Browsing by Autor "Fernando Gil"

Now showing 1 - 3 of 3

Clostridioides difficile major toxins remodel the intestinal epithelia, affecting spore adherence/internalization into intestinal tissue and their association with gut vitronectin
(2025) Pablo Castro-Córdova; Osiris K. Lopez-Garcia; Juan Camilo Orozco; Nicolás Montes-Bravo; Fernando Gil; Marjorie Pizarro‐Guajardo; Daniel Paredes‐Sabja
The most common cause of healthcare-associated diarrhea and colitis in the U.S., is Clostridioides difficile, a spore-forming pathogen. Two toxins, TcdA and TcdB, are major virulence factors essential for disease manifestations, while C. difficile spores are essential for disease transmission and recurrence. Both toxins cause major damage to the epithelial barrier, trigger massive inflammation, and reshape the microbiome and metabolic composition, facilitating C. difficile colonization. C. difficile spores, essential for transmission and recurrence of the disease, persist adhered and internalized in the intestinal epithelia. Studies have suggested that toxin-neutralization in combination with antibiotic during CDI treatment in humans significantly reduces disease recurrence, suggesting a link between toxin-mediated damage and spore persistence. Here, we show that TcdA/TcdB-intoxication of intestinal epithelial Caco-2 cells leads to remodeling of accessible levels of fibronectin (Fn) and vitronectin (Vn) and their cognate alpha-integrin subunits. While TcdB-intoxication of intestinal tissue had no impact in accessible levels of Fn and Vn, but significantly increased levels of intracellular Vn. We observed that Fn and Vn released to the supernatant readily bind to C. difficile spores in vitro, while TcdB-intoxication of intestinal tissue led to increased association of C. difficile spores with gut Vn. Toxin-intoxication of the intestinal tissue also contributes to increased adherence and internalization of C. difficile spores. However, TcdB-intoxicated ligated loops infected of mice treated with Bezlotoxumanb (monoclonal anti-TcdB antibodies) did not prevent TcdB-mediated increased spore adherence and internalization into intestinal tissue. This study highlights the importance of studying the impact of C. difficile toxins of host tissues has in C. difficile interaction with host surfaces that may contribute to increased persistence and disease recurrence.
Interruption of Indigenous Measles Transmission in Bolivia since October 2000
(Oxford University Press, 2003) Rosario Quiroga; Oswaldo Barrezueta; Linda Venczel; Percy Halkyer; Fernando Gil; Eric Machicao; Mauricio Landaverde; Arturo Quiñonez; Héctor S. Izurieta
Measles incidence in Bolivia declined after the introduction of campaign strategies in the 1980s. From 1990 to 1993, the peak incidence of measles (59 cases/100,000 population) was in 1992. In 1994, after the goal of interruption of measles transmission was adopted, a national vaccination campaign targeting children <15 years old was conducted and achieved 96% coverage. During 1995-1997, cases declined, although routine coverage was <90% in most years. During 1998-2000, a nationwide epidemic occurred among 2567 case-patients, most of whom were unvaccinated. A national vaccination campaign, with strong supervision, was conducted during November and December 1999 and targeted areas with low coverage. Only 122 cases were confirmed in 2000, with the last confirmed case occurring in October. Crucial to the control of the outbreak were sufficient resources and political support, intensive local planning, door-to-door vaccination with strict supervision, and rapid house-to-house coverage monitoring that improved accountability at the local level and timely and thorough outbreak investigations.
Prevalence of measles antibody among children under 15 years of age in Santa Cruz, Bolivia: implications for vaccination strategies
(Oxford University Press, 1995) Felicity T. Cutts; Alessandro Bartoloni; P Guglielmetti; Fernando Gil; David Brown; M. L. Bianchi Bandinelli; Mimmo Roselli
We conducted a community-based survey in Santa Cruz city, Bolivia, to determine the age-specific prevalence of measles antibodies, determine factors associated with absence of detectable measles antibodies, and to compare results of salivary and serum measles immunoglobulin G (IgG) antibody assays. Serum samples from 1654 children were assayed for measles IgG antibody using the haemagglutination inhibition (HI) assay, and salivary samples were also obtained from 187 children and tested for measles IgG antibody using an antibody capture radioimmunoassay. Reported measles vaccine coverage in children aged 12-35 months was 77% (95% confidence interval [CI], 72-81%). Eighty-seven percent (95% CI 85-89%) had detectable HI antibody, but a high proportion had antibody levels below 200 miu (30-40% of 2-14 years old children). Measles seronegativity was associated with not being vaccinated against measles, a negative history of measles disease, living in the inner city, being a lifetime resident of Santa Cruz, and young age. Of 212 children without detectable measles antibody, 58% had a positive history of vaccination or measles disease, so that historical information was not sufficiently reliable to identify susceptibles. The salivary measles antibody assay was not sufficiently sensitive to be used for population screening; only 54% of 171 salivary samples from children who had detectable serum HI antibody were positive. A mass measles vaccination campaign of all children under 15 years of age is planned in Bolivia in 1994. Although only 7% of school-age children in Santa Cruz were seronegative, the effectiveness of a mass campaign in this age group depends in part on the response to revaccination of children with low, but detectable, antibody levels.