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Day 2 JapEnc Zika - Perreras
Day 2 JapEnc Zika - Perreras
1
OBJECTIVES
• To discuss the re-emergence of JE and Zika in the Philippines
• To discuss each disease entity
– signs and symptoms
– diagnostics
– treatment and prevention
2
DISCLAIMER
• Nothing to declare
• No conflict of interest
JAPANESE
ENCEPHALITIS
•\
JEFellow
ASPediatrician:
A PEDIATRICIAN
Kelangan ba tlga ng Jap
enceph vaccine?
8
`
Lopez et al.2014
9
10
mosquito bite -> WBCs -> CNS -> virus binds to
endothelial surfaces of the CNS spreading the virus
from the peripheral areas to the CNS
JEV may also reside in astrocytes, which are part
of the body’s BBB
Incubation period: virus resides in WBCs
11
1958 - 1993
Serologic surveys in the Phils.
1977 1982
1943 C.tritaeniorhynchus and JE Outbreak
1958 in Nueva
JEV Abs Cases reported C.vishnui mosquitoes -
discovered in Ilocos Sur Ecija
in Pampanga
horses
Lopez et al.2014 12
Summary:
Age group: youngest 6 months
- majority were less
than 15 years of age
Among those tested for JE, 3-92%
tested positive
Lopez et al.2014
13
Summary:
N = 257 laboratory-confirmed JE
cases
Among meningitis and encephalitis
cases, 7-18% were JE-+
Majority <15 years
14
2009
WHO -> Western Pacific 2012-2013
laboratory network for JE Northern Mindanao
2008 Surveillance Medical Center
Philippine Integrated Philippine Children’s
Disease Surveillance 2011 Medical Center
and Response, San Lazaro Hospital
surveillance for acute RITM Western Visayas
encephalitis Medical Center
syndrome (AES), as a Bicol Medical Center JEVaccine
proxy for JE
Lopez et al.2014 15
WORLDWIDE INCIDENCE
• 3 billion at
risk
• 50,000 -
68,000 cases
annually
• 40,000
annually in Solomon et al, 2000
the Western Lopez et al.2014
Pacific region
16
Yearly distribution of suspected and confirmed JE cases from
surveillance and clinician referral testing, January 2011 to December
2017
No. of No. tested No. of
suspected for JE laboratory
JE cases* confirmed
JE
2011** 199 64 16
2012** 352 129 24
2013** 392 237 25
2014** 226 67 8
2015*** 943 817 123
2016† 2,002 1,672 315
2017† 3,946 2,238 340
*Includes surveillance cases with and without specimens, and clinical referral cases
**Lopez AL, Aldaba JG, Roque VG Jr, Tandoc AO III, Sy AK, et al. (2015) Epidemiology of Japanese Encephalitis in the Philippines: A Systematic
Review. PLOS Neglected Tropical Diseases 9(3): e0003630. https://doi.org/10.1371/journal.pntd.0003630
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003630
***AMES database only
†Consolidated data from AES, AMES and Bacterial Meningitis database
JEV IN THE PHILIPPINES
18
JEV SURVEILLANCE
JUNE TO JULY 2018
21
22
CONFIRMED JE DEATHS
81 provinces
- 68 reported suspected JE
cases
- 20 reported confirmed JE
cases
Lopez et al.2014
24
WHO ARE AFFECTED?
Lopez et al.2014
25
Subject No. Year Age Type Citizenship Outcome Lab-confirmed JE vaccine
26
WHEN ARE WE AT RISK FOR JE?
Lopez et al.2014
27
WHICH PATIENTS BECOME SYMPTOMATIC?
Solomon et al 2000
28
CASE DEFINITION
Acute Encephalitis Syndrome (AES) Suspected JE Case - Meets clinical case definition
for AES
Person of any age, at any time of the
year with the acute onset of fever and
at least one of: Laboratory-confirmed JE: An AES case with JEV-specific
IgM Ab in CSF or serum detected by IgM-capture ELISA
Change in mental status - confusion,
disorientation, coma, inability
Probable JE: An AES case that occurs in close geographical
to talk
and temporal relationship to a laboratory-confirmed case of
JE, in the context of an outbreak.
New onset of seizures - excluding
BFC
AES - other agent: An AES case in which diagnostic testing
Other early clinical findings may include an is performed and an etiologic agent other than JE virus is
increase in irritability, somnolence or identified.
abnormal behavior greater than that seen
with usual febrile illness AES - unknown: An AES case in which no diagnostic testing
is performed or in which testing was performed but no
etiologic agent was identified or in which the test results
were indeterminate. Lopez et al.2014 29
ACUTE ENCEPHALITIS SYNDROME IS A NOTIFIABLE DISEASE
30
SIGNS AND SYMPTOMS
• 5-15 days incubation period
• non-specific febrile illness: coryza, diarrhea, rigors
• Mental status abnormalities
• abulia, masked facies, blank affect
• neurologic s/sxs -> headache, altered mental status, seizures
• hemiparesis, hemiplegia, cranial nerve palsies, movement disorders
Solomon et al 2000
31
SEIZURES
• occur in 85%
• predictor of poor outcome
• no particular seizure type: may be generalized tonic-clonic or subtle
motor types (twitching of a digit, eye, mouth, eye deviation, irregular
respiration)
Solomon et al 2000
32
PARKINSONIAN MOVEMENT DISORDERS
• acute stages and as part of sequelae
• mask-like facies, tremors, cogwheel rigidity
• generalized rigidity, opisthotonos, choreoathetosis, myoclonic jerks
Solomon et al 2000
33
34
POLIOMYELITIS-LIKE PARALYSIS
• short febrile illness -> rapid onset of flaccid paralysis in one or more
limbs
• normal level of consciousness
• weakness or flaccidity of limbs (legs>>arms) -> mostly the only feature
• reduced or absent reflexes
• 30% -> encephalitis
• acute flaccid paralysis similar to poliomyelitis
• can also occur in “classic” JE cases that follow the usual course
Solomon et al 2000
35
36
Symptoms No. of Cases (%) Symptoms No. of Cases (%)
N = 52 N = 52
Fever 52 (100)
Altered sensorium 45 (87)
Headache 35 (67)
Seizures 35 (67)
Vomiting 30 (58)
Dysphasia 35 (67)
Chills 23 (44) Paralysis 13 (25)
Nausea 11 (21) Behavioral changes 12 (23) San Luis, 1990
Dizziness 5 (10) 37
• abulia with masked facies
• variable changes in mentation
• relative absence of cranial nerve involvement
• lack of gross sensory deficit
• asymmetric and irregular motor and tone abnormality
38
RITM SENTINEL SURVEILLANCE FOR ETIOLOGIC
DIAGNOSIS OF
MENINGITIS/ENCEPHALITIS/MENINGOENCEPHALITIS IN
THE PHILIPPINES
ESPINO, 2014 (UNPUBLISHED)
• N = 251
• 2mos - 18 years old
• WHO case definition of CNS infection
• Analytic tests:
• CSF: latex agglutination for antibodies to bacterial pathogens
(Bactigen), JEV/DENV IgM-capture ELISA and real time PCR
• Serum: JEV/DENV IgM ELISA
39
PREDICTORS OF OUTCOME
• exposure to previous flavivirus infection protective due to cross-
reacting antibodies (Solomon, 2004 NEJM)
• serial infection with different dengue serotypes may be associated
with more severe disease -> antibody enhancement of infection
45
OUTCOMES
Lopez et al.2014
Solomon et al, 2000 46
• increased CSF opening pressure -> predictor of poor outcome
• CSF pleocytosis of 10-100 cells/mm3
– predominant lymphocytes
– mildly increased protein (50-200 mg%)
– normal CSF:serum glucose ratio
47
Occurrence of cross-
reaction with dengue virus
Ag
Year No. of JE
and DNV (+)
Samples
2002 4
• January 2002-October 2005
• San Lazaro Hospital, St. Luke’s Medical Center 2003 5
48
SUSPECTED VERSUS CONFIRMED CASES OF JE
JANUARY 2011 - MARCH 2014
2014 89 67 8 (12%)
(Jan-Mar)
49
SERUM AND CSF IGM
50
A serum sample should be obtained at admission. Because it may not yet be
positive in a JE-infected person, a second serum sample should be collected at
discharge or on the 10th day of illness onset (usually around 7 days after admission)
or at the time of death and tested for presence of JE virus specific IgM.
51
Severe sequelae
Outcome grade No (%) patients
Diagana (2007).
53
PREVENTION
Lopez et al.2014
54
ZIK A VIRUS
THE ZIKA
VIRUS
enveloped virus
Stable up to 40°C
Kostyuchenko, VA et al. (2016). Structure of the thermally stable Zika virus. Nature, advance
online publication. doi: 10.1038/nature17994
THE ZIKA VIRUS
RNA virus
Flavivirus genus,
Flaviviridae family
Oct 1, 2016
Thailand notifies
WHO of 2 babies
born with
microcephaly
(first cases in
SEA)
Mosquito bite
Protective immunity
Edward, B. Hayes. (2009). Zika Virus Outside Africa. Emerging Infectious Disease journal,
15(9), 1347. doi: 10.3201/eid1509.090442
ZIKA VIRUS DISEASE
Incubation Period: 3-14 days
For symptomatic persons with symptoms >2 weeks
after travel, transmission might be not travel associated.
1. Elisabeth, R. Krow-Lucal, Brad, J. Biggerstaff, & Staples, J. Erin. (2017). Estimated Incubation Period for
Zika Virus Disease. Emerging Infectious Disease journal, 23(5), 841. doi: 10.3201/eid2305.161715
2. Duffy, M.R., Chen, T.H., Hancock, W.T., Powers, A.M., Kool, J.L., et al. Zika virus outbreak on Yap
Island, Federated States of Micronesia. N Engl J Med. 2009; 360: 2536–2543
3. US CDC . Zika Virus: For Health Care Providers: Clinical Evaluation & Disease.
GOOD NEWS
Zika is a mild disease.
80%
of infected patients will be asymptomatic
1. Duffy, M.R., Chen, T.H., Hancock,W.T., Powers, A.M., Kool, J.L., Lanciotti, R.S. et al. Zika virus outbreak on Yap Island,
Federated States of Micronesia. N Engl J Med. 2009; 360: 2536–2543
2. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak — United States, 2016
Weekly / January 22, 2016 / 65(2);30–33
GOOD NEWS
Zika is a mild disease.
CLINICAL MANIFESTATIONS OF
ZVD
Mo, Yin, Brenda Mae Alferez Salada, and Paul Anantharajah Tambyah. "Zika Virus—a Review for
Clinicians." British Medical Bulletin 119, no. 1 (September 1, 2016 2016): 25-36.
CLINICAL MANIFESTATIONS OF
Symptom ZVD
Rio de Janeiro, 2015, n=57
Exanthema 56 (98)
Fever 38 (67)
Arthralgia 33 (58)
Headache 38 (67)
Myalgia 28 (49)
Retro-orbital pain 23 (40)
Conjunctivitis 22 (39)
Joint swelling 13 (23)
Cerbino-Neto J, Mesquita EC, Souza TML, Parreira V, Wittlin BB, Durovni B, et al. Clinical
manifestations of Zika virus infection, Rio de Janeiro, Brazil, 2015 [letter]. Emerg Infect Dis. 2016 Jul
[28 October 2016].
CLINICAL MANIFESTATIONS OF
Symptom
Macular or papular rash
ZVD
Rio de Janeiro, 2015, n=119
115 (97)
Severe weakness 94 (79)
Headache 78 (66)
Arthralgia 75 (63)
Myalgia 73 (61)
Non-purulent conjunctivitis 66 (56)
Retro-orbital pain 53 (45)
Lymph node enlargement 49 (41)
Fever 43 (36)
Anorexia 42 (35)
Photophobia 41 (35)
Brasil P, et al. Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization,
Epidemiological and Virological Aspects. PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636. doi:
10.1371/journal.pntd.0004636. eCollection 2016.
W.E.Villamil-Gómez, et al.
Dengue, Chikungunya and
Zika co-infection in a patient
from Colombia. J Infect
Public Health (2015)
Age Range
Number of Cases
Signs and Symptoms of Confirmed Zika Cases Tested in
RITM, February 18, 2016 – January 17, 2018 (n=68)*
Number of cases
*Multiple Responses
Map of Locally Confirmed Zika Cases,
February 18, 2016 – January 17, 2018 (n=68)
Region I = 3
Region III = 2
NCR = 24
CALABARZON = 20
Region V = 1
Region VI = 16
Region VII = 2
GOOD NEWS
Once a person has been infected, he or she
is likely to be protected from future
infections.
https://www.cdc.gov/zika/about/questions.html
Pardi, Norbert, Hogan, et al. (2017). Zika virus protection by a single low-dose nucleoside-modified
mRNA vaccination. Nature, 543(7644), 248-251. doi: 10.1038/nature21428
http://www.nature.com/nature/journal/v543/n7644/abs/nature21428.html#supplementary-information
BAD NEWS
ZIKV has been demonstrated to
exhibit neurotropism.
Guillain
MicrocephalyBarre Syndrome
ZIKA IN PREGNANT MOTHERS
• No clinical differences have been described between
pregnant and non-pregnant women
• Pregnant women who have a ZIKV infection experience
symptoms concordant with the rate observed in the
general population.
Recommendation
For confirmed cases, ensure the she is not
shedding virus anymore before pregnancy.
CAN ZIKA BE TRANSMITTED
BY:
Yes No Possible
Breastfeeding
• The virus has been detected in breast milk.
• BUT, breastfeeding-associated transmission has not
been reported so far
Musso, Didier, Susan L. Stramer, and Michael P. Busch. "Zika Virus: A New Challenge for Blood
Transfusion." The Lancet 387, no. 10032 (1993-94.
CAN ZIKA BE
TRANSMITTED BY:
Yes No Possible
Sexual transmission
• Zika has been found in genital fluids, including semen and vaginal
fluids.
• Studies are underway to find out how long (69-188 days)
• This includes vaginal, anal, and oral sex and the sharing of sex toys.
http://www.cdc.gov/zika/pdfs/zika-key-messages.pdf
HOW DO WE
DIAGNOSE
SYMPTOMATIC ZIKA
LOCALLY?
Detection of ZIKV RNA via PCR
in urine and blood specimens
National Reference Laboratory for Dengue and other
Arboviruses
at the Research Institute for Tropical Medicine
DOH CASE DEFINITIONS
SUSPECTED CASE OF ZIKA VIRUS INFECTION
A patient with skin rash and one of the following:
– Fever (<38.5ºC) or reported history of fever within the past five (5) days prior to
consultation
– Arthralgia
– Arthritis
– Conjunctivitis
B. A mother whose fetus, newborn or infant has any neurological condition listed
below that cannot be explained by other etiologies:
– Head circumference less than the -3 Standard Deviation (<-3SD) or occipito-frontal
circumference less than the 3rd percentile on standard growth charts, OR
– Disproportionately small head as compared to infant’s length, OR
– Intra-cranial calcifications
C. A fetus, newborn or infant whose mother had confirmed or presumed infection
with Zika virus during pregnancy.
D. All newly diagnosed Guillain-Barre Syndrome (GBS)
94
DOH DM 2016-0116A Interim Guidelines on the Zika Virus Disease Surveillance
SUMMARY OF SPECIMEN COLLECTION, STORAGE, AND
TRANSPORT FOR ZIKA TESTING
Cord Blood Immediately after birth For new born infant 5 ml Refrigerator, 2 to Transport within 48
of suspected 8°C hours/ 2 days after
mother collection
CSF Upon first contact or If with CNS 1 ml Refrigerator, 2 to Transport within 48
when possible manifestations 8°C hours/ 2 days after
collection
NPS/OPS Collect within 5 days If suspected for 1 VTM or UTM Refrigerator, 2 to Transport within 3
after onset when Measles or Rubella 8°C days after collection
suspecting for Measles
or Rubella 96
TRANSPORT TO RITM
6-8 frozen icepacks
Transported within 48
hours
Intact Correct Package and preserve
container temperature specimens
Arrange shipment
(Courier)
International Air Transport Association
Within time Properly (IATA) Regulations Compliant
limits labeled
TURN-AROUNT TIME (TAT)
5 working days from the time of receipt of
specimen at RITM.
GENERAL FLOW- CURRENT
Case
detection DOH Disease Prevention and Epidemiology
Control Program (DPCB) Bureau
Sample Storage in
Collection the hospital
Shipment to Lab Testing
from laboratory
RITM at RITM
suspected prior to
cases shipment