Adverse events following Quadrivalent HPV vaccination reported in Sao Paulo State, Brazil, in the first three years after introducing the vaccine for routine immunization (March 2014 to December 2016)

In March 2014, the Quadrivalent human papilloma virus vaccine (4vHPV) was introduced in the female adolescents vaccination schedule of the National Immunization Program (PNI). A school-based vaccination program was implemented. We conducted a retrospective, descriptive study of the adverse events that took place after HPV vaccination, reported to the Adverse Events Following Immunization (AEFI) Information System in Sao Paulo State, from March 2014 to December 2016. All reports that fit the definitions of the 2014 National Manual on AEFI surveillance were included. AEFI risk was estimated by dividing the number of reports by the number of vaccine doses administered in the period. In the three-year period, 3,390,376 HPV vaccine doses were administered and 465 AEFI reports were registered, with 1,378 signs and symptoms. The reporting rate was 13.72 per 100,000 vaccine doses administered. The reports peaked in the first year of the program. The most frequent AEFI was syncope, with 5.7 reports per 100,000 doses administered, followed by dizziness, malaise, headache and nausea. Overall, 39 AEFI cases (8.4%) were classified as severe , with a reporting rate of 1.15 per 100,000 vaccine doses administered. Most cases were classified as severe because of hospitalization. Among them, there were cases of Guillain-Barré Syndrome, deep vein thrombosis, seizures and miscarriage. All young women recovered without sequelae. We identified five clusters of AEFI reports in four cities; the larger AEFI cluster occurred in the city of Bertioga, in September 2014, involving 13 female adolescents. Our data are in accordance with those from other countries and corroborate the safety of HPV vaccines

Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease

Real-Time PCR in HIV/Trypanosoma cruzi Coinfection with and without Chagas Disease Reactivation: Association with HIV Viral Load and CD4+ Level

Chagas disease is endemic in Latin America and is caused by the flagellate protozoan T. cruzi. The acute phase is asymptomatic in the majority of the cases and rarely causes inflammation of the heart or the central nervous system. Most infected patients progress to a chronic phase, characterized by cardiac or digestive involvement when not asymptomatic. However, when patients are also exposed to an immunosuppressant (such as chemotherapy), neoplasia, or other infections such as HIV, T. cruzi infection may develop into a severe disease (Chagas disease reactivation) involving the heart and central nervous system. The current microscopic methods for diagnosing Chagas disease reactivation are not sensitive enough to prevent the high rate of death observed in these cases. Therefore, we propose a quantitative method to monitor blood levels of the parasite, which will allow therapy to be administered as early as possible, even if the patient has not yet presented symptoms

Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease

Cost-effectiveness analysis of universal childhood hepatitis A vaccination in Brazil: Regional analyses according to the endemic context

Objective: To To conduct a cost-effectiveness analysis of a universal childhood hepatitis A vaccination program in Brazil. Methods: An age and time-dependent dynamic model was developed to estimate the incidence of hepatitis A for 24 years. The analysis was run separately according to the pattern of regional endemicity, one for South + Southeast (low endemicity) and one for the North + Northeast + Midwest (intermediate endemicity). The decision analysis model compared universal childhood vaccination with current program of vaccinating high risk individuals. Epidemiologic and cost estimates were based on data from a nationwide seroprevalence survey of viral hepatitis, primary data collection, National Health Information Systems and literature. The analysis was conducted from both the health system and societal perspectives. Costs are expressed in 2008 Brazilian currency (Real). Results: A universal immunization program would have a significant impact on disease epidemiology in all regions, resulting in 64% reduction in the number of cases of icteric hepatitis, 59% reduction in deaths for the disease and a 62% decrease of life years lost, in a national perspective. With a vaccine price of R$16.89 (US$7.23) per dose, vaccination against hepatitis A was a cost-saving strategy in the low and intermediate endemicity regions and in Brazil as a whole from both health system and society perspective. Results were most sensitive to the frequency of icteric hepatitis, ambulatory care and vaccine costs. Conclusions: Universal childhood vaccination program against hepatitis A could be a cost-saving strategy in all regions of Brazil. These results are useful for the Brazilian government for vaccine related decisions and for monitoring population impact if the vaccine is included in the National Immunization Program. (C) 2012 Elsevier Ltd. All rights reserved.Ministry of Health of BrazilMinistry of Health of BrazilNational Council of Technological and Scientific Development (CNPq)National Council of Technological and Scientific Development (CNPq)National Institute of Science and Technology for Health Technology Assessment (IATS)National Institute of Science and Technology for Health Technology Assessment (IATS)CNPq [306489/2010-4, 308311/2009-4]CNP

Force of HA infection by age (A), as estimated by the catalytic approach, for the intermediate and low endemicity areas (solid lines) and the corresponding 99% CIs for the curves (red dotted lines for the intermediate endemicity area and blue dashed lines for the low endemicity area).

<p>(B) Hepatitis A force of infection curves by age and the ratio between the intermediate and low endemicity areas for the North region (solid line) and its corresponding 99% CI (dashed lines). A value of 1 denotes an equal number of new infected individuals per year in both areas, an integer >1 indicates a higher number of new infected individuals per year in the intermediate endemicity area, and a value <1 indicates a higher number of infected individuals in the low endemicity area. (C) Proportion of new hepatitis A infections for the intermediate and low endemicity regions (red and blue solid lines, respectively) and the corresponding 99% CIs (dotted and dashed lines, respectively). (D) HA incidence ratio (solid line) between the intermediate and low endemicity areas by age and its 99% CI (dashed lines).</p