Zika virus, microcephaly and Guillain-Barré syndrome situation report

ZIKA VIRUS

ZIKA VIRUS MICROCEPHALY AND GUILLAIN-BARRÉ SYNDROME SITUATION REPORT 14 APRIL 2016 SUMMARY From 1 January 2007 to 13 April 2016, Zika virus transmission was documented in a total of 64 countries and territories. Mosquito-borne transmission:  42 countries are experiencing a first outbreak of Zika virus since 2015, with no previous evidence of circulation, and with ongoing transmission by mosquitos.  17 countries have reported evidence of Zika virus transmission prior to 2015, with or without ongoing transmission or have reported an outbreak since 2015 that is now over. Person-to-person transmission:  Six countries have now reported evidence of person-to-person transmission of Zika virus, other than mosquito-borne transmission (Argentina, Chile, France, Italy, New Zealand and the United States of America). In the week to the 13 April, two additional countries have reported mosquito-borne Zika virus transmission: Belize and Saint Lucia. Microcephaly and other fetal malformations potentially associated with Zika virus infection or suggestive of congenital infection have been reported in six countries (Brazil, Cabo Verde, Colombia, French Polynesia, Martinique and Panama). Two additional cases, each linked to a stay in Brazil, were detected in Slovenia and the United States of America. In the context of Zika virus circulation, 13 countries and territories worldwide have reported an increased incidence of Guillain-Barré syndrome (GBS) and/or laboratory confirmation of a Zika virus infection among GBS cases. Based on a growing body of research, there is scientific consensus that Zika virus is a cause of microcephaly and GBS. The global prevention and control strategy launched by the World Health Organization (WHO) as a Strategic Response Framework encompasses surveillance, response activities and research. This situation report is organized under those headings. 1

I. SURVEILLANCE Incidence of Zika virus  From 1 January 2007 to 13 April 2016, Zika virus transmission was documented in a total of 64 countries and territories (Fig. 1; Table 1). 42 countries are experiencing a first outbreak of Zika virus since 2015, with no previous evidence of circulation, and with ongoing transmission by mosquitos. 17 countries have reported evidence of Zika virus transmission prior to 2015, with or without ongoing transmission or have reported an outbreak since 2015 that is now over.  In the week to the 13 April, two additional countries have reported mosquito -borne Zika virus transmission: Belize and Saint Lucia.  Six countries have now reported evidence of person-to-person transmission of Zika virus, in the absence of mosquito-borne transmission (Argentina, Chile, France, Italy, New Zealand and the United States of America) (Table 2). Figure 1. Cumulative number of countries, territories and areas reporting Zika virus transmission in years, 2007-2014, and monthly from 1 January 2015 to 13 April 2016 70

Number of countries/territories/areas

60 50 40 30 20 10 0

2015

2016

 In the Region of the Americas, the geographical distribution of Zika virus has steadily widened since the presence of the virus was confirmed in October 2015. By 13 April 2016, 35 countries and territories in the Region of the Americas reported mosquitoborne transmission of the virus. In addition, three countries have reported sexual transmission of Zika virus (Fig. 2).  From 1 October 2015 to 2 April 2016, Colombia reported 61 778 suspected cases of Zika virus. The number of laboratory confirmed cases is 3061.1 1

http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Boletin%20epidemiologico%20semana%2013.pdf

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Table 1. Countries reporting vector-borne Zika virus transmission Classification WHO Regional Office AFRO Country / territory / area Cabo Verde Aruba*, Barbados, Belize§, Brazil, Bolivia (Plurinational State of), BONAIRE – Netherlands*, Colombia, Costa Rica, Cuba, Curaçao*, Dominica*, Dominican Republic, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana*, Haiti, Honduras, Jamaica, Martinique, Mexico, Nicaragua, Panama, Paraguay, Puerto Rico, Saint Lucia, Saint Martin, Saint Vincent and the Grenadines*, Sint Maarten*, Suriname, Trinidad & Tobago*, United States Virgin Islands, Venezuela (Bolivarian Republic of) Maldives* American Samoa, Fiji, Marshall Islands*, Samoa, Tonga* Gabon Bangladesh, Indonesia, Thailand Cambodia, Cook Islands, French Polynesia, Lao People’s Democratic Republic, Malaysia, Micronesia (Federated States of), New Caledonia, Papua New Guinea, Philippines, Solomon Islands, Vanuatu, Viet Nam ISLA DE PASCUA - Chile Total 1

Category 1. Countries experiencing a first outbreak AMRO/PAHO of Zika virus since 2015, with no previous evidence of circulation, and with ongoing transmission by mosquitos. SEARO WPRO Subtotal Category 2. Countries where SEARO there is evidence of Zika virus transmission prior to 2015, with or without ongoing WPRO transmission; or countries where an outbreak since 2015 is reported to be over. PAHO Subtotal Total AFRO

35

1 5 42 1 3

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1 17 59

*Additional information needed to better characterise the intensity of transmission § Mosquito-borne autochthonous transmission is very likely, but still under investigation. Categories are defined as follows: Category 1. Countries experiencing a first outbreak of Zika virus, with no previous evidence of circulation, and with ongoing transmission by mosquitos: countries where Zika virus has recently been introduced, with no evidence of circulation in the past and where there is ongoing transmission. These countries present a high risk of Guillain-Barré syndrome, microcephaly and other neurological disorders associated with Zika virus. Category 2. Countries where there is evidence of Zika virus transmission prior to 2015, with or without ongoing transmission or where the outbreak is reported to be over: this group includes countries that are not experiencing a first outbreak and where transmission has occurred at low levels in the past, and where transmission may or may not be ongoing or countries that have reported an outbreak since 2015 that is not over. This table lists countries that have experienced outbreaks after 2007, all countries with evidence of infection prior to 2007 are listed in http://www.who.int/bulletin/online_first/16-171082.pdf

Table 2. Countries reporting non vector-borne Zika virus transmission Classification WHO Regional Office Country / territory / area Argentina, Chile, United States of America France, Italy New Zealand Total 3 2 1 6 Countries with evidence of AMRO/PAHO person-to-person transmission of EURO Zika virus, other than mosquitoWPRO borne transmission Total

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Figure 2. Distribution of Zika virus, 2013-2016

ISLA DE PASCUA –Chile is not displayed in the map given the uncertainty in the start date. Circulation of Zika virus in Thailand, Cambodia and Lao People’s Democratic Republic started before 2013. Countries where sexual transmission occurred are not represented in this map. Available information does not permit measurement of the risk of infection in any country; the variation in transmission intensity among countries is therefore NOT represented on this map. Zika virus is not necessarily present throughout the countries/territories shaded in this map

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Figure 3. Countries, territories and areas reporting Zika virus, 2007-2016.

*These reports do not exclude the possibility that Zika virus is present in other countries, notably in Africa and Asia.

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 From 2007, locally acquired Zika virus cases have been reported in 17 countries and territories in the Western Pacific Region. In addition, one instance of sexual transmission in New Zealand has been reported. Nine of these countries and areas have reported mosquito-borne Zika virus infections in 2016 (American Samoa, Fiji, Marshall Islands, Micronesia (Federated States of), Papua New Guinea, Philippines, Samoa, Tonga and Viet Nam).  Cabo Verde, in the African Region, has reported that as of 11 April 2016, preliminary analysis of the 878 samples from suspected cases of Zika virus disease identified 198 with Zika virus IgM antibodies and 5 were positive for ELISA IgM. A total of 113 pregnant women were tested and found positive for Zika virus by serological and molecular tests.

Incidence of microcephaly  Microcephaly and/or CNS fetal malformations potentially associated with Zika virus infection or suggestive of congenital infection have been reported in Brazil (1113 cases), Cabo Verde (two cases), Colombia (seven cases), French Polynesia (eight cases), Martinique (three cases2) and Panama (three cases). Two additional cases, each linked to a stay in Brazil, were detected in Slovenia and the United States of America.  Between 22 October 2015 and 9 April 2016 a total of 7015 cases of microcephaly and/or central nervous system (CNS) malformations were reported by Brazil. Of these 7015 cases investigations have been concluded for 3179 and 1113 were suggestive of congenital infection (Table 3).3  These 7015 cases of microcephaly and/or CNS malformations reported in Brazil represent a sharp increase in comparison with the period from 2001 to 2014, when an average of 163 microcephaly cases was recorded nationwide per year. A detailed description of this increase is provided in a published paper.4  Microcephaly and/or CNS malformation cases have been detected in 21 out of 27 states in Brazil, but the reported increase is concentrated in the northeast region.  Among the 7015 cases of microcephaly and/or CNS malformation reported in Brazil, 235 child deaths occurred after birth or during pregnancy (including miscarriage or stillbirth); 50 of these had microcephaly and/or CNS malformation suggestive of congenital infection, 155 remain under investigation and 30 were discarded.  An outbreak of Zika virus in French Polynesia was followed by an increase in the number of CNS malformations in children born between March 2014 and May 2015.5 A total of 19 cases was reported including eight microcephaly cases during that period. This represents an increase compared to the national average of 0-2 cases per year. A recently published study estimated the risk to be 95 cases of microcephaly per 10 000 women infected during the first trimester.

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Two microcephaly cases and one fetal malformation. http://portalsaude.saude.gov.br/index.php/cidadao/principal/agencia-saude/23220-saude-confirma-1-113-casos-de-microcefalia-nopais 4 http://www.cdc.gov/mmwr/volumes/65/wr/mm6509e2er.htm?s_cid=mm6509e2er_w 5 http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00651-6.pdf

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Figure 4. Distribution of microcephaly and /or CNS malformation cases suggestive of congenital infections

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Table 3. Countries, territories and areas reporting microcephaly and /or CNS malformation cases potentially associated with Zika virus infection. Reporting country Brazil Cabo Verde Colombia French Polynesia Martinique Panama 6 Slovenia 7 United States of America Number of microcephaly and /or CNS malformation cases suggestive of congenital infections or potentially associated with a Zika virus infection 1113 2 7 8 3 3 1 1 Probable location of infection Brazil Cabo Verde Colombia French Polynesia Martinique Panama Brazil Brazil

 In the context of the Cabo Verde Zika virus outbreak, two microcephaly cases were reported. For the first case, samples from both the mother and the infant exhibited antiZika virus IgG antibodies confirmed by seroneutralization, while for the second case preliminary test of the woman’s serum yielded positive results for Zika virus IgM antibodies.  On 30 March, Colombia reported 50 live births with microcephaly between 4 January 2016 and 20 March 2016. This number represents an increase compared to the historical annual average expected (140 per year). So far, seven of the investigated cases presented Zika virus positive results by real-time PCR (Table 2).

Incidence of Guillain-Barré syndrome (GBS)  In the context of Zika virus circulation 13 countries or territories worldwide have reported increased GBS incidence and/or laboratory confirmation of a Zika virus infection among GBS cases (Table 4; Fig. 5). Table 4. Countries, territories or areas reporting Guillain-Barré syndrome (GBS) potentially related to Zika virus infection. Classification Reported increase in incidence of GBS cases, with at least one GBS case with confirmed Zika virus infection No increase in GBS incidence reported, with at least one GBS case with confirmed Zika virus infection

Country / territory / area Brazil, Colombia, Dominican Republic, El Salvador*, French Polynesia, Honduras, Suriname, Venezuela (Bolivarian Republic of) French Guiana, Haiti*, Martinique, Panama, Puerto Rico

*GBS cases with previous history of Zika virus infection were reported by the International Health Regulations (2005) National Focal Point in United States of America.

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http://www.nejm.org/doi/pdf/10.1056/NEJMoa1600651 http://governor.hawaii.gov/newsroom/doh-news-release-hawaii-department-of-health-receives-confirmation-of-zika-infection-in-babyborn-with-microcephaly/

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Figure 5. Distribution of reported cases of GBS with confirmed Zika virus infection

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Between October 2013 and April 2014, French Polynesia experienced the first Zika virus outbreak ever recorded in the country. During the outbreak, 42 patients were admitted to a hospital with GBS. This represents a 20-fold increase in incidence of GBS in French Polynesia compared with the previous four years. A published formal analysis of these data (a case-control study) showed a strong association between Zika infection and GBS.8 All 42 GBS cases were also confirmed for a Zika virus infection. Based on a 66% attack rate of Zika virus infection in the general population (judged from a serological survey), the risk of GBS was estimated to be 0.24 per 1000 Zika virus infections. In 2015, 42 GBS cases were reported in the Brazilian state of Bahia, among which 26 (62%) had a history of symptoms consistent with Zika virus infection.9 A total of 1708 cases of GBS were registered nationwide, representing a 19% increase from the previous year (1439 cases of GBS in 2014), though not all states reported an increase in incidence. From 1 December 2015 to 2 April 2016, Colombia reported 416 cases with neurological syndromes and clinical symptoms of Zika virus infection, of which 277 are GBS cases. In the context of polio surveillance, there has been a report of 39 acute flaccid paralysis cases, in children under 15 years old with a clinical history of Zika virus infection between 14 September 2015 and 19 March 2016. El Salvador recorded 178 GBS cases from 5 December 2015 to 22 March 2016, including five deaths, while the annual average number of GBS cases is 169. One GBS case has been laboratory confirmed for Zika virus infection. On 29 January 2016, Suriname reported an increased incidence of GBS: 10 GBS cases were reported in 2015 and four GBS cases were reported during the first weeks of 2016, while Suriname registers on average approximately four cases GBS per year. A Zika virus infection was confirmed by RT-PCR in two of the GBS cases reported in 2015. The Bolivarian Republic of Venezuela has also reported an increased incidence of GBS. Between 12 December 2015 and 9 March 2016, 578 GBS cases were reported, from which 235 presented symptoms consistent with Zika virus infection. In 2016, six GBS cases were confirmed by RT-PCR for Zika virus infection. The Dominican Republic has reported 11 GBS cases with history of Zika-like illness from 1 January to 12 March 2016. Six of these cases are children aged under 15 years and the remaining five are people aged over 50 years. Zika virus infection has been confirmed by RT-PCR in one GBS case, a one-year-old child and resident of the National District. The patient evolved favourably and has been discharged from the hospital. GBS cases with laboratory confirmed Zika virus infections were also reported from French Guiana (two cases), Haiti (one case), Honduras (one case), Martinique (six cases), Panama (two cases) and Puerto Rico (one case). Two reports, published in March 2016, describe other neurological disorders associated with Zika virus infection: a 15-year-old girl in Guadeloupe who developed an acute

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http://dx.doi.org/10.1016/S0140-6736(16)00562-6 http://apps.who.int/ihr/eventinformation/bulletin/31523-event-update-2015-07-17

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myelitis,10 a disorder caused by inflammation of the spinal cord, and in an 81-year-old man a case of meningoencephalitis, an inflammatory process involving both the brain and meninges.11 These reports highlight the need to better understand the range of neurological disorders associated with Zika virus infection.  Based on a growing body of research, there is scientific consensus that Zika virus is a cause of microcephaly, GBS and other CNS fetal malformations.12, 13, 14

II. RESPONSE  Key interventions being undertaken jointly by WHO and international, regional and national partners in response to this public health emergency are laid out in Table 4.  WHO and partners are working together on a combination of activities within six main areas of work; coordination, surveillance, care, vector control, risk communication and community engagement, and research at the global, regional and country level.  WHO, in collaboration with Zika response partners, has developed a Knowledge Attitude and Practices (KAP) survey resource pack as part of the Zika Strategic Response Framework. The resource pack is intended to be used by affected and at-risk countries, WHO, UN agencies and NGOs who plan to conduct KAP surveys in a community setting with adult respondents. It provides a bank of key questions in the domains of knowledge, attitudes and practices. It is intended that partners will identify key areas for investigation according to their operational priorities, select the most relevant questions and update them to reflect national and sub-national contexts. WHO will also coordinate the mapping of operational research on community perceptions and needs as results from the KAP surveys become available. The resource pack is currently available in English and it is being translated into Spanish and Portuguese.  WHO has developed new advice and information on diverse topics in the context of Zika virus.15 WHO’s latest information materials, news and resources to support risk communication, and community engagement are available online.16

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http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00644-9/fulltext http://www.nejm.org/doi/full/10.1056/NEJMc1602964?query=featured_zika 12 http://www.nejm.org/doi/full/10.1056/NEJMp1602708 13 http://www.nejm.org/doi/full/10.1056/NEJMsr1604338 14 http://www.who.int/mediacentre/factsheets/zika/en/ 15 See resources listed at end of report. 16 http://www.who.int/risk-communication/zika-virus/en/

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Table 4. Strategic Response Framework and Joint Operational Response Plan: summary of key response interventions Objectives Public health risk communication and community engagement activities Activities  Coordinate and collaborate with partners on risk communication messaging and community engagement for Zika.  Develop communication and knowledge packs and associated training on Zika virus and all related and evolving issues for communication experts.  Engage communities to communicate risks associated with Zika virus disease and promote vector control, personal protection measures, reduce anxiety, address stigma, and dispel rumours and cultural misperceptions.  Disseminate material on Zika and potentially associated complications for key audiences such as women of reproductive age, pregnant women, health workers, clinicians, and travel and transport sector stakeholders.  Conduct social science research to understand perceptions, attitudes, expectations and behaviours regarding fertility decisions, contraception, abortion, pregnancy care and care of infants with microcephaly and persons with GBS.  Support countries to monitor impact of risk communications.  Regularly update and disseminate guidelines/recommendations on emergency Aedes spp. mosquito control and surveillance.  Support insecticide resistance monitoring activities.  Support countries in vector surveillance and control, including provision of equipment, insecticides, personal protection equipment (PPE) and training.  Assess and support existing capacity and needs for health system strengthening, particularly around antenatal, birth and postnatal care, neurological and mental health services, and contraception and safe abortion.  Map access barriers limiting women’s capacity to protect themselves against unintended pregnancy.  Develop guidance for: families affected by microcephaly, GBS or other neurological conditions; women suspected or confirmed to have Zika virus infection, including women wanting to get pregnant, pregnant women and women who are breastfeeding; health workers on Zika virus health care, blood transfusion services, tools for triage of suspected Zika virus, chikungunya and dengue cases; and for health services management following a Zika virus outbreak.  Provide technical support to countries on health service delivery refinements and national level planning to support anticipated increases in service needs.  Procure and provide equipment and supplies to prepare their healthcare facilities in provision of specialized care for complications of Zika virus for prioritized countries and territories.

Vector control and personal protection against mosquitoes Care for those affected and advice for their caregivers

III. RESEARCH  Public health research is critical for establishing the causal link between Zika virus infection in pregnant women and congenital abnormalities in their babies and for understanding the pathogenesis of Zika virus infection. Technical assistance is being coordinated with various partner agencies globally and in affected countries to identify and answer critical questions (Table 5).  WHO convened several meetings among global experts on Zika and related topics during March 2016 to discuss evidence, answer pressing scientific questions and provide practical guidance to support countries responding to the outbreak and to cases of neurological disorders.  WHO will continue to lead the harmonisation, collection, review and analysis of data. 12

 Five key priority areas have been defined for public health research: 1. Establish causality between Zika virus infection and neurological disorders (in fetus, neonates, infants and adults): development of a causality framework and of a systematic review 2. Risk of adverse outcomes of pregnancy in women infected with Zika virus and follow-up of babies and infants: establish a cohort of pregnant women 3. Explore sexual transmission of Zika virus: establish a cohort of men and women and test regularly body fluids for the presence of Zika virus 4. Vector control research: evaluate interventions based on community and resistance of the vectors, develop surveillance system 5. Public health system research: evaluate the preparedness of health system to manage babies with microcephaly and assist their families, to manage patients with GBS; to evaluate the availability of contraception in health services to respond to the demand and assess abortion services. Table 5. Strategic Response Framework and Joint Operational Response Plan: research and development Objectives Fast-track research and development of new products including diagnostics, vaccines and therapeutics.

Activities      Identify research gaps. Support the conduct of research related to Zika virus diagnostics, therapeutics, vaccines and novel vector control approaches Convene research actors and stakeholders. Coordinate introduction of products after assessment and evaluation. Coordinate supportive research activities including regulatory support and data sharing mechanisms.

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Zika virus and potential complications WHO documents As of 13 April 2016

1. Epidemiology and Laboratory 1.1 Zika virus case definition AR │ CH │ EN │ FR │ RU │ SP │ PT AR │ CH │ EN │ FR │ RU │ SP │ PT AR │ CH │ EN │ FR │ RU │ SP │ PT

5. Health Systems 5.1 Maintaining a safe and adequate blood supply during Zika virus outbreaks AR │ CH │ EN │ FR │ RU │ SP │PT

1.2 Surveillance of Zika virus

1.3 Laboratory testing for Zika virus

6. International Health Regulations 6.1 Aircraft disinsection for mosquito control EN

2. Management of Complications 2.1 Prevention of potential sexual transmission of Zika virus AR │ CH │ EN │FR │ RU │ SP │ PT AR │ CH │ EN │ FR │RU │ SP │ PT

6.2 Travel health advice on Zika virus EN

2.2 Pregnancy management in the context of Zika virus 2.3 Assessment of infants with microcephaly in the context of Zika virus AR │ CH │ EN │ FR │RU │ SP │ PT

7. General Information Factsheets 7.1 Zika virus AR │ CH │ EN │FR │ RU │ SP │ PT AR │ CH │ EN │ FR │ RU │ SP AR │ CH │ EN │ FR │ RU │ SP

2.4 Identification and management of Guillain-Barré syndrome in the context of Zika virus AR │ CH │ EN │FR │ RU │ SP │ PT

7.2 Microcephaly

7.3 Guillain-Barré syndrome

2.5 Breastfeeding in the context of Zika virus AR │ CH │ EN │FR │ RU │ SP │ PT

2.6 Psychosocial support for pregnant women and for families with microcephaly and other neurological complications in the context of Zika virus infection EN │ SP │ PT

General information 7.4 Zika virus and potential complications: Questions and answers AR │ CH │EN │ FR │ RU │ SP

3. Vector Control 3.1 Monitoring and managing insecticide resistance in Aedes populations EN

7.5 Zika virus and safe blood supply: Questions and answers AR │ CH │ EN │FR │ RU │ SP AR │ CH │ EN │ FR │RU │ SP

7.6 Dispelling rumours around Zika and microcephaly 7.7 Information for travellers visiting Zika affected countries AR │ CH │ EN │ FR │ RU │ SP

3.2 Entomological surveillance for Aedes spp. in the context of Zika virus EN

7.8 Zika virus: video questions and answers EN

3.3 Protecting the occupational health and safety of workers in emergency vector control of Aedes mosquitos EN │FR │SP │ PT │

7.9 Zika Strategic Response Framework & Join Operations Plan EN

7.10 Zika virus disease timeline EN

4. Risk Communication and Community Engagement 4.1 Risk communications for Zika virus AR │ CH │ EN │ FR │RU │ SP │ PT

Information on research and data sharing 7.11 WHO involvement in Zika R&D AR │ CH │ EN │ FR │ RU │ SP

4.2 Knowledge, Attitudes and Practice surveys: Zika virus disease and potential complications EN │ SP │ PT

7.12 Data sharing in public health emergencies: a call to researchers EN EN

7.13 Zika Open