Wanderson Kleber de Oliveira

Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation

BACKGROUND In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. METHODS We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. FINDINGS Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores -1·54 vs -3·13, difference 1·58 [95% CI 1·45-1·72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 [95% CI 0·14-0·56]); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 [95% CI 0·27-0·42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above -2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. INTERPRETATION Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. FUNDING Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust.

Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis

A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age.

Pathology of congenital Zika syndrome in Brazil: a case series

BACKGROUND Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection. METHODS In this case series, formalin-fixed paraffin-embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month-old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains. FINDINGS Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015. INTERPRETATION These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions. FUNDING None.

The Epidemic of Zika Virus-Related Microcephaly in Brazil: Detection, Control, Etiology, and Future Scenarios.

We describe the epidemic of microcephaly in Brazil, its detection and attempts to control it, the suspected causal link with Zika virus infection during pregnancy, and possible scenarios for the future. In October 2015, in Pernambuco, Brazil, an increase in the number of newborns with microcephaly was reported. Mothers of the affected newborns reported rashes during pregnancy and no exposure to other potentially teratogenic agents. Women delivering in October would have been in the first trimester of pregnancy during the peak of a Zika epidemic in March. By the end of 2015, 4180 cases of suspected microcephaly had been reported. Zika spread to other American countries and, in February 2016, the World Health Organization declared the Zika epidemic a public health emergency of international concern. This unprecedented situation underscores the urgent need to establish the evidence of congenital infection risk by gestational week and accrue knowledge. There is an urgent call for a Zika vaccine, better diagnostic tests, effective treatment, and improved mosquito-control methods.

Zika Virus Infection and Associated Neurologic Disorders in Brazil

Zika virus has spread rapidly throughout the Americas and has been associated with fetal abnormalities and a variety of neurologic disorders. This report updates the epidemiologic findings over the past 2 years.

Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis

BACKGROUND On Nov 11, 2015, the Brazilian Ministry of Health declared a Public Health Emergency of National Concern in response to an increased number of microcephaly cases, possibly related to previous Zika virus outbreaks. We describe the course of the dual epidemics of the Zika virus infection during pregnancy and microcephaly in Brazil up to Nov 12, 2016, the first anniversary of this declaration. METHODS We used secondary data for Zika virus and microcephaly cases obtained through the Brazilian Ministry of Healths surveillance systems from Jan 1, 2015, to Nov 12, 2016. We deemed possible Zika virus infections during pregnancy as all suspected cases of Zika virus disease and all initially suspected, but later discarded, cases of dengue and chikungunya fever. We defined confirmed infection-related microcephaly in liveborn infants as the presence of a head circumference of at least 2 SDs below the mean for their age and sex, accompanied by diagnostic imaging consistent with an infectious cause, or laboratory, clinical, or epidemiological results positive for Zika virus or STORCH (infectious agents known to cause congenital infection, mainly syphilis, toxoplasmosis, cytomegalovirus, and herpes simplex virus). We excluded cases of congenital anomalies or death without microcephaly. We analyse the spatial clustering of these diseases in Brazil to obtain the kernel density estimation. FINDINGS Two distinct waves of possible Zika virus infection extended across all Brazilian regions in 2015 and 2016. 1 673 272 notified cases were reported, of which 41 473 (2·5%) were in pregnant women. During this period, 1950 cases of infection-related microcephaly were confirmed. Most cases (1373 [70·4%]) occurred in the northeast region after the first wave of Zika virus infection, with peak monthly occurrence estimated at 49·9 cases per 10 000 livebirths. After a major, well documented second wave of Zika virus infection in all regions of Brazil from September, 2015, to September, 2016, occurrence of microcephaly was much lower than that following the first wave of Zika virus infection, reaching epidemic levels in all but the south of Brazil, with estimated monthly peaks varying from 3·2 cases to 15 cases per 10 000 livebirths. INTERPRETATION The distribution of infection-related microcephaly after Zika virus outbreaks has varied across time and Brazilian regions. Reasons for these apparent differences remain to be elucidated. FUNDING None.

Association between microcephaly, Zika virus infection, and other risk factors in Brazil: final report of a case-control study

BACKGROUND A Zika virus epidemic emerged in northeast Brazil in 2015 and was followed by a striking increase in congenital microcephaly cases, triggering a declaration of an international public health emergency. This is the final report of the first case-control study evaluating the potential causes of microcephaly: congenital Zika virus infection, vaccines, and larvicides. The published preliminary report suggested a strong association between microcephaly and congenital Zika virus infection. METHODS We did a case-control study in eight public maternity hospitals in Recife, Brazil. Cases were neonates born with microcephaly, defined as a head circumference of 2 SD below the mean. Two controls without microcephaly were matched to each case by expected date of delivery and area of residence. We tested the serum of cases and controls and the CSF of cases for detection of Zika virus genomes with quantitative RT-PCR and for detection of IgM antibodies with capture-IgM ELISA. We also tested maternal serum with plaque reduction neutralisation assays for Zika and dengue viruses. We estimated matched crude and adjusted odds ratios with exact conditional logistic regression to determine the association between microcephaly and Zika virus infection. FINDINGS We screened neonates born between Jan 15 and Nov 30, 2016, and prospectively recruited 91 cases and 173 controls. In 32 (35%) cases, congenital Zika virus infection was confirmed by laboratory tests and no controls had confirmed Zika virus infections. 69 (83%) of 83 cases with known birthweight were small for gestational age, compared with eight (5%) of 173 controls. The overall matched odds ratio was 73·1 (95% CI 13·0-∞) for microcephaly and Zika virus infection after adjustments. Neither vaccination during pregnancy or use of the larvicide pyriproxyfen was associated with microcephaly. Results of laboratory tests for Zika virus and brain imaging results were available for 79 (87%) cases; within these cases, ten were positive for Zika virus and had cerebral abnormalities, 13 were positive for Zika infection but had no cerebral abnormalities, and 11 were negative for Zika virus but had cerebral abnormalities. INTERPRETATION The association between microcephaly and congenital Zika virus infection was confirmed. We provide evidence of the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines (tetanus, diphtheria, and acellular pertussis, measles and rubella, or measles, mumps, and rubella) during pregnancy, confirming the findings of an ecological study of pyriproxyfen in Pernambuco and previous studies on the safety of Tdap vaccine administration during pregnancy. FUNDING Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

Emergências de saúde pública: conceito, caracterização, preparação e resposta

during recent years, international concern about the spread of diseases or agents from infections and chemical or radio-nuclear sources has increased. aiming to adapt the concepts and measures to prevent or reduce the risk of this spread, countries have adopted the new concept of “public health emergency of international concern” under the IHR (2005), and implemented new strategies for strengthening activities to prepare for and respond to such emergencies. Based on contextualized risk analysis of health events that can spread internationally, the aim is to be able to fall back on more appropriate tools for the timely identification of and intervention in these events. the adaptation of this concept for the purpose of national health surveillance and health care services in Brazil has allowed for a better management of health events that may pose a risk of disease-spread or injury/death in national territory and provide a more timely response. the analysis of these events presented herein shows that the occurrence of environmental disasters, even if in lower number than infectious events, poses a greater threat to the public and causes more widespread damage. on the other hand, infectious events, which usually occur as outbreaks or epidemics, affect a larger number of municipalities and reap a higher death toll. the measures adopted in the country to improve the health surveillance system in terms of detection, preparedness and response to public health emergencies are described here, as are the main challenges faced in managing the system.

The risk of a pandemic with the influenza A (H1N1) virus

Cad. Saúde Pública, Rio de Janeiro, 25(6):1192-1193, jun, 2009 On April 24, 2009, the World Health Organization (WHO) announced a public health emergency of international importance, in accordance with the International Health Regulations, caused by infection with the new influenza A (H1N1) virus. Its beginning is possibly associated with an epidemic of febrile respiratory illness that first struck Mexico in March 2009. The epidemic behaved unusually when compared to seasonal influenza, since it occurred outside of winter, predominantly in young adults, and initially with more severe cases (although the latter has since proven not to characterize the epidemic). The virus was first positively identified in the United States, through tests performed in two children in California on April 17 (MMWR Morb Mortal Wkly Rep 2009; 58:400-2). Since then, spread of the virus elsewhere in the United States has been detected, including community transmission. Subsequent to spread of the virus in Mexico and the United States, cases were detected in Canada, where community transmission was also reported. By midMay, more than 40 countries had confirmed cases, Brazil included, and autochthonous transmission had also been reported outside of North America. This situation led the WHO to increase the pandemic alert to level 5 and adopt recommendations aimed at decreasing the epidemic’s effects, by activating the national preparedness plans for the influenza H5N1 pandemic, with the appropriate adaptations to the current epidemic. The new epidemic shows a predominance of cases in children and young adults and low case-fatality (< 1%), with a majority of mild and moderate cases of a flu syndrome and higher case fatality in patients with an underlying chronic illness, while most cases have recovered without specific treatment. Transmission occurs through either direct person-to-person contact or respiratory secretions from infected individuals. The first estimates based on analysis of cases in Mexico indicated lower transmissibility than for previous influenza pandemics (Fraser et al. Science 2009; Epub 14 May) or the epidemic of severe acute respiratory syndrome (SARS). Assuming that these characteristics hold out over the course of the epidemic, three possible scenarios can be predicted: (a) this epidemic will follow a similar pattern to that of a seasonal influenza epidemic; this scenario is further consistent with sustained transmission in other regions, but with a self-limited tendency; (b) after waning during the hot months in the Northern Hemisphere, the epidemic will recrudesce, with more severe cases; or (c) the epidemic will continue to spread unchecked to other countries and regions, acquiring the characteristics of a pandemic. Due to the high degree of uncertainly and (unfortunately) the lack of available information from affected countries, it is necessary to maintain the pandemic alert and activate the preparedness plans, with the needed adaptations to the various possible scenarios. Furthermore, we should always remember the experience with SARS, which was only managed effectively by sharing information and technologies with transparency, coordination, and solidarity, thereby favoring better knowledge of the disease, developing diagnostic methods, and adopting adequate control measures. For influenza, it will also be necessary to extend these benefits to production and universal access to vaccines and drugs. Finally, the measures that have been adopted to deal with the current epidemic should enable the structuring and strengthening of public health services for early detection and effective response to public health emergencies. The risk of a pandemic with the influenza A (H1N1) virus EDITORIAL

Características dos primeiros casos de microcefalia possivelmente relacionados ao vírus Zika notificados na Região Metropolitana de Recife, Pernambuco

OBJETIVO: describir los primeros casos de microcefalia en nacidos vivos reportados al Departamento de Salud del Estado de Pernambuco, en la region metropolitana de Recife, Pernambuco, 2015. METODOS: estudio epidemiologico descriptivo de serie de casos (reportados de 1 de agosto a 31 de octubre de 2015), con datos obtenidos de registros medicos y cuestionarios aplicados a las madres. RESULTADOS: 40 casos fueron confirmados con microcefalia, en ocho municipios de la region metropolitana de Recife, con mayor concentracion de casos en Recife (n=12); la circunferencia media de la cabeza fue 29 cm, perimetro toracico 31 cm y peso 2.628 gramos; examenes revelaron que 21/25 casos mostraron calcificacion, dilatacion ventricular o lisencefalia; de las 40 madres, 27 (68%) informan exantema durante la gestacion, 20 (74%) en el primer trimestre y siete (26%) en la segunda, ademas de prurito, dolor de cabeza, mialgia y ausencia de fiebre. CONCLUSION: la mayoria de los casos presenta caracteristicas de infeccion congenita; la mayoria de las madres mostro caracteristicas que sugieren infeccion por el virus Zika en el embarazo.OBJECTIVE to describe the first cases of microcephaly possibly related to Zika virus in live born babies reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. METHODS this was a descriptive case series study (cases reported between August 1st and October 31st 2015), using medical record data and data from a questionnaire answered by the mothers of the babies. RESULTS 40 microcephaly cases were confirmed, distributed in eight municipalities within the Metropolitan Region, with Recife itself having the highest concentration of cases (n=12); median head circumference was 29 cm, median chest girth was 31 cm and median weight was 2,628 grams; 21/25 cases had brain calcification, ventriculomegaly or lissencephaly; 27 of the 40 mothers reported rash during pregnancy, 20 in the first trimester and 7 in the second trimester, as well as itching, headache, myalgia and absence of fever. CONCLUSION the majority of the cases bore the characteristics of congenital infection; the clinical condition of the majority of mothers suggested Zika virus infection during pregnancy.