疾病管制署 認識茲卡病毒感染症

茲卡病毒感染症大事紀 於桃園機場發燒篩檢站攔檢首例境外移入感染個案（泰國籍），成為全球第11個有境外移入個案的國家 2016/01/10 媒體大幅報導茲卡病毒可能造成小頭畸形 2016/01/16 臺灣CDC公告為第二類法定傳染病 提升中南美洲及加勒比海地區旅遊警示為第二級（警示）、東南亞4國為第一級（注意） 2016/01/22 行政院第3485次院會，張善政院長指示續密切監測國內外疫情，適時發布訊息並加強宣導 2016/01/28 公佈「茲卡病毒感染症防治工作指引」 馬總統召開國安高層會議 WHO宣布列為國際性關注公共衛生緊急事件（PHEIC） 2016/02/01 成立中央流行疫情指揮中心三級開設 提升為第五類法定傳染病 2016/02/02

茲卡病毒（Zika virus） 最早在1947年從烏干達茲卡森林中的彌猴體內分離出來 與登革熱病毒同屬黃病毒科（Flaviviridae)裡的黃病毒屬（Flavivirus） 為單股正鏈RNA病毒 有包膜、二十面體 依據基因型別分為 非洲型：烏干達（1947）、奈及利亞（1968）、塞內迦爾（1984） 亞洲型：馬來西亞（1966）、密克羅尼西亞聯邦 （2007）、柬埔寨（2010） Haddow AD, Schuh AJ, Yasuda CY, Kasper MR, Heang V, Huy R, et al. (2012) Genetic Characterization of Zika Virus Strains: Geographic Expansion of the Asian Lineage. PLoS Negl Trop Dis 6(2): e1477. doi:10.1371/journal.pntd.0001477

流行病學 病毒被發現後，大多只在非洲及亞洲發現散發的人類病例 2013年10月─2014年2月法屬玻里尼西亞爆發疫情 2007年4─7月在密克羅尼西亞聯邦（Federated States of Micronesia）的雅蒲島（Yap）首度發生群聚 首度於亞洲及非洲以外之地區發生 推估島上>3歲的居民約73％被感染 2013年10月─2014年2月法屬玻里尼西亞爆發疫情 估計約11％的居民因茲卡感染就診 病毒從法屬玻里尼西亞傳至鄰近的其他島國，如：法屬新喀里多尼亞、庫克群島、復活島、萬那杜、所羅門群島 從發現這病毒之後過了近半世紀，大多只有散發的人類病例在非洲及亞洲被發現，直到西元2007年在密克羅尼西亞聯邦的雅蒲島爆發群聚疫情，才有比較多對這疾病的認識。最近一波則是2013年十月發生於法屬玻里尼西亞疫情，在2015年5月，美洲的巴西也發現到茲卡病毒在當地現蹤，因此，茲卡病毒被認為是一個會持續擴展到新地區的新興傳染病。 依據基因型別分為亞洲型和非洲型兩種型別，在中非、東南亞和印度等都有發現的紀錄，直至2015年六月仍未有人因為茲卡病毒感染而死亡的案例

WHO證實巴西東北部 出現本土茲卡病毒感 染確診病例，為美洲 地區首例。 之後疫情疫情擴增至中、南美洲多個國家/地區，包括巴西、哥倫比亞、薩爾瓦多、瓜地馬拉、墨西哥、巴拉圭、蘇利南、委內瑞拉、宏都拉斯、巴拿馬、法屬馬丁尼克、法屬圭亞那、波多黎各、海地等 2015.05 巴西 WHO證實巴西東北部 出現本土茲卡病毒感 染確診病例，為美洲 地區首例。

Countries and territories showing historical distribution of Zika virus, 1947 - 2016 1947: Scientists conducting routine surveillance for yellow fever in the Zika forest of Uganda isolate the Zika virus in samples taken from a captive, sentinel rhesus monkey.1 1948: The virus is recovered from the mosquito Aedes (Stegomyia) africanus, caught on a tree platform in the Zika forest.1,2 1952: The first human cases are detected in Uganda and the United Republic of Tanzania in a study demonstrating the presence of neutralizing antibodies to Zika virus in sera.3 1954: The virus is isolated from a young girl in Eastern Nigeria.4 1958: Two further Zika virus strains are isolated from Aedes africanus mosquitos caught in the Zika forest area.5 1964: A researcher in Uganda who fell ill while working with Zika strains isolated from mosquitoes provides the first proof, by virus isolation and re-isolation, that Zika virus causes human disease. Though a pink non-itchy rash lasting 5 days eventually covers most of his body, including the palms of his hands and soles of his feet, he reports his illness as “mild”, as he did not experience the “crippling bone pain” associated with dengue and chikungunya infections. Given the mild nature of the illness, the author concludes that “it is not surprising under normal circumstances the virus is not isolated frequently from man.”6 1960s-1980s: Zika is now being detected in mosquitos and sentinel rhesus monkeys used for field research studies in a narrow band of countries that stretch across equatorial Africa. Altogether, virus is isolated from more than 20 mosquito species, mainly in the genus Aedes. Sporadic human cases are identified, mostly by serological methods, but such cases are rare, and the disease is regarded as benign. No deaths or hospitalizations are reported, and seroprevalence studies consistently indicate widespread human exposure to the virus.7–14 Molecular studies of viruses will later map the disease as it moves from Uganda to western Africa and Asia in the first half of the 20th century.15,16 1969–1983: The known geographical distribution of Zika expands to equatorial Asia, including India, Indonesia, Malaysia and Pakistan, where the virus is detected in mosquitos. As in Africa, sporadic human cases occur but no outbreaks are detected and the disease in humans continues to be regarded as rare, with mild symptoms. Seroprevalence studies in Indonesia, Malaysia and Pakistan indicate widespread population exposure.16–19 Researchers later suggest that the clinical similarity of Zika infection with dengue and chikungunya may be one reason why the disease was so rarely reported in Asia.7 2007: Zika spreads from Africa and Asia to cause the first large outbreak in humans on the Pacific island of Yap, in the Federated States of Micronesia. Prior to this event, no outbreaks and only 14 cases of human Zika virus disease had been documented worldwide.20 House-to-house surveys among the island’s small population of 11 250 people identify 185 cases of suspected Zika virus disease. Of these, 49 are confirmed (RNA identified by PCR or a specific neutralizing antibody response to Zika virus in the serum) and 59 are classified as probable (patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response). An estimated 73% of Yap residents over three years of age were infected with Zika virus. No deaths, hospitalizations, or neurological complications are reported.21,23 Although wind-blown mosquitoes can travel distances of several hundred kilometres over the open ocean, introduction of the virus by travel or trade involving an infected person or an infected mosquito is considered the most likely source of this outbreak, especially as no monkeys were present on the island during the outbreak.7,21 The finding on Yap Island that Zika virus can cause an outbreak numbering more than one hundred confirmed and probable cases is striking. In the absence of any evidence that viral mutation can explain changes in epidemic behaviour, several other explanations are suggested including a lack of population immunity; that is, regular exposure to infection in Africa and Asia may have prevented the large outbreaks eventually seen on Pacific Islands and in the Americas. Under-reporting may also be a reason for missing previous outbreaks of infection, due to the clinical similarities of (mild) illness associated with Zika, dengue, and chikungunya infections, and the frequent co-circulation of all three viruses. 2008: A US scientist conducting field work in Senegal falls ill with Zika infection upon his return home to Colorado and infects his wife in what is probably the first documented case of sexual transmission of an infection usually transmitted by insects.24 2012: Researchers publish findings on the characterization of Zika virus strains collected in Cambodia, Malaysia, Nigeria, Senegal, Thailand and Uganda, and construct phylogenetic trees to assess the relationships. Two geographically distinct lineages of the virus, African and Asian, are identified. Analysis of virus from Yap Island strengthens previous epidemiological evidence that the outbreak on Yap Island originated in south-east Asia.7,21,23,25 2013–2014: The virus causes outbreaks in four other groups of Pacific islands: French Polynesia, Easter Island, the Cook Islands, and New Caledonia.26,27 The outbreak in French Polynesia, generating thousands of suspected infections, is intensively investigated. The results of retrospective investigations are reported to WHO on 24 November 2015 and 27 January 2016. These reports indicate a possible association between Zika virus infection and congenital malformations and severe neurological and autoimmune complications.28 In particular, an increase in the incidence of Zika infection towards the end of 2013 was followed by a rise in the incidence of Guillain-Barré syndrome.22,29 However, because the island was also experiencing an outbreak of dengue, the association between Zika infection and Guillain-Barré syndrome remains suggestive but unproven. The finding does, however, challenge the notion that Zika infection causes only mild illness.22,30,31 December 2013: A patient recovering from Zika infection on Tahiti Island in French Polynesia seeks treatment for bloody sperm. Zika virus is isolated from his semen, adding to the evidence that Zika can be sexually transmitted.32 20 March 2014: During the 2013–14 outbreak of Zika virus in French Polynesia, two mothers and their newborns are found to have Zika virus infection, confirmed by PCR performed on serum collected within four days of birth. The infants’ infections appear to have been acquired by transplacental transmission or during delivery.33 31 March 2014: During the same outbreak of Zika virus in French Polynesia, 1505 asymptomatic blood donors are reported to be positive for Zika by PCR. These findings alert authorities to the risk of post-transfusion Zika fever.34 2 March 2015: Brazil notifies WHO of reports of an illness characterized by skin rash in northeastern states. From February 2015 to 29 April 2015, nearly 7000 cases of illness with skin rash are reported in these states. All cases are mild, with no reported deaths. Of 425 blood samples taken for differential diagnosis, 13% are positive for dengue. Tests for chikungunya, measles, rubella, parvovirus B19, and enterovirus are negative. Zika was not suspected at this stage, and no tests for Zika were carried out. 29 March 2015: Brazil provides further details on reports of an illness, in four northeastern states, characterized by skin rash, with and without fever. The case definition used is “person having rash with or without fever, of unknown etiology, and whose clinical profile does not fit in suspected case definitions of dengue, measles or rubella.” Cases were first identified in Pernambuco in December 2014. In Maranhao, Rio Grade do Norte, and Bahia, cases were identified in February and March 2015. 29 April 2015: Bahia State Laboratory in Brazil informs WHO that samples have tested positive for Zika virus, but full laboratory confirmation is pending. 7 May 2015: Brazil’s National Reference Laboratory confirms, by PCR, Zika virus circulation in the country. This is the first report of locally acquired Zika disease in the Americas. 7 May 2015: The Pan American Health Organization and WHO issue an epidemiological alert to Zika virus infection.35 15 July 2015: Brazil reports laboratory-confirmed Zika cases in twelve states. 17 July 2015: Brazil reports detection of neurological disorders associated with a history of infection, primarily from the north-eastern state of Bahia. Among these reports, 49 cases were confirmed as Guillain-Barré syndrome. Of these cases, all but 2 had a prior history of infection with Zika, chikungunya or dengue. 5 October 2015: Health centres in the Republic of Cabo Verde begin reporting cases of illness with skin rash, with and without fever, in the capital city of Praia, on the island of Santiago. By 14 October, 165 suspected cases are reported. 8 October 2015: Brazil reports the results of a review of 138 clinical records of patients with a neurological syndrome, detected between March and August. Of the 138, 58 (42%) present neurological syndrome with a previous history of viral infection. Of the 58, 32 (55%) have symptoms that are said to be consistent with Zika or dengue infection. 8 October 2015: Colombia reports the results of a retrospective review of clinical records which reveals the occurrence, since July, of sporadic clinical cases with symptoms consistent with Zika infection. A sudden spike is reported between 11 and 26 September. Altogether, 90 cases are identified with clinical symptoms consistent with, but not proven to be, Zika infection. 16 October 2015: Colombia reports PCR confirmed cases of locally acquired Zika infection. 21 October 2015: Cabo Verde confirms, by PCR, the country’s first outbreak of Zika infection. 22 October 2015: Colombia confirms, by PCR, 156 cases of Zika in thirteen municipalities, with most confirmed cases concentrated in the densely populated Bolivar department. 30 October 2015: Brazil reports an unusual increase in the number of cases of microcephaly among newborns since August, numbering 54 by 30 October. 2 November 2015: Suriname reports two PCR confirmed cases of locally acquired Zika infection. 5 November 2015: Colombia confirms, by PCR, 239 cases of locally acquired Zika infection. 11 November 2015: Brazil reports 141 suspected cases of microcephaly in Pernambuco state. Further suspected cases are being investigated in two additional states, Paraiba and Rio Grande do Norte. 11 November 2015: Brazil declares a national public health emergency as cases of suspected microcephaly continue to increase. 12 November 2015: Suriname reports 5 PCR confirmed cases of locally acquired Zika infection. 12 November 2015: Panama reports cases with symptoms compatible with Zika. 17 November 2015: The Pan American Health Organization and WHO issue an epidemiological alert asking PAHO Member States to report observed increases of congenital microcephaly and other central nervous system malformations under the International Health Regulations.36 17 November 2015: Brazil reports the detection of Zika virus in amniotic fluid samples from two pregnant women from Paraiba whose fetuses were confirmed by ultrasound examinations to have microcephaly. Altogether, 399 cases of suspected microcephaly are being investigated in seven northeastern states. 21 November 2015: Brazil reports that 739 cases of microcephaly are being investigated in nine states. 24 November 2015: El Salvador reports its first 3 PCR confirmed cases of locally acquired Zika infection. 24 November 2015: French Polynesia reports the results of a retrospective investigation documenting an unusual increase in the number of central nervous system malformations in fetuses and infants from March 2014 to May 2015. At the date of reporting, at least 17 cases are identified with different severe cerebral malformations, including microcephaly, and neonatal brainstem dysfunction. 25 November 2015: Mexico reports three PCR confirmed cases of Zika infection, of which two were locally acquired. The third case had a travel history to Colombia. 26 November 2015: Guatemala reports its first PCR confirmed case of locally acquired Zika infection. 27 November 2015: Paraguay reports six PCR confirmed cases of locally acquired Zika infection. 27 November 2015: The Bolivarian Republic of Venezuela reports seven suspected cases of locally acquired Zika infection. Four samples test positive by PCR. 28 November 2015: Brazil detects Zika virus genome in the blood and tissue samples of a baby with microcephaly and other congenital anomalies who died within 5 minutes of birth. 28 November 2015: Brazil reports three deaths among two adults and a newborn associated with Zika infection. As deaths from Zika infection are extremely rare, these cases are reported in detail. 1 December 2015: The Pan American Health Organization and WHO issue an alert to the association of Zika virus infection with neurological syndrome and congenital malformations in the Americas. The alert includes guidelines for laboratory detection of the virus.37 2 December 2015: Panama reports its first 3 PCR confirmed cases of locally acquired Zika infection. 6 December 2015: Cabo Verde reports 4744 suspected cases of Zika. No neurological complications are reported. 14 December 2015: Panama reports four PCR confirmed cases of locally acquired Zika infection, and 95 cases with compatible symptoms. 15 December 2015: Samples taken from patients in Cabo Verde test positive, by PCR, for Zika. 16 December 2015: Honduras reports two PCR confirmed cases of locally acquired Zika infection. 21 December 2015: French Guiana and Martinique report their first two PCR confirmed cases of locally acquired Zika infection. 22 December 2015: Brazilian researchers publish evidence, drawn from case reports in several countries, that depictions of Zika as “a mild cousin of dengue” may not be accurate due to the possibility of more serious disease symptoms, especially in immunocompromised patients.38 30 December 2015: Brazil reports 2975 suspected cases of microcephaly, with the highest number occurring in the north-east region. 31 December 2015: The United States reports the first PCR confirmed case of locally acquired Zika infection in the Commonwealth of Puerto Rico, an unincorporated territory of the United States. 5 January 2016: Researchers report the first diagnoses of intrauterine transmission of the Zika virus in two pregnant women in Brazil whose fetuses were diagnosed with microcephaly, including severe brain abnormalities, by ultrasound. Although tests of blood samples from both women are negative, Zika virus is detected in amniotic fluid.39 7 January 2016: The Maldives reports that a Finnish national who worked in the country became ill upon his return to Finland, where he tested positive, by PCR, for Zika infection. 7 January 2016: Scientists in Guyana publish the results of Zika genome sequencing of viruses from four patients in Suriname whose sera were negative for dengue and chikungunya viruses but positive for Zika virus. Suriname strains belong to the Asian genotype and are almost identical to the strain that circulated in French Polynesia in 2013.40 7 January 2016: Ophthalmologists in Brazil report severe ocular malformations in three infants born with microcephaly.41 12 January 2016: In collaboration with health officials in Brazil, the United States Centers for Disease Control and Prevention release laboratory findings (notified to WHO under IHR protocol) of four microcephaly cases in Brazil (two newborns who died in the first 24 hours of life and two miscarriages) which indicate the presence of Zika virus RNA by PCR and by immunohistochemistry of brain tissue samples of the two newborns. In addition, placenta of the two fetuses miscarried during the first 12 weeks of pregnancy test positive by PCR. Clinical and epidemiological investigations in Brazil confirm that all four women presented fever and rash during their pregnancy. The findings are considered the strongest evidence to date of an association between Zika infection and microcephaly.42 14 January 2016: Guyana reports its first PCR confirmed case of locally acquired Zika infection. 15 January 2016: The Unites States issues interim travel guidance for pregnant women which, “out of an abundance of caution,” advises pregnant women in any trimester to consider postponing travel to areas with ongoing local transmission of the virus, or to take precautions against mosquito bites if they must travel.43 15 January 2016: Ecuador reports its first two PCR confirmed cases of locally acquired Zika infection. The next day, the country confirms an additional 6 cases, of which 2 are locally acquired, three imported from Columbia, and one from the Bolivarian Republic of Venezuela. 15 January 2016: Barbados reports its first three PCR confirmed cases of locally acquired Zika infection. 15 January 2016: The Hawaii Department of Health (USA) reports a case of microcephaly in Hawaii, born to a woman who had resided in Brazil early in her pregnancy. 16 January 2016: The Plurinational State of Bolivia reports its first PCR confirmed case of locally acquired Zika infection. 18 January 2016: Haiti reports its first five PCR confirmed cases of locally acquired Zika. 18 January 2016: France reports the first PCR confirmed case of locally acquired Zika in Saint Martin. 19 January 2016: El Salvador reports an unusual increase of Guillain-Barré syndrome. From 1 December 2015 to 6 January 2016, 46 cases of the syndrome were reported, including two deaths.44 Of the 22 patients with a medical history, 12 (54%) presented with fever and skin rash in the 7 to 15 days before the onset of symptoms consistent with Guillain-Barré syndrome. 21 January 2016: Brazil reports 3893 suspected cases of microcephaly, including 49 deaths. Of these, 3381 are under investigation. In six cases, Zika virus was detected in samples from newborns or stillbirths. 22 January 2016: Brazil reports that 1708 cases of Guillain-Barré syndrome have been registered by hospitals between January and November 2015. Most states reporting cases are experiencing simultaneous outbreaks of Zika, chikungunya, and dengue. The potential cause of the upsurge in this syndrome cannot be established. 23 January 2016: The Dominican Republic reports its first 10 PCR confirmed cases of Zika infection, of which 8 were locally acquired and 2 were imported from El Salvador. 25 January 2016: France reports two confirmed cases of Guillain-Barré syndrome in Martinique. Both cases require admission to an intensive care unit. One patient tests positive for Zika virus infection. 25 January 2016: The United States reports the first PCR confirmed case of locally acquired Zika infection in St Croix, one of the three main islands in the United States Virgin Islands. 27 January 2016: Nicaragua reports its first two PCR confirmed cases of locally acquired Zika infection. 27 January 2016: French Polynesia reports retrospective data on its Zika outbreak, which coincided with a dengue outbreak. From 7 October 2013 to 6 April 2015, 8750 suspected cases of Zika were reported, with 383 PCR confirmed cases and an estimated 32 000 clinical consultations (11.5% of the total population). The outbreak ended in April 2014. During the outbreak, 42 cases of Guillain-Barré syndrome were diagnosed, representing a 20-fold increase in incidence over previous years. Though 10 of these patients required admission to an intensive care unit, none died. All 42 cases tested positive for Zika and dengue. Tests excluded other known causes of Guillain-Barré syndrome, including Campylobacter jejuni, cytomegalovirus, HIV, Epstein–Barr and herpes simplex viruses. The investigation concluded that successive dengue and Zika virus infections might be a predisposing factor for developing Guillain-Barré syndrome. 28 January 2016: Curacao reports its first PCR confirmed case of locally acquired Zika. 29 January 2016: Suriname reports 1,107 suspected cases of Zika, of which 308 are confirmed, by PCR, for Zika virus. 30 January 2016: Jamaica reports its first PCR confirmed case of locally acquired Zika. 1 February 2016: WHO declares that the recent association of Zika infection with clusters of microcephaly and other neurological disorders constitutes a Public Health Emergency of International Concern. 1 February 2016: Cabo Verde reports 7081 suspected cases of Zika between end September 2015 and 17 January 2016. The number of cases peaked at the end of November and began to decline. Though the reporting of cases of microcephaly is mandatory, no neurological complications are detected. 2 February 2016: Chile reports its first three PCR confirmed cases of Zika virus on the mainland in travellers returning from Colombia, the Bolivarian Republic of Venezuela, and Brazil. 2 February 2016: The United States reports a case of sexual transmission of Zika infection in Texas. One patient developed symptoms of illness after returning from the Bolivarian Republic of Venezuela. The second patient had not recently travelled outside of the United States, but subsequently developed symptoms after sexual contact with the traveller. This is the third indication that the virus can be sexually transmitted, which appears to be a rare event.44 4 February 2016: Brazilian health officials confirm a case of Zika virus infection transmitted by transfused blood from an infected donor. 7 February 2016: Suriname reports an increase in Guillain-Barré syndrome, beginning in 2015, with 10 cases of Guillain-Barré syndrome positive for Zika (PCR test on urine sample). Four Zika-related deaths are reported over the preceding 2 weeks (including one Dutch visitor), with symptoms of diarrhoea or vomiting, dehydration and joint pain, rapidly followed by death. All deaths occurred in older males with underlying illnesses or risk factors that may have contributed to the fatal outcomes.

目前有茲卡病毒傳播的地方

茲卡病毒主要傳染途徑 原本藉由蚊子在動物間傳播 藉由蚊子在人類間傳播開來 蚊子叮咬人類後，人將病毒帶進都會區 叢林循環 都會循環

其他傳染途徑 母子垂直感染 性行為傳染 其他可能傳染途徑 輸血傳染 哺乳 實驗室傳染 器官移植

Reduced fetal movement Medical termination Weeks of gestation 發燒、肌肉痛、後眼窩痛、紅疹 2015.02 Become pregnant Reduced fetal movement Normal growth 25-years-old European woman living in Brazil ! Intrauterine growth retardation, microcephaly, brain calcification on ultrasound 13 29 32 Microcephaly: head circumference 26 cm (1st percentile) Jernej Mlakar, et al. N Engl J Med 2016; 374:951-958

Prenatal Ultrasonographic Images and Photographs of Coronal Slices of Brain. Figure 1 Prenatal Ultrasonographic Images and Photographs of Coronal Slices of Brain. Panel A shows numerous calcifications in various parts of the brain (some marked with arrows) and the dilated occipital horn of the lateral ventricle (Vp, marked with a measurement bar) as seen on transverse ultrasonography. Panel B shows numerous calcifications in the placenta. Panel C shows multifocal cortical and subcortical white calcifications (arrows) and almost complete loss of gyration of the cortex. The basal ganglia are developed but poorly delineated (black asterisks), and the sylvian fissures are widely open on both sides (arrowheads on the left). The third ventricle is not dilated (white asterisk). Panel D shows dilated body of the lateral ventricles (white arrowheads); the left is collapsed. Temporal horns of the lateral ventricles (black arrowheads) are also dilated. The thalami (black asterisks) and the left hippocampus (white asterisk) are well developed, whereas the contralateral structure is not recognizable owing to autolysis. Mlakar J et al. N Engl J Med 2016;374:951-958

Microscopic Analysis of Brain Tissue. Figure 2 Microscopic Analysis of Brain Tissue. Panel A shows thickened leptomeninges (black arrowhead) and irregular cortical and subcortical calcifications (asterisks) associated with cortical displacement (arrows), with preserved germinative matrix (white arrowhead); gyration is absent. Panel B shows higher magnification of calcifications with filamentous structures (arrow), possibly representing encrusted, damaged axons and dendrites, and oval and polygonal structures (arrowheads), possibly representing encrusted, damaged neuronal-cell bodies (hematoxylin and eosin staining in Panels A and B). Panel C shows immunohistochemical labeling of proliferated reactive astrocytes that extend into the subarachnoid space (asterisk) (glial fibrillary acid protein, clone 6F2 [Dako]). Panel D shows immunohistochemical labeling of numerous activated microglial cells and macrophages in the cortex (full thickness marked with a line) and subcortical white matter (lower part of the figure). Nonspecific staining of the calcifications is present (arrow). Focal leptomeningeal infiltrates of macrophages are seen (arrowhead) (HLA-DR, clone TAL 1B5 [Dako]). Panel E shows neurofilament immunohistochemical staining of axons in a cross-section of the lumbar spinal cord with severe Wallerian degeneration of the lateral corticospinal tracts (black asterisks), moderate involvement of other descending tracts (arrows), and well-preserved ascending tracts in the dorsal columns (white asterisk) (neurofilament, clone 2F11 [Dako]). Panel F shows indirect immunofluorescence of fetal brain tissue, revealing a green granular intracytoplasmic reaction (see also inset). The yellow signals adjacent to the green granules indicate autofluorescence of lipofuscin, suggesting that viral particles are located in the cytoplasm of neurons. Mlakar J et al. N Engl J Med 2016;374:951-958

Electron Microscopy of Ultrathin Sections of Fetal Brain and Staining of a Flavivirus-like Particle. Figure 3 Electron Microscopy of Ultrathin Sections of Fetal Brain and Staining of a Flavivirus-like Particle. Panel A shows a damaged brain cell with a cluster of dense virions located in the disrupted endoplasmic reticulum. Remains of membranes derived from different cellular compartments and filamentous structures are also seen. A magnified view of the boxed area with virions clearly visible (arrows) is shown in Panel B. Panel C shows a group of enveloped structures with a bright interior, presumably indicating viral replication (arrow). Panel D shows a negatively stained viral particle with morphologic characteristics consistent with those of Flaviviridae viruses (arrow). Mlakar J et al. N Engl J Med 2016;374:951-958

Zika virus in semen 44-year-old man in Tahiti developed asthenia, low grade fever and arthralgia 8 weeks later: fever, headache, arthralgia 2 weeks later: hematospermia Blood: rRT-PCR for ZIKV negative Semen: rRT-PCR for ZIKV positive 3 days later Urine: rRT-PCR for ZIKV positive Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis. 2015 Feb [date cited]. http://dx.doi.org/10.3201/eid2102.141363

Patients 1 and 2. Kobylinski (left), Foy (right), collecting mosquitoes in Senegal with medical entomologist Massamba Sylla. http://www.sciencemag.org/news/2011/04/sex-after-field-trip-yields-scientific-first

Swollen ankle, rash, fatigue, chills, arthralgia, prostatitis Left Senegal Swollen ankle, rash, fatigue, chills, arthralgia, prostatitis Hematospermia 5 10 15 20 (日數) Arthralgia Rash Malaise, chills, headache, photophobia, muscle pain Foy BD, Kobylinski KC, Foy JLC, Blitvich BJ, Travassos da Rosa A, Haddow AD, et al. Probable non–vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis [serial on the Internet]. 2011 May [date cited]. http://dx.doi.org/10.3201/eid1705.101939

Returned to Dallas from 1 week in Venezuela fever, rash and conjunctivitis lasting 3 days Serum: IgM positive PCR negative 5 10 15 20 (日數) Serum: IgM positive PCR negative Serum: IgM ND PCR negative fever, myalgia, headache, lethargy, and malaise Deckard DT, Chung WM, Brooks JT, et al. Male-to-Male Sexual Transmission of Zika Virus — Texas, January 2016. MMWR Morb Mortal Wkly Rep 2016;65:372–374. DOI: http://dx.doi.org/10.15585/mmwr.mm6514a3

Detection in breast milk Mother/Newborn 1 Normal vaginal delivery of baby at 38 weeks gestation Mother had rash 2 days before delivery, lasting 4 days Baby breastfed immediately; no symptoms observed by 5 days post-delivery Mother/Newborn 2 Mother with gestational diabetes had C-section delivery of 38 week gestation baby because of complications Mother had rash and fever on day 3 post-delivery Baby began breastfeeding on day 3 post-delivery; had transient diffuse rash after 3-hours of ultraviolet light session on day 4 Mothers and Newborns all had ZIKAV infection confirmed by positive RT-PCR result on at least one serum sample Mothers’ breast milk samples were RT-PCR positive, but no replicative Zika virus found Besnard M, Lastère S, Teissier A, Cao-Lormeau VM, Musso D. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014 . Euro Surveill. 2014;19(13):pii=20751. Article DOI: http://dx.doi.org/10.2807/1560-7917.ES2014.19.13.20751

Detection in donated blood Study conducted using blood collected during French Polynesia’s Zika/Dengue outbreak, November 2013–February 2014 11% of population affected by Zika virus Blood taken only from voluntary donors who were asymptomatic at the time of donation 42/1,505 (2.8 %) tested positive by NAT 3/34 (8.8%) were positive in culture Musso D, Nhan T, Robin E, Roche C, Bierlaire D, Zisou K, Shan Yan A, Cao-Lormeau VM, Broult J. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014 . Euro Surveill. 2014;19(14):pii=20761. Article DOI: http://dx.doi.org/10.2807/1560-7917.ES2014.19.14.20761

預後 症狀通常2─7日 需要住院的重症不常見 死亡個案罕見 神經學併發症：法屬玻里尼西亞疫情爆發期間發現Guillain-Barre Syndrome (GBS)增加，但其相關性尚未被證實 小頭畸形：巴西報導疫情爆發地區同時有小頭畸形新生兒增加，但其相關性尚未被證實

神經學與 自體免疫 併發症 8,503人 曾因疑似茲卡病毒感染就醫 29,000人 推測感染茲卡病毒 67人 神經學併發症 法屬玻里尼西亞流行期間… 神經學與 自體免疫 併發症 8,503人 曾因疑似茲卡病毒感染就醫 29,000人 推測感染茲卡病毒 67人 神經學併發症 41人Guillain-Barre Syndrome 26人其他神經學併發症 7人 自體免疫併發症 4人診斷為idiopathic thrombocytopenic purpura (ITP) 2人有眼科併發症 1人有心臟併發症 http://www.hygiene-publique.gov.pf/IMG/pdf/bulletin_zika-dengue_.pdf

小頭畸形 小頭畸形 (AP Photo/Felipe Dana)

巴西疑似與茲卡病毒相關之小頭畸形調查結果

小頭畸型之巴西經驗 證據 建議 定義：頭圍小於33公分（12/7/2015改為32公分） 曾在小頭畸形的新生兒及死亡的胎兒檢驗出茲卡病毒 巴西2015年5月有疫情後，於10月首次發出警訊，疑似有因茲卡病毒感染產下小頭畸形的新生兒 證據 建議 曾在小頭畸形的新生兒及死亡的胎兒檢驗出茲卡病毒 有些小頭畸形的新生兒檢驗後無茲卡病毒感染 2015年同期的小頭畸形為往年之20倍 因沒有長期監測的資料，目 前並沒有真正的基準值可做 比較 茲卡病毒感染與小頭畸形之 相關性仍待確認 建議懷孕婦女，不論妊娠期， 均應避免感染

2月1日WHO第1次茲卡緊急會議 宣布2015–2016年巴西與2014年法屬玻里尼西亞之小頭畸形及神經系統異常群聚，屬異常事件，符合國際間關注的公共衛生緊急事件（PHEIC，[Public Health Emergency of International Concern]） 符合PHEIC事件之理由如下： 強烈懷疑神經系統異常/新生兒畸形與茲卡病毒感染症之因果關係 病媒蚊（斑蚊）分佈與地理分佈擴散速度快速 易感人口眾多 尚缺乏可信的診斷試劑 無疫苗及專門的治療方法 資料來源：WHO EIS、WHO

茲卡病毒感染症防治措施 已於2月2日公告為第五類法定傳染病 應於24小時內通報 病人發病期間應防蚊隔離，避免被病媒蚊叮咬 不幸死亡，遺體不需火化或深埋

A1+B1 或 A1+B2 或 A2B 茲卡病毒感染症病例定義 A. 臨床條件 B. 流病條件 通報條件 1. 有紅疹或發燒，且有下列任一（含）項以上症狀：關節痛（arthralgia）、關節炎（arthritis）、非化膿性或充血性結膜炎（non-purulent /hyperemic conjunctivitis），無法以其他醫學診斷解釋者 1. 發病前二週，住家或活動範圍附近有茲卡病毒感染症確定病例或與茲卡病毒感染症確定病例有接觸史 2. 小頭畸形*新生兒或其母親（母子垂直感染） *小頭畸形定義：依據年齡、性別及出生時妊娠期之生長曲線，頭圍小於第3個百分位（3rd percentile），且與身長、體重不成比例，經專科醫師評估為小頭畸形者 2. 發病前二週，有茲卡病毒感染症流行地區相關活動史 通報條件 A1+B1 或 A1+B2 或 A2B

茲卡病毒感染症病例定義 確定病例： C1 或 C2 或 C4 極可能病例：B1+C3 或 B2+C3 B. 流病條件 C. 檢驗條件 1. 發病前二週，住家或活動範圍附近有茲卡病毒感染症確定病例或與茲卡病毒感染症確定病例有接觸史 臨床檢體分離並鑑定出茲卡病毒 臨床檢體分子生物學核酸檢測陽性 急性期（或初次採檢）血清中，茲卡病毒特異性 IgM 或 IgG 抗體為陽性，並排除其他黃病毒交叉反應 成對血清（恢復期及急性期）中，茲卡病毒特異性 IgM 或 IgG 抗體（二者任一）有陽轉或≥4 倍上升 2. 發病前二週，有茲卡病毒感染症流行地區相關活動史 疾病分類 確定病例： C1 或 C2 或 C4 極可能病例：B1+C3 或 B2+C3

Aedes albopictus (yellow area) Aedes aegypti (red area) Geographically limited to Southern Taiwan Most common indoor habitat A “nervous feeder” leading to higher transmission rates Aedes albopictus (yellow area) Distributed throughout the island Below the sea level of 1500 m Most common outdoor habitat We believe the difference is because in the south, we have the mosquito Aedes aegypti, which has a different habitat compared to Aedes albopictus. Aedes aegypti are limited to southern Taiwan, as shown in red. These mosquitos are usually found indoors. They are nervous feeders, that they take in many small feeds and are easily disturbed by movement. Once feeding is interrupted, but they are still hungry, they go on to bite the next person. In the rest of Taiwan, the predominant mosquitos are aedes albopictus. These mosquitos usually stay outdoors. When they bite, they usually take in a full blood meal, instead of taking multiple bites. Today, Ae. aegypti is a cosmotropical species between latitudes 45°N and 35°S. Ae. aegypti is a highly domesticated, strongly anthropophilic, nervous feeder (i.e. it bites more than one host to complete one blood meal) and is a discordant species (i.e. it needs more than one feed for the completion of the gonotropic cycle). These habits epidemiologically result in the generation of multiple cases and the clustering of dengue cases in cities. More than 90% of the Ae. aegypti population rests on non-sprayable surfaces, namely dark, humid, secluded places inside houses or buildings, including bedrooms, closets, bathrooms and kitchens. Less often is it found outdoors in vegetation or other protected sites. The preferred indoor resting surfaces are the undersides of furniture, hanging objects such as clothes and curtains, and walls. Hence, indoor residual spray is not an option for its control as with malaria vectors. The adult Ae. aegypti has a lifespan of about 3–4 weeks. On the contrary, Ae. albopictus still maintains feral moorings and partly invades peripheral areas of urban cities, and thus feeds on both humans and animals. It is an aggressive feeder and a concordant species, i.e. the species can complete its blood meal in one go on one person and also does not require a second blood meal for the completion of the gonotropic cycle. Hence, Ae. albopictus carries poor vectorial capacity in an urban epidemic cycle. Basically Ae. albopictus is a feral species most commonly found in fringe areas of forests. Lin C, et al. The Study of Dengue Vector Distribution in Taiwan from 2009 to 2011. Taiwan Epidemiology Bulletin 2014;30. http://www.cdc.gov.tw/english/downloadfile.aspx?fid=412EEBD7DA1C783B

預防茲卡病毒感染 避免病媒蚊叮咬 穿著長袖長褲 清除積水容器 使用DEET防蚊液 目前無疫苗可預防，避免病媒蚊叮咬是最重要的預防方法 長時間戶外活動時，應穿著長袖衣褲，並可在衣服上噴灑防蚊液，增強保護效果 至流行地區活動時，應選擇裝有紗窗或空調設備的居住場所 清除家戶內外孳生源 如果確診為茲卡病毒感染症，發病期間要待在蚊帳內或室內，避免被蚊子叮咬造成傳染 使用DEET防蚊液 清除積水容器

孕婦須知 如無必要應暫緩前往流行地區 若必須前往請做好防蚊措施 美國環境保護署已認定孕婦可使用DEET，不會造成孕婦或胎兒的疾病 離開流行地區後應持續自主健康監測至少二週，如有任何疑似症狀，應儘速就醫，並告知醫師旅遊史

我剛從茲卡病毒流行地區疫區回來，要注意什麼？ 自主健康監測 至少二週 若有疑似茲卡病毒感染 的症狀，請及時就醫， 並告知醫師旅遊/暴露史 性行為：返國後28日內 請進行安全性行為 捐血：暫緩捐血28日

Zika virus in semen 44-year-old man in Tahiti developed asthenia, low grade fever and arthralgia 8 weeks later: fever, headache, arthralgia 2 weeks later: hematospermia Blood: rRT-PCR for ZIKV negative Semen: rRT-PCR for ZIKV positive 3 days later Urine: rRT-PCR for ZIKV positive Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis. 2015 Feb [date cited]. http://dx.doi.org/10.3201/eid2102.141363

Zika virus in Blood Study conducted using blood donated during outbreak of Zika virus in French Polynesia Blood donated during November 2013 to February 2014 were tested All blood donors were asymptomatic for Zika virus infection 42 (2.8%) of 1,505 donated blood were found positive for ZIKAV by PCR  Musso D, Nhan T, Robin E, Roche C, Bierlaire D, Zisou K, Shan Yan A, Cao-Lormeau VM, Broult J. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014 . Euro Surveill. 2014;19(14):pii=20761. Article DOI: http://dx.doi.org/10.2807/1560-7917.ES2014.19.14.20761

醫院來了一位自茲卡病毒疫區返國患者，怎麼辦？ 詳細詢問病史、旅遊地、接觸史等 理學檢查 有疑似茲卡病毒感染症症狀： 通報：24小時內 檢驗：血清 病人發病期間應 防蚊隔離，避免 被病媒蚊叮咬

懷孕婦女有茲卡病毒感染症流行地區活動史之通報與檢驗流程 懷孕婦女自茲卡病毒感染症流行地區返國 旅遊期間或返國後2週內有疑似症狀 旅遊期間或返國後2週內無疑似症狀 請求檢驗2 通報1 茲卡病毒檢驗1 檢驗陽性3／不確定 檢驗陰性 胎兒超音波4追蹤，每4週做一次 考慮做羊水茲卡病毒感染檢驗6 胎兒超音波4, 5 公衛單位追蹤訪視 胎兒有小頭畸形或顱內鈣化 胎兒沒有小頭畸形或顱內鈣化 茲卡病毒檢驗 考慮做羊水茲卡病毒感染檢驗6 常規產前檢查 注意： 1．建議只針對有疑似茲卡病毒感染症狀的孕婦做檢驗。且有疑似症狀之孕婦應通報並採檢送驗。茲卡病毒感染症臨床定義為：有紅疹或發燒，且有下列任一（含）項以上症狀：關節痛（arthralgia）、關節炎（arthritis）、非化膿性或充血性結膜炎（non-purulent /hyperemic conjunctivitis），無法以其他醫學診斷解釋者。 2．懷孕婦女若有茲卡病毒感染症流行地區相關活動史且要求檢驗，應於離開流行地區後2至12週檢驗。 3．檢驗陽性定義：1）臨床檢體分離並鑑定出茲卡病毒；2）臨床檢體分子生物學核酸檢測陽性；3）成對血清（恢復期及急性期）中，茲卡病毒特異性IgM或IgG抗體（二者任一）有陽轉或≥4倍上升。 4．胎兒超音波可能要到第二孕期後期或第三孕期前期才能檢測到小頭畸形或顱內鈣化。 5．可每4週追蹤一次。 6．羊水檢驗應於妊娠期第15週之後執行。羊水檢驗的敏感性及特異性目前不明。

傳染病個案通報系統通報畫面 通報與偵測>傳染病通報系統>傳染病個案(含疑似病例)報告單-新增

符合病例定義，通報茲卡病毒感染症 通報疾病>第五類法定傳染病>茲卡病毒感染症

無症狀孕婦請求檢驗，通報其他傳染病 通報疾病>其他傳染病>其他 其它病名請填寫:茲卡病毒篩檢 手寫、必填

各頁籤中欄位資料填寫完成後確定通報 通報與偵測>傳染病通報系統>傳染病個案(含疑似病例)報告單-新增 送出完成通報

考慮通報 發現小頭畸形的新生兒， 怎麼辦？ 尋找原因 1 2 TORCH: toxoplasma, OTHERS, rubella, CMV, HSV “Others”含syphilis, varicella-zoster, parvovirus B19 其他非感染症原因 1 發現小頭畸形的新生兒， 怎麼辦？ 考慮通報 若有新生兒疑似因感染茲卡病毒造成小頭畸形，應通報並採檢送驗 小頭畸形新生兒之母親應同時接受檢驗 2

新生兒小頭畸形要怎麼追蹤？ 照會遺傳諮詢專科醫師 照會兒童神經內科醫師，來決定是否需進一步進行腦部影像學的相關檢查 照會兒童神經內科醫師，來決定是否需進一步進行腦部影像學的相關檢查  進行梅毒（syphilis）、弓漿蟲（toxoplasmosis）、德國麻疹（rubella）、巨細胞病毒感染（cytomegalovirus [CMV]）、淋巴球性脈絡叢腦膜炎病毒（lymphocytic choriomeningitis virus [LCMV]）、單純皰疹病毒（herpes simplex）感染等相關檢驗，並考慮照會小兒感染科醫師 抽血檢驗血球數及血小板狀況，以及AST、ALT、bilirubin等肝功能指數 評估遺傳學方面的因素，以及考量其他可能導致畸形或先天異常的原因

進一步評估 腦部超音波 身體檢查 聽力評估 眼科檢查 發現疑似先天性 茲卡感染新生兒， 怎麼辦？ 是否有：神經系統異常、外觀異常、肝脾腫大、皮膚紅疹等症狀？可考慮照會專科醫師 腦部超音波 如果在第三孕程的產前胎兒超音波檢查並無發現胎兒腦部異常，可考慮不用再檢查 發現疑似先天性 茲卡感染新生兒， 怎麼辦？ 身體檢查 全面性的評估，包括測量頭圍、身長、體重及評估妊娠年齡 聽力評估 以誘發性耳聲傳射檢查(evoked otoacoustic emissions testing)或腦幹聽性反應檢查(auditory brainstem response testing)評估聽力 可在出院返家前或出生一個月內檢查 如果有聽力異常，建議照會專科醫師 眼科檢查 進行眼睛含視網膜的評估檢查 可在出院返家前或出生一個月內檢查 如有異常，建議照會小兒眼科醫師

疑似感染茲卡病毒新生兒長期追蹤 滿6個月時再做一次聽力追蹤檢查 第一年內須密切觀察評估新生兒的頭圍以及生長發育情形，如有發現異常，請照會相關專科醫師

結論 茲卡病毒近期於中南美洲流行，東南亞目前流行狀況不明 前往流行地區應確實做好防蚊，避免感染 因茲卡病毒感染疑似與產下小頭畸形新生兒相關，建議孕婦避免前往流行地區 疑似感染茲卡病毒的孕婦應接受積極追蹤

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