Investigating vertical transmission of chikungunya,dengue and zika virus infection: a prospective observational cohort study of pregnant women and infants in Jamaica

Background• Dengue (DENV), chikungunya (CHKV) and

zika virus (ZIKV) outbreaks have occurred in Jamaica in recent years, where all three viruses now circulate endemically

• The ZIKV outbreak in Jamaica peaked in June 2016.

• Many knowledge gaps remain with respect to ZIKV infection in pregnancy, including rate and risks of vertical transmission, pregnancy and birth outcomes and the natural history of congenital infection

• The roles of re-infection and co-infection are also unclear

Methods

Results

Conclusions

Funding: This project has received funding from the European Union’s

Horizon 2020 research and innovation programme under grant

agreement No 734857.

Ethical approvals: University Hospital of the West Indies, Jamaican

Ministry of Health Medico-legal Ethics Panel, University College London

Acknowledgments: We would like to thank the women and their children participating in

this study. We would also like to thank Tiziana Grossele, Andrea Oletto, Francesca Viero,

Amanda Rousseau, Sofier Scott, Brittiana Brown, Marilyn Grindley, Jacynth Moore, Yakima

Phillips, Keisha Francis, Dr Yanique Brown, Dr Tracia James-Powell, Dr Andrea Garbutt,

ShreeAnn Simon, Donna Kamicka and all other members of the ZIKAction team .

Enrolments and follow-up§ By March 2018, 349 pregnant women enrolled§ Key characteristics in Table 1§ 187 had 2nd pregnancy visits, 56 had 3rd visits and

nine had a 4th visit§ One symptomatic (headache and joint pains)

subject, 3rd trimester

§ These initial results provide important preliminary data on the background sero-prevalence of ZIKV, CHKV and DENV in our cohort of pregnant women in Jamaica

§ Although some laboratory results are pending, the few incident infections are consistent with our clinical and national arbovirus surveillance data, with breakthrough endemic arbovirus infections now being identified

Laboratory methods

§ Prospective cohort study following pregnant women at risk of DENV, ZIKV and CHKV infection until delivery / the end of pregnancy in order to identify pregnant women with markers of recent DENV, ZIKV or CHKV infection

§ Birth cohort of their infants followed to age 24 months§ Those whose mothers had markers of

recent infection in pregnancy§ Control group born to women without

markers of recent infection§ Inclusion criteria: Any pregnant woman aged

≥16 years attending for antenatal care at a participating site, who plans to deliver at a participating maternity hospital; written informed consent

§ Enrolment started in June 2017; for first month all women attending for antenatal care were invited to enrol, regardless of gestational age. Subsequently, only women newly booking for antenatal care were enrolled.

§ Blood and urine sampling at enrolment and study-specific follow-up visits at 20, 28 and 36 gestational weeks

§ All women to receive at least one ultrasound scan

§ Women with arboviral symptoms investigated per national standard of care, with additional specimens and data on clinical presentation.

§ Additional samples taken at non study follow-up visits for routine care stored if possible.

§ Data are managed in REDCap

Characteristic % or median [IQR]

Age at enrolment (years) 26 [21, 32]Left school <16 years (n=329) 0.6%

Marital status (n=336)Single 14%

Married 32%Cohabiting 52%

Other 2%Current pregnancy unplanned

(n=328) 76%Previous pregnancy (n=337)

None123

4+

34%26%19%9%11%

Gestational weeks at enrolmentAll

After first month of enrolments21 [15, 28]17 [13, 25]

Table 1: Maternal characteristics

Preliminary serological results§ Almost all women had evidence of previous Dengue infection

§ IgM results: DENV (n=528) positive (P):28 equivocal (E):8; CHKV(n=528) P:14 E:15; ZIKV Novatec (n=530) P:17, E:12; ZIKV InBios(n=526) 4 possible, 21 presumptive, 3 presumptive other flavivirus

§ Results of PCR testing and IgG sero-conversions pending

C D Christie1, C Thorne

2, J Anzinger

3, H Bailey

2, P Palmer

1, O Morgan

4,5, L Bryan

4, S Mair

1, R Pierre

1, A Onyonyor

4,6, P Mitchell

4,7,

R Melbourne-Chambers1, K Webster-Kerr

8, John Lindo

3,8, R Lundin

9, D Brown

10, A Bispo

10, E Nastouli

2, C Giaquinto

9,11

1Dept of Child and Adolescent Health, University of the West Indies (UWI), Kingston, Jamaica; 2University College London, UK; 3Dept of Microbiology, Division of Virology, UWI, Kingston, Jamaica; 4Dept of Obstetrics and Gynecology, UWI, Kingston, Jamaica; 5Victoria Jubilee Maternity Hospital, Kingston, Jamaica; 6Kingston and Spanish Town Hospital, St Catherine, Jamaica; 7Victoria Jubilee Maternity Hospital, Kingston, Jamaica; 8Ministry of Health, Epidemiology Unit, Jamaica, and UWI, Kingston, Jamaica; 9PENTA Foundation, Padua, Italy; 10Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 11University of Padua, Italy

PurposeTo present preliminary results from this ongoing prospective cohort study of pregnant women and their infants in the Greater Kingston Metropolis of Jamaica, specifically:• estimates of initial background sero-

prevalence of DENV, CHKV and ZIKV infections

• preliminary results on incident infections (IgM results)

• pregnancy outcomes to date

web: zikaction.org@zikaction

Study sites • Clinics with large patient populations in high

mosquito burden areas chosen in the Greater Kingston Metropolis

• 5 feeder antenatal clinics to 3 hospitals • Greater Portmore Health Centre, St Jago Park Health

Centre, Windward Road Health Centre, Edna Manley Health Centre, UWI Hospital Antenatal Clinic

• Spanish Town Hospital, Victoria Jubilee Maternity Hospital, University of the West Indies Hospital

Pregnancy outcomes to date§ Eight pregnancy losses (7 miscarriages, 1ectopic

pregnancy)§ 201 deliveries, with 204 newborns (three twin

pairs) § 200 live births, four (2%) were preterm§ Four still births and five neonatal deaths § Placental abruption (two), preterm twins 28/40

with twin-twin transfusion (one), preterm (one), perinatal asphyxia APGAR 1-1-3 (one)

§ Perinatal mortality rate was 44.1/1000 live births. § Four (2%) live newborns were microcephalic

(WHO criteria)

Implementation of the study• Following ethical approval, administrative clearance required

from multiple authorities / sites• Training research team on protocol, informed consent, data

sheets & SOPs plus sensitization of hospital staff• Purchase of two ultrasound machines for public hospitals was

required as no working machines• “24-point clinic enrolment process” demonstrates complexity

of study• “Fun fact”: most women wore wigs or hair weaves, which

increased OFCs by several cms• Challenges include women’s fear of blood draws, conspiracy

theories (e.g. “cloning”), maintaining follow-up in pregnancy, couriering samples to the lab (done by research nurses) and ensuring deliveries are not missed

• IgM & IgG on blood at every visit

• PCR on blood and urine in women with serological evidence of recent infection (i.e. IgG seroconversion, a rise in IgG titer, or IgM+)

Table 2: IgG serology results (enrolment)