Curiculum vitae

Dr. Anggraini Alam, dr., SpA(K)

Dokter Spesialis Anak konsultan Infeksi & Penyakit Tropis

Departemen Ilmu Kesehatan Anak
RSUP Dr Hasan Saddikin- FK Universitas Padjadjaran

Education:
MD, Pediatrician, and Doctor graduates from Faculty of Medicine Universitas Padjadjaran
Pediatric Consultant of Infection & Tropical Medicine from Indonesian Pediatric College 2011

Organization:
Ketua UKK Infeksi & Penyakit Tropis IDAI
Pengurus Harian Kolegium Ilmu Kesehatan Anak Indonesia
Board Member of Asia Society of Pediatric Infectious Diseases (ASPID)
Komli Difteri Kemenkes RI
Panli HIV/AIDS Kemenkes RI
Secretary of Internal Advisory of IPS West Java Branch
Member of Pharmacy Task Force of IPS
Member of Infectious Diseases Outbreak Response of IPS
Member of HIV Task Force of IPS
Member of Infection Control, AMR, HIV/AIDS, and Outbreak Response in Hasan Sadikin GH
Anggraini Alam
Anggraini Alam
 UKK Infeksi & Penyakit Tropis IDAI

Koinfeksi Dengue dan COVID-19

Anggraini Alam
Outline
• Epidemiologi
• Dengue atau COVID-19?
• Perawatan pasien
• Mortalitas dengue vs COVID-19
• Cross immunity?
• Dampak lockdown pada dengue

Anggraini Alam
Background

• The COVID-19 pandemic continues to spread worldwide

• It is likely to overlap with the dengue epidemics in tropical countries.

• Due to overlapping clinical and laboratory features, it may be difficult

to distinguish dengue from COVID-19

• misdiagnosing COVID-19 as dengue has serious implications in

outcomes for the patient, vice versa

Anggraini Alam
 Dengue versus COVID-19 cases, 2020 year to date*

Indonesia and the Philippines are experiencing outbreaks of the coronavirus and dengue fever simultaneously.
Singapore, which has just managed to regain control of COVID-19, is now contending with record levels of dengue fever.
Anggraini Alam
 Anggraini Alam
Is it COVID-19 or dengue?
22% of COVID-19 infections may be falsely identified as dengue

Lus\g Y, et al. Clin Infect Dis 2020:ciaa1207.

Anggraini Alam

Nacher M, et al. PLOS

Neglected Tropical
Diseases 14(8):
e0008426.
Anggraini Alam
 Anggraini Alam
Henrina J, et al. SN Comprehensive Clinical Medicine
https://doi.org/10.1007/s42399-020-00364-3
 Kelainan hematologi dasar
Parameter COVID-19 Demam dengue Severe dengue
Hb Normal/↓ Normal ↑↑

Ht Normal/↓ Normal/↑ ↑↑

Lekosit • Normal/↓ Normal lalu menjadi ↓ • Awal demam: normal atau +

• Dapat ↑ pada neutrofilia
infeksi sekunder • Leukopenia (≤5000/mm3)

Limfosit ↓ (absolut dan persentase) • ↑ (limfositosis relatif) • ↑ (limfositosis relatif)

• Atipikal limfosit ↑ • Atipikal limfosit ↑
Anggraini Alam

Neutrophyl to ↑ (cut-off 3,13 – 6,2) ↓ ↓↓

Lymphocyte Ratio (NLR) (neutrofil < limfosit)
Platelet to Lymphocyte ↑ (cut-off 180 à prediktor ↓ ↓
Ratio (PLT) derajat keparahan)
Trombosit Normal/↓ ringan ↓ ↓↓
Test: COVID vs Dengue
Dengue COVID-19
• The lack of adequate laboratories
• Primary health care:
across the country
• CBC
• NS-1/Combo • low testing rate of Covid-19 patient

Anggraini Alam
• Misdiagnosis due to serology cross- • Antibody for MIS-C
reactivity between Covid-19 and
dengue (1st reported in Singapore);
possible cross-reactivity between
dengue virus and SARS-CoV-2

<< à could hamper the diagnosis and management

Misdiagnosis between dengue and Covid-19

COVID-19 and dengue fever are difficult to

differentiate because they share clinical and
laboratory features

Anggraini Alam
 The consequences of COVID-19
and dengue misdiagnosis

• ineffective patient management

• patient death

Anggraini Alam
• unsuccessful prevention strategies
• rapid patient isolation (in the case of COVID-19)

• vector control (in the case of dengue fever)

Wilder-Smith A, et al. Am. J. Trop. Med. Hyg., 103(2), 2020, pp. 570–571
 The structure differences between SARS-CoV-2 and DENV
Anggraini Alam
MIS-C vs Severe Dengue
• Severe dengue, with fever, abdominal symptoms, rash, shock, myocardial

Anggraini Alam
dysfunction, and bicytopenia closely mimics MIS-C
• Differentiate MIS-C from severe dengue:
• oral mucosal findings
• raised inflammatory parameters
• anemia
• coronary artery abnormalities
• no plasma leakage
• MIS-C should be considered in the syndrome of fever with
rash/thrombocytopenia, which includes dengue fever, rickettsial,
meningococcal infection, malaria, leptospirosis, and viral exanthems.

Samprathi M, et al. Indian J Pediatr. 2020;1-2.

 Pathophysiological similarities between DHF and Covid-19
Anggraini Alam

Harapan H, et al. Rev Med Virol. 2020;e2161.

 IsolaTng a paTent with COVID-19 and dengue
• Continuous hemodynamic monitoring and management in coinfection cases are remain
crucial
• Patient should be monitored closely
• The pitfall in dengue: identifying the poor signs of peripheral perfusion, as early sign of
shock during dengue critical phase, when a patient is treated in COVID-19 isolation room
• The pitfall in COVID-19: silent or “happy” hypoxia in COVID and shock in MIS-C

Educate the care giver how to do CCTVR

check RR and 02 saturation (if monitor not available)
Anggraini Alam
Alam A, et al. Am J Trop Med Hyg. 2021 Feb 24;104(4):1456–60
Which is more lethal?

Anggraini Alam
 Kasus dengue s.d Minggu Ke-49, 2020
(Kemenkes RI)
Golongan Kasus dengue Meninggal
umur
2019 s.d minggu 2019 s.d minggu
n= ke-49, n= ke-49,
2020 2020
n = 95.893 n=661
2.7%

< 1 tahun 2,13% 3,13 % 3,0% 10,32 %

1–4 9,23% 14,88 % 16,0% 28,57 %

tahun
5 – 14 41,72% 33,97 % 47,0% 34,13 %,

Anggraini Alam
tahun
15 – 44 37,25% 37,45 % 26,0% 15,87 %
tahun
> 44 9,67% 11,57 % 8,0% 11,11 %
tahun

Angka kematian 0,69%

Dengue may provide COVID-19 immunity

Anggraini Alam
• 2351 participants with coronavirus
disease 2019
• 1177 (50%) reported previous
dengue infection.
• Those without previous dengue
had a higher risk of death in 60-
day follow-up.

Anggraini Alam
Silvestre OM, et al. Clin Infect Dis. 2020 Dec 29:ciaa1895.
doi: 10.1093/cid/ciaa1895. Epub ahead of print.
Anggraini Alam

A. Kaplan-Meier es\mates of the probability of death in pa\ents with COVID-19 according to the history of dengue.
B. Associa\on of history of dengue, clinical characteris\cs, and treatment with mortality in pa\ents with COVID-19

Silvestre OM, et al. Clin Infect Dis. 2020 Dec 29:ciaa1895.

doi: 10.1093/cid/ciaa1895. Epub ahead of print.
What Is the Impact of Lockdowns on Dengue?

Anggraini Alam
 Why Understanding the Impact of
Lockdowns on Dengue Is Important
PosiTve impact of lockdown
• movement restrictions could slow or
even prevent the spread of a dengue
Anggraini Alam
epidemic
• countries that have yet to make a full
transition to web-based reporting
systems
• pollution was reduced during the
lockdown period ~ vector breeding
Brady O, et al. Current Infectious Disease Reports (2021) 23: 2
Negative impact of lockdown
• Disruption to routine vector control
programmes
• more people spending more time at
home rather than their usual visited
locations, lockdowns are likely to
influence the contact rate between
human and mosquito
• disrupt detection and reporting of
dengue cases by routine surveillance
systems.
• Underreporting and accuracy (?))
• Competes dengue vs COVID-19 for
triage, clinical diagnosis, laboratory
testing and treatment resources
Take home messages
• Potensi dual infection dengue dan COVID dapat terjadi pada era pandemic COVID-19 di
area endemic dengue
• Coinfection of COVID-19 and dengue should be considered in feverish children living in endemic
tropical region of dengue, especially on dengue peak cases period (by the end of rainfall season)
• Sindrom klinis dapat terjadi akibat terjadi koinfeksi dan kemungkinan adanya serological
cross-reactivity dapat memengaruhi diagnosis kedua infeksi tersebut
• The symptom similarities of COVID-19 and dengue is a new challenge for healthcare professionals,
risking missed diagnoses and incorrect treatment.
• Clinicians should keep a high index of suspicion of COVID-19 even in a child with a positive dengue
rapid test, vice versa.
• Walaupun studi epidemiologi memperlihatkan bahwa previous dengue infection
mereduksi kasus COVID-19 berat dan fatal (imunisasi dengue?), namun hal ini perlu
penelitian lebih lanjut sebagaimana pemberian BCG dan MMR

Anggraini Alam
Anggraini Alam
Terima kasih
Anggraini Alam
Anggraini Alam
DHMOSH - PUBLIC HEALTH UNIT
COVID-19: DIAGNOSIS AND CO-INFECTIONS dos-dhmosh-public-health@un.org
23 JUNE 2020 Anggraini Alam
• The COVID-19 epidemic did not slow the onset of dengue fever.
• The lockdowns that require people to stay at home for their safety
exposes them to Aedes mosquitoes.
• People worried about seeking out medical assistance at hospitals
over fears they might be exposed to COVID-19
• Longer-term, changing patterns of rainfall, humidity and temperature
linked to climate change, are leading to longer mosquito breeding
spells and shorter disease incubation

Potentially to overwhelm health systems

Anggraini Alam
Infeksi Dengue

Anggraini Alam
Anggraini Alam
 METODE COVID-19 DENGUE
Isolasi virus SARS-CoV-2 DENV 1-4 (butuh waktu 2-4 minggu)
Deteksi asam • RT-PCR • Deteksi DENV 1-4 dengan PCR baik
nukleat • Sequencing konvensional maupun RT-PCR
• Hasil: positif/negatif • Hasil: Positif DENV1/DENV2 /DENV3 /DENV4
Negatif
Serologi antigen • Antigen SARS-CoV-2 • Deteksi Non-Structural Protein 1 (NS1)
• Deteksi dini fase akut • Dapat terdeteksi 3-4 hari pertama /fase akut
• Sensitivity 93.9% (86.5-97.4%) • Lebih baik pada infeksi primer
• Specificity 100% (92.1-100%) • NS-1 ELISA NS1 sensitivity 56.4%, specificity
100%
Serologi antibodi Deteksi IgM, IgG, Total Antibodi anti SARS- Deteksi IgM, IgG, IgA Anti Dengue Infeksi Primer:
CoV-2 • IgM terdeteksi hari ke3-5, dapat terdeteksi 3-8
• IgM mulai terdeteksi 7 hari, puncak hari ke- bulan
28, menghilang hari ke-42
Anggraini Alam

• IgG terdeteksi hari ke14

• IgG mulai terdeteksi 10 hari, puncak hari • IgA terdeteksi hari ke6, puncak hari ke-8,
ke-49 menghilang hari ke-40
Infeksi Sekunder:
• IgM kadar rendah, dapat tidak terdeteksi
• IgG & IgA terdeteksi hari ke2
• Antibodies to SARSCoV might accentuate disease through antibody-
dependent enhancement of viral entry and amplification of viral replication,
as observed in dengue,92–94 or by triggering a host inflammatory response
through the formation of immune complexes or direct antitissue antibody
activation or cellular activation, or both
• Some have postulated that there may be a mechanism similar to dengue
fever in which the existence of antibodies contributes to an increased
severity of secondary infection. Antibody dependent enhancement (ADE)
causes severe Dengue infection, including Dengue shock and Dengue
haemorrhagic fever. In ADE, the virus uses the phagocytotic process to
enhance its own viral replication and causes the death of the immune cells.
This leads to distributive shock and multi organ failure.

Anggraini Alam