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 Health's 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.

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.

Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis.

BACKGROUND: In 2006, Brazil began routine immunization of infants <15 wk of age with a single-strain rotavirus vaccine. We evaluated whether the rotavirus vaccination program was associated with declines in childhood diarrhea deaths and hospital admissions by monitoring disease trends before and after vaccine introduction in all five regions of Brazil with varying disease burden and distinct socioeconomic and health indicators. METHODS AND FINDINGS: National data were analyzed with an interrupted time-series analysis that used diarrhea-related mortality or hospitalization rates as the main outcomes. Monthly mortality and admission rates estimated for the years after rotavirus vaccination (2007-2009) were compared with expected rates calculated from pre-vaccine years (2002-2005), adjusting for secular and seasonal trends. During the three years following rotavirus vaccination in Brazil, rates for diarrhea-related mortality and admissions among children <5 y of age were 22% (95% confidence interval 6%-44%) and 17% (95% confidence interval 5%-27%) lower than expected, respectively. A cumulative total of ~1,500 fewer diarrhea deaths and 130,000 fewer admissions were observed among children <5 y during the three years after rotavirus vaccination. The largest reductions in deaths (22%-28%) and admissions (21%-25%) were among children younger than 2 y, who had the highest rates of vaccination. In contrast, lower reductions in deaths (4%) and admissions (7%) were noted among children two years of age and older, who were not age-eligible for vaccination during the study period. CONCLUSIONS: After the introduction of rotavirus vaccination for infants, significant declines for three full years were observed in under-5-y diarrhea-related mortality and hospital admissions for diarrhea in Brazil. The largest reductions in diarrhea-related mortality and hospital admissions for diarrhea were among children younger than 2 y, who were eligible for vaccination as infants, which suggests that the reduced diarrhea burden in this age group was associated with introduction of the rotavirus vaccine. These real-world data are consistent with evidence obtained from clinical trials and strengthen the evidence base for the introduction of rotavirus vaccination as an effective measure for controlling severe and fatal childhood diarrhea.

Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.

Zika virus outbreak in Brazil.

Zika virus (ZIKV) infection is spreading rapidly within the Americas after originating from an outbreak in Brazil. We describe the current ZIKV infection epidemic in Brazil and the neurological symptoms arising. First cases of an acute exanthematic disease were reported in Brazil's Northeast region at the end of 2014. In March 2015, autochthonous ZIKV was determined to be the causative agent of the exanthematic disease. As cases of neurological syndromes in regions where ZIKV, dengue and/or Chikungunya viruses co-circulate were reported, ZIKV was also identified in the cerebrospinal fluid of patients with acute neurological syndromes and previous exanthematic disease. By the end of September 2015, an increasing number of infants with small head circumference or microcephaly were noted in Brazil's Northeast which was estimated to be 29 cases between August and October. ZIKV was identified in blood and tissue samples of a newborn and in mothers who had given birth to infants with microcephaly and ophthalmological anomalies. In 2015, there were an estimated 440,000 - 1,300,000 Zika cases in Brazil. There have been 4,783 suspected cases of microcephaly, most of them in the Northeast of Brazil associated with 76 deaths. The Ministry of Health is intensifying control measures against the mosquito Aedes aegypti and implemented intensive surveillance actions. Further studies are needed to confirm the suspected association between ZIKV infection and microcephaly; to identify antiviral, immunotherapy, or prophylactic vaccine; to introduce diagnostic ELISA testing. Clinical and epidemiological studies must be performed to describe viral dynamics and expansion of the outbreak.

Uptake of pandemic influenza (H1N1)-2009 vaccines in Brazil, 2010.

In 2010, the Brazilian Ministry of Health organized a mass vaccination campaign of selected priority groups in response to the 2009 H1N1 influenza pandemic. The campaign was conducted in six phases from March to July, 2010. Priority groups included healthcare professionals, indigenous persons, pregnant women, young children, persons with chronic illnesses and otherwise healthy adults 20-39 years of age. Over 89 million doses of pandemic influenza vaccines were administered, surpassing immunization targets among several priority groups, including healthcare professionals. We reviewed strategies used in Brazil to promote vaccination against pandemic influenza as well as factors external to the campaign that may have contributed to vaccine uptake among priority groups.

Influenza like illness monitoring in adults of the State Capitals and Federal District in Brazil by telephone survey.

OBJECTIVES: In order to estimate the prevalence of influenza like illness (ILI) in adults from all state capitals and geographic regions in Brazil, a periodical monitoring of ILI cases by the national telephone survey (VIGITEL) was carried out in 2010. METHOD: A cross-sectional study with 47,876 telephone interviews in the state capitals and Federal District, a probabilistic sample of adult population (>18 years-old) with landline telephone. Questions concerning the results of ILI cases and pandemic influenza (H1N1) 2009, from January 10 to November 30, were analyzed. The proportion of cases stratified by sociodemographic characteristics and Brazilian geographic region was weighted with data from the National Survey with Household Sampling (PNAD) 2008. RESULTS: The prevalence of ILI cases in the last 30 days before interview was 31.2% (95%CI 30.2-32.2%) for all state capitals and the Federal District. This prevalence was higher among women, young adults (18 to 29 years-old) and individuals with 9 to 11 years of schooling. According to the geographic region analysis, Northern Brazil presented the highest prevalence of ILI cases. A tendency to increase with further decrease was observed among the geographic regions, except the Northeast. Need for health care assistance was reported by 26.8% (95%CI 25.1-28.5) from ILI cases. Among ILI cases that sought health care assistance, 2.6% (95%CI 1.8-3.4) reported pandemic influenza (H1N1) 2009 medical suspicion. CONCLUSION: The results of this survey supported influenza surveillance as it provided timeliness and useful surveillance information, which were not captured by the traditional surveillance system, as the occurrence of ILI and need of health care assistance.