05/01/2023

The current epidemiology of Zika virus

George W. Rutherford, M.D.Global Health SciencesMarch 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

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

19992000

20012002

20032004

20052006

20072008

20092010

20112012

20132014

20150

100

200

300

400

500

600

700

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

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 fitnessPhuc, 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