Guilherme Amaral Calvet

Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects

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 short-termed. 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.

First detection of autochthonous Zika virus transmission in a HIV-infected patient in Rio de Janeiro, Brazil

Since May 2015, Brazils Ministry of Health has reported autochthonous transmission of Zika virus (ZIKV) in some states of the country. Simultaneous circulation of Dengue, Chikungunya and ZIKV in the country hinder both the diagnosis and the therapeutic approach of patients seeking care with acute febrile illnesses especially in patients with comorbidities. The association between HIV infection and endemic diseases has been described especially in tropical regions with varying levels of complications, although there has been no report of ZIKV in HIV-infected patients. We report the first autochthonous case of laboratory confirmed ZIKV infection in a HIV-infected patient in Rio de Janeiro, Brazil. He evolved with only mild symptoms and recovered well without major laboratory abnormalities. Phylogenetic analysis of the ZIKV detected in the patient sera clustered within the Asian clade. To the best of our knowledge, this is the first time that Zika virus co-infection is reported in a HIV-infected patient.

Zika virus infection: epidemiology, clinical manifestations and diagnosis.

Purpose of review Zika virus (ZIKV) is an arbovirus previously believed to cause only a mild and self-limiting illness. Recently, it has emerged as a new public health threat that caused a large outbreak in French Polynesia in 2013–2014 and since 2015 an explosive outbreak in Brazil, with an increase in severe congenital malformations (microcephaly) and neurological complications, mainly Guillain–Barré syndrome (GBS). Since then, it has spread through the Americas. On 1 February 2016, the WHO declared the ZIKV epidemic in Brazil a Public Health Emergency of International Concern. We reviewed the epidemiology of ZIKV infection, clinical presentations and diagnosis. We highlighted the clinical features and nonvector borne transmission of the virus. Recent findings Association between ZIKV infection and severe foetal outcomes, including microcephaly and other birth defects; increased rate of GBS and other neurological complications due to the ongoing ZIKV outbreak; increased evidence to date of ZIKV being the only arbovirus linked to sexual transmission; the challenge of ZIKV diagnosis; and the need for a specific point-of care test in epidemic scenarios. Summary The findings illustrate the emergence of a viral disease with the identification of new associated disorders, new modes of transmission, including maternal–foetal and sexual transmission.

Accuracy of Zika virus disease case definition during simultaneous Dengue and Chikungunya epidemics

Background Zika is a new disease in the American continent and its surveillance is of utmost importance, especially because of its ability to cause neurological manifestations as Guillain-Barré syndrome and serious congenital malformations through vertical transmission. The detection of suspected cases by the surveillance system depends on the case definition adopted. As the laboratory diagnosis of Zika infection still relies on the use of expensive and complex molecular techniques with low sensitivity due to a narrow window of detection, most suspected cases are not confirmed by laboratory tests, mainly reserved for pregnant women and newborns. In this context, an accurate definition of a suspected Zika case is crucial in order for the surveillance system to gauge the magnitude of an epidemic. Methodology We evaluated the accuracy of various Zika case definitions in a scenario where Dengue and Chikungunya viruses co-circulate. Signs and symptoms that best discriminated PCR confirmed Zika from other laboratory confirmed febrile or exanthematic diseases were identified to propose and test predictive models for Zika infection based on these clinical features. Results and discussion Our derived score prediction model had the best performance because it demonstrated the highest sensitivity and specificity, 86·6% and 78·3%, respectively. This Zika case definition also had the highest values for auROC (0·903) and R2 (0·417), and the lowest Brier score 0·096. Conclusions In areas where multiple arboviruses circulate, the presence of rash with pruritus or conjunctival hyperemia, without any other general clinical manifestations such as fever, petechia or anorexia is the best Zika case definition.

Exanthema associated with Zika virus infection

A 39-year-old man presented to the Acute Febrile Illness walk-in clinic with acute onset of rash and conjunctival swelling after 2 days of frontal headache, sore throat, and diff use myalgia. He did not have fever, diaphoresis, photophobia, or bleeding symptoms and reported no comorbidities. At physical examination, he had oedema and erythema of the malar region of the face and conjunctival injection (fi gure A) and a macular rash on the trunk and abdomen (fi gure B). Hyperaemia and petechiae were seen in the hard palate (fi gure C). There was a tender, mobile, soft lymph node, approximately 15 mm in diameter, behind the left ear (fi gure D), and multiple smaller palpable submandibular and cervical nodes bilaterally. Results of blood tests were within normal limits and urinalysis revealed haematuria. The patient lived in an impoverished area of Rio de Janeiro that is endemic for dengue, had not travelled recently to other areas of the country, and was not aware of any contact with other ill people. As part of the syndromic diagnosis, serology tests were performed for dengue, cytomegalovirus, toxoplasmosis, Epstein–Barr virus, syphilis, and HIV, the results of which were all negative. RT-PCR for dengue and chikungunya were also negative. Because of the recent introduction of Zika virus in the country, we did specifi c RT-PCR for Zika virus RNA, with a positive result. The patient had no alarm signs for severe dengue fever and was instructed to return the following day for re-evaluation. He returned 14 days after the onset of symptoms for reassessment, and had completely recovered. At the time of writing, the patient was healthy. Zika virus is transmitted by mosquitoes of the genus Aedes, which are widespread in Brazil and contribute to dengue transmission. The emergence of Zika in a naive population with high susceptibility to transmission requires physicians to be alert to its occurrence in order to characterise its manifestations and establish robust and reliable clinical surveillance.

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

BackgroundZika 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.MethodsThis observational cohort study will recruit non-pregnant participants aged 18xa0years 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 12xa0months.DiscussionThis 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 registrationNCT03106714. Registration Date: April, 7, 2017