Evaluation of the immunogenicity of the quadrivalent HPV vaccine using 2 versus 3 doses at month 21: An epidemiological surveillance mechanism for alternate vaccination schemes.

The cost of HPV vaccines and the need for 3 doses remains a barrier for their inclusion in routine vaccination schedules for girls in low and middle income countries. In a non-inferiority study, we aimed to compare the immunogenicity of a standard 3 doses and a 2 doses schedule. We enrolled 450 participants in an open-label non-randomized clinical trial to evaluate the immunogenicity induced at different ages by the licensed HPV6/11/16/18 quadrivalent vaccine in a 2 doses schedule (0-6 months, n = 150 girls aged 9-10 y) and 3 doses schedule (0, 2, and 6 months; n = 150 girls aged 9-10 y and n=150 women aged 18 to 24 years). To assess the antibody response, blood samples were obtained at Month 7 and 21 after the first vaccination from participants in all study groups. cLIA testing was performed at Merck Research Laboratories. Antibody levels were expressed as milli-Merck units (mMU) per ml. Primary outcome was non-inferiority (95% CI, lower bound >0.5) of the geometric mean titers (GMT) ratios for HPV6, HPV11, HPV16 and HPV18 antibodies 7 and 21 months after the first dose among girls receiving 2 doses compared with young women and girls receiving 3 doses. All vaccinees were seropositive for both HPV16 and HPV18 antibodies at month 7. At month 21, 98.5 and 56.6% of women 18-24 y old were seropositive for HPV16 and 18, respectively. For girls in the three doses group, seropositivity rates were 99.3 and 86.3% for HPV16 and 18, respectively. For girls in the two doses group rates were 99.3 and 70.2% for HPV16 and 18, respectively. The two doses schedule was non-inferior compared to the 3 doses schedule in same-age girls and to the group of adult women after 21 months of the first vaccine dose. Our results are in agreement with similar trials evaluating the immune response of a 2 doses schedule of both HPV vaccines, supporting the recent WHO recommendation as well as the Mexican policy to incorporate the 2 doses schedule for girls aged 9-11 y.

Inside the outbreak of the 2009 influenza A (H1N1)v virus in Mexico.

BACKGROUND: Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1)v which occurred in Mexico City as well as the spread of the virus throughout the entire country. METHODOLOGY AND FINDINGS: From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at 220 outpatient clinics and 28 hospitals distributed throughout Mexico City. Analysis of samples using real time RT-PCR revealed that 202 patients out of the 751 subjects (26.9%) were confirmed to be infected with the new virus. All confirmed cases of human infection with the strain influenza (H1N1)v suffered respiratory symptoms. The greatest number of confirmed cases during the outbreak of the 2009 influenza A (H1N1)v were seen in neighbourhoods on the northeast side of Mexico City including Iztapalapa, Gustavo A. Madero, Iztacalco, and Tlahuac which are the most populated areas in Mexico City. Using these data, together with data reported by the Mexican Secretariat of Health (MSH) to date, we plot the course of influenza (H1N1)v activity throughout Mexico. CONCLUSIONS: Our data, which is backed up by MSH data, show that the greatest numbers of the 2009 influenza A (H1N1) cases were seen in the most populated areas. We speculate on conditions in Mexico which may have sparked this flu pandemic, the first in 41 years. We accept the hypothesis that high population density and a mass gathering which took in Iztapalapa contributed to the rapid spread of the disease which developed in three peaks of activity throughout the Country.

Identification of influenza A pandemic (H1N1) 2009 variants during the first 2009 influenza outbreak in Mexico City.

BACKGROUND: In March 2009, public health surveillance detected increased numbers of influenza-like illness presenting to hospitals in Mexico City. The aetiological agent was subsequently determined to be a novel influenza A (H1N1) triple reassortant, which has spread worldwide. As a consequence the World Health Organisation has declared the first Influenza pandemic of the 21st century. OBJECTIVES: To describe clinically and molecularly the first outbreak of influenza A pH1N1 (2009) during 1-5 May to establish a baseline of epidemiological data for pH1N1. Also, to monitor for the emergence of antiviral resistance, and mutations affecting virulence and transmissibility. STUDY DESIGN: Samples were collected from 751 patients with influenza-like symptoms throughout Mexico City and were tested for influenza A pH1N1 (2009) using real-time PCR. In the samples that were positive for influenza A pH1N1 (2009) fragments from the haemagglutinin (H1) and neuraminidase (N1) genes were sequenced. RESULTS: A total of 203/751 (27%) patients were positive for the pandemic H1N1 (2009) virus (53% male and 47% female). The 0-12-year-old group was the most affected 85/751 (42%). Sequence analysis showed five new variants of the pandemic H1N1 (2009) virus for NA: G249E (GQ292900), M269I (GQ292892), Y274H (GQ292913), T332A (GQ292933), N344K (GQ292882), and four variants for HA: N461K (GQ293006), K505R (GQ292989), I435V (GQ292995), I527N (GQ292997). CONCLUSIONS: We have provided a baseline of epidemiological data from the first outbreak of influenza A pH1N1 (2009) during 1-5 May in Mexico City. The sequencing of partial fragments of the HA and NA genes did not show the presence of previously described mutations affecting known sites of antiviral resistance in seasonal influenza A such as the H275Y (oseltamivir resistance), R293 or N295 etc.