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3/9/2016
The current
epidemiology of Zika
virus
George W. Rutherford, M.D.
Global Health Sciences
March 7, 2016
The current epidemiology of Zika
virus
George W. Rutherford, M.D.
Global Health Sciences
March 7, 2016
Zika virus epidemiology
• Zika virus originally isolated from primates in
the Zika forest of Uganda in 1947
• First detected serologically in humans in
Nigeria in 1968
• Endemic across Western, Central and Eastern
tropical Africa
• Spread to Asia by 2007
• Basically follows the Aedes spp footprint
Range of Ae. aegypti
From: Hayes EB. Zika virus outside Africa. Emerg Infect Dis 2009; 15:1347-50.
More recent epidemiology
• Spread across the Pacific
– Yap Island (Micronesia) 2007
– French Polynesia 2013
– Cook Islands, New Calendonia 2014
– Easter Island February 2014
– Now in American Samoa, Samoa and Tonga
• First Latin American cases in Brazil in May 2015
• Spread through tropical Latin America and the
Caribbean
1948
Expansion other countries in Africa 1947-1948
1977
Pakistan, Malaysia, Indonesia 1977-1978
1978
Pakistan, Malaysia, Indonesia 1977-1978
2007
Yap Island (Micronesia) and Guam, 2007
2007
2014
New Caledonia (FR) and Cook Islands, 2014Easter Island (CHILE), 2014
2015
Brazil, May 2015
2016
Active transmission in the Americas 2016 (and other areas worldwide in previous 15 months, ECDC)
May 2015
October 2015
November 2015
December 2015
January 2016
Zika virus in the United States
• Reported from:
– Yap Island, Federated States of Micronesia (180)
– American Samoa (4)
– Puerto Rico (102)
– U.S. Virgin Islands (1)
– 154 travel-associated cases (not autochthonous
transmission) in US states and Puerto Rico
• Florida (42)
• New York (23)
• Texas (15)
• California (10)
Countries in the Americas with current
Zika virus transmission
Latin America
• Boliva
• Brazil
• Costa Rica
• Dominican
Republic
• Colombia
• Ecuador
• El Salvador
• French Guiana
• Guatemala
• Guyana
• Haiti
• Honduras
• Mexico
• Nicaragua
• Panama
• Paraguay
• Suriname
• Venezuela
Caribbean
• Aruba
• Barbados
• Bonaire
• Curacao
• Guadeloupe
• Jamaica
• Martinique
• Puerto Rico
• Saint Martin
• Saint Vincent and the
Grenadines
• Trinidad and Tobago
• US Virgin Islands
Sexual transmission
• 8 cases of male-to-female transmission
– Intercourse few days before onset of symptoms
• 3 cases of replication-competent Zika virus isolated
from semen 2-10 weeks after illness onset (persisted
longer than in blood)
• In all cases men were symptomatic and had
hematospermia
• CDC recommends abstinence or condoms for men
who may have been exposed and their pregnant
sexual partners
• Unknowns:
– Transmission without symptomatic infection
– Transmission from women to men
Why Zika and why now?
• Zika is a “new” pathogen that has been
introduced into a non-immune population and
has spread rapidly
• Aided in this case by widespread presence of
Ae. aegypti in the tropical Americas
• Zika will likely remain endemic as have West
Nile virus and yellow fever
Zika virus
• Single stranded RNA virus
• Mosquito-borne flavivirus
• Replicates in dendritic
cells at site of inoculation,
spreads to lymph nodes
and blood stream
• Can be found in blood
from day of onset of
clinical illness to 11 days
post onset
Flaviviridae
• Flavivirus
– Dengue virus
– Japanese encephalitis virus
– St. Louis encephalitis virus
– Tick-borne encephalitis virus
– West Nile virus
– Yellow fever
– Zika virus
• Hepacivirus
– Hepatitis C virus
• Pegivirus
– GBV-C (hepatitis G)
• Pestivirus
– Hog cholera
Zika virus transmission
• Primarily mosquito-
borne
– Aedes aegypti, Ae.
africanus, Ae.
apicoargenteus, Ae.
vitattus, Ae. furcifer, Ae.
polynesiensis
• From infected mother
to her fetus
• Blood transfusion
• Sexual transmission
Zika virus clinical manifestations
• 80 percent of infections are asymptomatic
• When symptomatic, generally mild
– Fever
– Rash
– Arthralgia
– Conjunctivitis
– Lasts several days to a week
• No specific treatment, avoid aspirin in children
• NIAID is screening antiviral compounds
From: Duffy MR, Chen T-H, Hancock T, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J
Med 2009; 360:2536-43.
Ae. aegypti range, United States
Reported complications for Zika virus
infection
• Microcephaly
• Guillain-Barré syndrome
• Thrombocytopenic purpura
• Leukopenia
• In French Polynesian outbreak in 2013, of
10,000 registered cases, there were 70 (0.7%)
severe cases
Microcephaly
• Abnormally small cranial vault secondary
to abnormal brain growth
• Clinical manifestations
– Seizures, developmental delay, intellectual
disability, problems with movement and
balance, dysphagia, hearing and vision loss
• Incidence 2-12/10,000 live births in the
U.S.
• Causes
– Infection (rubella, toxoplasmosis,
cytomegalovirus)
– Severe malnutrition
– Toxin exposures (e.g., alcohol)
Microcephaly cases by head diameter,
Pernambuco State, Brazil, 1999-2015
0
100
200
300
400
500
600
700
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
32-33 cm
<32 cm
Source: SENAC, SES-PE. Courtesy of PAHO
<32 cm is <3rd percentile, z-score ≤-3; 32-33 cm is <15th percentile, z-score <-2
Epidemic curve of microcephaly cases among at-term newborns and
preceding Zika virus circulation in: Pernambuco State, Brazil, 2015
Outbreak Rash & Fever
Detected by EBS
DEN test (-) ZIKV lab confirmed
Isolation of Zika virus from brains and
fetal tissue
• Zika isolated by RT-PCR from
brains of two infants with
microcephaly (36 and 38 weeks
gestation) who died within 20
hours of birth and from
products of conception of two
first trimester stillbirths from
Rio Grande do Norte state
• All four mothers had clinical
illnesses compatible with Zika
virus infection
• Newborn brains had
parenchymal calcification,
microglial nodules, gliosis, cell
degeneration and necrosis
Prevention
• Avoidance of areas with active transmission
• Avoiding Aedes mosquito bites
– Long-sleeved shirts and pants
– Permethrin-treated clothing
– Insect repellents
• DEET, picaridin and IR 3535 safe to use during pregnancy
– If infected, don’t feed the mosquitos
• Avoiding pregnancy (five countries)
• Condoms if potential for sexual exposure
Prevention
• Immunization
– Three strategies being pursued at NIAID:
• DNA vaccine (strategy similar to WNV vaccine)
• Attenuated live virus vaccine (similar to dengue vaccine)
• Genetically engineered VSV (similar to Ebola vaccine)
– Phase I trials in 2016?
• Natural infection to achieve immunity before
becoming pregnant
• Herd immunity (some evidence from Polynesia)
New mosquito control strategies
• Release of Insects carrying Dominant Lethal
genes (RIDL)
– Males carry lethal dominant trait
– Can be treated with artificial diet
– Released into wild and mate with WT females
– Offspring do not survive
• Endosymbiotic bacteria (Wolbachia)
– Inhibit replication of flaviviruses without affecting
Aedes fitness
Phuc, HK, Andreasen, MH, Burton, RS et al. Late-acting dominant lethal genetic systems and mosquito control. BMC
Biology. 2007; 5: 1–11.
Carvalho, DO, McKemey, AR, Garziera, L et al. Suppression of a field population of Aedes aegypti in Brazil by sustained
release of transgenic male mosquitoes. PLoS Neglect Trop Dis. 2015; 9: e0003864.
Walker, T, Johnson, PH, Moreira, LA et al. The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti
populations. Nature. 2011; 476: 450–453.
Mosquito control involves larviciding and adulticiding. The other strategy is to
remove habitat where standing water can facilitate mosquito breeding.
Guidelines for pregnant women
• Two scenarios:
– Pregnant women with history of travel to an area
with ongoing Zika virus transmission
– Pregnant women residing in an areas with ongoing
Zika virus transmission
• With or without symptomatic infection
There are 30 million passengers who fly to the United States each year from Zika-endemic
countries in Latin America and the Caribbean. 2.7 million from Brazil alone.
Why Zika and why now?
• This is a 21st century example of the Columbian
exchange although it came from West not East

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The current epidemiology of Zika virus

  • 1. 3/9/2016 The current epidemiology of Zika virus George W. Rutherford, M.D. Global Health Sciences March 7, 2016
  • 2. The current epidemiology of Zika virus George W. Rutherford, M.D. Global Health Sciences March 7, 2016
  • 3.
  • 4.
  • 5. Zika virus epidemiology • Zika virus originally isolated from primates in the Zika forest of Uganda in 1947 • First detected serologically in humans in Nigeria in 1968 • Endemic across Western, Central and Eastern tropical Africa • Spread to Asia by 2007 • Basically follows the Aedes spp footprint
  • 6. Range of Ae. aegypti
  • 7. From: Hayes EB. Zika virus outside Africa. Emerg Infect Dis 2009; 15:1347-50.
  • 8. More recent epidemiology • Spread across the Pacific – Yap Island (Micronesia) 2007 – French Polynesia 2013 – Cook Islands, New Calendonia 2014 – Easter Island February 2014 – Now in American Samoa, Samoa and Tonga • First Latin American cases in Brazil in May 2015 • Spread through tropical Latin America and the Caribbean
  • 9. 1948 Expansion other countries in Africa 1947-1948
  • 12. 2007 Yap Island (Micronesia) and Guam, 2007 2007
  • 13. 2014 New Caledonia (FR) and Cook Islands, 2014Easter Island (CHILE), 2014
  • 15. 2016 Active transmission in the Americas 2016 (and other areas worldwide in previous 15 months, ECDC)
  • 21. Zika virus in the United States • Reported from: – Yap Island, Federated States of Micronesia (180) – American Samoa (4) – Puerto Rico (102) – U.S. Virgin Islands (1) – 154 travel-associated cases (not autochthonous transmission) in US states and Puerto Rico • Florida (42) • New York (23) • Texas (15) • California (10)
  • 22. Countries in the Americas with current Zika virus transmission Latin America • Boliva • Brazil • Costa Rica • Dominican Republic • Colombia • Ecuador • El Salvador • French Guiana • Guatemala • Guyana • Haiti • Honduras • Mexico • Nicaragua • Panama • Paraguay • Suriname • Venezuela Caribbean • Aruba • Barbados • Bonaire • Curacao • Guadeloupe • Jamaica • Martinique • Puerto Rico • Saint Martin • Saint Vincent and the Grenadines • Trinidad and Tobago • US Virgin Islands
  • 23. Sexual transmission • 8 cases of male-to-female transmission – Intercourse few days before onset of symptoms • 3 cases of replication-competent Zika virus isolated from semen 2-10 weeks after illness onset (persisted longer than in blood) • In all cases men were symptomatic and had hematospermia • CDC recommends abstinence or condoms for men who may have been exposed and their pregnant sexual partners • Unknowns: – Transmission without symptomatic infection – Transmission from women to men
  • 24. Why Zika and why now? • Zika is a “new” pathogen that has been introduced into a non-immune population and has spread rapidly • Aided in this case by widespread presence of Ae. aegypti in the tropical Americas • Zika will likely remain endemic as have West Nile virus and yellow fever
  • 25.
  • 26.
  • 27.
  • 28. Zika virus • Single stranded RNA virus • Mosquito-borne flavivirus • Replicates in dendritic cells at site of inoculation, spreads to lymph nodes and blood stream • Can be found in blood from day of onset of clinical illness to 11 days post onset
  • 29. Flaviviridae • Flavivirus – Dengue virus – Japanese encephalitis virus – St. Louis encephalitis virus – Tick-borne encephalitis virus – West Nile virus – Yellow fever – Zika virus • Hepacivirus – Hepatitis C virus • Pegivirus – GBV-C (hepatitis G) • Pestivirus – Hog cholera
  • 30. Zika virus transmission • Primarily mosquito- borne – Aedes aegypti, Ae. africanus, Ae. apicoargenteus, Ae. vitattus, Ae. furcifer, Ae. polynesiensis • From infected mother to her fetus • Blood transfusion • Sexual transmission
  • 31. Zika virus clinical manifestations • 80 percent of infections are asymptomatic • When symptomatic, generally mild – Fever – Rash – Arthralgia – Conjunctivitis – Lasts several days to a week • No specific treatment, avoid aspirin in children • NIAID is screening antiviral compounds
  • 32. From: Duffy MR, Chen T-H, Hancock T, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009; 360:2536-43.
  • 33. Ae. aegypti range, United States
  • 34.
  • 35. Reported complications for Zika virus infection • Microcephaly • Guillain-Barré syndrome • Thrombocytopenic purpura • Leukopenia • In French Polynesian outbreak in 2013, of 10,000 registered cases, there were 70 (0.7%) severe cases
  • 36. Microcephaly • Abnormally small cranial vault secondary to abnormal brain growth • Clinical manifestations – Seizures, developmental delay, intellectual disability, problems with movement and balance, dysphagia, hearing and vision loss • Incidence 2-12/10,000 live births in the U.S. • Causes – Infection (rubella, toxoplasmosis, cytomegalovirus) – Severe malnutrition – Toxin exposures (e.g., alcohol)
  • 37.
  • 38. Microcephaly cases by head diameter, Pernambuco State, Brazil, 1999-2015 0 100 200 300 400 500 600 700 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 32-33 cm <32 cm Source: SENAC, SES-PE. Courtesy of PAHO <32 cm is <3rd percentile, z-score ≤-3; 32-33 cm is <15th percentile, z-score <-2
  • 39. Epidemic curve of microcephaly cases among at-term newborns and preceding Zika virus circulation in: Pernambuco State, Brazil, 2015 Outbreak Rash & Fever Detected by EBS DEN test (-) ZIKV lab confirmed
  • 40. Isolation of Zika virus from brains and fetal tissue • Zika isolated by RT-PCR from brains of two infants with microcephaly (36 and 38 weeks gestation) who died within 20 hours of birth and from products of conception of two first trimester stillbirths from Rio Grande do Norte state • All four mothers had clinical illnesses compatible with Zika virus infection • Newborn brains had parenchymal calcification, microglial nodules, gliosis, cell degeneration and necrosis
  • 41. Prevention • Avoidance of areas with active transmission • Avoiding Aedes mosquito bites – Long-sleeved shirts and pants – Permethrin-treated clothing – Insect repellents • DEET, picaridin and IR 3535 safe to use during pregnancy – If infected, don’t feed the mosquitos • Avoiding pregnancy (five countries) • Condoms if potential for sexual exposure
  • 42. Prevention • Immunization – Three strategies being pursued at NIAID: • DNA vaccine (strategy similar to WNV vaccine) • Attenuated live virus vaccine (similar to dengue vaccine) • Genetically engineered VSV (similar to Ebola vaccine) – Phase I trials in 2016? • Natural infection to achieve immunity before becoming pregnant • Herd immunity (some evidence from Polynesia)
  • 43. New mosquito control strategies • Release of Insects carrying Dominant Lethal genes (RIDL) – Males carry lethal dominant trait – Can be treated with artificial diet – Released into wild and mate with WT females – Offspring do not survive • Endosymbiotic bacteria (Wolbachia) – Inhibit replication of flaviviruses without affecting Aedes fitness Phuc, HK, Andreasen, MH, Burton, RS et al. Late-acting dominant lethal genetic systems and mosquito control. BMC Biology. 2007; 5: 1–11. Carvalho, DO, McKemey, AR, Garziera, L et al. Suppression of a field population of Aedes aegypti in Brazil by sustained release of transgenic male mosquitoes. PLoS Neglect Trop Dis. 2015; 9: e0003864. Walker, T, Johnson, PH, Moreira, LA et al. The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature. 2011; 476: 450–453.
  • 44. Mosquito control involves larviciding and adulticiding. The other strategy is to remove habitat where standing water can facilitate mosquito breeding.
  • 45. Guidelines for pregnant women • Two scenarios: – Pregnant women with history of travel to an area with ongoing Zika virus transmission – Pregnant women residing in an areas with ongoing Zika virus transmission • With or without symptomatic infection
  • 46.
  • 47.
  • 48.
  • 49. There are 30 million passengers who fly to the United States each year from Zika-endemic countries in Latin America and the Caribbean. 2.7 million from Brazil alone.
  • 50. Why Zika and why now? • This is a 21st century example of the Columbian exchange although it came from West not East