Evidence of Zika Virus Reinfection by Genome Diversity and Antibody Response Analysis, Brazil.

We generated 238 Zika virus (ZIKV) genomes from 135 persons in Brazil who had samples collected over 1 year to evaluate virus persistence. Phylogenetic inference clustered the genomes together with previously reported ZIKV strains from northern Brazil, showing that ZIKV has been remained relatively stable over time. Temporal phylogenetic analysis revealed limited within-host diversity among most ZIKV-persistent infected associated samples. However, we detected unusual virus temporal diversity from >5 persons, uncovering the existence of divergent genomes within the same patient. All those patients showed an increase in neutralizing antibody levels, followed by a decline at the convalescent phase of ZIKV infection. Of interest, in 3 of those patients, titers of neutralizing antibodies increased again after 6 months of ZIKV infection, concomitantly with real-time reverse transcription PCR re-positivity, supporting ZIKV reinfection events. Altogether, our findings provide evidence for the existence of ZIKV reinfection events.

Detection and persistence of Zika virus in body fluids and associated factors: a prospective cohort study.

This study aimed to analyze the detection and duration of the Zika virus (ZIKV) in plasma, urine, saliva, sweat, rectal swabs, vaginal secretions, breast milk, and semen and to explore risk factors associated with prolonged viral persistence. A prospective cohort study of symptomatic patients and their household contacts was conducted in Brazil from July 2017 to June 2019. A total of 260 individuals (184 women and 76 men) with confirmed ZIKV infection were enrolled and followed up for 12 months. ZIKV RNA was present in all body fluid specimens and detectable for extended periods in urine, sweat, rectal swabs, and semen. The longest detection duration was found in semen, with high viral loads in the specimens. ZIKV RNA clearance was associated with several factors, including age, sex, education level, body mass index, non-purulent conjunctivitis, joint pain, and whether the participant had a history of yellow fever vaccination. The influence of each of these factors on the low or fast viral clearance varied according to the specific body fluid under investigation. Recurrent ZIKV detection events after total viral clearance were observed in the cohort. Our findings provide valuable insights into the persistence and potential recurrence of ZIKV infection, highlighting the need for continued monitoring and follow-up of individuals infected with ZIKV and for effective prevention measures to reduce the risk of transmission.

An initiative of cooperation in Zika virus research: the experience of the ZIKABRA study in Brazil.

BACKGROUND: The Zika virus outbreak has triggered a set of local and global actions for a rapid, effective, and timely public health response. A World Health Organization (WHO) initiative, supported by the Department of Chronic Condition Diseases and Sexually Transmitted Infections (DCCI) of the Health Surveillance Secretariat (SVS), Brazil Ministry of Health (MoH) and other public health funders, resulted in the start of the "Study on the persistence of Zika virus in body fluids of patients with ZIKV infection in Brazil - ZIKABRA study". The ZIKABRA study was designed to increase understanding of how long ZIKV persists in bodily fluids and informing best measures to prevent its transmission. Data collection began in July 2017 and the last follow up visit occurred in 06/26/2020. METHODS: A framework for the ZIKABRA Cooperation initiative is provided through a description and analysis of the mechanisms, strategies and the ethos that have guided the models of international governance and technical cooperation in health for scientific exchange in the context of a public health emergency. Among the methodological strategies, we included a review of the legal documents that supported the ZIKABRA Cooperation; weekly documents produced in the meetings and working sessions; technical reports; memorandum of understanding and the research protocol. CONCLUSION: We highlight the importance of working in cooperation between different institutional actors to achieve more significant results than that obtained by each group working in isolation. In addition, we point out the advantages of training activities, ongoing supervision, the construction of local installed research capacity, training academic and non-academic human resources, improvement of laboratory equipment, knowledge transfer and the availability of the ZIKABRA study protocol for development of similar studies, favoring the collective construction of knowledge to provide public health emergency responses. Strategy harmonization; human resources and health services; timing and recruiting particularities and processing institutional clearance in the different sites can be mentioned as challenges in this type of initiative.

Zika virus RNA excretion in sweat with concomitant detection in other body fluid specimens.

We evaluated sweat, blood and urine specimens obtained from an ongoing cohort study in Brazil. Samples were collected at pre-established intervals after the initial rash presentation and tested for Zika virus (ZIKV) RNA presence by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 254 participants with confirmed infection, ZIKV RNA was detected in the sweat of 46 individuals (18.1%). Sweat presented a median cycle threshold (Ct) of 34.74 [interquartile range (IQR) 33.44-36.04], comparable to plasma (Ct 35.96 - IQR 33.29-36.69) and higher than urine (Ct 30.78 - IQR 28.72-33.22). Concomitant detection with other specimens was observed in 33 (72%) of 46 participants who had a positive result in sweat. These findings represent an unusual and not yet investigated virus shedding through eccrine glands.

Cohort profile: Study on Zika virus infection in Brazil (ZIKABRA study).

Zika virus (ZIKV) has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood to one week after the onset of symptoms and has been found to persist longer in urine and semen. To better understand virus dynamics, a prospective cohort study was conducted in Brazil to assess the presence and duration of ZIKV and related markers (viral RNA, antibodies, T cell response, and innate immunity) in blood, semen, saliva, urine, vaginal secretions/menstrual blood, rectal swab and sweat. The objective of the current manuscript is to describe the cohort, including an overview of the collected data and a description of the baseline characteristics of the participants. Men and women ≥ 18 years with acute illness and their symptomatic and asymptomatic household contacts with positive reverse transcriptase-polymerase chain reaction test for ZIKV in blood and/or urine were included. All participants were followed up for 12 months. From July 2017 to June 2019, a total of 786 participants (284 men, 502 women) were screened. Of these, 260 (33.1%) were enrolled in the study; index cases: 64 men (24.6%), 162 (62.3%) women; household contacts: 12 men (4.6%), 22 (8.5%) women. There was a statistically significant difference in age and sex between enrolled and not enrolled participants (p<0.005). Baseline sociodemographic and medical data were collected at enrollment from all participants. The median and interquartile range (IQR) age was 35 (IQR; 25.3, 43) for men and 36.5 years (IQR; 28, 47) for women. Following rash, which was one of the inclusion criteria for index cases, the most reported symptoms in the enrollment visit since the onset of the disease were fever, itching, arthralgia with or without edema, non-purulent conjunctivitis, headache, and myalgia. Ten hospitalizations were reported by eight patients (two patients were hospitalized twice) during follow up, after a median of 108 days following symptom onset (range 7 to 266 days) and with a median of 1.5 days (range 1 to 20 days) of hospital stay. A total of 4,137 visits were performed, 223 (85.8%) participants have attended all visits and 37 (14.2%) patients were discontinued.

Syphilis prevalence and risk factors among young men presenting to the Brazilian Army in 2016: Results from a national survey.

The Conscripts Survey has been conducted periodically by the Brazilian Department of Sexually Transmitted Infections (STIs), AIDS, and Viral Hepatitis (DIAHV) in collaboration with the Brazilian Ministry of Defense for over 2 decades. It aims to assess the syphilis prevalence and obtain data on knowledge regarding STIs and their risk factors among conscripts enlisted for the Brazilian Army.This cross-sectional study was conducted among conscripts across Brazil aged 17 to 22 years from August to December 2016. It included a self-reported questionnaire and blood testing for syphilis, HIV, and hepatitis B and C.In total 38,247 conscripts were enrolled; after exclusion due to a lack of information, 37,282 (93.2%) conscripts were included. The estimated syphilis prevalence rates were: 1.63%, 1.09%, and 0.62% for screened, confirmed, and active syphilis, respectively. Among those with active syphilis, 81.1% reported not having syphilis infection in their lifetime. Higher confirmed syphilis prevalence rates were observed in the South region, followed by North and Southeast regions. Independent factors associated with confirmed syphilis infection were: self-reported STIs in one's lifetime (odds ratio [OR] = 7.24; P < .001), same-sex sexual relationships (OR = 3.43; P = .001), and having the 1st sexual intercourse encounter before 15 years of age (OR = 2.62; P = .04). The proportion of conscripts who reported having sex with other men (MSM) was 4.3%, and the estimated syphilis prevalence in this group was 5.23%, 4.61%, and 3.60% for screened, confirmed, and active syphilis, respectively. The sexual behaviors most frequently associated with confirmed syphilis were: sexual relationship with casual partners in the last year (P < .001), same-sex sexual relationships (P < .001), more than 10 partners (P = .006), and having sexual intercourse before 15 years of age (P = .003). Although not significant, only 25.4% of the conscripts who had a confirmed syphilis reported the use of condoms with steady partners, 32.4% with casual partner, and 24.3% with any partner.We found that syphilis is on the rise among the young Brazilian male population. The increase in its prevalence, particularly among MSM, highlights the need for urgent public health interventions, action plans, and implementation of risk reduction strategies aimed at this population.

Study on the persistence of Zika virus (ZIKV) in body fluids of patients with ZIKV infection in Brazil.

BACKGROUND: Zika virus (ZIKV) has been identified in several body fluids of infected individuals. In most cases, it remained detected in blood from few days to 1 week after the onset of symptoms, and can persist longer in urine and in semen. ZIKV infection can have dramatic consequences such as microcephaly and Guillain-Barré syndrome. ZIKV sexual transmission has been documented. A better understanding of ZIKV presence and persistence across biologic compartments is needed to devise rational measures to prevent its transmission. METHODS: This observational cohort study will recruit non-pregnant participants aged 18 years and above with confirmed ZIKV infection [positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in blood and/or urine]: symptomatic men and women in ZIKV infection acute phase, and their symptomatic or asymptomatic household/sexual infected contacts. Specimens of blood, urine, semen, vaginal secretion/menstrual blood, rectal swab, oral fluids, tears, sweat, urine and breast milk (if applicable) will be collected at pre-established intervals and tested for ZIKV RNA presence by RT-PCR, other co-infection (dengue, Chikungunya, HIV, hepatitis B and C, syphilis), antibody response (including immunoglobulins M and G), plaque reduction neutralization test (if simultaneously positive for ZIKV and dengue), and ZIKV culture and RNA sequencing. Data on socio-demographic characteristics and comorbidities will be collected in parallel. Participants will be followed up for 12 months. DISCUSSION: This prolonged longitudinal follow-up of ZIKV infected persons with regular biologic testing and data collection will offer a unique opportunity to investigate the presence and persistence of ZIKV in various biologic compartments, their clinical and immunological correlates as well as the possibility of ZIKV reactivation/reinfection over time. This valuable information will substantially contribute to the body of knowledge on ZIKV infection and serve as a base for the development of more effective recommendation on the prevention of ZIKV transmission. TRIAL REGISTRATION: NCT03106714 . Registration Date: April, 7, 2017.

Prevalence of papillomavirus in Brazil: a systematic review protocol.

INTRODUCTION: Human papillomavirus (HPV) infection is a cause of premalignant and malignant cancer in the lower genital and digestive tracts. In Brazil, there have been no prevalence studies that included a nationwide sample, and the prevalence of HPV has not been determined in many regions. METHODS: We will search the EMBASE, LILACS, MEDLINE, Web of Science and SciELO databases and previously published review articles to identify original research articles assessing HPV prevalence of the perineal (cervical, penile and anal) and oral areas. No exclusion criteria related to language or publication date will apply. 2 reviewers will independently screen for eligibility and perform data extraction. Discrepancies will be resolved through consensus; the opinion of a third reviewer will be sought as necessary. Relevant measures and data about study and population characteristics will be extracted from the included studies. Where possible, study prevalence will be pooled using a random-effects meta-analysis. The methodological quality of the studies will be assessed using an adapted version of the NIH 'Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies'. The overall quality of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). ETHICS AND DISSEMINATION: We expect to estimate the prevalence of perineal and oral HPV infection in the general population as well as the prevalence of HPV infection in individuals with premalignant and malignant lesions in Brazil and its 5 geographic regions. This systematic review does not require ethical approval. TRIAL REGISTRATION NUMBER: CRD42016032751.

Clinical investigations for SUS, the Brazilian public health system.

CONTEXT AND OBJECTIVE: Scientific and technological development is crucial for advancing the Brazilian health system and for promoting quality of life. The way in which the Brazilian Ministry of Health has supported clinical research to provide autonomy, self-sufficiency, competitiveness and innovation for the healthcare industrial production complex, in accordance with the National Policy on Science, Technology and Innovation in Healthcare, was analyzed. DESIGN AND SETTING: Descriptive investigation, based on secondary data, conducted at the Department of Science and Technology, Ministry of Health. METHODS: The Ministry of Health's research management database, PesquisaSaúde, was analyzed from 2002 to 2009, using the key word "clinical research" in the fields "primary sub-agenda" or "secondary sub-agenda". The 368 projects retrieved were sorted into six categories: basic biomedical research, preclinical studies, expanded clinical research, clinical trials, infrastructure support and health technology assessment. From a structured review on "clinical research funding", results from selected countries are presented and discussed. RESULTS: The amount invested was R$ 140 million. The largest number of projects supported "basic biomedical research", while the highest amounts invested were in "clinical trials" and "infrastructure support". The southeastern region had the greatest proportion of projects and financial resources. In some respects, Brazil is ahead of other BRICS countries (Russia, India, China and South Africa), especially with regard to establishing a National Clinical Research Network. CONCLUSION: The Ministry of Health ensured investments to encourage clinical research in Brazil and contributed towards promoting cohesion between investigators, health policies and the healthcare industrial production complex.

Association of human T lymphotropic virus 1 amplification of periodontitis severity with altered cytokine expression in response to a standard periodontopathogen infection.

BACKGROUND: Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. METHODS: In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1-seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1-seronegative individuals (control group). RESULTS: Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor alpha and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. CONCLUSIONS: HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.

Freqüência de doenças reumáticas em indivíduos infectados pelo HTLV-1 / Frequency of rheumatic diseases in individuals infected with HTLV-1

INTRODUÇÃO: o HTLV-1 é um retrovírus humano associado à leucemia de células T do adulto e à mielopatia associada ao HTLV-1 ou paraparesia espástica tropical, que tem sido implicado também no desenvolvimento de auto-imunidade. OBJETIVO: o objetivo deste estudo foi determinar a freqüência de doenças reumáticas auto-imunes em pacientes infectados pelo HTLV-1. PACIENTES E MÉTODOS: foram incluídos nesse estudo 137 indivíduos infectados pelo HTLV-1 atendidos no Ambulatório Multidisciplinar do Serviço de Imunologia do Hospital Universitário Professor Edgard Santos (HUPES) da Universidade Federal da Bahia (UFBA), no período de janeiro de 2003 a maio de 2004. Os pacientes responderam a um questionário geral relacionado a manifestações reumatológicas e questionários específicos para confirmação dos critérios diagnósticos de artrite reumatóide (AR), lúpus eritematoso sistêmico (LES), síndrome de Sjõgren e polimiosite. Adicionalmente, todos eles foram submetidos a exames clínicos específicos e avaliação complementar. RESUTADOS: 24 pacientes tiveram o diagnóstico de síndrome de Sjõgren (SS) provável (17,5 por cento), 18 pacientes (13,1 por cento) de AR, uma paciente teve diagnóstico de LES e uma de doença mista do tecido conjuntivo (0,7 por cento, respectivamente). Suspeita de artropatia relacionada ao vírus foi encontrada em 22 pacientes (16,1 por cento). Síndrome de Sjõgren e AR foram mais freqüentes nos pacientes com mielopatia (33,3 e 25,9 por cento, respectivamente) do que nos portadores assintomáticos (13,6 e 10 por cento, respectivamente). Artropatia relacionada ao HTLV-1 ocorreu com freqüência semelhante em ambos os grupos. CONCLUSÃO: foi observado neste trabalho alta prevalência de síndrome de Sjõgren e de AR entre os indivíduos infectados pelo HTLV-1, principalmente naqueles com mielopatia. Diante desses resultados, que reforçam os dados da literatura, deve-se estar atento para a ocorrência de doenças reumáticas auto-imunes nesses pacientes.

INTRODUCTION: the HTLV-1 is a human retrovirus associated with adult T-cell leukaemia (ATL) and with HTLV-1- associated myelopathy or tropical spastic paraparesis, which has also been implicated in the development of autoimmunity. OBJECTIVE: the aim of this study was to determine the frequency of autoimmune rheumatic diseases in patients infected with HTLV-1. PATIENTS AND METHODS: it was included 137 individuals infected with HTLV-1 from the Multidisciplinary Ambulatory of Immunology Service, HUPES-UFBA, Salvador (BA), from January 2003 to May 2004. All participants answered to a general questionnaire regarding rheumathological manifestations and specific questionnaires to confirm the diagnose criteria of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), SjõgrenÆs syndrome (SS) and polymyositis. Additionally, they were submitted to specific clinical exams, besides complementary evaluations. RESULTS: 24 patients had diagnose of probable SjõgrenÆs syndrome (17.5 percent), 18 patients (13.1 percent) had RA, one patient had diagnose of SLE (0.7 percent) and another of mixed connective tissue disease (0.7 percent, respectively). HTLV-1-associated arthropathy (HAAP) was suspected in 22 individuals (16.1 percent). SjõgrenÆs syndrome and RA were more frequent in patients with myelopathy (33.3 and 25.9 percent, respectively) than in asymptomatic carriers (13.6 and 10 percent, respectively). The frequency of HTLV-1-associated arthropathy was the same in both groups. CONCLUSION: in this study it was observed a high frequency of SjõgrenÆs syndrome and RA in individuals infected with HTLV-1, mainly in those with myelopathy. Therefore, with this results that support data in the literature, we should call attention to the occurrence of autoimmune rheumatic diseases in these kind of patients.