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Antígenos Bacterianos/inmunología , Coxiella burnetii/inmunología , Epítopos de Linfocito T/inmunología , Fiebre Q/inmunología , Anciano , Antibacterianos/uso terapéutico , Antígenos Bacterianos/química , Antígenos Bacterianos/genética , Vacunas Bacterianas/química , Vacunas Bacterianas/inmunología , Enfermedad Crónica , Convalecencia , Coxiella burnetii/patogenicidad , Ensayo de Immunospot Ligado a Enzimas , Epítopos de Linfocito T/química , Epítopos de Linfocito T/genética , Femenino , Expresión Génica , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Prueba de Histocompatibilidad , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Masculino , Persona de Mediana Edad , Péptidos/genética , Péptidos/inmunología , Fiebre Q/tratamiento farmacológico , Fiebre Q/genética , Fiebre Q/prevención & control , Linfocitos T/inmunología , Linfocitos T/microbiologíaRESUMEN
BACKGROUND & AIMS: Sufficient protein intake is of great importance in hemodialysis (HD) patients, especially for maintaining muscle mass. Daily protein needs are generally estimated using bodyweight (BW), in which individual differences in body composition are not accounted for. As body protein mass is best represented by fat free mass (FFM), there is a rationale to apply FFM instead of BW. The agreement between both estimations is unclear. Therefore, the aim of this study is to compare protein needs based on either FFM or BW in HD patients. METHODS: Protein needs were estimated in 115 HD patients by three different equations; FFM, BW and BW adjusted for low or high BMI. FFM was measured by multi-frequency bioelectrical impedance spectroscopy and considered the reference method. Estimations of FFM x 1.5 g/kg and FFM x 1.9 g/kg were compared with (adjusted)BW x 1.2 and x 1.5, respectively. Differences were assessed with repeated measures ANOVA and Bland-Altman plots. RESULTS: Mean protein needs estimated by (adjusted)BW were higher compared to those based on FFM, across all BMI categories (P < 0.01) and most explicitly in obese patients. In females with BMI >30, protein needs were 69 ± 17.4 g/day higher based on BW and 45 ± 9.3 g/day higher based on BMI adjusted BW, compared to FFM. In males with BMI >30, protein needs were 51 ± 20.4 g/day and 23 ± 20.9 g/day higher compared to FFM, respectively. CONCLUSIONS: Our data show large differences and possible overestimations of protein needs when comparing BW to FFM. We emphasize the importance of more research and discussion on this topic.
Asunto(s)
Composición Corporal , Obesidad , Peso Corporal , Impedancia Eléctrica , Femenino , Humanos , Masculino , Obesidad/terapia , Diálisis RenalRESUMEN
In the Netherlands, attendance rates for breast cancer screening are much lower among Dutch women born in Turkey and Morocco than they are among native Dutch. The reasons for this trend are not yet known. Currently, mortality and incidence rates for these migrant groups are much lower than those of the native population. However, studies show convergence towards the rates of the native Dutch population. We therefore performed a narrative literature review to study the reasons behind the low participation rate for breast cancer screening among Turkish and Moroccan women in the Netherlands. No truly relevant research on this topic was available. Information acquired from articles only applicable to certain areas of the research question showed that reasons pertaining to lack of awareness and knowledge, organizational issues and socio-cultural aspects are most likely to be responsible for the low attendance. To increase attendance rates, more research is needed to obtain insight into these aspects and into the reasons given by Turkish and Moroccan women.