Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.

BACKGROUND: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. METHODS: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. RESULTS: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. CONCLUSIONS: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden.

Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine.

Our objective was to develop a multivalent prophylactic HPV vaccine that protects against infection and disease caused by HPV16/18 (oncogenic types in existing prophylactic vaccines) plus additional oncogenic types by conducting 3 Phase II studies comparing the immunogenicity (i.e., anti-HPV6/11/16/18 geometric mean titers [GMT]) and safety of 7 vaccine candidates with the licensed quadrivalent HPV6/11/16/18 vaccine (qHPV vaccine) in young women ages 16-26. In the first study (Study 1), subjects received one of 3 dose formulations of an 8-valent HPV6/11/16/18/31/45/52/58 vaccine or qHPV vaccine (control). In Study 2, subjects received one of 3 dose formulations (termed low-, mid-, and high-dose formulations, respectively) of a 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine (9vHPV vaccine) or qHPV vaccine (control). In Study 3, subjects concomitantly received qHPV vaccine plus 5-valent HPV31/33/45/52/58 or qHPV vaccine plus placebo (control). All vaccines were administered at day 1/month 2/month 6. In studies 1 and 3, anti-HPV6/11/16/18 GMTs at month 7 were non-inferior in the experimental arms compared with the control arm; however, there was a trend for lower antibody responses for all 4 HPV types. In Study 2, this immune interference was overcome with the mid- and high-dose formulations of the 9vHPV vaccine by increasing antigen and adjuvant doses. In all 3 studies, all vaccine candidates were strongly immunogenic with respect to HPV31/33/45/52/58 and were well tolerated. Based on the totality of the results, the middle dose formulation of the 9vHPV vaccine was selected for Phase III evaluation. Each 0.5mL dose contains 30µg/40µg/60µg/40µg/20µg/20µg/20µg/20µg/20µg of HPV6/11/16/18/31/33/45/52/58 virus-like particles, and 500µg of amorphous aluminum hydroxyphosphate sulfate adjuvant.ClinicalTrials.gov numbers NCT00260039, NCT00543543, and NCT00551187.

Diagnóstico de tuberculosis: desdelo tradicional hasta el desarrollo actual / Diagnosis of tuberculosis: from the traditional to the present development

Resumen: la tuberculosis es un problema de salud pública que afecta a millones de personas, siendo la cuarta causa de muerte por enfermedad infecciosa en el mundo. En su más reciente reporte, la Organización Mundial de la Salud (OMS) menciona que la infección tuberculosa es curable con un tratamiento adecuado; sin embargo, es una necesidad la detección precoz de casos y la mejora del diagnóstico como medida de control. En esta revisión se presenta una recopilación de los métodos de detección de tuberculosis desde los tradicionales hasta las nuevas alternativas en desarrollo. Como métodos convencionales de diagnóstico para la detección de la tuberculosis se han usado el examen directo con coloración de esputo y el cultivo para determinar la presencia de la micobacteria; estos métodos presentan desventajas importantes que afectan la sensibilidad y tiempo para el diagnóstico.Recientes avances en pruebas rápidas incluyen el desarrollo de técnicas moleculares e inmunoensayosque pueden detectar micobacterias resistentes a antibióticos y anticuerpos de la respuesta inmune del hospedero. Sin embargo, esta enfermedad no cuenta con una prueba de diagnóstico precisa que permita la detección y el diagnóstico rápido con la mínima pérdida de pacientes. Frente a estos retos, en la actualidad se encuentran en desarrollo nuevas pruebas basadas en biosensores mediante el uso de biomarcadores adecuados de la enfermedad.

Abstract: Tuberculosis is a public health problem that affects millions of people, being the fourth common cause of death due infectious disease in the world. In a recent report, the World Health Organization (WHO) argues that tuberculosis infection is curable with proper treatment; however its early detection and improved diagnosis tools are necessary for tuberculosis control. In this review, a compilation of methods for detecting tuberculosis from traditional to new developing alternatives are presented. As conventional diagnostic methods for detecting tuberculosis have been used direct sputumsmear and cell culture to establish the presence of mycobacteria; however, these methods have significant disadvantages which include sensitivity and time for diagnosis. Among recent advances in rapid tests are the development of molecular techniques and immunoassays to detect antibiotics mycobacteria resistance and antibodies from the host immune response. However, this disease does not have an accuracy diagnostic test that allows rapid detection and diagnosis with minimal loss of patients. Currently, to deal with these challenges, new tests based on biosensors are developing, using appropriate biomarkers of disease.

[Thin layer agar represents a cost-effective alternative for the rapid diagnosis of multi-drug resistant tuberculosis]. / Agar de capa delgada: Una opción costo-efectiva para el diagnóstico rápido de tuberculosis multirresistente.

OBJECTIVE: Using cost-benefit analysis for comparing the thin-layer agar culture method to the standard multiple proportion method used in diagnosing multidrug-resistant tuberculosis (MDR TB). METHODS: A cost-benefit evaluation of two diagnostic tests was made at the Corporación para Investigaciones Biológicas (CIB) in Medellín, Colombia. RESULTS: 100 patients were evaluated; 10.8% rifampicin resistance and 14.3% isoniazid resistance were found. A computer-based decision tree model was used for cost-effectiveness analysis (Treeage Pro); the thin-layer agar culture method was most cost-effective, having 100% sensitivity, specificity and predictive values for detecting rifampicin and isoniazid resistance. The multiple proportion method value was calculated as being US$ 71 having an average 49 day report time compared to US$ 18 and 14 days for the thin-layer agar culture method. DISCUSSION: New technologies have been developed for diagnosing tuberculosis which are apparently faster and more effective; their operating characteristics must be evaluated as must their effectiveness in terms of cost-benefit. The present study established that using thin-layer agar culture was cheaper, equally effective and could provide results more quickly than the traditional method. This implies that a patient could receive MDR TB treatment more quickly.

Agar de capa delgada: Una opción costo-efectiva para el diagnóstico rápido de tuberculosis multirresistente / Thin layer agar represents a cost-effective alternative for the rapid diagnosis of multi-drug resistant tuberculosis

Objetivo Realizar un análisis de costo efectividad comparando el método de cultivo en agar de capa delgada y el método estándar de proporciones múltiples, utilizados en el diagnóstico de Tuberculosis Multi-drogorresistente (TB MDR). Métodos Estudio de evaluación económica en el cual se evalúan los costos y la efectividad de dos pruebas diagnósticas, ejecutado en la Corporación para Investigaciones Biológicas-CIB en Medellín, Colombia. Resultados Se evaluaron 100 pacientes, encontrando una prevalencia de resistencia a la Rifampicina de 10,8 % y resistencia a Isoniazida de 14,3 %. Se presenta un análisis en términos de costo-efectividad mediante el diseño de un árbol de decisiones (Treeage Pro ®), resultando ser la prueba basada en cultivo en agar de capa delgada más costo-efectiva; con valores de sensibilidad, especificidad y predictivos del 100 % para detectar resistencia a Rifampicina e Isoniazida. El valor del método de las proporciones múltiples fue calculado en US$ 71, con una media de tiempo para ser reportado de 49 días versus US$ 18 y 14 días respectivamente para el cultivo en agar de capa delgada. Discusión Se han desarrollado nuevas tecnologías para el diagnóstico de Tuberculosis, aparentemente más rápidas y efectivas, que deben ser evaluadas no solo en sus características operativas, sino también en términos de costo-efectividad. El presente estudio establece que el empleo de la capa delgada es menos costoso, igualmente efectivo, y puede aportar resultados más rápidamente; cuando se compara con el método tradicional. Esto implica, entre otros aspectos, que el paciente pueda recibir más oportunamente el tratamiento dirigido para TB MDR.

Objective Using cost-benefit analysis for comparing the thin-layer agar culture method to the standard multiple proportion method used in diagnosing multidrug-resistant tuberculosis (MDR TB). Methods A cost-benefit evaluation of two diagnostic tests was made at the Corporación para Investigaciones Biológicas (CIB) in Medellín, Colombia. Results 100 patients were evaluated; 10.8 % rifampicin resistance and 14.3 % isoniazid resistance were found. A computer-based decision tree model was used for cost-effectiveness analysis (Treeage Pro); the thin-layer agar culture method was most cost-effective, having 100 % sensitivity, specificity and predictive values for detecting rifampicin and isoniazid resistance. The multiple proportion method value was calculated as being US$ 71 having an average 49 day report time compared to US$ 18 and 14 days for the thin-layer agar culture method. Discussion New technologies have been developed for diagnosing tuberculosis which are apparently faster and more effective; their operating characteristics must be evaluated as must their effectiveness in terms of cost-benefit. The present study established that using thin-layer agar culture was cheaper, equally effective and could provide results more quickly than the traditional method. This implies that a patient could receive MDR TB treatment more quickly.