17DD Yellow Fever Revaccination and Heightened Long-Term Immunity in Populations of Disease-Endemic Areas, Brazil.

We evaluated the duration of neutralizing antibodies and the status of 17DD vaccine-specific T- and B-cell memory following primary and revaccination regimens for yellow fever (YF) in Brazil. We observed progressive decline of plaque-reduction neutralization test (PRNT) seropositivity and of the levels of effector memory CD4+ and CD8+ T cells, as well as interferon-γ+CD8+ T cells, 10 years after primary vaccination. Revaccination restored PRNT seropositivity as well as the levels of effector memory CD4+, CD8+, and interferon-γ+CD8+ T cells. Moreover, secondary or multiple vaccinations guarantee long-term persistence of PRNT positivity and cell-mediated memory 10 years after booster vaccination. These findings support the relevance of booster doses to heighten the 17DD-YF-specific immune response to guarantee the long-term persistence of memory components. Secondary or multiple vaccinations improved the correlates of protection triggered by 17DD-YF primary vaccination, indicating that booster regimens are needed to achieve efficient immunity in areas with high risk for virus transmission.

Serologic status of women in an urban population in Brazil before and after rubella immunization campaign using routine screening data.

BACKGROUND: Serologic immunity studies are necessary to evaluate immunization policies for rubella control and prevention of congenital rubella syndrome (CRS), and serologic data from regular testing for clinical follow-up can be used to complement surveillance information. METHODS: To assess immunity to rubella after an immunization campaign in 12-29-year-old girls and women, we retrospectively reviewed immunoglobulin (Ig) G tests performed from 2000 to 2003 in 9610 serum samples from pregnant subjects in Niterói, Rio de Janeiro, Brazil. Serologic tests for rubella were performed using commercial enzyme immunoassays. RESULTS: Rubella IgG were positive in 83.9% of serum samples collected before the campaign and in 92.5% after the campaign. The proportion of seropositive subjects was inversely related to age (P < .001). The proportion of immune girls or women aged 12-29 years, targeted by the campaign, was significantly increased after the campaign, whereas women aged ≥ 30 years, not targeted by the campaign, had no change in serologic immunity. Geometric mean titers for rubella IgG were significantly higher among pregnant girls and women after the vaccination campaign. CONCLUSIONS: The convenience sample provided evidence of increased population immunity among the girls and women targeted by the campaign, but with a coverage of only 83% there remains a significant population at risk for rubella and thus congenital rubella syndrome.

Cytokine signatures of innate and adaptive immunity in 17DD yellow fever vaccinated children and its association with the level of neutralizing antibody.

BACKGROUND: The live attenuated yellow fever (YF) vaccines have been available for decades and are considered highly effective and one of the safest vaccines worldwide. METHODS: The impact of YF-17DD-antigens recall on cytokine profiles of YF-17DD-vaccinated children were characterized using short-term cultures of whole blood samples and single-cell flow cytometry. This study enrolled seroconverters and nonseroconverters after primovaccination (PV-PRNT⁺ and PV-PRNT⁻), seroconverters after revaccination (RV-PRNT⁺), and unvaccinated volunteers (UV-PRNT⁻). RESULTS: The analysis demonstrated in the PV-PRNT⁺ group a balanced involvement of pro-inflammatory/regulatory adaptive immunity with a prominent participation of innate immunity pro-inflammatory events (IL-12⁺ and TNF-α⁺ NEU and MON). Using the PV-PRNT⁺ cytokine signature as a reference profile, PV-PRNT⁻ presented a striking lack of innate immunity proinflammatory response along with an increased adaptive regulatory profile (IL-4⁺CD4⁺ T cells and IL-10⁺ and IL-5⁺CD8⁺ T cells). Conversely, the RV-PRNT⁺ shifted the overall cytokine signatures toward an innate immunity pro-inflammatory profile and restored the adaptive regulatory response. CONCLUSIONS: The data demonstrated that the overall cytokine signature was associated with the levels of PRNT antibodies with a balanced innate/adaptive immunity with proinflammatory/regulatory profile as the hallmark of PV-PRNT(MEDIUM⁺), whereas a polarized regulatory response was observed in PV-PRNT⁻ and a prominent proinflammatory signature was the characteristic of PV-PRNT(HIGH⁺).

Occurrence of yellow fever outbreaks in a partially vaccinated population: An analysis of the effective reproduction number.

BACKGROUND: Yellow fever is endemic in Africa and the Americas, occurring in urban or sylvatic environments. The infection presents varying symptoms, with high case-fatality among severe cases. In 2016, Brazil had sylvatic yellow fever outbreaks with more than 11 thousand cases, predominantly affecting the country's Southeast region. The state of Minas Gerais accounted for 30% of cases, even after the vaccine had been included in the immunization calendar for at least 30 years. METHODOLOGY AND PRINCIPAL FINDINGS: We applied parameters described in the literature from yellow fever disease into a compartmental model of vector-borne diseases, using namely generation time intervals, vital host and vector parameters, and force of infection, using macroregions as the spatial unit and epidemiological weeks as the time interval. The model permits obtaining the reproduction number, which we analyzed from reported cases of yellow fever from 2016 to 2018 in residents of the state of Minas Gerais, Brazil. Minas Gerais recorded two outbreak periods, starting in EW 51/2016 and EW 51/2017. Of all the reported cases (3,304), 57% were men 30 to 59 years of age. Approximately 27% of cases (905) were confirmed, and 22% (202) of these individuals died. The estimated effective reproduction number varied from 2.7 (95% CI: 2.0-3.6) to 7.2 (95% CI: 4.4-10.9], found in the Oeste and Nordeste regions, respectively. Vaccination coverage in children under one year of age showed heterogeneity among the municipalities comprising the macroregions. CONCLUSION: The outbreaks in multiple parts of the state and the estimated Re values raise concern since the state population was partially vaccinated. Heterogeneity in vaccination coverage may have been associated with the occurrence of outbreaks in the first period, while the subsequent intense vaccination campaign may have determined lower Re values in the second period.

Tuberculosis among the Xavante Indians of the Brazilian Amazon: an epidemiological and ethnographic assessment.

BACKGROUND: Despite broad availability of a national tuberculosis (TB) control program that has proved effective in Brazil, TB remains a major cause of morbidity and mortality among indigenous peoples. AIM: We report the results of an interdisciplinary investigation of TB epidemiology, healthcare services, and ethnomedicine among the Xavante Indians of Central Brazil. SUBJECTS AND METHODS: Fieldwork components included clinical assessment of TB (479 subjects, 89.3% of the population = 1 year of age), analysis of medical health records, and ethnographic research. RESULTS: We found TB to constitute a major health risk, with moderately high annual risk of infection (0.94%), moderate prevalence of infection, high percentage of X-ray images suggestive of TB (14.2% in subjects > or = 10 years of age), and a relatively low percentage of individuals with reactive TB skin tests (16.6% of reactions > or = 10 mm) despite high BCG vaccine coverage. We also found a high rate of TB patients showing no evidence of prior infection. Ethnographic interviews show that Xavante and biomedical health perspectives are simultaneously divergent in their etiologies but pragmatically compatible. CONCLUSION: Ineffective diagnosis procedures compromise the efficacy of existing TB prevention efforts and threaten to undermine otherwise favorable institutional and cultural conditions.

Duration of post-vaccination humoral immunity against yellow fever in children.

INTRODUCTION: Vaccination is the most important measure for prevention and control of yellow fever. It is recommended by the World Health Organization (WHO) for residents of endemic areas and travelers to risk areas. In 2013, the WHO discontinued the recommendation of booster doses every 10 years, indicating a single dose as sufficient for lifelong protection. OBJECTIVE: Considering the lower immune response to YF vaccine in children compared to adults, this study was set out to assess the duration of immunity to YF in children vaccinated in the first two years of life. METHODS: This cross-sectional study involved children aged 9 months to 12 years with accessible vaccination records recruited in primary care units from a metropolitan area in Southeast Brazil. The serologic status (negative, indeterminate and positive), and geometric mean titers (GMT, inverse dilution) of neutralizing antibodies against YF obtained by Plaque Reduction Neutralization Test was assessed across categories of time after YF vaccination. The strength of association of seropositivity with time was assessed by the odds ratio (OR) taking recent vaccination (1-6 months) as reference. RESULTS: A total of 824 children recruited from August 2010 to July 2011were tested. The proportion of seropositivity (95% C.I.) and GMT (95% C.I.) dropped markedly across time periods: from 86.7% (80.5-91.4%), GMT 47.9 (38.3-59.9) in newly vaccinated to 59.0% (49.7-67.8%), GMT 14.8 (11.6-19.1) and 42.2% (33.8-51.0), GMT 8.6 (7.1-12.1), respectively in the subgroups vaccinated 31-72 months and 73-100 months before. CONCLUSIONS: Analogous to previous findings in adults, these data support the need for revaccination of children living in areas with yellow fever virus circulation in humans or in other primates. The data also supported the change of a booster dose to 4 years of age for those primarily vaccinated for yellow fever in the first two years of life.

Acute arthropathy in patients with rash diseases: a comparative study.

The aim of this study was to assess the association of acute arthropathy and selected clinical features in patients with acute rash diseases. Serum samples from 1,554 patients were tested for anti-measles, dengue, human parvovirus B19, and rubella virus IgM using enzyme immunoassay. Sera from children, in whom these infections were excluded, were studied for anti-human herpesvirus type 6 IgG antibodies using an indirect immunofluorescence test. Joint complaints occurred in 31.2% of the 862 patients with an etiologic diagnosis and were more frequently seen in adults than in children (OR 8.5). Among the adults, arthropathy prevailed in women compared to men (OR 1.8). Arthropathy was most frequently reported in rubella (41.2%) and in dengue fever cases (41.1%) than in the other rash diseases studied (p < 0.0001). Joint complaints were more frequently seen in patients with fever (OR 1.6) and with five or more days of onset of the disease (OR 1.6), regardless of serological diagnosis. Arthropathy appeared as a frequent condition in rash diseases, typically with low severity and no specific pattern of joint involvement.