Epidemiology and entomology of the Zika virus outbreak M A T T H E W B A Y L I S I N S T I T U T E O F I N F E C T I O N A N D G L O B A L H E A L T H U N I V E R S I T Y O F L I V E R P O O L
Zika in the news After ~70 years of obscurity Rapid spread in South America Declared a Public Health Emergency of International Concern by WHO The first major infectious disease linked to human birth defects discovered in > 50 years
Zika virus - Flaviviridae WEST NILE JAPANESE ENCEPHALITIS ST LOUIS ENCEPHALITIS Zika virus external structure (3.8 A resolution cryo-em. Science, March 2016 10.1126/science.aaf5316 DENGUE: 1-4 ZIKA YELLOW FEVER
Discovery of Zika virus Discovered in a rhesus monkey in the Ziika forest of Uganda, 1947 First human case in 1952
Spread of Zika, 1950-2015 2013 1954 1954-1963 2007 2015 1947 Nigeria, 1953: first recognition of human illness caused by Zika virus Only 13 more cases reported in next 57 years! Yap (Micronesia), 2007: 5000 infections out of 6700 population (75% incidence) French Polynesia, 2013-14: 32,000 infections
Zika in South America March 2015: First detected in Bahia, Brazil [outbreak of rash] Oct 2015: first case in Colombia* Dec 2015: estimated 1.3M cases in Brazil March 2016: 51,500 cases in Colombia. Now present in 33 countries in Americas Sep 2015: rise in infants born with microcephaly Feb 2016: 4300 cases recorded Retrospectively: foetal abnormalities reported in French Polynesia * First case in S America outside of Brazil
Symptoms of Zika 74-81% of patients have no symptoms For others, mild, dengue-like symptoms Fever 65% Rash 90% Aches 65% Conjunctivitis 55% Also: myalgia, headache, retro-orbital pain, oedema, vomiting
Guillain-Barré syndrome Temporary paralysis - often triggered by recent infection. Autoimmune disease damages myelin sheath Recovery takes several weeks but can be fatal (5%), or cause persistent disability. Surge in G-B was detected in French Polynesia in 2013 when they had Zika (38 of 28,000 cases). In a recent case-control study: Strong association between G-B and previous Zika infection (Odds ratio > 34).
Microcephaly small brain/head Surge in reports in 2015
Zika causes microcephaly? Zika virus RNA detected in amniotic fluid of foetuses with microcephaly Zika virus RNA detected in brain tissue of foetuses and infants with microcephaly. High rate of microcephaly in infants born to mothers with past Zika infection Greatest risk in 1 st trimester Foetal abnormalities detected in 29% of women infected with Zika during pregnancy
Detection of Zika Detection of viral RNA by RT-PCR Transient, low-level infection Most successful within 1 week of clinical onset IgM-capture ELISA (MAC-ELISA) IgM appears as viraemia wanes one week after clinical onset Persists months RT-PCR + MAC-ELISA gives best diagnostic yield Cross-reactivity of ELISA with dengue Problem of original antigenic sin patients may respond to Zika with dengue antibody!
Zika transmission cycle Sylvatic cycle only seen (so far) in Africa Urban cycle: main vectors are: Aedes aegypti Aedes albopictus But also: Aedes hensilli (Yap) Aedes polynesiensis (French Polynesia) Petersen LR et al. N Engl J Med 2016;374:1552-1563.
Transmission by mosquitoes Aedes aegypti Yellow Fever mosquito Aedes albopictus Asian Tiger mosquito
Yellow fever mosquito
Asian tiger mosquito
Asian tiger mosquito
Experimental studies of vector competence Origin Source Virus Titre (logs) Field Singapore Uganda 1947 Field Field Brazil/USA/ other Madeira (ae) France (al) Ae aegypti v Ae albopictus (ae v al) New Caledonia, 2014 New Caledonia 2014 7 7.5 Temp Result Ref 29 C 100% ae 100% al 7 28 C 10% ae 5% al Li et al (2012) Wong et al (2013) Chouin- Carnero et al (2016) 7 28 C Both low Jupille et al (2016) Ae aegypti feeds often, only on people. albopictus feeds less often, and on animals. Vectorial capacity of Ae aegypti >> Ae albopictus
Is Britain at risk? If a tourist comes back with Zika, will it spread here? (452 imported cases into 17 EU countries by 4 May 2016) No Ae. aegypti or Ae. albopictus in UK but do have 34 other species
Are our mosquitoes competent? Collect mosquito larvae from field
Are our mosquitoes competent? Reared to adulthood in lab
Feed on blood + virus
Saliva extraction and testing After incubation, collect saliva. Determine vector competence by qrt- PCR of saliva to detect viral RNA Aim: to assess vector competence, the EIP and threshold temperature.
What should be done about Zika? Develop vaccines? May take 10-20 years Do nothing? Herd immunity may control infection; Endemic stability may control disease
Mosquito control with insecticides? But resistance is widespread. And if it worked, why is dengue still a problem?
SIT: Sterile insect technique Most insects only mate once; So a female mated to a sterlised male produces no offspring ever Mass release of sterile males can control populations Using radiation Using GM - OXITEC
Wolbachia Wolbachia in males sterilises them. Females are not sterilised and pass Wolbachia to their eggs. Wolbachia spreads through the population It also reduces the ability of mosquitoes to spread viruses
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