Hantavirus infection

Clinical manifestations and management

Muhammad Hussein Gasem

mhgasem@gmail.com
Bagian dari studi tentang “clinical aspects of dengue infection in adults”
Subyek : penderita dengan demam akut yang memenuhi kriteria dengue
(WHO 1997) tetapi secara serologi, diagnosis dengue tidak confirmed.
Hantavirus infection (HFRS) in selected countries in Asia

Bi et al, J Infect Developing Countries 2008; 2(1):3-23

 Human hantavirus infections
Clinical manifestations

Clinical manifestations are mostly atypical mimicking other infectious diseases

like dengue infection, leptospirosis, or other acute febrile illnesses

Two important clinical syndromes :

-Haemorrhagic fever with renal syndrome (HFRS) in Asia and Europe
-Hantavirus cardiopulmonary syndrome (HPS/HCPS) in the Americas

Hantavirus disease/fever may be an inclusive terminology since pathogenesis

and clinical features of these syndromes overlap
 Hantaviruses associated with
human infections

Bi et al, J Infect Developing Countries 2008; 2(1):3-23

 Fig 1. Map of Old World and New World hantavirus genotypes reported to be pathogenic for humans.

Tian H, Stenseth NC (2019) The ecological dynamics of hantavirus diseases: From environmental variability to disease prevention largely based
on data from China. PLOS Neglected Tropical Diseases 13(2): e0006901. https://doi.org/10.1371/journal.pntd.0006901
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006901
 Human hantavirus infections
Clinical manifestations

Clinical manifestations are mostly atypical mimicking other infectious diseases

like dengue infection, leptospirosis, or other acute febrile illnesses

Two important clinical syndromes :

-Haemorrhagic fever with renal syndrome (HFRS) in Asia and Europe
-Hantavirus cardiopulmonary syndrome (HPS/HCPS) in the Americas

Hantavirus disease/fever may be an inclusive terminology since pathogenesis

and clinical features of these syndromes overlap
 Leptospirosis, dengue and hantavirus infections
worldwide (2002)

Hantavirus
Leptospirosis Dengue
infection (HFRS)

Total number Unknown 50.000.000 Unknown

annually

Severe forms** 300.000 – 500.000 400.000 150.000 – 200.000

Mortality (severe 5 – 20%*** 5 – 15% 3 – 10%***

forms)

HFRS : Hemorrhagic Fever with Renal Syndrome

** Leptospirosis & Hantavirus infection with hospitalization; Dengue, DHF
*** Mortality of 40% and higher reported for a number of
outbreaks and/or strains or forms of disease R. Hartskeerl (2011)
Hantavirus Pulmonary Syndrome, USA, 1993–2009

MacNeil A et al . EID. 2011;17:1195-1200

 Hantavirus Pulmonary Syndrome, USA, 1993–2009

A: Annual number of cases of hantavirus pulmonary syndrome (HPS)

B: Percentage of cases by month of onset

MacNeil A et al . EID. 2011;17:1195-1200

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 9,
September 2004
Junior VLP et al . J Infect Dev Ctries 2014; 8(2):137-142
Clinical course of hantavirus pulmonary syndrome (HPS/HCPS)
Clinical features of Hantavirus Infection
Hemorrhagic Fever with Renal Syndrome (HFRS)
Clinical course and symptoms of hemorrhagic fever with renal syndrome (HFRS)

Bi et al, J Infect Developing Countries 2008; 2(1):3-23

 Comparison of HFRS and HPS / HCPS

HCPS : Hantavirus Cardio-Pulmonary Syndrome

Hanta virus infection misdiagnosis sebagai Leptospirosis ringan/berat
 Leptospirosis
Clinical diagnosis
Suspect case

 Acute febrile illness ( ≥ 38.5 C ) AND/OR severe headache

with:
 Myalgia
 Prostration AND/OR
 Conjunctival suffusion, AND
 History of exposure to Leptospira-contaminated
environment & occupational risk factors
 Leptospirosis
Probable case (1)
Clinical diagnosis
Suspect case with any two of the following:
Calf tenderness
Meningeal irritation
Cough with/without hemoptysis
Jaundice (icterus)
Haemorrhagic manifestations
Anuria / oliguria and/or proteinuria
Dyspneu (ARDS)
Cardiac arrhythmias
Probable case (2) Leptospirosis
If laboratory tests are available Clinical diagnosis

Suspect case with:

Positive of Rapid tests (Lepto Lateral Flow or Dri dot)

AND / OR
Any three of the following:
Urinary findings: proteinuria, blood
Relative neutrophilia (>80%) with lymphopenia
Thrombocytes < 100,000 / cu mm
Elevated serum bilirubin > 2 mg%; liver enzymes moderately raised
(SGPT, SGOT, Amylase, CPK)
Two cases of hantavirus infection initially misdiagnosed as leptospirosis and later
further investigated and diagnosed as hantavirus infections. They had clinical pictures
of a combination of both HFRS and HPS and the central nervous system (CNS)
involvement as well. Both cases were serologically confirmed as hantavirus infections.

Case 1
Case 2
 Hantavirus Infection in patients with
“Unconfirmed Probable Leptospirosis”

?
Subyek adalah penderita probable leptospirosis, dg serologi MAT tidak confirmed (negatif),
 pemeriksaan serologi IgM anti hantavirus positif.
Catatan: PCR untuk Leptospirosis dan Hantavirus pada saat itu belum dikerjakan
Lisa Novi Puspitasari, Arif Mulyono, Farida D Handayani, Muhammad Hussein Gasem, unpublished
Laporan kasus

A confirmed leptospirosis and hantavirus co-infection

LN Puspitasari, A Mulyono, FD Handayani, MH Gasem (unpublished)

 Fig 1. Map of Old World and New World hantavirus genotypes reported to be pathogenic for humans.

Tian H, Stenseth NC (2019) The ecological dynamics of hantavirus diseases: From environmental variability to disease prevention largely based
on data from China. PLOS Neglected Tropical Diseases 13(2): e0006901. https://doi.org/10.1371/journal.pntd.0006901
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006901
Case 1

Case 2

Clinical diagnosis on admission

Case 1: Dengue infection
Case 2 : Typhoid fever

Lie et al. BMC Infectious Diseases (2018) 18:578

Lie et al. BMC Infectious Diseases (2018) 18:578
Clinical symptoms common for HFRS, also for HPS/HCPS

Clement J et al. EID 2019 Feb; 25(2): 387–388

Clinical management

Antiviral treatment
No specific antiviral drugs for treatment of hantavirus infections.
Ribavirin has exhibited some in vivo and in vitro effects against replication of
hantaviruses but remains ineffective for the treatment of HPS/HCPS).

Supportive therapy
Best method to control progression towards life-threatening symptoms in HFRS/HCPS.
Careful fluid management, electrolyte balance and haemodynamic monitoring .
i.e. ventilatory support (HCPS), dialysis (HFRS) etc as indicated

Chandy S, Mathai D. Indian J Med Microbiol 2017;35:165-75

Junior VLP et al . J Infect Dev Ctries 2014; 8(2):137-142
terimakasih
 Diskusi
Populasi 120 orang:
• Sedang bergejala demam 14 orang
• Positif Typhoid dari yang bergejala 5 orang
• Positif Hantavirus 3 orang (1 bergejala, 2 tidak bergejala)
• Postif Leptospirosis 2 orang dari yang bergejala
Apakah kasus hanta bersifat carrier?
Prof Gassem:
- Sebaiknya pada populasi tersebut dilakukan pemeriksaan serologi
IgG untuk lepto dan hanta
- IgM kasus lepto 100% muncul pada hari ke 11 demam
- IgM kasus hanta biasa muncul mulai hari ke 5 demam
- Kasus hanta yang paling ringang manifetasi klinisnya sperti ILI
- Kasus hanta bisa self limited atau bertambah berat
Puskesmas Cakung
• Apakah sensitiffitas RDT lepto berbeda karena jumlah
sampel? Atau memang berbeda karena daya tahan tubuh
yang berbeda?
• Pada kasus yang RDT (-) atau PCR (-) namun secara klinis
mengarah pada lepto, apakah akan berpengaruh jika
diberikan antibiotik selama 7 hari?
berikan antibiotic pada kasus yang dicurigai disebabkan oleh
virus atau bakteri
• Apakah ada gejala khas hantavirus? Tidak ada, oleh
karenanya cara mengenalinya melalui pendekatan
diagnosa banding pada kasus dengue, atau lepto
• RSUD Pasar Rebo
Apakah hantavirus bisa berkembang menjadi penyakit
kronik? Belum ada suatu penelitian yang menyatakan
hal tsb. Namun pada kasus lepto kemungkinan tersebut
ada

Dinkes Pacitan
- Pada situasi KLB hepatitis A yang saat ini terjadi
perlukah ada kecurigaan yang lain? Lepto?
Pasien harus dilakukan pemeriksaan IgM HAV, jika sudah
confirm maka memang benar itu karena Hep A.
Kecurigaan lepto tetap mungkin saja, penegakan hanya
melalui confirm lab
Apakah pada lokasi sentinel lepto akan dilakukan
pemeriksaan lanjut untuk hanta?
• Puskesmas Merdeka Palembang
Pada pasien yang sudah pernah kena hanta dan
lepto apakah ada kemungkinan kena lagi?
Ya, belum ada kekebalan seumur hidup, sehingga
mungkin muncul kembali jika ada paparan
• RSUD Serang
Apakah ada materi berbahasa Indonesia untuk
memudahkan sosialisasi hanta?
Pada kasus dengue perlu dipikirkan DD lepto dan
hanta
• Sudinkes Jaktim
Pola kasus lepto dan dengue memiliki kesamaan.
Apakah ada kemungkinan kasus dengue tersebut
merupakan kasus lepto juga? Y
• RSUD Pasar Minggu
Apakah sudah ada penelitian pada kasus MAT (-)
lepto berapa % yang (+) hanta? belum
Kapan kecurigaan hanta atau lepto ? Demam,
trombositopenia, gagal ginjal
Apakah sudah ada penelitian yang menyatakan
adanya mutase Hantavirus yang bisa menular
antar manusia? belum
• BBTKLPP Jakarta
Apakah pemeriksaan hanta bisa dilakukan sampai
skeunsing
• Dinkes Kab. Tangerang
Apakah pada kasus lepto bisa juga dilakukan
pemeriksaan hanta di B2P2VRP salatiga?
• df
• HP: 08122806399