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BACKGROUND: We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. METHODS: CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 µg in 0·5 mL of ß-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. FINDINGS: Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9-63·9] at day 0 vs 128·9 [105·6-157·4] at day 28; seropositive controls 53·3 [45·4-62·5] at day 0 vs 202·0 [174·8-233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. INTERPRETATION: By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

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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.

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BACKGROUND: This study aimed to identify the transmission pattern of hepatitis A (HA) infection based on a primary dataset from the Brazilian National Hepatitis Survey in a pre-vaccination context. The national survey conducted in urban areas disclosed two epidemiological scenarios with low and intermediate HA endemicity. METHODS: A catalytic model of HA transmission was built based on a national seroprevalence survey (2005 to 2009). The seroprevalence data from 7,062 individuals aged 5-69 years from all the Brazilian macro-regions were included. We built up three models: fully homogeneous mixing model, with constant contact pattern; the highly assortative model and the highly assortative model with the additional component accounting for contacts with infected food/water. Curves of prevalence, force of infection (FOI) and the number of new infections with 99% confidence intervals (CIs) were compared between the intermediate (North, Northeast, Midwest and Federal District) and low (South and Southeast) endemicity areas. A contour plot was also constructed. RESULTS: The anti- HAV IgG seroprevalence was 68.8% (95% CI, 64.8%-72.5%) and 33.7% (95% CI, 32.4%-35.1%) for the intermediate and low endemicity areas, respectively, according to the field data analysis. The models showed that a higher force of infection was identified in the 10- to 19-year-old age cohort (∼9,000 infected individuals per year per 100,000 susceptible persons) in the intermediate endemicity area, whereas a higher force of infection occurred in the 15- to 29-year-old age cohort (∼6,000 infected individuals per year per 100,000 susceptible persons) for the other macro-regions. CONCLUSION: Our findings support the shift of Brazil toward intermediate and low endemicity levels with the shift of the risk of infection to older age groups. These estimates of HA force of infection stratified by age and endemicity levels are useful information to characterize the pre-vaccination scenario in Brazil.

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OBJECTIVE: 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.

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OBJECTIVE: To analyze the cost-effectiveness of a meningococcal C vaccination program in Brazil. METHODS: A hypothetical cohort of 3,194,038 children born in Brazil in 2006 was followed for 10 years. A decision tree model was developed using the TreeAge Pro 2007 software program to compare universal infant vaccination with the current program. Epidemiological and cost estimates were based on data retrieved from National Health Information Systems and the literature. The analysis was conducted from the public health care system and societal perspectives. Costs are expressed in 2006 Brazilian reals (R$). RESULTS: At 94% coverage, the program would avoid 1,218 cases, 210 deaths, and 14,473 life-years lost, a reduction of, respectively, 45%, 44%, and 44%, for the 10-year period. Vaccination costs of R$320.9 million would not be offset by R$4 to R$7.9 million decreases in disease treatment costs. A national vaccination program would cost R$21,620 per life-year saved from the perspective of the health-care system and R$21,896 per life-year saved from society's perspective. Results were most sensitive to case fatality rate, disease incidence, and vaccine cost. CONCLUSIONS: A universal childhood vaccination program against meningococcal C proved to be a cost-effective strategy, supporting the recent decision of the Brazilian government. These results could contribute to defining the most favorable price of the vaccine and to monitoring its impact on the population.

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Chronic Trypanosoma cruzi infection can reactivate in patients with immunosuppression related to human immunodeficiency virus (HIV) infection, resulting in severe meningoencephalitis or myocarditis and high parasitemia. The effects of T. cruzi on HIV infection are unknown. We describe an HIV-infected patient with chronic Chagas' disease who experienced an asymptomatic T. cruzi reactivation characterized by the finding of the parasite in direct microscopic examination of blood. The patient's HIV viral load had increased simultaneously with the exacerbation of T. cruzi parasitemia and decreased to previous levels after successful antiparasitic treatment. This otherwise unexplained finding suggests that T. cruzi infection might up-regulate HIV replication, which may affect HIV disease progression. Asymptomatic reactivation of Chagas' disease has not been reported before. This could mean that the severe clinical manifestations related to the reactivation of trypanosomiasis are just the tip of the iceberg.

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This study evaluated Trypanosoma cruzi parasitemia in persons with chronic Chagas disease, compared the parasitemia in human immunodeficiency virus (HIV)-positive and -negative subjects, and, for HIV-positive subjects, analyzed the association between parasitemia and occurrence of acquired immunodeficiency syndrome-defining illnesses, CD4 cell counts, HIV loads, and antiretroviral therapy. In total, 110 adults with chronic Chagas disease (29 HIV positive, 81 HIV negative) were studied. T. cruzi parasitemia was evaluated by xenodiagnosis, blood culture, and direct microscopic examination of blood. T. cruzi parasitemia was detected significantly more frequently in HIV-positive than in HIV-negative subjects (odds ratio, 12.3; 95% confidence interval, 3.7-41.2). HIV-positive patients also had higher levels of parasitemia. No statistically significant association was seen between parasitemia and the variables of interest among the HIV-positive subjects.

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O compromentimento do coraçäo é uma complicaçäo da AIDS, observada mais frequentemente nas fases adiantadas da doença. O aumento do número de infectados e a melhora da sobrevida graças às drogas antiretrovirais poderäo aumentar os casos de complicaçäes cardíacas associadas à AIDS. A infecçäo pelo HIV, agente responsável pela AIDS, é adquirida por contato sexual, por sangue, por uso de seringas contaminadas e durante a gestaçäo, o parto ou a amamentaçäo. O vírus infecta células que expressam o receptor CD4 na superfície. O vírus penetra na célula, incorpora-se ao seu DNA e depois gera modificaçöes funcionais ou até mesmo a destrói. As células principalmente atingidas säo os linfócitos T auxiliadores ("helper"), os monócitos e os macrófagos, responsáveis pela imunidade celular. O comprometimento dessa imunidade favorece o aparecimento de infecçöes por agentes oportunistas e de neoplasias. O envolvimento cardíaco é relativamente frequente em estudos de autópsias, porém sem importância clínica. Miocardite por agentes oportunistas, por etiologia auto-imune, por açäo de drogas usadas na doença ou mesmo por açäo direta do vírus está entre as possíveis explicaçöes para as alteraçöes observadas nesses pacientes. Além disso, foram observados o comprometimento pericárdico, a hipertensäo pulmonar, as neoplasias e as endocardites, principalmente entre os usuários de drogas intravenosas. Mais frequente, porém, é a presença de patologias cardíacas entre os pacientes com AIDS. Valvopatias, hipertensäo arterial, insuficiência coronária, insuficiência cardíaca congestiva ou arritmias podem ser diagnosticadas nessa populaçäo. A coexistência de uma doença com mau prognóstico pode interferir nas opçöes terapêuticas das doenças cardíacas. Esse aspecto deve ser considerado e ser fonte de futuros estudos que envolvam esses pacientes.

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