Parliamentary and Scientific Committee. Zika Meeting

Transcription

1 Parliamentary and Scientific Cmmittee Zika Meeting Event held as a cntributin twards British Science Week Prfessr Jimmy Whitwrth Department f Infectius Disease Epidemilgy at Lndn Schl f Hygiene and Trpical Medicine. Prfessr Whitwrth is c-rdinating the schls respnse t Zika. Intrductin t Zika virus Zika was first identified in Uganda first in mnkeys (1947), then in humans (1952). At first cnfined t equatrial Africa, then mved int Suth East Asia and t the Pacific Islands. In 2015 it was recrded in Central and Suth America. Zika is a flavivirus generally transmitted by the Aedes genus f msquites (these als carry dengue, chikungunya and yellw fever), althugh sme sexual transmissin ccurs. Symptms f Zika are usually mild and may include a rash, itching, fever, muscle pain and cnjunctivitis, hwever there are tw cnditins thught t be assciated with Zika which are especially wrrying: Micrcephaly - babies brn with small and malfrmed craniums, and a nn-fully develped brain S far an increase in micrcephaly cases, ther nenatal malfrmatins and adverse pregnancy utcmes has been reprted nly in Brazil and Clumbia (abut 1000 cases cnfirmed) **UPDATE** as f April 13 th, 2016, the link between Zika and micrcephaly has been cnfirmed. See Guillan-Barre syndrme (GBS) a temprary ascending paralysis, which is seen n recvery frm a number f viral infectins 8 cuntries have reprted an increased incidence f Guillain-Barré syndrme and/r labratry cnfirmatin f Zika virus infectin amng GBS cases (abut 1000 reprted) These additinal cnditins are nly seen in Central and Suth America, and the Caribbean Genetic analysis f the virus shwed it arrived in Brazil in 2014, and the gegraphical distributin has steadily widened since. It was nt nticed and recrded until There were 1 millin cases in Brazil in 2015, and 4 millin are expected in Active transmissin has been reprted in 31 cuntries. Actins n Zika in Active Transmissin Zne A Public Health Emergency f Internatinal Cncern was declared by WHO in February 2016 their highest emergency categry due t the pssible links t micrcephaly and GBS, rather than the infectin itself. Launched a Strategic Respnse Framewrk, which incrprates: crdinatin, surveillance, care, vectr cntrl risk cmmunicatin and cmmunity engagement research at glbal, reginal and cuntry levels $56 millin ver 6 mnths has been requested by the WHO (Wrld Health Organizatin) fr the respnse in the active transmissin zne Actins n Zika utside active transmissin zne

2 Zika virus is likely t be transmitted and detected in ther cuntries within the gegraphical range f cmpetent msquit vectrs, especially Aedes aegypti s there is a need t assess and mitigate the risk f spread by lking at: Msquit distributin Preparedness f health services Anti-msquit measures and plans Disinsectin f aircraft spraying f insecticide inside planes Travel infected humans r msquits can spread the infectin 10 cuntries have reprted imprted cases frm this utbreak 9 imprted cases in the UK Evidence f sexual transmissin, and transmissin via bld transfusin What is the UK Gvernment currently ding abut Zika? Public Health England are supprting WHO cntrl activities thrugh expert assistance Cntributin t WHO Cntingency Fund fr Emergencies Funding research thrugh rapid respnse calls (MRC, DFID, EC) DFID is: helping African cuntries prepare fr future ptential spread f Zika prviding health sectr supprt in Caribbean assisting disease surveillance in SE Asia Cntributing t utbreak respnse in Haiti What mre d we need t be ding abut Zika? Urgent: Develp a reliable diagnstic test ideally we need diagnstics that can be used at the bedside t give a quick answer, rather than in the lab, but at the mment any reliable test wuld be an advance Assess mdern anti-msquit measures currently relying n ld methds Assess risks f micrcephaly and GBS currently nt able t give accurate risk predictins Als need t understand when transmissin frm mther t fetus ccurs in pregnancy Cmmunity engagement and cmmunicatin need t get messages arund risk clear hard t d fr a disease which is usually mild, but can have devastating cnsequences Need t wrk ut hw best t prvide infrmatin and advice n risks, pregnancy, cntraceptin, abrtin Medium term: Vaccine develpment vaccines are at least 18 mnths away Drug develpment - althugh if develped, culd pssibly be prblematic hw d yu persuade peple, especially thse wh are pregnant, t take drugs fr a disease which generally has mild symptms? Establish hst range in vectrs need t establish which msquites culd start acting as vectrs Plans t care fr thse with disability thse with micrcephaly will need life-lng supprt Questins Q: Sir Peter Bttmley What was the histric impact f Zika? Why has it nly just cme t ur attentin? A: The disease used t be fairly inffensive. It was nly in Plynesia (5 years ag) that we started t see epidemics Q: Stuart Taylr (Ryal Sciety) Is it knwn when in pregnancy that birth defects arise? A: It is knwn frm studying Rubella that the first trimester is the mst risky stage f pregnancy. But early wrk n Zika seems t suggest any stage is risky Zika infectin in pregnancy has led t miscarriage at 37 weeks. Q: Barness Tnge have we seen micrcephaly assciated with Zika virus befre?

3 A: It is nt thught there were the same epidemics in humans befre the virus was mainly endemic in primates, nly 7-10% f the human ppulatin in endemic areas wuld have caught it. Q: Claire Mucht (French Embassy) des the virus stay in the bdy and have lnger term effects? A: Currently n evidence f such. Q: Hw lng after infectin is the virus fund in semen? A: Knwn t stay in bld in urine fr a week. Lnger in semen, but nt knwn hw lng exactly. Dr James Lgan Senir Lecturer in Medical Entmlgy at the Lndn Schl fr Hygiene and Trpical Medicine, and Directr f arctec The main vectrs Primary vectr: Aedes aegypti a msquit species highly adapted t the urban envirnment Aggressive biters bite even thrugh clthing, and will take multiple bld meals Bite during day and night, indrs and utdrs D nt fly far: ~50m s cntrl measures arund hmes/schls can be effective Mainly absent frm Eurpe t cld here Secndary vectr: Aedes albpictus Less adapted t urban envirnment frest dwellers Less aggressive biters Usually smaller ppulatins Can survive in temperate regins There are ppulatins in suthern Eurpe prbably nly a matter f time befre they arrive in the UK

4 Figure 1 - Glbal map f the predicted distributin f the tw main vectrs: Aedes aegypti tp, and Aedes albpictus bttm. The maps depict the prbability f ccurrence (frm 0 blue t 1 red) at a spatial reslutin f 5 km 5 km. Taken frm (Kraemer et al. 2015) The disease has als been islated frm certain species f the fllwing genera f msquit, but nt t the extent t prve them as vectrs: Anpheles (malaria vectr) Aedes (ther) (vectr f dengue, chikungunya, yellw fever) Culex (vectr f filariasis and West Nile virus) What vectr cntrl is being dne? Insecticides are used t kill adult msquites Results f fgging with insecticides are ften shrt lived resident msquites killed, but there is influx f msquites frm surrunding ppulatins Mre f a PR exercise? Very visual, but evidence fr effectiveness is sparse. Residual spraying is lng lasting but expensive Insecticide resistance is an issue msquites can adapt t survive treatment with insecticides Can als use insecticides t target the larvae, which grw in stagnant water Temephs resistance has develped Bti and Pyriprxifen shw n resistance Can als just remve stagnant water frm neighburhds cheap but very labur intensive Water pls in rubbish, tyres, flat rfs, etc Prmtin f bed net usage gd fr malaria (as the vectr msquites bite at night), but nt s helpful fr Zika, which is vectred by day biting msquites But imprtantly they still have a rle fr thse sleeping during the day eg. children napping, shift wrkers, thse taking a siesta s shuld be recmmended There is evidence that vectr cntrl reduces msquit ppulatins, but in practice there are many challenges: Resistance Educatin f cmmunities

5 C-rdinatin and sustainability Lack f evidence fr effectiveness in cntaining the disease due t lack f studies mre research needed Insect repellents are highly recmmended t prvide persnal prtectin. Are being given ut t pregnant wmen in Brazil by gvernment and clinics. Fur main active ingredients: DEET (diethyl-m-tluamide): a synthetic repellent - the best and mst widely used % cncentratin recmmended. Recmmended fr pregnant wmen. Safety prven. PMD (p-menthane dil): a natural repellent frm lemn eucalyptus Icaridin (Bayrepel): synthetic repellent IR3535 : synthetic repellent Ø Latter three are effective but require mre frequent reapplicatin than DEET Hwever, resistance t DEET has been shwn t develp after just ne generatin in the lab (Stanczyk et al. 2010), s needs t be mnitred in the wild. Repellents have nt been used n this scale befre, s need t watch clsely fr resistance. Jury is ut n effectiveness f repellents in cntrlling disease. There have been eight trials f the effectiveness f repellents against malaria, fur f which are adequate fr meta-analysis. Meta-analysis fund there was a nn-significant reductin f 30% in risk f P. falciparum infectin (Wilsn et al. 2014) - mre trials needed. Aircraft disinsectin cabin crew spray inside cabin with aersl insecticide. Very little evidence this wrks; further trials needed yet recmmendatins (fr usage) have been made. Wearable technlgies clthing impregnated with repellent r insecticide prvides % prtectin against bites, and lasts fr 4-5 mnths. Affective even against resistant msquites. Culd be used t prtect against msquites that transmit malaria, Zika, dengue and ther insectbrne diseases Further wrk underway at LSHTM and via arctec and a new spin-ut cmpany frm LSHTM called Vectech t develp this technlgy further Ptential new methds f vectr cntrl GM Msquites develped by Oxitec, a startup based in Oxfrd. Engineered t nt prduce viable ffspring. Trials have been carried ut in Brazil (several lcatins), Cayman Islands and Panama. They shwed up t 90+% suppressin f ttal Aedes aegypti msquites (measured by direct cunting f larvae). Over 150 millin Oxitec msquites released wrldwide; n adverse effects n peple r the envirnment. Ptential issues: Scial dislike, reinvasin f adults frm ther areas, technlgy is species specific, scale up is hard Ø This is nt an immediate slutin, but it has ptential Ø There is a gd pprtunity nw t take this technlgy t the next level and investigate its efficacy further Anther ptential methd f cntrl is the use f the bacteria Wlbachia. This is an endsymbitic bacteria which lives inside cells and infects >65% f insects. It is maternally inherited and manipulates hst reprductin t enhance transmissin. Imprtantly it inhibits the replicatin f Dengue, Chikungunya & Zika viruses in Aedes aegypti msquites. Rapidly invades and establishes in wild msquit ppulatins Released in wild msquit ppulatins in Brazil, Indnesia, Vietnam and Australia This technlgy is currently in very early stages but this utbreak is a gd pprtunity t develp it further. We may be able t explit humans natural differential attractiveness t msquites. It has been estimated that 10% f the ppulatin are unattractive t msquites if we can understand why we may be able t make thers unattractive t msquites t. This has never been investigated in disease endemic cuntries again this is a gd pprtunity. We knw that pregnant wmen are mre attractive t malarial msquites is it the same fr Aedes?

6 Attractiveness t msquites is under strng genetic cntrl s culd there be ppulatins that have evlved natural repellency? (Fernández-Grandn et al. 2015) If the genes can be identified, then a pill culd be develped that upregulates the genes in questin, and generates an aurra f repellency arund individuals. Needs ging frward Glbal msquit database currently n glbal database f msquit vectrs f disease Guidelines & training fr vectr cntrl in S. America Cmmunity educatinal campaigns Guidelines fr vectr cntrl fr mitigatin and rapid respnse in at risk cuntries Define accurate levels f resistance t insecticides & repellents Develpment and large trials f new technlgies Questins Q: Stephen Metcalfe MP Are sme cuntries better at vectr cntrl than thers? A: Yes it s very much wealth dependant. Different cuntries als have different techniques they favur and these are nt necessarily the mst efficient. Q: Lrd Selburne Hw practical is it lking t scale up the prductin f msquites by Oxitec? A: They think it is feasible, just a matter f getting enugh funding. They have just built a secnd factry in Brazil will be able t prtect 1 millin peple. Are als able t build temprary factries in trucks. Hwever fr scale up t be effective they need t develp methds f aerial deplyment (currently just thrw msquites ut f lrries) and that will require mre research. Q: Sally Cutter D we knw hw Zika virus interacts with the msquit hst? A: Nt yet mre research needed! Q: Are there reservirs in ther animals? A: Dn t yet knw hw wide the hst range is but primates are definitely imprtant. Ri has frested areas in the city, which hld animals which act as reservirs. Prfessr Trudie Lang Prfessr f Glbal Health Research; Directr f the Glbal Health Netwrk and Senir Research Scientist in Trpical Medicine, Nuffield Department f Medicine; Senir Research Fellw, Green Templetn Cllege Overview Drugs: culd assess existing anti-viral drugs - nthing n the shelf as there was with Ebla as it was nt seen as a threat Culd be effective t late t stp effect n pregnancies because anti-virals wrk best at early stages f infectin and typically there are little r n symptms t prmpt treatment. Als issues in giving drugs t pregnant wmen, and s it is unlikely that drug therapy research will be a pririty Vaccines: Prgress with DNA vaccine NIH prgram has been in news will have Phase 1 trails by the summer But wh d we target the vaccine at? Hw d we plan clinical trials and then scale it up? Issues with price and access will it be affrdable and available t the cuntries affected? Vaccine manufacture is als an imprtant issue. Traditinal vaccine slwer but wrk was underway t develp a vaccine fr similar viruses like Western Nile disease. Need a diagnstic test t use in cmmunity settings - sme prgress has been made, but there is crss reactivity with Dengue r yellw fever It is als imprtant t include fetal scanning in the discussin n diagnstics. Here standardised assessments need t be agreed and validated t determine what is abnrmal and what is happening

7 when in regard t the viral infectin and develping baby. It needs t als be remembered that very few wmen in lw-incme cuntries have access t scans, and that abrtin is illegal in mst f the cuntries affected by Zika. What did we learn frm Ebla abut drug, vaccine and diagnstic research and develpment during utbreaks? Scientists were nly just starting t reflect n the Ebla respnse when Zika appeared s they are having t apply lessns frm Ebla straight away, befre there has been time t embed them int internatinal respnses. In West Africa, fr Ebla, there was very minimal clinical trial capacity and this slwed the respnse and resulted in utside rganisatins having t take the lead. Research infrastructure needs t be imprved in lw-resurce cuntries s that they are able t respnd t utbreaks lcally. Still managed t set up trials in 16 weeks (usually takes 18 mnths) but this is nt fast enugh. We have t embed research int immediate respnse t a new utbreak in rder that the disease can be understd and drug and vaccines can be evaluated within the very limited time within which an utbreak ccurs Need t ensure this the research effrt is crdinated and led by a neutral agency, such as the WHO, and nt by any ne cuntry WHO have develped an R&D framewrk - It is imprtant that the respnse is strngly led and key questins such as which studies t priritise are agreed by all. That way all stakehlders are able t cntribute t the develpment f respnse. Cllabrative effrts with Zika shws the need and imprtance f integrated research platfrms which typically cannt get funded. These need t perate utside f utbreaks t increase reginal research capacity fr tackling n ging health issues and then are able t respnd in utbreaks as they are already trained and active. Zika has required crdinatin between maternal health researchers, epidemilgists, vectr experts, which just shws hw this ability t cllabrate and share knwledge via research platfrms is s imprtant as s many different types f research and research disciplines are needed and they need t cmmunicate, share and engage. Fr example, data capture standards are really imprtant eg. InterGrwth are wrking t unify hw baby measurements are taken imprtant if we are t have wrldwide knwledge f the extent f micrcephaly. Nw their tls The Internatinal Fetal and Newbrn Grwth Standards fr the 21st Century - are recmmended by the WHO and 11,728 have been dwnladed, in 163 cuntries, frm The Glbal Health Netwrk ( This means everyne is measuring in the same way, and therefre can agree what is abnrmal and the situatin can be prperly assessed. ISARIC are crdinating an internatinal research respnse and develping sharing prtcls and data capture tls. The Glbal Health Netwrk is prviding ISARIC with a secure, nline, digital infrmatin platfrm fr sharing these research dcuments, standards and as a mechanism fr agreeing research pririties, lgging wh is ding what and fr prviding training, tls and guidance - This wrk is lead by researchers in Brazil and everything is translated int Spanish and Prtuguese It is vital t put in place the ability t undertake research in areas f the wrld where the next utbreak is likely t be. There will be thers new diseases and we are nt ready fr future utbreaks, because it takes t lng t set up research studies In 2014 WHO said that unless lw incme cuntries becme generatrs rather than receivers f research and data, then we are nt prepared fr future utbreaks. This has nt happened. Need a change in mind-set in lw incme cuntries research is seen as a Western thing. Start with simple pragmatic trials, then build up research base. Health and labratry wrkers in these regins need t be engaged, supprted and trained. There will be ther utbreaks and we are nt prepared. Glbal travel and urbanisatin are raising the stakes n a future utbreak. Therefre it is vital we wrk t develp (and get funding fr) crss cutting research capacity develpment platfrms. If we had these systems in place befre Zika arse we wuld be much better able t answer all these unknwns much faster.

8 Imprtant that MRC, DFID and the Wellcme Trust need t change their funding framewrks t reflect this, and fund capacity develpment and research platfrms that perate in between utbreaks and therefre have the ability t respnd. We als need t lk at what slws the prcess f setting up new studies. Delays such as regulatry apprval and cntracts can be slved ahead f time and this shuld be reslved thrugh WHO wrking grups running crss-cutting prjects t put slutins in place. Questins Q: Stephen Metcalfe MP Hw much f this needs t be glbal? A: It all des; and the UK takes a key leadership rle, such as the wrk that the Wellcme Trust is ding. UK Organisatins such as the MRC, DFID and the Wellcme Trust wrk alngside and in clse partnership with WHO and Gates Fundatin etc. t drive internatinal effrt and cllabratin. Cmment: Stuart Taylr (Ryal Sciety) There has already been a call fr freedm f infrmatin surrunding Zika research. Nature and Springer [science publishers] have agreed Zika papers are n lnger behind a paywall. Respnse: This is a very imprtant and game changing annuncement is a huge shift in the wrkings f science. But it will take time t see the full impact. Imprtant t remember the need t enable the cllectin f data in the first place, and that it needs t be standardised and f gd quality s that it is ready fr sharing. Wider questins aimed at all the speakers Q: Stephen Metcalfe MP Is ur gvernment ding enugh? A: JW - The UK is secnd in terms f funding dnated (nly the US have dnated mre), and have made a cnsiderable cntributin t the cntingency fund fr the emergency. But we are nt acting in Central and Suth America (instead the fcus is n strategic areas in Africa and Caribbean) s the gvernment shuld think abut expanding their respnse int the Americas. A: JL - Als need cncrete plans fr what t d if Aedes albipictus is fund in the UK including where funding fr a respnse wuld cme frm. Currently the nly mnitring is thrugh the public sending in samples nt gd enugh. The msquit has already been fund in France and Belgium culd easily cme ver this summer, like Bluetngue disease did last year. Q: Lrd Selburne If Oxitec s msquites are s prmising, shuld the UK be leading n the scale up research? A: JL Wuld agree that this is the time t fcus n scale up but warns that the trials will take arund 2 years, and we need viable cntrl slutins nw. Gd success frm ther techniques t need t scale up accessible tech. Cnventinal tls shuld nt be ignred. Q: Tim Rberts (Institute f Patent Attrneys) The Nagya prtcl f 2014 requires the cuntry f sample rigin t give permissin fr any genetic research des this raise difficulties fr Zika research? A: JW At the level we wrk we haven t seen any impact. But there has been discussin ging n at high levels in the WHO and Dept f Health. Mre likely t have an impact f influenza research? Thught article 4.4 if research is fr glbal health research in a pandemic then it is excepted may be f help. Q: What are we ding abut screening bld prducts fr Zika? A: Minimal risk in UK, s n need as yet. A: This is an issue in Puert Ric, and they are having t imprt bld frm the US. Q: Barness Tnge Is there prf f the link between micrcephaly and Zika? Culd it nt be ther reasns eg. Crp spraying? A: TL The link is indeed nt prven yet, and nrmal base levels f birth defects are hard t establish as recrding is limited in many affected cuntries. Other factrs are imprtant t cnsider. Need mre backgrund research.

9 May be that in Africa the human ppulatin has been previusly expsed t Zika and s there are lwer cases f micrcephaly because wmen becme immune befre they reach child bearing age but this is nt prven either. **UPDATE** - as f April 13 th, 2016, the link between Zika and micrcephaly has been cnfirmed. See Q: Dr Jane Pritchard (GAIN) GBS is treated with bld prducts, s d we need t mbilise such prducts frm Zika-free areas? A: The pririty treatment fr GBS in affected areas in currently ventilatin in the ICU (intensive care unit) patients get better ver time withut the need fr bld prducts. But healthcare facilities are hugely variable in Central and Suth America. Q: Cheryl Tweed when/why did all this hit the news? A: TL The utbreak was widely knwn abut in the medical cmmunity in early December, but in the UK the press were nly mbilised when patients brught Zika back t the UK. BBC respnse has been very respnsible. Great pprtunity t explain why research is needed in lw incme regins f the wrld and in neglected trpical diseases, which nrmally gets ignred. Q: is this incursin int Suth America f a certain subtype f Zika virus? A: JW There are tw factrs t cnsider: The strain f Zika seen is the Asian strain (nt the African strain), which is mre transmissible. The Central and Suthern American ppulatin is naive have nt encuntered the disease befre s mre susceptible t the disease. Hard t say which f these factrs is mre imprtant in this epidemic. A: TL Recent research has shwn that this virus is quite highly cnserved (similar genetically t ther strains) s it seems likely that this has ccurred because these ppulatins have nt previusly been expsed t the virus and s the prblems arise as wmen are being infected fr the first time when they are pregnant, when the fetal damage is ccurring but this is still a thery. References Fernández-Grandn, G.M. et al., Heritability f attractiveness t msquites. PlS ne, 10(4), p.e Available at: [Accessed February 14, 2016]. Kraemer, M.U.G. et al., The glbal distributin f the arbvirus vectrs Aedes aegypti and Ae. albpictus. elife, 4, p.e Available at: [Accessed June 30, 2015]. Stanczyk, N.M. et al., Behaviral insensitivity t DEET in Aedes aegypti is a genetically determined trait residing in changes in sensillum functin. Prceedings f the Natinal Academy f Sciences f the United States f America, 107(19), pp Available at: [Accessed March 23, 2016]. Wilsn, A.L. et al., Are tpical insect repellents effective against malaria in endemic ppulatins? A systematic review and meta-analysis. Malaria jurnal, 13, p.446. Available at: [Accessed March 23, 2016].