Prediction of poor outcome in clostridioides difficile infection: A multicentre external validation of the toxin B amplification cycle

Producción CientíficaClassification of patients according to their risk of poor outcomes in Clostridioides difficile infection (CDI) would enable implementation of costly new treatment options in a subset of patients at higher risk of poor outcome. In a previous study, we found that low toxin B amplification cycle thresholds (Ct) were independently associated with poor outcome CDI. Our objective was to perform a multicentre external validation of a PCR-toxin B Ct as a marker of poor outcome CDI. We carried out a multicentre study (14 hospitals) in which the characteristics and outcome of patients with CDI were evaluated. A subanalysis of the results of the amplification curve of real-time PCR gene toxin B (XpertTM C. difficile) was performed. A total of 223 patients were included. The median age was 73.0 years, 50.2% were female, and the median Charlson index was 3.0. The comparison of poor outcome and non–poor outcome CDI episodes revealed, respectively, the following results: median age (years), 77.0 vs 72.0 (p = 0.009); patients from nursing homes, 24.4% vs 10.8% (p = 0.039); median leukocytes (cells/μl), 10,740.0 vs 8795.0 (p = 0.026); and median PCR-toxin B Ct, 23.3 vs 25.4 (p = 0.004). Multivariate analysis showed that a PCR-toxin B Ct cut-off <23.5 was significantly and independently associated with poor outcome CDI (p = 0.002; OR, 3.371; 95%CI, 1.565–7.264). This variable correctly classified 68.5% of patients. The use of this microbiological marker could facilitate early selection of patients who are at higher risk of poor outcome and are more likely to benefit from newer and more costly therapeutic options

Prevalence of high-risk HPV genotypes, categorised by their quadrivalent and nine-valent HPV vaccination coverage, and the genotype association with high-grade lesions

BACKGROUND: The new nine-valent vaccine against human papillomavirus (HPV) includes the four HPV genotypes (6, 11, 16, and 18) that are targeted by the older quadrivalent HPV vaccine, plus five additional oncogenic types (31, 33, 45, 52, and 58) remain significantly associated with high grade lesions. We aimed to determine the prevalence of high-risk HPV genotypes in unvaccinated subjects and the association of these genotypes with the incidence of high-grade lesions. We also assessed which, if either, of these two HPV vaccines could have prevented these cases. METHODS: This cross-sectional study, conducted from 4 January 2010 to 30 December 2011, was composed of 595 women attending the Hospital General Universitario de Elche (Spain) gynaecology department who were positively screened for opportunistic cervical cancer by pap smears and HPV detection during a routine gynaecological health check. The pap smear results were classified using the Bethesda system. HPV genotyping was performed with the Linear Array HPV genotyping test, and viruses were classified by the International Agency for Research on Cancer assessment of HPV carcinogenicity. Odds ratios (ORs) with their 95% confidence intervals (95% CI) were estimated by logistic regression, adjusting for age and immigrant status. The prevented fraction among those exposed (PFe-adjusted) was determined as a measure of impact. RESULTS: At least one of the additional five high-risk HPV genotypes present in the nine-valent HPV vaccine was detected in 20.5% of subjects. After excluding women with genotype 16 and/or 18 co-infection, high-risk genotypes (31, 33, 45, 52, and 58) were associated with a higher risk of intraepithelial lesion or malignancy: adjusted OR?=?3.51 (95% CI, 1.29-9.56), PFe-adjusted?=?0.72 (95% CI, 0.22-0.90). Genotypes that are still non-vaccine-targeted were detected in 17.98% of the women, but these were not significantly associated with high-grade lesions. CONCLUSION: The greater protection of the nine-valent HPV vaccine is likely to have a positive impact because, in the absence of genotype 16 or 18 infection, these five genotypes on their own remained significantly associated with high-grade lesions

Characterization of cervical infection by Human Papillomavirus. Application of new techniques of molecular microbiology in the study of infection by genotype 16

Introducción: La infección persistente por el Virus del Papiloma Humano (VPH) de alto riesgo genotipo 16 es el factor principal en el desarrollo de Cáncer de Cérvix (CC). La carga y el subtipo viral podrían modular esta asociación, por lo que resulta importante su detección y el establecimiento de su relación con lesiones precursoras de CC. Metodología: Estudio transversal en 595 mujeres con infección cervical por VPH, con diferentes grados de alteración citológica. De estas, se seleccionaron las mujeres con infección simple o múltiple por VPH 16 (n=176) para la determinación de la carga viral, mediante PCR en tiempo real y la variante viral por PCR anidada y posterior secuenciación. Mediante regresión logística no condicional, se estimaron Odds Ratios (OR) crudas y ajustadas junto con sus intervalos de confianza al 95% (IC95%) para evaluar la asociación entre la carga y variante virales y la existencia de lesiones cervicales. Resultados: VPH 16 y VPH 52 fueron los genotipos más prevalentes, presentes en el 30,08% y 14,29% de las mujeres con infección por el VPH. El genotipo 16 fue el genotipo asociado de forma más fuerte con el riesgo de lesión intraepitelial de alto grado (HSIL) o carcinoma: Odds Ratio ajustada (ORa) por edad e inmigración 12,02 (IC95% 4,92-29,39). La edad (por cada 10 años más) y el estatus inmigrante se asociaron de forma independiente con un aumento de 2,35 (IC95% 1,40-3,94) y 4,31 (IC95% 1,06-17,51) veces del riesgo de lesión de alto grado respectivamente. El hecho de tener una carga viral por encima de la mediana (>1367,79 copias/célula), se asoció de forma independiente con un aumento significativo del riesgo de lesión intraepitelial de alto grado o carcinoma tras ajustar por edad, estatus inmigrante, y variante viral: ORa=7,60 (IC95% 2,70-21,36); además esta asociación mostró un patrón dosis respuesta estadísticamente significativo al categorizar en base a los tertiles de la carga viral: ORa para una carga superior al tercer tertil=16,57 (IC95% 4,09-67,06), p de tendencia lineal ajustada <0,001. No se encontraron diferencias estadísticamente significativas en relación a la variante viral detectada o infección múltiple, aunque se observó una mayor frecuencia de infección múltiple en mujeres menores de 34 años. Conclusiones: La carga viral del VPH humano, específicamente la del genotipo 16, podría ser útil como biomarcador pronóstico de la infección. Este trabajo contribuye al entendimiento del efecto de la carga viral en la historia natural del CC; sin embargo, estudios prospectivos son necesarios para confirmar estos resultados