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References1Campos GS, Bandeira AC, Sardi SI. Zika Virus Outbreak, Bahia, Brazil. Emerg Infect Dis 2015; 21: 1885–1886.CrossRef,PubMed,Web of Science® Times Cited: 22Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika virus epidemiology and recent epidemics.Medecine et maladies infectieuses 2014; 44: 302–307.CrossRef,PubMed,Web of Science® Times Cited: 43Besnard M, Lastere S, Teissier A, Cao-Lormeau V, Musso D. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill 2014; 19.CrossRef,PubMed,Web of Science® Times Cited: 54Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 2008; 8: 1232–1239.CrossRef,CAS,Web of Science® Times Cited: 405Centers for Disease Control and Prevention (CDC). Intrauterine West Nile virus infection--New York, 2002. MMWR Morb Mortal Wkly Rep 2002; 51: 1135–1136.PubMed6Faye O, Freire CC, Iamarino A, Faye O, de Oliveira JV, Diallo M, Zanotto PM, Sall AA. Molecular evolution of Zika virus during its emergence in the 20(th) century. PLoS Negl Trop Dis 2014; 8: e2636.CrossRef,PubMed,Web of Science® Times Cited: 87Goenaga S, Kenney JL, Duggal NK, Delorey M, Ebel GD, Zhang B, Levis SC, Enria DA, Brault AC. Potential for Co-Infection of a Mosquito-Specific Flavivirus, Nhumirim Virus, to Block West Nile Virus Transmission in Mosquitoes. Viruses 2015; 7: 5801–5812.CrossRef,PubMed,Web of Science®

In the meantime, in Paraiba state, six children diagnosed with Zika virus were born to mothers who were apparently symptomatic during pregnancy, all of them with neonatal HC below the 10th percentile. Fetal neurosonograms showed two cases with cerebellar involvement and three with brain calcifications. One had severe arthrogryposis. Intrauterine infections affecting the brain are relatively rare; cytomegalovirus (CMV), toxoplasmosis, herpes virus, syphilis and rubella are well known vectors of fetal disease. Among the Flaviviruses there have been only isolated reports linking West Nile encephalitis virus to fetal brain insults[5]. The presence of calcifications was suggestive of an intrauterine infection but severe damage of the cerebellum, brainstem and thalami is rarely associated with intrauterine infection. Both cases showed some similarities to CMV cases but with a more severe and destructive pattern and they lacked the nodules characteristic of toxoplasmosis. Interestingly, the reported case of fetal West Nile virus infection has similar characteristics[5]. It is difficult to explain why there have been no fetal cases of Zika virus infection reported until now but this may be due to the underreporting of cases, possible early acquisition of immunity in endemic areas or due to the rarity of the disease until now. As genomic changes in the virus have been reported[6], the possibility of a new, more virulent, strain needs to be considered. Until more cases are diagnosed and histopathological proof is obtained, the possibility of other etiologies cannot be ruled out. As with other intrauterine infections, it is possible that the reported cases of microcephaly represent only the more severely affected children and that newborns with less severe disease, affecting not only the brain but also other organs, have not yet been diagnosed. If patients diagnosed in other states are found to be seropositive for Zika virus, this represents a severe health threat that needs to be controlled expeditiously. The Brazilian authorities reacted rapidly by declaring a state of national health emergency. As there is no known medical treatment for this disease, a serious attempt will be needed to eradicate the mosquito and prevent the spread of the disease to other Brazilian states and across the border[7].

Figure 2. Case 2: (a) Anterior coronal view shows severe asymmetric ventriculomegaly with cystic formation (arrow). (b) Posterior horn of the lateral ventricle (LV) in coronal view is dilated. Note calcifications in the fourth ventricle (arrows). (c) The thalamus is absent (arrow) and the brainstem and pons are thin and difficult to visualize (sagittal view). (d) Axial view shows calcifications in both eyes (arrows). Note that the proximal eye is very small and lacks normal anatomic landmarks.

In Case 2, fetal ultrasound examination was performed at 29.2 weeks' gestation. HC was 229 mm (3.1 SD below expected value) and estimated fetal weight was 1018 g (19th percentile). AC was below the 3rd percentile but FL was normal. The cerebral hemispheres were markedly asymmetric with severe unilateral ventriculomegaly, displacement of the midline, thinning of the parenchyma on the dilated side, failure to visualize the corpus callosum and almost complete disappearance or failure to develop the thalami. The pons and brainstem were thin and continuous with a non-homogeneous small mass at the position of the basal ganglia. Brain calcifications were more subtle than in Case 1 and located around the lateral ventricles and fourth ventricle. Both eyes had cataracts and intraocular calcifications, and one eye was smaller than the other (Figure 2).

Figure 1. Case 1: (a) Transabdominal axial ultrasound image shows cerebral calcifications with failure of visualization of a normal vermis (large arrow). Calcifications are also present in the brain parenchyma (small arrow). (b) Transvaginal sagittal image shows dysgenesis of the corpus callosum (small arrow) and vermis (large arrow). (c) Coronal plane shows a wide interhemispheric fissure (large arrow) due to brain atrophy and bilateral parenchymatic coarse calcifications (small arrows). (d) Calcifications are visible in this more posterior coronal view and can be seen to involve the caudate (arrows).

In Case 1, fetal ultrasound examination was performed at 30.1 weeks' gestation. Head circumference (HC) was 246 mm (2.6 SD below expected value) and weight was estimated as 1179 g (21st percentile). Abdominal circumference (AC), femur length (FL) and transcranial Doppler were normal for gestational age as was the width of the lateral ventricles. Anomalies were limited to the brain and included brain atrophy with coarse calcifications involving the white matter of the frontal lobes, including the caudate, lentostriatal vessels and cerebellum. Corpus callosal and vermian dysgenesis and enlarged cisterna magna were observed (Figure 1).

An unexpected upsurge in diagnosis of fetal and pediatric microcephaly has been reported in the Brazilian press recently. Cases have been diagnosed in nine Brazilian states so far. By 28 November 2015, 646 cases had been reported in Pernambuco state alone. Although reports have circulated regarding the declaration of a state of national health emergency, there is no information on the imaging and clinical findings of affected cases. Authorities are considering different theories behind the ‘microcephaly outbreak’, including a possible association with the emergence of Zika virus disease within the region, the first case of which was detected in May 2015[1]. Zika virus is a mosquito-borne disease closely related to yellow fever, dengue, West Nile and Japanese encephalitis viruses[2]. It was first identified in 1947 in the Zika Valley in Uganda and causes a mild disease with fever, erythema and arthralgia. Interestingly, vertical transmission to the fetus has not been reported previously, although two cases of perinatal transmission, occurring around the time of delivery and causing mild disease in the newborns, have been described[3]. We have examined recently two pregnant women from the state of Paraiba who were diagnosed with fetal microcephaly and were considered part of the ‘microcephaly cluster’ as both women suffered from symptoms related to Zika virus infection. Although both patients had negative blood results for Zika virus, amniocentesis and subsequent quantitative real-time polymerase chain reaction[4], performed after ultrasound diagnosis of fetal microcephaly and analyzed at the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, was positive for Zika virus in both patients, most likely representing the first diagnoses of intrauterine transmission of the virus. The sequencing analysis identified in both cases a genotype of Asian origin.

Physician Alert You have free access to this contentZika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?A. S. Oliveira Melo1, G. Malinger2,*, R. Ximenes3, P. O. Szejnfeld4, S. Alves Sampaio5 andA. M. Bispo de Filippis5Article first published online: 5 JAN 2016 DOI: 10.1002/uog.15831 Author Information1Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Instituto de Saúde Elpidio de Almeida (ISEA), Campina Grande, Brazil 2Division of Ultrasound in Obstetrics & Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 3Fetal Medicine Foundation Latinamerica – FMFLA, Centrus – Fetal Medicine, Campinas, Brazil 4FIDI - Fundação Instituto de Ensino e Pesquisa em Diagnóstico por Imagem, Departamento de Diagnóstico por Imagem -DDI- UNIFESP, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil 5Laboratório de Flavivírus, Instituto Oswaldo Cruz – FIOCRUZ, Rio de Janeiro, Brazil *Correspondence. (e-mail: [email protected])

Ultrasound paper on two infants from Brazil that were PCR confirmed for Zika virus. http://onlinelibrary.wiley.com/doi/10.1002/uog.15831/abstract

ReferencesHayes EB. Zika virus outside Africa. Emerg Infect Dis 2009;15:1347–50. CrossRef PubMedCDC. Zika virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. http://www.cdc.gov/zika/index.html.Duffy MR, Chen TH, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009;360:2536–43. CrossRef PubMedCDC. CDC health advisory: recognizing, managing, and reporting Zika virus infections in travelers returning from Central America, South America, the Caribbean and Mexico. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. http://emergency.cdc.gov/han/han00385.asp.Oehler E, Watrin L, Larre P, et al. Zika virus infection complicated by Guillain-Barre syndrome—case report, French Polynesia, December 2013. Euro Surveill 2014;19:4–6. CrossRefPubMedMusso D, Nilles EJ, Cao-Lormeau VM. Rapid spread of emerging Zika virus in the Pacific area. Clin Microbiol Infect 2014;20:O595–6. CrossRef PubMedBesnard M, Lastere S, Teissier A, Cao-Lormeau V, Musso D. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill 2014;19:13–6.CrossRef PubMedOliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 2016;47:6–7. CrossRef PubMedEuropean Centre for Disease Prevention and Control. Rapid risk assessment. Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. Stockholm, Sweden: European Centre for Disease Prevention and Control; 2015. http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf.CDC. Travelers’ health. CDC issues interim travel guidance related to Zika virus for 14 countries and territories in Central and South America and the Caribbean. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. http://wwwnc.cdc.gov/travel/notices.CDC. Travelers’ health: avoid bug bites. Atlanta, GA: US Department of Health and Human Services, CDC; 2013. http://wwwnc.cdc.gov/travel/page/avoid-bug-bites.CDC. Zika virus: prevention. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/zika/prevention/index.html.Schaffner F, Mathis A. Dengue and dengue vectors in the WHO European region: past, present, and scenarios for the future. Lancet Infect Dis 2014;14:1271–80. CrossRef PubMedCDC. West Nile virus: insect repellent use & safety. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/westnile/faq/repellent.html.CDC. Travelers’ health: protection against mosquitoes, ticks, & other arthropods. Atlanta, GA: US Department of Health and Human Services, CDC; 2015.http://wwwnc.cdc.gov/travel/yellowbook/2016/the-pre-travel-consultation/protection-against-mosquitoes-ticks-other-arthropods.CDC. Chikungunya virus: clinical evaluation & disease. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/chikungunya/hc/clinicalevaluation.html.World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. Geneva, Switzerland: World Health Organization; 2009.http://apps.who.int/iris/bitstream/10665/44188/1/9789241547871_eng.pdf.CDC. Zika virus. For health care providers: diagnostic testing. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/zika/hc-providers/diagnostic.html.Akolekar R, Beta J, Picciarelli G, Ogilvie C, D’Antonio F. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015;45:16–26. CrossRef PubMedAmerican Academy of Pediatrics/American College of Obstetricians and Gynecologists. Guidelines for perinatal care. 7th ed. Elk Grove Village, IL: American Academy of Pediatrics/American College of Obstetricians and Gynecologists; 2012.Rasmussen SA, Kissin DM, Yeung LF, et al. ; Pandemic Influenza and Pregnancy Working Group. Preparing for influenza after 2009 H1N1: special considerations for pregnant women and newborns. Am J Obstet Gynecol 2011;204(Suppl 1):S13–20. CrossRef PubMed

FIGURE. Interim guidance: testing algorithm*,†,§ for a pregnant woman with history of travel to an area¶ with Zika virus transmission, with or without clinical illness** consistent with Zika virus disease

CDC has developed interim guidelines for health care providers in the United States caring for pregnant women during a Zika virus outbreak. These guidelines include recommendations for pregnant women considering travel to an area with Zika virus transmission and recommendations for screening, testing, and management of pregnant returning travelers. Updates on areas with ongoing Zika virus transmission are available online (http://wwwnc.cdc.gov/travel/notices/). Health care providers should ask all pregnant women about recent travel. Pregnant women with a history of travel to an area with Zika virus transmission and who report two or more symptoms consistent with Zika virus disease (acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis) during or within 2 weeks of travel, or who have ultrasound findings of fetal microcephaly or intracranial calcifications, should be tested for Zika virus infection in consultation with their state or local health department. Testing is not indicated for women without a travel history to an area with Zika virus transmission. In pregnant women with laboratory evidence of Zika virus infection, serial ultrasound examination should be considered to monitor fetal growth and anatomy and referral to a maternal-fetal medicine or infectious disease specialist with expertise in pregnancy management is recommended. There is no specific antiviral treatment for Zika virus; supportive care is recommended. Zika virus is a mosquito-borne flavivirus transmitted primarily by Aedes aegypti mosquitoes (1,2). These vectors also transmit dengue and chikungunya virus and are found throughout much of the Americas, including parts of the United States. An estimated 80% of persons infected with Zika virus are asymptomatic (2,3). Symptomatic disease is generally mild and characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. Symptoms usually last from several days to 1 week. Severe disease requiring hospitalization is uncommon, and fatalities are rare. Guillain-Barré syndrome has been reported in patients following suspected Zika virus infection (4–6). Pregnant women can be infected with Zika virus in any trimester (4,7,8). The incidence of Zika virus infection in pregnant women is not currently known, and data on pregnant women infected with Zika virus are limited. No evidence exists to suggest that pregnant women are more susceptible to Zika virus infection or experience more severe disease during pregnancy. Maternal-fetal transmission of Zika virus has been documented throughout pregnancy (4,7,8). Although Zika virus RNA has been detected in the pathologic specimens of fetal losses (4), it is not known if Zika virus caused the fetal losses. Zika virus infections have been confirmed in infants with microcephaly (4), and in the current outbreak in Brazil, a marked increase in the number of infants born with microcephaly has been reported (9). However, it is not known how many of the microcephaly cases are associated with Zika virus infection. Studies are under way to investigate the association of Zika virus infection and microcephaly, including the role of other contributory factors (e.g., prior or concurrent infection with other organisms, nutrition, and environment). The full spectrum of outcomes that might be associated with Zika virus infections during pregnancy is unknown and requires further investigation. Top Recommendations for Pregnant Women Considering Travel to an Area of Zika Virus TransmissionBecause there is neither a vaccine nor prophylactic medications available to prevent Zika virus infection, CDC recommends that all pregnant women consider postponing travel to areas where Zika virus transmission is ongoing (10). If a pregnant woman travels to an area with Zika virus transmission, she should be advised to strictly follow steps to avoid mosquito bites (11,12). Mosquitoes that spread Zika virus bite both indoors and outdoors, mostly during the daytime; therefore, it is important to ensure protection from mosquitoes throughout the entire day (13). Mosquito prevention strategies include wearing long-sleeved shirts and long pants, using U.S. Environmental Protection Agency (EPA)–registered insect repellents, using permethrin-treated clothing and gear, and staying and sleeping in screened-in or air-conditioned rooms. When used as directed on the product label, insect repellents containing DEET, picaridin, and IR3535 are safe for pregnant women (14,15). Further guidelines for using insect repellents are available online (http://wwwnc.cdc.gov/travel/page/avoid-bug-bites) (11,15). Top Recommendations for Pregnant Women with History of Travel to an Area of Zika Virus TransmissionHealth care providers should ask all pregnant women about recent travel. Women who traveled to an area with ongoing Zika virus transmission during pregnancy should be evaluated for Zika virus infection and tested in accordance with CDC Interim Guidance (Figure). Because of the similar geographic distribution and clinical presentation of Zika, dengue, and chikungunya virus infection, patients with symptoms consistent with Zika virus disease should also be evaluated for dengue and chikungunya virus infection, in accordance with existing guidelines (16,17). Zika virus testing of maternal serum includes reverse transcription-polymerase chain reaction (RT-PCR) testing for symptomatic patients with onset of symptoms within the previous week. Immunoglobulin M (IgM) and neutralizing antibody testing should be performed on specimens collected ≥4 days after onset of symptoms. Cross-reaction with related flaviviruses (e.g., dengue or yellow fever) is common with antibody testing, and thus it might be difficult to distinguish Zika virus infection from other flavivirus infections. Consultation with state or local health departments might be necessary to assist with interpretation of results (18). Testing of asymptomatic pregnant women is not recommended in the absence of fetal microcephaly or intracranial calcifications. Zika virus RT-PCR testing can be performed on amniotic fluid (7,9). Currently, it is unknown how sensitive or specific this test is for congenital infection. Also, it is unknown if a positive result is predictive of a subsequent fetal abnormality, and if so, what proportion of infants born after infection will have abnormalities. Amniocentesis is associated with an overall 0.1% risk of pregnancy loss when performed at less than 24 weeks of gestation (19). Amniocentesis performed ≥15 weeks of gestation is associated with lower rates of complications than those performed at earlier gestational ages, and early amniocentesis (≤14 weeks of gestation) is not recommended (20). Health care providers should discuss the risks and benefits of amniocentesis with their patients. A positive RT-PCR result on amniotic fluid would be suggestive of intrauterine infection and potentially useful to pregnant women and their health care providers (20). For a live birth with evidence of maternal or fetal Zika virus infection, the following tests are recommended: histopathologic examination of the placenta and umbilical cord; testing of frozen placental tissue and cord tissue for Zika virus RNA; and testing of cord serum for Zika and dengue virus IgM and neutralizing antibodies. CDC is developing guidelines for infants infected by Zika virus. If a pregnancy results in a fetal loss in a woman with history of travel to an area of Zika virus transmission with symptoms consistent with Zika virus disease during or within 2 weeks of travel or findings of fetal microcephaly, Zika virus RT-PCR and immunohistochemical staining should be performed on fetal tissues, including umbilical cord and placenta. There is no commercially available test for Zika virus. Testing for Zika virus infection is performed at CDC and several state health departments. Health care providers should contact their state or local health department to facilitate testing and for assistance with interpreting results (4). Top How to Treat Pregnant Women with Diagnoses of Zika Virus DiseaseNo specific antiviral treatment is available for Zika virus disease. Treatment is generally supportive and can include rest, fluids, and use of analgesics and antipyretics (4). Fever should be treated with acetaminophen (21). Although aspirin and other nonsteroidal anti-inflammatory drugs are not typically used in pregnancy, these medications should specifically be avoided until dengue can be ruled out to reduce the risk for hemorrhage (4,9,17). In a pregnant woman with laboratory evidence of Zika virus in serum or amniotic fluid, serial ultrasounds should be considered to monitor fetal anatomy and growth every 3–4 weeks. Referral to a maternal-fetal medicine or infectious disease specialist with expertise in pregnancy management is recommended. *Availability of Zika virus testing is limited; consult your state or local health department to facilitate testing. Tests include Zika virus reverse transcription–polymerase chain reaction (RT-PCR) and Zika virus immunoglobulin M (IgM) and neutralizing antibodies on serum specimens. Given the overlap of symptoms and endemic areas with other viral illnesses, evaluate for possible dengue or chikungunya virus infection. † Laboratory evidence of maternal Zika virus infection: 1) Zika virus RNA detected by RT-PCR in any clinical specimen; or 2) positive Zika virus IgM with confirmatory neutralizing antibody titers that are ≥4-fold higher than dengue virus neutralizing antibody titers in serum. Testing would be considered inconclusive if Zika virus neutralizing antibody titers are <4-fold higher than dengue virus neutralizing antibody titers. § Amniocentesis is not recommended until after 15 weeks of gestation. Amniotic fluid should be tested for Zika virus RNA by RT-PCR. ¶ Updates on areas with ongoing Zika virus transmission are available online (http://wwwnc.cdc.gov/travel/notices/). ** Clinical illness is consistent with Zika virus disease if two or more symptoms (acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis) are present.

Interim Guidelines for Pregnant Women During a Zika Virus Outbreak — United States, 2016Weekly / January 22, 2016 / 65(2);30–33 Format:Select onePDF [131 KB]Recommend on FacebookTweetOn January 19, 2016, this report was posted as an MMWR Early Release on the MMWR website (http://www.cdc.gov/mmwr). Emily E. Petersen, MD1; J. Erin Staples, MD, PhD2; Dana Meaney-Delman,, MD3; Marc Fischer, MD2; Sascha R. Ellington, MSPH1; William M. Callaghan, MD1; Denise J. Jamieson, MD1 Corresponding author: Denise Jamieson, [email protected], 770-488-6377. Top 1Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC; 2Arboviral Diseases Branch, National Center for Emerging and Zoonotic Infectious Diseases, CDC; 3Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

CDC has developed Zika virus interim guidelines for pregnant women in the US - early release MMWR. http://www.cdc.gov/mmwr/volumes/65/wr/mm6502e1.htm

ReferencesHayes EB. Zika virus outside Africa. Emerg Infect Dis 2009;15:1347–50. CrossRef PubMedDuffy MR, Chen TH, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009;360:2536–43. CrossRef PubMedMusso D, Nilles EJ, Cao-Lormeau VM. Rapid spread of emerging Zika virus in the Pacific area. Clin Microbiol Infect 2014;20:O595–6. CrossRef PubMedZanluca C, de Melo VC, Mosimann AL, Dos Santos GI, Dos Santos CN, Luz K. First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz 2015;110:569–72.CrossRef PubMedEuropean Centre for Disease Prevention and Control. Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. Stockholm, Sweden: European Centre for Disease Prevention and Control; 2015. http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf.Pan American Health Organization. Zika virus infection. Washington, DC: World Health Organization, Pan American Health Organization; 2016. http://www.paho.org/hq/index.php?option=com_topics&view=article&id=427&Itemid=41484&lang=en.CDC. Zika virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. http://www.cdc.gov/zika/index.html.Pan American Health Organization. Epidemiological alert: neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas. Washington, DC: World Health Organization, Pan American Health Organization; 2015. http://www.paho.org/hq/index.php?option=com_docman&task=doc_download&Itemid=&gid=32405&lang=en.CDC. Chikungunya virus: clinical evaluation & disease. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. www.cdc.gov/chikungunya/hc/clinicalevaluation.html.World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. Geneva, Switzerland: World Health Organization; 2009.http://apps.who.int/iris/bitstream/10665/44188/1/9789241547871_eng.pdf.Lanciotti RS, Kosoy OL, Laven JJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 2008;14:1232–9. CrossRefPubMedNasci RS, Wirtz RA, Brogdon WG. Protection against mosquitoes, ticks, and other arthropods. In: CDC health information for international travel, 2016. New York, NY: Oxford University Press; 2015. http://wwwnc.cdc.gov/travel/yellowbook/2016/the-pre-travel-consultation/protection-against-mosquitoes-ticks-other-arthropods.Petersen EE, Staples JE, Meaney-Delman D, et al. Interim guidelines for pregnant women during a Zika virus outbreak—United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65:30–3.CrossRef Top * Barbados, Bolivia, Brazil, Colombia, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, Saint Martin, Suriname, and Venezuela. † CDC. Traveler’s health notices. http://wwwnc.cdc.gov/travel/notices/. § The interim case definition for suspected Zika virus disease is an illness characterized by acute onset of two or more of the following: fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis not explained by other medical conditions, in a person who resides in or has visited an area with ongoing Zika virus transmission within 2 weeks before the onset of symptoms.

FIGURE. Countries and territories with documented local transmission of Zika virus infection reported to the Pan American Health Organization — Region of the Americas, 2015–2016 Top Suggested citation for this article: Hennessey M, Fischer M, Staples JE. Zika Virus Spreads to New Areas — Region of the Americas, May 2015–January 2016. MMWR Morb Mortal Wkly Rep 2016;65(Early Release):1–4. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e1er.

Zika virus is a mosquito-borne flavivirus that was first identified in Uganda in 1947 (1). Before 2007, only sporadic human disease cases were reported from countries in Africa and Asia. In 2007, the first documented outbreak of Zika virus disease was reported in Yap State, Federated States of Micronesia; 73% of the population aged ≥3 years is estimated to have been infected (2). Subsequent outbreaks occurred in Southeast Asia and the Western Pacific (3). In May 2015, the World Health Organization reported the first local transmission of Zika virus in the Region of the Americas (Americas), with autochthonous cases identified in Brazil (4). In December, the Ministry of Health estimated that 440,000–1,300,000 suspected cases of Zika virus disease had occurred in Brazil in 2015 (5). By January 20, 2016, locally-transmitted cases had been reported to the Pan American Health Organization from Puerto Rico and 19 other countries or territories in the Americas* (Figure) (6). Further spread to other countries in the region is being monitored closely. Although local transmission of Zika virus has not been documented in the continental United States, Zika virus infections have been reported in returning travelers (7). In light of the recent outbreaks in the Americas, the number of Zika virus disease cases among travelers visiting or returning to the United States is likely to increase. These imported cases might result in local human-to-mosquito-to-human spread of the virus in limited areas of the continental United States that have the appropriate mosquito vectors. Zika virus is transmitted primarily by Aedes aegypti mosquitoes (1,7). Aedes albopictus mosquitoes also might transmit the virus. Aedes aegyptiand Ae. albopictus mosquitoes are found throughout much of the Americas, including parts of the United States, and also transmit dengue and chikungunya viruses. In addition to mosquito-to-human transmission, Zika virus infections have been documented through intrauterine transmission resulting in congenital infection, intrapartum transmission from a viremic mother to her newborn, sexual transmission, blood transfusion, and laboratory exposure (5). There is a theoretical concern that transmission could occur through organ or tissue transplantation, and although Zika virus RNA has been detected in breast milk, transmission through breastfeeding has not been documented (5). During outbreaks, humans are the primary amplifying host for Zika virus. An estimated 80% of persons who are infected with Zika virus are asymptomatic (2). Symptomatic disease generally is mild and characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. Symptoms usually last from several days to 1 week. Based on information from previous outbreaks, severe disease requiring hospitalization is uncommon, and fatalities are rare. During the current outbreak in Brazil, Zika virus RNA has been identified in tissues from several infants with microcephaly and from fetal losses in women who were infected during pregnancy (5,7,8). The Brazil Ministry of Health has reported a marked increase in the number of infants born with microcephaly in 2015, although it is not known how many of these cases are associated with Zika virus infection (8). Guillain-Barré syndrome also has been reported in patients following suspected Zika virus infection (5). Studies are under way to evaluate the risks for Zika virus transmission during pregnancy, the spectrum of outcomes associated with congenital infection, and the possible association between Zika virus infection and Guillain-Barré syndrome. Zika virus infection should be considered in patients with acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis, who traveled to areas with ongoing transmission in the 2 weeks preceding illness onset. Because dengue and chikungunya virus infections share a similar geographic distribution with Zika virus and symptoms of infection are similar, patients with suspected Zika virus infections also should be evaluated and managed for possible dengue or chikungunya virus infection (9,10). Other considerations in the differential diagnosis include malaria, rubella, measles, parvovirus, adenovirus, enterovirus, leptospirosis, rickettsia, and group A streptococcal infections. There is no commercially available test for Zika virus. Zika virus testing is performed in the United States at CDC and four state health department laboratories, and CDC is working to expand laboratory diagnostic testing to additional states. Health care providers should contact their state or local health department to facilitate testing. To evaluate for evidence of Zika virus infection, reverse transcription–polymerase chain reaction (RT-PCR) testing should be performed on serum specimens collected within the first week of illness (11). Immunoglobulin M and neutralizing antibody testing should be performed on specimens collected ≥4 days after onset of illness; however, these serologic assays can be positive because of cross-reacting antibodies against related flaviviruses (e.g., dengue and yellow fever viruses). Virus-specific cross-neutralization testing can be used to discriminate between cross-reacting antibodies in primary flavivirus infections, although neutralizing antibodies might still yield cross-reactive results in persons who were previously infected or vaccinated against a related flavivirus (i.e., secondary flavivirus infection). No specific antiviral treatment is available for Zika virus disease. Treatment is generally supportive and can include rest, fluids, and use of analgesics and antipyretics. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided until dengue can be ruled out to reduce the risk of hemorrhage. Febrile pregnant women should be treated with acetaminophen. Persons infected with Zika, dengue, or chikungunya virus should be protected from further mosquito exposure during the first few days of illness to reduce the risk for local transmission. No vaccine to prevent Zika virus infection is available. The best way to prevent Zika virus infection is to avoid mosquito bites by using air conditioning or window and door screens when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Most Environmental Protection Agency (EPA)–registered repellents, including N,N-diethyl-m-toluamide (DEET), can be used on children aged >2 months (12). When used according to the product label, EPA-registered insect repellents also are safe for pregnant and lactating women. All travelers should take steps to avoid mosquito bites to prevent Zika virus infection and other mosquito-borne diseases. Until more is known, and out of an abundance of caution, pregnant women should consider postponing travel to any area where Zika virus transmission is ongoing.† Pregnant women who do travel to one of these areas should talk to their health care provider before traveling and strictly follow steps to avoid mosquito bites during travel. Pregnant women who develop a clinically compatible illness during or within 2 weeks of returning from an area with Zika virus transmission should be tested for Zika virus infection (13). Fetuses and infants of women infected with Zika virus during pregnancy should be evaluated for possible congenital infection. Health care providers are encouraged to report suspected Zika virus disease cases§ to their state or local health departments to facilitate diagnosis and mitigate the risk for local transmission in areas where Aedes species mosquitoes are currently active. State health departments are requested to report laboratory-confirmed cases to CDC. CDC is working with the Council of State and Territorial Epidemiologists and other partners to develop a surveillance case definition, to provide further guidance and mechanisms for evaluating and reporting cases, and to track the outcomes of pregnant women infected with Zika virus and their babies.

SummaryWhat is already known on this topic? Zika virus is a mosquito-borne flavivirus transmitted primarily by Aedes aegyptimosquitoes. Most infections are asymptomatic, and symptomatic disease generally is mild. In May 2015, the first local transmission of Zika virus in the Region of the Americas was reported in Brazil. Following the spread of Zika virus in Brazil, there has been a marked reported increase in the number of infants born with microcephaly; it is not known how many of these cases are associated with Zika virus infection. What is added by this report? By mid-January 2016, local Zika virus transmission had been reported to the Pan American Health Organization from 20 countries or territories in the Region of the Americas; spread to other countries in the region is likely. Although local transmission of Zika virus has not been documented in the continental United States, infections have been reported among travelers visiting or returning to the United States, and these likely will increase. Imported cases might result in local transmission in limited areas of the continental United States. What are the implications for public health practice? The best way to prevent Zika virus infection is to avoid mosquito bites by avoiding exposure and eliminating mosquito breeding areas. Until more is known, pregnant women should consider postponing travel to any area with ongoing Zika virus transmission. Health care providers should contact their state or local health department about testing patients with symptoms of Zika virus infection and a compatible travel history.

Zika Virus Spreads to New Areas — Region of the Americas, May 2015–January 2016Early Release / January 22, 2016 / 65(3);1–4 Format:Select onePDF [2 MB]Recommend on FacebookTweetMorgan Hennessey, DVM1; Marc Fischer, MD1; J. Erin Staples, MD, PhD1 Corresponding author: Marc Fischer, [email protected], 970-221-6400. Top 1Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

CDC has put out an MMWR early release on Zika virus spread. http://www.cdc.gov/mmwr/volumes/65/wr/mm6503e1er.htm?s_cid=mm6503e1er.htm_w

Second MERS case found in Thailand24 Jan 2016 at 11:47 5,246 viewed1 commentsWRITER: ONLINE REPORTERSA 71-year-old man from Oman was tested positive for MERS by Thai hospitals. (Photo by Kitja Apichonrojarek) The Public Health Ministry on Sunday announced the country's second confirmed case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The patient is a 71-year-old man from Oman who travelled to Thailand on Jan 22 after having been treated at a hospital in that country for about one week for fever and a cough, according to Public Health Minister Piyasakol Sakolsatayadorn. The man tested positive for MERS at Bamrungrad and Chulalongkorn hospitals. The man was referred to Bamrasnaradura Infectious Diseases Institute on Saturday at 6.20pm and another laboratory test by the Medical Science Department confirmed he had contracted MERS. Dr Piyasakol said the Omani man is now being quarantined at the Bamrasnaradura Infectious Diseases Institute of the Diseases Control Department. The Public Health Ministry is looking for people who had contact with the patient. They included a relative who accompanied the patient, 218 crew and passengers who are still in Thailand, one taxi driver, a hotel employee, and 30 hospital staff. These people will be kept under close surveillance for 14 days. Of them, 37 are categorised as high-risk. They are the patient's relative, 23 air passengers, the taxi driver, the hotel employee, and 11 hospital staff. Those with a high risk will also be quarantied. Thailand confirmed its first case of MERS on June 18, last year. The patient was a 75-year-old male who travelled from Oman to Thailand. He was treated and declared free from the virus and was allowed to leave the kingdom. The disease did not spread to others. http://www.bangkokpost.com/news/general/837040/second-mers-case-found-in-thailand

Health | Sun Jan 24, 2016 12:04am ESTRelated: WORLD, HEALTHThailand reports second MERS case as virus detected in Omani manBANGKOK A woman wearing a mask walks past an information banner on Middle East Respiratory Syndrome (MERS) at the entrance of Bamrasnaradura Infectious Diseases Institute in Nonthaburi province, on the outskirts of Bangkok, Thailand, June 19, 2015.REUTERS/CHAIWAT SUBPRASOM Thailand has confirmed its second case of the Middle East Respiratory Syndrome (MERS) virus on Sunday, the country's health minister said. The virus was detected in a 71-year-old Omani man traveling to Bangkok on Friday, Public Health Minister Piyasakol Sakolsatayadorn told a news conference. "After taking a taxi to a hotel, he was checked for the virus at a hospital and the MERS virus was found," he said. "This case was found quickly, so the public should not panic," he added. The health minister said 37 others were being monitored for the virus, including the man's son who traveled with him. Thailand's first MERS case was detected last year in a businessman from Oman who survived the disease. MERS is caused by a coronavirus from the same family as the one that triggered China's deadly 2003 outbreak of Severe Acute Respiratory Syndrome (SARS). MERS was first identified in humans in Saudi Arabia in 2012 and the majority of cases have been in the Middle East. (Reporting Manunphattr Dhanananphorn; Writing by Orathai Sriring; Editing by Simon Cameron-Moore and Muralikumar Anantharaman) http://www.reuters.com/article/us-thailand-mers-idUSKCN0V202D

Thailand Confirms Second Case of MERSOmani national, 71, arrived in Bangkok on Friday to seek treatment for fever, cough ENLARGEA medical worker puts on a face shield during a drill at a private hospital in Bangkok in June, 2015, shortly after Thailand’s first case of Middle East respiratory syndrome was diagnosed. PHOTO: ATHIT PERAWONGMETHA/REUTERSBy WILAWAN WATCHARASAKWETJan. 24, 2016 12:36 a.m. ET0 COMMENTSBANGKOK—Health officials in Thailand on Sunday confirmed the country’s second case Middle East respiratory syndrome, or MERS. The patient, a 71-year-old Omani national, arrived in Bangkok on Friday to seek treatment for a persistent fever and cough. He had previously sought treatment in his home country but opted to travel to Thailand, a popular destination for patients from the Middle East, when his condition didn’t improve, health ministry officials said. He was tested and found positive for the virus, and is currently at Bamrasnaradura Infectious Diseases Institute on the outskirts of Bangkok, where a second round of tests confirmed that he has MERS Ministry officials said they have quarantined, and are monitoring, 37 people who had close contact with the man, including family members who traveled with him, as well as a taxi driver, passengers who sat near him, flight attendants and hospital personnel. Sophon Mekthon, permanent secretary Thailand’s health ministry said an earlier MERS case in June last year, involving a businessman from Oman, had led to improved detection and monitoring procedures, which assisted in the swift identification and treatment of the virus. MERS belongs to the same family of viruses as the common cold and severe acute respiratory syndrome, or SARS, and kills more than one-third of the people it infects, largely through respiratory infections. Symptoms include fever, cough and shortness of breath. No vaccine exists. Last year, South Korea struggled with an outbreak that killed 36 people. Write to Wilawan Watcharasakwet [email protected] http://www.wsj.com/articles/thailand-confirms-second-case-of-mers-1453613813

MERS case, 71M, ex-Oman has been confirmed in Thailand.

I just posted the sequence. The authors at link below should have technical info http://www.ncbi.nlm.nih.gov/nuccore/969945756