Publications by authors named "Andre Ricardo Ribas Freitas"

30 Publications

  • Page 1 of 1

The emergence of novel SARS-CoV-2 variant P.1 in Amazonas (Brazil) was temporally associated with a change in the age and sex profile of COVID-19 mortality: A population based ecological study.

Lancet Reg Health Am 2021 Sep 13;1:100021. Epub 2021 Jul 13.

Centro de Farmacovigilância, Segurança Clínica e Gestao de Risco do Instituto Butantan, Brazil.

Background: Since the end of 2020, there has been a great deal of international concern about the variants of SARS-COV-2 B.1.1.7, identified in the United Kingdom; B.1.351 discovered in South Africa and P.1, originating from the Brazilian state of Amazonas. The three variants were associated with an increase in transmissibility and worsening of the epidemiological situation in the places where they expanded. The lineage B.1.1.7 was associated with the increase in case fatality rate in the United Kingdom. There are still no studies on the case fatality rate of the other two variants. The aim of this study was to analyze the mortality profile before and after the emergence of the P.1 strain in the Amazonas state.

Methods: We analyzed data from the Influenza Epidemiological Surveillance Information System, SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), comparing two distinct epidemiological periods: during the peak of the first wave, between April and May 2020, and in January 2021 (the second wave), the month in which the new variant came to predominate. We calculated mortality rates, overall case fatality rate and case fatality rate among hospitalized patients; all rates were calculated by age and gender and 95% confidence intervals (95% CI) were determined.

Findings: We observed that in the second wave there were a higher incidence and an increase in the proportion of cases of COVID-19 in the younger age groups. There was also an increase in the proportion of women among Severe Acute Respiratory Infection (SARI) cases from 40% (2,709) in the first wave to 47% (2,898) in the second wave and in the proportion of deaths due to COVID-19 between the two periods varying from 34% (1,051) to 47% (1,724), respectively. In addition, the proportion of deaths among people between 20 and 59 years old has increased in both sexes. The case fatality rate among those hospitalized in the population between 20 and 39 years old during the second wave was 2.7 times the rate observed in the first wave (female rate ratio = 2.71; 95% CI: 1.9-3.9], p <0.0001; male rate ratio = 2.70, 95%CI:2.0-3.7), and in the general population the rate ratios were 1.15 (95% CI: 1.1-1.2) in females and 0.78 (95% CI: 0.7-0.8) in males].

Interpretation: Based on this prompt analysis of the epidemiological scenario in the Amazonas state, the observed changes in the pattern of mortality due to COVID-19 between age groups and gender simultaneously with the emergence of the P.1 strain suggest changes in the pathogenicity and virulence profile of this new variant. Further studies are needed to better understanding of SARS-CoV-2 variants profile and their impact for the health population.

Funding: There was no funding for this study.
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http://dx.doi.org/10.1016/j.lana.2021.100021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421758PMC
September 2021

A prospective, multicentre, cohort study to assess the incidence of dengue illness in households from selected communities in Brazil (2014-2018).

Int J Infect Dis 2021 Jul 21;108:443-453. Epub 2021 Apr 21.

Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos/Fiocruz, Avenida Brasil 4.365, Manguinhos, Rio de Janeiro - RJ, 21.040-900, Brazil.

Objectives: To estimate the incidence of dengue infection across geographically distinct areas of Brazil.

Methods: This prospective, household-based, cohort study enrolled participants in five areas and followed them up for up to 4 years (2014-2018). Dengue seroprevalence was assessed at each scheduled visit. Suspected dengue cases were identified through enhanced passive and active surveillance. Acute symptomatic dengue infection was confirmed through reverse-transcriptase quantitative polymerase chain reaction in combination with an antigenic assay (non-structural protein 1) and serology.

Results: Among 3300 participants enrolled, baseline seroprevalence was 76.2%, although only 23.3% of participants reported a history of dengue. Of 1284 suspected symptomatic dengue cases detected, 50 (3.9%) were laboratory-confirmed. Based on 8166.5 person-years (PY) of follow-up, the incidence of laboratory-confirmed symptomatic infection (primary endpoint) was 6.1 per 1000 PY (95% confidence interval [CI]: 4.5, 8.1). Incidence varied substantially in different years (1.8-7.4 per 1000 PY). The incidence of inapparent primary dengue infection was substantially higher: 41.7 per 1000 PY (95% CI: 31.1, 54.6).

Conclusions: Our findings, highlighting that the incidence of dengue infection is underestimated in Brazil, will inform the design and implementation of future dengue vaccine trials.

Clinical Trial Registration: NCT01751139.
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http://dx.doi.org/10.1016/j.ijid.2021.04.062DOI Listing
July 2021

Seroprevalence, spatial dispersion and factors associated with flavivirus and chikungunha infection in a risk area: a population-based seroprevalence study in Brazil.

BMC Infect Dis 2020 Nov 24;20(1):881. Epub 2020 Nov 24.

Programa de Pós-graduação em Saúde Coletiva, Universidade Federal do Ceará, Fortaleza, CE, Brazil.

Background: The State of Ceará, in Northeastern Brazil, suffers from a triple burden of arboviruses (dengue, Zika and chikungunya). We measured the seroprevalence of chikungunya, dengue and Zika and its associated factors in the population of Juazeiro do Norte, Southern Ceará State, Brazil.

Methods: A cross-sectional study of analytical and spatial analysis was performed to estimate the seroprevalence of dengue, Zika and chikungunya, in the year 2018. Participants were tested for IgM and IgG against these three viruses. Those with IgM and/or IgG positive tests results were considered positive. Poisson regression was used to analyze the factors associated with positive cases, in the same way that the spatial analysis of positive cases was performed to verify whether the cases were grouped.

Results: Of the 404 participants, 25.0% (103/404) were positive for CHIKV, 92.0% (373/404) for flavivirus (dengue or Zika) and of these, 37.9% (153/404) samples were classified as probable dengue infection. Of those who reported having had an arbovirus in the past, positive CHIKV cases had 58.7% arthralgia (PR = 4.31; 95% CI: 2.06-9.03; p = 0.000) mainly in the hands, ankles and feet. Age over 60 years had a positive association with cases of flavivirus (PR = 1.29; 95% CI: 1.09-1.54; p = 0.000). Fever, muscle pain, joint pain and skin rash were the most reported symptoms (46.1, 41.0, 38.3 and 28.41%, respectively). The positive cases of chikungunya and dengue or Zika were grouped in space and the city center was most affected area.

Conclusions: Four years after the introduction of CHIKV, where DENV has been in circulation for over 30 years, 1/4 of the population has already been exposed, showing the extent of the epidemic. The measured prevalence was much higher than that reported by local epidemiological surveillance.
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http://dx.doi.org/10.1186/s12879-020-05611-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685300PMC
November 2020

Tracking excess deaths associated with the COVID-19 epidemic as an epidemiological surveillance strategy-preliminary results of the evaluation of six Brazilian capitals.

Rev Soc Bras Med Trop 2020 6;53:e20200558. Epub 2020 Nov 6.

Universidade Federal do Ceará, Programa de Pós-graduação em Saúde Coletiva, Fortaleza, CE, Brasil.

Introduction: In March 2020, the World Health Organization declared the coronavirus disease (COVID-19) outbreak a pandemic. In Brazil, 110 thousand cases and 5,901 deaths were confirmed by the end of April 2020. The scarcity of laboratory resources, the overload on the service network, and the broad clinical spectrum of the disease make it difficult to document all the deaths due to COVID-19. The aim of this study was to assess the mortality rate in Brazilian capitals with a high incidence of COVID-19.

Methods: We assessed the weekly mortality between epidemiological week 1 and 16 in 2020 and the corresponding period in 2019. We estimated the expected mortality at 95% confidence interval by projecting the mortality in 2019 to the population in 2020, using data from the National Association of Civil Registrars (ARPEN-Brasil).

Results: In the five capitals with the highest incidence of COVID-19, we identified excess deaths during the pandemic. The age group above 60 years was severely affected, while 31% of the excess deaths occurred in the age group of 20-59 years. There was a strong correlation (r = 0.94) between excess deaths and the number of deaths confirmed by epidemiological monitoring. The epidemiological surveillance captured only 52% of all mortality associated with the COVID-19 pandemic in the cities examined.

Conclusions: Considering the simplicity of the method and its low cost, we believe that the assessment of excess mortality associated with the COVID-19 pandemic should be used as a complementary tool for regular epidemiological surveillance.
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http://dx.doi.org/10.1590/0037-8682-0558-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670756PMC
November 2020

Fatal outcome of chikungunya virus infection in Brazil.

Clin Infect Dis 2020 Aug 7. Epub 2020 Aug 7.

Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.

Background: Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused ~2.1 million cases and over 600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological and virus genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil.

Methods: Sera, cerebrospinal fluid (CSF) and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue (DENV) and Zika virus (ZIKV). Clinical, epidemiological and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases.

Results: 68 fatal cases had CHIKV infection confirmed by RT-qPCR (52.9%), viral antigen (41.1%), and/or specific-IgM (63.2%). Co-detection of CHIKV with DENV were found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV-deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the sub-acute phase. Genetic analysis showed circulation of two CHIKV-East Central South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome.

Conclusion: The investigation of the largest cross-sectional cohort of CHIKV-deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and non-risk groups, including young adults.
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http://dx.doi.org/10.1093/cid/ciaa1038DOI Listing
August 2020

Estimated mortality rate and leading causes of death among individuals with chikungunya in 2016 and 2017 in Brazil.

Rev Soc Bras Med Trop 2020 9;53:e20190580. Epub 2020 Apr 9.

Universidade de Brasília, Programa de Pós-Graduação em Medicina Tropical, Brasília, DF, Brasil.

Introduction: In 2014, the first cases of autochthonous chikungunya (CHIK) were recorded in Brazil. Lethality associated with this disease is underestimated. Thus, this study aimed to analyze the causes of death among individuals with CHIK in Brazil.

Methods: A descriptive observational study was conducted on individuals with CHIK who died within 6 months from symptom onset. Data pairing between the Information System for Notifiable Diseases and the Mortality Information System was performed. Deaths were classified according to case confirmation criterion, mention of CHIK in the death certificates (DCs), and disease phase. The lethality rate per 1,000 cases was corrected for underreporting and was estimated according to region, sex, age, years of education, race/color, and cause groups.

Results: We identified 3,135 deaths (mention of CHIK in the DCs, 764 [24.4%]). In 17.6% of these cases, CHIK was the underlying cause. Most deaths occurred in the acute (38.1%) and post-acute (29.6%) phases. The corrected LR (5.7; x1,000) was 6.8 times higher than that obtained from the Information System for Notifiable Diseases (0.8). The highest corrected LRs were estimated for among individuals living in the Northeast region (6.2), men (7.4), those with low years of education and those aged <1 year (8.6), 65-79 years (20.7), and ≥80 years (75.4).

Conclusions: The LR of CHIK estimates based on information system linkage help to reveal the relevance of this disease as the direct cause or as a cause associated with serious or fatal events, provide timely interventions, and increase the knowledge about this disease.
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http://dx.doi.org/10.1590/0037-8682-0580-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182291PMC
April 2020

Assessing the severity of COVID-19.

Epidemiol Serv Saude 2020 04 6;29(2):e2020119. Epub 2020 Apr 6.

Universidade Estadual de Campinas, Departamento de Saúde Coletiva, Campinas, SP, Brasil.

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http://dx.doi.org/10.5123/S1679-49742020000200008DOI Listing
April 2020

Chikungunya Case Classification after the Experience with Dengue Classification: How Much Time Will We Lose?

Am J Trop Med Hyg 2020 02;102(2):257-259

Aggeu Magalhães Institute, Oswaldo Cruz Foundation - FIOCRUZ, Recife, Brazil.

In 2013, cases of chikungunya virus (CHIKV) infection were first detected in the Caribbean. Chikungunya virus rapidly spread through Central and South America, causing explosive outbreaks in naive populations. Since its emergence in 2004, the number of case and series reports describing severe, atypical manifestations seen in chikungunya patients has increased substantially, calling into question whether clinicians and health services are failing to diagnose these atypical cases because of not only insufficient knowledge but also limitations in the case classification. Although this classification based on the duration of the musculoskeletal (acute, subacute, and chronic forms) complaints helped guide therapeutic approaches directed to these manifestations, patients presenting severe or complicated forms, which are less frequent but produce most of the fatal outcomes, were not properly addressed. In Brazil and the Caribbean, a clear temporal and spatial association between excess overall mortality and the occurrence of chikungunya epidemics has been shown, supporting the hypothesis that many of these excess deaths were a consequence of CHIKV infections. Thus, accumulated experience has highlighted that the current chikungunya case classification does not encompass the actual needs presented by certain cases with atypical features nor does it contribute to early detection and management of potentially severe cases. With continued CHIKV circulation in three continents and recent reemergence in Asia and Europe, we need a classification that is prospective and informed both by initial clinical presentation and by progression of signs and symptoms.
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http://dx.doi.org/10.4269/ajtmh.19-0608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008335PMC
February 2020

Biological view of vaccination described by mathematical modellings: from rubella to dengue vaccines.

Math Biosci Eng 2019 04;16(4):3195-3214

Department of epidemiology, Faculty of Medicina São Leopoldo Mandic, Campinas, SP, Brazil.

The only rubella vaccine available in North America is the RA27/3 strain (isolated from the kidney of a rubella-infected fetus and attenuated) licensed in 1979, which substituted HPV77/DE5 strain vaccine due to concerns about waning immunity. The first dengue vaccine (Dengvaxia CYDTDV) was first registered in Mexico in December, 2015, which is a live recombinant tetravalent dengue vaccine. Rubella vaccine was applied since 1969, but tetravalent dengue vaccine is being used in large scale nowadays. In the past, based on unavailable information regarded to rubella vaccine, mathematical models were used to design vaccination schemes in order to avoid congenital rubella syndrome (CRS). Currently, knowing that vaccine does not result in CRS, rubella vaccination is modelled as usual childhood infection. This experience of updated biological knowledge that influenced mathematical modellings of rubella vaccination is taken into account to reflect about the tetravalent dengue vaccine. We also address a discussion about the security of vaccination strategies.
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http://dx.doi.org/10.3934/mbe.2019159DOI Listing
April 2019

ZIKV-Specific NS1 Epitopes as Serological Markers of Acute Zika Virus Infection.

J Infect Dis 2019 06;220(2):203-212

Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.

Background: Zika virus (ZIKV) infections have reemerged as a global health issue due to serious clinical complications. Development of specific serological assays to detect and differentiate ZIKV from other cocirculating flaviviruses for accurate diagnosis remains a challenge.

Methods: We investigated antibody responses in 51 acute ZIKV-infected adult patients from Campinas, Brazil, including 7 pregnant women who later delivered during the study. Using enzyme-linked immunosorbent assays, levels of antibody response were measured and specific epitopes identified.

Results: Several antibody-binding hot spots were identified in ZIKV immunogenic antigens, including membrane, envelope (E) and nonstructural protein 1 (NS1). Interestingly, specific epitopes (2 from E and 2 from NS1) strongly recognized by ZIKV-infected patients' antibodies were identified and were not cross-recognized by dengue virus (DENV)-infected patients' antibodies. Corresponding DENV peptides were not strongly recognized by ZIKV-infected patients' antibodies. Notably, ZIKV-infected pregnant women had specific epitope recognition for ZIKV NS1 (amino acid residues 17-34), which could be a potential serological marker for early ZIKV detection.

Conclusions: This study identified 6 linear ZIKV-specific epitopes for early detection of ZIKV infections. We observed differential epitope recognition between ZIKV-infected and DENV-infected patients. This information will be useful for developing diagnostic methods that differentiate between closely related flaviviruses.
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http://dx.doi.org/10.1093/infdis/jiz092DOI Listing
June 2019

Excess deaths associated with the 2014 chikungunya epidemic in Jamaica.

Pathog Glob Health 2019 02 4;113(1):27-31. Epub 2019 Feb 4.

e Faculdade de Ciências Médicas , Universidade Estadual de Campinas , Campinas , Brasil.

Although traditionally chikungunya virus is considered non-fatal, recent studies suggest that there may be in fact underreporting of deaths in some situations. A major chikungunya epidemic hit Jamaica in 2014 but no chikungunya-associated deaths were reported. We assessed the excess of all-cause deaths during this epidemic. Excess deaths were estimated by difference between observed and expected mortality based on the average age-specific mortality rate of 2012-2013, using the 99% confidence interval. There was an excess of 2,499 deaths during the epidemic (91.9/100,000 population), and a strong positive correlation between the monthly incidence of chikungunya and the excess of deaths (Rho = 0.939, p < 0.005). No significant concomitant epidemiological or climatic phenomenon occurred. Chikungunya is a major contributor to morbidity during epidemics and may be an unrecognized cause of death. Thus, it is urgent to review clinical protocols and improve the investigations of specific-cause deaths during chikungunya epidemics. Excess deaths could be a strategic tool for epidemiological surveillance.
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http://dx.doi.org/10.1080/20477724.2019.1574111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427614PMC
February 2019

Excess Mortality and Causes Associated with Chikungunya, Puerto Rico, 2014-2015.

Emerg Infect Dis 2018 12 17;24(12):2352-2355. Epub 2018 Dec 17.

During 2014-2015, a total of 31 deaths were associated with the first chikungunya epidemic in Puerto Rico. We analyzed excess mortality from various causes for the same months during the previous 4 years and detected 1,310 deaths possibly attributable to chikungunya. Our findings raise important questions about increased mortality rates associated with chikungunya.
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http://dx.doi.org/10.3201/eid2412.170639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256393PMC
December 2018

Excess mortality profile during the Asian genotype chikungunya epidemic in the Dominican Republic, 2014.

Trans R Soc Trop Med Hyg 2018 10;112(10):443-449

State University of Campinas, Faculty of Medical Sciences, Public Health, Campinas, São Paulo.

Background: In 2014 there was a large chikungunya epidemic in the Dominican Republic, with 539 099 reported cases and 6 deaths. Although chikungunya is considered a low-mortality disease, studies have suggested this is an underestimation. This study assessed deaths associated with the epidemic.

Methods: Mortality data were obtained from the National Statistics Office, the surveillance system for acute febrile illnesses, and the National Epidemiological Surveillance System. Expected all-cause mortality by age group was estimated using the years 2010-2012 as the baseline. The excess deaths were calculated as the difference between observed and expected deaths during the epidemic.

Results: The mortality rate increased during the chikungunya epidemic in 2014. There was a strong correlation between monthly excess of deaths and chikungunya cases (Pearson's r=0.89). There was an excess of deaths (>99% confidence interval) among individuals <5 y and >40 y of age. The mortality rates were higher among the elderly. The death excess was 2853. Correcting for the estimated underreporting, there were 4952 deaths during the chikungunya epidemic (49.8 deaths/100 000 population).

Conclusion: This study suggests that chikungunya is an important cause of death (underlying or contributing). It is urgent to review clinical protocols and investigate the causes associated with deaths during chikungunya epidemics.
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http://dx.doi.org/10.1093/trstmh/try072DOI Listing
October 2018

Transmission Dynamics and Disease Severity in Children Infected With East Central South African (ECSA) or ECSA-diverged Clades of Chikungunya Virus.

Clin Infect Dis 2019 01;68(1):171-172

Universidade Federal da Bahia/Instituto de Saúde Coletiva, Rua Basílio da Gama, s/n.Canela, Salvador, Bahia, Brazil.

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http://dx.doi.org/10.1093/cid/ciy534DOI Listing
January 2019

A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus.

Front Bioeng Biotechnol 2018 11;6:31. Epub 2018 Apr 11.

RECOD Laboratory, Institute of Computing (IC), University of Campinas, Campinas, Brazil.

Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus) identification. Reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a "fingerprint" for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening-faster and more accurate-with improved cost-effectiveness when compared to existing technologies.
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http://dx.doi.org/10.3389/fbioe.2018.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904215PMC
April 2018

Efficient detection of Zika virus RNA in patients' blood from the 2016 outbreak in Campinas, Brazil.

Sci Rep 2018 03 5;8(1):4012. Epub 2018 Mar 5.

Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Infection with Zika virus (ZIKV), a mosquito-borne flavivirus has been casually linked with increased congenital microcephaly in Brazil from 2015 through 2016. Sensitive and specific diagnosis of patients with Zika fever (ZIKF) remains critical for patient management. We developed a ZIKV NS5 qRT-PCR assay by combining primers described by Balm et al. and a new Taqman probe. The assay was evaluated and compared with another assay described by Lanciotti et al. (ZIKV 1107) using 51 blood and 42 urine samples from 54 suspected ZIKV patients. ZIKV NS5 performed better in terms of sensitivity with more samples detected as ZIKV-positive (n = 37) than ZIKV 1107 (n = 34) for urine, and ZIKV-positive (n = 29) than ZIKV 1107 (n = 26) for blood. Both assays displayed good overall agreement for urine (κappa = 0.770) and blood (κappa = 0.825) samples. Improved availability of validated diagnostic tests, such ZIKV NS5 qRT-PCR, will be critical to ensure adequate and accurate ZIKV diagnosis.
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http://dx.doi.org/10.1038/s41598-018-22159-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838246PMC
March 2018

Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil.

Front Immunol 2017 8;8:1903. Epub 2018 Jan 8.

Department of Public Health, School of Medical Sciences, University of Campinas, Campinas, Brazil.

Purpose: In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with different predominant virus strains.

Methods: We performed a time trend study to evaluated excess of mortality for pneumonia and influenza, respiratory disease, and all-causes in southern region of Brazil, from 2002 to 2015. After considering other models, we opted for Serfling regression. Excess of death rates per 100,000 inhabitants were analyzed in specific age groups (24-59, 60-69, 70-79, ≥80 years) and by year of occurrence. Mortality information were taken from Brazilian Mortality Information System and etiological data were accessed in Sentinel Virological Surveillance database, getting the weekly positivity of the immunofluorescence tests for influenza A (H1N1, H3N2), and B.

Results: In southern Brazil, there is an evident seasonal pattern of all death outcomes among different age groups in the dry and cold season (April-September). The highest excess mortality rates occurs among older, particularly in years of circulation of influenza AH3N2, especially among people ≥80 years, in 2003 and 2007-years of great severity of influenza activity. After 2009, with the introduction of the pandemic influenza AH1N1, we observed a lower impact on the mortality of the elderly compared to <60 years.

Discussion: A cross reactivity antibody response from past exposure probably provided protection against disease in the elderly. Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance.

Conclusion: The reduced immune response to infection, and to vaccination, and presence of comorbidities recommend a special attention to this age group in Brazil. Besides medical assistance, the timeliness of vaccine campaigns, its composition, and etiological surveillance of respiratory diseases are some of the preventive and public health measures.
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http://dx.doi.org/10.3389/fimmu.2017.01903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767013PMC
January 2018

Excess Mortality Related to Chikungunya Epidemics in the Context of Co-circulation of Other Arboviruses in Brazil.

PLoS Curr 2017 Nov 13;9. Epub 2017 Nov 13.

Department of Public Health, Faculty of Medical Sciences Unicamp, Campinas, SP, Brazil.

Introduction: Chikungunya is an emerging arbovirus that reached the Western Hemisphere at the end of 2013. Studies in the Indian Ocean and India suggest that passive surveillance systems cannot recognize many of deaths associated with chikungunya, which can be inferred by an increase in the overall mortality observed during chikungunya epidemics.

Objective: We assess the mortality associated with chikungunya epidemics in the most affected states in Brazil, from 2015 and 2016.

Methods: We studied the monthly mortality by age group, comparing a period without epidemics to a chikungunya epidemic period, which we defined arbitrarily as consecutive months with incidences of more than 50 cases/100,000 persons.

Results: We obtained official data from the National System of Reported Diseases (SINAN) and the Mortality Information System (SIM), both maintained by the Ministry of Health. We identified a significant increase in the all-cause mortality rate during chikungunya epidemics, while there was no similar mortality in the previous years, even during dengue epidemics. We estimated an excess of 4,505 deaths in Pernambuco during the chikungunya epidemics (47.9 per 100,000 persons).The most affected age groups were the elderly and those under 1 year of age, and the same pattern occurred in all the states.

Discussion: Further studies at other sites are needed to confirm the association between increased mortality and chikungunya epidemics indifferent age groups. If these findings are confirmed, it will be necessary to revise the guidelines to recognize the actual mortality associated with chikungunya and to improve therapeutic approaches and protective measures in the most vulnerable groups.
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http://dx.doi.org/10.1371/currents.outbreaks.14608e586cd321d8d5088652d7a0d884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731794PMC
November 2017

Specific Biomarkers Associated With Neurological Complications and Congenital Central Nervous System Abnormalities From Zika Virus-Infected Patients in Brazil.

J Infect Dis 2017 07;216(2):172-181

Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (Unicamp), São Paulo.

Background: Zika virus (ZIKV) infections have been linked to different levels of clinical outcomes, ranging from mild rash and fever to severe neurological complications and congenital malformations.

Methods: We investigated the clinical and immunological response, focusing on the immune mediators profile in 95 acute ZIKV-infected adult patients from Campinas, Brazil. These patients included 6 pregnant women who later delivered during the course of this study. Clinical observations were recorded during hospitalization. Levels of 45 immune mediators were quantified using multiplex microbead-based immunoassays.

Results: Whereas 11.6% of patients had neurological complications, 88.4% displayed mild disease of rash and fever. Several immune mediators were specifically higher in ZIKV-infected patients, and levels of interleukin 10, interferon gamma-induced protein 10 (IP-10), and hepatocyte growth factor differentiated between patients with or without neurological complications. Interestingly, higher levels of interleukin 22, monocyte chemoattractant protein 1, TNF-α, and IP-10 were observed in ZIKV-infected pregnant women carrying fetuses with fetal growth-associated malformations. Notably, infants with congenital central nervous system deformities had significantly higher levels of interleukin 18 and IP-10 but lower levels of hepatocyte growth factor than those without such abnormalities born to ZIKV-infected mothers.

Conclusions: This study identified several key markers for the control of ZIKV pathogenesis. This will allow a better understanding of the molecular mechanisms of ZIKV infection in patients.
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http://dx.doi.org/10.1093/infdis/jix261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853428PMC
July 2017

Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya.

Mem Inst Oswaldo Cruz 2017 Aug;112(8):583-585

Fundação Oswaldo Cruz-Fiocruz, Campo Grande, MS, Brasil.

Did death occur DUE TO dengue, or in a patient WITH dengue virus infection? It seems a matter of semantics, but in fact, it underscores how challenging it is to distinguish whether the disease contributed to death, or was itself the underlying cause of death. Can a death be attributed to chikungunya virus, when some deaths occur after the acute phase? Did the virus decompensate the underlying diseases, leading to death? Did prolonged hospitalisation lead to infection, resulting in the patient's progression to death? Were there iatrogenic complications during patient care? The dengue question, for which there has not yet been a definitive response, resurfaces prominently under the chikungunya surveillance scenario. We are facing an epidemic of a disease that seems to be more lethal than previously thought. The major challenge ahead is to investigate deaths suspected of occurring due to arbovirus infections and to understand the role of each infection in the unfavourable outcome.
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http://dx.doi.org/10.1590/0074-02760160537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530552PMC
August 2017

Arboviruses emerging in Brazil: challenges for clinic and implications for public health.

Rev Saude Publica 2017 Apr 10;51:30. Epub 2017 Apr 10.

Programa Municipal de Controle de Arboviroses. Departamento de Vigilância em Saúde. Secretaria Municipal de Saúde de Campinas. Campinas, SP, Brasil.

Arboviruses have been emerging in different parts of the world due to genetic changes in the virus, alteration of the host and vector population dynamics, or because of anthropogenic environmental factors. These viruses' capacity for adaptation is notable, as well as the likelihood of their emergence and establishment in new geographic areas. In Brazilian epidemiologic scenario, the most common arboviruses are DENV, CHIKV, and ZIKV, although others may spread in the country. Little is yet known of the impact of viral co-circulation, which would theoretically result in more intense viremia or other immunological alterations that could trigger autoimmune diseases, such as Guillain-Barré syndrome. The impact on morbidity and mortality intensifies as extensive epidemics lead to a high number of affected individuals, severe cases, and implications for health services, mainly due to the absence of treatment, vaccines, and effective prevention and control measures. RESUMO Notifica-se a emergência de arboviroses em diferentes regiões do planeta em decorrência de mudanças genéticas no vírus, alteração da dinâmica populacional de hospedeiros e vetores ou por fatores ambientais de origem antropogênica. É notável a capacidade de adaptação desses vírus e a possibilidade de emergirem e se estabelecerem em novas áreas geográficas. No contexto epidemiológico brasileiro, os arbovírus de maior circulação são DENV, CHIKV e ZIKV, embora existam outros com potencial de disseminação no País. O impacto da cocirculação viral ainda é pouco conhecido, a qual teoricamente resultaria em viremias mais intensas ou outras alterações imunológicas que poderiam ser o gatilho para doenças autoimunes, como a síndrome de Guillain-Barré. O impacto na morbidade e mortalidade se intensifica à medida que extensas epidemias pressupõem grande número de indivíduos acometidos, casos graves e implicações sobre os serviços de saúde, principalmente diante da ausência de tratamento, vacinas e medidas efetivas de prevenção e controle.
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http://dx.doi.org/10.1590/S1518-8787.2017051006889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396504PMC
April 2017

Could clinical symptoms be a predictor of complications in Zika virus infection?

Lancet 2016 Jul;388(10042):338

Laboratory of Spatial Analysis of Epidemiological Data, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.

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http://dx.doi.org/10.1016/S0140-6736(16)31104-7DOI Listing
July 2016

Respiratory syncytial virus seasonality in Brazil: implications for the immunisation policy for at-risk populations.

Mem Inst Oswaldo Cruz 2016 May 29;111(5):294-301. Epub 2016 Mar 29.

Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. The aim of this study was to analyse RSV seasonality in the five distinct regions of Brazil using time series analysis (wavelet and Fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for RSV identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to RSV in children under 5 years old (codes CID-10 J12.1, J20.5, J21.0 and J21.9). A total of 12,501 samples with 11.6% positivity for RSV (95% confidence interval 11 - 12.2), varying between 7.1 and 21.4% in the five Brazilian regions, was analysed. A strong trend for annual cycles with a stable stationary pattern in the five regions was identified through wavelet analysis of the indicators. The timing of RSV activity by Fourier analysis was similar between the two indicators analysed and showed regional differences. This study reinforces the importance of adjusting the immunisation period for high risk population with the monoclonal antibody palivizumab taking into account regional differences in seasonality of RSV.
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http://dx.doi.org/10.1590/0074-02760150341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878298PMC
May 2016

Fitting the Incidence Data from the City of Campinas, Brazil, Based on Dengue Transmission Modellings Considering Time-Dependent Entomological Parameters.

PLoS One 2016 24;11(3):e0152186. Epub 2016 Mar 24.

Coordenadoria de Vigilância Sanitária (COVISA), Campinas, SP, Brazil.

Four time-dependent dengue transmission models are considered in order to fit the incidence data from the City of Campinas, Brazil, recorded from October 1st 1995 to September 30th 2012. The entomological parameters are allowed to depend on temperature and precipitation, while the carrying capacity and the hatching of eggs depend only on precipitation. The whole period of incidence of dengue is split into four periods, due to the fact that the model is formulated considering the circulation of only one serotype. Dengue transmission parameters from human to mosquito and mosquito to human are fitted for each one of the periods. The time varying partial and overall effective reproduction numbers are obtained to explain the incidence of dengue provided by the models.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152186PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807111PMC
August 2016

INTRODUCTION AND TRANSMISSION OF ZIKA VIRUS IN BRAZIL: NEW CHALLENGES FOR THE AMERICAS.

Rev Inst Med Trop Sao Paulo 2016 22;58:24. Epub 2016 Mar 22.

Departamento de Saúde Coletiva, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil,

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http://dx.doi.org/10.1590/S1678-9946201658024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804561PMC
August 2016

Chikungunya in Brazil: an emerging challenge.

Rev Bras Epidemiol 2015 Jan-Mar;18(1):283-5. Epub 2015 Mar 1.

Faculdade São Leopoldo Mandic, Campinas, SP, Brazil.

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http://dx.doi.org/10.1590/1980-5497201500010022DOI Listing
December 2016

Mortality associated with influenza in tropics, state of são paulo, Brazil, from 2002 to 2011: the pre-pandemic, pandemic, and post-pandemic periods.

Influenza Res Treat 2013 12;2013:696274. Epub 2013 Jun 12.

Epidemiology, Department of Public Health, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 126 Tessália Vieira de Camargo, 13083889 Campinas, SP, Brazil ; São Leopoldo Mandic Medical College, Campinas, SP, Brazil ; Campinas Department of Public Health, Campinas, SP, Brazil.

The impact of the seasonal influenza and 2009 AH1N1 pandemic influenza on mortality is not yet completely understood, particularly in tropical and subtropical countries. The trends of influenza related mortality rate in different age groups and different outcomes on a area in tropical and subtropical climate with more than 41 million people (State of São Paulo, Brazil), were studied from 2002 to 2011 were studied. Serfling-type regression analysis was performed using weekly mortality registries and virological data obtained from sentinel surveillance. The prepandemic years presented a well-defined seasonality during winter and a clear relationship between activity of AH3N2 and increase of mortality in all ages, especially in individuals older than 60 years. The mortality due to pneumonia and influenza and respiratory causes associated with 2009 pandemic influenza in the age groups 0-4 years and older than 60 was lower than the previous years. Among people aged 5-19 and 20-59 years the mortality was 2.6 and 4.4 times higher than that in previous periods, respectively. The mortality in all ages was higher than the average of the previous years but was equal mortality in epidemics of AH3N2. The 2009 pandemic influenza mortality showed significant differences compared to other years, especially considering the age groups most affected.
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http://dx.doi.org/10.1155/2013/696274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694379PMC
July 2013

Schistosomal myeloradiculopathy in a low-prevalence area: 27 cases (14 autochthonous) in Campinas, São Paulo, Brazil.

Mem Inst Oswaldo Cruz 2010 Jul;105(4):398-408

Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.

Schistosomal myeloradiculopathy (SMR) is a form of schistosomiasis that is not linked with a high worm burden but rather is found in patients who have been sporadically exposed to Schistosoma mansoni. This paper aims to determine the occurrence of SMR in a low-endemic area with urban transmission in Campinas, São Paulo, Brazil. A retrospective study was performed, identifying confirmed cases in the two largest public hospitals on the region. Patients were diagnosed with SMR using standardised criteria, common clinical parameters, evidence of schistosomal infection and exclusion of other causes of myelopathy. A total of 27 patients were identified; 19 (85.2%) were men and four (14.8%) were women, ranging from 13-57 years of age (mean = 31.2; standard deviation = 12.8). Patients were classified as autochthonous (n = 14; 51.9%) or allochthonous (n = 11; 40.7%) and epidemiological data could not be obtained for two patients (7.4%). The clinical parameters of these patients were not different from previous studies. The sensitivity of serum immune reactions, cerebrospinal fluid immune reactions and parasitological stool examinations in identifying infected individuals was 87.5%, 93.8% and 40%, respectively. The epidemiological importance of these findings and their relationship with the control policies of schistosomiasis are discussed.
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http://dx.doi.org/10.1590/s0074-02762010000400009DOI Listing
July 2010
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