Curriculum Vitae

Prof Dr dr Sri Rezeki S Hadinegoro Sp.A(K)

Staf pengajar
Departemen Ilmu Kes Anak FKUI/RSCM
Jakarta
• Pendidikan
– Dokter umum – FK.UNPAD 1972
– Spesialis anak – FK.UI 1983
– Doktor – FK.UI 1996
– Guru Besar – FK.UI 2000

• Organisasi
– Ketua Indonesian Technical Advisory Group on Immunization (ITAGI)
– Anggota Satuan Tugas Imunisasi IDAI
– Anggota KOMNAS PP KIPI – KEMKES
– Board member of Asian Society of Pediatric Infectious Disease (ASPID)
– Member of Asia-Pacific Dengue Prevention Board (APDPB)
– Member of Asia Dengue Vaccine Advocacy (ADVA)
– President Elect of International Society of Tropical Pediatrics (ISTP)
Dengue versus Chikungunya
Infection
diagnosis & management

Sri Rezeki Hadinegoro

Department of Child Health
FKUI-RSCM Jakarta

Presented at PKB – IDAI Jawa Tengah, Semarang 8-9 January 2017

 Outlines
• Geographical distribution
• Natural course of illness
• Clinical & laboratory diagnosis
• Differential diagnosis
• Clinical management
• Prevention
Geographical Distribution
Countries at risk of dengue transmission,
2008
 Chikungunya, countries or areas at
risk

WHO Fact sheet N°327, updated March 2014

Geographical distribution of Chikungunya
cases, 2001-2007
Dengue or Chikungunya?
Natural Course of Illness & Diagnosis
Natural Course of Dengue Virus Infection
 Dengue infection
• Asymptomatic (40%- 80%), • In the severe cases
mild, serious illness, can – Bleeding
cause death – Abdominal pain
• Incubation period 3 -14 days – Persistent vomiting
average of 4- 7 days
– Somnolence
• Main symptoms
– Irritability
– Sudden onset,high fever ( 39°-
40°C) – Hypotension
– Severe headache, muscle pain, – Vomiting
moderate joint pain
– Breathing difficulty
– retro-orbital pain
– Shock
• Skin maculopapular , itching
• Fatigue, nausea, loss of
appetite
WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
 Clinical manifestation of Dengue Infection
Dengue Outbreak, 6 referal hospital in Jakarta 2004
Clinical Manifestation DF DHF Total
n=241 n=1494
Gr I + II Gr II+III
n=1051 n=202
Fever before admission (day) 3,0±1,4 3,5±1,6 3,9±1,3 3,5±1,5
Length of fever (days) 4,2±1,5 4,8±1,7 5,0±1,7 4,7±1,7
Vomiting [n (%)] 101 (41,9) 473 (45,0) 130 (64,7) 704 (47,1)
Nausea 81 (33,6) 404 (38,4) 85 (42,3) 570 (38,2)
Diarrhoea 19 (7,9) 83 (7,9) 18 (9,0) 120 (8,0)
Cough 129 (53,5) 391 (37,2) 55 (27,4) 575 (38,5)
Convulsion 6 (2,5) 24 (2,3) 16 (8,0) 46 (3,1)
Unconciousness 0 (0) 6 (0,6) 27 (13,4) 33 (2,2)
Abdominal pain 61 (25,3) 461 (43,8) 116 (57,7) 638 (42,7)
Hepatomegaly [n (%)] 28 (11,6) 263 (25,0) 103 (51,2) 394 (26,4)
Ref. Endah Citraresmi, Sri Rezeki Hadinegoro. Sari Ped 2007;8:8-14.
Differential diagnosis in Dengue Infection
febrile phase
• Influenza,
• Measles
Flu-like • Chikungunya
syndromes
• Febrile convulsion
• Encephalitis

CNS Febrile Acute

infections phase exanthema

• Rubella, measles
• Scarlatina
• Meningococcal infections
• Enteric infection Diarrhoeal • Chikungunya,
• Rotavirus diseases • Drug fever
WHO SEARO 2011
Chikungunya virus infection
Clinical manifestations

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
Chikungunya infection
Clinical manifestations

Maculopular skin rash Chronic phase

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
Case definition

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
 Chikungunya infection
• Symptomatic in • Intense back pain
approximately 70%
person • Haeadache
• Incubation period 2 -12 • Skin maculopapular rash
days average of 2 -7 days appears on 48 hours (trunk,
• The main symptoms hands, feet)
– Abrupt onset of high fever • Muscle pain,
(over 39°C)
• Joint swelling
– Severe joint pain - mainly
on the hands, feet, ankles • Nausea/vomit
and wrists
• Conjunctivitis, photophobia
– Most people recover fully
but in some cases, joint • Sore throat
pain may continue for
weeks or become chronic • Fatigue
WHO Fact sheet N°327, Updated March 2014
Clinical signs & symptoms
 DD versus CHIKV versus DBD
Gejala klinis Demam Dengue Chikungunya DBD
Demam ++ ++ ++
Nyeri kepala ++ +++ ++
Mialgia/ artralgia ++ +++ ++
Ruam + ++ ++
Perdarahan + - +++
Nyeri tenggorokan ++ + ++
Batuk ++ + ++
Mual/muntah ++ + ++
Diare ++ + ++
Nyeri perut ++ + ++
Anoreksia +++ + +++
Jumlah leukosit rendah normal rendah
Hematokrit meningkat normal meningkat
Trombositopenia + tidak ada/kadang ++
Transaminase meningkat + tidak +++
 Univariate anaylsis of variables at first presentation to hospital

Lee VJ, Chow A, Zheng X, Carrasco LR, Cook AR, et al. (2012) Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections
in Adults. PLOS Neglected Tropical Diseases 6(9): e1786. doi:10.1371/journal.pntd.0001786
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001786
Laboratory Diagnosis
 Ht, Plt, atypical lymphocyte (limfosit plasma
biru) at day of illness
Hematocrit ✜
50 ✪ ✜  250
✜
✪ ✪ ✜
✪ ✜
✪
40 ✜ ✪   200
✪ ✜ ✪
Hematocrite vol%

Platelet x1000/l
 ✜
30 ✪ 150

✪
Platelet 
20  100

 
✜
10  50
✜
Atypical lymphocyte
0 0
0 1 2 3 4 5 6 7 8 9 10
Day of illness
Febrile phase Critical phase Recovery phase
 Time course analysis of selected variables

Lee VJ, Chow A, Zheng X, Carrasco LR, Cook AR, et al. (2012) Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections
in Adults. PLOS Neglected Tropical Diseases 6(9): e1786. doi:10.1371/journal.pntd.0001786
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001786
 Dengue antigen detection & serological
test

1 2 3 4 5 9 day of fever
 Viremia
IgG
Virus isolation

RNA, NS1, other antigen

Antibody titer

IgM

Primary infection Secondary infection

Time
Onset of symptom
Laboratory diagnosis

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
 Diagnostic testing algorithm

WHO Fact sheet N°327, Updated March 2014

 Diagnostic testing algorithm

WHO Fact sheet N°327, Updated March 2014

 Figure 2. Decision tree models for discrimination.
Decision tree models for discrimination
A B

C D

Lee VJ, Chow A, Zheng X, Carrasco LR, Cook AR, et al. (2012) Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections
in Adults. PLOS Neglected Tropical Diseases 6(9): e1786. doi:10.1371/journal.pntd.0001786
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001786
 Algorithm for Flavivirus
detection
Suspected case
Acute phase Onset of symptoms vs Convalescent phase
1-5 days after onset taking of samples ≥6 days after onset

RT-PCR/NS-1 dengue IgM dengue IgM CHIKV

Positive Negative
DENV confirmed Consider CHIKV Positive Positive
Presumptive DENV Presumptive CHIKV

Negative
(RT)-PCR CHIKV Consider ZIKV
Positive Negative
CHIKV confirmed CHIKV confirmed
IgM ZIKV
Positive Negative
Presumptive ZIKV ZIKV
(RT)-PCR ZIKV
Positive Negative
ZIKV confirmed ZIKV
www//who.int 2016
Management
 Suspected Dengue Infection
• Fever <7 days
• Skin rash
• Bleeding manifestations
(tourniquet test/spontaneous)
• Headache, retroorbital pain, myalgia,
arthralgia
• Leucopenia (4000/mL)
• Dengue case in the neighborhood

Warning signs
• No clinical improvement at afebrile phase • Bleeding tendency: epistaxis, black stool, hematemesis,
• Refused oral intake menorrhagia, black color urine
• Recurrent vomiting (haemoglobinuria) or hematuria
• Severe abdominal pain • Giddines
• Lethargy, change of behavior • Pale, cold extrimities
• Decreased diuresis within 4-6 hours
No Yes

No • Co-morbidity Yes Hospitalization Clinical & lab follow-up

• Social indication

Send home Warning DHF DHF with Expanded Dengue

managed at signs shock Syndrome
out patient • Organ involvement
clinic • Complication
• Co-morbidity
UKK IPT IDAI, 2014
Closed follow-up • Co-infection
 Compensated Dengue Shock Syndrome
• Give oxygen 2-4L/minute
• Check hematocrit
•Crystalloid RL/RA 10-20ml/kg.BW within 10-20 minutes

Yes Shock recovered No

IVFD 10ml/kg.BW, 1-2 hours Check Ht, blood gas, blood glucose,
calcium, bleeding (A-B-C-S)
Correction soon for acidosis,
Stabile, hypoglycemia, hypocalcaemia
Decreased IVFD gradually
7, 5, 3 , and 1,5 Ht increased Ht decreased
ml/kg.BW/hour
2nd bolus for crystalloid
Or colloid 10-20ml/kg.BW Bleeding
within 10-20 minutes Unclear
Stop IVFD
maximal 48 hours
after shock recover Colloid 10-20ml/kg.BB
within 10-20menit, if shock
Blood transfusion
persist suggested blood
UKK IPT IDAI, 2014
transfusion
 Chikungunya

1. Acute stage of the illness

2. Chronic stage (sequelae)

Chikungunya disease is very rarely fatal, but the

virus sometimes causes serious complications
mostly in elderly, infants or people
with underlying medical conditions
 Management in Acute Stage
• No specific antiviral drug
• Symptomatic treatment
• Paracetamol is drug of choice, aspirin is
avoided
• No indication for steroid in acute phase
• Exercise and physiotherapy is recommended
in convalescent phase
• Mosquitos control to avoid transmission
www:cdc.gov/chikungunya
Treatment
Sequelae
• Persistent arthralgia form were observed
– Complete resolutions 87.8%
– Episodic stiffness & pain 3.7%
– Persistent stiffness without pain 2.8%
– Persistent pain for restriction of joint movement
5.6%
– Tendinitis of tendon Achilles 53%
– Others: neurological, emotional and
dermatological sequelae
WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
 Osteo-artricular problems
• Usually subside in one to two weeks’ time
– 20% cases, disappear after a few weeks
– <10% cases, persist for months
– 10 % cases, reappear with every other febrile illness
for many months (joints get swollen, mild effusion and
symptoms persist for a week or two)
• In chronic cases, a short course of steroids may
be useful
– care must be taken to monitor all adverse reactions

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
Neurological problems
• 40% complain of various neurological symptoms
– 10% will persistent
– Peripheral neuropathy 5- 8%
– Paresthesia, pins and needles sensations, like carpal
tunnel syndrome
– Motor neuropathy is rare
– Anti-neuralgic drugs (carbamazepine, gabapentin)

• Ocular involvement
– During the acute phase in less than 0.5%
– Progressive defects in vision due to uveitis or
retinitis may have treatment with steroids.

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
Dermatological problems
• Skin manifestations subside after the acute
phase is over and rarely require long term care
– Psoriatic lesions and atopic lesions: require
specific management
– Hyperpigmentation and papular eruptions: zinc
oxide cream and/or calamine lotion
– Aphthous-like ulcers on the skin and inter-
triginous areas: saline compresses, topical or
systemic antibiotics if secondarily infected

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
Psycho-somatic problems
• Neuropsychiatric/emotional problems have
been observed in up to 15% cases
– more likely in persons with pre-morbid disorders
– a family history of mood disorders
• The emotional and psychosocial issues need
individual assessment
– Psychosocial support and reassurance may solve
some of the problems

WHO SEARO. Guidelines on Clinical Management of Chikungunya Fever, New Delhi 2008
Prevention
Conclusions
• Chikungunya and dengue infection are viral
diseases cause by a human-mosquito-human
transmission
• Should be differentiate at acute stage
– signs and symptoms are quite similar
– first step is to differentiate between dengue and
chikungunya infection
• dengue has higher incidence, can cause death, and
different prognosis
• confirmed diagnosis by antigen detection or serological
test
Conclusions
• No specific anti viral treatment
• Sequelae
– no sequelae in dengue infection
– some chikungunya cases have persistent
arthralgia, neurological disorders, or other
chronic problems
• Prevention by mosquitos control