BACKGROUND In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. METHODS We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. RESULTS We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. CONCLUSIONS This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa0805715

Zika virus outbreak on Yap Island, Federated States of Micronesia.

Summary A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reversetranscriptase–polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.

/pdf/zika-virus-associated-with-microcephaly-17xnqgmn4f.pdf

Zika Virus Associated with Microcephaly

1. (1) The isolation of what is believed to be a hitherto unrecorded virus is described. The first isolation was made in April 1947 from the serum of a pyrexial rhesus monkey caged in the canopy of Zika Forest. The second isolation was made from a lot of A. africanus taken in January, 1948, in the same forest. The virus has been called Zika virus after the locality from where the isolations were made. 2. (2) Cross neutralization tests indicate that Zika virus is not related to yellow fever, Hawaii dengue nor to the FA and GD VII strains of Theiler's mouse encephalomyelitis virus. Neutralization tests with Zika virus and the antisera of some other viruses which are neurotropic in mice gave no evidence of any identity of these with Zika virus.

Zika Virus (I). Isolations and serological specificity

Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda from a sentinel monkey in 1947. Mosquito and sentinel animal surveillance studies have demonstrated that ZIKV is endemic to Africa and Southeast Asia, yet reported human cases are rare, with <10 cases reported in the literature. In June 2007, an epidemic of fever and rash associated with ZIKV was detected in Yap State, Federated States of Micronesia. We report the genetic and serologic properties of the ZIKV associated with this epidemic.

/pdf/genetic-and-serologic-properties-of-zika-virus-associated-2i6zeoxpim.pdf

Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00562-6.pdf

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study

1.	
(1) A description is given of the adaptation to mice of two strains of Zika virus. Zika is the name of a forest area near Entebbe, Uganda, where both strains of virus were isolated. One of the strains was isolated from a pyrexial rhesus monkey which was being employed as a yellow fever sentinel and the other was obtained from a batch of A. africanus.

2.	
(2) The signs of infection in mice are described. While mice of all ages tested are susceptible to intracerebral inoculations with Zika mouse brain virus, mice of 2 weeks of age and over can rarely be infected by the intraperitoneal route. Mice younger than 2 weeks are highly susceptible to intraperitoneal inoculation of the virus.

3.	
(3) Zika virus is highly neurotropic in mice and no virus has been recovered from tissues other than the brains of infected mice.

4.	
(4) Cotton-rats, guineapigs and rabbits show no clinical signs of infection after intracerebral inoculation of late passage mouse brain virus.

5.	
(5) Monkeys develop an inapparent infection after subcutaneous inoculation with mouse brain virus. After intracerebral inoculation one of five monkeys showed a mild pyrexia, the others showed no signs of infection. Viraemia during the first week after inoculation has been found in all monkeys tested and antibody has been demonstrated by the 14th day after inoculation.

6.	
(6) Of 99 human sera tested, 6 (6.1 per cent.)-have neutralized more than 100 LD50 of virus. Antibody has also been found in the serum of one of 15 wild monkeys tested.

7.	
(7) The size of Zika virus is estimated to eb in the region of 30 to 45 mμ in diameter. The virus may be preserved up to 6 months in 50 per cent. glycerol and up to 30 months after drying. It is susceptible to anaesthetic ether and the thermal death point is 58°C. for 30 minutes.

8.	
(8) Neuronal degeneration, cellular infiltration and areas of softening are present in infected mouse brains. Cowdry type A inclusion bodies have been found, particularly in the brains of young mice showing extensive lesions.

Zika virus (II). Pathogenicity and physical properties

Epidemiological notes on some viruses isolated in Uganda; Yellow fever, Rift Valley fever, Bwamba fever, West Nile, Mengo, Semliki forest, Bunyamwera, Ntaya, Uganda S and Zika viruses.

1. (1) The isolation of what is believed to be a hitherto undescribed virus is recorded. Although the origin of the agent is uncertain, the evidence which has been presented indicates that it was isolated from one of the following species of mosquitoes: Aedes (F.) longipalpis, A. (F.) ingrami, A. (A.) natronius. 2. (2) Studies on the immunological relationship of Uganda S virus to other viruses are presented elsewhere (DICK, to be published); they indicate that Uganda S virus is not identical with any previously described virus. Neutralization tests have demonstrated antibody to Uganda S virus in high titre in 5.8 per cent. of sera from residents of Western Uganda and in the serum of one of six wild monkeys. 3. (3) The pathogenicity of Uganda S virus for mice, cotton-rats, guineapigs and for rhesus, grivet and redtail monkeys is described. The agent is highly neurotropic for mice only and has produced no clinical signs of infection in the other animals tested. Monkeys vary in their susceptibility to Uganda S virus as evidenced by the circulation of virus and development of antibody. 4. (4) Uganda S virus would appear to have a particle size of between 75 and 112 mμ. This estimate is subject to revision when other methods of size estimation have been applied. It would appear to be one of the more unstable viruses when in suspensions, but is readily preserved by desiccation. No studies have as yet been made on the susceptibility of Uganda S virus to chemicals, nor have attempts been made to cultivate it in chick embryos. 5. (5) Nothing is known of the natural history of the virus or of the disease, if any, which it produces in man or animals.

Uganda S virus; a hitherto unrecorded virus isolated from mosquitoes in Uganda. I. Isolation and pathogenicity.

(1948). Implication of the Mosquito aedes (Stegomyia) Africanus Theobald in the Forest Cycle of Yellow Fever in Uganda. Annals of Tropical Medicine & Parasitology: Vol. 42, No. 2, pp. 218-223.

G. W. A. Dick

Papers

Zika Virus (I). Isolations and serological specificity

Zika virus (II). Pathogenicity and physical properties

Epidemiological notes on some viruses isolated in Uganda; Yellow fever, Rift Valley fever, Bwamba fever, West Nile, Mengo, Semliki forest, Bunyamwera, Ntaya, Uganda S and Zika viruses.

Uganda S virus; a hitherto unrecorded virus isolated from mosquitoes in Uganda. I. Isolation and pathogenicity.

Implication of the Mosquito aëdes (Stegomyia) Africanus Theobald in the Forest Cycle of Yellow Fever in Uganda