'If I hadn't seen this picture, I'd be smoking'-perceptions about innovations in health warnings for cigarette packages in Brazil: a focus group study.

OBJECTIVE: To investigate the perceptions of young people and adults, smokers and non-smokers about the current set of innovations introduced in 2018 into the Brazilian tobacco products' health warnings. METHODS: Twenty focus groups were conducted in five state capitals in Brazil. The participants (n=163) were segmented by smoking status, age (15-17 years, 18-55 years) and social grade (C, D-E classes) to examine cigarette packaging and explore the participants' perceptions of health warnings. RESULTS: Health warnings capture attention, eliciting apprehension, fear, disgust and concern about the negative consequences of cigarette consumption. The 2018 Brazil health warnings are spontaneously recalled by participants, even without the presence of cigarette packages. However, the analysis also reveals the challenges of overcoming communication barriers and distorted interpretations, especially among smokers. The inclusion of direct and provocative stimuli, such as the use of the word 'you', attracts attention and creates more proximity to the recipient of the message. The results also highlight the interest and fear elicited by warnings on toxic constituents and the importance of using contrasting colours in warnings, which differentiate them from the colours of cigarette packs. CONCLUSION: Introducing innovative components in health warnings can catch consumers' attention but considering that the interviewees encountered difficulties interpreting textual warnings about toxic constituents in cigarettes, the study reinforces the importance of adopting direct language and pictures, instead of text, which can visually transmit the warning messages and the use of specific wording that generates proximity between the emitter and receiver.

Homeopathic Treatment of Subclinical Hypothyroidism-A Series of 19 Cases.

BACKGROUND: Subclinical hypothyroidism (SCH) is a common clinical problem. Controversy surrounds the definition, clinical importance, and need for prompt diagnosis and treatment of the mild form of SCH. AIM: The aim of the study was to analyze the evolution of serum thyroid stimulating hormone (TSH) levels after a therapeutic homeopathic intervention in women older than 40 years with SCH. METHODS: This study is a retrospective series of 19 cases of SCH, with serum TSH levels between 5 and 10 mIU/L, treated exclusively with homeopathic medicines prescribed on an individualized basis. RESULTS: Nineteen patients were included according to the inclusion and exclusion criteria. Their mean age was 56 years, they were followed for a mean duration of 69 months, the mean number of serum TSH level measurements was 18, and the intervention was successful for 13 patients. CONCLUSION: The homeopathic therapeutic intervention was successful in 68% of the patients, with serum TSH levels back within the normal range (0.5-5.0 mIU/L).

Validation of a yellow fever vaccine model using data from primary vaccination in children and adults, re-vaccination and dose-response in adults and studies with immunocompromised individuals.

BACKGROUND: An effective yellow fever (YF) vaccine has been available since 1937. Nevertheless, questions regarding its use remain poorly understood, such as the ideal dose to confer immunity against the disease, the need for a booster dose, the optimal immunisation schedule for immunocompetent, immunosuppressed, and pediatric populations, among other issues. This work aims to demonstrate that computational tools can be used to simulate different scenarios regarding YF vaccination and the immune response of individuals to this vaccine, thus assisting the response of some of these open questions. RESULTS: This work presents the computational results obtained by a mathematical model of the human immune response to vaccination against YF. Five scenarios were simulated: primovaccination in adults and children, booster dose in adult individuals, vaccination of individuals with autoimmune diseases under immunomodulatory therapy, and the immune response to different vaccine doses. Where data were available, the model was able to quantitatively replicate the levels of antibodies obtained experimentally. In addition, for those scenarios where data were not available, it was possible to qualitatively reproduce the immune response behaviours described in the literature. CONCLUSIONS: Our simulations show that the minimum dose to confer immunity against YF is half of the reference dose. The results also suggest that immunological immaturity in children limits the induction and persistence of long-lived plasma cells are related to the antibody decay observed experimentally. Finally, the decay observed in the antibody level after ten years suggests that a booster dose is necessary to keep immunity against YF.

Immunogenicity and safety of the combined vaccine for measles, mumps, and rubella isolated or combined with the varicella component administered at 3-month intervals: randomised study.

BACKGROUND: Field testing required to license the combined measles, mumps, and rubella (MMR) vaccine must take into account the current recommendation of the vaccine in Brazil: first dose at 12 months and second dose at 15 months of age in combination with a varicella vaccine. OBJECTIVES: This study aimed to evaluate the clinical consistency, immunogenicity, and reactogenicity of three batches of MMR vaccine prepared with active pharmaceutical ingredients (API) from Bio-Manguinhos, Fiocruz (MMR-Bio), and compare it to a vaccine (MMR produced by GlaxoSmithKline) with different API. METHODS: This was a phase III, randomised, double-blind, non-inferiority study of the MMR-Bio administered in infants immunised at health care units in Pará, Brazil, from February 2015 to January 2016. Antibody levels were titrated by immunoenzymatic assays. Adverse events were recorded in diaries. FINDINGS: Seropositivity levels after MMR-Bio were 97.6% for measles, 84.7% for mumps, and 98.0% for rubella. After the MMRV vaccine, seroconversion rates and GMT increased substantially for mumps. In contrast, approximately 35% of the children had no detectable antibodies to varicella. Systemic adverse events were more frequent than local events. CONCLUSION: The demonstration of batch consistency and non-inferiority of the Bio-MMR vaccine completed the technology transfer. This is a significant technological achievement with implications for immunisation programs.

Children Born to Mothers with Rash During Zika Virus Epidemic in Brazil: First 18 Months of Life.

OBJECTIVE: To better understand the clinical spectrum and course of congenital Zika syndrome (CZS) during the first 18 months of life of children whose mothers had rash during pregnancy. METHODS: This longitudinal observational study evaluated the clinical progress from birth until 18 months of life of children of mothers who developed rash during or up to 3 months before gestation. Maternal rash occurred from November 2015 to May 2017. The study subjects were divided into three groups: children whose mothers tested positive by RT-qPCR for Zika virus (ZIKV) (Group 1), children whose mothers tested negative by RT-qPCR for ZIKV (Group 2), and children whose mothers did not undergo any testing for ZIKV (Group 3) but tested negative for other congenital infections. RESULTS: Between April 2016 and July 2018, we studied 108 children: 43 in Group 1, 26 in Group 2 and 39 in Group 3. The majority of children were admitted into the study within 6 months of life. CZS was diagnosed in 26 children, equally distributed in Groups 1 and 3. Of 18 children with microcephaly, 6 were in Group 1 (1 postnatal) and 12 were in Group 3 (5 postnatal). Maternal rash frequency was 10 times higher during the first trimester than in the other trimesters (OR: 10.35; CI 95%: 3.52-30.41). CZS was diagnosed during the follow-up period in 14 (54%) cases. Developmental delays and motor abnormalities occurred in all children and persisted up to 18 months. Epilepsy occurred in 18 (69%) of the cases. CONCLUSIONS: Infants born of mothers exposed to ZIKV during pregnancy showed progression of developmental, motor and neurologic abnormalities even if they were born asymptomatic. Continued postnatal monitoring of such newborns is necessary to preclude disability-associated complications.

Clinical and Laboratory Factors Associated with Severe Dengue: A Case-Control Study of Hospitalized Children.

Background: More than half of the hospitalizations because of dengue in Brazil occurred in children <15 years of age in 2007 and 2008, an unexpected change in the epidemiological pattern. We sought to determine clinical and laboratory parameters associated with severity. Methods: A case-control study was conducted in three pediatric hospitals in Rio de Janeiro, Brazil; 233 laboratory-confirmed dengue patients were included: 69 cases and 164 controls. Specific clinical and laboratory factors were assessed using univariate and multivariate logistic regression models. Results: Lethargy [adjusted odds ratio (ORa): 9.15, 95% confidence interval (CI): 3.08-27.12], dyspnea (ORa: 8.24, 95% CI: 3.27-20.72) and abdominal pain (ORa: 6.78, 95% CI: 1.44-31.84) were independently associated with severe dengue in children. Lethargy and dyspnea presented as early as 72 and 48 h, respectively, before shock. Conclusions: Abdominal pain and lethargy confirmed their role as warning signs, which along with dyspnea might be helpful in identifying cases progressing to severe dengue.

Barriers in household access to medicines for chronic conditions in three Latin American countries.

BACKGROUND: Access to medicines is one of the major challenges in health policy. The high out-of-pocket expenditures on medicines in the Latin American and Caribbean (LAC) region represents important barrier to affordable access to care for NCDs. This paper aim to identify key barriers in access to medicines for household members with a diagnosed chronic condition in three Central America countries. METHODS: This was a cross-sectional analytic study, based on data from three household surveys using a common methodology. We examined associated factors to: (1) seeking care for chronic illness from a trained clinician in the formal health system, and (2) obtaining all medicines sought for the chronic conditions reported. RESULTS: A chronic condition was reported in 29.8 % (827) of 2761 households - 47.0, 30.7 and 11.8 % in Nicaragua, Honduras and Guatemala, respectively. The three main chronic conditions reported were hypertension, arthritis, and diabetes. Seeking care in the formal health system ranged from 73.4 % in Nicaragua to 83.1 % in Honduras, while full access to medicines varied from 71.6 % in Guatemala to 88.0 % in Honduras. The main associated factors of seeking care in the formal health system were geographic location, household head gender, Spanish literacy, patient age, perceived health status, perceived quality of public sector care, household economic level, and having health insurance. Seeking care in the formal health system was the main bivariate associated factor of obtaining full access to medicines (OR: 4.3 95 % CI 2.6 - 7.0). The odds of full access to medicines were significantly higher when the household head was older than 65 years, medicines were obtained for free, households had higher socioeconomic status, and health care was sought in the private sector. CONCLUSIONS: The nature of the health system plays an important role in access to medicines. Access is better when public facilities are available and function effectively, or when private sector care is affordable. Thus, understanding how people seek care in a given setting and strengthening key health system components will be important strategies to improve access to medicines, especially for populations at high risk of poor access.

Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline.

BACKGROUND: The live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine. METHODS: Neutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees. RESULTS AND DISCUSSION: The results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10). CONCLUSIONS: The analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine.

Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program.

A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR) immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0) seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.

Duration of post-vaccination immunity to yellow fever in volunteers ten years after a dose-response study - A complementary study.

A single dose of standard yellow fever (YF) vaccine is considered to provide life-long protection. In this study, we evaluate the seropositivity conferred by lower doses 10 years post-vaccination. In 2009, Bio-Manguinhos/Fiocruz performed a dose-response study with the 17DD yellow fever vaccine, administering the vaccine in the usual mean dose of 27.476 IU and in decreasing doses (10.447 IU, 3.013 IU, 587 IU, 158 IU and 31 IU), with the usual volume and route (0,5 ml subcutaneous). The decreasing doses were obtained by dilution in the laboratory of the manufacturer and the lots in test had standard quality control and were produced by good manufacturing practices (GMP). Around 30 days after the vaccination, doses down to 587 IU had similar immunogenicity and the 158 IU and 31 IU were inferior to the full dose. The seropositivity was maintained for 10 months, except on the 31 IU group. Eight years after, 85 % of 318 participants evaluated in a follow-up, maintained seropositivity that was similar across groups. Consistently, antibody titers in the reduced-dose groups were also comparable to those of the full-dose group. The current study, 10 years later, showed similarity between the vaccine groups (six arms who received the YF vaccine in decreasing doses: 27.476 IU, 10.447 IU, 3.013 IU, 587 IU, 158 IU, 31 IU) both in relation of seropositivity and in the evaluation of the geometric mean titers. The seropositivity rates across subgroups were 83,1%, 90 %, 87 %, 93 %, 83,8% and 85 %, correspondingly. These findings provides further support to the long-term immunogenicity of lower doses. Clinical trial registry: NCT04416477.

Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults.

The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30-45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30-45) as compared to NV(D0) (532vs398). Moreover, PV(D30-45) exhibited increased levels of Terminal Effector (CD45RA+CCR7-) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30-45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

Immune response induced by standard and fractional doses of 17DD yellow fever vaccine.

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

[Tuberculosis in indigenous peoples in the Brazilian Amazon: an epidemiological study in the Upper Rio Negro region]. / Tuberculose em indígenas da Amazônia brasileira: estudo epidemiológico na região do Alto Rio Negro.

OBJECTIVE: To describe the sociodemographic, clinical, and epidemiological characteristics of reported tuberculosis cases among indigenous individuals of São Gabriel de Cachoeira, State of Amazonas, Brazil, and to identify the factors associated with mortality during treatment; and to estimate the prevalence of latent tuberculosis infection (LTBI) and associated factors and obtain information on the therapeutic course and the individual perceptions regarding acquistion of tuberculosis in the district of Iauaretê. METHODS: Firstly, a retrospective epidemiological study (1997 to 2007) was conducted using data from the Brazilian Notifiable Diseases Surveillance System (SINAN). Next, a cross-sectional study (2010) was conducted with respiratory symptomatic subjects and contacts of Iauaretê. RESULTS: Seven hundred and twenty-three new cases were reported, with incidence of 273.4/100 000 and mortality of 13.2/100 000. There was a predominance of males (57%), aged > 45 years (37.6%), people with no schooling (42.7%), and cases from rural areas (76.9%). Patients aged 0 to 20 years were at lower risk of death when compared to those aged > 45 years (OR = 0.3; IC95%: 0.1 a 0.9). In Iauaretê, with 15.3% of the reported cases, 184 people were interviewed. A prevalence of LTB of 76.1% was reported. Tuberculin skin test > 5 mm was associated with the > 15-year old age group, history of active tuberculosis, and radiological alterations. A previous history of tuberculosis was cited by 54 people (29.3%). The main explanation for the disease was "puffing/poisoning" (24.1%). The therapeutic course included industrialized drugs (42.6%), medicinal plants/roots, shamanism, and prayer (42.7%). CONCLUSIONS: The risk of tuberculosis infection and disease in this population was high. Despite the reduced incidence resulting from recent efforts, tuberculosis control requires closer surveillance of contacts and improvement in communication strategies between health teams and indigenous populations.

Standardization, validation, and comparative evaluation of a faster and high-performance test for quantification of yellow fever neutralizing antibodies.

Although it is considered the reference for quantification of neutralizing antibodies, classical method of the plaque reduction neutralization test (PRNT) is labor intensive, requires specific equipment and inputs, besides a long time for its finalization, even in the micro-PRNT version (in 96-well plates). It has a higher sample throughput, however the smaller wells make the reading of plaques more difficult. With an immunoenzymatic revelation step and a semi-automated reading, the µFRN-HRP (micro Focus Reduction Neutralization - Horseradish Peroxidase) is a faster and more efficient test for the quantification of YF neutralizing antibodies. This study aimed to standardize, validate, and compare it with the reference method in 6-well plates (PRNT). Once the execution protocol was standardized, precision, accuracy, selectivity, and robustness were evaluated to validate the µFRN-HRP. In addition, 200 sera of vaccinees were processed by the µFRN-HRP and by the micro-PRNT to compare with the reference test, estimating agreement by Intraclass Correlation Coefficient (ICC). The standardization and validation of the µFRN-HRP was carried out successfully. Weak to moderate agreement was observed between µFRN-HRP and PRNT for titers in reciprocal dilution, while the same comparison between the classical tests resulted in a better ICC. However, titers in milli-international units obtained by µFRN-HRP showed a substantial agreement with PRNT, while the agreement between micro-PRNT and PRNT was inferior. Therefore, µFRN-HRP can be used in the confirmation of natural YF infection and immune response to vaccination, replacing the micro-PRNT, gaining agility, while preserving the specificity of the result.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

Reliability and accuracy of the screening for adverse events in Brazilian hospitals.

OBJECTIVE: To analyze the reliability and accuracy of the screening for adverse events (AEs) conducted by nurses taking the assessment by medical residents as the reference. DESIGN: A validation study of the screening phase of a previous retrospective cohort study based on the patient record review that estimated the incidence of AEs (base study). SETTING: Three general teaching hospitals in the State of Rio de Janeiro, Brazil. PARTICIPANTS: A subsample of 242 medical records randomly selected from an original sample of 1103 previously evaluated records. MAIN OUTCOME MEASURE(S): A two-step approach was used for analysis: the identification of at least one screening criterion (first endpoint) and the validation of each identified criterion (second endpoint), taking the assessment by medical residents as the reference. Kappa coefficient; simple percentage agreement; sensitivity; specificity; positive and negative predictive values were calculated. RESULTS: The total agreement between medical residents and nurses on the presence of screening criteria was moderate (78.9%, K = 0.55). Specificity (81.6%) was higher than sensitivity (74.4%). Nurses detected more screening criteria that were later confirmed as true AEs (179 vs. 171, respectively). Significant differences in the detection of the screening criteria: 'Other complications', 'Hospitalization injury' and 'Prior admission' were observed. CONCLUSION: The results suggested a good performance of the nurses in the screening for detection of AE and showed significant differences in relation to detection of specific screening criteria among reviewers. A better understanding of the screening process and the performance of reviewers was provided.

Parvovirus B19 seroconversion in a cohort of human immunodeficiency virus-infected patients.

Erythrovirus B19 (B19V) infection may cause red cell aplasia in patients infected with human immunodeficiency virus (HIV). The introduction of highly active antiretroviral therapy (HAART) has improved the immune function of these patients by modifying the course of B19V infection. The purpose of this study was to estimate the frequency of B19 seroconversion in a cohort of HIV-infected patients and evaluate the occurrence of B19V-related anaemia during the seroconversion period. Adult HIV-infected patients were studied at a public hospital in Niterói, state of Rio de Janeiro, Brazil. IgG and IgM antibodies against B19V were detected by an enzyme-linked immunosorbent assay and B19 viraemia was assayed by polymerase chain reaction. Medical records were reviewed for any clinical evaluation of anaemia. Seroconversion was detected in 31.8% of the 88 individuals who began the study as anti-B19V IgG-negative. No clinical manifestations of B19V infection were detected during the period of seroconversion. Patients who seroconverted were 5.40 times more likely to have anaemia than those who did not [odds ratio 5.40 (95% confidence interval: 1.33-22.93)]. Anaemia was detected in eight patients. All patients recovered from anaemia by either beginning or continuing HAART, without requiring blood transfusions. In the HAART era, B19V infection may only be associated with a course of disease characterised by less severe chronic anaemia. This milder course of B19V-associated disease is likely due to the increased immune function of HAART-treated patients.

Pregnancy outcomes following rubella vaccination: a prospective study in the state of Rio de Janeiro, Brazil, 2001-2002.

BACKGROUND: A rubella mass vaccination campaign targeting 15-29-year-old women was performed in Brazil in 2001-2002. Rubella vaccination was contraindicated during pregnancy. A follow-up protocol was implemented for pregnant women who were vaccinated as well as their newborns. The risks of congenital rubella syndrome (CRS) and congenital rubella infection (CRI) after vaccination were assessed according to the pregnant women's immune status. METHODS: This was a prospective, noncontrolled study of pregnancy outcomes in women vaccinated against rubella in the state of Rio de Janeiro, including clinical and laboratory evaluations. RESULTS: Of 2292 reported pregnant women who were vaccinated, 1636 had known outcomes: there were 1577 newborns (96.4%), 52 miscarriages (3.2%), and 7 stillbirths (0.4%). Gestational age at vaccination was ≤ 5 weeks in 75% of the susceptible, vaccinated pregnant women. Nine newborns were positive for immunoglobulin M; 4 were born to susceptible pregnant women, for a 2.0% CRI rate (95% confidence interval, .5%-4.9%); 4 were born to vaccinated pregnant women with indeterminate or unknown status; and 1 had CRS, with a wild-type virus infection. CONCLUSIONS: The absence of vaccine-related CRS cases further supports recommendations to not interrupt a pregnancy exposed to rubella vaccine virus. Monitoring pregnancy outcomes and CRI with vaccine virus can distinguish between wild-type and vaccine virus infections, especially in situations of viral circulation.

[Yellow fever prevention and control: assessment of surveillance activities in a previously unaffected area in Brazil]. / Prevenção e controle da febre amarela: avaliação de ações de vigilância em área indene no Brasil.

Following the reemergence of yellow fever in 2014/2015, Brazil recorded its largest yellow fever epidemic in recent decades, mainly affecting the country's Southeast region. Yellow fever is a hemorrhagic viral disease caused by a flavivirus transmitted by sylvatic mosquitos (Haemagogus; Sabethes). In the urban cycle, eradicated in Brazil since 1942, the virus is transmitted by Aedes aegypti. Nonhuman primates are the principal hosts of the virus and constitute "sentinels" in yellow fever surveillance. This article describes the control and prevention activities launched during the yellow fever epidemic in the State of Espírito Santo, Brazil, and the implementation of vaccination, through an ecological study with a spatial approach. The study revealed the lack of detection of epizootics in nonhuman primates by surveillance services in Espírito Santo, with simultaneous detection in humans. The study presented the evolution of vaccination activities, reaching 85% overall coverage for the state in six months, varying widely, from 59% to 122%, between municipalities (counties). Importantly, 55% of the municipalities with timely immunization, considering the interval adopted for this study, did not present human cases. The intensification of surveillance activities, communication between areas, and multidisciplinary teams in managing the epidemic optimized the detection and diagnosis of human cases and allowed control of the epidemic. The study identifies progress and points to some late measures and gaps in surveillance that require improvements.

A partir da reemergência da febre amarela em 2014/2015, o Brasil registrou nos anos sequentes sua maior epidemia de febre amarela das últimas décadas, atingindo principalmente a região sudeste. A febre amarela, doença viral hemorrágica, é causada por um flavivírus, transmitido por mosquitos silvestres (Haemagogus; Sabethes). Na ocorrência do ciclo urbano, erradicado no Brasil desde 1942, a transmissão se dá pelo Aedes aegypti. Primatas não humanos são os principais hospedeiros do vírus e constituem "sentinelas" na vigilância da febre amarela. Este artigo descreve as ações de controle e prevenção desencadeadas durante a epidemia de febre amarela no Estado do Espírito Santo, Brasil, e a implementação da vacinação por meio de um estudo ecológico com abordagem espacial. O estudo evidenciou a falha na detecção de epizootias em primatas não humanos pelos serviços de vigilância do Espírito Santo, sendo simultânea à detecção em humanos. Apresentou a evolução das ações de vacinação, com alcance de 85% de cobertura vacinal geral para o estado em seis meses, sendo heterogênea entre os municípios (de 59% a 122%). Destaca-se que 55% dos municípios com ações de imunização em tempo oportuno, considerando o intervalo adotado para este estudo, não apresentaram casos em humanos. A intensificação das ações de vigilância, interlocução entre as áreas e equipes multidisciplinares na condução da epidemia otimizou a detecção e o diagnóstico dos casos em humanos e viabilizou o controle da epidemia. Foi possível reconhecer avanços, apontar algumas medidas tardias e lacunas na vigilância que necessitam melhorias.

A partir del resurgimiento de la fiebre amarilla en 2014/2015, Brasil registró los años siguientes su mayor epidemia de fiebre amarilla de las últimas décadas, alcanzando principalmente la región sudeste. La fiebre amarilla, enfermedad viral hemorrágica, es causada por un flavivirus, transmitido por mosquitos silvestres (Haemagogus; Sabethes). Respecto a la ocurrencia del ciclo urbano, erradicado en Brasil desde 1942, la transmisión se produce por el Aedes aegypti. Primates no humanos son los principales huéspedes del virus, y constituyen "centinelas" en la vigilancia de la fiebre amarilla. Este artículo describe las acciones de control y prevención desencadenadas durante la epidemia de fiebre amarilla en el Estado de Espírito Santo, Brasil, y la implementación de la vacunación mediante un estudio ecológico con abordaje espacial. El estudio evidenció el fallo en la detección de epizootias en primates no humanos por los servicios de vigilancia de Espírito Santo, siendo simultánea a la detección en humanos. Presentó la evolución de las acciones de vacunación, con alcance de un 85% de cobertura en la vacunación general para el estado en seis meses, siendo heterogénea entre los municipios (de 59% a 122%). Se destaca que un 55% de los municipios con acciones de inmunización en tiempo oportuno, considerando el intervalo adoptado para este estudio, no presentaron casos humanos. La intensificación de las acciones de vigilancia, interlocución entre las áreas y equipos multidisciplinarios en la gestión de la epidemia optimizó la detección y diagnóstico de los casos humanos y viabilizó el control de la epidemia. Fue posible reconocer avances, apuntar algunas medidas tardías y lagunas en la vigilancia que necesitan mejorías.