RESUMO
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.
Assuntos
Infecção por Zika virus , Zika virus , Humanos , Zika virus/genética , Infecção por Zika virus/epidemiologia , Formação de Anticorpos , Brasil/epidemiologia , Filogenia , Reinfecção , Anticorpos NeutralizantesRESUMO
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.
Assuntos
Líquidos Corporais , Infecção por Zika virus , Zika virus , Masculino , Humanos , Feminino , Zika virus/genética , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Estudos Prospectivos , RNA ViralRESUMO
Oropharyngeal dysphagia (OD) is a swallowing disorder that involves difficulty in safely passing the food bolus from the oral cavity to the stomach. OD is a common problem in children with congenital Zika virus syndrome (CZS). In this case series, we describe the clinical and acoustic alterations of swallowing in children exposed to the Zika virus during pregnancy in a cohort from Amazonas, Brazil. From July 2019 to January 2020, 22 children were evaluated, 6 with microcephaly and 16 without microcephaly. The mean age among the participants was 35 months (±4.6 months). All children with microcephaly had alterations in oral motricity, mainly in the lips and cheeks. Other alterations were in vocal quality, hard palate, and soft palate. Half of the children with microcephaly showed changes in cervical auscultation during breast milk swallowing. In children without microcephaly, the most frequently observed alteration was in lip motricity, but alterations in auscultation during the swallowing of breast milk were not observed. Regarding swallowing food of a liquid and pasty consistency, the most frequent alterations were incomplete verbal closure, increased oral transit time, inadequacy in capturing the spoon, anterior labial leakage, and increased oral transit time. Although these events are more frequent in microcephalic children, they can also be seen in non-microcephalic children, which points to the need for an indistinct evaluation of children exposed in utero to ZIKV.
Assuntos
Microcefalia , Malformações do Sistema Nervoso , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Gravidez , Criança , Feminino , Humanos , Lactente , Pré-Escolar , Infecção por Zika virus/complicações , Infecção por Zika virus/congênito , Deglutição , Brasil/epidemiologiaRESUMO
OBJECTIVE: Emergency contraception (EC) is an effective and safe method for preventing unplanned pregnancy after unprotected sexual intercourse among adolescents but is infrequently prescribed by pediatricians. Because of the scarcity of data on the discomfort with EC prescription among physicians in Brazil, this study aimed to identify associated factors with discomfort with EC prescription among pediatricians in the state of Amazonas. METHODS: A web-based, cross-sectional study including sociodemographic data, knowledge, attitudes, and discomfort with EC prescription was used. Multivariate logistic regression and artificial intelligence methods such as decision tree and random forest analysis were used to identify factors associated with discomfort with EC prescriptions. RESULTS: Among 151 physicians who responded to the survey, 53.0% were uncomfortable with prescribing EC, whereas only 33.1% had already prescribed it. Inexperience was significantly associated with discomfort with EC prescription (odds ratio 4.47, 95% confidence interval 1.71-11.66). Previous EC prescription was protective against discomfort with EC prescription in the three models. CONCLUSIONS: EC is still infrequently prescribed by pediatricians because of inexperience and misconceptions. Training these professionals needs to be implemented as part of public health policies to reduce unplanned adolescent pregnancy.
Assuntos
Anticoncepção Pós-Coito , Gravidez , Feminino , Humanos , Adolescente , Inteligência Artificial , Estudos Transversais , Inquéritos e Questionários , Pediatras , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
The high incidence of Zika virus (ZIKV) infection in the period of 2015-2016 in Brazil may have affected linear height growth velocity (GV) in children exposed in utero to ZIKV. This study describes the growth velocity and nutritional status based on the World Organization (WHO) standards of children exposed to ZIKV during pregnancy and followed up in a tertiary unit, a reference for tropical and infectious diseases in the Amazon. Seventy-one children born between March 2016 and June 2018 were monitored for anthropometric indices: z-score for body mass index (BMI/A); weight (W/A); height (H/A) and head circumference (HC/A); and growth velocity. The mean age at the last assessment was 21.1 months (SD ± 8.93). Four children had congenital microcephaly and severe neurological impairment. The other 67 were non-microcephalic children (60 normocephalic and 7 macrocephalic); of these; 24.2% (16 children) had neurological alterations, and 28.8% (19 children) had altered neuropsychomotor development. Seventeen (24.2%) children had inadequate GV (low growth velocity). The frequencies of low growth among microcephalic and non-microcephalic patients are 25% (1 of 4 children) and 23.9% (16 of 67 children); respectively. Most children had normal BMI/A values during follow-up. Microcephalic patients showed low H/A and HC/A throughout the follow-up, with a significant reduction in the HC/A z-score. Non-microcephalic individuals are within the regular ranges for H/A; HC/A; and W/A, except for the H/A score for boys. This study showed low growth velocity in children with and without microcephaly, highlighting the need for continuous evaluation of all children born to mothers exposed to ZIKV during pregnancy.
Assuntos
Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Gravidez , Masculino , Feminino , Humanos , Criança , Lactente , Infecção por Zika virus/complicações , Estado Nutricional , Brasil/epidemiologiaRESUMO
Abstract Objective: Emergency contraception (EC) is an effective and safe method for preventing unplanned pregnancy after unprotected sexual intercourse among adolescents but is infrequently prescribed by pediatricians. Because of the scarcity of data on the discomfort with EC prescription among physicians in Brazil, this study aimed to identify associated factors with discomfort with EC prescription among pediatricians in the state of Amazonas. Methods: A web-based, cross-sectional study including sociodemographic data, knowledge, attitudes, and discomfort with EC prescription was used. Multivariate logistic regression and artificial intelligence methods such as decision tree and random forest analysis were used to identify factors associated with discomfort with EC prescriptions. Results: Among 151 physicians who responded to the survey, 53.0% were uncomfortable with prescribing EC, whereas only 33.1% had already prescribed it. Inexperience was significantly associated with discomfort with EC prescription (odds ratio 4.47, 95% confidence interval 1.71-11.66). Previous EC prescription was protective against discomfort with EC prescription in the three models. Conclusions: EC is still infrequently prescribed by pediatricians because of inexperience and misconceptions. Training these professionals needs to be implemented as part of public health policies to reduce unplanned adolescent pregnancy.
RESUMO Objetivo: A contracepção de emergência (CE) é um método eficaz e seguro para prevenir gravidez não planejada após relação sexual desprotegida entre adolescentes, mas raramente prescrito por pediatras. Diante da escassez de dados sobre o desconforto com a prescrição de CE entre médicos no Brasil, o objetivo deste estudo foi identificar fatores associados a esse desconforto entre pediatras do estado do Amazonas. Métodos: Uma pesquisa do tipo e-survey coletou dados sociodemográficos, conhecimento, atitudes e desconforto com relação à prescrição de CE. Métodos de regressão logística multivariada e inteligência artificial, como árvore de decisão e random forest, foram usados para identificar fatores associados ao desconforto para a prescrição de CE. Resultados: Entre os 151 médicos que responderam à pesquisa, 53,0% sentiam-se desconfortáveis para prescrever CE e apenas 33,1% já a haviam prescrito. A inexperiência foi associada a esse desconforto (odds ratio — OR 4,47, intervalo de confiança — IC95% 1,71-11,66). A prescrição prévia de CE foi fator de proteção com relação ao desconforto nos três modelos. Conclusões: A CE ainda é pouco prescrita por pediatras. Apesar de sua segurança e eficácia, a inexperiência e conceitos equivocados foram associados ao desconforto para sua prescrição. Investigações sobre o assunto são importantes para subsidiar políticas públicas de saúde para a redução da gravidez não intencional na adolescência.
RESUMO
Infections with Flavivirus in pregnant women are not associated with vertical transmission. However, in 2015, severe cases of congenital infection were reported during the Zika virus outbreak in Brazil. More subtle infections in children born to mothers with ZIKV still remain uncertain and the spectrum of this new congenital syndrome is still under construction. This study describes outcomes regarding neurodevelopment and neurological examination in the first years of life, of a cohort of 77 children born to pregnant women with ZIKV infection in Manaus, Brazil, from 2017 to 2020. In the group of normocephalic children (92.2%), most showed satisfactory performance in neuropsychomotor development, with a delay in 29.6% and changes in neurological examination in 27.1%, with two children showing muscle-strength deficits. All microcephalic children (5.2%) evolved with severe neuropsychomotor-development delay, spastic tetraparesis, and alterations in the imaging exam. In this cohort, 10.5% of the children had macrocephaly at birth, but only 2.6% remained in this classification. Although microcephaly has been considered as the main marker of congenital-Zika-virus syndrome in previous studies, its absence does not exclude the possibility of the syndrome. This highlights the importance of clinical follow-up, regardless of the classification of head circumference at birth.
Assuntos
Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Recém-Nascido , Humanos , Criança , Gravidez , Feminino , Lactente , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/complicações , Brasil/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , PrognósticoRESUMO
BACKGROUND: In the clinical course of diseases such as arboviruses, skin rashes may appear, as is often seen in other infectious diseases. The aim of this study was to estimate the prevalence of arboviruses and other infectious causes of skin rash in a tertiary health unit in Manaus, Amazonas state, Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: This was a cross-sectional study of patients presenting with rash who sought care at Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) from February 2018 to May 2019. Individuals of either gender, aged over 18 years, were invited to participate voluntarily. Infection by Zika virus (ZIKV), dengue virus (DENV), chikungunya virus (CHIKV), Mayaro virus (MAYV), Oropouche virus (OROV) and measles was evaluated using RT-qPCR (real-time polymerase chain reaction). Immunodiagnostic tests for EBV, CMV, HIV, syphilis, rubella and measles were also performed. A total of 340 participants were included, most were female (228, 67.1%) with an average age of 36.5 years (SD ± 12.2 years). The highest prevalence was of ZIKV monoinfections (65.3%, 222/340), followed by DENV (0.9%, 3/340) and CHIKV infection (0.3%, 1/340). No cases of MAYV, OROV or rubella were found. Other causes of skin rash were detected: measles (2.9%, 10/340), parvovirus B19 (0.9% 3/340), HIV (0.3%, 1/340) and syphilis 0.6% (2/340). The co-infections identified were ZIKV+HIV (0.3%, 1/340), ZIKV+measles (0.3%, 1/340), ZIKV+parvovirus B19 (0.3%, 1/340), ZIKV+EBV (0.3%, 1/340), EBV+parvovirus B19 (0.3%, 1/340), CMV+parvovirus B19 (0.6%, 2/340), CMV+syphilis (0.3%, 1/340), ZIKV+EBV+parvovirus B19 (0.3%, 1/340) and CMV+EBV+parvovirus B19 (0.9%, 3/340). Approximately one quarter of patients had no defined cause for their skin rash (25.3%, 86/340). CONCLUSIONS: Despite the benign clinical evolution of most of the diseases diagnosed in this series of cases, syndromic surveillance of diseases such as syphilis and HIV are of utmost importance. Periodic serosurveillance might also aid in evaluating the trends of endemic diseases and eventual outbreaks.
Assuntos
Arbovírus , Febre de Chikungunya , Infecções por Citomegalovirus , Dengue , Exantema , Infecções por HIV , Sarampo , Rubéola (Sarampo Alemão) , Sífilis , Infecção por Zika virus , Zika virus , Adulto , Brasil/epidemiologia , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Estudos Transversais , Dengue/diagnóstico , Dengue/epidemiologia , Exantema/epidemiologia , Exantema/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologiaRESUMO
BACKGROUND: Zika virus infection is commonly described as a mild and self-limiting illness. However, cardiac complications were associated with acute Zika virus infection. CASE PRESENTATION: A 46-year-old woman without previous comorbidities with a 1-day history of symptoms tested positive for ZIKV by real time reverse transcriptase polymerase chain reaction (rRT-PCR). She was admitted two days after with clinical worsening, cardiac enzymes elevated, and cardiac imaging findings, and the diagnosis of myopericarditis was made. The patient was treated and presented significant clinical improvement after one year. CONCLUSIONS: Cardiac complication following ZIKV infection appears to be infrequent. Here, we report a rare case of viral myopericarditis caused by ZIKV infection.
Assuntos
Infecção por Zika virus , Zika virus , Feminino , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Zika virus/genética , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnósticoRESUMO
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.
Assuntos
Infecção por Zika virus , Zika virus , Brasil/epidemiologia , Surtos de Doenças/prevenção & controle , Humanos , Saúde Pública , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controleRESUMO
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.
Assuntos
RNA Viral/genética , Suor/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Sangue/virologia , Brasil/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , RNA Viral/classificação , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Urina/virologia , Zika virus/genética , Infecção por Zika virus/epidemiologiaRESUMO
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.
Assuntos
Leite Humano/virologia , RNA Viral/sangue , Saliva/virologia , Infecção por Zika virus/virologia , Zika virus/isolamento & purificação , Adulto , Brasil , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carga Viral , Eliminação de Partículas Virais , Adulto JovemRESUMO
The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in the babies of ZIKV-infected women. The frequency of adverse outcomes of Zika virus infection (ZIKVi) in pregnancy differs depending on the characteristics of exposure to infection, the time of recruitment of research participants, and the outcomes to be observed. This study provides a descriptive analysis-from the onset of symptoms to delivery-of a cohort registered as having maternal ZIKVi in pregnancy, from November 2015 to December 2016. Suspected cases were registered at a referral center for infectious and tropical diseases in Manaus, in the Amazonian region of Brazil. Of 834 women notified, 762 women with confirmed pregnancies were enrolled. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed ZIKVi in 42.3% of the cohort. In 35.2% of the cohort, ZIKV was the sole infection identified. Severe adverse pregnancy outcomes (miscarriage, stillbirth, or microcephaly) were observed in both RT-PCR ZIKV-positive (5.0%) and ZIKV-negative (1.8%) cases (RR 3.1; 95% IC 1.4-7.3; p < 0.05), especially during the first trimester of pregnancy (RR 6.2, 95% IC 2.3-16.5; p < 0.001). Although other infectious rash diseases were observed in the pregnant women in the study, having confirmed maternal ZIKVi was the most important risk factor for serious adverse pregnancy events.
Assuntos
Exantema/epidemiologia , Exantema/etiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Zika virus/fisiologia , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Avaliação de Resultados da Assistência ao Paciente , Gravidez , Análise Espaço-Temporal , Adulto Jovem , Infecção por Zika virus/virologiaRESUMO
Cryptic Plasmodium niches outside the liver possibly represent a major source of hypnozoite-unrelated recrudescences in malaria. Maurizio Ascoli, an Italian physician and scientist, suggested that infection was maintained as a result of the persistence of endoerythrocytic parasites in the circulatory bed of some internal organs, mainly the spleen. This would explain a proportion of the recurrences in patients, regardless of the Plasmodium species. Ascoli proposed a method that included the co-administration of adrenaline, in order to induce splenic contraction, and quinine to clear expelled forms in major vessels. Driven by controversy regarding safety and effectiveness, along with the introduction of new drugs, the Ascoli method was abandoned and mostly forgotten by the malaria research community. To date, however, the existence of cryptic parasites outside the liver is gaining supportive data. This work is a historical retrospective of cryptic malaria infections and the Ascoli method, highlighting key knowledge gaps regarding these possible parasite reservoirs.
Assuntos
Antimaláricos/administração & dosagem , Infecções Assintomáticas , Epinefrina/administração & dosagem , Malária/prevenção & controle , Quinina/administração & dosagem , Baço/efeitos dos fármacos , Doença Crônica/prevenção & controle , História do Século XXRESUMO
The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil.
Assuntos
Transtornos do Neurodesenvolvimento/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Zika virus/patogenicidade , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Microcefalia , Mães , Transtornos do Neurodesenvolvimento/virologia , Exame Neurológico , Gravidez , Adulto Jovem , Infecção por Zika virus/fisiopatologiaRESUMO
The immune status of women changes during and after pregnancy, differs between blood compartments at delivery and is affected by environmental factors particularly in tropical areas endemic for multiple infections. We quantified the plasma concentration of a set of thirty-one TH1, TH2, TH17 and regulatory cytokines, pro-inflammatory and anti-inflammatory cytokines and chemokines, and growth factors (altogether biomarkers), in a cohort of 540 pregnant women from five malaria-endemic tropical countries. Samples were collected at recruitment (first antenatal visit), delivery (periphery, cord and placenta) and postpartum, allowing a longitudinal analysis. We found the lowest concentration of biomarkers at recruitment and the highest at postpartum, with few exceptions. Among them, IL-6, HGF and TGF-ß had the highest levels at delivery, and even higher concentrations in the placenta compared to peripheral blood. Placental concentrations were generally higher than peripheral, except for eotaxin that was lower. We also compared plasma biomarker concentrations between the tropical cohort and a control group from Spain at delivery, presenting overall higher biomarker levels the tropical cohort, particularly pro-inflammatory cytokines and growth factors. Only IL-6 presented lower levels in the tropical group. Moreover, a principal component analysis of biomarker concentrations at delivery showed that women from Spain grouped more homogenously, and that IL-6 and IL-8 clustered together in the tropical cohort but not in the Spanish one. Plasma cytokine concentrations correlated with Plasmodium antibody levels at postpartum but not during pregnancy. This basal profiling of immune mediators over gestation and in different compartments at delivery is important to subsequently understand response to infections and clinical outcomes in mothers and infants in tropical areas.
Assuntos
Quimiocinas/sangue , Citocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Malária/sangue , Malária/imunologia , Plasmodium/imunologia , Complicações Parasitárias na Gravidez/sangue , Adulto , Brasil/epidemiologia , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Guatemala/epidemiologia , Fator de Crescimento de Hepatócito/sangue , Humanos , Imunoglobulina G/imunologia , Índia/epidemiologia , Interleucina-6/sangue , Interleucina-8/sangue , Malária/parasitologia , Papua Nova Guiné/epidemiologia , Placenta/metabolismo , Gravidez , Gestantes , Espanha , Fator de Crescimento Transformador beta/sangueRESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Adulto , Suor/virologia , RNA Viral/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Urina/virologia , Sangue/virologia , Brasil/epidemiologia , RNA Viral/isolamento & purificação , RNA Viral/classificação , Estudos de Coortes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Reação em Cadeia da Polimerase em Tempo Real , Zika virus/genética , Infecção por Zika virus/epidemiologiaRESUMO
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.
Assuntos
Líquidos Corporais/virologia , Infecção por Zika virus/virologia , Zika virus/patogenicidade , Adulto , Brasil , Febre de Chikungunya/virologia , Estudos de Coortes , Coinfecção , Dengue/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Leite Humano/virologia , Testes de Neutralização , Sêmen/virologia , Zika virus/genéticaRESUMO
BACKGROUND: Despite that over 90 million pregnancies are at risk of Plasmodium vivax infection annually, little is known about the epidemiology and impact of the infection in pregnancy. METHODOLOGY AND PRINCIPAL FINDINGS: We undertook a health facility-based prospective observational study in pregnant women from Guatemala (GT), Colombia (CO), Brazil (BR), India (IN) and Papua New Guinea PNG). Malaria and anemia were determined during pregnancy and fetal outcomes assessed at delivery. A total of 9388 women were enrolled at antennal care (ANC), of whom 53% (4957) were followed until delivery. Prevalence of P. vivax monoinfection in maternal blood at delivery was 0.4% (20/4461) by microscopy [GT 0.1%, CO 0.5%, BR 0.1%, IN 0.2%, PNG 1.2%] and 7% (104/1488) by PCR. P. falciparum monoinfection was found in 0.5% (22/4463) of women by microscopy [GT 0%, CO 0.5%, BR 0%, IN 0%, PNG 2%]. P. vivax infection was observed in 0.4% (14/3725) of placentas examined by microscopy and in 3.7% (19/508) by PCR. P. vivax in newborn blood was detected in 0.02% (1/4302) of samples examined by microscopy [in cord blood; 0.05% (2/4040) by microscopy, and 2.6% (13/497) by PCR]. Clinical P. vivax infection was associated with increased risk of maternal anemia (Odds Ratio-OR, 5.48, [95% CI 1.83-16.41]; p = 0.009), while submicroscopic vivax infection was not associated with increased risk of moderate-severe anemia (Hb<8g/dL) (OR, 1.16, [95% CI 0.52-2.59]; p = 0.717), or low birth weight (<2500g) (OR, 0.52, [95% CI, 0.23-1.16]; p = 0.110). CONCLUSIONS: In this multicenter study, the prevalence of P. vivax infection in pregnancy by microscopy was overall low across all endemic study sites; however, molecular methods revealed a significant number of submicroscopic infections. Clinical vivax infection in pregnancy was associated with maternal anemia, which may be deleterious for infant's health. These results may help to guide maternal health programs in settings where vivax malaria is endemic; they also highlight the need of addressing a vulnerable population such as pregnant women while embracing malaria elimination in endemic countries.
Assuntos
Malária Vivax/complicações , Plasmodium vivax , Complicações Parasitárias na Gravidez/patologia , Adolescente , Adulto , Brasil/epidemiologia , Colômbia/epidemiologia , Feminino , Sangue Fetal , Guatemala/epidemiologia , Humanos , Índia/epidemiologia , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Malária Vivax/epidemiologia , Papua Nova Guiné/epidemiologia , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Adulto JovemRESUMO
P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy. Antibody responses against all antigens were detected in all populations, with PNG women presenting the highest levels overall. P. vivax infection at sample collection time was positively associated with antibody levels against PvLP1 (fold-increase: 1.60 at recruitment -first antenatal visit-) and PvLP2 (fold-increase: 1.63 at delivery), and P. falciparum co-infection was found to increase those responses (for PvLP1 at recruitment, fold-increase: 2.25). Levels of IgG against two VIR proteins at delivery were associated with higher birth weight (27 g increase per duplicating antibody levels, p<0.05). Peripheral blood mononuclear cells from PNG uninfected pregnant women had significantly higher antigen-specific IFN-γ TH1 responses (p=0.006) and secreted less pro-inflammatory cytokines TNF and IL-6 after PvLP2 stimulation than P. vivax-infected women (p<0.05). These data demonstrate that VIR antigens induce the natural acquisition of antibody and T cell memory responses that might be important in immunity to P. vivax during pregnancy in very diverse geographical settings.