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Summary What is already known about this topic? Congenital Zika virus infection can cause microcephaly and severe brain abnormalities. As more information about the associated clinical syndrome becomes available, the phenotype is expanding to include other, sometimes less severe features, such as brain abnormalities without congenital microcephaly. What is added by this report? Although infants with congenital Zika virus infection who have a normal head size have been described in large series, sufficient description of the features of congenital Zika syndrome in these infants has not been available. This report of a series of 13 infants with laboratory evidence of congenital Zika virus infection with normal head size at birth includes the findings from extensive imaging, neurologic, ophthalmologic, auditory, and orthopedic examinations. Follow-up of these infants has shown that for most, head growth deceleration occurs to the point of microcephaly after birth and significant neurologic sequelae are evident. What are the implications for public health practice? Additional information is needed to fully describe the spectrum of findings associated with congenital Zika virus infection; however, microcephaly might not be evident at birth but can develop after birth in infants with underlying brain abnormalities. These findings underscore the importance of early neuroimaging for infants exposed to Zika virus prenatally.

Vanessa van der Linden, MD1*; André Pessoa, MD2*; William Dobyns, MD3; A. James Barkovich, MD4; Hélio van der Linden Júnior, MD5; Epitacio Leite Rolim Filho, MD, PhD1,6; Erlane Marques Ribeiro, MD, PhD2; Mariana de Carvalho Leal, MD, PhD6,7; Pablo Picasso de Araújo Coimbra, MD8; Maria de Fátima Viana Vasco Aragão, MD, PhD9,10; Islane Verçosa, MD11; Camila Ventura, MD, PhD12,13; Regina Coeli Ramos, MD12; Danielle Di Cavalcanti Sousa Cruz, MD13; Marli Tenório Cordeiro, PhD14; Vivian Maria Ribeiro Mota15; Mary Dott, MD16; Christina Hillard, MA17; Cynthia A. Moore, MD, PhD17 Corresponding author: Cynthia A. Moore, [email protected]; 770-488-7100. Top 1Association for Assistance of Disabled Children, Recife, Pernambuco, Brazil; 2Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil; 3University of Washington and Seattle Children’s Research Institute, Seattle; 4University of California-San Francisco; 5Dr. Henrique Santillo Rehabilitation Center, Goiania, Brazil; 6Federal University of Pernambuco, Recife, Pernambuco, Brazil; 7Agamenon Magalhães Hospital (HAM), Recife, Pernambuco Brazil; 8Uniclinic Diagnóstico por Imagem, Fortaleza, Brazil; 9Centro Diagnóstico Multimagem, Recife, Pernambuco, Brazil; 10Mauricio de Nassau University, Recife, Pernambuco, Brazil; 11Caviver Clinical, Fortaleza, Ceará, Brazil; 12Altino Ventura Foundation, Recife, Pernambuco, Brazil; 13Pernambuco’s Eye Hospital, Recife, Pernambuco, Brazil; 12Oswaldo Cruz University Hospital, Recife, Pernambuco, Brazil; 13Professor Fernando Figueira Integral Medicine Institute, Recife, Pernambuco, Brazil; 14Centro de Pesquisas Aggeu Magalhães-Fiocruz, Recife, Pernambuco, Brazil; 15University of Fortaleza, Fortaleza, Brazil; 16Center for Surveillance, Epidemiology and Laboratory Services, CDC; 17National Center on Birth Defects and Developmental Disabilities, CDC. Top * These authors contributed equally to this report.

Description of 13 Infants Born During October 2015–January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth — Brazil Early Release / November 22, 2016 / 65 http://www.cdc.gov/mmwr/volumes/65/wr/mm6547e2.htm?s_cid=mm6547e2_w

week conf discard untested total weekly increase 45 58 227 424 709 37 44 58 225 389 672 19 43 57 223 373 653 29 42 54 216 354 624 22 41 47 213 342 602 16 40 46 208 332 586 25 39 42 204 315 561 23 38 42 200 296 538 55 37 41 196 246 483 32 36 40 195 216 451 12 35 40 190 209 439 13 34 38 168 220 426 25 33 34 158 209 401 16 32 29 102 254 385 18 31 24 101 242 367 23 30 22 97 225 344 24 29 21 92 207 320 23 28 21 80 196 297 41 27 21 75 160 256 62 26 18 64 112 194 13 25 13 56 112 181 17 24 11 51 102 164 27 23 6 50 81 137 19 22 6 43 69 118 23 21 6 41 48 95 7 20 5 26 57 88 7 19 5 26 50 81 9 18 5 24 43 72 14 17 5 21 32 58 8 16 4 20 26 50 6 15 4 18 22 44 11

Intense surveillance of microcephaly and other defects Congenital central nervous system Review on November 18, 2016 Between the epidemiological weeks 01 to 45 of 2016, Confirmed (58) fifty-eight cases of associated microcephaly To the Zika virus, 227 cases were discarded and 424 cases were study. http://www.ins.gov.co/boletin-epidemiologico/Boletn Epidemiolgico/2016 Boletín epidemiológico semana 45.pdf

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Tuesday, November 22, 2016 Press release from: Senate Administration for Justice and Consumer Protection Four dead salvaged from the Landwehr Canal swans of influenza virus was yesterday in the State Laboratory Berlin-Brandenburg detected type H5. The final confirmation by the National Reference Laboratory - the Friedrich Loeffler Institute - (FLI) is still pending. All animals are swans from the Landwehrkanal near the Baerwald bridge. Thus, the boundaries of the restricted area on Friday set up accordingly up to this north-south connection: Underground station Alt Tempelhof, Schöneberg Street / Manteuffelstraße , Kreuz Schöneberg Bayerischer Platz, wittenbergplatz, S-Bahn station Bellevue, Central Station, S-Bahnhof Oranienburger Str. Since the first outbreak of avian influenza pollen of type H5N8 in wild animals on Lake Plön in Schleswig-Holstein on 08.11.2016 37 wild birds from Berlin were examined for the presence of the virus of avian influenza of subtype H5 in the state laboratory Berlin-Brandenburg. Up to now, 5 animals have been positively evaluated. The risk that by this hotspot of the virus could be introduced into poultry flocks are mitigated by the establishment of a Sperrbezirks, an observation area and a freewheeling prohibition of dogs and cats in the forbidden area. Poultry farmers throughout Berlin have aufzustallen their animals and the locations with the prescribed Biosafety measures. For further information, please contact your local office. http://www.xhain.net/pm/senatsverwaltung-fur-justiz-und-verbraucherschutz

Four dead salvaged from the Landwehr Canal swans of influenza virus was yesterday in the State Laboratory Berlin-Brandenburg detected type H5. The final confirmation by the National Reference Laboratory - the Friedrich Loeffler Institute - (FLI) is still pending. All animals are swans from the Landwehrkanal near the Baerwald bridge. http://www.xhain.net/pm/2016/gefluegelpest-weitere-infizierte-schwaene-im-landwehrkanal

On November 18 FLI confirmed the first H5N8 wild bird case in Berlin (Mute swan that died on November 16 in Landwehr Canal). On November 19 media reports cited collection of six more swans on Saturday, and today media reports cited H5 confirmation in the first four (bringing the total number of H5 confirmations of dead swans in central Berlin to five.

week conf discard untested total weekly increase 44 58 225 389 672 19 43 57 223 373 653 29 42 54 216 354 624 22 41 47 213 342 602 16 40 46 208 332 586 25 39 42 204 315 561 23 38 42 200 296 538 55 37 41 196 246 483 32 36 40 195 216 451 12 35 40 190 209 439 13 34 38 168 220 426 25 33 34 158 209 401 16 32 29 102 254 385 18 31 24 101 242 367 23 30 22 97 225 344 24 29 21 92 207 320 23 28 21 80 196 297 41 27 21 75 160 256 62 26 18 64 112 194 13 25 13 56 112 181 17 24 11 51 102 164 27 23 6 50 81 137 19 22 6 43 69 118 23 21 6 41 48 95 7 20 5 26 57 88 7 19 5 26 50 81 9 18 5 24 43 72 14 17 5 21 32 58 8 16 4 20 26 50 6 15 4 18 22 44 11

Entre las semanas epidemiológicas 01 a la 44 de 2016 se han confirmado cincuenta y ocho (58) casos de microcefalias asociadas al virus Zika, 225 casos fueron descartados y 389 casos están en estudio. http://www.ins.gov.co/boletin-epidemiologico/Boletn Epidemiolgico/2016 Boletín epidemiológico semana 44.pdf

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Highly pathogenic avian influenza, Japan Information received on 22/11/2016 from Dr Kazuo Ito, Director, International Animal Health Affairs Office, Animal Health Division, Food Safety and Consumer Affairs Bureau, Ministry of Agriculture, Forestry and Fisheries, Tokyo, Japan Summary Report type Immediate notification Date of start of the event 15/11/2016 Date of confirmation of the event 21/11/2016 Report date 21/11/2016 Date submitted to OIE 22/11/2016 Reason for notification Reoccurrence of a listed disease Date of previous occurrence 17/02/2015 Manifestation of disease Clinical disease Causal agent Highly pathogenic avian influenza virus Serotype H5N6 Nature of diagnosis Clinical, Laboratory (basic), Laboratory (advanced) This event pertains to a defined zone within the country New outbreaks (2) Outbreak 1 Akita-shi, AKITA Date of start of the outbreak 15/11/2016 Outbreak status Resolved (15/11/2016) Epidemiological unit Zoo Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Black Swan:Cygnus atratus(Anatidae) 1 1 0 0 Outbreak 2 Akita-shi, AKITA Date of start of the outbreak 17/11/2016 Outbreak status Resolved (17/11/2016) Epidemiological unit Zoo Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Black Swan:Cygnus atratus(Anatidae) 1 1 0 0 Summary of outbreaks Total outbreaks: 2 Total animals affected Species Susceptible Cases Deaths Destroyed Slaughtered Black Swan:Cygnus atratus(Anatidae) 2 2 0 0 Outbreak statistics Species Apparent morbidity rate Apparent mortality rate Apparent case fatality rate Proportion susceptible animals lost* Black Swan:Cygnus atratus(Anatidae) ** ** 100.00% ** *Removed from the susceptible population through death, destruction and/or slaughter **Not calculated because of missing information Epidemiology Source of the outbreak(s) or origin of infection Unknown or inconclusive Epidemiological comments On 15th November 2016, one death case of Cygnus atratus (black swan) was found in the zoo and its sample was tested by antigen-capture kit with positive result for influenza A virus. On 17th November 2016, another death case of Cygnus atratus was found in the same facility and positive result was gained by antigen-capture kit. On 21st November 2016, the two dead cases were confirmed to be positive for H5N6 subtype influenza A virus. Control measures Measures applied Screening Vaccination prohibited No treatment of affected animals Measures to be applied No other measures Diagnostic test results Laboratory name and type Species Test Test date Result Hokkaido University (OIE Reference Laboratory) Black Swan haemagglutination inhibition test (HIT) 19/11/2016 Positive Hokkaido University (OIE Reference Laboratory) Black Swan neuraminidase inhibition assay 20/11/2016 Positive Hokkaido University (OIE Reference Laboratory) Black Swan reverse transcription - polymerase chain reaction (RT-PCR) 19/11/2016 Positive Hokkaido University (OIE Reference Laboratory) Black Swan reverse transcription - polymerase chain reaction (RT-PCR) 20/11/2016 Positive Hokkaido University (OIE Reference Laboratory) Black Swan virus isolation 19/11/2016 Positive Hokkaido University (OIE Reference Laboratory) Black Swan virus sequencing 21/11/2016 Positive Future Reporting The event is continuing. Weekly follow-up reports will be submitted. Map of outbreak locations

On 15th November 2016, one death case of Cygnus atratus (black swan) was found in the zoo and its sample was tested by antigen-capture kit with positive result for influenza A virus. On 17th November 2016, another death case of Cygnus atratus was found in the same facility and positive result was gained by antigen-capture kit. On 21st November 2016, the two dead cases were confirmed to be positive for H5N6 subtype influenza A virus. http://www.oie.int/wahis_2/public/wahid.php/Reviewreport/Review?page_refer=MapFullEventReport&reportid=21608

South Korea confirms highly pathogenic H5N6 bird flu outbreaks, ramps up quarantine A quarantine vehicle sprays disinfectant along the bank of a stream in Cheonan, Seoul, following the discovery of the avian influenza virus in wild bird excrement.PHOTO: EPA PUBLISHED 22 MIN AGO FACEBOOK0TWITTEREMAIL SEOUL (REUTERS) - South Korea has confirmed the country's first outbreaks of the highly pathogenic H5N6 bird flu virus and has ramped up quarantine measures in response, agriculture ministry officials said on Friday (Nov 18). The outbreaks occurred at two poultry farms in the central and southern parts of the country after the ministry reported last week that the H5N6 strain of the virus had been found in the faeces of migratory birds. Cases of human infection from the H5N6 virus have previously been reported in places including China and Hong Kong, with the virus killing six people in China since April 2014, according to data from the South Korean ministry. The discoveries come as cases of the different H5N8 virus have been reported in several European countries including France. South Korea's ministry said just over 62,000 birds had been culled to prevent the spread of the virus and that it had a issued a "movement control order" within a radius of 10km around the farms. There are no indications that the virus has spread more widely, a ministry official said. South Korea's last bird flu outbreak occurred in March, when the H5N8 strain was detected at a duck farm, leading to the slaughter of at least 11,000 birds. http://www.straitstimes.com/asia/east-asia/south-korea-confirms-highly-pathogenic-h5n6-bird-flu-outbreaks-ramps-up-quarantine

South Korea con firms two H5N6 poultry outbreaks, which follows detection of H5N6 in feces of wild birds.

http://www.renseradio.com/listenlive.htm

week conf discard untested total weekly increase 43 57 223 373 653 29 42 54 216 354 624 22 41 47 213 342 602 16 40 46 208 332 586 25 39 42 204 315 561 23 38 42 200 296 538 55 37 41 196 246 483 32 36 40 195 216 451 12 35 40 190 209 439 13 34 38 168 220 426 25 33 34 158 209 401 16 32 29 102 254 385 18 31 24 101 242 367 23 30 22 97 225 344 24 29 21 92 207 320 23 28 21 80 196 297 41 27 21 75 160 256 62 26 18 64 112 194 13 25 13 56 112 181 17 24 11 51 102 164 27 23 6 50 81 137 19 22 6 43 69 118 23 21 6 41 48 95 7 20 5 26 57 88 7 19 5 26 50 81 9 18 5 24 43 72 14 17 5 21 32 58 8 16 4 20 26 50 6 15 4 18 22 44 11

Intensified monitoring of microcephaly and other Congenital defects of the Central Nervous System Review November 4, 2016 Between the epidemiological weeks 01 to 43 of 2016, Confirmed (57) fifty-seven cases of associated microcephaly To the Zika virus, 223 cases were discarded and 373 cases were study. http://www.ins.gov.co/boletin-epidemiologico/Boletn Epidemiolgico/2016 Boletin epidemiologico semana 43.pdf

Report type Follow-up report No. 1 Date of start of the event 08/11/2016 Date of confirmation of the event 10/11/2016 Report date 17/11/2016 Date submitted to OIE 17/11/2016 Reason for notification Reoccurrence of a listed disease Date of previous occurrence 2006 Manifestation of disease Clinical disease Causal agent Highly pathogenic avian influenza virus Serotype H5N8 Nature of diagnosis Laboratory (advanced) This event pertains to the whole country Related reports Immediate notification (11/11/2016) Follow-up report No. 1 (17/11/2016) New outbreaks (5) Outbreak 1 (HPAIwb H5N8 2016/5) Kalvehave, Vordingborg, EAST Date of start of the outbreak 10/11/2016 Outbreak status Continuing (or date resolved not provided) Epidemiological unit Not applicable Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Laridae (unidentified):Laridae (incognita)(Laridae) 2 2 0 0 Affected population On November 10th, two gulls were found dead in Kalvehave harbor. Outbreak 2 (HPAIwb H5N8 2016/6) Bøjden, Faaborg-Midtfyn, EAST Date of start of the outbreak 10/11/2016 Outbreak status Continuing (or date resolved not provided) Epidemiological unit Not applicable Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Tufted Duck:Aythya fuligula(Anatidae) 2 2 0 0 Affected population On November 10th, two dead tufted duck were found in a wetland area near the town Bøjden on the Island Funen. Outbreak 3 (HPAIwb H5N8 2016/3) Darup, Roskilde, EAST Date of start of the outbreak 10/11/2016 Outbreak status Continuing (or date resolved not provided) Epidemiological unit Not applicable Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Tufted Duck:Aythya fuligula(Anatidae) 8 8 0 0 Affected population On November 10th, eight dead tufted ducks were found in a gravel pit near the village Darup. Outbreak 4 (HPAIwb H5N8 2016/4) Lindholm, Vordingborg, EAST Date of start of the outbreak 10/11/2016 Outbreak status Continuing (or date resolved not provided) Epidemiological unit Not applicable Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Great black-backed Gull:Larus marinus(Laridae) 1 1 0 0 Mute Swan:Cygnus olor(Anatidae) 1 1 0 0 Affected population On November 10th, a mute swan and a great black-backed gull were found dead on the Island Lindholm southeast of Zealand. Outbreak 5 (HPAIwb H5N8 2016/7) Høruphav, Sønderborg, WEST Date of start of the outbreak 11/11/2016 Outbreak status Continuing (or date resolved not provided) Epidemiological unit Not applicable Affected animals Species Susceptible Cases Deaths Destroyed Slaughtered Great black-backed Gull:Larus marinus(Laridae) 2 2 0 0 Affected population On November 11th, two great black-backed gull were found dead in Høruphav harbor on the Island Als. Summary of outbreaks Total outbreaks: 5 Total animals affected Species Susceptible Cases Deaths Destroyed Slaughtered Laridae (unidentified):Laridae (incognita)(Laridae) 2 2 0 0 Tufted Duck:Aythya fuligula(Anatidae) 10 10 0 0 Great black-backed Gull:Larus marinus(Laridae) 3 3 0 0 Mute Swan:Cygnus olor(Anatidae) 1 1 0 0 Outbreak statistics Species Apparent morbidity rate Apparent mortality rate Apparent case fatality rate Proportion susceptible animals lost* Laridae (unidentified):Laridae (incognita)(Laridae) ** ** 100.00% ** Tufted Duck:Aythya fuligula(Anatidae) ** ** 100.00% ** Great black-backed Gull:Larus marinus(Laridae) ** ** 100.00% ** Mute Swan:Cygnus olor(Anatidae) ** ** 100.00% ** *Removed from the susceptible population through death, destruction and/or slaughter **Not calculated because of missing information Epidemiology Source of the outbreak(s) or origin of infection Contact with wild species Epidemiological comments All shows and other gatherings of birds and poultry are prohibited. Danish Veterinary and Food Administration has ordered that it is mandatory to keep poultry indoor. Control measures Measures applied Movement control inside the country Vaccination prohibited No treatment of affected animals Measures to be applied No other measures Diagnostic test results Laboratory name and type Species Test Test date Result National Veterinary Institute (National laboratory) Tufted Duck reverse transcription - polymerase chain reaction (RT-PCR) 11/11/2016 Positive National Veterinary Institute (National laboratory) Tufted Duck reverse transcription - polymerase chain reaction (RT-PCR) 15/11/2016 Positive Future Reporting The event is continuing. Weekly follow-up reports will be submitted. Map of outbreak locations