challenges in diagnostic and control Jaime E. Castellanos, Ph.D. - PowerPoint PPT Presentation

Colombian ZIKV epidemic, challenges in diagnostic and control Jaime E. Castellanos, Ph.D. Instituto de Virología - Universidad El Bosque Bogotá – Colombia castellanosjaime@unbosque.edu.co

COLOMBIA, THE NORTHWEST CORNER OF SOUTHAMERICA 2

3 1,122 municipalities 718 (62,2%) below 2,000 m.a.s.l. Aedes aegypti 90% positive for A. aegypti distribution in Colombia (2017) House Index > 4% Aedes albopictus House Index < 4% 452 inspected municipalities Inspected & Negative 41 positive (9.1%) Non Inspected 33 of them in Valle and Cauca Provinces 100.000 – 200.000 dengue cases by year / 150 fatalities Source: Colombian Natl. Institute of Health & Ministry of Health

4 ZIKA VIRUS DISEASE IN AMERICA 2015 – 2016 REPORTED AND CONFIRMED CASES Colombia 31st, March 2016 25th, December 2015 105,000 16th, October 2015 31st, December 2016 30th, June 2016 31st, January 2016 cases 18,000 Pregnant women http://www.healthmap.org/zika/#timeline

5 WEEKLY DISTRIBUTION OF ZVD AND MICROCEPHALY CASES - COLOMBIA ZIKV ZVD cases Microcephaly associated ZVD cases Lab in Pregnant confirmed Microcephaly Méndez et al. Archives of Public Health (2017) 75:65

6 ZIKA VIRUS, LABORATORY DETECTION AND DIAGNOSTICS PERSISTENCE OF ZIKV INFECTION ISOLATION, HAVERSTING IN A NURSING MOTHER AND TITRATION OF ZIKV MW S S(C-) BM BM(C-) U U(C-) Z(+) Z (-) 500 300 December 21st, 2016 100 500 300 March 13th, 2017 100 S: Serum BM: Breast milk U: Urine Castellanos et al., Clin Laboratory Intl 2017; 41:14-19

7 Easy and inexpensive molecular detection of DENV, CHIKV and ZIKV in febrile patients using a triplex nested PCR Calvo EP et al., Acta Tropica 2016; 163:32-37

8 DENGUE DIAGNOSTIC TOOLS FOR CASE CONFIRMATION IN CHILDREN, CALI-COLOMBIA - 2018 Febrile children enrolled (n=152) Admission diagnosis July 2018 to February 2019 • Febrile syndrome – Fever (50.7%) • Dengue (17.3%) Under 2 year (49.7%) 2 to 5 years old (20.4%) • Respiratory febrile syndrome (13.3%) 6 to 12 years old (23.2%) • Viral infection (12.7%) Over 13 years (6.8%) Laboratory Diagnostic Tests CHIKV RT-PCR+ (68.4%) IgM ELISA CHIKV+ (28.6%) CHIKV qPCR-Lanciotti (11.5%) IgM ELISA DENV+ (1.3%) DENV-1+ (3.3%) Capture IgG DENV+ (2.0%) ZIKV RT-PCR (2.0%) Castellanos JE. et al, CHIKV outbreak in a pediatric hospital. Int. J Infect Dis, 2019 Submitted.

Activation of cross-reactive T cells upon sequential dengue and ZIKV infection (in the search of the vaccine ZIKV donors U. El Bosque-Colombia & Inst. Pasteur Paris) Lymphocyte specific IFN- g response to ZIKV peptides in ZIKV ZIKV/DENV donors donors and ZIKV/DENV donors The numbers below each graph represent percentages of the total response for each protein. Many peptides of ZIKV NS3/NS5 crossreact with dengue patients 9 Delgado FG et al., Improved Immune Responses Against Zika Virus After lymphocytes. Sequential Dengue and Zika Virus Infection in Humans. Viruses. 2018 Sep 7;10(9).

Microcephaly Potentially 10 Associated with Zika Virus 2015: Infection During Pregnancy 11,800 ZVD probable cases 2016-2018 110 microcephaly cases Colombian NIH Prevalence 2.1 x 10,000 births Natl Center on Birth Defects, USA - CDC (Passive surveillance) Colombia’s Instituto Nacional de 2016: Salud (INS) maintains national 93,200 ZVD probable cases surveillance for birth defects, 476 microcephaly cases including microcephaly and other Prevalence 9.6 x 10,000 births central nervous system defects. (Active surveillance, 4,6X increase) Peak 24 weeks after ZVD infection Brazil prevalence 2015: 0.7 x 10,000 births 2016: 5.5 x 10,000 births (8X increase) Cuevas et al., Morbidity Mortality Weekly Report 2016; 65: 49: 1409-1414

11 1.- CENTRAL NERVOUS SYSTEM DEFECTS AND MICROCEPHALY SURVEILLANCE IN COLOMBIA 2015 - 2017 1,239 Reported cases of Analysis of all reported cases of nervous congenital defects and system congenital defects: microcephaly *.- Active surveillance *.- Clinical form fulfilling *.- STORCH-Z tests and karyotype 858 cases with full information (69.2%) *.- Classification (infectious, genetics, multifactorial) *.- Health service following 502 cases 356 cases of nervous Other etiology (58.5%) congenital defects and ZIKV associated microcephaly (41.5%) Mercado M. et al. Zika Virus associated defects. N Eng J Med July, 2019

12 2.- SPECIAL SURVEILLANCE IN PREGNANT WOMEN WITH ZIKA IN COLOMBIA 2016 – 2018 (VEZ Study, Vigilancia de Embarazadas con Zika) Analysis of pregnant women consulting with ZIKV infection ZIKV PCR + signs and symptoms: (15%) *.- Pregnancy following, 1,223 recruited 68 cases ZIKV IgM + echography, pregnant women (10.5%) ZIKV laboratory tests. With ZIKV associated *.- Placenta examination, disease ZIKV & IgM + microcephaly pregnancy outcome symptoms (2.5%) (5.5%) recording, imaging. (1,236 babies) *.- Babies following by 24 No Laboratory months, examination each Tests (71.9%) 6 months. Mercado M. et al. Zika Virus associated defects. N Eng J Med July, 2019

13 3.- CHILDREN WITH PRENATAL EXPOSITION TO ZIKV IN COLOMBIA - (2 Year Following) *.- ZIKV infected mothers (n=242) *.- Clinical evaluation by pediatrician, Congenital ZIKV Syndrome neuropediatrician, ophthalmologist, (n=68) dentists and genetics. • Severe Microcephaly (74%) *.- Children Development score *.- Retinoscopy, Auditory evoked potentials, • Neuroimaging: Calcification, Corpus Electroencephalography callosum anomaly, ventriculomegaly (92%) • Seizures (62%), Sensory Hypoacusis (14%), ZIKV Exposed without abnormal swallowing (86%) Congenital Syndrome • Retina and optic nerve damage (37%) (n=174) • Arthrogryposis (7%) • Hearing and speech development • Generalized hypertonia (85%) anomalies (39%) • Hemiparesis (4.6%), Convulsive syndrome (2.1%) • Sensory Hypoacusis (2.7%) Mercado M. et al. Zika Virus associated defects. N Eng J Med July, 2019

Conclusion • There was a temporary reduction of arboviral cases after ZIKV epidemic due to vector control (2016-2017) • CHIKV is circulating with wide distribution in Colombia and replacing endemic DENV infections • Clinical syndrome for arboviruses are identical in children, new diagnostic approaches are required • Asymptomatic ZIKV infection in pregnant women could lead to neurological damage in children. • Despite ZIKV transmission is low during this period, we expect an epidemic rebound. castellanosjaime@unbosque.edu.co