PENDIDIKAN
– Dokter umum – FK UGM Llulus1990 – Spesialis anak – FK UGM lulus 2003 – Konsultan – FK UNPAD (on going) – Program Doktor – FK UGM (on going)
ORGANISASI
– Ketua Satgas Dengue RSUP Dr Sardjito
– Ketua Pokja Dengue, Pusat Kedokteran Tropis FK UGM
– Anggota panitia PPI RSUP Dr Sardjito
– Anggota Komisi Ahli Arbovirus , Kementerian Kesehatan RI
– Wakil Ketua IDAI Cab DIY
– Member of Asian Society of Pediatric Infectious Disease (ASPID)
– Member of European Society of Pediatric Infectious Disease (ESPID)
– Member of International Society of Pediatric
Divisi Infeksi dan Penyakit Tropis - Departemen Ilmu
Kes Anak
FK UGM/ RSUP DR. Sardjito
CURRICULUM VITAE
Clinical approach in dis.nguishing Dengue,
Chikungunya and Zika
Ida Safitri Laksono
Division of Infec<ous and Tropical Disease
Department of Pediatric
Faculty of Medicine
PaIerson J et al, West J Emerg Med, 2016
Vector: Aedes mosquito
•
Aedes spesies
–
Ae aegyp.
–
Ae albopictus
Dengue virus
Family:
Flaviridae
Genus:
Flavivirus
ssRNA posi<ve genome
Enveloped virus
4 serotype:
(DEN1,DEN2,DEN3,DEN4)
Clinical manifesta<on
Clinical spectrum of dengue infec<on
7
Asymptoma<c Undifferen<ated fever
Dengue
Fever(DF)
Dengue
Hemorrhagic
Fever (DHF)
8
Course of Dengue
•
Dengue is a
systemic and dynamic disease
.
•
A wide clinical spectrum that includes severe and
non-severe forms of clinical manifestations.
•
After the incubation period, the illness begins
abruptly and will be followed by 3 phases:
–
Febrile phase
–
Critical phase and
1 2 3 4 5 6 7 8 9 10
40
Viraemia
Course of dengue illness: Febrile Critical Recovery Phases Shock Bleeding Reabsorption Fluid overload Dehydration Organ Impairment Days of illness
Temperature Potential clinical issues Laboratory changes Serology and virology Platelet Hematocrit IgM/IgG
Manifestasi infeksi virus dengue
(WHO 2011, UKK infeksi IDAI 2014)
11
11
When a child should be suspected of having
dengue infection?
à
Presumptive Diagnosis
•
Fever and 2 of the following criteria:
–
Anorexia and nausea
–
Rash
–
Aches and pains
–
Warning signs
–
Tourniquet test positive
–
Leucopenia
Recent history : live in/ travel to endemic area
12
Clinical approach
Part. No. Participant Organisation Name Country
1 Heidelberg University Hospital (UKL-HD) (Coordinator)
Germany
2 Oxford University (UOXF.AT) – OUCRU Vietnam UK
3 Liverpool School of Tropical Medicine (LSTM) UK
4 Fondazione per l’Istituto di Ricerca in Biomedicina (IRB) Switzerland
5 World Health Organization - Special Programme for Training and Research in Tropical Diseases (WHO)
Switzerland / Int. Partner
6 University of Malaya Medical Center (UMAL) Malaysia
7 Universitas Gadjah Madah (UGM) Indonesia
8 Angkor Hospital for Children (AHC) – Friends Without a Border Cambodia (USA)
9 Instituto Pedro Kouri (IPK) Cuba
10 Ministry of Health - Hospital National de Ninos Benjamin Bloom (HNNBB) El Salvador
11 Fundacao Universidade Estadual do Ceara (UECE) Brazil
12 Environmental Research Group Oxford Limited (ERGO) UK
13 INDEPTH-network (INDEPTH) Ghana
14 Red Cross / Red Crescent Climate Centre (RCCC) Netherlands
15 University of Carabobo Venezuela
16 FIOCRUZ (Recife, Rio de Janeiro) Brazil
Objec<ves clinical observa<onal study
(WP1 / WP2)
Objec<ves
1.
To iden<fy factors which differen<ate between dengue
and non-dengue illness during the early febrile phase
2.
To iden<fy factors among dengue infected pa<ents that
predict likely progression to a more severe disease
course.
3.
To iden<fy virological correlates of severe dengue – in
par<cular to assess plasma viremia and NS1 an<genemia
within the first 72 hours of fever in pa<ents with
confirmed dengue.
4.
To iden<fy early serological correlates of severe dengue, in
order to characterize differences between severe and
Study design (WP1): Clinical evalua<on of
dengue and risk factors for severe disease
•
Prospec<ve mul<-centre observa<onal study
•
Target N: ~ 7,500-8,000 pa<ents (undifferen<ated fever)
•
Pa<ents: > 5 years presen<ng with a febrile illness consistent
with possible dengue to outpa<ent clinics in urban centres
•
Inclusion: Fever for < 72 hours, in outpa<ent department
•
Exclusion: Localizing signs sugges<ng another diagnosis, features
of severe disease already present, Pa<ent thought unlikely to
Characteris<c of pa<ents with fever < 72 hours who came to
five outpa<ent clinics in Yogyakarta
Characteris<cs
Dengue
N (%)
99 (28.21)
Non Dengue
N (%)
252 (71.79)
Total
N (%)
351 (100)
Age
< 18 y.o (children)
44 (29.93)
103 (70.07)
147
> 18 y.o(adult)
55 (26.96)
149 (73.04)
204
Sex
Male
60 (28.99)
147 (71.01)
207
Female
39 (27.08)
105 (72.92)
144
Day onset of illness
Day of fever 1
19 (20.43)
74 (79.57)
93
Day of fever 2
43 (31.16)
95 (68.84)
138
Day of fever 3
37 (30.83)
83 (69.17)
120
DHF 5%
DF 95%
Clinical Diagnosis
Primary 90% Secondary
10%
Type of Infec<on
Confirmed Dengue 99 (28.21%) Total enrolment
24%
76%
Ns1
POS
NEG
14%
86%
PCR
POS NEG
11%
89%
IgM
•
DENV 1 = 46.94%
•
DENV 2 = 24.48%
•
DENV 3 = 22.46%
Clinical Sign & Symptoms at Enrolment Dengue N=99 n(%) Non Dengue N=252 n(%)
P -value
Anorexia 51 (34) 99 (66) 0.03*
Nausea 78 (35.45) 142 (64.55) 0.00*
Vomiong 33 (35.11) 61 (64.89) 0.08
Diarrhoea 2 (10.53) 17 (89.47) 0.07
Abdominal pain 30 (28.85) 74 (71.15) 0.86
Sore throat 9 (9.57) 85 (90.43) 0.00*
Headache 79 (28.83) 195 (71.17) 0.67
Joint pain 43 (27.92) 111 (72.08) 0.87
Muscle pain 47 (30.32) 108 (69.68) 0.54
Retroorbital pain 26 (31.71) 56 (68.29) 0.43
Cough 23 (20.54) 89 (79.46) 0.03*
Petechiae 2 (28.57) 5 (71.43) 0.98
Mucosal bleeding 4 (33.33) 8 (66.67) 0.67
Injeksi konjung<va 10 (58.82) 7 (41.18) 0.00*
Chill 43 (29.66) 102 (70.34) 0.63
Feeling Dizzy 29 (25) 87 (75) 0.325
Skin rash 2 (20) 8 (80) 0.55
Laboratory Dengue (Mean ± SD)
NonDengue
(Mean ± SD) P -value
Platelet count (10k/µl) 182.19 ± 66.15 234.61 ± 77.65 0.00*
Total WBC (k/µl) 5.01 ± 2.49 8.27 ± 3.94 0.00*
Haemoglobin (mg/dl) 14 ±1.48 13.95 ±1.64 0.86
Lymphocyte (%) 21.22 ± 11.83 19.92 ± 9.84 0.48
Monocyte (%) 11.76 ± 4.88 9.99 ±3.93 0.00*
0. 00 0. 25 0. 50 0. 75 1. 00 Se n si tivi ty
0.00 0.25 0.50 0.75 1.00
1 - Specificity
24
24
Critical Phase – Warning signs
•
Around the time of defervescence, patients can
either improve or deteriorate
•
Warning signs are the result of a significant
increase in capillary permeability.
•
Marks the beginning of the critical phase.
Warning Signs
•
Abdominal pain or tenderness
•
Persistent vomiting
•
Clinical fluid accumulation
•
Mucosal bleed
•
Lethargy; restlessness
•
Liver enlargement >2cm
Early Diagnosis Late Diagnosis
days -4 0 4 6 14-21 >50
Hematology Tes<ng Molecular Detec<on (RT-PCR)
Virus Isola<on Viral An<gen Detec<on
Neutralisation Test
Hemaglutination Inhibition
Serology Methods IgG / IgM
By Elisa or Rapid Tests
Virus RNA
Family Flaviviridae
Genus Flavivirus
Countries with ac<ve transmission of zika virus
per 29 Oct 2016
ZIKV in Indonesia
–
Zika was reported among adult patients in Klaten
Hospital (serology)
à
1981
–
Australian tourist return from Indonesia
à
confirmed
infected by ZIKV (2013)
Transmision
•
By mosquito bites
à
Aedes (A. aegypti and A.
albopictus)
•
Transmision via other mode:
–
Mother to foetus
–
During delivery (perinatal)
–
Sexual transmission (possible)
–
Blood transfusion (possible)
•
Transmision occur in first week after biting
Who can be infected?
•
Every one
•
People who traveling to endemic areas
•
Never exposed by ZIKV
Sign and symptoms
•
1 of 5 persons infected with ZIKV will develop illness
•
80% of infected persons
à
asymptomatic
Sign and symptoms
•
Mostly are asymptomatic or very mild
•
Incubation period : several days – 1 week
•
Symptoms:
–
Fever
–
Rash
–
Myalgia / arthralgia
–
Conjungtivitis
–
Headache
Zika infection in pregnant women
•
Impact can be occurred
during pregnancy.
•
Neurological impact
à
Diagnosis dan lab test
•
Diagnosis based on clinical and lab findings
•
RT-PCR
à
sebelum hari ke-5 sejak <mbul gejala
•
IgM atau IgG an< Zika
à
setelah hari ke-5 sejak
<mbul gejala
à
hasil bisa
cross-reac.on
dengan
dengue
à
menunjukkan peningkatan <ter pada
paired sera ( 2 weeks interval)
Countries and territories where chikungunya cases have been reported*
(as of April 22, 2016)
*Does not include countries or territories where only imported cases have been
Most common clinical manifesta<ons of
CHIK in children and adults
Children
•
Maculopapular rashes (33–
60%).
•
Changes in pigmenta<on
(42%).
•
Bullous rashes/skin abrasions
in infants <6 months of age
(38–48%).
•
Seizures, acute
encephalopathy,
meningoencephali<s (14–
32%).
Adults
• Maculopapular rashes on trunk and limbs (35–50%).
• Headache (40–81%).
• Symmetrical arthri<s/arthralgia, more commonly affec<ng distal joints (87– 99%).
• Conjunc<vi<s (3–56%).
• Tenosynovi<s (common).
• Back pain.
• Myalgia (60–93%).
• Persistent or recurring arthralgia for a year in more than 57%.
Abrupt onset of fever >38.9 °C, dura<on of 1–8 days (76–100%)
Symptoms and signs - frequency (%)
•
Fever
•
Polyarthralgia
•
Headache
•
Myalgias
•
Backpain
•
Nausea
•
Vomi<ng
•
Rash
•
Polyarthri<s
•
Conjunc<vi<s
Symptoms
•
Most people infected with chikungunya virus will develop some symptoms.
•
Symptoms usually begin 3–7 days auer being biIen by an infected mosquito.
•
The most common symptoms are
fever and joint pain
.
•
Other symptoms may include headache, muscle pain, joint swelling, or rash.
•
Chikungunya disease does not ouen result in death, but the symptoms can
be
severe and disabling
.
•
Most pa<ents feel beIer within a week. In some people,
the joint pain may
persist for months.
•
People at risk for more severe disease include newborns infected around the
<me of birth, older adults (≥65 years), and people with medical condi<ons such
as high blood pressure, diabetes, or heart disease.
•
Once a person has been infected, he or she is likely to be
protected from future infec<ons.
Clinical comparison of dengue,
chikungunya and Zika.
Symptoms
Dengue
CHIK
ZIKA
Fever
++++
+++
+++
Myalgia/ Arthralgia +++
++++
++
Edema on limb
-
-
++
Maculopapular
exanthema
++
++
+++
Retro orbital pain
++
+
++
Conjunc<vi<s
-
+
+++
Lymphadenopathy ++
++
+
Hepatomegaly
+++
-
-
Challenges
•
Clinical manifesta<on varies among diseases
•
Diagnos<c test should be applied
appropriately
•
Lack of test for Chik and Zika
•
Strengthening surveillance
•
Simple hematology test should be performed
at the early stage of disease
à
dengue
Summary
•
Diagnosis of dengue, chikungunya
and Zika is mainly clinical.
•
In regions where the risk of dengue is
significant, it is important to
inten<onally look for warning signs,
with a comprehensive medical history
and physical examina<on in addi<on
to a complete blood count
