Immunogenicity and safety of a tetravalent dengue vaccine and a bivalent HPV vaccine given concomitantly or sequentially in girls aged 9 to 14 years in Mexico.

Dengue is endemic in several regions, and the global incidence is increasing. The recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is recommended for dengue seropositive individuals ≥ 9 years. Human papillomavirus (HPV) vaccination is recommended for girls aged 9-14 years to prevent HPV infection-related cancers. This study assessed the immunogenicity and safety of a bivalent HPV (types 16 and 18) vaccine and CYD-TDV when co-administered concomitantly or sequentially. This was a Phase IIIb, randomized, open-label, multicenter study in girls aged 9-14 years in Mexico (NCT02979535). Participants were randomized 1:1 to receive three doses of CYD-TDV 6 months apart and two doses of bivalent HPV vaccine either concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Antibody levels were measured at baseline and 28-days after each vaccine dose for all participants, using an enzyme-linked immunosorbent assay for HPV-16 and HPV-18 antibodies, and a plaque reduction neutralization test for the four dengue serotypes; results are reported only for participants who were seropositive at baseline. Safety was assessed for all randomized participants throughout the study. Of the randomized participants, 305/478 (63.8%) were seropositive for dengue at baseline: 154 in the concomitant group and 151 in the sequential group. After the last HPV vaccine dose, the antibody titers for HPV were comparable in seropositive participants between treatment groups, with between group titer ratios of 0.966 for HPV-16 and 0.999 for HPV-18. After dose 3 of CYD-TDV, antibody titers were comparable for the concomitant and sequential groups across all serotypes, with between-group ratios close to 1 (serotype 1: 0.977; serotype 2: 0.911; serotype 3: 0.921; serotype 4: 0.931). CYD-TDV and a bivalent HPV vaccine administered concomitantly or sequentially in dengue seropositive girls aged 9-14 years elicited comparable immune responses with similar safety profiles.

Zika and Dengue Interactions in the Context of a Large Dengue Vaccine Clinical Trial in Latin America.

A phase III dengue vaccine trial including 9- to 16-year-olds in Latin America (NCT01374516) was ongoing at the time of a Zika outbreak. We explored interactions between dengue and Zika, in the context of dengue vaccination. Symptomatic virologically confirmed Zika (VCZ) was evaluated using acute-phase sera from febrile participants (January 2013-March 2018). Neutralizing antibody geometric mean titers (GMTs) were evaluated pre- and post-Zika outbreak (months 25 and 72) in 2,000 randomly selected participants. Baseline dengue serostatus was determined using the plaque reduction neutralization test or inferred post hoc using nonstructural protein 1 IgG ELISA at M13 (case-cohort analysis). Vaccine efficacy against VCZ and serologically suspected Zika (SSZ) was estimated. Overall, 239/10,157 (2.4%) acute-phase samples were VCZ positive during the study. Dengue vaccine efficacy against VCZ was 27.8% (95% CI: 0.3; 47.7) among baseline dengue-seropositive participants. No vaccine effect was evident against SSZ. Zika antibody GMTs increased from pre- to post-Zika epidemic, with smaller increases observed for participants who were dengue seropositive at baseline than for those who were dengue seronegative: post-/pre-Zika GMT ratios for baseline dengue-seropositive participants were 21.5 (vaccine group) and 30.8 (placebo); and for dengue seronegatives, 88.1 and 89.5, respectively. Dengue antibody GMTs post-Zika were higher in dengue vaccine and placebo recipients with SSZ than those without SSZ in both dengue seropositives and seronegatives. Dengue vaccine did not enhance symptomatic Zika illness in dengue-seropositive individuals, rather it reduced the risk of VCZ. Zika infection boosted preexisting vaccine-induced or naturally occurring dengue-neutralizing antibodies.

Immunogenicity and safety of a multi-dose quadrivalent inactivated influenza vaccine in individuals aged 6 months to 17 years: a randomized phase III trial.

Annual vaccination is the most effective way to prevent seasonal influenza. Influenza vaccines in multi-dose vial (MDV) formats can facilitate timely vaccination of large populations by reducing per-dose costs and cold storage requirements compared to single-dose pre-filled syringe (PFS) formats. MDV vaccines require thiomersal or another preservative to prevent microbial contamination. We conducted a randomized, open-label trial in 302 healthy subjects aged 6 months to 17 years to evaluate the immunogenicity and safety of a quadrivalent influenza vaccine (QIV) in a thiomersal-containing MDV format compared to the licensed thiomersal-free PFS format. Subjects were randomly assigned in a 1:1 ratio to receive the MDV (n = 153) or PFS (n = 149) format. Post-vaccination hemagglutination inhibition titers for all four vaccine strains were ≥4.9-fold higher than baseline titers with no difference in magnitude between the MDV and PFS groups. Seroconversion rates per strain were also comparable between the two groups. There were no differences in reactogenicity or safety between the two vaccine formats. These results showed that the MDV format of QIV was as safe and immunogenic as the PFS format in infants, children, and adolescents. These findings support the use of MDV QIV as a resource-saving alternative for seasonal influenza vaccination.

Blood SC5b-9 complement levels increase at parturition during term and preterm labor.

We explored the hypothesis that complement, an innate and adaptive immune effector, is active in the plasma of parturient women and is deposited on fetal membranes collected after delivery. A cross-sectional study was designed to evaluate complement activity at parturition. Pregnant women (n = 97) between 15 and 41 years of age were enrolled in a hospital protocol during the perinatal period to assess both SC5b-9 complement activity in blood and complement deposition on fetal membranes during parturition. Soluble SC5b-9 complement activity in plasma fractions was measured using a standard enzyme-linked immunosorbent assay (ELISA) that included specific anti-complement antibodies. Complement deposition on membranes was analyzed using immuno-dot blots and immunohistochemistry. Soluble SC5b-9 complement complex levels were increased in the plasma of women during term labor (TL; median 3361; range 1726-5670 ng/mL), preterm labor (PL; median 2958; range 1552-7092 ng/mL), and preterm premature rupture of membranes (PPROM; median 2272; range 167-6540 ng/mL) compared with pregnant women who were not in labor (P; median 1384; range 174-4570 ng/mL; P < 0.001, Kruskal-Wallis test). Active complement, as assessed by the C9 neo-antigen in C5b-9 complexes, was deposited on fetal membranes, with no difference between term and preterm delivery. The deposition of active complement on fetal membranes was confirmed by immunohistochemistry. Women who underwent non-labor-indicated Cesarean sections did not exhibit complement deposition. Soluble SC5b-9 complement complex levels increased in the plasma of women during parturition, and complement C5b-9 complexes were deposited on fetal membranes.

Anticapsular polysaccharide IgG concentrations in Mexican children formerly immunized with Haemophilus influenzae b PRP-T vaccine.

BACKGROUND: In 1999 H. influenzae b (Hib) PRP-T vaccine was introduced into primary immunization schedule in Mexico. There have been no studies evaluating antibody response after widespread immunization in our country. It is now recognized that Hib conjugates induce significant initial antibody levels that in some cases wane over time. This study relies on the measurement of IgG serum antibody concentrations to Hib capsular polysaccharide (PS) and is interpreted in the light of the accepted levels > or =0.15 microg/mL for short-term protection against Hib invasive disease and > or =5.0 microg/mL for protection against Hib oropharyngeal carriage. METHODS: Using a validated ELISA assay, we measured the IgG serum antibody concentrations in 115 children between 7 and 93 months of age who had received three doses of PRP-T. We used the standard reference serum US FDA 1983 for quantification of PS antibody levels. Concentrations were estimated using 3(rd) degree polynomial regression lines. As there was no unvaccinated group available (>95% of Mexican children have received the Hib vaccine), the study was designed as a cross-sectional. RESULTS: All children had serum IgG concentrations > or =0.15 microg/mL [range 0.24-54.64 microg/mL]; 69.6 % (80/115) had > or =1.0 microg/mL and 14 % (16/115) showed concentrations > or =5.0 microg/mL. The vaccine elicited geometric mean concentrations (GMC) of 4.0, 1.6, 1.4 and 2.4 microg/mL in groups of 7-12, 13-24, 25-48 and 49-93 month-old respectively. CONCLUSIONS: PRP-T vaccination in this group of Mexican children has resulted in serum IgG concentrations > or =0.15 microg/mL, suggesting that Hib immunization has conferred protection against invasive disease.

Dietary utilisation of protein and energy from fresh and ensiled coffee pulp by the Nile tilapia, Oreochromis niloticus

Dietary protein and energy utilisation of diets containing fresh and ensiled coffee pulp were studied on 3.2 ± 0.2 g Nile tilapia for 28 days. Diets formulation and feeding were designed on the basis of daily dietary protein and energy allowance. A control diet A (100 percent protein and 100 percent energy allowance) corresponding to 15 g CP kg-1 day-1 and 750 kJ kg-1 day-1, a low protein control diet B (80 percent protein and 100 percent energy allowance), two diets C and E (100 percent protein and 100 percent energy allowance) where 20 percent of protein were supplied by coffee pulp, and two diets D and F with the same amount of coffee pulp than in C and E and supplementation in non-protein energy. Inclusion of coffee pulp in the diet strongly impaired growth and feed utilisation. Silage process improved overall feed utilisation comparing to fresh coffee pulp. Results showed that fresh or ensiled coffee pulp was not a suitable feedstuff for Nile tilapia. However, better knowledge on modification occurring during silage process could allow finding the way to significantly improve nutritive value of coffee pulp by-products

Evidencia de actividad antimicrobiana del líquido folicular: estudio evaluatorio y analítico de muestras obtenidas en un programa de reproducción asistida / Evidence of antimicrobial activity of follicular fluid: evaluatory and analytical study of samples obtained in an assisted reproduction program

Ante la evidente ausencia de infección en pacientes a quienes se les realiza punción ovárica para captura ovular se evaluó la hipótesis de la posible acción antibacteriana que pudiera existir en el líquido folicular. Por lo anterior se tomaron 110 muestras de dicho fluido para análisis antibacteriano de las cuales fueron estudiadas 37, por ser las más claras y no contaminadas. Dichas muestras fueron obtenidas de pacientes hiperestimuladas que estaban a captura ovular a través de vagina por medio de guía ultrasonográfica. Se preparó inóculo bacteriana para evaluar la actividad antimicrobiana del líquido folicular contra cepas de E. coli, P. aeuroginosa, S. agalactie, L. monicitogenesis y C. albicans. Se efectuó recuento de colonias bacterianas a la 2,4,6,12 y 24 horas. El resumen de los resultados informa actividad bacteriostática en todas las cepas estudiadas de la cual E. coli y S. agalactie parecen ser las más sensibles. Seguidos por P. aeuroginosa S. aureus y L. monoatogenes: siendo más evidente, pero aún presente, en C. albicans. Por los resultados obtenidos se concluye que el líquido folicular tiene una acción antibacteriana, probablemente selectiva y que el mantenimiento en ésta línea de investigación corroborará este hallazgo y posiblemente determinará los factores implicados en el mismo

Nuevas alternativas en el tratamiento de la vaginosis bacteriana / New treatment alternatives in bacterial vaginosis

Se comparó la eficacia y seguridad de clindamicina crema vaginal al 2 por ciento con metronidazol oral en el tratamiento de 184 mujeres con vaginosis bacteriana sintomática en un estudio multicéntrico, aleatorio, doble-ciego, controlado. La duración del tratamiento fue de siete días, utilizando placebo en cápsulas en el grupo clindamicina y placebo crema en el grupo metronidazol. Las pacientes fueron observadas durante las visitas de seguimiento (4-13 y 20-43 días después de completar su terapia). El resultado global del tratamiento, indicó que clindamicina en crama vaginal ofrece una eficacia similar a la demostrada con metronidazol oral. Los porcentajes de curación/mejoría fueron 87 por ciento para el grupo de clindamicina y 79 por ciento para el grupo de metronidazol, sin diferencias significativas (p> 0.22). No se observaron recaídas en el grupo de clindamicina mientras que el grupo de metronidazol, se presentaron en 7 por ciento de los casos. El porcentaje de fracaso fue menor en el grupo de clindamicina (3 por ciento) que en el grupo que recibió metronidazol oral (15 por ciento). Ambos fármacos fueron bien tolerados. Los efectos secundarios más frecuentemente observados fueron irritación vulvovaginal y el desarrollo de vaginitis/cervicitis. El único efecto secundario clasificado como serio fue erupción cutánea generalizada en una paciente que recibió metronidazol. Se concluye que la clindamicina en crema vaginal al 2 por ciento es una alternativa eficaz y segura al metronidazol oral, para el tratamiento de la vaginosis bacteriana; siendo el tratamiento de elección para las mujeres durante el primer trimestre de la gestación

Determinación de glucosa como índice pronóstico de infección intraamniótica / Glucose determination as prognostic index of intraamniotic infection

La infección intraamniótica es un problema frecuente en Obstetricia, relacionándose con un importante impacto materno y fetal, destacando parto pretérmino y ruptura prematura de membranas. La prueba de "oro" para esta entidad es el cultivo bacteriológico (CB). Su uso se limita en función de tiempo (más de dos días) y disponibilidad. El diagnostico rápido de infección es vital para iniciar manejo antimicrobiano y evaluar evacuación uterina. Las concentraciones bajas de glucosa (G) se han utilizado como pronóstico de infección en diferentes compartimientos biológicos. El objetivo de este trabajo fue evaluar la utilidad de G como índice pronóstico de infección intraamniótica (IPIIA) comprado con tinción (TG) y CB. Sesenta y cuatro pacientes fueron incluidas. Grupo (n=33) con infección y grupo II (n=31 sin infección. El promedio de G para el grupo I fue 19.96 +- 7.61 ES y 114.48 +- 20.09. Es para el grupo II, con una p < 0.001. La sensibilidad (S), especificidad (E), valor predictivo positivo (VP+) y negativo (VP+) y negativo (VP-) para una concentración de G en líquido amniótico menor a 15 mg/di fue 72, 77, 77 y 72 por ciento respectivamente. La S, E, VP+VP- para G menor a 10 mg/mi fue de 69,87,85 y 73 por ciento. La tinción de gram observo una S, E, VP+ y VP- de 57, 83, 79, 65 por ciento. Si ambas determinaciones son conjuntadas (G y TG) se aprecia una S de 88 por ciento, E 77 por ciento, VP+80 Y VP-85 por ciento. Se incluye que 1) La determinación de glucosa en líquido amniótico es un método útil, de bajo costo y rápido para predecir infección intraaminiótica, 2) La más alta especificidad se observa con una concentración de 10 o < mg/di, 3) La G es más sensible y menos específica que la tinción de gram como IPIIA y 4) La evaluación conjunta de TG y G es confiable para identificar enfermas con infección intraaminióticas.