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

Aedes aegypti distribution in Colombia (2017)

House Index > 4% House Index < 4% Inspected & Negative Non Inspected

Source: Colombian Natl. Institute of Health & Ministry of Health 1,122 municipalities 718 (62,2%) below 2,000 m.a.s.l. 90% positive for A. aegypti Aedes albopictus 452 inspected municipalities 41 positive (9.1%) 33 of them in Valle and Cauca Provinces

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100.000 – 200.000 dengue cases by year / 150 fatalities

ZIKA VIRUS DISEASE IN AMERICA 2015 – 2016 REPORTED AND CONFIRMED CASES

16th, October 2015 25th, December 2015 31st, January 2016 31st, March 2016 30th, June 2016 31st, December 2016

Colombia 105,000 cases 18,000 Pregnant women

http://www.healthmap.org/zika/#timeline

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WEEKLY DISTRIBUTION OF ZVD AND MICROCEPHALY CASES - COLOMBIA

Méndez et al. Archives of Public Health (2017) 75:65 ZVD cases ZVD cases in Pregnant ZIKV Microcephaly associated Lab confirmed Microcephaly

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ISOLATION, HAVERSTING AND TITRATION OF ZIKV

500 300 100 500 300 100

MW S S(C-) BM BM(C-) U U(C-) Z(+) Z (-) December 21st, 2016 S: Serum BM: Breast milk U: Urine March 13th, 2017

PERSISTENCE OF ZIKV INFECTION IN A NURSING MOTHER

ZIKA VIRUS, LABORATORY DETECTION AND DIAGNOSTICS

Castellanos et al., Clin Laboratory Intl 2017; 41:14-19

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Easy and inexpensive molecular detection of DENV, CHIKV and ZIKV in febrile patients using a triplex nested PCR

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Calvo EP et al., Acta Tropica 2016; 163:32-37

DENGUE DIAGNOSTIC TOOLS FOR CASE CONFIRMATION IN CHILDREN, CALI-COLOMBIA - 2018

Febrile children enrolled (n=152) July 2018 to February 2019

Under 2 year (49.7%) 2 to 5 years old (20.4%) 6 to 12 years old (23.2%) Over 13 years (6.8%)

Castellanos JE. et al, CHIKV outbreak in a pediatric hospital. Int. J Infect Dis, 2019 Submitted.

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IgM ELISA CHIKV+ (28.6%) IgM ELISA DENV+ (1.3%) Capture IgG DENV+ (2.0%)

• Febrile syndrome – Fever (50.7%)
• Dengue (17.3%)
• Respiratory febrile syndrome (13.3%)
• Viral infection (12.7%)

Admission diagnosis

Laboratory Diagnostic Tests

CHIKV RT-PCR+ (68.4%) CHIKV qPCR-Lanciotti (11.5%) DENV-1+ (3.3%) ZIKV RT-PCR (2.0%)

Activation of cross-reactive T cells upon sequential dengue and ZIKV infection (in the search of the vaccine

• U. El Bosque-Colombia

& Inst. Pasteur Paris) Lymphocyte specific IFN-g response to ZIKV peptides in ZIKV donors and ZIKV/DENV donors

ZIKV donors 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 lymphocytes.

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Delgado FG et al., Improved Immune Responses Against Zika Virus After Sequential Dengue and Zika Virus Infection in Humans. Viruses. 2018 Sep 7;10(9).

Microcephaly Potentially

Associated with Zika Virus Infection During Pregnancy 2016-2018

Colombian NIH Natl Center on Birth Defects, USA - CDC

Colombia’s Instituto Nacional de

Salud (INS) maintains national surveillance for birth defects, including microcephaly and other central nervous system defects. 2015: 11,800 ZVD probable cases 110 microcephaly cases Prevalence 2.1 x 10,000 births (Passive surveillance) 2016: 93,200 ZVD probable cases 476 microcephaly cases Prevalence 9.6 x 10,000 births (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

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1.- CENTRAL NERVOUS SYSTEM DEFECTS AND

MICROCEPHALY SURVEILLANCE IN COLOMBIA 2015 - 2017

1,239 Reported cases of congenital defects and microcephaly 858 cases with full information (69.2%) Analysis of all reported cases of nervous system congenital defects: *.- Active surveillance *.- Clinical form fulfilling *.- STORCH-Z tests and karyotype *.- Classification (infectious, genetics, multifactorial) *.- Health service following

Mercado M. et al. Zika Virus associated defects. N Eng J Med July, 2019

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502 cases Other etiology (58.5%)

356 cases of nervous congenital defects and ZIKV associated microcephaly (41.5%)

2.- SPECIAL SURVEILLANCE IN PREGNANT WOMEN WITH

ZIKA IN COLOMBIA 2016 – 2018

(VEZ Study, Vigilancia de Embarazadas con Zika)

1,223 recruited pregnant women With ZIKV disease symptoms (1,236 babies) Analysis of pregnant women consulting with ZIKV infection signs and symptoms: *.- Pregnancy following, echography, laboratory tests. *.- Placenta examination, pregnancy outcome recording, imaging. *.- Babies following by 24 months, examination each 6 months.

Mercado M. et al. Zika Virus associated defects. N Eng J Med July, 2019

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ZIKV PCR + (15%) ZIKV IgM + (10.5%) ZIKV & IgM + (2.5%) No Laboratory Tests (71.9%)

68 cases ZIKV associated microcephaly (5.5%)

3.- CHILDREN WITH PRENATAL EXPOSITION TO

ZIKV IN COLOMBIA - (2 Year Following)

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Mercado M. et al. Zika Virus associated defects. N Eng J Med July, 2019

*.- ZIKV infected mothers (n=242) *.- Clinical evaluation by pediatrician, neuropediatrician, ophthalmologist, dentists and genetics. *.- Children Development score *.- Retinoscopy, Auditory evoked potentials, Electroencephalography

• Severe Microcephaly (74%)
• Neuroimaging: Calcification, Corpus

callosum anomaly, ventriculomegaly (92%)

• Seizures (62%), Sensory Hypoacusis (14%),

abnormal swallowing (86%)

• Retina and optic nerve damage (37%)
• Arthrogryposis (7%)
• Generalized hypertonia (85%)

Congenital ZIKV Syndrome (n=68) ZIKV Exposed without Congenital Syndrome (n=174)

• Hearing and speech development

anomalies (39%)

• Hemiparesis (4.6%),

Convulsive syndrome (2.1%)

• Sensory Hypoacusis (2.7%)

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