Author
André M. Siqueira
Other affiliations: National Institutes of Health, National Institute of Standards and Technology, Federal University of Amazonas ...read more
Bio: André M. Siqueira is an academic researcher from Oswaldo Cruz Foundation. The author has contributed to research in topics: Plasmodium vivax & Malaria. The author has an hindex of 32, co-authored 65 publications receiving 5670 citations. Previous affiliations of André M. Siqueira include National Institutes of Health & National Institute of Standards and Technology.
Topics: Plasmodium vivax, Malaria, Medicine, Chikungunya, Dengue fever
Papers
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TL;DR: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities.
Abstract: BackgroundZika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. MethodsWe enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase–polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. ResultsA total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By Jul...
1,711 citations
24 Apr 2020
TL;DR: The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir.
Abstract: Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04323527
852 citations
TL;DR: ZIKV was first identified in Brazil in 2015 by reverse transcriptase–polymerase chain reaction assays of serum specimens from patients who presented with a dengue-like illness that was characterized by rash, fever, myalgias, arthralgias, and conjunctivitis.
Abstract: (ed from N Engl J Med 2016; DOI: 10.1056/NEJMoa1602412) Zika virus (ZIKV) was first identified in Brazil in 2015 by reverse transcriptase–polymerase chain reaction assays of serum specimens from patients who presented with a dengue-like illness that was characterized by rash, fever, myalgias, arthralgias, and conjunctivitis. Zika virus has been linked to neonatal microcephaly.
453 citations
TL;DR: A 24-year-old housekeeper presented to hospital in Rio de Janeiro in June, 2014, with headache, fever, and a rash, 5 days after waking with a severe generalised headache, retro-orbital pain, weakness, and paraesthesia of the hands and feet, which highlights the potential for neurotropism of Zika virus.
264 citations
TL;DR: It is demonstrated that ZIKV was circulating in Rio de Janeiro as early as January 2015, and pruritus, the second most common clinical sign presented by the confirmed cases, should be added to the PAHO case definition, while fever could be given less emphasis.
Abstract: Background
In 2015, Brazil was faced with the cocirculation of three arboviruses of major public health importance. The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between diseases caused by
ZIKV, Dengue (DENV) and Chikungunya (CHIKV) and the lack of validated serological
assays for ZIKV make accurate diagnosis difficult.
Methodology / Principal Findings
The outpatient service for acute febrile illnesses in Fiocruz initiated a syndromic clinical observational study in 2007 to capture unusual presentations of DENV infections. In January
2015, an increase of cases with exanthematic disease was observed. Trained physicians
evaluated the patients using a detailed case report form that included clinical
assessment and laboratory investigations. The laboratory diagnostic algorithm included
assays for detection of ZIKV, CHIKV and DENV. 364 suspected cases of Zika virus disease
were identified based on clinical criteria between January and July 2015. Of these, 262
(71.9%) were tested and 119 (45.4%) were confirmed by the detection of ZIKV RNA. All of
the samples with sequence information available clustered within the Asian genotype. Conclusions / Significance
This is the first report of a ZIKV outbreak in the state of Rio de Janeiro, based on a large
number of suspected (n = 364) and laboratory confirmed cases (n = 119). We were able to
demonstrate that ZIKV was circulating in Rio de Janeiro as early as January 2015. The
peak of the outbreak was documented in May/June 2015. More than half of the patients
reported headache, arthralgia, myalgia, non-purulent conjunctivitis, and lower back pain,
consistent with the case definition of suspected ZIKV disease issued by the Pan American
Health Organization (PAHO). However, fever, when present, was low-intensity and shorttermed.
In our opinion, pruritus, the second most common clinical sign presented by the
confirmed cases, should be added to the PAHO case definition, while fever could be given
less emphasis. The emergence of ZIKV as a new pathogen for Brazil in 2015 underscores
the need for clinical vigilance and strong epidemiological and laboratory surveillance.
252 citations
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TL;DR: The data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.
Abstract: Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducte...
5,532 citations
01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
4,408 citations
TL;DR: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities.
Abstract: BackgroundZika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. MethodsWe enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase–polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. ResultsA total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By Jul...
1,711 citations
TL;DR: It is concluded that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies and needs to intensify efforts toward the prevention of adverse outcomes caused by congenital Zika virus infections.
Abstract: Summary The Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. Prenatal Zika virus infection has been linked to adverse pregnancy and birth outcomes, most notably microcephaly and other serious brain anomalies. To determine whether Zika virus infection during pregnancy causes these adverse outcomes, we evaluated available data using criteria that have been proposed for the assessment of potential teratogens. On the basis of this review, we conclude that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Evidence that was used to support this causal relationship included Zika virus infection at times during prenatal development that were consistent with the defects observed; a specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection; and data that strongly support biologic plausibility, including the identification of Zika virus in the brain tissue of affected fetuses and infants. Given the recognition of this causal relationship, we need to intensify our efforts toward the prevention of adverse outcomes caused by congenital Zika virus infection. However, many questions that are critical to our prevention efforts remain, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy, and factors that might affect a woman’s risk of adverse pregnancy or birth outcomes. Addressing these questions will improve our ability to reduce the burden of the effects of Zika virus infection during pregnancy.
1,692 citations