Public health and budget impacts of switching from a trivalent to a quadrivalent inactivated influenza vaccine in Paraguay.

This study aimed to investigate the public health and economic benefit of using a quadrivalent influenza vaccine (QIV) instead of a trivalent influenza vaccine (TIV) in past seasons in Paraguay. The budget impact of switching from TIV to QIV in the Immunization Program was also evaluated. The adapted model includes two modules. The first compared retrospectively Health and Economic outcomes resulting from the use of QIV instead of TIV. The second forecast the spending and savings that would be associated with the switch from TIV to QIV. Our findings estimate that the switch from TIV to QIV during the seasons 2012 to 2017 could have prevented around 2,600 influenza cases, 67 hospitalizations and 10 deaths. An alternative scenario using standardized estimates of the burden of influenza showed that 234 influenza-related hospitalizations and 29 deaths could have been prevented. The estimated annual budget impact of a full switch from TIV to QIV was around USD1,6 million both from the payer and societal perspectives. Those results are mainly driven by vaccine prices and coverage rate. In sum, this manuscript describes how the use of QIV instead of TIV could have prevented influenza cases and subsequent complications that led to hospitalizations and deaths. This could have generated savings for the health system and society, offsetting part of the additional investment needed to switch from TIV to QIV.

Switching from trivalent to quadrivalent inactivated influenza vaccines in Uruguay: a cost-effectiveness analysis.

We evaluated the cost-utility of replacing trivalent influenza vaccine (TIV) with quadrivalent influenza vaccine (QIV) in the current target populations in Uruguay. An existing decision-analytic static cost-effectiveness model was adapted for Uruguay. The population was stratified into age groups. Costs and outcomes were estimated for an average influenza season, based on observed rates from 2013 to 2019 inclusive. Introducing QIV instead of TIV in Uruguay would avoid around 740 additional influenza cases, 500 GP consultations, 15 hospitalizations, and three deaths, and save around 300 workdays, for the same vaccination coverage during an average influenza season. Most of the influenza-related consultations and hospitalizations would be avoided among children ≤4 and adults ≥65 years of age. Using QIV rather than TIV would cost an additional ~US$729,000, but this would be partially offset by savings in consultations and hospitalization costs. The incremental cost per quality-adjusted life-year (QALY) gained with QIV would be in the order of US$18,000 for both the payor and societal perspectives, for all age groups, and around US$12,000 for adults ≥65 years of age. The main drivers influencing the incremental cost-effectiveness ratio were the vaccine efficacy against the B strains and the percentage of match each season with the B strain included in TIV. Probabilistic sensitivity analysis showed that switching to QIV would provide a favorable cost-utility ratio for 50% of simulations at a willingness-to-pay per QALY of US$20,000. A switch to QIV is expected to be cost-effective for the current target populations in Uruguay, particularly for older adults.

Associations of human papillomavirus (HPV) genotypes and related risk factors in a cohort of women living with HIV in a Brazilian countryside city.

The human papillomavirus (HPV) is associated with cervical abnormalities. People living with HIV are more susceptible to HPV. Campos dos Goytacazes implemented the quadrivalent HPV vaccine (4vHPV) for women living with HIV (WLWH) in 2011, 4 years before the Brazilian public vaccination program. We aimed to characterize the genomic diversity and predictors of HPV infection in WLWH through a prospective cohort study. After the consent form was received, a questionnaire was applied and an endocervical sample was collected. For genotyping, a microarray HPV technique was performed. Two intervention moments were performed: T1, the initial moment, with collection and vaccination; T2 moment, 2 years after T1. Univariate and multivariate analyses were performed. The T1 moment cohort was formed by 146 women,107 belonging to Group 1(HPV-negative) and 39 to Group 2 (HPV-positive). The variables age, marital status, number of children, number of sexual partners, and CD4 count were protective against HPV. The variables number of sexual partners, marital status, and the number of children lost significance in multivariate analysis. Concerning T2 moment, 42 patients were followed with three positive cases. The use of 4vHPV is beneficial for this population and should also be recommended at an age from 26 to 45 years inside the public vaccination program.

Cost-effectiveness analysis of switching from a trivalent to a quadrivalent inactivated influenza vaccine in the Peruvian immunisation programme.

BACKGROUND: Seasonal influenza is an acute respiratory infection mostly caused by type A and B influenza viruses. The severe form of the infection can be life-threatening and lead to a significant burden. Vaccination is the most efficient way of preventing influenza infections and limit this burden. OBJECTIVES: To assess the cost-effectiveness of switching from a trivalent influenza vaccine (TIV) to a quadrivalent influenza vaccine (QIV) in the vaccination programme in Peru, and to evaluate the health and economic impact of reaching the vaccination coverage rate targeted by the Ministry of Health. METHODS: A decision-analytic static cost-effectiveness model, was adapted to the Peruvian setting under both payer and societal perspectives. RESULTS: A switch from TIV to QIV would prevent 29,126 additional cases (including 12,815 consultations), 54 hospitalisations, and 23 deaths related to influenza, mostly in the population <2 years-old and >60 years-old. This would lead to a saving of US $505,206 under the payer perspective, that would partially offset the investment necessary to introduce QIV into the immunisation programme. The resulting incremental cost-effectiveness ratio (ICER) is $16,649 per QALYs gained. The main drivers of the model results were vaccine efficacy against influenza B viruses, degree of match, vaccines prices and proportion of cases attributable to influenza B. The robustness of the results seems satisfactory as QIV has the probability of being a cost-effective strategy of 83.8% (considering a threshold of three GDP per capita). Reaching the coverage targeted by the Ministry of Health would result in health benefits and disease management savings, and lower ICERs. CONCLUSION: Introducing QIV instead of TIV in the Peruvian immunisation programme is expected to be a cost-effective strategy, especially in younger children and the elderly. The benefit of QIV would be even more important if the coverage targeted by the Ministry of Health would be reached in the most vulnerable groups.

Cost-Effectiveness Analysis of Switching from Trivalent to Quadrivalent Seasonal Influenza Vaccine in Argentina.

The burden of seasonal influenza disease in Argentina is considerable. The cost-effectiveness of trivalent (TIV) versus quadrivalent influenza vaccine (QIV) in Argentina was assessed. An age-stratified, static, decision-tree model compared the costs and benefits of vaccination for an average influenza season. Main outcomes included: numbers of influenza cases; general practitioner (GP) visits; complicated ambulatory cases; hospitalizations; deaths averted; and costs per quality-adjusted life years (QALYs) gained. Epidemiological data from Argentina for 2014-2019 were used to determine the proportion of A and B strain cases, and the frequency of mismatch between vaccine and circulating B strains. To manage uncertainty, one-way and probabilistic sensitivity analyses were performed. Switching from TIV to QIV would prevent 19,128 influenza cases, 16,164 GP visits, 2440 complicated ambulatory cases, 524 hospitalizations, and 82 deaths. Incremental cost-effectiveness ratios (ICERs) per QALY were 13,590 and 11,678 USD from the payer's and societal perspectives, respectively. The greatest health benefits and direct medical cost savings would occur in ≥ 65-year-olds. One-way sensitivity analyses demonstrated the principal drivers of ICER to be vaccine acquisition costs, environmental B strain predominance, and B strain mismatch. Introducing QIV in Argentina would be beneficial and cost-effective relative to TIV, particularly in older adults.

Treatment Following Erythema Multiforme in the Oral Mucosa After qHPV Vaccine with Low-Level Laser Therapy: case Report / Tratamiento del Eritema Multiforme en la Mucosa Oral Después de la Vacuna Contra el qHPV con Terapia con Láser de Baja Potencia: reporte de un Caso

Erythema multiforme (EM) is a mucocutaneous condition of uncertain etiology, although the hypersensitivity reaction to a wide variety of agents may be related to the onset of the lesions. In about half of the affected patients it is possible to identify a previous infection. This article aims to report a case of EM in the oralmucosa after qHPV vaccine (Gardasil®), to highlight the diagnostic process and the proposed treatment. Female patient, 16 years old, after 10 days of receiving the first dose of the qHPV vaccine. On physical examination, she presented multiple ulcers and hemorrhagic crusts to the touch, based on the clinical picture and the history of the disease, a diagnostic hypothesis was EM. Low-level laser therapy (LLLT) was chosen as an alternative treatment, since the exercises applied were not successful. The patient was followed up, reported decreased pain and burn and, after one year of treatment, there was no recurrence of the lesions. Laser treatment showed an effective treatment alternative, in addition to the low cost and ease of application.

El eritema multiforme (EM) es una afección mucocutánea de etiología incierta, aunque la reacción de hipersensibilidad a una amplia variedad de agentes puede estar relacionada con la aparición de las lesiones. En aproximadamente la mitad de los pacientes afectados es posible identificar una infección previa. Este artículo tiene como objetivo informar un caso de EM en la mucosa oral después de la vacuna qHPV (Gardasil®), para resaltar el proceso de diagnóstico y el tratamiento propuesto. Paciente de 16 años, después de 10 días de recibir la primera dosis de la vacuna qHPV. En el examen físico, presentó múltiples úlceras y costras hemorrágicas al tacto, según el cuadro clínico y la historia de la enfermedad, una hipótesis diagnóstica fue EM. La terapia con láser de baja potencia (TLBP) se eligió como un tratamiento alternativo, ya que los ejercicios aplicados no tuvieron éxito. La paciente fue seguida, informó disminución del dolor y las quemaduras y, después de un año de tratamiento, no hubo recurrencia de las lesiones. El tratamiento con láser mostró una alternativa de tratamiento efectivo, además del bajo costo y la facilidad de aplicación.

Human papillomavirus prevalence, genomic diversity and related risk factors in HIV-positive women from a countryside city in the state of Rio de Janeiro.

Human papillomavirus (HPV) can cause genital warts and HPV-related cancer.People living with human immunodeficiency virus (HIV)are more symptomatic for HPV infections.Campos dos Goytacazes,a municipality of Rio de Janeiro,introduced the quadrivalent HPV vaccine (4vHPV)for HIV-positive women four years before initiation of a public vaccination program.This study analyzed the prevalence of HPV infection in HIV-positive women and the variables associated with infectionTwo groups were evaluated:group 1,with Pap smear and HPV-negative polymerase chain reaction (PCR);group 2, individuals with at least one positive result for HPV in PCR or pap smear.PCR was performed in endocervical samples using generic primers, and the LCD-Array Kit was used for genotyping.Univariate and multivariate analyzes were performed.Results in 109 women (Group 1 n = 70; group 2 n = 39)showed an overall HPV prevalence of 36%.Results also showed that 88% (n = 23) and 96% (n = 25)of typed viruses (total of typed viruses n = 26)were included in 4vHPV and 9vHPV (nonavalent HPV),respectively.In univariate analysis,age less than 45 years, a high number of sexual partners,and HIV-viral load were risk factors for infection.However, a CD4 indicator was associated with protection.Although HIV infection is generally related to multiple and rare types of HPV,this study showed that a vast majority of the HPV types found are included in 4vHPV.Considering that age less than 45 years is a risk factor, the use of 4vHPV in Brazil should be extended in the public vaccination program to HIV seropositive women up to age 45 years.

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in patients with juvenile dermatomyositis: a real-world multicentre study.

BACKGROUND: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients. METHODS: JDM patients aged from 9 to 20 years and healthy controls (HC) were enrolled to receive a 3-dose schedule of qHPV vaccine from March/2014 to March/2016. Study visits were performed before the first dose, 1 month after the second and third doses, and 6 months after the third dose. Participants completed a diary of possible adverse events for 14 days following each dose of vaccination (AEFV). Disease activity and current therapy were analyzed at each visit for JDM patients. In addition, serum samples from all participants were collected to test antibody concentrations against HPV16 and 18 at each visit. Participant recruitment was conducted in ten Brazilian centres. From 47 eligible JDM patients and 41 HC, 42 and 35, respectively, completed the 3-dose schedule of the vaccine, given that five JDM patients and two HC had received doses prior to their inclusion in the study. RESULTS: The AEFVs presented by the participants were mild and in general did not differ between JDM and HC groups. No severe AEFVs were related to the vaccination. Disease activity was stable, or even improved during the follow-up. One month after the third dose of the vaccine the JDM group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the HC group, who presented 100% for both serotypes (p = 1.000). Six months after the third dose the seropositivity for the patient group was 94% for both HPV types. CONCLUSIONS: The HPV vaccination in this cohort of JDM patients was safe and immunogenic. Since the seropositivity against HPV16 and 18 was very high after the 3-dose schedule, this regimen should be recommended for JDM patients. TRIAL REGISTRATION: Brazilian Clinical Trials Registry, number: RBR-9ypbtf . Registered 20 March 2018 - Retrospectively registered.

Impact of quadrivalent influenza vaccines in Brazil: a cost-effectiveness analysis using an influenza transmission model.

BACKGROUND: Influenza epidemics significantly weight on the Brazilian healthcare system and its society. Public health authorities have progressively expanded recommendations for vaccination against influenza, particularly to the pediatric population. However, the potential mismatch between the trivalent influenza vaccine (TIV) strains and those circulating during the season remains an issue. Quadrivalent vaccines improves vaccines effectiveness by preventing any potential mismatch on influenza B lineages. METHODS: We evaluate the public health and economic benefits of the switch from TIV to QIV for the pediatric influenza recommendation (6mo-5yo) by using a dynamic epidemiological model able to consider the indirect impact of vaccination. Results of the epidemiological model are then imputed in a health-economic model adapted to the Brazilian context. We perform deterministic and probabilistic sensitivity analysis to account for both epidemiological and economical sources of uncertainty. RESULTS: Our results show that switching from TIV to QIV in the Brazilian pediatric population would prevent 406,600 symptomatic cases, 11,300 hospitalizations and almost 400 deaths by influenza season. This strategy would save 3400 life-years yearly for an incremental direct cost of R$169 million per year, down to R$86 million from a societal perspective. Incremental cost-effectiveness ratios for the switch would be R$49,700 per life-year saved and R$26,800 per quality-adjusted life-year gained from a public payer perspective, and even more cost-effective from a societal perspective. Our results are qualitatively similar in our sensitivity analysis. CONCLUSIONS: Our analysis shows that switching from TIV to QIV to protect children aged 6mo to 5yo in the Brazilian influenza epidemiological context could have a strong public health impact and represent a cost-effective strategy from a public payer perspective, and a highly cost-effective one from a societal perspective.

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.

Immunogenicity and safety of MenACWY-TT, a meningococcal conjugate vaccine, co-administered with routine childhood vaccine in healthy infants: A phase III, randomized study.

BACKGROUND: Invasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants. METHODS: In this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15-18 months; group ACWY3+1); 1+1 (at 6 and 15-18 months; group ACWY1+1) or single-dose at 15-18 months (group ACWY1). All infants received PHiD-CV and DTPa-IPV/Hib at ages 2, 4, 6, 15-18 months. Immune responses to MenACWY-TT were assessed by rSBA and hSBA at 7 months (groups ACWY3+1, ACWY1+1) and pre- and post-vaccination at 15-18 months of age (all groups). Immune responses to co-administered vaccines, reactogenicity and safety were also evaluated. RESULTS: Immunogenicity of MenACWY-TT at 1 month post-primary vaccination was demonstrated in group ACWY3+1: the lower limit of the 95% confidence interval for the percentage of infants with rSBA titers ≥8 was >80% for each serogroup. At 7 months of age, ≥93.9% of MenACWY-TT-primed infants had rSBA titers ≥8. Post-MenACWY-TT vaccination at age 15-18 months, ≥96.3% of participants in all groups had rSBA titers ≥8, regardless of the number of doses received previously. The percentage of infants with hSBA titers ≥4 were ≥87.2% and ≥89.7% at post-primary and booster/single-dose vaccination, respectively. Immune responses to PHiD-CV and DTPa-IPV/Hib did not seem impacted by co-administration with MenACWY-TT in infancy. The incidence of all adverse events was similar among groups. Serious adverse events were reported for 63/750 children in all groups; none were considered vaccine-related by investigators. CONCLUSION: Primary vaccination with 3 or 1 dose(s) of MenACWY-TT when co-administered with routine pediatric vaccines in infants is immunogenic and well-tolerated.

HPV vacina: conhecer e aceitar para assegurar a eficácia / HPV vaccine: knowledge and acceptance to ensure effectiveness

The new Vaccine technologies against transmissible and non-transmissible diseases, such as cancer, have had an impact on international public health. The human papillomavirus (HPV) vaccine is used on a large scale in immunization programs in more than 58 countries, with resultant efficacy and safety for precursor lesions of cervical cancer, in addition to anogenital lesions. After the introduction of quadrivalent HPV vaccine (6,11,16 and 18) in Brazil in 2014, monitoring the vaccination coverage and the development of HPV prevalence incidence of cervical abnormalities and precancerous lesions must be observed, as well as morbidity and mortality trends from in situ and invasive cancer. Encouraging information, counseling and continuing education is recommended as a strategy to broaden vaccine acceptance in order to sediment its implementation and ensure effectiveness in reducing new cases of cervical cancer in the future.

As novas tecnologias em vacina contra doenças transmissíveis e não transmissíveis como o câncer, tiveram impacto na saúde pública internacional, especificamente a vacina para o papiloma vírus humano (HPV) utilizada em larga escala nos programas de imunização em mais de 58 países, com resultados de eficácia e segurança para lesões precursoras do câncer de colo do útero além de lesões anogenitais. Após a introdução em território Nacional da vacina quadrivalente para o HPV (6,11,16 e 18) desde 2014, ressalta-se a importância do monitoramento da cobertura vacinal e o desenvolvimento de estudos de prevalência de HPV em logo prazo, de incidência de anormalidades cervicais e lesões pré-cancerosas bem como de tendência de morbimortalidade por câncer in situ e invasivo. O incentivo às informações, aconselhamento e educação continuada é recomendado como uma estratégia para ampliar a aceitação da vacina a fim de sedimentar sua implantação e assegurar a eficácia na redução dos novos casos de câncer de colo do útero para o futuro.

Conocimientos sobre el virus del papiloma humano y su vacuna en padres de familia de Rivera, Huila en el 2015 / Knowledge of human papillomavirus and its vaccine in parents of Rivera, Huila in 2015

RESUMEN Introducción: la vacuna contra el virus del papiloma humano es la medida preventiva más reciente y controversial para el cáncer de cuello uterino. En 2014 Colombia tuvo una serie de supuestas reacciones adversas ante la vacuna que provocó la caída de su cobertura. Objetivo: describir los conocimientos frente al virus del papiloma humano y su vacuna en los padres de Rivera, Huila. Materiales y método: estudio transversal con muestra por conveniencia de 124 padres de niños menores de 18 años, a través de una encuesta sociodemográfica donde fue medido el conocimiento acerca del virus, su vacuna y el cáncer de cérvix. Análisis cuantitativo por medio de la técnica de frecuencias simples. Resultados: el nivel de conocimiento fue bajo (44,35%); el 43,54% identifican al virus del papiloma humano como agente etiológico del cáncer de cuello uterino; sólo el 7,4% considera útil la vacuna como método preventivo y la vacuna fue aceptada por el 87% de los padres. Conclusiones: El conocimiento del virus del papiloma humano y el cáncer de cuello uterino es bajo y se ve afectado por el desconocimiento de las diferentes estrategias preventivas del cáncer de cuello uterino, así como por la falta de información sobre la acción de la vacuna contra el virus. Sin embargo, la aceptabilidad de la vacuna es alta. MÉD.UIS. 2017;30(1):13-9.

ABSTRACT Introduction: Human Papillomavirus Vaccine is the most recent and controversial step for cervical cancer prevention. During 2014, in Colombia, a series of suspected adverse reactions to the vaccine caused a decline in its coverage. Objective: the aim of this study is to describe the knowledge about Human Papillomavirus and its vaccine from parents of Rivera, Huila. Materials and method: cross-sectional study with a convenient sample of 124 parents whose children were under 18 years old; through a socio-demographic questionnaire, knowledge about issues related to the virus, related to cervical cancer and its vaccine was measured. A quantitative analysis was performed by simple frequency analysis. Results: the level of knowlodge was low (44,35%); 43,54% of the parents identify Human Papillomavirus as an etiological cervical cancer agent, just 7,4% of the parents consider the vaccine as an useful preventive method and the vaccine was accepted by 87% of the parents. Conclusions: the knowledge level of the parents of Rivera, Huila about Human Papillomavirus and cervical cancer is low and it is affected by the ignorance of the different cervical cancer preventive strategies, as well as the lack of information of the action of Human Papillomavirus vaccine. However, the vaccine acceptability is high. MÉD.UIS. 2017;30(1):13-9.

Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil

Abstract The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines.In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18–60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed.A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults.The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Public health impact and economic benefits of quadrivalent influenza vaccine in Latin America.

Annual trivalent influenza vaccines (TIV) containing 2 A strains and one B lineage have been recommended for the prevention of influenza in most of Latin American countries. However, the circulation of 2 B lineages (Victoria and Yamagata) and difficulties in predicting the predominating lineage have led to the development of quadrivalent influenza vaccines (QIV), including both B lineages. Thus, the objective was to estimate the public health impact and influenza-related costs if QIV would have been used instead of TIV in 3 Latin American countries. We used a static model over the seasons 2010-2014 in Brazil, 2007-2014 in Colombia and 2006-2014 in Panama, focusing on population groups targeted by local vaccination recommendations: young children, adults with risk factors and the elderly. In Brazil, between 2010 and 2014, using QIV instead of TIV would have avoided US$ 6,200 per 100,000 person-years in societal costs, based on 168 influenza cases, 89 consultations, 3.2 hospitalizations and 0.38 deaths per 100,000 person-years. In Colombia and Panama, these would have ranged from US$ 1,000 to 12,700 (based on 34 cases, 13-25 consultations, 0.6-8.9 hospitalizations and 0.04-1.74 deaths) and from US$ 3,000 to 33,700 (based on 113 cases, 55-82 consultations, 0.5-27.8 hospitalizations and 0.08-6.87 deaths) per 100,000 person-years, respectively. Overall, the broader protection offered by QIV would have reduced the influenza humanistic and economic burden in the 3 countries. Despite the lack of local data leading to several extrapolations, this study is the first to give quantitative estimates of the potential benefits of QIV in Latin America.

Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil.

The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines. In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18-60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed. A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults. The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Impacto precoce na redução de anormalidades cervicais em campos dos goytacazes, rj, brasil, depois da introdução de vacina quadrivalente de hpv em meninas de 11 a 15 anos: é hora de pensar em vacinas hpv para rapazes? / Early impact in reducing cervical abnormalities in campos dos goytacazes, rj, brazil, after introduction of the quadrivalent hpv vaccine for girls 11­15: is it time to think about hpv vaccine in boys?

O papilomavírus humano (HPV) é uma grande preocupação na saúde pública e privada. A prevenção dessa condição é a combinação do uso do exame de Papanicolaou, de preservativos e de vacinas contra o HPV. Campos dos Goytacazes é o primeiro município brasileiro a implementar em setembro de 2010 a vacina quadrivalente contra o HPV (Gardasil®) para meninas de 11 a 15 anos de idade em uma estratégia híbrida de vacinação (escolas e centros de saúde). Em 2014, a vacinação começou para os meninos na mesma época em que o Ministério da Saúde introduziu a vacina para as meninas. Objetivo: O objetivo do estudo foi analisar as tendências na redução de anormalidades cervicais de baixo grau cinco anos depois da introdução da vacina quadrivalente de HPV na cidade (resultado primário). Além disso, esta investigação avaliou o risco relativo de cada grupo analisado, de maneira a explicar o efeito protetor da vacina (resultado secundário). Métodos: A análise ecológica avaliou o impacto da vacinação contra o HPV como um fator protetor contra o baixo risco de anormalidades pelo HPV. Os resultados do teste de Papanicolaou, obtidos por meio do Sistema de Informação do Câncer do Colo do Útero (Siscolo) do Ministério da Saúde, foram categorizados em anormalidades de baixo grau (LGA) e anormalidades de alto grau (HGA). Este estudo preliminar foi centrado nas taxas de LGA, as quais foram estimadas para o período de um mês e estratificadas por quatro grupos etários (<20; 20-24; 25- 30; >30 anos) de 2007 a 2014. A comparação quantitativa das tendências temporais de LGA antes e depois da vacinação foi feita com análise de regressão de Quase-Poisson. O efeito protetor da vacina ao longo do tempo foi avaliado por cálculo do risco relativo em cada grupo de idade. Resultados: O estudo mostrou diminuição significativa de mais de 60% em LGA em mulheres de <20 anos de idade e de pelo menos cerca de 50% para os outros grupos. A vacina contra o HPV foi um fator de proteção, por causa do resultado do risco relativo de <0,0001 em todas as idades. Conclusões: Embora os estudos mostrem que as lesões pré-neoplásicas do HPV possam ser reversíveis espontaneamente, é inegável que a vacina contribuiu grandemente para as taxas elevadas de redução, associadas com a alta cobertura vacinal. Esses resultados são os primeiros no Brasil e podem dirigir no futuro a necessidade de discutir a vacinação dos meninos no contexto dos mesmos resultados obtidos na Austrália

Human papillomavirus (HPV) is a huge concern in public and private health. The prevention of this condition is the combination of the use of Papanicolaou smear test, condoms and HPV vaccines. Campos dos Goytacazes, RJ, is the first Brazilian municipality to implement in September 2010 the quadrivalent HPV vaccine (Gardasil®) for girls in the age group of 11­15 years, in a hybrid strategy of vaccination (schools and health centers). In 2014, the vaccination was started also for boys, at the same time that the Ministry of Health introduced it for girls. Objective: The aim of the study was to analyze the trends in reduction of low-grade cervical abnormalities five years after the introduction of the quadrivalent HPV vaccine in this municipality (primary outcome). Furthermore, this study evaluated the relative risk (RR) of each of the groups studied, in order to explain the protective effect of the vaccine (secondary outcome). Methods: The ecological analysis evaluated the impact of HPV vaccination as a protective factor against low risk of HPV abnormalities. Results of the Pap smear test obtained from the Brazilian Ministry of Health's Sistema de Informação do Câncer do Colo do Útero (SISCOLO) were categorized in low-grade abnormalities (LGA) and high-grade abnormalities (HGA). This preliminary study focused in LGA rates, which were estimated for a 1-month period and then stratified by four age groups (<20; 20­24; 25­30; >30 years) from 2007 to 2014. A quantitative comparison of LGA temporal trends before and after vaccination was done with Quasi-Poisson regression analysis. The protective effect of the vaccine over time was evaluated by calculating the RR in each age group. Results: The study showed significant decrease of more than 60% in LGA in women <20 years old, and less, almost 50% for the other groups. HPV vaccine was a protective factor, because the RR result was <0.0001 in all age groups. Conclusions: Although the studies show that the pre-HPV neoplastic lesions may be reversible spontaneously, it is undeniable that the vaccine contributes greatly to the high reduction rates, associated with high vaccination coverage. These results are the first in Brazil and in future may address the necessity to discuss the vaccination for boys in the context of the same results obtained in Australia.

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.

Enfermedad meningocóccica: siempre presente. Cambios en los serogrupos en el Cono Sur / Meningococcal disease: always present. Serogroup changes in the Southern Cone

Meningococcal disease (MD) caused by Neisseria meningitidis is a condition with high mortality rates in childhood. Serogroup W135 N. meningitidis (MenW135) is usually associated with 1 to 8% of MD cases worldwide, and with a low carriage rate. During March 2000, an increase in the number of cases of MenW135 in Saudi Arabia was reported that coincided with the Hajj pilgrimage (Hajj-2000 strain). Mayer et al studied MenW135 strains from outbreaks related with this pilgrimage and found that all had been caused by the same hypervirulent clone (ST-11/complex ET-37). The circulation of this strain could also be documented in Latin America. In the last years, changes in serogroup prevalence have been observed in the region, the increase of MenW135 in the Southern Cone being the most significant. N. meningitidis infections of several serogroups including MenW135 may be prevented with chemoprophylaxis with antibiotics and quadrivalent vaccines. Better knowledge of the global epidemiology through the new molecular techniques, jointly with the availability of vaccines are the most relevant tools to control hyperendemic or epidemic periods of MD.

La enfermedad meningocóccica (EM) producida por Neisseria meningitidis es una causa de alta mortalidad en la niñez. N. meningitidis serogrupo W135 (MenW135) es habitualmente asociado en el mundo con el 1 al 8% de los casos de EM y con una baja tasa de portadores. En 2000 en Arabia Saudita se informó un aumento del MenW135 coincidente con la peregrinación a la Meca, Hajj (cepa Hajj-2000). Mayer y cols. estudiaron cepas MenW135 de brotes relacionados con la peregrinación, y hallaron que todos los casos fueron producidos por el mismo clon hipervirulento (ST-11/complejo ET-37), cepa cuya circulación también se pudo documentar en América Latina. En los últimos años en la región se han producido cambios en la prevalencia de serogrupos, siendo el más significativo el aumento de MenW135 en el Cono Sur. Para la prevención de las infecciones por N. meningitidis de los diversos serogrupos incluyendo MenW135, se dispone de la quimioprofilaxis a través del uso de antimicrobianos y de las vacunas cuadrivalentes. El mejor conocimiento de la epidemiología global a través de las nuevas técnicas de laboratorio moleculares, junto con la disponibilidad de las vacunas, son las herramientas más relevantes para controlar períodos hiperendémicos o epidémicos de EM.

Vacunas meningocócicas / Meningococcal Vaccines

La enfermedad meningocócica, aunque poco frecuente, es severa y puede causar la muerte en 10% de quienes la contraen, de allí la importancia de la inmunización para prevenirla. existen varias clases de vacunas, como las polisacáridas que aun cuando pueden inducir protección, no son inmunogénicas en niños menores de 2 años ni inducen inmunidad de rebaño. la administración de dosis de refuerzoproduce hiporespuesta. Las vacunas conjugadas pueden ser monovalentes como la serogrupo c que demostró una reducción en un 93% de la enfermedad en poblaciones con altas coberturas vacunales, y las tetravalentes Ac W135, y/d (conjugada al toxoide diftérico y A; c, W135, y/crM139 conjugada a una mutante no tóxica de toxina diftérica Ambas son inmunogénicas y seguras. estudios epidemiológicos con A; c; W135, y/d descartan aumento de riesgo al síndrome de Guillain Barre (sGB) posterior a su administración. se recomienda administrar dosis única a adolescentes más un refuerzo. el personal de alto riesgo a la enfermedad (Asplenia anatómica o funcional, alteración del complemento, déficit de Properdina, vIh) deben recibir dos dosis más refuerzos cada cinco años

Meningococcal disease is a rare but serious infection, up to 10% of persons who contract disease die, so it is very important to immunized for Meningococcal disease protection and prevention. there are two types of vaccine: Polysaccharides that even though induces protection ,is not immunogenic in children younger of 2 years, don’t induce herd immunity and produce hypo responsivenessto a booster dose. conjugate vaccines can be monovalent serogroup: c which demonstrated 93% reduction of serogroups c disease in population with high vaccine coverage. Also there are two quadrivalent serogroups A;c;W135;y vaccines one conjugate to d(difteric toxoid) and other to /crM 139(mutant no toxic of dfsteric toxin. studies showed their immunogenicity up to 55 years and boths are safes. epidemiological study with A;c;W135,y/d disproves any evidence of increased risk to sGB after its administration recommended schedule is to immunized all adolescent, with a dose plus a booster. high risk people of invasive meningococcal disease (anatomic or functional asplenia,terminal complement or prperdin deficiencies,hIv) should rereceived, 2 doses, plus boostersevery 5 years