Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

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Establishment and cryptic transmission of Zika virus in Brazil and the Americas

Estabelecimento e transmissão crítica do vírus Zika no Brasil e nas Américas/Establishment and cryptic transmission of Zika virus in Brazil and the Americas

The first confirmed case of Zika virus infection in the Americas was reported in Northeast Brazil in May 2015, although phylogenetic studies indicate virus introduction as early as 2013. Zika rapidly spread across Brazil and to more than 50 other countries and territories on the American continent. The Aedesaegypti mosquito is thought to be the principal vector responsible for the widespread transmission of the virus. However, sexual transmission has also been reported. The explosively emerging epidemic has had diverse impacts on population health, coinciding with cases of Guillain-Barre Syndrome and an unexpected epidemic of newborns with microcephaly and other neurological impairments. This led to Brazil declaring a national public health emergency in November 2015, followed by a similar decision by the World Health Organization three months later. While dengue virus serotypes took several decades to spread across Brazil, the Zika virus epidemic diffused within months, extending beyond the area of permanent dengue transmission, which is bound by a climatic barrier in the south and low population density areas in the north. This rapid spread was probably due to a combination of factors, including a massive susceptible population, climatic conditions conducive for the mosquito vector, alternative non-vector transmission, and a highly mobile population. The epidemic has since subsided, but many unanswered questions remain. In this article, we provide an overview of the discovery of Zika virus in Brazil, including its emergence and spread, epidemiological surveillance, vector and non-vector transmission routes, clinical complications, and socio-economic impacts. We discuss gaps in the knowledge and the challenges ahead to anticipate, prevent, and control emerging and re-emerging epidemics of arboviruses in Brazil and worldwide.

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The Zika Virus Epidemic in Brazil: From Discovery to Future Implications.

Intermittent outbreaks of infectious diseases have had profound and lasting effects on societies throughout history. Those events have powerfully shaped the economic, political, and social aspects of human civilization, with their effects often lasting for centuries. Epidemic outbreaks have defined some of the basic tenets of modern medicine, pushing the scientific community to develop principles of epidemiology, prevention, immunization, and antimicrobial treatments. This chapter outlines some of the most notable outbreaks that took place in human history and are relevant for a better understanding of the rest of the material. Starting with religious texts, which heavily reference plagues, this chapter establishes the fundamentals for our understanding of the scope, social, medical, and psychological impact that some pandemics effected on civilization, including the Black Death (a plague outbreak from the fourteenth century), the Spanish Flu of 1918, and the more recent outbreaks in the twenty-first century, including SARS, Ebola, and Zika.

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Brief History of Pandemics (Pandemics Throughout History)

For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

https://onlinelibrary.wiley.com/doi/pdf/10.1038/cti.2016.72

Dengue virus antibodies enhance Zika virus infection

Introduction Zika, a flavivirus transmitted mainly by mosquitos in the genus Aedes, was discovered in 1947 in Uganda. (1) From the 1960s to 1980s, human infections were found across Africa and Asia, typically accompanied by mild illness. The first large outbreak of disease caused by Zika infection was reported from the island of Yap (Federated States of Micronesia) in 2007, as the virus moved from south-east Asia across the Pacific. During an outbreak in French Polynesia in 2013-2014, Guillain-Barre syndrome was linked to Zika infection and cases of microcephaly in newborn children were also retrospectively linked to this outbreak. The World Health Organization (WHO) received the first reports of locally-transmitted infection from Brazil in May 2015. In July 2015, health ministry officials from Brazil reported an association between Zika virus infection and Guillain-Barre syndrome in adults. In October 2015, WHO received reports from Brazil of microcephaly in babies whose mothers had been exposed to Zika during pregnancy. At this time, there was no proof of a causal link between Zika infection and these neurological complications. In February 2016, as infection moved rapidly through the range occupied by Aedes mosquitos in the Americas, WHO declared that Zika infection associated with microcephaly and other neurological disorders constituted a Public Health Emergency of International Concern (PHEIC). By the start of February 2016, local transmission of Zika infection had been reported from more than 20 countries and territories in the Americas and an outbreak numbering thousands of cases was under way in Cabo Verde in western Africa. Beyond the range of its mosquito vectors, Zika virus infections are expected to be carried worldwide by people as they travel and be transmitted by travellers to sexual partners who have not been to places where the virus is endemic. Methods To illustrate the spread of Zika virus and associated neurological complications, we did a literature search in PubMed using "Zika" and "ZIKV" as the search terms and cross-checked our findings for completeness against other published reviews. (2, 3) In addition, we drew on formal notifications to WHO under the International Health Regulations (IHR), (4) which are archived in the WHO Event Information Site (EIS). EIS contains information about public health events of potential international concern notified to WHO as required by the IHR. EIS notifications sometimes contain confidential patient information and therefore are not publicly available. Other details of specific events can be provided by the authors on request. Results The first reported case of Zika virus dates to 1947 when the virus was isolated in samples taken from a captive sentinel rhesus monkey by scientists conducting routine surveillance for yellow fever in the Zika forest of Uganda. (1) The virus was recovered from Aedes (Stegomyia) africanus, caught on a tree platform in the forest. (1) Laboratory infection experiments showed the virus to be neurotropic in mice. (5) The timeline presented in this paper includes numerous serological surveys that purportedly detected antibodies to Zika virus in the 1950s and 1960s in Africa and Asia. Because serological (antibody detection) tests for Zika cross-react with antibodies stimulated by other viral infections, the presence of Zika virus is ideally confirmed by the detection of viral nucleic acids by polymerase chain reaction (PCR) testing or by virus isolation. A chronological map of the presence of Zika in those countries for which there is evidence of autochthonous transmission by mosquitos is presented in Fig. 1. The map excludes the many countries from which imported Zika infections have been reported. The country-by-country spread of Zika virus infections, from the earliest published report in 1947 to a World Health Organization, avenue Appia 20, 1211 Geneva 27, Switzerland. January 2014 is summarized in Table 1. …

Ravi Shankar Santhana

Papers

Zika: the origin and spread of a mosquito-borne virus.